A survey of experts to identify methods to detect problematic studies: Stage 1 of the INSPECT-SR Project.

Background: Randomised controlled trials (RCTs) inform healthcare decisions. Unfortunately, some published RCTs contain false data, and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs which have been conducted on a given topic. This means that any of these 'problematic studies' are likely to be included, but there are no agreed methods for identifying them. The INSPECT-SR project is developing a tool to identify problematic RCTs in systematic reviews of healthcare-related interventions. The tool will guide the user through a series of 'checks' to determine a study's authenticity. The first objective in the development process is to assemble a comprehensive list of checks to consider for inclusion. Methods: We assembled an initial list of checks for assessing the authenticity of research studies, with no restriction to RCTs, and categorised these into five domains: Inspecting results in the paper; Inspecting the research team; Inspecting conduct, governance, and transparency; Inspecting text and publication details; Inspecting the individual participant data. We implemented this list as an online survey, and invited people with expertise and experience of assessing potentially problematic studies to participate through professional networks and online forums. Participants were invited to provide feedback on the checks on the list, and were asked to describe any additional checks they knew of, which were not featured in the list. Results: Extensive feedback on an initial list of 102 checks was provided by 71 participants based in 16 countries across five continents. Fourteen new checks were proposed across the five domains, and suggestions were made to reword checks on the initial list. An updated list of checks was constructed, comprising 116 checks. Many participants expressed a lack of familiarity with statistical checks, and emphasized the importance of feasibility of the tool. Conclusions: A comprehensive list of trustworthiness checks has been produced. The checks will be evaluated to determine which should be included in the INSPECT-SR tool.

Large walking and wellbeing behaviour benefits of co-designed sustainable park improvements: A natural experimental study in a UK deprived urban area.

There is little robust evidence of how sustainable park interventions impact on physical activity and other behaviours important for wellbeing. This controlled natural experimental study aimed to examine the effects of co-designing a sustainable park intervention, in a deprived UK urban area, on walking and other wellbeing behaviours. Behaviour observations were conducted at two intervention sites and two matched comparison sites (n = 4,783). Walking observations (primary outcome), wellbeing behaviours (vigorous, sedentary, social and take notice activities) and demographic characteristics were assessed at pre-intervention, and post-intervention (3 and 15 months). Outcomes were compared between intervention and comparison groups, controlling for pre-intervention using multilevel negative binomial regression models. Additional behaviour observations were conducted in two unchanged nearby sites to assess changes in general local activity. Intercept surveys (n = 623) assessed change in self-reported outdoor space usage at intervention and control areas. Post-intervention, walking increased 203 % at 3 months (IRR 2·03, 95 % CI 1·01-4·09) and 351 % at 15 months (IRR 3·51, 95 % CI 2·07-5·93), for intervention sites relative to comparison sites. Large increases for other wellbeing behaviours were also observed. The proportion of non-white persons increased substantially post-intervention, compared to comparison sites. Nearby unchanged sites showed little evidence of general increased activity. Self-reported outdoor usage increased more in the intervention sites (p=<0·001). Sustainable solutions can yield large increases in walking and wellbeing in deprived areas, especially where interventions are co-designed with residents. More collaborative and robust natural experimental studies like this are needed to better inform decision-makers how to maximise health and wellbeing outcomes from sustainable interventions.

When to randomize patients in a randomized controlled trial?

The timing of randomization should be considered carefully in the context of each trial because it has implications for the particular research question answered. In most instances, randomization should be delayed until as close as practically possible to the moment of intervention. In some cases, early randomization may offer certain advantages, but trialists should balance these, including any administrative complexity or inconvenience, against the risk of avoidable protocol violations and avoidable drop out.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

INTRODUCTION: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions. METHODS AND ANALYSIS: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare. ETHICS AND DISSEMINATION: The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.

Some common, fatal flaws in systematic reviews of observational studies.

When evidence from randomized controlled trials about the effectiveness and safety of an intervention is unclear, researchers may choose to review the nonrandomized evidence. All systematic reviews pose considerable challenges, and the level of methodological expertise required to undertake a useful review of nonrandomized intervention studies is both high and often severely underestimated. Using the example of the endometrial receptivity array, we review some common, critical flaws in systematic reviews of this nature, including errors in critical appraisal and meta-analysis.

Mothers working to prevent early stillbirth study (MiNESS 20-28): a case-control study protocol.

