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The authors conducted a prospective longitudinal study from 2009 to 2016 to assess the short and long-term impact of a formal mentorship program on junior faculty satisfaction and productivity. Junior faculty mentees enrolled in the program and junior faculty without formal mentorship were administered surveys before and after the program to assess satisfaction with their mentoring experiences. Long-term retention, promotion, and funding data were also collected. Twenty-three junior faculty mentees and 91 junior faculty controls were included in the study. Mentees came from the Departments of Radiation Oncology and Anesthesia, Critical Care, and Pain Management. After participating in the mentorship program, mentees demonstrated an increase in satisfaction from baseline in five of seven domains related to mentoring, while controls experienced no significant change in satisfaction in six of the seven domains. At long-term follow up, mentees were more likely than controls to hold senior faculty positions (percent senior faculty: 47% vs. 13%, p = 0.030) despite no difference in initial administrative rank. When comparing the subset of faculty who were Instructors at baseline, mentees were more likely to be funded and/or promoted than controls (p = 0.030). A majority of mentees reported that the program strengthened their long-term success, and many maintained their original mentoring relationships and formed new ones, highlighting the strong culture of mentorship that was instilled. Several short-term and long-term benefits were fostered from this formal mentorship program. These findings highlight the potential impact of mentorship programs in propagating a culture of mentorship and excellence. [ABSTRACT FROM AUTHOR]

A lack of physician scientists as well as a high female dropout rate from academic medicine and basic life sciences is a concern in many countries. The current study analyzes academic career intentions within a sample of recent doctoral graduates from medicine and basic life sciences (N = 1109), focusing on research self-efficacy beliefs as explanatory variable of gender and disciplinary differences. To ensure that differences in research self-efficacy could not be attributed solely to objective scientific performance, we controlled for number of publications and dissertation grade. The results of multivariate analyses pointed to a strong and significant association between research self-efficacy and academic career intentions (ß = 0.49, p<0.001). The lower academic career intentions of medical doctoral graduates were no longer significant when controlling for research self-efficacy. Within the field of medicine, female doctoral graduates expressed lower research self-efficacy beliefs and academic career intentions. When controlling for research self-efficacy, the correlation between gender and academic career intention was no longer significant. In contrast, no gender differences were found within the basic life sciences with respect to neither academic career intentions nor research self-efficacy. [ABSTRACT FROM AUTHOR]

Objectives: Choosing the right mentor is crucial for effective mentorship. Yet, many medical students have difficulties finding a suitable mentor. Thus we developed mentoring speed dating (MSD) as a promising matching tool to connect students and faculty mentors successfully. The purpose of this study was to explore mentees’ and mentors’ experience with MSD and investigate the impact of MSD on the perceived mentorship quality and continuance of the mentoring relationship. Methods: The authors completed a mixed methods study at the University Medical Center Hamburg-Eppendorf, Germany, between June 2011 and March 2014. They conducted four focus groups with mentees and mentors who participated in a mentoring speed dating event and analyzed transcripts using conventional content analysis with inductive categorizing. In addition, three mentoring cohorts (two matched via MSD, one matched via conventional online profiles) were surveyed on mentorship satisfaction and the 1-year continuance of their mentorship was monitored. Fifteen mentees and fifteen mentors participated in the focus groups. The authors identified several themes such as short and long term benefits of MSD and fulfillment of expectations. Benefits included finding out about the personal connection, matching expectations, providing an efficient overview of candidates. The survey was completed by 93 students (n = 29 without MSD; n = 64 with MSD). Independent t-tests and multivariate analysis of variance were used to analyze the impact of MSD on student’s mentorship satisfaction. Results: There were significant differences in responses to the items “Commitment of mentor” (p = .019) and “Constructive feedback” (p = .038) among the students who attended MSD and the students without MSD. After one year far more mentoring relationships existed among those mentees who participated in MSD in comparison to the “no MSD group”. Conclusion: MSD is a valuable matching tool with beneficial effects on the mentorship quality. It enhances essential factors in the mentoring relationship such as commitment and satisfaction. [ABSTRACT FROM AUTHOR]

3-dimensional (3D) culture models have the potential to bridge the gap between monolayer cell culture and in vivo studies. To benefit anti-cancer drug discovery from 3D models, new techniques are needed that enable their use in high-throughput (HT) screening amenable formats. We have established miniaturized 3D culture methods robust enough for automated HT screens. We have applied these methods to evaluate the sensitivity of normal and tumorigenic breast epithelial cell lines against a panel of oncology drugs when cultured as monolayers (2D) and spheroids (3D). We have identified two classes of compounds that exhibit preferential cytotoxicity against cancer cells over normal cells when cultured as 3D spheroids: microtubule-targeting agents and epidermal growth factor receptor (EGFR) inhibitors. Further improving upon our 3D model, superior differentiation of EC50 values in the proof-of-concept screens was obtained by co-culturing the breast cancer cells with normal human fibroblasts and endothelial cells. Further, the selective sensitivity of the cancer cells towards chemotherapeutics was observed in 3D co-culture conditions, rather than as 2D co-culture monolayers, highlighting the importance of 3D cultures. Finally, we examined the putative mechanisms that drive the differing potency displayed by EGFR inhibitors. In summary, our studies establish robust 3D culture models of human cells for HT assessment of tumor cell-selective agents. This methodology is anticipated to provide a useful tool for the study of biological differences within 2D and 3D culture conditions in HT format, and an important platform for novel anti-cancer drug discovery. [ABSTRACT FROM AUTHOR]

Background: Recent qualitative studies indicated that physicians interact with pharmaceutical representatives depending on the relative weight of the benefits to the risks and are also influenced by a variety of experiences and circumstances. However, these studies do not provide enough information about if, when, how and why their attitudes and behaviors change over time. Methods and Findings: A qualitative study using semi-structured face-to-face individual interviews was conducted on 9 Japanese physicians who attended a symposium on conflicts of interest held in Tokyo. Interviews were designed to explore chronological changes in individual physicians' attitude and behavior concerning relationships with pharmaceutical representatives and factors affecting such changes. Their early interaction with pharmaceutical representatives was passive as physicians were not explicitly aware of the meaning of such interaction. They began to think on their own about how to interact with pharmaceutical representatives as they progressed in their careers. Their attitude toward pharmaceutical representatives changed over time. Factors affecting attitudinal change included work environment (local regulations and job position), role models, views of patients and the public, acquisition of skills in information seeking and evidence-based medicine, and learning about the concepts of professionalism and conflict of interest. However, the change in attitude was not necessarily followed by behavioral change, apparently due to rationalization and conformity to social norms. Conclusions: Physicians' attitudes toward relationships with pharmaceutical representatives changed over time and factors affecting such changes were various. Paying attention to these factors and creating new social norms may be both necessary to produce change in behavior consistent with change in attitude. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify the factors perceived by surgeons that promote surgery as an attractive or unattractive career choice for today’s graduates. In addition, it examined whether the perspectives of surgeons in different professional situations converges. The content of work, contextual work conditions, and calling to this job are discussed in the context of choosing surgery as a career. Methods: Eight hundred sixty-nine surgeons were asked to answer open-ended questions regarding the factors that promote surgery as an attractive or unattractive career choice for today’s graduates. Four hundred ninety-two surgeons participated, and 1,525 statements were analyzed using Mayring’s content-analyses method. Chi-square tests were used to analyze the differences among hierarchical positions. Results: With respect to the factors that promote surgery as a profession, 40.8% (209/492) of the surgeons stated that surgery is a calling, 29.1% (149/492) of the surgeons provided at least one argument related to the positive task characteristics, and 12.9% (66/492) of the surgeons provided statements related to the positive contextual factors. With respect to the factors that discourage surgery as a profession, 45.7% (234/492) of the surgeons provided at least one argument related to the discouraging work characteristics, and 67.6% (346/492) of the surgeons provided problematic contextual characteristics. Conclusion: This study emphasizes the importance of the calling to surgery as an important factor for choosing surgery as a career. However, the extensive workload, training, and poor work-family balance have been identified as factors that discourage graduates from choosing surgery as a career. The identified positive factors could be used to attract and maintain graduates in surgical disciplines. [ABSTRACT FROM AUTHOR]

