Subclinical myocardial disease by cardiac magnetic resonance imaging and spectroscopy in healthy HIV/Hepatitis C virus-coinfected persons.

Objective The contribution of hepatitis C virus (HCV) infection to the risk of heart failure in human immunodeficiency virus (HIV)-coinfected persons is unknown. The objective was to characterize cardiac function and morphology in HIV-treated coinfected persons. Methods In a cross-sectional study, HIV-infected patients virologically suppressed on antiretroviral therapy without known cardiovascular disease or diabetes mellitus underwent cardiac magnetic resonance imaging and spectroscopy for measures of cardiac function, myocardial fibrosis, and steatosis. Results The study included 18 male patients with a median age of 44 years. Of these, 10 had untreated HCV coinfection and eight had HIV monoinfection. Global systolic and diastolic function in the cohort were normal, and median myocardial fat content was 0.48% (interquartile range 0.35-1.54). Left ventricular (LV) mass index and LV mass/volume ratio were significantly greater in the HIV/HCV-coinfected group compared with the HIV-monoinfected group. In the HIV-monoinfected group, there was more myocardial fibrosis as measured by extracellular volume fraction. Conclusions There were differences between HIV/HCV-coinfected and HIV-monoinfected patients in cardiac structure and morphology. Larger studies are needed to examine whether HIV and HCV independently contribute to mechanisms of heart failure

Associations of physician burnout with career engagement and quality of patient care: systematic review and meta-analysis.

To examine the association of physician burnout with the career engagement and the quality of patient care globally. Systematic review and meta-analysis. Medline, PsycINFO, Embase, and CINAHL were searched from database inception until May 2021. Observational studies assessing the association of physician burnout (including a feeling of overwhelming emotional exhaustion, feelings of cynicism and detachment from job defined as depersonalisation, and a sense of ineffectiveness and little personal accomplishment) with career engagement (job satisfaction, career choice regret, turnover intention, career development, and productivity loss) and the quality of patient care (patient safety incidents, low professionalism, and patient satisfaction). Data were double extracted by independent reviewers and checked through contacting all authors, 84 (49%) of 170 of whom confirmed their data. Random-effect models were used to calculate the pooled odds ratio, prediction intervals expressed the amount of heterogeneity, and meta-regressions assessed for potential moderators with significance set using a conservative level of P<0.10. 4732 articles were identified, of which 170 observational studies of 239 246 physicians were included in the meta-analysis. Overall burnout in physicians was associated with an almost four times decrease in job satisfaction compared with increased job satisfaction (odds ratio 3.79, 95% confidence interval 3.24 to 4.43, I =97%, k=73 studies, n=146 980 physicians). Career choice regret increased by more than threefold compared with being satisfied with their career choice (3.49, 2.43 to 5.00, I =97%, k=16, n=33 871). Turnover intention also increased by more than threefold compared with retention (3.10, 2.30 to 4.17, I =97%, k=25, n=32 271). Productivity had a small but significant effect (1.82, 1.08 to 3.07, I =83%, k=7, n=9581) and burnout also affected career development from a pooled association of two studies (3.77, 2.77 to 5.14, I =0%, n=3411). Overall physician burnout doubled patient safety incidents compared with no patient safety incidents (2.04, 1.69 to 2.45, I =87%, k=35, n=41 059). Low professionalism was twice as likely compared with maintained professionalism (2.33, 1.96 to 2.70, I =96%, k=40, n=32 321), as was patient dissatisfaction compared with patient satisfaction (2.22, 1.38 to 3.57, I =75%, k=8, n=1002). Burnout and poorer job satisfaction was greatest in hospital settings (1.88, 0.91 to 3.86, P=0.09), physicians aged 31-50 years (2.41, 1.02 to 5.64, P=0.04), and working in emergency medicine and intensive care (2.16, 0.98 to 4.76, P=0.06); burnout was lowest in general practitioners (0.16, 0.03 to 0.88, P=0.04). However, these associations did not remain significant in the multivariable regressions. Burnout and patient safety incidents were greatest in physicians aged 20-30 years (1.88, 1.07 to 3.29, P=0.03), and people working in emergency medicine (2.10, 1.09 to 3.56, P=0.02). The association of burnout with low professionalism was smallest in physicians older than 50 years (0.36, 0.19 to 0.69, P=0.003) and greatest in physicians still in training or residency (2.27, 1.45 to 3.60, P=0.001), in those who worked in a hospital (2.16, 1.46 to 3.19, P<0.001), specifically in emergency medicine specialty (1.48, 1.01 to 2.34, P=0.042), or situated in a low to middle income country (1.68, 0.94 to 2.97, P=0.08). This meta-analysis provides compelling evidence that physician burnout is associated with poor function and sustainability of healthcare organisations primarily by contributing to the career disengagement and turnover of physicians and secondarily by reducing the quality of patient care. Healthcare organisations should invest more time and effort in implementing evidence-based strategies to mitigate physician burnout across specialties, and particularly in emergency medicine and for physicians in training or residency. PROSPERO number CRD42021249492. [Abstract copyright: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Vision-threatening retinal abnormalities in chronic kidney disease stages 3 to 5

SUMMARY: BACKGROUND AND OBJECTIVES: Retinal abnormalities are common in inherited and acquired renal disease. This study determined the prevalence of retinal abnormalities in chronic kidney disease (CKD) stages 3 to 5. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: One hundred fifty patients with CKD stages 3 to 5 and 150 age- and gender-matched hospital patients with CKD stages 1 to 2 underwent bilateral retinal photography. These images were reviewed for incidental abnormalities, microvascular (Wong and Mitchell classification) and diabetic retinopathy (Airlie House criteria), and macular degeneration (Seddon classification). RESULTS: Three (2%) patients with CKD stages 3 to 5 had retinal features characteristic of inherited renal disease (atrophy in Myopathy, Encephalopathy, Lactic Acidosis, Stroke-like episodes [MELAS] syndrome; and 2 with drusen in dense deposit disease). Fifty-nine (39%) patients had moderate-severe microvascular retinopathy (hemorrhages, exudates, etc.) compared with 19 (13%) with CKD stages 1 to 2. Forty-one (28%) had moderate-severe diabetic retinopathy (microaneurysms, exudates, etc.) compared with 16 (11%) with CKD stages 1 to 2. Ten (7%) had severe macular degeneration (geographic atrophy, hemorrhage, exudates, membranes) compared with one (1%) with CKD stages 1 to 2. Renal failure was an independent risk factor for microvascular retinopathy, diabetic retinopathy, and macular degeneration. Eleven (7.3%) patients with renal failure and one (0.7%) with CKD stages 1 to 2 had previously unrecognized vision-threatening retinal abnormalities that required immediate ophthalmologic attention. CONCLUSIONS: Retinal abnormalities are common in CKD stages 3 to 5, and are more severe and more likely to threaten vision than in hospital patients with CKD stages 1 to 2

Germline MBD4 deficiency causes a multi-tumor predisposition syndrome

We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic MBD4 variants within four families and these individuals had a personal and/or family history of adenomatous colorectal polyposis, acute myeloid leukemia, and uveal melanoma. MBD4 encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5′-methylcytosine. The colorectal adenomas from MBD4-deficient individuals showed a mutator phenotype attributable to mutational signature SBS1, consistent with the function of MBD4. MBD4-deficient polyps harbored somatic mutations in similar driver genes to sporadic colorectal tumors, although AMER1 mutations were more common and KRAS mutations less frequent. Our findings expand the role of BER deficiencies in tumor predisposition. Inclusion of MBD4 in genetic testing for polyposis and multi-tumor phenotypes is warranted to improve disease management