INTRODUCTION: In the UK, 1600 babies die every year before, during or immediately after birth at 20-28 weeks' gestation. This bereavement has a similar impact on parental physical and psychological well-being to late stillbirth (>28 weeks' gestation). Improved understanding of potentially modifiable risk factors for late stillbirth (including supine going-to-sleep position) has influenced international clinical practice. Information is now urgently required to similarly inform clinical practice and aid decision-making by expectant mothers/parents, addressing inequalities in pregnancy loss between 20 and 28 weeks. METHODS AND ANALYSIS: This study focuses on what portion of risk of pregnancy loss 20-28 weeks' gestation is associated with exposures amenable to public health campaigns/antenatal care adaptation. A case-control study of non-anomalous singleton baby loss (via miscarriage, stillbirth or early neonatal death) 20+0 to 27+6 (n=316) and randomly selected control pregnancies (2:1 ratio; n=632) at group-matched gestations will be conducted. Data is collected via participant recall (researcher-administered questionnaire) and extraction from contemporaneous medical records. Unadjusted/confounder-adjusted ORs will be calculated. Exposures associated with early stillbirth at OR≥1.5 will be detectable (p<0.05, ß>0.80) assuming exposure prevalence of 30%-60%. ETHICS AND DISSEMINATION: NHS research ethical approval has been obtained from the London-Seasonal research ethics committee (23/LO/0622). The results will be presented at international conferences and published in peer-reviewed open-access journals. Information from this study will enable development of antenatal care and education for healthcare professionals and pregnant people to reduce risk of early stillbirth. TRIAL REGISTRATION NUMBER: NCT06005272.

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

BACKGROUND: During a stimulated cycle of in vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI), women receive daily doses of gonadotropin follicle-stimulating hormone (FSH) to induce multifollicular development in the ovaries. A normal response to stimulation (e.g. retrieval of 5 to 15 oocytes) is considered desirable. Generally, the number of eggs retrieved is associated with the dose of FSH. Both hyper-response and poor response are associated with an increased chance of cycle cancellation. In hyper-response, this is due to increased risk of ovarian hyperstimulation syndrome (OHSS), while poor response cycles are cancelled because the quantity and quality of oocytes is expected to be low. Clinicians often individualise the FSH dose using patient characteristics predictive of ovarian response. Traditionally, this meant women's age, but increasingly, clinicians use various ovarian reserve tests (ORTs). These include basal FSH (bFSH), antral follicle count (AFC), and anti-Müllerian hormone (AMH). It is unclear whether individualising FSH dose improves clinical outcomes. This review updates the 2018 version. OBJECTIVES: To assess the effects of individualised gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, and two trial registers in February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared (a) different doses of FSH in women with a defined ORT profile (i.e. predicted low, normal, or high responders based on AMH, AFC, and/or bFSH) or (b) an individualised dosing strategy (based on at least one ORT measure) versus uniform dosing or a different individualised dosing algorithm. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Primary outcomes were live birth/ongoing pregnancy and severe OHSS. MAIN RESULTS: We included 26 studies, involving 8520 women (6 new studies added to 20 studies included in the previous version). We treated RCTs with multiple comparisons as separate trials for the purpose of this review. Meta-analysis was limited due to clinical heterogeneity. Evidence certainty ranged from very low to low, with the main limitations being imprecision and risk of bias associated with lack of blinding. Direct dose comparisons according to predicted response in women Due to differences in dose comparisons, caution is required when interpreting the RCTs in predicted low responders. All evidence was low or very low certainty. Effect estimates were very imprecise, and increased FSH dosing may or may not have an impact on rates of live birth/ongoing pregnancy, OHSS, and clinical pregnancy. Similarly, in predicted normal responders (10 studies, 4 comparisons), higher doses may or may not impact the probability of live birth/ongoing pregnancy (e.g. 200 versus 100 international units (IU): odds ratio (OR) 0.88, 95% confidence interval (CI) 0.57 to 1.36; I2 = 0%; 2 studies, 522 women) or clinical pregnancy. Results were imprecise, and a small benefit or harm remains possible. There were too few events for the OHSS outcome to enable inferences. In predicted high responders, lower doses may or may not affect live birth/ongoing pregnancy (OR 0.98, 95% CI 0.66 to 1.46; 1 study, 521 women), severe OHSS, and clinical pregnancy. It is also unclear whether lower doses reduce moderate or severe OHSS (Peto OR 2.31, 95% CI 0.80 to 6.67; 1 study, 521 participants). ORT-algorithm studies Eight trials compared an ORT-based algorithm to a non-ORT control group. It is unclear whether live birth/ongoing pregnancy and clinical pregnancy are increased using an ORT-based algorithm (live birth/ongoing pregnancy: OR 1.12, 95% CI 0.98 to 1.29; I2 = 30%; 7 studies, 4400 women; clinical pregnancy: OR 1.04, 95% CI 0.91 to 1.18; I2 = 18%; 7 studies, 4400 women; low-certainty evidence). However, ORT algorithms may reduce moderate or severe OHSS (Peto OR 0.60, 95% CI 0.42 to 0.84; I2 = 0%; 7 studies, 4400 women; low-certainty evidence). There was insufficient evidence to determine whether the groups differed in rates of severe OHSS (Peto OR 0.74, 95% CI 0.42 to 1.28; I2 = 0%; 5 studies, 2724 women; low-certainty evidence). Our findings suggest that if the chance of live birth with a standard starting dose is 25%, the chance with ORT-based dosing would be between 25% and 31%. If the chance of moderate or severe OHSS with a standard starting dose is 5%, the chance with ORT-based dosing would be between 2% and 5%. These results should be treated cautiously due to heterogeneity in the algorithms: some algorithms appear to be more effective than others. AUTHORS' CONCLUSIONS: We did not find that tailoring the FSH dose in any particular ORT population (low, normal, high ORT) affected live birth/ongoing pregnancy rates, but we could not rule out differences, due to sample size limitations. Low-certainty evidence suggests that it is unclear if ORT-based individualisation leads to an increase in live birth/ongoing pregnancy rates compared to a policy of giving all women 150 IU. The confidence interval is consistent with an increase of up to around six percentage points with ORT-based dosing (e.g. from 25% to 31%) or a very small decrease (< 1%). A difference of this magnitude could be important to many women. It is unclear if this is driven by improved outcomes in a particular subgroup. Further, ORT algorithms reduced the incidence of OHSS compared to standard dosing of 150 IU. However, the size of the effect is also unclear. The included studies were heterogeneous in design, which limited the interpretation of pooled estimates. It is likely that different ORT algorithms differ in their effectiveness. Current evidence does not provide a clear justification for adjusting the dose of 150 IU in poor or normal responders, especially as increased dose is associated with greater total FSH dose and cost. It is unclear whether a decreased dose in predicted high responders reduces OHSS, although this would appear to be the most likely explanation for the results.

