Factors influencing the participation of pregnant and lactating women in clinical trials: A mixed-methods systematic review.

BACKGROUND: Poor representation of pregnant and lactating women and people in clinical trials has marginalised their health concerns and denied the maternal-fetal/infant dyad benefits of innovation in therapeutic research and development. This mixed-methods systematic review synthesised factors affecting the participation of pregnant and lactating women in clinical trials, across all levels of the research ecosystem. METHODS AND FINDINGS: We searched 8 databases from inception to 14 February 2024 to identify qualitative, quantitative, and mixed-methods studies that described factors affecting participation of pregnant and lactating women in vaccine and therapeutic clinical trials in any setting. We used thematic synthesis to analyse the qualitative literature and assessed confidence in each qualitative review finding using the GRADE-CERQual approach. We compared quantitative data against the thematic synthesis findings to assess areas of convergence or divergence. We mapped review findings to the Theoretical Domains Framework (TDF) and Capability, Opportunity, and Motivation Model of Behaviour (COM-B) to inform future development of behaviour change strategies. We included 60 papers from 27 countries. We grouped 24 review findings under 5 overarching themes: (a) interplay between perceived risks and benefits of participation in women's decision-making; (b) engagement between women and the medical and research ecosystems; (c) gender norms and decision-making autonomy; (d) factors affecting clinical trial recruitment; and (e) upstream factors in the research ecosystem. Women's willingness to participate in trials was affected by: perceived risk of the health condition weighed against an intervention's risks and benefits, therapeutic optimism, intervention acceptability, expectations of receiving higher quality care in a trial, altruistic motivations, intimate relationship dynamics, and power and trust in medicine and research. Health workers supported women's participation in trials when they perceived clinical equipoise, had hope for novel therapeutic applications, and were convinced an intervention was safe. For research staff, developing reciprocal relationships with health workers, having access to resources for trial implementation, ensuring the trial was visible to potential participants and health workers, implementing a woman-centred approach when communicating with potential participants, and emotional orientations towards the trial were factors perceived to affect recruitment. For study investigators and ethics committees, the complexities and subjectivities in risk assessments and trial design, and limited funding of such trials contributed to their reluctance in leading and approving such trials. All included studies focused on factors affecting participation of cisgender pregnant women in clinical trials; future research should consider other pregnancy-capable populations, including transgender and nonbinary people. CONCLUSIONS: This systematic review highlights diverse factors across multiple levels and stakeholders affecting the participation of pregnant and lactating women in clinical trials. By linking identified factors to frameworks of behaviour change, we have developed theoretically informed strategies that can help optimise pregnant and lactating women's engagement, participation, and trust in such trials.

Recommended measurement instruments for genitourinary symptoms associated with menopause: the COMMA (Core outcomes in menopause) consortium.

OBJECTIVE: The aim of the study is to identify appropriate definitions and patient-reported outcome measures (PROMs) for each of the eight core outcomes previously selected for genitourinary symptoms associated with menopause: pain with sex, vulvovaginal dryness, vulvovaginal discomfort or irritation, discomfort or pain when urinating, change in most bothersome symptom, distress, bother or interference of genitourinary symptoms, satisfaction with treatment, and side effects. METHODS: We conducted a systematic review to identify possible definitions and PROMs, including their measurement properties. Identified definitions and relevant PROMs with acceptable measurement properties were entered into an international consensus process involving 28 participants from 10 countries to achieve final recommendations for each core outcome. RESULTS: A total of 87 publications reporting on 34 PROMs were identified from 21,207 publications screened. Of these 34 PROMs, 29 were not considered to sufficiently map onto the core outcomes, and 26 of these also had insufficient measurement properties. Therefore, only five PROMs corresponding to two core outcomes were considered for recommendation. We recommend the PROMIS Scale v2.0 - Sexual Function and Satisfaction: Vaginal Discomfort with Sexual Activity to measure the outcome of "pain with sexual activity" and the Day-to-Day Impact of Vaginal Aging (DIVA) Questionnaire to measure "distress, bother or interference" from genitourinary symptoms. Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events in study participants, which is a requirement of Good Clinical Practice. CONCLUSIONS: Suitable PROMs and definitions were identified to measure three of eight core outcomes. Because of the lack of existing measures, which align with the core outcomes and have evidence of high-quality measurement properties, future work will focus on developing or validating PROMs for the remaining five core outcomes.

