Citations

BACKGROUNDBurnout is a syndrome affecting the entirety of work life and characterized by cynicism, detachment, and inefficacy. Despite longstanding concerns about burnout in hospital medicine, few data about burnout in hospitalists have been published.PURPOSEA systematic review of the literature on burnout in inpatient‐based and outpatient‐based physicians worldwide was undertaken to determine whether inpatient physicians experience more burnout than outpatient physicians.DATA SOURCESFive medical databases were searched for relevant terms with no language restrictions. Authors were contacted for unpublished data and clarification of the practice location of study subjects.STUDY SELECTIONTwo investigators independently reviewed each article. Included studies provided a measure of burnout in inpatient and/or outpatient nontrainee physicians.DATA EXTRACTIONFifty‐four studies met inclusion criteria, 15 of which provided direct comparisons of inpatient and outpatient physicians. Twenty‐eight studies used the same burnout measure and therefore were amenable to statistical analysis.DATA SYNTHESISOutpatient physicians reported more emotional exhaustion than inpatient physicians. No statistically significant differences in depersonalization or personal accomplishment were found. Further comparisons were limited by the heterogeneity of instruments used to measure burnout and the lack of available information about practice location in many studies.CONCLUSIONSThe existing literature does not support the widely held belief that burnout is more frequent in hospitalists than outpatient physicians. Better comparative studies of hospitalist burnout are needed. Journal of Hospital Medicine 2013;8:653–664. © 2013 Society of Hospital Medicine

Background: Cardiovascular (CV) disease is the leading cause of death in U.S. women. Although women are becoming more aware of CV disease, there remains a dichotomy between awareness and perceived risk. We sought to characterize this dichotomy in women attracted to a CV health–screening event, in order to improve strategies to reduce CV risk. Methods: During CV health events held in Rochester, Minnesota, from 2007 through 2011, 294 women underwent screening for blood chemistry, body mass index, and blood pressure. Participants also completed surveys about knowledge of CV disease, risk factors, and perceived risk. Risk level was determined from the 2011 American Heart Association Effectiveness-Based Guidelines for Women. Results: Among participants (age, mean [standard deviation], 53 [15.3] years; white, 98%), 99% were aware that CV disease is the leading cause of death in women. Almost half (47%) perceived themselves to be at personal risk, although 65% were determined to be “at risk” and 12% to be at “high risk” according to guidelines, while 22% were uncategorized. Of the 228 participants “at risk” or “high risk,” 48% and 21%, respectively, did not perceive themselves to be at any risk. Conclusions : Women attracted to CV health events were aware that CV disease is the leading cause of death for women. However, the magnitude of awareness did not directly translate into perception or understanding of actual personal risk. To decrease the rate of CV disease in women, continued efforts are needed to personalize the importance of, and the methods for reducing, CV risk factors.

Although comorbidity among complex diseases (e.g., drug dependence syndromes) is well documented, genetic variants contributing to the comorbidity are still largely unknown. The discovery of genetic variants and their interactions contributing to comorbidity will likely shed light on underlying pathophysiological and etiological processes, and promote effective treatments for comorbid conditions. For this reason, studies to discover genetic variants that foster the development of comorbidity represent high‐priority research projects, as manifested in the behavioral genetics studies now underway. The yield from these studies can be enhanced by adopting novel statistical approaches, with the capacity of considering multiple genetic variants and possible interactions. For this purpose, we propose a bivariate Mann‐Whitney (BMW) approach to unravel genetic variants and interactions contributing to comorbidity, as well as those unique to each comorbid condition. Through simulations, we found BMW outperformed two commonly adopted approaches in a variety of underlying disease and comorbidity models. We further applied BMW to datasets from the Study of Addiction: Genetics and Environment, investigating the contribution of 184 known nicotine dependence (ND) and alcohol dependence (AD) single nucleotide polymorphisms (SNPs) to the comorbidity of ND and AD. The analysis revealed a candidate SNP from CHRNA5, rs16969968, associated with both ND and AD, and replicated the findings in an independent dataset with a P‐value of 1.06 × 10–03.

