Calibrating the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) for detecting alcohol-related problems among Canadian, UK and US soldiers: cross-sectional pre-deployment and post-deployment survey results

Objectives
Excessive alcohol use can bring about adverse health and work-related consequences in civilian and military populations. Screening for excessive drinking can help identify individuals at risk for alcohol-related problems who may require clinical interventions. The brief validated measures of alcohol use such as the Alcohol Use Disorders Identification Test (AUDIT), or abbreviated AUDIT-Consumption (AUDIT-C), are often included in military deployment screening and epidemiologic surveys, but appropriate cut-points must be used to effectively identify individuals at risk. Although the conventional AUDIT-C cut-points ≥4 for men and ≥3 for women are commonly used, recent validation studies of veterans and civilians recommend higher cut-points to minimise misclassification and overestimation of alcohol-related problems. This study aims to ascertain optimal AUDIT-C cut-points for detecting alcohol-related problems among serving Canadian, UK and US soldiers.

Design
Cross-sectional pre/post-deployment survey data were used.

Settings
Comprised Army locations in Canada and UK, and selected US Army units.

Participants
Included soldiers in each of the above-mentioned settings.

Outcome measures
Soldiers’ AUDIT scores for hazardous and harmful alcohol use or high levels of alcohol problems served as a benchmark against which optimal sex-specific AUDIT-C cut-points were assessed.

Results
Across the three-nation samples, AUDIT-C cut-points of ≥6/7 for men and ≥5/6 for women performed well in detecting hazardous and harmful alcohol use and provided comparable prevalence estimates to AUDIT scores ≥8 for men and ≥7 for women. The AUDIT-C cut-point ≥8/9 for both men and women performed fair-to-good when benchmarked against AUDIT ≥16, although inflated AUDIT-C-derived prevalence estimates and low positive predictive values were observed.

Conclusion
This multi-national study provides valuable information regarding appropriate AUDIT-C cut-points for detecting hazardous and harmful alcohol use, and high levels of alcohol problems among soldiers. Such information can be useful for population surveillance, pre-deployment/post-deployment screening of military personnel, and clinical practice.

Leggi
Maggio 2023

Validation of a rapid SARS-CoV-2 antibody test in general practice

Objectives
To validate a rapid serological test (RST) for SARS-CoV-2 antibodies used in seroprevalence studies in healthcare providers, including primary healthcare providers (PHCPs) in Belgium.

Design
A phase III validation study of the RST (OrientGene) within a prospective cohort study.

Setting
Primary care in Belgium.

Participants
Any general practitioner (GP) working in primary care in Belgium and any other PHCP from the same GP practice who physically manages patients were eligible in the seroprevalence study. For the validation study, all participants who tested positive (376) on the RST at the first testing timepoint (T1) and a random sample of those who tested negative (790) and unclear (24) were included.

Intervention
At T2, 4 weeks later, PHCPs performed the RST with fingerprick blood (index test) immediately after providing a serum sample to be analysed for the presence of SARS-CoV-2 immunoglobulin G antibodies using a two-out-of-three assay (reference test).

Primary and secondary outcome measures
The RST accuracy was estimated using inverse probability weighting to correct for missing reference test data, and considering unclear RST results as negative for the sensitivity and positive for the specificity. Using these conservative estimates, the true seroprevalence was estimated both for T2 and RST-based prevalence values found in a cohort study with PHCPs in Belgium.

Results
1073 paired tests (403 positive on the reference test) were included. A sensitivity of 73% (a specificity of 92%) was found considering unclear RST results as negative (positive). For an RST-based prevalence at T1 (13.9), T2 (24.9) and T7 (70.21), the true prevalence was estimated to be 9.1%, 25.9% and 95.7%, respectively.

Conclusion
The RST sensitivity (73%) and specificity (92%) make an RST-based seroprevalence below (above) 23% overestimate (underestimate) the true seroprevalence.

Trial registration number
NCT04779424.

Leggi
Maggio 2023

COVID-19 vaccine effectiveness and variants in Nepal: study protocol for a test-negative case-control study with SARS-CoV-2 genetic sequencing

Introduction
Inactivated, viral vector and mRNA vaccines have been used in the Nepali COVID-19 vaccination programme but there is little evidence on the effectiveness of these vaccines in this setting. The aim of this study is to describe COVID-19 vaccine effectiveness in Nepal and provide information on infections with SARS-CoV-2 variants.