Recommended measurement instruments for menopausal vasomotor symptoms: the COMMA (Core Outcomes in Menopause) consortium.

OBJECTIVE: The aim of the study is to identify suitable definitions and patient-reported outcome measures (PROMs) to assess each of the six core outcomes previously identified through the COMMA (Core Outcomes in Menopause) global consensus process relating to vasomotor symptoms: frequency, severity, distress/bother/interference, impact on sleep, satisfaction with treatment, and side effects. METHODS: A systematic review was conducted to identify relevant definitions for the outcome of side-effects and PROMs with acceptable measurement properties for the remaining five core outcomes. The consensus process, involving 36 participants from 16 countries, was conducted to review definitions and PROMs and make final recommendations for the measurement of each core outcome. RESULTS: A total of 21,207 publications were screened from which 119 reporting on 40 PROMs were identified. Of these 40 PROMs, 36 either did not adequately map onto the core outcomes or lacked sufficient measurement properties. Therefore, only four PROMs corresponding to two of the six core outcomes were considered for recommendation. We recommend the Hot Flash Related Daily Interference Scale to measure the domain of distress, bother, or interference of vasomotor symptoms and to capture impact on sleep (one item in the Hot Flash Related Daily Interference Scale captures interference with sleep). Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events, which is a requirement of Good Clinical Practice. CONCLUSIONS: We identified suitable definitions and PROMs for only three of the six core outcomes. No suitable PROMs were found for the remaining three outcomes (frequency and severity of vasomotor symptoms and satisfaction with treatment). Future studies should develop and validate PROMs for these outcomes.

Arriving at the empirically based conceptualization of restricted and repetitive behaviors: A systematic review and meta-analytic examination of factor analyses.

An empirically based understanding of the factor structure of the restricted and repetitive behaviors (RRB) domain is a prerequisite for interpreting studies attempting to understand the correlates and mechanisms underpinning RRB and for measurement development. Therefore, this study aimed to conduct a systematic review and meta-analysis of RRB factor analytic studies. Sets of meta-analyses were performed to examine (a) the factor structure of individual RRB instruments, (b) associations between RRB subdomains across instruments, and (c) the association between RRB factors and other variables. Searches for peer-reviewed articles evaluating the factor structure of the RRB domain were performed in PsycINFO (Ovid), Medline (Ovid), and Embase (Ovid). No age, measurement, or informant-type limits were imposed. Quality and risk of bias for individual studies were assessed using relevant COSMIN sections. Among the 53 studies retained for review, 41 examined RRB factor structures among individuals with autism spectrum disorder (ASD) and 12 among non-ASD samples. Meta-analysis of factor correlations provided evidence that the RRB domain encompasses the following eight specific factors: repetitive motor behaviors, insistence on sameness, restricted interests, unusual interests, sensory sensitivity, and repetitive, stereotyped language. Although interrelated, RRB factors were distinct, showing a unique pattern of associations with demographic, cognitive, and clinical correlates. Meta-analyses of the associations between RRB factors and specific correlates, specifically adaptive functioning and communication impairments, should be considered preliminary due to the limited number of studies. Despite limitations, this review provides important insights into the factor structure of the RRB domain and highlights critical conceptual, measurement, and methodological limitations of the current research that will need to be addressed in order to improve our understanding of RRB.

Intimate Partner Violence and Child and Adolescent Cognitive Development: A Systematic Review.