Objective: To describe an innovative approach for developing and implementing an in-service curriculum in China for staff of the newly established health emergency response offices (HEROs), and that is generalisable to other settings. Methods: The multi-method training needs assessment included reviews of the competency domains needed to implement the International Health Regulations (2005) as well as China’s policies and emergency regulations. The review, iterative interviews and workshops with experts in government, academia, the military, and with HERO staff were reviewed critically by an expert technical advisory panel. Findings: Over 1600 participants contributed to curriculum development. Of the 18 competency domains identified as essential for HERO staff, nine were developed into priority in-service training modules to be conducted over 2.5 weeks. Experts from academia and experienced practitioners prepared and delivered each module through lectures followed by interactive problem-solving exercises and desktop simulations to help trainees apply, experiment with, and consolidate newly acquired knowledge and skills. Conclusion: This study adds to the emerging literature on China’s enduring efforts to strengthen its emergency response capabilities since the outbreak of SARS in 2003. The multi-method approach to curriculum development in partnership with senior policy-makers, researchers, and experienced practitioners can be applied in other settings to ensure training is responsive and customized to local needs, resources and priorities. Ongoing curriculum development should reflect international standards and be coupled with the development of appropriate performance support systems at the workplace for motivating staff to apply their newly acquired knowledge and skills effectively and creatively. [ABSTRACT FROM AUTHOR]

Background: The interaction between physicians and the pharmaceutical industry influences physicians' attitudes and prescribing behavior. Although largely studied in the US, this topic has not been well studied in resource-poor settings, where a close relationship between physicians and industry still exists. Objective: To describe physician interactions with and attitudes towards the pharmaceutical industry in a public general hospital in Lima, Peru. Design: Descriptive, cross-sectional study through an anonymous, self-filled questionnaire distributed among faculty and trainee physicians of five different clinical departments working in a Peruvian public general hospital. A transcultural validation of an existing Spanish questionnaire was performed. Exposure to marketing activities, motivations to contact pharmaceutical representatives and attitudes towards industry were studied. Collected data was analyzed by degree of training, clinical department, gender and teaching status. Attitudes were measured on a four-point LIKERT scale. Results: 155 physicians completed the survey, of which 148 were included in the study sample. 94.5% of attending physicians reported ongoing encounters with pharmaceutical representatives. The most common industry-related activities were receiving medical samples (91.2%), promotional material (87.8%) and attending meetings in restaurants (81.8%). Respondents considered medical samples and continuing medical education the most ethically acceptable benefits. We found significant differences between attendings and residents, and teaching and non-teaching attendings. An association between the amount of encounters with pharmaceutical representatives, and attitudes towards industry and acceptance of medical samples was found. Conclusions: A close physician-industry relationship exists in the population under study. The contact is established mainly through pharmaceutical representatives. Medical samples are the most received and ethically accepted benefit. The attitudes of physicians on the ethical standards of acceptance of medical samples and other benefits are closely related with their exposure to the pharmaceutical industry. Future studies could explore the motivations of physicians working in resource-poor settings to maintain a close relationship with industry. [ABSTRACT FROM AUTHOR]

Background: Worldwide, attending physicians train residents to become competent providers of patient care. To assess adequate training, attending physicians are increasingly evaluated on their teaching performance. Research suggests that personality traits affect teaching performance, consistent with studied effects of personality traits on job performance and academic performance in medicine. However, up till date, research in clinical teaching practice did not use quantitative methods and did not account for specialty differences. We empirically studied the relationship of attending physicians' personality traits with their teaching performance across surgical and non-surgical specialties. Method: We conducted a survey across surgical and non-surgical specialties in eighteen medical centers in the Netherlands. Residents evaluated attending physicians' overall teaching performance, as well as the specific domains learning climate, professional attitude, communication, evaluation, and feedback, using the validated 21-item System for Evaluation of Teaching Qualities (SETQ). Attending physicians self-evaluated their personality traits on a 5-point scale using the validated 10-item Big Five Inventory (BFI), yielding the Five Factor model: extraversion, conscientiousness, neuroticism, agreeableness and openness. Results: Overall, 622 (77%) attending physicians and 549 (68%) residents participated. Extraversion positively related to overall teaching performance (regression coefficient, B: 0.05, 95% CI: 0.01 to 0.10, P = 0.02). Openness was negatively associated with scores on feedback for surgical specialties only (B: −0.10, 95% CI: −0.15 to −0.05, P<0.001) and conscientiousness was positively related to evaluation of residents for non-surgical specialties only (B: 0.13, 95% CI: 0.03 to 0.22, p = 0.01). Conclusions: Extraverted attending physicians were consistently evaluated as better supervisors. Surgical attending physicians who display high levels of openness were evaluated as less adequate feedback-givers. Non-surgical attending physicians who were conscientious seem to be good at evaluating residents. These insights could contribute to future work on development paths of attending physicians in medical education. [ABSTRACT FROM AUTHOR]

Background: Death certificates are a primary data source for assessing the population burden of diseases; however, there are concerns regarding their accuracy. Diagnosis-Related Group (DRG) coding of a terminal hospitalization may provide an alternative view. We analyzed the rate and patterns of disagreement between death certificate data and hospital claims for patients who died during an inpatient hospitalization. Methods: We studied respondents from the Health and Retirement Study (a nationally representative sample of older Americans who had an inpatient death documented in the linked Medicare claims from 1993–2007). Causes of death abstracted from death certificates were aggregated to the standard National Center for Health Statistics List of 50 Rankable Causes of Death. Centers for Medicare and Medicaid Services (CMS)-DRGs were manually aggregated into a parallel classification. We then compared the two systems via 2×2, focusing on concordance. Our primary analysis was agreement between the two data sources, assessed with percentages and Cohen's kappa statistic. Results: 2074 inpatient deaths were included in our analysis. 36.6% of death certificate cause-of-death codes agreed with the reason for the terminal hospitalization in the Medicare claims at the broad category level; when re-classifying DRGs without clear alignment as agreements, the concordance only increased to 61%. Overall Kappa was 0.21, or “fair.” Death certificates in this cohort redemonstrated the conventional top 3 causes of death as diseases of the heart, malignancy, and cerebrovascular disease. However, hospitalization claims data showed infections, diseases of the heart, and cerebrovascular disease as the most common diagnoses for the same terminal hospitalizations. Conclusion: There are significant differences between Medicare claims and death certificate data in assigning cause of death for inpatients. The importance of infections as proximal causes of death is underestimated by current death certificate-based strategies. [ABSTRACT FROM AUTHOR]

