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Agreement on Dyspnea Severity
Breathlessness, or dyspnea, is defined as a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity.[1] Dyspnea is a leading reason for patients presenting for emergency care,[2] and it is an important predictor for hospitalization and mortality in patients with cardiopulmonary disease.[3, 4, 5]
Several professional societies' guidelines recommend that patients should be asked to quantify the intensity of their breathlessness using a standardized scale, and that these ratings should be documented in medical records to guide dyspnea awareness and management.[1, 6, 7] During the evaluation and treatment of patients with acute cardiopulmonary conditions, the clinician estimates the severity of the illness and response to therapy based on multiple objective measures as well as the patient's perception of dyspnea. A patient‐centered care approach depends upon the physicians having a shared understanding of what the patient is experiencing. Without this appreciation, the healthcare provider cannot make appropriate treatment decisions to ensure alleviation of presenting symptoms. Understanding the severity of patients' dyspnea is critical to avoid under‐ or overtreatment of patients with acute cardiopulmonary conditions, but only a few studies have compared patient and provider perceptions of dyspnea intensity.[8, 9] Discordance between physician's impression of severity of dyspnea and patient's perception may result in suboptimal management and patient dissatisfaction with care. Furthermore, several studies have shown that, when physicians and patients agree with the assessment of well‐being, treatment adherence and outcomes improve.[10, 11]
Therefore, we evaluated the extent and directionality of agreement between patients' perception and healthcare providers' impression of dyspnea and explored which factors contribute to discordance. Additionally, we examined how healthcare providers document dyspnea severity.
METHODS
Study Setting and Population
The study was conducted between June 2012 and August 2012 at Baystate Medical Center (BMC), a 740‐bed tertiary care hospital in western Massachusetts. In 2012, the BMC hospitalist group had 48 attending physicians, of whom 47% were female, 48% had 0 to 3 years of attending experience, and 16% had 10 years of experience.
We enrolled consecutive admissions of English‐speaking adult patients, with a working diagnosis of heart failure (HF), chronic obstructive pulmonary disease (COPD), asthma, pneumonia, or a generic diagnosis of shortness of breath. Because we surveyed only hospitalists, we did not include patients admitted to an intensive care unit.
All participants gave informed consent to be part of the study. The research protocol was approved by the Baystate Health Institutional Review Board, Springfield, Massachusetts.
Dyspnea Assessment
Dyspnea intensity was assessed on an 11‐point (010) numerical rating scale (NRS).[12, 13] A trained research assistant interviewed patients on day 1 and 2 after admission, and on the day of discharge between 8 am and 12 pm on weekdays. The patient was asked: On a scale from 0 to 10, how bad is your shortness of breath at rest now, with 0 being no shortness of breath and 10 the worst shortness of breath you could ever imagine? The hospitalist or the senior resident and day‐shift nurse taking care of the patients were asked by the research assistant to rate the patient's dyspnea using the same scoring instrument shortly after they saw the patient. The physicians and nurses based their determination of dyspnea on their usual interview/examination of the patient. The patient, physician and the nurse were not aware of each other's rating. The research assistant scheduled the interviews to minimize the time intervals between the patient assessment and provider's rating. For this reason, the number of assessments per patient varied. Nurses were more readily available than physicians, which resulted in a larger number of patient‐nurse response pairs than patient‐physician pairs. All assessments were done in the morning, between 9 am and 12 pm, with a range of 3 hours between provider's assessment of the patient and the interview.
Dyspnea Agreement
Agreement was defined as a score within 1 between patient and healthcare provider; differences of 2 points were considered over‐ or underestimations. The decision to use this cutoff was based on prior studies, which found that a difference in the range of 1.6 to 2.2 cm was meaningful for the patient when assessment was done on the visual analog scale.[8, 14, 15] We also evaluated the direction of discordance. If the patient's rating of dyspnea severity was higher than the provider's rating, we defined this as underestimation by the provider; in the instance where a provider's score of dyspnea severity was higher than the patient's score, we defined this as overestimation. In a sensitivity analysis, agreement was defined as a score within 2 between patient and healthcare provider, and any difference 3 was considered disagreement.
Other Variables
We obtained information from the medical records about patient demographics, body mass index (BMI), smoking status, and vital signs. We calculated the oxygen saturation index as the ratio between the oxygen saturation and the fractional inspired oxygen (SpO2/FIO2). Comorbidities were assessed based on the International Classification od Diseases, Ninth Revision, Clinical Modification codes from the hospital financial decision support system. We calculated an overall combined comorbidity score based on the method described by Gagne, which is based on elements from the Charlson Comorbidity Index and from the Elixhauser comorbidities.[16]
Charts of the patients included in the study were retrospectively reviewed for physicians' and nurses' documentation of dyspnea at admission and at discharge. We recorded if dyspnea was mentioned and how it was assessed: whether it was described as present/absent; graded as mild, moderate, or severe; used a quantitative scale (010); used descriptors (eg, dyspnea when climbing stairs); and whether it was defined as improved or worsened without other qualifiers.
Statistical Analysis
Descriptive statistics of dyspnea scores, patient characteristics, comorbidities and vital signs were calculated and presented as medians with interquartile range (IQR) for continuous variables, and counts with percentages for categorical factors. Every patient‐provider concurrent scoring was included in the analysis as 1 dyad, which resulted in patients being included multiple times in the analysis. Patient‐physician and patient‐nurse dyads of dyspnea assessment were examined separately. Analyses included all dyads that were within same assessment period (same day and same time window).
The relationship between patient self‐perceived dyspnea severity and provider rating of was assessed in several ways. First, a weighted kappa coefficient was used as a measure of agreement between patient and nurse or physician scores. A weighted kappa analysis was chosen because it penalizes disagreements that are further apart from each other.
Second, we defined an indicator of discordance and constructed multivariable generalized estimating equation models that account for clustering of multiple dyads per patient, to assess the relationship of patient characteristics with discordance. Finally, we developed additional models to predict underestimation when compared to agreement or overestimation of dyspnea by the healthcare provider relative to the patient. Using the same definitions for agreement, we also compared the dyspnea assessment estimation between physicians and nurses.
We present the differences in dyspnea assessment between patient and healthcare provider and between nurses and physicians by Bland‐Altman plots.
All analyses were performed using SAS (version 9.3; SAS institute, Inc., Cary, NC), Stata (Stata statistical software release 13; StataCorp, College Station, TX), and RStudio version 0.99.892 (Bland‐Altman plots, R package version 0.3.1; The R Foundation for Statistical Computing, Vienna, Austria).[8, 9, 17]
RESULTS
Patient Characteristics
Among the 219 patients who met the screening criteria, 81 were not enrolled (Figure 1). Data from 138 patients, with both patient information and provider data on dyspnea assessment, were included. The median age of the patients was 72 years (IQR, 5880 years), 56.5% were women, 75.4% were white, and 28.3% were current smokers. Approximately 30% had a diagnosis of HF, 30% of COPD, and 13.0% of pneumonia. The median comorbidity score was 4 (IQR, 26), and 37.0% of the patients had a BMI 30. At admission, the median oxygen saturation index was 346 (IQR, 287.5460) indicating mild to moderate levels of hypoxia. (Table 1).
| Value | |
|---|---|
| |
| Age, median (IQR), y | 72 (5880) |
| Gender | |
| Female | 78 (56.5) |
| Male | 60 (43.5) |
| Race | |
| White | 104 (75.4) |
| Black | 16 (11.6) |
| Hispanic | 17 (12.3) |
| Other | 1 (0.7) |
| Body mass index, median (IQR) | 28 (23.334.6) |
| Obese (BMI 30) | 51 (37.0) |
| Smoker, current | 39 (28.3) |
| Admitting diagnosis | |
| Heart failure | 46 (33.3) |
| COPD/asthma | 41 (29.7) |
| Pneumonia | 18 (13.0) |
| Other | 33 (23.9) |
| Depression | 32 (23.2) |
| Comorbidity score, median (IQR) | 4 (26) |
| Respiratory rate at admission, median (IQR) | 20 (1924) |
| Oxygen saturation index at admission, median (IQR) | 346.4 (287.5460) |
| Patient NRS, median (IQR) | |
| At admission | 9 (710) |
| At discharge | 2 (14) |
| Discharged on home oxygen | 45 (32.6) |
| Respiratory rate at discharge, median (IQR) | 20 (1820) |
| Oxygen saturation index at discharge, median (IQR) | 475 (350485) |
Agreement Between Patients' Self‐Assessment and Providers' Assessment of Dyspnea Severity
Not all patients had complete data points, and more nurses were interviewed than physicians. Overall, 96 patient‐physician and 138 patient‐nurse pairs participated in the study. A total of 336 patient‐nurse rating dyad assessments of dyspnea and 124 patient‐physician rating dyads assessments were collected (Figure 1). The mean difference between patient and physicians and patient and nurses assessments of dyspnea was 1.23 (IQR, 3 to 0) and 0.21 (IQR, 2 to 2) respectively (a negative score means underestimation by the provider, a positive score means overestimation).
The unadjusted agreement on the severity of dyspnea was 36.3% for the patient‐physician dyads and 44.1% for the patient‐nurse dyads. Physicians underestimated their patients' dyspnea 37.9% of the time and overestimated it 25.8% of the time; nurses underestimated it 43.5% of the time and overestimated it in 12.4% of the study patients (Table 2). In 28.2% of the time, physicians were discordant more than 4 points of the patient assessment. Bland‐Altman plots show that there is greater variation in differences of dyspnea assessments with increase in shortness of breath scores (Figure 2). Nurses underestimated more when the dyspnea score was on the lower end. Physicians also tended to estimate either lower or higher when compared to patients when the dyspnea scores were <2 (Figure 2A,B).
| Underestimation | Concordance | Overestimation | |||||||
|---|---|---|---|---|---|---|---|---|---|
| 3 | 2 | %* | 0 | 1 | % | 2 | 3 | % | |
| |||||||||
| Patient‐nurse dyads | 110 | 48 | 43.5 | 82 | 78 | 44.1 | 17 | 28 | 12.4 |
| Patient‐physician dyads | 33 | 14 | 37.9 | 21 | 24 | 36.3 | 12 | 20 | 25.8 |
The weighted kappa coefficient for agreement was 0.11 (95% confidence interval [CI]: 0.01 to 0.21) for patient‐physician assessment, 0.18 (95% CI: 0.12 to 0.24) for patient‐nurse, and 0.09 (0.02 to 0.20) for physician‐nurse indicating poor agreement. In a sensitivity analysis in which we used a higher threshold for defining discordance (difference of more than 2 points), the kappa coefficient increased to 0.21 (95% CI: 0.06 to 0.36) for patient‐physician assessments, to 0.24 (95% CI: 0.15 to 0.33) for patient‐nurse, and to 0.24 (95% CI: 0.09 to 0.39) for nurse‐physician assessments.
Predictors of Discordance and Underestimation of Dyspnea Severity Assessment
Principal diagnosis was the only factor associated with the physicians' discordant assessment of patients' dyspnea. Patients with admission diagnoses other than HF, COPD, or pneumonia (eg, pulmonary embolism) were more likely to have an accurate assessment of their dyspnea by providers (Table 3). Similar results were obtained in the sensitivity analysis by using a higher cutoff for defining discordance and when assessing predictors for underestimation (results not shown).
| Modeling Probability of Discordance | ||
|---|---|---|
| Physician‐Patient Dyads, OR (95% CI), N = 124 | Nurse‐Patient Dyads, OR (95% CI), N = 363 | |
| ||
| Univariate Analysis | ||
| Body mass index | 1.00 (0.991.01) | 1.00 (0.991.00) |
| Comorbidity score | 1.01 (0.981.05) | 0.99 (0.961.01) |
| Respiratory rate at admission | 1.00 (0.991.02) | 0.99 (0.981.00) |
| Oxygen saturation at admission | 1.00 (1.001.00) | 1.00 (1.001.00) |
| Age (binary) | ||
| 65 years | Referent | Referent |
| >65 years | 1.21 (0.572.55) | 0.96 (0.571.64) |
| Gender | ||
| Female | Referent | Referent |
| Male | 1.10 (0.522.32) | 0.81 (0.481.37) |
| Race | ||
| White | Referent | Referent |
| Nonwhite | 1.02 (0.442.37) | 1.06 (0.581.95) |
| Obese (BMI >30) | 1.43 (0.663.11) | 0.76 (0.441.30) |
| Smoker | 1.36 (0.613.05) | 1.04 (0.591.85) |
| Admitting diagnosis | ||
| Heart failure | Referent | Referent |
| COPD/asthma | 0.68 (0.251.83) | 1.91 (0.983.73)* |
| Pneumonia | 0.38 (0.101.40) | 1.07 (0.462.45) |
| Other | 0.30 (0.110.82)* | 1.54 (0.763.11) |
| Depression | 1.21 (0.572.55) | 1.01 (0.541.86) |
| Multivariable analysis | ||
| Admitting diagnosis | ||
| Congestive heart failure | Referent | Referent |
| COPD | 0.68 (0.251.83) | 1.91 (0.983.73)* |
| Pneumonia | 0.38 (0.101.40) | 1.07 (0.462.45) |
| Other | 0.30 (0.110.82)* | 1.54 (0.763.11) |
In the multivariable analysis that assessed patient‐nurse dyads, the diagnosis of COPD was associated with a marginally significant likelihood of discordance (OR: 1.91; 95% CI: 0.98 to 3.73) (Table 3). Similarly, multivariable analysis identified principal diagnosis to be the only predictor of underestimation, and COPD diagnosis was associated with increased odds of dyspnea underestimation by nurses. When we used a higher cutoff to define discordance, the principal diagnosis of COPD (OR: 3.43, 95% CI: 1.76 to 6.69) was associated with an increased risk of discordance, and smoking (OR: 0.54, 95% CI: 0.29 to 0.99) was associated with a decreased risk of discordance. Overall, 45 patients (32.6%) were discharged on oxygen. The odds of discrepancy (under‐ or overestimation) in dyspnea scores between patient and nurse were 1.7 times higher compared to patients who were not discharged on oxygen, but this association did not reach statistical significance; the odds of discrepancy between patient and physician were 3.88 (95% CI: 1.07 to 14.13).
Documentation of Dyspnea
We found that dyspnea was mentioned in the admission notes in 96% of the charts reviewed; physicians used a qualitative rating (mild, moderate, or severe) to indicate the severity of dyspnea in only 16% of cases, and in 53% a descriptor was added (eg, dyspnea with climbing stairs, gradually increased in the prior week). Nurses were more likely than physicians to use qualitative ratings of dyspnea (26% of cases), and they used a more uniform description of the patient's dyspnea (eg, at rest, at rest and on exertion, or on exertion) than physicians. At discharge, 83% of physicians noted in their discharge summary that dyspnea improved compared with admission but did not refer to the patient's baseline level of dyspnea.
DISCUSSION
In this prospective study of 138 patients hospitalized with cardiopulmonary disease, we found that the agreement between patient's experience of dyspnea and providers' assessment was poor, and the discordance was higher for physicians than for nurses. In more than half of the cases, differences between patient and healthcare providers' assessment of dyspnea were present. One‐third of the time, both physicians and nurses underestimated patients' reported levels of dyspnea. Admitting diagnosis was the only patient factor predicting lack of agreement, and patients with COPD were more likely to have their dyspnea underestimated by nurses. Healthcare providers predominantly documented the presence or absence of dyspnea and rarely used a more nuanced scale.
Discrepancies between patient and provider assessments for pain, depression, and overall health have been reported.[8, 18, 19, 20, 21] One explanation is that patients and healthcare providers measure different factors despite using the same terminology. Furthermore, patient's assessment may be confounded by other symptoms such as anxiety, fatigue, or pain. Physicians and nurses may underevaluate and underestimate the level of breathlessness; however, from the physician perspective, dyspnea is only 1 data point, and providers rely on other measures, such as oxygen saturation, heart rate, respiratory rate, evidence of increasing breathing effort, and arterial blood gas to drive decision making. In a recent study that evaluated the attitudes and beliefs of hospitalists regarding the assessment and management of dyspnea, we found that most hospitalists indicated that awareness of dyspnea severity influences their decision for treatment, diagnostic testing, and timing of the discharge. Moreover, whereas less than half of the respondents reported experience with standardized assessment of dyspnea severity, most stated that such data would be very useful in their practice.[22]
What is the clinical significance of having discordance between patients self‐assessment and providers impression of the patient's severity of dyspnea? First, inaccurate assessment of dyspnea by providers can lead to inadequate treatment and workup. For example, a physician who underestimates the severity of dyspnea may fail to recognize when a complication of the underlying disease develops or may underutilize symptomatic methods for relief of dyspnea. In contrast, a physician who overestimates dyspnea may continue with aggressive treatment when this is not necessary. Second, lack of awareness of dyspnea severity experienced by the patient may result in premature discharge and patient's frustration with the provider, as was shown in several studies evaluating physician‐patient agreement for pain perception.[21, 23] We found that discrepancy between patients and healthcare providers was more pronounced for patients with COPD. In another study using the same patient cohort, we reported that compared to patients with congestive heart failure, those with COPD had more residual dyspnea at discharge; 1 in 4 patients was discharged with a dyspnea score of 5 of greater, and almost half reported symptoms above their baseline.[24] The results from the current study may explain in part why patients with COPD are discharged with higher levels of dyspnea and should alert healthcare providers on the importance of patient‐reported breathlessness. Third, the high level of discordance between healthcare providers and patients may explain the undertreatment of dyspnea in patients with advanced disease. This is supported by our findings that the discordance between patients and physicians was higher if the patient was discharged on oxygen.
One key role of the provider during a clinical encounter is to elicit the patient's symptoms and achieve a shared understanding of what the patient is experiencing. From the patient's perspective, their self‐assessment of dyspnea is more important that the physician's assessment. Fortunately, there is a growing recognition and emphasis on using outcomes that matter to patients, such as dyspnea, to inform judgment about patient care and for clinical research. Numerical measures for assessment of dyspnea exist, are easy to use, and are sensitive to change in patients' dyspnea.[6, 25, 26, 27] Still, it is not standard practice for healthcare providers to ask patients to provide a rating of their dyspnea. When we examined the documentation of dyspnea in the medical record, we found that the description was vague, and providers did not use a standardized validated assessment. Although the dyspnea score decreased during hospitalization, the respiratory rate did not significantly change, indicating that this objective measure may not be reliable in patient assessment. The providers' knowledge of the intensity of the symptom expressed by patients will enable them to track improvement in symptoms over time or in response to therapy. In addition, in this era of multiple handoffs within a hospitalization or from primary care to the hospital, a more uniform assessment could allow providers to follow the severity and time course of dyspnea. The low level of agreement we found between patients and the providers lends support to recommendations regarding a structured dyspnea assessment into routine hospital practice.
Study Strengths and Limitations
This study has several strengths. This is 1 of the very few studies to report on the level of agreement between patients' and providers' assessments of dyspnea. We used a validated, simple dyspnea scale that provides consistency in rating.[28, 29] We enrolled patients with a broad set of diagnoses and complaints, which increases the generalizability of our results, and we surveyed both physicians and nurses. Last, our findings were robust across different cutoff points utilized to characterize discordance and across 3 frequent diagnoses.
The study has several limitations. First, we included only English‐speaking patients, and the results cannot be generalized to patients from other cultures who do not speak English. Second, this is a single‐center study, and practices may be different in other centers; for example, some hospitals may have already implemented a dyspnea assessment tool. Third, we did not collect information on the physician and nurse characteristics such as years in practice. However, a recent study that describes the agreement of breathlessness assessment between nurses, physicians, and mechanically ventilated patients found that underestimation of breathlessness by providers was not associated with professional competencies, previous patient care, or years of working in an intensive care unit.[9] In addition, a systematic review found that length of professional experience is often unrelated to performance measures and outcomes.[30] Finally, although we asked for physicians and nurses assessment close to their visit to the patient, assessment was done from memory, not at the bedside observing the patient.
CONCLUSION
We found that the extent of agreement between a structured patient self‐assessment of dyspnea and healthcare providers' assessment was low. Future studies should prospectively test whether routine assessment of dyspnea results in better acute and long‐term patient outcomes.
Acknowledgements
The authors acknowledge Ms. Anu Joshi for her help with formatting the manuscript and assisting with table preparations. The authors also acknowledge Ms. Katherine Dempsey, Jahnavi Sagi, Sashi Ariyaratne, and Mr. Pradeep Kumbaham for their help with collecting the data.
Disclosures: M.S.S. is the guarantor for this article and had full access to all of the data in the study, and takes responsibility for the integrity and accuracy of the data analysis. M.S.S., P.K.L., E.N., and M.B.R. conceived of the study. M.S.S. and B.M. acquired the data. M.S.S., A.P., P.S.P., R.J.G., and P.K.L. analyzed and interpreted the data. M.S.S. drafted the manuscript. All authors critically reviewed the manuscript for intellectual content. M.S.S. is supported by grant 1K01HL114631‐01A1 from the National Heart, Lung, and Blood Institute of the National Institutes of Health and by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through grant UL1RR025752. The authors report no conflicts of interest.
- , , , et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012;185(4):435–452.
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- , , , . Dyspnea is a better predictor of 5‐year survival than airway obstruction in patients with COPD. Chest. 2002;121(5):1434–1440.
- , , . A multidimensional grading system (BODE index) as predictor of hospitalization for COPD. Chest. 2005;128(6):3810–3816.
- , , , et al. American College of Chest Physicians consensus statement on the management of dyspnea in patients with advanced lung or heart disease. Chest. 2010;137(3):674–691.
- , , , et al. Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: a Canadian Thoracic Society clinical practice guideline. Can Respir J. 2011;18(2):69–78.
- , , . Physician vs patient assessment of dyspnea during acute decompensated heart failure. Congest Heart Fail. 2010;16(2):60–64.
- , , , , , . Underestimation of Patient Breathlessness by Nurses and Physicians during a Spontaneous Breathing Trial. Am J Respir Crit Care Med. 2015;192(12):1440–1448.
- , , , , , . The influence of patient‐practitioner agreement on outcome of care. Am J Public Health. 1981;71(2):127–131.
- , , , , , . Listening to parents: The role of symptom perception in pediatric palliative home care. Palliat Support Care. 2016;14(1):13–19.
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- , , , , , . Dyspnea scales in the assessment of illiterate patients with chronic obstructive pulmonary disease. Am J Med Sci. 2000;320(4):240–243.
