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Background: Inhibition of the mammalian target of rapamycin (mTor) pathway after heart transplantation has been associated with reduced progression of coronary allograft vasculopathy (CAV). The application of low-dose mTOR inhibition in the setting of modern immunosuppression, including tacrolimus, remains an area of limited exploration., Methods: This retrospective study included patients who received heart transplantation between January 2009 and January 2019 and had baseline, 1-year and 2-3-year coronary angiography with intravascular ultrasound (IVUS). Intimal thickness in 5 segments along the left anterior descending artery was compared across imaging time points in patients who were transitioned to low-dose mTOR inhibitor (sirolimus) vs standard treatment with mycophenolate on a background of tacrolimus. Long-term adverse cardiovascular outcomes (revascularization, severe CAV, retransplant, and cardiovascular death) were also assessed., Results: Among 216 patients (mean age 51.5 ± 11.9 years, 77.8% men, 80.1% white), 81 individuals (37.5%) were switched to mTOR inhibition. mTOR inhibition was associated with a reduction in intimal thickness by 0.05 mm (95% CI 0.02-0.07; P < 0.001). This reduction was driven by patients who met the criteria for rapidly progressive CAV 1-year post-transplant (0.12 mm; P = 0.016 for interaction). After a median follow-up of 8.6 (IQR 6.6-11) years, 40 patients had major adverse cardiovascular outcomes. The use of mTOR inhibitors was not significantly associated with cardiovascular outcomes (P = 0.669)., Conclusion: Transitioning patients after heart transplantation to an immunosuppression regimen composed of low-dose mTOR inhibition and tacrolimus was associated with a lack of progression of CAV, particularly in those with rapidly progressive CAV at 1 year, but not with long-term cardiovascular outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

One of the most recognized paintings of Western medicine, Luke Fildes' The Doctor aimed to represent a caring physician in a humble setting during an era when people living with poverty rarely had access to health care and nearly all physicians were White men. The Doctor challenges us to think about what good doctoring is., (Copyright 2022 American Medical Association. All Rights Reserved.)

The popularity of portraits of clinicians during the COVID-19 pandemic suggested the importance of visual representation of what mass illness demands of us all-and particularly those on the front lines of health care. In addition to surges in variants of the SARS-CoV-2 virus, persons of Asian descent have endured waves of bigotry and violence. With the myriad of natural and man-made threats confronting the world today, an ancient Confucian proverb on the common good prompts us to recognize humanity's shared future. Although text-based, calligraphy is visually engaging and reminds us of the importance and poignancy of words that are well chosen and beautifully rendered. This article displays and describes Chinese calligraphies by Terry Zhizhong Yuan, commissioned by the AMA Journal of Ethics, to commemorate the American Medical Association's 175th anniversary and the extraordinary times in which we live., (Copyright 2022 American Medical Association. All Rights Reserved.)

Numerous studies have documented deteriorating occupational health among practicing physicians. This trend poses a serious risk not only for physicians but also for the many patients under their care. Past research finds that one protective factor involves the quality of physicians' motivation. When physicians are more autonomously motivated, they tend to experience better occupational health. However, few studies have identified antecedent factors that support physicians' autonomous work motivation. To identify and model potential root causes of physicians' autonomous work motivation and occupational health, the current study assessed physicians' intrinsic aspirations and need satisfaction at work. Hypotheses were tested in a sample of 2,116 U.S. practicing physicians. Structural equation modeling showed that physicians who endorsed intrinsic aspirations more strongly reported better occupational health, and that this association was mediated by physicians' need satisfaction and autonomous work motivation. Implications for designing more effective individual- and system-level interventions to improve physician occupational health are discussed.