Clinical practice guidelines (CPGs) have been developed to summarize evidence about the management of rheumatoid arthritis (RA) and facilitate the uptake of evidence-based knowledge by consumers, health professionals, health administrators and policy makers. The objectives of this review was to assess the quality of CPGS on non-pharmacological management of RA with a standardized and validated instrument - the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool and summarize the key recommendations from these CPGs. Scientific literature databases from 2001 to 2013 were systematically searched and a total of 13 CPGs for RA was identified. Only a minority of AGREE II domains were effectively addressed by the CPGS. Scope and purpose was effectively addressed in 10 out of 13 CPGs, stakeholder involvement in 11 CPGs, rigor of development in 6 CPGs, clarity/presentation in 9 CPGs, editorial independence in 1 CPGs, and applicability in none of the CPGs. The overall quality of the included CPGs according to the 7-point AGREE II scoring system was 4.8±1.04. Patient education/self-management, aerobic, dynamic and stretching exercises were the commonly recommended for the non-pharmacological management of RA by the high-quality CPGs. The general clinical management recommendations tended to be similar among high-quality CPGs. Non-pharmacological management interventions were superficially addressed in more than half of the selected CPGs. CPGs creators should use the AGREE II criteria when developing guidelines. Innovative and effective methods of CPGs implementation to users are needed to ultimately enhance the quality of life of arthritic individuals. In addition, it was difficult to establish between strongly recommended, recommended and weakly recommended, as there is no consensus between the strength of the recommendations between the appraised CPGs. [ABSTRACT FROM AUTHOR]

Retinal neovascularization (RNV) is an eye disease that can cause retinal detachment and even lead to blindness. RNV mainly occurs in the elderly population. The pathogenesis of RNV has been previously reported to be highly related to the expression of vascular endothelial growth factor A (VEGFA), basic fibroblast growth factor (bFGF) and other angiogenic factors. It has also been reported that VEGFA and other factors associated with RNV could be regulated by certain microRNAs (miRNA), a group of small non-coding RNAs which are able to regulate the expression of many genes in vivo. Here, we demonstrate that the miRNA miR-410 is highly expressed in mice within two weeks after birth. miR-410 could suppress VEGFA expression through interaction with the 3′UTR of the VEGFA messenger RNA. Overexpressing a miR-410 mimic effectively suppresses VEGFA expression in various cell lines. Further experiments on oxygen-induced retinopathy (OIR) in mice revealed that eye drops containing large amounts of miR-410 efficiently downregulate VEGFA expression, prevent retinal angiogenesis and effectively treat RNV. These results not only show the underlying mechanism of how miR-410 targets VEGFA but also provide a potential treatment strategy for RNV that might be used in the near future. [ABSTRACT FROM AUTHOR]

Background: Substantial residual cardiovascular risk remains after optimal LDL lowering in patients of established coronary artery disease. A number of therapeutic agents that raise HDL-C have been tested in clinical trials to cover this risk. However, the results of clinical trials are conflicting. Objectives: To determine whether raising HDL-C with pharmacologic therapies translates into beneficial cardiovascular outcomes and to find out if this change was proportional to the percentage change in HDL levels. Methods: Electronic and printed sources were searched up to August, 2013 for randomised controlled trials (RCTs) using at least one of the HDL raising therapies for secondary prevention of adverse cardiovascular events over optimal LDL levels. Data from eligible studies were pooled for the following outcomes: all cause mortality, cardiovascular disease mortality, hospitalization for unstable angina, non-fatal myocardial infarction, coronary revascularization and ischemic stroke. Mantel Haensnzel fixed effect model was used preferentially. Meta-regression was done to see the correlation of change in HDL levels and cardiovascular outcomes. Pooled odds ratios with 95% confidence interval (CI) were calculated. Results: A total of 12 RCTs including 26,858 patients with follow up period ranging from 1 year to 6.2 years were included in the analysis. Pooled analysis showed no significant difference in all-cause mortality between the treatment and control group (Pooled OR 1.07; 95% CI 0.98–1.16, p = 0.15). No significant difference was found between the groups for any of the secondary outcomes. Similarly no correlation was seen between percentage change in HDL and adverse cardiovascular outcomes on meta-regression analysis. Conclusion: Increasing HDL levels via pharmacological manipulation beyond optimal lipid lowering therapy for secondary prevention is not beneficial. [ABSTRACT FROM AUTHOR]

Given that integrin β1 is an important component of the connection to maintain glomerular structural integrity, by binding with multiple extracellular matrix proteins and mediating intracellular signaling. Focal adhesion kinase (FAK) is the most essential intracellular integrator in the integrin β1-FAK signalling pathway. Here, we investigated the changes of the two molecules and visualized the possbile interaction between them under various hemodynamic conditions in podocytes. Mice kidney tissues were prepared using in vivo cryotechnique (IVCT) and then were stained and observed using light microscopy, confocal laser scanning microscopy and immunoelectron microscopy. The expression of these molecules were examined by western blot. Under the normal condition, integrin β1 stained continually and evenly at the membrane, and FAK was located in the cytoplasm and nuclei of the podocytes. There were significant colocalized plaques of two molecules. But under acute hypertensive and cardiac arrest conditions, integrin β1 decreased and stained intermittently. Similarly, FAK decreased and appeared uneven. Additionally, FAK translocated to the nuclei of the podocytes. As a result, the colocalization of integrin β1 and FAK reduced obviously under these conditions. Western blot assay showed a consistent result with the immunostaining. Collectively, the abnormal redistribution and decreased expressions of integrin β1 and FAK are important molecular events in regulating the functions of podocytes under abnormal hemodynamic conditions. IVCT could offer considerable advantages for morphological analysis when researching renal diseases. [ABSTRACT FROM AUTHOR]

Background: We aimed to assess medical students' empathy and its associations with gender, stage of medical school, quality of life and burnout. Method: A cross-sectional, multi-centric (22 medical schools) study that employed online, validated, self-reported questionnaires on empathy (Interpersonal Reactivity Index), quality of life (The World Health Organization Quality of Life Assessment) and burnout (the Maslach Burnout Inventory) in a random sample of medical students. Results: Out of a total of 1,650 randomly selected students, 1,350 (81.8%) completed all of the questionnaires. Female students exhibited higher dispositional empathic concern and experienced more personal distress than their male counterparts (p<0.05; d≥0.5). There were minor differences in the empathic dispositions of students in different stages of their medical training (p<0.05; f<0.25). Female students had slightly lower scores for physical and psychological quality of life than male students (p<0.05; d<0.5). Female students scored higher on emotional exhaustion and lower on depersonalization than male students (p<0.001; d<0.5). Students in their final stage of medical school had slightly higher scores for emotional exhaustion, depersonalization and personal accomplishment (p<0.05; f<0.25). Gender (β = 0.27; p<0.001) and perspective taking (β = 0.30; p<0.001) were significant predictors of empathic concern scores. Depersonalization was associated with lower empathic concern (β = −0.18) and perspective taking (β = −0.14) (p<0.001). Personal accomplishment was associated with higher perspective taking (β = 0.21; p<0.001) and lower personal distress (β = −0.26; p<0.001) scores. Conclusions: Female students had higher empathic concern and personal distress dispositions. The differences in the empathy scores of students in different stages of medical school were small. Among all of the studied variables, personal accomplishment held the most important association with decreasing personal distress and was also a predicting variable for perspective taking. [ABSTRACT FROM AUTHOR]