- , , , , . Measuring the dyspnea of decompensated heart failure with a visual analog scale: how much improvement is meaningful? Congest Heart Fail. 2004;10(4):188–191.
- , , , , , . Clinically meaningful changes in quantitative measures of asthma severity. Acad Emerg Med. 2000;7(4):327–334.
- , , , , . A combined comorbidity score predicted mortality in elderly patients better than existing scores. J Clin Epidemiol. 2011;64(7):749–759.
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- , , , et al. Depression symptomatology and diagnosis: discordance between patients and physicians in primary care settings. BMC Fam Pract. 2008;9:1.
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- , , , et al. The influence of discordance in pain assessment on the functional status of patients with chronic nonmalignant pain. Am J Med Sci. 2006;332(1):18–23.
- , , , et al. Hospitalist attitudes toward the assessment and management of dyspnea in patients with acute cardiopulmonary diseases. J Hosp Med. 2015;10(11):724–730.
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Breathlessness, or dyspnea, is defined as a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity.[1] Dyspnea is a leading reason for patients presenting for emergency care,[2] and it is an important predictor for hospitalization and mortality in patients with cardiopulmonary disease.[3, 4, 5]
Several professional societies' guidelines recommend that patients should be asked to quantify the intensity of their breathlessness using a standardized scale, and that these ratings should be documented in medical records to guide dyspnea awareness and management.[1, 6, 7] During the evaluation and treatment of patients with acute cardiopulmonary conditions, the clinician estimates the severity of the illness and response to therapy based on multiple objective measures as well as the patient's perception of dyspnea. A patient‐centered care approach depends upon the physicians having a shared understanding of what the patient is experiencing. Without this appreciation, the healthcare provider cannot make appropriate treatment decisions to ensure alleviation of presenting symptoms. Understanding the severity of patients' dyspnea is critical to avoid under‐ or overtreatment of patients with acute cardiopulmonary conditions, but only a few studies have compared patient and provider perceptions of dyspnea intensity.[8, 9] Discordance between physician's impression of severity of dyspnea and patient's perception may result in suboptimal management and patient dissatisfaction with care. Furthermore, several studies have shown that, when physicians and patients agree with the assessment of well‐being, treatment adherence and outcomes improve.[10, 11]
Therefore, we evaluated the extent and directionality of agreement between patients' perception and healthcare providers' impression of dyspnea and explored which factors contribute to discordance. Additionally, we examined how healthcare providers document dyspnea severity.
METHODS
Study Setting and Population
The study was conducted between June 2012 and August 2012 at Baystate Medical Center (BMC), a 740‐bed tertiary care hospital in western Massachusetts. In 2012, the BMC hospitalist group had 48 attending physicians, of whom 47% were female, 48% had 0 to 3 years of attending experience, and 16% had 10 years of experience.
We enrolled consecutive admissions of English‐speaking adult patients, with a working diagnosis of heart failure (HF), chronic obstructive pulmonary disease (COPD), asthma, pneumonia, or a generic diagnosis of shortness of breath. Because we surveyed only hospitalists, we did not include patients admitted to an intensive care unit.
All participants gave informed consent to be part of the study. The research protocol was approved by the Baystate Health Institutional Review Board, Springfield, Massachusetts.
Dyspnea Assessment
Dyspnea intensity was assessed on an 11‐point (010) numerical rating scale (NRS).[12, 13] A trained research assistant interviewed patients on day 1 and 2 after admission, and on the day of discharge between 8 am and 12 pm on weekdays. The patient was asked: On a scale from 0 to 10, how bad is your shortness of breath at rest now, with 0 being no shortness of breath and 10 the worst shortness of breath you could ever imagine? The hospitalist or the senior resident and day‐shift nurse taking care of the patients were asked by the research assistant to rate the patient's dyspnea using the same scoring instrument shortly after they saw the patient. The physicians and nurses based their determination of dyspnea on their usual interview/examination of the patient. The patient, physician and the nurse were not aware of each other's rating. The research assistant scheduled the interviews to minimize the time intervals between the patient assessment and provider's rating. For this reason, the number of assessments per patient varied. Nurses were more readily available than physicians, which resulted in a larger number of patient‐nurse response pairs than patient‐physician pairs. All assessments were done in the morning, between 9 am and 12 pm, with a range of 3 hours between provider's assessment of the patient and the interview.
Dyspnea Agreement
Agreement was defined as a score within 1 between patient and healthcare provider; differences of 2 points were considered over‐ or underestimations. The decision to use this cutoff was based on prior studies, which found that a difference in the range of 1.6 to 2.2 cm was meaningful for the patient when assessment was done on the visual analog scale.[8, 14, 15] We also evaluated the direction of discordance. If the patient's rating of dyspnea severity was higher than the provider's rating, we defined this as underestimation by the provider; in the instance where a provider's score of dyspnea severity was higher than the patient's score, we defined this as overestimation. In a sensitivity analysis, agreement was defined as a score within 2 between patient and healthcare provider, and any difference 3 was considered disagreement.
Other Variables
We obtained information from the medical records about patient demographics, body mass index (BMI), smoking status, and vital signs. We calculated the oxygen saturation index as the ratio between the oxygen saturation and the fractional inspired oxygen (SpO2/FIO2). Comorbidities were assessed based on the International Classification od Diseases, Ninth Revision, Clinical Modification codes from the hospital financial decision support system. We calculated an overall combined comorbidity score based on the method described by Gagne, which is based on elements from the Charlson Comorbidity Index and from the Elixhauser comorbidities.[16]
Charts of the patients included in the study were retrospectively reviewed for physicians' and nurses' documentation of dyspnea at admission and at discharge. We recorded if dyspnea was mentioned and how it was assessed: whether it was described as present/absent; graded as mild, moderate, or severe; used a quantitative scale (010); used descriptors (eg, dyspnea when climbing stairs); and whether it was defined as improved or worsened without other qualifiers.
Statistical Analysis
Descriptive statistics of dyspnea scores, patient characteristics, comorbidities and vital signs were calculated and presented as medians with interquartile range (IQR) for continuous variables, and counts with percentages for categorical factors. Every patient‐provider concurrent scoring was included in the analysis as 1 dyad, which resulted in patients being included multiple times in the analysis. Patient‐physician and patient‐nurse dyads of dyspnea assessment were examined separately. Analyses included all dyads that were within same assessment period (same day and same time window).
The relationship between patient self‐perceived dyspnea severity and provider rating of was assessed in several ways. First, a weighted kappa coefficient was used as a measure of agreement between patient and nurse or physician scores. A weighted kappa analysis was chosen because it penalizes disagreements that are further apart from each other.
Second, we defined an indicator of discordance and constructed multivariable generalized estimating equation models that account for clustering of multiple dyads per patient, to assess the relationship of patient characteristics with discordance. Finally, we developed additional models to predict underestimation when compared to agreement or overestimation of dyspnea by the healthcare provider relative to the patient. Using the same definitions for agreement, we also compared the dyspnea assessment estimation between physicians and nurses.
We present the differences in dyspnea assessment between patient and healthcare provider and between nurses and physicians by Bland‐Altman plots.
All analyses were performed using SAS (version 9.3; SAS institute, Inc., Cary, NC), Stata (Stata statistical software release 13; StataCorp, College Station, TX), and RStudio version 0.99.892 (Bland‐Altman plots, R package version 0.3.1; The R Foundation for Statistical Computing, Vienna, Austria).[8, 9, 17]
RESULTS
Patient Characteristics
Among the 219 patients who met the screening criteria, 81 were not enrolled (Figure 1). Data from 138 patients, with both patient information and provider data on dyspnea assessment, were included. The median age of the patients was 72 years (IQR, 5880 years), 56.5% were women, 75.4% were white, and 28.3% were current smokers. Approximately 30% had a diagnosis of HF, 30% of COPD, and 13.0% of pneumonia. The median comorbidity score was 4 (IQR, 26), and 37.0% of the patients had a BMI 30. At admission, the median oxygen saturation index was 346 (IQR, 287.5460) indicating mild to moderate levels of hypoxia. (Table 1).
| Value | |
|---|---|
| |
| Age, median (IQR), y | 72 (5880) |
| Gender | |
| Female | 78 (56.5) |
| Male | 60 (43.5) |
| Race | |
| White | 104 (75.4) |
| Black | 16 (11.6) |
| Hispanic | 17 (12.3) |
| Other | 1 (0.7) |
| Body mass index, median (IQR) | 28 (23.334.6) |
| Obese (BMI 30) | 51 (37.0) |
| Smoker, current | 39 (28.3) |
| Admitting diagnosis | |
| Heart failure | 46 (33.3) |
| COPD/asthma | 41 (29.7) |
| Pneumonia | 18 (13.0) |
| Other | 33 (23.9) |
| Depression | 32 (23.2) |
| Comorbidity score, median (IQR) | 4 (26) |
| Respiratory rate at admission, median (IQR) | 20 (1924) |
| Oxygen saturation index at admission, median (IQR) | 346.4 (287.5460) |
| Patient NRS, median (IQR) | |
| At admission | 9 (710) |
| At discharge | 2 (14) |
| Discharged on home oxygen | 45 (32.6) |
| Respiratory rate at discharge, median (IQR) | 20 (1820) |
| Oxygen saturation index at discharge, median (IQR) | 475 (350485) |
Agreement Between Patients' Self‐Assessment and Providers' Assessment of Dyspnea Severity
Not all patients had complete data points, and more nurses were interviewed than physicians. Overall, 96 patient‐physician and 138 patient‐nurse pairs participated in the study. A total of 336 patient‐nurse rating dyad assessments of dyspnea and 124 patient‐physician rating dyads assessments were collected (Figure 1). The mean difference between patient and physicians and patient and nurses assessments of dyspnea was 1.23 (IQR, 3 to 0) and 0.21 (IQR, 2 to 2) respectively (a negative score means underestimation by the provider, a positive score means overestimation).
The unadjusted agreement on the severity of dyspnea was 36.3% for the patient‐physician dyads and 44.1% for the patient‐nurse dyads. Physicians underestimated their patients' dyspnea 37.9% of the time and overestimated it 25.8% of the time; nurses underestimated it 43.5% of the time and overestimated it in 12.4% of the study patients (Table 2). In 28.2% of the time, physicians were discordant more than 4 points of the patient assessment. Bland‐Altman plots show that there is greater variation in differences of dyspnea assessments with increase in shortness of breath scores (Figure 2). Nurses underestimated more when the dyspnea score was on the lower end. Physicians also tended to estimate either lower or higher when compared to patients when the dyspnea scores were <2 (Figure 2A,B).
| Underestimation | Concordance | Overestimation | |||||||
|---|---|---|---|---|---|---|---|---|---|
| 3 | 2 | %* | 0 | 1 | % | 2 | 3 | % | |
| |||||||||
| Patient‐nurse dyads | 110 | 48 | 43.5 | 82 | 78 | 44.1 | 17 | 28 | 12.4 |
| Patient‐physician dyads | 33 | 14 | 37.9 | 21 | 24 | 36.3 | 12 | 20 | 25.8 |
The weighted kappa coefficient for agreement was 0.11 (95% confidence interval [CI]: 0.01 to 0.21) for patient‐physician assessment, 0.18 (95% CI: 0.12 to 0.24) for patient‐nurse, and 0.09 (0.02 to 0.20) for physician‐nurse indicating poor agreement. In a sensitivity analysis in which we used a higher threshold for defining discordance (difference of more than 2 points), the kappa coefficient increased to 0.21 (95% CI: 0.06 to 0.36) for patient‐physician assessments, to 0.24 (95% CI: 0.15 to 0.33) for patient‐nurse, and to 0.24 (95% CI: 0.09 to 0.39) for nurse‐physician assessments.
Predictors of Discordance and Underestimation of Dyspnea Severity Assessment
Principal diagnosis was the only factor associated with the physicians' discordant assessment of patients' dyspnea. Patients with admission diagnoses other than HF, COPD, or pneumonia (eg, pulmonary embolism) were more likely to have an accurate assessment of their dyspnea by providers (Table 3). Similar results were obtained in the sensitivity analysis by using a higher cutoff for defining discordance and when assessing predictors for underestimation (results not shown).
| Modeling Probability of Discordance | ||
|---|---|---|
| Physician‐Patient Dyads, OR (95% CI), N = 124 | Nurse‐Patient Dyads, OR (95% CI), N = 363 | |
| ||
| Univariate Analysis | ||
| Body mass index | 1.00 (0.991.01) | 1.00 (0.991.00) |
| Comorbidity score | 1.01 (0.981.05) | 0.99 (0.961.01) |
| Respiratory rate at admission | 1.00 (0.991.02) | 0.99 (0.981.00) |
| Oxygen saturation at admission | 1.00 (1.001.00) | 1.00 (1.001.00) |
| Age (binary) | ||
| 65 years | Referent | Referent |
| >65 years | 1.21 (0.572.55) | 0.96 (0.571.64) |
| Gender | ||
| Female | Referent | Referent |
| Male | 1.10 (0.522.32) | 0.81 (0.481.37) |
| Race | ||
| White | Referent | Referent |
| Nonwhite | 1.02 (0.442.37) | 1.06 (0.581.95) |
| Obese (BMI >30) | 1.43 (0.663.11) | 0.76 (0.441.30) |
| Smoker | 1.36 (0.613.05) | 1.04 (0.591.85) |
| Admitting diagnosis | ||
| Heart failure | Referent | Referent |
| COPD/asthma | 0.68 (0.251.83) | 1.91 (0.983.73)* |
| Pneumonia | 0.38 (0.101.40) | 1.07 (0.462.45) |
| Other | 0.30 (0.110.82)* | 1.54 (0.763.11) |
| Depression | 1.21 (0.572.55) | 1.01 (0.541.86) |
| Multivariable analysis | ||
| Admitting diagnosis | ||
| Congestive heart failure | Referent | Referent |
| COPD | 0.68 (0.251.83) | 1.91 (0.983.73)* |
| Pneumonia | 0.38 (0.101.40) | 1.07 (0.462.45) |
| Other | 0.30 (0.110.82)* | 1.54 (0.763.11) |
In the multivariable analysis that assessed patient‐nurse dyads, the diagnosis of COPD was associated with a marginally significant likelihood of discordance (OR: 1.91; 95% CI: 0.98 to 3.73) (Table 3). Similarly, multivariable analysis identified principal diagnosis to be the only predictor of underestimation, and COPD diagnosis was associated with increased odds of dyspnea underestimation by nurses. When we used a higher cutoff to define discordance, the principal diagnosis of COPD (OR: 3.43, 95% CI: 1.76 to 6.69) was associated with an increased risk of discordance, and smoking (OR: 0.54, 95% CI: 0.29 to 0.99) was associated with a decreased risk of discordance. Overall, 45 patients (32.6%) were discharged on oxygen. The odds of discrepancy (under‐ or overestimation) in dyspnea scores between patient and nurse were 1.7 times higher compared to patients who were not discharged on oxygen, but this association did not reach statistical significance; the odds of discrepancy between patient and physician were 3.88 (95% CI: 1.07 to 14.13).
Documentation of Dyspnea
We found that dyspnea was mentioned in the admission notes in 96% of the charts reviewed; physicians used a qualitative rating (mild, moderate, or severe) to indicate the severity of dyspnea in only 16% of cases, and in 53% a descriptor was added (eg, dyspnea with climbing stairs, gradually increased in the prior week). Nurses were more likely than physicians to use qualitative ratings of dyspnea (26% of cases), and they used a more uniform description of the patient's dyspnea (eg, at rest, at rest and on exertion, or on exertion) than physicians. At discharge, 83% of physicians noted in their discharge summary that dyspnea improved compared with admission but did not refer to the patient's baseline level of dyspnea.
DISCUSSION
In this prospective study of 138 patients hospitalized with cardiopulmonary disease, we found that the agreement between patient's experience of dyspnea and providers' assessment was poor, and the discordance was higher for physicians than for nurses. In more than half of the cases, differences between patient and healthcare providers' assessment of dyspnea were present. One‐third of the time, both physicians and nurses underestimated patients' reported levels of dyspnea. Admitting diagnosis was the only patient factor predicting lack of agreement, and patients with COPD were more likely to have their dyspnea underestimated by nurses. Healthcare providers predominantly documented the presence or absence of dyspnea and rarely used a more nuanced scale.
Discrepancies between patient and provider assessments for pain, depression, and overall health have been reported.[8, 18, 19, 20, 21] One explanation is that patients and healthcare providers measure different factors despite using the same terminology. Furthermore, patient's assessment may be confounded by other symptoms such as anxiety, fatigue, or pain. Physicians and nurses may underevaluate and underestimate the level of breathlessness; however, from the physician perspective, dyspnea is only 1 data point, and providers rely on other measures, such as oxygen saturation, heart rate, respiratory rate, evidence of increasing breathing effort, and arterial blood gas to drive decision making. In a recent study that evaluated the attitudes and beliefs of hospitalists regarding the assessment and management of dyspnea, we found that most hospitalists indicated that awareness of dyspnea severity influences their decision for treatment, diagnostic testing, and timing of the discharge. Moreover, whereas less than half of the respondents reported experience with standardized assessment of dyspnea severity, most stated that such data would be very useful in their practice.[22]
What is the clinical significance of having discordance between patients self‐assessment and providers impression of the patient's severity of dyspnea? First, inaccurate assessment of dyspnea by providers can lead to inadequate treatment and workup. For example, a physician who underestimates the severity of dyspnea may fail to recognize when a complication of the underlying disease develops or may underutilize symptomatic methods for relief of dyspnea. In contrast, a physician who overestimates dyspnea may continue with aggressive treatment when this is not necessary. Second, lack of awareness of dyspnea severity experienced by the patient may result in premature discharge and patient's frustration with the provider, as was shown in several studies evaluating physician‐patient agreement for pain perception.[21, 23] We found that discrepancy between patients and healthcare providers was more pronounced for patients with COPD. In another study using the same patient cohort, we reported that compared to patients with congestive heart failure, those with COPD had more residual dyspnea at discharge; 1 in 4 patients was discharged with a dyspnea score of 5 of greater, and almost half reported symptoms above their baseline.[24] The results from the current study may explain in part why patients with COPD are discharged with higher levels of dyspnea and should alert healthcare providers on the importance of patient‐reported breathlessness. Third, the high level of discordance between healthcare providers and patients may explain the undertreatment of dyspnea in patients with advanced disease. This is supported by our findings that the discordance between patients and physicians was higher if the patient was discharged on oxygen.
One key role of the provider during a clinical encounter is to elicit the patient's symptoms and achieve a shared understanding of what the patient is experiencing. From the patient's perspective, their self‐assessment of dyspnea is more important that the physician's assessment. Fortunately, there is a growing recognition and emphasis on using outcomes that matter to patients, such as dyspnea, to inform judgment about patient care and for clinical research. Numerical measures for assessment of dyspnea exist, are easy to use, and are sensitive to change in patients' dyspnea.[6, 25, 26, 27] Still, it is not standard practice for healthcare providers to ask patients to provide a rating of their dyspnea. When we examined the documentation of dyspnea in the medical record, we found that the description was vague, and providers did not use a standardized validated assessment. Although the dyspnea score decreased during hospitalization, the respiratory rate did not significantly change, indicating that this objective measure may not be reliable in patient assessment. The providers' knowledge of the intensity of the symptom expressed by patients will enable them to track improvement in symptoms over time or in response to therapy. In addition, in this era of multiple handoffs within a hospitalization or from primary care to the hospital, a more uniform assessment could allow providers to follow the severity and time course of dyspnea. The low level of agreement we found between patients and the providers lends support to recommendations regarding a structured dyspnea assessment into routine hospital practice.
Study Strengths and Limitations
This study has several strengths. This is 1 of the very few studies to report on the level of agreement between patients' and providers' assessments of dyspnea. We used a validated, simple dyspnea scale that provides consistency in rating.[28, 29] We enrolled patients with a broad set of diagnoses and complaints, which increases the generalizability of our results, and we surveyed both physicians and nurses. Last, our findings were robust across different cutoff points utilized to characterize discordance and across 3 frequent diagnoses.
The study has several limitations. First, we included only English‐speaking patients, and the results cannot be generalized to patients from other cultures who do not speak English. Second, this is a single‐center study, and practices may be different in other centers; for example, some hospitals may have already implemented a dyspnea assessment tool. Third, we did not collect information on the physician and nurse characteristics such as years in practice. However, a recent study that describes the agreement of breathlessness assessment between nurses, physicians, and mechanically ventilated patients found that underestimation of breathlessness by providers was not associated with professional competencies, previous patient care, or years of working in an intensive care unit.[9] In addition, a systematic review found that length of professional experience is often unrelated to performance measures and outcomes.[30] Finally, although we asked for physicians and nurses assessment close to their visit to the patient, assessment was done from memory, not at the bedside observing the patient.
CONCLUSION
We found that the extent of agreement between a structured patient self‐assessment of dyspnea and healthcare providers' assessment was low. Future studies should prospectively test whether routine assessment of dyspnea results in better acute and long‐term patient outcomes.
Acknowledgements
The authors acknowledge Ms. Anu Joshi for her help with formatting the manuscript and assisting with table preparations. The authors also acknowledge Ms. Katherine Dempsey, Jahnavi Sagi, Sashi Ariyaratne, and Mr. Pradeep Kumbaham for their help with collecting the data.
Disclosures: M.S.S. is the guarantor for this article and had full access to all of the data in the study, and takes responsibility for the integrity and accuracy of the data analysis. M.S.S., P.K.L., E.N., and M.B.R. conceived of the study. M.S.S. and B.M. acquired the data. M.S.S., A.P., P.S.P., R.J.G., and P.K.L. analyzed and interpreted the data. M.S.S. drafted the manuscript. All authors critically reviewed the manuscript for intellectual content. M.S.S. is supported by grant 1K01HL114631‐01A1 from the National Heart, Lung, and Blood Institute of the National Institutes of Health and by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through grant UL1RR025752. The authors report no conflicts of interest.