Background: Statins are recommended in heart transplant patients, but are sometimes poorly tolerated. Alternative agents are often considered including proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i). We sought to investigate the use of PCSK9i after heart transplantation., Methods and Results: We identified patients who received a heart transplant from 1999 to 2019 and were started on PCSK9i at our institution. Clinical, laboratory, and coronary angiography with intravascular ultrasound results were compared. Among 65 patients initiated on PCSK9i (48 for statin intolerance and 17 for refractory hyperlipidemia), the median time from transplant was 5.5 years (interquartile range [IQR], 2.8-9.9 years) with a median PCSK9 treatment duration of 1.6 years (IQR, 0.8-3.2 years) and 80% still on treatment. Evolocumab was used in 73.8%, alirocumab in 12.3%, and both in 13.8% owing to insurance coverage. All patients required prior authorization; initial denial occurred in 18.5% and 32.3% had denials in subsequent years. The median low-density lipoprotein cholesterol decreased from 130 mg/dL (IQR, 102-148 mg/dL) to 55 mg/dL (IQR, 35-74 mg/dL) after starting PCSK9i (P < .001), with 72% of patients achieving a low-density lipoprotein cholesterol of <70 mg/dL after treatment. There were also significant reductions of total cholesterol, non-high-density lipoprotein cholesterol, total/high-density lipoprotein cholesterol ratio, and triglycerides, with a modest increase in high-density lipoprotein cholesterol. These changes were durable at latest follow-up. In 33 patients with serial coronary angiography and intravascular ultrasound, PCSK9i were associated with stable coronary plaque thickness and lumen area., Conclusions: Among heart transplant recipients, PCSK9i are effective in lowering cholesterol levels and stabilizing coronary intimal hyperplasia with minimal side effects. Despite favorable effects, access and affordability remain a challenge., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Donor-transmitted atherosclerosis (DTA) and rapidly progressive cardiac allograft vasculopathy (CAV) at 1 year are intravascular ultrasound (IVUS)-derived measures shown to predict adverse cardiovascular outcomes in the setting of early generation immunosuppressive agents. Given the paucity of data on the prognostic value of IVUS-derived measurements in the current era, we sought to explore their association with adverse outcomes after heart transplantation., Methods and Results: This is a retrospective cohort analysis of patients who underwent heart transplantation at our center between January 2009 and June 2016 with baseline and 1-year IVUS. Five IVUS sections were prospectively analyzed for intimal thickness and lumen area. DTA was defined as maximum intimal thickness of 0.5 mm or greater at baseline, and rapidly progressive CAV as an increase in maximum intimal thickness by 0.5 mm or more at 1 year. Our primary analysis assessed the relationship of IVUS and other clinical data on a composite outcome: coronary intervention, CAV stage 2 or 3 (defined by the International Society for Heart and Lung Transplantation 2010 nomenclature), or cardiovascular death. Among 249 patients (mean age 51.0 ± 12.2 years and 74.3% male) included in the analysis, DTA was detected in 118 patients (51.4%). Over a median follow-up of 6.1 years (interquartile range 4.2-8.0 years), 45 patients met the primary end point (23 percutaneous coronary intervention, 11 CAV 2 or 3, and 11 cardiovascular deaths as first event). DTA and rapidly progressive CAV were not associated with the primary end point, all-cause mortality, or retransplantation. In an additional analysis including post-transplant events, incident rejection was strongly associated with poor outcomes, although cytomegalovirus infection was not., Conclusions: In this contemporary cohort, IVUS-derived DTA and rapidly progressive CAV were not associated with medium- to long-term adverse events after heart transplantation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: Philanthropy is an increasingly important source of support for health care institutions. There is little empirical evidence to inform ethical guidelines., Objective: To assess public attitudes regarding specific practices used by health care institutions to encourage philanthropic donations from grateful patients., Design, Setting, and Participants: Using the Ipsos KnowledgePanel, a probability-based sample representative of the US population, a survey solicited opinions from a primary cohort representing the general population and 3 supplemental cohorts (with high income, cancer, and with heart disease, respectively)., Exposures: Web-based questionnaire., Main Outcomes and Measures: Descriptive analyses (with percentages weighted to make the sample demographically representative of the US population) evaluated respondents' attitudes regarding the acceptability of strategies hospitals may use to identify, solicit, and thank donors; perceptions of the effect of physicians discussing donations with their patients; and opinions regarding gift use and stewardship., Results: Of 831 individuals targeted for the general population sample, 513 (62%) completed surveys, of whom 246 (48.0%) were women and 345 (67.3%) non-Hispanic white. In the weighted sample, 47.0% (95% CI, 42.3%-51.7%) responded that physicians giving patient names to hospital fundraising staff after asking patients' permission was definitely or probably acceptable; 8.5% (95% CI, 5.7%-11.2%) endorsed referring without asking permission. Of the participants, 79.5% (95% CI, 75.6%-83.4%) reported it acceptable for physicians to talk to patients about donating if patients have brought it up; 14.2% (95% CI, 10.9%-17.6%) reported it acceptable when patients have not brought it up; 9.9% (95% CI, 7.1%-12.8%) accepted hospital development staff performing wealth screening using publicly available data to identify patients capable of large donations. Of the participants, 83.2% (95% CI, 79.5%-86.9%) agreed that physicians talking with their patients about donating may interfere with the patient-physician relationship. For a hypothetical patient who donated $1 million, 50.1% (95% CI, 45.4%-54.7%) indicated it would be acceptable for the hospital to show thanks by providing nicer hospital rooms, 26.0% (95% CI, 21.9%-30.1%) by providing expedited appointments, and 19.8% (95% CI, 16.1%-23.5%) by providing physicians' cell phone numbers., Conclusions and Relevance: In this survey study of participants drawn from the general US population, a substantial proportion did not endorse legally allowable approaches for identifying, engaging, and thanking patient-donors.

The intestinal microbiome is emerging as a novel therapeutic target owing to the wide range of potential health benefits that could result by manipulating the microbiota composition through relatively simple interventions. Ingestion of the prebiotic Bimuno™ galacto-oligosaccharide (B-GOS ® ) is one such intervention that has been shown to attenuate olanzapine-induced weight gain and improve cognitive flexibility in rats, potentially through mechanisms involving acetate, the major short-chain fatty acid (SCFA) that is produced by B-GOS ® fermentation. The present study investigated the individual influences of B-GOS ® and sodium acetate intake on brain histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities, cortical and hippocampal expression of HDAC1-4 and N-methyl-d-aspartate receptor subunits in saline or olanzapine injected female rats. The effect of sodium acetate on olanzapine-induced weight gain was also investigated. Daily ingestion of B-GOS ® for 21 days, reduced HDAC activity and hippocampal HDAC-4, and elevated levels of cortical HDAC-1 and HDAC-3 mRNAs. Sodium acetate supplementation significantly decreased HAT, but not HDAC, activity and increased hippocampal HDAC-3 and HDAC-4 mRNAs. Olanzapine-induced weight gain and fourteen genera of intestinal bacteria, were not influenced by sodium acetate intake. Together these data suggests the effects of B-GOS ® in rats cannot be replicated by acetate ingestion, and that mechanisms beyond the production of this SCFA are likely to underlie the psychotropic and metabolic actions of this prebiotic., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Poor occupational health among physicians poses a serious risk both to physicians themselves and the patients under their care. Prior research has found that occupational health among nonphysicians is associated with both degree and type of work motivation., Objective: The main purpose of this article was to assess the association between physician work motivation and their occupational health., Research Design: This study was a national survey of practicing physicians. A split-sample method was used to validate a measure of work motivation adapted for physicians., Subjects: In total, 3589 physicians were selected from the American Medical Association Physician Masterfile among whom 2247 physicians completed a survey (response rate of 62.6%)., Measures: Eight-item measure adapted from the Work Extrinsic and Intrinsic Motivation Scale. Grounded in self-determination theory, this measure includes 2 superordinate subscales of autonomous and controlled work motivation (characterized by feeling free and volitional versus pressured or compelled, respectively). Indicators of physicians' occupational health included single-item measures of general health, burnout, job satisfaction, intention to leave their practice, and intention to leave medicine, and a 2-item measure of depression risk., Results: Confirmatory factor analyses found that an 8-item, 2 superordinate (4 subordinate subscale) measure had good factor structure [χ(14, n=500)=35.62, P<0.001; χ(14, n=1747)=108.85, P<0.001]. Autonomous work motivation was found to be positively related to all 6 indicators of physicians' occupational health. Controlled work motivation was negatively related to 3 of 6 occupational health indicators., Conclusions: Physicians who are more autonomously motivated at work reported having better occupational health. Fostering a health care work environment that supports autonomous motivation may benefit the well-being of physicians and their patients.

