Short term complications in mesh augmented vaginal repair of pelvic organ prolapse are not higher when compared with native tissue repair.

INTRODUCTION AND HYPOTHESIS: Accumulating evidence regarding the negative long-term consequences of transvaginal mesh-based procedures for pelvic organ prolapse has led to a sharp decline in mesh-based procedures. We aimed to evaluate the short-term complications of mesh-based procedures for carefully selected patients with pelvic organ prolapse after Food and Drug Administration warnings. METHODS: A retrospective database review of the ACS NSQIP database was completed to examine 30-day complications including re-operation, prolonged length of stay, blood transfusion, surgical site infection, urinary tract infection, readmission and wound dehiscence in mesh-augmented and native tissue-based transvaginal procedures for pelvic organ prolapse. RESULTS: A total of 36,234 patients were included in the analysis, with only 7.1% (2574 women) having mesh-augmented repair. Using a multivariable logistical regression analysis adjusting for confounders, we found that the primary composite outcome (re-operation, hospital stay, blood transfusion and surgical site infection) was less common in the mesh group compared with the native tissue repair group (adjusted OR 0.80, CI 0.67-0.95, p = 0.009). The secondary outcomes (urinary tract infection, re-admission and wound dehiscence) were not different between the group. CONCLUSION: These results suggest that in well-chosen patients, short-term complications are not increased when using transvaginal mesh for pelvic organ prolapse repair.

Investigation of the Gut Microbiome in Patients with Schizophrenia and Clozapine-Induced Weight Gain: Protocol and Clinical Characteristics of First Patient Cohorts.

BACKGROUND: Emerging evidence suggests an important role of the human gut microbiome in psychiatry and neurodevelopmental disorders. An increasing body of literature based on animal studies has reported that the gut microbiome influences brain development and behavior by interacting with the gut-brain axis. Furthermore, as the gut microbiome has an important role in metabolism and is known to interact with pharmaceuticals, recent evidence suggests a role for the microbiome in antipsychotic-induced metabolic side effects in animals and humans. PURPOSE: Here we present the protocol for a two-phase study investigating the gut microbiome in healthy controls and in patients with schizophrenia treated with antipsychotics. METHODS: Phase I of our study involves humans exclusively. We recruit 25 patients who are chronically treated with clozapine and compare them with 25 healthy controls matched for age, sex, BMI, and smoking status. A second cohort consists of 25 patients newly starting on clozapine, and a third cohort includes 25 antipsychotic-naive patients. The patients in the second cohort and third cohort are prospectively assessed for up to 6 and 12 weeks, respectively. Phase II of this study will incorporate microbiota humanized mouse models to examine the influence of human fecal transplant on metabolic parameters and the gut-brain axis. Progress and Future Directions: We are underway with the first participants enrolled in all phase I treatment cohorts. This study will contribute to elucidating the role of the gut microbiome in schizophrenia and metabolic side effects. In addition, its results may help to explore potential therapeutic targets for antipsychotic-induced metabolic side effects.

Clinical implications of APOE genotyping for late-onset Alzheimer's disease (LOAD) risk estimation: a review of the literature.

Alzheimer's disease is a genetically complex neurodegenerative disorder representing the leading cause of dementia. Advances in personal genomics are increasing the public uptake of genetic susceptibility testing for complex diseases such as late-onset Alzheimer's disease (LOAD). For LOAD, the discovery of the major risk ε4 allele of the APOE gene has prompted a debate on the ethics and utility of presymptomatic (i.e., predictive) testing. Although the mechanistic contribution of APOE to disease onset remains uncertain, presymptomatic genetic testing provides a relative risk of developing LOAD. Presymptomatic testing for complex disorders, such as LOAD is much less conclusive than early-onset Alzheimer's disease (EOAD) which follows a Mendelian inheritance pattern. Given the lack of preventive strategies available for EOAD or LOAD, APOE genotyping offers limited clinical utility, thus, raising ethical and practical questions. We conducted a systematic search of five electronic databases or primary studies published during January 2008-January 2018 which investigated practical and ethical issues of presymptomatic APOE genotyping for LOAD risk estimation. We identified 31 articles which suggested that APOE genotyping for LOAD susceptibility provides potential benefits to at-risk patients and can guide changes in positive health-related behaviors. However, other individuals may experience test-related anxiety, depression and psychological distress. Future research should focus on developing an integrated risk assessment tool to enhance the utility of APOE genotyping. Furthermore, empirical research is required to understand actual psychological and social implications associated with testing.

Interventions to Improve Metabolic Risk Screening Among Adult Patients Taking Antipsychotic Medication: A Systematic Review.

OBJECTIVE: Antipsychotic use is associated with elevated cardiometabolic risk. Guidelines for metabolic risk screening of individuals taking antipsychotics have been issued, but with little uptake into clinical practice. This review systematically assessed interventions that address this guideline-to-practice gap and described their quality, improvement strategies, and effect on screening rates. METHODS: Studies of interventions that addressed metabolic risk screening of adult patients taking antipsychotics, published from inception to July 2018, were selected from MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane Reviews databases. Information was extracted on study characteristics; improvement strategies at the provider, patient, and system levels; and screening rates in the intervention and comparison groups. RESULTS: The review included 30 complex interventions that used between one and nine unique improvement strategies. Social influence to shift provider and health organization culture to encourage metabolic risk screening was a common strategy, as were clinical prompts and monitoring tools to capture provider attention. Most studies were deemed at high risk of bias. Relative to comparison groups, the interventions were associated with an increase in median screening rates for glucose (28% to 65%), lipids (22% to 61%), weight (19% to 67%), and blood pressure (22% to 80%). CONCLUSIONS: This knowledge synthesis points to shortcomings of current interventions to improve antipsychotic metabolic risk screening, both in quality and in outcomes. Findings may be used to inform the design of future programs. Additional interventions are needed to address the current guideline-to-practice gap, in which approximately one-third of patients are unscreened for metabolic risk.

Optimizing the methodology for measuring supraclavicular skin temperature using infrared thermography; implications for measuring brown adipose tissue activity in humans.

The discovery of brown adipose tissue (BAT) in adults has sparked interest in its role as a therapeutic target in metabolic disorders. Infrared thermography is a promising way to quantify BAT; however, a standardized methodology has not been established. This study aims to establish a standardized and reproducible protocol to measure thermal response to cold in the supraclavicular area using thermographic imaging. In Phase 1, we compared the thermal response to 12 °C cold after acclimation at either 32 °C or room temperature using thermographic imaging. Repeatability of the 32 °C acclimation trial was studied in a second group in Phase 2. Phase 1 included 28 men (mean age 23.9 ± 5.9 y; mean BMI 25.2 ± 3.9 kg/m2) and Phase 2 included 14 men (mean age 20.9 ± 2.4 y; mean BMI 23.6 ± 3.1 kg/m2). The thermal response was greater after 32 °C than after room temperature acclimation (0.22 ± 0.19 vs 0.13 ± 0.17 °C, p = 0.05), was not related to outdoor temperature (r = -0.35, p = 0.07), did not correlate with supraclavicular fat (r = -0.26, p = 0.21) measured with dual-energy x-ray absorptiometry and was repeatable [ICC 0.69 (0.14-0.72)]. Acclimation at 32 °C followed by cold generates a reproducible change in supraclavicular skin temperature measurable by thermal imaging that may be indicative of BAT metabolic activity.