Survey of overnight academic hospitalist supervision of trainees

In 2003, Accreditation Council for Graduate Medical Education (ACGME) announced the first in a series of guidelines related to the residency training. The most recent recommendations include explicit recommendations regarding the provision of on‐site clinical supervision for trainees of internal medicine. To meet these standards, many internal medicine residency programs turned to hospitalist programs to fill that need. However, much is unknown about the current relationships between hospitalist and residency programs, specifically with regard to supervisory roles and supervision policies. We aimed to describe how academic hospitalists currently supervise housestaff during the on‐call, or overnight, period and hospitalist program leader their perceptions of how these new policies would impact trainee‐hospitalist interactions. Journal of Hospital Medicine 2012; © 2012 Society of Hospital MedicinePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93713/1/1961_ftp.pd

Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations

Background: Heterozygous mutations in OPA1 are a common cause of autosomal dominant optic atrophy, sometimes associated with extra-ocular manifestations. Few cases harboring compound heterozygous OPA1 mutations have been described manifesting complex neurodegenerative disorders in addition to optic atrophy. Results: We report here three patients: one boy showing an early-onset mitochondrial disorder with hypotonia, ataxia and neuropathy that was severely progressive, leading to early death because of multiorgan failure; two unrelated sporadic girls manifesting a spastic ataxic syndrome associated with peripheral neuropathy and, only in one, optic atrophy. Using a targeted resequencing of 132 genes associated with mitochondrial disorders, in two probands we found compound heterozygous mutations in OPA1: in the first a 5 nucleotide deletion, causing a frameshift and insertion of a premature stop codon (p.Ser64Asnfs*7), and a missense change (p.Ile437Met), which has recently been reported to have clinical impact; in the second, a novel missense change (p.Val988Phe) co-occurred with the p.Ile437Met substitution. In the third patient a homozygous mutation, c.1180G > A (p.Ala394Thr) in OPA1 was detected by a trio-based whole exome sequencing approach. One of the patients presented also variants in mitochondrial DNA that may have contributed to the peculiar phenotype. The deleterious effect of the identified missense changes was experimentally validated in yeast model. OPA1 level was reduced in available patients\u2019 biological samples, and a clearly fragmented mitochondrial network was observed in patients\u2019 fibroblasts. Conclusions: This report provides evidence that bi-allelic OPA1 mutations may lead to complex and severe multi-system recessive mitochondrial disorders, where optic atrophy might not represent the main feature

Clinical-genetic features and peculiar muscle histopathology in infantile DNM1L-related mitochondrial epileptic encephalopathy

Mitochondria are highly dynamic organelles, undergoing continuous fission and fusion. The DNM1L gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family, responsible for fission of mitochondria, and having a role in the division of peroxisomes, as well. DRP1 impairment is implicated in several neurological disorders and associated with either de novo dominant or compound heterozygous mutations. In five patients presenting with severe epileptic encephalopathy we identified 5 de novo dominant DNM1L variants, the pathogenicity of which was validated in a yeast model. Fluorescence microscopy revealed abnormally elongated mitochondria and aberrant peroxisomes in mutant fibroblasts, indicating impaired fission of these organelles. Moreover, a very peculiar finding in our cohort of patients was the presence, in muscle biopsy, of core like areas with oxidative enzyme alterations, suggesting an abnormal distribution of mitochondria in the muscle tissue

US public opinion regarding proposed limits on resident physician work hours

<p>Abstract</p> <p>Background</p> <p>In both Europe and the US, resident physician work hour reduction has been a source of controversy within academic medicine. In 2008, the Institute of Medicine (IOM) recommended a reduction in resident physician work hours. We sought to assess the American public perspective on this issue.</p> <p>Methods</p> <p>We conducted a national survey of 1,200 representative members of the public via random digit telephone dialing in order to describe US public opinion on resident physician work hour regulation, particularly with reference to the IOM recommendations.</p> <p>Results</p> <p>Respondents estimated that resident physicians currently work 12.9-h shifts (95% CI 12.5 to 13.3 h) and 58.3-h work weeks (95% CI 57.3 to 59.3 h). They believed the maximum shift duration should be 10.9 h (95% CI 10.6 to 11.3 h) and the maximum work week should be 50 h (95% CI 49.4 to 50.8 h), with 1% approving of shifts lasting >24 h (95% CI 0.6% to 2%). A total of 81% (95% CI 79% to 84%) believed reducing resident physician work hours would be very or somewhat effective in reducing medical errors, and 68% (95% CI 65% to 71%) favored the IOM proposal that resident physicians not work more than 16 h over an alternative IOM proposal permitting 30-h shifts with ≥5 h protected sleep time. In all, 81% believed patients should be informed if a treating resident physician had been working for >24 h and 80% (95% CI 78% to 83%) would then want a different doctor.</p> <p>Conclusions</p> <p>The American public overwhelmingly favors discontinuation of the 30-h shifts without protected sleep routinely worked by US resident physicians and strongly supports implementation of restrictions on resident physician work hours that are as strict, or stricter, than those proposed by the IOM. Strong support exists to restrict resident physicians' work to 16 or fewer consecutive hours, similar to current limits in New Zealand, the UK and the rest of Europe.</p

