Hospital Medicine

For many patients hospitalized with COVID-19, the impact of the illness continues well beyond hospital discharge.¹ Heavy burdens of persistent symptoms have been reported, albeit often from regional and single-hospital samples.^2-7 Critically, not all initial reports capture information on pre-COVID-19 symptom burden, so it is unclear whether these highly prevalent problems are truly new; an alternative explanation might be that patients already with symptoms were more likely to be infected with or seek care for SARS-CoV-2.⁸

Fewer data are available about patients’ abilities to go about the activities of their lives, nor is as much known about the relationships between new symptoms and other impacts. Most of the available information is from health systems during the initial surge of COVID-19 in early 2020—when testing for SARS-CoV-2 was limited even in the inpatient setting; when hospitals’ postdischarge care systems may have been heavily disrupted; and when clinicians were often reasonably focused primarily on reducing mortality in their first cases of COVID-19 rather than promoting recovery from an often-survivable illness. Increasing evidence shows that the inpatient case-fatality rate of COVID-19 is improving over time^9,10; this makes unclear the generalizability of outcomes data from early COVID-19 patients to more recent patients.¹¹

Therefore, we report multicenter measurements of incident levels of persistent cardiopulmonary symptoms, disability, return to baseline, and impact on employment among a recent cohort of COVID-19 patients hospitalized around the United States during the “third wave” of COVID-19—fall and winter 2020-2021. We focus on the 1-month time point after hospital discharge, as this time point is still in the early vulnerable period during which hospital transition-of-care programs are understood to have responsibility.

The first 253 patients who completed 1-month postdischarge telephone follow-up surveys from the ongoing nationwide BLUE CORAL study were included. BLUE CORAL will enroll up to 1,500 hospitalized COVID-19 patients at 36 US centers (the identities of which are reported in Appendix 1) as a part of the National Heart, Lung, and Blood Institute’s Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. We report here on survey questions that allowed for a clear comparison to be made between 1-month follow-up responses and pre-COVID baseline variables; these comparisons were based on (1) previous in-hospital assessment; (2) explicitly asking patients to compare to pre-COVID-19 levels; or (3) explicitly asking patients for changes in relation to their COVID-19 hospitalization. Items were chosen for inclusion in this report without looking at their association with other variables.

This research was approved by the Vanderbilt Institutional Review Board (IRB), serving as central IRB for the PETAL Network; patients or their surrogates provided informed consent.

Participants

Patients with COVID-19 were identified during hospitalization and within 14 days of a positive molecular test for SARS-CoV-2. Eligible patients presented with fever and/or respiratory signs/symptoms, such as hypoxemia, shortness of breath, or infiltrates on chest imaging. Patients were enrolled within the first 72 hours of hospitalization (in order to avoid oversampling patients with relatively longer stays, and to study the biology of early COVID-19), and excluded if they had comfort-care orders (because of their limited likelihood of surviving to follow-up), or were incarcerated (because of difficulties in obtaining truly open informed consent and likely difficulties in follow-up). Pertinently, patients were not required to be in the intensive care unit.

Surviving patients who spoke English or Spanish, were not homeless on hospital admission, and were neither significantly disabled nor significantly cognitively impaired were eligible for follow-up. “Not significantly disabled” was defined as having limitations due to health on no more than three activities of daily living before their COVID-19 hospitalization, as assessed at BLUE CORAL enrollment; this was chosen because of the potentially limited sensitivity of many of our questionnaires to detect an impact of COVID-19 in patients with greater than this level of disability. We included patients who were able to consent for themselves in the study, or for whom the legally appointed representative consenting on their behalf in the hospital reported no evidence of cognitive impairment, defined as no more than four of the problems on the eight-item Alzheimer’s Dementia (AD8) scale.^12-14

Data Collection

One-month surveys were administered to patients or, when necessary, their proxies; the complete English- and Spanish-language instruments are presented in Appendix 2. Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Michigan.^15,16

Patients were contacted via phone by trained interviewers beginning 21 days after hospital discharge; interviews were completed a median of 47 days after discharge (interquartile range [IQR], 26-61). Efforts prioritized former patients completing surveys themselves by phone, but a well-informed proxy was approached if needed. Proxies, who included spouses, adult children, or other relatives, family friends, or primary caregivers, were in regular contact with the patient and understood the patient’s health status. If necessary, the survey could be completed over multiple phone calls, and a written, mail-back option was available. Other best practices in accurate survey data collection and cohort retention were used.^17-19 Participants were given a $10 gift card.

New cardiopulmonary symptoms were queried with symptom-targeted questions informed by the Airways Questionnaire 20,²⁰ the Kansas City Cardiomyopathy Questionnaire,^21,22 and the Seattle Angina Questionnaire.²³ Whenever a respondent reported a given symptom, they were asked, “Compared to 1 month before your COVID-19 hospitalization, is this better, worse, or about the same?” We counted the number of symptoms which the patient reported as worse.

Using wording from the Health and Retirement Study,²⁴ disability was assessed based on a self-report of any of 14 health-related limitations in activities of daily living or instrumental activities of daily living, as in past studies²⁵: dressing, walking across a room, bathing, eating, getting out of bed, using a toilet, using a map, preparing a hot meal, shopping for groceries, making a phone call, taking medications, paying bills, carrying 10 lb (eg, a heavy bag of groceries), and, as a combined single item, stooping, kneeling, or crouching. Well-chosen proxy reports appear reliable for these items.²⁶ We counted the number of activities for which the patient reported a limitation, comparing those reported at 1 month to those reported during the in-hospital survey assessing pre-illness functioning.

The financial consequences of the COVID-19 hospitalization were assessed in two ways. First, we used a modified version of a World Health Organization Disability Assessment Schedule (WHODAS) 2.0 question²⁷: “Since your COVID-19 hospitalization, how much has your health been a drain on the financial resources of you or your family?” Second, we used the financial toxicity items developed with the Mi-COVID19 study³ based on extensive qualitative interviews with respiratory failure survivors²⁸; these questions were anchored explicitly on “the financial cost of dealing with your COVID-19 hospitalization and related care.”

Data Analysis

There were few missing data, and almost all were on outcome variables. Where present, the degree of missingness is reported and casewise deletion used. Because this was a planned early look at responses to an ongoing survey, with analysis based on the number of accrued responses, the ultimate denominator for response rate calculation is unknown. Therefore, two bounds are presented—the minimum, on the assumption that all remaining uncompleted surveys will be missed; and the maximum, as if the uncompleted surveys were not yet in the eligible denominator.

Variables were summarized with medians and IQRs. Multilevel logistic regression was used to test for differences across demographic characteristics in the rates of development of any new symptom or disability; site-level differences were modeled using a random effect. Gender, race/ethnicity, and age were included in all regressions unless noted otherwise; age was included with both linear and quadratic terms when used as a control variable. For the degree of return to baseline and for the number of new limitations in activities of daily living, we explored associations as dichotomized variables (any/none, using multilevel logistic regression) and as continuous variables (using multilevel linear regression). Percent of variance explained was calculated using the R² in unadjusted linear regression, and Spearman rank correlations were used to allow nonlinearities in comparisons across outcomes. All adjusted models are presented in Appendix Table 1. Analyses were conducted in Stata 16.1 (StataCorp, 2020); analytic code is presented in Appendix 3, and a log file of all analyses is in Appendix 4.

The 250th 1-month follow-up was completed on February 26, 2021. One month prior, 647 patients had been recruited at 26 centers in the inpatient phase of the study. Patient demographics for the 253 patients surveyed through that date are shown in Appendix Table 2. On the day of the early look at the data, 460 patients had become eligible for 1-month follow-up and 64 patients had been missed for 1-month follow-up (maximum response rate of 79.8%, minimum possible final response rate of 55.0%) (Figure 1). Seven surveys were completed by proxies. Respondents’ median age was 60 years (IQR, 45-68), and 111 (43.4%) were female. Their median hospital length of stay was 5 days(IQR, 3-8) . A total of 236 (93.3%) patients were discharged home, including 197 (77.9%) without home care services and 39 (15.4%) with home care services.

One hundred and thirty-nine patients (56.5%; 95% CI, 50.1%-62.8%) reported at least one new or worsened cardiopulmonary symptom after their COVID-19 hospitalization (Table; seven patients did not respond to these questions). Most patients with new symptoms had one (48 [19.5%]; 95% CI, 14.8%-25.0%) or two (32 [13%]; 95% CI, 9.7%-17.7%) of the new symptoms queried. The most common new cardiopulmonary symptom was cough, reported by 57 (23.2%; 95% CI, 18.0%-29.0%) patients. New oxygen use was reported by 28 (11.4%; 95% CI, 7.7%-16.0%) patients, with another 11 (4.5%; 95% CI, 2.3%-7.9%) reporting increased oxygen requirements. Women were twice as likely as men to report any new cardiopulmonary symptom (adjusted odds ratio [aOR], 2.24; 95% CI, 1.29-3.90) and non-Hispanic Black and Hispanic patients were less likely than White patients to report new symptoms (aOR, 0.31; 95% CI, 0.12-0.83; and aOR, 0.38; 95% CI, 0.21-0.71, respectively). Longer lengths of hospital stay were associated with greater 1-month cardiopulmonary symptoms (aOR, 1.82 per additional week in the hospital; 95% CI, 1.11-2.98), but discharge destination was not (aOR, 0.92; 95% CI, 0.39-1.71).

New limitations in activities of daily living or instrumental activities of daily living were present in 130 (52.8%; 95% CI, 46.4%-59.5%) patients (seven not responding), all of whom had 0 to 3 limitations before their COVID-19 hospitalization. Indeed, 62 (25.2%; 95% CI, 19.9%-31.1%) reported 3 or more new health-related limitations in activities of daily living or instrumental activities of daily living compared to their pre-COVID-19 baseline, as assessed separately during their hospitalization (Figure 2; rates of limitations in individual activities are shown in Appendix Table 3). Older patients were more likely to report a new health-related limitation, and Hispanic patients were less likely to have a new limitation. New limitations were common among patients discharged home without home health services. The number of new cardiopulmonary symptoms explained 11.2% of the variance in the number of new limitations in activities of daily living, a Spearman rank correlation of 0.30 (P < .0001; see Appendix Table 4). More than three in four COVID-19 patients reported new or worsened cardiopulmonary symptoms or new health-related limitations in activities of daily living at 1 month—only 62 (24.5%) patients reported neither.

At 1 month after hospital discharge, 213 (84.2%) patients reported that they were not fully back to their pre-COVID-19 level of functioning (3 declined to answer the question). When asked, “On a scale of 1 to 100, with 100 being all the way back to what you could do before COVID, how close to being back are you?” the median response was 80, with an IQR of 64-95 (Figure 3). Forty-two (16.8%; 95% CI, 12.4%-22.0%) patients reported a level of 50 or below. Women and older patients reported lower levels of return of functioning, as did those with longer hospital stays and new or worsened cardiopulmonary symptoms. Each additional week in hospital length of stay was associated with a 7.5-point lower response to the question (95% CI, –11.2 to –3.8), but discharge destination was not associated with the answer after adjusting for demographics. Patients with and without new limitations in activities of daily living and with and without new cardiopulmonary symptoms were found across the range of self-reported degree of recovery, although patients without a new problem in one of those domains were rarer among those reporting recovery of less than 70. The number of new cardiopulmonary symptoms explained 19.7% of the variance in the response to this question, a Spearman rank correlation of 0.47 (P < .0001).

More than half of respondents (115 [55.0%]; 95% CI, 48.0%-61.9%; 44 not responding) stated that their COVID-19 hospitalization had been a drain on the finances of their family; 53 (25.4%; 95% CI, 19.6%-31.8%; 44 not responding) rated that drain as moderate, severe, or extreme within the first month after hospital discharge. Forty-nine patients (19.8%; 95% CI, 15.1%-25.4%; 6 not responding) reported that they had to change their work because of their COVID-19 hospitalization, and 93 patients (37.8%; 95% CI, 31.7%-44.2%; 7 not responding) reported that a loved one had taken time off work to care for them. Altogether, one in five COVID-19 patients reported that, within the first month after hospital discharge, they used all or most of their savings because of their COVID-19 illness or hospitalization (58 [23.2%]; 95% CI, 18.1%-29.9%; 3 not responding). There were no demographic differences in the likelihood of losing a job or having a loved one take time off for caregiving, but non-Hispanic Black and Hispanic patients were much more likely to report having used all or most of their savings (aOR, 2.96; 95% CI, 1.09-8.04; and aOR, 2.68; 95% CI, 1.35-5.31, respectively) than White patients. Hospital length of stay and discharge destination were not consistently associated with these financial toxicities. The development of new or worsened cardiopulmonary symptoms was not associated with job change or having a caregiver take time off but was associated with increased likelihood of having used all or most savings (aOR, 2.30; 95% CI, 1.12-4.37).

In a geographically and demographically diverse national US cohort, we found that a decline in perceived health, new or worsened cardiopulmonary symptoms, new limitations in activities of daily living, and new financial stresses were common among patients hospitalized during the US third wave of COVID-19 at 1 month after hospital discharge. The new cardiopulmonary symptoms were significantly associated with the self-report of incomplete recovery and financial stress, but less closely associated with incident disability, inability to work, and caregiving receipt. There were not consistent differences between any demographic groups on these outcomes. Patients with longer lengths of stay generally reported more problems. New problems were very common among patients discharged directly home without home health services.

These data suggest a broad range of new problems among survivors of COVID-19 hospitalization. Moreover, these problems are not well-correlated with each other. This raises the possibility that there may be multiple phenotypes of post-acute sequelae after COVID-19 hospitalization. It is not clear to what extent these differences are mediated by differences in tissue damage from or immunologic response to SARS-CoV-2, distinct from or interacting with other elements of treatment, hospitalization, or the illness experience. The degree of financial stress, savings loss, and job dislocation reported here suggests these patients will face substantial challenges in guiding their own recovery in the absence of a dedicated set of services.^28,29The persistent symptoms faced by these COVID-19 patients can be considered in the context of post-acute sequelae among survivors of community-acquired pneumonia in previous studies, as summarized in a recent systematic review.³⁰ For example, only 35% of a large cohort of adults with community-acquired pneumonia who were evaluated in the emergency department were completely free of pneumonia-related symptoms 6 weeks after antibiotic therapy.^31,32 Limitations in activities of daily living have been reported at 1 month after community-acquired pneumonia³³; rehospitalization and early post-discharge mortality rates may also be similar.^34,35 These findings suggest that the persistent problems of both COVID-19 and other pneumonia patients may highlight important opportunities for improvements in healthcare systems,³⁶ and that burdensome postacute sequelae of COVID-19 may not be attributable solely to distinctive features of the SARS-CoV-2 virus.

A majority of patients discharged home without home health services reported new difficulties in their activities of daily living; 77% of patients with new disability at 1 month had been discharged without home services. These data, however, do not show to what extent this lack of home health services resulted from lack of referral for services, home health provider unavailability, or patient refusal of recommended services. Nonetheless, this nonreceipt of home health services may have been consequential. Among hospitalized patients recovering from pneumonia pre-COVID, the use of post-hospital physical and occupational therapy was associated with reduced risk of readmissions and death.³⁷ This association was greater among patients with lower baseline mobility scores and in patients discharged to home directly. Further, the risk of poor outcomes decreased in a dose-response fashion with increased post-hospital therapy delivery. Failure to provide services for postdischarge disability was previously identified as a potential vulnerability of patients during COVID-19.³⁸

This study adds to the literature. The focus on sequelae perceived by the patient to be incident, as distinguished from symptoms and disability existing before COVID-19, increases the likelihood that these data reflect the influence of the COVID-19 hospitalization. These data emphasize that, despite relatively brief hospitalizations, diverse problems are quite common and consequential for patients’ ability to return to their pre-COVID-19 roles. They further add to the literature by demonstrating the relatively loose coupling between various ways in which postacute sequelae of COVID-19 might be defined: the cardiopulmonary symptoms examined here, the patient’s reported completeness of recovery, the financial stresses the hospitalization placed on the patient and their family, or the development of new limitations in activities of daily living.

Our findings highlight a potential second public health crisis from COVID, related to post-COVID recovery, resulting from the incident disability and economic loss among COVID survivors. While much attention is paid to deaths from COVID, there is less (albeit growing) recognition of the long-term consequences in survivors of COVID-19.³⁹ The downstream economic impacts from job loss and financial insolvency for COVID-19 survivors have ramifications for caregivers, family units that include dependents, and the broader US economy—and may do so for generations if uncorrected, as has been suggested after the 1918 influenza pandemic.⁴⁰ These data may, indeed, look worse at later follow-up given the delay in hospital billing and new expenses in the wake of illness and hospitalization.^28,36,41 It is important that the healthcare system and policymakers consider early investments in post-hospital rehabilitation and adaptive services to allow workers to return to the workforce as soon as possible, and prepare for an increased need for financial support for recovering COVID patients.⁴²

Importantly, these data cannot distinguish between the impact of SARS-CoV-2 infection itself from the treatment received for COVID-19 or other non-COVID-19-specific aspects of hospital care. COVID-19 inpatient case fatality rates and management have changed over time, and so generalizability to future cohorts is unknown.^9-11 This cohort was recruited in the inpatient setting at largely teaching hospitals; therefore, these patients’ experience may be not be representative of all hospitalized COVID-19 patients during this time period. The generalizability of hospital-based studies to patients not hospitalized for COVID-19 remains a subject of active inquiry. We only interviewed patients who were not homeless (excluding 7 of 588 eligible, 1.2%) and who spoke English or Spanish (excluding 4 of 588 eligible, 0.7%); these and other inclusion/exclusion criteria should be considered when evaluating the generalizability of these findings to other patients. We did not prospectively collect measures of fatigue to examine this important and complex symptom, nor did we evaluate outpatient therapy. Finally, self-report was used, rather than using objective measurements of what the patient did or did not do in their home environment. This is consistent with clinical practice that emphasizes patients as primary reporters of their present state, but may introduce measurement error compared to more invasive strategies if those are considered the gold standard.

Patients who survived hospitalization from COVID-19 during the period of August 2020 to January 2021 continued to face significant burdens of new cardiopulmonary symptoms, incomplete recovery, disability, and financial toxicity, all of which extend to patients discharged directly home without services. The correlations between these potential symptoms are no more than partial, and an exclusive focus on one area may neglect other areas of patient need.

The authors thank the patients and families of the Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study for their generous sharing of their time with us. We acknowledge Hallie C Prescott (University of Michigan and VA Ann Arbor) for her assistance in developing the financial toxicity questions.

For many patients hospitalized with COVID-19, the impact of the illness continues well beyond hospital discharge.¹ Heavy burdens of persistent symptoms have been reported, albeit often from regional and single-hospital samples.^2-7 Critically, not all initial reports capture information on pre-COVID-19 symptom burden, so it is unclear whether these highly prevalent problems are truly new; an alternative explanation might be that patients already with symptoms were more likely to be infected with or seek care for SARS-CoV-2.⁸

Fewer data are available about patients’ abilities to go about the activities of their lives, nor is as much known about the relationships between new symptoms and other impacts. Most of the available information is from health systems during the initial surge of COVID-19 in early 2020—when testing for SARS-CoV-2 was limited even in the inpatient setting; when hospitals’ postdischarge care systems may have been heavily disrupted; and when clinicians were often reasonably focused primarily on reducing mortality in their first cases of COVID-19 rather than promoting recovery from an often-survivable illness. Increasing evidence shows that the inpatient case-fatality rate of COVID-19 is improving over time^9,10; this makes unclear the generalizability of outcomes data from early COVID-19 patients to more recent patients.¹¹

Therefore, we report multicenter measurements of incident levels of persistent cardiopulmonary symptoms, disability, return to baseline, and impact on employment among a recent cohort of COVID-19 patients hospitalized around the United States during the “third wave” of COVID-19—fall and winter 2020-2021. We focus on the 1-month time point after hospital discharge, as this time point is still in the early vulnerable period during which hospital transition-of-care programs are understood to have responsibility.

The first 253 patients who completed 1-month postdischarge telephone follow-up surveys from the ongoing nationwide BLUE CORAL study were included. BLUE CORAL will enroll up to 1,500 hospitalized COVID-19 patients at 36 US centers (the identities of which are reported in Appendix 1) as a part of the National Heart, Lung, and Blood Institute’s Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. We report here on survey questions that allowed for a clear comparison to be made between 1-month follow-up responses and pre-COVID baseline variables; these comparisons were based on (1) previous in-hospital assessment; (2) explicitly asking patients to compare to pre-COVID-19 levels; or (3) explicitly asking patients for changes in relation to their COVID-19 hospitalization. Items were chosen for inclusion in this report without looking at their association with other variables.

This research was approved by the Vanderbilt Institutional Review Board (IRB), serving as central IRB for the PETAL Network; patients or their surrogates provided informed consent.

Participants

Patients with COVID-19 were identified during hospitalization and within 14 days of a positive molecular test for SARS-CoV-2. Eligible patients presented with fever and/or respiratory signs/symptoms, such as hypoxemia, shortness of breath, or infiltrates on chest imaging. Patients were enrolled within the first 72 hours of hospitalization (in order to avoid oversampling patients with relatively longer stays, and to study the biology of early COVID-19), and excluded if they had comfort-care orders (because of their limited likelihood of surviving to follow-up), or were incarcerated (because of difficulties in obtaining truly open informed consent and likely difficulties in follow-up). Pertinently, patients were not required to be in the intensive care unit.

Surviving patients who spoke English or Spanish, were not homeless on hospital admission, and were neither significantly disabled nor significantly cognitively impaired were eligible for follow-up. “Not significantly disabled” was defined as having limitations due to health on no more than three activities of daily living before their COVID-19 hospitalization, as assessed at BLUE CORAL enrollment; this was chosen because of the potentially limited sensitivity of many of our questionnaires to detect an impact of COVID-19 in patients with greater than this level of disability. We included patients who were able to consent for themselves in the study, or for whom the legally appointed representative consenting on their behalf in the hospital reported no evidence of cognitive impairment, defined as no more than four of the problems on the eight-item Alzheimer’s Dementia (AD8) scale.^12-14

Data Collection

One-month surveys were administered to patients or, when necessary, their proxies; the complete English- and Spanish-language instruments are presented in Appendix 2. Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Michigan.^15,16

Patients were contacted via phone by trained interviewers beginning 21 days after hospital discharge; interviews were completed a median of 47 days after discharge (interquartile range [IQR], 26-61). Efforts prioritized former patients completing surveys themselves by phone, but a well-informed proxy was approached if needed. Proxies, who included spouses, adult children, or other relatives, family friends, or primary caregivers, were in regular contact with the patient and understood the patient’s health status. If necessary, the survey could be completed over multiple phone calls, and a written, mail-back option was available. Other best practices in accurate survey data collection and cohort retention were used.^17-19 Participants were given a $10 gift card.

New cardiopulmonary symptoms were queried with symptom-targeted questions informed by the Airways Questionnaire 20,²⁰ the Kansas City Cardiomyopathy Questionnaire,^21,22 and the Seattle Angina Questionnaire.²³ Whenever a respondent reported a given symptom, they were asked, “Compared to 1 month before your COVID-19 hospitalization, is this better, worse, or about the same?” We counted the number of symptoms which the patient reported as worse.

Using wording from the Health and Retirement Study,²⁴ disability was assessed based on a self-report of any of 14 health-related limitations in activities of daily living or instrumental activities of daily living, as in past studies²⁵: dressing, walking across a room, bathing, eating, getting out of bed, using a toilet, using a map, preparing a hot meal, shopping for groceries, making a phone call, taking medications, paying bills, carrying 10 lb (eg, a heavy bag of groceries), and, as a combined single item, stooping, kneeling, or crouching. Well-chosen proxy reports appear reliable for these items.²⁶ We counted the number of activities for which the patient reported a limitation, comparing those reported at 1 month to those reported during the in-hospital survey assessing pre-illness functioning.

The financial consequences of the COVID-19 hospitalization were assessed in two ways. First, we used a modified version of a World Health Organization Disability Assessment Schedule (WHODAS) 2.0 question²⁷: “Since your COVID-19 hospitalization, how much has your health been a drain on the financial resources of you or your family?” Second, we used the financial toxicity items developed with the Mi-COVID19 study³ based on extensive qualitative interviews with respiratory failure survivors²⁸; these questions were anchored explicitly on “the financial cost of dealing with your COVID-19 hospitalization and related care.”

Data Analysis

There were few missing data, and almost all were on outcome variables. Where present, the degree of missingness is reported and casewise deletion used. Because this was a planned early look at responses to an ongoing survey, with analysis based on the number of accrued responses, the ultimate denominator for response rate calculation is unknown. Therefore, two bounds are presented—the minimum, on the assumption that all remaining uncompleted surveys will be missed; and the maximum, as if the uncompleted surveys were not yet in the eligible denominator.

Variables were summarized with medians and IQRs. Multilevel logistic regression was used to test for differences across demographic characteristics in the rates of development of any new symptom or disability; site-level differences were modeled using a random effect. Gender, race/ethnicity, and age were included in all regressions unless noted otherwise; age was included with both linear and quadratic terms when used as a control variable. For the degree of return to baseline and for the number of new limitations in activities of daily living, we explored associations as dichotomized variables (any/none, using multilevel logistic regression) and as continuous variables (using multilevel linear regression). Percent of variance explained was calculated using the R² in unadjusted linear regression, and Spearman rank correlations were used to allow nonlinearities in comparisons across outcomes. All adjusted models are presented in Appendix Table 1. Analyses were conducted in Stata 16.1 (StataCorp, 2020); analytic code is presented in Appendix 3, and a log file of all analyses is in Appendix 4.

The 250th 1-month follow-up was completed on February 26, 2021. One month prior, 647 patients had been recruited at 26 centers in the inpatient phase of the study. Patient demographics for the 253 patients surveyed through that date are shown in Appendix Table 2. On the day of the early look at the data, 460 patients had become eligible for 1-month follow-up and 64 patients had been missed for 1-month follow-up (maximum response rate of 79.8%, minimum possible final response rate of 55.0%) (Figure 1). Seven surveys were completed by proxies. Respondents’ median age was 60 years (IQR, 45-68), and 111 (43.4%) were female. Their median hospital length of stay was 5 days(IQR, 3-8) . A total of 236 (93.3%) patients were discharged home, including 197 (77.9%) without home care services and 39 (15.4%) with home care services.

One hundred and thirty-nine patients (56.5%; 95% CI, 50.1%-62.8%) reported at least one new or worsened cardiopulmonary symptom after their COVID-19 hospitalization (Table; seven patients did not respond to these questions). Most patients with new symptoms had one (48 [19.5%]; 95% CI, 14.8%-25.0%) or two (32 [13%]; 95% CI, 9.7%-17.7%) of the new symptoms queried. The most common new cardiopulmonary symptom was cough, reported by 57 (23.2%; 95% CI, 18.0%-29.0%) patients. New oxygen use was reported by 28 (11.4%; 95% CI, 7.7%-16.0%) patients, with another 11 (4.5%; 95% CI, 2.3%-7.9%) reporting increased oxygen requirements. Women were twice as likely as men to report any new cardiopulmonary symptom (adjusted odds ratio [aOR], 2.24; 95% CI, 1.29-3.90) and non-Hispanic Black and Hispanic patients were less likely than White patients to report new symptoms (aOR, 0.31; 95% CI, 0.12-0.83; and aOR, 0.38; 95% CI, 0.21-0.71, respectively). Longer lengths of hospital stay were associated with greater 1-month cardiopulmonary symptoms (aOR, 1.82 per additional week in the hospital; 95% CI, 1.11-2.98), but discharge destination was not (aOR, 0.92; 95% CI, 0.39-1.71).

New limitations in activities of daily living or instrumental activities of daily living were present in 130 (52.8%; 95% CI, 46.4%-59.5%) patients (seven not responding), all of whom had 0 to 3 limitations before their COVID-19 hospitalization. Indeed, 62 (25.2%; 95% CI, 19.9%-31.1%) reported 3 or more new health-related limitations in activities of daily living or instrumental activities of daily living compared to their pre-COVID-19 baseline, as assessed separately during their hospitalization (Figure 2; rates of limitations in individual activities are shown in Appendix Table 3). Older patients were more likely to report a new health-related limitation, and Hispanic patients were less likely to have a new limitation. New limitations were common among patients discharged home without home health services. The number of new cardiopulmonary symptoms explained 11.2% of the variance in the number of new limitations in activities of daily living, a Spearman rank correlation of 0.30 (P < .0001; see Appendix Table 4). More than three in four COVID-19 patients reported new or worsened cardiopulmonary symptoms or new health-related limitations in activities of daily living at 1 month—only 62 (24.5%) patients reported neither.

At 1 month after hospital discharge, 213 (84.2%) patients reported that they were not fully back to their pre-COVID-19 level of functioning (3 declined to answer the question). When asked, “On a scale of 1 to 100, with 100 being all the way back to what you could do before COVID, how close to being back are you?” the median response was 80, with an IQR of 64-95 (Figure 3). Forty-two (16.8%; 95% CI, 12.4%-22.0%) patients reported a level of 50 or below. Women and older patients reported lower levels of return of functioning, as did those with longer hospital stays and new or worsened cardiopulmonary symptoms. Each additional week in hospital length of stay was associated with a 7.5-point lower response to the question (95% CI, –11.2 to –3.8), but discharge destination was not associated with the answer after adjusting for demographics. Patients with and without new limitations in activities of daily living and with and without new cardiopulmonary symptoms were found across the range of self-reported degree of recovery, although patients without a new problem in one of those domains were rarer among those reporting recovery of less than 70. The number of new cardiopulmonary symptoms explained 19.7% of the variance in the response to this question, a Spearman rank correlation of 0.47 (P < .0001).

More than half of respondents (115 [55.0%]; 95% CI, 48.0%-61.9%; 44 not responding) stated that their COVID-19 hospitalization had been a drain on the finances of their family; 53 (25.4%; 95% CI, 19.6%-31.8%; 44 not responding) rated that drain as moderate, severe, or extreme within the first month after hospital discharge. Forty-nine patients (19.8%; 95% CI, 15.1%-25.4%; 6 not responding) reported that they had to change their work because of their COVID-19 hospitalization, and 93 patients (37.8%; 95% CI, 31.7%-44.2%; 7 not responding) reported that a loved one had taken time off work to care for them. Altogether, one in five COVID-19 patients reported that, within the first month after hospital discharge, they used all or most of their savings because of their COVID-19 illness or hospitalization (58 [23.2%]; 95% CI, 18.1%-29.9%; 3 not responding). There were no demographic differences in the likelihood of losing a job or having a loved one take time off for caregiving, but non-Hispanic Black and Hispanic patients were much more likely to report having used all or most of their savings (aOR, 2.96; 95% CI, 1.09-8.04; and aOR, 2.68; 95% CI, 1.35-5.31, respectively) than White patients. Hospital length of stay and discharge destination were not consistently associated with these financial toxicities. The development of new or worsened cardiopulmonary symptoms was not associated with job change or having a caregiver take time off but was associated with increased likelihood of having used all or most savings (aOR, 2.30; 95% CI, 1.12-4.37).

In a geographically and demographically diverse national US cohort, we found that a decline in perceived health, new or worsened cardiopulmonary symptoms, new limitations in activities of daily living, and new financial stresses were common among patients hospitalized during the US third wave of COVID-19 at 1 month after hospital discharge. The new cardiopulmonary symptoms were significantly associated with the self-report of incomplete recovery and financial stress, but less closely associated with incident disability, inability to work, and caregiving receipt. There were not consistent differences between any demographic groups on these outcomes. Patients with longer lengths of stay generally reported more problems. New problems were very common among patients discharged directly home without home health services.

These data suggest a broad range of new problems among survivors of COVID-19 hospitalization. Moreover, these problems are not well-correlated with each other. This raises the possibility that there may be multiple phenotypes of post-acute sequelae after COVID-19 hospitalization. It is not clear to what extent these differences are mediated by differences in tissue damage from or immunologic response to SARS-CoV-2, distinct from or interacting with other elements of treatment, hospitalization, or the illness experience. The degree of financial stress, savings loss, and job dislocation reported here suggests these patients will face substantial challenges in guiding their own recovery in the absence of a dedicated set of services.^28,29The persistent symptoms faced by these COVID-19 patients can be considered in the context of post-acute sequelae among survivors of community-acquired pneumonia in previous studies, as summarized in a recent systematic review.³⁰ For example, only 35% of a large cohort of adults with community-acquired pneumonia who were evaluated in the emergency department were completely free of pneumonia-related symptoms 6 weeks after antibiotic therapy.^31,32 Limitations in activities of daily living have been reported at 1 month after community-acquired pneumonia³³; rehospitalization and early post-discharge mortality rates may also be similar.^34,35 These findings suggest that the persistent problems of both COVID-19 and other pneumonia patients may highlight important opportunities for improvements in healthcare systems,³⁶ and that burdensome postacute sequelae of COVID-19 may not be attributable solely to distinctive features of the SARS-CoV-2 virus.

A majority of patients discharged home without home health services reported new difficulties in their activities of daily living; 77% of patients with new disability at 1 month had been discharged without home services. These data, however, do not show to what extent this lack of home health services resulted from lack of referral for services, home health provider unavailability, or patient refusal of recommended services. Nonetheless, this nonreceipt of home health services may have been consequential. Among hospitalized patients recovering from pneumonia pre-COVID, the use of post-hospital physical and occupational therapy was associated with reduced risk of readmissions and death.³⁷ This association was greater among patients with lower baseline mobility scores and in patients discharged to home directly. Further, the risk of poor outcomes decreased in a dose-response fashion with increased post-hospital therapy delivery. Failure to provide services for postdischarge disability was previously identified as a potential vulnerability of patients during COVID-19.³⁸

This study adds to the literature. The focus on sequelae perceived by the patient to be incident, as distinguished from symptoms and disability existing before COVID-19, increases the likelihood that these data reflect the influence of the COVID-19 hospitalization. These data emphasize that, despite relatively brief hospitalizations, diverse problems are quite common and consequential for patients’ ability to return to their pre-COVID-19 roles. They further add to the literature by demonstrating the relatively loose coupling between various ways in which postacute sequelae of COVID-19 might be defined: the cardiopulmonary symptoms examined here, the patient’s reported completeness of recovery, the financial stresses the hospitalization placed on the patient and their family, or the development of new limitations in activities of daily living.

Our findings highlight a potential second public health crisis from COVID, related to post-COVID recovery, resulting from the incident disability and economic loss among COVID survivors. While much attention is paid to deaths from COVID, there is less (albeit growing) recognition of the long-term consequences in survivors of COVID-19.³⁹ The downstream economic impacts from job loss and financial insolvency for COVID-19 survivors have ramifications for caregivers, family units that include dependents, and the broader US economy—and may do so for generations if uncorrected, as has been suggested after the 1918 influenza pandemic.⁴⁰ These data may, indeed, look worse at later follow-up given the delay in hospital billing and new expenses in the wake of illness and hospitalization.^28,36,41 It is important that the healthcare system and policymakers consider early investments in post-hospital rehabilitation and adaptive services to allow workers to return to the workforce as soon as possible, and prepare for an increased need for financial support for recovering COVID patients.⁴²

Importantly, these data cannot distinguish between the impact of SARS-CoV-2 infection itself from the treatment received for COVID-19 or other non-COVID-19-specific aspects of hospital care. COVID-19 inpatient case fatality rates and management have changed over time, and so generalizability to future cohorts is unknown.^9-11 This cohort was recruited in the inpatient setting at largely teaching hospitals; therefore, these patients’ experience may be not be representative of all hospitalized COVID-19 patients during this time period. The generalizability of hospital-based studies to patients not hospitalized for COVID-19 remains a subject of active inquiry. We only interviewed patients who were not homeless (excluding 7 of 588 eligible, 1.2%) and who spoke English or Spanish (excluding 4 of 588 eligible, 0.7%); these and other inclusion/exclusion criteria should be considered when evaluating the generalizability of these findings to other patients. We did not prospectively collect measures of fatigue to examine this important and complex symptom, nor did we evaluate outpatient therapy. Finally, self-report was used, rather than using objective measurements of what the patient did or did not do in their home environment. This is consistent with clinical practice that emphasizes patients as primary reporters of their present state, but may introduce measurement error compared to more invasive strategies if those are considered the gold standard.

Patients who survived hospitalization from COVID-19 during the period of August 2020 to January 2021 continued to face significant burdens of new cardiopulmonary symptoms, incomplete recovery, disability, and financial toxicity, all of which extend to patients discharged directly home without services. The correlations between these potential symptoms are no more than partial, and an exclusive focus on one area may neglect other areas of patient need.

The authors thank the patients and families of the Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study for their generous sharing of their time with us. We acknowledge Hallie C Prescott (University of Michigan and VA Ann Arbor) for her assistance in developing the financial toxicity questions.

For many patients hospitalized with COVID-19, the impact of the illness continues well beyond hospital discharge.¹ Heavy burdens of persistent symptoms have been reported, albeit often from regional and single-hospital samples.^2-7 Critically, not all initial reports capture information on pre-COVID-19 symptom burden, so it is unclear whether these highly prevalent problems are truly new; an alternative explanation might be that patients already with symptoms were more likely to be infected with or seek care for SARS-CoV-2.⁸

Fewer data are available about patients’ abilities to go about the activities of their lives, nor is as much known about the relationships between new symptoms and other impacts. Most of the available information is from health systems during the initial surge of COVID-19 in early 2020—when testing for SARS-CoV-2 was limited even in the inpatient setting; when hospitals’ postdischarge care systems may have been heavily disrupted; and when clinicians were often reasonably focused primarily on reducing mortality in their first cases of COVID-19 rather than promoting recovery from an often-survivable illness. Increasing evidence shows that the inpatient case-fatality rate of COVID-19 is improving over time^9,10; this makes unclear the generalizability of outcomes data from early COVID-19 patients to more recent patients.¹¹

Therefore, we report multicenter measurements of incident levels of persistent cardiopulmonary symptoms, disability, return to baseline, and impact on employment among a recent cohort of COVID-19 patients hospitalized around the United States during the “third wave” of COVID-19—fall and winter 2020-2021. We focus on the 1-month time point after hospital discharge, as this time point is still in the early vulnerable period during which hospital transition-of-care programs are understood to have responsibility.