Background: Primary health care and patient triage are two basic functions of rural hospitals. As a routine test, the diagnostic radiology is still unavailable in some rural hospitals in China. Therefore, high-level hospitals are often the first choice of rural residents when they feel unwell. It brings serious social problems. This study was designed to propose an on-the-job drilling schema with integration of practical medical recordings and experienced radiological doctors as tutors to improve skills in diagnostic radiology of rural physicians. Methods: The information technology was used to help the contact between rural doctors and tutors. In a longitudinal pre/post-test control study design, a cohort of 20 young physicians, each of whom was working in a rural hospital and had a work experience less than two years, were established as the trial group over one year. Another 20 similar counterparts were established as the control group. Participants' performances were evaluated in four categories at five-time point (TP). Results: The trial group significantly outscored the control group on the style of writing at the second TP (d = 2.28); on the accuracy of the image description at final TP (d = 1.11); on the accuracy of the diagnosis at the fourth TP (d = 3.62); and on the correct treatment selection at the third TP (d = 6.45). The aspects with the most improvement were the accuracies of the diagnosis and the treatment selection. Conclusion: This study provided the detailed evidences that applying the on-the-job drilling schema has a significant effect on the skills improvement in diagnostic radiology of rural physicians. It was also concluded that the educational intervention based on practical cases was better than that only based on didactic slides presentation. [ABSTRACT FROM AUTHOR]

Introduction: Staff time is a relevant resource in the delivery of health care interventions. Its measurement is a prerequisite for unit costing but usually complex. The aim of this study was to analyse the distribution of surgeons' work time among types and places of activities. A second aim was to use these data to calculate costs per unit of output. Methods: A self-reporting work sampling study was carried out at a department of Urology. All of twelve surgeons involved in clinical care participated in a two-week analysis of their work time. Results: A total of 2,485 data-points were collected, representing about 1,242 hours of work time. Surgeons spent the greater part of their work time in direct patient care, but substantial shares were required for documentation and organisation. Assistants were mainly required at the wards and consultants at the operating theatre and the outpatient unit. Staff costs of surgeons were 32 € and 29 € per patient day at the wards, respectively, 1.30 € per minute at the operating theatre and 32 € per visit at the outpatient unit. Conclusion: Results provided a basis for costing of health care interventions at the study site. However, future research should focus on the establishment of standardised terminology in order to increase transferability of results. [ABSTRACT FROM AUTHOR]

Background: The decision to discharge a patient from a hospital is a complex process governed by many medical and non-medical factors, while the actual reasons for discharge frequently remain ill-defined. Aim: To define relevant discharge criteria as perceived by doctors, nurses and patients for the development of a standard hospital discharge policy, we collected actual reasons and most pivotal medical and organisational criteria for discharge among all stakeholders. Setting: A tertiary referral university teaching hospital. Methods: We conducted a mixed methods analysis, using patient questionnaires, interviews and a focus group with caregivers, and observations during the daily rounds of doctors, nurses and patients during their hospital stay. Fourteen wards of the Surgery, Paediatrics and Neurology departments contributed. Results: We observed 426 patients during their hospital stay. Forty doctors and nurses were interviewed, and 7 senior nurses attended a focus group. The most commonly used discharge criteria were clinical factors, organisational discharge issues and patient-related factors. A total of 269 patients returned their questionnaires. About one third of the adult patients and nearly half of the children (or their parents) felt their personal situation and assistance needed at home was insufficiently taken into account before discharge. Patients were least satisfied with the information given about what they were allowed to do or should avoid after discharge and their involvement in the planning of their discharge. Thus, besides obvious medical reasons for discharge, several non-medical reasons were signalled by all stakeholders as important issues to be improved. Conclusions: A set of discharge criteria could be defined that is useful for a more uniform hospital discharge policy that may help reduce unnecessary length of stay and improve patient satisfaction. [ABSTRACT FROM AUTHOR]

Background: Internal medicine fellowship programs have an incentive to select fellows who will ultimately publish. Whether an applicant's publication record predicts long term publishing remains unknown. Methods: Using records of fellowship bound internal medicine residents, we analyzed whether publications at time of fellowship application predict publications more than 3 years (2 years into fellowship) and up to 7 years after fellowship match. We calculate the sensitivity, specificity, positive and negative predictive values and likelihood ratios for every cutoff number of application publications, and plot a receiver operator characteristic curve of this test. Results: Of 307 fellowship bound residents, 126 (41%) published at least one article 3 to 7 years after matching, and 181 (59%) of residents do not publish in this time period. The area under the receiver operator characteristic curve is 0.59. No cutoff value for application publications possessed adequate test characteristics. Conclusion: The number of publications an applicant has at time of fellowship application is a poor predictor of who publishes in the long term. These findings do not validate the practice of using application publications as a tool for selecting fellows. [ABSTRACT FROM AUTHOR]

Background: Patient chart review is the gold standard for detection of potential patient hazards (i.e. medication errors or failure to follow up actionable results) in both routine clinical care and patient safety research. However, advanced medical students’ ability to read patient charts and to identify patient hazards is rather poor. We therefore investigated whether it is possible to teach advanced medical students how to identify patient hazards independent of context (i.e. cancer versus cardiac failure) in patient charts. Methods: All fifth-year medical students in one semester (n = 123) were randomized into two groups. One group (IC) received a patient chart review-training first and then a control-intervention and the other group (CI) received the control-intervention first and then the patient chart review-training. Before and after the teaching sessions, students reviewed different scenarios with standardized fictional patient charts containing 12 common patient hazards. Two blinded raters rated the students’ notes for any patient hazard addressed in the notes using a checklist. The students were blinded to the study question and design. There was no external funding and no harm for the participating students. Results: A total of 35 data sets had to be excluded because of missing data. Overall, the students identified 17% (IQR 8–29%) of the patient hazards before the training and 56% (IQR 41–66%) of the patient hazards after the training. At the second assessment students identified more patient hazards than at the first. They identified even more in the third. The effect was most pronounced after the patient chart review training (all p<.01). Conclusion: Patient chart review exercises and problem-based patient chart review training improve students’ abilities to recognize patient hazards independent of context during patient chart review. [ABSTRACT FROM AUTHOR]

Theory suggests that personality traits evolved to have costs and benefits, with the effectiveness of a trait dependent on how these costs and benefits relate to the present circumstances. This suggests that traits that are generally viewed as positive can have a ‘dark side’ and those generally viewed as negative can have a ‘bright side’ depending on changes in context. We test this in a sample of 220 UK medical students with respect to associations between the Big 5 personality traits and learning outcomes across the 5 years of a medical degree. The medical degree offers a changing learning context from pre-clinical years (where a more methodical approach to learning is needed) to the clinical years (where more flexible learning is needed, in a more stressful context). We argue that while trait conscientiousness should enhance pre-clinical learning, it has a ‘dark side’ reducing the acquisition of knowledge in the clinical years. We also suggest that anxiety has a ‘bright side’ enhancing the acquisition of skills in the clinical years. We also explore if intelligence enhances learning across the medical degree. Using confirmatory factor analysis and structural equation modelling we show that medical skills and knowledge assessed in the pre-clinical and clinical years are psychometrically distinguishable, forming a learning ‘backbone’, whereby subsequent learning outcomes are predicted by previous ones. Consistent with our predictions conscientiousness enhanced preclinical knowledge acquisition but reduced the acquisition of clinical knowledge and anxiety enhanced the acquisition of clinical skills. We also identified a curvilinear U shaped association between Surgency (extraversion) and pre-clinical knowledge acquisition. Intelligence predicted initial clinical knowledge, and had a positive total indirect effect on clinical knowledge and clinical skill acquisition. For medical selection, this suggests that selecting students high on conscientiousness may be problematic, as it may be excluding those with some degree of moderate anxiety. [ABSTRACT FROM AUTHOR]