Identifying employee, workplace and population characteristics associated with COVID-19 outbreaks in the workplace: a population-based study.

OBJECTIVES: To identify risk factors that contribute to outbreaks of COVID-19 in the workplace and quantify their effect on outbreak risk. METHODS: We identified outbreaks of COVID-19 cases in the workplace and investigated the characteristics of the individuals, the workplaces, the areas they work and the mode of commute to work, through data linkages based on Middle Layer Super Output Areas in England between 20 June 2021 and 20 February 2022. We estimated population-level associations between potential risk factors and workplace outbreaks, adjusting for plausible confounders identified using a directed acyclic graph. RESULTS: For most industries, increased physical proximity in the workplace was associated with increased risk of COVID-19 outbreaks, while increased vaccination was associated with reduced risk. Employee demographic risk factors varied across industry, but for the majority of industries, a higher proportion of black/African/Caribbean ethnicities and living in deprived areas, was associated with increased outbreak risk. A higher proportion of employees in the 60-64 age group was associated with reduced outbreak risk. There were significant associations between gender, work commute modes and staff contract type with outbreak risk, but these were highly variable across industries. CONCLUSIONS: This study has used novel national data linkages to identify potential risk factors of workplace COVID-19 outbreaks, including possible protective effects of vaccination and increased physical distance at work. The same methodological approach can be applied to wider occupational and environmental health research.

Potential contribution of vaccination uptake to occupational differences in risk of SARS-CoV-2: analysis of the ONS COVID-19 Infection Survey.