The first 253 patients who completed 1-month postdischarge telephone follow-up surveys from the ongoing nationwide BLUE CORAL study were included. BLUE CORAL will enroll up to 1,500 hospitalized COVID-19 patients at 36 US centers (the identities of which are reported in Appendix 1) as a part of the National Heart, Lung, and Blood Institute’s Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. We report here on survey questions that allowed for a clear comparison to be made between 1-month follow-up responses and pre-COVID baseline variables; these comparisons were based on (1) previous in-hospital assessment; (2) explicitly asking patients to compare to pre-COVID-19 levels; or (3) explicitly asking patients for changes in relation to their COVID-19 hospitalization. Items were chosen for inclusion in this report without looking at their association with other variables.

This research was approved by the Vanderbilt Institutional Review Board (IRB), serving as central IRB for the PETAL Network; patients or their surrogates provided informed consent.

Participants

Patients with COVID-19 were identified during hospitalization and within 14 days of a positive molecular test for SARS-CoV-2. Eligible patients presented with fever and/or respiratory signs/symptoms, such as hypoxemia, shortness of breath, or infiltrates on chest imaging. Patients were enrolled within the first 72 hours of hospitalization (in order to avoid oversampling patients with relatively longer stays, and to study the biology of early COVID-19), and excluded if they had comfort-care orders (because of their limited likelihood of surviving to follow-up), or were incarcerated (because of difficulties in obtaining truly open informed consent and likely difficulties in follow-up). Pertinently, patients were not required to be in the intensive care unit.

Surviving patients who spoke English or Spanish, were not homeless on hospital admission, and were neither significantly disabled nor significantly cognitively impaired were eligible for follow-up. “Not significantly disabled” was defined as having limitations due to health on no more than three activities of daily living before their COVID-19 hospitalization, as assessed at BLUE CORAL enrollment; this was chosen because of the potentially limited sensitivity of many of our questionnaires to detect an impact of COVID-19 in patients with greater than this level of disability. We included patients who were able to consent for themselves in the study, or for whom the legally appointed representative consenting on their behalf in the hospital reported no evidence of cognitive impairment, defined as no more than four of the problems on the eight-item Alzheimer’s Dementia (AD8) scale.^12-14

Data Collection

One-month surveys were administered to patients or, when necessary, their proxies; the complete English- and Spanish-language instruments are presented in Appendix 2. Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Michigan.^15,16

Patients were contacted via phone by trained interviewers beginning 21 days after hospital discharge; interviews were completed a median of 47 days after discharge (interquartile range [IQR], 26-61). Efforts prioritized former patients completing surveys themselves by phone, but a well-informed proxy was approached if needed. Proxies, who included spouses, adult children, or other relatives, family friends, or primary caregivers, were in regular contact with the patient and understood the patient’s health status. If necessary, the survey could be completed over multiple phone calls, and a written, mail-back option was available. Other best practices in accurate survey data collection and cohort retention were used.^17-19 Participants were given a $10 gift card.

New cardiopulmonary symptoms were queried with symptom-targeted questions informed by the Airways Questionnaire 20,²⁰ the Kansas City Cardiomyopathy Questionnaire,^21,22 and the Seattle Angina Questionnaire.²³ Whenever a respondent reported a given symptom, they were asked, “Compared to 1 month before your COVID-19 hospitalization, is this better, worse, or about the same?” We counted the number of symptoms which the patient reported as worse.

Using wording from the Health and Retirement Study,²⁴ disability was assessed based on a self-report of any of 14 health-related limitations in activities of daily living or instrumental activities of daily living, as in past studies²⁵: dressing, walking across a room, bathing, eating, getting out of bed, using a toilet, using a map, preparing a hot meal, shopping for groceries, making a phone call, taking medications, paying bills, carrying 10 lb (eg, a heavy bag of groceries), and, as a combined single item, stooping, kneeling, or crouching. Well-chosen proxy reports appear reliable for these items.²⁶ We counted the number of activities for which the patient reported a limitation, comparing those reported at 1 month to those reported during the in-hospital survey assessing pre-illness functioning.

The financial consequences of the COVID-19 hospitalization were assessed in two ways. First, we used a modified version of a World Health Organization Disability Assessment Schedule (WHODAS) 2.0 question²⁷: “Since your COVID-19 hospitalization, how much has your health been a drain on the financial resources of you or your family?” Second, we used the financial toxicity items developed with the Mi-COVID19 study³ based on extensive qualitative interviews with respiratory failure survivors²⁸; these questions were anchored explicitly on “the financial cost of dealing with your COVID-19 hospitalization and related care.”

Data Analysis

There were few missing data, and almost all were on outcome variables. Where present, the degree of missingness is reported and casewise deletion used. Because this was a planned early look at responses to an ongoing survey, with analysis based on the number of accrued responses, the ultimate denominator for response rate calculation is unknown. Therefore, two bounds are presented—the minimum, on the assumption that all remaining uncompleted surveys will be missed; and the maximum, as if the uncompleted surveys were not yet in the eligible denominator.

Variables were summarized with medians and IQRs. Multilevel logistic regression was used to test for differences across demographic characteristics in the rates of development of any new symptom or disability; site-level differences were modeled using a random effect. Gender, race/ethnicity, and age were included in all regressions unless noted otherwise; age was included with both linear and quadratic terms when used as a control variable. For the degree of return to baseline and for the number of new limitations in activities of daily living, we explored associations as dichotomized variables (any/none, using multilevel logistic regression) and as continuous variables (using multilevel linear regression). Percent of variance explained was calculated using the R² in unadjusted linear regression, and Spearman rank correlations were used to allow nonlinearities in comparisons across outcomes. All adjusted models are presented in Appendix Table 1. Analyses were conducted in Stata 16.1 (StataCorp, 2020); analytic code is presented in Appendix 3, and a log file of all analyses is in Appendix 4.

The 250th 1-month follow-up was completed on February 26, 2021. One month prior, 647 patients had been recruited at 26 centers in the inpatient phase of the study. Patient demographics for the 253 patients surveyed through that date are shown in Appendix Table 2. On the day of the early look at the data, 460 patients had become eligible for 1-month follow-up and 64 patients had been missed for 1-month follow-up (maximum response rate of 79.8%, minimum possible final response rate of 55.0%) (Figure 1). Seven surveys were completed by proxies. Respondents’ median age was 60 years (IQR, 45-68), and 111 (43.4%) were female. Their median hospital length of stay was 5 days(IQR, 3-8) . A total of 236 (93.3%) patients were discharged home, including 197 (77.9%) without home care services and 39 (15.4%) with home care services.

One hundred and thirty-nine patients (56.5%; 95% CI, 50.1%-62.8%) reported at least one new or worsened cardiopulmonary symptom after their COVID-19 hospitalization (Table; seven patients did not respond to these questions). Most patients with new symptoms had one (48 [19.5%]; 95% CI, 14.8%-25.0%) or two (32 [13%]; 95% CI, 9.7%-17.7%) of the new symptoms queried. The most common new cardiopulmonary symptom was cough, reported by 57 (23.2%; 95% CI, 18.0%-29.0%) patients. New oxygen use was reported by 28 (11.4%; 95% CI, 7.7%-16.0%) patients, with another 11 (4.5%; 95% CI, 2.3%-7.9%) reporting increased oxygen requirements. Women were twice as likely as men to report any new cardiopulmonary symptom (adjusted odds ratio [aOR], 2.24; 95% CI, 1.29-3.90) and non-Hispanic Black and Hispanic patients were less likely than White patients to report new symptoms (aOR, 0.31; 95% CI, 0.12-0.83; and aOR, 0.38; 95% CI, 0.21-0.71, respectively). Longer lengths of hospital stay were associated with greater 1-month cardiopulmonary symptoms (aOR, 1.82 per additional week in the hospital; 95% CI, 1.11-2.98), but discharge destination was not (aOR, 0.92; 95% CI, 0.39-1.71).

New limitations in activities of daily living or instrumental activities of daily living were present in 130 (52.8%; 95% CI, 46.4%-59.5%) patients (seven not responding), all of whom had 0 to 3 limitations before their COVID-19 hospitalization. Indeed, 62 (25.2%; 95% CI, 19.9%-31.1%) reported 3 or more new health-related limitations in activities of daily living or instrumental activities of daily living compared to their pre-COVID-19 baseline, as assessed separately during their hospitalization (Figure 2; rates of limitations in individual activities are shown in Appendix Table 3). Older patients were more likely to report a new health-related limitation, and Hispanic patients were less likely to have a new limitation. New limitations were common among patients discharged home without home health services. The number of new cardiopulmonary symptoms explained 11.2% of the variance in the number of new limitations in activities of daily living, a Spearman rank correlation of 0.30 (P < .0001; see Appendix Table 4). More than three in four COVID-19 patients reported new or worsened cardiopulmonary symptoms or new health-related limitations in activities of daily living at 1 month—only 62 (24.5%) patients reported neither.

At 1 month after hospital discharge, 213 (84.2%) patients reported that they were not fully back to their pre-COVID-19 level of functioning (3 declined to answer the question). When asked, “On a scale of 1 to 100, with 100 being all the way back to what you could do before COVID, how close to being back are you?” the median response was 80, with an IQR of 64-95 (Figure 3). Forty-two (16.8%; 95% CI, 12.4%-22.0%) patients reported a level of 50 or below. Women and older patients reported lower levels of return of functioning, as did those with longer hospital stays and new or worsened cardiopulmonary symptoms. Each additional week in hospital length of stay was associated with a 7.5-point lower response to the question (95% CI, –11.2 to –3.8), but discharge destination was not associated with the answer after adjusting for demographics. Patients with and without new limitations in activities of daily living and with and without new cardiopulmonary symptoms were found across the range of self-reported degree of recovery, although patients without a new problem in one of those domains were rarer among those reporting recovery of less than 70. The number of new cardiopulmonary symptoms explained 19.7% of the variance in the response to this question, a Spearman rank correlation of 0.47 (P < .0001).

More than half of respondents (115 [55.0%]; 95% CI, 48.0%-61.9%; 44 not responding) stated that their COVID-19 hospitalization had been a drain on the finances of their family; 53 (25.4%; 95% CI, 19.6%-31.8%; 44 not responding) rated that drain as moderate, severe, or extreme within the first month after hospital discharge. Forty-nine patients (19.8%; 95% CI, 15.1%-25.4%; 6 not responding) reported that they had to change their work because of their COVID-19 hospitalization, and 93 patients (37.8%; 95% CI, 31.7%-44.2%; 7 not responding) reported that a loved one had taken time off work to care for them. Altogether, one in five COVID-19 patients reported that, within the first month after hospital discharge, they used all or most of their savings because of their COVID-19 illness or hospitalization (58 [23.2%]; 95% CI, 18.1%-29.9%; 3 not responding). There were no demographic differences in the likelihood of losing a job or having a loved one take time off for caregiving, but non-Hispanic Black and Hispanic patients were much more likely to report having used all or most of their savings (aOR, 2.96; 95% CI, 1.09-8.04; and aOR, 2.68; 95% CI, 1.35-5.31, respectively) than White patients. Hospital length of stay and discharge destination were not consistently associated with these financial toxicities. The development of new or worsened cardiopulmonary symptoms was not associated with job change or having a caregiver take time off but was associated with increased likelihood of having used all or most savings (aOR, 2.30; 95% CI, 1.12-4.37).

In a geographically and demographically diverse national US cohort, we found that a decline in perceived health, new or worsened cardiopulmonary symptoms, new limitations in activities of daily living, and new financial stresses were common among patients hospitalized during the US third wave of COVID-19 at 1 month after hospital discharge. The new cardiopulmonary symptoms were significantly associated with the self-report of incomplete recovery and financial stress, but less closely associated with incident disability, inability to work, and caregiving receipt. There were not consistent differences between any demographic groups on these outcomes. Patients with longer lengths of stay generally reported more problems. New problems were very common among patients discharged directly home without home health services.

These data suggest a broad range of new problems among survivors of COVID-19 hospitalization. Moreover, these problems are not well-correlated with each other. This raises the possibility that there may be multiple phenotypes of post-acute sequelae after COVID-19 hospitalization. It is not clear to what extent these differences are mediated by differences in tissue damage from or immunologic response to SARS-CoV-2, distinct from or interacting with other elements of treatment, hospitalization, or the illness experience. The degree of financial stress, savings loss, and job dislocation reported here suggests these patients will face substantial challenges in guiding their own recovery in the absence of a dedicated set of services.^28,29The persistent symptoms faced by these COVID-19 patients can be considered in the context of post-acute sequelae among survivors of community-acquired pneumonia in previous studies, as summarized in a recent systematic review.³⁰ For example, only 35% of a large cohort of adults with community-acquired pneumonia who were evaluated in the emergency department were completely free of pneumonia-related symptoms 6 weeks after antibiotic therapy.^31,32 Limitations in activities of daily living have been reported at 1 month after community-acquired pneumonia³³; rehospitalization and early post-discharge mortality rates may also be similar.^34,35 These findings suggest that the persistent problems of both COVID-19 and other pneumonia patients may highlight important opportunities for improvements in healthcare systems,³⁶ and that burdensome postacute sequelae of COVID-19 may not be attributable solely to distinctive features of the SARS-CoV-2 virus.

A majority of patients discharged home without home health services reported new difficulties in their activities of daily living; 77% of patients with new disability at 1 month had been discharged without home services. These data, however, do not show to what extent this lack of home health services resulted from lack of referral for services, home health provider unavailability, or patient refusal of recommended services. Nonetheless, this nonreceipt of home health services may have been consequential. Among hospitalized patients recovering from pneumonia pre-COVID, the use of post-hospital physical and occupational therapy was associated with reduced risk of readmissions and death.³⁷ This association was greater among patients with lower baseline mobility scores and in patients discharged to home directly. Further, the risk of poor outcomes decreased in a dose-response fashion with increased post-hospital therapy delivery. Failure to provide services for postdischarge disability was previously identified as a potential vulnerability of patients during COVID-19.³⁸

This study adds to the literature. The focus on sequelae perceived by the patient to be incident, as distinguished from symptoms and disability existing before COVID-19, increases the likelihood that these data reflect the influence of the COVID-19 hospitalization. These data emphasize that, despite relatively brief hospitalizations, diverse problems are quite common and consequential for patients’ ability to return to their pre-COVID-19 roles. They further add to the literature by demonstrating the relatively loose coupling between various ways in which postacute sequelae of COVID-19 might be defined: the cardiopulmonary symptoms examined here, the patient’s reported completeness of recovery, the financial stresses the hospitalization placed on the patient and their family, or the development of new limitations in activities of daily living.

Our findings highlight a potential second public health crisis from COVID, related to post-COVID recovery, resulting from the incident disability and economic loss among COVID survivors. While much attention is paid to deaths from COVID, there is less (albeit growing) recognition of the long-term consequences in survivors of COVID-19.³⁹ The downstream economic impacts from job loss and financial insolvency for COVID-19 survivors have ramifications for caregivers, family units that include dependents, and the broader US economy—and may do so for generations if uncorrected, as has been suggested after the 1918 influenza pandemic.⁴⁰ These data may, indeed, look worse at later follow-up given the delay in hospital billing and new expenses in the wake of illness and hospitalization.^28,36,41 It is important that the healthcare system and policymakers consider early investments in post-hospital rehabilitation and adaptive services to allow workers to return to the workforce as soon as possible, and prepare for an increased need for financial support for recovering COVID patients.⁴²

Importantly, these data cannot distinguish between the impact of SARS-CoV-2 infection itself from the treatment received for COVID-19 or other non-COVID-19-specific aspects of hospital care. COVID-19 inpatient case fatality rates and management have changed over time, and so generalizability to future cohorts is unknown.^9-11 This cohort was recruited in the inpatient setting at largely teaching hospitals; therefore, these patients’ experience may be not be representative of all hospitalized COVID-19 patients during this time period. The generalizability of hospital-based studies to patients not hospitalized for COVID-19 remains a subject of active inquiry. We only interviewed patients who were not homeless (excluding 7 of 588 eligible, 1.2%) and who spoke English or Spanish (excluding 4 of 588 eligible, 0.7%); these and other inclusion/exclusion criteria should be considered when evaluating the generalizability of these findings to other patients. We did not prospectively collect measures of fatigue to examine this important and complex symptom, nor did we evaluate outpatient therapy. Finally, self-report was used, rather than using objective measurements of what the patient did or did not do in their home environment. This is consistent with clinical practice that emphasizes patients as primary reporters of their present state, but may introduce measurement error compared to more invasive strategies if those are considered the gold standard.

Patients who survived hospitalization from COVID-19 during the period of August 2020 to January 2021 continued to face significant burdens of new cardiopulmonary symptoms, incomplete recovery, disability, and financial toxicity, all of which extend to patients discharged directly home without services. The correlations between these potential symptoms are no more than partial, and an exclusive focus on one area may neglect other areas of patient need.

The authors thank the patients and families of the Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study for their generous sharing of their time with us. We acknowledge Hallie C Prescott (University of Michigan and VA Ann Arbor) for her assistance in developing the financial toxicity questions.

The American Board of Medical Specialties approved subspecialty designation for the field of pediatric hospital medicine (PHM) in 2016.¹ For those who started independent practice prior to July 2019, there were two options for board eligibility: the “practice pathway” or completion of a PHM fellowship. The practice pathway allows for pediatric and combined internal medicine–pediatric (med-peds) providers who graduated by July 2019 to sit for the PHM board-certification examination if they meet specific criteria in their pediatric practice.² For pediatric and med-peds residents who graduated after July 2019, PHM board eligibility is available only through completion of a PHM fellowship.

PHM subspecialty designation with fellowship training requirements may pose unique challenges to med-peds residents interested in practicing both pediatric and adult hospital medicine (HM).^3,4 Each year, an estimated 25% of med-peds residency graduates go on to practice HM.⁵ The majority (62%-83%) of currently practicing med-peds–trained hospitalists care for both adults and children.^5,6 Further, med-peds–trained hospitalists comprise at least 10% of the PHM workforce⁵ and play an important role in caring for adult survivors of childhood diseases.³

Limited existing data suggest that the future practice patterns of med-peds residents may be affected by PHM fellowship requirements. One previous survey study indicated that, although med-peds residents see value in additional training opportunities offered by fellowship, the majority are less likely to pursue PHM as a result of the new requirements.⁴ Prominent factors dissuading residents from pursuing PHM fellowship included forfeited earnings during fellowship, student loan obligations, family obligations, and the perception that training received during residency was sufficient. Although these data provide important insights into potential changes in practice patterns, they do not explore qualities of PHM fellowship that may make additional training more appealing to med-peds residents and promote retention of med-peds–trained providers in the PHM workforce.

Further, there is no existing literature exploring if and how PHM fellowship programs are equipped to support the needs of med-peds–trained fellows. Other subspecialties have supported med-peds trainees in combined fellowship training programs, including rheumatology, neurology, pediatric emergency medicine, allergy/immunology, physical medicine and rehabilitation, and psychiatry.^7,8 However, the extent to which PHM fellowships follow a similar model to accommodate the career goals of med-peds participants is unclear.

Given the large numbers of med-peds residents who go on to practice combined PHM and adult HM, it is crucial to understand the training needs of this group within the context of PHM fellowship and board certification. The primary objectives of this study were to understand (1) the perceived PHM fellowship needs of med-peds residents interested in HM, and (2) how the current PHM fellowship training environment can meet those needs. Understanding that additional training requirements to practice PHM may affect the career trajectory of residents interested in HM, secondary objectives included describing perceptions of med-peds residents on PHM specialty designation and whether designation affected their career plans.

Study Design

This cross-sectional study took place over a 3-month period from May to July 2019 and included two surveys of different populations to develop a comprehensive understanding of stakeholder perceptions of PHM fellowship. The first survey (resident survey) invited med-peds residents who were members of the National Med-Peds Residents’ Association (NMPRA)⁹ in 2019 and who were interested in HM. The second survey (fellowship director [FD] survey) included PHM FDs. The study was determined to be exempt by the University of Pittsburgh Institutional Review Board.

Study Population and Recruitment

Resident Survey

Two attempts were made to elicit participation via the NMPRA electronic mailing list. The NMPRA membership includes med-peds residents and chief residents from US med-peds residency programs. As of May 2019, 77 med-peds residency programs and their residents were members of NMPRA, which encompassed all med-peds programs in the United States and its territories. NMPRA maintains a listserv for all members, and all existing US/territory programs were members at the time of the survey. Med-peds interns, residents, and chief residents interested in HM were invited to participate in this study.

FD Survey

Forty-eight FDs, representing member institutions of the PHM Fellowship Directors’ Council, were surveyed via the PHM Fellowship Directors listserv.

Survey Instruments

We constructed two de novo surveys consisting of multiple-choice and short-answer questions (Appendix 1 and Appendix 2). To enhance the validity of survey responses, questions were designed and tested using an iterative consensus process among authors and additional participants, including current med-peds PHM fellows, PHM fellowship program directors, med-peds residency program directors, and current med-peds residents. These revisions were repeated for a total of four cycles. Items were created to increase knowledge on the following key areas: resident-perceived needs in fellowship training, impact of PHM subspecialty designation on career choices related to HM, health system structure of fellowship programs, and ability to accommodate med-peds clinical training within a PHM fellowship. A combined med-peds fellowship, as defined in the survey and referenced in this study, is a “combined internal medicine–pediatrics hospital medicine fellowship whereby you would remain eligible for PHM board certification.” To ensure a broad and inclusive view of potential needs of med-peds trainees considering fellowship, all respondents were asked to complete questions pertaining to anticipated fellowship needs regardless of their indicated interest in fellowship.

Data Collection

Survey completion was voluntary. Email identifiers were not linked to completed surveys. Study data were collected and managed by using Qualtrics XM. Only completed survey entries were included in analysis.

Statistical Methods and Data Analysis

R software version 4.0.2 (R Foundation for Statistical Computing) was used for statistical analysis. Demographic data were summarized using frequency distributions. The intent of the free-text questions for both surveys was qualitative explanatory thematic analysis. Authors EB, HL, and AJ used a deductive approach to identify common themes that elucidated med-peds resident–anticipated needs in fellowship and PHM program strategies and barriers to accommodate these needs. Preliminary themes and action items were reviewed and discussed among the full authorship team until consensus was reached.

Demographic Data

Resident Survey

A total of 466 med-peds residents completed the resident survey. There are approximately 1300 med-peds residents annually, creating an estimated response rate of 35.8% of all US med-peds residents. The majority (n = 380, 81.5%) of respondents were med-peds postgraduate years 1 through 3 and thus only eligible for PHM board certification via the PHM fellowship pathway (Table 1). Most (n = 446, 95.7%) respondents had considered a career in adult, pediatric, or combined HM at some point. Of those med-peds residents who considered a career in HM (Appendix Table 1), 92.8% (n = 414) would prefer to practice combined adult HM and PHM.

FD Survey

Twenty-eight FDs completed the FD survey, representing 58.3% of 2019 PHM fellowship programs. Of the responding programs, 23 (82.1%) were associated with a freestanding children’s hospital, and 24 (85.7%) were integrated or affiliated with a health system that provides adult inpatient care (Table 2). Sixteen (57.1%) programs had a med-peds residency program at their institution.

Med-Peds Resident Perceptions of PHM Fellowship

In considering the importance of PHM board certification for physicians practicing PHM, 59.0% (n= 275) of respondents rated board certification as “not at all important” (Appendix Table 2). Most (n = 420, 90.1%) med-peds trainees responded that PHM subspecialty designation “decreased” or “significantly decreased” their desire to pursue a career that includes PHM. Of the respondents who reported no interest in hospital medicine, eight (40%) reported that PHM subspecialty status dissuaded them from a career in HM at least a moderate amount (Appendix Table 3). Roughly one third (n=158, 33.9%) of respondents reported that PHM subspecialty designation increased or significantly increased their desire to pursue a career that includes adult HM (Appenidx Table 2). Finally, although the majority (n = 275, 59%) of respondents said they had no interest in a HM fellowship, 114 (24.5%) indicated interest in a combined med-peds HM fellowship (Appendix Table 1). Short-answer questions revealed that commitment to additional training on top of a 4-year residency program was a possible deterring factor, particularly in light of student loan debt and family obligations. Respondents reported adequate clinical training during residency as another deterring factor.

Med-Peds Resident–Perceived Needs in PHM Fellowship

Regardless of interest in completing a PHM fellowship, all resident survey respondents were asked how their ideal PHM fellowship should be structured. Almost all (n = 456, 97.9%) respondents indicated that they would prefer to complete a combined med-peds HM fellowship (Table 3), and most preferred to complete a fellowship in 2 years. Only 10 (2.1%) respondents preferred to complete a PHM fellowship alone in 2 or 3 years. More than half (n=253, 54.3%) of respondents indicated that it would be ideal to obtain a master’s degree as part of fellowship.

Three quarters (n = 355, 75.8%) of med-peds residents reported that they would want 41% or more of clinical time in an ideal fellowship dedicated to adult HM. Importantly, most (n = 322, 69.1%) of the med-peds residents did not consider moonlighting alone in either PHM or adult HM to be enough to maintain training. In addition, many (n = 366, 78.5%) respondents felt that it was important or very important for scholarly work during fellowship to bridge pediatrics and internal medicine.

Short-answer questions indicated that the ability to practice both internal medicine and pediatrics during fellowship emerged as an important deciding factor, with emphasis on adequate opportunities to maintain internal medicine knowledge base (Figure). Similarly, access to med-peds mentorship was an important component of the decision. Compensation both during fellowship and potential future earnings was also a prominent consideration.

Capacity of PHM Programs to Support Med-Peds Fellows

Fifteen (53.6%) FDs reported that their programs were able to accommodate both PHM and adult HM clinical time during fellowship, 11 (39.3%) were unsure, and 2 (7.1%) were unable to accommodate both (Table 2).

The options for adult HM clinical time varied by institution and included precepted time on adult HM, full attending privileges on adult HM, and adult HM time through moonlighting only. Short-answer responses from FDs with experience training med-peds fellows cited using PHM elective time for adult HM and offering moonlighting in adult HM as ways to address career goals of med-peds trainees. Scholarship time for fellows was preserved by decreasing required time on pediatric intensive care unit and complex care services.

Accessibility of Med-Peds Mentorship

As noted above, med-peds residents identified mentorship as an important factor in consideration of PHM fellowship. A total of 23 (82.1%) FDs reported their programs had med-peds faculty members within their PHM team (Table 2). The majority (n = 21, 91.3%) of those med-peds faculty had both PHM and adult HM clinical time.

This study characterized the ideal PHM fellowship structure from the perspective of med-peds residents and described the current ability of PHM fellowships to support med-peds residents. The majority of residents stated that they had no interest in an HM fellowship. However, for med-peds residents who considered a career in HM, 88.8% preferred to complete a combined internal medicine and pediatrics HM fellowship with close to half of clinical time dedicated to adult HM. Just over half (53.6%) of programs reported that they could currently accommodate both PHM and adult clinical time during fellowship, and all but two programs reported that they could accommodate both PHM and HM time in the future.

PHM subspecialty designation with associated fellowship training requirements decreased desire to practice HM among med-peds residents who responded to our survey. This reflects findings from a recently published study that evaluated whether PHM fellowship requirements for board certification influenced pediatric and med-peds residents’ decision to pursue PHM in 2018.⁴ Additionally, Chandrasekar et al⁴ found that 87% of respondents indicated that sufficient residency training was an important factor in discouraging them from pursuing PHM fellowship. We noted similar findings in our open-ended survey responses, which indicate that med-peds respondents perceived that the intended purpose of PHM fellowship was to provide additional clinical training, and that served as a deterrent for fellowship. However, the survey by Chandrasekar et al⁴ assessed only four factors for understanding what was important in encouraging pursuit of a PHM fellowship: opportunity to gain new skills, potential increase in salary, opportunity for a master’s degree, and increased prestige. Our survey expands on med-peds residents’ needs, indicating that med-peds residents want a combined med-peds/HM fellowship that allows them to meet PHM board-eligibility requirements while also continuing to develop their adult HM clinical practice and other nonclinical training objectives in a way that combines both adult HM and PHM. Both surveys demonstrate the role that residency program directors and other resident mentors can have in counseling trainees on the nonclinical training objectives of PHM fellowship, including research, quality improvement, medical education, and leadership and clinical operations. Additional emphasis can be placed on opportunities for an individualized curriculum to address the specific career aims of each resident.

In this study, med-peds trainees viewed distribution of clinical time during fellowship as an important factor in pursuing PHM fellowship. The perceived importance of balancing clinical time is not surprising considering that most survey respondents interested in HM ultimately intend to practice both PHM and adult HM. This finding corresponds with current practice patterns of med-peds hospitalists, the majority of whom care for both children and adults.^4,5 Moonlighting in adult medicine was not considered sufficient, suggesting desire for mentorship and training integration on the internal medicine side. Opportunities for trainees to maintain and expand their internal medicine knowledge base and clinical decision-making outside of moonlighting will be key to meeting the needs of med-peds residents in PHM fellowship.

Fortunately, more than half of responding programs reported that they could allow for adult HM practice during PHM fellowship. Twelve programs were unsure if they could accommodate adult HM clinical time, and only two programs reported they could not. We suspect that the ability to support this training with clinical time in both adult HM and PHM is more likely available at programs with established internal medicine relationships, often in the form of med-peds residency programs and med-peds faculty. Further, these established relationships may be more common at pediatric health systems that are integrated or affiliated with an adult health system. Most PHM fellowships surveyed indicated that their pediatric institution had an affiliation with an adult facility, and most had med-peds HM faculty.

Precedent for supporting med-peds fellows is somewhat limited given that only five of the responding PHM fellowship programs reported having fellows with med-peds residency training. However, discrepancies between the expressed needs of med-peds residents and the current Accreditation Council for Graduate Medical Education (ACGME)–accredited PHM fellowship structure highlight opportunities to tailor fellowship training to support the career goals of med-peds residents. The current PHM fellowship structure consists of 26 educational units, with each unit representing 4 calendar weeks. A minimum of eight units are spent on each of the following: core clinical rotations, systems and scholarship, and individualized curriculum.^10,11 The Society of Hospital Medicine has published core competencies for both PHM and adult HM, which highlight significant overlap in each field’s skill competency, particularly in areas such as quality improvement, legal issues and risk management, and handoffs and transitions of care.^12,13 We contend that competencies addressed within PHM fellowship core clinical rotations may overlap with adult HM. Training in adult HM could be completed as part of the individualized curriculum with the ACGME, allowing adult HM practice to count toward this requirement. This would offer med-peds fellows the option to maintain their adult HM knowledge base without eliminating all elective time. Ultimately, it will be important to be creative in how training is accomplished and skills are acquired during both core clinical and individualized training blocks for med-peds trainees completing PHM fellowship.

In order to meet the expressed needs of med-peds residents interested in incorporating both adult HM and PHM into their future careers through PHM fellowship, we offer key recommendations for consideration by the ACGME, PHM FDs, and med-peds program directors (Figure). We encourage current PHM fellowship programs to establish relationships with adult HM programs to develop structured clinical opportunities that will allow fellows to gain the additional clinical training desired.

There were important limitations in this study. First, our estimated response rate for the resident survey was 35.8% of all med-peds residents in 2019, which may be interpreted as low. However, it is important to note that the survey was targeted to residents interested in HM. More than 25% of med-peds residents pursue a career in HM,⁵ suggesting our response rate may be attributed to residents who did not complete the survey because they were interested in other fields. The program director survey response rate was higher at 58.3%, though it is possible that response bias resulted in a higher response rate from programs with the ability to support med-peds trainees. Regardless, data from programs with the ability to support med-peds trainees are highly valuable in describing how PHM fellowship can be inclusive of med-peds–trained physicians interested in pursuing HM.

Both surveys were completed in 2019, prior to the ACGME accreditation of PHM fellowship, which likely presents new, unique challenges to fellowship programs trying to support the needs of med-peds fellows. However, insights noted above from programs with experience training med-peds fellows are still applicable within the constraints of ACGME requirements.

Many med-peds residents express strong interest in practicing HM and including PHM as part of their future hospitalist practice. With the introduction of PHM subspecialty board certification through the American Board of Pediatrics, med-peds residents face new considerations when choosing a career path after residency. The majority of resident respondents express the desire to spend a substantial portion of their clinical practice and/or fellowship practicing adult HM. A majority of PHM fellowships can or are willing to explore how to provide both pediatric and adult hospitalist training to med-peds residency–trained fellows. Understanding the facilitators and barriers to recruiting med-peds trainees for PHM fellowship ultimately has significant implications for the future of the PHM workforce. Incorporating the recommendations noted in this study may increase retention of med-peds providers in PHM by enabling fellowship training and ultimately board certification. Collaboration among the ACGME, PHM program directors, and med-peds residency program directors could help to develop PHM fellowship training programs that will meet the needs of med-peds residents interested in practicing PHM while still meeting ACGME requirements for PHM board eligibility.

The authors thank Dr Anoop Agrawal of National Med-Peds Residents’ Association (NMPRA).

The American Board of Medical Specialties approved subspecialty designation for the field of pediatric hospital medicine (PHM) in 2016.¹ For those who started independent practice prior to July 2019, there were two options for board eligibility: the “practice pathway” or completion of a PHM fellowship. The practice pathway allows for pediatric and combined internal medicine–pediatric (med-peds) providers who graduated by July 2019 to sit for the PHM board-certification examination if they meet specific criteria in their pediatric practice.² For pediatric and med-peds residents who graduated after July 2019, PHM board eligibility is available only through completion of a PHM fellowship.

PHM subspecialty designation with fellowship training requirements may pose unique challenges to med-peds residents interested in practicing both pediatric and adult hospital medicine (HM).^3,4 Each year, an estimated 25% of med-peds residency graduates go on to practice HM.⁵ The majority (62%-83%) of currently practicing med-peds–trained hospitalists care for both adults and children.^5,6 Further, med-peds–trained hospitalists comprise at least 10% of the PHM workforce⁵ and play an important role in caring for adult survivors of childhood diseases.³

Limited existing data suggest that the future practice patterns of med-peds residents may be affected by PHM fellowship requirements. One previous survey study indicated that, although med-peds residents see value in additional training opportunities offered by fellowship, the majority are less likely to pursue PHM as a result of the new requirements.⁴ Prominent factors dissuading residents from pursuing PHM fellowship included forfeited earnings during fellowship, student loan obligations, family obligations, and the perception that training received during residency was sufficient. Although these data provide important insights into potential changes in practice patterns, they do not explore qualities of PHM fellowship that may make additional training more appealing to med-peds residents and promote retention of med-peds–trained providers in the PHM workforce.

Further, there is no existing literature exploring if and how PHM fellowship programs are equipped to support the needs of med-peds–trained fellows. Other subspecialties have supported med-peds trainees in combined fellowship training programs, including rheumatology, neurology, pediatric emergency medicine, allergy/immunology, physical medicine and rehabilitation, and psychiatry.^7,8 However, the extent to which PHM fellowships follow a similar model to accommodate the career goals of med-peds participants is unclear.

Given the large numbers of med-peds residents who go on to practice combined PHM and adult HM, it is crucial to understand the training needs of this group within the context of PHM fellowship and board certification. The primary objectives of this study were to understand (1) the perceived PHM fellowship needs of med-peds residents interested in HM, and (2) how the current PHM fellowship training environment can meet those needs. Understanding that additional training requirements to practice PHM may affect the career trajectory of residents interested in HM, secondary objectives included describing perceptions of med-peds residents on PHM specialty designation and whether designation affected their career plans.

Study Design

This cross-sectional study took place over a 3-month period from May to July 2019 and included two surveys of different populations to develop a comprehensive understanding of stakeholder perceptions of PHM fellowship. The first survey (resident survey) invited med-peds residents who were members of the National Med-Peds Residents’ Association (NMPRA)⁹ in 2019 and who were interested in HM. The second survey (fellowship director [FD] survey) included PHM FDs. The study was determined to be exempt by the University of Pittsburgh Institutional Review Board.

Study Population and Recruitment

Resident Survey

Two attempts were made to elicit participation via the NMPRA electronic mailing list. The NMPRA membership includes med-peds residents and chief residents from US med-peds residency programs. As of May 2019, 77 med-peds residency programs and their residents were members of NMPRA, which encompassed all med-peds programs in the United States and its territories. NMPRA maintains a listserv for all members, and all existing US/territory programs were members at the time of the survey. Med-peds interns, residents, and chief residents interested in HM were invited to participate in this study.

FD Survey

Forty-eight FDs, representing member institutions of the PHM Fellowship Directors’ Council, were surveyed via the PHM Fellowship Directors listserv.

Survey Instruments

We constructed two de novo surveys consisting of multiple-choice and short-answer questions (Appendix 1 and Appendix 2). To enhance the validity of survey responses, questions were designed and tested using an iterative consensus process among authors and additional participants, including current med-peds PHM fellows, PHM fellowship program directors, med-peds residency program directors, and current med-peds residents. These revisions were repeated for a total of four cycles. Items were created to increase knowledge on the following key areas: resident-perceived needs in fellowship training, impact of PHM subspecialty designation on career choices related to HM, health system structure of fellowship programs, and ability to accommodate med-peds clinical training within a PHM fellowship. A combined med-peds fellowship, as defined in the survey and referenced in this study, is a “combined internal medicine–pediatrics hospital medicine fellowship whereby you would remain eligible for PHM board certification.” To ensure a broad and inclusive view of potential needs of med-peds trainees considering fellowship, all respondents were asked to complete questions pertaining to anticipated fellowship needs regardless of their indicated interest in fellowship.

Data Collection

Survey completion was voluntary. Email identifiers were not linked to completed surveys. Study data were collected and managed by using Qualtrics XM. Only completed survey entries were included in analysis.

