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BACKGROUND - Kaposi sarcoma (KS) remains common among HIV-infected persons. To better understand KS etiology and to help target prevention efforts, we comprehensively examined a variety of CD4 T-cell count and HIV-1 RNA viral load (VL) measures, as well as antiretroviral therapy (ART) use, to determine independent predictors of KS risk.
SETTING - North American AIDS Cohort Collaboration on Research and Design.
METHODS - We followed HIV-infected persons during 1996-2009 from 18 cohorts. We used time-updated Cox regression to model relationships between KS risk and recent, lagged, trajectory, and cumulative CD4 count or VL measures, as well as ART use. We used Akaike's information criterion and global P values to derive a final model.
RESULTS - In separate models, the relationship between each measure and KS risk was highly significant (P < 0.0001). Our final mutually adjusted model included recent CD4 count [hazard ratio (HR) for <50 vs. ≥500 cells/μL = 12.4; 95% confidence interval (CI): 6.5 to 23.8], recent VL (HR for ≥100,000 vs. ≤500 copies/mL = 3.8; 95% CI: 2.0 to 7.3), and cumulative (time-weighted mean) VL (HR for ≥100,000 vs. ≤500 copies/mL = 2.5; 95% CI: 1.0 to 5.9). Each P-trend was <0.0001. After adjusting for these measures, we did not detect an independent association between ART use and KS risk.
CONCLUSIONS - Our results suggested a multifactorial etiology for KS, with early and late phases of development. The cumulative VL effect suggested that controlling HIV replication promptly after HIV diagnosis is important for KS prevention. We observed no evidence for direct anti-KS activity of ART, independent of CD4 count and VL.
Disruption of continuous retention in care (discontinuity) is associated with HIV disease progression. We examined sex, race, and HIV risk disparities in discontinuity after antiretroviral therapy (ART) initiation among patients in North America. Adults (≥18 years of age) initiating ART from 2000 to 2010 were included. Discontinuity was defined as first disruption of continuous retention (≥2 visits separated by >90 days in the calendar year). Relative hazard ratio (HR) and times from ART initiation until discontinuity by race, sex, and HIV risk were assessed by modeling of the cumulative incidence function (CIF) in the presence of the competing risk of death. Models were adjusted for cohort site, baseline age, and CD4 cell count within 1 year before ART initiation; nadir CD4 cell count after ART, but before a study event, was assessed as a mediator. Among 17,171 adults initiating ART, median follow-up time was 3.97 years, and 49% were observed to have ≥1 discontinuity of care. In adjusted regression models, the hazard of discontinuity for patients was lower for females versus males [HR: 0.84; 95% confidence interval (CI): 0.79-0.89] and higher for blacks versus nonblacks (HR: 1.17; 95% CI: 1.12-1.23) and persons with injection drug use (IDU) versus non-IDU risk (HR: 1.33; 95% CI: 1.25-1.41). Sex, racial, and HIV risk differences in clinical retention exist, even accounting for access to care and known competing risks for discontinuity. These results point to vulnerable populations at greatest risk for discontinuity in need of improved outreach to prevent disruptions of HIV care.
OBJECTIVES - Registry-based clinical research in nephrolithiasis is critical to advancing quality in urinary stone disease management and ultimately reducing stone recurrence. A need exists to develop Health Insurance Portability and Accountability Act (HIPAA)-compliant registries that comprise integrated electronic health record (EHR) data using prospectively defined variables. An EHR-based standardized patient database-the Registry for Stones of the Kidney and Ureter (ReSKU™)-was developed, and herein we describe our implementation outcomes.
MATERIALS AND METHODS - Interviews with academic and community endourologists in the United States, Canada, China, and Japan identified demographic, intraoperative, and perioperative variables to populate our registry. Variables were incorporated into a HIPAA-compliant Research Electronic Data Capture database linked to text prompts and registration data within the Epic EHR platform. Specific data collection instruments supporting New patient, Surgery, Postoperative, and Follow-up clinical encounters were created within Epic to facilitate automated data extraction into ReSKU.