Breathlessness, or dyspnea, is defined as a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity.[1] Dyspnea is a leading reason for patients presenting for emergency care,[2] and it is an important predictor for hospitalization and mortality in patients with cardiopulmonary disease.[3, 4, 5]
Several professional societies' guidelines recommend that patients should be asked to quantify the intensity of their breathlessness using a standardized scale, and that these ratings should be documented in medical records to guide dyspnea awareness and management.[1, 6, 7] During the evaluation and treatment of patients with acute cardiopulmonary conditions, the clinician estimates the severity of the illness and response to therapy based on multiple objective measures as well as the patient's perception of dyspnea. A patient‐centered care approach depends upon the physicians having a shared understanding of what the patient is experiencing. Without this appreciation, the healthcare provider cannot make appropriate treatment decisions to ensure alleviation of presenting symptoms. Understanding the severity of patients' dyspnea is critical to avoid under‐ or overtreatment of patients with acute cardiopulmonary conditions, but only a few studies have compared patient and provider perceptions of dyspnea intensity.[8, 9] Discordance between physician's impression of severity of dyspnea and patient's perception may result in suboptimal management and patient dissatisfaction with care. Furthermore, several studies have shown that, when physicians and patients agree with the assessment of well‐being, treatment adherence and outcomes improve.[10, 11]
Therefore, we evaluated the extent and directionality of agreement between patients' perception and healthcare providers' impression of dyspnea and explored which factors contribute to discordance. Additionally, we examined how healthcare providers document dyspnea severity.
METHODS
Study Setting and Population
The study was conducted between June 2012 and August 2012 at Baystate Medical Center (BMC), a 740‐bed tertiary care hospital in western Massachusetts. In 2012, the BMC hospitalist group had 48 attending physicians, of whom 47% were female, 48% had 0 to 3 years of attending experience, and 16% had 10 years of experience.
We enrolled consecutive admissions of English‐speaking adult patients, with a working diagnosis of heart failure (HF), chronic obstructive pulmonary disease (COPD), asthma, pneumonia, or a generic diagnosis of shortness of breath. Because we surveyed only hospitalists, we did not include patients admitted to an intensive care unit.
All participants gave informed consent to be part of the study. The research protocol was approved by the Baystate Health Institutional Review Board, Springfield, Massachusetts.
Dyspnea Assessment
Dyspnea intensity was assessed on an 11‐point (010) numerical rating scale (NRS).[12, 13] A trained research assistant interviewed patients on day 1 and 2 after admission, and on the day of discharge between 8 am and 12 pm on weekdays. The patient was asked: On a scale from 0 to 10, how bad is your shortness of breath at rest now, with 0 being no shortness of breath and 10 the worst shortness of breath you could ever imagine? The hospitalist or the senior resident and day‐shift nurse taking care of the patients were asked by the research assistant to rate the patient's dyspnea using the same scoring instrument shortly after they saw the patient. The physicians and nurses based their determination of dyspnea on their usual interview/examination of the patient. The patient, physician and the nurse were not aware of each other's rating. The research assistant scheduled the interviews to minimize the time intervals between the patient assessment and provider's rating. For this reason, the number of assessments per patient varied. Nurses were more readily available than physicians, which resulted in a larger number of patient‐nurse response pairs than patient‐physician pairs. All assessments were done in the morning, between 9 am and 12 pm, with a range of 3 hours between provider's assessment of the patient and the interview.
Dyspnea Agreement
Agreement was defined as a score within 1 between patient and healthcare provider; differences of 2 points were considered over‐ or underestimations. The decision to use this cutoff was based on prior studies, which found that a difference in the range of 1.6 to 2.2 cm was meaningful for the patient when assessment was done on the visual analog scale.[8, 14, 15] We also evaluated the direction of discordance. If the patient's rating of dyspnea severity was higher than the provider's rating, we defined this as underestimation by the provider; in the instance where a provider's score of dyspnea severity was higher than the patient's score, we defined this as overestimation. In a sensitivity analysis, agreement was defined as a score within 2 between patient and healthcare provider, and any difference 3 was considered disagreement.
Other Variables
We obtained information from the medical records about patient demographics, body mass index (BMI), smoking status, and vital signs. We calculated the oxygen saturation index as the ratio between the oxygen saturation and the fractional inspired oxygen (SpO2/FIO2). Comorbidities were assessed based on the International Classification od Diseases, Ninth Revision, Clinical Modification codes from the hospital financial decision support system. We calculated an overall combined comorbidity score based on the method described by Gagne, which is based on elements from the Charlson Comorbidity Index and from the Elixhauser comorbidities.[16]
Charts of the patients included in the study were retrospectively reviewed for physicians' and nurses' documentation of dyspnea at admission and at discharge. We recorded if dyspnea was mentioned and how it was assessed: whether it was described as present/absent; graded as mild, moderate, or severe; used a quantitative scale (010); used descriptors (eg, dyspnea when climbing stairs); and whether it was defined as improved or worsened without other qualifiers.
Statistical Analysis
Descriptive statistics of dyspnea scores, patient characteristics, comorbidities and vital signs were calculated and presented as medians with interquartile range (IQR) for continuous variables, and counts with percentages for categorical factors. Every patient‐provider concurrent scoring was included in the analysis as 1 dyad, which resulted in patients being included multiple times in the analysis. Patient‐physician and patient‐nurse dyads of dyspnea assessment were examined separately. Analyses included all dyads that were within same assessment period (same day and same time window).
The relationship between patient self‐perceived dyspnea severity and provider rating of was assessed in several ways. First, a weighted kappa coefficient was used as a measure of agreement between patient and nurse or physician scores. A weighted kappa analysis was chosen because it penalizes disagreements that are further apart from each other.
Second, we defined an indicator of discordance and constructed multivariable generalized estimating equation models that account for clustering of multiple dyads per patient, to assess the relationship of patient characteristics with discordance. Finally, we developed additional models to predict underestimation when compared to agreement or overestimation of dyspnea by the healthcare provider relative to the patient. Using the same definitions for agreement, we also compared the dyspnea assessment estimation between physicians and nurses.
We present the differences in dyspnea assessment between patient and healthcare provider and between nurses and physicians by Bland‐Altman plots.
All analyses were performed using SAS (version 9.3; SAS institute, Inc., Cary, NC), Stata (Stata statistical software release 13; StataCorp, College Station, TX), and RStudio version 0.99.892 (Bland‐Altman plots, R package version 0.3.1; The R Foundation for Statistical Computing, Vienna, Austria).[8, 9, 17]
RESULTS
Patient Characteristics
Among the 219 patients who met the screening criteria, 81 were not enrolled (Figure 1). Data from 138 patients, with both patient information and provider data on dyspnea assessment, were included. The median age of the patients was 72 years (IQR, 5880 years), 56.5% were women, 75.4% were white, and 28.3% were current smokers. Approximately 30% had a diagnosis of HF, 30% of COPD, and 13.0% of pneumonia. The median comorbidity score was 4 (IQR, 26), and 37.0% of the patients had a BMI 30. At admission, the median oxygen saturation index was 346 (IQR, 287.5460) indicating mild to moderate levels of hypoxia. (Table 1).
| Value | |
|---|---|
| |
| Age, median (IQR), y | 72 (5880) |
| Gender | |
| Female | 78 (56.5) |
| Male | 60 (43.5) |
| Race | |
| White | 104 (75.4) |
| Black | 16 (11.6) |
| Hispanic | 17 (12.3) |
| Other | 1 (0.7) |
| Body mass index, median (IQR) | 28 (23.334.6) |
| Obese (BMI 30) | 51 (37.0) |
| Smoker, current | 39 (28.3) |
| Admitting diagnosis | |
| Heart failure | 46 (33.3) |
| COPD/asthma | 41 (29.7) |
| Pneumonia | 18 (13.0) |
| Other | 33 (23.9) |
| Depression | 32 (23.2) |
| Comorbidity score, median (IQR) | 4 (26) |
| Respiratory rate at admission, median (IQR) | 20 (1924) |
| Oxygen saturation index at admission, median (IQR) | 346.4 (287.5460) |
| Patient NRS, median (IQR) | |
| At admission | 9 (710) |
| At discharge | 2 (14) |
| Discharged on home oxygen | 45 (32.6) |
| Respiratory rate at discharge, median (IQR) | 20 (1820) |
| Oxygen saturation index at discharge, median (IQR) | 475 (350485) |
Agreement Between Patients' Self‐Assessment and Providers' Assessment of Dyspnea Severity
Not all patients had complete data points, and more nurses were interviewed than physicians. Overall, 96 patient‐physician and 138 patient‐nurse pairs participated in the study. A total of 336 patient‐nurse rating dyad assessments of dyspnea and 124 patient‐physician rating dyads assessments were collected (Figure 1). The mean difference between patient and physicians and patient and nurses assessments of dyspnea was 1.23 (IQR, 3 to 0) and 0.21 (IQR, 2 to 2) respectively (a negative score means underestimation by the provider, a positive score means overestimation).
The unadjusted agreement on the severity of dyspnea was 36.3% for the patient‐physician dyads and 44.1% for the patient‐nurse dyads. Physicians underestimated their patients' dyspnea 37.9% of the time and overestimated it 25.8% of the time; nurses underestimated it 43.5% of the time and overestimated it in 12.4% of the study patients (Table 2). In 28.2% of the time, physicians were discordant more than 4 points of the patient assessment. Bland‐Altman plots show that there is greater variation in differences of dyspnea assessments with increase in shortness of breath scores (Figure 2). Nurses underestimated more when the dyspnea score was on the lower end. Physicians also tended to estimate either lower or higher when compared to patients when the dyspnea scores were <2 (Figure 2A,B).
| Underestimation | Concordance | Overestimation | |||||||
|---|---|---|---|---|---|---|---|---|---|
| 3 | 2 | %* | 0 | 1 | % | 2 | 3 | % | |
| |||||||||
| Patient‐nurse dyads | 110 | 48 | 43.5 | 82 | 78 | 44.1 | 17 | 28 | 12.4 |
| Patient‐physician dyads | 33 | 14 | 37.9 | 21 | 24 | 36.3 | 12 | 20 | 25.8 |
The weighted kappa coefficient for agreement was 0.11 (95% confidence interval [CI]: 0.01 to 0.21) for patient‐physician assessment, 0.18 (95% CI: 0.12 to 0.24) for patient‐nurse, and 0.09 (0.02 to 0.20) for physician‐nurse indicating poor agreement. In a sensitivity analysis in which we used a higher threshold for defining discordance (difference of more than 2 points), the kappa coefficient increased to 0.21 (95% CI: 0.06 to 0.36) for patient‐physician assessments, to 0.24 (95% CI: 0.15 to 0.33) for patient‐nurse, and to 0.24 (95% CI: 0.09 to 0.39) for nurse‐physician assessments.
Predictors of Discordance and Underestimation of Dyspnea Severity Assessment
Principal diagnosis was the only factor associated with the physicians' discordant assessment of patients' dyspnea. Patients with admission diagnoses other than HF, COPD, or pneumonia (eg, pulmonary embolism) were more likely to have an accurate assessment of their dyspnea by providers (Table 3). Similar results were obtained in the sensitivity analysis by using a higher cutoff for defining discordance and when assessing predictors for underestimation (results not shown).
| Modeling Probability of Discordance | ||
|---|---|---|
| Physician‐Patient Dyads, OR (95% CI), N = 124 | Nurse‐Patient Dyads, OR (95% CI), N = 363 | |
| ||
| Univariate Analysis | ||
| Body mass index | 1.00 (0.991.01) | 1.00 (0.991.00) |
| Comorbidity score | 1.01 (0.981.05) | 0.99 (0.961.01) |
| Respiratory rate at admission | 1.00 (0.991.02) | 0.99 (0.981.00) |
| Oxygen saturation at admission | 1.00 (1.001.00) | 1.00 (1.001.00) |
| Age (binary) | ||
| 65 years | Referent | Referent |
| >65 years | 1.21 (0.572.55) | 0.96 (0.571.64) |
| Gender | ||
| Female | Referent | Referent |
| Male | 1.10 (0.522.32) | 0.81 (0.481.37) |
| Race | ||
| White | Referent | Referent |
| Nonwhite | 1.02 (0.442.37) | 1.06 (0.581.95) |
| Obese (BMI >30) | 1.43 (0.663.11) | 0.76 (0.441.30) |
| Smoker | 1.36 (0.613.05) | 1.04 (0.591.85) |
| Admitting diagnosis | ||
| Heart failure | Referent | Referent |
| COPD/asthma | 0.68 (0.251.83) | 1.91 (0.983.73)* |
| Pneumonia | 0.38 (0.101.40) | 1.07 (0.462.45) |
| Other | 0.30 (0.110.82)* | 1.54 (0.763.11) |
| Depression | 1.21 (0.572.55) | 1.01 (0.541.86) |
| Multivariable analysis | ||
| Admitting diagnosis | ||
| Congestive heart failure | Referent | Referent |
| COPD | 0.68 (0.251.83) | 1.91 (0.983.73)* |
| Pneumonia | 0.38 (0.101.40) | 1.07 (0.462.45) |
| Other | 0.30 (0.110.82)* | 1.54 (0.763.11) |
In the multivariable analysis that assessed patient‐nurse dyads, the diagnosis of COPD was associated with a marginally significant likelihood of discordance (OR: 1.91; 95% CI: 0.98 to 3.73) (Table 3). Similarly, multivariable analysis identified principal diagnosis to be the only predictor of underestimation, and COPD diagnosis was associated with increased odds of dyspnea underestimation by nurses. When we used a higher cutoff to define discordance, the principal diagnosis of COPD (OR: 3.43, 95% CI: 1.76 to 6.69) was associated with an increased risk of discordance, and smoking (OR: 0.54, 95% CI: 0.29 to 0.99) was associated with a decreased risk of discordance. Overall, 45 patients (32.6%) were discharged on oxygen. The odds of discrepancy (under‐ or overestimation) in dyspnea scores between patient and nurse were 1.7 times higher compared to patients who were not discharged on oxygen, but this association did not reach statistical significance; the odds of discrepancy between patient and physician were 3.88 (95% CI: 1.07 to 14.13).
Documentation of Dyspnea
We found that dyspnea was mentioned in the admission notes in 96% of the charts reviewed; physicians used a qualitative rating (mild, moderate, or severe) to indicate the severity of dyspnea in only 16% of cases, and in 53% a descriptor was added (eg, dyspnea with climbing stairs, gradually increased in the prior week). Nurses were more likely than physicians to use qualitative ratings of dyspnea (26% of cases), and they used a more uniform description of the patient's dyspnea (eg, at rest, at rest and on exertion, or on exertion) than physicians. At discharge, 83% of physicians noted in their discharge summary that dyspnea improved compared with admission but did not refer to the patient's baseline level of dyspnea.
DISCUSSION
In this prospective study of 138 patients hospitalized with cardiopulmonary disease, we found that the agreement between patient's experience of dyspnea and providers' assessment was poor, and the discordance was higher for physicians than for nurses. In more than half of the cases, differences between patient and healthcare providers' assessment of dyspnea were present. One‐third of the time, both physicians and nurses underestimated patients' reported levels of dyspnea. Admitting diagnosis was the only patient factor predicting lack of agreement, and patients with COPD were more likely to have their dyspnea underestimated by nurses. Healthcare providers predominantly documented the presence or absence of dyspnea and rarely used a more nuanced scale.
Discrepancies between patient and provider assessments for pain, depression, and overall health have been reported.[8, 18, 19, 20, 21] One explanation is that patients and healthcare providers measure different factors despite using the same terminology. Furthermore, patient's assessment may be confounded by other symptoms such as anxiety, fatigue, or pain. Physicians and nurses may underevaluate and underestimate the level of breathlessness; however, from the physician perspective, dyspnea is only 1 data point, and providers rely on other measures, such as oxygen saturation, heart rate, respiratory rate, evidence of increasing breathing effort, and arterial blood gas to drive decision making. In a recent study that evaluated the attitudes and beliefs of hospitalists regarding the assessment and management of dyspnea, we found that most hospitalists indicated that awareness of dyspnea severity influences their decision for treatment, diagnostic testing, and timing of the discharge. Moreover, whereas less than half of the respondents reported experience with standardized assessment of dyspnea severity, most stated that such data would be very useful in their practice.[22]
What is the clinical significance of having discordance between patients self‐assessment and providers impression of the patient's severity of dyspnea? First, inaccurate assessment of dyspnea by providers can lead to inadequate treatment and workup. For example, a physician who underestimates the severity of dyspnea may fail to recognize when a complication of the underlying disease develops or may underutilize symptomatic methods for relief of dyspnea. In contrast, a physician who overestimates dyspnea may continue with aggressive treatment when this is not necessary. Second, lack of awareness of dyspnea severity experienced by the patient may result in premature discharge and patient's frustration with the provider, as was shown in several studies evaluating physician‐patient agreement for pain perception.[21, 23] We found that discrepancy between patients and healthcare providers was more pronounced for patients with COPD. In another study using the same patient cohort, we reported that compared to patients with congestive heart failure, those with COPD had more residual dyspnea at discharge; 1 in 4 patients was discharged with a dyspnea score of 5 of greater, and almost half reported symptoms above their baseline.[24] The results from the current study may explain in part why patients with COPD are discharged with higher levels of dyspnea and should alert healthcare providers on the importance of patient‐reported breathlessness. Third, the high level of discordance between healthcare providers and patients may explain the undertreatment of dyspnea in patients with advanced disease. This is supported by our findings that the discordance between patients and physicians was higher if the patient was discharged on oxygen.
One key role of the provider during a clinical encounter is to elicit the patient's symptoms and achieve a shared understanding of what the patient is experiencing. From the patient's perspective, their self‐assessment of dyspnea is more important that the physician's assessment. Fortunately, there is a growing recognition and emphasis on using outcomes that matter to patients, such as dyspnea, to inform judgment about patient care and for clinical research. Numerical measures for assessment of dyspnea exist, are easy to use, and are sensitive to change in patients' dyspnea.[6, 25, 26, 27] Still, it is not standard practice for healthcare providers to ask patients to provide a rating of their dyspnea. When we examined the documentation of dyspnea in the medical record, we found that the description was vague, and providers did not use a standardized validated assessment. Although the dyspnea score decreased during hospitalization, the respiratory rate did not significantly change, indicating that this objective measure may not be reliable in patient assessment. The providers' knowledge of the intensity of the symptom expressed by patients will enable them to track improvement in symptoms over time or in response to therapy. In addition, in this era of multiple handoffs within a hospitalization or from primary care to the hospital, a more uniform assessment could allow providers to follow the severity and time course of dyspnea. The low level of agreement we found between patients and the providers lends support to recommendations regarding a structured dyspnea assessment into routine hospital practice.
Study Strengths and Limitations
This study has several strengths. This is 1 of the very few studies to report on the level of agreement between patients' and providers' assessments of dyspnea. We used a validated, simple dyspnea scale that provides consistency in rating.[28, 29] We enrolled patients with a broad set of diagnoses and complaints, which increases the generalizability of our results, and we surveyed both physicians and nurses. Last, our findings were robust across different cutoff points utilized to characterize discordance and across 3 frequent diagnoses.
The study has several limitations. First, we included only English‐speaking patients, and the results cannot be generalized to patients from other cultures who do not speak English. Second, this is a single‐center study, and practices may be different in other centers; for example, some hospitals may have already implemented a dyspnea assessment tool. Third, we did not collect information on the physician and nurse characteristics such as years in practice. However, a recent study that describes the agreement of breathlessness assessment between nurses, physicians, and mechanically ventilated patients found that underestimation of breathlessness by providers was not associated with professional competencies, previous patient care, or years of working in an intensive care unit.[9] In addition, a systematic review found that length of professional experience is often unrelated to performance measures and outcomes.[30] Finally, although we asked for physicians and nurses assessment close to their visit to the patient, assessment was done from memory, not at the bedside observing the patient.
CONCLUSION
We found that the extent of agreement between a structured patient self‐assessment of dyspnea and healthcare providers' assessment was low. Future studies should prospectively test whether routine assessment of dyspnea results in better acute and long‐term patient outcomes.
Acknowledgements
The authors acknowledge Ms. Anu Joshi for her help with formatting the manuscript and assisting with table preparations. The authors also acknowledge Ms. Katherine Dempsey, Jahnavi Sagi, Sashi Ariyaratne, and Mr. Pradeep Kumbaham for their help with collecting the data.
Disclosures: M.S.S. is the guarantor for this article and had full access to all of the data in the study, and takes responsibility for the integrity and accuracy of the data analysis. M.S.S., P.K.L., E.N., and M.B.R. conceived of the study. M.S.S. and B.M. acquired the data. M.S.S., A.P., P.S.P., R.J.G., and P.K.L. analyzed and interpreted the data. M.S.S. drafted the manuscript. All authors critically reviewed the manuscript for intellectual content. M.S.S. is supported by grant 1K01HL114631‐01A1 from the National Heart, Lung, and Blood Institute of the National Institutes of Health and by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through grant UL1RR025752. The authors report no conflicts of interest.
- , , , et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012;185(4):435–452.
- , , . National Hospital Ambulatory Medical Care Survey: 2007 emergency department summary. Natl Health Stat Report. 2010;(26):1–31.
- , , , et al. The body‐mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1005–1012.
- , , , . Dyspnea is a better predictor of 5‐year survival than airway obstruction in patients with COPD. Chest. 2002;121(5):1434–1440.
- , , . A multidimensional grading system (BODE index) as predictor of hospitalization for COPD. Chest. 2005;128(6):3810–3816.
- , , , et al. American College of Chest Physicians consensus statement on the management of dyspnea in patients with advanced lung or heart disease. Chest. 2010;137(3):674–691.
- , , , et al. Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: a Canadian Thoracic Society clinical practice guideline. Can Respir J. 2011;18(2):69–78.
- , , . Physician vs patient assessment of dyspnea during acute decompensated heart failure. Congest Heart Fail. 2010;16(2):60–64.
- , , , , , . Underestimation of Patient Breathlessness by Nurses and Physicians during a Spontaneous Breathing Trial. Am J Respir Crit Care Med. 2015;192(12):1440–1448.
- , , , , , . The influence of patient‐practitioner agreement on outcome of care. Am J Public Health. 1981;71(2):127–131.
- , , , , , . Listening to parents: The role of symptom perception in pediatric palliative home care. Palliat Support Care. 2016;14(1):13–19.
- , . Validity of the numeric rating scale as a measure of dyspnea. Am J Crit Care. 1998;7(3):200–204.
- , , , , , . Dyspnea scales in the assessment of illiterate patients with chronic obstructive pulmonary disease. Am J Med Sci. 2000;320(4):240–243.
- , , , , . Measuring the dyspnea of decompensated heart failure with a visual analog scale: how much improvement is meaningful? Congest Heart Fail. 2004;10(4):188–191.
- , , , , , . Clinically meaningful changes in quantitative measures of asthma severity. Acad Emerg Med. 2000;7(4):327–334.
