Thrombophilia screening in women with recurrent first trimester miscarriage: is it time to stop testing? – a cohort study and systematic review of the literature

Objective
There are numerous studies reporting a disproportionally high prevalence of thrombophilia in women with a history of recurrent miscarriage (RM), which has led to overdiagnosis and treatment without an improvement in clinical outcomes. The objective of our study was to assess the prevalence of inherited and acquired thrombophilia in a large cohort of women with a history of early RM using internationally agreed diagnostic criteria and inclusion parameters and compare it to the meta-analysis results of existing literature.

Methods

Design
Retrospective cohort study and systematic review of literature.

Setting
This is a retrospective cohort study set-up in two dedicated tertiary centres for women with RM in Southwest London and Surrey. We reviewed all the available literature related to causes of RMs. We ascertained the prevalence of thrombophilia in the study population and compared it with historical and published prevalence in the general population.

Participants
1155 women between 2012 and 2017. All patients had three or more first trimester miscarriages and a full thrombophilia screen.

Results
The overall prevalence of thrombophilia in our study population is 9.2% (106/1155) with 8.1% (94/1155) of cases positive for inherited thrombophilia, which is similar to the general population; Factor V Leiden (4.9%; 57/1155) and prothrombin gene mutation (2.9%; 34/1155) were the most common inherited thrombophilias, while only 1% (12/1155) tested positive for acquired thrombophilia. Persistent positive lupus anticoagulant (LA) was found in 0.5% (6/1155) and persistent positive anticardiolipin (ACL) antibodies with a value ≥40 U/mL was found in 0.5% (6/1155) of patients. Tests for LA/ACL were performed a minimum of 12 weeks apart thus meeting the revised Sapporo criteria for a diagnosis of antiphospholipid syndrome.

Conclusion
The findings of our study demonstrate that the prevalence of inherited thrombophilia is similar in women with RM to that in the general population. Similarly, the prevalence of acquired thrombophilia, using the revised Sapporo criteria, in the cohort of RMs is similar to that in the general population. Therefore, we do not recommend investigation or treatment of inherited or acquired thrombophilia in women with RM.

PROSPERO registration number
CRD42020223554.

Leggi
Luglio 2022

Association between university students two-staged health screening and student health care utilisation: register based observational study

Objectives
The aim of this study was to explore how university students’ participation in a two-staged health screening at the beginning of university studies associates with student health care utilisation in a 6-year follow-up.

Design
Nationwide, observational, register-based cohort study with a 6-year follow-up.

Setting
Student health care in Finland. Finnish Student Health Service (FSHS) provides statutory student health services to university students in Finland. The two-staged health screening of FSHS includes the electronic health questionnaire (eHQ) provided annually to university entrants and a subsequent health check, when necessary, based on students eHQ response.

Participants
A national cohort of university entrants from the 2011–2012 academic year (N=15 723) was assessed. After exclusions the study population consisted of 12 972 students, n (female)=7368, n (male)=5604.

Outcome measures
The primary outcome measures were students’ health service utilisation pattern obtained by clustering analyses method and the students’ participation in different stages of the health examination process.

Results
Four distinguishable health care utilisation patterns were identified: (1) constant low use, (2) constant high use, (3) increasing use and (4) decreasing use. The students’ OR for belonging to the constant high use group was significantly higher among females (OR 4.0, 95% CI 3.5 to 4.6) and students who attended the health check (OR 4.7, 95% CI 3.9 to 5.6).

Conclusions
Participating in the two-staged health screening was associated with increase in health care utilisation. The process detects students with health problems.

Leggi
Luglio 2022

Meta-analysis of COVID-19 prevalence during preoperative COVID-19 screening in asymptomatic patients

Objectives
Patients with COVID-19 may be asymptomatic and are able to transmit COVID-19 during a surgical procedure, resulting in increased pressure on healthcare and reduced control of COVID-19 spread. There remains uncertainty about the implementation of preoperative screening for COVID-19 in asymptomatic surgical patients. Therefore, this study aims to determine the prevalence of preoperative COVID-19, confirmed by reverse transcriptase PCR (RT-PCR), in asymptomatic patients.

Design
Systematic review and meta-analysis.

Data sources
Pubmed and Embase databases were searched through 20 February 2022.