Background: An evidence-based approach to health care is recognized internationally as a key competency for healthcare practitioners. This overview systematically evaluated and organized evidence from systematic reviews on teaching evidence-based health care (EBHC). Methods/Findings: We searched for systematic reviews evaluating interventions for teaching EBHC to health professionals compared to no intervention or different strategies. Outcomes covered EBHC knowledge, skills, attitudes, practices and health outcomes. Comprehensive searches were conducted in April 2013. Two reviewers independently selected eligible reviews, extracted data and evaluated methodological quality. We included 16 systematic reviews, published between 1993 and 2013. There was considerable overlap across reviews. We found that 171 source studies included in the reviews related to 81 separate studies, of which 37 are in more than one review. Studies used various methodologies to evaluate educational interventions of varying content, format and duration in undergraduates, interns, residents and practicing health professionals. The evidence in the reviews showed that multifaceted, clinically integrated interventions, with assessment, led to improvements in knowledge, skills and attitudes. Interventions improved critical appraisal skills and integration of results into decisions, and improved knowledge, skills, attitudes and behaviour amongst practicing health professionals. Considering single interventions, EBHC knowledge and attitude were similar for lecture-based versus online teaching. Journal clubs appeared to increase clinical epidemiology and biostatistics knowledge and reading behavior, but not appraisal skills. EBHC courses improved appraisal skills and knowledge. Amongst practicing health professionals, interactive online courses with guided critical appraisal showed significant increase in knowledge and appraisal skills. A short workshop using problem-based approaches, compared to no intervention, increased knowledge but not appraisal skills. Conclusions: EBHC teaching and learning strategies should focus on implementing multifaceted, clinically integrated approaches with assessment. Future rigorous research should evaluate minimum components for multifaceted interventions, assessment of medium to long-term outcomes, and implementation of these interventions. [ABSTRACT FROM AUTHOR]

Liver fibrosis results from the co-ordinated actions of myofibroblasts and macrophages, a proportion of which are of bone marrow origin. The functional effect of such bone marrow-derived cells on liver fibrosis is unclear. We examine whether changing bone marrow genotype can down-regulate the liver's fibrotic response to injury and investigate mechanisms involved. Proteinase activated receptor 1 (PAR1) is up-regulated in fibrotic liver disease in humans, and deficiency of PAR1 is associated with reduced liver fibrosis in rodent models. In this study, recipient mice received bone marrow transplantation from PAR1-deficient or wild-type donors prior to carbon tetrachloride-induced liver fibrosis. Bone marrow transplantation alone from PAR1-deficient mice was able to confer significant reductions in hepatic collagen content and activated myofibroblast expansion on wild-type recipients. This effect was associated with a decrease in hepatic scar-associated macrophages and a reduction in macrophage recruitment from the bone marrow. In vitro, PAR1 signalling on bone marrow-derived macrophages directly induced their chemotaxis but did not stimulate proliferation. These data suggest that the bone marrow can modulate the fibrotic response of the liver to recurrent injury. PAR1 signalling can contribute to this response by mechanisms that include the regulation of macrophage recruitment. [ABSTRACT FROM AUTHOR]

Thrombin and hypoxia are important players in breast cancer progression. Breast cancers often develop drug resistance, but mechanisms linking thrombin and hypoxia to drug resistance remain unresolved. Our studies using Doxorubicin (DOX) resistant MCF7 breast cancer cells reveals a mechanism linking DOX exposure with hypoxic induction of DOX resistance. Global expression changes between parental and DOX resistant MCF7 cells were examined. Westerns, Northerns and immunocytochemistry were used to validate drug resistance and differentially expressed genes. A cluster of genes involved in the anticoagulation pathway, with Tissue Factor Pathway Inhibitor 1 (TFPI1) the top hit, was identified. Plasmids overexpressing TFPI1 were utilized, and 1% O2 was used to test the effects of hypoxia on drug resistance. Lastly, microarray datasets from patients with drug resistant breast tumors were interrogated for TFPI1 expression levels. TFPI1 protein levels were found elevated in 3 additional DOX resistant cells lines, from humans and rats, indicating evolutionarily conservation of the effect. Elevated TFPI1 in DOX resistant cells was active, as thrombin protein levels were coincidentally low. We observed elevated HIF1α protein in DOX resistant cells, and in cells with forced expression of TFPI1, suggesting TFPI1 induces HIF1α. TFPI1 also induced c-MYC, c-SRC, and HDAC2 protein, as well as DOX resistance in parental cells. Growth of cells in 1% O2 induced elevated HIF1α, BCRP and MDR-1 protein, and these cells were resistant to DOX. Our in vitro results were consistent with in vivo patient datasets, as tumors harboring increased BCRP and MDR-1 expression also had increased TFPI1 expression. Our observations are clinically relevant indicating that DOX treatment induces an anticoagulation cascade, leading to inhibition of thrombin and the expression of HIF1α. This in turn activates a pathway leading to drug resistance. [ABSTRACT FROM AUTHOR]

Background: Publication of scientific research papers is important for professionals working in academic medical centres. Quantitative measures of scientific output determine status and prestige, and serve to rank universities as well as individuals. The pressure to generate maximum scientific output is high, and quantitative aspects may tend to dominate over qualitative ones. How this pressure influences professionals’ perception of science and their personal well-being is unknown. Methods and Findings: We performed an online survey inviting all medical professors (n = 1206) of the 8 academic medical centres in The Netherlands to participate. They were asked to fill out 2 questionnaires; a validated Publication Pressure Questionnaire and the Maslach Burnout Inventory. In total, 437 professors completed the questionnaires. among them, 54% judge that publication pressure ‘has become excessive’, 39% believe that publication pressure ‘affects the credibility of medical research’ and 26% judge that publication pressure has a ‘sickening effect on medical science’. The burn out questionnaire indicates that 24% of medical professors have signs of burn out. The number of years of professorship was significantly related with experiencing less publication pressure. Significant and strong associations between burn out symptoms and the level of perceived publication pressure were found. The main limitation is the possibility of response bias. Conclusion: A substantial proportion of medical professors believe that publication pressure has become excessive, and have a cynical view on the validity of medical science. These perceptions are statistically correlated to burn out symptoms. Further research should address the effects of publication pressure in more detail and identify alternative ways to stimulate the quality of medical science. [ABSTRACT FROM AUTHOR]

The broad diversity in physicians’ judgments on controversial health care topics may reflect differences in religious characteristics, political ideologies, and moral intuitions. We tested an existing measure of moral intuitions in a new population (U.S. physicians) to assess its validity and to determine whether physicians’ moral intuitions correlate with their views on controversial health care topics as well as other known predictors of these intuitions such as political affiliation and religiosity. In 2009, we mailed an 8-page questionnaire to a random sample of 2000 practicing U.S. physicians from all specialties. The survey included the Moral Foundations Questionnaire (MFQ30), along with questions on physicians’ judgments about controversial health care topics including abortion and euthanasia (no moral objection, some moral objection, strong moral objection). A total of 1032 of 1895 (54%) physicians responded. Physicians’ overall mean moral foundations scores were 3.5 for harm, 3.3 for fairness, 2.8 for loyalty, 3.2 for authority, and 2.7 for sanctity on a 0–5 scale. Increasing levels of religious service attendance, having a more conservative political ideology, and higher sanctity scores remained the greatest positive predictors of respondents objecting to abortion (β = 0.12, 0.23, 0.14, respectively, each p<0.001) as well as euthanasia (β = 0.08, 0.17, and 0.17, respectively, each p<0.001), even after adjusting for demographics. Higher authority scores were also significantly negatively associated with objection to abortion (β = −0.12, p<0.01), but not euthanasia. These data suggest that the relative importance physicians place on the different categories of moral intuitions may predict differences in physicians’ judgments about morally controversial topics and may interrelate with ideology and religiosity. Further examination of the diversity in physicians’ moral intuitions may prove illustrative in describing and addressing moral differences that arise in medical practice. [ABSTRACT FROM AUTHOR]

