A geospatial approach to identify patterns of antibiotic susceptibility at a neighborhood level in Wisconsin, United States.

The global threat of antimicrobial resistance (AMR) varies regionally. This study explores whether geospatial analysis and data visualization methods detect both clinically and statistically significant variations in antibiotic susceptibility rates at a neighborhood level. This observational multicenter geospatial study collected 10 years of patient-level antibiotic susceptibility data and patient addresses from three regionally distinct Wisconsin health systems (UW Health, Fort HealthCare, Marshfield Clinic Health System [MCHS]). We included the initial Escherichia coli isolate per patient per year per sample source with a patient address in Wisconsin (N = 100,176). Isolates from U.S. Census Block Groups with less than 30 isolates were excluded (n = 13,709), resulting in 86,467 E. coli isolates. The primary study outcomes were the results of Moran's I spatial autocorrelation analyses to quantify antibiotic susceptibility as spatially dispersed, randomly distributed, or clustered by a range of - 1 to + 1, and the detection of statistically significant local hot (high susceptibility) and cold spots (low susceptibility) for variations in antibiotic susceptibility by U.S. Census Block Group. UW Health isolates collected represented greater isolate geographic density (n = 36,279 E. coli, 389 = blocks, 2009-2018), compared to Fort HealthCare (n = 5110 isolates, 48 = blocks, 2012-2018) and MCHS (45,078 isolates, 480 blocks, 2009-2018). Choropleth maps enabled a spatial AMR data visualization. A positive spatially-clustered pattern was identified from the UW Health data for ciprofloxacin (Moran's I = 0.096, p = 0.005) and trimethoprim/sulfamethoxazole susceptibility (Moran's I = 0.180, p < 0.001). Fort HealthCare and MCHS distributions were likely random. At the local level, we identified hot and cold spots at all three health systems (90%, 95%, and 99% CIs). AMR spatial clustering was observed in urban areas but not rural areas. Unique identification of AMR hot spots at the Block Group level provides a foundation for future analyses and hypotheses. Clinically meaningful differences in AMR could inform clinical decision support tools and warrants further investigation for informing therapy options.

Tailored Metabolic Workup for Urolithiasis - The Debate Continues.

Urolithiasis is one of the commonest afflictions of the urinary tract. Stones are of various chemical compositions, some share some common etiology; but most are specific to the structure and composition of stone. In view of highly recurrent nature of this condition, it is logical to have strategies for prevention. However, due to multiple factors most patients receive no or fragmented information on prevention. The current controversy is to the extent of metabolic workup in adult first time stone former. This requires longitudinal studies to show benefit in prevention strategies. Patients at high risk can have recurrence in weeks to years, depending upon the composition and attending risk factor. They should be targeted with concentric and tailored prevention protocols. The major urological guidelines (EAU and AUA) recommend basic stone workup for all patients. However, indication for detailed workup are less well documented, so one potential solution is to tailor metaphylaxis strategies for individual patient.

Urology training in the developing world: The trainers' perspective.

CONTEXT: Despite producing some of the leading urologists in the world, urological training in the developing world is marred by inconsistency, and a lack of structure and focus on evidence-based practice. In this review we address these issues from the trainers' perspective. INTRODUCTION: Teaching the art and science of urological practice is a demanding task. It not only involves helping the resident to develop the depth of cognitive knowledge, but also to have an appropriate surgical judgement, and an ability to act quickly but thoughtfully and, when necessary, decisively. DISCUSSION: The surgeon must have compassion, communication skills, be perceptive and dedicated. Most importantly, however, he or she should have the ability to cut and suture. Not all of these can be inculcated in the training programme, even with the best of efforts. The selection of an appropriate candidate therefore becomes an issue of pivotal importance. The changing focus of urological training incorporates research and evidence-based practice as essential components. It is particularly important in the developing world, as there is a dearth of standardised practice models across the healthcare system. Encouraging female residents can be done by improving and tailoring the working conditions. The 'brain drain' is a major problem in the developing world, and bureaucracy and government need to take appropriate measures to provide high-quality healthcare facilities with room for professional growth. CONCLUSIONS: The future of urology will depend on improved education and training, leading to high-quality urological care, and to developing a service that is patient focused.

Reliability of OSTE in the health professions education exit examination of college of physicians and surgeons, Pakistan: a psychometric analysis.