Eligibility criteria
All COVID-19 articles including preoperative asymptomatic patients were included.

Data extraction and synthesis
Two independent reviewers extracted data and assessed risk of bias. Meta-analysis was performed to determine the prevalence of COVID-19 with 95% CI. Moreover, estimated positive predictive value (PPV), negative predictive value, false-positives (FP) and false-negatives were calculated for preoperative asymptomatic patients.

Results
Twenty-seven studies containing 27 256 asymptomatic preoperative screened patients were included, of which 431 were positive for COVID-19 by RT-PCR test. In addition, the meta-analysis revealed a pooled COVID-19 prevalence of 0.76% (95% CI 0.36% to 1.59%). The calculated PPV for this prevalence is 40.8%.

Conclusions
The pooled COVID-19 prevalence in asymptomatic patients tested preoperatively was 0.76%, with low corresponding PPV. Consequently, nearly three-quarters of postponed surgical procedures in asymptomatic preoperative patients may be FP. In the event of similar pandemics, modification of preoperative mandatory RT-PCR COVID-19 testing in asymptomatic patients may be considered.

Leggi
Luglio 2022

Point-of-care lung ultrasonography for early identification of mild COVID-19: a prospective cohort of outpatients in a Swiss screening center

Objectives
Early identification of SARS-CoV-2 infection is important to guide quarantine and reduce transmission. This study evaluates the diagnostic performance of lung ultrasound (LUS), an affordable, consumable-free point-of-care tool, for COVID-19 screening.

Design, setting and participants
This prospective observational cohort included adults presenting with cough and/or dyspnoea at a SARS-CoV-2 screening centre of Lausanne University Hospital between 31 March and 8 May 2020.

Interventions
Investigators recorded standardised LUS images and videos in 10 lung zones per patient. Two blinded independent experts reviewed LUS recording and classified abnormal findings according to prespecified criteria to investigate their predictive value to diagnose SARS-CoV-2 infection according to PCR on nasopharyngeal swabs (COVID-19 positive vs COVID-19 negative).

Primary and secondary outcome measures
We finally combined LUS and clinical findings to derive a multivariate logistic regression diagnostic score.

Results
Of 134 included patients, 23% (n=30/134) were COVID-19 positive and 77% (n=103/134) were COVID-19 negative; 85%, (n=114/134) cases were previously healthy healthcare workers presenting within 2–5 days of symptom onset (IQR). Abnormal LUS findings were significantly more frequent in COVID-19 positive compared with COVID-19 negative (45% vs 26%, p=0.045) and mostly consisted of focal pathologic B lines. Combining clinical findings in a multivariate logistic regression score had an area under the receiver operating curve of 80.3% to detect COVID-19, and slightly improved to 84.5% with the addition of LUS features.

Conclusions
COVID-19-positive patients are significantly more likely to have lung pathology by LUS. However, LUS has an insufficient sensitivity and is not an appropriate screening tool in outpatients. LUS only adds little value to clinical features alone.

Leggi
Giugno 2022

Development and internal validation of the Edmonton Obesity Staging System-2 Risk screening Tool (EOSS-2 Risk Tool) for weight-related health complications: a case-control study in a representative sample of Australian adults with overweight and obesity

Objective
Excess weight and related health complications remain under diagnosed and poorly treated in general practice. We aimed to develop and validate a brief screening tool for determining the presence of unknown clinically significant weight-related health complications for potential application in general practice.

Design
We considered 14 self-reported candidate predictors of clinically significant weight-related health complications according to the Edmonton Obesity Staging System (EOSS score of ≥2) and developed models using multivariate logistic regression across training and test data sets. The final model was chosen based on the area under the receiver operating characteristic curve and the Hosmer-Lemeshow statistic; and validated using sensitivity, specificity and positive predictive value.

Setting and participants
We analysed cross-sectional data from the Australian Health Survey 2011–2013 sample aged between 18 and 65 years (n=7518) with at least overweight and obesity.