The treatment of infected wounds is one possible therapeutic aspect of plasma medicine. Chronic wounds are often associated with microbial biofilms which limit the efficacy of antiseptics. The present study investigates two different surface barrier discharges with air plasma to compare their efficacy against microbial biofilms with chlorhexidine digluconate solution (CHX) as representative of an important antibiofilm antiseptic. Pseudomonas aeruginosa SG81 and Staphylococcus epidermidis RP62A were cultivated on polycarbonate discs. The biofilms were treated for 30, 60, 150, 300 or 600 s with plasma or for 600 s with 0.1% CHX, respectively. After treatment, biofilms were dispensed by ultrasound and the antimicrobial effects were determined as difference in the number of the colony forming units by microbial culture. A high antimicrobial efficacy on biofilms of both plasma sources in comparison to CHX treatment was shown. The efficacy differs between the used strains and plasma sources. For illustration, the biofilms were examined under a scanning electron microscope before and after treatment. Additionally, cytotoxicity was determined by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay with L929 mouse fibroblast cell line. The cell toxicity of the used plasma limits its applicability on human tissue to maximally 150 s. The emitted UV irradiance was measured to estimate whether UV could limit the application on human tissue at the given parameters. It was found that the UV emission is negligibly low. In conclusion, the results support the assumption that air plasma could be an option for therapy of chronic wounds. [ABSTRACT FROM AUTHOR]

Background: In fledgling areas of research, evidence supporting causal assumptions is often scarce due to the small number of empirical studies conducted. In many studies it remains unclear what impact explicit and implicit causal assumptions have on the research findings; only the primary assumptions of the researchers are often presented. This is particularly true for research on the effect of faculty’s teaching performance on their role modeling. Therefore, there is a need for robust frameworks and methods for transparent formal presentation of the underlying causal assumptions used in assessing the causal effects of teaching performance on role modeling. This study explores the effects of different (plausible) causal assumptions on research outcomes. Methods: This study revisits a previously published study about the influence of faculty’s teaching performance on their role modeling (as teacher-supervisor, physician and person). We drew eight directed acyclic graphs (DAGs) to visually represent different plausible causal relationships between the variables under study. These DAGs were subsequently translated into corresponding statistical models, and regression analyses were performed to estimate the associations between teaching performance and role modeling. Results: The different causal models were compatible with major differences in the magnitude of the relationship between faculty’s teaching performance and their role modeling. Odds ratios for the associations between teaching performance and the three role model types ranged from 31.1 to 73.6 for the teacher-supervisor role, from 3.7 to 15.5 for the physician role, and from 2.8 to 13.8 for the person role. Conclusions: Different sets of assumptions about causal relationships in role modeling research can be visually depicted using DAGs, which are then used to guide both statistical analysis and interpretation of results. Since study conclusions can be sensitive to different causal assumptions, results should be interpreted in the light of causal assumptions made in each study. [ABSTRACT FROM AUTHOR]

Background: The number of visits to hospital emergency departments (EDs) in England has increased by 20% since 2007-08, placing unsustainable pressure on the National Health Service (NHS). Some patients attend EDs because they are unable to access primary care services. This study examined the association between access to primary care and ED visits in England. Methods: A cross-sectional, population-based analysis of patients registered with 7,856 general practices in England was conducted, for the time period April 2010 to March 2011. The outcome measure was the number of self-referred discharged ED visits by the registered population of a general practice. The predictor variables were measures of patient-reported access to general practice services; these were entered into a negative binomial regression model with variables to control for the characteristics of patient populations, supply of general practitioners and travel times to health services. Main Result and Conclusion: General practices providing more timely access to primary care had fewer self-referred discharged ED visits per registered patient (for the most accessible quintile of practices, RR = 0.898; P<0.001). Policy makers should consider improving timely access to primary care when developing plans to reduce ED utilisation. [ABSTRACT FROM AUTHOR]

Growing evidence has demonstrated a neuroprotective role of autophagy in Alzheimer’s disease (AD). Thus, autophagy has been regarded as a potential therapeutic target, attracting increasing interest in pharmaceutical autophagy modulation by small molecules. We designed a two-cycle screening strategy on the basis of imaging high-throughout screening (HTS) and cellular toxicity assay, and have identified a novel autophagy inducer known as GTM-1. We further showed that GTM-1 exhibits dual activities, such as autophagy induction and antagonism against Aβ-oligomer toxicity. GTM-1 modulates autophagy in an Akt-independent and mTOR-independent manner. In addition, we demonstrated that GTM-1 enhances autophagy clearance and reverses the downregulation of autophagy flux by thapsigargin and asparagine. Furthermore, administration of GTM-1 attenuated Aβ pathology and ameliorated cognitive deficits in AD mice. [ABSTRACT FROM AUTHOR]

Background: Errors in consuming drugs are associated with significant morbidity and mortality, besides an impact on the already overburdened health-care system. Misunderstanding drug labels and prescriptions plays an important role in contributing to adverse drug events. Objective: To evaluate abilities to understand prescriptions and drug labels among patients attending tertiary care hospital in Karachi. Methods: A cross sectional study was conducted at the Aga Khan University Hospital (AKUH), from January to March 2009. After informed consent, 181 adult patients and their healthy attendants were interviewed at AKUH using a standardized questionnaire, which ascertained patient demographics, factors that might increase exposure to health-care personnel as well as the basic knowledge and understanding of prescriptions and drug labels. Results: Out of 181, majority 137(76%) had received graduate or post-graduate degrees. 16 (9%) had received no formal education; of which all were females and 89(84%) of the total females were housewives. Overall, 130(72%) followed only a single doctor’s prescription. Majority failed to understand various medical terminologies related to dosage. In the high literacy group, 45(33%) understood once daily OD (p = 0.003), 27(20%) thrice daily TID (p = 0.05), 29(21%) twice daily BD (p = 0.01), 31(23%) thrice daily TDS (p = 0.002) and 43(31%) as needed SOS (p = 0.003) as compared to the group with no formal education, who were unable to comprehend the terms. The most common reason for using more than one prescription was decreased satisfaction with the doctor in 19(39%) and multiple co-morbids as responded by 17(35%) of patients. Knowledge regarding various medical terminologies used for dosage and routes of drug administration were also understood more frequently among the English medium respondents. The elderly identified medicine through color (47%, p<0.001), and were less likely to understand drug indications (p = 0.05) compared to younger subjects. Conclusion: Understanding of drug prescriptions is alarmingly low in the community, even amongst the educated. Care givers need to revisit this often ignored aspect of patient care. [ABSTRACT FROM AUTHOR]