- , , , , . A combined comorbidity score predicted mortality in elderly patients better than existing scores. J Clin Epidemiol. 2011;64(7):749–759.
- . BlandAltmanLeh: plots (slightly extended) Bland‐Altman plots. Available at: https://cran.r‐project.org/web/packages/BlandAltmanLeh/index.html. Published December 23, 2015. Accessed March 10, 2016.
- , , , , . Correlation of patient and caregiver ratings of cancer pain. J Pain Symptom Manage. 1991;6(2):53–57.
- , , , et al. Depression symptomatology and diagnosis: discordance between patients and physicians in primary care settings. BMC Fam Pract. 2008;9:1.
- , , , , , . Patient‐physician discordance in assessments of global disease severity in rheumatoid arthritis. Arthritis Care Res (Hoboken) 2010;62(6):857–864.
- , , , et al. The influence of discordance in pain assessment on the functional status of patients with chronic nonmalignant pain. Am J Med Sci. 2006;332(1):18–23.
- , , , et al. Hospitalist attitudes toward the assessment and management of dyspnea in patients with acute cardiopulmonary diseases. J Hosp Med. 2015;10(11):724–730.
- , , , , . Brief report: patient‐physician agreement as a predictor of outcomes in patients with back pain. J Gen Intern Med. 2005;20(10):935–937.
- , , , , , . The trajectory of dyspnea in hospitalized patients [published online November 24, 2015]. J Pain Symptom Manage. doi: 10.1016/j.jpainsymman.2015.11.005.
- , , , , . Measurement of breathlessness in advanced disease: a systematic review. Respir Med. 2007;101(3):399–410.
- . Review of dyspnoea quantification in the emergency department: is a rating scale for breathlessness suitable for use as an admission prediction tool? Emerg Med Australas. 2007;19(5):394–404.
- , , , . Validation of a verbal dyspnoea rating scale in the emergency department. Emerg Med Australas. 2008;20(6):475–481.
- , , . Measurement of dyspnea: word labeled visual analog scale vs. verbal ordinal scale. Respir Physiol Neurobiol. 2003;134(2):77–83.
- , , , , , . Verbal numerical scales are as reliable and sensitive as visual analog scales for rating dyspnea in young and older subjects. Respir Physiol Neurobiol. 2007;157(2–3):360–365.
- , , . Systematic review: the relationship between clinical experience and quality of health care. Ann Intern Med. 2005;142(4):260–273.
- , , , et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012;185(4):435–452.
- , , . National Hospital Ambulatory Medical Care Survey: 2007 emergency department summary. Natl Health Stat Report. 2010;(26):1–31.
- , , , et al. The body‐mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1005–1012.
- , , , . Dyspnea is a better predictor of 5‐year survival than airway obstruction in patients with COPD. Chest. 2002;121(5):1434–1440.
- , , . A multidimensional grading system (BODE index) as predictor of hospitalization for COPD. Chest. 2005;128(6):3810–3816.
- , , , et al. American College of Chest Physicians consensus statement on the management of dyspnea in patients with advanced lung or heart disease. Chest. 2010;137(3):674–691.
- , , , et al. Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: a Canadian Thoracic Society clinical practice guideline. Can Respir J. 2011;18(2):69–78.
- , , . Physician vs patient assessment of dyspnea during acute decompensated heart failure. Congest Heart Fail. 2010;16(2):60–64.
- , , , , , . Underestimation of Patient Breathlessness by Nurses and Physicians during a Spontaneous Breathing Trial. Am J Respir Crit Care Med. 2015;192(12):1440–1448.
- , , , , , . The influence of patient‐practitioner agreement on outcome of care. Am J Public Health. 1981;71(2):127–131.
- , , , , , . Listening to parents: The role of symptom perception in pediatric palliative home care. Palliat Support Care. 2016;14(1):13–19.
- , . Validity of the numeric rating scale as a measure of dyspnea. Am J Crit Care. 1998;7(3):200–204.
- , , , , , . Dyspnea scales in the assessment of illiterate patients with chronic obstructive pulmonary disease. Am J Med Sci. 2000;320(4):240–243.
- , , , , . Measuring the dyspnea of decompensated heart failure with a visual analog scale: how much improvement is meaningful? Congest Heart Fail. 2004;10(4):188–191.
- , , , , , . Clinically meaningful changes in quantitative measures of asthma severity. Acad Emerg Med. 2000;7(4):327–334.
- , , , , . A combined comorbidity score predicted mortality in elderly patients better than existing scores. J Clin Epidemiol. 2011;64(7):749–759.
- . BlandAltmanLeh: plots (slightly extended) Bland‐Altman plots. Available at: https://cran.r‐project.org/web/packages/BlandAltmanLeh/index.html. Published December 23, 2015. Accessed March 10, 2016.
- , , , , . Correlation of patient and caregiver ratings of cancer pain. J Pain Symptom Manage. 1991;6(2):53–57.
- , , , et al. Depression symptomatology and diagnosis: discordance between patients and physicians in primary care settings. BMC Fam Pract. 2008;9:1.
- , , , , , . Patient‐physician discordance in assessments of global disease severity in rheumatoid arthritis. Arthritis Care Res (Hoboken) 2010;62(6):857–864.
- , , , et al. The influence of discordance in pain assessment on the functional status of patients with chronic nonmalignant pain. Am J Med Sci. 2006;332(1):18–23.
- , , , et al. Hospitalist attitudes toward the assessment and management of dyspnea in patients with acute cardiopulmonary diseases. J Hosp Med. 2015;10(11):724–730.
- , , , , . Brief report: patient‐physician agreement as a predictor of outcomes in patients with back pain. J Gen Intern Med. 2005;20(10):935–937.
- , , , , , . The trajectory of dyspnea in hospitalized patients [published online November 24, 2015]. J Pain Symptom Manage. doi: 10.1016/j.jpainsymman.2015.11.005.
- , , , , . Measurement of breathlessness in advanced disease: a systematic review. Respir Med. 2007;101(3):399–410.
- . Review of dyspnoea quantification in the emergency department: is a rating scale for breathlessness suitable for use as an admission prediction tool? Emerg Med Australas. 2007;19(5):394–404.
- , , , . Validation of a verbal dyspnoea rating scale in the emergency department. Emerg Med Australas. 2008;20(6):475–481.
- , , . Measurement of dyspnea: word labeled visual analog scale vs. verbal ordinal scale. Respir Physiol Neurobiol. 2003;134(2):77–83.
- , , , , , . Verbal numerical scales are as reliable and sensitive as visual analog scales for rating dyspnea in young and older subjects. Respir Physiol Neurobiol. 2007;157(2–3):360–365.
- , , . Systematic review: the relationship between clinical experience and quality of health care. Ann Intern Med. 2005;142(4):260–273.
Effective psoriasis therapy may reduce coronary plaque burden
CHICAGO – Improvement in psoriasis was associated with a significant reduction in coronary plaque burden within 1 year in a pilot study conducted at the National Heart, Lung, and Blood Institute, Joseph B. Lerman reported at the annual meeting of the American College of Cardiology.
“If you look at psoriatic plaque on the skin, it’s spewing out cytokines such as tumor necrosis factor–alpha and interleukin-17 which are highly linked to atherosclerosis. What we’ve found is that if you treat those plaques and reduce the severity of psoriasis, we’ve noticed small but statistically significant regression in the early noncalcified plaque. It’s a very exciting observation,” said Mr. Lerman, a medical student at Mount Sinai School of Medicine, New York.
He presented an observational study involving 50 consecutive patients with mild to moderate psoriasis of roughly 20 years duration and a median baseline Framingham Risk Score of 4. They underwent measurement of coronary plaque burden by coronary CT angiography at baseline and 1 year later.
During the study year, 33 patients showed significant improvement in their psoriasis as reflected in a decline in their mean Psoriasis Area and Severity Index score from 5.6 to 3.1. Those patients also showed significant improvement in their total and noncalcified plaque burden, with total plaque burden adjusted for luminal attenuation declining from 126 mm2 to 117 mm2. The association remained significant even after adjustment for traditional cardiovascular risk factors, the use of statin therapy, body mass index, and the use of systemic psoriasis therapies, including biologic agents.
Importantly, the reduction in plaque burden appeared to be largely concentrated in the subgroup of 31 patients on methotrexate or a biologic. And while this was a naturalistic observational study, the investigators have followed up with a prospective study of psoriasis patients placed on tumor necrosis factor inhibitors and confirmed that they, too, experienced a reduction in coronary plaque as measured by coronary CT angiography.
The investigators plan to expand the size of the study in order to confirm the findings. Mr. Lerman said the next question they would like to address is, how early does a measurable reduction in coronary plaque burden occur in response to clinical improvement in psoriasis? In order to explore this, the investigators will have to obtain institutional approval of a new investigative protocol which permits more frequent use of coronary CT angiography. At present the imaging study can be conducted only once per year due to the radiation exposure.
Mr. Lerman was involved in the psoriasis study while participating in the National Institutes of Health Medical Research Scholars Program. Senior investigator in the pilot study was Dr. Nehal Mehta, chief of the Section of Inflammation and Metabolic Disease at NHLBI in Bethesda, Md.
Mr. Lerman reported having no financial conflicts of interest.
CHICAGO – Improvement in psoriasis was associated with a significant reduction in coronary plaque burden within 1 year in a pilot study conducted at the National Heart, Lung, and Blood Institute, Joseph B. Lerman reported at the annual meeting of the American College of Cardiology.
“If you look at psoriatic plaque on the skin, it’s spewing out cytokines such as tumor necrosis factor–alpha and interleukin-17 which are highly linked to atherosclerosis. What we’ve found is that if you treat those plaques and reduce the severity of psoriasis, we’ve noticed small but statistically significant regression in the early noncalcified plaque. It’s a very exciting observation,” said Mr. Lerman, a medical student at Mount Sinai School of Medicine, New York.
He presented an observational study involving 50 consecutive patients with mild to moderate psoriasis of roughly 20 years duration and a median baseline Framingham Risk Score of 4. They underwent measurement of coronary plaque burden by coronary CT angiography at baseline and 1 year later.
During the study year, 33 patients showed significant improvement in their psoriasis as reflected in a decline in their mean Psoriasis Area and Severity Index score from 5.6 to 3.1. Those patients also showed significant improvement in their total and noncalcified plaque burden, with total plaque burden adjusted for luminal attenuation declining from 126 mm2 to 117 mm2. The association remained significant even after adjustment for traditional cardiovascular risk factors, the use of statin therapy, body mass index, and the use of systemic psoriasis therapies, including biologic agents.
Importantly, the reduction in plaque burden appeared to be largely concentrated in the subgroup of 31 patients on methotrexate or a biologic. And while this was a naturalistic observational study, the investigators have followed up with a prospective study of psoriasis patients placed on tumor necrosis factor inhibitors and confirmed that they, too, experienced a reduction in coronary plaque as measured by coronary CT angiography.
The investigators plan to expand the size of the study in order to confirm the findings. Mr. Lerman said the next question they would like to address is, how early does a measurable reduction in coronary plaque burden occur in response to clinical improvement in psoriasis? In order to explore this, the investigators will have to obtain institutional approval of a new investigative protocol which permits more frequent use of coronary CT angiography. At present the imaging study can be conducted only once per year due to the radiation exposure.
Mr. Lerman was involved in the psoriasis study while participating in the National Institutes of Health Medical Research Scholars Program. Senior investigator in the pilot study was Dr. Nehal Mehta, chief of the Section of Inflammation and Metabolic Disease at NHLBI in Bethesda, Md.
Mr. Lerman reported having no financial conflicts of interest.
CHICAGO – Improvement in psoriasis was associated with a significant reduction in coronary plaque burden within 1 year in a pilot study conducted at the National Heart, Lung, and Blood Institute, Joseph B. Lerman reported at the annual meeting of the American College of Cardiology.
“If you look at psoriatic plaque on the skin, it’s spewing out cytokines such as tumor necrosis factor–alpha and interleukin-17 which are highly linked to atherosclerosis. What we’ve found is that if you treat those plaques and reduce the severity of psoriasis, we’ve noticed small but statistically significant regression in the early noncalcified plaque. It’s a very exciting observation,” said Mr. Lerman, a medical student at Mount Sinai School of Medicine, New York.
He presented an observational study involving 50 consecutive patients with mild to moderate psoriasis of roughly 20 years duration and a median baseline Framingham Risk Score of 4. They underwent measurement of coronary plaque burden by coronary CT angiography at baseline and 1 year later.
During the study year, 33 patients showed significant improvement in their psoriasis as reflected in a decline in their mean Psoriasis Area and Severity Index score from 5.6 to 3.1. Those patients also showed significant improvement in their total and noncalcified plaque burden, with total plaque burden adjusted for luminal attenuation declining from 126 mm2 to 117 mm2. The association remained significant even after adjustment for traditional cardiovascular risk factors, the use of statin therapy, body mass index, and the use of systemic psoriasis therapies, including biologic agents.
Importantly, the reduction in plaque burden appeared to be largely concentrated in the subgroup of 31 patients on methotrexate or a biologic. And while this was a naturalistic observational study, the investigators have followed up with a prospective study of psoriasis patients placed on tumor necrosis factor inhibitors and confirmed that they, too, experienced a reduction in coronary plaque as measured by coronary CT angiography.
The investigators plan to expand the size of the study in order to confirm the findings. Mr. Lerman said the next question they would like to address is, how early does a measurable reduction in coronary plaque burden occur in response to clinical improvement in psoriasis? In order to explore this, the investigators will have to obtain institutional approval of a new investigative protocol which permits more frequent use of coronary CT angiography. At present the imaging study can be conducted only once per year due to the radiation exposure.
Mr. Lerman was involved in the psoriasis study while participating in the National Institutes of Health Medical Research Scholars Program. Senior investigator in the pilot study was Dr. Nehal Mehta, chief of the Section of Inflammation and Metabolic Disease at NHLBI in Bethesda, Md.
Mr. Lerman reported having no financial conflicts of interest.
AT ACC 16
Key clinical point: Improved PASI scores were linked to regression of early noncalcified coronary plaque.
Major finding: Reduction in skin inflammation in psoriasis patients may cause regression of coronary plaque.
Data source: This prospective study of 50 patients with mild to moderate psoriasis featured precise measurements of coronary plaque burden at baseline and 1 year later.
Disclosures: The study was sponsored by the National Heart, Lung, and Blood Institute. The presenter reported having no financial conflicts of interest.
Rosacea patients have higher risk of dementia
Patients with rosacea have a higher risk of being diagnosed with certain forms of dementia, particularly Alzheimer’s disease (AD), according to Dr. Alexander Egeberg and his associates.
“We hypothesized that patients with rosacea may have increased risk of AD, because we have clinically observed a familial overrepresentation of AD in patients with rosacea, and because of the overlap of proinflammatory mediators between rosacea and AD,” wrote Dr. Egeberg of the National Allergy Research Center at the University of Copenhagen.
The researchers studied more than 5 million Danish citizens 18 years and older from Jan. 1, 1997, to Dec. 31, 2012. After excluding some people from the analysis for various reasons, including incomplete information, the cohort size was 5,591,718. Overall, 82,439 individuals had rosacea, and 29,193 of patients were diagnosed with AD.
“We found a significant association with dementia, and especially AD, in patients with rosacea,” the investigators wrote. They said the associations were strongest in people aged 60 or under at baseline, and “the results remained consistent in a range of sensitivity analyses and after adjustment for potential confounding factors.”
Future research might focus on symptoms of cognitive dysfunction in patients with rosacea, they wrote.
Find the study here.
Patients with rosacea have a higher risk of being diagnosed with certain forms of dementia, particularly Alzheimer’s disease (AD), according to Dr. Alexander Egeberg and his associates.
“We hypothesized that patients with rosacea may have increased risk of AD, because we have clinically observed a familial overrepresentation of AD in patients with rosacea, and because of the overlap of proinflammatory mediators between rosacea and AD,” wrote Dr. Egeberg of the National Allergy Research Center at the University of Copenhagen.
The researchers studied more than 5 million Danish citizens 18 years and older from Jan. 1, 1997, to Dec. 31, 2012. After excluding some people from the analysis for various reasons, including incomplete information, the cohort size was 5,591,718. Overall, 82,439 individuals had rosacea, and 29,193 of patients were diagnosed with AD.
“We found a significant association with dementia, and especially AD, in patients with rosacea,” the investigators wrote. They said the associations were strongest in people aged 60 or under at baseline, and “the results remained consistent in a range of sensitivity analyses and after adjustment for potential confounding factors.”
Future research might focus on symptoms of cognitive dysfunction in patients with rosacea, they wrote.
Find the study here.
Patients with rosacea have a higher risk of being diagnosed with certain forms of dementia, particularly Alzheimer’s disease (AD), according to Dr. Alexander Egeberg and his associates.
“We hypothesized that patients with rosacea may have increased risk of AD, because we have clinically observed a familial overrepresentation of AD in patients with rosacea, and because of the overlap of proinflammatory mediators between rosacea and AD,” wrote Dr. Egeberg of the National Allergy Research Center at the University of Copenhagen.
The researchers studied more than 5 million Danish citizens 18 years and older from Jan. 1, 1997, to Dec. 31, 2012. After excluding some people from the analysis for various reasons, including incomplete information, the cohort size was 5,591,718. Overall, 82,439 individuals had rosacea, and 29,193 of patients were diagnosed with AD.
“We found a significant association with dementia, and especially AD, in patients with rosacea,” the investigators wrote. They said the associations were strongest in people aged 60 or under at baseline, and “the results remained consistent in a range of sensitivity analyses and after adjustment for potential confounding factors.”
Future research might focus on symptoms of cognitive dysfunction in patients with rosacea, they wrote.
Find the study here.
FROM ANNALS OF NEUROLOGY
Algorithm predicts late liver disease ICU benefit
AT THE INTERNATIONAL LIVER CONGRESS 2016
BARCELONA – An algorithm that has been developed to help clinicians decide whether or not to refer a patient with end-stage liver disease (ESLD) with organ failure for intensive care treatment predicted mortality in the vast majority of cases, but came under fire during discussion as being potentially “quite dangerous” at the International Liver Congress.
When retrospectively applied to data on 465 patients with end-stage liver disease (ESLD), the algorithm correctly predicted 30-day mortality in 87% of cases.
Determining which patients with severe cirrhosis and acute-on-chronic liver failure (ACLF) should be transferred for intensive care is challenging, explained presenting study author Dr. Katrine Lindvig of Odense University Hospital in Denmark.
“More than 30 studies have looked at mortality in cirrhotic patients with organ failure, and we know that the mortality ranges from 35% to 89% between 15 centers,” Dr. Lindvig said at the meeting sponsored by the European Association for the Study of the Liver. But, she asked, what is an acceptable mortality rate? With limited health care resources was there a point of no return at which referral for intensive care became futile or perhaps unethical?
Dr. Lindvig and colleagues developed an algorithm to help decide if a patient with ESLD is a candidate or not for intensive care based on three scoring systems: the premorbid Child-Pugh Score, the Model of End stage Liver Disease (MELD) score, and the ACLF grade. Data were obtained from four centers in Belgium, Austria, and Denmark, which included two hepatology wards and two ICUs.
A green light for ICU referral was given to patients’ with premorbid Child-Pugh A or B, or a premorbid MELD score of less than 20. Patients with premorbid Child-Pugh C or higher MELD score could also be referred if they had an ACLF grade of 2 or less.
Conversely, patients with Child-Pugh C or a premorbid MELD score of 20 or higher and who had an ACLF grade of 3 or more were given a red light as they would be unlikely to benefit from ICU therapy. Special cases could be discussed, of course, such as those listed for liver transplantation.
Results showed that 394 would get the green light to be referred to ICU and 70 would get a red light, indicating that there would probably be no benefit. Of these 155 (39%) and 53 (75%) in each group, respectively, died within 30 days. Of the 17 patients who survived in the red light group, 12 were still alive at 6 months, and nine were still alive at 1 year.
Comparing the results with the ACLF, there were 35 (30%) of 114 patients with a score of three or higher that were still alive at 30 days and had been coded red by the algorithm. Dr. Lindvig noted, however, that the ACLF was purely descriptive and not developed as a predictive tool.
“However, when we combine the ACLF with the premorbid liver function the algorithm is significantly superior to the ACLF grade alone,” Dr. Lindvig said.
“We have no intention to replace good clinical judgment,” she added. “We simply want to assist the clinical decision making to make the decision more objective.” A computer-based program and app is now being developed in order to optimize and test the algorithm further.
“If the first duty of a physician is to do no harm, then we must continually review our decision-making tools and favor those that have the highest predictive value of treatment success and – importantly – treatment failure,” EASL spokesman Dr. Tom Hemming Karlsen of Oslo University Hospital Rikhospitalet said in a press release. “This study adds to our knowledge of existing, well-recognized scoring systems, and provides an interesting approach for review and wider discussion by the liver community.”
However, the dichotomous nature of the algorithm’s output was criticized during the discussion session by several concerned delegates who felt that it was oversimplified and potentially “quite dangerous” to be giving a green or red light for ICU referral. “There are lots of different variables to consider,” maintained one. Another argued that futility was “clearly not proven” in almost one-third of cases when compared with using the ACLF. Another said that the output should “not be a verdict.”
Nevertheless, others thought that while it was “provocative,” there were perhaps signs of “getting close” to a very good prediction tool.
In an interview, Dr. Lindvig defended the algorithm by reemphasizing that this was envisaged purely as a decision aid. “It is dichotomous, and we are just trying to aid the decision-making process,” she said, noting that this was particularly relevant perhaps for more junior doctors who may have to make a life-saving decision in the middle of the night.
Dr. Lindvig had nothing to disclose.
AT THE INTERNATIONAL LIVER CONGRESS 2016
BARCELONA – An algorithm that has been developed to help clinicians decide whether or not to refer a patient with end-stage liver disease (ESLD) with organ failure for intensive care treatment predicted mortality in the vast majority of cases, but came under fire during discussion as being potentially “quite dangerous” at the International Liver Congress.
When retrospectively applied to data on 465 patients with end-stage liver disease (ESLD), the algorithm correctly predicted 30-day mortality in 87% of cases.
Determining which patients with severe cirrhosis and acute-on-chronic liver failure (ACLF) should be transferred for intensive care is challenging, explained presenting study author Dr. Katrine Lindvig of Odense University Hospital in Denmark.