Statistical Methods and Data Analysis

R software version 4.0.2 (R Foundation for Statistical Computing) was used for statistical analysis. Demographic data were summarized using frequency distributions. The intent of the free-text questions for both surveys was qualitative explanatory thematic analysis. Authors EB, HL, and AJ used a deductive approach to identify common themes that elucidated med-peds resident–anticipated needs in fellowship and PHM program strategies and barriers to accommodate these needs. Preliminary themes and action items were reviewed and discussed among the full authorship team until consensus was reached.

Demographic Data

Resident Survey

A total of 466 med-peds residents completed the resident survey. There are approximately 1300 med-peds residents annually, creating an estimated response rate of 35.8% of all US med-peds residents. The majority (n = 380, 81.5%) of respondents were med-peds postgraduate years 1 through 3 and thus only eligible for PHM board certification via the PHM fellowship pathway (Table 1). Most (n = 446, 95.7%) respondents had considered a career in adult, pediatric, or combined HM at some point. Of those med-peds residents who considered a career in HM (Appendix Table 1), 92.8% (n = 414) would prefer to practice combined adult HM and PHM.

FD Survey

Twenty-eight FDs completed the FD survey, representing 58.3% of 2019 PHM fellowship programs. Of the responding programs, 23 (82.1%) were associated with a freestanding children’s hospital, and 24 (85.7%) were integrated or affiliated with a health system that provides adult inpatient care (Table 2). Sixteen (57.1%) programs had a med-peds residency program at their institution.

Med-Peds Resident Perceptions of PHM Fellowship

In considering the importance of PHM board certification for physicians practicing PHM, 59.0% (n= 275) of respondents rated board certification as “not at all important” (Appendix Table 2). Most (n = 420, 90.1%) med-peds trainees responded that PHM subspecialty designation “decreased” or “significantly decreased” their desire to pursue a career that includes PHM. Of the respondents who reported no interest in hospital medicine, eight (40%) reported that PHM subspecialty status dissuaded them from a career in HM at least a moderate amount (Appendix Table 3). Roughly one third (n=158, 33.9%) of respondents reported that PHM subspecialty designation increased or significantly increased their desire to pursue a career that includes adult HM (Appenidx Table 2). Finally, although the majority (n = 275, 59%) of respondents said they had no interest in a HM fellowship, 114 (24.5%) indicated interest in a combined med-peds HM fellowship (Appendix Table 1). Short-answer questions revealed that commitment to additional training on top of a 4-year residency program was a possible deterring factor, particularly in light of student loan debt and family obligations. Respondents reported adequate clinical training during residency as another deterring factor.

Med-Peds Resident–Perceived Needs in PHM Fellowship

Regardless of interest in completing a PHM fellowship, all resident survey respondents were asked how their ideal PHM fellowship should be structured. Almost all (n = 456, 97.9%) respondents indicated that they would prefer to complete a combined med-peds HM fellowship (Table 3), and most preferred to complete a fellowship in 2 years. Only 10 (2.1%) respondents preferred to complete a PHM fellowship alone in 2 or 3 years. More than half (n=253, 54.3%) of respondents indicated that it would be ideal to obtain a master’s degree as part of fellowship.

Three quarters (n = 355, 75.8%) of med-peds residents reported that they would want 41% or more of clinical time in an ideal fellowship dedicated to adult HM. Importantly, most (n = 322, 69.1%) of the med-peds residents did not consider moonlighting alone in either PHM or adult HM to be enough to maintain training. In addition, many (n = 366, 78.5%) respondents felt that it was important or very important for scholarly work during fellowship to bridge pediatrics and internal medicine.

Short-answer questions indicated that the ability to practice both internal medicine and pediatrics during fellowship emerged as an important deciding factor, with emphasis on adequate opportunities to maintain internal medicine knowledge base (Figure). Similarly, access to med-peds mentorship was an important component of the decision. Compensation both during fellowship and potential future earnings was also a prominent consideration.

Capacity of PHM Programs to Support Med-Peds Fellows

Fifteen (53.6%) FDs reported that their programs were able to accommodate both PHM and adult HM clinical time during fellowship, 11 (39.3%) were unsure, and 2 (7.1%) were unable to accommodate both (Table 2).

The options for adult HM clinical time varied by institution and included precepted time on adult HM, full attending privileges on adult HM, and adult HM time through moonlighting only. Short-answer responses from FDs with experience training med-peds fellows cited using PHM elective time for adult HM and offering moonlighting in adult HM as ways to address career goals of med-peds trainees. Scholarship time for fellows was preserved by decreasing required time on pediatric intensive care unit and complex care services.

Accessibility of Med-Peds Mentorship

As noted above, med-peds residents identified mentorship as an important factor in consideration of PHM fellowship. A total of 23 (82.1%) FDs reported their programs had med-peds faculty members within their PHM team (Table 2). The majority (n = 21, 91.3%) of those med-peds faculty had both PHM and adult HM clinical time.

This study characterized the ideal PHM fellowship structure from the perspective of med-peds residents and described the current ability of PHM fellowships to support med-peds residents. The majority of residents stated that they had no interest in an HM fellowship. However, for med-peds residents who considered a career in HM, 88.8% preferred to complete a combined internal medicine and pediatrics HM fellowship with close to half of clinical time dedicated to adult HM. Just over half (53.6%) of programs reported that they could currently accommodate both PHM and adult clinical time during fellowship, and all but two programs reported that they could accommodate both PHM and HM time in the future.

PHM subspecialty designation with associated fellowship training requirements decreased desire to practice HM among med-peds residents who responded to our survey. This reflects findings from a recently published study that evaluated whether PHM fellowship requirements for board certification influenced pediatric and med-peds residents’ decision to pursue PHM in 2018.⁴ Additionally, Chandrasekar et al⁴ found that 87% of respondents indicated that sufficient residency training was an important factor in discouraging them from pursuing PHM fellowship. We noted similar findings in our open-ended survey responses, which indicate that med-peds respondents perceived that the intended purpose of PHM fellowship was to provide additional clinical training, and that served as a deterrent for fellowship. However, the survey by Chandrasekar et al⁴ assessed only four factors for understanding what was important in encouraging pursuit of a PHM fellowship: opportunity to gain new skills, potential increase in salary, opportunity for a master’s degree, and increased prestige. Our survey expands on med-peds residents’ needs, indicating that med-peds residents want a combined med-peds/HM fellowship that allows them to meet PHM board-eligibility requirements while also continuing to develop their adult HM clinical practice and other nonclinical training objectives in a way that combines both adult HM and PHM. Both surveys demonstrate the role that residency program directors and other resident mentors can have in counseling trainees on the nonclinical training objectives of PHM fellowship, including research, quality improvement, medical education, and leadership and clinical operations. Additional emphasis can be placed on opportunities for an individualized curriculum to address the specific career aims of each resident.

In this study, med-peds trainees viewed distribution of clinical time during fellowship as an important factor in pursuing PHM fellowship. The perceived importance of balancing clinical time is not surprising considering that most survey respondents interested in HM ultimately intend to practice both PHM and adult HM. This finding corresponds with current practice patterns of med-peds hospitalists, the majority of whom care for both children and adults.^4,5 Moonlighting in adult medicine was not considered sufficient, suggesting desire for mentorship and training integration on the internal medicine side. Opportunities for trainees to maintain and expand their internal medicine knowledge base and clinical decision-making outside of moonlighting will be key to meeting the needs of med-peds residents in PHM fellowship.

Fortunately, more than half of responding programs reported that they could allow for adult HM practice during PHM fellowship. Twelve programs were unsure if they could accommodate adult HM clinical time, and only two programs reported they could not. We suspect that the ability to support this training with clinical time in both adult HM and PHM is more likely available at programs with established internal medicine relationships, often in the form of med-peds residency programs and med-peds faculty. Further, these established relationships may be more common at pediatric health systems that are integrated or affiliated with an adult health system. Most PHM fellowships surveyed indicated that their pediatric institution had an affiliation with an adult facility, and most had med-peds HM faculty.

Precedent for supporting med-peds fellows is somewhat limited given that only five of the responding PHM fellowship programs reported having fellows with med-peds residency training. However, discrepancies between the expressed needs of med-peds residents and the current Accreditation Council for Graduate Medical Education (ACGME)–accredited PHM fellowship structure highlight opportunities to tailor fellowship training to support the career goals of med-peds residents. The current PHM fellowship structure consists of 26 educational units, with each unit representing 4 calendar weeks. A minimum of eight units are spent on each of the following: core clinical rotations, systems and scholarship, and individualized curriculum.^10,11 The Society of Hospital Medicine has published core competencies for both PHM and adult HM, which highlight significant overlap in each field’s skill competency, particularly in areas such as quality improvement, legal issues and risk management, and handoffs and transitions of care.^12,13 We contend that competencies addressed within PHM fellowship core clinical rotations may overlap with adult HM. Training in adult HM could be completed as part of the individualized curriculum with the ACGME, allowing adult HM practice to count toward this requirement. This would offer med-peds fellows the option to maintain their adult HM knowledge base without eliminating all elective time. Ultimately, it will be important to be creative in how training is accomplished and skills are acquired during both core clinical and individualized training blocks for med-peds trainees completing PHM fellowship.

In order to meet the expressed needs of med-peds residents interested in incorporating both adult HM and PHM into their future careers through PHM fellowship, we offer key recommendations for consideration by the ACGME, PHM FDs, and med-peds program directors (Figure). We encourage current PHM fellowship programs to establish relationships with adult HM programs to develop structured clinical opportunities that will allow fellows to gain the additional clinical training desired.

There were important limitations in this study. First, our estimated response rate for the resident survey was 35.8% of all med-peds residents in 2019, which may be interpreted as low. However, it is important to note that the survey was targeted to residents interested in HM. More than 25% of med-peds residents pursue a career in HM,⁵ suggesting our response rate may be attributed to residents who did not complete the survey because they were interested in other fields. The program director survey response rate was higher at 58.3%, though it is possible that response bias resulted in a higher response rate from programs with the ability to support med-peds trainees. Regardless, data from programs with the ability to support med-peds trainees are highly valuable in describing how PHM fellowship can be inclusive of med-peds–trained physicians interested in pursuing HM.

Both surveys were completed in 2019, prior to the ACGME accreditation of PHM fellowship, which likely presents new, unique challenges to fellowship programs trying to support the needs of med-peds fellows. However, insights noted above from programs with experience training med-peds fellows are still applicable within the constraints of ACGME requirements.

Many med-peds residents express strong interest in practicing HM and including PHM as part of their future hospitalist practice. With the introduction of PHM subspecialty board certification through the American Board of Pediatrics, med-peds residents face new considerations when choosing a career path after residency. The majority of resident respondents express the desire to spend a substantial portion of their clinical practice and/or fellowship practicing adult HM. A majority of PHM fellowships can or are willing to explore how to provide both pediatric and adult hospitalist training to med-peds residency–trained fellows. Understanding the facilitators and barriers to recruiting med-peds trainees for PHM fellowship ultimately has significant implications for the future of the PHM workforce. Incorporating the recommendations noted in this study may increase retention of med-peds providers in PHM by enabling fellowship training and ultimately board certification. Collaboration among the ACGME, PHM program directors, and med-peds residency program directors could help to develop PHM fellowship training programs that will meet the needs of med-peds residents interested in practicing PHM while still meeting ACGME requirements for PHM board eligibility.

The authors thank Dr Anoop Agrawal of National Med-Peds Residents’ Association (NMPRA).

The American Board of Medical Specialties approved subspecialty designation for the field of pediatric hospital medicine (PHM) in 2016.¹ For those who started independent practice prior to July 2019, there were two options for board eligibility: the “practice pathway” or completion of a PHM fellowship. The practice pathway allows for pediatric and combined internal medicine–pediatric (med-peds) providers who graduated by July 2019 to sit for the PHM board-certification examination if they meet specific criteria in their pediatric practice.² For pediatric and med-peds residents who graduated after July 2019, PHM board eligibility is available only through completion of a PHM fellowship.

PHM subspecialty designation with fellowship training requirements may pose unique challenges to med-peds residents interested in practicing both pediatric and adult hospital medicine (HM).^3,4 Each year, an estimated 25% of med-peds residency graduates go on to practice HM.⁵ The majority (62%-83%) of currently practicing med-peds–trained hospitalists care for both adults and children.^5,6 Further, med-peds–trained hospitalists comprise at least 10% of the PHM workforce⁵ and play an important role in caring for adult survivors of childhood diseases.³

Limited existing data suggest that the future practice patterns of med-peds residents may be affected by PHM fellowship requirements. One previous survey study indicated that, although med-peds residents see value in additional training opportunities offered by fellowship, the majority are less likely to pursue PHM as a result of the new requirements.⁴ Prominent factors dissuading residents from pursuing PHM fellowship included forfeited earnings during fellowship, student loan obligations, family obligations, and the perception that training received during residency was sufficient. Although these data provide important insights into potential changes in practice patterns, they do not explore qualities of PHM fellowship that may make additional training more appealing to med-peds residents and promote retention of med-peds–trained providers in the PHM workforce.

Further, there is no existing literature exploring if and how PHM fellowship programs are equipped to support the needs of med-peds–trained fellows. Other subspecialties have supported med-peds trainees in combined fellowship training programs, including rheumatology, neurology, pediatric emergency medicine, allergy/immunology, physical medicine and rehabilitation, and psychiatry.^7,8 However, the extent to which PHM fellowships follow a similar model to accommodate the career goals of med-peds participants is unclear.

Given the large numbers of med-peds residents who go on to practice combined PHM and adult HM, it is crucial to understand the training needs of this group within the context of PHM fellowship and board certification. The primary objectives of this study were to understand (1) the perceived PHM fellowship needs of med-peds residents interested in HM, and (2) how the current PHM fellowship training environment can meet those needs. Understanding that additional training requirements to practice PHM may affect the career trajectory of residents interested in HM, secondary objectives included describing perceptions of med-peds residents on PHM specialty designation and whether designation affected their career plans.

Study Design

This cross-sectional study took place over a 3-month period from May to July 2019 and included two surveys of different populations to develop a comprehensive understanding of stakeholder perceptions of PHM fellowship. The first survey (resident survey) invited med-peds residents who were members of the National Med-Peds Residents’ Association (NMPRA)⁹ in 2019 and who were interested in HM. The second survey (fellowship director [FD] survey) included PHM FDs. The study was determined to be exempt by the University of Pittsburgh Institutional Review Board.

Study Population and Recruitment

Resident Survey

Two attempts were made to elicit participation via the NMPRA electronic mailing list. The NMPRA membership includes med-peds residents and chief residents from US med-peds residency programs. As of May 2019, 77 med-peds residency programs and their residents were members of NMPRA, which encompassed all med-peds programs in the United States and its territories. NMPRA maintains a listserv for all members, and all existing US/territory programs were members at the time of the survey. Med-peds interns, residents, and chief residents interested in HM were invited to participate in this study.

FD Survey

Forty-eight FDs, representing member institutions of the PHM Fellowship Directors’ Council, were surveyed via the PHM Fellowship Directors listserv.

Survey Instruments

We constructed two de novo surveys consisting of multiple-choice and short-answer questions (Appendix 1 and Appendix 2). To enhance the validity of survey responses, questions were designed and tested using an iterative consensus process among authors and additional participants, including current med-peds PHM fellows, PHM fellowship program directors, med-peds residency program directors, and current med-peds residents. These revisions were repeated for a total of four cycles. Items were created to increase knowledge on the following key areas: resident-perceived needs in fellowship training, impact of PHM subspecialty designation on career choices related to HM, health system structure of fellowship programs, and ability to accommodate med-peds clinical training within a PHM fellowship. A combined med-peds fellowship, as defined in the survey and referenced in this study, is a “combined internal medicine–pediatrics hospital medicine fellowship whereby you would remain eligible for PHM board certification.” To ensure a broad and inclusive view of potential needs of med-peds trainees considering fellowship, all respondents were asked to complete questions pertaining to anticipated fellowship needs regardless of their indicated interest in fellowship.

Data Collection

Survey completion was voluntary. Email identifiers were not linked to completed surveys. Study data were collected and managed by using Qualtrics XM. Only completed survey entries were included in analysis.

Statistical Methods and Data Analysis

R software version 4.0.2 (R Foundation for Statistical Computing) was used for statistical analysis. Demographic data were summarized using frequency distributions. The intent of the free-text questions for both surveys was qualitative explanatory thematic analysis. Authors EB, HL, and AJ used a deductive approach to identify common themes that elucidated med-peds resident–anticipated needs in fellowship and PHM program strategies and barriers to accommodate these needs. Preliminary themes and action items were reviewed and discussed among the full authorship team until consensus was reached.

Demographic Data

Resident Survey

A total of 466 med-peds residents completed the resident survey. There are approximately 1300 med-peds residents annually, creating an estimated response rate of 35.8% of all US med-peds residents. The majority (n = 380, 81.5%) of respondents were med-peds postgraduate years 1 through 3 and thus only eligible for PHM board certification via the PHM fellowship pathway (Table 1). Most (n = 446, 95.7%) respondents had considered a career in adult, pediatric, or combined HM at some point. Of those med-peds residents who considered a career in HM (Appendix Table 1), 92.8% (n = 414) would prefer to practice combined adult HM and PHM.

FD Survey

Twenty-eight FDs completed the FD survey, representing 58.3% of 2019 PHM fellowship programs. Of the responding programs, 23 (82.1%) were associated with a freestanding children’s hospital, and 24 (85.7%) were integrated or affiliated with a health system that provides adult inpatient care (Table 2). Sixteen (57.1%) programs had a med-peds residency program at their institution.

Med-Peds Resident Perceptions of PHM Fellowship

In considering the importance of PHM board certification for physicians practicing PHM, 59.0% (n= 275) of respondents rated board certification as “not at all important” (Appendix Table 2). Most (n = 420, 90.1%) med-peds trainees responded that PHM subspecialty designation “decreased” or “significantly decreased” their desire to pursue a career that includes PHM. Of the respondents who reported no interest in hospital medicine, eight (40%) reported that PHM subspecialty status dissuaded them from a career in HM at least a moderate amount (Appendix Table 3). Roughly one third (n=158, 33.9%) of respondents reported that PHM subspecialty designation increased or significantly increased their desire to pursue a career that includes adult HM (Appenidx Table 2). Finally, although the majority (n = 275, 59%) of respondents said they had no interest in a HM fellowship, 114 (24.5%) indicated interest in a combined med-peds HM fellowship (Appendix Table 1). Short-answer questions revealed that commitment to additional training on top of a 4-year residency program was a possible deterring factor, particularly in light of student loan debt and family obligations. Respondents reported adequate clinical training during residency as another deterring factor.

Med-Peds Resident–Perceived Needs in PHM Fellowship

Regardless of interest in completing a PHM fellowship, all resident survey respondents were asked how their ideal PHM fellowship should be structured. Almost all (n = 456, 97.9%) respondents indicated that they would prefer to complete a combined med-peds HM fellowship (Table 3), and most preferred to complete a fellowship in 2 years. Only 10 (2.1%) respondents preferred to complete a PHM fellowship alone in 2 or 3 years. More than half (n=253, 54.3%) of respondents indicated that it would be ideal to obtain a master’s degree as part of fellowship.

Three quarters (n = 355, 75.8%) of med-peds residents reported that they would want 41% or more of clinical time in an ideal fellowship dedicated to adult HM. Importantly, most (n = 322, 69.1%) of the med-peds residents did not consider moonlighting alone in either PHM or adult HM to be enough to maintain training. In addition, many (n = 366, 78.5%) respondents felt that it was important or very important for scholarly work during fellowship to bridge pediatrics and internal medicine.

Short-answer questions indicated that the ability to practice both internal medicine and pediatrics during fellowship emerged as an important deciding factor, with emphasis on adequate opportunities to maintain internal medicine knowledge base (Figure). Similarly, access to med-peds mentorship was an important component of the decision. Compensation both during fellowship and potential future earnings was also a prominent consideration.

Capacity of PHM Programs to Support Med-Peds Fellows

Fifteen (53.6%) FDs reported that their programs were able to accommodate both PHM and adult HM clinical time during fellowship, 11 (39.3%) were unsure, and 2 (7.1%) were unable to accommodate both (Table 2).

The options for adult HM clinical time varied by institution and included precepted time on adult HM, full attending privileges on adult HM, and adult HM time through moonlighting only. Short-answer responses from FDs with experience training med-peds fellows cited using PHM elective time for adult HM and offering moonlighting in adult HM as ways to address career goals of med-peds trainees. Scholarship time for fellows was preserved by decreasing required time on pediatric intensive care unit and complex care services.

Accessibility of Med-Peds Mentorship

As noted above, med-peds residents identified mentorship as an important factor in consideration of PHM fellowship. A total of 23 (82.1%) FDs reported their programs had med-peds faculty members within their PHM team (Table 2). The majority (n = 21, 91.3%) of those med-peds faculty had both PHM and adult HM clinical time.

This study characterized the ideal PHM fellowship structure from the perspective of med-peds residents and described the current ability of PHM fellowships to support med-peds residents. The majority of residents stated that they had no interest in an HM fellowship. However, for med-peds residents who considered a career in HM, 88.8% preferred to complete a combined internal medicine and pediatrics HM fellowship with close to half of clinical time dedicated to adult HM. Just over half (53.6%) of programs reported that they could currently accommodate both PHM and adult clinical time during fellowship, and all but two programs reported that they could accommodate both PHM and HM time in the future.

PHM subspecialty designation with associated fellowship training requirements decreased desire to practice HM among med-peds residents who responded to our survey. This reflects findings from a recently published study that evaluated whether PHM fellowship requirements for board certification influenced pediatric and med-peds residents’ decision to pursue PHM in 2018.⁴ Additionally, Chandrasekar et al⁴ found that 87% of respondents indicated that sufficient residency training was an important factor in discouraging them from pursuing PHM fellowship. We noted similar findings in our open-ended survey responses, which indicate that med-peds respondents perceived that the intended purpose of PHM fellowship was to provide additional clinical training, and that served as a deterrent for fellowship. However, the survey by Chandrasekar et al⁴ assessed only four factors for understanding what was important in encouraging pursuit of a PHM fellowship: opportunity to gain new skills, potential increase in salary, opportunity for a master’s degree, and increased prestige. Our survey expands on med-peds residents’ needs, indicating that med-peds residents want a combined med-peds/HM fellowship that allows them to meet PHM board-eligibility requirements while also continuing to develop their adult HM clinical practice and other nonclinical training objectives in a way that combines both adult HM and PHM. Both surveys demonstrate the role that residency program directors and other resident mentors can have in counseling trainees on the nonclinical training objectives of PHM fellowship, including research, quality improvement, medical education, and leadership and clinical operations. Additional emphasis can be placed on opportunities for an individualized curriculum to address the specific career aims of each resident.

In this study, med-peds trainees viewed distribution of clinical time during fellowship as an important factor in pursuing PHM fellowship. The perceived importance of balancing clinical time is not surprising considering that most survey respondents interested in HM ultimately intend to practice both PHM and adult HM. This finding corresponds with current practice patterns of med-peds hospitalists, the majority of whom care for both children and adults.^4,5 Moonlighting in adult medicine was not considered sufficient, suggesting desire for mentorship and training integration on the internal medicine side. Opportunities for trainees to maintain and expand their internal medicine knowledge base and clinical decision-making outside of moonlighting will be key to meeting the needs of med-peds residents in PHM fellowship.

Fortunately, more than half of responding programs reported that they could allow for adult HM practice during PHM fellowship. Twelve programs were unsure if they could accommodate adult HM clinical time, and only two programs reported they could not. We suspect that the ability to support this training with clinical time in both adult HM and PHM is more likely available at programs with established internal medicine relationships, often in the form of med-peds residency programs and med-peds faculty. Further, these established relationships may be more common at pediatric health systems that are integrated or affiliated with an adult health system. Most PHM fellowships surveyed indicated that their pediatric institution had an affiliation with an adult facility, and most had med-peds HM faculty.

Precedent for supporting med-peds fellows is somewhat limited given that only five of the responding PHM fellowship programs reported having fellows with med-peds residency training. However, discrepancies between the expressed needs of med-peds residents and the current Accreditation Council for Graduate Medical Education (ACGME)–accredited PHM fellowship structure highlight opportunities to tailor fellowship training to support the career goals of med-peds residents. The current PHM fellowship structure consists of 26 educational units, with each unit representing 4 calendar weeks. A minimum of eight units are spent on each of the following: core clinical rotations, systems and scholarship, and individualized curriculum.^10,11 The Society of Hospital Medicine has published core competencies for both PHM and adult HM, which highlight significant overlap in each field’s skill competency, particularly in areas such as quality improvement, legal issues and risk management, and handoffs and transitions of care.^12,13 We contend that competencies addressed within PHM fellowship core clinical rotations may overlap with adult HM. Training in adult HM could be completed as part of the individualized curriculum with the ACGME, allowing adult HM practice to count toward this requirement. This would offer med-peds fellows the option to maintain their adult HM knowledge base without eliminating all elective time. Ultimately, it will be important to be creative in how training is accomplished and skills are acquired during both core clinical and individualized training blocks for med-peds trainees completing PHM fellowship.

In order to meet the expressed needs of med-peds residents interested in incorporating both adult HM and PHM into their future careers through PHM fellowship, we offer key recommendations for consideration by the ACGME, PHM FDs, and med-peds program directors (Figure). We encourage current PHM fellowship programs to establish relationships with adult HM programs to develop structured clinical opportunities that will allow fellows to gain the additional clinical training desired.

There were important limitations in this study. First, our estimated response rate for the resident survey was 35.8% of all med-peds residents in 2019, which may be interpreted as low. However, it is important to note that the survey was targeted to residents interested in HM. More than 25% of med-peds residents pursue a career in HM,⁵ suggesting our response rate may be attributed to residents who did not complete the survey because they were interested in other fields. The program director survey response rate was higher at 58.3%, though it is possible that response bias resulted in a higher response rate from programs with the ability to support med-peds trainees. Regardless, data from programs with the ability to support med-peds trainees are highly valuable in describing how PHM fellowship can be inclusive of med-peds–trained physicians interested in pursuing HM.

Both surveys were completed in 2019, prior to the ACGME accreditation of PHM fellowship, which likely presents new, unique challenges to fellowship programs trying to support the needs of med-peds fellows. However, insights noted above from programs with experience training med-peds fellows are still applicable within the constraints of ACGME requirements.

Many med-peds residents express strong interest in practicing HM and including PHM as part of their future hospitalist practice. With the introduction of PHM subspecialty board certification through the American Board of Pediatrics, med-peds residents face new considerations when choosing a career path after residency. The majority of resident respondents express the desire to spend a substantial portion of their clinical practice and/or fellowship practicing adult HM. A majority of PHM fellowships can or are willing to explore how to provide both pediatric and adult hospitalist training to med-peds residency–trained fellows. Understanding the facilitators and barriers to recruiting med-peds trainees for PHM fellowship ultimately has significant implications for the future of the PHM workforce. Incorporating the recommendations noted in this study may increase retention of med-peds providers in PHM by enabling fellowship training and ultimately board certification. Collaboration among the ACGME, PHM program directors, and med-peds residency program directors could help to develop PHM fellowship training programs that will meet the needs of med-peds residents interested in practicing PHM while still meeting ACGME requirements for PHM board eligibility.

The authors thank Dr Anoop Agrawal of National Med-Peds Residents’ Association (NMPRA).

Invasive bacterial infections (IBI; ie, bacterial meningitis, bacteremia) are an uncommon but potentially devastating occurrence in young febrile infants. The challenge for clinicians is that physical examination cannot reliably exclude such infections. Thus, these infants have historically received comprehensive emergency department evaluation, including routine cerebrospinal fluid (CSF) assessment, and, often, required hospitalization for parenteral antibiotic administration while awaiting CSF culture results. The new American Academy of Pediatrics (AAP) guidelines were necessary given changing bacteriology, advances in diagnostic testing, greater insight into the differential risk of poor outcomes by site of infection, and better appreciation of the potential harms of unnecessary care and interventions.¹ The 21 recommendations apply to well-appearing febrile infants 8 to 60 days of age, with recommendations stratified by age group, and exclude infants with certain conditions, including prematurity, focal bacterial infection, congenital or chromosomal abnormalities, and bronchiolitis. Four key recommendations are highlighted.

Recommendation 1: Diagnostic evaluation. For all age groups, blood culture and urinalysis (UA) are routinely recommended. For infants 8 to 21 days old, urine culture is routinely recommended. For older infants, urine culture is recommended if the UA is positive. All specimens for culture should be obtained via catheterization or suprapubic aspiration.

Infants 8 to 21 days old

• May assess inflammatory markers (grade B, weak).
• Should obtain CSF for analysis and culture (grade A, strong).

Infants 22 to 28 days old

• Should assess inflammatory markers (grade B, strong).
• May obtain CSF for analysis and culture even if no inflammatory marker obtained is abnormal (grade B, moderate).
• Should obtain CSF for analysis and culture if any inflammatory marker obtained is abnormal (procalcitonin >0.5 ng/mL [preferred]; C-reactive protein >20 mg/L; absolute neutrophil count >4000-5200/mm³; or temperature >38.5 °C) (grade B, moderate).

Infants 29 to 60 days old

• Should assess inflammatory markers (grade B, moderate).
• May obtain CSF for analysis and culture if any inflammatory marker is abnormal, (grade C, weak).
• Need not obtain CSF for analysis if all inflammatory markers obtained are normal (grade B, moderate).

Recommendation 2: Initial disposition decision

Infants 8 to 21 days old

• Admit (grade B, moderate).

Infants 22 to 28 days old

• Admit if CSF analysis is abnormal, UA is positive (A, strong), or if CSF is not obtained or is uninterpretable (grade B, weak).
• May manage at home if UA is normal, inflammatory markers are normal, CSF is normal or enterovirus positive, family has received verbal and written home monitoring instructions for concerning signs that should prompt immediate return for care, follow-up plan for reevaluation in 24 hours is in place, and means of communication for change in clinical status has been established (grade B, moderate).

Infants 29 to 60 days old

• Admit if CSF analysis is abnormal (grade A strong).
• May hospitalize if any inflammatory marker obtained is abnormal (grade B, moderate).
• Should manage at home if all the following are present: CSF is normal, if obtained; UA is negative; all inflammatory markers obtained are normal; teaching is complete; follow-up plan for reevaluation in 24 hours is in place; and means of communication for change in clinical status has been established (grade B, moderate).

Recommendation 3: Empiric antimicrobial treatment

Infants 8 to 21 days old

• Should initiate parenteral antimicrobial therapy (grade A, strong).
• This recommendation is based on the high prevalence of IBIs in this age category, and IBI may be present despite a negative UA and/or normal inflammatory markers.

Infants 22 to 28 days old

• Should initiate parenteral antimicrobial therapy if either CSF analysis suggests bacterial meningitis or UA is positive (grade A, strong).
• May administer parenteral antimicrobial therapy if any inflammatory marker is abnormal (grade B, moderate).
• May administer parenteral antimicrobial therapy even if everything is reassuring (grade B, weak).
• Should administer parenteral antimicrobial therapy to infant who will be managed at home even if all evaluation is reassuring (grade C, moderate).

Infants 29 to 60 days old

• Should start parenteral antimicrobials if CSF analysis suggests bacterial meningitis (grade A, strong).
• May use parenteral antimicrobials if any inflammatory marker is abnormal (grade B, moderate).
• Should initiate oral antimicrobial therapy if CSF is normal (if obtained), UA is positive, and no inflammatory markers obtained are abnormal (grade B, strong).
• Need not start antimicrobials if CSF is normal or enterovirus positive, UA is negative, and no inflammatory marker obtained is abnormal (grade B, moderate).

Recommendation 4: Hospital discharge decision

Infants 8 to 21 days old AND Infants 22 to 28 days ol

• Discontinue antibiotics and discharge infant when culture results are negative for 24 to 36 hours (or positive only for contaminants), the infant is well or improving, and there are no other reasons for hospitalization (grade B, strong).

Infants 29 to 60 days old

• Although no specific parameters are given for infants without UTI, presumably the discharge criteria for younger infants would also apply for this group.
• For infants with UTI, discharge if blood and CSF cultures are negative, infant is well or improving, and no other reasons for hospitalization remain (grade B, strong).

The guideline provides opportunities for safely doing less in a vulnerable population. For example, infants with UTIs may be managed differently (eg, often with oral antibiotics) from those with IBIs, which represents an important change from conventional practice.² Additional strengths are the incorporation of procalcitonin, which has emerged as the most accurate marker for risk stratification;³ and deemphasis of complete blood count results.

Multiple exclusions for relatively common scenarios represent missed opportunities for a more complete set of recommendations for the febrile infant population. The decision to exclude infants in the first week of life is perplexing since infants 0 to 7 days old will receive CSF analysis, require admission, and generally be managed comparably to infants 8 to 21 days old. Infants with bronchiolitis are excluded; the absence of uniform guidance may perpetuate variability in management within and across institutions. Finally, exclusion of infants in whom perinatal or congenital herpes simplex virus is a consideration is not ideal. The requirement to consult separate guidance for herpes simplex virus evaluation fragments decision-making and may lead to inadvertent omissions of critical tests or treatment in at-risk infants.

Methods in Preparing the Guideline

The guideline working group included stakeholders from multiple specialties including general pediatrics, emergency medicine, hospital medicine, infectious diseases, and family medicine. In addition to published studies, the committee considered an Agency for Healthcare Research and Quality commissioned systematic review, as well as analyses of additional data solicited from previously published peer-reviewed studies. Once recommendations were formulated, additional input from physician focus groups and parents was solicited. Recommendations were rated based on strength of available evidence (A, B, C, D, X) as well as assessment of the benefit/harm profile (strong, moderate, weak).

Sources of Potential Conflicts of Interest or Bias

The guideline writing group was predominantly male, though we note that the broader working group was diverse in gender and specialty. No significant conflicts of interest were noted.

Generalizability

The complexity of this guideline, including age stratification, multiple exclusions, and multistep processes could lead to challenges in implementation; a health information technology application (app) could substantially ease the difficulty of implementation at the point of care.

Additional areas in need of guidance include neonates with bronchiolitis and fever and neonates with focal infection. For the former, there is an abundance of evidence;⁴ what is needed is consensus. For the latter, additional study is needed such as the role of inflammatory markers in stratifying infants with focal infection who need additional evaluation prior to treatment.

Invasive bacterial infections (IBI; ie, bacterial meningitis, bacteremia) are an uncommon but potentially devastating occurrence in young febrile infants. The challenge for clinicians is that physical examination cannot reliably exclude such infections. Thus, these infants have historically received comprehensive emergency department evaluation, including routine cerebrospinal fluid (CSF) assessment, and, often, required hospitalization for parenteral antibiotic administration while awaiting CSF culture results. The new American Academy of Pediatrics (AAP) guidelines were necessary given changing bacteriology, advances in diagnostic testing, greater insight into the differential risk of poor outcomes by site of infection, and better appreciation of the potential harms of unnecessary care and interventions.¹ The 21 recommendations apply to well-appearing febrile infants 8 to 60 days of age, with recommendations stratified by age group, and exclude infants with certain conditions, including prematurity, focal bacterial infection, congenital or chromosomal abnormalities, and bronchiolitis. Four key recommendations are highlighted.

Recommendation 1: Diagnostic evaluation. For all age groups, blood culture and urinalysis (UA) are routinely recommended. For infants 8 to 21 days old, urine culture is routinely recommended. For older infants, urine culture is recommended if the UA is positive. All specimens for culture should be obtained via catheterization or suprapubic aspiration.

Infants 8 to 21 days old

• May assess inflammatory markers (grade B, weak).
• Should obtain CSF for analysis and culture (grade A, strong).

Infants 22 to 28 days old

• Should assess inflammatory markers (grade B, strong).
• May obtain CSF for analysis and culture even if no inflammatory marker obtained is abnormal (grade B, moderate).
• Should obtain CSF for analysis and culture if any inflammatory marker obtained is abnormal (procalcitonin >0.5 ng/mL [preferred]; C-reactive protein >20 mg/L; absolute neutrophil count >4000-5200/mm³; or temperature >38.5 °C) (grade B, moderate).

Infants 29 to 60 days old

• Should assess inflammatory markers (grade B, moderate).
• May obtain CSF for analysis and culture if any inflammatory marker is abnormal, (grade C, weak).
• Need not obtain CSF for analysis if all inflammatory markers obtained are normal (grade B, moderate).

Recommendation 2: Initial disposition decision

Infants 8 to 21 days old

• Admit (grade B, moderate).

Infants 22 to 28 days old

• Admit if CSF analysis is abnormal, UA is positive (A, strong), or if CSF is not obtained or is uninterpretable (grade B, weak).
• May manage at home if UA is normal, inflammatory markers are normal, CSF is normal or enterovirus positive, family has received verbal and written home monitoring instructions for concerning signs that should prompt immediate return for care, follow-up plan for reevaluation in 24 hours is in place, and means of communication for change in clinical status has been established (grade B, moderate).

Infants 29 to 60 days old

• Admit if CSF analysis is abnormal (grade A strong).
• May hospitalize if any inflammatory marker obtained is abnormal (grade B, moderate).
• Should manage at home if all the following are present: CSF is normal, if obtained; UA is negative; all inflammatory markers obtained are normal; teaching is complete; follow-up plan for reevaluation in 24 hours is in place; and means of communication for change in clinical status has been established (grade B, moderate).

Recommendation 3: Empiric antimicrobial treatment

Infants 8 to 21 days old

• Should initiate parenteral antimicrobial therapy (grade A, strong).
• This recommendation is based on the high prevalence of IBIs in this age category, and IBI may be present despite a negative UA and/or normal inflammatory markers.

Infants 22 to 28 days old

• Should initiate parenteral antimicrobial therapy if either CSF analysis suggests bacterial meningitis or UA is positive (grade A, strong).
• May administer parenteral antimicrobial therapy if any inflammatory marker is abnormal (grade B, moderate).
• May administer parenteral antimicrobial therapy even if everything is reassuring (grade B, weak).
• Should administer parenteral antimicrobial therapy to infant who will be managed at home even if all evaluation is reassuring (grade C, moderate).

