Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.

When patients are admitted to the hospital, the focus for the first 24 hours is on the work-up: What do the data point values tell you about how sick this patient is, and what will they need to get better? While the goal for this information is to develop the appropriate treatment and management for the patient’s acute problem, it could be leveraged to help with other parts of the patient’s hospital stay as well. In particular, it could help avoid unnecessarily long stays in the hospital caused by patients’ waiting for a bed at a lower level of care.

Monisha Bhatia, a native of Nashville, Tenn., is a fourth-year medical student at Vanderbilt University in Nashville. She is hoping to pursue either a residency in internal medicine or a combined internal medicine/emergency medicine program. Prior to medical school, she completed a JD/MPH program at Boston University, and she hopes to use her legal training in working with regulatory authorities to improve access to health care for all Americans.

Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.

When patients are admitted to the hospital, the focus for the first 24 hours is on the work-up: What do the data point values tell you about how sick this patient is, and what will they need to get better? While the goal for this information is to develop the appropriate treatment and management for the patient’s acute problem, it could be leveraged to help with other parts of the patient’s hospital stay as well. In particular, it could help avoid unnecessarily long stays in the hospital caused by patients’ waiting for a bed at a lower level of care.

Monisha Bhatia, a native of Nashville, Tenn., is a fourth-year medical student at Vanderbilt University in Nashville. She is hoping to pursue either a residency in internal medicine or a combined internal medicine/emergency medicine program. Prior to medical school, she completed a JD/MPH program at Boston University, and she hopes to use her legal training in working with regulatory authorities to improve access to health care for all Americans.

Editor’s Note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experience on a monthly basis.

When patients are admitted to the hospital, the focus for the first 24 hours is on the work-up: What do the data point values tell you about how sick this patient is, and what will they need to get better? While the goal for this information is to develop the appropriate treatment and management for the patient’s acute problem, it could be leveraged to help with other parts of the patient’s hospital stay as well. In particular, it could help avoid unnecessarily long stays in the hospital caused by patients’ waiting for a bed at a lower level of care.

Monisha Bhatia, a native of Nashville, Tenn., is a fourth-year medical student at Vanderbilt University in Nashville. She is hoping to pursue either a residency in internal medicine or a combined internal medicine/emergency medicine program. Prior to medical school, she completed a JD/MPH program at Boston University, and she hopes to use her legal training in working with regulatory authorities to improve access to health care for all Americans.

The Food and Drug Administration has approved gemtuzumab ozogamicin (Mylotarg) for the treatment of newly diagnosed CD33-positive acute myeloid leukemia in adults, according to a press release.

Approval was based on results from three clinical trials. In the first, newly diagnosed AML patients who received gemtuzumab ozogamicin plus chemotherapy had significantly longer event-free survival than did patients who received chemotherapy alone. In a second trial, patients who received gemtuzumab ozogamicin alone had better overall survival compared to those who received only best supportive care. In the third clinical trial, 26% of patients who had experienced a relapse and received gemtuzumab ozogamicin experienced a remission.

[email protected]

The Food and Drug Administration has approved gemtuzumab ozogamicin (Mylotarg) for the treatment of newly diagnosed CD33-positive acute myeloid leukemia in adults, according to a press release.

Approval was based on results from three clinical trials. In the first, newly diagnosed AML patients who received gemtuzumab ozogamicin plus chemotherapy had significantly longer event-free survival than did patients who received chemotherapy alone. In a second trial, patients who received gemtuzumab ozogamicin alone had better overall survival compared to those who received only best supportive care. In the third clinical trial, 26% of patients who had experienced a relapse and received gemtuzumab ozogamicin experienced a remission.

[email protected]

The Food and Drug Administration has approved gemtuzumab ozogamicin (Mylotarg) for the treatment of newly diagnosed CD33-positive acute myeloid leukemia in adults, according to a press release.

Approval was based on results from three clinical trials. In the first, newly diagnosed AML patients who received gemtuzumab ozogamicin plus chemotherapy had significantly longer event-free survival than did patients who received chemotherapy alone. In a second trial, patients who received gemtuzumab ozogamicin alone had better overall survival compared to those who received only best supportive care. In the third clinical trial, 26% of patients who had experienced a relapse and received gemtuzumab ozogamicin experienced a remission.

[email protected]

Physicians will likely see a 0.31% uptick in their Medicare payments in 2018 and not the 0.5% promised in the Medicare Access and CHIP Reauthorization Act.

Officials at the Centers for Medicare and Medicaid Services were not able to find adequate funding in so-called misvalued codes to back the larger increase, as required by law, according to the proposed Medicare physician fee schedule for 2018.

TheaDesign/Thinkstock

[email protected]

Physicians will likely see a 0.31% uptick in their Medicare payments in 2018 and not the 0.5% promised in the Medicare Access and CHIP Reauthorization Act.

Officials at the Centers for Medicare and Medicaid Services were not able to find adequate funding in so-called misvalued codes to back the larger increase, as required by law, according to the proposed Medicare physician fee schedule for 2018.

TheaDesign/Thinkstock

[email protected]

Physicians will likely see a 0.31% uptick in their Medicare payments in 2018 and not the 0.5% promised in the Medicare Access and CHIP Reauthorization Act.

Officials at the Centers for Medicare and Medicaid Services were not able to find adequate funding in so-called misvalued codes to back the larger increase, as required by law, according to the proposed Medicare physician fee schedule for 2018.

TheaDesign/Thinkstock

[email protected]

In the early 1970s, clindamycin had only been on the market for a few years when patients taking the antibiotic began to present with diarrhea and associated colitis. Initial attempts to culture a pathologic organism were unsuccessful, so other possible pathophysiologic mechanisms, including medication toxicity, altered bacterial flora, or the emergence of a new bacterial or viral pathogen were considered. Patients were initially given treatments similar to those for ulcerative colitis, with systemic and topical steroids and colectomy. Several years later, Clostridium difficile infection (CDI) was identified as the culprit, and these presentations became increasingly common in U.S. hospitals, and later in community settings.

Incidentally, the organism had been discovered years earlier, in 1935, by a group of scientists studying normal bacterial flora in neonates, but it was not known to be pathogenic in adults. By 2007, CDI had become the most common cause of health care–associated infection in U.S. hospitals. This prompted the Centers for Disease Control and Prevention to begin active population- and laboratory-based surveillance for C. difficile through its Emerging Infections Program (EIP) with the goal of more accurately assessing disease burden, incidence, recurrence, and mortality by capturing data across the spectrum of health care delivery settings. The April 2015 issue of GI & Hepatology News highlighted a report of 2011 CDC data from 10 EIP sites (N Engl J Med. 372;9:825-34), demonstrating that CDI was responsible for nearly half a million infections and 29,000 deaths in that year across sites, with the hypervirulent NAP1 strain found to be more prevalent among health care–associated than community-associated infections.

Treatment of CDI continues to evolve. With increased use of fecal microbiota transplantation, emerging evidence regarding the efficacy of other novel therapies such as the monoclonal antibodies actoxumab and bezlotoxumab (providing passive immunity to toxins A and B, respectively), and development of preventive vaccines (currently in phase 2 trials), there is hope on the horizon of being able to improve patient outcomes and reduce the burden of CDI on the health care system.

Megan A. Adams, MD, JD, MSc, is a clinical lecturer in the division of gastroenterology at the University of Michigan, a gastroenterologist at the Ann Arbor, Mich., VA, and an investigator in the VA Ann Arbor Center for Clinical Management Research. She is an associate editor of GI & Hepatology News.

In the early 1970s, clindamycin had only been on the market for a few years when patients taking the antibiotic began to present with diarrhea and associated colitis. Initial attempts to culture a pathologic organism were unsuccessful, so other possible pathophysiologic mechanisms, including medication toxicity, altered bacterial flora, or the emergence of a new bacterial or viral pathogen were considered. Patients were initially given treatments similar to those for ulcerative colitis, with systemic and topical steroids and colectomy. Several years later, Clostridium difficile infection (CDI) was identified as the culprit, and these presentations became increasingly common in U.S. hospitals, and later in community settings.

Incidentally, the organism had been discovered years earlier, in 1935, by a group of scientists studying normal bacterial flora in neonates, but it was not known to be pathogenic in adults. By 2007, CDI had become the most common cause of health care–associated infection in U.S. hospitals. This prompted the Centers for Disease Control and Prevention to begin active population- and laboratory-based surveillance for C. difficile through its Emerging Infections Program (EIP) with the goal of more accurately assessing disease burden, incidence, recurrence, and mortality by capturing data across the spectrum of health care delivery settings. The April 2015 issue of GI & Hepatology News highlighted a report of 2011 CDC data from 10 EIP sites (N Engl J Med. 372;9:825-34), demonstrating that CDI was responsible for nearly half a million infections and 29,000 deaths in that year across sites, with the hypervirulent NAP1 strain found to be more prevalent among health care–associated than community-associated infections.

Treatment of CDI continues to evolve. With increased use of fecal microbiota transplantation, emerging evidence regarding the efficacy of other novel therapies such as the monoclonal antibodies actoxumab and bezlotoxumab (providing passive immunity to toxins A and B, respectively), and development of preventive vaccines (currently in phase 2 trials), there is hope on the horizon of being able to improve patient outcomes and reduce the burden of CDI on the health care system.

Megan A. Adams, MD, JD, MSc, is a clinical lecturer in the division of gastroenterology at the University of Michigan, a gastroenterologist at the Ann Arbor, Mich., VA, and an investigator in the VA Ann Arbor Center for Clinical Management Research. She is an associate editor of GI & Hepatology News.

In the early 1970s, clindamycin had only been on the market for a few years when patients taking the antibiotic began to present with diarrhea and associated colitis. Initial attempts to culture a pathologic organism were unsuccessful, so other possible pathophysiologic mechanisms, including medication toxicity, altered bacterial flora, or the emergence of a new bacterial or viral pathogen were considered. Patients were initially given treatments similar to those for ulcerative colitis, with systemic and topical steroids and colectomy. Several years later, Clostridium difficile infection (CDI) was identified as the culprit, and these presentations became increasingly common in U.S. hospitals, and later in community settings.

Incidentally, the organism had been discovered years earlier, in 1935, by a group of scientists studying normal bacterial flora in neonates, but it was not known to be pathogenic in adults. By 2007, CDI had become the most common cause of health care–associated infection in U.S. hospitals. This prompted the Centers for Disease Control and Prevention to begin active population- and laboratory-based surveillance for C. difficile through its Emerging Infections Program (EIP) with the goal of more accurately assessing disease burden, incidence, recurrence, and mortality by capturing data across the spectrum of health care delivery settings. The April 2015 issue of GI & Hepatology News highlighted a report of 2011 CDC data from 10 EIP sites (N Engl J Med. 372;9:825-34), demonstrating that CDI was responsible for nearly half a million infections and 29,000 deaths in that year across sites, with the hypervirulent NAP1 strain found to be more prevalent among health care–associated than community-associated infections.

Treatment of CDI continues to evolve. With increased use of fecal microbiota transplantation, emerging evidence regarding the efficacy of other novel therapies such as the monoclonal antibodies actoxumab and bezlotoxumab (providing passive immunity to toxins A and B, respectively), and development of preventive vaccines (currently in phase 2 trials), there is hope on the horizon of being able to improve patient outcomes and reduce the burden of CDI on the health care system.

Megan A. Adams, MD, JD, MSc, is a clinical lecturer in the division of gastroenterology at the University of Michigan, a gastroenterologist at the Ann Arbor, Mich., VA, and an investigator in the VA Ann Arbor Center for Clinical Management Research. She is an associate editor of GI & Hepatology News.

Fatigue is the most common clinical symptom of anemia and is a significant concern to patients.^1,2 In ambulatory patients, lower hemoglobin (Hb) concentration is associated with increased fatigue.^2,3 Accordingly, therapies that treat anemia by increasing Hb concentration, such as erythropoiesis stimulating agents,^4-7 often use fatigue as an outcome measure.

In hospitalized patients, transfusion of red blood cell increases Hb concentration and is the primary treatment for anemia. However, the extent to which transfusion and changes in Hb concentration affect hospitalized patients’ fatigue levels is not well established. Guidelines support transfusing patients with symptoms of anemia, such as fatigue, on the assumption that the increased oxygen delivery will improve the symptoms of anemia. While transfusion studies in hospitalized patients have consistently reported that transfusion at lower or “restrictive” Hb concentrations is safe compared with transfusion at higher Hb concentrations,^8-10 these studies have mainly used cardiac events and mortality as outcomes rather than patient symptoms, such as fatigue. Nevertheless, they have resulted in hospitals increasingly adopting restrictive transfusion policies that discourage transfusion at higher Hb levels.^11,12 Consequently, the rate of transfusion in hospitalized patients has decreased,¹³ raising questions of whether some patients with lower Hb concentrations may experience increased fatigue as a result of restrictive transfusion policies. Fatigue among hospitalized patients is important not only because it is an adverse symptom but because it may result in decreased activity levels, deconditioning, and losses in functional status.^14,15While the effect of alternative transfusion policies on fatigue in hospitalized patients could be answered by a randomized clinical trial using fatigue and functional status as outcomes, an important first step is to assess whether the Hb concentration of hospitalized patients is associated with their fatigue level during hospitalization. Because hospitalized patients often have acute illnesses that can cause fatigue in and of themselves, it is possible that anemia is not associated with fatigue in hospitalized patients despite anemia’s association with fatigue in ambulatory patients. Additionally, Hb concentration varies during hospitalization,¹⁶ raising the question of what measures of Hb during hospitalization might be most associated with anemia-related fatigue.

The objective of this study is to explore multiple Hb measures in hospitalized medical patients with anemia and test whether any of these Hb measures are associated with patients’ fatigue level.

Study Design

We performed a prospective, observational study of hospitalized patients with anemia on the general medicine services at The University of Chicago Medical Center (UCMC). The institutional review board approved the study procedures, and all study subjects provided informed consent.

Study Eligibility

Between April 2014 and June 2015, all general medicine inpatients were approached for written consent for The University of Chicago Hospitalist Project,¹⁷ a research infrastructure at UCMC. Among patients consenting to participate in the Hospitalist Project, patients were eligible if they had Hb <9 g/dL at any point during their hospitalization and were age ≥50 years. Hb concentration of <9 g/dL was chosen to include the range of Hb values covered by most restrictive transfusion policies.^8-10,18 Age ≥50 years was an inclusion criteria because anemia is more strongly associated with poor outcomes, including functional impairment, among older patients compared with younger patients.^14,19-21 If patients were not eligible for inclusion at the time of consent for the Hospitalist Project, their Hb values were reviewed twice daily until hospital discharge to assess if their Hb was <9 g/dL. Proxies were sought to answer questions for patients who failed the Short Portable Mental Status Questionnaire.²²

Patient Demographic Data Collection

Research assistants abstracted patient age and sex from the electronic health record (EHR), and asked patients to self-identify their race. The individual comorbidities included as part of the Charlson Comorbidity Index were identified using International Classification of Diseases, 9th Revision codes from hospital administrative data for each encounter and specifically included the following: myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, liver disease, diabetes, hemiplegia and/or paraplegia, renal disease, cancer, and human immunodeficiency virus/acquired immunodeficiency syndrome.²³ We also used Healthcare Cost and Utilization Project (www.hcup-us.ahrq.gov/toolssoftware/ccs/ccs.jsp) diagnosis categories to identify whether patients had sickle cell (SC) anemia, gastrointestinal bleeding (GIB), or a depressive disorder (DD) because these conditions are associated with anemia (SC and GIB) and fatigue (DD).²⁴

Measuring Anemia

Hb measures were available only when hospital providers ordered them as part of routine practice. The first Hb concentration <9 g/dL during a patient’s hospitalization, which made them eligible for study participation, was obtained through manual review of the EHR. All additional Hb values during the patient’s hospitalization were obtained from the hospital’s administrative data mart. All Hb values collected for each patient during the hospitalization were used to calculate summary measures of Hb during the hospitalization, including the mean Hb, median Hb, minimum Hb, maximum Hb, admission (first recorded) Hb, and discharge (last recorded) Hb. Hb measures were analyzed both as a continuous variable and as a categorical variable created by dividing the continuous Hb measures into integer ranges of 3 groups of approximately the same size.

Measuring Fatigue

Our primary outcome was patients’ level of fatigue reported during hospitalization, measured using the Functional Assessment of Chronic Illness Therapy (FACIT)-Anemia questionnaire. Fatigue was measured using a 13-question fatigue subscale,^1,2,25 which measures fatigue within the past 7 days. Scores on the fatigue subscale range from 0 to 52, with lower scores reflecting greater levels of fatigue. As soon as patients met the eligibility criteria for study participation during their hospitalization (age ≥50 years and Hb <9 g/dL), they were approached to answer the FACIT questions. Values for missing data in the fatigue subscale for individual subjects were filled in using a prorated score from their answered questions as long as >50% of the items in the fatigue subscale were answered, in accordance with recommendations for addressing missing data in the FACIT.²⁶ Fatigue was analyzed as a continuous variable and as a dichotomous variable created by dividing the sample into high (FACIT <27) and low (FACIT ≥27) levels of fatigue based on the median FACIT score of the population. Previous literature has shown a FACIT fatigue subscale score between 23 and 26 to be associated with an Eastern Cooperative Oncology Group (ECOG)²⁷ C Performance Status rating of 2 to 3³ compared to scores ≥27.

Statistical Analysis

Statistical analysis was performed using Stata statistical software (StataCorp, College Station, TX). Descriptive statistics were used to characterize patient demographics. Analysis of variance was used to test for differences in the mean fatigue levels across Hb measures. χ² tests were performed to test for associations between high fatigue levels and the Hb measures. Multivariable analysis, including both linear and logistic regression models, were used to test the association of Hb concentration and fatigue. P values <0.05 using a 2-tailed test were deemed statistically significant.

Patient Characteristics

During the study period, 8559 patients were admitted to the general medicine service. Of those, 5073 (59%) consented for participation in the Hospitalist Project, and 3670 (72%) completed the Hospitalist Project inpatient interview. Of these patients, 1292 (35%) had Hb <9 g/dL, and 784 (61%) were 50 years or older and completed the FACIT questionnaire.

Table 1 reports the demographic characteristics and comorbidities for the sample, the mean (standard deviation [SD]) for the 6 Hb measures, and mean (SD) and median FACIT scores.

Bivariate Association of Fatigue and Hb

Categorizing patients into low, middle, or high Hb for each of the 6 Hb measures, minimum Hb was strongly associated with fatigue, with a weaker association for mean Hb and no statistically significant association for the other measures.

Minimum Hb. Patients with a minimum Hb <7 g/dL and patients with Hb 7-8 g/dL had higher fatigue levels (FACIT = 25 for each) than patients with a minimum Hb ≥8 g/dL (FACIT = 29; P < 0.001; Table 2). When excluding patients with SC and/or GIB because their average minimum Hb differed from the average minimum Hb of the full population (P < 0.001), patients with a minimum Hb <7 g/dL or 7-8 g/dL had even higher fatigue levels (FACIT = 23 and FACIT = 24, respectively), with no change in the fatigue level of patients with a minimum Hb ≥8 g/dL (FACIT = 29; P < 0.001; Table 2). Lower minimum Hb continued to be associated with higher fatigue levels when analyzed in 0.5 g/dL increments (Figure).

Linear Regression of Fatigue on Hb

In linear regression models, minimum Hb consistently predicted patient fatigue, mean Hb had a less robust association with fatigue, and the other Hb measures were not associated with patient fatigue. Increases in minimum Hb (analyzed as a continuous variable) were associated with reduced fatigue (higher FACIT score; β = 1.4; P = 0.005). In models in which minimum Hb was a categorical variable, patients with a minimum Hb of <7 g/dL or 7-8 g/dL had greater fatigue (lower FACIT score) than patients whose minimum Hb was ≥8 g/dL (Hb <7 g/dL: β = −4.2; P ≤ 0.001; Hb 7-8 g/dL: β = −4.1; P < 0.001). These results control for patients’ age, sex, individual comorbidities, and whether their minimum Hb occurred before or after the measurement of fatigue during hospitalization (Model 1), and the results are unchanged when also controlling for the number of Hb laboratory draws patients had during their hospitalization (Model 2; Table 3). In a stratified analysis excluding patients with either SC and/or GIB, changes in minimum Hb were associated with larger changes in patient fatigue levels (Supplemental Table 1). We also stratified our analysis to include only patients whose minimum Hb occurred before the measurement of their fatigue level during hospitalization to avoid a spurious association of fatigue with minimum Hb occurring after fatigue was measured. In both Models 1 and 2, minimum Hb remained a predictor of patients’ fatigue levels with similar effect sizes, although in Model 2, the results did not quite reach a statistically significant level, in part due to larger confidence intervals from the smaller sample size of this stratified analysis (Supplemental Table 2a). We further stratified this analysis to include only patients whose transfusion, if they received one, occurred after their minimum Hb and the measurement of their fatigue level to account for the possibility that a transfusion could affect the fatigue level patients report. In this analysis, most of the estimates of the effect of minimum Hb on fatigue were larger than those seen when only analyzing patients whose minimum Hb occurred before the measurement of their fatigue level, although again, the smaller sample size of this additional stratified analysis does produce larger confidence intervals for these estimates (Supplemental Table 2b).

Logistic Regression of High Fatigue Level on Hb

Using logistic regression, minimum Hb analyzed as a categorical variable predicted increased odds of a high fatigue level. Patients with a minimum Hb <7 g/dL were 50% (odds ratio [OR] = 1.5; P = 0.03) more likely to have high fatigue and patients with a minimum Hb 7-8 g/dL were 90% (OR = 1.9; P < 0.001) more likely to have high fatigue compared with patients with a minimum Hb ≥8 g/dL in Model 1. These results were similar in Model 2, although the effect was only statistically significant in the 7-8 g/dL Hb group (Table 3). When excluding SC and/or GIB patients, the odds of having high fatigue as minimum Hb decreased were the same or higher for both models compared to the full population of patients. However, again, in Model 2, the effect was only statistically significant in the 7-8 g/dL Hb group (Supplemental Table 1).

