Disentangling the links between gastric emptying and binge eating v. purging in eating disorders using a case-control design.

BACKGROUND: Prior work supports delayed gastric emptying in anorexia nervosa and bulimia nervosa (BN) but not binge-eating disorder, suggesting that neither low body weight nor binge eating fully accounts for slowed gastric motility. Specifying a link between delayed gastric emptying and self-induced vomiting could offer new insights into the pathophysiology of purging disorder (PD). METHODS: Women (N = 95) recruited from the community meeting criteria for DSM-5 BN who purged (n = 26), BN with nonpurging compensatory behaviors (n = 18), PD (n = 25), or healthy control women (n = 26) completed assessments of gastric emptying, gut peptides, and subjective responses over the course of a standardized test meal under two conditions administered in a double-blind, crossover sequence: placebo and 10 mg of metoclopramide. RESULTS: Delayed gastric emptying was associated with purging with no main or moderating effects of binge eating in the placebo condition. Medication eliminated group differences in gastric emptying but did not alter group differences in reported gastrointestinal distress. Exploratory analyses revealed that medication caused increased postprandial PYY release, which predicted elevated gastrointestinal distress. CONCLUSIONS: Delayed gastric emptying demonstrates a specific association with purging behaviors. However, correcting disruptions in gastric emptying may exacerbate disruptions in gut peptide responses specifically linked to the presence of purging after normal amounts of food.

Effects of Sacubitril-Valsartan in Patients With Various Types of Heart Failure: A Meta-analysis.

ABSTRACT: We performed a meta-analysis investigating the efficacy and adverse effects of sacubitril-valsartan in various types of heart failure including more recent studies and a larger sample size. We conducted an electronic search through Cochrane, Web of Science, PubMed, and Embase. Included studies were randomized controlled trials analyzing the efficacy of sacubitril-valsartan compared with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) in patients with heart failure. Fourteen trials were included. Pooled estimates were analyzed using RevMan 5.4.1. The odds ratio (OR) of hospitalization from worsening heart failure that compared sacubitril-valsartan with control was 0.70 (95% CI, 0.51-0.97; P = 0.03) in patients with heart failure with reduced ejection fraction (HFrEF) with a relative risk reduction (RRR) of 24.3% and absolute risk reduction (ARR) of 3.4%. In patients with heart failure with midrange (HFmEF) and preserved (HFpEF) ejection fraction, the OR was 0.80 (95% CI, 0.71-0.90; P = 0.0001) with RRR of 14.5% and ARR of 3.3%. There was a significant reduction in cardiovascular deaths (OR = 0.79; 95% CI, 0.70-0.89; P = <0.0001) and all-cause mortality (OR = 0.84; 95% CI, 0.75-0.94; P = 0.002) in patients with HFrEF, with no significant differences in patients with HFmEF and HFpEF. Hospitalization rate was significantly reduced in patients taking sacubitril-valsartan across all analyzed cohorts. Sacubitril-valsartan significantly reduced the risk of all-cause mortality and cardiovascular death in patients with HFrEF but not in patients with HFmEF/HFpEF. These findings support sacubitril-valsartan use in reducing hospitalization of patients with HFmEF and HFpEF. More studies should be performed to further analyze the efficacy of sacubitril-valsartan in patients with HFmEF/HFpEF.

The Impact of Internal Medicine Clerkship Characteristics and NBME Subject Exams on USMLE Step 2 Clinical Knowledge Exam Performance.

BACKGROUND: Residency program directors will likely emphasize the United States Medical Licensing Exam (USMLE) Step 2 clinical knowledge (CK) exam more during residency application given the recent USMLE Step 1 transition to pass/fail scoring. We examined how internal medicine clerkship characteristics and NBME subject exam scores affect USMLE Step 2 CK performance. DESIGN: The authors used univariable and multivariable generalized estimating equations to determine associations between Step 2 CK performance and internal medicine clerkship characteristics and NBME subject exams. The sample had 21,280 examinees' first Step 2 CK scores for analysis. RESULTS: On multivariable analysis, Step 1 performance (standardized ß = 0.45, p < .001) and NBME medicine subject exam performance (standardized ß = 0.40, p < .001) accounted for approximately 60% of the variance in Step 2 CK performance. Students who completed the internal medicine clerkship last in the academic year scored lower on Step 2 CK (Mdiff = -3.17 p < .001). Students who had a criterion score for passing the NBME medicine subject exam scored higher on Step 2 CK (Mdiff = 1.10, p = .03). There was no association between Step 2 CK performance and other internal medicine clerkship characteristics (all p > 0.05) nor with the total NBME subject exams completed (ß=0.05, p = .78). CONCLUSION: Despite similarities between NBME subject exams and Step 2 CK, the authors did not identify improved Step 2 CK performance for students who had more NBME subject exams. The lack of association of Step 2 CK performance with many internal medicine clerkship characteristics and more NBME subject exams has implications for future clerkship structure and summative assessment. The improved Step 2 CK performance in students that completed their internal medicine clerkship earlier warrants further study given the anticipated increase in emphasis on Step 2 CK.