OBJECTIVES: To assess variation in vaccination uptake across occupational groups as a potential explanation for variation in risk of SARS-CoV-2 infection. DESIGN: We analysed data from the UK Office of National Statistics COVID-19 Infection Survey linked to vaccination data from the National Immunisation Management System in England from 1 December 2020 to 11 May 2022. We analysed vaccination uptake and SARS-CoV-2 infection risk by occupational group and assessed whether adjustment for vaccination reduced the variation in risk between occupational groups. RESULTS: Estimated rates of triple vaccination were high across all occupational groups (80% or above), but were lowest for food processing (80%), personal care (82%), hospitality (83%), manual occupations (84%) and retail (85%). High rates were observed for individuals working in health (95% for office based, 92% for those in patient-facing roles) and education (91%) and office-based workers not included in other categories (90%). The impact of adjusting for vaccination when estimating relative risks of infection was generally modest (ratio of hazard ratios across all occupational groups reduced from 1.37 to 1.32), but was consistent with the hypothesis that low vaccination rates contribute to elevated risk in some groups. CONCLUSIONS: Variation in vaccination coverage might account for a modest proportion of occupational differences in infection risk. Vaccination rates were uniformly very high in this cohort, which may suggest that the participants are not representative of the general population. Accordingly, these results should be considered tentative pending the accumulation of additional evidence.

Gynecological trials frequently exclude people based on their symptoms rather than their condition: a systematic review of Cochrane reviews and their component trials.

OBJECTIVES: To identify strategies used in recent randomized controlled trials (RCTs) and their associated Cochrane Reviews where patients with the same gynecological condition present with different symptoms but would plausibly benefit from a common intervention. STUDY DESIGN AND SETTING: We searched the Cochrane library (February 2022) for reviews in polycystic ovarian syndrome (PCOS) and endometriosis. Reviews were included if the intervention was intended to treat all condition-specific symptoms. For each trial we recorded the strategy used and the number of potentially eligible participants excluded as a direct result of the chosen strategy. For each review we recorded the numbers of RCTs and participants excluded on the basis of symptoms experienced. RESULTS: There were 89 distinct PCOS trials in 13 reviews, and 13 Endometriosis trials in 11 reviews. Most trials restricted their eligibility to participants with specific symptoms (55% PCOS, 46% endometriosis). The second most common strategy was to measure and analyze clinical outcomes that were not relevant to all participants (38% PCOS, 31% endometriosis). Reviews excluded 27% of trials in participants evaluating the same intervention in participants experiencing the same condition based on the outcomes measured in the trials. CONCLUSION: Most gynecological trials exclude patients who could benefit from treatment or measure outcomes not relevant to all participants. We introduce a taxonomy to describe trial design strategies for conditions with heterogeneous symptoms.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions.

Introduction: Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INSPECT-SR project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare related interventions. Methods and analysis: The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: 1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, 2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, 3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in 4) a consensus meeting to select checks to be included in a draft tool and to determine its format, 5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies, and will help patients by protecting them from the influence of false data on their healthcare.

A Multi-method Exploratory Evaluation of a Service Designed to Improve Medication Safety for Patients with Monitored Dosage Systems Following Hospital Discharge.

BACKGROUND AND OBJECTIVE: Medication safety problems are common post-hospital discharge, and an important global healthcare improvement target. The Transfers of Care Around Medicines (TCAM) service was launched by a National Health Service Trust in the North-West of England, initially focusing on patients with new or existing Monitored Dosage Systems (MDS). The TCAM service is designed to enable the prompt transfer of medication information, with referrals made by hospitals at discharge to a named community pharmacy. This study aimed to explore the utilisation and impact of the TCAM service on medication safety. METHODS: The evaluation included a descriptive analysis of 3033 anonymised patient referrals to 71 community pharmacies over a 1-year period alongside an assessment of the impact of the TCAM service on unintentional medication discrepancies and adverse drug events using a retrospective before-and-after study design. Impact data were collected across 18 general practices by 16 trained clinical pharmacists. RESULTS: Most patient referrals (70%, 2126/3033) were marked as 'completed' by community pharmacies, with 15% of completed referrals delayed beyond 30 days. Screening of 411 patient records by clinical pharmacists yielded no statistically significant difference in unintentional medication discrepancies or adverse drug event rates following TCAM implementation using a multivariable regression analysis (unintentional medication discrepancies adjusted odds ratio = 0.79 [95% confidence interval 0.44-1.44, p = 0.46]; and adverse drug events adjusted odds ratio = 1.19 [95% confidence interval 0.57-2.45, p = 0.63]), although there remained considerable uncertainty. CONCLUSIONS: The TCAM service facilitated a number of community pharmacy services offered to patients with monitored dosage systems; but the impact of the intervention on unintentional medication discrepancies and adverse drug event rates post-hospital discharge for this patient group was uncertain. The results of this exploratory study can inform the ongoing implementation of the TCAM service at hospital discharge and highlight the need to understand service implementation in different contexts, which may influence its impact on medication safety.

