Impact of sex and age on chemotherapy efficacy, toxicity and survival in localised oesophagogastric cancer: A pooled analysis of 3265 individual patient data from four large randomised trials (OE02, OE05, MAGIC and ST03).

Background: There is a lack of large-scale randomised data evaluating the impact of sex and age in patients undergoing chemotherapy followed by potentially curative surgery for oesophagogastric cancer.

Patients And Methods: Individual patient data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival analysis, hazard ratios (HRs) were calculated for patients aged <70 and ≥ 70 years, as well as between males and females.

Economic evaluation of short treatment for multidrug-resistant tuberculosis, Ethiopia and South Africa: the STREAM trial.

Objective: To investigate cost changes for health systems and participants, resulting from switching to short treatment regimens for multidrug-resistant (MDR) tuberculosis.

Methods: We compared the costs to health systems and participants of long (20 to 22 months) and short (9 to 11 months) MDR tuberculosis regimens in Ethiopia and South Africa. Cost data were collected from participants in the STREAM phase-III randomized controlled trial and we estimated health-system costs using bottom-up and top-down approaches.

The design and statistical aspects of VIETNARMS: a strategic post-licensing trial of multiple oral direct-acting antiviral hepatitis C treatment strategies in Vietnam.

Background: Eliminating hepatitis C is hampered by the costs of direct-acting antiviral treatment and the need to treat hard-to-reach populations. Access could be widened by shortening or simplifying treatment, but limited research means it is unclear which approaches could achieve sufficiently high cure rates to be acceptable. We present the statistical aspects of a multi-arm trial designed to test multiple strategies simultaneously and a monitoring mechanism to detect and stop individual randomly assigned groups with unacceptably low cure rates quickly.

Comparative Healthcare Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS): A prospective, multi-centre therapeutic phase II parallel Randomised Control Trial.

Introduction: Focal therapy (FT) targets individual areas of cancer within the prostate, providing oncological control with minimal side-effects. Early evidence demonstrates encouraging short-medium-term outcomes. With no randomized controlled trials (RCT) comparing FT to radical therapies, Comparative Healthcare Research Outcomes of Novel Surgery in prostate cancer (CHRONOS) will compare the cancer control of these two strategies.

Evaluation of the Coverage of 3 Antibiotic Regimens for Neonatal Sepsis in the Hospital Setting Across Asian Countries.

Importance: High levels of antimicrobial resistance in neonatal bloodstream isolates are being reported globally, including in Asia. Local hospital antibiogram data may include too few isolates to meaningfully examine the expected coverage of antibiotic regimens.

Objective: To assess the coverage offered by 3 antibiotic regimens for empirical treatment of neonatal sepsis in Asian countries.

Transcriptional biomarkers for predicting development of tuberculosis: progress and clinical considerations.

http://bit.ly/35WiozD

Acceptability of a first-line anti-tuberculosis formulation for children: qualitative data from the SHINE trial.

We conducted a qualitative exploration into the palatability and acceptability of a novel fixed-dose combination (FDC) anti-tuberculosis drug. This study was nested in the SHINE (Shorter treatment for minimal TB in children) trial, which compares the safety and efficacy of treating non-severe drug-susceptible tuberculosis (TB) with a 6 vs. 4 months anti-tuberculosis regimen in children aged 0-16 years.

Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial.

Background: Carboplatin and paclitaxel administered every 3 weeks is standard-of-care first-line chemotherapy for epithelial ovarian cancer. The Japanese JGOG3016 trial showed a significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly carboplatin. In this study, we aimed to compare efficacy and safety of two dose-dense weekly regimens to standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer.

Reversible effect on lipids by switching from tenofovir disoproxil fumarate to tenofovir alafenamide and back.

Objective: The aim of the current study is to assess the effect of tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) on lipids in patients switching from TDF to TAF and back.

Methods: Retrospective data collection on patients who were initially switched from TDF to TAF and switched back to TDF after generics of TDF became available.

Results: In total, 385 patients were included.

Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response: a sub-study of the NEAT001/ANRS143 randomized trial.

Objectives: NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure.

Methods: Non-linear mixed-effects models (NONMEM v.

Co-trimoxazole or multivitamin multimineral supplement for post-discharge outcomes after severe anaemia in African children: a randomised controlled trial.

Background: Severe anaemia is a leading cause of paediatric admission to hospital in Africa; post-discharge outcomes remain poor, with high 6-month mortality (8%) and re-admission (17%). We aimed to investigate post-discharge interventions that might improve outcomes.