The New Internal Medicine Subinternship Curriculum Guide: a Report from the Alliance for Academic Internal Medicine.

The internal medicine (IM) subinternship has been a long-established clinical experience in the final phase of medical school deemed by key stakeholders as a crucial rotation to prepare senior medical students for internship. Medical education has changed greatly since the first national curriculum for this course was developed in 2002 by the Clerkship Directors in Internal Medicine (CDIM). Most notably, competency-based medical education (CBME) has become a fixture in graduate medical education and has gradually expanded into medical school curricula. Still, residency program directors and empirical studies have identified gaps and inconsistencies in knowledge and skills among new interns. Recognizing these gaps, the Association of Program Directors in Internal Medicine (APDIM) surveyed its members in 2010 and identified four core skills essential for intern readiness. The Association of American Medical Colleges (AAMC) also published 13 core entrustable professional activities (EPAs) for entering residency to be expected of all medical school graduates. Results from the APDIM survey along with the widespread adoption of CBME informed this redesign of the IM subinternship curriculum. The authors provide an overview of this new guide developed by the Alliance for Academic Internal Medicine (AAIM) Medical Student-to-Resident Interface Committee (MSRIC).

Disturbance of gut satiety peptide in purging disorder.

OBJECTIVE: Little is known about biological factors that contribute to purging after normal amounts of food-the central feature of purging disorder (PD). This study comes from a series of nested studies examining ingestive behaviors in bulimic syndromes and specifically evaluated the satiety peptide YY (PYY) and the hunger peptide ghrelin in women with PD (n = 25), bulimia nervosa-purging (BNp) (n = 26), and controls (n = 26). Based on distinct subjective responses to a fixed meal in PD (Keel, Wolfe, Liddle, DeYoung, & Jimerson, ), we tested whether postprandial PYY response was significantly greater and ghrelin levels significantly lower in women with PD compared to controls and women with BNp. METHOD: Participants completed structured clinical interviews, self-report questionnaires, and laboratory assessments of gut peptide and subjective responses to a fixed meal. RESULTS: Women with PD demonstrated a significantly greater postprandial PYY response compared to women with BNp and controls, who did not differ significantly. PD women also endorsed significantly greater gastrointestinal distress, and PYY predicted gastrointestinal intestinal distress. Ghrelin levels were significantly greater in PD and BNp compared to controls, but did not differ significantly between eating disorders. Women with BNp endorsed significantly greater postprandial hunger, and ghrelin predicted hunger. DISCUSSION: PD is associated with a unique disturbance in PYY response. Findings contribute to growing evidence of physiological distinctions between PD and BNp. Future research should examine whether these distinctions account for differences in clinical presentation as this could inform the development of specific interventions for patients with PD.

Weight suppression and bulimic syndrome maintenance: Preliminary findings for the mediating role of leptin.

OBJECTIVE: Longitudinal studies support a prospective relationship between weight suppression (WS) and bulimic syndrome (BN-S) maintenance. Although biobehavioral mechanisms have been proposed to explain this link, such mechanisms have yet to be identified. Given that weight loss would reduce leptin levels which may influence eating, this study examined whether reduced leptin levels mediate the link between greater WS and longer illness duration. METHOD: Women (N = 53), ages 18-45 years, were recruited from the community if they met criteria for a BN-S, including either DSM-5 bulimia nervosa (BN; n = 33) or purging disorder (PD: n = 20), and fell within a healthy weight range (18.5-26.5 kg/m2 ). Participants completed clinical assessments and provided blood samples to measure circulating leptin. RESULTS: Significant associations were found among greater WS, lower leptin concentrations, and longer duration of illness. Mediation analyses using bootstrapping procedures indicated all paths were significant and that leptin mediated the link between WS and illness duration. An alternative model in which longer illness duration contributed to leptin, via greater WS, was not supported. DISCUSSION: Longitudinal research is needed to support temporal associations and explore behavioral mechanisms linking leptin to illness trajectory.