Occupational differences in the prevalence and severity of long-COVID: analysis of the Coronavirus (COVID-19) Infection Survey.

OBJECTIVES: To establish whether prevalence and severity of long-COVID symptoms vary by industry and occupation. METHODS: We used Office for National Statistics COVID-19 Infection Survey (CIS) data (February 2021-April 2022) of working-age participants (16-65 years). Exposures were industry, occupation and major Standard Occupational Classification (SOC) group. Outcomes were self-reported: (1) long-COVID symptoms and (2) reduced function due to long-COVID. Binary (outcome 1) and ordered (outcome 2) logistic regression were used to estimate odds ratios (OR)and prevalence (marginal means). RESULTS: Public facing industries, including teaching and education, social care, healthcare, civil service, retail and transport industries and occupations, had the highest likelihood of long-COVID. By major SOC group, those in caring, leisure and other services (OR 1.44, 95% CIs 1.38 to 1.52) had substantially elevated odds than average. For almost all exposures, the pattern of ORs for long-COVID symptoms followed SARS-CoV-2 infections, except for professional occupations (eg, some healthcare, education, scientific occupations) (infection: OR<1 ; long-COVID: OR>1). The probability of reporting long-COVID for industry ranged from 7.7% (financial services) to 11.6% (teaching and education); whereas the prevalence of reduced function by 'a lot' ranged from 17.1% (arts, entertainment and recreation) to 22%-23% (teaching and education and armed forces) and to 27% (not working). CONCLUSIONS: The risk and prevalence of long-COVID differs across industries and occupations. Generally, it appears that likelihood of developing long-COVID symptoms follows likelihood of SARS-CoV-2 infection, except for professional occupations. These findings highlight sectors and occupations where further research is needed to understand the occupational factors resulting in long-COVID.

Is the use of IVF add-on treatments driven by patients or clinics? Findings from a UK patient survey.

There are conflicting narratives over what drives demand for add-ons. We undertook an online survey of IVF patients to determine whether patients perceive that use of IVF add-ons is driven by patients or practitioners. People who underwent IVF in the UK in the previous five years were recruited via social media Survey questions focussed on the roles of clinician offer and patient request, including who first suggested use of add-ons in IVF consultations, where patients first heard about them, and which information sources they trusted. From a total of 261 responses, 224 met the inclusion criteria. Overall, 67% of respondents had used one or more IVF add-ons, most commonly: time-lapse imaging (27%), EmbryoGlue (27%), and endometrial scratching (26%). Overall, 81% of the add-ons used were offered to participants by clinicians (compared to 19% requested by themselves). Half (54%) reported being offered add-ons during consultations, compared to 24% who initiated discussion about add-ons. Higher proportions of private patients reported being offered (90%), requesting (47%) and using (74%) add-ons than those with NHS funding (74%, 29%, 52%, respectively). The main limitations of this study are the small sample size, recruitment via a convenience sample, and the self-reported data capture which is subject to recall bias.

Evaluating antenatal risk in twin pregnancies-A feasibility study to identify modifiable factors associated with adverse pregnancy outcomes.