Infants 29 to 60 days old

• Should start parenteral antimicrobials if CSF analysis suggests bacterial meningitis (grade A, strong).
• May use parenteral antimicrobials if any inflammatory marker is abnormal (grade B, moderate).
• Should initiate oral antimicrobial therapy if CSF is normal (if obtained), UA is positive, and no inflammatory markers obtained are abnormal (grade B, strong).
• Need not start antimicrobials if CSF is normal or enterovirus positive, UA is negative, and no inflammatory marker obtained is abnormal (grade B, moderate).

Recommendation 4: Hospital discharge decision

Infants 8 to 21 days old AND Infants 22 to 28 days ol

• Discontinue antibiotics and discharge infant when culture results are negative for 24 to 36 hours (or positive only for contaminants), the infant is well or improving, and there are no other reasons for hospitalization (grade B, strong).

Infants 29 to 60 days old

• Although no specific parameters are given for infants without UTI, presumably the discharge criteria for younger infants would also apply for this group.
• For infants with UTI, discharge if blood and CSF cultures are negative, infant is well or improving, and no other reasons for hospitalization remain (grade B, strong).

The guideline provides opportunities for safely doing less in a vulnerable population. For example, infants with UTIs may be managed differently (eg, often with oral antibiotics) from those with IBIs, which represents an important change from conventional practice.² Additional strengths are the incorporation of procalcitonin, which has emerged as the most accurate marker for risk stratification;³ and deemphasis of complete blood count results.

Multiple exclusions for relatively common scenarios represent missed opportunities for a more complete set of recommendations for the febrile infant population. The decision to exclude infants in the first week of life is perplexing since infants 0 to 7 days old will receive CSF analysis, require admission, and generally be managed comparably to infants 8 to 21 days old. Infants with bronchiolitis are excluded; the absence of uniform guidance may perpetuate variability in management within and across institutions. Finally, exclusion of infants in whom perinatal or congenital herpes simplex virus is a consideration is not ideal. The requirement to consult separate guidance for herpes simplex virus evaluation fragments decision-making and may lead to inadvertent omissions of critical tests or treatment in at-risk infants.

Methods in Preparing the Guideline

The guideline working group included stakeholders from multiple specialties including general pediatrics, emergency medicine, hospital medicine, infectious diseases, and family medicine. In addition to published studies, the committee considered an Agency for Healthcare Research and Quality commissioned systematic review, as well as analyses of additional data solicited from previously published peer-reviewed studies. Once recommendations were formulated, additional input from physician focus groups and parents was solicited. Recommendations were rated based on strength of available evidence (A, B, C, D, X) as well as assessment of the benefit/harm profile (strong, moderate, weak).

Sources of Potential Conflicts of Interest or Bias

The guideline writing group was predominantly male, though we note that the broader working group was diverse in gender and specialty. No significant conflicts of interest were noted.

Generalizability

The complexity of this guideline, including age stratification, multiple exclusions, and multistep processes could lead to challenges in implementation; a health information technology application (app) could substantially ease the difficulty of implementation at the point of care.

Additional areas in need of guidance include neonates with bronchiolitis and fever and neonates with focal infection. For the former, there is an abundance of evidence;⁴ what is needed is consensus. For the latter, additional study is needed such as the role of inflammatory markers in stratifying infants with focal infection who need additional evaluation prior to treatment.

Invasive bacterial infections (IBI; ie, bacterial meningitis, bacteremia) are an uncommon but potentially devastating occurrence in young febrile infants. The challenge for clinicians is that physical examination cannot reliably exclude such infections. Thus, these infants have historically received comprehensive emergency department evaluation, including routine cerebrospinal fluid (CSF) assessment, and, often, required hospitalization for parenteral antibiotic administration while awaiting CSF culture results. The new American Academy of Pediatrics (AAP) guidelines were necessary given changing bacteriology, advances in diagnostic testing, greater insight into the differential risk of poor outcomes by site of infection, and better appreciation of the potential harms of unnecessary care and interventions.¹ The 21 recommendations apply to well-appearing febrile infants 8 to 60 days of age, with recommendations stratified by age group, and exclude infants with certain conditions, including prematurity, focal bacterial infection, congenital or chromosomal abnormalities, and bronchiolitis. Four key recommendations are highlighted.

Recommendation 1: Diagnostic evaluation. For all age groups, blood culture and urinalysis (UA) are routinely recommended. For infants 8 to 21 days old, urine culture is routinely recommended. For older infants, urine culture is recommended if the UA is positive. All specimens for culture should be obtained via catheterization or suprapubic aspiration.

Infants 8 to 21 days old

• May assess inflammatory markers (grade B, weak).
• Should obtain CSF for analysis and culture (grade A, strong).

Infants 22 to 28 days old

• Should assess inflammatory markers (grade B, strong).
• May obtain CSF for analysis and culture even if no inflammatory marker obtained is abnormal (grade B, moderate).
• Should obtain CSF for analysis and culture if any inflammatory marker obtained is abnormal (procalcitonin >0.5 ng/mL [preferred]; C-reactive protein >20 mg/L; absolute neutrophil count >4000-5200/mm³; or temperature >38.5 °C) (grade B, moderate).

Infants 29 to 60 days old

• Should assess inflammatory markers (grade B, moderate).
• May obtain CSF for analysis and culture if any inflammatory marker is abnormal, (grade C, weak).
• Need not obtain CSF for analysis if all inflammatory markers obtained are normal (grade B, moderate).

Recommendation 2: Initial disposition decision

Infants 8 to 21 days old

• Admit (grade B, moderate).

Infants 22 to 28 days old

• Admit if CSF analysis is abnormal, UA is positive (A, strong), or if CSF is not obtained or is uninterpretable (grade B, weak).
• May manage at home if UA is normal, inflammatory markers are normal, CSF is normal or enterovirus positive, family has received verbal and written home monitoring instructions for concerning signs that should prompt immediate return for care, follow-up plan for reevaluation in 24 hours is in place, and means of communication for change in clinical status has been established (grade B, moderate).

Infants 29 to 60 days old

• Admit if CSF analysis is abnormal (grade A strong).
• May hospitalize if any inflammatory marker obtained is abnormal (grade B, moderate).
• Should manage at home if all the following are present: CSF is normal, if obtained; UA is negative; all inflammatory markers obtained are normal; teaching is complete; follow-up plan for reevaluation in 24 hours is in place; and means of communication for change in clinical status has been established (grade B, moderate).

Recommendation 3: Empiric antimicrobial treatment

Infants 8 to 21 days old

• Should initiate parenteral antimicrobial therapy (grade A, strong).
• This recommendation is based on the high prevalence of IBIs in this age category, and IBI may be present despite a negative UA and/or normal inflammatory markers.

Infants 22 to 28 days old

• Should initiate parenteral antimicrobial therapy if either CSF analysis suggests bacterial meningitis or UA is positive (grade A, strong).
• May administer parenteral antimicrobial therapy if any inflammatory marker is abnormal (grade B, moderate).
• May administer parenteral antimicrobial therapy even if everything is reassuring (grade B, weak).
• Should administer parenteral antimicrobial therapy to infant who will be managed at home even if all evaluation is reassuring (grade C, moderate).

Infants 29 to 60 days old

• Should start parenteral antimicrobials if CSF analysis suggests bacterial meningitis (grade A, strong).
• May use parenteral antimicrobials if any inflammatory marker is abnormal (grade B, moderate).
• Should initiate oral antimicrobial therapy if CSF is normal (if obtained), UA is positive, and no inflammatory markers obtained are abnormal (grade B, strong).
• Need not start antimicrobials if CSF is normal or enterovirus positive, UA is negative, and no inflammatory marker obtained is abnormal (grade B, moderate).

Recommendation 4: Hospital discharge decision

Infants 8 to 21 days old AND Infants 22 to 28 days ol

• Discontinue antibiotics and discharge infant when culture results are negative for 24 to 36 hours (or positive only for contaminants), the infant is well or improving, and there are no other reasons for hospitalization (grade B, strong).

Infants 29 to 60 days old

• Although no specific parameters are given for infants without UTI, presumably the discharge criteria for younger infants would also apply for this group.
• For infants with UTI, discharge if blood and CSF cultures are negative, infant is well or improving, and no other reasons for hospitalization remain (grade B, strong).

The guideline provides opportunities for safely doing less in a vulnerable population. For example, infants with UTIs may be managed differently (eg, often with oral antibiotics) from those with IBIs, which represents an important change from conventional practice.² Additional strengths are the incorporation of procalcitonin, which has emerged as the most accurate marker for risk stratification;³ and deemphasis of complete blood count results.

Multiple exclusions for relatively common scenarios represent missed opportunities for a more complete set of recommendations for the febrile infant population. The decision to exclude infants in the first week of life is perplexing since infants 0 to 7 days old will receive CSF analysis, require admission, and generally be managed comparably to infants 8 to 21 days old. Infants with bronchiolitis are excluded; the absence of uniform guidance may perpetuate variability in management within and across institutions. Finally, exclusion of infants in whom perinatal or congenital herpes simplex virus is a consideration is not ideal. The requirement to consult separate guidance for herpes simplex virus evaluation fragments decision-making and may lead to inadvertent omissions of critical tests or treatment in at-risk infants.

Methods in Preparing the Guideline

The guideline working group included stakeholders from multiple specialties including general pediatrics, emergency medicine, hospital medicine, infectious diseases, and family medicine. In addition to published studies, the committee considered an Agency for Healthcare Research and Quality commissioned systematic review, as well as analyses of additional data solicited from previously published peer-reviewed studies. Once recommendations were formulated, additional input from physician focus groups and parents was solicited. Recommendations were rated based on strength of available evidence (A, B, C, D, X) as well as assessment of the benefit/harm profile (strong, moderate, weak).

Sources of Potential Conflicts of Interest or Bias

The guideline writing group was predominantly male, though we note that the broader working group was diverse in gender and specialty. No significant conflicts of interest were noted.

Generalizability

The complexity of this guideline, including age stratification, multiple exclusions, and multistep processes could lead to challenges in implementation; a health information technology application (app) could substantially ease the difficulty of implementation at the point of care.

Additional areas in need of guidance include neonates with bronchiolitis and fever and neonates with focal infection. For the former, there is an abundance of evidence;⁴ what is needed is consensus. For the latter, additional study is needed such as the role of inflammatory markers in stratifying infants with focal infection who need additional evaluation prior to treatment.

The US Department of Veterans Affairs (VA) is the largest health care delivery system in the United States, comprising 1293 sites of care, including 171 medical centers.¹ One of the 4 statutory missions of the VA is to train health care professionals (HCPs) to meet the needs of the VA and the nation.² Through partnerships with more than 1800 accredited colleges, universities, and training programs, the VA provides training annually to nearly 118,000 health professions trainees (HPTs) across a variety of health care professions, and all of whom provide direct clinical care to veterans.³

In the VA, the Office of Academic Affiliations (OAA) is charged with overseeing health professions training and the VA’s partnership with medical and associated health (AH) professions schools, which was first codified in Policy Memorandum No. 2 in 1946.^4,5 Given the scope and breadth of health professions education offered through the VA, OAA is in a unique position to address health care shortage areas as well as influence the educational standards for certain professions.

Many of these health care professions fall under the rubric of AH, which include mental health (MH) specialties, rehabilitative specialties, and others. These professions are critical to address in the expanding world of health care in the United States with its increased specialization and emphasis on coordination of care with interprofessional teams. During the 2019/2020 academic year, the VA provided clinical training to approximately 21,000 AH HPTs from > 40 professions with just over 20% receiving financial support through the OAA. Of the HPTs who train at VA without compensation, most spend shorter amounts of time in clinical rotations in the VA, are in pregraduate-degree education programs where payment for clinical rotations is not expected and may not be eligible for hire immediately on completion of their clinical training experience. The 17 funded professions have been strategically selected by the OAA to ensure a robust pipeline of HCPs to meet the needs of veterans and the nation.

To meet the demands of AH professionals (AHPs), the OAA implemented targeted expansion over the past 10 years. While not exhaustive, this paper describes several expansion efforts based on VA special initiatives, including enhancing clinical access in rural settings and shifting toward postgraduate-degree training and specialization. By aligning expansion with VA priorities as well as trends in health care more broadly, the OAA can ensure that there is a supply of well-trained AHPs who have developed the requisite competencies to contribute to our nation’s health care needs. Further, expansion can help train and recruit health professionals who can be hired into VA positions ready to care for the complex needs of veterans.

Associated Health Professionals

Overseen by the OAA, AH expansion is designed to address the specific needs of the VA and the US health care system. Data from the VA Workforce Management and Consulting (WMC) shows that the VA employment of AHPs has grown from 87,351 AHPs hired in fiscal year (FY) 2010 to 119,120 as of April 2020. This represents an average yearly growth rate of 3.4% and a total growth rate of 36%. The Bureau of Labor Statistics predictions for 2019/2029 suggest that certain AHPs are expected to have a 10-year growth rates of 20% or more to meet the changing health care needs of patients especially as the population ages; the growth rates for many AHPs far surpasses that of physicians, which is anticipated to be 4% (Table).^6,7 The VA WMC expects an additional 52,283 AHPs will be hired by the VA by FY 2030 based on the 10-year average growth rate (Kali Clark, Veterans Health Administration Workforce Management and Consulting Office, email communication, May 28, 2020).

One of the driving forces behind the growth rate is the move toward using AHPs to supplement health care for a variety of health conditions.^8,9 Examples include the integration of rehabilitation professionals, alternative care professionals (eg, massage therapists, practitioners who offer training in yoga and meditation), chiropractors, MH professionals, and pharmacists in the treatment of chronic pain, the use of a wider range of professionals in the treatment of MH conditions, and the integration of MH professionals into traditional medical settings, such as primary care. This intentional move to a more well-integrated model of interprofessional care is apparent in many other health care systems throughout the United States. Within the VA, this shift may be most evident through the introduction of the Whole Health model of care. The Whole Health model of care uses an interprofessional team to assess and care for veterans, using a personalized health plan addressing medical and MH conditions as well as behavioral, social, or spiritual concerns.¹⁰ The Whole Health model of care provides veterans with access to a variety of health care services, including but not limited to MH services, spiritual interventions, exercise-based programs, yoga, meditation, and nutrition counseling.

The OAA and AH education division have focused expansion to meet the increased need for MH and rehabilitation providers, to enhance interprofessional education, and to emphasize postgraduate-degree clinical training. This focus reflects the trends seen in health care training broadly throughout the nation and the intentional pivot is a model of these trends and a model for how to intentionally address these trends. Specific to the VA, focused expansion plans have allowed OAA to address VA strategic initiatives such as pain management and caring for rural veterans.

Funded Training Positions

As a result of recent AH expansion efforts, there has been a 33% increase in stipend-funded positions during the past 10 years, a rate that directly corresponds with the growth of AHPs in the VA. Recent AH expansion efforts can contribute to a particularly positive impact in highly rural and underserved areas where recruiting providers remains challenging.

The OAA launched the Mental Health Education Expansion (MHEE) initiative in 2012, which has now added 782 funded training slots across 10 health professions, 8 of which are psychology, pharmacy, chaplaincy, professional MH counseling, marriage and family therapy (MFT), social work (SW), occupational therapy (OT), and physician assistant (PA). Through the MHEE initiative, the VA has established funded internships for licensed professional mental health counselors and marriage and family therapists, as these professions are targeted for expanding the overall MH workforce in the VA. The OAA currently funds more than 50 total HPT positions for these 2 professions with an aim of increasing their recruitment to the VA MH workforce over the next decade. The MHEE is aligned with specified VA priorities to train a future VA workforce prepared for interprofessional collaboration and clinical care in an increasingly integrated and complex environment. This expansion effort also aligns with an increasing understanding of the importance of addressing the MH needs of our nation by ensuring there is an adequate supply of competent, well-trained clinicians entering the workforce.

The OAA has created and expanded residencies and fellowships in multiple rehabilitation professions, including chiropractic, physical therapy (PT), and OT. With the increased focus on the management of chronic pain in the nation combined with a specific emphasis on this clinical need in the VA, chiropractors have been deemed essential HCPs. In 2014, the VA established 5 chiropractic residency programs while partnering with the Council on Chiropractic Education to develop accreditation standards for residency training. OAA’s efforts have yielded 5 accredited residency programs, the first in the United States. In 2020, the VA doubled the number of available chiropractic residency programs, and future expansion is anticipated. Since 2010, PT residencies have expanded from 1 to 28 programs (42 funded positions) across 4 board certification specialties: cardiovascular-pulmonary, geriatric, neurologic, and orthopedic. Similarly, the VA was one of the first organizations to achieve accreditation for OT fellowships; there are currently 5 accredited OT fellowship programs across 3 areas of practice: assistive technology, MH, and physical rehabilitation. The VA OT fellowship program focused on assistive technology is the only program in the United States at this time.

Interprofessional Education

As one of the primary focus areas for AH expansion, interprofessional education (IPE) has been recognized as increasingly important for the provision of health care and the development of HPT programs. IPE can develop professionals who appreciate the roles of diverse professions and can use teamwork to enhance clinical outcomes for patients.¹¹ There also are a growing number of professional organizations supporting the Interprofessional Education Collaborative with many representing AHPs.¹² Collaboration across HCPs is an important way of reducing health care costs by enhancing clinical outcomes, communication, and teamwork.^13-16 The VA and the nation’s health care system benefit from the by-products of interprofessional collaboration through investment in targeted training programs. In each phase of the AH expansion, special consideration was given to applicant programs offering unique and innovative clinical and educational experiences consistent with the promotion of interprofessional care. In doing so, increased numbers of AH HPTs have engaged in team-based clinical care.

Pain Management Pharmacy

The efforts of AH to align expansion with high-priority agency-wide efforts has resulted in the growth of pharmacy residency positions focused on pain management. Pharmacy postgraduate year (PGY) 2 residencies focusing on opioid reduction are an example of VA efforts to improve response to managing chronic pain and the long-term risks from opioid use during this national public health crisis.¹⁷ These residency programs focus on strategies to reduce the use of opioid medications in the clinical setting and teaching effective clinical interventions for reducing the rates of opioid addiction in veterans while still recognizing the need to identify and treat chronic pain. Before expansion efforts in 2018, there were 6 pharmacy residency programs focused on opioid use reduction in the VA, 8 pharmacy PGY2 residency positions were added in academic year 2019/2020, an additional 5 positions are being added in academic year 2021/2022 with the explicit goal of managing patients with high-risk chronic pain.

Rural Health

The lack of MH providers in rural areas has received much attention and is particularly important in the VA because veterans are more likely to live in less populated areas.¹⁸ The VA mandate to address this population was codified by the creation of the Office of Rural Health in 2006 via 38 USC § 7308.¹⁹Creating health professions training programs in rural settings provides HPTs the opportunity to learn professional competencies and train with faculty knowledgeable about this population—all of which provide a comprehensive training experience and serve as a recruitment pathway to hire HPTs into staff positions at these sites.¹⁹

When MHEE was initiated, not all regions of the country had funded VA psychology training programs, and this geographic gap in psychology training was a contributing factor to recruitment difficulties for psychologists in rural areas. As a result, the request for proposal process in the OAA highlighted and incentivized rurality when considering funding for new training programs. The OAA defined rurality as the number of patients served by the proposed health care facility who lived in a rural or highly rural zip code according to VA Support Service Center Capital Assets data.²⁰ As a result, VA psychology doctoral internships expanded to be available in all states, the District of Columbia, and Puerto Rico. MH training programs were started in the highly rural states of Montana and Wyoming. These expansion efforts promise to be an essential component to addressing the gaps in coverage in rural settings as noted in recent research.²¹

Pregraduate to Postgraduate Programs

The OAA AH education division supports a significant number of pregraduate-degree and postgraduate-degree training. Some professions, such as psychology, pharmacy, SW, PT, speech pathology, OT, and nutrition/dietetics receive funding at both levels of training. More recent, the OAA has started to move funding from pregraduate to postgraduate-degree positions, specifically within professions where pregraduate funding is uncommon for both federal and nonfederal training positions. The effort is designed to better align stipend-paid training programs with the VA Professional Qualification Standards and the final level of training required for employment in the VA.²²This means that HPTs receive stipend support during the highest level of their clinical training before degree conferral, eligibility for VA employment, or while participating in a postgraduate-degree residency or fellowship.

Additionally, this shift in focus and the resulting internal assessment of professions has allowed the OAA to fund more specialized training opportunities, which sometimes go beyond what is required by accrediting bodies or for recruitment into VA positions. For example, the OAA is supporting SW fellowship programs and PA residency positions to allow for greater specialization within these professions; the accrediting agencies for both professions have recently finalized their accreditation standards, and the OAA played a role in moving these standards forward.

While postgraduate residencies and fellowships are not required for all AH HPTs or for employment in the VA, there is a shift in some professions to encourage postgraduate training in advanced competencies in specialized areas. Participation in a residency or fellowship training program affords HPTs additional time and diverse clinical experiences to acquire clinical skills, all while under the supervision of a highly trained practitioner. This additional training also allows for a longitudinal assessment of the HPT to ensure an alignment of the HPTs’ knowledge, abilities, and skills with the expectation should they pursue VA employment.

In academic year 2019/2020, the OAA AH education division in conjunction with the PA national program office transitioned the entirety of the PA pregraduate-degree student positions (415 funded positions) to residency positions, increasing residency positions from 19 to 32 funded positions. This shift in emphasis for funding did not negatively impact the total number of pregraduate PA students receiving training in the VA and has created a pipeline of residency graduates who are ready to enter VA staff positions. To date, the VA has 14 PA residency programs across 3 specialties: emergency medicine (EM), MH, and primary care/geriatrics. Of these tracks, the VA offers 5 EM and 4 MH residencies that position graduates to be eligible for specialty certification. The National Commission on Certification of Physician Assistants established Certificates of Added Qualifications (CAQ) to recognize and document specialty knowledge, skills, and experience. The VA MH residency programs have been established to align with the CAQ expectations, and residents immediately qualify to take the CAQ examination after the completion of training.

Currently, the same process to move pregraduate to postgraduate funding is being implemented for PT and OT. Within the PT profession, there is increased momentum toward residency and fellowship training programs to respond to the changing complexity of the health care systemand reduce the need of complex care to be provided by non-VA providers in the community.²³ Both PT and OT have entered the initial phases of transitioning to residency or fellowship-funded positions. The OAA is partnering with these professions to move positions to postgraduate degree within the next 3 years with a commensurate increase in funding. The initial data indicate that 80% of graduated VA PT residents are board-certification eligible, and 89% of those who are eligible passed the examination on their first attempt.

Since 2013, the VA psychology training also has realized a growth in postgraduate-degree residencies. Psychology residency positions have increased 99% to 453 funded positions. This growth represents increased specialization in neuropsychology, geropsychology, rehabilitation psychology, and health psychology. Additionally, postgraduate residencies meet most jurisdictional requirements for postdoctoral supervised experience and better prepare HPTs to enter specialty staff positions that are necessary to care for aging veterans.

Additional professions are being targeted for postgraduate-degree training programs, including dietetics and speech pathology, to align with upcoming changes in the qualification standards for employment. While the process to transition positions to postgraduate-degree training programs can take 3 to 5 years, the outcomes are expected to result in better prepared HPTs who can fill staff vacancies in the VA.

Conclusions

Through its funding and oversight of numerous professions, the OAA is uniquely situated to adapt its portfolio to meet the needs of the VA and the nation. Over the past 10 years, the OAA has expanded its total number of HPT positions to enhance interprofessional care, respond to the VA’s strategic initiatives, address the care needs of rural veterans, and shift positions to postgraduate training programs. The OAA’s investment in high-quality training programs builds a strong health care workforce ready to meet the needs of an increasingly complex and integrated health care environment.

The OAA anticipates future expansion, especially related to promoting rural training opportunities and shifting to postgraduate training programs as a means of promoting advanced health care and health system competencies while continuing to align with workforce projections. Furthermore, while there are data on the percentage of VA staff who participated in OAA training program through the VA All Employee Survey (AES), the range for AH professions is wide. For example, about 37% of rehabilitative staff reported participating in an OAA training program, and 72% of VA psychologists reported having an OAA training experience. To maximize the hiring of HPTs, OAA will continue its partnership with WMC to enact programs aimed at streamlining the hiring process so that veterans have access to HCPs who are specifically trained to work with them.

The US Department of Veterans Affairs (VA) is the largest health care delivery system in the United States, comprising 1293 sites of care, including 171 medical centers.¹ One of the 4 statutory missions of the VA is to train health care professionals (HCPs) to meet the needs of the VA and the nation.² Through partnerships with more than 1800 accredited colleges, universities, and training programs, the VA provides training annually to nearly 118,000 health professions trainees (HPTs) across a variety of health care professions, and all of whom provide direct clinical care to veterans.³

In the VA, the Office of Academic Affiliations (OAA) is charged with overseeing health professions training and the VA’s partnership with medical and associated health (AH) professions schools, which was first codified in Policy Memorandum No. 2 in 1946.^4,5 Given the scope and breadth of health professions education offered through the VA, OAA is in a unique position to address health care shortage areas as well as influence the educational standards for certain professions.

Many of these health care professions fall under the rubric of AH, which include mental health (MH) specialties, rehabilitative specialties, and others. These professions are critical to address in the expanding world of health care in the United States with its increased specialization and emphasis on coordination of care with interprofessional teams. During the 2019/2020 academic year, the VA provided clinical training to approximately 21,000 AH HPTs from > 40 professions with just over 20% receiving financial support through the OAA. Of the HPTs who train at VA without compensation, most spend shorter amounts of time in clinical rotations in the VA, are in pregraduate-degree education programs where payment for clinical rotations is not expected and may not be eligible for hire immediately on completion of their clinical training experience. The 17 funded professions have been strategically selected by the OAA to ensure a robust pipeline of HCPs to meet the needs of veterans and the nation.

To meet the demands of AH professionals (AHPs), the OAA implemented targeted expansion over the past 10 years. While not exhaustive, this paper describes several expansion efforts based on VA special initiatives, including enhancing clinical access in rural settings and shifting toward postgraduate-degree training and specialization. By aligning expansion with VA priorities as well as trends in health care more broadly, the OAA can ensure that there is a supply of well-trained AHPs who have developed the requisite competencies to contribute to our nation’s health care needs. Further, expansion can help train and recruit health professionals who can be hired into VA positions ready to care for the complex needs of veterans.

Associated Health Professionals

Overseen by the OAA, AH expansion is designed to address the specific needs of the VA and the US health care system. Data from the VA Workforce Management and Consulting (WMC) shows that the VA employment of AHPs has grown from 87,351 AHPs hired in fiscal year (FY) 2010 to 119,120 as of April 2020. This represents an average yearly growth rate of 3.4% and a total growth rate of 36%. The Bureau of Labor Statistics predictions for 2019/2029 suggest that certain AHPs are expected to have a 10-year growth rates of 20% or more to meet the changing health care needs of patients especially as the population ages; the growth rates for many AHPs far surpasses that of physicians, which is anticipated to be 4% (Table).^6,7 The VA WMC expects an additional 52,283 AHPs will be hired by the VA by FY 2030 based on the 10-year average growth rate (Kali Clark, Veterans Health Administration Workforce Management and Consulting Office, email communication, May 28, 2020).

One of the driving forces behind the growth rate is the move toward using AHPs to supplement health care for a variety of health conditions.^8,9 Examples include the integration of rehabilitation professionals, alternative care professionals (eg, massage therapists, practitioners who offer training in yoga and meditation), chiropractors, MH professionals, and pharmacists in the treatment of chronic pain, the use of a wider range of professionals in the treatment of MH conditions, and the integration of MH professionals into traditional medical settings, such as primary care. This intentional move to a more well-integrated model of interprofessional care is apparent in many other health care systems throughout the United States. Within the VA, this shift may be most evident through the introduction of the Whole Health model of care. The Whole Health model of care uses an interprofessional team to assess and care for veterans, using a personalized health plan addressing medical and MH conditions as well as behavioral, social, or spiritual concerns.¹⁰ The Whole Health model of care provides veterans with access to a variety of health care services, including but not limited to MH services, spiritual interventions, exercise-based programs, yoga, meditation, and nutrition counseling.

The OAA and AH education division have focused expansion to meet the increased need for MH and rehabilitation providers, to enhance interprofessional education, and to emphasize postgraduate-degree clinical training. This focus reflects the trends seen in health care training broadly throughout the nation and the intentional pivot is a model of these trends and a model for how to intentionally address these trends. Specific to the VA, focused expansion plans have allowed OAA to address VA strategic initiatives such as pain management and caring for rural veterans.

Funded Training Positions

As a result of recent AH expansion efforts, there has been a 33% increase in stipend-funded positions during the past 10 years, a rate that directly corresponds with the growth of AHPs in the VA. Recent AH expansion efforts can contribute to a particularly positive impact in highly rural and underserved areas where recruiting providers remains challenging.

The OAA launched the Mental Health Education Expansion (MHEE) initiative in 2012, which has now added 782 funded training slots across 10 health professions, 8 of which are psychology, pharmacy, chaplaincy, professional MH counseling, marriage and family therapy (MFT), social work (SW), occupational therapy (OT), and physician assistant (PA). Through the MHEE initiative, the VA has established funded internships for licensed professional mental health counselors and marriage and family therapists, as these professions are targeted for expanding the overall MH workforce in the VA. The OAA currently funds more than 50 total HPT positions for these 2 professions with an aim of increasing their recruitment to the VA MH workforce over the next decade. The MHEE is aligned with specified VA priorities to train a future VA workforce prepared for interprofessional collaboration and clinical care in an increasingly integrated and complex environment. This expansion effort also aligns with an increasing understanding of the importance of addressing the MH needs of our nation by ensuring there is an adequate supply of competent, well-trained clinicians entering the workforce.

The OAA has created and expanded residencies and fellowships in multiple rehabilitation professions, including chiropractic, physical therapy (PT), and OT. With the increased focus on the management of chronic pain in the nation combined with a specific emphasis on this clinical need in the VA, chiropractors have been deemed essential HCPs. In 2014, the VA established 5 chiropractic residency programs while partnering with the Council on Chiropractic Education to develop accreditation standards for residency training. OAA’s efforts have yielded 5 accredited residency programs, the first in the United States. In 2020, the VA doubled the number of available chiropractic residency programs, and future expansion is anticipated. Since 2010, PT residencies have expanded from 1 to 28 programs (42 funded positions) across 4 board certification specialties: cardiovascular-pulmonary, geriatric, neurologic, and orthopedic. Similarly, the VA was one of the first organizations to achieve accreditation for OT fellowships; there are currently 5 accredited OT fellowship programs across 3 areas of practice: assistive technology, MH, and physical rehabilitation. The VA OT fellowship program focused on assistive technology is the only program in the United States at this time.

Interprofessional Education

As one of the primary focus areas for AH expansion, interprofessional education (IPE) has been recognized as increasingly important for the provision of health care and the development of HPT programs. IPE can develop professionals who appreciate the roles of diverse professions and can use teamwork to enhance clinical outcomes for patients.¹¹ There also are a growing number of professional organizations supporting the Interprofessional Education Collaborative with many representing AHPs.¹² Collaboration across HCPs is an important way of reducing health care costs by enhancing clinical outcomes, communication, and teamwork.^13-16 The VA and the nation’s health care system benefit from the by-products of interprofessional collaboration through investment in targeted training programs. In each phase of the AH expansion, special consideration was given to applicant programs offering unique and innovative clinical and educational experiences consistent with the promotion of interprofessional care. In doing so, increased numbers of AH HPTs have engaged in team-based clinical care.

Pain Management Pharmacy

The efforts of AH to align expansion with high-priority agency-wide efforts has resulted in the growth of pharmacy residency positions focused on pain management. Pharmacy postgraduate year (PGY) 2 residencies focusing on opioid reduction are an example of VA efforts to improve response to managing chronic pain and the long-term risks from opioid use during this national public health crisis.¹⁷ These residency programs focus on strategies to reduce the use of opioid medications in the clinical setting and teaching effective clinical interventions for reducing the rates of opioid addiction in veterans while still recognizing the need to identify and treat chronic pain. Before expansion efforts in 2018, there were 6 pharmacy residency programs focused on opioid use reduction in the VA, 8 pharmacy PGY2 residency positions were added in academic year 2019/2020, an additional 5 positions are being added in academic year 2021/2022 with the explicit goal of managing patients with high-risk chronic pain.

Rural Health

The lack of MH providers in rural areas has received much attention and is particularly important in the VA because veterans are more likely to live in less populated areas.¹⁸ The VA mandate to address this population was codified by the creation of the Office of Rural Health in 2006 via 38 USC § 7308.¹⁹Creating health professions training programs in rural settings provides HPTs the opportunity to learn professional competencies and train with faculty knowledgeable about this population—all of which provide a comprehensive training experience and serve as a recruitment pathway to hire HPTs into staff positions at these sites.¹⁹

When MHEE was initiated, not all regions of the country had funded VA psychology training programs, and this geographic gap in psychology training was a contributing factor to recruitment difficulties for psychologists in rural areas. As a result, the request for proposal process in the OAA highlighted and incentivized rurality when considering funding for new training programs. The OAA defined rurality as the number of patients served by the proposed health care facility who lived in a rural or highly rural zip code according to VA Support Service Center Capital Assets data.²⁰ As a result, VA psychology doctoral internships expanded to be available in all states, the District of Columbia, and Puerto Rico. MH training programs were started in the highly rural states of Montana and Wyoming. These expansion efforts promise to be an essential component to addressing the gaps in coverage in rural settings as noted in recent research.²¹

Pregraduate to Postgraduate Programs

The OAA AH education division supports a significant number of pregraduate-degree and postgraduate-degree training. Some professions, such as psychology, pharmacy, SW, PT, speech pathology, OT, and nutrition/dietetics receive funding at both levels of training. More recent, the OAA has started to move funding from pregraduate to postgraduate-degree positions, specifically within professions where pregraduate funding is uncommon for both federal and nonfederal training positions. The effort is designed to better align stipend-paid training programs with the VA Professional Qualification Standards and the final level of training required for employment in the VA.²²This means that HPTs receive stipend support during the highest level of their clinical training before degree conferral, eligibility for VA employment, or while participating in a postgraduate-degree residency or fellowship.

Additionally, this shift in focus and the resulting internal assessment of professions has allowed the OAA to fund more specialized training opportunities, which sometimes go beyond what is required by accrediting bodies or for recruitment into VA positions. For example, the OAA is supporting SW fellowship programs and PA residency positions to allow for greater specialization within these professions; the accrediting agencies for both professions have recently finalized their accreditation standards, and the OAA played a role in moving these standards forward.

While postgraduate residencies and fellowships are not required for all AH HPTs or for employment in the VA, there is a shift in some professions to encourage postgraduate training in advanced competencies in specialized areas. Participation in a residency or fellowship training program affords HPTs additional time and diverse clinical experiences to acquire clinical skills, all while under the supervision of a highly trained practitioner. This additional training also allows for a longitudinal assessment of the HPT to ensure an alignment of the HPTs’ knowledge, abilities, and skills with the expectation should they pursue VA employment.

In academic year 2019/2020, the OAA AH education division in conjunction with the PA national program office transitioned the entirety of the PA pregraduate-degree student positions (415 funded positions) to residency positions, increasing residency positions from 19 to 32 funded positions. This shift in emphasis for funding did not negatively impact the total number of pregraduate PA students receiving training in the VA and has created a pipeline of residency graduates who are ready to enter VA staff positions. To date, the VA has 14 PA residency programs across 3 specialties: emergency medicine (EM), MH, and primary care/geriatrics. Of these tracks, the VA offers 5 EM and 4 MH residencies that position graduates to be eligible for specialty certification. The National Commission on Certification of Physician Assistants established Certificates of Added Qualifications (CAQ) to recognize and document specialty knowledge, skills, and experience. The VA MH residency programs have been established to align with the CAQ expectations, and residents immediately qualify to take the CAQ examination after the completion of training.

Currently, the same process to move pregraduate to postgraduate funding is being implemented for PT and OT. Within the PT profession, there is increased momentum toward residency and fellowship training programs to respond to the changing complexity of the health care systemand reduce the need of complex care to be provided by non-VA providers in the community.²³ Both PT and OT have entered the initial phases of transitioning to residency or fellowship-funded positions. The OAA is partnering with these professions to move positions to postgraduate degree within the next 3 years with a commensurate increase in funding. The initial data indicate that 80% of graduated VA PT residents are board-certification eligible, and 89% of those who are eligible passed the examination on their first attempt.

Since 2013, the VA psychology training also has realized a growth in postgraduate-degree residencies. Psychology residency positions have increased 99% to 453 funded positions. This growth represents increased specialization in neuropsychology, geropsychology, rehabilitation psychology, and health psychology. Additionally, postgraduate residencies meet most jurisdictional requirements for postdoctoral supervised experience and better prepare HPTs to enter specialty staff positions that are necessary to care for aging veterans.

Additional professions are being targeted for postgraduate-degree training programs, including dietetics and speech pathology, to align with upcoming changes in the qualification standards for employment. While the process to transition positions to postgraduate-degree training programs can take 3 to 5 years, the outcomes are expected to result in better prepared HPTs who can fill staff vacancies in the VA.

Conclusions

Through its funding and oversight of numerous professions, the OAA is uniquely situated to adapt its portfolio to meet the needs of the VA and the nation. Over the past 10 years, the OAA has expanded its total number of HPT positions to enhance interprofessional care, respond to the VA’s strategic initiatives, address the care needs of rural veterans, and shift positions to postgraduate training programs. The OAA’s investment in high-quality training programs builds a strong health care workforce ready to meet the needs of an increasingly complex and integrated health care environment.

The OAA anticipates future expansion, especially related to promoting rural training opportunities and shifting to postgraduate training programs as a means of promoting advanced health care and health system competencies while continuing to align with workforce projections. Furthermore, while there are data on the percentage of VA staff who participated in OAA training program through the VA All Employee Survey (AES), the range for AH professions is wide. For example, about 37% of rehabilitative staff reported participating in an OAA training program, and 72% of VA psychologists reported having an OAA training experience. To maximize the hiring of HPTs, OAA will continue its partnership with WMC to enact programs aimed at streamlining the hiring process so that veterans have access to HCPs who are specifically trained to work with them.