Intimate partner violence (IPV) is a public health and human rights issue, with millions of children affected worldwide. While several reviews have explored the emotional-behavioural functioning of children exposed to IPV, this review aimed to examine the relationship between children's exposure to IPV and their cognitive development, and to identify associated factors such as aspects of parenting. The databases MEDLINE, PsycInfo, EMBASE, Family and Society Studies Worldwide, CINAHL, and ERIC were searched using key words related to IPV, such as domestic, family, partner, interparental, spousal, marital, violence, abuse, aggression, assault, combined with key words related to cognitive functioning, such as neuropsychological, executive, intelligence, learning, memory, and key words related to children and adolescents. A total of 38 studies met the criteria for review which included reporting an estimate of the relationship between IPV and cognition using direct assessments of cognitive functioning. Approximately 70% of studies found a relationship between IPV and poorer cognitive functioning, with general IQ the most frequently assessed domain of functioning, followed by verbal abilities and academic skills. Most studies assessed skills during early childhood, with fewer studies assessing children during middle childhood and adolescence. Results were consistent across cognitive domains and developmental stages. In terms of factors associated with IPV and cognition, a range of demographic, individual, and family factors were included, with several studies exploring mediating and moderating mechanisms. The findings suggest that IPV in childhood is associated with poorer cognitive skills across a range of domains. Implications for policy, practice and research are discussed.

Examining Effectiveness and Predictors of Treatment Response of Pivotal Response Treatment in Autism: An Umbrella Review and a Meta-Analysis.

The current study aimed to provide a comprehensive appraisal of the current evidence on the effectiveness of Pivotal Response Training (PRT) for individuals with autism spectrum disorder (ASD) and to explore predictors of treatment response. We conducted a systematic review of the following electronic databases and registers: PsycINFO, Medline, Embase, Cochrane Central Register of Controlled Trials, ERIC, Linguistics and Language Behavior Abstracts. Six systematic reviews were identified, two with meta-analytic component. Identified reviews varied widely in terms of their aims, outcomes, and designs which precluded a unified and consistent set of conclusions and recommendations. Ten RCTs were identified. Eight of identified RCTs reported at least one language and communication-related outcome. Statistically significant effects of PRT were identified across a majority of identified RCTs for a range of language and communication skills. However, evidence for positive treatment effects of PRT on outcome measures assessing other domains was less robust and/or specific. Overall, both previous systematic reviews and new meta-analysis of the RCTs suggest that PRT shows promise for improving language and communication. Only four RCTs examined the association between baseline child characteristics and treatment outcomes, however, no consistent pattern emerged. This review has identified several key methodological and design improvements that are needed to enable our field to fully capitalize on the potential of RCT designs and characterize detailed profiles of treatment responders. These findings are essential for informing the development of evidence-based guidelines for clinicians on what works for whom and why.

Improving the translation of search strategies using the Polyglot Search Translator: a randomized controlled trial.

BACKGROUND: Searching for studies to include in a systematic review (SR) is a time- and labor-intensive process with searches of multiple databases recommended. To reduce the time spent translating search strings across databases, a tool called the Polyglot Search Translator (PST) was developed. The authors evaluated whether using the PST as a search translation aid reduces the time required to translate search strings without increasing errors. METHODS: In a randomized trial, twenty participants were randomly allocated ten database search strings and then randomly assigned to translate five with the assistance of the PST (PST-A method) and five without the assistance of the PST (manual method). We compared the time taken to translate search strings, the number of errors made, and how close the number of references retrieved by a translated search was to the number retrieved by a reference standard translation. RESULTS: Sixteen participants performed 174 translations using the PST-A method and 192 translations using the manual method. The mean time taken to translate a search string with the PST-A method was 31 minutes versus 45 minutes by the manual method (mean difference: 14 minutes). The mean number of errors made per translation by the PST-A method was 8.6 versus 14.6 by the manual method. Large variation in the number of references retrieved makes results for this outcome inconclusive, although the number of references retrieved by the PST-A method was closer to the reference standard translation than the manual method. CONCLUSION: When used to assist with translating search strings across databases, the PST can increase the speed of translation without increasing errors. Errors in search translations can still be a problem, and search specialists should be aware of this.

Associations between multimorbidity, all-cause mortality and glycaemia in people with type 2 diabetes: A systematic review.