“More than 30 studies have looked at mortality in cirrhotic patients with organ failure, and we know that the mortality ranges from 35% to 89% between 15 centers,” Dr. Lindvig said at the meeting sponsored by the European Association for the Study of the Liver. But, she asked, what is an acceptable mortality rate? With limited health care resources was there a point of no return at which referral for intensive care became futile or perhaps unethical?
Dr. Lindvig and colleagues developed an algorithm to help decide if a patient with ESLD is a candidate or not for intensive care based on three scoring systems: the premorbid Child-Pugh Score, the Model of End stage Liver Disease (MELD) score, and the ACLF grade. Data were obtained from four centers in Belgium, Austria, and Denmark, which included two hepatology wards and two ICUs.
A green light for ICU referral was given to patients’ with premorbid Child-Pugh A or B, or a premorbid MELD score of less than 20. Patients with premorbid Child-Pugh C or higher MELD score could also be referred if they had an ACLF grade of 2 or less.
Conversely, patients with Child-Pugh C or a premorbid MELD score of 20 or higher and who had an ACLF grade of 3 or more were given a red light as they would be unlikely to benefit from ICU therapy. Special cases could be discussed, of course, such as those listed for liver transplantation.
Results showed that 394 would get the green light to be referred to ICU and 70 would get a red light, indicating that there would probably be no benefit. Of these 155 (39%) and 53 (75%) in each group, respectively, died within 30 days. Of the 17 patients who survived in the red light group, 12 were still alive at 6 months, and nine were still alive at 1 year.
Comparing the results with the ACLF, there were 35 (30%) of 114 patients with a score of three or higher that were still alive at 30 days and had been coded red by the algorithm. Dr. Lindvig noted, however, that the ACLF was purely descriptive and not developed as a predictive tool.
“However, when we combine the ACLF with the premorbid liver function the algorithm is significantly superior to the ACLF grade alone,” Dr. Lindvig said.
“We have no intention to replace good clinical judgment,” she added. “We simply want to assist the clinical decision making to make the decision more objective.” A computer-based program and app is now being developed in order to optimize and test the algorithm further.
“If the first duty of a physician is to do no harm, then we must continually review our decision-making tools and favor those that have the highest predictive value of treatment success and – importantly – treatment failure,” EASL spokesman Dr. Tom Hemming Karlsen of Oslo University Hospital Rikhospitalet said in a press release. “This study adds to our knowledge of existing, well-recognized scoring systems, and provides an interesting approach for review and wider discussion by the liver community.”
However, the dichotomous nature of the algorithm’s output was criticized during the discussion session by several concerned delegates who felt that it was oversimplified and potentially “quite dangerous” to be giving a green or red light for ICU referral. “There are lots of different variables to consider,” maintained one. Another argued that futility was “clearly not proven” in almost one-third of cases when compared with using the ACLF. Another said that the output should “not be a verdict.”
Nevertheless, others thought that while it was “provocative,” there were perhaps signs of “getting close” to a very good prediction tool.
In an interview, Dr. Lindvig defended the algorithm by reemphasizing that this was envisaged purely as a decision aid. “It is dichotomous, and we are just trying to aid the decision-making process,” she said, noting that this was particularly relevant perhaps for more junior doctors who may have to make a life-saving decision in the middle of the night.
Dr. Lindvig had nothing to disclose.
AT THE INTERNATIONAL LIVER CONGRESS 2016
BARCELONA – An algorithm that has been developed to help clinicians decide whether or not to refer a patient with end-stage liver disease (ESLD) with organ failure for intensive care treatment predicted mortality in the vast majority of cases, but came under fire during discussion as being potentially “quite dangerous” at the International Liver Congress.
When retrospectively applied to data on 465 patients with end-stage liver disease (ESLD), the algorithm correctly predicted 30-day mortality in 87% of cases.
Determining which patients with severe cirrhosis and acute-on-chronic liver failure (ACLF) should be transferred for intensive care is challenging, explained presenting study author Dr. Katrine Lindvig of Odense University Hospital in Denmark.
“More than 30 studies have looked at mortality in cirrhotic patients with organ failure, and we know that the mortality ranges from 35% to 89% between 15 centers,” Dr. Lindvig said at the meeting sponsored by the European Association for the Study of the Liver. But, she asked, what is an acceptable mortality rate? With limited health care resources was there a point of no return at which referral for intensive care became futile or perhaps unethical?
Dr. Lindvig and colleagues developed an algorithm to help decide if a patient with ESLD is a candidate or not for intensive care based on three scoring systems: the premorbid Child-Pugh Score, the Model of End stage Liver Disease (MELD) score, and the ACLF grade. Data were obtained from four centers in Belgium, Austria, and Denmark, which included two hepatology wards and two ICUs.
A green light for ICU referral was given to patients’ with premorbid Child-Pugh A or B, or a premorbid MELD score of less than 20. Patients with premorbid Child-Pugh C or higher MELD score could also be referred if they had an ACLF grade of 2 or less.
Conversely, patients with Child-Pugh C or a premorbid MELD score of 20 or higher and who had an ACLF grade of 3 or more were given a red light as they would be unlikely to benefit from ICU therapy. Special cases could be discussed, of course, such as those listed for liver transplantation.
Results showed that 394 would get the green light to be referred to ICU and 70 would get a red light, indicating that there would probably be no benefit. Of these 155 (39%) and 53 (75%) in each group, respectively, died within 30 days. Of the 17 patients who survived in the red light group, 12 were still alive at 6 months, and nine were still alive at 1 year.
Comparing the results with the ACLF, there were 35 (30%) of 114 patients with a score of three or higher that were still alive at 30 days and had been coded red by the algorithm. Dr. Lindvig noted, however, that the ACLF was purely descriptive and not developed as a predictive tool.
“However, when we combine the ACLF with the premorbid liver function the algorithm is significantly superior to the ACLF grade alone,” Dr. Lindvig said.
“We have no intention to replace good clinical judgment,” she added. “We simply want to assist the clinical decision making to make the decision more objective.” A computer-based program and app is now being developed in order to optimize and test the algorithm further.
“If the first duty of a physician is to do no harm, then we must continually review our decision-making tools and favor those that have the highest predictive value of treatment success and – importantly – treatment failure,” EASL spokesman Dr. Tom Hemming Karlsen of Oslo University Hospital Rikhospitalet said in a press release. “This study adds to our knowledge of existing, well-recognized scoring systems, and provides an interesting approach for review and wider discussion by the liver community.”
However, the dichotomous nature of the algorithm’s output was criticized during the discussion session by several concerned delegates who felt that it was oversimplified and potentially “quite dangerous” to be giving a green or red light for ICU referral. “There are lots of different variables to consider,” maintained one. Another argued that futility was “clearly not proven” in almost one-third of cases when compared with using the ACLF. Another said that the output should “not be a verdict.”
Nevertheless, others thought that while it was “provocative,” there were perhaps signs of “getting close” to a very good prediction tool.
In an interview, Dr. Lindvig defended the algorithm by reemphasizing that this was envisaged purely as a decision aid. “It is dichotomous, and we are just trying to aid the decision-making process,” she said, noting that this was particularly relevant perhaps for more junior doctors who may have to make a life-saving decision in the middle of the night.
Dr. Lindvig had nothing to disclose.
Key clinical point:The algorithm could aid clinical decision making but requires further validation.
Major finding: 30-day mortality in the ICU was accurately predicted in 87% of cases.
Data source: Retrospective study of 465 patients with end-stage liver disease.
Disclosures: Dr. Lindvig had nothing to disclose.
Multiple Morphologically Distinct Cutaneous Granular Cell Tumors Occurring in a Single Patient
Case Report
A 27-year-old black man was admitted to the hospital with chills; night sweats; unintentional 25-lb weight loss; and multiple widespread, painful, progressively enlarging skin nodules of 3 months’ duration. The lesions had first developed on the back and later appeared on the face, trunk, arms, thighs, and genital region. He denied dysuria or urethral discharge. He had a remote history of adequately treated chlamydia infection but no other remarkable personal or family history.
 | ||
| Figure 1. Firm subcutaneous nodules on the back with no epidermal change. | ||
 | ||
| Figure 2. Firm dermal papule on the anterior aspect of the left shoulder with violaceous hyperpigmentation (dermatofibromalike). |
Physical examination revealed a thin man with more than 20 lesions on the face, trunk, arms, thighs, and genital region ranging in size from 1 to 4 cm. Lesion morphologies varied greatly and included subcutaneous firm nodules with no epidermal change (Figure 1); dermatofibromalike nodules with overlying erythema and hyperpigmentation (Figure 2); condylomalike, verrucous, pink papulonodules (Figure 3); ulcerated angular plaques with rolled borders and palpable tumor extension deep (1–2 cm) to the subcutis (Figure 4); and a vegetative, eroded, exophytic tumor with palpable deep extension (Figure 4). A diffuse, erythematous, macular eruption also was noted on the trunk and bilateral arms and legs including the soles of both feet along with nontender cervical, axillary, and inguinal lymphadenopathy. The ocular, oral, and nasal mucosae were not affected.
The differential diagnosis for each lesion differed based on morphology. Infectious, inflammatory, and neoplastic processes were considered, including syphilis, dermatofibroma, dermatofibrosarcoma protuberans, metastatic disease, leukemia cutis, sarcoidosis, panniculitis, condyloma acuminatum, and vegetative herpes simplex virus infection (inguinal lesion).
Laboratory data revealed a reactive rapid plasma reagin with treponemal IgG titers of 1:64. Urine chlamydia RNA probe and lymphogranuloma venereum (LGV) serum antibodies also were positive. Human immunodeficiency virus screening was negative. Positron emission tomography–computerized tomography revealed enlarged and hypermetabolic lymphadenopathy above and below the diaphragm.
After therapy with intravenous penicillin G and oral doxycycline for concurrent secondary syphilis and LGV, the patient’s macular eruption and constitutional symptoms resolved within weeks of the initial presentation. His lymphadenopathy improved, his rapid plasma reagin titer decreased, and his chlamydia RNA became undetectable. However, the skin lesions remained unchanged.
Incisional biopsies of 4 clinically distinct skin lesions revealed well-delineated dermal proliferations of cells with eosinophilic granular cytoplasm and indistinct cell borders (Figure 5). Two specimens displayed marked epidermal hyperplasia (Figure 6).
No atypical mitotic figures were identified. Immunohistochemistry for S-100 protein was diffusely positive in the neoplastic cells. Immunohistochemistry for Treponema pallidum was negative.
No mycobacterial or fungal organisms were identified in acid-fast bacillus, periodic acid–Schiff, or Gomori methenamine-silver–stained sections. All 4 lesions had histopathologic findings characteristic of granular cell tumors (GCTs). A lesion in the left inguinal region (Figure 4 [medial lesion]), which initially was thought to be condyloma latum or a squamous cell carcinoma (SCC), also was later confirmed to be a GCT.
Repeat positron emission tomography–computerized tomography several weeks later confirmed resolution of the previously noted lymphadenopathy. Although 2 GCTs have not recurred after biopsy, the other 2, which the patient refused to have completely excised, continued to grow. Follow-up 2.5 years after hospitalization revealed persistence of the lesions with no remarkable morphological changes.
 |  | |
| Figure 3. Verrucous pink papule on the right side of the neck. | Figure 4. Ulcerated angular plaque in the left inguinal/genital area with rolled borders and tumor extension deep to the subcutis adjacent to a vegetative, eroded, exophytic tumor with palpable deep extension. | |
 |  | |
Figure 5. Large polygonal cells with eosinophilic granular cytoplasm, prominent bland nuclei, and indistinct cell borders (H&E, original magnification ×40). | Figure 6. Marked pseudoepitheliomatous hyperplasia (H&E, original magnification ×10). |
Comment
First described in 1854, GCTs are uncommon neoplasms of probable Schwann cell origin that can arise in almost any location of the body but most often appear on the skin and in the subcutaneous tissues and oral cavity.1,2 The commonly regarded rule of thirds describes its most favored locations: one-third on the tongue, one-third on the skin, and one-third in internal organs.3,4 Granular cell tumors occur with greater frequency in adults, females, and black individuals.1-5
Cutaneous GCTs usually present as solitary asymptomatic masses; however, multiple tumors have been noted in up to 25% of reported cases.4,6 In children, multiple cutaneous GCTs have been reported in the setting of neurofibromatosis type I as well as with other disorders.2,5,7-9
Cutaneous GCTs have been reported to range from sessile, pedunculated, or verrucous nodules to subcutaneous papules and nodules with no epidermal change. Our case not only illustrated the diverse clinical appearance of cutaneous GCTs but also demonstrated multiple morphologically distinct cutaneous GCTs occurring in a single patient. Of particular interest is our patient’s coexisting secondary syphilis and LGV infections, which can pose a diagnostic dilemma to the unsuspecting clinician. The manifold appearances of this patient’s GCTs resulted in a broad differential diagnosis. Syphilis (condyloma latum), condyloma acuminatum, LGV, metastatic disease, Kaposi sarcoma, lymphoma, dermatofibrosarcoma protuberans, leiomyoma, SCC, and deep fungal and atypical mycobacterial infection were all considerations. In 1981, Apisarnthanarax1 reviewed 88 cases of GCTs seen over a 15-year period and discovered that the preoperative clinical diagnoses were incorrect in all cases. Skin biopsy is necessary to diagnose GCT, and our patient’s case underscores the need for a thorough history, physical examination, and laboratory evaluation to rule out coexisting diseases.
Histopathology of cutaneous GCTs shows an unencapsulated dermal proliferation of large monotonous polygonal cells with blurred cell borders and fine, granular, eosinophilic cytoplasm arranged in irregular sheets and nests. Nuclei are small, uniform, round, centrally located, and rarely contain mitoses.3 The presence of mitotic activity on histopathology does not necessarily portend malignant biological behavior.5 Overlying pseudoepitheliomatous hyperplasia has been reported in as many as 85% of GCTs and may mimic SCC.10 The neoplastic cells stain positively with S-100 protein, neuron-specific enolase, and peripheral nerve myelin proteins.3,4 The cytoplasmic granules are positive on periodic acid–Schiff staining and diastase resistant and will sometimes stain for CD68.1 Electron microscopy shows degraded myelinated axons intracellularly.4
Malignancy is rare and reportedly occurs in 1% to 3% of cases.4,5 Consideration of both clinical behavior and histopathology is important in distinguishing benign from malignant lesions. According to published reports, in GCTs that were regarded as malignant, size tended to be greater than 4 cm, growth was rapid, and metastases to regional lymph nodes were observed.4,5 Histologically, nuclear pleomorphism and atypia, cell spindling, vesicular nuclei with prominent nucleoli, necrosis, and high mitotic activity favor malignancy.1,3
Treatment is complete surgical excision. Observation is acceptable if tumors are asymptomatic and do not impede function. Regression of some GCTs has been induced with use of intralesional corticosteroids.5 Spontaneous regression is rare. Prior reports have emphasized the importance of long-term follow-up in patients with multiple GCTs to monitor for development of systemic lesions.4
1. Apisarnthanarax P. Granular cell tumor. an analysis of 16 cases and review of the literature. J Am Acad Dermatol. 1981;5:171-182.
2. Guiglia MC, Prendiville JS. Multiple granular cell tumors associated with giant speckled lentiginous nevus and nevus flammeus in a child. J Am Acad Dermatol. 1991;24(2, pt 2):359-363.
3. Hazan C, Fangman W. Multiple cutaneous granular-cell tumors. Dermatol Online J. 2007;13:4.
4. Gross VL, Lynfield Y. Multiple cutaneous granular cell tumors: a case report and review of the literature. Cutis. 2002;69:343-346.
5. Martin RW 3rd, Neldner KH, Boyd AS, et al. Multiple cutaneous granular cell tumors and neurofibromatosis in childhood. a case report and review of the literature. Arch Dermatol. 1990;126:1051-1056.
6. Janousková G, Campr V, Konkol’ová R, et al. Multiple granular cell tumour. J Eur Acad Dermatol Venereol. 2004;18:347-349.
7. Gunson TH, Hashim N, Sharpe GR. Generalized lentiginosis, short stature, and multiple cutaneous nodules—quiz case. LEOPARD syndrome (LS) associated with multiple granular cell tumors (GCTs). Arch Dermatol. 2010;146:337-342.
8. De Raeve L, Roseeuw D, Otten J. Multiple cutaneous granular cell tumors in a child in remission for Hodgkin’s disease. J Am Acad Dermatol. 2002;47(2 suppl):S180-S182.
9. Ramaswamy PV, Storm CA, Filiano JJ, et al. Multiple granular cell tumors in a child with Noonan syndrome. Pediatr Dermatol. 2010;27:209-211.
10. Bangle R Jr. A morphological and histochemical study of the granular-cell myoblastoma. Cancer. 1952;5:950-965.
Case Report
A 27-year-old black man was admitted to the hospital with chills; night sweats; unintentional 25-lb weight loss; and multiple widespread, painful, progressively enlarging skin nodules of 3 months’ duration. The lesions had first developed on the back and later appeared on the face, trunk, arms, thighs, and genital region. He denied dysuria or urethral discharge. He had a remote history of adequately treated chlamydia infection but no other remarkable personal or family history.
| ||
| Figure 1. Firm subcutaneous nodules on the back with no epidermal change. | ||
| ||
| Figure 2. Firm dermal papule on the anterior aspect of the left shoulder with violaceous hyperpigmentation (dermatofibromalike). |
Physical examination revealed a thin man with more than 20 lesions on the face, trunk, arms, thighs, and genital region ranging in size from 1 to 4 cm. Lesion morphologies varied greatly and included subcutaneous firm nodules with no epidermal change (Figure 1); dermatofibromalike nodules with overlying erythema and hyperpigmentation (Figure 2); condylomalike, verrucous, pink papulonodules (Figure 3); ulcerated angular plaques with rolled borders and palpable tumor extension deep (1–2 cm) to the subcutis (Figure 4); and a vegetative, eroded, exophytic tumor with palpable deep extension (Figure 4). A diffuse, erythematous, macular eruption also was noted on the trunk and bilateral arms and legs including the soles of both feet along with nontender cervical, axillary, and inguinal lymphadenopathy. The ocular, oral, and nasal mucosae were not affected.
The differential diagnosis for each lesion differed based on morphology. Infectious, inflammatory, and neoplastic processes were considered, including syphilis, dermatofibroma, dermatofibrosarcoma protuberans, metastatic disease, leukemia cutis, sarcoidosis, panniculitis, condyloma acuminatum, and vegetative herpes simplex virus infection (inguinal lesion).
Laboratory data revealed a reactive rapid plasma reagin with treponemal IgG titers of 1:64. Urine chlamydia RNA probe and lymphogranuloma venereum (LGV) serum antibodies also were positive. Human immunodeficiency virus screening was negative. Positron emission tomography–computerized tomography revealed enlarged and hypermetabolic lymphadenopathy above and below the diaphragm.
After therapy with intravenous penicillin G and oral doxycycline for concurrent secondary syphilis and LGV, the patient’s macular eruption and constitutional symptoms resolved within weeks of the initial presentation. His lymphadenopathy improved, his rapid plasma reagin titer decreased, and his chlamydia RNA became undetectable. However, the skin lesions remained unchanged.
Incisional biopsies of 4 clinically distinct skin lesions revealed well-delineated dermal proliferations of cells with eosinophilic granular cytoplasm and indistinct cell borders (Figure 5). Two specimens displayed marked epidermal hyperplasia (Figure 6).
No atypical mitotic figures were identified. Immunohistochemistry for S-100 protein was diffusely positive in the neoplastic cells. Immunohistochemistry for Treponema pallidum was negative.
No mycobacterial or fungal organisms were identified in acid-fast bacillus, periodic acid–Schiff, or Gomori methenamine-silver–stained sections. All 4 lesions had histopathologic findings characteristic of granular cell tumors (GCTs). A lesion in the left inguinal region (Figure 4 [medial lesion]), which initially was thought to be condyloma latum or a squamous cell carcinoma (SCC), also was later confirmed to be a GCT.
Repeat positron emission tomography–computerized tomography several weeks later confirmed resolution of the previously noted lymphadenopathy. Although 2 GCTs have not recurred after biopsy, the other 2, which the patient refused to have completely excised, continued to grow. Follow-up 2.5 years after hospitalization revealed persistence of the lesions with no remarkable morphological changes.
| | |
| Figure 3. Verrucous pink papule on the right side of the neck. | Figure 4. Ulcerated angular plaque in the left inguinal/genital area with rolled borders and tumor extension deep to the subcutis adjacent to a vegetative, eroded, exophytic tumor with palpable deep extension. | |
| | |
Figure 5. Large polygonal cells with eosinophilic granular cytoplasm, prominent bland nuclei, and indistinct cell borders (H&E, original magnification ×40). | Figure 6. Marked pseudoepitheliomatous hyperplasia (H&E, original magnification ×10). |
Comment
First described in 1854, GCTs are uncommon neoplasms of probable Schwann cell origin that can arise in almost any location of the body but most often appear on the skin and in the subcutaneous tissues and oral cavity.1,2 The commonly regarded rule of thirds describes its most favored locations: one-third on the tongue, one-third on the skin, and one-third in internal organs.3,4 Granular cell tumors occur with greater frequency in adults, females, and black individuals.1-5
Cutaneous GCTs usually present as solitary asymptomatic masses; however, multiple tumors have been noted in up to 25% of reported cases.4,6 In children, multiple cutaneous GCTs have been reported in the setting of neurofibromatosis type I as well as with other disorders.2,5,7-9
Cutaneous GCTs have been reported to range from sessile, pedunculated, or verrucous nodules to subcutaneous papules and nodules with no epidermal change. Our case not only illustrated the diverse clinical appearance of cutaneous GCTs but also demonstrated multiple morphologically distinct cutaneous GCTs occurring in a single patient. Of particular interest is our patient’s coexisting secondary syphilis and LGV infections, which can pose a diagnostic dilemma to the unsuspecting clinician. The manifold appearances of this patient’s GCTs resulted in a broad differential diagnosis. Syphilis (condyloma latum), condyloma acuminatum, LGV, metastatic disease, Kaposi sarcoma, lymphoma, dermatofibrosarcoma protuberans, leiomyoma, SCC, and deep fungal and atypical mycobacterial infection were all considerations. In 1981, Apisarnthanarax1 reviewed 88 cases of GCTs seen over a 15-year period and discovered that the preoperative clinical diagnoses were incorrect in all cases. Skin biopsy is necessary to diagnose GCT, and our patient’s case underscores the need for a thorough history, physical examination, and laboratory evaluation to rule out coexisting diseases.