The US Department of Veterans Affairs (VA) is the largest health care delivery system in the United States, comprising 1293 sites of care, including 171 medical centers.¹ One of the 4 statutory missions of the VA is to train health care professionals (HCPs) to meet the needs of the VA and the nation.² Through partnerships with more than 1800 accredited colleges, universities, and training programs, the VA provides training annually to nearly 118,000 health professions trainees (HPTs) across a variety of health care professions, and all of whom provide direct clinical care to veterans.³

In the VA, the Office of Academic Affiliations (OAA) is charged with overseeing health professions training and the VA’s partnership with medical and associated health (AH) professions schools, which was first codified in Policy Memorandum No. 2 in 1946.^4,5 Given the scope and breadth of health professions education offered through the VA, OAA is in a unique position to address health care shortage areas as well as influence the educational standards for certain professions.

Many of these health care professions fall under the rubric of AH, which include mental health (MH) specialties, rehabilitative specialties, and others. These professions are critical to address in the expanding world of health care in the United States with its increased specialization and emphasis on coordination of care with interprofessional teams. During the 2019/2020 academic year, the VA provided clinical training to approximately 21,000 AH HPTs from > 40 professions with just over 20% receiving financial support through the OAA. Of the HPTs who train at VA without compensation, most spend shorter amounts of time in clinical rotations in the VA, are in pregraduate-degree education programs where payment for clinical rotations is not expected and may not be eligible for hire immediately on completion of their clinical training experience. The 17 funded professions have been strategically selected by the OAA to ensure a robust pipeline of HCPs to meet the needs of veterans and the nation.

To meet the demands of AH professionals (AHPs), the OAA implemented targeted expansion over the past 10 years. While not exhaustive, this paper describes several expansion efforts based on VA special initiatives, including enhancing clinical access in rural settings and shifting toward postgraduate-degree training and specialization. By aligning expansion with VA priorities as well as trends in health care more broadly, the OAA can ensure that there is a supply of well-trained AHPs who have developed the requisite competencies to contribute to our nation’s health care needs. Further, expansion can help train and recruit health professionals who can be hired into VA positions ready to care for the complex needs of veterans.

Associated Health Professionals

Overseen by the OAA, AH expansion is designed to address the specific needs of the VA and the US health care system. Data from the VA Workforce Management and Consulting (WMC) shows that the VA employment of AHPs has grown from 87,351 AHPs hired in fiscal year (FY) 2010 to 119,120 as of April 2020. This represents an average yearly growth rate of 3.4% and a total growth rate of 36%. The Bureau of Labor Statistics predictions for 2019/2029 suggest that certain AHPs are expected to have a 10-year growth rates of 20% or more to meet the changing health care needs of patients especially as the population ages; the growth rates for many AHPs far surpasses that of physicians, which is anticipated to be 4% (Table).^6,7 The VA WMC expects an additional 52,283 AHPs will be hired by the VA by FY 2030 based on the 10-year average growth rate (Kali Clark, Veterans Health Administration Workforce Management and Consulting Office, email communication, May 28, 2020).

One of the driving forces behind the growth rate is the move toward using AHPs to supplement health care for a variety of health conditions.^8,9 Examples include the integration of rehabilitation professionals, alternative care professionals (eg, massage therapists, practitioners who offer training in yoga and meditation), chiropractors, MH professionals, and pharmacists in the treatment of chronic pain, the use of a wider range of professionals in the treatment of MH conditions, and the integration of MH professionals into traditional medical settings, such as primary care. This intentional move to a more well-integrated model of interprofessional care is apparent in many other health care systems throughout the United States. Within the VA, this shift may be most evident through the introduction of the Whole Health model of care. The Whole Health model of care uses an interprofessional team to assess and care for veterans, using a personalized health plan addressing medical and MH conditions as well as behavioral, social, or spiritual concerns.¹⁰ The Whole Health model of care provides veterans with access to a variety of health care services, including but not limited to MH services, spiritual interventions, exercise-based programs, yoga, meditation, and nutrition counseling.

The OAA and AH education division have focused expansion to meet the increased need for MH and rehabilitation providers, to enhance interprofessional education, and to emphasize postgraduate-degree clinical training. This focus reflects the trends seen in health care training broadly throughout the nation and the intentional pivot is a model of these trends and a model for how to intentionally address these trends. Specific to the VA, focused expansion plans have allowed OAA to address VA strategic initiatives such as pain management and caring for rural veterans.

Funded Training Positions

As a result of recent AH expansion efforts, there has been a 33% increase in stipend-funded positions during the past 10 years, a rate that directly corresponds with the growth of AHPs in the VA. Recent AH expansion efforts can contribute to a particularly positive impact in highly rural and underserved areas where recruiting providers remains challenging.

The OAA launched the Mental Health Education Expansion (MHEE) initiative in 2012, which has now added 782 funded training slots across 10 health professions, 8 of which are psychology, pharmacy, chaplaincy, professional MH counseling, marriage and family therapy (MFT), social work (SW), occupational therapy (OT), and physician assistant (PA). Through the MHEE initiative, the VA has established funded internships for licensed professional mental health counselors and marriage and family therapists, as these professions are targeted for expanding the overall MH workforce in the VA. The OAA currently funds more than 50 total HPT positions for these 2 professions with an aim of increasing their recruitment to the VA MH workforce over the next decade. The MHEE is aligned with specified VA priorities to train a future VA workforce prepared for interprofessional collaboration and clinical care in an increasingly integrated and complex environment. This expansion effort also aligns with an increasing understanding of the importance of addressing the MH needs of our nation by ensuring there is an adequate supply of competent, well-trained clinicians entering the workforce.

The OAA has created and expanded residencies and fellowships in multiple rehabilitation professions, including chiropractic, physical therapy (PT), and OT. With the increased focus on the management of chronic pain in the nation combined with a specific emphasis on this clinical need in the VA, chiropractors have been deemed essential HCPs. In 2014, the VA established 5 chiropractic residency programs while partnering with the Council on Chiropractic Education to develop accreditation standards for residency training. OAA’s efforts have yielded 5 accredited residency programs, the first in the United States. In 2020, the VA doubled the number of available chiropractic residency programs, and future expansion is anticipated. Since 2010, PT residencies have expanded from 1 to 28 programs (42 funded positions) across 4 board certification specialties: cardiovascular-pulmonary, geriatric, neurologic, and orthopedic. Similarly, the VA was one of the first organizations to achieve accreditation for OT fellowships; there are currently 5 accredited OT fellowship programs across 3 areas of practice: assistive technology, MH, and physical rehabilitation. The VA OT fellowship program focused on assistive technology is the only program in the United States at this time.

Interprofessional Education

As one of the primary focus areas for AH expansion, interprofessional education (IPE) has been recognized as increasingly important for the provision of health care and the development of HPT programs. IPE can develop professionals who appreciate the roles of diverse professions and can use teamwork to enhance clinical outcomes for patients.¹¹ There also are a growing number of professional organizations supporting the Interprofessional Education Collaborative with many representing AHPs.¹² Collaboration across HCPs is an important way of reducing health care costs by enhancing clinical outcomes, communication, and teamwork.^13-16 The VA and the nation’s health care system benefit from the by-products of interprofessional collaboration through investment in targeted training programs. In each phase of the AH expansion, special consideration was given to applicant programs offering unique and innovative clinical and educational experiences consistent with the promotion of interprofessional care. In doing so, increased numbers of AH HPTs have engaged in team-based clinical care.

Pain Management Pharmacy

The efforts of AH to align expansion with high-priority agency-wide efforts has resulted in the growth of pharmacy residency positions focused on pain management. Pharmacy postgraduate year (PGY) 2 residencies focusing on opioid reduction are an example of VA efforts to improve response to managing chronic pain and the long-term risks from opioid use during this national public health crisis.¹⁷ These residency programs focus on strategies to reduce the use of opioid medications in the clinical setting and teaching effective clinical interventions for reducing the rates of opioid addiction in veterans while still recognizing the need to identify and treat chronic pain. Before expansion efforts in 2018, there were 6 pharmacy residency programs focused on opioid use reduction in the VA, 8 pharmacy PGY2 residency positions were added in academic year 2019/2020, an additional 5 positions are being added in academic year 2021/2022 with the explicit goal of managing patients with high-risk chronic pain.

Rural Health

The lack of MH providers in rural areas has received much attention and is particularly important in the VA because veterans are more likely to live in less populated areas.¹⁸ The VA mandate to address this population was codified by the creation of the Office of Rural Health in 2006 via 38 USC § 7308.¹⁹Creating health professions training programs in rural settings provides HPTs the opportunity to learn professional competencies and train with faculty knowledgeable about this population—all of which provide a comprehensive training experience and serve as a recruitment pathway to hire HPTs into staff positions at these sites.¹⁹

When MHEE was initiated, not all regions of the country had funded VA psychology training programs, and this geographic gap in psychology training was a contributing factor to recruitment difficulties for psychologists in rural areas. As a result, the request for proposal process in the OAA highlighted and incentivized rurality when considering funding for new training programs. The OAA defined rurality as the number of patients served by the proposed health care facility who lived in a rural or highly rural zip code according to VA Support Service Center Capital Assets data.²⁰ As a result, VA psychology doctoral internships expanded to be available in all states, the District of Columbia, and Puerto Rico. MH training programs were started in the highly rural states of Montana and Wyoming. These expansion efforts promise to be an essential component to addressing the gaps in coverage in rural settings as noted in recent research.²¹

Pregraduate to Postgraduate Programs

The OAA AH education division supports a significant number of pregraduate-degree and postgraduate-degree training. Some professions, such as psychology, pharmacy, SW, PT, speech pathology, OT, and nutrition/dietetics receive funding at both levels of training. More recent, the OAA has started to move funding from pregraduate to postgraduate-degree positions, specifically within professions where pregraduate funding is uncommon for both federal and nonfederal training positions. The effort is designed to better align stipend-paid training programs with the VA Professional Qualification Standards and the final level of training required for employment in the VA.²²This means that HPTs receive stipend support during the highest level of their clinical training before degree conferral, eligibility for VA employment, or while participating in a postgraduate-degree residency or fellowship.

Additionally, this shift in focus and the resulting internal assessment of professions has allowed the OAA to fund more specialized training opportunities, which sometimes go beyond what is required by accrediting bodies or for recruitment into VA positions. For example, the OAA is supporting SW fellowship programs and PA residency positions to allow for greater specialization within these professions; the accrediting agencies for both professions have recently finalized their accreditation standards, and the OAA played a role in moving these standards forward.

While postgraduate residencies and fellowships are not required for all AH HPTs or for employment in the VA, there is a shift in some professions to encourage postgraduate training in advanced competencies in specialized areas. Participation in a residency or fellowship training program affords HPTs additional time and diverse clinical experiences to acquire clinical skills, all while under the supervision of a highly trained practitioner. This additional training also allows for a longitudinal assessment of the HPT to ensure an alignment of the HPTs’ knowledge, abilities, and skills with the expectation should they pursue VA employment.

In academic year 2019/2020, the OAA AH education division in conjunction with the PA national program office transitioned the entirety of the PA pregraduate-degree student positions (415 funded positions) to residency positions, increasing residency positions from 19 to 32 funded positions. This shift in emphasis for funding did not negatively impact the total number of pregraduate PA students receiving training in the VA and has created a pipeline of residency graduates who are ready to enter VA staff positions. To date, the VA has 14 PA residency programs across 3 specialties: emergency medicine (EM), MH, and primary care/geriatrics. Of these tracks, the VA offers 5 EM and 4 MH residencies that position graduates to be eligible for specialty certification. The National Commission on Certification of Physician Assistants established Certificates of Added Qualifications (CAQ) to recognize and document specialty knowledge, skills, and experience. The VA MH residency programs have been established to align with the CAQ expectations, and residents immediately qualify to take the CAQ examination after the completion of training.

Currently, the same process to move pregraduate to postgraduate funding is being implemented for PT and OT. Within the PT profession, there is increased momentum toward residency and fellowship training programs to respond to the changing complexity of the health care systemand reduce the need of complex care to be provided by non-VA providers in the community.²³ Both PT and OT have entered the initial phases of transitioning to residency or fellowship-funded positions. The OAA is partnering with these professions to move positions to postgraduate degree within the next 3 years with a commensurate increase in funding. The initial data indicate that 80% of graduated VA PT residents are board-certification eligible, and 89% of those who are eligible passed the examination on their first attempt.

Since 2013, the VA psychology training also has realized a growth in postgraduate-degree residencies. Psychology residency positions have increased 99% to 453 funded positions. This growth represents increased specialization in neuropsychology, geropsychology, rehabilitation psychology, and health psychology. Additionally, postgraduate residencies meet most jurisdictional requirements for postdoctoral supervised experience and better prepare HPTs to enter specialty staff positions that are necessary to care for aging veterans.

Additional professions are being targeted for postgraduate-degree training programs, including dietetics and speech pathology, to align with upcoming changes in the qualification standards for employment. While the process to transition positions to postgraduate-degree training programs can take 3 to 5 years, the outcomes are expected to result in better prepared HPTs who can fill staff vacancies in the VA.

Conclusions

Through its funding and oversight of numerous professions, the OAA is uniquely situated to adapt its portfolio to meet the needs of the VA and the nation. Over the past 10 years, the OAA has expanded its total number of HPT positions to enhance interprofessional care, respond to the VA’s strategic initiatives, address the care needs of rural veterans, and shift positions to postgraduate training programs. The OAA’s investment in high-quality training programs builds a strong health care workforce ready to meet the needs of an increasingly complex and integrated health care environment.

The OAA anticipates future expansion, especially related to promoting rural training opportunities and shifting to postgraduate training programs as a means of promoting advanced health care and health system competencies while continuing to align with workforce projections. Furthermore, while there are data on the percentage of VA staff who participated in OAA training program through the VA All Employee Survey (AES), the range for AH professions is wide. For example, about 37% of rehabilitative staff reported participating in an OAA training program, and 72% of VA psychologists reported having an OAA training experience. To maximize the hiring of HPTs, OAA will continue its partnership with WMC to enact programs aimed at streamlining the hiring process so that veterans have access to HCPs who are specifically trained to work with them.

From the Department of Internal Medicine, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, New York, NY (Dr. Gandhi), and the School of Medicine, Seth Gordhandas Sunderdas Medical College, and King Edward Memorial Hospital, Mumbai, India (Drs. Gandhi and Tiwari).

Objective: Calculation of HEART score to (1) stratify patients as low-risk, intermediate-risk, high-risk, and to predict the short-term incidence of major adverse cardiovascular events (MACE), and (2) demonstrate feasibility of HEART score in our local settings.

Design: A prospective cohort study of patients with a chief complaint of chest pain concerning for acute coronary syndrome.

Setting: Participants were recruited from the emergency department (ED) of King Edward Memorial Hospital, a tertiary care academic medical center and a resource-limited setting in Mumbai, India.

Participants: We evaluated 141 patients aged 18 years and older presenting to the ED and stratified them using the HEART score. To assess patients’ progress, a follow-up phone call was made within 6 weeks after presentation to the ED.

Measurements: The primary outcomes were a risk stratification, 6-week occurrence of MACE, and performance of unscheduled revascularization or stress testing. The secondary outcomes were discharge or death.

Results: The 141 participants were stratified into low-risk, intermediate-risk, and high-risk groups: 67 (47.52%), 44 (31.21%), and 30 (21.28%), respectively. The 6-week incidence of MACE in each category was 1.49%, 18.18%, and 90%, respectively. An acute myocardial infarction was diagnosed in 24 patients (17.02%), 15 patients (10.64%) underwent percutaneous coronary intervention (PCI), and 4 patients (2.84%) underwent coronary artery bypass graft (CABG). Overall, 98.5% of low-risk patients and 93.33% of high-risk patients had an uneventful recovery following discharge; therefore, extrapolation based on results demonstrated reduced health care utilization. All the survey respondents found the HEART score to be feasible. The patient characteristics and risk profile of the patients with and without MACE demonstrated that: patients with MACE were older and had a higher proportion of males, hypertension, type 2 diabetes mellitus, smoking, hypercholesterolemia, prior history of PCI/CABG, and history of stroke.

Conclusion: The HEART score seems to be a useful tool for risk stratification and a reliable predictor of outcomes in chest pain patients and can therefore be used for triage.

Keywords: chest pain; emergency department; HEART score; acute coronary syndrome; major adverse cardiac events; myocardial infarction; revascularization.

Cardiovascular diseases (CVDs), especially coronary heart disease (CHD), have epidemic proportions worldwide. Globally, in 2012, CVD led to 17.5 million deaths,^1,2 with more than 75% of them occurring in developing countries. In contrast to developed countries, where mortality from CHD is rapidly declining, it is increasing in developing countries.^1,3 Current estimates from epidemiologic studies from various parts of India indicate the prevalence of CHD in India to be between 7% and 13% in urban populations and 2% and 7% in rural populations.⁴

Premature mortality in terms of years of life lost because of CVD in India increased by 59% over a 20-year span, from 23.2 million in 1990 to 37 million in 2010.⁵ Studies conducted in Mumbai (Mumbai Cohort Study) reported very high CVD mortality rates, approaching 500 per 100 000 for men and 250 per 100 000 for women.^6,7 However, to the best of our knowledge, in the Indian population, there are minimal data on utilization of a triage score, such as the HEART score, in chest pain patients in the emergency department (ED) in a resource-limited setting.

The most common reason for admitting patients to the ED is chest pain.⁸ There are various cardiac and noncardiac etiologies of chest pain presentation. Acute coronary syndrome (ACS) needs to be ruled out first in every patient presenting with chest pain. However, 80% of patients with ACS have no clear diagnostic features on presentation.⁹ The timely diagnosis and treatment of patients with ACS improves their prognosis. Therefore, clinicians tend to start each patient on ACS treatment to reduce the risk, which often leads to increased costs due to unnecessary, time-consuming diagnostic procedures that may place burdens on both the health care system and the patient.¹⁰

Several risk-stratifying tools have been developed in the last few years. Both the GRACE and TIMI risk scores have been designed for risk stratification of patients with proven ACS and not for the chest pain population at the ED.¹¹ Some of these tools are applicable to patients with all types of chest pain presenting to the ED, such as the Manchester Triage System. Other, more selective systems are devoted to the risk stratification of suspected ACS in the ED. One is the HEART score.¹²

The first study on the HEART score—an acronym that stands for History, Electrocardiogram, Age, Risk factors, and Troponin—was done by Backus et al, who proved that the HEART score is an easy, quick, and reliable predictor of outcomes in chest pain patients.¹⁰ The HEART score predicts the short-term incidence of major adverse cardiac events (MACE), which allows clinicians to stratify patients as low-risk, intermediate-risk, and high-risk and to guide their clinical decision-making accordingly. It was developed to provide clinicians with a simple, reliable predictor of cardiac risk on the basis of the lowest score of 0 (very low-risk) up to a score of 10 (very high-risk).

We studied the clinical performance of the HEART score in patients with chest pain, focusing on the efficacy and safety of rapidly identifying patients at risk of MACE. We aimed to determine (1) whether the HEART score is a reliable predictor of outcomes of chest pain patients presenting to the ED; (2) whether the score is feasible in our local settings; and (3) whether it describes the risk profile of patients with and without MACE.

Methods

Setting

Participants were recruited from the ED of King Edward Memorial Hospital, a municipal teaching hospital in Mumbai. The study institute is a tertiary care academic medical center located in Parel, Mumbai, Maharashtra, and is a resource-limited setting serving urban, suburban, and rural populations. Participants requiring urgent attention are first seen by a casualty officer and then referred to the emergency ward. Here, the physician on duty evaluates them and decides on admission to the various wards, like the general ward, medical intensive care unit (ICU), coronary care unit (CCU), etc. The specialist’s opinion may also be obtained before admission. Critically ill patients are initially admitted to the emergency ward and stabilized before being shifted to other areas of the hospital.

Participants

Patients aged 18 years and older presenting with symptoms of acute chest pain or suspected ACS were stratified by priority using the chest pain scoring system—the HEART score. Only patients presenting to the ED were eligible for the study. Informed consent from the patient or next of kin was mandatory for participation in the study.

Patients were determined ineligible for the following reasons: a clear cause for chest pain other than ACS (eg, trauma, diagnosed aortic dissection), persisting or recurrent chest pain caused by rheumatic diseases or cancer (a terminal illness), pregnancy, unable or unwilling to provide informed consent, or incomplete data.

Study design

We conducted a prospective observational study of patients arriving at the tertiary care hospital with a chief complaint of “chest pain” concerning for ACS. All participants provided witnessed written informed consent. Patients were screened over approximately a 3-month period, from July 2019 to October 2019, after acquiring approval from the Institutional Ethics Committee. Any patient who was admitted to the ED due to chest pain, prehospital referrals based on a physician’s suspicions of a heart condition, and previous medical treatment due to ischemic heart disease (IHD) was eligible. All patients were stratified by priority in our ED using the chest pain scoring system—the HEART score—and were followed up by phone within 6 weeks after presenting to the ED, to assess their progress.

We conducted our study to determine the importance of calculating the HEART score in each patient, which will help to correctly place them into low-, intermediate-, and high-risk groups for clinically important, irreversible adverse cardiac events and guide the clinical decision-making. Patients with low risk will avoid costly tests and hospital admissions, thus decreasing the cost of treatment and ensuring timely discharge from the ED. Patients with high risk will be treated immediately, to possibly prevent a life-threatening, ACS-related incident. Thus, the HEART score will serve as a quick and reliable predictor of outcomes in chest pain patients and help clinicians to make accurate diagnostic and therapeutic choices in uncertain situations.

HEART score

The total number of points for History, Electrocardiogram (ECG), Age, Risk factors, and Troponin was noted as the HEART score (Table 1).

For this study, the patient’s history and ECGs were interpreted by internal medicine attending physicians in the ED. The ECG taken in the emergency room was reviewed and classified, and a copy of the admission ECG was added to the file. The recommendation for patients with a HEART score in a particular range was evaluated. Notably, those with a score of 3 or lower led to a recommendation of reassurance and early discharge. Those with a HEART score in the intermediate range (4-6) were admitted to the hospital for further clinical observation and testing, whereas a high HEART score (7-10) led to admission for intensive monitoring and early intervention. In the analysis of HEART score data, we only used those patients having records for all 5 parameters, excluding patients without an ECG or troponin test.

Results

Myocardial infarction (MI) was defined based on Universal Definition of Myocardial Infarction.¹³ Coronary revascularization was defined as angioplasty with or without stent placement or coronary artery bypass surgery.¹⁴ Percutaneous coronary intervention (PCI) was defined as any therapeutic catheter intervention in the coronary arteries. Coronary artery bypass graft (CABG) surgery was defined as any cardiac surgery in which coronary arteries were operated on.

The primary outcomes in this study were the (1) risk stratification of chest pain patients into low-risk, intermediate-risk, and high-risk categories; (2) incidence of a MACE within 6 weeks of initial presentation. MACE consists of acute myocardial infarction (AMI), PCI, CABG, coronary angiography revealing procedurally correctable stenosis managed conservatively, and death due to any cause.

Our secondary outcomes were discharge or death due to any cause within 6 weeks after presentation.

Follow-up

Within 6 weeks after presentation to the ED, a follow-up phone call was placed to assess the patient’s progress. The follow-up focused on the endpoint of MACE, comprising all-cause death, MI, and revascularization. No patient was lost to follow-up.

Statistical analysis

We aimed to find a difference in the 6-week MACE between low-, intermediate-, and high-risk categories of the HEART score. The prevalence of CHD in India is 10%,⁴ and assuming an α of 0.05, we needed a sample of 141 patients from the ED patient population. Continuous variables were presented by mean (SD), and categorical variables as percentages. We used t test and the Mann-Whitney U test for comparison of means for continuous variables, χ² for categorical variables, and Fisher’s exact test for comparison of the categorical variables. Results with P < .05 were considered statistically significant.

We evaluated 141 patients presenting to the ED with chest pain concerning for ACS during the study period, from July 2019 to October 2019. Patients were 57.54 (13.13) years of age. The male to female distribution was 85 to 56. Other patient characteristics are shown in Table 2.

Primary outcomes

The risk stratification of the HEART score in chest pain patients and the incidence of 6-week MACE are outlined in Table 3 and Table 4, respectively.

The distribution of the HEART score’s 5 elements in the groups with or without MACE endpoints is shown in Table 5. Notice the significant differences between the groups. A follow-up phone call was made within 6 weeks after the presentation to the ED to assess the patient’s progress. The 6-week follow-up call data are included in Table 6.

Of 141 patients, 36 patients (25.53%) were diagnosed with MACE within 6 weeks of presentation. An AMI was diagnosed in 24 patients (17.02%). Coronary angiography was performed in 31 of 141 patients (21.99%), 15 patients (10.64%) underwent PCI, and 4 patients (2.84%) underwent CABG. The rest of the patients were treated with medications only.

Myocardial infarction—An AMI was diagnosed in 24 of the 141 patients (17.02%). Twenty-one of those already had positive markers on admission (apparently, these AMI had started before their arrival to the emergency room). One AMI occurred 2 days after admission in a 66-year-old male, and another occurred 10 days after discharge. A further AMI occurred 2 weeks after discharge. All 3 patients belonged to the intermediate-risk group.

Revascularization—Coronary angiography was performed in 31 of 141 patients (21.99%). Revascularization was performed in 19 patients (13.48%), of which 15 were PCIs (10.64%) and 4 were CABGs (2.84%).

Mortality—One patient died from the study population. He was a 72-year-old male who died 14 days after admission. He had a HEART score of 8.

Among the 67 low-risk patients:

• MACE: Coronary angiography was performed in 1 patient (1.49%). Among the 67 patients in the low-risk category, there was no cases of AMI or deaths. The remaining 66 patients (98.51%) had an uneventful recovery following discharge.
• General practitioner (GP) visits/readmissions following discharge: Two of 67 patients (2.99%) had GP visits following discharge, of which 1 was uneventful. The other patient, a 64-year-old male, was readmitted due to a recurrent history of chest pain and underwent coronary angiography.

Among the 44 intermediate-risk patients:

• MACE: Of the 7 of 44 patients (15.91%) who had coronary angiography, 3 patients (6.82%) had AMI, of which 1 occurred 2 days after admission in a 66-year-old male. Two patients had AMI following discharge. There were no deaths. Overall, 42 of 44 patients (95.55%) had an uneventful recovery following discharge.
• GP visits/readmissions following discharge: Three of 44 patients (6.82%) had repeated visits following discharge. One was a GP visit that was uneventful. The remaining 2 patients were diagnosed with AMI and readmitted following discharge. One AMI occurred 10 days after discharge in a patient with a HEART score of 6; another occurred 2 weeks after discharge in a patient with a HEART score of 5.

Among the 30 high-risk patients:

• MACE: Twenty-three of 30 patients (76.67%) underwent coronary angiography. One patient died 5 days after discharge. The patient had a HEART score of 8. Most patients however, had an uneventful recovery following discharge (28, 93.33%).
• GP visits/readmissions following discharge: Five of 30 patients (16.67%) had repeated visits following discharge. Two were uneventful. Two patients had a history of recurrent chest pain that resolved on Sorbitrate. One patient was readmitted 2 weeks following discharge due to a complication: a left ventricular clot was found. The patient had a HEART score of 10.

Secondary outcome—Overall, 140 of 141 patients were discharged. One patient died: a 72-year-old male with a HEART score of 8.

Feasibility—To determine the ease and feasibility of performing a HEART score in chest pain patients presenting to the ED, a survey was distributed to the internal medicine physicians in the ED. In the survey, the Likert scale was used to rate the ease of utilizing the HEART score and whether the physicians found it feasible to use it for risk stratification of their chest pain patients. A total of 12 of 15 respondents (80%) found it “easy” to use. Of the remaining 3 respondents, 2 (13.33%) rated the HEART score “very easy” to use, while 1 (6.66%) considered it “difficult” to work with. None of the respondents said that it was not feasible to perform a HEART score in the ED.

Risk factors for reaching an endpoint:

We compared risk profiles between the patient groups with and without an endpoint. The group of patients with MACE were older and had a higher proportion of males than the group of patients without MACE. Moreover, they also had a higher prevalence of hypertension, type 2 diabetes mellitus, smoking, hypercholesterolemia, prior history of PCI/CABG, and history of stroke. These also showed a significant association with MACE. Obesity was not included in our risk factors as we did not have data collected to measure body mass index. Results are represented in Table 7.

Discussion

Our study described a patient population presenting to an ED with chest pain as their primary complaint. The results of this prospective study confirm that the HEART score is an excellent system to triage chest pain patients. It provides the clinician with a reliable predictor of the outcome (MACE) after the patient’s arrival, based on available clinical data and in a resource-limited setting like ours.

Cardiovascular epidemiology studies indicate that this has become a significant public health problem in India.¹ Several risk scores for ACS have been published in European and American guidelines. However, in the Indian population, minimal data are available on utilization of such a triage score (HEART score) in chest pain patients in the ED in a resource-limited setting, to the best of our knowledge. In India, only 1 such study is reported,¹⁵ at the Sundaram Medical Foundation, a 170-bed community hospital in Chennai. In this study, 13 of 14 patients (92.86%) with a high HEART score had MACE, indicating a sensitivity of 92.86%; in the 44 patients with a low HEART score, 1 patient (2.22%) had MACE, indicating a specificity of 97.78%; and in the 28 patients with a moderate HEART score, 12 patients (42.86%) had MACE.  

In looking for the optimal risk-stratifying system for chest pain patients, we analyzed the HEART score. The first study on the HEART score was done Backus et al, proving that the HEART score is an easy, quick, and reliable predictor of outcomes in chest pain patients.¹⁰ The HEART score had good discriminatory power, too. The C statistic for the HEART score for ACS occurrence shows a value of 0.83. This signifies a good-to-excellent ability to stratify all-cause chest pain patients in the ED for their risk of MACE. The application of the HEART score to our patient population demonstrated that the majority of the patients belonged to the low-risk category, as reported in the first cohort study that applied the HEART score.⁸ The relationship between the HEART score category and occurrence of MACE within 6 weeks showed a curve with 3 different patterns, corresponding to the 3 risk categories defined in the literature.^11,12 The risk stratification of chest pain patients using the 3 categories (0-3, 4-6, 7-10) identified MACE with an incidence similar to the multicenter study of Backus et al,^10,11 but with a greater risk of MACE in the high-risk category (Figure).

Thus, our study confirmed the utility of the HEART score categories to predict the 6-week incidence of MACE. The sensitivity, specificity, and positive and negative predictive values for the established cut-off scores of 4 and 7 are shown in Table 8. The patients in the low-risk category, corresponding to a score < 4, had a very high negative predictive value, thus identifying a small-risk population. The patients in the high-risk category (score ≥ 7) showed a high positive predictive value, allowing the identification of a high-risk population, even in patients with more atypical presentations. Therefore, the HEART score may help clinicians to make accurate management choices by being a strong predictor of both event-free survival and potentially life-threatening cardiac events.^11,12

Our study tested the efficacy of the HEART score pathway in helping clinicians make smart diagnostic and therapeutic choices. It confirmed that the HEART score was accurate in predicting the short-term incidence of MACE, thus stratifying patients according to their risk severity. In our study, 67 of 141 patients (47.52%) had low-risk HEART scores, and we found the 6-week incidence of MACE to be 1.49%. We omitted the diagnostic and treatment evaluation for patients in the low-risk category and moved onto discharge. Overall, 66 of 67 patients (98.51%) in the low-risk category had an uneventful recovery following discharge. Only 2 of 67 these patients (2.99%) of patients had health care utilization following discharge. Therefore, extrapolation based on results demonstrates reduced health care utilization. Previous studies have shown similar results.^9,12,14,16 For instance, in a prospective study conducted in the Netherlands, low-risk patients representing 36.4% of the total were found to have a low MACE rate (1.7%).⁹ These low-risk patients were categorized as appropriate and safe for ED discharge without additional cardiac evaluation or inpatient admission.⁹ Another retrospective study in Portugal,¹² and one in Chennai, India,¹⁵ found the 6-week incidence of MACE to be 2.00% and 2.22%, respectively. The results of the first HEART Pathway Randomized Control Trial¹⁴ showed that the HEART score pathway reduces health care utilization (cardiac testing, hospitalization, and hospital length of stay). The study also showed that these gains occurred without any of the patients that were identified for early discharge, suffering from MACE at 30 days, or secondary increase in cardiac-related hospitalizations. Similar results were obtained by a randomized trial conducted in North Carolina¹⁷ that also demonstrated a reduction in objective cardiac testing, a doubling of the rate of early discharge from the ED, and a reduced length of stay by half a day. Another study using a modified HEART score also demonstrated that when low-risk patients are evaluated with cardiac testing, the likelihood for false positives is high.¹⁶ Hoffman et al also reported that patients randomized to coronary computed tomographic angiography (CCTA) received > 2.5 times more radiation exposure.¹⁶ Thus, low-risk patients may be safely discharged without the need for stress testing or CCTA.

In our study, 30 out of 141 patients (21.28%) had high-risk HEART scores (7-10), and we found the 6-week incidence of MACE to be 90%. Based on the pathway leading to inpatient admission and intensive treatment, 23 of 30 patients (76.67%) patients in our study underwent coronary angiography and further therapeutic treatment. In the high-risk category, 28 of 30 patients (93.33%) patients had an uneventful recovery following discharge. Previous studies have shown similar results. A retrospective study in Portugal showed that 76.9% of the high-risk patients had a 6-week incidence of MACE.¹² In a study in the Netherlands,⁹ 72.7% of high-risk patients had a 6-week incidence of MACE. Therefore, a HEART score of ≥ 7 in patients implies early aggressive treatment, including invasive strategies, when necessary, without noninvasive treatment preceding it.⁸

In terms of intermediate risk, in our study 44 of 141 patients (31.21%) patients had an intermediate-risk HEART score (4-6), and we found the 6-week incidence of MACE to be 18.18%. Based on the pathway, they were kept in the observation ward on admission. In our study, 7 of 44 patients (15.91%) underwent coronary angiography and further treatment; 42 of 44 patients (95.55%) had an uneventful recovery following discharge. In a prospective study in the Netherlands, 46.1% of patients with an intermediate score had a 6-week MACE incidence of 16.6%.¹⁰ Similarly, in another retrospective study in Portugal, the incidence of 6-week MACE in intermediate-risk patients (36.7%) was found to be 15.6%.¹² Therefore, in patients with a HEART score of 4-6 points, immediate discharge is not an option, as this figure indicates a risk of 18.18% for an adverse outcome. These patients should be admitted for clinical observation, treated as an ACS awaiting final diagnosis, and subjected to noninvasive investigations, such as repeated troponin. Using the HEART score as guidance in the treatment of chest pain patients will benefit patients on both sides of the spectrum.^11,12

Our sample presented a male predominance, a wide range of age, and a mean age similar to that of previous studies.^12.16 Some risk factors, we found, can increase significantly the odds of chest pain being of cardiovascular origin, such as male gender, smoking, hypertension, type 2 diabetes mellitus, and hypercholesterolemia. Other studies also reported similar findings.^8,12,16 Risk factors for premature CHD have been quantified in the case-control INTERHEART study.¹ In the INTERHEART study, 8 common risk factors explained > 90% of AMIs in South Asian and Indian patients. The risk factors include dyslipidemia, smoking or tobacco use, known hypertension, known diabetes, abdominal obesity, physical inactivity, low fruit and vegetable intake, and psychosocial stress.¹ Regarding the feasibility of treating physicians using the HEART score in the ED, we observed that, based on the Likert scale, 80% of survey respondents found it easy to use, and 100% found it feasible in the ED.

However, there were certain limitations to our study. It involved a single academic medical center and a small sample size, which limit generalizability of the findings. In addition, troponin levels are not calculated at our institution, as it is a resource-limited setting; therefore, we used a positive and negative as +2 and 0, respectively.

Conclusion

The HEART score provides the clinician with a quick and reliable predictor of outcome of patients with chest pain after arrival to the ED and can be used for triage. For patients with low HEART scores (0-3), short-term MACE can be excluded with greater than 98% certainty. In these patients, one may consider reserved treatment and discharge policies that may also reduce health care utilization. In patients with high HEART scores (7-10), the high risk of MACE (90%) may indicate early aggressive treatment, including invasive strategies, when necessary. Therefore, the HEART score may help clinicians make accurate management choices by being a strong predictor of both event-free survival and potentially life-threatening cardiac events. Age, gender, and cardiovascular risk factors may also be considered in the assessment of patients. This study confirmed the utility of the HEART score categories to predict the 6-week incidence of MACE.

Corresponding author: Smrati Bajpai Tiwari, MD, DNB, FAIMER, Department of Medicine, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Acharya Donde Marg, Parel, Mumbai 400 012, Maharashtra, India; [email protected].

Financial disclosures: None.

From the Department of Internal Medicine, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, New York, NY (Dr. Gandhi), and the School of Medicine, Seth Gordhandas Sunderdas Medical College, and King Edward Memorial Hospital, Mumbai, India (Drs. Gandhi and Tiwari).

Objective: Calculation of HEART score to (1) stratify patients as low-risk, intermediate-risk, high-risk, and to predict the short-term incidence of major adverse cardiovascular events (MACE), and (2) demonstrate feasibility of HEART score in our local settings.

Design: A prospective cohort study of patients with a chief complaint of chest pain concerning for acute coronary syndrome.

Setting: Participants were recruited from the emergency department (ED) of King Edward Memorial Hospital, a tertiary care academic medical center and a resource-limited setting in Mumbai, India.

Participants: We evaluated 141 patients aged 18 years and older presenting to the ED and stratified them using the HEART score. To assess patients’ progress, a follow-up phone call was made within 6 weeks after presentation to the ED.

Measurements: The primary outcomes were a risk stratification, 6-week occurrence of MACE, and performance of unscheduled revascularization or stress testing. The secondary outcomes were discharge or death.