Background: Similarities in the symptoms of chronic fatigue syndrome (CFS) and inflammatory bowel disease (IBD) have been observed as follows: severe disease activity in IBD correlates with severe fatigue, major psychiatric signs, the common use of medication, and bacterial translocation. One of several hypotheses for explaining the mechanisms underlying CFS suggests a similarity to the impaired intestinal mucosa of IBD. "This study investigated the risk of incident CFS among patients with IBD"., Methods: We conducted a population-based retrospective cohort study by using Taiwan's National Health Insurance Research Database to evaluate the subsequent risk of CFS in patients with IBD, according to demographic characteristics and comorbidities. The exposure cohort comprised 2163 patients with new diagnoses of IBD. Each patient was randomly selected and frequency matching according to gender and age with four participants from the general population who had no history of CFS at the index date (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between IBD and the subsequent risk of CFS., Results: The exposure cohort had a significantly higher overall risk of subsequent CFS than that of the control group [adjusted hazard ratio (Christophi in Inflamm Bowel Dis 18(12):2342-2356, 2012) = 2.25, 95%, confidence interval (Aaron and Buchwald in Ann Intern Med 134(9 Pt 2):868-881, 2001; Farraye et al. in Am J Gastroenterol 112:241, 2017) 1.70-2.99]. Further analysis indicated a significantly higher risk of CFS in patients who were male (HR = 3.23, 95% CI 2.12-4.91), were older than 35 years, and had IBD but without comorbidity status, e.g. Cancers, diabetes, obesity, depression, anxiety, sleep disorder, renal disease (HR = 2.50, 95% CI 1.63-3.84) after adjustment., Conclusion: The findings from this population-based retrospective cohort study suggest that IBD, especially Crohn's disease, is associated with an increased risk of subsequent CFS.

Background: Primary care physicians generally earn less than specialists. Studies of other occupations have identified perception of pay fairness as a predictor of work- and life-related outcomes. We evaluated whether physicians' pay fairness perceptions were associated with their work satisfaction, turnover intention, and personal health., Methods: Three thousand five hundred eighty-nine physicians were surveyed. Agreement with "my total compensation is fair" was used to assess pay fairness perceptions. Total compensation was self-reported, and we used validated measures of work satisfaction, likelihood of leaving current practice, and health status. Hierarchical logistic regressions were used to assess the associations between pay fairness perceptions and work/life-related outcomes., Results: A total of 2263 physicians completed surveys. Fifty-seven percent believed their compensation was fair; there was no difference between physicians in internal medicine and non-primary care specialties (P = 0.58). Eighty-three percent were satisfied at work, 70% reported low likelihood of leaving their practice, and 77% rated their health as very good or excellent. Higher compensation levels were associated with greater work satisfaction and lower turnover intention, but most associations became statistically non-significant after adjusting for pay fairness perceptions. Perceived pay fairness was associated with greater work satisfaction (OR, 4.90; 95% CI, 3.94-6.08; P < 0.001), lower turnover intention (OR, 2.46; 95% CI, 2.01-3.01; P < 0.001), and better health (OR, 1.33; 95% CI, 1.08-1.65; P < 0.01)., Discussion: Physicians who thought their pay was fair reported greater work satisfaction, lower likelihood of leaving their practice, and better overall health. Addressing pay fairness perceptions may be important for sustaining a satisfied and healthy physician workforce, which is necessary to deliver high-quality care.

Olanzapine is an effective antipsychotic drug but since it causes significant weight gain, it is not well tolerated by psychosis patients. The prebiotic, B-GOS ® , attenuates metabolic dysfunction in obese subjects, and in rodents, alters central NMDA receptors and may affect serotonin receptors that are relevant in psychosis. We have determined whether B-GOS ® influenced olanzapine-associated weight gain and central NMDA and serotonin receptors. Circulating acetate, IL-1β, IL-8 and TNFα, liver acetyl-CoA carboxylase (ACC), white adipose tissue (WAT) acetate receptor GPR43, and specific faecal bacteria genera were also measured to provide mechanistic information. Adult female Sprague-Dawley rats were administered a B-GOS ® (0.5 g/kg/day) solution or water for 21 days, and received a single, daily, intraperitoneal injection of olanzapine or saline on days 8-21. The intake of B-GOS ® significantly attenuated olanzapine-induced weight gain without altering frontal cortex 5-HT2AR blockade. Cortical GluN1 levels were elevated by olanzapine in the presence of B-GOS ® . Plasma acetate concentrations increased following B-GOS ® or olanzapine administration alone, but reduced when prebiotic and drug were administered in combination. This pattern was paralleled by hepatic ACC mRNA expression. The abundance of WAT GPR43 mRNA was reduced by olanzapine, only in the absence of B-GOS ® . Co-administration of B-GOS ® and olanzapine also elevated plasma TNFα, which is reported to influence lipid metabolism. Finally, B-GOS ® elevated faecal Bifidobacterium spp. and reduced some bacteria in the Firmicutes phylum, whilst olanzapine treatment either alone or with B-GOS ® , was without effect. These data suggest that inclusion of B-GOS ® as an adjunct to olanzapine treatment in schizophrenia may prevent weight gain and have benefits on cognitive function in psychosis. The role of acetate in these effects requires further investigation.