Histopathology of cutaneous GCTs shows an unencapsulated dermal proliferation of large monotonous polygonal cells with blurred cell borders and fine, granular, eosinophilic cytoplasm arranged in irregular sheets and nests. Nuclei are small, uniform, round, centrally located, and rarely contain mitoses.3 The presence of mitotic activity on histopathology does not necessarily portend malignant biological behavior.5 Overlying pseudoepitheliomatous hyperplasia has been reported in as many as 85% of GCTs and may mimic SCC.10 The neoplastic cells stain positively with S-100 protein, neuron-specific enolase, and peripheral nerve myelin proteins.3,4 The cytoplasmic granules are positive on periodic acid–Schiff staining and diastase resistant and will sometimes stain for CD68.1 Electron microscopy shows degraded myelinated axons intracellularly.4
Malignancy is rare and reportedly occurs in 1% to 3% of cases.4,5 Consideration of both clinical behavior and histopathology is important in distinguishing benign from malignant lesions. According to published reports, in GCTs that were regarded as malignant, size tended to be greater than 4 cm, growth was rapid, and metastases to regional lymph nodes were observed.4,5 Histologically, nuclear pleomorphism and atypia, cell spindling, vesicular nuclei with prominent nucleoli, necrosis, and high mitotic activity favor malignancy.1,3
Treatment is complete surgical excision. Observation is acceptable if tumors are asymptomatic and do not impede function. Regression of some GCTs has been induced with use of intralesional corticosteroids.5 Spontaneous regression is rare. Prior reports have emphasized the importance of long-term follow-up in patients with multiple GCTs to monitor for development of systemic lesions.4
Case Report
A 27-year-old black man was admitted to the hospital with chills; night sweats; unintentional 25-lb weight loss; and multiple widespread, painful, progressively enlarging skin nodules of 3 months’ duration. The lesions had first developed on the back and later appeared on the face, trunk, arms, thighs, and genital region. He denied dysuria or urethral discharge. He had a remote history of adequately treated chlamydia infection but no other remarkable personal or family history.
| ||
| Figure 1. Firm subcutaneous nodules on the back with no epidermal change. | ||
| ||
| Figure 2. Firm dermal papule on the anterior aspect of the left shoulder with violaceous hyperpigmentation (dermatofibromalike). |
Physical examination revealed a thin man with more than 20 lesions on the face, trunk, arms, thighs, and genital region ranging in size from 1 to 4 cm. Lesion morphologies varied greatly and included subcutaneous firm nodules with no epidermal change (Figure 1); dermatofibromalike nodules with overlying erythema and hyperpigmentation (Figure 2); condylomalike, verrucous, pink papulonodules (Figure 3); ulcerated angular plaques with rolled borders and palpable tumor extension deep (1–2 cm) to the subcutis (Figure 4); and a vegetative, eroded, exophytic tumor with palpable deep extension (Figure 4). A diffuse, erythematous, macular eruption also was noted on the trunk and bilateral arms and legs including the soles of both feet along with nontender cervical, axillary, and inguinal lymphadenopathy. The ocular, oral, and nasal mucosae were not affected.
The differential diagnosis for each lesion differed based on morphology. Infectious, inflammatory, and neoplastic processes were considered, including syphilis, dermatofibroma, dermatofibrosarcoma protuberans, metastatic disease, leukemia cutis, sarcoidosis, panniculitis, condyloma acuminatum, and vegetative herpes simplex virus infection (inguinal lesion).
Laboratory data revealed a reactive rapid plasma reagin with treponemal IgG titers of 1:64. Urine chlamydia RNA probe and lymphogranuloma venereum (LGV) serum antibodies also were positive. Human immunodeficiency virus screening was negative. Positron emission tomography–computerized tomography revealed enlarged and hypermetabolic lymphadenopathy above and below the diaphragm.
After therapy with intravenous penicillin G and oral doxycycline for concurrent secondary syphilis and LGV, the patient’s macular eruption and constitutional symptoms resolved within weeks of the initial presentation. His lymphadenopathy improved, his rapid plasma reagin titer decreased, and his chlamydia RNA became undetectable. However, the skin lesions remained unchanged.
Incisional biopsies of 4 clinically distinct skin lesions revealed well-delineated dermal proliferations of cells with eosinophilic granular cytoplasm and indistinct cell borders (Figure 5). Two specimens displayed marked epidermal hyperplasia (Figure 6).
No atypical mitotic figures were identified. Immunohistochemistry for S-100 protein was diffusely positive in the neoplastic cells. Immunohistochemistry for Treponema pallidum was negative.
No mycobacterial or fungal organisms were identified in acid-fast bacillus, periodic acid–Schiff, or Gomori methenamine-silver–stained sections. All 4 lesions had histopathologic findings characteristic of granular cell tumors (GCTs). A lesion in the left inguinal region (Figure 4 [medial lesion]), which initially was thought to be condyloma latum or a squamous cell carcinoma (SCC), also was later confirmed to be a GCT.
Repeat positron emission tomography–computerized tomography several weeks later confirmed resolution of the previously noted lymphadenopathy. Although 2 GCTs have not recurred after biopsy, the other 2, which the patient refused to have completely excised, continued to grow. Follow-up 2.5 years after hospitalization revealed persistence of the lesions with no remarkable morphological changes.
| | |
| Figure 3. Verrucous pink papule on the right side of the neck. | Figure 4. Ulcerated angular plaque in the left inguinal/genital area with rolled borders and tumor extension deep to the subcutis adjacent to a vegetative, eroded, exophytic tumor with palpable deep extension. | |
| | |
Figure 5. Large polygonal cells with eosinophilic granular cytoplasm, prominent bland nuclei, and indistinct cell borders (H&E, original magnification ×40). | Figure 6. Marked pseudoepitheliomatous hyperplasia (H&E, original magnification ×10). |
Comment
First described in 1854, GCTs are uncommon neoplasms of probable Schwann cell origin that can arise in almost any location of the body but most often appear on the skin and in the subcutaneous tissues and oral cavity.1,2 The commonly regarded rule of thirds describes its most favored locations: one-third on the tongue, one-third on the skin, and one-third in internal organs.3,4 Granular cell tumors occur with greater frequency in adults, females, and black individuals.1-5
Cutaneous GCTs usually present as solitary asymptomatic masses; however, multiple tumors have been noted in up to 25% of reported cases.4,6 In children, multiple cutaneous GCTs have been reported in the setting of neurofibromatosis type I as well as with other disorders.2,5,7-9
Cutaneous GCTs have been reported to range from sessile, pedunculated, or verrucous nodules to subcutaneous papules and nodules with no epidermal change. Our case not only illustrated the diverse clinical appearance of cutaneous GCTs but also demonstrated multiple morphologically distinct cutaneous GCTs occurring in a single patient. Of particular interest is our patient’s coexisting secondary syphilis and LGV infections, which can pose a diagnostic dilemma to the unsuspecting clinician. The manifold appearances of this patient’s GCTs resulted in a broad differential diagnosis. Syphilis (condyloma latum), condyloma acuminatum, LGV, metastatic disease, Kaposi sarcoma, lymphoma, dermatofibrosarcoma protuberans, leiomyoma, SCC, and deep fungal and atypical mycobacterial infection were all considerations. In 1981, Apisarnthanarax1 reviewed 88 cases of GCTs seen over a 15-year period and discovered that the preoperative clinical diagnoses were incorrect in all cases. Skin biopsy is necessary to diagnose GCT, and our patient’s case underscores the need for a thorough history, physical examination, and laboratory evaluation to rule out coexisting diseases.
Histopathology of cutaneous GCTs shows an unencapsulated dermal proliferation of large monotonous polygonal cells with blurred cell borders and fine, granular, eosinophilic cytoplasm arranged in irregular sheets and nests. Nuclei are small, uniform, round, centrally located, and rarely contain mitoses.3 The presence of mitotic activity on histopathology does not necessarily portend malignant biological behavior.5 Overlying pseudoepitheliomatous hyperplasia has been reported in as many as 85% of GCTs and may mimic SCC.10 The neoplastic cells stain positively with S-100 protein, neuron-specific enolase, and peripheral nerve myelin proteins.3,4 The cytoplasmic granules are positive on periodic acid–Schiff staining and diastase resistant and will sometimes stain for CD68.1 Electron microscopy shows degraded myelinated axons intracellularly.4
Malignancy is rare and reportedly occurs in 1% to 3% of cases.4,5 Consideration of both clinical behavior and histopathology is important in distinguishing benign from malignant lesions. According to published reports, in GCTs that were regarded as malignant, size tended to be greater than 4 cm, growth was rapid, and metastases to regional lymph nodes were observed.4,5 Histologically, nuclear pleomorphism and atypia, cell spindling, vesicular nuclei with prominent nucleoli, necrosis, and high mitotic activity favor malignancy.1,3
Treatment is complete surgical excision. Observation is acceptable if tumors are asymptomatic and do not impede function. Regression of some GCTs has been induced with use of intralesional corticosteroids.5 Spontaneous regression is rare. Prior reports have emphasized the importance of long-term follow-up in patients with multiple GCTs to monitor for development of systemic lesions.4
1. Apisarnthanarax P. Granular cell tumor. an analysis of 16 cases and review of the literature. J Am Acad Dermatol. 1981;5:171-182.
2. Guiglia MC, Prendiville JS. Multiple granular cell tumors associated with giant speckled lentiginous nevus and nevus flammeus in a child. J Am Acad Dermatol. 1991;24(2, pt 2):359-363.
3. Hazan C, Fangman W. Multiple cutaneous granular-cell tumors. Dermatol Online J. 2007;13:4.
4. Gross VL, Lynfield Y. Multiple cutaneous granular cell tumors: a case report and review of the literature. Cutis. 2002;69:343-346.
5. Martin RW 3rd, Neldner KH, Boyd AS, et al. Multiple cutaneous granular cell tumors and neurofibromatosis in childhood. a case report and review of the literature. Arch Dermatol. 1990;126:1051-1056.
6. Janousková G, Campr V, Konkol’ová R, et al. Multiple granular cell tumour. J Eur Acad Dermatol Venereol. 2004;18:347-349.
7. Gunson TH, Hashim N, Sharpe GR. Generalized lentiginosis, short stature, and multiple cutaneous nodules—quiz case. LEOPARD syndrome (LS) associated with multiple granular cell tumors (GCTs). Arch Dermatol. 2010;146:337-342.
8. De Raeve L, Roseeuw D, Otten J. Multiple cutaneous granular cell tumors in a child in remission for Hodgkin’s disease. J Am Acad Dermatol. 2002;47(2 suppl):S180-S182.
9. Ramaswamy PV, Storm CA, Filiano JJ, et al. Multiple granular cell tumors in a child with Noonan syndrome. Pediatr Dermatol. 2010;27:209-211.
10. Bangle R Jr. A morphological and histochemical study of the granular-cell myoblastoma. Cancer. 1952;5:950-965.
1. Apisarnthanarax P. Granular cell tumor. an analysis of 16 cases and review of the literature. J Am Acad Dermatol. 1981;5:171-182.
2. Guiglia MC, Prendiville JS. Multiple granular cell tumors associated with giant speckled lentiginous nevus and nevus flammeus in a child. J Am Acad Dermatol. 1991;24(2, pt 2):359-363.
3. Hazan C, Fangman W. Multiple cutaneous granular-cell tumors. Dermatol Online J. 2007;13:4.
4. Gross VL, Lynfield Y. Multiple cutaneous granular cell tumors: a case report and review of the literature. Cutis. 2002;69:343-346.
5. Martin RW 3rd, Neldner KH, Boyd AS, et al. Multiple cutaneous granular cell tumors and neurofibromatosis in childhood. a case report and review of the literature. Arch Dermatol. 1990;126:1051-1056.
6. Janousková G, Campr V, Konkol’ová R, et al. Multiple granular cell tumour. J Eur Acad Dermatol Venereol. 2004;18:347-349.
7. Gunson TH, Hashim N, Sharpe GR. Generalized lentiginosis, short stature, and multiple cutaneous nodules—quiz case. LEOPARD syndrome (LS) associated with multiple granular cell tumors (GCTs). Arch Dermatol. 2010;146:337-342.
8. De Raeve L, Roseeuw D, Otten J. Multiple cutaneous granular cell tumors in a child in remission for Hodgkin’s disease. J Am Acad Dermatol. 2002;47(2 suppl):S180-S182.
9. Ramaswamy PV, Storm CA, Filiano JJ, et al. Multiple granular cell tumors in a child with Noonan syndrome. Pediatr Dermatol. 2010;27:209-211.
10. Bangle R Jr. A morphological and histochemical study of the granular-cell myoblastoma. Cancer. 1952;5:950-965.
Practice Points
- Granular cell tumors (GCTs) typically present as solitary lesions; however, multiple lesions occur in approximately 25% of cases.
- Granular cell tumors have a variable clinical appearance and may mimic malignant neoplasms (eg, squamous cell carcinoma) as well as infectious diseases (eg, condyloma, syphilis).
- The histological features of GCTs are distinctive, including an unencapsulated dermal proliferation of monotonous polygonal cells with indistinct borders and fine, granular, eosinophilic cytoplasm arranged in irregular sheets and nests.
Low transformation rate in nodular lymphocyte–predominant Hodgkin lymphoma
Fewer than 8% of cases of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) transformed to diffuse large B-cell lymphoma (DLBCL), based on a large prospective single-center study with long-term follow-up.
This rate was lower than the risk of transformation reported for transformed follicular lymphoma or chronic lymphocytic leukemia, according to Dr. Saad Kenderian and his associates at the Mayo Clinic, Rochester, Minn. Transformation was significantly associated with splenic involvement at presentation and with prior chemotherapy exposure, but did not worsen overall survival, they added.
“To our knowledge, this cohort represents the largest analysis to date of consecutive patients with NLPHL,” they said.
The study comprised 222 patients with newly diagnosed NLPHL who were treated at Mayo Clinic between 1970 and 2011. Median age at diagnosis was 40 years, and two-thirds of patients were men. The median follow-up period was 16 years (Blood 2016;12:1960-6. doi: 10.1182/blood-2015-08-665505).
During follow up, 17 cases (7.6%) transformed to DLBCL, for a transformation rate of 0.74 cases for every 100 patient-years, the investigators said. Median time to transformation was 35 months (range, 6-268 months). Predictors of transformation included any prior chemotherapy exposure (P = .04) and splenic involvement (P = .03). The rates of 40-year freedom from transformation were 87% when there was no splenic involvement and 21% when the spleen was involved, and were 87% if radiation therapy was used as a single modality compared with 77% in patients treated with prior chemotherapy or chemoradiation.
Five-year overall survival was 76% in patients with transformed disease, which was similar to overall survival among patients whose disease did not transform to DLBCL, the researchers noted.
Other studies of NLPHL have reported anywhere from a 2% to a 17% transformation rate, but those studies had smaller sample sizes, shorter follow-up periods, and less rigorous enrollment criteria and methods to confirm transformation, the investigators noted. “The finding of splenic involvement as a risk factor for transformation was reported by previous investigators. Interestingly, the association between exposure to prior chemotherapy and reduced freedom from transformation has not been reported in the past, but it has been observed in other low-grade lymphoma studies,” they added. “In contrast to follicular lymphoma, transformed NLPHL is not associated with an adverse impact on OS, suggesting a possibly different biology of transformation.”
The research was partially supported by Lymphoma SPORE and the Predolin Foundation. The investigators had no disclosures.
Kenderian et al. report a lower rate of transformation (7.6%) to diffuse large B-cell lymphoma for patients with nodular lymphocyte–predominant Hodgkin lymphoma compared with other series and found that transformation did not have a negative impact on overall survival. Reassuringly, even if transformation occurs, it is generally at a low rate. Also, these patients do well with additional treatment and do not have worse overall survival. At the MD Anderson Cancer Center, we have used a regimen based on R-CHOP and have not seen transformations. But only through large cooperative clinical trials can we determine whether R-CHOP or other more novel regimens are actually superior to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or rituximab (R)-ABVD for patients at high risk of transformation.
Dr. Michelle Fanale is at the University of Texas MD Anderson Cancer Center, Houston. She had no disclosures. These comments are from her editorial (Blood 2016;1927:1946-7 doi: 10.1182/blood-2016-03-699108).
Kenderian et al. report a lower rate of transformation (7.6%) to diffuse large B-cell lymphoma for patients with nodular lymphocyte–predominant Hodgkin lymphoma compared with other series and found that transformation did not have a negative impact on overall survival. Reassuringly, even if transformation occurs, it is generally at a low rate. Also, these patients do well with additional treatment and do not have worse overall survival. At the MD Anderson Cancer Center, we have used a regimen based on R-CHOP and have not seen transformations. But only through large cooperative clinical trials can we determine whether R-CHOP or other more novel regimens are actually superior to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or rituximab (R)-ABVD for patients at high risk of transformation.
Dr. Michelle Fanale is at the University of Texas MD Anderson Cancer Center, Houston. She had no disclosures. These comments are from her editorial (Blood 2016;1927:1946-7 doi: 10.1182/blood-2016-03-699108).
Kenderian et al. report a lower rate of transformation (7.6%) to diffuse large B-cell lymphoma for patients with nodular lymphocyte–predominant Hodgkin lymphoma compared with other series and found that transformation did not have a negative impact on overall survival. Reassuringly, even if transformation occurs, it is generally at a low rate. Also, these patients do well with additional treatment and do not have worse overall survival. At the MD Anderson Cancer Center, we have used a regimen based on R-CHOP and have not seen transformations. But only through large cooperative clinical trials can we determine whether R-CHOP or other more novel regimens are actually superior to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or rituximab (R)-ABVD for patients at high risk of transformation.
Dr. Michelle Fanale is at the University of Texas MD Anderson Cancer Center, Houston. She had no disclosures. These comments are from her editorial (Blood 2016;1927:1946-7 doi: 10.1182/blood-2016-03-699108).
Fewer than 8% of cases of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) transformed to diffuse large B-cell lymphoma (DLBCL), based on a large prospective single-center study with long-term follow-up.
This rate was lower than the risk of transformation reported for transformed follicular lymphoma or chronic lymphocytic leukemia, according to Dr. Saad Kenderian and his associates at the Mayo Clinic, Rochester, Minn. Transformation was significantly associated with splenic involvement at presentation and with prior chemotherapy exposure, but did not worsen overall survival, they added.
“To our knowledge, this cohort represents the largest analysis to date of consecutive patients with NLPHL,” they said.
The study comprised 222 patients with newly diagnosed NLPHL who were treated at Mayo Clinic between 1970 and 2011. Median age at diagnosis was 40 years, and two-thirds of patients were men. The median follow-up period was 16 years (Blood 2016;12:1960-6. doi: 10.1182/blood-2015-08-665505).
During follow up, 17 cases (7.6%) transformed to DLBCL, for a transformation rate of 0.74 cases for every 100 patient-years, the investigators said. Median time to transformation was 35 months (range, 6-268 months). Predictors of transformation included any prior chemotherapy exposure (P = .04) and splenic involvement (P = .03). The rates of 40-year freedom from transformation were 87% when there was no splenic involvement and 21% when the spleen was involved, and were 87% if radiation therapy was used as a single modality compared with 77% in patients treated with prior chemotherapy or chemoradiation.
Five-year overall survival was 76% in patients with transformed disease, which was similar to overall survival among patients whose disease did not transform to DLBCL, the researchers noted.
Other studies of NLPHL have reported anywhere from a 2% to a 17% transformation rate, but those studies had smaller sample sizes, shorter follow-up periods, and less rigorous enrollment criteria and methods to confirm transformation, the investigators noted. “The finding of splenic involvement as a risk factor for transformation was reported by previous investigators. Interestingly, the association between exposure to prior chemotherapy and reduced freedom from transformation has not been reported in the past, but it has been observed in other low-grade lymphoma studies,” they added. “In contrast to follicular lymphoma, transformed NLPHL is not associated with an adverse impact on OS, suggesting a possibly different biology of transformation.”
The research was partially supported by Lymphoma SPORE and the Predolin Foundation. The investigators had no disclosures.
Fewer than 8% of cases of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) transformed to diffuse large B-cell lymphoma (DLBCL), based on a large prospective single-center study with long-term follow-up.
This rate was lower than the risk of transformation reported for transformed follicular lymphoma or chronic lymphocytic leukemia, according to Dr. Saad Kenderian and his associates at the Mayo Clinic, Rochester, Minn. Transformation was significantly associated with splenic involvement at presentation and with prior chemotherapy exposure, but did not worsen overall survival, they added.
“To our knowledge, this cohort represents the largest analysis to date of consecutive patients with NLPHL,” they said.
The study comprised 222 patients with newly diagnosed NLPHL who were treated at Mayo Clinic between 1970 and 2011. Median age at diagnosis was 40 years, and two-thirds of patients were men. The median follow-up period was 16 years (Blood 2016;12:1960-6. doi: 10.1182/blood-2015-08-665505).
During follow up, 17 cases (7.6%) transformed to DLBCL, for a transformation rate of 0.74 cases for every 100 patient-years, the investigators said. Median time to transformation was 35 months (range, 6-268 months). Predictors of transformation included any prior chemotherapy exposure (P = .04) and splenic involvement (P = .03). The rates of 40-year freedom from transformation were 87% when there was no splenic involvement and 21% when the spleen was involved, and were 87% if radiation therapy was used as a single modality compared with 77% in patients treated with prior chemotherapy or chemoradiation.
Five-year overall survival was 76% in patients with transformed disease, which was similar to overall survival among patients whose disease did not transform to DLBCL, the researchers noted.
Other studies of NLPHL have reported anywhere from a 2% to a 17% transformation rate, but those studies had smaller sample sizes, shorter follow-up periods, and less rigorous enrollment criteria and methods to confirm transformation, the investigators noted. “The finding of splenic involvement as a risk factor for transformation was reported by previous investigators. Interestingly, the association between exposure to prior chemotherapy and reduced freedom from transformation has not been reported in the past, but it has been observed in other low-grade lymphoma studies,” they added. “In contrast to follicular lymphoma, transformed NLPHL is not associated with an adverse impact on OS, suggesting a possibly different biology of transformation.”
The research was partially supported by Lymphoma SPORE and the Predolin Foundation. The investigators had no disclosures.
FROM BLOOD
Key clinical point: The risk of transformation to diffuse large B-cell lymphoma is low in patients with nodular lymphocyte–predominant Hodgkin lymphoma.