Patients with a mean Hb <8 g/dL were 20% to 30% more likely to have high fatigue and patients with mean Hb 8-9 g/dL were 50% more likely to have high fatigue compared with patients with a mean Hb ≥9 g/dL, but the effects were only statistically significant for patients with a mean Hb 8-9 g/dL in both Models 1 and 2 (Table 3). These results were similar when excluding patients with SC and/or GIB, but they were only significant for patients with a mean Hb 8-9 g/dL in Model 1 and patients with a mean Hb <8 g/dL in the Model 2 (Supplemental Table 3).

These results demonstrate that minimum Hb during hospitalization is associated with fatigue in hospitalized patients age ≥50 years, and the association is stronger among patients without SC and/or GIB as comorbidities. The analysis of Hb as a continuous and categorical variable and the use of both linear and logistic regression models support the robustness of these associations and illuminate their clinical significance. For example, in linear regression with minimum Hb a continuous variable, the coefficient of 1.4 suggests that an increase of 2 g/dL in Hb, as might be expected from transfusion of 2 units of red blood cells, would be associated with about a 3-point improvement in fatigue. Additionally, as a categorical variable, a minimum Hb ≥8 g/dL compared with a minimum Hb <7 g/dL or 7-8 g/dL is associated with a 3- to 4-point improvement in fatigue. Previous literature suggests that a difference of 3 in the FACIT score is the minimum clinically important difference in fatigue,³ and changes in minimum Hb in either model predict changes in fatigue that are in the range of potential clinical significance.

The clinical significance of the findings is also reflected in the results of the logistic regressions, which may be mapped to potential effects on functional status. Specifically, the odds of having a high fatigue level (FACIT <27) increase 90% for persons with a minimum Hb 7–8 g/dL compared with persons with a minimum Hb ≥8 g/dL. For persons with a minimum Hb <7 g/dL, point estimates suggest a smaller (50%) increase in the odds of high fatigue, but the 95% confidence interval overlaps heavily with the estimate of patients whose minimum Hb is 7-8 g/dL. While it might be expected that patients with a minimum Hb <7 g/dL have greater levels of fatigue compared with patients with a minimum Hb 7-8 g/dL, we did not observe such a pattern. One reason may be that the confidence intervals of our estimated effects are wide enough that we cannot exclude such a pattern. Another possible explanation is that in both groups, the fatigue levels are sufficiently severe, such that the difference in their fatigue levels may not be clinically meaningful. For example, a FACIT score of 23 to 26 has been shown to be associated with an ECOG performance status of 2 to 3, requiring bed rest for at least part of the day.³ Therefore, patients with a minimum Hb 7-8 g/dL (mean FACIT score = 24; Table 2) or a minimum Hb of <7 g/dL (mean FACIT score = 23; Table 2) are already functionally limited to the point of being partially bed bound, such that further decreases in their Hb may not produce additional fatigue in part because they reduce their activity sufficiently to prevent an increase in fatigue. In such cases, the potential benefits of increased Hb may be better assessed by measuring fatigue in response to a specific and provoked activity level, a concept known as fatigability.²⁰

That minimum Hb is more strongly associated with fatigue than any other measure of Hb during hospitalization may not be surprising. Mean, median, maximum, and discharge Hb may all be affected by transfusion during hospitalization that could affect fatigue. Admission Hb may not reflect true oxygen-carrying capacity because of hemoconcentration.

The association between Hb and fatigue in hospitalized patients is important because increased fatigue could contribute to slower clinical recovery in hospitalized patients. Additionally, increased fatigue during hospitalization and at hospital discharge could exacerbate the known deleterious consequences of fatigue on patients and their health outcomes^14,15 after hospital discharge. Although one previous study, the Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS)⁸ trial, did not report differences in patients’ fatigue levels at 30 and 60 days postdischarge when transfused at restrictive (8 g/dL) compared with liberal (10 g/dL) Hb thresholds, confidence in the validity of this finding is reduced by the fact that more than half of the patients were lost to follow-up at the 30- and 60-day time points. Further, patients in the restrictive transfusion arm of FOCUS were transfused to maintain Hb levels at or above 8 g/dL. This transfusion threshold of 8 g/dL may have mitigated the high levels of fatigue that are seen in our study when patients’ Hb drops below 8 g/dL, and maintaining a Hb level of 7 g/dL is now the standard of care in stable hospitalized patients. Lastly, FOCUS was limited to postoperative hip fracture patients, and the generalizability of FOCUS to hospitalized medicine patients with anemia is limited.

Therefore, our results support guideline suggestions that practitioners incorporate the presence of patient symptoms such as fatigue into transfusion decisions, particularly if patients’ Hb is <8 g/dL.¹⁸ Though reasonable, the suggestion to incorporate symptoms such as fatigue into transfusion decisions has not been strongly supported by evidence so far, and it may often be neglected in practice. Definitive evidence to support such recommendations would benefit from study through an optimal trial¹⁸ that incorporates symptoms into decision making. Our findings add support for a study of transfusion strategies that incorporates patients’ fatigue level in addition to Hb concentration.

This study has several limitations. Although our sample size is large and includes patients with a range of comorbidities that we believe are representative of hospitalized general medicine patients, as a single-center, observational study, our results may not be generalizable to other centers. Additionally, although these data support a reliable association between hospitalized patients’ minimum Hb and fatigue level, the observational design of this study cannot prove that this relationship is causal. Also, patients’ Hb values were measured at the discretion of their clinician, and therefore, the measures of Hb were not uniformly measured for participating patients. In addition, fatigue was only measured at one time point during a patient’s hospitalization, and it is possible that patients’ fatigue levels change during hospitalization in relation to variables we did not consider. Finally, our study was not designed to assess the association of Hb with longer-term functional outcomes, which may be of greater concern than fatigue.

In hospitalized patients ≥50 years old, minimum Hb is reliably associated with patients’ fatigue level. Patients whose minimum Hb is <8 g/dL experience higher fatigue levels compared to patients whose minimum Hb is ≥8 g/dL. Additional studies are warranted to understand if patients may benefit from improved fatigue levels by correcting their anemia through transfusion.

Fatigue is the most common clinical symptom of anemia and is a significant concern to patients.^1,2 In ambulatory patients, lower hemoglobin (Hb) concentration is associated with increased fatigue.^2,3 Accordingly, therapies that treat anemia by increasing Hb concentration, such as erythropoiesis stimulating agents,^4-7 often use fatigue as an outcome measure.

In hospitalized patients, transfusion of red blood cell increases Hb concentration and is the primary treatment for anemia. However, the extent to which transfusion and changes in Hb concentration affect hospitalized patients’ fatigue levels is not well established. Guidelines support transfusing patients with symptoms of anemia, such as fatigue, on the assumption that the increased oxygen delivery will improve the symptoms of anemia. While transfusion studies in hospitalized patients have consistently reported that transfusion at lower or “restrictive” Hb concentrations is safe compared with transfusion at higher Hb concentrations,^8-10 these studies have mainly used cardiac events and mortality as outcomes rather than patient symptoms, such as fatigue. Nevertheless, they have resulted in hospitals increasingly adopting restrictive transfusion policies that discourage transfusion at higher Hb levels.^11,12 Consequently, the rate of transfusion in hospitalized patients has decreased,¹³ raising questions of whether some patients with lower Hb concentrations may experience increased fatigue as a result of restrictive transfusion policies. Fatigue among hospitalized patients is important not only because it is an adverse symptom but because it may result in decreased activity levels, deconditioning, and losses in functional status.^14,15While the effect of alternative transfusion policies on fatigue in hospitalized patients could be answered by a randomized clinical trial using fatigue and functional status as outcomes, an important first step is to assess whether the Hb concentration of hospitalized patients is associated with their fatigue level during hospitalization. Because hospitalized patients often have acute illnesses that can cause fatigue in and of themselves, it is possible that anemia is not associated with fatigue in hospitalized patients despite anemia’s association with fatigue in ambulatory patients. Additionally, Hb concentration varies during hospitalization,¹⁶ raising the question of what measures of Hb during hospitalization might be most associated with anemia-related fatigue.

The objective of this study is to explore multiple Hb measures in hospitalized medical patients with anemia and test whether any of these Hb measures are associated with patients’ fatigue level.

Study Design

We performed a prospective, observational study of hospitalized patients with anemia on the general medicine services at The University of Chicago Medical Center (UCMC). The institutional review board approved the study procedures, and all study subjects provided informed consent.

Study Eligibility

Between April 2014 and June 2015, all general medicine inpatients were approached for written consent for The University of Chicago Hospitalist Project,¹⁷ a research infrastructure at UCMC. Among patients consenting to participate in the Hospitalist Project, patients were eligible if they had Hb <9 g/dL at any point during their hospitalization and were age ≥50 years. Hb concentration of <9 g/dL was chosen to include the range of Hb values covered by most restrictive transfusion policies.^8-10,18 Age ≥50 years was an inclusion criteria because anemia is more strongly associated with poor outcomes, including functional impairment, among older patients compared with younger patients.^14,19-21 If patients were not eligible for inclusion at the time of consent for the Hospitalist Project, their Hb values were reviewed twice daily until hospital discharge to assess if their Hb was <9 g/dL. Proxies were sought to answer questions for patients who failed the Short Portable Mental Status Questionnaire.²²

Patient Demographic Data Collection

Research assistants abstracted patient age and sex from the electronic health record (EHR), and asked patients to self-identify their race. The individual comorbidities included as part of the Charlson Comorbidity Index were identified using International Classification of Diseases, 9th Revision codes from hospital administrative data for each encounter and specifically included the following: myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, liver disease, diabetes, hemiplegia and/or paraplegia, renal disease, cancer, and human immunodeficiency virus/acquired immunodeficiency syndrome.²³ We also used Healthcare Cost and Utilization Project (www.hcup-us.ahrq.gov/toolssoftware/ccs/ccs.jsp) diagnosis categories to identify whether patients had sickle cell (SC) anemia, gastrointestinal bleeding (GIB), or a depressive disorder (DD) because these conditions are associated with anemia (SC and GIB) and fatigue (DD).²⁴

Measuring Anemia

Hb measures were available only when hospital providers ordered them as part of routine practice. The first Hb concentration <9 g/dL during a patient’s hospitalization, which made them eligible for study participation, was obtained through manual review of the EHR. All additional Hb values during the patient’s hospitalization were obtained from the hospital’s administrative data mart. All Hb values collected for each patient during the hospitalization were used to calculate summary measures of Hb during the hospitalization, including the mean Hb, median Hb, minimum Hb, maximum Hb, admission (first recorded) Hb, and discharge (last recorded) Hb. Hb measures were analyzed both as a continuous variable and as a categorical variable created by dividing the continuous Hb measures into integer ranges of 3 groups of approximately the same size.

Measuring Fatigue

Our primary outcome was patients’ level of fatigue reported during hospitalization, measured using the Functional Assessment of Chronic Illness Therapy (FACIT)-Anemia questionnaire. Fatigue was measured using a 13-question fatigue subscale,^1,2,25 which measures fatigue within the past 7 days. Scores on the fatigue subscale range from 0 to 52, with lower scores reflecting greater levels of fatigue. As soon as patients met the eligibility criteria for study participation during their hospitalization (age ≥50 years and Hb <9 g/dL), they were approached to answer the FACIT questions. Values for missing data in the fatigue subscale for individual subjects were filled in using a prorated score from their answered questions as long as >50% of the items in the fatigue subscale were answered, in accordance with recommendations for addressing missing data in the FACIT.²⁶ Fatigue was analyzed as a continuous variable and as a dichotomous variable created by dividing the sample into high (FACIT <27) and low (FACIT ≥27) levels of fatigue based on the median FACIT score of the population. Previous literature has shown a FACIT fatigue subscale score between 23 and 26 to be associated with an Eastern Cooperative Oncology Group (ECOG)²⁷ C Performance Status rating of 2 to 3³ compared to scores ≥27.

Statistical Analysis

Statistical analysis was performed using Stata statistical software (StataCorp, College Station, TX). Descriptive statistics were used to characterize patient demographics. Analysis of variance was used to test for differences in the mean fatigue levels across Hb measures. χ² tests were performed to test for associations between high fatigue levels and the Hb measures. Multivariable analysis, including both linear and logistic regression models, were used to test the association of Hb concentration and fatigue. P values <0.05 using a 2-tailed test were deemed statistically significant.

Patient Characteristics

During the study period, 8559 patients were admitted to the general medicine service. Of those, 5073 (59%) consented for participation in the Hospitalist Project, and 3670 (72%) completed the Hospitalist Project inpatient interview. Of these patients, 1292 (35%) had Hb <9 g/dL, and 784 (61%) were 50 years or older and completed the FACIT questionnaire.

Table 1 reports the demographic characteristics and comorbidities for the sample, the mean (standard deviation [SD]) for the 6 Hb measures, and mean (SD) and median FACIT scores.

Bivariate Association of Fatigue and Hb

Categorizing patients into low, middle, or high Hb for each of the 6 Hb measures, minimum Hb was strongly associated with fatigue, with a weaker association for mean Hb and no statistically significant association for the other measures.

Minimum Hb. Patients with a minimum Hb <7 g/dL and patients with Hb 7-8 g/dL had higher fatigue levels (FACIT = 25 for each) than patients with a minimum Hb ≥8 g/dL (FACIT = 29; P < 0.001; Table 2). When excluding patients with SC and/or GIB because their average minimum Hb differed from the average minimum Hb of the full population (P < 0.001), patients with a minimum Hb <7 g/dL or 7-8 g/dL had even higher fatigue levels (FACIT = 23 and FACIT = 24, respectively), with no change in the fatigue level of patients with a minimum Hb ≥8 g/dL (FACIT = 29; P < 0.001; Table 2). Lower minimum Hb continued to be associated with higher fatigue levels when analyzed in 0.5 g/dL increments (Figure).

Linear Regression of Fatigue on Hb

In linear regression models, minimum Hb consistently predicted patient fatigue, mean Hb had a less robust association with fatigue, and the other Hb measures were not associated with patient fatigue. Increases in minimum Hb (analyzed as a continuous variable) were associated with reduced fatigue (higher FACIT score; β = 1.4; P = 0.005). In models in which minimum Hb was a categorical variable, patients with a minimum Hb of <7 g/dL or 7-8 g/dL had greater fatigue (lower FACIT score) than patients whose minimum Hb was ≥8 g/dL (Hb <7 g/dL: β = −4.2; P ≤ 0.001; Hb 7-8 g/dL: β = −4.1; P < 0.001). These results control for patients’ age, sex, individual comorbidities, and whether their minimum Hb occurred before or after the measurement of fatigue during hospitalization (Model 1), and the results are unchanged when also controlling for the number of Hb laboratory draws patients had during their hospitalization (Model 2; Table 3). In a stratified analysis excluding patients with either SC and/or GIB, changes in minimum Hb were associated with larger changes in patient fatigue levels (Supplemental Table 1). We also stratified our analysis to include only patients whose minimum Hb occurred before the measurement of their fatigue level during hospitalization to avoid a spurious association of fatigue with minimum Hb occurring after fatigue was measured. In both Models 1 and 2, minimum Hb remained a predictor of patients’ fatigue levels with similar effect sizes, although in Model 2, the results did not quite reach a statistically significant level, in part due to larger confidence intervals from the smaller sample size of this stratified analysis (Supplemental Table 2a). We further stratified this analysis to include only patients whose transfusion, if they received one, occurred after their minimum Hb and the measurement of their fatigue level to account for the possibility that a transfusion could affect the fatigue level patients report. In this analysis, most of the estimates of the effect of minimum Hb on fatigue were larger than those seen when only analyzing patients whose minimum Hb occurred before the measurement of their fatigue level, although again, the smaller sample size of this additional stratified analysis does produce larger confidence intervals for these estimates (Supplemental Table 2b).

Logistic Regression of High Fatigue Level on Hb

Using logistic regression, minimum Hb analyzed as a categorical variable predicted increased odds of a high fatigue level. Patients with a minimum Hb <7 g/dL were 50% (odds ratio [OR] = 1.5; P = 0.03) more likely to have high fatigue and patients with a minimum Hb 7-8 g/dL were 90% (OR = 1.9; P < 0.001) more likely to have high fatigue compared with patients with a minimum Hb ≥8 g/dL in Model 1. These results were similar in Model 2, although the effect was only statistically significant in the 7-8 g/dL Hb group (Table 3). When excluding SC and/or GIB patients, the odds of having high fatigue as minimum Hb decreased were the same or higher for both models compared to the full population of patients. However, again, in Model 2, the effect was only statistically significant in the 7-8 g/dL Hb group (Supplemental Table 1).

Patients with a mean Hb <8 g/dL were 20% to 30% more likely to have high fatigue and patients with mean Hb 8-9 g/dL were 50% more likely to have high fatigue compared with patients with a mean Hb ≥9 g/dL, but the effects were only statistically significant for patients with a mean Hb 8-9 g/dL in both Models 1 and 2 (Table 3). These results were similar when excluding patients with SC and/or GIB, but they were only significant for patients with a mean Hb 8-9 g/dL in Model 1 and patients with a mean Hb <8 g/dL in the Model 2 (Supplemental Table 3).

These results demonstrate that minimum Hb during hospitalization is associated with fatigue in hospitalized patients age ≥50 years, and the association is stronger among patients without SC and/or GIB as comorbidities. The analysis of Hb as a continuous and categorical variable and the use of both linear and logistic regression models support the robustness of these associations and illuminate their clinical significance. For example, in linear regression with minimum Hb a continuous variable, the coefficient of 1.4 suggests that an increase of 2 g/dL in Hb, as might be expected from transfusion of 2 units of red blood cells, would be associated with about a 3-point improvement in fatigue. Additionally, as a categorical variable, a minimum Hb ≥8 g/dL compared with a minimum Hb <7 g/dL or 7-8 g/dL is associated with a 3- to 4-point improvement in fatigue. Previous literature suggests that a difference of 3 in the FACIT score is the minimum clinically important difference in fatigue,³ and changes in minimum Hb in either model predict changes in fatigue that are in the range of potential clinical significance.

The clinical significance of the findings is also reflected in the results of the logistic regressions, which may be mapped to potential effects on functional status. Specifically, the odds of having a high fatigue level (FACIT <27) increase 90% for persons with a minimum Hb 7–8 g/dL compared with persons with a minimum Hb ≥8 g/dL. For persons with a minimum Hb <7 g/dL, point estimates suggest a smaller (50%) increase in the odds of high fatigue, but the 95% confidence interval overlaps heavily with the estimate of patients whose minimum Hb is 7-8 g/dL. While it might be expected that patients with a minimum Hb <7 g/dL have greater levels of fatigue compared with patients with a minimum Hb 7-8 g/dL, we did not observe such a pattern. One reason may be that the confidence intervals of our estimated effects are wide enough that we cannot exclude such a pattern. Another possible explanation is that in both groups, the fatigue levels are sufficiently severe, such that the difference in their fatigue levels may not be clinically meaningful. For example, a FACIT score of 23 to 26 has been shown to be associated with an ECOG performance status of 2 to 3, requiring bed rest for at least part of the day.³ Therefore, patients with a minimum Hb 7-8 g/dL (mean FACIT score = 24; Table 2) or a minimum Hb of <7 g/dL (mean FACIT score = 23; Table 2) are already functionally limited to the point of being partially bed bound, such that further decreases in their Hb may not produce additional fatigue in part because they reduce their activity sufficiently to prevent an increase in fatigue. In such cases, the potential benefits of increased Hb may be better assessed by measuring fatigue in response to a specific and provoked activity level, a concept known as fatigability.²⁰

That minimum Hb is more strongly associated with fatigue than any other measure of Hb during hospitalization may not be surprising. Mean, median, maximum, and discharge Hb may all be affected by transfusion during hospitalization that could affect fatigue. Admission Hb may not reflect true oxygen-carrying capacity because of hemoconcentration.

The association between Hb and fatigue in hospitalized patients is important because increased fatigue could contribute to slower clinical recovery in hospitalized patients. Additionally, increased fatigue during hospitalization and at hospital discharge could exacerbate the known deleterious consequences of fatigue on patients and their health outcomes^14,15 after hospital discharge. Although one previous study, the Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS)⁸ trial, did not report differences in patients’ fatigue levels at 30 and 60 days postdischarge when transfused at restrictive (8 g/dL) compared with liberal (10 g/dL) Hb thresholds, confidence in the validity of this finding is reduced by the fact that more than half of the patients were lost to follow-up at the 30- and 60-day time points. Further, patients in the restrictive transfusion arm of FOCUS were transfused to maintain Hb levels at or above 8 g/dL. This transfusion threshold of 8 g/dL may have mitigated the high levels of fatigue that are seen in our study when patients’ Hb drops below 8 g/dL, and maintaining a Hb level of 7 g/dL is now the standard of care in stable hospitalized patients. Lastly, FOCUS was limited to postoperative hip fracture patients, and the generalizability of FOCUS to hospitalized medicine patients with anemia is limited.

Therefore, our results support guideline suggestions that practitioners incorporate the presence of patient symptoms such as fatigue into transfusion decisions, particularly if patients’ Hb is <8 g/dL.¹⁸ Though reasonable, the suggestion to incorporate symptoms such as fatigue into transfusion decisions has not been strongly supported by evidence so far, and it may often be neglected in practice. Definitive evidence to support such recommendations would benefit from study through an optimal trial¹⁸ that incorporates symptoms into decision making. Our findings add support for a study of transfusion strategies that incorporates patients’ fatigue level in addition to Hb concentration.

This study has several limitations. Although our sample size is large and includes patients with a range of comorbidities that we believe are representative of hospitalized general medicine patients, as a single-center, observational study, our results may not be generalizable to other centers. Additionally, although these data support a reliable association between hospitalized patients’ minimum Hb and fatigue level, the observational design of this study cannot prove that this relationship is causal. Also, patients’ Hb values were measured at the discretion of their clinician, and therefore, the measures of Hb were not uniformly measured for participating patients. In addition, fatigue was only measured at one time point during a patient’s hospitalization, and it is possible that patients’ fatigue levels change during hospitalization in relation to variables we did not consider. Finally, our study was not designed to assess the association of Hb with longer-term functional outcomes, which may be of greater concern than fatigue.

In hospitalized patients ≥50 years old, minimum Hb is reliably associated with patients’ fatigue level. Patients whose minimum Hb is <8 g/dL experience higher fatigue levels compared to patients whose minimum Hb is ≥8 g/dL. Additional studies are warranted to understand if patients may benefit from improved fatigue levels by correcting their anemia through transfusion.