With the US health care system facing a primary care physician shortage, we evaluated whether medical students who saw medicine as a calling were more likely to enter a family medicine, internal medicine, or pediatrics residency program. Of the 591 4th-year medical students who responded to a survey item on medicine as a calling, 237 strongly agreed that the "practice of medicine is a calling." Students who strongly agreed that medicine was a calling had higher odds ( P =.003) of selecting a primary care-related residency. Identifying with medicine as a calling may increase the likelihood of pursuing a primary care career., Competing Interests: Conflicts of interest: authors report none., (© 2018 Annals of Family Medicine, Inc.)

Objective: To evaluate the association between degree of professional burnout and physicians' sense of calling., Participants and Methods: US physicians across all specialties were surveyed between October 24, 2014, and May 29, 2015. Professional burnout was assessed using a validated single-item measure. Sense of calling, defined as committing one's life to personally meaningful work that serves a prosocial purpose, was assessed using 6 validated true-false items. Associations between burnout and identification with calling items were assessed using multivariable logistic regressions., Results: A total of 2263 physicians completed surveys (63.1% response rate). Among respondents, 28.5% (n=639) reported experiencing some degree of burnout. Compared with physicians who reported no burnout symptoms, those who were completely burned out had lower odds of finding their work rewarding (odds ratio [OR], 0.05; 95% CI, 0.02-0.10; P<.001), seeing their work as one of the most important things in their lives (OR, 0.38; 95% CI, 0.21-0.69; P<.001), or thinking their work makes the world a better place (OR, 0.38; 95% CI, 0.17-0.85; P=.02). Burnout was also associated with lower odds of enjoying talking about their work to others (OR, 0.23; 95% CI, 0.13-0.41; P<.001), choosing their work life again (OR, 0.11; 95% CI, 0.06-0.20; P<.001), or continuing with their current work even if they were no longer paid if they were financially stable (OR, 0.30; 95% CI, 0.15-0.59; P<.001)., Conclusion: Physicians who experience more burnout are less likely to identify with medicine as a calling. Erosion of the sense that medicine is a calling may have adverse consequences for physicians as well as those for whom they care., (Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Manipulating the intestinal microbiota for the benefit of the brain is a concept that has become widely acknowledged. Prebiotics are nondigestible nutrients (i.e., fibers, carbohydrates, or various saccharides) that proliferate intrinsic, beneficial gut bacteria, and so provide an alternative strategy for effectively altering the enteric ecosystem, and thence brain function. Rodent studies demonstrating neurobiological changes following prebiotic intake are slowly emerging, and have thus far revealed significant benefits in disease models, including antiinflammatory and neuroprotective actions. There are also compelling data showing the robust and favorable effects of prebiotics on several behavioral paradigms including, anxiety, learning, and memory. At present, studies in humans are limited, though there is strong evidence for prebiotics modulating emotional processes and the neuroendocrine stress response that may underlie the pathophysiology of anxiety. While the mechanistic details linking the enteric microbiota to the central nervous system remain to be elucidated, there are a number of considerations that can guide future studies. These include the modulation of intestinal endocrine systems and inflammatory cascades, as well as direct interaction with the enteric nervous system and gut mucosa. Our knowledge of gut microbiome-brain communication is steadily progressing, and thorough investigations validating the use of prebiotics in the treatment of neuropsychiatric disorders would be highly valued and are encouraged., (© 2016 Elsevier Inc. All rights reserved.)

Weight gain and metabolic disturbances represent serious side-effects in antipsychotic (AP) treatment, particularly with clozapine and olanzapine. The methylenetetrahydrofolate reductase (MTHFR) gene is a key determinant in the folate metabolism and previous studies reported a significant effect on AP-induced weight gain and related metabolic abnormalities. Thus, we investigated MTHFR gene variants and changes in several important metabolic parameters in AP-treated patients. In this study, two functional MTHFR polymorphisms, rs1801133 (C677T) and rs1801131 (A1298C), were investigated for changes in weight and metabolic parameters. Genotypic associations were evaluated in a large population (n = 347 including 66 first episode psychosis, FEP patients) treated mostly with clozapine and olanzapine. We did not detect any genotypic association with weight changes (p > 0.05) in our total sample and in the sample refined for ancestry and medication. In our allelic analyses, we observed a trend for the 677-C allele to be associated with weight gain in the total sample (p = 0.03). This effect appeared to be driven by the FEP patients where those carrying the C-allele gained, on average, twice as much weight. Exploratory analyses revealed a significant association between the C677T and the A1298C polymorphism with HDL cholesterol serum levels in patients (p = 0.031). Overall we did not detect a major effect of two functional MTHFR gene variants and AP-induced weight gain. However, our findings suggest an effect of the C677T polymorphism in FEP patients and changes in weight and cholesterol levels. Further investigations in a larger sample are required., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Antipsychotic medications are used to effectively treat various symptoms for different psychiatric conditions. Unfortunately, antipsychotic-induced weight gain (AIWG) is a common side effect that frequently results in obesity and secondary medical conditions. Twin and sibling studies have indicated that genetic factors are likely to be highly involved in AIWG. Over recent years, there has been considerable progress in this area, with several consistently replicated findings, as well as the identification of new genes and implicated pathways. Here, we will review the most recent genetic studies related to AIWG using the Medline database (PubMed) and Google Scholar. Among the steadiest findings associated with AIWG are serotonin 2C receptors (HTR2C) and leptin promoter gene variants, with more recent studies implicating MTHFR and, in particular, MC4R genes. Additional support was reported for the HRH1, BDNF, NPY, CNR1, GHRL, FTO and AMPK genes. Notably, some of the reported variants appear to have relatively large effect sizes. These findings have provided insights into the mechanisms involved in AIWG and will help to develop predictive genetic tests in the near future.

