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BackgroundIndependent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada.MethodsWe examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.ResultsAmong 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P

Introduction: Despite large-scale quality improvement initiatives, substantial proportions of patients with ST-elevation myocardial infarction (STEMI) transferred to percutaneous coronary intervention centers do not receive percutaneous coronary intervention within the recommended 120 minutes. We sought to examine the contributory role of emergency medical services (EMS) activation relative to percutaneous coronary intervention center activation in the timeliness of care for patients transferred with STEMI.Methods: We conducted a retrospective analysis of interfacility transfers from emergency departments (ED) to a single percutaneous coronary intervention center between 2011–2014. We included emergency department (ED) patients transferred to the percutaneous coronary intervention center and excluded scene transfers and those given fibrinolytics. We calculated descriptive statistics and used multivariable linear regression to model the association of variables with ED time intervals (arrival to electrocardiogram [ECG], ECG-to-EMS activation, and ECG-to-STEMI alert) adjusting for patient age, gender, mode of arrival, weekday hour presentation, facility transfers in the past year, and transferring facility distance.Results: We identified 159 patients who met inclusion criteria. Subjects were a mean of 59 years old (standard deviation 13), 22% female, and 93% White; 59% arrived by private vehicle, and 24% presented after weekday hours. EDs transferred a median of 9 STEMIs (interquartile range [IQR] 3, 15) in the past year and a median of 65 miles (IQR 35, 90) from the percutaneous coronary intervention center. Median ED length of stay was 65 minutes (IQR 51, 85). Among component intervals, arrival to ECG was 6%, ECG-to-EMS activation 32%, and ECG-to-STEMI alert was 49% of overall ED length of stay. Only 18% of transfers had EMS activation earlier than STEMI alert. ECG-to-EMS activation was shorter in EDs achieving length of stay ≤60 minutes compared to those >60 minutes (12 vs 31 minutes, P

IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.

IntroductionAdvances in ST-segment elevation myocardial infarction (STEMI) management have involved improving the clinical processes connecting patients with timely emergency cardiovascular care. Screening upon emergency department (ED) arrival for an early ECG to diagnose STEMI, however, is not optimal for all patients. In addition, the degree to which timely screening and diagnosis are associated with improved time to intervention and postpercutaneous coronary intervention outcomes, under more contemporary practice conditions, is not known.MethodsWe present the methods for a retrospective multicentre cohort study anticipated to include 1220 patients across seven EDs to (1) evaluate the relationship between timely screening and diagnosis with treatment and postintervention clinical outcomes; (2) introduce novel measures for cross-facility performance comparisons of screening and diagnostic care team performance including: door-to-screening, door-to-diagnosis and door-to-catheterisation laboratory arrival times and (3) describe the use of electronic health record data in tandem with an existing disease registry.Ethics and disseminationThe completion of this study will provide critical feedback on the quality of screening and diagnostic performance within the contemporary STEMI care pathway that can be used to (1) improve emergency care delivery for patients with STEMI presenting to the ED, (2) present novel metrics for the comparison of screening and diagnostic care and (3) inform the development of screening and diagnostic support tools that could be translated to other care environments. We will disseminate our results via publication and quality performance data sharing with each site. Institutional ethics review approval was received prior to study initiation.

Background: HIV incidence among women of reproductive age and vertical HIV transmission rates remain high in Latin America. We, therefore, quantified HIV care continuum barriers and outcomes among pregnant women living with HIV (WLWH) in Latin America. Methods: WLWH (aged [greater than or equal to]16 years) enrolling at Caribbean, Central and South America network for HIV epidemiology (CCA-SAnet) sites from 2000 to 2017 who had HIV diagnosis, pregnancy and delivery dates contributed. Logistic regression produced adjusted odds ratios (aOR) and 95% confidence intervals (CI) for retention in care ([greater than or equal to]2 visits [greater than or equal to]3 months apart) and virological suppression (viral load Results: Among 579 WLWH, median postpartum follow-up was 4.34 years (IQR 1.91, 7.35); 459 (79%) were HIV-diagnosed before pregnancy confirmation, 445 (77%) retained in care and 259 (45%) virologically suppressed at 12 months of postpartum. Cumulative incidence of LTFU was 21% by 12 months and 40% by five years postpartum. Those HIV-diagnosed during pregnancy had lower odds of retention (aOR = 0.58, 95% CI: 0.35 to 0.97) and virological suppression (aOR = 0.50, 95% CI: 0.31 to 0.82) versus those HIV-diagnosed before. Conclusion: HIV diagnosis during pregnancy was associated with poorer 12-month retention and virological suppression. Young women should be tested and linked to HIV care earlier to narrow these disparities. Keywords: HIV care continuum; HIV epidemiology; retention; vertical transmission; women; Latin America and the Caribbean (Region), 1 | INTRODUCTION Over 2 million people are currently living with HIV in Latin America and the Caribbean [1]. Rates of new infections are especially high among women of reproductive [...]