Fatigue is the most common clinical symptom of anemia and is a significant concern to patients.^1,2 In ambulatory patients, lower hemoglobin (Hb) concentration is associated with increased fatigue.^2,3 Accordingly, therapies that treat anemia by increasing Hb concentration, such as erythropoiesis stimulating agents,^4-7 often use fatigue as an outcome measure.

In hospitalized patients, transfusion of red blood cell increases Hb concentration and is the primary treatment for anemia. However, the extent to which transfusion and changes in Hb concentration affect hospitalized patients’ fatigue levels is not well established. Guidelines support transfusing patients with symptoms of anemia, such as fatigue, on the assumption that the increased oxygen delivery will improve the symptoms of anemia. While transfusion studies in hospitalized patients have consistently reported that transfusion at lower or “restrictive” Hb concentrations is safe compared with transfusion at higher Hb concentrations,^8-10 these studies have mainly used cardiac events and mortality as outcomes rather than patient symptoms, such as fatigue. Nevertheless, they have resulted in hospitals increasingly adopting restrictive transfusion policies that discourage transfusion at higher Hb levels.^11,12 Consequently, the rate of transfusion in hospitalized patients has decreased,¹³ raising questions of whether some patients with lower Hb concentrations may experience increased fatigue as a result of restrictive transfusion policies. Fatigue among hospitalized patients is important not only because it is an adverse symptom but because it may result in decreased activity levels, deconditioning, and losses in functional status.^14,15While the effect of alternative transfusion policies on fatigue in hospitalized patients could be answered by a randomized clinical trial using fatigue and functional status as outcomes, an important first step is to assess whether the Hb concentration of hospitalized patients is associated with their fatigue level during hospitalization. Because hospitalized patients often have acute illnesses that can cause fatigue in and of themselves, it is possible that anemia is not associated with fatigue in hospitalized patients despite anemia’s association with fatigue in ambulatory patients. Additionally, Hb concentration varies during hospitalization,¹⁶ raising the question of what measures of Hb during hospitalization might be most associated with anemia-related fatigue.

The objective of this study is to explore multiple Hb measures in hospitalized medical patients with anemia and test whether any of these Hb measures are associated with patients’ fatigue level.

Study Design

We performed a prospective, observational study of hospitalized patients with anemia on the general medicine services at The University of Chicago Medical Center (UCMC). The institutional review board approved the study procedures, and all study subjects provided informed consent.

Study Eligibility

Between April 2014 and June 2015, all general medicine inpatients were approached for written consent for The University of Chicago Hospitalist Project,¹⁷ a research infrastructure at UCMC. Among patients consenting to participate in the Hospitalist Project, patients were eligible if they had Hb <9 g/dL at any point during their hospitalization and were age ≥50 years. Hb concentration of <9 g/dL was chosen to include the range of Hb values covered by most restrictive transfusion policies.^8-10,18 Age ≥50 years was an inclusion criteria because anemia is more strongly associated with poor outcomes, including functional impairment, among older patients compared with younger patients.^14,19-21 If patients were not eligible for inclusion at the time of consent for the Hospitalist Project, their Hb values were reviewed twice daily until hospital discharge to assess if their Hb was <9 g/dL. Proxies were sought to answer questions for patients who failed the Short Portable Mental Status Questionnaire.²²

Patient Demographic Data Collection

Research assistants abstracted patient age and sex from the electronic health record (EHR), and asked patients to self-identify their race. The individual comorbidities included as part of the Charlson Comorbidity Index were identified using International Classification of Diseases, 9th Revision codes from hospital administrative data for each encounter and specifically included the following: myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, liver disease, diabetes, hemiplegia and/or paraplegia, renal disease, cancer, and human immunodeficiency virus/acquired immunodeficiency syndrome.²³ We also used Healthcare Cost and Utilization Project (www.hcup-us.ahrq.gov/toolssoftware/ccs/ccs.jsp) diagnosis categories to identify whether patients had sickle cell (SC) anemia, gastrointestinal bleeding (GIB), or a depressive disorder (DD) because these conditions are associated with anemia (SC and GIB) and fatigue (DD).²⁴

Measuring Anemia

Hb measures were available only when hospital providers ordered them as part of routine practice. The first Hb concentration <9 g/dL during a patient’s hospitalization, which made them eligible for study participation, was obtained through manual review of the EHR. All additional Hb values during the patient’s hospitalization were obtained from the hospital’s administrative data mart. All Hb values collected for each patient during the hospitalization were used to calculate summary measures of Hb during the hospitalization, including the mean Hb, median Hb, minimum Hb, maximum Hb, admission (first recorded) Hb, and discharge (last recorded) Hb. Hb measures were analyzed both as a continuous variable and as a categorical variable created by dividing the continuous Hb measures into integer ranges of 3 groups of approximately the same size.

Measuring Fatigue

Our primary outcome was patients’ level of fatigue reported during hospitalization, measured using the Functional Assessment of Chronic Illness Therapy (FACIT)-Anemia questionnaire. Fatigue was measured using a 13-question fatigue subscale,^1,2,25 which measures fatigue within the past 7 days. Scores on the fatigue subscale range from 0 to 52, with lower scores reflecting greater levels of fatigue. As soon as patients met the eligibility criteria for study participation during their hospitalization (age ≥50 years and Hb <9 g/dL), they were approached to answer the FACIT questions. Values for missing data in the fatigue subscale for individual subjects were filled in using a prorated score from their answered questions as long as >50% of the items in the fatigue subscale were answered, in accordance with recommendations for addressing missing data in the FACIT.²⁶ Fatigue was analyzed as a continuous variable and as a dichotomous variable created by dividing the sample into high (FACIT <27) and low (FACIT ≥27) levels of fatigue based on the median FACIT score of the population. Previous literature has shown a FACIT fatigue subscale score between 23 and 26 to be associated with an Eastern Cooperative Oncology Group (ECOG)²⁷ C Performance Status rating of 2 to 3³ compared to scores ≥27.

Statistical Analysis

Statistical analysis was performed using Stata statistical software (StataCorp, College Station, TX). Descriptive statistics were used to characterize patient demographics. Analysis of variance was used to test for differences in the mean fatigue levels across Hb measures. χ² tests were performed to test for associations between high fatigue levels and the Hb measures. Multivariable analysis, including both linear and logistic regression models, were used to test the association of Hb concentration and fatigue. P values <0.05 using a 2-tailed test were deemed statistically significant.

Patient Characteristics

During the study period, 8559 patients were admitted to the general medicine service. Of those, 5073 (59%) consented for participation in the Hospitalist Project, and 3670 (72%) completed the Hospitalist Project inpatient interview. Of these patients, 1292 (35%) had Hb <9 g/dL, and 784 (61%) were 50 years or older and completed the FACIT questionnaire.

Table 1 reports the demographic characteristics and comorbidities for the sample, the mean (standard deviation [SD]) for the 6 Hb measures, and mean (SD) and median FACIT scores.

Bivariate Association of Fatigue and Hb

Categorizing patients into low, middle, or high Hb for each of the 6 Hb measures, minimum Hb was strongly associated with fatigue, with a weaker association for mean Hb and no statistically significant association for the other measures.

Minimum Hb. Patients with a minimum Hb <7 g/dL and patients with Hb 7-8 g/dL had higher fatigue levels (FACIT = 25 for each) than patients with a minimum Hb ≥8 g/dL (FACIT = 29; P < 0.001; Table 2). When excluding patients with SC and/or GIB because their average minimum Hb differed from the average minimum Hb of the full population (P < 0.001), patients with a minimum Hb <7 g/dL or 7-8 g/dL had even higher fatigue levels (FACIT = 23 and FACIT = 24, respectively), with no change in the fatigue level of patients with a minimum Hb ≥8 g/dL (FACIT = 29; P < 0.001; Table 2). Lower minimum Hb continued to be associated with higher fatigue levels when analyzed in 0.5 g/dL increments (Figure).

Linear Regression of Fatigue on Hb

In linear regression models, minimum Hb consistently predicted patient fatigue, mean Hb had a less robust association with fatigue, and the other Hb measures were not associated with patient fatigue. Increases in minimum Hb (analyzed as a continuous variable) were associated with reduced fatigue (higher FACIT score; β = 1.4; P = 0.005). In models in which minimum Hb was a categorical variable, patients with a minimum Hb of <7 g/dL or 7-8 g/dL had greater fatigue (lower FACIT score) than patients whose minimum Hb was ≥8 g/dL (Hb <7 g/dL: β = −4.2; P ≤ 0.001; Hb 7-8 g/dL: β = −4.1; P < 0.001). These results control for patients’ age, sex, individual comorbidities, and whether their minimum Hb occurred before or after the measurement of fatigue during hospitalization (Model 1), and the results are unchanged when also controlling for the number of Hb laboratory draws patients had during their hospitalization (Model 2; Table 3). In a stratified analysis excluding patients with either SC and/or GIB, changes in minimum Hb were associated with larger changes in patient fatigue levels (Supplemental Table 1). We also stratified our analysis to include only patients whose minimum Hb occurred before the measurement of their fatigue level during hospitalization to avoid a spurious association of fatigue with minimum Hb occurring after fatigue was measured. In both Models 1 and 2, minimum Hb remained a predictor of patients’ fatigue levels with similar effect sizes, although in Model 2, the results did not quite reach a statistically significant level, in part due to larger confidence intervals from the smaller sample size of this stratified analysis (Supplemental Table 2a). We further stratified this analysis to include only patients whose transfusion, if they received one, occurred after their minimum Hb and the measurement of their fatigue level to account for the possibility that a transfusion could affect the fatigue level patients report. In this analysis, most of the estimates of the effect of minimum Hb on fatigue were larger than those seen when only analyzing patients whose minimum Hb occurred before the measurement of their fatigue level, although again, the smaller sample size of this additional stratified analysis does produce larger confidence intervals for these estimates (Supplemental Table 2b).

Logistic Regression of High Fatigue Level on Hb

Using logistic regression, minimum Hb analyzed as a categorical variable predicted increased odds of a high fatigue level. Patients with a minimum Hb <7 g/dL were 50% (odds ratio [OR] = 1.5; P = 0.03) more likely to have high fatigue and patients with a minimum Hb 7-8 g/dL were 90% (OR = 1.9; P < 0.001) more likely to have high fatigue compared with patients with a minimum Hb ≥8 g/dL in Model 1. These results were similar in Model 2, although the effect was only statistically significant in the 7-8 g/dL Hb group (Table 3). When excluding SC and/or GIB patients, the odds of having high fatigue as minimum Hb decreased were the same or higher for both models compared to the full population of patients. However, again, in Model 2, the effect was only statistically significant in the 7-8 g/dL Hb group (Supplemental Table 1).

Patients with a mean Hb <8 g/dL were 20% to 30% more likely to have high fatigue and patients with mean Hb 8-9 g/dL were 50% more likely to have high fatigue compared with patients with a mean Hb ≥9 g/dL, but the effects were only statistically significant for patients with a mean Hb 8-9 g/dL in both Models 1 and 2 (Table 3). These results were similar when excluding patients with SC and/or GIB, but they were only significant for patients with a mean Hb 8-9 g/dL in Model 1 and patients with a mean Hb <8 g/dL in the Model 2 (Supplemental Table 3).

These results demonstrate that minimum Hb during hospitalization is associated with fatigue in hospitalized patients age ≥50 years, and the association is stronger among patients without SC and/or GIB as comorbidities. The analysis of Hb as a continuous and categorical variable and the use of both linear and logistic regression models support the robustness of these associations and illuminate their clinical significance. For example, in linear regression with minimum Hb a continuous variable, the coefficient of 1.4 suggests that an increase of 2 g/dL in Hb, as might be expected from transfusion of 2 units of red blood cells, would be associated with about a 3-point improvement in fatigue. Additionally, as a categorical variable, a minimum Hb ≥8 g/dL compared with a minimum Hb <7 g/dL or 7-8 g/dL is associated with a 3- to 4-point improvement in fatigue. Previous literature suggests that a difference of 3 in the FACIT score is the minimum clinically important difference in fatigue,³ and changes in minimum Hb in either model predict changes in fatigue that are in the range of potential clinical significance.

The clinical significance of the findings is also reflected in the results of the logistic regressions, which may be mapped to potential effects on functional status. Specifically, the odds of having a high fatigue level (FACIT <27) increase 90% for persons with a minimum Hb 7–8 g/dL compared with persons with a minimum Hb ≥8 g/dL. For persons with a minimum Hb <7 g/dL, point estimates suggest a smaller (50%) increase in the odds of high fatigue, but the 95% confidence interval overlaps heavily with the estimate of patients whose minimum Hb is 7-8 g/dL. While it might be expected that patients with a minimum Hb <7 g/dL have greater levels of fatigue compared with patients with a minimum Hb 7-8 g/dL, we did not observe such a pattern. One reason may be that the confidence intervals of our estimated effects are wide enough that we cannot exclude such a pattern. Another possible explanation is that in both groups, the fatigue levels are sufficiently severe, such that the difference in their fatigue levels may not be clinically meaningful. For example, a FACIT score of 23 to 26 has been shown to be associated with an ECOG performance status of 2 to 3, requiring bed rest for at least part of the day.³ Therefore, patients with a minimum Hb 7-8 g/dL (mean FACIT score = 24; Table 2) or a minimum Hb of <7 g/dL (mean FACIT score = 23; Table 2) are already functionally limited to the point of being partially bed bound, such that further decreases in their Hb may not produce additional fatigue in part because they reduce their activity sufficiently to prevent an increase in fatigue. In such cases, the potential benefits of increased Hb may be better assessed by measuring fatigue in response to a specific and provoked activity level, a concept known as fatigability.²⁰

That minimum Hb is more strongly associated with fatigue than any other measure of Hb during hospitalization may not be surprising. Mean, median, maximum, and discharge Hb may all be affected by transfusion during hospitalization that could affect fatigue. Admission Hb may not reflect true oxygen-carrying capacity because of hemoconcentration.

The association between Hb and fatigue in hospitalized patients is important because increased fatigue could contribute to slower clinical recovery in hospitalized patients. Additionally, increased fatigue during hospitalization and at hospital discharge could exacerbate the known deleterious consequences of fatigue on patients and their health outcomes^14,15 after hospital discharge. Although one previous study, the Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS)⁸ trial, did not report differences in patients’ fatigue levels at 30 and 60 days postdischarge when transfused at restrictive (8 g/dL) compared with liberal (10 g/dL) Hb thresholds, confidence in the validity of this finding is reduced by the fact that more than half of the patients were lost to follow-up at the 30- and 60-day time points. Further, patients in the restrictive transfusion arm of FOCUS were transfused to maintain Hb levels at or above 8 g/dL. This transfusion threshold of 8 g/dL may have mitigated the high levels of fatigue that are seen in our study when patients’ Hb drops below 8 g/dL, and maintaining a Hb level of 7 g/dL is now the standard of care in stable hospitalized patients. Lastly, FOCUS was limited to postoperative hip fracture patients, and the generalizability of FOCUS to hospitalized medicine patients with anemia is limited.

Therefore, our results support guideline suggestions that practitioners incorporate the presence of patient symptoms such as fatigue into transfusion decisions, particularly if patients’ Hb is <8 g/dL.¹⁸ Though reasonable, the suggestion to incorporate symptoms such as fatigue into transfusion decisions has not been strongly supported by evidence so far, and it may often be neglected in practice. Definitive evidence to support such recommendations would benefit from study through an optimal trial¹⁸ that incorporates symptoms into decision making. Our findings add support for a study of transfusion strategies that incorporates patients’ fatigue level in addition to Hb concentration.

This study has several limitations. Although our sample size is large and includes patients with a range of comorbidities that we believe are representative of hospitalized general medicine patients, as a single-center, observational study, our results may not be generalizable to other centers. Additionally, although these data support a reliable association between hospitalized patients’ minimum Hb and fatigue level, the observational design of this study cannot prove that this relationship is causal. Also, patients’ Hb values were measured at the discretion of their clinician, and therefore, the measures of Hb were not uniformly measured for participating patients. In addition, fatigue was only measured at one time point during a patient’s hospitalization, and it is possible that patients’ fatigue levels change during hospitalization in relation to variables we did not consider. Finally, our study was not designed to assess the association of Hb with longer-term functional outcomes, which may be of greater concern than fatigue.

In hospitalized patients ≥50 years old, minimum Hb is reliably associated with patients’ fatigue level. Patients whose minimum Hb is <8 g/dL experience higher fatigue levels compared to patients whose minimum Hb is ≥8 g/dL. Additional studies are warranted to understand if patients may benefit from improved fatigue levels by correcting their anemia through transfusion.

Illustration: Kimberly Martens for OBG Management

Sexual function is a complex, multifaceted process mediated by neurologic functions, hormonal regulation, and psychological factors. What could possibly go wrong?

As it turns out, quite a lot. Female sexual dysfunction is a common, vastly undertreated sexual health problem that can have wide-reaching effects on a woman’s life. These effects may include impaired body image, self-confidence, and self-worth. Sexual dysfunction also can contribute to relationship dissatisfaction and leave one feeling less connected with her partner.^1,2 Studies have shown women with sexual dysfunction have higher health care expenditures³ and that depression and fatigue are common comorbidities, as is frequently seen in other chronic conditions such as diabetes and back pain.⁴

Understanding the pathogenesis of female sexual dysfunction helps to guide our approach to its management. Indeed, increased understanding of its pathology has helped to usher in new and emerging treatment options, as well as a personalized, biopsychosocial approach to its management.

Related article:
2016 Update on female sexual dysfunction

In this Update, I discuss the interplay of physiologic and psychological factors that affect female sexual function as well as the latest options for its management. I have also assembled a panel of experts to discuss 2 cases representative of sexual dysfunction that you may encounter in your clinical practice and how prescribing decisions are made for their management.

Read about factors that impact sexual function and agents to help manage dysfunction.

Multiple transmitters in the brain can increase or decrease sexual desire and function

Neurotransmitters involved in sexual excitation include brain dopamine, melanocortin, oxytocin, vasopressin, and norepinephrine, whereas brain opioids, serotonin, prolactin, and endocannabinoids function as sexual inhibitors. Inhibitory transmitters are activated normally during sexual refractoriness but also from primary aversion or secondary avoidance disorders.¹ Drugs or conditions that reduce brain dopamine levels, increase the action of brain serotonin, or enhance brain opioid pathways have been shown to inhibit sexual desire, while those that increase hypothalamic and mesolimbic dopamine or decrease serotonin release have been shown to stimulate sexual desire.¹ 

Estradiol and progesterone can impact sexual function and desire

In addition to the neurotransmitters, hormones are important modulators of female sexual function. Decreasing levels of circulating estrogen after menopause lead to physiologic, biologic, and clinical changes in the urogenital tissues, such as decreased elastin, thinning of the epithelium, reduced vaginal blood flow, diminished lubrication, and decreased flexibility and elasticity. These changes result in the symptoms of genitourinary syndrome of menopause (GSM), which affects as many as half of all menopausal women.^5,6 In clinical trials, dyspareunia and vaginal dryness are the most bothersome GSM symptoms reported.⁷

The role of hormonal regulation in sexual dysfunction among premenopausal women is not yet fully understood, but we do know that estradiol has been shown to improve sexual desire, progesterone tends to dampen sexual desire, and that testosterone at physiological levels has been shown in most studies to have a neutral effect on sexual desire in a well-estrogenized patient.⁸

Related article:
Focus on treating genital atrophy symptoms

Experience and behavior modulate or reinforce sexual dysfunction

The most common psychological factors that trigger or amplify female sexual dysfunction are depression, anxiety, distraction, negative body image, sexual abuse, and emotional neglect.⁹ Contextual or sociocultural factors, such as relationship discord, life-stage stressors (the empty nest syndrome or anxiety and sleep deprivation from a new baby), as well as cultural or religious values that suppress sexuality, also should be considered.⁹ Experience-based neuroplasticity (changes in brain pathways that become solidified by negative or positive experiences) may elucidate how a multimodal approach, utilizing medical and psychological treatment, can be beneficial for patients, particularly those with hypoactive sexual desire disorder (HSDD).¹

New and emerging approaches to managing female sexual dysfunction

Three agents, one of which has been available for prescription for some time, one that is newly available, and one in the pipeline, are or may soon be in the gynecologist's armamentarium.

Flibanserin

Medications that target excitatory pathways or blunt inhibitory pathways are in development, and one, flibanserin (Addyi), has been US Food and Drug Administration (FDA)-approved for the treatment of acquired, generalized HSDD in premenopausal women.^1,10 Flibanserin is a nonhormonal, centrally acting, postsynaptic serotonin 1A receptor agonist and a serotonin 2A receptor antagonist that is taken daily at bedtime (100 mg); several weeks are usually needed before any effects are noted.¹ It is not approved for postmenopausal women and has a boxed warning about the risks of hypotension and syncope; its use is contraindicated in women who drink alcohol, in those who have hepatic impairment, and with the use of moderate or strong CYP3A4 inhibitors.¹¹

Also keep in mind that flibanserin is only available through a Risk Evaluation and Mitigation Strategy program, so clinicians who wish to prescribe it must enroll in and complete training to become certified providers.⁹

Related article:
What you need to know (and do) to prescribe the new drug flibanserin

Prasterone

Prasterone (Intrarosa), a once-daily intravaginal dehydroepiandrosterone (DHEA) product, is a prohormone that increases local estrogen and testosterone and has the advantage of improved sexual function, desire, arousal, lubrication, orgasm, satisfaction, as well as pain at sexual activity.¹² It was approved by the FDA in November 2016 to treat moderate to severe dyspareunia and has been available for prescribing since July 2017. Its cost is comparable to topical estrogen products, with a $25 copay program.

Because prasterone is not an estrogen, it does not have the boxed warning that all estrogen products are mandated by the FDA to have. This may make it more acceptable to patients, who often decline to use an estrogen product after seeing the boxed warning on the package. The Centers for Medicare and Medicaid Services (CMS) does not have prasterone on its list of potentially hazardous drugs for the elderly. However, keep in mind that because its label is for dyspareunia and not specifically for GSM, CMS considers it a drug of choice--in other words, like sildenafil (Viagra), a lifestyle choice and not for treatment of a medical condition. As such, at the present time, Medicare does not cover it.