Arsenic (As) contamination of groundwater is a significant public health concern. In this study, the removal of arsenic from groundwater using biological processes was investigated. The efficiency of arsenite (As(III)) bacterial oxidation and subsequent arsenate (As(V)) removal from contaminated groundwater using bacterial biomass was examined. A novel As(III)-oxidizing bacterium (As7325) was isolated from the aquifer in the blackfoot disease (BFD) endemic area in Taiwan. As7325 oxidized 2300μg/l As(III) using in situ As(III)-contaminated groundwater under aerobic conditions within 1d. After the oxidation of As(III) to As(V), As(V) removal was further examined using As7325 cell pellets. The results showed that As(V) could be adsorbed efficiently by lyophilized As7325 cell pellets, the efficiency of which was related to lyophilized cell pellet concentration. Our study conducted the examination of an alternative technology for the removal of As(III) and As(V) from groundwater, indicating that the oxidation of As(III)-contaminated groundwater by native isolated bacterium, followed by As(V) removal using bacterial biomass is a potentially effective technology for the treatment of As(III)-contaminated groundwater., (© 2013.)

Genetic testing may help to improve treatment outcomes in order to avoid non-response or severe side effects to psychotropic medication. Most robust data have been obtained for gene variants in CYP2D6 and CYP2C19 enzymes for antipsychotics and antidepressant treatment. We reviewed original articles indexed in PubMed from 2008-2013 on CYP2D6 and CYP2C19 gene variants and treatment outcome to antidepressant or antipsychotic medication. We have started providing CYP2D6 and CYP2C19 genotype information to physicians and conducted a survey where preliminary results are reported. Studies provided mixed results regarding the impact of CYP2D6 and CYP2C19 gene variation on treatment response. Plasma levels were mostly found associated with CYP metabolizer status. Higher occurrence/severity of side effects were reported in non-extensive CYP2D6 or CYP2C19 metabolizers. Results showed that providing genotypic information is feasible and generally well accepted by both patients and physicians. Although currently available studies are limited by small sample sizes and infrequent plasma drug level assessment, research to date indicates that CYP2D6 and CYP2C19 testing may be beneficial particularly for non-extensive metabolizing patients. In summary, clinical assessment of CYP2D6 and CYP2C19 metabolizer status is feasible, well accepted and optimizes drug treatment in psychiatry.

Background: Heart failure (HF) patients have a high risk of death, and implantable cardioverter defibrillators (ICDs) are effective in preventing sudden cardiac death (SCD). However, a certain percentage of patients may not be immediate candidates for ICDs, particularly those having a short duration of risk or an uncertain amount of risk. This includes the newly diagnosed patients, as well as those on the cardiac transplant list or NYHA class IV heart failure patients who do not already have an ICD. In these patients, a wearable cardioverter defibrillator (WCD) may be used until long term risk of SCD is defined. The purpose of this study was to determine the incidence of SCD in this population, and the efficacy of early defibrillation by a WCD., Methods: Ten enrolling centers identified 89 eligible HF patients who were either listed for cardiac transplantation, diagnosed with dilated cardiomyopathy, or receiving inotropic medications. Data collected included medical history, device records, and outcomes (including 90 day mortality)., Results: Out of 89 patients, final data on 82 patients has been collected. Patients wore the device for 75±58 days. Mean age was 56.8±13.2, and 72% were male. Most patients (98.8%) were diagnosed with dilated cardiomyopathy with a low ejection fraction (<40%) and twelve were listed for cardiac transplantation. Four patients were on inotropes. There were no sudden cardiac arrests or deaths during the study. Interestingly, 41.5% of patients were much improved after WCD use, while 34.1% went on to receive an ICD., Conclusions: In conclusion, the WCD monitored HF patients until further assessment of risk. The leading reasons for end of WCD use were improvement in left ventricular ejection fraction (LVEF) or ICD implantation if there was no significant improvement in LVEF.

Purpose: To determine the effect of educational interventions on medical students' attitudes toward pharmaceutical industry marketing practices and whether restrictive medical school policies governing medicine-industry interactions are associated with student support for banning such interactions., Method: Prospective cohort study involving the graduating classes of 2009 (intervention, n=474) and 2010 (control, n=459) at four U.S. medical schools. Intervention students experienced a former pharmaceutical representative's presentation, faculty debate, and a Web-based course. Both groups completed baseline and follow-up attitude surveys about pharmaceutical marketing., Results: A total of 482 students (51.6%) completed both surveys. In regression analyses, intervention students were more likely than control students to think that physicians are strongly or moderately influenced by pharmaceutical marketing (OR, 2.29; 95% CI, 1.46-3.59) and believed they would be more likely to prescribe a company's drug if they accepted that company's gifts and food (OR, 1.68; 95% CI, 1.12-2.52). Intervention students were more likely to support banning interactions between pharmaceutical representatives and students (OR, 4.82; 95% CI, 3.02-7.68) and with physicians (OR, 6.88; 95% CI, 4.04-11.70). Students from schools with more restrictive policies were more likely to support banning interactions between pharmaceutical representatives and students (OR, 1.99; 95% CI, 1.26-3.16) and with physicians (OR, 3.44; 95% CI, 2.05-5.79)., Conclusions: Education about pharmaceutical marketing practices and more restrictive policies governing medicine-industry interactions seem to increase medical students' skepticism about the appropriateness of such marketing practices and disapproval of pharmaceutical representatives in the learning environment.