Results: The 141 participants were stratified into low-risk, intermediate-risk, and high-risk groups: 67 (47.52%), 44 (31.21%), and 30 (21.28%), respectively. The 6-week incidence of MACE in each category was 1.49%, 18.18%, and 90%, respectively. An acute myocardial infarction was diagnosed in 24 patients (17.02%), 15 patients (10.64%) underwent percutaneous coronary intervention (PCI), and 4 patients (2.84%) underwent coronary artery bypass graft (CABG). Overall, 98.5% of low-risk patients and 93.33% of high-risk patients had an uneventful recovery following discharge; therefore, extrapolation based on results demonstrated reduced health care utilization. All the survey respondents found the HEART score to be feasible. The patient characteristics and risk profile of the patients with and without MACE demonstrated that: patients with MACE were older and had a higher proportion of males, hypertension, type 2 diabetes mellitus, smoking, hypercholesterolemia, prior history of PCI/CABG, and history of stroke.

Conclusion: The HEART score seems to be a useful tool for risk stratification and a reliable predictor of outcomes in chest pain patients and can therefore be used for triage.

Keywords: chest pain; emergency department; HEART score; acute coronary syndrome; major adverse cardiac events; myocardial infarction; revascularization.

Cardiovascular diseases (CVDs), especially coronary heart disease (CHD), have epidemic proportions worldwide. Globally, in 2012, CVD led to 17.5 million deaths,^1,2 with more than 75% of them occurring in developing countries. In contrast to developed countries, where mortality from CHD is rapidly declining, it is increasing in developing countries.^1,3 Current estimates from epidemiologic studies from various parts of India indicate the prevalence of CHD in India to be between 7% and 13% in urban populations and 2% and 7% in rural populations.⁴

Premature mortality in terms of years of life lost because of CVD in India increased by 59% over a 20-year span, from 23.2 million in 1990 to 37 million in 2010.⁵ Studies conducted in Mumbai (Mumbai Cohort Study) reported very high CVD mortality rates, approaching 500 per 100 000 for men and 250 per 100 000 for women.^6,7 However, to the best of our knowledge, in the Indian population, there are minimal data on utilization of a triage score, such as the HEART score, in chest pain patients in the emergency department (ED) in a resource-limited setting.

The most common reason for admitting patients to the ED is chest pain.⁸ There are various cardiac and noncardiac etiologies of chest pain presentation. Acute coronary syndrome (ACS) needs to be ruled out first in every patient presenting with chest pain. However, 80% of patients with ACS have no clear diagnostic features on presentation.⁹ The timely diagnosis and treatment of patients with ACS improves their prognosis. Therefore, clinicians tend to start each patient on ACS treatment to reduce the risk, which often leads to increased costs due to unnecessary, time-consuming diagnostic procedures that may place burdens on both the health care system and the patient.¹⁰

Several risk-stratifying tools have been developed in the last few years. Both the GRACE and TIMI risk scores have been designed for risk stratification of patients with proven ACS and not for the chest pain population at the ED.¹¹ Some of these tools are applicable to patients with all types of chest pain presenting to the ED, such as the Manchester Triage System. Other, more selective systems are devoted to the risk stratification of suspected ACS in the ED. One is the HEART score.¹²

The first study on the HEART score—an acronym that stands for History, Electrocardiogram, Age, Risk factors, and Troponin—was done by Backus et al, who proved that the HEART score is an easy, quick, and reliable predictor of outcomes in chest pain patients.¹⁰ The HEART score predicts the short-term incidence of major adverse cardiac events (MACE), which allows clinicians to stratify patients as low-risk, intermediate-risk, and high-risk and to guide their clinical decision-making accordingly. It was developed to provide clinicians with a simple, reliable predictor of cardiac risk on the basis of the lowest score of 0 (very low-risk) up to a score of 10 (very high-risk).

We studied the clinical performance of the HEART score in patients with chest pain, focusing on the efficacy and safety of rapidly identifying patients at risk of MACE. We aimed to determine (1) whether the HEART score is a reliable predictor of outcomes of chest pain patients presenting to the ED; (2) whether the score is feasible in our local settings; and (3) whether it describes the risk profile of patients with and without MACE.

Methods

Setting

Participants were recruited from the ED of King Edward Memorial Hospital, a municipal teaching hospital in Mumbai. The study institute is a tertiary care academic medical center located in Parel, Mumbai, Maharashtra, and is a resource-limited setting serving urban, suburban, and rural populations. Participants requiring urgent attention are first seen by a casualty officer and then referred to the emergency ward. Here, the physician on duty evaluates them and decides on admission to the various wards, like the general ward, medical intensive care unit (ICU), coronary care unit (CCU), etc. The specialist’s opinion may also be obtained before admission. Critically ill patients are initially admitted to the emergency ward and stabilized before being shifted to other areas of the hospital.

Participants

Patients aged 18 years and older presenting with symptoms of acute chest pain or suspected ACS were stratified by priority using the chest pain scoring system—the HEART score. Only patients presenting to the ED were eligible for the study. Informed consent from the patient or next of kin was mandatory for participation in the study.

Patients were determined ineligible for the following reasons: a clear cause for chest pain other than ACS (eg, trauma, diagnosed aortic dissection), persisting or recurrent chest pain caused by rheumatic diseases or cancer (a terminal illness), pregnancy, unable or unwilling to provide informed consent, or incomplete data.

Study design

We conducted a prospective observational study of patients arriving at the tertiary care hospital with a chief complaint of “chest pain” concerning for ACS. All participants provided witnessed written informed consent. Patients were screened over approximately a 3-month period, from July 2019 to October 2019, after acquiring approval from the Institutional Ethics Committee. Any patient who was admitted to the ED due to chest pain, prehospital referrals based on a physician’s suspicions of a heart condition, and previous medical treatment due to ischemic heart disease (IHD) was eligible. All patients were stratified by priority in our ED using the chest pain scoring system—the HEART score—and were followed up by phone within 6 weeks after presenting to the ED, to assess their progress.

We conducted our study to determine the importance of calculating the HEART score in each patient, which will help to correctly place them into low-, intermediate-, and high-risk groups for clinically important, irreversible adverse cardiac events and guide the clinical decision-making. Patients with low risk will avoid costly tests and hospital admissions, thus decreasing the cost of treatment and ensuring timely discharge from the ED. Patients with high risk will be treated immediately, to possibly prevent a life-threatening, ACS-related incident. Thus, the HEART score will serve as a quick and reliable predictor of outcomes in chest pain patients and help clinicians to make accurate diagnostic and therapeutic choices in uncertain situations.

HEART score

The total number of points for History, Electrocardiogram (ECG), Age, Risk factors, and Troponin was noted as the HEART score (Table 1).

For this study, the patient’s history and ECGs were interpreted by internal medicine attending physicians in the ED. The ECG taken in the emergency room was reviewed and classified, and a copy of the admission ECG was added to the file. The recommendation for patients with a HEART score in a particular range was evaluated. Notably, those with a score of 3 or lower led to a recommendation of reassurance and early discharge. Those with a HEART score in the intermediate range (4-6) were admitted to the hospital for further clinical observation and testing, whereas a high HEART score (7-10) led to admission for intensive monitoring and early intervention. In the analysis of HEART score data, we only used those patients having records for all 5 parameters, excluding patients without an ECG or troponin test.

Results

Myocardial infarction (MI) was defined based on Universal Definition of Myocardial Infarction.¹³ Coronary revascularization was defined as angioplasty with or without stent placement or coronary artery bypass surgery.¹⁴ Percutaneous coronary intervention (PCI) was defined as any therapeutic catheter intervention in the coronary arteries. Coronary artery bypass graft (CABG) surgery was defined as any cardiac surgery in which coronary arteries were operated on.

The primary outcomes in this study were the (1) risk stratification of chest pain patients into low-risk, intermediate-risk, and high-risk categories; (2) incidence of a MACE within 6 weeks of initial presentation. MACE consists of acute myocardial infarction (AMI), PCI, CABG, coronary angiography revealing procedurally correctable stenosis managed conservatively, and death due to any cause.

Our secondary outcomes were discharge or death due to any cause within 6 weeks after presentation.

Follow-up

Within 6 weeks after presentation to the ED, a follow-up phone call was placed to assess the patient’s progress. The follow-up focused on the endpoint of MACE, comprising all-cause death, MI, and revascularization. No patient was lost to follow-up.

Statistical analysis

We aimed to find a difference in the 6-week MACE between low-, intermediate-, and high-risk categories of the HEART score. The prevalence of CHD in India is 10%,⁴ and assuming an α of 0.05, we needed a sample of 141 patients from the ED patient population. Continuous variables were presented by mean (SD), and categorical variables as percentages. We used t test and the Mann-Whitney U test for comparison of means for continuous variables, χ² for categorical variables, and Fisher’s exact test for comparison of the categorical variables. Results with P < .05 were considered statistically significant.

We evaluated 141 patients presenting to the ED with chest pain concerning for ACS during the study period, from July 2019 to October 2019. Patients were 57.54 (13.13) years of age. The male to female distribution was 85 to 56. Other patient characteristics are shown in Table 2.

Primary outcomes

The risk stratification of the HEART score in chest pain patients and the incidence of 6-week MACE are outlined in Table 3 and Table 4, respectively.

The distribution of the HEART score’s 5 elements in the groups with or without MACE endpoints is shown in Table 5. Notice the significant differences between the groups. A follow-up phone call was made within 6 weeks after the presentation to the ED to assess the patient’s progress. The 6-week follow-up call data are included in Table 6.

Of 141 patients, 36 patients (25.53%) were diagnosed with MACE within 6 weeks of presentation. An AMI was diagnosed in 24 patients (17.02%). Coronary angiography was performed in 31 of 141 patients (21.99%), 15 patients (10.64%) underwent PCI, and 4 patients (2.84%) underwent CABG. The rest of the patients were treated with medications only.

Myocardial infarction—An AMI was diagnosed in 24 of the 141 patients (17.02%). Twenty-one of those already had positive markers on admission (apparently, these AMI had started before their arrival to the emergency room). One AMI occurred 2 days after admission in a 66-year-old male, and another occurred 10 days after discharge. A further AMI occurred 2 weeks after discharge. All 3 patients belonged to the intermediate-risk group.

Revascularization—Coronary angiography was performed in 31 of 141 patients (21.99%). Revascularization was performed in 19 patients (13.48%), of which 15 were PCIs (10.64%) and 4 were CABGs (2.84%).

Mortality—One patient died from the study population. He was a 72-year-old male who died 14 days after admission. He had a HEART score of 8.

Among the 67 low-risk patients:

• MACE: Coronary angiography was performed in 1 patient (1.49%). Among the 67 patients in the low-risk category, there was no cases of AMI or deaths. The remaining 66 patients (98.51%) had an uneventful recovery following discharge.
• General practitioner (GP) visits/readmissions following discharge: Two of 67 patients (2.99%) had GP visits following discharge, of which 1 was uneventful. The other patient, a 64-year-old male, was readmitted due to a recurrent history of chest pain and underwent coronary angiography.

Among the 44 intermediate-risk patients:

• MACE: Of the 7 of 44 patients (15.91%) who had coronary angiography, 3 patients (6.82%) had AMI, of which 1 occurred 2 days after admission in a 66-year-old male. Two patients had AMI following discharge. There were no deaths. Overall, 42 of 44 patients (95.55%) had an uneventful recovery following discharge.
• GP visits/readmissions following discharge: Three of 44 patients (6.82%) had repeated visits following discharge. One was a GP visit that was uneventful. The remaining 2 patients were diagnosed with AMI and readmitted following discharge. One AMI occurred 10 days after discharge in a patient with a HEART score of 6; another occurred 2 weeks after discharge in a patient with a HEART score of 5.

Among the 30 high-risk patients:

• MACE: Twenty-three of 30 patients (76.67%) underwent coronary angiography. One patient died 5 days after discharge. The patient had a HEART score of 8. Most patients however, had an uneventful recovery following discharge (28, 93.33%).
• GP visits/readmissions following discharge: Five of 30 patients (16.67%) had repeated visits following discharge. Two were uneventful. Two patients had a history of recurrent chest pain that resolved on Sorbitrate. One patient was readmitted 2 weeks following discharge due to a complication: a left ventricular clot was found. The patient had a HEART score of 10.

Secondary outcome—Overall, 140 of 141 patients were discharged. One patient died: a 72-year-old male with a HEART score of 8.

Feasibility—To determine the ease and feasibility of performing a HEART score in chest pain patients presenting to the ED, a survey was distributed to the internal medicine physicians in the ED. In the survey, the Likert scale was used to rate the ease of utilizing the HEART score and whether the physicians found it feasible to use it for risk stratification of their chest pain patients. A total of 12 of 15 respondents (80%) found it “easy” to use. Of the remaining 3 respondents, 2 (13.33%) rated the HEART score “very easy” to use, while 1 (6.66%) considered it “difficult” to work with. None of the respondents said that it was not feasible to perform a HEART score in the ED.

Risk factors for reaching an endpoint:

We compared risk profiles between the patient groups with and without an endpoint. The group of patients with MACE were older and had a higher proportion of males than the group of patients without MACE. Moreover, they also had a higher prevalence of hypertension, type 2 diabetes mellitus, smoking, hypercholesterolemia, prior history of PCI/CABG, and history of stroke. These also showed a significant association with MACE. Obesity was not included in our risk factors as we did not have data collected to measure body mass index. Results are represented in Table 7.

Discussion

Our study described a patient population presenting to an ED with chest pain as their primary complaint. The results of this prospective study confirm that the HEART score is an excellent system to triage chest pain patients. It provides the clinician with a reliable predictor of the outcome (MACE) after the patient’s arrival, based on available clinical data and in a resource-limited setting like ours.

Cardiovascular epidemiology studies indicate that this has become a significant public health problem in India.¹ Several risk scores for ACS have been published in European and American guidelines. However, in the Indian population, minimal data are available on utilization of such a triage score (HEART score) in chest pain patients in the ED in a resource-limited setting, to the best of our knowledge. In India, only 1 such study is reported,¹⁵ at the Sundaram Medical Foundation, a 170-bed community hospital in Chennai. In this study, 13 of 14 patients (92.86%) with a high HEART score had MACE, indicating a sensitivity of 92.86%; in the 44 patients with a low HEART score, 1 patient (2.22%) had MACE, indicating a specificity of 97.78%; and in the 28 patients with a moderate HEART score, 12 patients (42.86%) had MACE.  

In looking for the optimal risk-stratifying system for chest pain patients, we analyzed the HEART score. The first study on the HEART score was done Backus et al, proving that the HEART score is an easy, quick, and reliable predictor of outcomes in chest pain patients.¹⁰ The HEART score had good discriminatory power, too. The C statistic for the HEART score for ACS occurrence shows a value of 0.83. This signifies a good-to-excellent ability to stratify all-cause chest pain patients in the ED for their risk of MACE. The application of the HEART score to our patient population demonstrated that the majority of the patients belonged to the low-risk category, as reported in the first cohort study that applied the HEART score.⁸ The relationship between the HEART score category and occurrence of MACE within 6 weeks showed a curve with 3 different patterns, corresponding to the 3 risk categories defined in the literature.^11,12 The risk stratification of chest pain patients using the 3 categories (0-3, 4-6, 7-10) identified MACE with an incidence similar to the multicenter study of Backus et al,^10,11 but with a greater risk of MACE in the high-risk category (Figure).

Thus, our study confirmed the utility of the HEART score categories to predict the 6-week incidence of MACE. The sensitivity, specificity, and positive and negative predictive values for the established cut-off scores of 4 and 7 are shown in Table 8. The patients in the low-risk category, corresponding to a score < 4, had a very high negative predictive value, thus identifying a small-risk population. The patients in the high-risk category (score ≥ 7) showed a high positive predictive value, allowing the identification of a high-risk population, even in patients with more atypical presentations. Therefore, the HEART score may help clinicians to make accurate management choices by being a strong predictor of both event-free survival and potentially life-threatening cardiac events.^11,12

Our study tested the efficacy of the HEART score pathway in helping clinicians make smart diagnostic and therapeutic choices. It confirmed that the HEART score was accurate in predicting the short-term incidence of MACE, thus stratifying patients according to their risk severity. In our study, 67 of 141 patients (47.52%) had low-risk HEART scores, and we found the 6-week incidence of MACE to be 1.49%. We omitted the diagnostic and treatment evaluation for patients in the low-risk category and moved onto discharge. Overall, 66 of 67 patients (98.51%) in the low-risk category had an uneventful recovery following discharge. Only 2 of 67 these patients (2.99%) of patients had health care utilization following discharge. Therefore, extrapolation based on results demonstrates reduced health care utilization. Previous studies have shown similar results.^9,12,14,16 For instance, in a prospective study conducted in the Netherlands, low-risk patients representing 36.4% of the total were found to have a low MACE rate (1.7%).⁹ These low-risk patients were categorized as appropriate and safe for ED discharge without additional cardiac evaluation or inpatient admission.⁹ Another retrospective study in Portugal,¹² and one in Chennai, India,¹⁵ found the 6-week incidence of MACE to be 2.00% and 2.22%, respectively. The results of the first HEART Pathway Randomized Control Trial¹⁴ showed that the HEART score pathway reduces health care utilization (cardiac testing, hospitalization, and hospital length of stay). The study also showed that these gains occurred without any of the patients that were identified for early discharge, suffering from MACE at 30 days, or secondary increase in cardiac-related hospitalizations. Similar results were obtained by a randomized trial conducted in North Carolina¹⁷ that also demonstrated a reduction in objective cardiac testing, a doubling of the rate of early discharge from the ED, and a reduced length of stay by half a day. Another study using a modified HEART score also demonstrated that when low-risk patients are evaluated with cardiac testing, the likelihood for false positives is high.¹⁶ Hoffman et al also reported that patients randomized to coronary computed tomographic angiography (CCTA) received > 2.5 times more radiation exposure.¹⁶ Thus, low-risk patients may be safely discharged without the need for stress testing or CCTA.

In our study, 30 out of 141 patients (21.28%) had high-risk HEART scores (7-10), and we found the 6-week incidence of MACE to be 90%. Based on the pathway leading to inpatient admission and intensive treatment, 23 of 30 patients (76.67%) patients in our study underwent coronary angiography and further therapeutic treatment. In the high-risk category, 28 of 30 patients (93.33%) patients had an uneventful recovery following discharge. Previous studies have shown similar results. A retrospective study in Portugal showed that 76.9% of the high-risk patients had a 6-week incidence of MACE.¹² In a study in the Netherlands,⁹ 72.7% of high-risk patients had a 6-week incidence of MACE. Therefore, a HEART score of ≥ 7 in patients implies early aggressive treatment, including invasive strategies, when necessary, without noninvasive treatment preceding it.⁸

In terms of intermediate risk, in our study 44 of 141 patients (31.21%) patients had an intermediate-risk HEART score (4-6), and we found the 6-week incidence of MACE to be 18.18%. Based on the pathway, they were kept in the observation ward on admission. In our study, 7 of 44 patients (15.91%) underwent coronary angiography and further treatment; 42 of 44 patients (95.55%) had an uneventful recovery following discharge. In a prospective study in the Netherlands, 46.1% of patients with an intermediate score had a 6-week MACE incidence of 16.6%.¹⁰ Similarly, in another retrospective study in Portugal, the incidence of 6-week MACE in intermediate-risk patients (36.7%) was found to be 15.6%.¹² Therefore, in patients with a HEART score of 4-6 points, immediate discharge is not an option, as this figure indicates a risk of 18.18% for an adverse outcome. These patients should be admitted for clinical observation, treated as an ACS awaiting final diagnosis, and subjected to noninvasive investigations, such as repeated troponin. Using the HEART score as guidance in the treatment of chest pain patients will benefit patients on both sides of the spectrum.^11,12

Our sample presented a male predominance, a wide range of age, and a mean age similar to that of previous studies.^12.16 Some risk factors, we found, can increase significantly the odds of chest pain being of cardiovascular origin, such as male gender, smoking, hypertension, type 2 diabetes mellitus, and hypercholesterolemia. Other studies also reported similar findings.^8,12,16 Risk factors for premature CHD have been quantified in the case-control INTERHEART study.¹ In the INTERHEART study, 8 common risk factors explained > 90% of AMIs in South Asian and Indian patients. The risk factors include dyslipidemia, smoking or tobacco use, known hypertension, known diabetes, abdominal obesity, physical inactivity, low fruit and vegetable intake, and psychosocial stress.¹ Regarding the feasibility of treating physicians using the HEART score in the ED, we observed that, based on the Likert scale, 80% of survey respondents found it easy to use, and 100% found it feasible in the ED.

However, there were certain limitations to our study. It involved a single academic medical center and a small sample size, which limit generalizability of the findings. In addition, troponin levels are not calculated at our institution, as it is a resource-limited setting; therefore, we used a positive and negative as +2 and 0, respectively.

Conclusion

The HEART score provides the clinician with a quick and reliable predictor of outcome of patients with chest pain after arrival to the ED and can be used for triage. For patients with low HEART scores (0-3), short-term MACE can be excluded with greater than 98% certainty. In these patients, one may consider reserved treatment and discharge policies that may also reduce health care utilization. In patients with high HEART scores (7-10), the high risk of MACE (90%) may indicate early aggressive treatment, including invasive strategies, when necessary. Therefore, the HEART score may help clinicians make accurate management choices by being a strong predictor of both event-free survival and potentially life-threatening cardiac events. Age, gender, and cardiovascular risk factors may also be considered in the assessment of patients. This study confirmed the utility of the HEART score categories to predict the 6-week incidence of MACE.

Corresponding author: Smrati Bajpai Tiwari, MD, DNB, FAIMER, Department of Medicine, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Acharya Donde Marg, Parel, Mumbai 400 012, Maharashtra, India; [email protected].

Financial disclosures: None.

From the Department of Internal Medicine, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, New York, NY (Dr. Gandhi), and the School of Medicine, Seth Gordhandas Sunderdas Medical College, and King Edward Memorial Hospital, Mumbai, India (Drs. Gandhi and Tiwari).

Objective: Calculation of HEART score to (1) stratify patients as low-risk, intermediate-risk, high-risk, and to predict the short-term incidence of major adverse cardiovascular events (MACE), and (2) demonstrate feasibility of HEART score in our local settings.

Design: A prospective cohort study of patients with a chief complaint of chest pain concerning for acute coronary syndrome.

Setting: Participants were recruited from the emergency department (ED) of King Edward Memorial Hospital, a tertiary care academic medical center and a resource-limited setting in Mumbai, India.

Participants: We evaluated 141 patients aged 18 years and older presenting to the ED and stratified them using the HEART score. To assess patients’ progress, a follow-up phone call was made within 6 weeks after presentation to the ED.

Measurements: The primary outcomes were a risk stratification, 6-week occurrence of MACE, and performance of unscheduled revascularization or stress testing. The secondary outcomes were discharge or death.

Results: The 141 participants were stratified into low-risk, intermediate-risk, and high-risk groups: 67 (47.52%), 44 (31.21%), and 30 (21.28%), respectively. The 6-week incidence of MACE in each category was 1.49%, 18.18%, and 90%, respectively. An acute myocardial infarction was diagnosed in 24 patients (17.02%), 15 patients (10.64%) underwent percutaneous coronary intervention (PCI), and 4 patients (2.84%) underwent coronary artery bypass graft (CABG). Overall, 98.5% of low-risk patients and 93.33% of high-risk patients had an uneventful recovery following discharge; therefore, extrapolation based on results demonstrated reduced health care utilization. All the survey respondents found the HEART score to be feasible. The patient characteristics and risk profile of the patients with and without MACE demonstrated that: patients with MACE were older and had a higher proportion of males, hypertension, type 2 diabetes mellitus, smoking, hypercholesterolemia, prior history of PCI/CABG, and history of stroke.

Conclusion: The HEART score seems to be a useful tool for risk stratification and a reliable predictor of outcomes in chest pain patients and can therefore be used for triage.

Keywords: chest pain; emergency department; HEART score; acute coronary syndrome; major adverse cardiac events; myocardial infarction; revascularization.

Cardiovascular diseases (CVDs), especially coronary heart disease (CHD), have epidemic proportions worldwide. Globally, in 2012, CVD led to 17.5 million deaths,^1,2 with more than 75% of them occurring in developing countries. In contrast to developed countries, where mortality from CHD is rapidly declining, it is increasing in developing countries.^1,3 Current estimates from epidemiologic studies from various parts of India indicate the prevalence of CHD in India to be between 7% and 13% in urban populations and 2% and 7% in rural populations.⁴

Premature mortality in terms of years of life lost because of CVD in India increased by 59% over a 20-year span, from 23.2 million in 1990 to 37 million in 2010.⁵ Studies conducted in Mumbai (Mumbai Cohort Study) reported very high CVD mortality rates, approaching 500 per 100 000 for men and 250 per 100 000 for women.^6,7 However, to the best of our knowledge, in the Indian population, there are minimal data on utilization of a triage score, such as the HEART score, in chest pain patients in the emergency department (ED) in a resource-limited setting.

The most common reason for admitting patients to the ED is chest pain.⁸ There are various cardiac and noncardiac etiologies of chest pain presentation. Acute coronary syndrome (ACS) needs to be ruled out first in every patient presenting with chest pain. However, 80% of patients with ACS have no clear diagnostic features on presentation.⁹ The timely diagnosis and treatment of patients with ACS improves their prognosis. Therefore, clinicians tend to start each patient on ACS treatment to reduce the risk, which often leads to increased costs due to unnecessary, time-consuming diagnostic procedures that may place burdens on both the health care system and the patient.¹⁰

Several risk-stratifying tools have been developed in the last few years. Both the GRACE and TIMI risk scores have been designed for risk stratification of patients with proven ACS and not for the chest pain population at the ED.¹¹ Some of these tools are applicable to patients with all types of chest pain presenting to the ED, such as the Manchester Triage System. Other, more selective systems are devoted to the risk stratification of suspected ACS in the ED. One is the HEART score.¹²

The first study on the HEART score—an acronym that stands for History, Electrocardiogram, Age, Risk factors, and Troponin—was done by Backus et al, who proved that the HEART score is an easy, quick, and reliable predictor of outcomes in chest pain patients.¹⁰ The HEART score predicts the short-term incidence of major adverse cardiac events (MACE), which allows clinicians to stratify patients as low-risk, intermediate-risk, and high-risk and to guide their clinical decision-making accordingly. It was developed to provide clinicians with a simple, reliable predictor of cardiac risk on the basis of the lowest score of 0 (very low-risk) up to a score of 10 (very high-risk).

We studied the clinical performance of the HEART score in patients with chest pain, focusing on the efficacy and safety of rapidly identifying patients at risk of MACE. We aimed to determine (1) whether the HEART score is a reliable predictor of outcomes of chest pain patients presenting to the ED; (2) whether the score is feasible in our local settings; and (3) whether it describes the risk profile of patients with and without MACE.

Methods

Setting

Participants were recruited from the ED of King Edward Memorial Hospital, a municipal teaching hospital in Mumbai. The study institute is a tertiary care academic medical center located in Parel, Mumbai, Maharashtra, and is a resource-limited setting serving urban, suburban, and rural populations. Participants requiring urgent attention are first seen by a casualty officer and then referred to the emergency ward. Here, the physician on duty evaluates them and decides on admission to the various wards, like the general ward, medical intensive care unit (ICU), coronary care unit (CCU), etc. The specialist’s opinion may also be obtained before admission. Critically ill patients are initially admitted to the emergency ward and stabilized before being shifted to other areas of the hospital.

Participants

Patients aged 18 years and older presenting with symptoms of acute chest pain or suspected ACS were stratified by priority using the chest pain scoring system—the HEART score. Only patients presenting to the ED were eligible for the study. Informed consent from the patient or next of kin was mandatory for participation in the study.

Patients were determined ineligible for the following reasons: a clear cause for chest pain other than ACS (eg, trauma, diagnosed aortic dissection), persisting or recurrent chest pain caused by rheumatic diseases or cancer (a terminal illness), pregnancy, unable or unwilling to provide informed consent, or incomplete data.

Study design

We conducted a prospective observational study of patients arriving at the tertiary care hospital with a chief complaint of “chest pain” concerning for ACS. All participants provided witnessed written informed consent. Patients were screened over approximately a 3-month period, from July 2019 to October 2019, after acquiring approval from the Institutional Ethics Committee. Any patient who was admitted to the ED due to chest pain, prehospital referrals based on a physician’s suspicions of a heart condition, and previous medical treatment due to ischemic heart disease (IHD) was eligible. All patients were stratified by priority in our ED using the chest pain scoring system—the HEART score—and were followed up by phone within 6 weeks after presenting to the ED, to assess their progress.

We conducted our study to determine the importance of calculating the HEART score in each patient, which will help to correctly place them into low-, intermediate-, and high-risk groups for clinically important, irreversible adverse cardiac events and guide the clinical decision-making. Patients with low risk will avoid costly tests and hospital admissions, thus decreasing the cost of treatment and ensuring timely discharge from the ED. Patients with high risk will be treated immediately, to possibly prevent a life-threatening, ACS-related incident. Thus, the HEART score will serve as a quick and reliable predictor of outcomes in chest pain patients and help clinicians to make accurate diagnostic and therapeutic choices in uncertain situations.

HEART score

The total number of points for History, Electrocardiogram (ECG), Age, Risk factors, and Troponin was noted as the HEART score (Table 1).

For this study, the patient’s history and ECGs were interpreted by internal medicine attending physicians in the ED. The ECG taken in the emergency room was reviewed and classified, and a copy of the admission ECG was added to the file. The recommendation for patients with a HEART score in a particular range was evaluated. Notably, those with a score of 3 or lower led to a recommendation of reassurance and early discharge. Those with a HEART score in the intermediate range (4-6) were admitted to the hospital for further clinical observation and testing, whereas a high HEART score (7-10) led to admission for intensive monitoring and early intervention. In the analysis of HEART score data, we only used those patients having records for all 5 parameters, excluding patients without an ECG or troponin test.

Results

Myocardial infarction (MI) was defined based on Universal Definition of Myocardial Infarction.¹³ Coronary revascularization was defined as angioplasty with or without stent placement or coronary artery bypass surgery.¹⁴ Percutaneous coronary intervention (PCI) was defined as any therapeutic catheter intervention in the coronary arteries. Coronary artery bypass graft (CABG) surgery was defined as any cardiac surgery in which coronary arteries were operated on.

The primary outcomes in this study were the (1) risk stratification of chest pain patients into low-risk, intermediate-risk, and high-risk categories; (2) incidence of a MACE within 6 weeks of initial presentation. MACE consists of acute myocardial infarction (AMI), PCI, CABG, coronary angiography revealing procedurally correctable stenosis managed conservatively, and death due to any cause.

Our secondary outcomes were discharge or death due to any cause within 6 weeks after presentation.

Follow-up

Within 6 weeks after presentation to the ED, a follow-up phone call was placed to assess the patient’s progress. The follow-up focused on the endpoint of MACE, comprising all-cause death, MI, and revascularization. No patient was lost to follow-up.

Statistical analysis

We aimed to find a difference in the 6-week MACE between low-, intermediate-, and high-risk categories of the HEART score. The prevalence of CHD in India is 10%,⁴ and assuming an α of 0.05, we needed a sample of 141 patients from the ED patient population. Continuous variables were presented by mean (SD), and categorical variables as percentages. We used t test and the Mann-Whitney U test for comparison of means for continuous variables, χ² for categorical variables, and Fisher’s exact test for comparison of the categorical variables. Results with P < .05 were considered statistically significant.

We evaluated 141 patients presenting to the ED with chest pain concerning for ACS during the study period, from July 2019 to October 2019. Patients were 57.54 (13.13) years of age. The male to female distribution was 85 to 56. Other patient characteristics are shown in Table 2.

Primary outcomes

The risk stratification of the HEART score in chest pain patients and the incidence of 6-week MACE are outlined in Table 3 and Table 4, respectively.

The distribution of the HEART score’s 5 elements in the groups with or without MACE endpoints is shown in Table 5. Notice the significant differences between the groups. A follow-up phone call was made within 6 weeks after the presentation to the ED to assess the patient’s progress. The 6-week follow-up call data are included in Table 6.

Of 141 patients, 36 patients (25.53%) were diagnosed with MACE within 6 weeks of presentation. An AMI was diagnosed in 24 patients (17.02%). Coronary angiography was performed in 31 of 141 patients (21.99%), 15 patients (10.64%) underwent PCI, and 4 patients (2.84%) underwent CABG. The rest of the patients were treated with medications only.

Myocardial infarction—An AMI was diagnosed in 24 of the 141 patients (17.02%). Twenty-one of those already had positive markers on admission (apparently, these AMI had started before their arrival to the emergency room). One AMI occurred 2 days after admission in a 66-year-old male, and another occurred 10 days after discharge. A further AMI occurred 2 weeks after discharge. All 3 patients belonged to the intermediate-risk group.

Revascularization—Coronary angiography was performed in 31 of 141 patients (21.99%). Revascularization was performed in 19 patients (13.48%), of which 15 were PCIs (10.64%) and 4 were CABGs (2.84%).

Mortality—One patient died from the study population. He was a 72-year-old male who died 14 days after admission. He had a HEART score of 8.

Among the 67 low-risk patients:

• MACE: Coronary angiography was performed in 1 patient (1.49%). Among the 67 patients in the low-risk category, there was no cases of AMI or deaths. The remaining 66 patients (98.51%) had an uneventful recovery following discharge.
• General practitioner (GP) visits/readmissions following discharge: Two of 67 patients (2.99%) had GP visits following discharge, of which 1 was uneventful. The other patient, a 64-year-old male, was readmitted due to a recurrent history of chest pain and underwent coronary angiography.

Among the 44 intermediate-risk patients:

• MACE: Of the 7 of 44 patients (15.91%) who had coronary angiography, 3 patients (6.82%) had AMI, of which 1 occurred 2 days after admission in a 66-year-old male. Two patients had AMI following discharge. There were no deaths. Overall, 42 of 44 patients (95.55%) had an uneventful recovery following discharge.
• GP visits/readmissions following discharge: Three of 44 patients (6.82%) had repeated visits following discharge. One was a GP visit that was uneventful. The remaining 2 patients were diagnosed with AMI and readmitted following discharge. One AMI occurred 10 days after discharge in a patient with a HEART score of 6; another occurred 2 weeks after discharge in a patient with a HEART score of 5.

Among the 30 high-risk patients:

• MACE: Twenty-three of 30 patients (76.67%) underwent coronary angiography. One patient died 5 days after discharge. The patient had a HEART score of 8. Most patients however, had an uneventful recovery following discharge (28, 93.33%).
• GP visits/readmissions following discharge: Five of 30 patients (16.67%) had repeated visits following discharge. Two were uneventful. Two patients had a history of recurrent chest pain that resolved on Sorbitrate. One patient was readmitted 2 weeks following discharge due to a complication: a left ventricular clot was found. The patient had a HEART score of 10.

Secondary outcome—Overall, 140 of 141 patients were discharged. One patient died: a 72-year-old male with a HEART score of 8.

Feasibility—To determine the ease and feasibility of performing a HEART score in chest pain patients presenting to the ED, a survey was distributed to the internal medicine physicians in the ED. In the survey, the Likert scale was used to rate the ease of utilizing the HEART score and whether the physicians found it feasible to use it for risk stratification of their chest pain patients. A total of 12 of 15 respondents (80%) found it “easy” to use. Of the remaining 3 respondents, 2 (13.33%) rated the HEART score “very easy” to use, while 1 (6.66%) considered it “difficult” to work with. None of the respondents said that it was not feasible to perform a HEART score in the ED.

Risk factors for reaching an endpoint:

We compared risk profiles between the patient groups with and without an endpoint. The group of patients with MACE were older and had a higher proportion of males than the group of patients without MACE. Moreover, they also had a higher prevalence of hypertension, type 2 diabetes mellitus, smoking, hypercholesterolemia, prior history of PCI/CABG, and history of stroke. These also showed a significant association with MACE. Obesity was not included in our risk factors as we did not have data collected to measure body mass index. Results are represented in Table 7.

Discussion

Our study described a patient population presenting to an ED with chest pain as their primary complaint. The results of this prospective study confirm that the HEART score is an excellent system to triage chest pain patients. It provides the clinician with a reliable predictor of the outcome (MACE) after the patient’s arrival, based on available clinical data and in a resource-limited setting like ours.

Cardiovascular epidemiology studies indicate that this has become a significant public health problem in India.¹ Several risk scores for ACS have been published in European and American guidelines. However, in the Indian population, minimal data are available on utilization of such a triage score (HEART score) in chest pain patients in the ED in a resource-limited setting, to the best of our knowledge. In India, only 1 such study is reported,¹⁵ at the Sundaram Medical Foundation, a 170-bed community hospital in Chennai. In this study, 13 of 14 patients (92.86%) with a high HEART score had MACE, indicating a sensitivity of 92.86%; in the 44 patients with a low HEART score, 1 patient (2.22%) had MACE, indicating a specificity of 97.78%; and in the 28 patients with a moderate HEART score, 12 patients (42.86%) had MACE.  

In looking for the optimal risk-stratifying system for chest pain patients, we analyzed the HEART score. The first study on the HEART score was done Backus et al, proving that the HEART score is an easy, quick, and reliable predictor of outcomes in chest pain patients.¹⁰ The HEART score had good discriminatory power, too. The C statistic for the HEART score for ACS occurrence shows a value of 0.83. This signifies a good-to-excellent ability to stratify all-cause chest pain patients in the ED for their risk of MACE. The application of the HEART score to our patient population demonstrated that the majority of the patients belonged to the low-risk category, as reported in the first cohort study that applied the HEART score.⁸ The relationship between the HEART score category and occurrence of MACE within 6 weeks showed a curve with 3 different patterns, corresponding to the 3 risk categories defined in the literature.^11,12 The risk stratification of chest pain patients using the 3 categories (0-3, 4-6, 7-10) identified MACE with an incidence similar to the multicenter study of Backus et al,^10,11 but with a greater risk of MACE in the high-risk category (Figure).