Valproate, thalidomide and ethyl alcohol alter the migration of HTR-8/SVneo cells

BACKGROUND: Valproate, thalidomide and alcohol (ethanol) exposure during the first trimester of pregnancy is known to cause several developmental disorders. All these teratogens are known to pass the placental barrier and interfere directly with the normal development of the fetus. However, these teratogens also alter the formation and function of the placenta itself which may in turn affect the proper nourishment and development of the fetus. Optimum development of the placenta requires adequate invasion of trophoblast into the maternal uterine tissues. Changes in the migratory behavior of trophoblast by maternal exposure to these teratogens during placentogenesis may therefore alter the structure and function of the placenta. METHODS: In the present study, the effects of sodium valproate, thalidomide and alcohol on the migration of human first trimester trophoblast cell line (HTR-8/SVneo) were examined in vitro. Cells were cultured in the wells of 48-well culture plates as mono or multilayers. Circular patches of cells were removed from the center of the wells by suction, and the migration of cells into the wound was studied using microscopy. Effects of low and high concentrations of valproate, thalidomide and alcohol were examined on the healing of wounds and on the migration rate of cells by determining the wound areas at 0, 3, 6, 12, 24 and 48 h. Effects of drugs and alcohol on the proliferation and the expression levels of integrin subunits beta1 and alpha5 in cells were examined. RESULTS: The migration rates of trophoblast differed between wounds created in mono and multilayers of cells. Exposure to teratogens altered the migration of trophoblast into mono and multilayer wounds. The effects of valproate, thalidomide and alcohol on the proliferation of cells during the rapid migratory phase were mild. Drug exposure caused significant changes in the expression levels of beta1 and alpha5 integrin subunits. CONCLUSION: Results suggest that exposure to valproate, thalidomide or alcohol during the first trimester of pregnancy may change the ultrastructure of the placenta by altering the migration of trophoblast cells and this effect may be mediated by drug- or alcohol-induced changes in the expression levels of beta1 and alpha5 integrin subunits

Novel NDUFA12 variants are associated with isolated complex I defect and variable clinical manifestation.

Isolated biochemical deficiency of mitochondrial complex I is the most frequent signature amongst mitochondrial diseases and is associated with a wide variety of clinical symptoms. Leigh syndrome represents the most frequent neuroradiological finding in patients with complex I defect and >80 monogenic causes have been involved in the disease. In this report, we describe 7 patients from four unrelated families harbouring novel NDUFA12 variants, 6 of them presenting with Leigh syndrome. Molecular genetic characterization was performed using next generation sequencing combined with the Sanger method. Biochemical and protein studies were achieved by enzymatic activities, blue native gel electrophoresis and Western blotting. All patients displayed novel homozygous mutations in the NDUFA12 gene leading to the virtual absence of the corresponding protein. Surprisingly, despite in none of the analyzed patients NDUFA12 protein was detected, they present a different onset and clinical course of the disease. Our report expands the array of genetic alterations in NDUFA12 and underlines phenotype variability associated with NDUFA12 defect. This article is protected by copyright. All rights reserved

Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies

Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31–1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29–1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40–1·66; p<0·0001) and endometrioid (1·42, 1·20–1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07–1·46, p=0·005). Interpretation The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users

SOSORT consensus paper: school screening for scoliosis. Where are we today?

This report is the SOSORT Consensus Paper on School Screening for Scoliosis discussed at the 4th International Conference on Conservative Management of Spinal Deformities, presented by SOSORT, on May 2007. The objectives were numerous, 1) the inclusion of the existing information on the issue, 2) the analysis and discussion of the responses by the meeting attendees to the twenty six questions of the questionnaire, 3) the impact of screening on frequency of surgical treatment and of its discontinuation, 4) the reasons why these programs must be continued, 5) the evolving aim of School Screening for Scoliosis and 6) recommendations for improvement of the procedure