Barth syndrome is an X-linked disorder characterized by dilated cardiomyopathy, cyclic neutropenia, skeletal myopathy, abnormal mitochondria, and growth deficiency. The primary defect is a mutation in the TAZ gene on the X chromosome at Xq28, resulting in abnormal phospholipid biosynthesis and cardiolipin deficiency. To date, there has been no systematic evaluation of the cardiac phenotype. We report five cases of cardiac arrest and/or placement of an internal cardiac defibrillator with documented ventricular arrhythmia. We suggest that ventricular arrhythmia is part of the primary phenotype of the disorder and that patients should be screened accordingly.

Purpose: Oath taking is an important aspect of professionalization that all physicians share. The authors conducted a content analysis of the medical oaths administered at all allopathic and osteopathic medical schools in the United States to evaluate variations in ethical content., Method: The authors collected medical oaths administered at all accredited allopathic and osteopathic medical schools (122 and 19, respectively) in the year 2000. Using a modified conceptual framework developed by Baker, the oaths were analyzed for differences in their substantive content. Content differences based on schools' characteristics were also analyzed., Results: Just over half (62 of 122) of the allopathic schools administered an oath other than the Hippocratic Oath or a modified version of it. Thirty allopathic schools administered an oath written by students and/or faculty, and 18 schools offered students more than one oath option. All 19 osteopathic schools used the Osteopathic Oath. Nearly all allopathic and osteopathic schools' oaths included content protecting patients' confidentiality (129 schools), but few cited the importance of avoiding sexual misconduct with patients (four schools). Although the Osteopathic Oath prohibits physician-assisted suicide or euthanasia, only six allopathic schools administered an oath with such a prohibition. One allopathic school's oath explicitly prohibited abortion. There were no major content differences in the oaths administered based on a school's ownership status, religious affiliation, or use of white coat ceremony., Conclusion: Many medical schools' oaths differ in substantive content. The impact of using a nonstandardized medical oath on physicians' professionalism and the inculcation of common ethical values and principles remains unknown.

Objective: To assess Medicare beneficiaries' willingness to cost share in order to minimize disruptions in coverage from HMO plan withdrawals., Design: Cross-sectional survey of Medicare beneficiaries from February 1999 to March 1999., Setting: Ten U.S. counties with the highest HMO plan withdrawal rates., Patients/participants: Seven hundred one Medicare beneficiaries for response rate of 69%., Measurements and Main Results: Percentage of respondents willing to accept more out-of-pocket costs in order to continue their Medicare HMO coverage. Most respondents (67%) were willing to pay more out-of-pocket costs so that their HMO could have continued Medicare coverage. Those who were white (P =.03), had higher incomes (P =.01), and returned to traditional fee-for-service Medicare (P =.004) were more likely than other respondents to accept increased patient cost sharing. Most beneficiaries preferred Medicare policies requiring HMOs to sign longer-term Health Care Financing Administration (HCFA) contracts (72%) and to offer coverage to beneficiaries regardless of where they lived in a given state (87%). However, respondents' preferences for such policy options were not associated with the amount of cost sharing that respondents were willing to accept., Conclusions: Most Medicare beneficiaries are willing to accept increased patient cost sharing in order to reduce disruptions in their HMO coverage. Policies intended to reduce HMO plan withdrawals, such as requiring health plans to sign longer-term HCFA contracts, are supported by many Medicare beneficiaries, but these policy preferences were not related to willingness to cost share. In light of an apparent willingness to pay more out-of-pocket medical costs, Medicare beneficiaries in general may accept increased cost sharing in order to retain their HMO coverage.

Context: Few data are available regarding the consequences of patients' problems with interpersonal aspects of medical care., Objective: To assess the relationships between outpatient problem experiences and patients' trust in their physicians, ratings of their physicians, and consideration of changing physicians. We classified as problem experiences patients' reports that their physician does not always 1) give them enough time to explain the reason for the visit, 2) give answers to questions that are understandable, 3) take enough time to answer questions, 4) ask about how their family or living situation affects their health, 5) give as much medical information as they want, or 6) involve them in decisions as much as they want., Design: Telephone survey during 1997., Participants: Patients (N=2,052; 58% response) insured by a large national health insurer., Measurements: Patient trust, overall ratings of physicians, and having considered changing physicians., Results: Most patients (78%) reported at least 1 problem experience. In multivariable analyses, each problem experience was independently associated with lower trust (all P <.001) and 5 of 6 with lower overall ratings (P <.001). Three problem experiences were independently related to considering changing physicians: physicians not always giving answers to questions that are understandable (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.3 to 3.0), not always taking enough time to answer questions (OR, 3.3; 95% CI, 2.2 to 5.2), and not always giving enough medical information (OR, 4.0; 95% CI, 2.4 to 6.6)., Conclusions: Problem experiences in the ambulatory setting are strongly related to lower trust. Several are also associated with lower overall ratings and with considering changing physicians, particularly problems related to communication of health information. Efforts to improve patients' experiences may promote more trusting relationships and greater continuity and therefore should be a priority for physicians, educators, and health care organizations.