RESULTS - The number of variables within each instrument includes the following: New patient-60, Surgery-80, Postoperative-64, and Follow-up-64. With manual data entry, the mean times to complete each of the clinic-based instruments were (minutes) as follows: New patient-12.06 ± 2.30, Postoperative-7.18 ± 1.02, and Follow-up-8.10 ± 0.58. These times were significantly reduced with the use of ReSKU structured clinic note templates to the following: New patient-4.09 ± 1.73, Postoperative-1.41 ± 0.41, and Follow-up-0.79 ± 0.38. With automated data extraction from Epic, manual entry is obviated.
CONCLUSIONS - ReSKU is a longitudinal prospective nephrolithiasis registry that integrates EHR data, lowering the barriers to performing high quality clinical research and quality outcome assessments in urinary stone disease.
Epilepsy surgery is under-utilized, but recent studies reach conflicting conclusions regarding whether epilepsy surgery rates are currently declining, increasing, or remaining steady. However, data in these prior studies are biased toward high-volume epilepsy centers, or originate from sources that do not disaggregate various procedure types. All major epilepsy surgery procedures were extracted from the Centers for Medicare and Medicaid Services Part B National Summary Data File and the American College of Surgeons National Surgical Quality Improvement Program. Procedure rates, trends, and complications were analyzed, and patient-level predictors of postoperative adverse events were identified. Between 2000-2013, 6200 cases of epilepsy surgery were identified. Temporal lobectomy was the most common procedure (59% of cases), and most did not utilize electrocorticography (63-64%). Neither temporal nor extratemporal lobe epilepsy surgery rates changed significantly during the study period, suggesting no change in utilization. Adverse events, including major and minor complications, occurred in 15.3% of temporal lobectomies and 55.6% of hemispherectomies. Our findings suggest stagnant rates of both temporal and extratemporal lobe epilepsy surgery across U.S. surgical centers over the past decade. This finding contrasts with prior reports suggesting a recent dramatic decline in temporal lobectomy rates at high-volume epilepsy centers. We also observed higher rates of adverse events when both low- and high-volume centers were examined together, as compared to reports from high-volume centers alone. This is consistent with the presence of a volume-outcome relationship in epilepsy surgery.
Copyright © 2016 Elsevier B.V. All rights reserved.
There is an increasing awareness and clinical interest in cardiac safety during cancer therapy as well as in optimally addressing cardiac issues in cancer survivors. Although there is an emerging expertise in this area, known as cardio-oncology, there is a lack of organization in the essential components of contemporary training. This proposal, an international consensus statement organized by the International Cardioncology Society and the Canadian Cardiac Oncology Network, attempts to marshal the important ongoing efforts for training the next generation of cardio-oncologists. The necessary elements are outlined, including the expectations for exposure necessary to develop adequate training. There should also be a commitment to local, regional, and international education and research in cardio-oncology as a requirement for advancement in the field.
Copyright © 2016 Elsevier Inc. All rights reserved.
Although the role of complete gene inactivation by two loss-of-function mutations inherited in trans is well-established in recessive Mendelian diseases, we have not yet explored how such gene knockouts (KOs) could influence complex human phenotypes. Here, we developed a statistical framework to test the association between gene KOs and quantitative human traits. Our method is flexible, publicly available, and compatible with common genotype format files (e.g. PLINK and vcf). We characterized gene KOs in 4498 participants from the NHLBI Exome Sequence Project (ESP) sequenced at high coverage (>100×), 1976 French Canadians from the Montreal Heart Institute Biobank sequenced at low coverage (5.7×), and >100 000 participants from the Genetic Investigation of ANthropometric Traits (GIANT) Consortium genotyped on an exome array. We tested associations between gene KOs and three anthropometric traits: body mass index (BMI), height and BMI-adjusted waist-to-hip ratio (WHR). Despite our large sample size and multiple datasets available, we could not detect robust associations between specific gene KOs and quantitative anthropometric traits. Our results highlight several limitations and challenges for future gene KO studies in humans, in particular when there is no prior knowledge on the phenotypes that might be affected by the tested gene KOs. They also suggest that gene KOs identified with current DNA sequencing methodologies probably do not strongly influence normal variation in BMI, height, and WHR in the general human population.