INTRODUCTION: Twin pregnancies have significantly higher rates of perinatal morbidity and mortality compared to singleton pregnancies; current attempts to reduce perinatal mortality have been less successful in twin pregnancies. The paucity of information about modifiable risk factors for adverse neonatal outcomes in twin pregnancies, as well as independent effects of chorionicity may have contributed to this outcome. This study aimed to explore the feasibility of an observational study to identify modifiable factors associated with adverse neonatal outcomes in twin pregnancies. MATERIAL AND METHODS: Patients pregnant with twins at six UK hospitals between December 2019-March 2021 completed researcher-administered questionnaires at approximately 20-, 28- and 36-weeks' gestation, recording a wide range of self-reported social, lifestyle and demographic factors, alongside prospectively recorded clinical data from maternity records. Descriptive statistics were used to describe frequencies of exposures; logistic regression was used to determine whether factors were associated with a composite measure of adverse neonatal outcome. RESULTS: Data were collected from 65% (181/277) of eligible participants. A total of 98% (175) of participants had positive views about their participation. Some exposures, including cigarette smoking, supine sleep position and reduced fetal movements were less frequent in twin pregnancies compared to singletons, whereas fertility treatment was more common. Furthermore, different patterns of exposure were seen between monochorionic and dichorionic twins. This pilot study found some associations with adverse neonatal outcomes including: low BMI (OR 8.36, 95% CI: 1.02-68.87), maternal age ≥41 years (OR 9.0 95% CI: 1.07-75.84), maternally perceived high-stress levels (OR 1.96, 95% CI: 1.03-3.75) and inadequate antenatal screening (OR 1.44, 95% CI: 1.01-2.06). Sleep duration ≥9 h and right-sided going to sleep position were more frequent among pregnancies with adverse outcomes. Participants who reported receiving no information on fetal movement and reduced maternal perception of movements were more likely to have an adverse outcome, but sample size prohibited analysis based upon chorionicity. CONCLUSIONS: An observational study of modifiable factors in twin pregnancy is feasible. Differences in the frequencies of exposures between twin and singleton pregnancies highlight the need for twin-specific studies to identify modifiable factors and develop preventative strategies for morbidity and mortality in twin pregnancies.

Information about fetal movements and stillbirth trends: Analysis of time series data.

OBJECTIVE: To investigate the implementation of the Count the Kicks campaign in Iowa to increase maternal awareness of fetal movements and its association with stillbirth rates. DESIGN: Time series analysis. SETTING: Iowa, Illinois, Minnesota and Missouri, USA. SAMPLE: Women giving birth between 2005 and 2018. METHODS: Data regarding campaign activity, including uptake of the app and the distribution of information materials, and population-level data on stillbirth rates and potential confounding risk factors were obtained from publicly available data for 2005-2018. Data were plotted over time and examined in relation to key implementation phases. MAIN OUTCOME MEASURE: Stillbirth. RESULTS: App users were largely centred on Iowa, and increased over time, although the numbers were modest relative to the number of births. Only Iowa demonstrated a reduction in stillbirth (OR 0.96, 95% CI 0.96-1.00 per year; interaction between state and time, p < 0.001); there was a decline from 2008 to 2013 (before the launch of the app), an increase from 2014 to 2016 and a decrease from 2017 to 2018, which coincided with increased app use (interaction between period and time, p = 0.06). With the exception of smoking (which fell from approx. 20% in 2005 to approx. 15% in 2018 in Iowa), all risk factors increased in prevalence, so are unlikely to account for a reduction in stillbirth. CONCLUSIONS: There was a reduction in the stillbirth rate in Iowa, where an information campaign about fetal movements was active; this reduction was not present in neighbouring states. Large-scale intervention studies are needed to determine whether the temporal associations between app use and stillbirth rate are causally related.

Exploring the relationship between job characteristics and infection: Application of a COVID-19 job exposure matrix to SARS-CoV-2 infection data in the United Kingdom.

OBJECTIVE: This study aimed to assess whether workplace exposures as estimated via a COVID-19 job exposure matrix (JEM) are associated with SARS-CoV-2 in the UK. METHODS: Data on 244 470 participants were available from the Office for National Statistics Coronavirus Infection Survey (CIS) and 16 801 participants from the Virus Watch Cohort, restricted to workers aged 20-64 years. Analysis used logistic regression models with SARS-CoV-2 as the dependent variable for eight individual JEM domains (number of workers, nature of contacts, contact via surfaces, indoor or outdoor location, ability to social distance, use of face covering, job insecurity, and migrant workers) with adjustment for age, sex, ethnicity, index of multiple deprivation (IMD), region, household size, urban versus rural area, and health conditions. Analyses were repeated for three time periods (i) February 2020 (Virus Watch)/April 2020 (CIS) to May 2021), (ii) June 2021 to November 2021, and (iii) December 2021 to January 2022. RESULTS: Overall, higher risk classifications for the first six domains tended to be associated with an increased risk of infection, with little evidence of a relationship for domains relating to proportion of workers with job insecurity or migrant workers. By time there was a clear exposure-response relationship for these domains in the first period only. Results were largely consistent across the two UK cohorts. CONCLUSIONS: An exposure-response relationship exists in the early phase of the COVID-19 pandemic for number of contacts, nature of contacts, contacts via surfaces, indoor or outdoor location, ability to social distance and use of face coverings. These associations appear to have diminished over time.