Objective: There is increasing public discussion of the value of disclosing how physicians are paid. However, little is known about patients' awareness of and interest in physician payment information or its potential impact on patients' evaluation of their care., Design: Cross-sectional survey, Setting: Managed care and indemnity plans of a large, national health insurer., Participants: Telephone interviews were conducted with 2,086 adult patients in Atlanta, Ga; Baltimore, Md/Washington DC; and Orlando, Fla (response rate, 54%)., Measurements and Main Results: Patients were interviewed to assess perceptions of their physicians' payment method, preference for disclosure, and perceived effect of different financial incentives on quality of care. Non-managed fee-for-service patients (44%) were more likely to correctly identify how their physicians were paid than those with salaried (32%) or capitated (16%) physicians. Just over half (54%) wanted to be informed about their physicians' payment, Method: Patients of capitated and salaried physicians were as likely to want disclosure as patients of fee-for-service physicians. College graduates were more likely to prefer disclosure than other patients. Many patients (76%) thought a bonus paid for ordering fewer than the average number of tests would adversely affect the quality of their care. About half of the patients (53%) thought a particular type of withhold would adversely affect the quality of their care. White patients, college graduates, and those who had higher incomes were more likely to think that these types of bonuses and withholds would have a negative impact on their care. Among patients who believed that these types of bonuses adversely affected care, those with non-managed fee-for-service insurance and college graduates were more willing to pay a higher deductible or co-payment in order to get tests that they thought were necessary., Conclusions: Most patients were unaware of how their physicians are paid, and only about half wanted to know. Most believed that bonuses or withholds designed to reduce the use of services would adversely affect the quality of their care. Lack of knowledge combined with strong attitudes about various financial incentives suggest that improved patient education could clarify patient understanding of the nature and rationale for different types of incentives. More public discussion of this important topic is warranted.

Objective: While dizziness has traditionally been considered solely as a symptom of discrete diseases, recent findings from population-based studies of older persons suggest that it may often be a geriatric syndrome with multiple predisposing risk factors, representing impairments in diverse systems. To validate these findings, we identified predisposing risk factors for dizziness in a clinic-based population., Design: Cross-sectional study., Setting: Geriatric assessment center., Participants: 262 consecutive, eligible patients., Measurements: Medical history and physical examination data were ascertained and characteristics of patients with and without a report of dizziness were compared., Results: Seven factors were independently associated with a report of dizziness, namely depressive symptoms, cataracts, abnormal balance or gait, postural hypotension, diabetes, past myocardial infarction, and the use of three or more medications. Of patients with none of these risk factors, none reported dizziness. This proportion rose from 6% among patients with one factor, to 12%, 26%, and 51% among patients with two, three, and four or more factors, respectively., Conclusions: The finding of similar factors associated with dizziness in previous community-based cohorts and the present clinic-based cohort supports the possibility of a multifactorial etiology of dizziness in many older persons. A multifactorial intervention targeting the factors identified in these studies may be effective at reducing the frequency or severity of dizziness in older patients.

Context: Trust is the cornerstone of the patient-physician relationship. Payment methods that place physicians at financial risk have raised concerns about patients' trust in physicians to act in patients' best interests., Objective: To evaluate the extent to which methods of physician payment are related to patient trust., Design: Cross-sectional telephone interview survey done between January and June 1997., Setting: Health plans of a large national insurer in Atlanta, Ga, the Baltimore, Md-Washington, DC, area, and Orlando, Fla., Participants: A total of 2086 adult managed care and indemnity patients., Main Outcome Measure: A 10-item scale (alpha = .94) assessing patients' trust in physicians., Results: More fee-for-service (FFS) indemnity patients (94%) completely or mostly trust their physicians to "put their health and well-being above keeping down the health plan's costs" than salary (77%), capitated (83%), or FFS managed care patients (85%) (P<.001 for pairwise comparisons). In multivariate analyses that adjusted for potentially confounding factors, FFS indemnity patients also had higher scores on the 10-item trust scale than salary (P<.001), capitated (P<.001), or FFS managed care patients (P<.01). The effects of payment method on patient trust were reduced when a measure based on patients' reports about physician behavior (eg, Does your physician take enough time to answer your questions?) was included in the regression analyses, but the differences remained statistically significant, except for the comparison between FFS managed care and FFS indemnity patients (P=.08). Patients' perceptions of how their physicians were paid were not independently associated with trust, but the 37.7% who said they did not know how their physicians were paid had higher levels of trust than other patients (P<.01). A total of 30.2% of patients were incorrect about their physicians' method of payment., Conclusions: Most patients trusted their physicians, but FFS indemnity patients have higher levels of trust than salary, capitated, or FFS managed care patients. Patients' reports of physician behavior accounted for part of the variation in patients' trust in physicians who are paid differently. The impact of payment methods on patient trust may be mediated partly by physician behavior.

Objective: To evaluate the extent to which physician choice, length of patient-physician relationship, and perceived physician payment method predict patients' trust in their physician., Design: Survey of patients of physicians in Atlanta, Georgia., Patients: Subjects were 292 patients aged 18 years and older., Measurements and Main Results: Scale of patients' trust in their physician was the main outcome measure. Most patients completely trusted their physicians "to put their needs above all other considerations" (69%). Patients who reported having enough choice of physician (p < .05), a longer relationship with the physician (p < .001), and who trusted their managed care organization (p < .001) were more likely to trust their physician. Approximately two thirds of all respondents did not know the method by which their physician was paid. The majority of patients believed paying a physician each time a test is done rather than a fixed monthly amount would not affect their care (72.4%). However, 40.5% of all respondents believed paying a physician more for ordering fewer than the average number of tests would make their care worse. Of these patients, 53.3% would accept higher copayments to obtain necessary medical tests., Conclusions: Patients' trust in their physician is related to having a choice of physicians, having a longer relationship with their physician, and trusting their managed care organization. Most patients are unaware of their physician's payment method, but many are concerned about payment methods that might discourage medical use.

