The Efficacy and Safety of Immune Checkpoint Inhibitors in Adrenocortical Carcinoma: A Systematic Review and Meta-Analysis.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of different malignancies. However, their efficacy in advanced adrenocortical carcinoma (ACC) remains uncertain. Thus, we conducted a systematic review and meta-analysis to summarize the efficacy and tolerability of ICIs in patients with advanced ACC. We searched PubMed, Scopus, and CENTRAL for studies that used ICIs in ACC. Studies with more than five patients were included in the meta-analysis of the objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and grade 3/4 adverse events. Twenty studies with 23 treatment arms and 250 patients were included. Single-agent anti-PD1 or anti-PD-L1 treatment was utilized in 13 treatment arms, whereas an anti-PD1 or anti-PD-L1 and anti-CTLA4 combination was used in 4 treatment arms. Other anti-PD1- or anti-PD-L1-based combinations were used in five treatment arms. The ORR was 14% (95% CI = 10-19%, I2 = 0%), and the DCR was 43% (95% CI = 37-50%, I2 = 13%). The combination anti-PD1- or anti-PD-L1-based treatment strategies did not correlate with higher responses compared with monotherapy. The median OS was 13.9 months (95% CI = 7.85-23.05), and the median PFS was 2.8 months (95% CI = 1.8-5.4). ICIs have a modest efficacy in advanced ACC but a good OS. Further studies are needed to investigate predictive biomarkers for ICI response and to compare ICI-based strategies with the current standard of care.

Sex differences in clinical features, utilization of oral anticoagulant agents, and 1-year outcome in Middle Eastern patients with atrial fibrillation.

OBJECTIVE: Studies have revealed that sex can predict differences in multiple aspects of atrial fibrillation (AF). These differences are underreported in the Middle East. This study aims to describe sex-specific differences in risk factors, symptomatology, management, and outcomes in Middle Eastern patients with AF. METHODS: The JoFib (Jordan-Atrial-Fibrillation) study is an observational, prospective, multicenter, nationwide registry in AF. Comparisons were made between female and male patients using Pearson chi-square and Mann-Whitney U tests. Multivariable regression models were constructed to investigate whether the female sex was predictive of any AF-related outcomes (all-cause death, cardiovascular death, ischemic stroke or systemic embolism [IS/SE], major bleeding, and clinically relevant non-major bleeding). RESULTS: Of 2,020 patients with AF, 54% (n = 1091) were females. Females with AF were older (median age 71 vs. 69, p <.001), but had less heart failure (20.9% vs. 27.2%, p = .001) and coronary artery disease (7.5% vs. 14.7%, p <.001). Females with AF were more symptomatic (74.7% vs. 66.5%, p <.001) and frequently received anticoagulant therapy (84.4% vs. 78.9%, p = .001). Rhythm control was pursued less frequently in females (23.4% vs. 27.3%, p = .04). All studied outcomes occurred with similar frequencies in females and males, and sex was not significantly predictive of any outcome. CONCLUSION: Females with AF are more symptomatic, yet they are treated less with rhythm control. Despite higher risk, females have similar risk-adjusted all-cause cardiovascular death and stroke rates compared to males. Future studies should explore how treatments and interventions can influence quality-of-life and cardiovascular outcomes in females with AF.

Association Between Clinic-Reported Third Next Available Appointment and Patient-Reported Access to Primary Care.

This cross-sectional study examines the association of the third next available appointment with patient-reported measures of access in primary care settings.

Retention on antiretroviral therapy during Universal Test and Treat implementation in Zomba district, Malawi: a retrospective cohort study.

INTRODUCTION: Since June 2016, the national HIV programme in Malawi has adopted Universal Test and Treat (UTT) guidelines requiring that all persons who test HIV positive will be referred to start antiretroviral therapy (ART). Although there is strong evidence from clinical trials that early initiation of ART leads to reduced morbidity and mortality, the impact of UTT on retention on ART in real-life programmatic settings in Africa is not yet known. METHODS: We conducted a retrospective cohort study in Zomba district, Malawi to compare ART outcomes of patients who initiated ART under 2016 UTT guidelines and those who started ART prior to rollout of UTT (pre-UTT). We analysed data from 32 rural and urban health facilities of various sizes. Cox proportional hazards modelling was used to determine the independent risk factors of attrition from ART at 12 months. All analyses were adjusted for clustering by health facility using a robust standard errors approach. RESULTS: Among 1492 patients (mean age 34.4 years, 933 (63%) female) who initiated ART during the study period, 501 were enrolled in the pre-UTT cohort and 911 during UTT. At 12 months, retention on ART in the UTT cohort was higher than in the pre-UTT cohort 83.0% (95% confidence interval (CI): 81.0% to 85.0%) versus 76.2% (95% CI 73.9% to 78.5%). Adolescents, aged 10 to 19 years (adjusted hazard ratio (aHR) 1.53; 95% CI 1.01 to 2.32), and women who were pregnant or breastfeeding at ART initiation (aHR 1.87; 95% CI 1.30 to 2.38) were at higher risk of attrition in the combined pre-UTT and UTT cohort. CONCLUSIONS: Retention on ART was nearly 6% higher after UTT introduction. Young adults and women who were pregnant or breastfeeding at the start of ART were at increased risk of attrition, emphasizing the need for targeted interventions for these groups to achieve the 90-90-90 UNAIDS targets in the UTT era.

Correction to: The Toronto cognitive assessment (TorCA): normative data and validation to detect amnestic mild cognitive impairment.

Upon publication of this article [1], it was brought to our attention that one of the 303 participants in the normative study should have been deleted from the database.

The Toronto Cognitive Assessment (TorCA): normative data and validation to detect amnestic mild cognitive impairment.

BACKGROUND: A need exists for easily administered assessment tools to detect mild cognitive changes that are more comprehensive than screening tests but shorter than a neuropsychological battery and that can be administered by physicians, as well as any health care professional or trained assistant in any medical setting. The Toronto Cognitive Assessment (TorCA) was developed to achieve these goals. METHODS: We obtained normative data on the TorCA (n = 303), determined test reliability, developed an iPad version, and validated the TorCA against neuropsychological assessment for detecting amnestic mild cognitive impairment (aMCI) (n = 50/57, aMCI/normal cognition). For the normative study, healthy volunteers were recruited from the Rotman Research Institute registry. For the validation study, the sample was comprised of participants with aMCI or normal cognition based on neuropsychological assessment. Cognitively normal participants were recruited from both healthy volunteers in the normative study sample and the community. RESULTS: The TorCA provides a stable assessment of multiple cognitive domains. The total score correctly classified 79% of participants (sensitivity 80%; specificity 79%). In an exploratory logistic regression analysis, indices of Immediate Verbal Recall, Delayed Verbal and Visual Recall, Visuospatial Function, and Working Memory/Attention/Executive Control, a subset of the domains assessed by the TorCA, correctly classified 92% of participants (sensitivity 92%; specificity 91%). Paper and iPad version scores were equivalent. CONCLUSIONS: The TorCA can improve resource utilization by identifying patients with aMCI who may not require more resource-intensive neuropsychological assessment. Future studies will focus on cross-validating the TorCA for aMCI, and validation for disorders other than aMCI.