Abstract Because studies of the association between tricyclic antidepressant (TCA) treatment and risk of fracture have shown inconsistent findings, we sought to assess whether people who take TCAs are at increased risk of fracture. Relevant studies published by June 2012 were identified through database searches of Scopus, MEDLINE, EMBASE, PsycINFO, ISI Web of Science, and WorldCat Dissertations and Theses from their inception, and manual searching of reference lists. Only original studies that examined the association between TCA treatment and risk of fracture were included. Two investigators independently conducted literature searches, study selection, study appraisal, and data abstraction using a standardized protocol. Disagreements were resolved by consensus. Twelve studies met inclusion criteria. Because of the heterogeneity of these studies, random-effects models were used to pool estimates of effect. Overall, TCA use was associated with significantly increased fracture risk (relative risk [RR], 1.45; 95% confidence interval [CI], 1.31–1.60; p < 0.001). Increased fracture risk associated with TCA use was also observed in studies that adjusted for bone mineral density (RR, 1.54; 95% CI, 1.24–1.90; p < 0.001) or depression (RR, 1.49; 95% CI, 1.28–1.67; p < 0.001). Strength of association with TCA exposure duration ≥6 weeks (RR, 1.13; 95% CI, 1.00–1.28) was substantially weaker than association with TCA exposure duration <6 weeks (RR, 2.40; 95% CI, 1.41–4.08). Prior TCA exposure had no significant effect on fracture risk (RR, 1.04; 95% CI, 0.86–1.26; p = 0.70). After accounting for publication bias, we found the overall association between TCA use and fracture risk to be slightly weaker (RR, 1.36; 95% CI, 1.24–1.50) but still significant (p < 0.001). Findings of this meta-analysis indicate that treatment with TCAs may convey an increased risk of fracture, independent of depression and bone mineral density. © 2013 American Society for Bone and Mineral Research.

Background and Purpose— Telestroke reduces acute stroke care disparities between urban stroke centers and rural hospitals. Current technologies used to conduct remote patient assessments have high start-up costs, yet they cannot consistently establish quality timely connections. Smartphones can be used for high-quality video teleconferencing. They are inexpensive and ubiquitous among health care providers. We aimed to study the reliability of high-quality video teleconferencing using smartphones for conducting the National Institutes of Health Stroke Scale (NIHSS). Methods— Two vascular neurologists assessed 100 stroke patients with the NIHSS. The remote vascular neurologist assessed subjects using smartphone videoconferencing with the assistance of a bedside medical aide. The bedside vascular neurologist scored patients contemporaneously. Each vascular neurologist was blinded to the other’s NIHSS scores. We tested the inter-method agreement and physician satisfaction with the device. Results— We demonstrated high total NIHSS score correlation between the methods ( r =0.949; P <0.001). The mean total NIHSS scores for bedside and remote assessments were 7.93±8.10 and 7.28±7.85, with ranges, of 0 to 35 and 0 to 37, respectively. Eight categories had high agreement: level of consciousness (questions), level of consciousness (commands), visual fields, motor left and right (arm and leg), and best language. Six categories had moderate agreement: level of consciousness (consciousness), best gaze, facial palsy, sensory, dysarthria, and extinction/inattention. Ataxia had poor agreement. There was high physician satisfaction with the smartphone. Conclusions— Smartphone high-quality video teleconferencing is reliable, easy to use, affordable for telestroke NIHSS administration, and has high physician satisfaction.

Common complex diseases are likely influenced by the interplay of hundreds, or even thousands, of genetic variants. Converging evidence shows that genetic variants with low marginal effects (LMEs) play an important role in disease development. Despite their potential significance, discovering LME genetic variants and assessing their joint association on high‐dimensional data (e.g., genome‐wide data) remain a great challenge. To facilitate joint association analysis among a large ensemble of LME genetic variants, we proposed a computationally efficient and powerful approach, which we call Trees Assembling Mann‐Whitney (TAMW). Through simulation studies and an empirical data application, we found that TAMW outperformed multifactor dimensionality reduction (MDR) and the likelihood ratio‐based Mann‐Whitney approach (LRMW) when the underlying complex disease involves multiple LME loci and their interactions. For instance, in a simulation with 20 interacting LME loci, TAMW attained a higher power (power = 0.931) than both MDR (power = 0.599) and LRMW (power = 0.704). In an empirical study of 29 known Crohn's disease (CD) loci, TAMW also identified a stronger joint association with CD than those detected by MDR and LRMW. Finally, we applied TAMW to Wellcome Trust CD GWAS to conduct a genome‐wide analysis. The analysis of 459K single nucleotide polymorphisms was completed in 40 hrs using parallel computing, and revealed a joint association predisposing to CD (P‐value = 2.763 × 10−19). Further analysis of the newly discovered association suggested that 13 genes, such as ATG16L1 and LACC1, may play an important role in CD pathophysiological and etiological processes.