Background: Because prolonged survival of heart transplant recipients is expected with the current immunosuppressive treatment, the functional capacity of these long-term survivors is of interest. Previous exercise studies showed no objective improvement in exercise tolerance several years after transplantation, but the extent to which chronotropic incompetence and allograft diastolic dysfunction observed early after transplantation may improve over time has not been defined., Methods: Thirteen untrained heart transplant recipients without symptoms, between 27 and 70 months after transplantation, and 13 age-matched sedentary normal controls underwent maximal upright bicycle exercise testing with simultaneous hemodynamic, radionuclide, and expired gas measurements., Results: Systolic function as measured by ejection fraction was supranormal at rest in the transplant group and normalized with exercise. Despite their maximal exercise effort, transplant recipients had a 60% reduction in their exercise capacity compared with nontransplant recipients. Peak oxygen consumption was similarly reduced by 52%. Cardiac output response to exercise was 43% lower in the transplant group because of a 78% reduction in heart rate reserve and an 18% reduction in maximal stroke volume. Ventricular volumes were similarly reduced after transplantation, but filling pressures remained normal, indicating allograft diastolic dysfunction. Despite the significantly reduced maximal cardiac output, maximal arteriovenous oxygen difference was 25% lower in the transplant recipients, suggesting a peripheral deficit in oxygen handling., Conclusions: Therefore, patients, 2 to 6 years after transplantation, continue to have a significant reduction in exercise tolerance as a result of a combination of severe chronotropic incompetence, limited stroke volume reserve caused by a reduced ventricular size and allograft diastolic dysfunction, and an abnormality in peripheral oxygen delivery or use. Efforts aimed at improving these factors may further enhance the functional capacity of these long-term survivors of heart transplantation.

Background: Functional capacity and quality of life are subjectively improved after cardiac transplantation. However, the objective improvement in exercise tolerance after transplantation has been disappointing. The extent to which allograft diastolic dysfunction contributes to this exercise intolerance has not been defined., Methods and Results: Thirty cardiac transplant recipients between 3 and 16 months after transplantation and 30 age-matched normal control subjects underwent maximal symptom-limited graded upright bicycle exercise testing with simultaneous radionuclide angiography, invasive hemodynamic monitoring, and breath-by-breath gas analysis. Mean blood pressure was higher in the transplant group at supine rest (112.1 versus 97.7 mm Hg), normalized with upright posture, and became lower than normal at peak exercise (121.1 versus 133.2 mm Hg). Systolic function as measured by ejection fraction was normal in both groups. However, the cardiac transplant recipients had significantly lower exercise tolerance, achieving a mean maximal work rate of 390 kilopond-meters per minute (kpm/min), compared with 825 kpm/min in the normal subjects. Peak oxygen consumption was 12.3 mL.min-1.kg-1 in the transplant group, 46% lower than the normal group's value of 22.9 mL.min-1.kg-1. The transplant patients had a resting tachycardia (94 beats per minute) and a 79% reduction in exercise heart rate reserve compared with normal. Despite this chronotropic incompetence, stroke index response to exercise was consistently lower after transplantation, accounting for a 41% reduction in cardiac index at maximal exercise. The lower stroke index was accompanied by a 32% lower end-diastolic volume index at rest and a 14% lower end-diastolic volume index at peak exercise. Despite the smaller ventricular volumes after transplantation, pulmonary capillary wedge pressure was 35% higher than normal at supine rest and 50% higher at maximal exercise. Right atrial and mean pulmonary arterial pressures were similarly elevated. The ratio of pulmonary capillary wedge pressure to end-diastolic volume index was significantly higher during the postural change and exercise, suggesting allograft diastolic dysfunction. Arteriovenous oxygen difference was similar between groups at rest and with submaximal exercise but was 24% lower at maximal exercise in the transplant group, suggesting an abnormality in peripheral oxygen uptake or utilization., Conclusions: Exercise tolerance is severely limited during the first 16 months after cardiac transplantation despite preservation of allograft left ventricular systolic function. This intolerance is due to an inadequate cardiac index response from a combination of chronotropic incompetence and diastolic dysfunction limiting the appropriate compensatory use of the Starling mechanism. In addition, there is a peripheral abnormality in oxygen transport or utilization that may partially reflect the effects of deconditioning.

The mitogen-induced activation of Na+-H+ exchange was investigated in two cultured human fibroblast strains (HSWP and WI-38 cells) that, based on previous studies, differed in their response to the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (L. M. Vincentini and M. L. Villereal, Proc. Natl. Acad. Sci. USA 82: 8053-8056, 1985). The role of protein kinase C in the activation of Na+-H+ exchange was investigated by comparing the effects of TPA on Na+ influx, in vitro phosphorylation, and in vivo phosphorylation in both cell types. Although both cell types have significant quantities of protein kinase C activity that can be activated by TPA in intact cells, the addition of TPA to intact cells stimulates Na+ influx in WI-38 cells but not in HSWP cells, indicating that in HSWP cells the stimulation of protein kinase C is not sufficient to activate the Na+-H+ exchanger. Cells were then depleted of protein kinase C activity by chronic treatment with high doses of TPA. Both HSWP and WI-38 cells were rendered protein kinase C deficient by this treatment as determined by in vitro and in vivo phosphorylation studies. Protein kinase C-deficient HSWP cells lose the ability for TPA to inhibit the serum-induced activation of Na+-H+ exchange, but there is no reduction in the stimulation of Na+ influx by serum, bradykinin, vasopressin, melittin, or vanadate, indicating that protein kinase C activity is not necessary for the mitogen-induced activation of Na+-H+ exchange in HSWP cells by agents known to stimulate phosphatidylinositol turnover (G. A. Jamieson and M. Villereal. Arch. Biochem. Biophys. 252: 478-486, 1987). In contrast, depletion of protein kinase C activity in WI-38 cells significantly reduces both the TPA- and the serum-induced activation of the Na+-H+ exchange system, suggesting that protein kinase C activity is necessary for at least a portion of the mitogen-induced activation of the Na+-H+ exchanger in WI-38 cells. These results indicate that the mechanisms for regulating Na+-H+ exchange can differ dramatically between different types of fibroblasts.