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.

Prevalence, incidence and longevity of antibodies against SARS-CoV-2 among primary healthcare providers in Belgium: a prospective cohort study with 12 months of follow-up.

OBJECTIVES: To estimate the prevalence, incidence and longevity of antibodies against SARS-CoV-2 among primary healthcare providers (PHCPs). DESIGN: Prospective cohort study with 12 months of follow-up. 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 (examines, tests, treats) patients were eligible. A convenience sample of 3648 eligible PHCPs from 2001 GP practices registered for this study (3044 and 604 to start in December 2020 and January 2021, respectively). 3390 PHCPs (92,9%) participated in their first testing time point (2820 and 565, respectively) and 2557 PHCPs (70,1%) in the last testing time point (December 2021). INTERVENTIONS: Participants were asked to perform a rapid serological test targeting IgM and IgG against the receptor binding domain of SARS-CoV-2 and to complete an online questionnaire at each of maximum eight testing time points. PRIMARY AND SECONDARY OUTCOME MEASURES: The prevalence, incidence and longevity of antibodies against SARS-CoV-2 both after natural infection and after vaccination. RESULTS: Among all participants, 67% were women and 77% GPs. Median age was 43 years. The seroprevalence in December 2020 (before vaccination availability) was 15.1% (95% CI 13.5% to 16.6%), increased to 84.2% (95% CI 82.9% to 85.5%) in March 2021 (after vaccination availability) and reached 93.9% (95% CI 92.9% to 94.9%) in December 2021 (during booster vaccination availability and fourth (delta variant dominant) COVID-19 wave). Among not (yet) vaccinated participants the first monthly incidence of antibodies against SARS-CoV-2 was estimated to be 2.91% (95% CI 1.80% to 4.01%). The longevity of antibodies is higher in PHCPs with self-reported COVID-19 infection. CONCLUSIONS: This study confirms that occupational health measures provided sufficient protection when managing patients. High uptake of vaccination resulted in high seroprevalence of SARS-CoV-2 antibodies in PHCPs in Belgium. Longevity of antibodies was supported by booster vaccination and virus circulation. TRIAL REGISTRATION NUMBER: NCT04779424.

Study protocol for a randomised controlled trial on the use of intraoperative ultrasound-guided laparoscopic ovarian cystectomy (UGLOC) as a method of fertility preservation in the management of benign ovarian cysts.

INTRODUCTION: The lifetime risk of women undergoing surgery for the presence of benign ovarian pathology in the UK is 5%-10%. Despite minimally invasive surgical techniques, evidence suggests a number of healthy ovarian follicles and tissues are resected intraoperatively, resulting in subsequent decline of ovarian reserve. As such, there is an increasing demand for the implementation of fertility preservation surgery (FPS). This study will evaluate the effect on ovarian reserve following two different surgical interventions for the management of benign ovarian cysts. METHODS AND ANALYSIS: We will conduct a two-armed randomised controlled trial comparing laparoscopic ovarian cystectomy, considered gold standard treatment as per the Royal College of Obstetricians and Gynaecologists (RCOG) Green Top guidelines for the management of benign ovarian cysts, with ultrasound-guided laparoscopic ovarian cystectomy (UGLOC), a novel method of FPS. The study commencement date was October 2021, with a completion date aimed for October 2024. The primary outcome will be the difference in anti-Müllerian hormone (AMH) (pmol/L) and antral follicle count (AFC) measured 3 and 6 months postoperatively from the preoperative baseline. Secondary outcomes include assessment of various surgical and histopathological findings, including duration of hospital stay (days), duration of surgery (minutes), presence of intraoperative cyst rupture (yes/no), presence of ovarian tissue within the resected specimen (yes/no) and the grade of follicles excised within the specimen (grade 0-4). We aim to randomise 94 patients over 3 years to achieve power of 80% at an alpha level of 0.05. ETHICS AND DISSEMINATION: Findings will be published in peer-reviewed journals and presented at national and international conferences and scientific meetings. The Chelsea NHS Research and Ethics Committee have awarded ethical approval of the study (21/LO/036). TRIAL REGISTRATION NUMBER: NCT05032846.