Thus, our study confirmed the utility of the HEART score categories to predict the 6-week incidence of MACE. The sensitivity, specificity, and positive and negative predictive values for the established cut-off scores of 4 and 7 are shown in Table 8. The patients in the low-risk category, corresponding to a score < 4, had a very high negative predictive value, thus identifying a small-risk population. The patients in the high-risk category (score ≥ 7) showed a high positive predictive value, allowing the identification of a high-risk population, even in patients with more atypical presentations. Therefore, the HEART score may help clinicians to make accurate management choices by being a strong predictor of both event-free survival and potentially life-threatening cardiac events.^11,12

Our study tested the efficacy of the HEART score pathway in helping clinicians make smart diagnostic and therapeutic choices. It confirmed that the HEART score was accurate in predicting the short-term incidence of MACE, thus stratifying patients according to their risk severity. In our study, 67 of 141 patients (47.52%) had low-risk HEART scores, and we found the 6-week incidence of MACE to be 1.49%. We omitted the diagnostic and treatment evaluation for patients in the low-risk category and moved onto discharge. Overall, 66 of 67 patients (98.51%) in the low-risk category had an uneventful recovery following discharge. Only 2 of 67 these patients (2.99%) of patients had health care utilization following discharge. Therefore, extrapolation based on results demonstrates reduced health care utilization. Previous studies have shown similar results.^9,12,14,16 For instance, in a prospective study conducted in the Netherlands, low-risk patients representing 36.4% of the total were found to have a low MACE rate (1.7%).⁹ These low-risk patients were categorized as appropriate and safe for ED discharge without additional cardiac evaluation or inpatient admission.⁹ Another retrospective study in Portugal,¹² and one in Chennai, India,¹⁵ found the 6-week incidence of MACE to be 2.00% and 2.22%, respectively. The results of the first HEART Pathway Randomized Control Trial¹⁴ showed that the HEART score pathway reduces health care utilization (cardiac testing, hospitalization, and hospital length of stay). The study also showed that these gains occurred without any of the patients that were identified for early discharge, suffering from MACE at 30 days, or secondary increase in cardiac-related hospitalizations. Similar results were obtained by a randomized trial conducted in North Carolina¹⁷ that also demonstrated a reduction in objective cardiac testing, a doubling of the rate of early discharge from the ED, and a reduced length of stay by half a day. Another study using a modified HEART score also demonstrated that when low-risk patients are evaluated with cardiac testing, the likelihood for false positives is high.¹⁶ Hoffman et al also reported that patients randomized to coronary computed tomographic angiography (CCTA) received > 2.5 times more radiation exposure.¹⁶ Thus, low-risk patients may be safely discharged without the need for stress testing or CCTA.

In our study, 30 out of 141 patients (21.28%) had high-risk HEART scores (7-10), and we found the 6-week incidence of MACE to be 90%. Based on the pathway leading to inpatient admission and intensive treatment, 23 of 30 patients (76.67%) patients in our study underwent coronary angiography and further therapeutic treatment. In the high-risk category, 28 of 30 patients (93.33%) patients had an uneventful recovery following discharge. Previous studies have shown similar results. A retrospective study in Portugal showed that 76.9% of the high-risk patients had a 6-week incidence of MACE.¹² In a study in the Netherlands,⁹ 72.7% of high-risk patients had a 6-week incidence of MACE. Therefore, a HEART score of ≥ 7 in patients implies early aggressive treatment, including invasive strategies, when necessary, without noninvasive treatment preceding it.⁸

In terms of intermediate risk, in our study 44 of 141 patients (31.21%) patients had an intermediate-risk HEART score (4-6), and we found the 6-week incidence of MACE to be 18.18%. Based on the pathway, they were kept in the observation ward on admission. In our study, 7 of 44 patients (15.91%) underwent coronary angiography and further treatment; 42 of 44 patients (95.55%) had an uneventful recovery following discharge. In a prospective study in the Netherlands, 46.1% of patients with an intermediate score had a 6-week MACE incidence of 16.6%.¹⁰ Similarly, in another retrospective study in Portugal, the incidence of 6-week MACE in intermediate-risk patients (36.7%) was found to be 15.6%.¹² Therefore, in patients with a HEART score of 4-6 points, immediate discharge is not an option, as this figure indicates a risk of 18.18% for an adverse outcome. These patients should be admitted for clinical observation, treated as an ACS awaiting final diagnosis, and subjected to noninvasive investigations, such as repeated troponin. Using the HEART score as guidance in the treatment of chest pain patients will benefit patients on both sides of the spectrum.^11,12

Our sample presented a male predominance, a wide range of age, and a mean age similar to that of previous studies.^12.16 Some risk factors, we found, can increase significantly the odds of chest pain being of cardiovascular origin, such as male gender, smoking, hypertension, type 2 diabetes mellitus, and hypercholesterolemia. Other studies also reported similar findings.^8,12,16 Risk factors for premature CHD have been quantified in the case-control INTERHEART study.¹ In the INTERHEART study, 8 common risk factors explained > 90% of AMIs in South Asian and Indian patients. The risk factors include dyslipidemia, smoking or tobacco use, known hypertension, known diabetes, abdominal obesity, physical inactivity, low fruit and vegetable intake, and psychosocial stress.¹ Regarding the feasibility of treating physicians using the HEART score in the ED, we observed that, based on the Likert scale, 80% of survey respondents found it easy to use, and 100% found it feasible in the ED.

However, there were certain limitations to our study. It involved a single academic medical center and a small sample size, which limit generalizability of the findings. In addition, troponin levels are not calculated at our institution, as it is a resource-limited setting; therefore, we used a positive and negative as +2 and 0, respectively.

Conclusion

The HEART score provides the clinician with a quick and reliable predictor of outcome of patients with chest pain after arrival to the ED and can be used for triage. For patients with low HEART scores (0-3), short-term MACE can be excluded with greater than 98% certainty. In these patients, one may consider reserved treatment and discharge policies that may also reduce health care utilization. In patients with high HEART scores (7-10), the high risk of MACE (90%) may indicate early aggressive treatment, including invasive strategies, when necessary. Therefore, the HEART score may help clinicians make accurate management choices by being a strong predictor of both event-free survival and potentially life-threatening cardiac events. Age, gender, and cardiovascular risk factors may also be considered in the assessment of patients. This study confirmed the utility of the HEART score categories to predict the 6-week incidence of MACE.

Corresponding author: Smrati Bajpai Tiwari, MD, DNB, FAIMER, Department of Medicine, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Acharya Donde Marg, Parel, Mumbai 400 012, Maharashtra, India; [email protected].

Financial disclosures: None.

Hospital medicine procedure services have proliferated in recent years, driven by multiple synergistic factors, including an interest in improving hospital throughput, bolstering resident education, and ensuring full-spectrum practice for hospitalists. These services have become established and have demonstrated their capabilities, further catalyzed by emerging interest—and expertise—in point-of-care ultrasonography by hospitalists.

Most hospital medicine procedure services (HMPSs) focus on performing ultrasound-assisted procedures at bedside, providing purported advantages in convenience, cost, and potentially timing when compared to services performed by interventional radiology. The scope of procedures performed by HPMSs reflects the populations cared for by hospitalists, including paracentesis, thoracentesis, central venous catheter placement, lumbar puncture and, more recently, pigtail chest tube placement.^1,2 Fitting with the early development of HMPSs, initial reports regarding these services centered on optimal development of services and emphasized the question, “Are hospital medicine procedure services able to do [procedure x] as safely as radiology or the primary team?”²

Ensuring safety and quality is fundamental to implementing new workflows; however, it is now clear that HMPSs provide high-quality, safe, patient-centered bedside procedures; these services are no longer novel.³ As HMPSs mature, so too must their evaluation, research, and scholarship. It is no longer enough to document that a HMPS can perform procedures as well as interventional radiology or a standard hospital medicine care team—instead, we must identify how these services affect patient outcomes, improve education, add value, and influence the overall process of care in the hospital.

In this issue of the Journal of Hospital Medicine, Ritter and colleagues⁴ describe an important first step in this maturing field by evaluating how a HMPS affects process outcomes in the context of paracentesis. The faster time from admission to paracentesis observed in the HMPS population compared with radiology services has important implications for patient satisfaction (symptom relief) and morbidity and mortality (time to peritonitis diagnosis). Ritter et al also demonstrated shorter length of stay (LOS) among patients who had paracenteses performed by the HMPS compared with the radiology service; this finding is consistent with previous studies that, while not evaluating a HMPS per se, demonstrated shorter LOS with bedside paracentesis. While there were some limitations, such as the findings representing a single-site experience and group differences that necessitated assessment of multiple confounders (some of which may remain unknown), the authors’ efforts to shift focus toward patient and high-value care outcomes should be applauded.

The evaluation of HMPSs has reached an inflection point. The field must now focus on assessing outcomes. Does the appropriateness of procedures improve when those with internal medicine training are performing the procedures rather than radiologists, who have more focused procedural knowledge but less general medical training? What procedures are not or should not be performed by HMPSs? What does the shift of procedures to HMPSs do to the flow of patients and procedures in interventional radiology, and do other patients indirectly benefit? How should hospital medicine groups and hospitals account for lower work relative value unit productivity of HMPSs compared with other traditional rounding services? In what ways do HMPSs provide cost-effective care compared with alternatives? There has been limited evaluation of cost-savings realized when performing paracentesis at the bedside as opposed to in the interventional radiology suite.⁵

Additionally, most HMPSs are staffed by a small number of hospitalists within a group. It is unclear how a HMPS will affect general hospitalist procedural competence, and whether that even matters. Should we still expect every hospitalist to be able to perform procedures, or are HMPSs a step in the evolution of subspecialties in hospital medicine? Such subspecialties exist already, including perioperative medicine and transitional care specialists.

Now that more HMPSs have been established, the next step in their evolution must go beyond feasibility and safety assessments and toward evaluation of their effectiveness. It has become clear that HMPSs can perform procedures safely, but what can they do better?

Hospital medicine procedure services have proliferated in recent years, driven by multiple synergistic factors, including an interest in improving hospital throughput, bolstering resident education, and ensuring full-spectrum practice for hospitalists. These services have become established and have demonstrated their capabilities, further catalyzed by emerging interest—and expertise—in point-of-care ultrasonography by hospitalists.

Most hospital medicine procedure services (HMPSs) focus on performing ultrasound-assisted procedures at bedside, providing purported advantages in convenience, cost, and potentially timing when compared to services performed by interventional radiology. The scope of procedures performed by HPMSs reflects the populations cared for by hospitalists, including paracentesis, thoracentesis, central venous catheter placement, lumbar puncture and, more recently, pigtail chest tube placement.^1,2 Fitting with the early development of HMPSs, initial reports regarding these services centered on optimal development of services and emphasized the question, “Are hospital medicine procedure services able to do [procedure x] as safely as radiology or the primary team?”²

Ensuring safety and quality is fundamental to implementing new workflows; however, it is now clear that HMPSs provide high-quality, safe, patient-centered bedside procedures; these services are no longer novel.³ As HMPSs mature, so too must their evaluation, research, and scholarship. It is no longer enough to document that a HMPS can perform procedures as well as interventional radiology or a standard hospital medicine care team—instead, we must identify how these services affect patient outcomes, improve education, add value, and influence the overall process of care in the hospital.

In this issue of the Journal of Hospital Medicine, Ritter and colleagues⁴ describe an important first step in this maturing field by evaluating how a HMPS affects process outcomes in the context of paracentesis. The faster time from admission to paracentesis observed in the HMPS population compared with radiology services has important implications for patient satisfaction (symptom relief) and morbidity and mortality (time to peritonitis diagnosis). Ritter et al also demonstrated shorter length of stay (LOS) among patients who had paracenteses performed by the HMPS compared with the radiology service; this finding is consistent with previous studies that, while not evaluating a HMPS per se, demonstrated shorter LOS with bedside paracentesis. While there were some limitations, such as the findings representing a single-site experience and group differences that necessitated assessment of multiple confounders (some of which may remain unknown), the authors’ efforts to shift focus toward patient and high-value care outcomes should be applauded.

The evaluation of HMPSs has reached an inflection point. The field must now focus on assessing outcomes. Does the appropriateness of procedures improve when those with internal medicine training are performing the procedures rather than radiologists, who have more focused procedural knowledge but less general medical training? What procedures are not or should not be performed by HMPSs? What does the shift of procedures to HMPSs do to the flow of patients and procedures in interventional radiology, and do other patients indirectly benefit? How should hospital medicine groups and hospitals account for lower work relative value unit productivity of HMPSs compared with other traditional rounding services? In what ways do HMPSs provide cost-effective care compared with alternatives? There has been limited evaluation of cost-savings realized when performing paracentesis at the bedside as opposed to in the interventional radiology suite.⁵

Additionally, most HMPSs are staffed by a small number of hospitalists within a group. It is unclear how a HMPS will affect general hospitalist procedural competence, and whether that even matters. Should we still expect every hospitalist to be able to perform procedures, or are HMPSs a step in the evolution of subspecialties in hospital medicine? Such subspecialties exist already, including perioperative medicine and transitional care specialists.

Now that more HMPSs have been established, the next step in their evolution must go beyond feasibility and safety assessments and toward evaluation of their effectiveness. It has become clear that HMPSs can perform procedures safely, but what can they do better?

Hospital medicine procedure services have proliferated in recent years, driven by multiple synergistic factors, including an interest in improving hospital throughput, bolstering resident education, and ensuring full-spectrum practice for hospitalists. These services have become established and have demonstrated their capabilities, further catalyzed by emerging interest—and expertise—in point-of-care ultrasonography by hospitalists.

Most hospital medicine procedure services (HMPSs) focus on performing ultrasound-assisted procedures at bedside, providing purported advantages in convenience, cost, and potentially timing when compared to services performed by interventional radiology. The scope of procedures performed by HPMSs reflects the populations cared for by hospitalists, including paracentesis, thoracentesis, central venous catheter placement, lumbar puncture and, more recently, pigtail chest tube placement.^1,2 Fitting with the early development of HMPSs, initial reports regarding these services centered on optimal development of services and emphasized the question, “Are hospital medicine procedure services able to do [procedure x] as safely as radiology or the primary team?”²

Ensuring safety and quality is fundamental to implementing new workflows; however, it is now clear that HMPSs provide high-quality, safe, patient-centered bedside procedures; these services are no longer novel.³ As HMPSs mature, so too must their evaluation, research, and scholarship. It is no longer enough to document that a HMPS can perform procedures as well as interventional radiology or a standard hospital medicine care team—instead, we must identify how these services affect patient outcomes, improve education, add value, and influence the overall process of care in the hospital.

In this issue of the Journal of Hospital Medicine, Ritter and colleagues⁴ describe an important first step in this maturing field by evaluating how a HMPS affects process outcomes in the context of paracentesis. The faster time from admission to paracentesis observed in the HMPS population compared with radiology services has important implications for patient satisfaction (symptom relief) and morbidity and mortality (time to peritonitis diagnosis). Ritter et al also demonstrated shorter length of stay (LOS) among patients who had paracenteses performed by the HMPS compared with the radiology service; this finding is consistent with previous studies that, while not evaluating a HMPS per se, demonstrated shorter LOS with bedside paracentesis. While there were some limitations, such as the findings representing a single-site experience and group differences that necessitated assessment of multiple confounders (some of which may remain unknown), the authors’ efforts to shift focus toward patient and high-value care outcomes should be applauded.

The evaluation of HMPSs has reached an inflection point. The field must now focus on assessing outcomes. Does the appropriateness of procedures improve when those with internal medicine training are performing the procedures rather than radiologists, who have more focused procedural knowledge but less general medical training? What procedures are not or should not be performed by HMPSs? What does the shift of procedures to HMPSs do to the flow of patients and procedures in interventional radiology, and do other patients indirectly benefit? How should hospital medicine groups and hospitals account for lower work relative value unit productivity of HMPSs compared with other traditional rounding services? In what ways do HMPSs provide cost-effective care compared with alternatives? There has been limited evaluation of cost-savings realized when performing paracentesis at the bedside as opposed to in the interventional radiology suite.⁵

Additionally, most HMPSs are staffed by a small number of hospitalists within a group. It is unclear how a HMPS will affect general hospitalist procedural competence, and whether that even matters. Should we still expect every hospitalist to be able to perform procedures, or are HMPSs a step in the evolution of subspecialties in hospital medicine? Such subspecialties exist already, including perioperative medicine and transitional care specialists.

Now that more HMPSs have been established, the next step in their evolution must go beyond feasibility and safety assessments and toward evaluation of their effectiveness. It has become clear that HMPSs can perform procedures safely, but what can they do better?

Throughout North America, hospitalizations and deaths due to SARS-CoV-2 have fallen substantially due to the rapid roll-out of COVID-19 vaccines. Despite this monumental success, however, transmission of the virus will unfortunately persist for the foreseeable future due to a variety of factors, including incomplete population vaccination, emergence of variants, and increased exposures as social and economic activity return to normal.¹ Therefore, it is of critical importance to continue to track the burden of COVID-19 by region. Specifically, the incidence of hospitalizations due to COVID-19 will be a key metric, as highlighted by Tsai et al² in this issue of the Journal of Hospital Medicine.

Tsai et al² explored the challenge of accurately determining the burden of hospitalization due to COVID-19, focusing on the potential for misclassification leading to overestimations. They rigorously evaluated the proportion of overall COVID-19–associated hospitalizations reported to Los Angeles County Department of Public Health that were potentially misclassified as caused by COVID-19 because of incidentally detected virus in patients who were hospitalized for unrelated reasons. In their study, they reviewed medical records from a randomly selected subset of hospital discharges with a clinical diagnosis of COVID-19 to determine whether a clinical diagnosis of COVID-19 was warranted. Among 618 patients, COVID-19 was deemed incidental to the reason for hospitalization in 12% (95% CI, 9%-16%) of admissions.

Incidental viral detection is more common during periods of high case prevalence and when case presentations overlap with nonclassic COVID symptoms.³ Incidental viral detection also occurs when broad testing of asymptomatic patients is instituted prior to admission, procedures, or high-risk medical therapies. Residual postinfectious shedding and false-positive results may further falsely increase case counts. The clinical and infection control implications of detectable virus is further complicated by vaccination, which leads to milder forms of the infection with less capacity for transmission.⁴

Why is establishing an overestimation COVID-19 hospitalization important? First, if misclassification leads to an overestimate of the number of hospitalizations caused by COVID-19, public health restrictions might be increased to protect overloading acute care sites when such measures are unnecessary, resulting in unintended social and economic fallouts.⁵ Second, healthcare resource allocation depends on accurate estimates of disease burden—overestimation of COVID-19–related hospitalization can lead to misallocation of scarce resources, including personnel, equipment, and medication to units or hospitals.⁶ Relatedly, cancelling of “nonurgent” tests, procedures, and clinic visits to reallocate resources to COVID-19–related care delays diagnosis and treatment of potentially serious illnesses. Last, overattributing hospitalizations due to COVID-19, particularly in patients who are now fully vaccinated, may lead researchers to underestimate the efficacy of vaccination efforts on the individual and population level, especially in the era of evolving variant strains.

How could this research change future practice? As the authors astutely state, the purpose of the investigation is not to alter practice on the individual patient level, but rather to help public health officials to make better decisions. One solution (similar to census adjustment) based on future research would be to potentially apply a corrective factor to “adjust” COVID-19 hospitalizations downward to explicitly account for the recognition that some proportion of patients hospitalized with COVID-19 were not actually hospitalized because of COVID-19.

Although vaccination continues to be highly successful at curbing the pandemic, transmission of COVID-19 persists due to gaps in vaccination and emergence of variants. Therefore, continued ongoing vigilance for disease burden, specifically focused on the most vulnerable aspects of the health care system—acute care centers—is critical to informing optimal public health restrictions and resource allocation.

Throughout North America, hospitalizations and deaths due to SARS-CoV-2 have fallen substantially due to the rapid roll-out of COVID-19 vaccines. Despite this monumental success, however, transmission of the virus will unfortunately persist for the foreseeable future due to a variety of factors, including incomplete population vaccination, emergence of variants, and increased exposures as social and economic activity return to normal.¹ Therefore, it is of critical importance to continue to track the burden of COVID-19 by region. Specifically, the incidence of hospitalizations due to COVID-19 will be a key metric, as highlighted by Tsai et al² in this issue of the Journal of Hospital Medicine.

Tsai et al² explored the challenge of accurately determining the burden of hospitalization due to COVID-19, focusing on the potential for misclassification leading to overestimations. They rigorously evaluated the proportion of overall COVID-19–associated hospitalizations reported to Los Angeles County Department of Public Health that were potentially misclassified as caused by COVID-19 because of incidentally detected virus in patients who were hospitalized for unrelated reasons. In their study, they reviewed medical records from a randomly selected subset of hospital discharges with a clinical diagnosis of COVID-19 to determine whether a clinical diagnosis of COVID-19 was warranted. Among 618 patients, COVID-19 was deemed incidental to the reason for hospitalization in 12% (95% CI, 9%-16%) of admissions.

Incidental viral detection is more common during periods of high case prevalence and when case presentations overlap with nonclassic COVID symptoms.³ Incidental viral detection also occurs when broad testing of asymptomatic patients is instituted prior to admission, procedures, or high-risk medical therapies. Residual postinfectious shedding and false-positive results may further falsely increase case counts. The clinical and infection control implications of detectable virus is further complicated by vaccination, which leads to milder forms of the infection with less capacity for transmission.⁴

Why is establishing an overestimation COVID-19 hospitalization important? First, if misclassification leads to an overestimate of the number of hospitalizations caused by COVID-19, public health restrictions might be increased to protect overloading acute care sites when such measures are unnecessary, resulting in unintended social and economic fallouts.⁵ Second, healthcare resource allocation depends on accurate estimates of disease burden—overestimation of COVID-19–related hospitalization can lead to misallocation of scarce resources, including personnel, equipment, and medication to units or hospitals.⁶ Relatedly, cancelling of “nonurgent” tests, procedures, and clinic visits to reallocate resources to COVID-19–related care delays diagnosis and treatment of potentially serious illnesses. Last, overattributing hospitalizations due to COVID-19, particularly in patients who are now fully vaccinated, may lead researchers to underestimate the efficacy of vaccination efforts on the individual and population level, especially in the era of evolving variant strains.

How could this research change future practice? As the authors astutely state, the purpose of the investigation is not to alter practice on the individual patient level, but rather to help public health officials to make better decisions. One solution (similar to census adjustment) based on future research would be to potentially apply a corrective factor to “adjust” COVID-19 hospitalizations downward to explicitly account for the recognition that some proportion of patients hospitalized with COVID-19 were not actually hospitalized because of COVID-19.

Although vaccination continues to be highly successful at curbing the pandemic, transmission of COVID-19 persists due to gaps in vaccination and emergence of variants. Therefore, continued ongoing vigilance for disease burden, specifically focused on the most vulnerable aspects of the health care system—acute care centers—is critical to informing optimal public health restrictions and resource allocation.

Throughout North America, hospitalizations and deaths due to SARS-CoV-2 have fallen substantially due to the rapid roll-out of COVID-19 vaccines. Despite this monumental success, however, transmission of the virus will unfortunately persist for the foreseeable future due to a variety of factors, including incomplete population vaccination, emergence of variants, and increased exposures as social and economic activity return to normal.¹ Therefore, it is of critical importance to continue to track the burden of COVID-19 by region. Specifically, the incidence of hospitalizations due to COVID-19 will be a key metric, as highlighted by Tsai et al² in this issue of the Journal of Hospital Medicine.

Tsai et al² explored the challenge of accurately determining the burden of hospitalization due to COVID-19, focusing on the potential for misclassification leading to overestimations. They rigorously evaluated the proportion of overall COVID-19–associated hospitalizations reported to Los Angeles County Department of Public Health that were potentially misclassified as caused by COVID-19 because of incidentally detected virus in patients who were hospitalized for unrelated reasons. In their study, they reviewed medical records from a randomly selected subset of hospital discharges with a clinical diagnosis of COVID-19 to determine whether a clinical diagnosis of COVID-19 was warranted. Among 618 patients, COVID-19 was deemed incidental to the reason for hospitalization in 12% (95% CI, 9%-16%) of admissions.

Incidental viral detection is more common during periods of high case prevalence and when case presentations overlap with nonclassic COVID symptoms.³ Incidental viral detection also occurs when broad testing of asymptomatic patients is instituted prior to admission, procedures, or high-risk medical therapies. Residual postinfectious shedding and false-positive results may further falsely increase case counts. The clinical and infection control implications of detectable virus is further complicated by vaccination, which leads to milder forms of the infection with less capacity for transmission.⁴

Why is establishing an overestimation COVID-19 hospitalization important? First, if misclassification leads to an overestimate of the number of hospitalizations caused by COVID-19, public health restrictions might be increased to protect overloading acute care sites when such measures are unnecessary, resulting in unintended social and economic fallouts.⁵ Second, healthcare resource allocation depends on accurate estimates of disease burden—overestimation of COVID-19–related hospitalization can lead to misallocation of scarce resources, including personnel, equipment, and medication to units or hospitals.⁶ Relatedly, cancelling of “nonurgent” tests, procedures, and clinic visits to reallocate resources to COVID-19–related care delays diagnosis and treatment of potentially serious illnesses. Last, overattributing hospitalizations due to COVID-19, particularly in patients who are now fully vaccinated, may lead researchers to underestimate the efficacy of vaccination efforts on the individual and population level, especially in the era of evolving variant strains.

How could this research change future practice? As the authors astutely state, the purpose of the investigation is not to alter practice on the individual patient level, but rather to help public health officials to make better decisions. One solution (similar to census adjustment) based on future research would be to potentially apply a corrective factor to “adjust” COVID-19 hospitalizations downward to explicitly account for the recognition that some proportion of patients hospitalized with COVID-19 were not actually hospitalized because of COVID-19.

Although vaccination continues to be highly successful at curbing the pandemic, transmission of COVID-19 persists due to gaps in vaccination and emergence of variants. Therefore, continued ongoing vigilance for disease burden, specifically focused on the most vulnerable aspects of the health care system—acute care centers—is critical to informing optimal public health restrictions and resource allocation.

“Being a role model is the most powerful form of educating.”

—John Wooden

The typical approach to faculty development in education often emphasizes specific teaching skills, such as rounding and teaching styles, providing expectations, and giving feedback. Before these strategies can be applied, however, we must first take note that memorable and influential physicians share common practices of compassionate, person-centered care. Role models are important in professional, character, and career development.¹ Role modeling compassionate patient care gains learners’ respect and engagement, and, ideally, inspires them to grow as people and physicians. An often-overlooked foundation of improving as a medical educator is working to improve our bedside interactions and role modeling compassionate care.

As new roles and promotions draw us away from clinical commitments and toward administrative work, it is easy to become disconnected from the value of clinical medicine. We risk unintentionally perpetuating a hidden curriculum that undervalues humanistic care when we do not explicitly endorse empathic values and behaviors. Exemplary teaching physicians respect patients, care for their well-being, and consider the big picture.² Next time you are rounding, remember the importance of bedside patient interactions.

With that in mind, here are three key strategies to consider for effective physician-patient interactions.

1. Start strong: It is crucial to get off to a good start by leading with respect and kindness. Knocking and pausing before entering the patient’s hospital room shows you remember that they are in vulnerable positions, with little privacy. Smiling warmly when greeting patients shows you are happy to see them. Greet them using their preferred honorific and introduce yourself and your team each day. Ask whether it’s okay to mute the television, but remember to turn the volume back up when leaving. Convey warmth with appropriate touch, consider small acts to make the patient more comfortable, and, when possible, sit at a patient’s eye level.

2. Show empathy: Be patient and remind yourself that hospitalized patients and their families are often in the most difficult times of their lives. In addition to being in vulnerable positions, patients are often lonely and anxious. Humanistic physicians get to know patients as people and beyond their medical illness by talking about nonmedical topics.³ Ask about their family, their pets, memorable moments in their lives, sports teams, favorite shows, and how they pass the time while hospitalized. Are there any photos they would like to share with you? Ask, too, before you leave the room whether they need you to reach something for them. Use humor thoughtfully, and always with kindness. Demonstrate humility about your own abilities, and what you know and do not know about the patient’s diagnoses, and their lived experience.

3. Strive for trustworthiness: Advocate for the patient and show them and your learners that you care. Make shared decisions when straying from guideline-directed care. Aim for trustworthiness; patients’ distrust is an adaptive response to how they have experienced healthcare, so while you do not have to take distrust personally, you should take addressing it as a personal obligation. Be aware of your own privilege, and that how patients perceive you is a reflection of how they have experienced the world, including other clinicians. Model vulnerability, including showing appropriate sadness when there is bad news to report and acknowledging grief.

Being a better clinical teacher starts with being a better doctor. Role modeling compassionate and person-centered care is a cornerstone of being an exceptional clinical teacher.

We gratefully acknowledge SHM’s Physician-in-Training Committee, whose support made this collaboration possible.

“Being a role model is the most powerful form of educating.”

—John Wooden

The typical approach to faculty development in education often emphasizes specific teaching skills, such as rounding and teaching styles, providing expectations, and giving feedback. Before these strategies can be applied, however, we must first take note that memorable and influential physicians share common practices of compassionate, person-centered care. Role models are important in professional, character, and career development.¹ Role modeling compassionate patient care gains learners’ respect and engagement, and, ideally, inspires them to grow as people and physicians. An often-overlooked foundation of improving as a medical educator is working to improve our bedside interactions and role modeling compassionate care.

As new roles and promotions draw us away from clinical commitments and toward administrative work, it is easy to become disconnected from the value of clinical medicine. We risk unintentionally perpetuating a hidden curriculum that undervalues humanistic care when we do not explicitly endorse empathic values and behaviors. Exemplary teaching physicians respect patients, care for their well-being, and consider the big picture.² Next time you are rounding, remember the importance of bedside patient interactions.

With that in mind, here are three key strategies to consider for effective physician-patient interactions.

1. Start strong: It is crucial to get off to a good start by leading with respect and kindness. Knocking and pausing before entering the patient’s hospital room shows you remember that they are in vulnerable positions, with little privacy. Smiling warmly when greeting patients shows you are happy to see them. Greet them using their preferred honorific and introduce yourself and your team each day. Ask whether it’s okay to mute the television, but remember to turn the volume back up when leaving. Convey warmth with appropriate touch, consider small acts to make the patient more comfortable, and, when possible, sit at a patient’s eye level.

2. Show empathy: Be patient and remind yourself that hospitalized patients and their families are often in the most difficult times of their lives. In addition to being in vulnerable positions, patients are often lonely and anxious. Humanistic physicians get to know patients as people and beyond their medical illness by talking about nonmedical topics.³ Ask about their family, their pets, memorable moments in their lives, sports teams, favorite shows, and how they pass the time while hospitalized. Are there any photos they would like to share with you? Ask, too, before you leave the room whether they need you to reach something for them. Use humor thoughtfully, and always with kindness. Demonstrate humility about your own abilities, and what you know and do not know about the patient’s diagnoses, and their lived experience.

3. Strive for trustworthiness: Advocate for the patient and show them and your learners that you care. Make shared decisions when straying from guideline-directed care. Aim for trustworthiness; patients’ distrust is an adaptive response to how they have experienced healthcare, so while you do not have to take distrust personally, you should take addressing it as a personal obligation. Be aware of your own privilege, and that how patients perceive you is a reflection of how they have experienced the world, including other clinicians. Model vulnerability, including showing appropriate sadness when there is bad news to report and acknowledging grief.

Being a better clinical teacher starts with being a better doctor. Role modeling compassionate and person-centered care is a cornerstone of being an exceptional clinical teacher.

We gratefully acknowledge SHM’s Physician-in-Training Committee, whose support made this collaboration possible.

“Being a role model is the most powerful form of educating.”

—John Wooden

The typical approach to faculty development in education often emphasizes specific teaching skills, such as rounding and teaching styles, providing expectations, and giving feedback. Before these strategies can be applied, however, we must first take note that memorable and influential physicians share common practices of compassionate, person-centered care. Role models are important in professional, character, and career development.¹ Role modeling compassionate patient care gains learners’ respect and engagement, and, ideally, inspires them to grow as people and physicians. An often-overlooked foundation of improving as a medical educator is working to improve our bedside interactions and role modeling compassionate care.

As new roles and promotions draw us away from clinical commitments and toward administrative work, it is easy to become disconnected from the value of clinical medicine. We risk unintentionally perpetuating a hidden curriculum that undervalues humanistic care when we do not explicitly endorse empathic values and behaviors. Exemplary teaching physicians respect patients, care for their well-being, and consider the big picture.² Next time you are rounding, remember the importance of bedside patient interactions.

With that in mind, here are three key strategies to consider for effective physician-patient interactions.

1. Start strong: It is crucial to get off to a good start by leading with respect and kindness. Knocking and pausing before entering the patient’s hospital room shows you remember that they are in vulnerable positions, with little privacy. Smiling warmly when greeting patients shows you are happy to see them. Greet them using their preferred honorific and introduce yourself and your team each day. Ask whether it’s okay to mute the television, but remember to turn the volume back up when leaving. Convey warmth with appropriate touch, consider small acts to make the patient more comfortable, and, when possible, sit at a patient’s eye level.

2. Show empathy: Be patient and remind yourself that hospitalized patients and their families are often in the most difficult times of their lives. In addition to being in vulnerable positions, patients are often lonely and anxious. Humanistic physicians get to know patients as people and beyond their medical illness by talking about nonmedical topics.³ Ask about their family, their pets, memorable moments in their lives, sports teams, favorite shows, and how they pass the time while hospitalized. Are there any photos they would like to share with you? Ask, too, before you leave the room whether they need you to reach something for them. Use humor thoughtfully, and always with kindness. Demonstrate humility about your own abilities, and what you know and do not know about the patient’s diagnoses, and their lived experience.

3. Strive for trustworthiness: Advocate for the patient and show them and your learners that you care. Make shared decisions when straying from guideline-directed care. Aim for trustworthiness; patients’ distrust is an adaptive response to how they have experienced healthcare, so while you do not have to take distrust personally, you should take addressing it as a personal obligation. Be aware of your own privilege, and that how patients perceive you is a reflection of how they have experienced the world, including other clinicians. Model vulnerability, including showing appropriate sadness when there is bad news to report and acknowledging grief.

Being a better clinical teacher starts with being a better doctor. Role modeling compassionate and person-centered care is a cornerstone of being an exceptional clinical teacher.

We gratefully acknowledge SHM’s Physician-in-Training Committee, whose support made this collaboration possible.

Study Overview

Objective. To compare the risk of subsequent fractures after an initial traumatic or nontraumatic fracture in postmenopausal women.

Design. A prospective observational study utilizing data from the Women’s Health Initiative (WHI) Study, WHI Clinical Trials (WHI-CT), and WHI Bone Density Substudy to evaluate rates at which patients who suffered a traumatic fracture vs nontraumatic fracture develop a subsequent fracture.

Setting and participants. The WHI study, implemented at 40 United States clinical sites, enrolled 161 808 postmenopausal women aged 50 to 79 years at baseline between 1993 and 1998. The study cohort consisted of 75 335 patients who had self-reported fractures from September 1994 to December 1998 that were confirmed by the WHI Bone Density Substudy and WHI-CT. Of these participants, 253 (0.3%) were excluded because of a lack of follow-up information regarding incident fractures, and 8208 (10.9%) were excluded due to incomplete information on covariates, thus resulting in an analytic sample of 66 874 (88.8%) participants. Prospective fracture ascertainment with participants was conducted at least annually and the mechanism of fracture was assessed to differentiate traumatic vs nontraumatic incident fractures. Traumatic fractures were defined as fractures caused by motor vehicle collisions, falls from a height, falls downstairs, or sports injury. Nontraumatic fractures were defined as fractures caused by a trip and fall.

Main outcome measures. The primary outcome was an incident fracture at an anatomically distinct body part. Fractures were classified as upper extremity (carpal, elbow, lower or upper end of humerus, shaft of humerus, upper radius/ulna, or radius/ulna), lower extremity (ankle, hip, patella, pelvis, shaft of femur, tibia/fibula, or tibial plateau), or spine (lumbar and/or thoracic spine). Self-reported fractures were verified via medical chart review by WHI study physicians; hip fractures were confirmed by review of written reports of radiographic studies; and nonhip fractures were confirmed by review of radiography reports or clinical documentations.

Main results. In total, 66 874 women in the study (mean [SD] age) 63.1 (7.0) years without clinical fracture and 65.3 (7.2) years with clinical fracture at baseline were followed for 8.1 (1.6) years. Of these participants, 7142 (10.7%) experienced incident fracture during the study follow-up period (13.9 per 1000 person-years), and 721 (10.1%) of whom had a subsequent fracture. The adjusted hazard ratio (aHR) of subsequent fracture after an initial fracture was 1.49 (95% CI, 1.38-1.61, P < .001). Covariates adjusted were age, race, ethnicity, body mass index, treated diabetes, frequency of falls in the previous year, and physical function and activity. In women with initial traumatic fracture, the association between initial and subsequent fracture was increased (aHR, 1.25; 95% CI, 1.06-1.48, P = .01). Among women with initial nontraumatic fracture, the association between initial and subsequent fracture was also increased (aHR, 1.52; 95% CI, 1.37-1.68, P < .001). The confidence intervals for the 2 preceding associations for traumatic and nontraumatic initial fracture strata were overlapping.

Conclusion. Fractures, regardless of mechanism of injury, are similarly associated with an increased risk of subsequent fractures in postmenopausal women aged 50 years and older. Findings from this study provide evidence to support reevaluation of current clinical guidelines to include traumatic fracture as a trigger for osteoporosis screening.