Methods and analysis
This is a hospital-based, prospective test-negative case–control study conducted at Patan Hospital, Kathmandu. All patients >18 years of age presenting to Patan Hospital with COVID-19-like symptoms who have received a COVID-19 antigen/PCR test are eligible for inclusion. The primary outcome is vaccine effectiveness of licensed COVID-19 vaccines against laboratory-confirmed COVID-19 disease.
After enrolment, information will be collected on vaccine status, date of vaccination, type of vaccine, demographics and other medical comorbidities. The primary outcome of interest is laboratory-confirmed SARS-CoV-2 infection. Cases (positive for SARS-CoV-2) and controls (negative for SARS-CoV-2) will be enrolled in a 1:4 ratio. Vaccine effectiveness against COVID-19 disease will be analysed by comparing vaccination status with SARS-CoV-2 test results.
Positive SARS-CoV-2 samples will be sequenced to identify circulating variants and estimate vaccine effectiveness against common variants.
Measuring vaccine effectiveness and identifying SARS-CoV-2 variants in Nepal will help to inform public health efforts. Describing disease severity in relation to specific SARS-CoV-2 variants and vaccine status will also inform future prevention and care efforts.

Ethics and dissemination
Ethical approval was obtained from the University of Oxford Tropical Ethics Committee (OxTREC) (ref: 561-21) and the Patan Academy of Health Sciences Institutional Review Board (ref: drs2111121578). The protocol and supporting study documents were approved for use by the Nepal Health Research Council (NHRC 550-2021). Results will be disseminated in peer-reviewed journals and to the public health authorities in Nepal.

Leggi
Aprile 2023

Diagnostic accuracy of cryptococcal antigen test in pulmonary cryptococcosis: a protocol for a systematic review and meta-analysis

Background
The cryptococcal antigen (CrAg) test was proposed as a rapid diagnostic tool to identify cryptococcal meningitis in patients suffering from AIDS. Several studies have demonstrated its diagnostic performance in cryptococcal meningitis. However, the diagnostic performance of the CrAg test in serum or bronchoalveolar lavage fluid in patients with pulmonary cryptococcosis remains uncertain. Therefore, the purpose of this systematic review is to summarise the evidence concerning diagnostic performance of the CrAg test in patients with pulmonary cryptococcosis.

Methods and analysis
Databases such as PubMed, EMBASE, Cochrane Database of Systematic Reviews, Web of Science, ClinicalTrials.gov, International Clinical Trials Registry Platform, Wanfang Database and China National Knowledge Infrastructure will be searched systematically. The titles and abstracts will be reviewed by two independent reviewers. The Quality Assessment of Diagnostic Accuracy Studies 2 tool will be used to evaluate the risk of bias and clinical applicability of each study. Potential sources of heterogeneity will be investigated through visual inspection of the paired forest plots and summary receiver operating characteristic plots. The pooled summary statistics for the area under the curve, sensitivities, specificities, likelihood ratios and diagnostic ORs with 95% CI will be reported.

Ethics and dissemination
The underlying study is based on published articles thus does not require ethical approval. The findings of the systematic review and meta-analysis will be published in a peer-reviewed journal and disseminated in various scientific conferences and seminars.

PROSPERO registration number
CRD42022373321.

Leggi
Aprile 2023

The MaxCombo Test Severely Violates the Type I Error Rate

To the Editor In their recent systematic review and meta-analysis in JAMA Oncology, Mukhopadhyay et al compare 3 statistical tests based on historic immuno-oncology trials with registrational intent. Unsurprisingly, they conclude that the so-called MaxCombo test has higher power to demonstrate a treatment difference. However, they misleadingly cite one of our articles, claiming that this test controls the type I error. On the contrary, our publications demonstrate that MaxCombo is not valid to show benefit of a candidate drug. A better alternative to the standard log-rank test is the modestly weighted test.

Leggi
Aprile 2023

THE PRECIOUS STUDY: A PROSPECTIVE, OBSERVATIONAL STUDY OF CD8+ BIOMARKER BASED PROGNOSTIC TEST IN NORTH AMERICAN IBD PATIENTS

The clinical course of IBD varies considerably among patients1. One barrier to personalized medicine in IBD is the lack of a reliable prognostic assay that can be used at diagnosis to guide effective therapy for each patient, to optimize clinical outcomes and minimize complications. To address this need, a whole-blood qPCR-based prognostic assay was developed to divide IBD patients into two subgroups2. This transcriptional signature yields CD8 T-cell exhaustion level data that correlated with disease outcomes among IBD patients in UK2.

Leggi
Marzo 2023

FDA Approves First Over-the-counter Combined COVID-19 and Flu Test

In late February, the US Food and Drug Administration (FDA) granted an Emergency Use Authorization to an at-home diagnostic test that identifies SARS-CoV-2, the virus that causes COVID-19, as well as influenza strains A and B. The test detected 100% of negative and 88.3% of positive COVID-19 samples, 99.3% of negative and 90% of positive influenza A samples, and 99.9% of negative influenza B samples.

Leggi
Marzo 2023