INTRODUCTION: Type 2 diabetes (T2D) is a major health priority worldwide and the majority of people with diabetes live with multimorbidity (MM) (the co-occurrence of ≥2 chronic conditions). The aim of this systematic review was to explore the association between MM and all-cause mortality and glycaemic outcomes in people with T2D. METHODS: The search strategy centred on: T2D, MM, comorbidity, mortality and glycaemia. Databases searched: MEDLINE, EMBASE, CINAHL Complete, The Cochrane Library, and SCOPUS. Restrictions included: English language, quantitative empirical studies. Two reviewers independently carried out: abstract and full text screening, data extraction, and quality appraisal. Disagreements adjudicated by a third reviewer. RESULTS: Of the 4882 papers identified; 41 met inclusion criteria. The outcome was all-cause mortality in 16 studies, glycaemia in 24 studies and both outcomes in one study. There were 28 longitudinal cohort studies and 13 cross-sectional studies, with the number of participants ranging from 96-892,223. Included studies were conducted in high or upper-middle-income countries. Fifteen of 17 studies showed a statistically significant association between increasing MM and higher mortality. Ten of 14 studies showed no significant associations between MM and HbA1c. Four of 14 studies found higher levels of MM associated with higher HbA1c. Increasing MM was significantly associated with hypoglycaemia in 9/10 studies. There was no significant association between MM and fasting glucose (one study). No studies explored effects on glycaemic variability. CONCLUSIONS: This review demonstrates that MM in T2D is associated with higher mortality and hypoglycaemia, whilst evidence regarding the association with other measures of glycaemic control is mixed. The current single disease focused approach to management of T2D seems inappropriate. Our findings highlight the need for clinical guidelines to support a holistic approach to the complex care needs of those with T2D and MM, accounting for the various conditions that people with T2D may be living with. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews CRD42017079500.

Impact of multimorbidity count on all-cause mortality and glycaemic outcomes in people with type 2 diabetes: a systematic review protocol.

INTRODUCTION: Type 2 diabetes (T2D) is a leading health priority worldwide. Multimorbidity (MM) is a term describing the co-occurrence of two or more chronic diseases or conditions. The majority of people living with T2D have MM. The relationship between MM and mortality and glycaemia in people with T2D is not clear. METHODS AND ANALYSIS: Medline, Embase, Cumulative Index of Nursing and Allied Health Complete, The Cochrane Library, and SCOPUS will be searched with a prespecified search strategy. The searches will be limited to quantitative empirical studies in English with no restriction on publication date. One reviewer will perform title screening and two review authors will independently screen the abstract and full texts using Covidence software, with disagreements adjudicated by a third reviewer. Data will be extracted using a using a Population, Exposure, Comparator and Outcomes framework. Two reviewers will independently extract data and undertake the risk of bias (quality) assessment. Disagreements will be resolved by consensus. A narrative synthesis of the results will be conducted and meta-analysis considered if appropriate. Quality appraisal will be undertaken using the Newcastle-Ottawa quality assessment scale and the quality of the cumulative evidence of the included studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. This protocol was prepared in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines to ensure the quality of our review. ETHICS AND DISSEMINATION: This review will synthesise the existing evidence about the impact of MM on mortality and glycaemic outcomes in people living with T2D and increase our understanding of this subject and will inform future practice and policy. Findings will be disseminated via conference presentations, social media and peer-reviewed publication. PROSPERO REGISTRATION NUMBER: CRD42017079500.

What Works in Youth Suicide Prevention? A Systematic Review and Meta-Analysis.

BACKGROUND: Young people require specific attention when it comes to suicide prevention, however efforts need to be based on robust evidence. METHODS: We conducted a systematic review and meta-analysis of all studies examining the impact of interventions that were specifically designed to reduce suicide-related behavior in young people. FINDINGS: Ninety-nine studies were identified, of which 52 were conducted in clinical settings, 31 in educational or workplace settings, and 15 in community settings. Around half were randomized controlled trials. Large scale interventions delivered in both clinical and educational settings appear to reduce self-harm and suicidal ideation post-intervention, and to a lesser extent at follow-up. In community settings, multi-faceted, place-based approaches seem to have an impact. Study quality was limited. INTERPRETATION: Overall whilst the number and range of studies is encouraging, gaps exist. Few studies were conducted in low-middle income countries or with demographic populations known to be at increased risk. Similarly, there was a lack of studies conducted in primary care, universities and workplaces. However, we identified that specific youth suicide-prevention interventions can reduce self-harm and suicidal ideation; these types of intervention need testing in high-quality studies.