Effectiveness of inactivated COVID-19 vaccines against SARS-CoV-2 infections among healthcare personnel in Pakistan: a test-negative case-control study

Objective
During the COVID-19 pandemic, several vaccines that were efficacious in randomised controlled trials were authorised for mass vaccination. In developing countries, inactivated vaccines were widely administered. While inactivated vaccines have been deemed effective in reducing disease severity, for healthcare personnel (HCP), effectiveness against SARS-CoV-2 infections is essential to reduce the risk to vulnerable patients and ensure a stable healthcare workforce. There are limited studies examining inactivated vaccines’ effectiveness against SARS-CoV-2 variants of concern (VOCs) in real-world settings. We estimated the effectiveness of inactivated vaccines (BBIBP-CorV and CoronaVac) against reverse transcription PCR (RT-PCR)-confirmed SARS-CoV-2 infections among HCP in the setting of emerging SARS-CoV-2 VOCs in Pakistan.

Design
A retrospective matched, test-negative case–control analysis using existing data from an Employee Health database on HCP at a large, private healthcare system in Pakistan.

Participants
4599 HCP were tested between 1 April and 30 September 2021. Each case (PCR positive) was matched to two to six controls (PCR negative) by the date of the RT-PCR test (±7 days) to reduce bias.

Primary and secondary outcome measures
The primary outcome was vaccine effectiveness (VE) against SARS-CoV-2 infection. The secondary outcome was VE against symptomatic SARS-CoV-2 infection. Per cent VE was calculated using (1-OR)*100, with the OR of getting a PCR-confirmed SARS-COV-2 infection estimated using conditional logistic regression, after adjusting for age, gender, work area and history of SARS-CoV-2 infection.

Results
Inactivated vaccines were ineffective against SARS-CoV-2 infections after receiving the first dose (VE 17%, 95% CI –10, 39; p=0.261). They showed modest effectiveness ≥14 days after the second dose against SARS-CoV-2 infections (VE 30%, 95% CI 7, 48; p=0.015) and symptomatic SARS-CoV-2 infections (VE 33%, 95% CI 6, 52; p=0.002).

Conclusions
Inactivated vaccines show modest effectiveness against SARS-CoV-2 infections in the setting of emerging VOCs. This builds a strong case for boosters and/or additional vaccination.

Leggi
Giugno 2023

Interpreting a Negative Trial as a Negative Test for Efficacy

As noted in JAMA more than 30 years ago, randomized clinical trials are like diagnostic tests in several ways. Clinical trials are designed to detect hypothesized treatment effects in the same way diagnostic tests are designed to detect an abnormality or target illness. A trial’s statistical power, namely the probability that it can detect the treatment effect given that the hypothesized effect exists, is analogous to a diagnostic test’s sensitivity, namely the probability a positive test result is obtained when the target condition is present. Just as the sensitivity of a diagnostic test can be affected by the severity of illness, an effect called “spectrum bias,” the power of a clinical trial, is strongly influenced by the magnitude of the true treatment benefit associated with the experimental treatment. The specificity of a diagnostic test, namely the fraction of all persons free of disease who have a true-negative test result, is analogous in clinical trial design to 1 −α, where α is the maximum statistically significant 1-tailed P value (eg, .025) defined for the trial (ie, the type I error risk, or the risk of a false-positive result if there is no treatment effect).

Leggi
Giugno 2023

Can we do better? A qualitative study in the East of England investigating patient experience and acceptability of using the faecal immunochemical test in primary care

Objectives
The faecal immunochemical test (FIT) is increasingly used in UK primary care to triage patients presenting with symptoms and at different levels of colorectal cancer risk. Evidence is scarce on patients’ views of using FIT in this context. We aimed to explore patients’ care experience and acceptability of using FIT in primary care.

Design
A qualitative semi-structured interview study. Interviews were conducted via Zoom between April and October 2020. Transcribed recordings were analysed using framework analysis.

Setting
East of England general practices.

Participants
Consenting patients (aged ≥40 years) who presented in primary care with possible symptoms of colorectal cancer, and for whom a FIT was requested, were recruited to the FIT-East study. Participants were purposively sampled for this qualitative substudy based on age, gender and FIT result.