The Risk of Endometrial Malignancy and Other Endometrial Pathology in Women with Abnormal Uterine Bleeding: An Ultrasound-Based Model Development Study by the IETA Group.

OBJECTIVES: The aim of this study was to develop a model that can discriminate between different etiologies of abnormal uterine bleeding. DESIGN: The International Endometrial Tumor Analysis 1 study is a multicenter observational diagnostic study in 18 bleeding clinics in 9 countries. Consecutive women with abnormal vaginal bleeding presenting for ultrasound examination (n = 2,417) were recruited. The histology was obtained from endometrial sampling, D&C, hysteroscopic resection, hysterectomy, or ultrasound follow-up for >1 year. METHODS: A model was developed using multinomial regression based on age, body mass index, and ultrasound predictors to distinguish between: (1) endometrial atrophy, (2) endometrial polyp or intracavitary myoma, (3) endometrial malignancy or atypical hyperplasia, (4) proliferative/secretory changes, endometritis, or hyperplasia without atypia and validated using leave-center-out cross-validation and bootstrapping. The main outcomes are the model's ability to discriminate between the four outcomes and the calibration of risk estimates. RESULTS: The median age in 2,417 women was 50 (interquartile range 43-57). 414 (17%) women had endometrial atrophy; 996 (41%) had a polyp or myoma; 155 (6%) had an endometrial malignancy or atypical hyperplasia; and 852 (35%) had proliferative/secretory changes, endometritis, or hyperplasia without atypia. The model distinguished well between malignant and benign histology (c-statistic 0.88 95% CI: 0.85-0.91) and between all benign histologies. The probabilities for each of the four outcomes were over- or underestimated depending on the centers. LIMITATIONS: Not all patients had a diagnosis based on histology. The model over- or underestimated the risk for certain outcomes in some centers, indicating local recalibration is advisable. CONCLUSIONS: The proposed model reliably distinguishes between four histological outcomes. This is the first model to discriminate between several outcomes and is the only model applicable when menopausal status is uncertain. The model could be useful for patient management and counseling, and aid in the interpretation of ultrasound findings. Future research is needed to externally validate and locally recalibrate the model.

Antibiotic prescribing rate after optimal near-patient C-reactive protein testing in acutely ill children presenting to ambulatory care (ARON project): protocol for a cluster-randomized pragmatic trial.

INTRODUCTION: Children become ill quite often, mainly because of infections, most of which can be managed in the community. Many children are prescribed antibiotics which contributes to antimicrobial resistance and reinforces health-seeking behaviour. Point-of-care C reactive protein (POC CRP) testing, prescription guidance and safety-netting advice can help safely reduce antibiotic prescribing to acutely ill children in ambulatory care as well as save costs at a systems level. METHODS AND ANALYSIS: The ARON (Antibiotic prescribing Rate after Optimal Near-patient testing in acutely ill children in ambulatory care) trial is a pragmatic cluster randomized controlled superiority trial with a nested process evaluation and will assess the clinical and cost effectiveness of a diagnostic algorithm, which includes a standardised clinical assessment, a POC CRP test, and safety-netting advice, in acutely ill children aged 6 months to 12 years presenting to ambulatory care. The primary outcome is antibiotic prescribing at the index consultation; secondary outcomes include clinical recovery, reconsultation, referral/admission to hospital, additional testing, mortality and patient satisfaction. We aim to recruit a total sample size of 6111 patients. All outcomes will be analysed according to the intent-to-treat approach. We will use a mixed-effect logistic regression analysis to account for the clustering at practice level. ETHICS AND DISSEMINATION: The study will be conducted in compliance with the principles of the Declaration of Helsinki (current version), the principles of Good Clinical Practice and in accordance with all applicable regulatory requirements. Ethics approval for this study was obtained on 10 November 2020 from the Ethics Committee Research of University Hospitals Leuven under reference S62005. We will ensure that the findings of the study will be disseminated to relevant stakeholders other than the scientific world including the public, healthcare providers and policy-makers. The process evaluation that is part of this trial may provide a basis for an implementation strategy. If our intervention proves to be clinically and cost-effective, it will be essential to educate physicians about introducing the diagnostic algorithm including POC CRP testing and safety-netting advice in their daily practice. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04470518. Protocol V.2.0 date 2 October 2020. (Pre-results).