Comprehensive Geriatric Assessment in Older Persons With HIV.

With increased longevity related to the advent of antiretroviral therapy, there are increasing proportions of older persons with HIV (PWH). Prior studies have demonstrated increased prevalence of geriatric syndromes in older PWH and recommended the Comprehensive Geriatric Assessment (CGA) in this population. However, there is currently no peer-reviewed literature that outlines how to perform the CGA in PWH in the clinical setting. In this article, we offer a review on how to perform the CGA in PWH, outline domains of the CGA and their importance in PWH, and describe screening tools for each domain focusing on tools that have been validated in PWH, are easy to administer, and/or are already commonly used in the field of geriatrics.

Which Internal Medicine Clerkship Characteristics Are Associated With Students' Performance on the NBME Medicine Subject Exam? A Multi-Institutional Analysis.

PURPOSE: To identify which internal medicine clerkship characteristics may relate to NBME Medicine Subject Examination scores, given the growing trend toward earlier clerkship start dates. METHOD: The authors used linear mixed effects models (univariable and multivariable) to determine associations between medicine exam performance and clerkship characteristics (longitudinal status, clerkship length, academic start month, ambulatory clinical experience, presence of a study day, involvement in a combined clerkship, preclinical curriculum type, medicine exam timing). Additional covariates included number of NBME clinical subject exams used, number of didactic hours, use of a criterion score for passing the medicine exam, whether medicine exam performance was used to designate clerkship honors, and United States Medical Licensing Examination Step 1 performance. The sample included 24,542 examinees from 62 medical schools spanning 3 academic years (2011-2014). RESULTS: The multivariable analysis found no significant association between clerkship length and medicine exam performance (all pairwise P > .05). However, a small number of examinees beginning their academic term in January scored marginally lower than those starting in July (P < .001). Conversely, examinees scored higher on the medicine exam later in the academic year (all pairwise P < .001). Examinees from schools that used a criterion score for passing the medicine exam also scored higher than those at schools that did not (P < .05). Step 1 performance remained positively associated with medicine exam performance even after controlling for all other variables in the model (P < .001). CONCLUSIONS: In this sample, the authors found no association between many clerkship variables and medicine exam performance. Instead, Step 1 performance was the most powerful predictor of medicine exam performance. These findings suggest that medicine exam performance reflects the overall medical knowledge students accrue during their education rather than any specific internal medicine clerkship characteristics.

Examining weight suppression as a transdiagnostic factor influencing illness trajectory in bulimic eating disorders.

Recent research indicates that weight suppression (WS: defined as the difference between highest lifetime and current weight) prospectively predicts illness trajectory across eating disorders characterized by binge eating, including AN binge-purge subtype (ANbp), bulimia nervosa (BN), and binge eating disorder (BED), collectively referred to as bulimic eating disorders. Through a series of studies, we have developed a model to explain the link between WS and illness trajectory in bulimic eating disorders. Our model posits that WS contributes to reduced circulating leptin, which leads to reduced postprandial glucagon-like peptide 1 (GLP-1) response. Diminished leptin and GLP-1 function contribute to alterations in two reward-related constructs in the Research Domain Criteria (RDoC): reward value/effort and reward satiation. Respectively, these changes increase drive/motivation to consume food and decrease ability for food consumption to lead to a state of satiation/satisfaction. Combined, these alterations increase risk for experiencing large, out-of-control binge-eating episodes. The following review presents evidence that contributed to the development of this model as well as preliminary findings from an on-going project funded to test this model.

Application of Geriatric Principles and Care Models in HIV and Aging.

People aging with HIV present a unique challenge for providers. HIV-infected patients experience accentuated aging and multimorbidity, but are typically disconnected from geriatric care, which is limited by a shortage of geriatric providers worldwide. Consequently, HIV providers are tasked with managing multiple age-related illnesses, within service networks that are historically not designed to care for aging patients. While comfortable with the management of antiretroviral therapy, HIV providers may have limited training on how to recognize or manage geriatric syndromes, especially in the context of multimorbidity. The result is an emerging, vulnerable population, and the question is how to best care for them. As part of the answer, we offer examples of how providers can use geriatric principles to improve the care of aging HIV-infected patients. We begin by describing basic geriatric concepts and examples of care models, and subsequently use a patient case to illustrate their applications at the patient level. At the system level, we discuss how HIV service networks can use components of geriatric care models to meet the needs of aging HIV-infected patients. Lastly, we identify aging-specific guidelines and service integration as important areas for future endeavors.

Caring for Older Adults with the Human Immunodeficiency Virus.