Results
An EOSS≥2 classification was present in 78% of the sample. Of 14 candidate risk factors, 6 (family history of diabetes, hypertension, high sugar in blood/urine, high cholesterol and self-reported bodily pain and disability) were automatically included based on definitional or obvious correlational criteria. Three variables were retained in the final multivariate model (age, self-assessed health and history of depression/anxiety). The EOSS-2 Risk Tool (index test) classified 89% of those at ‘extremely high risk’ (≥25 points), 67% of those at ‘very high risk’ (7–24 points) and 42% of those at ‘high risk’ (

Leggi
Giugno 2022

Personalised Lung Cancer Screening (PLuS) study to assess the importance of coexisting chronic conditions to clinical practice and policy: protocol for a multicentre observational study

Introduction
Lung cancer is the leading cause of cancer death in the USA and worldwide, and lung cancer screening (LCS) with low-dose CT (LDCT) has the potential to improve lung cancer outcomes. A critical question is whether the ratio of potential benefits to harms found in prior LCS trials applies to an older and potentially sicker population. The Personalised Lung Cancer Screening (PLuS) study will help close this knowledge gap by leveraging real-world data to fully characterise LCS recipients. The principal goal of the PLuS study is to characterise the comorbidity burden of individuals undergoing LCS and quantify the benefits and harms of LCS to enable informed decision-making.

Methods and analysis
PLuS is a multicentre observational study designed to assemble an LCS cohort from the electronic health records of ~40 000 individuals undergoing annual LCS with LDCT from 2016 to 2022. Data will be integrated into a unified repository to (1) examine the burden of multimorbidity by race/ethnicity, socioeconomic status and age; (2) quantify potential benefits and harms; and (3) use the observational data with validated simulation models in the Cancer Intervention and Surveillance Modeling Network (CISNET) to provide LCS outcomes in the real-world US population. We will fit a multivariable logistic regression model to estimate the adjusted ORs of comorbidity, functional limitations and impaired pulmonary function adjusted for relevant covariates. We will also estimate the cumulative risk of LCS outcomes using discrete-time survival models. To our knowledge, this is the first study to combine observational data and simulation models to estimate the long-term impact of LCS with LDCT.

Ethics and dissemination
The study was approved by the Kaiser Permanente Southern California Institutional Review Board and VA Portland Health Care System. The results will be disseminated through publications and presentations at national and international conferences. Safety considerations include protection of patient confidentiality.

Leggi
Giugno 2022

School-based screening for childhood anxiety problems and intervention delivery: a codesign approach

Objectives
A very small proportion of children with anxiety problems receive evidence-based treatment. Barriers to access include difficulties with problem identification, concerns about stigma and a lack of clarity about how to access specialist services and their limited availability. A school-based programme that integrates screening to identify those children who are most likely to be experiencing anxiety problems with the offer of intervention has the potential to overcome many of these barriers. This article is a process-based account of how we used codesign to develop a primary school-based screening and intervention programme for child anxiety problems.

Design
Codesign.

Setting
UK primary schools.

Participants
Data were collected from year 4 children (aged 8–9 years), parents, school staff and mental health practitioners.

Results
We report how the developed programme was experienced and perceived by a range of users, including parents, children, school staff and mental health practitioners, as well as how the programme was adapted following user feedback.

Conclusions
We reflect on the mitigation techniques we employed, the lessons learnt from the codesign process and give recommendations that may inform the development and implementation of future school-based screening and intervention programmes.

Leggi
Giugno 2022

Feasible approaches and implementation challenges to atrial fibrillation screening: a qualitative study of stakeholder views in 11 European countries

Objectives
Atrial fibrillation (AF) screening may increase early detection and reduce complications of AF. European, Australian and World Heart Federation guidelines recommend opportunistic screening, despite a current lack of clear evidence supporting a net benefit for systematic screening. Where screening is implemented, the most appropriate approaches are unknown. We explored the views of European stakeholders about opportunities and challenges of implementing four AF screening scenarios.

Design
Telephone-based semi-structured interviews with results reported using Consolidated criteria for Reporting Qualitative research guidelines. Data were thematically analysed using the framework approach.

Setting
AF screening stakeholders in 11 European countries.

Participants
Healthcare professionals and regulators (n=24) potentially involved in AF screening implementation.

Intervention
Four AF screening scenarios: single time point opportunistic, opportunistic prolonged, systematic single time point/prolonged and patient-led screening.

Primary outcome measures
Stakeholder views about the challenges and feasibility of implementing the screening scenarios in the respective national/regional healthcare system.