Major finding: Only 7.6% of cases transformed over a median of 16 years of follow-up, and transformation did not worsen overall survival.
Data source: A prospective single-center study of 222 consecutive adults with NLPHL.
Disclosures: The research was partially supported by Lymphoma SPORE and the Predolin Foundation. The investigators had no disclosures.
DAAs, HCV-positive livers could reduce transplant waiting list
BARCELONA – Using direct-acting antiviral therapy and livers from HCV-positive donors are separate approaches that could help reduce waiting lists and ensure that patients with HCV in most need get a liver transplant, according to data from two studies presented at the International Liver Congress.
In a retrospective European cohort study, 33% of HCV-positive patients with decompensated cirrhosis who were awaiting a transplant were no longer considered to be in urgent need and almost 20% could be removed from the list altogether 60 weeks after starting treatment with direct-acting antivirals (DAAs).
Dr. Luca Belli of Niguarda Hospital, Milan, who presented the findings at the meeting, cautioned that while the results were encouraging, it is not clear how long the clinical improvement will last. “It will be critical to assess the long-term risks of death, further redeterioration, and developments of hepatocellular carcinoma more specifically, as all these factors still need to be verified,” he said at the meeting, sponsored by the European Association for the Study of the Liver (EASL).
Meanwhile, data from a large analysis of all solid transplant recipients in the United States showed that using livers from HCV-positive donors in HCV-positive recipients was associated with long-term patient outcomes similar to outcomes of using livers from non–HCV-negative donors in HCV-positive recipients, with no difference in mortality or graft survival.
“Over the past 2 decades, the use of HCV-positive organs for liver transplantation has tripled in the United States,” said Maria Stepanova, Ph.D., a senior biostatistician for Inova Health System in Falls Church, Va., who presented her findings at the meeting.
“Despite this, the medium- to long-term outcomes of HCV-positive liver transplant recipients transplanted from HCV-positive donors were not affected by HCV-positivity of a donor,” added Dr. Stepanova, who also works at the Center for Outcomes Research in Liver Disease in Washington, D.C.
Dr. Zobair Younossi, chairman of the department of medicine at Inova Fairfax (Va.) Hospital, and coauthor of the study, said during a press briefing that this does not mean that livers from HCV-positive donor could be used in HCV-negative recipients. The reason for that is that it would be causing an acute infection regardless of whether or not antiviral treatment is available and “at this point the evidence is not there,” he said.
Dr. Laurent Castera of Hôpital Beaujon in Paris, and Dr. Tom Hemming Karlsen of Oslo University Hospital Rikshospitalet in Norway commented on the significance of these data in press releases issued by the EASL. Both experts, who were not involved in the studies, noted the findings could help take the strain off the liver transplant list in the future.
“Treating patients with direct-acting antiviral therapy could result in those with a more pressing need for a liver transplant receiving the donation they need, potentially reducing the number of deaths that occur on the waiting list,” Dr. Castera said.
“With the number of people waiting for a liver transplant expected to rise, the study results should give hope over the coming years for those on the waiting list,” Dr. Karlsen said. Referring to the U.S. study, he said the results “clearly demonstrate a greater opportunity for use of HCV-positive livers over the coming years due to their comparable outcomes with healthy livers.”
The European study presented by Dr. Belli involved 134 patients with HCV and decompensated cirrhosis but without hepatocellular carcinoma listed for liver transplant between February 2014 and February 2015 at 11 centers in Austria, Italy, and France. Of these patients, 103 had been treated with DAAs while on the transplant list; approximately half had been treated with a single DAA (sofosbuvir plus ribavirin for 24-48 weeks) and half with two DAAs (sofosbuvir with either daclatasvir or ledipasvir for 12-24 weeks).
The primary endpoint was the probability of being “inactivated” and then “delisted.” Inactivated meant that there was clinical improvement resulting in patients being put “on hold,” and “delisted” was defined as patients being taken off the transplant list after a variable period of inactivation.
The median age of patients in the study was 54 years and 68% were male. Just under 50% of patients had a low (less than 16) MELD score, around 37% had a MELD score of 16-20, and 13% had a MELD score of more than 20. Around 45% had Child-Pugh B and 55% had Child-Pugh C cirrhosis. Two-thirds had medically controlled and 26% had medically uncontrolled ascites, and 46% had medically controlled and 1% had medically uncontrolled hepatic encephalopathy.
Good virologic efficacy was seen with both single- and dual-agent DAA therapy, with rapid virologic responses of 61% and 67% and early virologic responses of 98% and 98%. Of the 52 patients given single-agent DAA treatment, 22 had a transplant and one patient had a posttransplant relapse. Of the remaining 30 patients on the transplant list, four relapsed. Nineteen of 51 patients given dual-DAA therapy were transplanted and there was one relapse, with no relapses in the 32 patients who remained on the transplant list.
After about 60 weeks of follow-up, one in three patients were “inactivated” and not considered in urgent need of a transplant, but inactivation occurred as early as 12 weeks after DAA therapy, Dr. Belli observed.
Inactivation was associated with a 3.3 decrease in MELD score, a 2-point reduction in Child-Turcotte-Pugh score, and a 0.5-g/dL increase in serum albumin after 24 weeks. There was also regression or improvement in ascites and hepatic encephalopathy in most patients. The median time of delisting was 48 weeks.
These results suggest that there could be a wider role for DAA therapy even in the sickest of HCV-positive patients who are urgently awaiting a liver transplant. Another approach to increase the number of people receiving a transplant is to use HCV-positive livers. The practice has been increasing over the years, but it is not known if the approach is safe and if the risks outweigh the benefits.
To investigate, Dr. Stepanova and associates obtained data from the Scientific Registry of Transplant Recipients (SRTR) on all liver transplants performed in the United States between 1995 and 2003 involving HCV-positive patients. A total of 37,317 records were found, of which 33,668 had data on the donors’ HCV status and on the recipients’ mortality status. Of these, 1,930 (5.7%) had received a liver from an HCV-positive donor. Dr. Stepanova noted that there had been an increase in the percentage of patients who had received an HCV-positive liver, from less than 3% in 1995 to more than 9% in 2013.
Compared with HCV-negative donors, HCV-positive donors were older, were more likely to have a history of drug abuse, and more likely to be non–heart beating at the time of procurement.
The HCV-positive liver recipients also tended to be older, to be of African-American ethnicity, and to have liver cancer but lower MELD scores than those who received an HCV-negative liver. “So these are patients that cannot wait for a long time so maybe elect to use an HCV-positive donor,” Dr. Younossi said.
Adjusted hazard ratios (aHR) showed no statistically significant difference in posttransplant survival or posttransplant graft loss between HCV-positive and HCV-negative livers; aHR were a respective 1.03 and 0.905, with tight 95% confidence intervals. However, a more recent year of transplant did appear to suggest a possible advantage of using an HCV-positive donor liver in an HCV-positive patient, with lower mortality (aHR = 0.978 per year, P less than .0001) and graft failure (aHR = 0.960 per year, P less than .0001) rates.
While the use of HCV-positive livers in HCV-positive recipients was felt to be “reasonably safe,” these findings “cannot be used in support of indiscriminate use of HCV-positive donors,” Dr. Stepanova observed. Further studies are needed to establish criteria on which to select donors that would provide patients with the best possible risk-to-benefit ratio, she said.
Further avenues for research would also be to see if HCV-positive livers could be given to HCV-negative patients and if genotype matters. It would also need to be seen if posttransplantation antiviral treatment would be necessary.
Dr. Belli has received research support from Gilead, AbbVie and BMS and acted as a consultant to Gilead. Dr. Stepanova did not have conflicts of interest to disclose. Dr. Younossi has acted as a consultant to BMS, AbbVie, Gilead, GlaxoSmithKline, and Intercept. Dr. Castera and Dr. Karlsen had no conflicts of interest to disclose.
BARCELONA – Using direct-acting antiviral therapy and livers from HCV-positive donors are separate approaches that could help reduce waiting lists and ensure that patients with HCV in most need get a liver transplant, according to data from two studies presented at the International Liver Congress.
In a retrospective European cohort study, 33% of HCV-positive patients with decompensated cirrhosis who were awaiting a transplant were no longer considered to be in urgent need and almost 20% could be removed from the list altogether 60 weeks after starting treatment with direct-acting antivirals (DAAs).
Dr. Luca Belli of Niguarda Hospital, Milan, who presented the findings at the meeting, cautioned that while the results were encouraging, it is not clear how long the clinical improvement will last. “It will be critical to assess the long-term risks of death, further redeterioration, and developments of hepatocellular carcinoma more specifically, as all these factors still need to be verified,” he said at the meeting, sponsored by the European Association for the Study of the Liver (EASL).
Meanwhile, data from a large analysis of all solid transplant recipients in the United States showed that using livers from HCV-positive donors in HCV-positive recipients was associated with long-term patient outcomes similar to outcomes of using livers from non–HCV-negative donors in HCV-positive recipients, with no difference in mortality or graft survival.
“Over the past 2 decades, the use of HCV-positive organs for liver transplantation has tripled in the United States,” said Maria Stepanova, Ph.D., a senior biostatistician for Inova Health System in Falls Church, Va., who presented her findings at the meeting.
“Despite this, the medium- to long-term outcomes of HCV-positive liver transplant recipients transplanted from HCV-positive donors were not affected by HCV-positivity of a donor,” added Dr. Stepanova, who also works at the Center for Outcomes Research in Liver Disease in Washington, D.C.
Dr. Zobair Younossi, chairman of the department of medicine at Inova Fairfax (Va.) Hospital, and coauthor of the study, said during a press briefing that this does not mean that livers from HCV-positive donor could be used in HCV-negative recipients. The reason for that is that it would be causing an acute infection regardless of whether or not antiviral treatment is available and “at this point the evidence is not there,” he said.
Dr. Laurent Castera of Hôpital Beaujon in Paris, and Dr. Tom Hemming Karlsen of Oslo University Hospital Rikshospitalet in Norway commented on the significance of these data in press releases issued by the EASL. Both experts, who were not involved in the studies, noted the findings could help take the strain off the liver transplant list in the future.
“Treating patients with direct-acting antiviral therapy could result in those with a more pressing need for a liver transplant receiving the donation they need, potentially reducing the number of deaths that occur on the waiting list,” Dr. Castera said.
“With the number of people waiting for a liver transplant expected to rise, the study results should give hope over the coming years for those on the waiting list,” Dr. Karlsen said. Referring to the U.S. study, he said the results “clearly demonstrate a greater opportunity for use of HCV-positive livers over the coming years due to their comparable outcomes with healthy livers.”
The European study presented by Dr. Belli involved 134 patients with HCV and decompensated cirrhosis but without hepatocellular carcinoma listed for liver transplant between February 2014 and February 2015 at 11 centers in Austria, Italy, and France. Of these patients, 103 had been treated with DAAs while on the transplant list; approximately half had been treated with a single DAA (sofosbuvir plus ribavirin for 24-48 weeks) and half with two DAAs (sofosbuvir with either daclatasvir or ledipasvir for 12-24 weeks).
The primary endpoint was the probability of being “inactivated” and then “delisted.” Inactivated meant that there was clinical improvement resulting in patients being put “on hold,” and “delisted” was defined as patients being taken off the transplant list after a variable period of inactivation.
The median age of patients in the study was 54 years and 68% were male. Just under 50% of patients had a low (less than 16) MELD score, around 37% had a MELD score of 16-20, and 13% had a MELD score of more than 20. Around 45% had Child-Pugh B and 55% had Child-Pugh C cirrhosis. Two-thirds had medically controlled and 26% had medically uncontrolled ascites, and 46% had medically controlled and 1% had medically uncontrolled hepatic encephalopathy.
Good virologic efficacy was seen with both single- and dual-agent DAA therapy, with rapid virologic responses of 61% and 67% and early virologic responses of 98% and 98%. Of the 52 patients given single-agent DAA treatment, 22 had a transplant and one patient had a posttransplant relapse. Of the remaining 30 patients on the transplant list, four relapsed. Nineteen of 51 patients given dual-DAA therapy were transplanted and there was one relapse, with no relapses in the 32 patients who remained on the transplant list.
After about 60 weeks of follow-up, one in three patients were “inactivated” and not considered in urgent need of a transplant, but inactivation occurred as early as 12 weeks after DAA therapy, Dr. Belli observed.
Inactivation was associated with a 3.3 decrease in MELD score, a 2-point reduction in Child-Turcotte-Pugh score, and a 0.5-g/dL increase in serum albumin after 24 weeks. There was also regression or improvement in ascites and hepatic encephalopathy in most patients. The median time of delisting was 48 weeks.
These results suggest that there could be a wider role for DAA therapy even in the sickest of HCV-positive patients who are urgently awaiting a liver transplant. Another approach to increase the number of people receiving a transplant is to use HCV-positive livers. The practice has been increasing over the years, but it is not known if the approach is safe and if the risks outweigh the benefits.
To investigate, Dr. Stepanova and associates obtained data from the Scientific Registry of Transplant Recipients (SRTR) on all liver transplants performed in the United States between 1995 and 2003 involving HCV-positive patients. A total of 37,317 records were found, of which 33,668 had data on the donors’ HCV status and on the recipients’ mortality status. Of these, 1,930 (5.7%) had received a liver from an HCV-positive donor. Dr. Stepanova noted that there had been an increase in the percentage of patients who had received an HCV-positive liver, from less than 3% in 1995 to more than 9% in 2013.
Compared with HCV-negative donors, HCV-positive donors were older, were more likely to have a history of drug abuse, and more likely to be non–heart beating at the time of procurement.
The HCV-positive liver recipients also tended to be older, to be of African-American ethnicity, and to have liver cancer but lower MELD scores than those who received an HCV-negative liver. “So these are patients that cannot wait for a long time so maybe elect to use an HCV-positive donor,” Dr. Younossi said.
Adjusted hazard ratios (aHR) showed no statistically significant difference in posttransplant survival or posttransplant graft loss between HCV-positive and HCV-negative livers; aHR were a respective 1.03 and 0.905, with tight 95% confidence intervals. However, a more recent year of transplant did appear to suggest a possible advantage of using an HCV-positive donor liver in an HCV-positive patient, with lower mortality (aHR = 0.978 per year, P less than .0001) and graft failure (aHR = 0.960 per year, P less than .0001) rates.
While the use of HCV-positive livers in HCV-positive recipients was felt to be “reasonably safe,” these findings “cannot be used in support of indiscriminate use of HCV-positive donors,” Dr. Stepanova observed. Further studies are needed to establish criteria on which to select donors that would provide patients with the best possible risk-to-benefit ratio, she said.
Further avenues for research would also be to see if HCV-positive livers could be given to HCV-negative patients and if genotype matters. It would also need to be seen if posttransplantation antiviral treatment would be necessary.
Dr. Belli has received research support from Gilead, AbbVie and BMS and acted as a consultant to Gilead. Dr. Stepanova did not have conflicts of interest to disclose. Dr. Younossi has acted as a consultant to BMS, AbbVie, Gilead, GlaxoSmithKline, and Intercept. Dr. Castera and Dr. Karlsen had no conflicts of interest to disclose.
BARCELONA – Using direct-acting antiviral therapy and livers from HCV-positive donors are separate approaches that could help reduce waiting lists and ensure that patients with HCV in most need get a liver transplant, according to data from two studies presented at the International Liver Congress.
In a retrospective European cohort study, 33% of HCV-positive patients with decompensated cirrhosis who were awaiting a transplant were no longer considered to be in urgent need and almost 20% could be removed from the list altogether 60 weeks after starting treatment with direct-acting antivirals (DAAs).
Dr. Luca Belli of Niguarda Hospital, Milan, who presented the findings at the meeting, cautioned that while the results were encouraging, it is not clear how long the clinical improvement will last. “It will be critical to assess the long-term risks of death, further redeterioration, and developments of hepatocellular carcinoma more specifically, as all these factors still need to be verified,” he said at the meeting, sponsored by the European Association for the Study of the Liver (EASL).
Meanwhile, data from a large analysis of all solid transplant recipients in the United States showed that using livers from HCV-positive donors in HCV-positive recipients was associated with long-term patient outcomes similar to outcomes of using livers from non–HCV-negative donors in HCV-positive recipients, with no difference in mortality or graft survival.
“Over the past 2 decades, the use of HCV-positive organs for liver transplantation has tripled in the United States,” said Maria Stepanova, Ph.D., a senior biostatistician for Inova Health System in Falls Church, Va., who presented her findings at the meeting.
“Despite this, the medium- to long-term outcomes of HCV-positive liver transplant recipients transplanted from HCV-positive donors were not affected by HCV-positivity of a donor,” added Dr. Stepanova, who also works at the Center for Outcomes Research in Liver Disease in Washington, D.C.
Dr. Zobair Younossi, chairman of the department of medicine at Inova Fairfax (Va.) Hospital, and coauthor of the study, said during a press briefing that this does not mean that livers from HCV-positive donor could be used in HCV-negative recipients. The reason for that is that it would be causing an acute infection regardless of whether or not antiviral treatment is available and “at this point the evidence is not there,” he said.
Dr. Laurent Castera of Hôpital Beaujon in Paris, and Dr. Tom Hemming Karlsen of Oslo University Hospital Rikshospitalet in Norway commented on the significance of these data in press releases issued by the EASL. Both experts, who were not involved in the studies, noted the findings could help take the strain off the liver transplant list in the future.
“Treating patients with direct-acting antiviral therapy could result in those with a more pressing need for a liver transplant receiving the donation they need, potentially reducing the number of deaths that occur on the waiting list,” Dr. Castera said.
“With the number of people waiting for a liver transplant expected to rise, the study results should give hope over the coming years for those on the waiting list,” Dr. Karlsen said. Referring to the U.S. study, he said the results “clearly demonstrate a greater opportunity for use of HCV-positive livers over the coming years due to their comparable outcomes with healthy livers.”
The European study presented by Dr. Belli involved 134 patients with HCV and decompensated cirrhosis but without hepatocellular carcinoma listed for liver transplant between February 2014 and February 2015 at 11 centers in Austria, Italy, and France. Of these patients, 103 had been treated with DAAs while on the transplant list; approximately half had been treated with a single DAA (sofosbuvir plus ribavirin for 24-48 weeks) and half with two DAAs (sofosbuvir with either daclatasvir or ledipasvir for 12-24 weeks).
The primary endpoint was the probability of being “inactivated” and then “delisted.” Inactivated meant that there was clinical improvement resulting in patients being put “on hold,” and “delisted” was defined as patients being taken off the transplant list after a variable period of inactivation.
The median age of patients in the study was 54 years and 68% were male. Just under 50% of patients had a low (less than 16) MELD score, around 37% had a MELD score of 16-20, and 13% had a MELD score of more than 20. Around 45% had Child-Pugh B and 55% had Child-Pugh C cirrhosis. Two-thirds had medically controlled and 26% had medically uncontrolled ascites, and 46% had medically controlled and 1% had medically uncontrolled hepatic encephalopathy.
Good virologic efficacy was seen with both single- and dual-agent DAA therapy, with rapid virologic responses of 61% and 67% and early virologic responses of 98% and 98%. Of the 52 patients given single-agent DAA treatment, 22 had a transplant and one patient had a posttransplant relapse. Of the remaining 30 patients on the transplant list, four relapsed. Nineteen of 51 patients given dual-DAA therapy were transplanted and there was one relapse, with no relapses in the 32 patients who remained on the transplant list.
After about 60 weeks of follow-up, one in three patients were “inactivated” and not considered in urgent need of a transplant, but inactivation occurred as early as 12 weeks after DAA therapy, Dr. Belli observed.
Inactivation was associated with a 3.3 decrease in MELD score, a 2-point reduction in Child-Turcotte-Pugh score, and a 0.5-g/dL increase in serum albumin after 24 weeks. There was also regression or improvement in ascites and hepatic encephalopathy in most patients. The median time of delisting was 48 weeks.
These results suggest that there could be a wider role for DAA therapy even in the sickest of HCV-positive patients who are urgently awaiting a liver transplant. Another approach to increase the number of people receiving a transplant is to use HCV-positive livers. The practice has been increasing over the years, but it is not known if the approach is safe and if the risks outweigh the benefits.
To investigate, Dr. Stepanova and associates obtained data from the Scientific Registry of Transplant Recipients (SRTR) on all liver transplants performed in the United States between 1995 and 2003 involving HCV-positive patients. A total of 37,317 records were found, of which 33,668 had data on the donors’ HCV status and on the recipients’ mortality status. Of these, 1,930 (5.7%) had received a liver from an HCV-positive donor. Dr. Stepanova noted that there had been an increase in the percentage of patients who had received an HCV-positive liver, from less than 3% in 1995 to more than 9% in 2013.
Compared with HCV-negative donors, HCV-positive donors were older, were more likely to have a history of drug abuse, and more likely to be non–heart beating at the time of procurement.
The HCV-positive liver recipients also tended to be older, to be of African-American ethnicity, and to have liver cancer but lower MELD scores than those who received an HCV-negative liver. “So these are patients that cannot wait for a long time so maybe elect to use an HCV-positive donor,” Dr. Younossi said.
Adjusted hazard ratios (aHR) showed no statistically significant difference in posttransplant survival or posttransplant graft loss between HCV-positive and HCV-negative livers; aHR were a respective 1.03 and 0.905, with tight 95% confidence intervals. However, a more recent year of transplant did appear to suggest a possible advantage of using an HCV-positive donor liver in an HCV-positive patient, with lower mortality (aHR = 0.978 per year, P less than .0001) and graft failure (aHR = 0.960 per year, P less than .0001) rates.
While the use of HCV-positive livers in HCV-positive recipients was felt to be “reasonably safe,” these findings “cannot be used in support of indiscriminate use of HCV-positive donors,” Dr. Stepanova observed. Further studies are needed to establish criteria on which to select donors that would provide patients with the best possible risk-to-benefit ratio, she said.
Further avenues for research would also be to see if HCV-positive livers could be given to HCV-negative patients and if genotype matters. It would also need to be seen if posttransplantation antiviral treatment would be necessary.
Dr. Belli has received research support from Gilead, AbbVie and BMS and acted as a consultant to Gilead. Dr. Stepanova did not have conflicts of interest to disclose. Dr. Younossi has acted as a consultant to BMS, AbbVie, Gilead, GlaxoSmithKline, and Intercept. Dr. Castera and Dr. Karlsen had no conflicts of interest to disclose.
AT THE INTERNATIONAL LIVER CONGRESS 2016
Key clinical point: Using direct-acting antiviral (DAA) therapy and HCV-positive livers could help reduce the strain on liver transplant lists.
