Community-based complex interventions to sustain independence in older people, stratified by frailty: a systematic review and network meta-analysis.

Background: Sustaining independence is important for older people, but there is insufficient guidance about which community health and care services to implement.

Objectives: To synthesise evidence of the effectiveness of community services to sustain independence for older people grouped according to their intervention components, and to examine if frailty moderates the effect.

Review Design: Systematic review and network meta-analysis.

Trial Protocol of a Phase II Study of mFOLFOXIRI after Metastasectomy in Patients with Oligometastatic Colorectal Cancer (FANTASTIC Study).

Background: The survival benefit of adjuvant chemotherapy after surgical resection of oligometastases from colorectal cancer (CRC) remains unclear. The prognostic role of circulating-tumor DNA (ctDNA) was reported recently and a risk stratification strategy based on monitoring minimal/molecular residual disease (MRD) has been proposed, however, which drug regimen is most effective for ctDNA-positive patients is unknown.

Methods/design: Oligometastatic CRC patients planning to undergo surgery were registered in this study.

Calculating the power of a planned individual participant data meta-analysis to examine prognostic factor effects for a binary outcome.

Collecting data for an individual participant data meta-analysis (IPDMA) project can be time consuming and resource intensive and could still have insufficient power to answer the question of interest. Therefore, researchers should consider the power of their planned IPDMA before collecting IPD. Here we propose a method to estimate the power of a planned IPDMA project aiming to synthesise multiple cohort studies to investigate the (unadjusted or adjusted) effects of potential prognostic factors for a binary outcome.

Heparin-induced thrombocytopenia with very high antibody titer is associated with slower platelet recovery and higher risk of thrombosis.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder mediated by platelet-activating antibodies targeting platelet factor 4 (PF4) and heparin complex. A higher antibody titer is reflected in a higher optical density (OD) by enzyme-linked immunosorbent assay for heparin-PF4 antibodies. This single-institution retrospective study of 116 HIT patients examined the effect of heparin-PF4 OD on time to platelet recovery, vascular thrombosis, and in-hospital mortality.

Development of the Community-based complex Interventions to sustain Independence in Older People (CII-OP) typology: a qualitative synthesis of interventions in randomised controlled trials.

Introduction: Community-based services to sustain independence for older people have varying configurations. A typology of these interventions would improve service provision and research by providing conceptual clarity and enabling the identification of effective configurations. We aimed to produce such a typology.

Community based complex interventions to sustain independence in older people: systematic review and network meta-analysis.

Objective: To synthesise evidence of the effectiveness of community based complex interventions, grouped according to their intervention components, to sustain independence for older people.

Design: Systematic review and network meta-analysis.

Data Sources: Medline, Embase, CINAHL, PsycINFO, CENTRAL, clinicaltrials.

Evaluation of clinical prediction models (part 2): how to undertake an external validation study.

External validation studies are an important but often neglected part of prediction model research. In this article, the second in a series on model evaluation, Riley and colleagues explain what an external validation study entails and describe the key steps involved, from establishing a high quality dataset to evaluating a model’s predictive performance and clinical usefulness.

A Deep Learning Decision Support Tool to Improve Risk Stratification and Reduce Unnecessary Biopsies in BI-RADS 4 Mammograms.

Purpose: To evaluate the performance of a biopsy decision support algorithmic model, the intelligent-augmented breast cancer risk calculator (iBRISK), on a multicenter patient dataset.

Materials And Methods: iBRISK was previously developed by applying deep learning to clinical risk factors and mammographic descriptors from 9700 patient records at the primary institution and validated using another 1078 patients. All patients were seen from March 2006 to December 2016.

Risk of bias assessments in individual participant data meta-analyses of test accuracy and prediction models: a review shows improvements are needed.

Objectives: Risk of bias assessments are important in meta-analyses of both aggregate and individual participant data (IPD). There is limited evidence on whether and how risk of bias of included studies or datasets in IPD meta-analyses (IPDMAs) is assessed. We review how risk of bias is currently assessed, reported, and incorporated in IPDMAs of test accuracy and clinical prediction model studies and provide recommendations for improvement.

Using temporal recalibration to improve the calibration of risk prediction models in competing risk settings when there are trends in survival over time.

We have previously proposed temporal recalibration to account for trends in survival over time to improve the calibration of predictions from prognostic models for new patients. This involves first estimating the predictor effects using data from all individuals (full dataset) and then re-estimating the baseline using a subset of the most recent data whilst constraining the predictor effects to remain the same. In this article, we demonstrate how temporal recalibration can be applied in competing risk settings by recalibrating each cause-specific (or subdistribution) hazard model separately.

Two-stage or not two-stage? That is the question for IPD meta-analysis projects.

Individual participant data meta-analysis (IPDMA) projects obtain, check, harmonise and synthesise raw data from multiple studies. When undertaking the meta-analysis, researchers must decide between a two-stage or a one-stage approach. In a two-stage approach, the IPD are first analysed separately within each study to obtain aggregate data (e.

Calculating the power of a planned individual participant data meta-analysis of randomised trials to examine a treatment-covariate interaction with a time-to-event outcome.

Before embarking on an individual participant data meta-analysis (IPDMA) project, researchers should consider the power of their planned IPDMA conditional on the studies promising their IPD and their characteristics. Such power estimates help inform whether the IPDMA project is worth the time and funding investment, before IPD are collected. Here, we suggest how to estimate the power of a planned IPDMA of randomised trials aiming to examine treatment-covariate interactions at the participant-level (i.