Results
Three themes developed. (1) Current screening approaches: there are no national AF screening programmes, with most AF detected in symptomatic patients. Patient-led screening exists via personal devices, creating screening inequity. (2) Feasibility of screening: single time point opportunistic screening in primary care using single-lead ECG devices was considered the most feasible. Software algorithms may aid identification of suitable patients and telehealth services have potential to support diagnosis. (3) Implementation requirements: sufficient evidence of benefit is required. National screening processes are required due to different payment mechanisms and health service regulations. Concerns about data security, and inclusivity for those without primary care access or personal devices must be addressed.

Conclusions
There is an overall awareness of AF screening. Opportunistic screening appears the most feasible across Europe. Challenges are health inequalities, identification of best target groups for screening, streamlined processes, the need for evidence of benefit and a tailored approach adapted to national realities.

Leggi
Giugno 2022

Patients acceptability and implementation outcomes of a case management approach to encourage participation in colorectal cancer screening for people with schizophrenia: a qualitative secondary analysis of a mixed-method randomised clinical trial

Objectives
We examined the efficacy of case management (CM) interventions to encourage participation in colorectal cancer screening for patients with schizophrenia. This study aimed to clarify patients’ acceptability of the intervention and the helpful components of the intervention. Simultaneously, the study aimed to determine the acceptability, appropriateness and feasibility of the intervention from the perspective of psychiatric care providers.

Study design and setting
This study was a secondary qualitative analysis of a mixed-method randomised controlled trial that evaluated the efficacy of the CM approach to encourage participation in cancer screening for people with schizophrenia. The intervention comprised education and patient navigation for colorectal cancer screening. Interviews were conducted with patients who received the intervention and staff from two psychiatric hospitals in Japan who delivered the intervention.

Participants
Of the 172 patients with schizophrenia who participated in the trial, 153 were included. In addition, three out of six providers were included.

Data collection and analysis
Using a structured interview, the case manager asked participants about patient acceptability and the helpful components of the intervention. Content analysis was conducted for the responses obtained, and the number of responses was tabulated by two researchers. For the interviews with the providers, opinions obtained from verbatim transcripts were extracted and summarised.

Results
Forty-three of the 56 patients perceived that the intervention was acceptable. For the intervention component, inperson counselling with an explanation of the screening process by psychiatric care providers was most frequently reported by the patients as helpful (48 of the 68 respondents). Psychiatric care providers evaluated the intervention as acceptable, appropriate and easy to understand and administer. However, providing the intervention to all patients simultaneously was considered difficult with the current human resources.

Conclusions
This study showed that the CM intervention was perceived as acceptable by patients and acceptable and appropriate by psychiatric care providers.

Trial registration number
UMIN000036017.

Leggi
Giugno 2022

Portable wide-field digital imaging for screening of neonatal visual impairment causes in Rio de Janeiro, Brazil: a budget impact analysis

Objective
To estimate the budget impact of portable wide-field digital imaging incorporation on screening neonatal causes of childhood blindness and visual impairment in Rio de Janeiro, Brazil.

Design
Budget impact analysis.

Setting
Rio de Janeiro, Brazil.

Primary and secondary outcome measures
The primary outcome was the direct cost of indirect binocular ophthalmoscopy, red reflex test and portable wide-field digital image screening comprising all babies born in Rio de Janeiro’s government maternity wards. The secondary outcome was the budget impact of implementing portable wide-field digital image screening in Rio de Janeiro, Brazil.

Results
Considering 100% coverage of maternity wards, the total budget impact between 2020 and 2024 would be US$3 820 706.04, ranging from US$3 139 844.34 to US$6 099 510.35. The additional cost would be US$3 124 457.28, ranging from US$2 714 492.26 to US$4 880 608.63.

Conclusion
The cost of universal digital imaging screening corresponds to less than 1% of the government health budget of the city of Rio de Janeiro. The information provided in this study may help government decision-makers evaluate the feasibility of implementing this new strategy in the municipal setting. Further health economic evaluations should be performed to verify the affordability of the implementation of this screening strategy in the Brazilian scenario, taking into account scarce human resources.

Leggi
Giugno 2022

Oral glucose tolerance testing as a complement to fasting plasma glucose in screening for type 2 diabetes: population-based cross-sectional analyses of 146 000 health examinations in Västerbotten, Sweden

Objective
To assess the effect of adding an oral glucose tolerance test (OGTT) to fasting plasma glucose (FPG) in terms of detection of type 2 diabetes (T2D) and impaired glucose tolerance (IGT).