Commentary

Osteoporosis is one of the most common age-associated disease that affects 1 in 4 women and 1 in 20 men over the age of 65.¹ It increases the risk of fracture, and its clinical sequelae include reduced mobility, health decline, and increased all-cause mortality. The high prevalence of osteoporosis poses a clinical challenge as the global population continues to age. Pharmacological treatments such as bisphosphonates are highly effective in preventing or slowing bone mineral density (BMD) loss and reducing risk of fragility fractures (eg, nontraumatic fractures of the vertebra, hip, and femur) and are commonly used to mitigate adverse effects of degenerative bone changes secondary to osteoporosis.¹

The high prevalence of osteoporosis and effectiveness of bisphosphonates raises the question of how to optimally identify adults at risk for osteoporosis so that pharmacologic therapy can be promptly initiated to prevent disease progression. Multiple osteoporosis screening guidelines, including those from the United States Preventive Services Task Force (USPSTF), American Association of Family Physicians, and National Osteoporosis Foundation, are widely used in the clinical setting to address this important clinical question. In general, the prevailing wisdom is to screen osteoporosis in postmenopausal women over the age of 65, women under the age of 65 who have a significant 10-year fracture risk, or women over the age of 50 who have experienced a fragility fracture.¹ In the study reported by Crandall et al, it was shown that the risks of having subsequent fractures were similar after an initial traumatic or nontraumatic (fragility) fracture in postmenopausal women aged 50 years and older.² This finding brings into question whether traumatic fractures should be viewed any differently than nontraumatic fractures in women over the age of 50 in light of evaluation for osteoporosis. Furthermore, these results suggest that most fractures in postmenopausal women may indicate decreased bone integrity, thus adding to the rationale that osteoporosis screening needs to be considered and expanded to include postmenopausal women under the age of 65 who endured a traumatic fracture.

Per current guidelines, a woman under the age of 65 is recommended for osteoporosis screening only if she has an increased 10-year fracture risk compared to women aged 65 years and older. This risk is calculated based on the World Health Organization fracture-risk algorithm (WHO FRAX) tool which uses multiple factors such as age, weight, and history of fragility fractures to predict whether an individual is at risk of developing a fracture in the next 10 years. The WHO FRAX tool does not include traumatic fractures in its risk calculation and current clinical guidelines do not account for traumatic fractures as a red flag to initiate osteoporosis screening. Therefore, postmenopausal women under the age of 65 are less likely to be screened for osteoporosis when they experience a traumatic fracture compared to a fragility fracture, despite being at a demonstrably higher risk for subsequent fracture. As an unintended consequence, this may lead to the under diagnosis of osteoporosis in postmenopausal women under the age of 65. Thus, Crandall et al conclude that a fracture due to any cause warrants follow up evaluation for osteoporosis including BMD testing in women older than 50 years of age.

Older men constitute another population who are commonly under screened for osteoporosis. The current USPSTF guidelines indicate that there is an insufficient body of evidence to screen men for osteoporosis given its lower prevalence.¹ However, it is important to note that men have significantly increased mortality after a hip fracture, are less likely to be on pharmacological treatment for osteoporosis, and are under diagnosed for osteoporosis.³ Consistent with findings from the current study, Leslie et al showed that high-trauma and low-trauma fractures have similarly elevated subsequent fracture risk in both men and women over the age of 40 in a Canadian study.⁴ Moreover, in the same study, BMD was decreased in both men and women who suffered a fracture regardless of the injury mechanism. This finding further underscores a need to consider traumatic fractures as a risk factor for osteoporosis. Taken together, given that men are under screened and treated for osteoporosis but have increased mortality post-fracture, considerations to initiate osteoporosis evaluation should be similarly given to men who endured a traumatic fracture.

The study conducted by Crandall et al has several strengths. It is noteworthy for the large size of the WHI cohort with participants from across the United States which enables the capture of a wider range of age groups as women under the age of 65 are not common participants of osteoporosis studies. Additionally, data ascertainment and outcome adjudication utilizing medical records and physician review assure data quality. A limitation of the study is that the study cohort consists exclusively of women and therefore the findings are not generalizable to men. However, findings from this study echo those from other studies that investigate the relationship between fracture mechanisms and subsequent fracture risk in men and women.^3,4 Collectively, these comparable findings highlight the need for additional research to validate traumatic fracture as a risk factor for osteoporosis and to incorporate it into clinical guidelines for osteoporosis screening.

Applications for Clinical Practice

The findings from the current study indicate that traumatic and fragility fractures may be more alike than previously recognized in regards to bone health and subsequent fracture prevention in postmenopausal women. If validated, these results may lead to changes in clinical practice whereby all fractures in postmenopausal women could trigger osteoporosis screening, assessment, and treatment if indicated for the secondary prevention of fractures.

Study Overview

Objective. To compare the risk of subsequent fractures after an initial traumatic or nontraumatic fracture in postmenopausal women.

Design. A prospective observational study utilizing data from the Women’s Health Initiative (WHI) Study, WHI Clinical Trials (WHI-CT), and WHI Bone Density Substudy to evaluate rates at which patients who suffered a traumatic fracture vs nontraumatic fracture develop a subsequent fracture.

Setting and participants. The WHI study, implemented at 40 United States clinical sites, enrolled 161 808 postmenopausal women aged 50 to 79 years at baseline between 1993 and 1998. The study cohort consisted of 75 335 patients who had self-reported fractures from September 1994 to December 1998 that were confirmed by the WHI Bone Density Substudy and WHI-CT. Of these participants, 253 (0.3%) were excluded because of a lack of follow-up information regarding incident fractures, and 8208 (10.9%) were excluded due to incomplete information on covariates, thus resulting in an analytic sample of 66 874 (88.8%) participants. Prospective fracture ascertainment with participants was conducted at least annually and the mechanism of fracture was assessed to differentiate traumatic vs nontraumatic incident fractures. Traumatic fractures were defined as fractures caused by motor vehicle collisions, falls from a height, falls downstairs, or sports injury. Nontraumatic fractures were defined as fractures caused by a trip and fall.

Main outcome measures. The primary outcome was an incident fracture at an anatomically distinct body part. Fractures were classified as upper extremity (carpal, elbow, lower or upper end of humerus, shaft of humerus, upper radius/ulna, or radius/ulna), lower extremity (ankle, hip, patella, pelvis, shaft of femur, tibia/fibula, or tibial plateau), or spine (lumbar and/or thoracic spine). Self-reported fractures were verified via medical chart review by WHI study physicians; hip fractures were confirmed by review of written reports of radiographic studies; and nonhip fractures were confirmed by review of radiography reports or clinical documentations.

Main results. In total, 66 874 women in the study (mean [SD] age) 63.1 (7.0) years without clinical fracture and 65.3 (7.2) years with clinical fracture at baseline were followed for 8.1 (1.6) years. Of these participants, 7142 (10.7%) experienced incident fracture during the study follow-up period (13.9 per 1000 person-years), and 721 (10.1%) of whom had a subsequent fracture. The adjusted hazard ratio (aHR) of subsequent fracture after an initial fracture was 1.49 (95% CI, 1.38-1.61, P < .001). Covariates adjusted were age, race, ethnicity, body mass index, treated diabetes, frequency of falls in the previous year, and physical function and activity. In women with initial traumatic fracture, the association between initial and subsequent fracture was increased (aHR, 1.25; 95% CI, 1.06-1.48, P = .01). Among women with initial nontraumatic fracture, the association between initial and subsequent fracture was also increased (aHR, 1.52; 95% CI, 1.37-1.68, P < .001). The confidence intervals for the 2 preceding associations for traumatic and nontraumatic initial fracture strata were overlapping.

Conclusion. Fractures, regardless of mechanism of injury, are similarly associated with an increased risk of subsequent fractures in postmenopausal women aged 50 years and older. Findings from this study provide evidence to support reevaluation of current clinical guidelines to include traumatic fracture as a trigger for osteoporosis screening.

Commentary

Osteoporosis is one of the most common age-associated disease that affects 1 in 4 women and 1 in 20 men over the age of 65.¹ It increases the risk of fracture, and its clinical sequelae include reduced mobility, health decline, and increased all-cause mortality. The high prevalence of osteoporosis poses a clinical challenge as the global population continues to age. Pharmacological treatments such as bisphosphonates are highly effective in preventing or slowing bone mineral density (BMD) loss and reducing risk of fragility fractures (eg, nontraumatic fractures of the vertebra, hip, and femur) and are commonly used to mitigate adverse effects of degenerative bone changes secondary to osteoporosis.¹

The high prevalence of osteoporosis and effectiveness of bisphosphonates raises the question of how to optimally identify adults at risk for osteoporosis so that pharmacologic therapy can be promptly initiated to prevent disease progression. Multiple osteoporosis screening guidelines, including those from the United States Preventive Services Task Force (USPSTF), American Association of Family Physicians, and National Osteoporosis Foundation, are widely used in the clinical setting to address this important clinical question. In general, the prevailing wisdom is to screen osteoporosis in postmenopausal women over the age of 65, women under the age of 65 who have a significant 10-year fracture risk, or women over the age of 50 who have experienced a fragility fracture.¹ In the study reported by Crandall et al, it was shown that the risks of having subsequent fractures were similar after an initial traumatic or nontraumatic (fragility) fracture in postmenopausal women aged 50 years and older.² This finding brings into question whether traumatic fractures should be viewed any differently than nontraumatic fractures in women over the age of 50 in light of evaluation for osteoporosis. Furthermore, these results suggest that most fractures in postmenopausal women may indicate decreased bone integrity, thus adding to the rationale that osteoporosis screening needs to be considered and expanded to include postmenopausal women under the age of 65 who endured a traumatic fracture.

Per current guidelines, a woman under the age of 65 is recommended for osteoporosis screening only if she has an increased 10-year fracture risk compared to women aged 65 years and older. This risk is calculated based on the World Health Organization fracture-risk algorithm (WHO FRAX) tool which uses multiple factors such as age, weight, and history of fragility fractures to predict whether an individual is at risk of developing a fracture in the next 10 years. The WHO FRAX tool does not include traumatic fractures in its risk calculation and current clinical guidelines do not account for traumatic fractures as a red flag to initiate osteoporosis screening. Therefore, postmenopausal women under the age of 65 are less likely to be screened for osteoporosis when they experience a traumatic fracture compared to a fragility fracture, despite being at a demonstrably higher risk for subsequent fracture. As an unintended consequence, this may lead to the under diagnosis of osteoporosis in postmenopausal women under the age of 65. Thus, Crandall et al conclude that a fracture due to any cause warrants follow up evaluation for osteoporosis including BMD testing in women older than 50 years of age.

Older men constitute another population who are commonly under screened for osteoporosis. The current USPSTF guidelines indicate that there is an insufficient body of evidence to screen men for osteoporosis given its lower prevalence.¹ However, it is important to note that men have significantly increased mortality after a hip fracture, are less likely to be on pharmacological treatment for osteoporosis, and are under diagnosed for osteoporosis.³ Consistent with findings from the current study, Leslie et al showed that high-trauma and low-trauma fractures have similarly elevated subsequent fracture risk in both men and women over the age of 40 in a Canadian study.⁴ Moreover, in the same study, BMD was decreased in both men and women who suffered a fracture regardless of the injury mechanism. This finding further underscores a need to consider traumatic fractures as a risk factor for osteoporosis. Taken together, given that men are under screened and treated for osteoporosis but have increased mortality post-fracture, considerations to initiate osteoporosis evaluation should be similarly given to men who endured a traumatic fracture.

The study conducted by Crandall et al has several strengths. It is noteworthy for the large size of the WHI cohort with participants from across the United States which enables the capture of a wider range of age groups as women under the age of 65 are not common participants of osteoporosis studies. Additionally, data ascertainment and outcome adjudication utilizing medical records and physician review assure data quality. A limitation of the study is that the study cohort consists exclusively of women and therefore the findings are not generalizable to men. However, findings from this study echo those from other studies that investigate the relationship between fracture mechanisms and subsequent fracture risk in men and women.^3,4 Collectively, these comparable findings highlight the need for additional research to validate traumatic fracture as a risk factor for osteoporosis and to incorporate it into clinical guidelines for osteoporosis screening.

Applications for Clinical Practice

The findings from the current study indicate that traumatic and fragility fractures may be more alike than previously recognized in regards to bone health and subsequent fracture prevention in postmenopausal women. If validated, these results may lead to changes in clinical practice whereby all fractures in postmenopausal women could trigger osteoporosis screening, assessment, and treatment if indicated for the secondary prevention of fractures.

Study Overview

Objective. To compare the risk of subsequent fractures after an initial traumatic or nontraumatic fracture in postmenopausal women.

Design. A prospective observational study utilizing data from the Women’s Health Initiative (WHI) Study, WHI Clinical Trials (WHI-CT), and WHI Bone Density Substudy to evaluate rates at which patients who suffered a traumatic fracture vs nontraumatic fracture develop a subsequent fracture.

Setting and participants. The WHI study, implemented at 40 United States clinical sites, enrolled 161 808 postmenopausal women aged 50 to 79 years at baseline between 1993 and 1998. The study cohort consisted of 75 335 patients who had self-reported fractures from September 1994 to December 1998 that were confirmed by the WHI Bone Density Substudy and WHI-CT. Of these participants, 253 (0.3%) were excluded because of a lack of follow-up information regarding incident fractures, and 8208 (10.9%) were excluded due to incomplete information on covariates, thus resulting in an analytic sample of 66 874 (88.8%) participants. Prospective fracture ascertainment with participants was conducted at least annually and the mechanism of fracture was assessed to differentiate traumatic vs nontraumatic incident fractures. Traumatic fractures were defined as fractures caused by motor vehicle collisions, falls from a height, falls downstairs, or sports injury. Nontraumatic fractures were defined as fractures caused by a trip and fall.

Main outcome measures. The primary outcome was an incident fracture at an anatomically distinct body part. Fractures were classified as upper extremity (carpal, elbow, lower or upper end of humerus, shaft of humerus, upper radius/ulna, or radius/ulna), lower extremity (ankle, hip, patella, pelvis, shaft of femur, tibia/fibula, or tibial plateau), or spine (lumbar and/or thoracic spine). Self-reported fractures were verified via medical chart review by WHI study physicians; hip fractures were confirmed by review of written reports of radiographic studies; and nonhip fractures were confirmed by review of radiography reports or clinical documentations.

Main results. In total, 66 874 women in the study (mean [SD] age) 63.1 (7.0) years without clinical fracture and 65.3 (7.2) years with clinical fracture at baseline were followed for 8.1 (1.6) years. Of these participants, 7142 (10.7%) experienced incident fracture during the study follow-up period (13.9 per 1000 person-years), and 721 (10.1%) of whom had a subsequent fracture. The adjusted hazard ratio (aHR) of subsequent fracture after an initial fracture was 1.49 (95% CI, 1.38-1.61, P < .001). Covariates adjusted were age, race, ethnicity, body mass index, treated diabetes, frequency of falls in the previous year, and physical function and activity. In women with initial traumatic fracture, the association between initial and subsequent fracture was increased (aHR, 1.25; 95% CI, 1.06-1.48, P = .01). Among women with initial nontraumatic fracture, the association between initial and subsequent fracture was also increased (aHR, 1.52; 95% CI, 1.37-1.68, P < .001). The confidence intervals for the 2 preceding associations for traumatic and nontraumatic initial fracture strata were overlapping.

Conclusion. Fractures, regardless of mechanism of injury, are similarly associated with an increased risk of subsequent fractures in postmenopausal women aged 50 years and older. Findings from this study provide evidence to support reevaluation of current clinical guidelines to include traumatic fracture as a trigger for osteoporosis screening.

Commentary

Osteoporosis is one of the most common age-associated disease that affects 1 in 4 women and 1 in 20 men over the age of 65.¹ It increases the risk of fracture, and its clinical sequelae include reduced mobility, health decline, and increased all-cause mortality. The high prevalence of osteoporosis poses a clinical challenge as the global population continues to age. Pharmacological treatments such as bisphosphonates are highly effective in preventing or slowing bone mineral density (BMD) loss and reducing risk of fragility fractures (eg, nontraumatic fractures of the vertebra, hip, and femur) and are commonly used to mitigate adverse effects of degenerative bone changes secondary to osteoporosis.¹

The high prevalence of osteoporosis and effectiveness of bisphosphonates raises the question of how to optimally identify adults at risk for osteoporosis so that pharmacologic therapy can be promptly initiated to prevent disease progression. Multiple osteoporosis screening guidelines, including those from the United States Preventive Services Task Force (USPSTF), American Association of Family Physicians, and National Osteoporosis Foundation, are widely used in the clinical setting to address this important clinical question. In general, the prevailing wisdom is to screen osteoporosis in postmenopausal women over the age of 65, women under the age of 65 who have a significant 10-year fracture risk, or women over the age of 50 who have experienced a fragility fracture.¹ In the study reported by Crandall et al, it was shown that the risks of having subsequent fractures were similar after an initial traumatic or nontraumatic (fragility) fracture in postmenopausal women aged 50 years and older.² This finding brings into question whether traumatic fractures should be viewed any differently than nontraumatic fractures in women over the age of 50 in light of evaluation for osteoporosis. Furthermore, these results suggest that most fractures in postmenopausal women may indicate decreased bone integrity, thus adding to the rationale that osteoporosis screening needs to be considered and expanded to include postmenopausal women under the age of 65 who endured a traumatic fracture.

Per current guidelines, a woman under the age of 65 is recommended for osteoporosis screening only if she has an increased 10-year fracture risk compared to women aged 65 years and older. This risk is calculated based on the World Health Organization fracture-risk algorithm (WHO FRAX) tool which uses multiple factors such as age, weight, and history of fragility fractures to predict whether an individual is at risk of developing a fracture in the next 10 years. The WHO FRAX tool does not include traumatic fractures in its risk calculation and current clinical guidelines do not account for traumatic fractures as a red flag to initiate osteoporosis screening. Therefore, postmenopausal women under the age of 65 are less likely to be screened for osteoporosis when they experience a traumatic fracture compared to a fragility fracture, despite being at a demonstrably higher risk for subsequent fracture. As an unintended consequence, this may lead to the under diagnosis of osteoporosis in postmenopausal women under the age of 65. Thus, Crandall et al conclude that a fracture due to any cause warrants follow up evaluation for osteoporosis including BMD testing in women older than 50 years of age.

Older men constitute another population who are commonly under screened for osteoporosis. The current USPSTF guidelines indicate that there is an insufficient body of evidence to screen men for osteoporosis given its lower prevalence.¹ However, it is important to note that men have significantly increased mortality after a hip fracture, are less likely to be on pharmacological treatment for osteoporosis, and are under diagnosed for osteoporosis.³ Consistent with findings from the current study, Leslie et al showed that high-trauma and low-trauma fractures have similarly elevated subsequent fracture risk in both men and women over the age of 40 in a Canadian study.⁴ Moreover, in the same study, BMD was decreased in both men and women who suffered a fracture regardless of the injury mechanism. This finding further underscores a need to consider traumatic fractures as a risk factor for osteoporosis. Taken together, given that men are under screened and treated for osteoporosis but have increased mortality post-fracture, considerations to initiate osteoporosis evaluation should be similarly given to men who endured a traumatic fracture.

The study conducted by Crandall et al has several strengths. It is noteworthy for the large size of the WHI cohort with participants from across the United States which enables the capture of a wider range of age groups as women under the age of 65 are not common participants of osteoporosis studies. Additionally, data ascertainment and outcome adjudication utilizing medical records and physician review assure data quality. A limitation of the study is that the study cohort consists exclusively of women and therefore the findings are not generalizable to men. However, findings from this study echo those from other studies that investigate the relationship between fracture mechanisms and subsequent fracture risk in men and women.^3,4 Collectively, these comparable findings highlight the need for additional research to validate traumatic fracture as a risk factor for osteoporosis and to incorporate it into clinical guidelines for osteoporosis screening.

Applications for Clinical Practice

The findings from the current study indicate that traumatic and fragility fractures may be more alike than previously recognized in regards to bone health and subsequent fracture prevention in postmenopausal women. If validated, these results may lead to changes in clinical practice whereby all fractures in postmenopausal women could trigger osteoporosis screening, assessment, and treatment if indicated for the secondary prevention of fractures.

Study Overview

Objective. To evaluate the efficacy and safety of the combination of nivolumab plus cabozantinib as compared with sunitinib monotherapy in the treatment of previously untreated advanced renal cell carcinoma (RCC).

Design. Multicenter, international, open-label, randomized, phase 3 trial.

Intervention. Patients were randomized in a 1:1 fashion to 1 of 2 treatment arms:

• Arm A: Nivolumab intravenously 240 mg every 2 weeks plus cabozantinib orally 40 mg once daily.
• Arm B: Sunitinib orally 50 mg daily for 4 weeks, followed by 2 weeks off therapy (6-week cycle).

Randomization was stratified by the International Metastatic RCC Database Consortium prognostic risk score (low-, intermediate-, and high-risk). Treatment was continued until disease progression or development of unacceptable toxic side effects with a maximum of 2-year duration of Nivolumab therapy.

Settings and participants. Adults with previously untreated advanced RCC with a clear cell component were eligible for enrollment. Subjects were excluded if they had active central nervous system metastases or active autoimmune disease.

Main outcome measures. The primary outcome of this study was progression-free survival (PFS) as assessed by an independent review committee. Secondary endpoints included overall survival, objective response rate, safety, and PFS as assessed by investigators. All subgroup analyses were prespecified. Efficacy was assessed in the intention-to-treat population, including all patients who underwent randomization.

Main results. A total of 651 patients underwent randomization: 323 to the nivolumab plus cabozantinib group, and 328 to the sunitinib group. Baseline demographics were balanced. The median follow-up period for overall survival (OS) was 18.1 months. The primary reason for treatment discontinuation in any group was disease progression. PFS as indicated by an independent review committee was significantly longer in the nivolumab plus cabozantinib group compared to the sunitinib group (median 16.6 months vs 8.2 months; hazard ratio [HR] 0.51, P < .001). The median OS was not reached for any group. Overall survival was longer in the nivolumab plus cabozantinib group compared to the sunitinib group (HR 0.60, 95% CI: 0.40-0.89; P = .001). The objective response rate was 55.7% with the nivolumab plus cabozantinib group versus 27.1% with sunitinib (P < .001). The complete response rate was 8% in the nivolumab plus cabozantinib group compared to 4.6% in the sunitinib group. The median time to response was 2.8 months with nivolumab plus cabozantinib and 4.2 months in the sunitinib group, while the median duration of response was 20.2 months and 11.5 months, respectively.

Nearly all patients (about 99% in each group) had an adverse event (AE). Hypertension was the most common side effect, with grade 3 or higher seen in 12.5% in the nivolumab plus cabzantinib group and 13.1% in the sunitinib group. Other grade 3 or higher side effects occurring in at least 10% of patients in any group were hyponatremia, diarrhea, palmar-plantar erythrodysesthesia, hypothyroidism, and fatigue. AEs of any cause leading to discontinuation of the therapy occurred in 19.7% in the nivolumab plus cabzantinib group vs 16.9% of the sunitinib group. One death was considered to be treatment-related (small intestinal perforation) in the nivolumab plus cabozantinib group vs 2 treatment-related deaths with sunitinib (pneumonia and respiratory distress). In the nivolumab plus cabozantinib group, 57% of the patients had a dose reduction of cabozantinib and 52% had a reduction in sunitinib dosage.

Using the Functional Assessment of Cancer Therapy-Kidney Symptoms Index, patients in the nivolumab plus cabozantinib group reported better health-related quality of life and less disease-related symptoms compared to the sunitinib group.

Commentary

The treatment landscape for frontline therapy for patients with advanced RCC has rapidly expanded over the last several years and has revolutionized cancer care. Ushered in by the results from the CheckMate 214 study highlighting the efficacy of dual checkpoint inhibition with nivolumab and ipilimumab in intermediate and poor risk patients, several subsequent trials have demonstrated improved outcomes with combination therapy with immune checkpoint inhibitors and tyrosine-kinase inhibitors (TKI). To date, data from Keynote-426 (pembrolizumab plus axitinib vs sunitinib), Javelin Renal 101 (avelumab plus axitinib vs sunitinib) and the CLEAR trial (lenvatinib plus pembrolizumab vs levatinib plus everolimus vs sunitinib) have demonstrated superiority of immune checkpoint inhibitor/TKI combinations over sunitinb in the first-line setting.^1-5

The current phase 3, CheckMate 9ER trial adds yet another dynamic option for patients with advanced clear cell RCC. While cross-trial comparisons are fraught with important caveats, the median PFS of almost 16.6 months and complete response rate of 8% the nivolumab plus cabozantinib group compares favorably with other combinations. Data from the CLEAR study with the combination of lenvatinib and pembrolizumab showed a complete response rate approaching 16%. Importantly, the current study highlights improved quality of life with the combination of cabozantinib and nivolumab compared to sunitinib alone adding to the efficacy and benefits of this combination treatment.

The selection of first line therapy for patients with advanced RCC should be always guided by individual patient characteristics, and any single immune checkpoint inhibitor/TKI combination is not “superior” to any other. Perhaps more importantly is developing an understanding of the overlapping toxicity profiles of checkpoint inhibitors and TKIs. Again, this trial results are consistent with prior studies in terms of the adverse event profile which were not trivial, and almost all patients (99%) experienced AEs. It is important for oncologists to understand the management of the toxicities with these combinations and dose reductions as appropriate. It is worth noting that 19% of patients with nivolumab plus cabozantinib received glucocorticoids for management of immune-related AEs.

While long-term follow-up data will be needed to further understand the durability of response to this combination, nivolumab-cabozantinib represents an exciting new option for patients with advanced clear cell RCC. As we continue to see improvement in outcomes in clear cell histology, further work must focus on optimization of therapy in non-clear cell RCC as this is a population that is not represented in these data sets. Furthermore, future efforts should begin to explore triplet combinations and biomarker driven patient selection for upfront therapy in ordercontinue to improve outcomes in patients with advanced RCC.

Applications for Clinical Practice

The combination of nivolumab plus cabozantinib adds to the growing list of highly active checkpoint inhibitor/TKI combinations for first-line treatment of advanced RCC. With significant higher response rates, improved outcomes, and improvement in the quality of life, this combination will add another standard treatment option for patients with previously untreated advanced RCC.

Study Overview

Objective. To evaluate the efficacy and safety of the combination of nivolumab plus cabozantinib as compared with sunitinib monotherapy in the treatment of previously untreated advanced renal cell carcinoma (RCC).

Design. Multicenter, international, open-label, randomized, phase 3 trial.

Intervention. Patients were randomized in a 1:1 fashion to 1 of 2 treatment arms:

• Arm A: Nivolumab intravenously 240 mg every 2 weeks plus cabozantinib orally 40 mg once daily.
• Arm B: Sunitinib orally 50 mg daily for 4 weeks, followed by 2 weeks off therapy (6-week cycle).

Randomization was stratified by the International Metastatic RCC Database Consortium prognostic risk score (low-, intermediate-, and high-risk). Treatment was continued until disease progression or development of unacceptable toxic side effects with a maximum of 2-year duration of Nivolumab therapy.

Settings and participants. Adults with previously untreated advanced RCC with a clear cell component were eligible for enrollment. Subjects were excluded if they had active central nervous system metastases or active autoimmune disease.

Main outcome measures. The primary outcome of this study was progression-free survival (PFS) as assessed by an independent review committee. Secondary endpoints included overall survival, objective response rate, safety, and PFS as assessed by investigators. All subgroup analyses were prespecified. Efficacy was assessed in the intention-to-treat population, including all patients who underwent randomization.

Main results. A total of 651 patients underwent randomization: 323 to the nivolumab plus cabozantinib group, and 328 to the sunitinib group. Baseline demographics were balanced. The median follow-up period for overall survival (OS) was 18.1 months. The primary reason for treatment discontinuation in any group was disease progression. PFS as indicated by an independent review committee was significantly longer in the nivolumab plus cabozantinib group compared to the sunitinib group (median 16.6 months vs 8.2 months; hazard ratio [HR] 0.51, P < .001). The median OS was not reached for any group. Overall survival was longer in the nivolumab plus cabozantinib group compared to the sunitinib group (HR 0.60, 95% CI: 0.40-0.89; P = .001). The objective response rate was 55.7% with the nivolumab plus cabozantinib group versus 27.1% with sunitinib (P < .001). The complete response rate was 8% in the nivolumab plus cabozantinib group compared to 4.6% in the sunitinib group. The median time to response was 2.8 months with nivolumab plus cabozantinib and 4.2 months in the sunitinib group, while the median duration of response was 20.2 months and 11.5 months, respectively.

Nearly all patients (about 99% in each group) had an adverse event (AE). Hypertension was the most common side effect, with grade 3 or higher seen in 12.5% in the nivolumab plus cabzantinib group and 13.1% in the sunitinib group. Other grade 3 or higher side effects occurring in at least 10% of patients in any group were hyponatremia, diarrhea, palmar-plantar erythrodysesthesia, hypothyroidism, and fatigue. AEs of any cause leading to discontinuation of the therapy occurred in 19.7% in the nivolumab plus cabzantinib group vs 16.9% of the sunitinib group. One death was considered to be treatment-related (small intestinal perforation) in the nivolumab plus cabozantinib group vs 2 treatment-related deaths with sunitinib (pneumonia and respiratory distress). In the nivolumab plus cabozantinib group, 57% of the patients had a dose reduction of cabozantinib and 52% had a reduction in sunitinib dosage.

Using the Functional Assessment of Cancer Therapy-Kidney Symptoms Index, patients in the nivolumab plus cabozantinib group reported better health-related quality of life and less disease-related symptoms compared to the sunitinib group.

Commentary

The treatment landscape for frontline therapy for patients with advanced RCC has rapidly expanded over the last several years and has revolutionized cancer care. Ushered in by the results from the CheckMate 214 study highlighting the efficacy of dual checkpoint inhibition with nivolumab and ipilimumab in intermediate and poor risk patients, several subsequent trials have demonstrated improved outcomes with combination therapy with immune checkpoint inhibitors and tyrosine-kinase inhibitors (TKI). To date, data from Keynote-426 (pembrolizumab plus axitinib vs sunitinib), Javelin Renal 101 (avelumab plus axitinib vs sunitinib) and the CLEAR trial (lenvatinib plus pembrolizumab vs levatinib plus everolimus vs sunitinib) have demonstrated superiority of immune checkpoint inhibitor/TKI combinations over sunitinb in the first-line setting.^1-5

The current phase 3, CheckMate 9ER trial adds yet another dynamic option for patients with advanced clear cell RCC. While cross-trial comparisons are fraught with important caveats, the median PFS of almost 16.6 months and complete response rate of 8% the nivolumab plus cabozantinib group compares favorably with other combinations. Data from the CLEAR study with the combination of lenvatinib and pembrolizumab showed a complete response rate approaching 16%. Importantly, the current study highlights improved quality of life with the combination of cabozantinib and nivolumab compared to sunitinib alone adding to the efficacy and benefits of this combination treatment.

The selection of first line therapy for patients with advanced RCC should be always guided by individual patient characteristics, and any single immune checkpoint inhibitor/TKI combination is not “superior” to any other. Perhaps more importantly is developing an understanding of the overlapping toxicity profiles of checkpoint inhibitors and TKIs. Again, this trial results are consistent with prior studies in terms of the adverse event profile which were not trivial, and almost all patients (99%) experienced AEs. It is important for oncologists to understand the management of the toxicities with these combinations and dose reductions as appropriate. It is worth noting that 19% of patients with nivolumab plus cabozantinib received glucocorticoids for management of immune-related AEs.

While long-term follow-up data will be needed to further understand the durability of response to this combination, nivolumab-cabozantinib represents an exciting new option for patients with advanced clear cell RCC. As we continue to see improvement in outcomes in clear cell histology, further work must focus on optimization of therapy in non-clear cell RCC as this is a population that is not represented in these data sets. Furthermore, future efforts should begin to explore triplet combinations and biomarker driven patient selection for upfront therapy in ordercontinue to improve outcomes in patients with advanced RCC.

Applications for Clinical Practice

The combination of nivolumab plus cabozantinib adds to the growing list of highly active checkpoint inhibitor/TKI combinations for first-line treatment of advanced RCC. With significant higher response rates, improved outcomes, and improvement in the quality of life, this combination will add another standard treatment option for patients with previously untreated advanced RCC.

Study Overview

Objective. To evaluate the efficacy and safety of the combination of nivolumab plus cabozantinib as compared with sunitinib monotherapy in the treatment of previously untreated advanced renal cell carcinoma (RCC).

Design. Multicenter, international, open-label, randomized, phase 3 trial.

Intervention. Patients were randomized in a 1:1 fashion to 1 of 2 treatment arms:

• Arm A: Nivolumab intravenously 240 mg every 2 weeks plus cabozantinib orally 40 mg once daily.
• Arm B: Sunitinib orally 50 mg daily for 4 weeks, followed by 2 weeks off therapy (6-week cycle).

Randomization was stratified by the International Metastatic RCC Database Consortium prognostic risk score (low-, intermediate-, and high-risk). Treatment was continued until disease progression or development of unacceptable toxic side effects with a maximum of 2-year duration of Nivolumab therapy.

Settings and participants. Adults with previously untreated advanced RCC with a clear cell component were eligible for enrollment. Subjects were excluded if they had active central nervous system metastases or active autoimmune disease.

Main outcome measures. The primary outcome of this study was progression-free survival (PFS) as assessed by an independent review committee. Secondary endpoints included overall survival, objective response rate, safety, and PFS as assessed by investigators. All subgroup analyses were prespecified. Efficacy was assessed in the intention-to-treat population, including all patients who underwent randomization.

Main results. A total of 651 patients underwent randomization: 323 to the nivolumab plus cabozantinib group, and 328 to the sunitinib group. Baseline demographics were balanced. The median follow-up period for overall survival (OS) was 18.1 months. The primary reason for treatment discontinuation in any group was disease progression. PFS as indicated by an independent review committee was significantly longer in the nivolumab plus cabozantinib group compared to the sunitinib group (median 16.6 months vs 8.2 months; hazard ratio [HR] 0.51, P < .001). The median OS was not reached for any group. Overall survival was longer in the nivolumab plus cabozantinib group compared to the sunitinib group (HR 0.60, 95% CI: 0.40-0.89; P = .001). The objective response rate was 55.7% with the nivolumab plus cabozantinib group versus 27.1% with sunitinib (P < .001). The complete response rate was 8% in the nivolumab plus cabozantinib group compared to 4.6% in the sunitinib group. The median time to response was 2.8 months with nivolumab plus cabozantinib and 4.2 months in the sunitinib group, while the median duration of response was 20.2 months and 11.5 months, respectively.

Nearly all patients (about 99% in each group) had an adverse event (AE). Hypertension was the most common side effect, with grade 3 or higher seen in 12.5% in the nivolumab plus cabzantinib group and 13.1% in the sunitinib group. Other grade 3 or higher side effects occurring in at least 10% of patients in any group were hyponatremia, diarrhea, palmar-plantar erythrodysesthesia, hypothyroidism, and fatigue. AEs of any cause leading to discontinuation of the therapy occurred in 19.7% in the nivolumab plus cabzantinib group vs 16.9% of the sunitinib group. One death was considered to be treatment-related (small intestinal perforation) in the nivolumab plus cabozantinib group vs 2 treatment-related deaths with sunitinib (pneumonia and respiratory distress). In the nivolumab plus cabozantinib group, 57% of the patients had a dose reduction of cabozantinib and 52% had a reduction in sunitinib dosage.

Using the Functional Assessment of Cancer Therapy-Kidney Symptoms Index, patients in the nivolumab plus cabozantinib group reported better health-related quality of life and less disease-related symptoms compared to the sunitinib group.

Commentary

The treatment landscape for frontline therapy for patients with advanced RCC has rapidly expanded over the last several years and has revolutionized cancer care. Ushered in by the results from the CheckMate 214 study highlighting the efficacy of dual checkpoint inhibition with nivolumab and ipilimumab in intermediate and poor risk patients, several subsequent trials have demonstrated improved outcomes with combination therapy with immune checkpoint inhibitors and tyrosine-kinase inhibitors (TKI). To date, data from Keynote-426 (pembrolizumab plus axitinib vs sunitinib), Javelin Renal 101 (avelumab plus axitinib vs sunitinib) and the CLEAR trial (lenvatinib plus pembrolizumab vs levatinib plus everolimus vs sunitinib) have demonstrated superiority of immune checkpoint inhibitor/TKI combinations over sunitinb in the first-line setting.^1-5

The current phase 3, CheckMate 9ER trial adds yet another dynamic option for patients with advanced clear cell RCC. While cross-trial comparisons are fraught with important caveats, the median PFS of almost 16.6 months and complete response rate of 8% the nivolumab plus cabozantinib group compares favorably with other combinations. Data from the CLEAR study with the combination of lenvatinib and pembrolizumab showed a complete response rate approaching 16%. Importantly, the current study highlights improved quality of life with the combination of cabozantinib and nivolumab compared to sunitinib alone adding to the efficacy and benefits of this combination treatment.

The selection of first line therapy for patients with advanced RCC should be always guided by individual patient characteristics, and any single immune checkpoint inhibitor/TKI combination is not “superior” to any other. Perhaps more importantly is developing an understanding of the overlapping toxicity profiles of checkpoint inhibitors and TKIs. Again, this trial results are consistent with prior studies in terms of the adverse event profile which were not trivial, and almost all patients (99%) experienced AEs. It is important for oncologists to understand the management of the toxicities with these combinations and dose reductions as appropriate. It is worth noting that 19% of patients with nivolumab plus cabozantinib received glucocorticoids for management of immune-related AEs.

While long-term follow-up data will be needed to further understand the durability of response to this combination, nivolumab-cabozantinib represents an exciting new option for patients with advanced clear cell RCC. As we continue to see improvement in outcomes in clear cell histology, further work must focus on optimization of therapy in non-clear cell RCC as this is a population that is not represented in these data sets. Furthermore, future efforts should begin to explore triplet combinations and biomarker driven patient selection for upfront therapy in ordercontinue to improve outcomes in patients with advanced RCC.

Applications for Clinical Practice

The combination of nivolumab plus cabozantinib adds to the growing list of highly active checkpoint inhibitor/TKI combinations for first-line treatment of advanced RCC. With significant higher response rates, improved outcomes, and improvement in the quality of life, this combination will add another standard treatment option for patients with previously untreated advanced RCC.