Introduction: Development of secondary hyperalgesia following a cutaneous injury is a centrally mediated, robust phenomenon. The pathophysiological role of endogenous opioid signalling to the development of hyperalgesia is unclear. Recent animal studies, carried out after the resolution of inflammatory pain, have demonstrated reinstatement of tactile hypersensitivity following administration of μ-opioid-receptor-antagonists. In the present study in humans, we analyzed the effect of naloxone when given after the resolution of secondary hyperalgesia following a first-degree burn injury. Methods: Twenty-two healthy volunteers were included in this placebo-controlled, randomized, double-blind, cross-over study. Following baseline assessment of thermal and mechanical thresholds, a first-degree burn injury (BI; 47°C, 7 minutes, thermode area 12.5 cm2) was induced on the lower leg. Secondary hyperalgesia areas around the BI-area, and separately produced by brief thermal sensitization on the contralateral thigh (BTS; 45°C, 3 minutes, area 12.5 cm2), were assessed using a polyamide monofilament at pre-BI and 1, 2, and 3 hours post-BI. At 72 hrs, BI and BTS secondary hyperalgesia areas were assessed prior to start of a 30 minutes intravenous infusion of naloxone (total dose 21 microg/kg) or placebo. Fifteen minutes after start of the infusion, BI and BTS secondary hyperalgesia areas were reassessed, along with mechanical and thermal thresholds. Results: Secondary hyperalgesia areas were demonstrable in all volunteers 1–3 hrs post-BI, but were not demonstrable at 72 hrs post-burn in 73–86% of the subjects. Neither magnitude of secondary hyperalgesia areas nor the mechanical and thermal thresholds were associated with naloxone-treated compared to placebo-treated subjects. Conclusion: Naloxone (21 microg/kg) did not reinstate secondary hyperalgesia when administered 72 hours after a first-degree burn injury and did not increase BTS-generated hyperalgesia. The negative results may be due to the low dose of naloxone or insufficient tissue injury to generate latent sensitization. [ABSTRACT FROM AUTHOR]

Objective: The need for encouraging pediatric drug research is widely recognized. However, hospital-based clinical trials of drug treatments are extremely time-consuming, and delays in trial implementation are common. The objective of this qualitative study was to collect information on the perceptions and experience of health professionals involved in hospital-based pediatric drug trials. Methods: Two independent researchers conducted in-depth semi-structured interviews with principal investigators (n = 17), pharmacists (n = 7), sponsor representatives (n = 4), and drug regulatory agency representatives (n = 3) who participated in institutionally sponsored clinical trials of experimental drugs in pediatric patients between 2002 and 2008. Results: Dissatisfaction was reported by 67% (16/24) of principal investigators and pharmacists: all 7 pharmacists felt they were involved too late in the trial implementation process, whereas 11 (65%) principal investigators complained of an excessive regulatory burden and felt they were insufficiently involved in the basic research questions. Both groups perceived clinical trial implementation as burdensome and time-consuming. The sponsor and regulatory agency representatives reported a number of difficulties but were not dissatisfied. Conclusions: The heavy burden related to regulatory requirements, and suboptimal communication across disciplines involved, seem to be the main reasons for the major delays in pediatric drug trial implementation. The pharmaceutical aspects are intrinsically tied to trial methodology and implementation and must therefore be examined, in particular by involving Clinical Research Pharmacists at early stages of study conception. [ABSTRACT FROM AUTHOR]

A Content, Context, Connection and Researching, Reasoning, Reflecting (3C3R) model is a conceptual framework for problem-based learning (PBL) problem design. We introduced the 3C3R-PBL method into a pediatric teaching plan, and evaluated its effectiveness and feasibility. The 3C3R model was applied in a pediatric problem design teaching plan “why the lips turn purple when a baby is crying”. All students were assigned either into a traditional PBL course or into a 9-step 3C3R model PBL course (3C3R-PBL). The performance outcomes of both groups were compared. For the PBL group, the proportion of students scoring ≥4 for content, context, and problem design connection, was 90.8%, 80.3%, and 64.5% respectively, while for tutors, it was 71.4%, 71.4%, and 28.6%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 81.6%, 55.3%, and 40.8%, while for tutors, it was 71.4%, 100%, and 57.1%. The learning difficulty was not considered high with only 31.6% of students and 42.9% of tutors rating the task as difficult. For the 3C3R-PBL group, the proportion of students scoring content, context, and connection, ≥4 was 100%, 98.4%, and 90.5%, while for tutors it was 100%, 100%, 83.3%; for researching, reasoning, and reflecting, the proportion of students scoring ≥4 was 95.2%, 88.9%, and 76.2%, while for tutors it was 100% for all 3 R components. Students and tutors were convinced by the content, case context, research process and reasoning process of both teaching plans, while scores for connection and reflecting were significantly improved when the PBL plan was amended by a 3C3R model (p<0.05) and the case learning difficulty was statistically increased (p<0.05). The 3C3R model, evaluated for the first time in China, was helpful for effective and reliable problem design in a pediatric PBL teaching plan for Chinese students. [ABSTRACT FROM AUTHOR]

Background: Peer review is the mainstay of editorial decision making for medical journals. There is a dearth of evaluations of journal peer review with regard to reliability and validity, particularly in the light of the wide variety of medical journals. Studies carried out so far indicate low agreement among reviewers. We present an analysis of the peer review process at a general medical journal, Deutsches Ärzteblatt International. Methodology/Principal Findings: 554 reviewer recommendations on 206 manuscripts submitted between 7/2008 and 12/2009 were analyzed: 7% recommended acceptance, 74% revision and 19% rejection. Concerning acceptance (with or without revision) versus rejection, there was a substantial agreement among reviewers (74.3% of pairs of recommendations) that was not reflected by Fleiss' or Cohen's kappa (<0.2). The agreement rate amounted to 84% for acceptance, but was only 31% for rejection. An alternative kappa-statistic, however, Gwet's kappa (AC1), indicated substantial agreement (0.63). Concordance between reviewer recommendation and editorial decision was almost perfect when reviewer recommendations were unanimous. The correlation of reviewer recommendations and citations as counted by Web of Science was low (partial correlation adjusted for year of publication: −0.03, n.s.). Conclusions/Significance: Although our figures are similar to those reported in the literature our conclusion differs from the widely held view that reviewer agreement is low: Based on overall agreement we consider the concordance among reviewers sufficient for the purposes of editorial decision making. We believe that various measures, such as positive and negative agreement or alternative Kappa values are superior to the application of Cohen's or Fleiss' Kappa in the analysis of nominal or ordinal level data regarding reviewer agreement. Also, reviewer recommendations seem to be a poor proxy for citations because, for example, manuscripts will be changed considerably during the revision process. [ABSTRACT FROM AUTHOR]

Background: Citation analysis has become an important tool for research performance assessment in the medical sciences. However, different areas of medical research may have considerably different citation practices, even within the same medical field. Because of this, it is unclear to what extent citation-based bibliometric indicators allow for valid comparisons between research units active in different areas of medical research. Methodology: A visualization methodology is introduced that reveals differences in citation practices between medical research areas. The methodology extracts terms from the titles and abstracts of a large collection of publications and uses these terms to visualize the structure of a medical field and to indicate how research areas within this field differ from each other in their average citation impact. Results: Visualizations are provided for 32 medical fields, defined based on journal subject categories in the Web of Science database. The analysis focuses on three fields: Cardiac & cardiovascular systems, Clinical neurology, and Surgery. In each of these fields, there turn out to be large differences in citation practices between research areas. Low-impact research areas tend to focus on clinical intervention research, while high-impact research areas are often more oriented on basic and diagnostic research. Conclusions: Popular bibliometric indicators, such as the h-index and the impact factor, do not correct for differences in citation practices between medical fields. These indicators therefore cannot be used to make accurate between-field comparisons. More sophisticated bibliometric indicators do correct for field differences but still fail to take into account within-field heterogeneity in citation practices. As a consequence, the citation impact of clinical intervention research may be substantially underestimated in comparison with basic and diagnostic research. [ABSTRACT FROM AUTHOR]