Major finding: One in three HCV-positive patients treated with DAAs were considered nonurgent cases and one in five could be delisted. HCV-positive livers were associated with similar graft and host survival.
Data source: A retrospective European cohort study of 103 patients with decompensated cirrhosis who were treated with DAAs while awaiting liver transplant and an analysis of more than 33,000 HCV patients awaiting a liver transplant in the United States.
Disclosures: Dr. Belli has received research support from Gilead, AbbVie, and BMS and acted as a consultant to Gilead. Dr. Stepanova did not have conflicts of interest to disclose. Dr. Younossi has acted as a consultant to BMS, AbbVie, Gilead, GlaxoSmithKline, and Intercept. Dr. Castera and Dr. Karlsen had no conflicts of interest to disclose.
Doppler ultrasound headset performs well at spotting sports-related concussion
VANCOUVER – A new transcranial Doppler platform that analyzes subtle changes in the cerebral blood flow waveform performed well in detecting sports-related concussion in a cohort study of 238 Los Angeles high school athletes.
The investigational headset device was able to differentiate between those with and without a recent concussion 83% of the time, investigators reported at the annual meeting of the American Academy of Neurology. In contrast, traditional transcranial Doppler analysis detected a recent concussion only 50%-60% of the time.
“Over the last few years, there has been growing evidence that cerebral hemodynamics are altered following sports-related concussion,” senior author Robert Hamilton, Ph.D., cofounder and chief science officer of Neural Analytics in Los Angeles, commented in a session and interview.
Most studies in this area have used MRI or traditional transcranial Doppler analysis, he said. However, the former is costly, time consuming, and not portable, and the latter has not proven very accurate.
As traditional Doppler analysis disregards the majority of waveform data, Dr. Hamilton and his colleagues developed an advanced platform that uses machine learning to analyze the entire shape of the cerebral blood flow velocity waveform through quantitative cerebral hemodynamics.
They compared the advanced analysis with traditional analysis among 69 high school athletes in contact sports who had sustained a concussion an average of 6 days earlier and a control group of 169 unaffected age-matched high school athletes from contact and noncontact sports.
Both groups had bilateral monitoring of blood flow in the middle cerebral artery with transcranial Doppler while they followed a standard cerebrovascular reactivity protocol that included rest and breath holding.
Results showed that for differentiating between athletes who did and did not have concussion, the advanced analysis had an area under the receiver operating characteristic curve of 83%. (Sensitivity was 72%, specificity was 82%, and overall accuracy was 80%.)
In comparison, the area under the curve was substantially lower for the traditional analysis measures: It was 55% for mean velocity (100% sensitivity, 0% specificity, 76% accuracy), 52% for the pulsatility index (86% sensitivity, 23% specificity, 61% accuracy), and 60% for the cerebrovascular reactivity index (51% sensitivity, 68% specificity, 64% accuracy).
“Unfortunately, concussion diagnostics and management today are basically subjective,” Dr. Hamilton commented. The advanced analysis may therefore improve the situation by providing objective evidence of blood flow dysfunction after injury.
The new analysis platform “is easy to use and portable, and [testing] can be done very quickly, within 5 minutes,” he noted. “The nice thing is it can be done on the sideline, in the emergency room, or in a doctor’s office.”
The investigators will next use the advanced analysis to track recovery of blood flow regulation after sports-related concussion and will compare its performance with that of additional modalities, such as MRI, according to Dr. Hamilton. Furthermore, they are testing it in various other populations: adolescents, college athletes, and members of the military.
“Ultimately, blood flow dysfunction is also important in a wide variety of conditions, such as stroke and dementia,” he pointed out. “So those are conditions that we are looking at to study this year and moving forward in the future.”
The research was supported by the National Institutes of Health and the National Science Foundation.
VANCOUVER – A new transcranial Doppler platform that analyzes subtle changes in the cerebral blood flow waveform performed well in detecting sports-related concussion in a cohort study of 238 Los Angeles high school athletes.
The investigational headset device was able to differentiate between those with and without a recent concussion 83% of the time, investigators reported at the annual meeting of the American Academy of Neurology. In contrast, traditional transcranial Doppler analysis detected a recent concussion only 50%-60% of the time.
“Over the last few years, there has been growing evidence that cerebral hemodynamics are altered following sports-related concussion,” senior author Robert Hamilton, Ph.D., cofounder and chief science officer of Neural Analytics in Los Angeles, commented in a session and interview.
Most studies in this area have used MRI or traditional transcranial Doppler analysis, he said. However, the former is costly, time consuming, and not portable, and the latter has not proven very accurate.
As traditional Doppler analysis disregards the majority of waveform data, Dr. Hamilton and his colleagues developed an advanced platform that uses machine learning to analyze the entire shape of the cerebral blood flow velocity waveform through quantitative cerebral hemodynamics.
They compared the advanced analysis with traditional analysis among 69 high school athletes in contact sports who had sustained a concussion an average of 6 days earlier and a control group of 169 unaffected age-matched high school athletes from contact and noncontact sports.
Both groups had bilateral monitoring of blood flow in the middle cerebral artery with transcranial Doppler while they followed a standard cerebrovascular reactivity protocol that included rest and breath holding.
Results showed that for differentiating between athletes who did and did not have concussion, the advanced analysis had an area under the receiver operating characteristic curve of 83%. (Sensitivity was 72%, specificity was 82%, and overall accuracy was 80%.)
In comparison, the area under the curve was substantially lower for the traditional analysis measures: It was 55% for mean velocity (100% sensitivity, 0% specificity, 76% accuracy), 52% for the pulsatility index (86% sensitivity, 23% specificity, 61% accuracy), and 60% for the cerebrovascular reactivity index (51% sensitivity, 68% specificity, 64% accuracy).
“Unfortunately, concussion diagnostics and management today are basically subjective,” Dr. Hamilton commented. The advanced analysis may therefore improve the situation by providing objective evidence of blood flow dysfunction after injury.
The new analysis platform “is easy to use and portable, and [testing] can be done very quickly, within 5 minutes,” he noted. “The nice thing is it can be done on the sideline, in the emergency room, or in a doctor’s office.”
The investigators will next use the advanced analysis to track recovery of blood flow regulation after sports-related concussion and will compare its performance with that of additional modalities, such as MRI, according to Dr. Hamilton. Furthermore, they are testing it in various other populations: adolescents, college athletes, and members of the military.
“Ultimately, blood flow dysfunction is also important in a wide variety of conditions, such as stroke and dementia,” he pointed out. “So those are conditions that we are looking at to study this year and moving forward in the future.”
The research was supported by the National Institutes of Health and the National Science Foundation.
VANCOUVER – A new transcranial Doppler platform that analyzes subtle changes in the cerebral blood flow waveform performed well in detecting sports-related concussion in a cohort study of 238 Los Angeles high school athletes.
The investigational headset device was able to differentiate between those with and without a recent concussion 83% of the time, investigators reported at the annual meeting of the American Academy of Neurology. In contrast, traditional transcranial Doppler analysis detected a recent concussion only 50%-60% of the time.
“Over the last few years, there has been growing evidence that cerebral hemodynamics are altered following sports-related concussion,” senior author Robert Hamilton, Ph.D., cofounder and chief science officer of Neural Analytics in Los Angeles, commented in a session and interview.
Most studies in this area have used MRI or traditional transcranial Doppler analysis, he said. However, the former is costly, time consuming, and not portable, and the latter has not proven very accurate.
As traditional Doppler analysis disregards the majority of waveform data, Dr. Hamilton and his colleagues developed an advanced platform that uses machine learning to analyze the entire shape of the cerebral blood flow velocity waveform through quantitative cerebral hemodynamics.
They compared the advanced analysis with traditional analysis among 69 high school athletes in contact sports who had sustained a concussion an average of 6 days earlier and a control group of 169 unaffected age-matched high school athletes from contact and noncontact sports.
Both groups had bilateral monitoring of blood flow in the middle cerebral artery with transcranial Doppler while they followed a standard cerebrovascular reactivity protocol that included rest and breath holding.
Results showed that for differentiating between athletes who did and did not have concussion, the advanced analysis had an area under the receiver operating characteristic curve of 83%. (Sensitivity was 72%, specificity was 82%, and overall accuracy was 80%.)
In comparison, the area under the curve was substantially lower for the traditional analysis measures: It was 55% for mean velocity (100% sensitivity, 0% specificity, 76% accuracy), 52% for the pulsatility index (86% sensitivity, 23% specificity, 61% accuracy), and 60% for the cerebrovascular reactivity index (51% sensitivity, 68% specificity, 64% accuracy).
“Unfortunately, concussion diagnostics and management today are basically subjective,” Dr. Hamilton commented. The advanced analysis may therefore improve the situation by providing objective evidence of blood flow dysfunction after injury.
The new analysis platform “is easy to use and portable, and [testing] can be done very quickly, within 5 minutes,” he noted. “The nice thing is it can be done on the sideline, in the emergency room, or in a doctor’s office.”
The investigators will next use the advanced analysis to track recovery of blood flow regulation after sports-related concussion and will compare its performance with that of additional modalities, such as MRI, according to Dr. Hamilton. Furthermore, they are testing it in various other populations: adolescents, college athletes, and members of the military.
“Ultimately, blood flow dysfunction is also important in a wide variety of conditions, such as stroke and dementia,” he pointed out. “So those are conditions that we are looking at to study this year and moving forward in the future.”
The research was supported by the National Institutes of Health and the National Science Foundation.
AT THE AAN 2016 ANNUAL MEETING
Key clinical point: Advanced transcranial Doppler analysis may improve identification of athletes with concussion at the point of care.
Major finding: For differentiating between athletes who did and did not have concussion, the advanced analysis had an area under the receiver operating characteristic curve of 83%.
Data source: A cohort study of 69 concussed and 169 nonconcussed high school athletes.
Disclosures: Dr. Hamilton disclosed that he is a cofounder and chief science officer of Neural Analytics. The study was supported by the National Institutes of Health and the National Science Foundation.
Product News: 05 2016
Aczone Gel 7.5%
Allergan announces US Food and Drug Administration approval of Aczone (dapsone) Gel 7.5% for the treatment of acne vulgaris in patients 12 years and older. The new formula contains a higher concentration of dapsone (versus the 5% concentration) with the same tolerability and enhanced efficacy to treat both inflammatory and noninflammatory acne. Once-daily application and the pump delivery system aid in improving adherence to treatment. For more information, visit www.aczonehcp.com.
Cutanea Life Sciences
Cutanea Life Sciences, Inc (CLS), an emerging US prescription product development company, unveils its new website, www.cutanea.com, to the dermatology community. The new digital presence demonstrates the company’s intent to change the way customers think about a valued dermatology partner. The CLS management team is well versed in the development and commercialization of dermatologic therapies. With product candidates in various stages of development that cover an array of skin conditions such as acne, rosacea, psoriasis, and warts caused by human papillomavirus, CLS is committed to focusing on underserved patient needs, which will help health care professionals optimize their practice time through CLS’s dermatologic products and services.
Sernivo Spray 0.05%
Promius Pharma, LLC, announces US Food and Drug Administration approval of Sernivo (betamethasone dipropionate) Spray 0.05%, a corticosteroid for the treatment of mild to moderate plaque psoriasis in patients 18 years and older. Sernivo Spray should be used twice daily for 4 weeks and not beyond. In clinical trials more participants showed treatment success with Sernivo Spray versus vehicle at day 15 and day 29. For more information, visit www.promiuspharma.com.
Teflaro
Allergan announces that the US Food and Drug Administration has accepted for filing a supplemental new drug application for Teflaro (ceftaroline fosamil) to expand the label to include the treatment of children 2 months and older with acute bacterial skin and skin structure infections (ABSSSI) including infections caused by methicillin-resistant Staphylococcus aureus and community-acquired bacterial pneumonia (CABP) caused by Staphylococcus pneumoniae and other designated susceptible bacteria. Teflaro is a bactericidal cephalosporin with activity against both gram-positive and gram-negative pathogens. Teflaro is already approved for ABSSSI and CABP in adult patients. For more information, visit www.teflaro.com.
If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].
Aczone Gel 7.5%
Allergan announces US Food and Drug Administration approval of Aczone (dapsone) Gel 7.5% for the treatment of acne vulgaris in patients 12 years and older. The new formula contains a higher concentration of dapsone (versus the 5% concentration) with the same tolerability and enhanced efficacy to treat both inflammatory and noninflammatory acne. Once-daily application and the pump delivery system aid in improving adherence to treatment. For more information, visit www.aczonehcp.com.
Cutanea Life Sciences
Cutanea Life Sciences, Inc (CLS), an emerging US prescription product development company, unveils its new website, www.cutanea.com, to the dermatology community. The new digital presence demonstrates the company’s intent to change the way customers think about a valued dermatology partner. The CLS management team is well versed in the development and commercialization of dermatologic therapies. With product candidates in various stages of development that cover an array of skin conditions such as acne, rosacea, psoriasis, and warts caused by human papillomavirus, CLS is committed to focusing on underserved patient needs, which will help health care professionals optimize their practice time through CLS’s dermatologic products and services.
Sernivo Spray 0.05%
Promius Pharma, LLC, announces US Food and Drug Administration approval of Sernivo (betamethasone dipropionate) Spray 0.05%, a corticosteroid for the treatment of mild to moderate plaque psoriasis in patients 18 years and older. Sernivo Spray should be used twice daily for 4 weeks and not beyond. In clinical trials more participants showed treatment success with Sernivo Spray versus vehicle at day 15 and day 29. For more information, visit www.promiuspharma.com.
Teflaro
Allergan announces that the US Food and Drug Administration has accepted for filing a supplemental new drug application for Teflaro (ceftaroline fosamil) to expand the label to include the treatment of children 2 months and older with acute bacterial skin and skin structure infections (ABSSSI) including infections caused by methicillin-resistant Staphylococcus aureus and community-acquired bacterial pneumonia (CABP) caused by Staphylococcus pneumoniae and other designated susceptible bacteria. Teflaro is a bactericidal cephalosporin with activity against both gram-positive and gram-negative pathogens. Teflaro is already approved for ABSSSI and CABP in adult patients. For more information, visit www.teflaro.com.
If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].
Aczone Gel 7.5%
Allergan announces US Food and Drug Administration approval of Aczone (dapsone) Gel 7.5% for the treatment of acne vulgaris in patients 12 years and older. The new formula contains a higher concentration of dapsone (versus the 5% concentration) with the same tolerability and enhanced efficacy to treat both inflammatory and noninflammatory acne. Once-daily application and the pump delivery system aid in improving adherence to treatment. For more information, visit www.aczonehcp.com.
Cutanea Life Sciences
Cutanea Life Sciences, Inc (CLS), an emerging US prescription product development company, unveils its new website, www.cutanea.com, to the dermatology community. The new digital presence demonstrates the company’s intent to change the way customers think about a valued dermatology partner. The CLS management team is well versed in the development and commercialization of dermatologic therapies. With product candidates in various stages of development that cover an array of skin conditions such as acne, rosacea, psoriasis, and warts caused by human papillomavirus, CLS is committed to focusing on underserved patient needs, which will help health care professionals optimize their practice time through CLS’s dermatologic products and services.
Sernivo Spray 0.05%
Promius Pharma, LLC, announces US Food and Drug Administration approval of Sernivo (betamethasone dipropionate) Spray 0.05%, a corticosteroid for the treatment of mild to moderate plaque psoriasis in patients 18 years and older. Sernivo Spray should be used twice daily for 4 weeks and not beyond. In clinical trials more participants showed treatment success with Sernivo Spray versus vehicle at day 15 and day 29. For more information, visit www.promiuspharma.com.
Teflaro
Allergan announces that the US Food and Drug Administration has accepted for filing a supplemental new drug application for Teflaro (ceftaroline fosamil) to expand the label to include the treatment of children 2 months and older with acute bacterial skin and skin structure infections (ABSSSI) including infections caused by methicillin-resistant Staphylococcus aureus and community-acquired bacterial pneumonia (CABP) caused by Staphylococcus pneumoniae and other designated susceptible bacteria. Teflaro is a bactericidal cephalosporin with activity against both gram-positive and gram-negative pathogens. Teflaro is already approved for ABSSSI and CABP in adult patients. For more information, visit www.teflaro.com.
If you would like your product included in Product News, please email a press release to the Editorial Office at [email protected].
Sexual Orientation and Cancer Risk
Young people in sexual minorities are at higher risk of cancer because they engage in risky behavior more often, say researchers from City University of New York, Harvard, Boston’s Children’s Hospital, and San Diego State University.
The researchers analyzed data from 9,958 participants in the national Growing Up Today Study (1999-2010). The study participants were the children of the women in the Nurses’ Health Study II; those women were invited in 1996 to enroll their 9- to 14-year-old children. Of the participants, 84.5% reported being “completely” heterosexual, 12.1% were “mostly” heterosexual, 1.8% were lesbian or gay, and 1.6% were bisexual.
Related: Native Americans Address LGBT Health Issues
The researchers measured responses about tobacco and alcohol, diet and physical activity, exposure to ultraviolet radiation, and sexually transmitted infections.
Compared with completely heterosexual women, lesbian, bisexual, and mostly heterosexual women more frequently engaged in multiple cancer-related risk behaviors. For instance, they were more likely to have smoked, to be overweight, and to have been physically inactive in the previous year. Bisexual and mostly heterosexual women were more likely to have had a sexually transmitted infection. Interestingly, heterosexual women were more likely to have used a tanning booth ≥ 10 times in the previous year.
Compared with heterosexual men, sexual-minority women were also more often engaged in risky behaviors. The differences between gay/bisexual men and heterosexual men were less marked, although gay men more often vomited to control their weight, compared with heterosexual men, and had a higher prevalence of STIs.
The literature, the researchers note, tends to focus on “ever or never” behavior. They were mindful, they say, that exposure to a potential carcinogen usually must occur over time, and that the likelihood of cancer increases with exposure, which is why they focused on assessing frequent engagement in each cancer-related risk behavior, long term. Their findings indicated that sexual minorities, relative to heterosexuals, are at risk for cancer through multiple risk behaviors—“concerning,” they add, because the “additive or synergistic effect of another cancer-related risk behavior may provoke or exacerbate a determinant of cancer: chronic inflammation.”
Source:
Rosario M, Li F, Wypij D, et al. Am J Public Health. 2016;106(4):698-706.
doi: 10.2105/AJPH.2015.302977.
Young people in sexual minorities are at higher risk of cancer because they engage in risky behavior more often, say researchers from City University of New York, Harvard, Boston’s Children’s Hospital, and San Diego State University.
The researchers analyzed data from 9,958 participants in the national Growing Up Today Study (1999-2010). The study participants were the children of the women in the Nurses’ Health Study II; those women were invited in 1996 to enroll their 9- to 14-year-old children. Of the participants, 84.5% reported being “completely” heterosexual, 12.1% were “mostly” heterosexual, 1.8% were lesbian or gay, and 1.6% were bisexual.
Related: Native Americans Address LGBT Health Issues
The researchers measured responses about tobacco and alcohol, diet and physical activity, exposure to ultraviolet radiation, and sexually transmitted infections.
Compared with completely heterosexual women, lesbian, bisexual, and mostly heterosexual women more frequently engaged in multiple cancer-related risk behaviors. For instance, they were more likely to have smoked, to be overweight, and to have been physically inactive in the previous year. Bisexual and mostly heterosexual women were more likely to have had a sexually transmitted infection. Interestingly, heterosexual women were more likely to have used a tanning booth ≥ 10 times in the previous year.
Compared with heterosexual men, sexual-minority women were also more often engaged in risky behaviors. The differences between gay/bisexual men and heterosexual men were less marked, although gay men more often vomited to control their weight, compared with heterosexual men, and had a higher prevalence of STIs.
The literature, the researchers note, tends to focus on “ever or never” behavior. They were mindful, they say, that exposure to a potential carcinogen usually must occur over time, and that the likelihood of cancer increases with exposure, which is why they focused on assessing frequent engagement in each cancer-related risk behavior, long term. Their findings indicated that sexual minorities, relative to heterosexuals, are at risk for cancer through multiple risk behaviors—“concerning,” they add, because the “additive or synergistic effect of another cancer-related risk behavior may provoke or exacerbate a determinant of cancer: chronic inflammation.”
Source:
Rosario M, Li F, Wypij D, et al. Am J Public Health. 2016;106(4):698-706.
doi: 10.2105/AJPH.2015.302977.
Young people in sexual minorities are at higher risk of cancer because they engage in risky behavior more often, say researchers from City University of New York, Harvard, Boston’s Children’s Hospital, and San Diego State University.
The researchers analyzed data from 9,958 participants in the national Growing Up Today Study (1999-2010). The study participants were the children of the women in the Nurses’ Health Study II; those women were invited in 1996 to enroll their 9- to 14-year-old children. Of the participants, 84.5% reported being “completely” heterosexual, 12.1% were “mostly” heterosexual, 1.8% were lesbian or gay, and 1.6% were bisexual.
Related: Native Americans Address LGBT Health Issues
The researchers measured responses about tobacco and alcohol, diet and physical activity, exposure to ultraviolet radiation, and sexually transmitted infections.
Compared with completely heterosexual women, lesbian, bisexual, and mostly heterosexual women more frequently engaged in multiple cancer-related risk behaviors. For instance, they were more likely to have smoked, to be overweight, and to have been physically inactive in the previous year. Bisexual and mostly heterosexual women were more likely to have had a sexually transmitted infection. Interestingly, heterosexual women were more likely to have used a tanning booth ≥ 10 times in the previous year.
Compared with heterosexual men, sexual-minority women were also more often engaged in risky behaviors. The differences between gay/bisexual men and heterosexual men were less marked, although gay men more often vomited to control their weight, compared with heterosexual men, and had a higher prevalence of STIs.
The literature, the researchers note, tends to focus on “ever or never” behavior. They were mindful, they say, that exposure to a potential carcinogen usually must occur over time, and that the likelihood of cancer increases with exposure, which is why they focused on assessing frequent engagement in each cancer-related risk behavior, long term. Their findings indicated that sexual minorities, relative to heterosexuals, are at risk for cancer through multiple risk behaviors—“concerning,” they add, because the “additive or synergistic effect of another cancer-related risk behavior may provoke or exacerbate a determinant of cancer: chronic inflammation.”
Source:
Rosario M, Li F, Wypij D, et al. Am J Public Health. 2016;106(4):698-706.
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