Introduction: Kaposi's sarcoma (KS) remains the most frequent malignancy in persons living with HIV (PWH) in Latin America. We examined KS trends and outcomes from Latin American clinical sites in the era of increased access to antiretroviral therapy (ART). Methods: Cohorts in Brazil, Peru, Mexico, Honduras, Argentina and Chile contributed clinical data of PWH [greater than or equal to]16 years old from 2000 to 2017, excluding patients with KS diagnosed before clinic enrolment. We compared KS incidence over time using multivariable incidence rate ratios. Predictors of KS before/at or after ART initiation and of mortality after KS were examined using Cox regression. Results: Of 25 981 PWH, 481 had incident KS, including 200 ART-naive and 281 ART-treated patients. From 2000 to 2017, the incidence of KS decreased from 55.1 to 3.0 per 1000 person-years. In models adjusting for CD4 and other factors, the relative risk for KS decreased from 2000 to 2008. Since 2010, the adjusted risk of KS increased in the periods before and 90 days after ART. In addition to low CD4 and male-to-male sex, KS risk after ART was associated with age and history of other AIDS-defining illnesses. Mortality after KS (approximately 25% after five years) was not associated with either year of KS diagnosis nor timing of diagnosis relative to ART initiation. Conclusions: KS incidence in Latin America has remained stable in recent years and risk is highest before and shortly after ART initiation. Early diagnosis of HIV and ART initiation remain critical priorities in the region. Keywords: Kaposi's sarcoma; HIV; antiretroviral therapy; incidence; mortality; Latin America, 1 | INTRODUCTION Kaposi's sarcoma (KS) is a frequent type of cancer among persons living with HIV (PWH) in Latin America [1]. In the United States, KS incidence dramatically fell [...]

Introduction: Identification of persons living with human immunodeficiency virus (HIV)-associated tuberculosis (TB) at increased risk for unfavourable TB outcomes would inform efforts to improve such outcomes. We sought to identify factors associated with a decreased risk of unfavourable TB treatment outcomes among people living with HIV-infection (PLHIV) in low- and middle-income countries (LMIC), with a specific focus on directly observed therapy (DOT) compared with self-administered therapy (SAT) during the continuation phase of anti-TB therapy. Methods: We conducted a retrospective cohort study among adults diagnosed with HIV-associated TB in Africa, Asia and the Americas from 2012 to 2013; data were collected from 2012 to 2016. Unfavourable TB treatment outcomes (death during TB treatment, and TB treatment failure or recurrence) were defined according to World Health Organization criteria. Receipt of DOT was obtained at the site level and defined as [greater than or equal to]5 days of DOT per week. The person administering DOT and treatment location varied by site. Lack of receipt of DOT was defined as SAT. Multivariable logistic regression estimated the adjusted odds of unfavourable TB treatment outcomes. Results: Among 1862 adults with HIV-associated TB included, 252 (13.5%) had unfavourable TB outcomes (226 deaths, 26 recurrences/failures). Overall, 1825 (98%) received DOT in the intensive phase and 1617 (87%) received DOT in the continuation phase. DOT in the continuation phase was not significantly associated with unfavourable TB outcomes (aOR 1.43, 95% CI 0.86 to 2.38) compared to SAT. Body mass index (BMI) change during anti-TB treatment (per 2 units increase, aOR 0.74, 95% CI 0.68 to 0.82) and CD[4.sup.+] count at TB diagnosis (200 vs. 50 cells/[micro]L, aOR 0.54, 95% CI 0.39 to 0.73) were both independently associated with decreased odds of unfavourable TB treatment outcomes. Conclusions: In this large, international cohort of people living with HIV-associated TB in LMIC who received intensive phase DOT, DOT during the continuation phase of anti-TB therapy was not associated with a decreased odds of unfavourable TB treatment outcomes compared to SAT. Randomized trials evaluating the effect of continuation-phase DOT on TB outcomes among PLHIV are needed. Keywords: tuberculosis; directly observed therapy; body mass index; human immunodeficiency virus infection; antiretroviral therapy, 1 | INTRODUCTION Tuberculosis (TB) remains a serious public health problem, particularly among people living with human immunodeficiency virus (PLHIV). TB is the leading cause of death among PLHIV worldwide, [...]

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown. Objectives: To compare the effects of lower (90% [range, 88–92%]), intermediate (94% [range, 92–96%]), and higher (98% [range, 96–100%]) oxygen-saturation targets on long-term outcomes. Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction. Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91–96%), 95% (93–97%), and 97% (95–99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92–2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62–1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83–1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life. Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes. [ABSTRACT FROM AUTHOR]