Bremelanotide

Late-stage trials of bremelanotide, a melanocortin receptor agonist, are underway. Its mechanism of action is somewhat like that of flibanserin in that both drugs increase dopamine and norepinephrine levels. The advantage of bremelanotide is that it is used as needed. It is dosed subcutaneously (1.75 mg) and it can be used as often as a woman would like to use it. The FDA is expected to consider it for approval in about a year. Unpublished data from poster sessions at recent meetings show that, in a phase 3 study of 1,247 premenopausal women with HSDD (who had already been screened for depression and were found to have a physiologic condition), improvements in desire, arousal, lubrication, and orgasm were shown with bremelanotide. About 18% of women stopped using the drug because of adverse effects (nausea, vomiting, flushing, or headache) versus 2% for placebo. Like flibanserin, it is expected to be approved for premenopausal women only. 

Read how 3 experts would manage differing GSM symptoms.

What would you prescribe for these patients? 

CASE Genitourinary syndrome of menopause (GSM) in a 55-year-old woman

A 55-year-old widow is beginning a new relationship. She has not had partnered sexual activity for several years, but she recently has begun a relationship. She describes pain with attempted penetration with her new partner. Her last menstrual period was 3 years ago and she has experienced very minor menopausal symptoms, which are not bothersome. On examination, the vulva and vagina are pale, with thin epithelium and absent rugae. The tissue lacks elasticity. A virginal speculum is needed to visualize the cervix.

How would you go about deciding which of the many options for management of GSM you will recommend for this patient? What do you weigh as you consider DHEA versus estrogen and topical versus oral therapy?
 
JoAnn V. Pinkerton, MD: Vulvovaginal atrophy (VVA), part of GSM, is associated with postmenopausal estrogen deficiency and includes the signs and symptoms seen on this patient's physical exam: vaginal narrowing, pallor, loss of elasticity, as well as pain with intercourse.⁶ Estrogen therapy is the most effective treatment for vaginal atrophy.¹³ Since she does not have significant menopausal symptoms, low-dose vaginal estrogen preparations are effective and generally safe treatments for VVA; these include creams, tablets containing estradiol or conjugated equine estrogen (CEE), and a low-dose vaginal estradiol ring--all available at doses that result in minimal systemic absorption.

Choice is usually made based on patient desire and likely adherence. If the patient prefers nonestrogen therapies that improve VVA and have been approved for relief of dyspareunia in postmenopausal women, I would discuss with the patient the oral selective estrogen receptor modulator ospemifene,¹⁴ and the new intravaginal DHEA suppositories, prasterone.¹⁵ Ospemifene is taken daily as an oral tablet, has a small risk of blood clots, and is my choice for women who do not need systemic hormone therapy and prefer to avoid vaginal therapy.

Andrew M. Kaunitz, MD: GSM is prevalent in menopausal women and, if not treated, causes progressive vaginal dryness and sexual discomfort. When the main indication for hormonal management in a menopausal woman is GSM (as opposed to treatment of vasomotor symptoms or prevention of osteoporosis), the treatment of choice is low-dose local vaginal estrogen, ospemifene, or prasterone (DHEA). Prasterone is a vaginally administered nonestrogen steroid that was approved by the FDA to treat dyspareunia associated with GSM. DHEA is an endogenous inactive steroid that is converted locally into androgens and estrogens; one vaginal insert is placed nightly.^16,17

This 55-year-old widow has not been sexually active for some time. The facts that attempted penetration was painful and only an ultrathin (virginal) speculum could be used for examination indicate that contraction of the pelvic floor muscles is likely present. Simply starting medical management may not lead to comfortable/successful penetrative sex for this woman. In addition to  medical management, she would likely benefit from referral for physical therapy. Using dilators and other strategies, along with the positive impact that medical management will have on the vaginal mucosa, a woman's physical therapist can work with this patient to help the pelvic floor muscles relax and facilitate comfortable penetrative sex.

James A. Simon, MD: With only minor vasomotor symptoms, I would assess the other potential benefits of a systemic therapy. These might include cardiovascular risk reduction (systemic estrogens or estrogens/progesterone in some), breast cancer risk reduction (some data suggesting ospemifene can accomplish this), osteoporosis prevention (systemic estrogens and estrogen/androgens), etc. If there is an option for a treatment to address more than one symptom, in this case GSM, assessing the risks/benefits of each of these therapies should be estimated for this specific patient.

If there are no systemic benefits to be had, then any of the local treatments should be helpful. As there are no head-to-head comparisons available, local estrogen cream, tablets, rings, local DHEA, or systemic ospemifene each should be considered possible treatments. I also feel this patient may benefit from supplementary self-dilation and/or physical therapy.

Related article:
2017 Update on menopause

 
CASE Dyspareunia and vasomotor symptoms in a 42-year-old breast cancer survivor

A 42-year-old woman with a BRCA1 mutation has undergone prophylactic mastectomies as well as hysterectomy with bilateral salpingo-oophorectomy. She reports mild to moderate hot flashes and bothersome vaginal dryness and dyspareunia. Examination confirms GSM.

Would you advise systemic hormone therapy for this patient? What would your recommendation be for management of her GSM symptoms?

Dr. Simon: While one's gut reaction would be to avoid systemic estrogen therapy in a patient with a BRCA1 mutation, the scientific information confirming this fear is lacking.¹⁸ Such patients may benefit significantly from systemic estrogen therapy (reduced risk of cardiovascular disease and cognitive decline, etc.), and with both breasts and both ovaries removed, estrogen's breast cancer risks, if any in this population, are largely avoided. The patient also may benefit from additional local therapy with either estrogens or DHEA.

Dr. Kaunitz: Due to her high lifetime risk of breast and ovarian cancer, this woman has proceeded with risk-reducing breast and gynecologic surgery. As more BRCA mutation carriers are being identified and undergo risk-reducing bilateral mastectomy (usually with reconstruction) and salpingo-oophorectomy, clinicians and mutation carriers more frequently face decisions regarding use of systemic hormone therapy.

Mutation carriers who have undergone bilateral risk-reducing mastectomy experience a very low baseline future risk for breast cancer; accordingly, concerns regarding this disease should not prevent use of systemic hormone therapy. Furthermore, without hormone replacement, induced menopause in women this age is associated with an elevated risk of osteoporosis, persistent vasomotor symptoms, cardiovascular disease, stroke, mood changes, dementia, Parkinson disease, and overall mortality. Recognizing the safety of estrogen therapy in this setting, this 42-year-old BRCA1 mutation carrier can initiate estrogen therapy. Standard dose estrogen therapy refers to oral estradiol 1.0 mg, conjugated equine estrogen 0.625 mg,or transdermal estradiol 0.05 mg. In younger women like this 42-year-old with surgically induced menopause, higher than standard replacement doses of estrogen are often appropriate.¹⁷

Due to concerns the hormone therapy might further increase future risk of breast cancer, some mutation carriers may delay or avoid risk-reducing bilateral salpingo-oophorectomy, a potentially lifesaving surgery which reduces not only future risk of ovarian cancer but also future risk for breast cancer.

Among mutation carriers with intact breasts, several studies address risk of breast cancer with use of systemic hormone therapy. Although limited in numbers of participants and years of follow-up, in aggregate, these studies provide reassurance that short-term use of systemic hormone therapy does not increase breast cancer risk in women with BRCA1 or BRCA2 mutations and intact breasts.¹⁹

Dr. Pinkerton: For this woman with early surgical menopause and hysterectomy, estrogen therapy could improve her vasomotor symptoms and decrease her risk of bone loss and GSM.¹⁷ In the Women's Health Initiative trial, there were 7 fewer breast cancers per 10,000 women-years in the estrogen-onlyarm.²⁰ Observational studies suggest that hormone therapy, when given to the average age of menopause, decreases the risks of heart disease, Parkinson disease, and dementia.²¹ Limited observational evidence suggests that hormone therapy use does not further increase risk of breast cancer in women following oophorectomy for BRCA1 or BRCA2 gene mutation.²²

The absolute risks observed with hormone therapy tended to be small, especially in younger, healthy women. Systemic hormone therapy could treat her hot flashes and her GSM symptoms and potentially decrease health risks associated with premature estrogen deficiency. Nonestrogen therapies for hot flashes include low-dose antidepressants, gabapentin, and mind-body options, such as cognitive behavioral therapy and hypnosis, but these would not decrease her health risks or treat her GSM.

If she only requests treatment of her GSM symptoms, she would be a candidate for low-dose vaginal estrogen therapy, given as a cream, tablet, or ring depending on her choice. I would not choose ospemifene as my first choice as she is having hot flashes, and there are no data yet on the drug's health benefits in early menopause. If she prefers nonestrogen vaginal therapy, the new intravaginal DHEA might be a good choice as both estrogen and testosterone are increased locally in the vagina while hormone levels remain in the postmenopausal range. There is no boxed warning on the patient insert, although safety in women with breast cancer or in those with elevated risk of breast cancer has not been tested.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Illustration: Kimberly Martens for OBG Management

Sexual function is a complex, multifaceted process mediated by neurologic functions, hormonal regulation, and psychological factors. What could possibly go wrong?

As it turns out, quite a lot. Female sexual dysfunction is a common, vastly undertreated sexual health problem that can have wide-reaching effects on a woman’s life. These effects may include impaired body image, self-confidence, and self-worth. Sexual dysfunction also can contribute to relationship dissatisfaction and leave one feeling less connected with her partner.^1,2 Studies have shown women with sexual dysfunction have higher health care expenditures³ and that depression and fatigue are common comorbidities, as is frequently seen in other chronic conditions such as diabetes and back pain.⁴

Understanding the pathogenesis of female sexual dysfunction helps to guide our approach to its management. Indeed, increased understanding of its pathology has helped to usher in new and emerging treatment options, as well as a personalized, biopsychosocial approach to its management.

Related article:
2016 Update on female sexual dysfunction

In this Update, I discuss the interplay of physiologic and psychological factors that affect female sexual function as well as the latest options for its management. I have also assembled a panel of experts to discuss 2 cases representative of sexual dysfunction that you may encounter in your clinical practice and how prescribing decisions are made for their management.

Read about factors that impact sexual function and agents to help manage dysfunction.

Multiple transmitters in the brain can increase or decrease sexual desire and function

Neurotransmitters involved in sexual excitation include brain dopamine, melanocortin, oxytocin, vasopressin, and norepinephrine, whereas brain opioids, serotonin, prolactin, and endocannabinoids function as sexual inhibitors. Inhibitory transmitters are activated normally during sexual refractoriness but also from primary aversion or secondary avoidance disorders.¹ Drugs or conditions that reduce brain dopamine levels, increase the action of brain serotonin, or enhance brain opioid pathways have been shown to inhibit sexual desire, while those that increase hypothalamic and mesolimbic dopamine or decrease serotonin release have been shown to stimulate sexual desire.¹ 

Estradiol and progesterone can impact sexual function and desire

In addition to the neurotransmitters, hormones are important modulators of female sexual function. Decreasing levels of circulating estrogen after menopause lead to physiologic, biologic, and clinical changes in the urogenital tissues, such as decreased elastin, thinning of the epithelium, reduced vaginal blood flow, diminished lubrication, and decreased flexibility and elasticity. These changes result in the symptoms of genitourinary syndrome of menopause (GSM), which affects as many as half of all menopausal women.^5,6 In clinical trials, dyspareunia and vaginal dryness are the most bothersome GSM symptoms reported.⁷

The role of hormonal regulation in sexual dysfunction among premenopausal women is not yet fully understood, but we do know that estradiol has been shown to improve sexual desire, progesterone tends to dampen sexual desire, and that testosterone at physiological levels has been shown in most studies to have a neutral effect on sexual desire in a well-estrogenized patient.⁸

Related article:
Focus on treating genital atrophy symptoms

Experience and behavior modulate or reinforce sexual dysfunction

The most common psychological factors that trigger or amplify female sexual dysfunction are depression, anxiety, distraction, negative body image, sexual abuse, and emotional neglect.⁹ Contextual or sociocultural factors, such as relationship discord, life-stage stressors (the empty nest syndrome or anxiety and sleep deprivation from a new baby), as well as cultural or religious values that suppress sexuality, also should be considered.⁹ Experience-based neuroplasticity (changes in brain pathways that become solidified by negative or positive experiences) may elucidate how a multimodal approach, utilizing medical and psychological treatment, can be beneficial for patients, particularly those with hypoactive sexual desire disorder (HSDD).¹

New and emerging approaches to managing female sexual dysfunction

Three agents, one of which has been available for prescription for some time, one that is newly available, and one in the pipeline, are or may soon be in the gynecologist's armamentarium.

Flibanserin

Medications that target excitatory pathways or blunt inhibitory pathways are in development, and one, flibanserin (Addyi), has been US Food and Drug Administration (FDA)-approved for the treatment of acquired, generalized HSDD in premenopausal women.^1,10 Flibanserin is a nonhormonal, centrally acting, postsynaptic serotonin 1A receptor agonist and a serotonin 2A receptor antagonist that is taken daily at bedtime (100 mg); several weeks are usually needed before any effects are noted.¹ It is not approved for postmenopausal women and has a boxed warning about the risks of hypotension and syncope; its use is contraindicated in women who drink alcohol, in those who have hepatic impairment, and with the use of moderate or strong CYP3A4 inhibitors.¹¹

Also keep in mind that flibanserin is only available through a Risk Evaluation and Mitigation Strategy program, so clinicians who wish to prescribe it must enroll in and complete training to become certified providers.⁹

Related article:
What you need to know (and do) to prescribe the new drug flibanserin

Prasterone

Prasterone (Intrarosa), a once-daily intravaginal dehydroepiandrosterone (DHEA) product, is a prohormone that increases local estrogen and testosterone and has the advantage of improved sexual function, desire, arousal, lubrication, orgasm, satisfaction, as well as pain at sexual activity.¹² It was approved by the FDA in November 2016 to treat moderate to severe dyspareunia and has been available for prescribing since July 2017. Its cost is comparable to topical estrogen products, with a $25 copay program.

Because prasterone is not an estrogen, it does not have the boxed warning that all estrogen products are mandated by the FDA to have. This may make it more acceptable to patients, who often decline to use an estrogen product after seeing the boxed warning on the package. The Centers for Medicare and Medicaid Services (CMS) does not have prasterone on its list of potentially hazardous drugs for the elderly. However, keep in mind that because its label is for dyspareunia and not specifically for GSM, CMS considers it a drug of choice--in other words, like sildenafil (Viagra), a lifestyle choice and not for treatment of a medical condition. As such, at the present time, Medicare does not cover it.

Bremelanotide

Late-stage trials of bremelanotide, a melanocortin receptor agonist, are underway. Its mechanism of action is somewhat like that of flibanserin in that both drugs increase dopamine and norepinephrine levels. The advantage of bremelanotide is that it is used as needed. It is dosed subcutaneously (1.75 mg) and it can be used as often as a woman would like to use it. The FDA is expected to consider it for approval in about a year. Unpublished data from poster sessions at recent meetings show that, in a phase 3 study of 1,247 premenopausal women with HSDD (who had already been screened for depression and were found to have a physiologic condition), improvements in desire, arousal, lubrication, and orgasm were shown with bremelanotide. About 18% of women stopped using the drug because of adverse effects (nausea, vomiting, flushing, or headache) versus 2% for placebo. Like flibanserin, it is expected to be approved for premenopausal women only. 

Read how 3 experts would manage differing GSM symptoms.

What would you prescribe for these patients? 

CASE Genitourinary syndrome of menopause (GSM) in a 55-year-old woman

A 55-year-old widow is beginning a new relationship. She has not had partnered sexual activity for several years, but she recently has begun a relationship. She describes pain with attempted penetration with her new partner. Her last menstrual period was 3 years ago and she has experienced very minor menopausal symptoms, which are not bothersome. On examination, the vulva and vagina are pale, with thin epithelium and absent rugae. The tissue lacks elasticity. A virginal speculum is needed to visualize the cervix.

How would you go about deciding which of the many options for management of GSM you will recommend for this patient? What do you weigh as you consider DHEA versus estrogen and topical versus oral therapy?
 
JoAnn V. Pinkerton, MD: Vulvovaginal atrophy (VVA), part of GSM, is associated with postmenopausal estrogen deficiency and includes the signs and symptoms seen on this patient's physical exam: vaginal narrowing, pallor, loss of elasticity, as well as pain with intercourse.⁶ Estrogen therapy is the most effective treatment for vaginal atrophy.¹³ Since she does not have significant menopausal symptoms, low-dose vaginal estrogen preparations are effective and generally safe treatments for VVA; these include creams, tablets containing estradiol or conjugated equine estrogen (CEE), and a low-dose vaginal estradiol ring--all available at doses that result in minimal systemic absorption.

Choice is usually made based on patient desire and likely adherence. If the patient prefers nonestrogen therapies that improve VVA and have been approved for relief of dyspareunia in postmenopausal women, I would discuss with the patient the oral selective estrogen receptor modulator ospemifene,¹⁴ and the new intravaginal DHEA suppositories, prasterone.¹⁵ Ospemifene is taken daily as an oral tablet, has a small risk of blood clots, and is my choice for women who do not need systemic hormone therapy and prefer to avoid vaginal therapy.

Andrew M. Kaunitz, MD: GSM is prevalent in menopausal women and, if not treated, causes progressive vaginal dryness and sexual discomfort. When the main indication for hormonal management in a menopausal woman is GSM (as opposed to treatment of vasomotor symptoms or prevention of osteoporosis), the treatment of choice is low-dose local vaginal estrogen, ospemifene, or prasterone (DHEA). Prasterone is a vaginally administered nonestrogen steroid that was approved by the FDA to treat dyspareunia associated with GSM. DHEA is an endogenous inactive steroid that is converted locally into androgens and estrogens; one vaginal insert is placed nightly.^16,17

This 55-year-old widow has not been sexually active for some time. The facts that attempted penetration was painful and only an ultrathin (virginal) speculum could be used for examination indicate that contraction of the pelvic floor muscles is likely present. Simply starting medical management may not lead to comfortable/successful penetrative sex for this woman. In addition to  medical management, she would likely benefit from referral for physical therapy. Using dilators and other strategies, along with the positive impact that medical management will have on the vaginal mucosa, a woman's physical therapist can work with this patient to help the pelvic floor muscles relax and facilitate comfortable penetrative sex.

James A. Simon, MD: With only minor vasomotor symptoms, I would assess the other potential benefits of a systemic therapy. These might include cardiovascular risk reduction (systemic estrogens or estrogens/progesterone in some), breast cancer risk reduction (some data suggesting ospemifene can accomplish this), osteoporosis prevention (systemic estrogens and estrogen/androgens), etc. If there is an option for a treatment to address more than one symptom, in this case GSM, assessing the risks/benefits of each of these therapies should be estimated for this specific patient.

If there are no systemic benefits to be had, then any of the local treatments should be helpful. As there are no head-to-head comparisons available, local estrogen cream, tablets, rings, local DHEA, or systemic ospemifene each should be considered possible treatments. I also feel this patient may benefit from supplementary self-dilation and/or physical therapy.

Related article:
2017 Update on menopause

 
CASE Dyspareunia and vasomotor symptoms in a 42-year-old breast cancer survivor

A 42-year-old woman with a BRCA1 mutation has undergone prophylactic mastectomies as well as hysterectomy with bilateral salpingo-oophorectomy. She reports mild to moderate hot flashes and bothersome vaginal dryness and dyspareunia. Examination confirms GSM.

Would you advise systemic hormone therapy for this patient? What would your recommendation be for management of her GSM symptoms?

Dr. Simon: While one's gut reaction would be to avoid systemic estrogen therapy in a patient with a BRCA1 mutation, the scientific information confirming this fear is lacking.¹⁸ Such patients may benefit significantly from systemic estrogen therapy (reduced risk of cardiovascular disease and cognitive decline, etc.), and with both breasts and both ovaries removed, estrogen's breast cancer risks, if any in this population, are largely avoided. The patient also may benefit from additional local therapy with either estrogens or DHEA.

Dr. Kaunitz: Due to her high lifetime risk of breast and ovarian cancer, this woman has proceeded with risk-reducing breast and gynecologic surgery. As more BRCA mutation carriers are being identified and undergo risk-reducing bilateral mastectomy (usually with reconstruction) and salpingo-oophorectomy, clinicians and mutation carriers more frequently face decisions regarding use of systemic hormone therapy.

Mutation carriers who have undergone bilateral risk-reducing mastectomy experience a very low baseline future risk for breast cancer; accordingly, concerns regarding this disease should not prevent use of systemic hormone therapy. Furthermore, without hormone replacement, induced menopause in women this age is associated with an elevated risk of osteoporosis, persistent vasomotor symptoms, cardiovascular disease, stroke, mood changes, dementia, Parkinson disease, and overall mortality. Recognizing the safety of estrogen therapy in this setting, this 42-year-old BRCA1 mutation carrier can initiate estrogen therapy. Standard dose estrogen therapy refers to oral estradiol 1.0 mg, conjugated equine estrogen 0.625 mg,or transdermal estradiol 0.05 mg. In younger women like this 42-year-old with surgically induced menopause, higher than standard replacement doses of estrogen are often appropriate.¹⁷

Due to concerns the hormone therapy might further increase future risk of breast cancer, some mutation carriers may delay or avoid risk-reducing bilateral salpingo-oophorectomy, a potentially lifesaving surgery which reduces not only future risk of ovarian cancer but also future risk for breast cancer.

Among mutation carriers with intact breasts, several studies address risk of breast cancer with use of systemic hormone therapy. Although limited in numbers of participants and years of follow-up, in aggregate, these studies provide reassurance that short-term use of systemic hormone therapy does not increase breast cancer risk in women with BRCA1 or BRCA2 mutations and intact breasts.¹⁹

Dr. Pinkerton: For this woman with early surgical menopause and hysterectomy, estrogen therapy could improve her vasomotor symptoms and decrease her risk of bone loss and GSM.¹⁷ In the Women's Health Initiative trial, there were 7 fewer breast cancers per 10,000 women-years in the estrogen-onlyarm.²⁰ Observational studies suggest that hormone therapy, when given to the average age of menopause, decreases the risks of heart disease, Parkinson disease, and dementia.²¹ Limited observational evidence suggests that hormone therapy use does not further increase risk of breast cancer in women following oophorectomy for BRCA1 or BRCA2 gene mutation.²²

The absolute risks observed with hormone therapy tended to be small, especially in younger, healthy women. Systemic hormone therapy could treat her hot flashes and her GSM symptoms and potentially decrease health risks associated with premature estrogen deficiency. Nonestrogen therapies for hot flashes include low-dose antidepressants, gabapentin, and mind-body options, such as cognitive behavioral therapy and hypnosis, but these would not decrease her health risks or treat her GSM.

If she only requests treatment of her GSM symptoms, she would be a candidate for low-dose vaginal estrogen therapy, given as a cream, tablet, or ring depending on her choice. I would not choose ospemifene as my first choice as she is having hot flashes, and there are no data yet on the drug's health benefits in early menopause. If she prefers nonestrogen vaginal therapy, the new intravaginal DHEA might be a good choice as both estrogen and testosterone are increased locally in the vagina while hormone levels remain in the postmenopausal range. There is no boxed warning on the patient insert, although safety in women with breast cancer or in those with elevated risk of breast cancer has not been tested.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Illustration: Kimberly Martens for OBG Management

Sexual function is a complex, multifaceted process mediated by neurologic functions, hormonal regulation, and psychological factors. What could possibly go wrong?

As it turns out, quite a lot. Female sexual dysfunction is a common, vastly undertreated sexual health problem that can have wide-reaching effects on a woman’s life. These effects may include impaired body image, self-confidence, and self-worth. Sexual dysfunction also can contribute to relationship dissatisfaction and leave one feeling less connected with her partner.^1,2 Studies have shown women with sexual dysfunction have higher health care expenditures³ and that depression and fatigue are common comorbidities, as is frequently seen in other chronic conditions such as diabetes and back pain.⁴

Understanding the pathogenesis of female sexual dysfunction helps to guide our approach to its management. Indeed, increased understanding of its pathology has helped to usher in new and emerging treatment options, as well as a personalized, biopsychosocial approach to its management.

Related article:
2016 Update on female sexual dysfunction

In this Update, I discuss the interplay of physiologic and psychological factors that affect female sexual function as well as the latest options for its management. I have also assembled a panel of experts to discuss 2 cases representative of sexual dysfunction that you may encounter in your clinical practice and how prescribing decisions are made for their management.

Read about factors that impact sexual function and agents to help manage dysfunction.

Multiple transmitters in the brain can increase or decrease sexual desire and function

Neurotransmitters involved in sexual excitation include brain dopamine, melanocortin, oxytocin, vasopressin, and norepinephrine, whereas brain opioids, serotonin, prolactin, and endocannabinoids function as sexual inhibitors. Inhibitory transmitters are activated normally during sexual refractoriness but also from primary aversion or secondary avoidance disorders.¹ Drugs or conditions that reduce brain dopamine levels, increase the action of brain serotonin, or enhance brain opioid pathways have been shown to inhibit sexual desire, while those that increase hypothalamic and mesolimbic dopamine or decrease serotonin release have been shown to stimulate sexual desire.¹ 

Estradiol and progesterone can impact sexual function and desire

In addition to the neurotransmitters, hormones are important modulators of female sexual function. Decreasing levels of circulating estrogen after menopause lead to physiologic, biologic, and clinical changes in the urogenital tissues, such as decreased elastin, thinning of the epithelium, reduced vaginal blood flow, diminished lubrication, and decreased flexibility and elasticity. These changes result in the symptoms of genitourinary syndrome of menopause (GSM), which affects as many as half of all menopausal women.^5,6 In clinical trials, dyspareunia and vaginal dryness are the most bothersome GSM symptoms reported.⁷

The role of hormonal regulation in sexual dysfunction among premenopausal women is not yet fully understood, but we do know that estradiol has been shown to improve sexual desire, progesterone tends to dampen sexual desire, and that testosterone at physiological levels has been shown in most studies to have a neutral effect on sexual desire in a well-estrogenized patient.⁸

Related article:
Focus on treating genital atrophy symptoms

Experience and behavior modulate or reinforce sexual dysfunction

The most common psychological factors that trigger or amplify female sexual dysfunction are depression, anxiety, distraction, negative body image, sexual abuse, and emotional neglect.⁹ Contextual or sociocultural factors, such as relationship discord, life-stage stressors (the empty nest syndrome or anxiety and sleep deprivation from a new baby), as well as cultural or religious values that suppress sexuality, also should be considered.⁹ Experience-based neuroplasticity (changes in brain pathways that become solidified by negative or positive experiences) may elucidate how a multimodal approach, utilizing medical and psychological treatment, can be beneficial for patients, particularly those with hypoactive sexual desire disorder (HSDD).¹

New and emerging approaches to managing female sexual dysfunction

Three agents, one of which has been available for prescription for some time, one that is newly available, and one in the pipeline, are or may soon be in the gynecologist's armamentarium.

Flibanserin

Medications that target excitatory pathways or blunt inhibitory pathways are in development, and one, flibanserin (Addyi), has been US Food and Drug Administration (FDA)-approved for the treatment of acquired, generalized HSDD in premenopausal women.^1,10 Flibanserin is a nonhormonal, centrally acting, postsynaptic serotonin 1A receptor agonist and a serotonin 2A receptor antagonist that is taken daily at bedtime (100 mg); several weeks are usually needed before any effects are noted.¹ It is not approved for postmenopausal women and has a boxed warning about the risks of hypotension and syncope; its use is contraindicated in women who drink alcohol, in those who have hepatic impairment, and with the use of moderate or strong CYP3A4 inhibitors.¹¹

Also keep in mind that flibanserin is only available through a Risk Evaluation and Mitigation Strategy program, so clinicians who wish to prescribe it must enroll in and complete training to become certified providers.⁹

Related article:
What you need to know (and do) to prescribe the new drug flibanserin

Prasterone

Prasterone (Intrarosa), a once-daily intravaginal dehydroepiandrosterone (DHEA) product, is a prohormone that increases local estrogen and testosterone and has the advantage of improved sexual function, desire, arousal, lubrication, orgasm, satisfaction, as well as pain at sexual activity.¹² It was approved by the FDA in November 2016 to treat moderate to severe dyspareunia and has been available for prescribing since July 2017. Its cost is comparable to topical estrogen products, with a $25 copay program.

Because prasterone is not an estrogen, it does not have the boxed warning that all estrogen products are mandated by the FDA to have. This may make it more acceptable to patients, who often decline to use an estrogen product after seeing the boxed warning on the package. The Centers for Medicare and Medicaid Services (CMS) does not have prasterone on its list of potentially hazardous drugs for the elderly. However, keep in mind that because its label is for dyspareunia and not specifically for GSM, CMS considers it a drug of choice--in other words, like sildenafil (Viagra), a lifestyle choice and not for treatment of a medical condition. As such, at the present time, Medicare does not cover it.

Bremelanotide

Late-stage trials of bremelanotide, a melanocortin receptor agonist, are underway. Its mechanism of action is somewhat like that of flibanserin in that both drugs increase dopamine and norepinephrine levels. The advantage of bremelanotide is that it is used as needed. It is dosed subcutaneously (1.75 mg) and it can be used as often as a woman would like to use it. The FDA is expected to consider it for approval in about a year. Unpublished data from poster sessions at recent meetings show that, in a phase 3 study of 1,247 premenopausal women with HSDD (who had already been screened for depression and were found to have a physiologic condition), improvements in desire, arousal, lubrication, and orgasm were shown with bremelanotide. About 18% of women stopped using the drug because of adverse effects (nausea, vomiting, flushing, or headache) versus 2% for placebo. Like flibanserin, it is expected to be approved for premenopausal women only. 

Read how 3 experts would manage differing GSM symptoms.

What would you prescribe for these patients? 

CASE Genitourinary syndrome of menopause (GSM) in a 55-year-old woman

A 55-year-old widow is beginning a new relationship. She has not had partnered sexual activity for several years, but she recently has begun a relationship. She describes pain with attempted penetration with her new partner. Her last menstrual period was 3 years ago and she has experienced very minor menopausal symptoms, which are not bothersome. On examination, the vulva and vagina are pale, with thin epithelium and absent rugae. The tissue lacks elasticity. A virginal speculum is needed to visualize the cervix.

How would you go about deciding which of the many options for management of GSM you will recommend for this patient? What do you weigh as you consider DHEA versus estrogen and topical versus oral therapy?
 
JoAnn V. Pinkerton, MD: Vulvovaginal atrophy (VVA), part of GSM, is associated with postmenopausal estrogen deficiency and includes the signs and symptoms seen on this patient's physical exam: vaginal narrowing, pallor, loss of elasticity, as well as pain with intercourse.⁶ Estrogen therapy is the most effective treatment for vaginal atrophy.¹³ Since she does not have significant menopausal symptoms, low-dose vaginal estrogen preparations are effective and generally safe treatments for VVA; these include creams, tablets containing estradiol or conjugated equine estrogen (CEE), and a low-dose vaginal estradiol ring--all available at doses that result in minimal systemic absorption.

Choice is usually made based on patient desire and likely adherence. If the patient prefers nonestrogen therapies that improve VVA and have been approved for relief of dyspareunia in postmenopausal women, I would discuss with the patient the oral selective estrogen receptor modulator ospemifene,¹⁴ and the new intravaginal DHEA suppositories, prasterone.¹⁵ Ospemifene is taken daily as an oral tablet, has a small risk of blood clots, and is my choice for women who do not need systemic hormone therapy and prefer to avoid vaginal therapy.

Andrew M. Kaunitz, MD: GSM is prevalent in menopausal women and, if not treated, causes progressive vaginal dryness and sexual discomfort. When the main indication for hormonal management in a menopausal woman is GSM (as opposed to treatment of vasomotor symptoms or prevention of osteoporosis), the treatment of choice is low-dose local vaginal estrogen, ospemifene, or prasterone (DHEA). Prasterone is a vaginally administered nonestrogen steroid that was approved by the FDA to treat dyspareunia associated with GSM. DHEA is an endogenous inactive steroid that is converted locally into androgens and estrogens; one vaginal insert is placed nightly.^16,17

This 55-year-old widow has not been sexually active for some time. The facts that attempted penetration was painful and only an ultrathin (virginal) speculum could be used for examination indicate that contraction of the pelvic floor muscles is likely present. Simply starting medical management may not lead to comfortable/successful penetrative sex for this woman. In addition to  medical management, she would likely benefit from referral for physical therapy. Using dilators and other strategies, along with the positive impact that medical management will have on the vaginal mucosa, a woman's physical therapist can work with this patient to help the pelvic floor muscles relax and facilitate comfortable penetrative sex.

James A. Simon, MD: With only minor vasomotor symptoms, I would assess the other potential benefits of a systemic therapy. These might include cardiovascular risk reduction (systemic estrogens or estrogens/progesterone in some), breast cancer risk reduction (some data suggesting ospemifene can accomplish this), osteoporosis prevention (systemic estrogens and estrogen/androgens), etc. If there is an option for a treatment to address more than one symptom, in this case GSM, assessing the risks/benefits of each of these therapies should be estimated for this specific patient.

If there are no systemic benefits to be had, then any of the local treatments should be helpful. As there are no head-to-head comparisons available, local estrogen cream, tablets, rings, local DHEA, or systemic ospemifene each should be considered possible treatments. I also feel this patient may benefit from supplementary self-dilation and/or physical therapy.

Related article:
2017 Update on menopause

 
CASE Dyspareunia and vasomotor symptoms in a 42-year-old breast cancer survivor

A 42-year-old woman with a BRCA1 mutation has undergone prophylactic mastectomies as well as hysterectomy with bilateral salpingo-oophorectomy. She reports mild to moderate hot flashes and bothersome vaginal dryness and dyspareunia. Examination confirms GSM.

Would you advise systemic hormone therapy for this patient? What would your recommendation be for management of her GSM symptoms?

Dr. Simon: While one's gut reaction would be to avoid systemic estrogen therapy in a patient with a BRCA1 mutation, the scientific information confirming this fear is lacking.¹⁸ Such patients may benefit significantly from systemic estrogen therapy (reduced risk of cardiovascular disease and cognitive decline, etc.), and with both breasts and both ovaries removed, estrogen's breast cancer risks, if any in this population, are largely avoided. The patient also may benefit from additional local therapy with either estrogens or DHEA.

Dr. Kaunitz: Due to her high lifetime risk of breast and ovarian cancer, this woman has proceeded with risk-reducing breast and gynecologic surgery. As more BRCA mutation carriers are being identified and undergo risk-reducing bilateral mastectomy (usually with reconstruction) and salpingo-oophorectomy, clinicians and mutation carriers more frequently face decisions regarding use of systemic hormone therapy.

Mutation carriers who have undergone bilateral risk-reducing mastectomy experience a very low baseline future risk for breast cancer; accordingly, concerns regarding this disease should not prevent use of systemic hormone therapy. Furthermore, without hormone replacement, induced menopause in women this age is associated with an elevated risk of osteoporosis, persistent vasomotor symptoms, cardiovascular disease, stroke, mood changes, dementia, Parkinson disease, and overall mortality. Recognizing the safety of estrogen therapy in this setting, this 42-year-old BRCA1 mutation carrier can initiate estrogen therapy. Standard dose estrogen therapy refers to oral estradiol 1.0 mg, conjugated equine estrogen 0.625 mg,or transdermal estradiol 0.05 mg. In younger women like this 42-year-old with surgically induced menopause, higher than standard replacement doses of estrogen are often appropriate.¹⁷

Due to concerns the hormone therapy might further increase future risk of breast cancer, some mutation carriers may delay or avoid risk-reducing bilateral salpingo-oophorectomy, a potentially lifesaving surgery which reduces not only future risk of ovarian cancer but also future risk for breast cancer.

Among mutation carriers with intact breasts, several studies address risk of breast cancer with use of systemic hormone therapy. Although limited in numbers of participants and years of follow-up, in aggregate, these studies provide reassurance that short-term use of systemic hormone therapy does not increase breast cancer risk in women with BRCA1 or BRCA2 mutations and intact breasts.¹⁹

Dr. Pinkerton: For this woman with early surgical menopause and hysterectomy, estrogen therapy could improve her vasomotor symptoms and decrease her risk of bone loss and GSM.¹⁷ In the Women's Health Initiative trial, there were 7 fewer breast cancers per 10,000 women-years in the estrogen-onlyarm.²⁰ Observational studies suggest that hormone therapy, when given to the average age of menopause, decreases the risks of heart disease, Parkinson disease, and dementia.²¹ Limited observational evidence suggests that hormone therapy use does not further increase risk of breast cancer in women following oophorectomy for BRCA1 or BRCA2 gene mutation.²²

The absolute risks observed with hormone therapy tended to be small, especially in younger, healthy women. Systemic hormone therapy could treat her hot flashes and her GSM symptoms and potentially decrease health risks associated with premature estrogen deficiency. Nonestrogen therapies for hot flashes include low-dose antidepressants, gabapentin, and mind-body options, such as cognitive behavioral therapy and hypnosis, but these would not decrease her health risks or treat her GSM.

If she only requests treatment of her GSM symptoms, she would be a candidate for low-dose vaginal estrogen therapy, given as a cream, tablet, or ring depending on her choice. I would not choose ospemifene as my first choice as she is having hot flashes, and there are no data yet on the drug's health benefits in early menopause. If she prefers nonestrogen vaginal therapy, the new intravaginal DHEA might be a good choice as both estrogen and testosterone are increased locally in the vagina while hormone levels remain in the postmenopausal range. There is no boxed warning on the patient insert, although safety in women with breast cancer or in those with elevated risk of breast cancer has not been tested.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Nevus sebaceous (NS)

Nevus sebaceous (NS) is a congenital hamartoma of the sebaceous glands that was first described by Josef Jadassohn, MD, in 1895. The lesion is caused by a post-zygotic somatic mutation in the KRAS or HRAS genes, which can lead to variable clinical mosaicism. In addition, hamartomatous presentations within different cell lines may occur if the pluripotent stem cells are affected. The lesion is present in about 0.3% of newborns and is equally represented among gender, race, and geography.

NS has three stages of presentation. At birth or early childhood, NS most commonly presents as a solitary, well-circumscribed, smooth, yellow to tan-brown plaque with associated hair loss in the vertex of the scalp, although it may less commonly present on the face, neck, or trunk. The lesion may be raised at birth. During puberty, hormonal variations alter the form of the lesion and the NS can become more verrucous and nodular. The clinical differential diagnosis for NS includes seborrheic keratosis, congenital nevus, and epidermal nevus.

About 24% of patients may develop appendageal tumors arising from the primary lesion. The majority of these tumors are benign, with trichoblastoma and syringocystadenoma papilliferum as the most common secondary growths. The most common malignant tumor that arises is basal cell carcinoma. Deletion of the patched gene has been implicated in the development of basal cell carcinoma within NS lesions. Many other tumors arising from NS lesions have been reported in the literature, including keratoacanthoma, apocrine cystadenoma, leiomyoma, and sebaceous cell carcinoma. More rarely, development of an eccrine or apocrine carcinoma within the NS can lead to widespread metastasis and death.

Because there is a chance of secondary tumor development, the decision to surgically excise the lesion or closely follow for transformation is controversial. Advocates of surgical excision reason that adolescence is the optimal time for removal because it is before pubertal enlargement and the patient would be able to tolerate anesthesia. If the patient chooses to clinically monitor the lesion, he or she should be informed that a full-thickness excision with wide margins will have to be performed if malignant transformation occurs.

A biopsy was performed of the erythematous papule that revealed an atypical sebaceous neoplasm with features of a sebaceoma. The patient had subsequent excision of the entire lesion that was read by a different dermatopathologist and revealed nevus sebaceous with syringocystadenoma papilliferum, no residual atypical sebaceous neoplasm, and clear margins.

This case and photo were submitted by Victoria Billero, University of Miami, and Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].

Nevus sebaceous (NS)

Nevus sebaceous (NS) is a congenital hamartoma of the sebaceous glands that was first described by Josef Jadassohn, MD, in 1895. The lesion is caused by a post-zygotic somatic mutation in the KRAS or HRAS genes, which can lead to variable clinical mosaicism. In addition, hamartomatous presentations within different cell lines may occur if the pluripotent stem cells are affected. The lesion is present in about 0.3% of newborns and is equally represented among gender, race, and geography.

NS has three stages of presentation. At birth or early childhood, NS most commonly presents as a solitary, well-circumscribed, smooth, yellow to tan-brown plaque with associated hair loss in the vertex of the scalp, although it may less commonly present on the face, neck, or trunk. The lesion may be raised at birth. During puberty, hormonal variations alter the form of the lesion and the NS can become more verrucous and nodular. The clinical differential diagnosis for NS includes seborrheic keratosis, congenital nevus, and epidermal nevus.

About 24% of patients may develop appendageal tumors arising from the primary lesion. The majority of these tumors are benign, with trichoblastoma and syringocystadenoma papilliferum as the most common secondary growths. The most common malignant tumor that arises is basal cell carcinoma. Deletion of the patched gene has been implicated in the development of basal cell carcinoma within NS lesions. Many other tumors arising from NS lesions have been reported in the literature, including keratoacanthoma, apocrine cystadenoma, leiomyoma, and sebaceous cell carcinoma. More rarely, development of an eccrine or apocrine carcinoma within the NS can lead to widespread metastasis and death.

Because there is a chance of secondary tumor development, the decision to surgically excise the lesion or closely follow for transformation is controversial. Advocates of surgical excision reason that adolescence is the optimal time for removal because it is before pubertal enlargement and the patient would be able to tolerate anesthesia. If the patient chooses to clinically monitor the lesion, he or she should be informed that a full-thickness excision with wide margins will have to be performed if malignant transformation occurs.

A biopsy was performed of the erythematous papule that revealed an atypical sebaceous neoplasm with features of a sebaceoma. The patient had subsequent excision of the entire lesion that was read by a different dermatopathologist and revealed nevus sebaceous with syringocystadenoma papilliferum, no residual atypical sebaceous neoplasm, and clear margins.

This case and photo were submitted by Victoria Billero, University of Miami, and Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].

Nevus sebaceous (NS)

Nevus sebaceous (NS) is a congenital hamartoma of the sebaceous glands that was first described by Josef Jadassohn, MD, in 1895. The lesion is caused by a post-zygotic somatic mutation in the KRAS or HRAS genes, which can lead to variable clinical mosaicism. In addition, hamartomatous presentations within different cell lines may occur if the pluripotent stem cells are affected. The lesion is present in about 0.3% of newborns and is equally represented among gender, race, and geography.

NS has three stages of presentation. At birth or early childhood, NS most commonly presents as a solitary, well-circumscribed, smooth, yellow to tan-brown plaque with associated hair loss in the vertex of the scalp, although it may less commonly present on the face, neck, or trunk. The lesion may be raised at birth. During puberty, hormonal variations alter the form of the lesion and the NS can become more verrucous and nodular. The clinical differential diagnosis for NS includes seborrheic keratosis, congenital nevus, and epidermal nevus.

About 24% of patients may develop appendageal tumors arising from the primary lesion. The majority of these tumors are benign, with trichoblastoma and syringocystadenoma papilliferum as the most common secondary growths. The most common malignant tumor that arises is basal cell carcinoma. Deletion of the patched gene has been implicated in the development of basal cell carcinoma within NS lesions. Many other tumors arising from NS lesions have been reported in the literature, including keratoacanthoma, apocrine cystadenoma, leiomyoma, and sebaceous cell carcinoma. More rarely, development of an eccrine or apocrine carcinoma within the NS can lead to widespread metastasis and death.

Because there is a chance of secondary tumor development, the decision to surgically excise the lesion or closely follow for transformation is controversial. Advocates of surgical excision reason that adolescence is the optimal time for removal because it is before pubertal enlargement and the patient would be able to tolerate anesthesia. If the patient chooses to clinically monitor the lesion, he or she should be informed that a full-thickness excision with wide margins will have to be performed if malignant transformation occurs.

A biopsy was performed of the erythematous papule that revealed an atypical sebaceous neoplasm with features of a sebaceoma. The patient had subsequent excision of the entire lesion that was read by a different dermatopathologist and revealed nevus sebaceous with syringocystadenoma papilliferum, no residual atypical sebaceous neoplasm, and clear margins.

This case and photo were submitted by Victoria Billero, University of Miami, and Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at edermatologynews.com. To submit a case for possible publication, send an email to [email protected].

Study Overview

Objective. To determine the effect of implementing an intervention to reduce catheter-associated urinary tract infections (CAUTIs) in nursing homes.

Design. Prospective implementation project.

Setting and participants. The study was conducted between March 2014 and August 2016 in 12-month cohorts of community-based nursing homes participating in the Agency for Healthcare Research and Quality Safety Program for Long-Term Care. A total of 568 nursing homes located across 48 states, Washington DC, and Puerto Rico were recruited to participate.

Intervention. The intervention was developed with the goal of modifying the elements of the Comprehensive Unit-Based Safety Program utilized in hospitals for adoption in nursing homes. The intervention included a technical bundle, that is, catheter removal, aseptic insertion, using regular assessments, training for catheter care, and incontinence care planning [1], as well as socioadaptive interventions focused on empowering teams, addressing implementation challenges, offering solutions, promoting resident safety culture, team building, leadership, and resident and family engagement. The interventions were implemented over a 12-month period. To be included in the data analysis, nursing homes need to remain active through the end of the 12-month period and report 2 months or more of outcome data and device-days. Nursing homes that reported large fluctuations in reported data were excluded from the analysis. A total of 433 nursing homes remained active throughout the intervention period.

Main outcome measures. The main study outcome measure was the CAUTI incidence rate, defined as the number of CAUTIs divided by the number of catheter-days and multiplied by 1000. National Healthcare Safety Network definitions were used. The criteria for UTI
included objective systemic and localizing clinical findings along with laboratory-based criteria. A secondary outcome was the urinary catheter utilization ratio, defined as the number of catheter-days divided by the number of resident-days multiplied by 100 and reported as a percentage. Participating nursing homes collected data on the daily number of CAUTIs, catheter days, resident days, and urine cultures for each month of the project period and these metrics were reported using the Health Research and Educational Trust, a research affiliate of the American Hospital Association, Comprehensive Data System.

Conclusion. A multicomponent intervention implemented in community-based nursing homes across the country was associated with a reduction in CAUTI rates. The study shows that the intervention to reduce CAUTI can be implemented on a large scale and can be associated with improvement in patient safety.

Commentary

Catheter-associated urinary tract infection is a common condition that affects nursing home residents, as nursing home residents often have an indwelling urinary catheter on admission to the nursing home. These infections can be costly, lead to hospital admissions, and can contribute to the development of multidrug-resistant organisms, which pose a significant public health threat [2]. CAUTIs, however, are potentially preventable through the use of practices that promote judicious use of urinary catheters and attention to aseptic insertion and catheter care [3,4]. Although prior randomized controlled trials demonstrated the potential impact of interventions that reduce incidence of urinary tract infections [5], the interventions have not been adopted widely.

Recognizing the importance of improving safety through reducing CAUTIs, the Agency for Healthcare Research and Quality has established toolkits and implementation guides for health care facilities to adopt better practices for reducing catheter-associated infections. This study adds to the current literature by demonstrating the feasibility and beneficial impact of widespread implementation of AHRQ tools.

The study evaluated the impact of the intervention in a large cohort of nursing homes, comparing outcome measures pre and post intervention. One limitation of the study is that other factors that were present concurrently may have contributed to the observed changes in CAUTI outcomes. The study also did not have a control group, and the changes in outcome rates were not compared with rates in homes that did not participate in the project. Also, it is not possible to examine the effect of the individual components of the intervention as this intervention had multiple components delivered simultaneously. Despite these drawbacks, the study makes a strong case that project implementation is associated with a reduction in CAUTI rates of more than 50%.

A next step to better understand how best to disseminate the intervention is to identify factors associated with greater improvements in outcomes among the cohort of nursing homes and also to understand the variations in how nursing homes are implementing the intervention and what impact these differences might have. This in turn may guide further efforts to broaden the impact through more nuanced application of the intervention.

Applications for Clinical Practice

This study demonstrates that CAUTI can be prevented through a multicomponent intervention that focuses on appropriate use and discontinuation of urinary catheters and proper catheter care. Given that these tools and guides are available for use through AHRQ, nursing homes should examine the potential for adoption in their facilities. This can enhance the safety for their residents by reducing the risk of a potentially preventable complication.

—William W. Hung, MD, MPH

Study Overview

Objective. To determine the effect of implementing an intervention to reduce catheter-associated urinary tract infections (CAUTIs) in nursing homes.

Design. Prospective implementation project.

Setting and participants. The study was conducted between March 2014 and August 2016 in 12-month cohorts of community-based nursing homes participating in the Agency for Healthcare Research and Quality Safety Program for Long-Term Care. A total of 568 nursing homes located across 48 states, Washington DC, and Puerto Rico were recruited to participate.

Intervention. The intervention was developed with the goal of modifying the elements of the Comprehensive Unit-Based Safety Program utilized in hospitals for adoption in nursing homes. The intervention included a technical bundle, that is, catheter removal, aseptic insertion, using regular assessments, training for catheter care, and incontinence care planning [1], as well as socioadaptive interventions focused on empowering teams, addressing implementation challenges, offering solutions, promoting resident safety culture, team building, leadership, and resident and family engagement. The interventions were implemented over a 12-month period. To be included in the data analysis, nursing homes need to remain active through the end of the 12-month period and report 2 months or more of outcome data and device-days. Nursing homes that reported large fluctuations in reported data were excluded from the analysis. A total of 433 nursing homes remained active throughout the intervention period.

Main outcome measures. The main study outcome measure was the CAUTI incidence rate, defined as the number of CAUTIs divided by the number of catheter-days and multiplied by 1000. National Healthcare Safety Network definitions were used. The criteria for UTI
included objective systemic and localizing clinical findings along with laboratory-based criteria. A secondary outcome was the urinary catheter utilization ratio, defined as the number of catheter-days divided by the number of resident-days multiplied by 100 and reported as a percentage. Participating nursing homes collected data on the daily number of CAUTIs, catheter days, resident days, and urine cultures for each month of the project period and these metrics were reported using the Health Research and Educational Trust, a research affiliate of the American Hospital Association, Comprehensive Data System.

Conclusion. A multicomponent intervention implemented in community-based nursing homes across the country was associated with a reduction in CAUTI rates. The study shows that the intervention to reduce CAUTI can be implemented on a large scale and can be associated with improvement in patient safety.

Commentary

Catheter-associated urinary tract infection is a common condition that affects nursing home residents, as nursing home residents often have an indwelling urinary catheter on admission to the nursing home. These infections can be costly, lead to hospital admissions, and can contribute to the development of multidrug-resistant organisms, which pose a significant public health threat [2]. CAUTIs, however, are potentially preventable through the use of practices that promote judicious use of urinary catheters and attention to aseptic insertion and catheter care [3,4]. Although prior randomized controlled trials demonstrated the potential impact of interventions that reduce incidence of urinary tract infections [5], the interventions have not been adopted widely.

Recognizing the importance of improving safety through reducing CAUTIs, the Agency for Healthcare Research and Quality has established toolkits and implementation guides for health care facilities to adopt better practices for reducing catheter-associated infections. This study adds to the current literature by demonstrating the feasibility and beneficial impact of widespread implementation of AHRQ tools.

The study evaluated the impact of the intervention in a large cohort of nursing homes, comparing outcome measures pre and post intervention. One limitation of the study is that other factors that were present concurrently may have contributed to the observed changes in CAUTI outcomes. The study also did not have a control group, and the changes in outcome rates were not compared with rates in homes that did not participate in the project. Also, it is not possible to examine the effect of the individual components of the intervention as this intervention had multiple components delivered simultaneously. Despite these drawbacks, the study makes a strong case that project implementation is associated with a reduction in CAUTI rates of more than 50%.

A next step to better understand how best to disseminate the intervention is to identify factors associated with greater improvements in outcomes among the cohort of nursing homes and also to understand the variations in how nursing homes are implementing the intervention and what impact these differences might have. This in turn may guide further efforts to broaden the impact through more nuanced application of the intervention.

Applications for Clinical Practice

This study demonstrates that CAUTI can be prevented through a multicomponent intervention that focuses on appropriate use and discontinuation of urinary catheters and proper catheter care. Given that these tools and guides are available for use through AHRQ, nursing homes should examine the potential for adoption in their facilities. This can enhance the safety for their residents by reducing the risk of a potentially preventable complication.

—William W. Hung, MD, MPH

Study Overview

Objective. To determine the effect of implementing an intervention to reduce catheter-associated urinary tract infections (CAUTIs) in nursing homes.

Design. Prospective implementation project.

Setting and participants. The study was conducted between March 2014 and August 2016 in 12-month cohorts of community-based nursing homes participating in the Agency for Healthcare Research and Quality Safety Program for Long-Term Care. A total of 568 nursing homes located across 48 states, Washington DC, and Puerto Rico were recruited to participate.

Intervention. The intervention was developed with the goal of modifying the elements of the Comprehensive Unit-Based Safety Program utilized in hospitals for adoption in nursing homes. The intervention included a technical bundle, that is, catheter removal, aseptic insertion, using regular assessments, training for catheter care, and incontinence care planning [1], as well as socioadaptive interventions focused on empowering teams, addressing implementation challenges, offering solutions, promoting resident safety culture, team building, leadership, and resident and family engagement. The interventions were implemented over a 12-month period. To be included in the data analysis, nursing homes need to remain active through the end of the 12-month period and report 2 months or more of outcome data and device-days. Nursing homes that reported large fluctuations in reported data were excluded from the analysis. A total of 433 nursing homes remained active throughout the intervention period.

Main outcome measures. The main study outcome measure was the CAUTI incidence rate, defined as the number of CAUTIs divided by the number of catheter-days and multiplied by 1000. National Healthcare Safety Network definitions were used. The criteria for UTI
included objective systemic and localizing clinical findings along with laboratory-based criteria. A secondary outcome was the urinary catheter utilization ratio, defined as the number of catheter-days divided by the number of resident-days multiplied by 100 and reported as a percentage. Participating nursing homes collected data on the daily number of CAUTIs, catheter days, resident days, and urine cultures for each month of the project period and these metrics were reported using the Health Research and Educational Trust, a research affiliate of the American Hospital Association, Comprehensive Data System.

Conclusion. A multicomponent intervention implemented in community-based nursing homes across the country was associated with a reduction in CAUTI rates. The study shows that the intervention to reduce CAUTI can be implemented on a large scale and can be associated with improvement in patient safety.

Commentary

Catheter-associated urinary tract infection is a common condition that affects nursing home residents, as nursing home residents often have an indwelling urinary catheter on admission to the nursing home. These infections can be costly, lead to hospital admissions, and can contribute to the development of multidrug-resistant organisms, which pose a significant public health threat [2]. CAUTIs, however, are potentially preventable through the use of practices that promote judicious use of urinary catheters and attention to aseptic insertion and catheter care [3,4]. Although prior randomized controlled trials demonstrated the potential impact of interventions that reduce incidence of urinary tract infections [5], the interventions have not been adopted widely.

Recognizing the importance of improving safety through reducing CAUTIs, the Agency for Healthcare Research and Quality has established toolkits and implementation guides for health care facilities to adopt better practices for reducing catheter-associated infections. This study adds to the current literature by demonstrating the feasibility and beneficial impact of widespread implementation of AHRQ tools.

The study evaluated the impact of the intervention in a large cohort of nursing homes, comparing outcome measures pre and post intervention. One limitation of the study is that other factors that were present concurrently may have contributed to the observed changes in CAUTI outcomes. The study also did not have a control group, and the changes in outcome rates were not compared with rates in homes that did not participate in the project. Also, it is not possible to examine the effect of the individual components of the intervention as this intervention had multiple components delivered simultaneously. Despite these drawbacks, the study makes a strong case that project implementation is associated with a reduction in CAUTI rates of more than 50%.

A next step to better understand how best to disseminate the intervention is to identify factors associated with greater improvements in outcomes among the cohort of nursing homes and also to understand the variations in how nursing homes are implementing the intervention and what impact these differences might have. This in turn may guide further efforts to broaden the impact through more nuanced application of the intervention.

Applications for Clinical Practice

This study demonstrates that CAUTI can be prevented through a multicomponent intervention that focuses on appropriate use and discontinuation of urinary catheters and proper catheter care. Given that these tools and guides are available for use through AHRQ, nursing homes should examine the potential for adoption in their facilities. This can enhance the safety for their residents by reducing the risk of a potentially preventable complication.

—William W. Hung, MD, MPH

EXPERT COMMENTARY

The American Society for Colposcopy and Cervical Pathology (ASCCP) has recommended HPV triage for ASC-US cytology for more than 15 years. Since the ALTS trial demonstrated improved detection of CIN2+ in women with ASC-US cytology, HPV testing has become the preferred triage strategy for women with ASC-US cytology, except for women under age 25.¹ However, we do not know the long-term outcomes for these women. The study by Cuzick and colleagues uniquely addresses this question.

Details of the study

The retrospective review of data from the New Mexico HPV Pap Registry examined the influence of HPV testing on outcomes in 20,677 women with ASC-US cytology between 2008 and 2012. Of those women, 80.5% had an HPV test, and the authors estimated that 80.6% of those HPV tests were for triage after ASC-US cytology as opposed to co-testing (that is, cytology and HPV testing together). Of note, the majority of these Pap tests were performed prior to the 2012 ASCCP guidelines that recommend HPV co-testing for all women aged 30 to 64 years regardless of cytology. Of the HPV tests performed, 43.1% were positive. The investigators then examined rates of CIN in the interval between ASC-US cytology and biopsy-confirmed CIN, and rates of loop electrosurgical excision procedures (LEEP) and results at 5 years.

The investigators found a non–statistically significant increase in overall detection of CIN3 (relative risk [RR], 1.16; 95% confidence interval [CI], 0.92–1.45) in women who had been triaged with HPV testing, and a significant increase in overall detection of CIN2 (RR, 1.27; 95% CI, 1.06–1.53) and CIN1 (RR, 1.76; 95% CI, 1.56–2.00). CIN1, CIN2, and CIN3 were detected significantly earlier in patients with HPV testing. As expected, the majority of CIN2 and CIN3 was diagnosed in women who were HPV positive.

Related article:
2017 Update on cervical disease

The proportion of women undergoing either endocervical curettage or cervical biopsy was higher in those with HPV testing (32.1% vs 20.6%, P<.001), as were LEEP rates (4.9% vs 4.0%, P = .03). LEEP rates were highest in the year after a positive HPV test and were mostly attributable to CIN1 results. However, the overall ratio of LEEP to CIN3+ diagnosis was similar in women who were tested for HPV compared with those who were not. A larger proportion of patients with HPV testing had follow-up compared with those without HPV testing (84.1% vs 78.9%, P<.001).

The authors concluded that HPV testing in women with ASC-US cytology leads to detecting high-grade disease earlier, but that HPV positivity results in more interventions, largely due to an overdiagnosis of CIN1. They also confirmed that the majority of high-grade lesions are found in women with positive HPV tests.

Related article:
2015 Update on cervical disease: New ammo for HPV prevention and screening

Study strengths and weaknesses

This is the first comprehensive long-term look at women with ASC-US cytology and the impact of HPV testing. The New Mexico HPV Pap Registry is the only US state-based registry with comprehensive follow-up data. This study’s results build on previous data that showed sensitivity is increased with the addition of HPV testing to cervical cytology,¹ and they support current ASCCP guidelines that emphasize HPV triage or co-testing for women age 25 or older.

Potential bias. While this study has the benefit of a large cohort, it is limited by biases inherent in retrospective study design. One important potential bias is the differential utilization of HPV testing or procedures by providers. The authors acknowledge preliminary analyses that show that some clinics (rural, federally qualified health centers, public health clinics) serving underserved populations may underutilize or inappropriately utilize HPV testing.

Further, the 2008–2012 study period may make the results less generalizable to current practices since the ASCCP guidelines were adjusted to include more HPV testing in women aged 25 and older in 2012.

Finally, this study examines CIN but does not specifically look at the impact of HPV testing on the ultimate outcome of interest, cervical cancer rates.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

The American Society for Colposcopy and Cervical Pathology (ASCCP) has recommended HPV triage for ASC-US cytology for more than 15 years. Since the ALTS trial demonstrated improved detection of CIN2+ in women with ASC-US cytology, HPV testing has become the preferred triage strategy for women with ASC-US cytology, except for women under age 25.¹ However, we do not know the long-term outcomes for these women. The study by Cuzick and colleagues uniquely addresses this question.

Details of the study

The retrospective review of data from the New Mexico HPV Pap Registry examined the influence of HPV testing on outcomes in 20,677 women with ASC-US cytology between 2008 and 2012. Of those women, 80.5% had an HPV test, and the authors estimated that 80.6% of those HPV tests were for triage after ASC-US cytology as opposed to co-testing (that is, cytology and HPV testing together). Of note, the majority of these Pap tests were performed prior to the 2012 ASCCP guidelines that recommend HPV co-testing for all women aged 30 to 64 years regardless of cytology. Of the HPV tests performed, 43.1% were positive. The investigators then examined rates of CIN in the interval between ASC-US cytology and biopsy-confirmed CIN, and rates of loop electrosurgical excision procedures (LEEP) and results at 5 years.

The investigators found a non–statistically significant increase in overall detection of CIN3 (relative risk [RR], 1.16; 95% confidence interval [CI], 0.92–1.45) in women who had been triaged with HPV testing, and a significant increase in overall detection of CIN2 (RR, 1.27; 95% CI, 1.06–1.53) and CIN1 (RR, 1.76; 95% CI, 1.56–2.00). CIN1, CIN2, and CIN3 were detected significantly earlier in patients with HPV testing. As expected, the majority of CIN2 and CIN3 was diagnosed in women who were HPV positive.

Related article:
2017 Update on cervical disease

The proportion of women undergoing either endocervical curettage or cervical biopsy was higher in those with HPV testing (32.1% vs 20.6%, P<.001), as were LEEP rates (4.9% vs 4.0%, P = .03). LEEP rates were highest in the year after a positive HPV test and were mostly attributable to CIN1 results. However, the overall ratio of LEEP to CIN3+ diagnosis was similar in women who were tested for HPV compared with those who were not. A larger proportion of patients with HPV testing had follow-up compared with those without HPV testing (84.1% vs 78.9%, P<.001).

The authors concluded that HPV testing in women with ASC-US cytology leads to detecting high-grade disease earlier, but that HPV positivity results in more interventions, largely due to an overdiagnosis of CIN1. They also confirmed that the majority of high-grade lesions are found in women with positive HPV tests.

Related article:
2015 Update on cervical disease: New ammo for HPV prevention and screening

Study strengths and weaknesses

This is the first comprehensive long-term look at women with ASC-US cytology and the impact of HPV testing. The New Mexico HPV Pap Registry is the only US state-based registry with comprehensive follow-up data. This study’s results build on previous data that showed sensitivity is increased with the addition of HPV testing to cervical cytology,¹ and they support current ASCCP guidelines that emphasize HPV triage or co-testing for women age 25 or older.

Potential bias. While this study has the benefit of a large cohort, it is limited by biases inherent in retrospective study design. One important potential bias is the differential utilization of HPV testing or procedures by providers. The authors acknowledge preliminary analyses that show that some clinics (rural, federally qualified health centers, public health clinics) serving underserved populations may underutilize or inappropriately utilize HPV testing.

Further, the 2008–2012 study period may make the results less generalizable to current practices since the ASCCP guidelines were adjusted to include more HPV testing in women aged 25 and older in 2012.

Finally, this study examines CIN but does not specifically look at the impact of HPV testing on the ultimate outcome of interest, cervical cancer rates.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

The American Society for Colposcopy and Cervical Pathology (ASCCP) has recommended HPV triage for ASC-US cytology for more than 15 years. Since the ALTS trial demonstrated improved detection of CIN2+ in women with ASC-US cytology, HPV testing has become the preferred triage strategy for women with ASC-US cytology, except for women under age 25.¹ However, we do not know the long-term outcomes for these women. The study by Cuzick and colleagues uniquely addresses this question.

Details of the study

The retrospective review of data from the New Mexico HPV Pap Registry examined the influence of HPV testing on outcomes in 20,677 women with ASC-US cytology between 2008 and 2012. Of those women, 80.5% had an HPV test, and the authors estimated that 80.6% of those HPV tests were for triage after ASC-US cytology as opposed to co-testing (that is, cytology and HPV testing together). Of note, the majority of these Pap tests were performed prior to the 2012 ASCCP guidelines that recommend HPV co-testing for all women aged 30 to 64 years regardless of cytology. Of the HPV tests performed, 43.1% were positive. The investigators then examined rates of CIN in the interval between ASC-US cytology and biopsy-confirmed CIN, and rates of loop electrosurgical excision procedures (LEEP) and results at 5 years.

The investigators found a non–statistically significant increase in overall detection of CIN3 (relative risk [RR], 1.16; 95% confidence interval [CI], 0.92–1.45) in women who had been triaged with HPV testing, and a significant increase in overall detection of CIN2 (RR, 1.27; 95% CI, 1.06–1.53) and CIN1 (RR, 1.76; 95% CI, 1.56–2.00). CIN1, CIN2, and CIN3 were detected significantly earlier in patients with HPV testing. As expected, the majority of CIN2 and CIN3 was diagnosed in women who were HPV positive.

Related article:
2017 Update on cervical disease

The proportion of women undergoing either endocervical curettage or cervical biopsy was higher in those with HPV testing (32.1% vs 20.6%, P<.001), as were LEEP rates (4.9% vs 4.0%, P = .03). LEEP rates were highest in the year after a positive HPV test and were mostly attributable to CIN1 results. However, the overall ratio of LEEP to CIN3+ diagnosis was similar in women who were tested for HPV compared with those who were not. A larger proportion of patients with HPV testing had follow-up compared with those without HPV testing (84.1% vs 78.9%, P<.001).

The authors concluded that HPV testing in women with ASC-US cytology leads to detecting high-grade disease earlier, but that HPV positivity results in more interventions, largely due to an overdiagnosis of CIN1. They also confirmed that the majority of high-grade lesions are found in women with positive HPV tests.

Related article:
2015 Update on cervical disease: New ammo for HPV prevention and screening

Study strengths and weaknesses

This is the first comprehensive long-term look at women with ASC-US cytology and the impact of HPV testing. The New Mexico HPV Pap Registry is the only US state-based registry with comprehensive follow-up data. This study’s results build on previous data that showed sensitivity is increased with the addition of HPV testing to cervical cytology,¹ and they support current ASCCP guidelines that emphasize HPV triage or co-testing for women age 25 or older.