Results
44 participants were interviewed with a mean age 61 years, and 25 (57%) being men: 8 (18%) received a positive FIT result. Three themes and seven subthemes were identified. Participants’ familiarity with similar tests and perceived risk of cancer influenced test experience and acceptability. All participants were happy to do the FIT themselves and to recommend it to others. Most participants reported that the test was straightforward, although some considered it may be a challenge to others. However, test explanation by healthcare professionals was often limited. Furthermore, while some participants received their results quickly, many did not receive them at all with the common assumption that ‘no news is good news’. For those with a negative result and persisting symptoms, there was uncertainty about any next steps.

Conclusions
While FIT is acceptable to patients, elements of communication with patients by the healthcare system show potential for improvement. We suggest possible ways to improve the FIT experience, particularly regarding communication about the test and its results.

Leggi
Giugno 2023

Ruling out acute coronary syndrome in primary care with a clinical decision rule and a capillary, high-sensitive troponin I point of care test: study protocol of a diagnostic RCT in the Netherlands (POB HELP)

Introduction
Chest pain is a common reason for consultation in primary care. To rule out acute coronary syndrome (ACS), general practitioners (GP) refer 40%–70% of patients with chest pain to the emergency department (ED). Only 10%–20% of those referred, are diagnosed with ACS. A clinical decision rule, including a high-sensitive cardiac troponin-I point-of-care test (hs-cTnI-POCT), may safely rule out ACS in primary care. Being able to safely rule out ACS at the GP level reduces referrals and thereby alleviates the burden on the ED. Moreover, prompt feedback to the patients may reduce anxiety and stress.

Methods and analysis
The POB HELP study is a clustered randomised controlled diagnostic trial investigating the (cost-)effectiveness and diagnostic accuracy of a primary care decision rule for acute chest pain, consisting of the Marburg Heart Score combined with a hs-cTnI-POCT (limit of detection 1.6 ng/L, 99th percentile 23 ng/L, cut-off value between negative and positive used in this study 3.8 ng/L). General practices are 2:1 randomised to the intervention group (clinical decision rule) or control group (regular care). In total 1500 patients with acute chest pain are planned to be included by GPs in three regions in The Netherlands. Primary endpoints are the number of hospital referrals and the diagnostic accuracy of the decision rule 24 hours, 6 weeks and 6 months after inclusion.

Ethics and dissemination
The medical ethics committee Leiden-Den Haag-Delft (the Netherlands) has approved this trial. Written informed consent will be obtained from all participating patients. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses.

Trial registration numbers
NL9525 and NCT05827237.

Leggi
Giugno 2023

Protocol for a systematic review and meta-analysis of the diagnostic test accuracy of host and HPV DNA methylation in cervical cancer screening and management

Introduction
Human papillomavirus (HPV) is necessary but not sufficient for cervical cancer development. During cervical carcinogenesis, methylation levels increase across host and HPV DNA. DNA methylation has been proposed as a test to diagnose cervical intraepithelial neoplasia (CIN); we present a protocol to evaluate the accuracy of methylation markers to detect high-grade CIN and cervical cancer.

Methods and analysis
We will search electronic databases (Medline, Embase and Cochrane Library), from inception, to identify studies examining DNA methylation as a diagnostic marker for CIN or cervical cancer, in a cervical screening population. The primary outcome will be to assess the diagnostic test accuracy of host and HPV DNA methylation for high-grade CIN; the secondary outcomes will be to examine the accuracy of different methylation cut-off thresholds, and accuracy in high-risk HPV positive women. Our reference standard will be histology. We will perform meta-analyses using Cochrane guidelines for diagnostic test accuracy. We will use the number of true positives, false negatives, true negatives and false positives from individual studies. We will use the bivariate mixed effect model to estimate sensitivity and specificity with 95% CIs; we will employ different bivariate models to estimate sensitivity and specificity at different thresholds if sufficient data per threshold. For insufficient data, the hierarchical summary receiver operating curve model will be used to calculate a summary curve across thresholds. If there is interstudy and intrastudy variation in thresholds, we will use a linear mixed effects model to calculate the optimum threshold. If few studies are available, we will simplify models by assuming no correlation between sensitivity and specificity and perform univariate, random-effects meta-analysis. We will assess the quality of studies using QUADAS-2 and QUADAS-C.

Ethics and dissemination
Ethical approval is not required. Results will be disseminated to academic beneficiaries, medical practitioners, patients and the public.

PROSPERO registration number
CRD42022299760.

Leggi
Giugno 2023