OBJECTIVE: To determine reliability and validity of objectively structured teaching examination (OSTE) and the difference in the examination scores of two consecutive Health Professions Education batches. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: The College of Physicians and Surgeons Pakistan, Karachi, from November 2011 to April 2012. METHODOLOGY: The OSTEs were designed on the basis of examination blueprints. Scores of participants of two consecutive years (group-I n = 14, group-II n = 15) were analyzed by using SPSS version 16. Mean + SD was computed and overall means were compared by t test. Reliability was determined by Cronbach's a coefficient. Standard error of measurement (SEM) was computed for precision of scores. OSTE stations were not uni-dimensional, factor analysis including varimax rotation was performed. For convergent validity (Pearson correlations) was determined between scores of OSTE, lectures delivered and workshops conducted. RESULTS: The overall mean score was 7.64 + 0.65 in group-I and 7.33 ± 1.03 in group-II (p = 0.429), (group-I SEM = 0.35 and group-II, SEM = 0.48). Factor analysis yielded four factors in group-I and five factors in group-II with Eigenvalues > 1. The Pearson's correlation of average scores of OSTE and lecture was significant for group-I (r = 0.61, p 0.019), and insignificant for group-II (r = 0.46, p = 0.08). Correlation between OSTE and workshops conducted was insignificant in group-I (r = 0.51, p = 0.057) and significant in group-II (r = 0.53, p = 0.04). CONCLUSION: OSTE is a reliable, valid assessment tool for discerning competency among learners of HPE program.

The genetics of neuroendocrine prostate cancers: a review of current and emerging candidates.

Prostate cancer (PC) displays a strong familial link and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions, and, ultimately, carcinogenesis. The most widely studied epigenetic event in PC is aberrant DNA methylation (hypo- and hypermethylation); besides this, chromatin remodeling and micro RNA (miRNA) are other studied alterations in PC. These all lead to genomic instability and inappropriate gene expression. Causative dysfunction of histone modifying enzymes results in generic and locus-specific changes in chromatin remodeling. miRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen-receptor signaling and apoptosis. These epigenetic alterations have the potential to act as biomarkers for PC for screening and diagnosis as well as prognosis and follow-up. The variable biological potential for a newly diagnosed PC is one of the biggest challenges. The other major clinical problem is in the management of castration-resistant PC. Neuroendocrine (NE) differentiation is one of the putative explanations for the development of castration-resistant disease. Most advanced and poorly differentiated cancer does not produce prostate-specific antigen (PSA) in response to disease progression. Circulating and tissue biomarkers like chromogranin A (CgA) thus become important tools. There is the potential to use various genetic and epigenetic alterations and NE differentiation as therapeutic targets in the management of PC. However, we are still some distance from developing clinically effective tools. Valuable insights into the nature of NE differentiation in PC have been gained in the last decades, but additional understanding of its pathogenetic mechanisms is needed. This will help in devising novel therapeutic strategies to develop targeted therapies. CgA has the potential to become an important marker of advanced castration-resistant PC in cases where prostate-specific antigen can no longer be relied upon. Aberrant androgen-receptor signaling at various levels provides evidence of the importance of this pathway for the development of castration-resistant PC. Many epigenetic influences - in particular, the role of changing miRNA expression - provide valuable insights. Currently, massive sequencing efforts are underway to define important somatic genetic alterations (amplifications, deletions, point mutations, translocations) in PC, and these alterations hold great promise as prognostic markers and for predicting response to therapy.

Current management of advanced and metastatic renal cell carcinoma.

INTRODUCTION: Unresectable renal cell carcinoma (RCC) is a technically incurable condition. Historically, RCC is resistant to chemotherapy and radiotherapy. Cytokine therapy was until recently considered the mainstay of treatment. However, responses are modest. Improvement in the understanding of the biology of RCC, particularly the hereditary types, is providing the basis for novel therapeutic targets. Our aim was to review the clinical utility of various systemic agents and surgery in the management of advanced RCC and suggest practice guidelines in the light of current literature. MATERIALS AND METHODS: Evidence was collected by review of current literature, guidelines of the American and European associations and the national comprehensive cancer network. RESULTS: Treatment of advanced RCC has recently undergone a major change with the development of targeted agents and potent angiogenesis inhibitors. Small-molecule multikinase inhibitors that target vascular endothelial growth factor receptors have a favorable toxicity profile and can prolong time to progression and preserve quality of life when used in newly diagnosed or previously treated patients; bevacizumab enhances the response rate and prolongs disease control when added to interferon-alpha. Temsirolimus, a mammalian target of rapamycin inhibitor, prolongs the survival duration of patients with poor-risk disease. All currently available agents have variable toxicity profile and they, at best, improve survival by a few months. Surgery still has a significant role in the management of stage IV RCC. CONCLUSION: Supportive care and surgery remain the mainstay of treatment even in the management of advanced and metastatic RCC. Systemic therapeutic agents are showing promising results.