Risk-of-bias assessment using Cochrane's revised tool for randomized trials (RoB 2) was useful but challenging and resource-intensive: observations from a systematic review.

Objectives: To report our experience using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2).

Study Design And Setting: Two reviewers independently applied RoB 2 to results of interest in a large systematic review of complex interventions and reached consensus. We recorded the time taken, and noted and discussed our difficulties using the tool, and the resolutions we adopted.

Predicting antipsychotic-induced weight gain in first episode psychosis - A field-wide systematic review and meta-analysis of non-genetic prognostic factors.

Background: Whether non-genetic prognostic factors significantly influence the variable prognosis of antipsychotic-induced weight gain (AIWG) has not yet been systematically explored.

Methods: Searches for both randomized and non-randomized studies were undertaken using four electronic databases, two trial registers, and via supplemental searching methods. Unadjusted and adjusted estimates were extracted.

Scope and mortality of adult medical ICU patients in an Eastern Cape tertiary hospital.

Background: The characteristics and mortality outcomes of patients admitted to South African intensive care units (ICUs) owing to medical conditions are unknown. Available literature is derived from studies based on data from high-income countries.

Objectives: To determine ICU utilisation by medical patients and evaluate the scope of admissions and clinical associations with hospital mortality in ICU patients 12 years and older admitted to an Eastern Cape tertiary ICU, particularly in the subset with HIV disease.

Minimum sample size for developing a multivariable prediction model using multinomial logistic regression.

Aims: Multinomial logistic regression models allow one to predict the risk of a categorical outcome with > 2 categories. When developing such a model, researchers should ensure the number of participants () is appropriate relative to the number of events () and the number of predictor parameters () for each category . We propose three criteria to determine the minimum required in light of existing criteria developed for binary outcomes.

Calculating the power to examine treatment-covariate interactions when planning an individual participant data meta-analysis of randomized trials with a binary outcome.

Before embarking on an individual participant data meta-analysis (IPDMA) project, researchers and funders need assurance it is worth their time and cost. This should include consideration of how many studies are promising their IPD and, given the characteristics of these studies, the power of an IPDMA including them. Here, we show how to estimate the power of a planned IPDMA of randomized trials to examine treatment-covariate interactions at the participant level (ie, treatment effect modifiers).

A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer.

Purpose: A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy and stereotactic body radiotherapy (SBRT) in patients with mTNBC.

Patients And Methods: In this single-arm, open-label Phase 2 trial, patients with mTNBC were treated with ADV/HSV-tk [5 × 1011 virus particles (vp)] intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab (200 mg, every 3 weeks). The primary endpoint was clinical benefit rate [CBR; complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks per RECIST version1.

BESPOKE IO protocol: a multicentre, prospective observational study evaluating the utility of ctDNA in guiding immunotherapy in patients with advanced solid tumours.

Introduction: Immunotherapy (IO) has transformed the treatment paradigm for a wide variety of solid tumours. However, assessment of response can be challenging with conventional radiological imaging (eg, iRECIST), which do not precisely capture the unique response patterns of tumours treated with IO. Emerging data suggest that circulating tumour DNA (ctDNA) can aid in response assessment in patients with solid tumours receiving IO.

The role of learning in farmer-led innovation.

Context: Farmer-led innovation brings farmers together with other stakeholders in a collaborative endeavour that recognises multiple forms of expertise. Critical engagement with mainstream models of agricultural science and technology (AST) development has drawn attention to the isolation of farmers as technology adopters within a compartmentalised model of AST development and dissemination. Academic, government and non-governmental actors and organisations are increasingly supporting facilitated processes in which farmers, scientists and engineers develop new knowledge, learning together about the nature of the problems being faced and the potential of different solution pathways.

Minimum sample size calculations for external validation of a clinical prediction model with a time-to-event outcome.

Previous articles in Statistics in Medicine describe how to calculate the sample size required for external validation of prediction models with continuous and binary outcomes. The minimum sample size criteria aim to ensure precise estimation of key measures of a model's predictive performance, including measures of calibration, discrimination, and net benefit. Here, we extend the sample size guidance to prediction models with a time-to-event (survival) outcome, to cover external validation in datasets containing censoring.

A phase 1/2 clinical trial of the nitric oxide synthase inhibitor L-NMMA and taxane for treating chemoresistant triple-negative breast cancer.

The inducible nitric oxide signaling (iNOS) pathway is associated with poor prognosis in triple-negative breast cancer (TNBC). Prior studies using in vivo models showed that inhibition of the iNOS signaling pathway using the pan-NOS inhibitor NG-monomethyl-l-arginine (L-NMMA) reduced tumor growth and enhanced survival in patients with TNBC. Here, we report a first-in-class phase 1/2 trial of L-NMMA combined with taxane for treating patients with chemorefractory, locally advanced breast cancer (LABC) or metastatic TNBC.

Primary diffuse large B-cell lymphoma of the uterus: A SEER database analysis.

Uterine diffuse large B-cell lymphoma (DLBCL) is a rare clinical condition. Most studies for uterine DLBCL are derived from case reports and series. Our main objective was to present a new case while also investigating the demographic, clinical characteristics, and survival of women with primary uterine DLBCL as compared to non-uterine DLBCL using the Surveillance, Epidemiology, and End Results incidence database.