Potential bias. While this study has the benefit of a large cohort, it is limited by biases inherent in retrospective study design. One important potential bias is the differential utilization of HPV testing or procedures by providers. The authors acknowledge preliminary analyses that show that some clinics (rural, federally qualified health centers, public health clinics) serving underserved populations may underutilize or inappropriately utilize HPV testing.

Further, the 2008–2012 study period may make the results less generalizable to current practices since the ASCCP guidelines were adjusted to include more HPV testing in women aged 25 and older in 2012.

Finally, this study examines CIN but does not specifically look at the impact of HPV testing on the ultimate outcome of interest, cervical cancer rates.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Abstract

• Background: Acute and prolonged exposure to hospital medical care can cause hospital-associated deconditioning with deleterious effects on patient care provision and quality of life. Physical rehabilitation provided by allied healthcare professionals can enable reacquisition of function via professional input into attainment of set goals. Separate to rehabilitative efforts, restorative care optimizes independence by motivating individuals to maintain and restore function. Nursing assistants (NAs) provide a significant amount of direct patient care and are well placed to deliver restorative care.
• Objective: To increase proportional restorative care interactions with hospitalized older adults by training NAs.
• Methods: A prospective cohort quality improvement (QI) project was undertaken at 3 acute hospital wards (patient minimum age 65 years) and 2 community subacute care wards in the UK. NAs working within the target settings received a 2-part restorative care training package. The primary evaluation tool was 51 hours in total of observation measuring the proportional change in restorative care events delivered by NAs.
• Results: NA-led restorative care events increased from 40 (pre-intervention) to 94 (post-intervention), representing a statistically significant proportional increase from 74% to 92% (χ2(1) 9.53, P = 0.002). NAs on occasions inadvertently emphasized restriction of function to manage risk and oblige with rest periods.
• Conclusion: Investing in NAs can influence the amount of restorative care delivered to hospitalized older adults at risk of hospital-associated deconditioning. Continued investment in NAs is indicated to influence top-down, mandated restorative care practice in this patient group.

Key words: older people; restorative care; hospital associated deconditioning; nursing assistants; rehabilitation; training.

Hospital-associated deconditioning is defined as a significant decline in functional abilities developed through acute and prolonged exposure to a medical care facility environment, and is independent of that attributed to primary pathologies resulting in acute admission [1]. Considerable research on iatrogenic complications in older hospitalized populations [1–5] has shown the impacts of hospital-associated deconditioning and associated dysfunctions on quality of life for patients and the resultant burden on health and social care provision [6].

Physical rehabilitation has been shown to restore function through high-dose repetition of task-specific activity [7], and the benefits attributed to extra physical therapy include improved mobility, activity, and participation [8]. Simply defined, physical rehabilitation is the reacquisition of function through multidisciplinary assessment and professional therapeutic input in attainment of set goals. A more recent nomenclature in health settings is “restorative care,” defined as a philosophy of care that encourages, enables, and motivates individuals to maintain and restore function, thereby optimizing independence [9]. It has been clearly defined as a philosophy separate from that of rehabilitation [9] and remote from task-related or “custodial care,” which is designed to assist in meeting patients’ daily activity needs without any therapeutic value.

In UK rehabilitation wards, nursing staff provide 4.5 times as much direct patient care time compared with allied health professionals, with paraprofessional nursing assistants (NAs, equivalent to certified nurse assistants [CNAs] in the United States) responsible for half of this direct nursing care [10]. Kessler’s group examined the evolving role of NAs in UK hospitals [11]. From a national survey of 700 NAs and 600 trained nurses, the authors upheld the view that NAs act as direct caregivers including through routine tasks traditionally delivered by nurses. They identified that NAs exhibit distinct qualities, which are valued by qualified nurses, including routine task fulfilment and abilities relating to patients, which enable NAs to enhance care quality. Indeed, the national findings of Kessler’s group were generalizable to our own clinical setting where a NA cohort was a well-placed, available, and motivated resource to deliver therapeutically focused care for our hospitalized older population.

The theoretical relationship between care approaches is complex and represents a challenge for service users and policy makers. For instance, comprehensive rehabilitation delivery during an acute care episode may lead to users not seeking custodial care at home. Conversely, day-to-day activities realized by custodial care at home may lead to users not seeking acute rehabilitative care [12]. With stable resources being assigned to more dependent users in higher numbers, reactive care regardless of environment has often been the model of choice.

However, an economic rationale has developed more recently where investment in maintenance and preventative models results in healthcare savings with models including the 4Rs; reablement, reactivation, rehabilitation, and restorative care [13]. In North America, restorative care approaches have resulted in favorable results in nursing home facilities [14] and at home [15], and restorative care education and motivation training for nursing assistants was effective in supporting a change in beliefs and practice behaviors [16]. While results show restorative care practices in the non-acute care sector are advantageous, it is unknown whether these approaches if adopted in hospital settings affect subsequent healthcare utilization in the non-acute facilities, or even if they are feasible to implement in acute facilities by a staff group able to do so. Therefore, the purpose of this QI project was to deploy a restorative care educational intervention for NA staff working with hospitalized older adults with the aim of increasing the proportion of restorative care delivered.

Methods
 

Context

This project was conducted at a UK National Health Service university teaching hospital trust at 3 acute hospital wards (patient minimum age 65 years) and 2 community subacute care wards for older patients. Participants consisted of all permanent or long-term temporary (> 3 months continuous employment) NAs working in the target settings (n = 36). The QI project design is summarized in Figure 1. The project applied the 4Es translational approach to regulate the QI intervention: Engage, Educate, Execute, and Evaluate [17]. The reporting of this study follows SQUIRE guidance [18].

Intervention

The QI activity was a holistic educational process for all NA participants.

Didactic Study Day

Each NA attended a study day led by a physical therapist (up to 10 NAs per group). A student-centered training approach was adopted, recognizing variations in adult learning styles [19], and included seminar style theory, video case scenarios, group work, practical skills, open discussion, and reflection. The training package outline was compiled following consensus among the multi-disciplinary team working in the target settings and the steering group. Topics covered were theory on the risk of hospitalization and benefits of early mobilization; case scenarios and examples of restorative care; identifying and overcoming barriers to restorative care; identifying appro-priate patients for a restorative care approach; practical skills, including assisting patients out of bed, ambulation, and eating/drinking; and challenging, problem-solving scenarios. All participants received a course handbook to facilitate learning.

Ward-Based Practice

Measures

Type of Care Event

The quantity and nature of all NA-patient functional task-related care events was established by independent systematic observation pre- and post-intervention. Observers rated the type of care for observed patients as either custodial or restorative events using a tool described below. In addition, the numbers of patients receiving no restorative care events at all during observation was calculated to capture changes in rates between patients observed. The observational tool used was adapted from that utilized in a North American study of a long-term care facility [20], which demonstrated favorable intra-rater reliability (person separation reliability of 0.77), inter-rater reliability (80% to 100% agreement on each of the care behaviors), and validity (evidence of unidimensionality and good fit of the items). Adaptations accommodated for data collection in a hospital environment and alteration to UK nomenclature.

Three blinded volunteer assessors undertook observations. The observers monitored for activity in any 1 of 8 functional domains: bed mobility, transfers, mobility, washing and dressing, exercise, hygiene (mouth care/shaving/hair/nail care), toileting, and eating. Patient activity observed within these domains was identified as either a restorative or custodial care event. For example: “asks or encourages patient to walk/independently propel wheelchair to bathroom/toilet/day room/activities and gives them time to perform activity” was identified as a restorative care event, while “utilizes wheelchair instead of encourages ambulation and does not encourage patient to self-propel” was considered a custodial care event. All observations were carried out by student physical therapists in training or physical therapy assistants, all of whom were familiar in working in the acute facility with hospitalized older people. In an attempt to optimize internal consistency, observer skill was quality-controlled by ensuring observers were trained and their competency assessed in the use of the evaluation measurement tool.

Bays of 3 to 6 beds comprised each observation space. Three 90-minute time epochs were selected for observation—awakening (early morning), lunchtime (middle of the day), and afternoon (before evening meal)—with the aim that each time frame be observed on a minimum of 1 occasion on each of the 5 wards to generate a minimum of 15 observation sessions. Resources dictated observational periods to be 90-minutes maximum, per epoch, on weekdays only. The mean (range) time between the didactic study day and the ward-based practice day was 4 (1–8) weeks, and between the ward-based practice day and the second observational period was 6 (1–14) weeks.

Patient Characteristics

Differences in the acuity of patients between pre- and post-QI activity in the observational environments could influence care demands. Therefore, patient characteristics before and after the QI activity were measured to assess for stability. Prior to each session, observers recorded  patient demographic details and current STRATIFY score, a predictive tool used at the time to segment fall risk [21], from patients’ clinical records. Two measures were used to offer contemporaneous representation of the observed population in the observation environment: a modified Barthel index [22], which provides a measure of activities of daily living [23], and the Abbreviated Mental Test Score [24], a simple diagnostic screen for cognitive impairment. All patients were considered as recuperating and thus eligible for observation except those with a “Patient-At-Risk” score ≥ 4, indicating physiological factors associated with established or impending critical illness [25], or if an end of life care plan was clearly detailed in the clinical record.

Data Analysis

Patient demographics are reported descriptively. Ordinal data are summarized using median and inter-quartile ranges (IQR), interval/ratio data using mean and standard deviation (SD) unless otherwise stated. Categorical data are reported as percentages. Comparison of observed patient samples before and after the QI period were compared with the Mann-Whitney U-test for ordinal data, 2 sample t tests for interval/ratio data, and chi squared tests of proportions for other variables.

Analyses were carried out using STATA 11 ME (StataCorp, College Station, TX) and SPSS v17 (SPSS, Chicago). Statistical significance was set at P ≤ 0.05.

Ethical Issues

This study was approved by the local UK NHS Trust clinical audit committee (Quality Improvement project 2038).

Results
 

Care Events by NAs

Observations were undertaken across the 5 wards on 14 workdays (Monday–Friday) over 6 weeks in the pre-QI period, and on 16 workdays over 4 weeks in the post-QI period, yielding a total of 51 hours of observation.

Overall, across all care environments, there was a statistically significant proportional increase in restorative care from 74% to 92% [χ2(1) 9.53, P = 0.002] (Figure 2). This represents an increase in restorative care events from 40 to 94. Observed custodial care events decreased from 14 to 8, a 43% reduction in custodial care events overall, a difference which remained irrespective of the environment (acute or subacute care), pre- and post-QI activity (P = 0.538 and P = 0.695, respectively).

There was a marked decrease in the number of patients receiving no NA-led restorative care events from 59 (74%) to 32 (48%) before and after QI activity respectively, [χ2 (1) 10.63, P = 0.001].

Patients Observed

Patient population characteristics remained stable during the course of the QI activity; there were no significant differences in the observed patient characteristics pre- and post-QI activity (Table). In 51 hours of observation undertaken by 3 independent observers there were 80 and 71 occupied beds before and after QI activity, respectively, representing a stable bed occupancy rate of 94% and 83% (P = 0.074). Of the occupied beds, 98.7% and 98.6% of patients (pre- and post-QI activity, respectively) were considered recuperating and therefore appropriate for a restorative care approach.

Discussion

Our study furthers research in methods of increasing restorative care events delivered by NAs. In a randomized controlled trial by Resnick et al [16], a structured 6-week restorative care program incorporating teaching NAs
restorative care philosophies (tier 1) and facilitating NAs to motivate residents to engage in functional activities (tier 2) was compared to placebo (a single 30-minute educational session in managing residents’ behavioral symptoms) [16]. Results showed the 6-week program led to more restorative care, with NAs demonstrating enhanced knowledge and expectations of restorative care outcomes and better job satisfaction. Our educational package (1 day) and ward-based-learning session (3–4 hours) was much shorter than Resnick et al’s 6-week intervention [16], and the optimal dose of educational packages for NAs is yet to be determined and needs to be addressed in future studies. Furthermore, while we found education increased restorative care across multiple environments, it is yet to be determined whether more restorative care has a positive impact on patient function downstream of an acute inpatient stay. In fact, determination of restorative care’s influence on augmenting rehabilitation outcomes is a neglected aspect of nursing-AHP practice that we aim to define and investigate in ongoing studies.

The patient population characteristics within the target wards were stable over the course of the QI project. Observed patients’ median Barthel (11) and Abbreviated Mental Test (6) scores remained stable and are indicative of high levels of day-to-day activity dependence [24,26–28]. Over the QI activity period it was therefore unsurprising that modest proportions of patients direc-ted their own care (28% and 33% pre and post-QI, respectively). Subsequently, demands on staff to lead patient care were substantial, leading to high risks of social or clinical iatrogenesis and hospital-associated deconditioning.

In a previous observational study, substantial patient inactivity was found in a highly dependent cohort of patients [29]. Fear of falling and insignificant emphasis on ambulation were cited as patient and organizational-centric reasons, respectively. Furthermore, in a selective observational study, patients receiving function-focused care (FFC; synonymous to restorative care) in an acute hospital environment developed less physical functional decline compared to those receiving custodial care [30]. However, patients who had fallen during their hospital stay received less FFC. The authors suggest limited FFC in fallers was deployed to minimize further risk but concluded there is need for nursing and therapy interventions that manage fall risks through endorsing functional activities instead of mobility restriction [30].

Limitations

While observational studies are more robust for measuring behavioral activities compared to self or proxy reporting [34], they are exposed to observer judgment and drift. An attempt was made to minimize this with the binary measurement of restorative versus custodial care and by random sampling of wards and time frames to capture an entire healthcare environment.

The observational study tool was based on one previously developed where acceptable reliability and validity was established and where observations were based on what individual care staff were practicing regardless of their operational environment [20]. In contrast, our observations were based in predetermined environmental spaces regardless of what care practice occurred within it. We consider our approach justifiable in minimizing observer influence on an individual’s practice by emphasizing to them that observers were interested in what happened in an environment [35,36]. However, we acknowledge the risk of under representation of care by observers not following the care delivery, and that local validity and reliability of our methods was not undertaken. Lastly, whilst training for observers was undertaken in this study to standardize the observations undertaken, validation of this method would be a feature required of any future experimental work.

Conclusions

Our findings support the current understanding of restorative care [14–16] and provides proof of concept that dedicating resources in a previously under-invested part of the workforce is feasible, well-accepted, and meaningful. The results are in keeping with the concept that the NA staff group is ready and able to fulfil their roles as direct caregivers, supporting and relieving other trained staff [11].

Corresponding author: Gareth D. Jones, MSc, Physiotherapy Dept, 3rd Fl Lambeth Wing, St Thomas’ Hospital, Westminster Bridge Rd, London SE1 7EH, UK, [email protected].

Funding/support: This work was supported by a small grants application to the Guy's and St Thomas' Charity, project code S100414.

Financial disclosures: No conflicts of interest to declare.

Acknowledgment: The authors acknowledge members of the steering group for their input: Rebekah Schiff, Carrie-Ann Wood, Judith Centofanti, Judith Hall, and Richard Page; Anne Bisset-Smith and Claudia Jacob for their initial pilot work; Amanda Buttery, Lottie Prowse, and Ryan Mackie for practical assistance; Siobhan Crichton for her statistical help; and Jacky Jones, Michael Thacker, Tisha Pryor, and Sarah Ritchie for helping review the manuscript.

Abstract

• Background: Acute and prolonged exposure to hospital medical care can cause hospital-associated deconditioning with deleterious effects on patient care provision and quality of life. Physical rehabilitation provided by allied healthcare professionals can enable reacquisition of function via professional input into attainment of set goals. Separate to rehabilitative efforts, restorative care optimizes independence by motivating individuals to maintain and restore function. Nursing assistants (NAs) provide a significant amount of direct patient care and are well placed to deliver restorative care.
• Objective: To increase proportional restorative care interactions with hospitalized older adults by training NAs.
• Methods: A prospective cohort quality improvement (QI) project was undertaken at 3 acute hospital wards (patient minimum age 65 years) and 2 community subacute care wards in the UK. NAs working within the target settings received a 2-part restorative care training package. The primary evaluation tool was 51 hours in total of observation measuring the proportional change in restorative care events delivered by NAs.
• Results: NA-led restorative care events increased from 40 (pre-intervention) to 94 (post-intervention), representing a statistically significant proportional increase from 74% to 92% (χ2(1) 9.53, P = 0.002). NAs on occasions inadvertently emphasized restriction of function to manage risk and oblige with rest periods.
• Conclusion: Investing in NAs can influence the amount of restorative care delivered to hospitalized older adults at risk of hospital-associated deconditioning. Continued investment in NAs is indicated to influence top-down, mandated restorative care practice in this patient group.

Key words: older people; restorative care; hospital associated deconditioning; nursing assistants; rehabilitation; training.

Hospital-associated deconditioning is defined as a significant decline in functional abilities developed through acute and prolonged exposure to a medical care facility environment, and is independent of that attributed to primary pathologies resulting in acute admission [1]. Considerable research on iatrogenic complications in older hospitalized populations [1–5] has shown the impacts of hospital-associated deconditioning and associated dysfunctions on quality of life for patients and the resultant burden on health and social care provision [6].

Physical rehabilitation has been shown to restore function through high-dose repetition of task-specific activity [7], and the benefits attributed to extra physical therapy include improved mobility, activity, and participation [8]. Simply defined, physical rehabilitation is the reacquisition of function through multidisciplinary assessment and professional therapeutic input in attainment of set goals. A more recent nomenclature in health settings is “restorative care,” defined as a philosophy of care that encourages, enables, and motivates individuals to maintain and restore function, thereby optimizing independence [9]. It has been clearly defined as a philosophy separate from that of rehabilitation [9] and remote from task-related or “custodial care,” which is designed to assist in meeting patients’ daily activity needs without any therapeutic value.

In UK rehabilitation wards, nursing staff provide 4.5 times as much direct patient care time compared with allied health professionals, with paraprofessional nursing assistants (NAs, equivalent to certified nurse assistants [CNAs] in the United States) responsible for half of this direct nursing care [10]. Kessler’s group examined the evolving role of NAs in UK hospitals [11]. From a national survey of 700 NAs and 600 trained nurses, the authors upheld the view that NAs act as direct caregivers including through routine tasks traditionally delivered by nurses. They identified that NAs exhibit distinct qualities, which are valued by qualified nurses, including routine task fulfilment and abilities relating to patients, which enable NAs to enhance care quality. Indeed, the national findings of Kessler’s group were generalizable to our own clinical setting where a NA cohort was a well-placed, available, and motivated resource to deliver therapeutically focused care for our hospitalized older population.

The theoretical relationship between care approaches is complex and represents a challenge for service users and policy makers. For instance, comprehensive rehabilitation delivery during an acute care episode may lead to users not seeking custodial care at home. Conversely, day-to-day activities realized by custodial care at home may lead to users not seeking acute rehabilitative care [12]. With stable resources being assigned to more dependent users in higher numbers, reactive care regardless of environment has often been the model of choice.

However, an economic rationale has developed more recently where investment in maintenance and preventative models results in healthcare savings with models including the 4Rs; reablement, reactivation, rehabilitation, and restorative care [13]. In North America, restorative care approaches have resulted in favorable results in nursing home facilities [14] and at home [15], and restorative care education and motivation training for nursing assistants was effective in supporting a change in beliefs and practice behaviors [16]. While results show restorative care practices in the non-acute care sector are advantageous, it is unknown whether these approaches if adopted in hospital settings affect subsequent healthcare utilization in the non-acute facilities, or even if they are feasible to implement in acute facilities by a staff group able to do so. Therefore, the purpose of this QI project was to deploy a restorative care educational intervention for NA staff working with hospitalized older adults with the aim of increasing the proportion of restorative care delivered.

Methods
 

Context

This project was conducted at a UK National Health Service university teaching hospital trust at 3 acute hospital wards (patient minimum age 65 years) and 2 community subacute care wards for older patients. Participants consisted of all permanent or long-term temporary (> 3 months continuous employment) NAs working in the target settings (n = 36). The QI project design is summarized in Figure 1. The project applied the 4Es translational approach to regulate the QI intervention: Engage, Educate, Execute, and Evaluate [17]. The reporting of this study follows SQUIRE guidance [18].

Intervention

The QI activity was a holistic educational process for all NA participants.

Didactic Study Day

Each NA attended a study day led by a physical therapist (up to 10 NAs per group). A student-centered training approach was adopted, recognizing variations in adult learning styles [19], and included seminar style theory, video case scenarios, group work, practical skills, open discussion, and reflection. The training package outline was compiled following consensus among the multi-disciplinary team working in the target settings and the steering group. Topics covered were theory on the risk of hospitalization and benefits of early mobilization; case scenarios and examples of restorative care; identifying and overcoming barriers to restorative care; identifying appro-priate patients for a restorative care approach; practical skills, including assisting patients out of bed, ambulation, and eating/drinking; and challenging, problem-solving scenarios. All participants received a course handbook to facilitate learning.

Ward-Based Practice

Measures

Type of Care Event

The quantity and nature of all NA-patient functional task-related care events was established by independent systematic observation pre- and post-intervention. Observers rated the type of care for observed patients as either custodial or restorative events using a tool described below. In addition, the numbers of patients receiving no restorative care events at all during observation was calculated to capture changes in rates between patients observed. The observational tool used was adapted from that utilized in a North American study of a long-term care facility [20], which demonstrated favorable intra-rater reliability (person separation reliability of 0.77), inter-rater reliability (80% to 100% agreement on each of the care behaviors), and validity (evidence of unidimensionality and good fit of the items). Adaptations accommodated for data collection in a hospital environment and alteration to UK nomenclature.

Three blinded volunteer assessors undertook observations. The observers monitored for activity in any 1 of 8 functional domains: bed mobility, transfers, mobility, washing and dressing, exercise, hygiene (mouth care/shaving/hair/nail care), toileting, and eating. Patient activity observed within these domains was identified as either a restorative or custodial care event. For example: “asks or encourages patient to walk/independently propel wheelchair to bathroom/toilet/day room/activities and gives them time to perform activity” was identified as a restorative care event, while “utilizes wheelchair instead of encourages ambulation and does not encourage patient to self-propel” was considered a custodial care event. All observations were carried out by student physical therapists in training or physical therapy assistants, all of whom were familiar in working in the acute facility with hospitalized older people. In an attempt to optimize internal consistency, observer skill was quality-controlled by ensuring observers were trained and their competency assessed in the use of the evaluation measurement tool.