© The Author 2016. Published by Oxford University Press.
UNLABELLED - ♦
BACKGROUND - In general, efforts to standardize care based on group consensus practice guidelines have resulted in lower morbidity and mortality. Although there are published guidelines regarding insertion and perioperative management of peritoneal dialysis (PD) catheters, variation in practice patterns between centers may exist. The objective of this study is to understand variation in PD catheter insertion practices in preparation for conducting future studies. ♦
METHODS - An electronic survey was developed by the research committee of the International Society for Peritoneal Dialysis - North American Research Consortium (ISPD-NARC) to be completed by physicians and nurses involved in PD programs across North America. It consisted of 45 questions related to 1) organizational characteristics; 2) PD catheter insertion practices; 3) current quality-improvement initiatives; and 4) interest in participation in PD studies. Invitation to participate in the survey was given to nephrologists and nurses in centers across Canada and the United States (US) identified by participation in the inaugural meeting of the ISPD-NARC. Descriptive statistics were applied to analyze the data. ♦
RESULTS - Fifty-one ISPD-NARC sites were identified (45% in Canada and 55% in the US) of which 42 responded (82%). Center size varied significantly, with prevalent PD population ranging from 6 - 300 (median: 60) and incident PD patients in the year prior to survey administration ranging from 3 - 180 (median: 20). The majority of centers placed fewer than 19 PD catheters/year, with a range of 0 - 50. Availability of insertion techniques varied significantly, with 83% of centers employing more than 1 insertion technique. Seventy-one percent performed laparoscopic insertion with advanced techniques (omentectomy, omentopexy, and lysis of adhesions), 62% of sites performed open surgical dissection, 10% performed blind insertion via trocar, and 29% performed blind placement with the Seldinger technique. Use of double-cuff catheters was nearly universal, with a near even distribution of catheters with pre-formed bend versus straight inter-cuff segments. There was also variation in the choice of perioperative antibiotics and perioperative flushing practices. Although 86% of centers had quality-improvement initiatives, there was little consensus as to appropriate targets. ♦
CONCLUSIONS - There is marked variability in PD catheter insertion techniques and perioperative management. Large multicenter studies are needed to determine associations between these practices and catheter and patient outcomes. This research could inform future trials and guidelines and improve practice. The ISPD-NARC is a network of PD units that has been formed to conduct multicenter studies in PD.
Copyright © 2016 International Society for Peritoneal Dialysis.
The proportion of overweight and obese adults in the United States and Canada has increased over the past decade, but temporal trends in body mass index (BMI) and weight gain on antiretroviral therapy (ART) among HIV-infected adults have not been well characterized. We conducted a cohort study comparing HIV-infected adults in the North America AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to United States National Health and Nutrition Examination Survey (NHANES) controls matched by sex, race, and age over the period 1998 to 2010. Multivariable linear regression assessed the relationship between BMI and year of ART initiation, adjusting for sex, race, age, and baseline CD4(+) count. Temporal trends in weight on ART were assessed using a generalized least-squares model further adjusted for HIV-1 RNA and first ART regimen class. A total of 14,084 patients from 17 cohorts contributed data; 83% were male, 57% were nonwhite, and the median age was 40 years. Median BMI at ART initiation increased from 23.8 to 24.8 kg/m(2) between 1998 and 2010 in NA-ACCORD, but the percentage of those obese (BMI ≥30 kg/m(2)) at ART initiation increased from 9% to 18%. After 3 years of ART, 22% of individuals with a normal BMI (18.5-24.9 kg/m(2)) at baseline had become overweight (BMI 25.0-29.9 kg/m(2)), and 18% of those overweight at baseline had become obese. HIV-infected white women had a higher BMI after 3 years of ART as compared to age-matched white women in NHANES (p = 0.02), while no difference in BMI after 3 years of ART was observed for HIV-infected men or non-white women compared to controls. The high prevalence of obesity we observed among ART-exposed HIV-infected adults in North America may contribute to health complications in the future.
SETTING - Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear.
OBJECTIVES - To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity.
DESIGN - Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV.
RESULTS - Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors.
CONCLUSION - The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred.