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Limited data are available to establish evidence-based management protocols for vestibulodynia (VBD), a chronic vulvar pain condition that affects approximately 14 million women in the U.S. For the purposes of the study, our group subdivided VBD subtypes that may benefit from different types of treatment: 1) VBD peripheral (VBD-p), characterized by pain localized to the vulvar vestibule and 2) VBD central (VBD-c), characterized by VBD alongside one or more other chronic overlapping pain conditions (e.g. irritable bowel syndrome, temporomandibular disorder, and fibromyalgia syndrome) that affect remote body regions. Here, we describe the rationale and design of an NIH-funded multicenter clinical trial comparing the effectiveness of topical and/or systemic medication for alleviating pain and normalizing pain- relevant biomarkers among women with VBD-p and VBD-c. Participants will be randomly assigned to one of four parallel arms: peripheral treatment with 5% lidocaine + 0.5 mg/ml 0.02% oestradiol compound cream + oral placebo pill, 2) central treatment with the tricyclic antidepressant nortriptyline + placebo cream, 3) combined peripheral cream and central pill treatments, or 4) placebo cream and placebo pill. The treatment phase will last 16 weeks, with outcome measures and biomarkers assessed at 4 time points (0, 8, 16, and 24 weeks). First, we will compare the efficacy of treatments in alleviating pain using standardized tampon insertion with a numeric rating scale and self-reported pain on the short form McGill Pain Questionnaire. Next, we will compare the efficacy of treatments in improving perceived physical, mental, and sexual health using standardized questionnaires. Finally, we will measure cytokines and microRNAs in local vaginal and circulating blood samples using multiplex assays and RNA sequencing, and determine the ability of these biomarkers to predict treatment response. This is the first multicenter randomized controlled trial to evaluate the efficacy of peripherally and centrally acting medications currently used in clinical practice for treating unique VBD subtypes based on distinct clinical and biological signatures. Vestibulodynia UPDATe is a multi-centre, two-by-two factorial designed randomized, double-blind, placebo-controlled trial registered at clinical trials.gov (NCT03844412). This work is supported by the R01 HD096331 awarded to Drs. Nackley, Rapkin, Geller and Carey by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Peripheral lidocaine and oestradiol and centrally-targeted nortriptyline medications are used for the treatment of pain in women with VBD, but there is a lack of data from well-powered RCTs. This two-by-two factorial RCT will test the efficacy of these medications in VBD subtypes characterized by distinct clinical characteristics and biomarker profiles. We hope that results will provide clinicians with scientific evidence of therapeutic efficacy in distinct VBD subtypes in an effort to direct and optimize treatment approaches. [ABSTRACT FROM AUTHOR]

Existing normative flow cytometry data have several limitations including small sample sizes, incompletely described study populations, variable flow cytometry methodology, and limited depth for defining lymphocyte subpopulations. To overcome these issues, we defined high-dimensional flow cytometry reference ranges for the healthy human immune system using Human Immunology Project Consortium methodologies after carefully screening 127 subjects deemed healthy through clinical and laboratory testing. We enrolled subjects in the following age cohorts: 18–29 years, 30–39, 40–49, and 50–66 and enrolled cohorts to ensure an even gender distribution and at least 30% non-Caucasians. From peripheral blood mononuclear cells, flow cytometry reference ranges were defined for >50 immune subsets including T-cell (activation, maturation, T follicular helper and regulatory T cell), B-cell, and innate cells. We also developed a web tool for visualization of the dataset and download of raw data. This dataset provides the immunology community with a resource to compare and extract data from rigorously characterized healthy subjects across age groups, gender and race. [ABSTRACT FROM AUTHOR]

Background: Professional guidelines have reduced the recommended minimum number to an average of 50 percutaneous coronary intervention (PCI) procedures performed annually by each operator. Operator volume patterns and associated outcomes since this change are unknown.Objectives: The authors describe herein PCI operator procedure volumes; characteristics of low-, intermediate-, and high-volume operators; and the relationship between operator volume and clinical outcomes in a large, contemporary, nationwide sample.Methods: Using data from the National Cardiovascular Data Registry collected between July 1, 2009, and March 31, 2015, we examined operator annual PCI volume. We divided operators into low- (<50 PCIs per year), intermediate- (50 to 100 PCIs per year), and high- (>100 PCIs per year) volume groups, and determined the adjusted association between annual PCI volume and in-hospital outcomes, including mortality.Results: The median annual number of procedures performed per operator was 59; 44% of operators performed <50 PCI procedures per year. Low-volume operators more frequently performed emergency and primary PCI procedures and practiced at hospitals with lower annual PCI volumes. Unadjusted in-hospital mortality was 1.86% for low-volume operators, 1.73% for intermediate-volume operators, and 1.48% for high-volume operators. The adjusted risk of in-hospital mortality was higher for PCI procedures performed by low- and intermediate-volume operators compared with those performed by high-volume operators (adjusted odds ratio: 1.16 for low versus high; adjusted odds ratio: 1.05 for intermediate vs. high volume) as was the risk for new dialysis post PCI. No volume relationship was observed for post-PCI bleeding.Conclusions: Many PCI operators in the United States are performing fewer than the recommended number of PCI procedures annually. Although absolute risk differences are small and may be partially explained by unmeasured differences in case mix between operators, there remains an inverse relationship between PCI operator volume and in-hospital mortality that persisted in risk-adjusted analyses. [ABSTRACT FROM AUTHOR]

IMPORTANCE Atypical antipsychotic medications are indicated for the treatment of irritability and agitation symptoms in children with autism spectrum disorder (ASD). Unfortunately, these medications are associated with weight gain and metabolic complications that are especially troubling in children and with long-term use. OBJECTIVE To evaluate the efficacy of metformin for weight gain associated with atypical antipsychotic medications in children and adolescents with ASD (defined in the protocol as DSM-IV diagnosis of autistic disorder, Asperger disorder, or pervasive developmental disorder not otherwise specified), aged 6 to 17 years. DESIGN, SETTING, AND PARTICIPANTS A 16-week, double-blind, placebo-controlled, randomized clinical trial was conducted at 4 centers in Toronto, Ontario, Canada; Columbus, Ohio; Pittsburgh, Pennsylvania; and Nashville, Tennessee. In all, 209 potential participants were screened by telephone, 69 individuals provided consent, and 61 participants were randomized to receivemetformin or placebo between April 26, 2013, and June 24, 2015. INTERVENTIONS Metformin or matching placebo titrated up to 500mg twice daily for children aged 6 to 9 years and 850mg twice daily for those 10 to 17 years. MAIN OUTCOMES AND MEASURES The primary outcome measurewas change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables. Safety, tolerability, and efficacy analyses all used a modified intent-to-treat sample comprising all participants who received at least 1 dose of medication. RESULTS Of the 61 randomized participants, 60 participants initiated treatment (45 [75%] male; mean [SD] age, 12.8 [2.7] years). Metformin reduced BMI z scores from baseline to week 16 significantly more than placebo (difference in 16-week change scores vs placebo, -0.10 [95%CI, -0.16 to -0.04]; P = .003). Statistically significant improvements were also noted in secondary body composition measures (raw BMI, -0.95 [95%CI, -1.46 to -0.45] and raw weight, -2.73 [95%CI, -4.04 to -1.43]) but not in metabolic variables. Overall, metformin was well tolerated. Five participants in the metformin group discontinued treatment owing to adverse events (agitation, 4; sedation, 1). Participants receiving metformin vs placebo experienced gastrointestinal adverse events during a significantly higher percentage of treatment days (25.1%vs 6.8%; P = .005). CONCLUSIONS AND RELEVANCE Metformin may be effective in decreasing weight gain associated with atypical antipsychotic use and is well tolerated by children and adolescents with ASD. [ABSTRACT FROM AUTHOR]

Background: Mechanical circulatory support (MCS) devices can be used in high-risk percutaneous coronary intervention (PCI). Our objective was to describe trends and outcomes of prophylactic MCS use in elective PCI for patients with stable coronary artery disease in the American College of Cardiology National Cardiovascular Data Registry's CathPCI registry. Methods: Among 2 108 715 consecutive patients with stable coronary artery disease undergoing elective PCI in the CathPCI registry between 2009 and 2018, we examined patterns of prophylactic use of MCS. Propensity score models with inverse probability of treatment weighting compared effectiveness (in-hospital death, cardiogenic shock, or new heart failure) and safety (stroke, tamponade, major bleeding, or vascular complication requiring treatment) between patients treated with intra-aortic balloon pump versus other MCS (Impella or extracorporeal membrane oxygenation). Results: Overall, 6905 (0.3%) patients underwent elective PCI with prophylactic MCS. MCS use trended up from 0.2% of elective PCIs in 2009 to 0.6% in 2018 (P <0.0001), driven by other MCS (P <0.0001), whereas intra-aortic balloon pump use remained low and constant (P =0.12). In-hospital major adverse cardiac events and cardiovascular complications occurred in 7.1% and 18.8% of elective PCI patients with prophylactic MCS use and 0.5% and 2.3% of patients without prophylactic MCS use. Intra-aortic balloon pump use was associated with a higher risk of major adverse cardiac events (9.6% versus 6.0%, adjusted odds ratio, 1.59 [95% CI, 1.32–1.91]) but lower risk of complications (18.2% versus 19.1%, adjusted odds ratio, 0.88 [95% CI, 0.77–0.99]) than use of other MCS. Conclusions: The use of prophylactic MCS has increased over time for elective PCI in patients with stable coronary artery disease. Intra-aortic balloon pump was associated with higher major adverse cardiac events but lower risk of procedural complications compared with other MCS. [ABSTRACT FROM AUTHOR]

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19., Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia., Design, Setting, and Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021., Interventions: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day)., Main Outcomes and Measures: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale., Results: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies., Conclusions and Relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo., Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

Objectives: Limited studies of percutaneous coronary intervention (PCI) of the left internal mammary artery (LIMA) graft exist. We compared outcomes of different bypass grafts to the left anterior descending (LAD) coronary artery., Methods: Participants ≥65 years old in the CathPCI Registry who underwent PCI of a bypass graft to the LAD between 2009 and 2014 were included. Individuals were divided by graft type: LIMA; saphenous vein graft (SVG); or other. Clinical characteristics and outcomes using Medicare claims data for mortality, rehospitalization for myocardial infarction (MI), stroke, or unplanned repeat revascularization at 1 year were examined., Results: There were 10,051 PCIs performed on grafts to the LAD: 6797 SVGs (67.6%), 3011 LIMA grafts (30.0%); and 243 other (2.4%). Procedural success rates (SVG 92.9%, LIMA 91.1%, other 93.4%; P=.65) and in-patient mortality rates (SVG 3.0%, LIMA 2.7%, other 2.1%; P=.61) were similar. However, dissection rates were higher in LIMA interventions (SVG 0.7%, LIMA 2.8%, other 2.5%; P<.001). At 1 year, mortality, MI, and repeat revascularization were lower in arterial grafts (mortality: SVG 16.6%, LIMA 14.8%, other 11.8% [P<.001]; MI: SVG 9.9%, LIMA, 6.6%, other 8.1% [P<.001]; revascularization: SVG 14.4%, LIMA 9.5%, other 10.4% [P<.001]). After multivariable adjustment, LIMA patients had lower rates of MI (hazard ratio, 0.71; 95% confidence interval, 0.60-0.84) and repeat revascularization (hazard ratio, 0.68; 95% confidence interval, 0.59-0.79) compared with the SVG group. Mortality was not significantly different., Conclusions: Despite similar procedural success rates compared with SVG and other graft types, LIMA interventions were independently associated with lower rates of recurrent MI and repeat revascularization at 1 year.

Background: Traditional methods of surveillance of catheter-associated urinary tract infections (CAUTIs) are error-prone and resource-intensive. To resolve these issues, we developed a highly sensitive electronic surveillance tool., Objective: To develop an electronic surveillance tool for CAUTIs and assess its performance., Methods: The study was conducted at a 947-bed tertiary care center. Patients included adults aged ≥18 years admitted to an intensive care unit between January 10 and June 30, 2012, with an indwelling urinary catheter during their admission. We identified CAUTIs using 4 methods: traditional surveillance (TS) (ie, manual chart review by ICPs), an electronic surveillance (ES) tool, augmented electronic surveillance (AES) (ie, ES with chart review on a subset of cases), and reference standard (RS) (ie, a subset of CAUTIs originally ascertained by TS or ES, confirmed by review). We assessed performance characteristics to RS for reviewed cases., Results: We identified 417 candidate CAUTIs in 308 patients; 175 (42.0%) of these candidate CAUTIs were selected for review, yielding 32 confirmed CAUTIs in 22 patients (RS). Compared with RS, the sensitivities of TS, ES, and AES were 43.8% (95% confidence interval [CI], 26.4%-62.3%), 100.0% (95% CI, 89.1%-100.0%), and 100.0% (95% CI, 89.1%-100.0%). Specificities were 82.5% (95% CI, 75.3%-88.4%), 2.8% (95% CI, 0.8%-7.0%), and 100.0% (95% CI, 97.5%-100.0%)., Conclusions: Electronic CAUTI surveillance offers a streamlined approach to improve reliability and resource burden of surveillance., (Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)