Bays of 3 to 6 beds comprised each observation space. Three 90-minute time epochs were selected for observation—awakening (early morning), lunchtime (middle of the day), and afternoon (before evening meal)—with the aim that each time frame be observed on a minimum of 1 occasion on each of the 5 wards to generate a minimum of 15 observation sessions. Resources dictated observational periods to be 90-minutes maximum, per epoch, on weekdays only. The mean (range) time between the didactic study day and the ward-based practice day was 4 (1–8) weeks, and between the ward-based practice day and the second observational period was 6 (1–14) weeks.

Patient Characteristics

Differences in the acuity of patients between pre- and post-QI activity in the observational environments could influence care demands. Therefore, patient characteristics before and after the QI activity were measured to assess for stability. Prior to each session, observers recorded  patient demographic details and current STRATIFY score, a predictive tool used at the time to segment fall risk [21], from patients’ clinical records. Two measures were used to offer contemporaneous representation of the observed population in the observation environment: a modified Barthel index [22], which provides a measure of activities of daily living [23], and the Abbreviated Mental Test Score [24], a simple diagnostic screen for cognitive impairment. All patients were considered as recuperating and thus eligible for observation except those with a “Patient-At-Risk” score ≥ 4, indicating physiological factors associated with established or impending critical illness [25], or if an end of life care plan was clearly detailed in the clinical record.

Data Analysis

Patient demographics are reported descriptively. Ordinal data are summarized using median and inter-quartile ranges (IQR), interval/ratio data using mean and standard deviation (SD) unless otherwise stated. Categorical data are reported as percentages. Comparison of observed patient samples before and after the QI period were compared with the Mann-Whitney U-test for ordinal data, 2 sample t tests for interval/ratio data, and chi squared tests of proportions for other variables.

Analyses were carried out using STATA 11 ME (StataCorp, College Station, TX) and SPSS v17 (SPSS, Chicago). Statistical significance was set at P ≤ 0.05.

Ethical Issues

This study was approved by the local UK NHS Trust clinical audit committee (Quality Improvement project 2038).

Results
 

Care Events by NAs

Observations were undertaken across the 5 wards on 14 workdays (Monday–Friday) over 6 weeks in the pre-QI period, and on 16 workdays over 4 weeks in the post-QI period, yielding a total of 51 hours of observation.

Overall, across all care environments, there was a statistically significant proportional increase in restorative care from 74% to 92% [χ2(1) 9.53, P = 0.002] (Figure 2). This represents an increase in restorative care events from 40 to 94. Observed custodial care events decreased from 14 to 8, a 43% reduction in custodial care events overall, a difference which remained irrespective of the environment (acute or subacute care), pre- and post-QI activity (P = 0.538 and P = 0.695, respectively).

There was a marked decrease in the number of patients receiving no NA-led restorative care events from 59 (74%) to 32 (48%) before and after QI activity respectively, [χ2 (1) 10.63, P = 0.001].

Patients Observed

Patient population characteristics remained stable during the course of the QI activity; there were no significant differences in the observed patient characteristics pre- and post-QI activity (Table). In 51 hours of observation undertaken by 3 independent observers there were 80 and 71 occupied beds before and after QI activity, respectively, representing a stable bed occupancy rate of 94% and 83% (P = 0.074). Of the occupied beds, 98.7% and 98.6% of patients (pre- and post-QI activity, respectively) were considered recuperating and therefore appropriate for a restorative care approach.

Discussion

Our study furthers research in methods of increasing restorative care events delivered by NAs. In a randomized controlled trial by Resnick et al [16], a structured 6-week restorative care program incorporating teaching NAs
restorative care philosophies (tier 1) and facilitating NAs to motivate residents to engage in functional activities (tier 2) was compared to placebo (a single 30-minute educational session in managing residents’ behavioral symptoms) [16]. Results showed the 6-week program led to more restorative care, with NAs demonstrating enhanced knowledge and expectations of restorative care outcomes and better job satisfaction. Our educational package (1 day) and ward-based-learning session (3–4 hours) was much shorter than Resnick et al’s 6-week intervention [16], and the optimal dose of educational packages for NAs is yet to be determined and needs to be addressed in future studies. Furthermore, while we found education increased restorative care across multiple environments, it is yet to be determined whether more restorative care has a positive impact on patient function downstream of an acute inpatient stay. In fact, determination of restorative care’s influence on augmenting rehabilitation outcomes is a neglected aspect of nursing-AHP practice that we aim to define and investigate in ongoing studies.

The patient population characteristics within the target wards were stable over the course of the QI project. Observed patients’ median Barthel (11) and Abbreviated Mental Test (6) scores remained stable and are indicative of high levels of day-to-day activity dependence [24,26–28]. Over the QI activity period it was therefore unsurprising that modest proportions of patients direc-ted their own care (28% and 33% pre and post-QI, respectively). Subsequently, demands on staff to lead patient care were substantial, leading to high risks of social or clinical iatrogenesis and hospital-associated deconditioning.

In a previous observational study, substantial patient inactivity was found in a highly dependent cohort of patients [29]. Fear of falling and insignificant emphasis on ambulation were cited as patient and organizational-centric reasons, respectively. Furthermore, in a selective observational study, patients receiving function-focused care (FFC; synonymous to restorative care) in an acute hospital environment developed less physical functional decline compared to those receiving custodial care [30]. However, patients who had fallen during their hospital stay received less FFC. The authors suggest limited FFC in fallers was deployed to minimize further risk but concluded there is need for nursing and therapy interventions that manage fall risks through endorsing functional activities instead of mobility restriction [30].

Limitations

While observational studies are more robust for measuring behavioral activities compared to self or proxy reporting [34], they are exposed to observer judgment and drift. An attempt was made to minimize this with the binary measurement of restorative versus custodial care and by random sampling of wards and time frames to capture an entire healthcare environment.

The observational study tool was based on one previously developed where acceptable reliability and validity was established and where observations were based on what individual care staff were practicing regardless of their operational environment [20]. In contrast, our observations were based in predetermined environmental spaces regardless of what care practice occurred within it. We consider our approach justifiable in minimizing observer influence on an individual’s practice by emphasizing to them that observers were interested in what happened in an environment [35,36]. However, we acknowledge the risk of under representation of care by observers not following the care delivery, and that local validity and reliability of our methods was not undertaken. Lastly, whilst training for observers was undertaken in this study to standardize the observations undertaken, validation of this method would be a feature required of any future experimental work.

Conclusions

Our findings support the current understanding of restorative care [14–16] and provides proof of concept that dedicating resources in a previously under-invested part of the workforce is feasible, well-accepted, and meaningful. The results are in keeping with the concept that the NA staff group is ready and able to fulfil their roles as direct caregivers, supporting and relieving other trained staff [11].

Corresponding author: Gareth D. Jones, MSc, Physiotherapy Dept, 3rd Fl Lambeth Wing, St Thomas’ Hospital, Westminster Bridge Rd, London SE1 7EH, UK, [email protected].

Funding/support: This work was supported by a small grants application to the Guy's and St Thomas' Charity, project code S100414.

Financial disclosures: No conflicts of interest to declare.

Acknowledgment: The authors acknowledge members of the steering group for their input: Rebekah Schiff, Carrie-Ann Wood, Judith Centofanti, Judith Hall, and Richard Page; Anne Bisset-Smith and Claudia Jacob for their initial pilot work; Amanda Buttery, Lottie Prowse, and Ryan Mackie for practical assistance; Siobhan Crichton for her statistical help; and Jacky Jones, Michael Thacker, Tisha Pryor, and Sarah Ritchie for helping review the manuscript.

Abstract

• Background: Acute and prolonged exposure to hospital medical care can cause hospital-associated deconditioning with deleterious effects on patient care provision and quality of life. Physical rehabilitation provided by allied healthcare professionals can enable reacquisition of function via professional input into attainment of set goals. Separate to rehabilitative efforts, restorative care optimizes independence by motivating individuals to maintain and restore function. Nursing assistants (NAs) provide a significant amount of direct patient care and are well placed to deliver restorative care.
• Objective: To increase proportional restorative care interactions with hospitalized older adults by training NAs.
• Methods: A prospective cohort quality improvement (QI) project was undertaken at 3 acute hospital wards (patient minimum age 65 years) and 2 community subacute care wards in the UK. NAs working within the target settings received a 2-part restorative care training package. The primary evaluation tool was 51 hours in total of observation measuring the proportional change in restorative care events delivered by NAs.
• Results: NA-led restorative care events increased from 40 (pre-intervention) to 94 (post-intervention), representing a statistically significant proportional increase from 74% to 92% (χ2(1) 9.53, P = 0.002). NAs on occasions inadvertently emphasized restriction of function to manage risk and oblige with rest periods.
• Conclusion: Investing in NAs can influence the amount of restorative care delivered to hospitalized older adults at risk of hospital-associated deconditioning. Continued investment in NAs is indicated to influence top-down, mandated restorative care practice in this patient group.

Key words: older people; restorative care; hospital associated deconditioning; nursing assistants; rehabilitation; training.

Hospital-associated deconditioning is defined as a significant decline in functional abilities developed through acute and prolonged exposure to a medical care facility environment, and is independent of that attributed to primary pathologies resulting in acute admission [1]. Considerable research on iatrogenic complications in older hospitalized populations [1–5] has shown the impacts of hospital-associated deconditioning and associated dysfunctions on quality of life for patients and the resultant burden on health and social care provision [6].

Physical rehabilitation has been shown to restore function through high-dose repetition of task-specific activity [7], and the benefits attributed to extra physical therapy include improved mobility, activity, and participation [8]. Simply defined, physical rehabilitation is the reacquisition of function through multidisciplinary assessment and professional therapeutic input in attainment of set goals. A more recent nomenclature in health settings is “restorative care,” defined as a philosophy of care that encourages, enables, and motivates individuals to maintain and restore function, thereby optimizing independence [9]. It has been clearly defined as a philosophy separate from that of rehabilitation [9] and remote from task-related or “custodial care,” which is designed to assist in meeting patients’ daily activity needs without any therapeutic value.

In UK rehabilitation wards, nursing staff provide 4.5 times as much direct patient care time compared with allied health professionals, with paraprofessional nursing assistants (NAs, equivalent to certified nurse assistants [CNAs] in the United States) responsible for half of this direct nursing care [10]. Kessler’s group examined the evolving role of NAs in UK hospitals [11]. From a national survey of 700 NAs and 600 trained nurses, the authors upheld the view that NAs act as direct caregivers including through routine tasks traditionally delivered by nurses. They identified that NAs exhibit distinct qualities, which are valued by qualified nurses, including routine task fulfilment and abilities relating to patients, which enable NAs to enhance care quality. Indeed, the national findings of Kessler’s group were generalizable to our own clinical setting where a NA cohort was a well-placed, available, and motivated resource to deliver therapeutically focused care for our hospitalized older population.

The theoretical relationship between care approaches is complex and represents a challenge for service users and policy makers. For instance, comprehensive rehabilitation delivery during an acute care episode may lead to users not seeking custodial care at home. Conversely, day-to-day activities realized by custodial care at home may lead to users not seeking acute rehabilitative care [12]. With stable resources being assigned to more dependent users in higher numbers, reactive care regardless of environment has often been the model of choice.

However, an economic rationale has developed more recently where investment in maintenance and preventative models results in healthcare savings with models including the 4Rs; reablement, reactivation, rehabilitation, and restorative care [13]. In North America, restorative care approaches have resulted in favorable results in nursing home facilities [14] and at home [15], and restorative care education and motivation training for nursing assistants was effective in supporting a change in beliefs and practice behaviors [16]. While results show restorative care practices in the non-acute care sector are advantageous, it is unknown whether these approaches if adopted in hospital settings affect subsequent healthcare utilization in the non-acute facilities, or even if they are feasible to implement in acute facilities by a staff group able to do so. Therefore, the purpose of this QI project was to deploy a restorative care educational intervention for NA staff working with hospitalized older adults with the aim of increasing the proportion of restorative care delivered.

Methods
 

Context

This project was conducted at a UK National Health Service university teaching hospital trust at 3 acute hospital wards (patient minimum age 65 years) and 2 community subacute care wards for older patients. Participants consisted of all permanent or long-term temporary (> 3 months continuous employment) NAs working in the target settings (n = 36). The QI project design is summarized in Figure 1. The project applied the 4Es translational approach to regulate the QI intervention: Engage, Educate, Execute, and Evaluate [17]. The reporting of this study follows SQUIRE guidance [18].

Intervention

The QI activity was a holistic educational process for all NA participants.

Didactic Study Day

Each NA attended a study day led by a physical therapist (up to 10 NAs per group). A student-centered training approach was adopted, recognizing variations in adult learning styles [19], and included seminar style theory, video case scenarios, group work, practical skills, open discussion, and reflection. The training package outline was compiled following consensus among the multi-disciplinary team working in the target settings and the steering group. Topics covered were theory on the risk of hospitalization and benefits of early mobilization; case scenarios and examples of restorative care; identifying and overcoming barriers to restorative care; identifying appro-priate patients for a restorative care approach; practical skills, including assisting patients out of bed, ambulation, and eating/drinking; and challenging, problem-solving scenarios. All participants received a course handbook to facilitate learning.

Ward-Based Practice

Measures

Type of Care Event

The quantity and nature of all NA-patient functional task-related care events was established by independent systematic observation pre- and post-intervention. Observers rated the type of care for observed patients as either custodial or restorative events using a tool described below. In addition, the numbers of patients receiving no restorative care events at all during observation was calculated to capture changes in rates between patients observed. The observational tool used was adapted from that utilized in a North American study of a long-term care facility [20], which demonstrated favorable intra-rater reliability (person separation reliability of 0.77), inter-rater reliability (80% to 100% agreement on each of the care behaviors), and validity (evidence of unidimensionality and good fit of the items). Adaptations accommodated for data collection in a hospital environment and alteration to UK nomenclature.

Three blinded volunteer assessors undertook observations. The observers monitored for activity in any 1 of 8 functional domains: bed mobility, transfers, mobility, washing and dressing, exercise, hygiene (mouth care/shaving/hair/nail care), toileting, and eating. Patient activity observed within these domains was identified as either a restorative or custodial care event. For example: “asks or encourages patient to walk/independently propel wheelchair to bathroom/toilet/day room/activities and gives them time to perform activity” was identified as a restorative care event, while “utilizes wheelchair instead of encourages ambulation and does not encourage patient to self-propel” was considered a custodial care event. All observations were carried out by student physical therapists in training or physical therapy assistants, all of whom were familiar in working in the acute facility with hospitalized older people. In an attempt to optimize internal consistency, observer skill was quality-controlled by ensuring observers were trained and their competency assessed in the use of the evaluation measurement tool.

Bays of 3 to 6 beds comprised each observation space. Three 90-minute time epochs were selected for observation—awakening (early morning), lunchtime (middle of the day), and afternoon (before evening meal)—with the aim that each time frame be observed on a minimum of 1 occasion on each of the 5 wards to generate a minimum of 15 observation sessions. Resources dictated observational periods to be 90-minutes maximum, per epoch, on weekdays only. The mean (range) time between the didactic study day and the ward-based practice day was 4 (1–8) weeks, and between the ward-based practice day and the second observational period was 6 (1–14) weeks.

Patient Characteristics

Differences in the acuity of patients between pre- and post-QI activity in the observational environments could influence care demands. Therefore, patient characteristics before and after the QI activity were measured to assess for stability. Prior to each session, observers recorded  patient demographic details and current STRATIFY score, a predictive tool used at the time to segment fall risk [21], from patients’ clinical records. Two measures were used to offer contemporaneous representation of the observed population in the observation environment: a modified Barthel index [22], which provides a measure of activities of daily living [23], and the Abbreviated Mental Test Score [24], a simple diagnostic screen for cognitive impairment. All patients were considered as recuperating and thus eligible for observation except those with a “Patient-At-Risk” score ≥ 4, indicating physiological factors associated with established or impending critical illness [25], or if an end of life care plan was clearly detailed in the clinical record.

Data Analysis

Patient demographics are reported descriptively. Ordinal data are summarized using median and inter-quartile ranges (IQR), interval/ratio data using mean and standard deviation (SD) unless otherwise stated. Categorical data are reported as percentages. Comparison of observed patient samples before and after the QI period were compared with the Mann-Whitney U-test for ordinal data, 2 sample t tests for interval/ratio data, and chi squared tests of proportions for other variables.

Analyses were carried out using STATA 11 ME (StataCorp, College Station, TX) and SPSS v17 (SPSS, Chicago). Statistical significance was set at P ≤ 0.05.

Ethical Issues

This study was approved by the local UK NHS Trust clinical audit committee (Quality Improvement project 2038).

Results
 

Care Events by NAs

Observations were undertaken across the 5 wards on 14 workdays (Monday–Friday) over 6 weeks in the pre-QI period, and on 16 workdays over 4 weeks in the post-QI period, yielding a total of 51 hours of observation.

Overall, across all care environments, there was a statistically significant proportional increase in restorative care from 74% to 92% [χ2(1) 9.53, P = 0.002] (Figure 2). This represents an increase in restorative care events from 40 to 94. Observed custodial care events decreased from 14 to 8, a 43% reduction in custodial care events overall, a difference which remained irrespective of the environment (acute or subacute care), pre- and post-QI activity (P = 0.538 and P = 0.695, respectively).

There was a marked decrease in the number of patients receiving no NA-led restorative care events from 59 (74%) to 32 (48%) before and after QI activity respectively, [χ2 (1) 10.63, P = 0.001].

Patients Observed

Patient population characteristics remained stable during the course of the QI activity; there were no significant differences in the observed patient characteristics pre- and post-QI activity (Table). In 51 hours of observation undertaken by 3 independent observers there were 80 and 71 occupied beds before and after QI activity, respectively, representing a stable bed occupancy rate of 94% and 83% (P = 0.074). Of the occupied beds, 98.7% and 98.6% of patients (pre- and post-QI activity, respectively) were considered recuperating and therefore appropriate for a restorative care approach.

Discussion

Our study furthers research in methods of increasing restorative care events delivered by NAs. In a randomized controlled trial by Resnick et al [16], a structured 6-week restorative care program incorporating teaching NAs
restorative care philosophies (tier 1) and facilitating NAs to motivate residents to engage in functional activities (tier 2) was compared to placebo (a single 30-minute educational session in managing residents’ behavioral symptoms) [16]. Results showed the 6-week program led to more restorative care, with NAs demonstrating enhanced knowledge and expectations of restorative care outcomes and better job satisfaction. Our educational package (1 day) and ward-based-learning session (3–4 hours) was much shorter than Resnick et al’s 6-week intervention [16], and the optimal dose of educational packages for NAs is yet to be determined and needs to be addressed in future studies. Furthermore, while we found education increased restorative care across multiple environments, it is yet to be determined whether more restorative care has a positive impact on patient function downstream of an acute inpatient stay. In fact, determination of restorative care’s influence on augmenting rehabilitation outcomes is a neglected aspect of nursing-AHP practice that we aim to define and investigate in ongoing studies.

The patient population characteristics within the target wards were stable over the course of the QI project. Observed patients’ median Barthel (11) and Abbreviated Mental Test (6) scores remained stable and are indicative of high levels of day-to-day activity dependence [24,26–28]. Over the QI activity period it was therefore unsurprising that modest proportions of patients direc-ted their own care (28% and 33% pre and post-QI, respectively). Subsequently, demands on staff to lead patient care were substantial, leading to high risks of social or clinical iatrogenesis and hospital-associated deconditioning.

In a previous observational study, substantial patient inactivity was found in a highly dependent cohort of patients [29]. Fear of falling and insignificant emphasis on ambulation were cited as patient and organizational-centric reasons, respectively. Furthermore, in a selective observational study, patients receiving function-focused care (FFC; synonymous to restorative care) in an acute hospital environment developed less physical functional decline compared to those receiving custodial care [30]. However, patients who had fallen during their hospital stay received less FFC. The authors suggest limited FFC in fallers was deployed to minimize further risk but concluded there is need for nursing and therapy interventions that manage fall risks through endorsing functional activities instead of mobility restriction [30].

Limitations

While observational studies are more robust for measuring behavioral activities compared to self or proxy reporting [34], they are exposed to observer judgment and drift. An attempt was made to minimize this with the binary measurement of restorative versus custodial care and by random sampling of wards and time frames to capture an entire healthcare environment.

The observational study tool was based on one previously developed where acceptable reliability and validity was established and where observations were based on what individual care staff were practicing regardless of their operational environment [20]. In contrast, our observations were based in predetermined environmental spaces regardless of what care practice occurred within it. We consider our approach justifiable in minimizing observer influence on an individual’s practice by emphasizing to them that observers were interested in what happened in an environment [35,36]. However, we acknowledge the risk of under representation of care by observers not following the care delivery, and that local validity and reliability of our methods was not undertaken. Lastly, whilst training for observers was undertaken in this study to standardize the observations undertaken, validation of this method would be a feature required of any future experimental work.

Conclusions

Our findings support the current understanding of restorative care [14–16] and provides proof of concept that dedicating resources in a previously under-invested part of the workforce is feasible, well-accepted, and meaningful. The results are in keeping with the concept that the NA staff group is ready and able to fulfil their roles as direct caregivers, supporting and relieving other trained staff [11].

Corresponding author: Gareth D. Jones, MSc, Physiotherapy Dept, 3rd Fl Lambeth Wing, St Thomas’ Hospital, Westminster Bridge Rd, London SE1 7EH, UK, [email protected].

Funding/support: This work was supported by a small grants application to the Guy's and St Thomas' Charity, project code S100414.

Financial disclosures: No conflicts of interest to declare.

Acknowledgment: The authors acknowledge members of the steering group for their input: Rebekah Schiff, Carrie-Ann Wood, Judith Centofanti, Judith Hall, and Richard Page; Anne Bisset-Smith and Claudia Jacob for their initial pilot work; Amanda Buttery, Lottie Prowse, and Ryan Mackie for practical assistance; Siobhan Crichton for her statistical help; and Jacky Jones, Michael Thacker, Tisha Pryor, and Sarah Ritchie for helping review the manuscript.