Methods: Within the two-stratum, open-label, multicentre, factorial randomised TRACT trial, children aged 2 months to 12 years with severe anaemia, defined as haemoglobin of less than 6 g/dL, at admission to hospital (three in Uganda, one in Malawi) were randomly assigned, using sequentially numbered envelopes linked to a second non-sequentially numbered set of allocations stratified by centre and severity, to enhanced nutritional supplementation with iron and folate-containing multivitamin multimineral supplements versus iron and folate alone at treatment doses (usual care), and to co-trimoxazole versus no co-trimoxazole.

Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer.

Purpose: In the CLASSIC and MAGIC trials, microsatellite instability (MSI)-high status was a favorable prognostic and potential negative predictive factor for neoadjuvant/adjuvant chemotherapy in resectable gastric cancer (GC). Given the low prevalence of MSI-high status in GC and its association with other positive prognostic variables, large data sets are needed to draw robust evidence of its prognostic/predictive value.

Patients And Methods: We performed a multinational, individual-patient-data meta-analysis of the prognostic/predictive role of MSI in patients with resectable GC enrolled in the MAGIC, CLASSIC, ARTIST, and ITACA-S trials.

Predictors of recurrence, early treatment failure and death from Staphylococcus aureus bacteraemia: Observational analyses within the ARREST trial.

Objectives: Adjunctive rifampicin did not reduce failure/recurrence/death as a composite endpoint in the ARREST trial of Staphylococcus aureus bacteraemia, but did reduce recurrences. We investigated clinically-defined 14-day treatment failure, and recurrence and S. aureus-attributed/unattributed mortality by 12-weeks to further define their predictors.

Transfusion Volume for Children with Severe Anemia in Africa.

Background: Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level.

Methods: In this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.

Immediate Transfusion in African Children with Uncomplicated Severe Anemia.

Background: The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes.

Methods: In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter.

Serum HE4 and diagnosis of ovarian cancer in postmenopausal women with adnexal masses.

Background: Transvaginal ultrasound and serum CA125 are routinely used for differential diagnosis of pelvic adnexal mass. Use of human epididymis 4 was approved in the United States in 2011. However, there is scarcity of studies evaluating the additional value of human epididymis 4.

Comparison of Transrectal Ultrasound Biopsy to Transperineal Template Mapping Biopsies Stratified by Multiparametric Magnetic Resonance Imaging Score in the PROMIS Trial.

Purpose: We evaluated the performance of transrectal ultrasound guided systematic and transperineal template mapping biopsies with a 5 mm sampling frame stratified by the multiparametric magnetic resonance imaging Likert score in the PROMIS (Prostate MR Imaging Study).

Materials And Methods: Biopsy naïve men due to undergo prostate biopsy for elevated prostate specific antigen and/or abnormal digital rectal examination underwent multiparametric magnetic resonance imaging, and transperineal template mapping and transrectal ultrasound guided systematic biopsies, which were performed and reported while blinded to other test results. Clinically significant prostate cancer was primarily defined as Gleason 4 + 3 or greater, or a maximum cancer core length of 6 mm or more of any grade.

Quality assurance of surgery in the randomized ST03 trial of perioperative chemotherapy in carcinoma of the stomach and gastro-oesophageal junction.

Background: The UK Medical Research Council ST03 trial compared perioperative epirubicin, cisplatin and capecitabine (ECX) chemotherapy with or without bevacizumab (B) in gastric and oesophagogastric junctional cancer. No difference in survival was noted between the arms of the trial. The present study reviewed the standards and performance of surgery in the context of the protocol-specified surgical criteria.

Correction to: Addressing challenges in scaling up TB and HIV treatment integration in rural primary healthcare clinics in South Africa (SUTHI): a cluster randomized controlled trial protocol.

Following publication of the original article [1], the authors reported an error in the wording of the study hypothesis. The error occurs in the Aims and Objectives sub-section of the Methods section and is highlighted in bold below.

High EMSY expression defines a BRCA-like subgroup of high-grade serous ovarian carcinoma with prolonged survival and hypersensitivity to platinum.

Background: Approximately half of high-grade serous ovarian carcinomas (HGSOCs) demonstrate homologous recombination repair (HR) pathway defects, resulting in a distinct clinical phenotype comprising hypersensitivity to platinum, superior clinical outcome, and greater sensitivity to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors. EMSY, which is known to be amplified in breast and ovarian cancers, encodes a protein reported to bind and inactivate BRCA2. Thus, EMSY overexpression may mimic BRCA2 mutation, resulting in HR deficiency.