Increasing proportions of older adults are living with the human immunodeficiency virus (HIV). It is estimated that more than 50% of individuals with HIV in the United States are aged 50 and older. Part of this group consists of individuals who have aged with chronic HIV infection, but a large proportion also results from new HIV diagnosis, with approximately 17% of new HIV diagnoses in 2013 occurring in individuals aged 50 and older. Although many of the recommendations on management of HIV infection are not age-specific, individuals with HIV aged 50 and older differ from their younger counterparts in many aspects, including immune response to antiretroviral therapy, multimorbidity, antiretroviral toxicities, and diagnostic considerations. This article outline these differences, offers a strategy on how to care for this unique population, and provides special considerations for problem-based management of individuals with HIV aged 50 and older.

Fourth-Year Medical Student Charting of Older Persons' Cognitive and Functional Status.

BACKGROUND AND OBJECTIVES: Functional and cognitive impairment correlates with medical outcomes in older persons, yet documentation in the medical record is often inadequate. The purpose of this pilot study was to evaluate fourth year (M4) medical students' charting performance of cognition and functional status in older persons during non-geriatric clerkships using an audit tool. METHODS: The research assistants used a chart abstracting tool to retrospectively review patients' charts. The abstracting tool contained keywords and phrases to prompt the research assistants to look for any documentation of patient status in four domains: (1) delirium or acute confusional state, (2) chronic cognitive impairment, (3) activities of daily living, and (4) instrumental activities of daily living. The threshold was any mention of keywords in these domains. RESULTS: On non-geriatrics M4 clerkships in the hospital, students documented acute cognitive status (ACS) and presence or absence of chronic cognitive impairment (CCI) in 57% and 68% of cases respectively, with physicians and/or nurses doing it more often at 63% and 84%. Both students and other care providers documented ACS and CCI in the same charts 41% and 59% of the time, respectively. Students documented activities of daily living (ADLs) and instrumental activities of daily living (IADLs) 31% and 3% respectively, physicians and/or nurses 59% and 0%. CONCLUSIONS: Documentation of cognitive status in hospital charts for students and physicians was somewhat higher than in the literature. This may be because geriatrics is integrated into our 4-year curriculum. Documentation by both students and physicians was better for ADLs than IADLs and poor for IADLs overall.

Efficacy, safety, and tolerability of etravirine with and without darunavir/ritonavir or raltegravir in treatment-experienced patients: analysis of the etravirine early access program in the United States.

BACKGROUND: Etravirine, a nonnucleoside reverse transcriptase inhibitor, was provided through an international early access program (EAP) prior to regulatory approval. METHODS: The Phase III, nonrandomized, open-label EAP investigated etravirine 200 mg twice daily plus a background regimen (BR) in patients who had failed multiple antiretroviral regimens. Efficacy and safety are reported for HIV-infected adults from the United States through week 48, including subgroups receiving etravirine +/- darunavir/ritonavir and/or raltegravir. RESULTS: The intent-to-treat population included 2578 patients; 62.4% and 56.7% of patients received darunavir/ritonavir and raltegravir, respectively, in their BR. At week 48, 62.3% of patients achieved viral loads <75 copies per milliliter; responses across subgroups were similar. Median CD4 count increase from baseline was >100 cells per cubic millimeter. No unexpected safety concerns emerged; serious AEs and deaths due to AEs, considered possibly related to etravirine, occurred in 2.0% and 0.3% of patients, respectively. Discontinuations due to AEs were low overall (4.4%) and comparable across subgroups. CONCLUSIONS: Etravirine combined with a BR, often including other new antiretrovirals, such as darunavir/ritonavir and/or raltegravir, provided an effective treatment option in treatment-experienced patients with HIV-1.

HIV in older adults.

The prevalence of HIV/AIDS in older adults continues to increase, and in 2005, 25% of those infected with HIV were older than 50. Successful treatment regimens allow people to live longer with HIV, but the incidence is also increasing, with older adults accounting for 15% of new HIV cases in 2005. Prevention, diagnosis, and management of HIV/AIDS in older adults are complex issues. The aging immune system may impact response to treatment with highly active antiretroviral therapy (HAART), and there is greater potential for drug-drug interactions and toxicities due to comorbidities and polypharmacy. Patients living longer with HIV are more likely to develop diseases associated with aging, and at an earlier age, than those without HIV. These include coronary artery disease, dyslipidemia, metabolic syndrome, diabetes, osteoporosis, and dementia. Geriatricians and primary care providers are increasingly responsible for managing these complex issues.