Design
Retrospective analysis of serial cross-sectional screening study.

Setting
Population-based health examinations within primary care in Västerbotten County, Sweden.

Participants
Individuals aged 40- 50 and 60 years with participation from 1985 to 2017. Those with previously diagnosed diabetes and FPG≥7 mmol/L were excluded.

Primary and secondary outcome measures
Prevalence of hyperglycaemia on the OGTT (IGT and T2D defined as 2-hour postload capillary plasma glucose of 8.9–12.1 mmol/L and ≥12.2 mmol/L, respectively). Analyses were further stratified by age, sex and risk factor burden to identify groups at high or low risk of IGT and T2D on testing. The numbers needed to screen (NNS) to prevent one case of T2D through detection and treatment of IGT was estimated, combining prevalence numbers with average progression rates and intervention effects from previous meta-analyses.

Results
The prevalence of IGT ranged from 0.9% (95% CI 0.7% to 1.1%) to 29.6% (95% CI 27.4% to 31.7%), and the prevalence of T2D ranged from 0.06% (95% CI 0.02% to 0.11%) to 7.0% (95% CI 5.9% to 8.3%), depending strongly on age, sex and risk factor burden. The estimated NNS to prevent one case of T2D through detection and lifestyle treatment of IGT ranged from 1332 among 40-year-old men without risk factors, to 39 among 60-year-old women with all risk factors combined.

Conclusions
The prevalence of hyperglycaemia on OGTT is highly dependent on age, sex and risk factor burden; OGTT should be applied selectively to high-risk groups to avoid unnecessary testing in the general population.

Leggi
Giugno 2022

Standardised protocol for a prospective cross-sectional multicentre clinical utility evaluation of two dual point-of-care tests in non-clinical settings for the screening of HIV and syphilis in men who have sex with men

Introduction
Point-of-care dual tests (POCTs) for simultaneously detecting antibodies to HIV and syphilis (dual HIV-syphilis POCTs) have been developed recently and show encouraging performance compared with the reference tests in laboratory-based studies. As community-based voluntary, counselling and testing (CBVCT) services are effective providers of HIV and syphilis testing and counselling with high acceptability among men who have sex with men (MSM), the evaluation of the utility of these dual tests in CBVCT services is a high priority. This prospective cross-sectional study will conduct a clinical utility evaluation of two dual POCTs in non-clinical settings for the screening of HIV and syphilis in MSM. This master protocol outlines the overall research approach that will be used in four countries.

Methods and analysis
MSM presenting at CBVCT services participating in the study for HIV/STI screening will be enrolled. The (WHO preapproved) dual POCTs to be evaluated will be SD Bioline HIV/Syphilis Duo (Abbot) and Dual Path Platform HIV-Syphilis Assay (Chembio). Trained staff will collect a capillary blood sample using finger prick blood to perform both POCTs according the manufacturers’ instructions. An analysis of the feasibility of introducing the dual POCT for the screening of HIV and syphilis in MSM at CBVCT services will be performed, by assessing its acceptability and usability at CBVCT service among MSM users and providers.

Ethics and dissemination
This core protocol was independently peer reviewed and approved by the Research Project Review Panel (RP2) of the WHO Department of Sexual and Reproductive Health and Research and by the WHO Ethics Review Committee (ERC). The protocol has been adapted to individual countries and approved by RP2, ERC and institutional review boards at each site. Results will be disseminated through peer-reviewed journals and relevant conferences.

Leggi
Giugno 2022

Active Eradication of Helicobacter pylori Within Organized Massive Screening Might Improve Survival of Gastric Cancer Patients

We read with the great interest the randomized controlled trial on gastric cancer prevention by active eradication of Helicobacter pylori in a high-risk area of southern China since 1994.1 During the long-term observation, the active eradication of H pylori significantly reduced gastric cancer incidence (adjusted hazard ratio, 0.57; 95% confidence interval, 0.33–0.98), compared to placebo. This experience might support the massive screening and eradication of H pylori in China, which has persistently high incidence and mortality of gastric cancer.

Leggi
Maggio 2022