To better understand clinical empathy and what factors can undermine its experience and outcome in care-giving settings, a large-scale study was conducted with 7,584 board certified practicing physicians. Online validated instruments assessing different aspects of empathy, distress, burnout, altruistic behavior, emotional awareness, and well-being were used. Compassion satisfaction was strongly associated with empathic concern, perspective taking and altruism, while compassion fatigue (burnout and secondary traumatic stress) was more closely related to personal distress and alexithymia. Gender had a highly selective effect on empathic concern, with women displaying higher values, which led to a wide array of negative and devalued feelings. Years of experience did not influence dispositional measures per se after controlling for the effect of age and gender. Participants who experienced compassion fatigue with little to no compassion satisfaction showed the highest scores on personal distress and alexithymia as well as the strongest indicators of compassion fatigue. Physicians who have difficulty regulating their negative arousal and describing and identifying emotions seem to be more prone to emotional exhaustion, detachment, and a low sense of accomplishment. On the contrary, the ability to engage in self-other awareness and regulate one’s emotions and the tendency to help others, seem to contribute to the sense of compassion that comes from assisting patients in clinical practice. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the talus (ONT) may severely affect the function of the ankle joint. Most orthopedists believe that ONT should be treated at an early stage, but a concise and effective surgical treatment is lacking. In this study, porous titanium alloy rods were prepared and implanted into the tali of sheep with early-stage ONT (IM group). The curative effect of the rods was compared to treatment by core decompression (DC group). No significant differences in bone reconstruction were observed between the two groups at 1 month after intervention. After 3 months, the macroscopic view of gross specimens of the IM group showed ordinary contours, but the specimens of the DC group showed obvious partial bone defects and cartilage degeneration. Quantitative analysis of the reconstructed trabeculae by micro-CT and histological study suggested that the curative effect of the IM group was superior to that of the DC group at 3 months after intervention. These favorable short-term results of the implantation of porous titanium alloy rods into the tali of sheep with early-stage ONT may provide insight into an innovative surgical treatment for ONT. [ABSTRACT FROM AUTHOR]

Context: Although qualitative studies are becoming more appreciated in healthcare, the number of publications of quality studies remains low. Little is known about the frequency and characteristics of citation in qualitative studies. Objective: To compare the academic impact of qualitative studies to that of two quantitative studies: systematic reviews and randomized controlled trials. Methods: Publications in BMJ between 1997 and 2006 (BMJ’s median impact factor was 7.04 during this period) employing qualitative methods were matched to two quantitative studies appearing the same year using PubMed. Using Web of Science, citations within a 24-month publication period were determined. Additionally, three hypotheses were examined: qualitative studies are 1) infrequently cited in original articles or reviews; 2) rarely cited by authors in non-English-speaking countries; and 3) more frequently cited in non-medical disciplines (e.g., psychology or sociology). Results: A total of 121 qualitative studies, 270 systematic reviews, and 515 randomised controlled trials were retrieved. Qualitative studies were cited a total of 1,089 times, with a median of 7.00 times (range, 0–34) for each study. Matched systematic reviews and randomized controlled trials were cited 2,411times and 1,600 times, respectively. With respect to citing documents, original articles and reviews exceeded 60% for each study design. Relative to quantitative studies, qualitative studies were cited more often by authors in English-speaking countries. With respect to subject area, medical disciplines were more frequently cited than non-medical disciplines for all three study designs (>80%). Conclusion: The median number of citations for qualitative studies was almost the same as the median of BMJ’s impact factor during the survey period. For a suitable evaluation of qualitative studies in healthcare, it will be necessary to develop a reporting framework and include explicit discussions of clinical implications when reporting findings. Coordination between researchers and editors will be needed to achieve this goal. [ABSTRACT FROM AUTHOR]

Objectives: To achieve international consensus across multiple specialties on a generic ultrasound rating scale using a Delphi technique. Methods: Ultrasound experts from Obstetrics-Gynaecology, Surgery, Urology, Radiology, Rheumatology, Emergency Medicine, and Gastro-Enterology representing North America, Australia, and Europe were identified. A multi-round survey was conducted to obtain consensus between these experts. Of 60 invited experts, 44 experts agreed to participate in the first Delphi round, 41 remained in the second round, and 37 completed the third Delphi round. Seven key elements of the ultrasound examination were identified from existing literature and recommendations from international ultrasound societies. All experts rated the importance of these seven elements on a five-point Likert scale in the first round and suggested potential new elements for the assessment of ultrasound skills. In the second round, the experts re-rated all elements and a third round was conducted to allow final comments. Agreement on which elements to include in the final rating scale was pre-defined as more than 80% of the experts rating an element four or five, on importance to the ultrasound examination. Results: Two additional elements were suggested by more than 10% of the experts in the first Delphi round. Consensus was obtained to include these two new elements along with five of the original elements in the final assessment instrument: 1) Indication for the examination 2) Applied knowledge of ultrasound equipment 3) Image optimization 4) Systematic examination 5) Interpretation of images 6) Documentation of examination and 7) Medical decision making. Conclusion: International multispecialty consensus was achieved on the content of a generic ultrasound rating scale. This is the first step to ensure valid assessment of clinicians in different medical specialties using ultrasound. [ABSTRACT FROM AUTHOR]

Introduction: Systematic reviewer authors intending to include all randomized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data. Objective: The objective of this paper is to provide systematic reviewer authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of randomized trials. Methods: This guide is based on a review of the Cochrane handbook and published methodological research. The guide deals with participants excluded from the analysis who were considered ‘non-adherent to the protocol’ but for whom data are available, and participants with missing data. Results: Systematic reviewer authors should include data from ‘non-adherent’ participants excluded from the primary study authors' analysis but for whom data are available. For missing, unavailable participant data, authors may conduct a complete case analysis (excluding those with missing data) as the primary analysis. Alternatively, they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data. When the primary analysis suggests important benefit, sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis. The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta-analysis. The proposed guide does not take into account the uncertainty associated with assumed events. Conclusions: This guide proposes methods for handling participants excluded from analyses of randomized trials. These methods can help in establishing the extent to which risk of bias impacts meta-analysis results. [ABSTRACT FROM AUTHOR]

FK506 binding protein-like (FKBPL) and its peptide derivatives exert potent anti-angiogenic activity in vitro and in vivo and control tumour growth in xenograft models, when administered exogenously. However, the role of endogenous FKBPL in angiogenesis is not well characterised. Here we investigated the molecular effects of the endogenous protein and its peptide derivative, AD-01, leading to their anti-migratory activity. Inhibition of secreted FKBPL using a blocking antibody or siRNA-mediated knockdown of FKBPL accelerated the migration of human microvascular endothelial cells (HMEC-1). Furthermore, MDA-MB-231 tumour cells stably overexpressing FKBPL inhibited tumour vascular development in vivo suggesting that FKBPL secreted from tumour cells could inhibit angiogenesis. Whilst FKBPL and AD-01 target CD44, the nature of this interaction is not known and here we have further interrogated this aspect. We have demonstrated that FKBPL and AD-01 bind to the CD44 receptor and inhibit tumour cell migration in a CD44 dependant manner; CD44 knockdown abrogated AD-01 binding as well as its anti-migratory activity. Interestingly, FKBPL overexpression and knockdown or treatment with AD-01, regulated CD44 expression, suggesting a co-regulatory pathway for these two proteins. Downstream of CD44, alterations in the actin cytoskeleton, indicated by intense cortical actin staining and a lack of cell spreading and communication were observed following treatment with AD-01, explaining the anti-migratory phenotype. Concomitantly, AD-01 inhibited Rac-1 activity, up-regulated RhoA and the actin binding proteins, profilin and vinculin. Thus the anti-angiogenic protein, FKBPL, and AD-01, offer a promising and alternative approach for targeting both CD44 positive tumours and vasculature networks. [ABSTRACT FROM AUTHOR]