Primary cilia serve as cellular antenna for various sensory signaling pathways. However, how the sensory receptors are properly targeted to the ciliary surface remains poorly understood. Here, we show that UBC-9, the sole E2 small ubiquitin-like modifier (SUMO)-conjugating enzyme, physically interacts with and SUMOylates the C terminus of small GTPase ARL-13, the worm orthologue of ARL13B that mutated in ciliopathy Joubert syndrome. Mutations that totally abolish the SUMOylation of ARL-13 do not affect its established role in ciliogenesis, but fail to regulate the proper ciliary targeting of various sensory receptors and consequently compromise the corresponding sensory functions. Conversely, constitutively SUMOylated ARL-13 fully rescues all ciliary defects of arl-13–null animals. Furthermore, SUMOylation modification of human ARL13B is required for the ciliary entry of polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease. Our data reveal a novel but conserved role for the SUMOylation modification of ciliary small GTPase ARL13B in specifically regulating the proper ciliary targeting of various sensory receptors.

AbstractMany common genetic variants have been associated with non-Hodgkin lymphoma (NHL), but individual study results are often conflicting. To confirm the role of putative risk alleles in B-cell NHL etiology, we performed a validation genotyping study of 67 candidate single nucleotide polymorphisms within InterLymph, a large international consortium of NHL case-control studies. A meta-analysis was performed on data from 5633 B-cell NHL cases and 7034 controls from 8 InterLymph studies. rs3789068 in the proapoptotic BCL2L11 gene was associated with an increased risk for B-cell NHL (odds ratio = 1.21, P random = 2.21 × 10−11), with similar risk estimates for common B-cell subtypes. PRRC2A rs3132453 in the HLA complex class III region conferred a reduced risk of B-cell NHL (odds ratio = 0.68, P random = 1.07 × 10−9) and was likewise evident for common B-cell subtypes. These results are consistent with the known biology of NHL and provide insights into shared pathogenic components, including apoptosis and immune regulation, for the major B-cell lymphoma subtypes.

Abstract Recent molecular and pathologic evidence indicate that high-grade serous carcinomas of the ovary, which are the most common type of epithelial carcinomas, may arise from the distal part of fallopian tubes or tubal carcinoma implants. Oviductal glycoprotein 1 (Ovgp1), a glycosylated protein found in the epithelial cells in the oviduct, is the only specific tubal marker so far. Ovgp1 promoter-driven SV40 large T-antigen transgenic mice develop tumors in the female reproductive organs. To characterize these tumors, we performed immunohistochemical analysis in paraffin-embedded sections. Mice were sacrificed at 8 or 13 weeks old. Macroscopically we observed large tumors in the uterus and cervix and markedly enlarged region in the oviduct. Due to the large tumor in the uterus and cervix, we could not keep the mice longer than 13 weeks. Histologically, there were no major differences in these affected regions between 8 weeks old and 13 weeks old mice. We observed, (i) relatively small ovaries and ovarian follicular hyperplasia, (ii) intact ovarian surface epithelium showing no atypical histology, (iii) atypical epithelial hyperplasia within the oviduct (with endometrioid architectural and cytologic features), (iv) leiomyosarcomatous proliferation in the myometrium, and (v) squamous carcinoma in situ in the cervix or early invasive cervical cancer with extensive papillary architecture. We did not detect metastasis from the tumor to other organs. The atypical abnormalities of the oviduct were more significant in the proximal site to the uterus than the distal site. The proximal oviduct demonstrated weak and spotty p53 expression, beneath the epithelium, similar to p53 signature in the human oviduct. We hypothesized that stem cell components may contribute to the tumor development and that putative cancer stem cells could be identified by stem cell markers. In the oviduct epithelium, Bmi1 expression was not detectable. Cytoplasmic expression of Sox2 was observed in all epithelial cells of the oviduct. There was little correlation between Sox2/Bmi1 staining and p53 staining in the oviduct. Interestingly, Sox2 and Bmi1 staining in the wild-type control mice showed immunoreactive cells interspersed between glandular structures, a pattern similar to previously described label-retaining cells in the endometrium. The expression pattern in Ovgp1-SV40 mice, Bmi1 and Sox2 expression were more obvious in the endometrial stromal area but not in the leiomyosarcoma region, which implies that stem cell components in the endometrial region may support the leiomyosarcoma progression in this mouse model. In conclusion, Ovgp1-SV40 transgenic mouse is a useful model for studies involving fallopian and lower genital tract carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3272. doi:1538-7445.AM2012-3272