BET 1: Do homemade or cloth face masks work as a preventive measure for respiratory virus transmission?

A short-cut review of the available medical literature was carried out to establish whether homemade or cloth face masks can prevent respiratory virus transmission or clinical illness. After abstract review, twelve papers were found to answer this clinical question using the detailed search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that there is currently no direct evidence to support the use of homemade or cloth masks by the general public for protection against viral infections.

Point-of-Care C-Reactive Protein Testing to Reduce Antibiotic Prescribing for Respiratory Tract Infections in Primary Care: Systematic Review and Meta-Analysis of Randomised Controlled Trials.

C-reactive protein (CRP) point-of-care testing (POCT) is increasingly being promoted to reduce diagnostic uncertainty and enhance antibiotic stewardship. In primary care, respiratory tract infections (RTIs) are the most common reason for inappropriate antibiotic prescribing, which is a major driver for antibiotic resistance. We systematically reviewed the available evidence on the impact of CRP-POCT on antibiotic prescribing for RTIs in primary care. Thirteen moderate to high-quality studies comprising 9844 participants met our inclusion criteria. Meta-analyses showed that CRP-POCT significantly reduced immediate antibiotic prescribing at the index consultation compared with usual care (RR 0.79, 95%CI 0.70 to 0.90, p = 0.0003, I2 = 76%) but not during 28-day (n = 7) follow-up. The immediate effect was sustained at 12 months (n = 1). In children, CRP-POCT reduced antibiotic prescribing when CRP (cut-off) guidance was provided (n = 2). Meta-analyses showed significantly higher rates of re-consultation within 30 days (n = 8, 1 significant). Clinical recovery, resolution of symptoms, and hospital admissions were not significantly different between CRP-POCT and usual care. CRP-POCT can reduce immediate antibiotic prescribing for RTIs in primary care (number needed to (NNT) for benefit = 8) at the expense of increased re-consultations (NNT for harm = 27). The increase in re-consultations and longer-term effects of CRP-POCT need further evaluation. Overall, the benefits of CRP-POCT outweigh the potential harms (NNTnet = 11).

Impact of point-of-care tests in community pharmacies: a systematic review and meta-analysis.

OBJECTIVES: To summarise the literature regarding the use of point-of-care test (POCT) in pharmacies versus control/usual care. DESIGN AND SETTING: Systematic review and random-effects meta-analysis in community pharmacy. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, Embase, ClinicalTrial.gov and Web of Science databases were searched. ELIGIBILITY CRITERIA: Articles were included if they: involved a POCT conducted by a community pharmacist, member of pharmacy staff or local equivalent; measured a clinically relevant outcome for example, clinical parameter monitoring. No clinical condition or language limits were set. PATIENT AND PUBLIC INVOLVEMENT: No patient involvement. DATA EXTRACTION AND SYNTHESIS: Data were independently extracted by two members of the review team to capture changes in clinical care that resulted from the use of the POCTs. The methodological quality of included studies was assessed, using the Cochrane Risk of Bias tool and Newcastle-Ottawa scale. RESULTS: Thirteen of the 1584 articles found were included in the meta-analyses. Studies covered four therapeutic areas: targeted anti-malarial therapy (n=3 studies), glycated haemoglobin (HbA1c) in diabetes (n=2 studies), lipid control (n=3 studies) and international normalised ratio (INR) control in patients taking warfarin (n=5 studies). POCT in pharmacies reduced the risk of receiving antimalarial treatment when not clinically indicated (risk ratio 0.34, 95% CI 0.31 to 0.37). Lipid and HbA1c control appeared largely unaffected by pharmacy POCTs, and the impact on INR time-in-therapeutic-range was inconclusive. CONCLUSIONS: Only 4 out of 13 included studies used a gold-standard randomised controlled trial (RCT) design, limiting our ability to conclusively determine the clinical utility of POCT conducted in pharmacies. Further RCTs are needed, particularly in areas such as upper respiratory tract infections, which have gathered momentum among service commissioners in recent years. PROSPERO REGISTRATION NUMBER: CRD42017048578.