Ultrasonographic Fetal Nuchal Translucency Measurements and Cytogenetic Outcomes.

Importance: Ultrasonographic measurement of fetal nuchal translucency is used in prenatal screening for trisomies 21 and 18 and other conditions. A cutoff of 3.5 mm or greater is commonly used to offer follow-up investigations, such as prenatal cell-free DNA (cfDNA) screening or cytogenetic testing. Recent studies showed a possible association with chromosomal anomalies for levels less than 3.5 mm, but extant evidence has limitations. Objective: To evaluate the association between different nuchal translucency measurements and cytogenetic outcomes on a population level. Design, Setting, and Participants: This population-based retrospective cohort study used data from the Better Outcomes Registry & Network, the perinatal registry for Ontario, Canada. All singleton pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, were included. Data were analyzed from March 17 to August 14, 2023. Exposures: Nuchal translucency measurements were identified through multiple-marker screening results. Main Outcomes and Measures: Chromosomal anomalies were identified through all Ontario laboratory-generated prenatal and postnatal cytogenetic tests. Cytogenetic testing results, supplemented with information from cfDNA screening and clinical examination at birth, were used to identify pregnancies without chromosomal anomalies. Multivariable modified Poisson regression with robust variance estimation and adjustment for gestational age was used to compare cytogenetic outcomes for pregnancies with varying nuchal translucency measurement categories and a reference group with nuchal translucency less than 2.0 mm. Results: Of 414 268 pregnancies included in the study (mean [SD] maternal age at estimated delivery date, 31.5 [4.7] years), 359 807 (86.9%) had a nuchal translucency less than 2.0 mm; the prevalence of chromosomal anomalies in this group was 0.5%. An increased risk of chromosomal anomalies was associated with increasing nuchal translucency measurements, with an adjusted risk ratio (ARR) of 20.33 (95% CI, 17.58-23.52) and adjusted risk difference (ARD) of 9.94% (95% CI, 8.49%-11.39%) for pregnancies with measurements of 3.0 to less than 3.5 mm. The ARR was 4.97 (95% CI, 3.45-7.17) and the ARD was 1.40% (95% CI, 0.77%-2.04%) when restricted to chromosomal anomalies beyond the commonly screened aneuploidies (excluding trisomies 21, 18, and 13 and sex chromosome aneuploidies). Conclusions and Relevance: In this cohort study of 414 268 singleton pregnancies, those with nuchal translucency measurements less than 2.0 mm were at the lowest risk of chromosomal anomalies. Risk increased with increasing measurements, including measurements less than 3.5 mm and anomalies not routinely screened by many prenatal genetic screening programs.

Reporting of equity in observational epidemiology: A methodological review.

Background: Observational studies can inform how we understand and address persisting health inequities through the collection, reporting and analysis of health equity factors. However, the extent to which the analysis and reporting of equity-relevant aspects in observational research are generally unknown. Thus, we aimed to systematically evaluate how equity-relevant observational studies reported equity considerations in the study design and analyses. Methods: We searched MEDLINE for health equity-relevant observational studies from January 2020 to March 2022, resulting in 16 828 articles. We randomly selected 320 studies, ensuring a balance in focus on populations experiencing inequities, country income settings, and coronavirus disease 2019 (COVID-19) topic. We extracted information on study design and analysis methods. Results: The bulk of the studies were conducted in North America (n = 95, 30%), followed by Europe and Central Asia (n = 55, 17%). Half of the studies (n = 171, 53%) addressed general health and well-being, while 49 (15%) focused on mental health conditions. Two-thirds of the studies (n = 220, 69%) were cross-sectional. Eight (3%) engaged with populations experiencing inequities, while 22 (29%) adapted recruitment methods to reach these populations. Further, 67 studies (21%) examined interaction effects primarily related to race or ethnicity (48%). Two-thirds of the studies (72%) adjusted for characteristics associated with inequities, and 18 studies (6%) used flow diagrams to depict how populations experiencing inequities progressed throughout the studies. Conclusions: Despite over 80% of the equity-focused observational studies providing a rationale for a focus on health equity, reporting of study design features relevant to health equity ranged from 0-95%, with over half of the items reported by less than one-quarter of studies. This methodological study is a baseline assessment to inform the development of an equity-focussed reporting guideline for observational studies as an extension of the well-known Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guideline.

Screening for depression in children and adolescents in primary care or non-mental health settings: a systematic review update.

BACKGROUND: The transition from childhood to adolescence is associated with an increase in rates of some psychiatric disorders, including major depressive disorder, a debilitating mood disorder. The aim of this systematic review is to update the evidence on the benefits and harms of screening for depression in primary care and non-mental health clinic settings among children and adolescents. METHODS: This review is an update of a previous systematic review, for which the last search was conducted in 2017. We searched Ovid MEDLINE® ALL, Embase Classic+Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and CINAHL on November 4, 2019, and updated on February 19, 2021. If no randomized controlled trials were found, we planned to conduct an additional search for non-randomized trials with a comparator group. For non-randomized trials, we applied a non-randomized controlled trial filter and searched the same databases except for Cochrane Central Register of Controlled Trials from January 2015 to February 2021. We also conducted a targeted search of the gray literature for unpublished documents. Title and abstract, and full-text screening were completed independently by pairs of reviewers. RESULTS: In this review update, we were unable to find any randomized controlled studies that satisfied our eligibility criteria and evaluated the potential benefits and harms of screening for depression in children and adolescents. Additionally, a search for non-randomized trials yielded no studies that met the inclusion criteria. CONCLUSIONS: The findings of this review indicate a lack of available evidence regarding the potential benefits and harms of screening for depression in children and adolescents. This absence of evidence emphasizes the necessity for well-conducted clinical trials to evaluate the effectiveness of depression screening among children and adolescents in primary care and non-mental health clinic settings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020150373 .

Screening for hypertension in adults: protocol for evidence reviews to inform a Canadian Task Force on Preventive Health Care guideline update.

PURPOSE: To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening in a primary care setting for hypertension in adults aged 18 years and older. This protocol outlines the scope and methods for a series of systematic reviews and one overview of reviews. METHODS: To evaluate the benefits and harms of screening for hypertension, the Task Force will rely on the relevant key questions from the 2021 United States Preventive Services Task Force systematic review. In addition, a series of reviews will be conducted to identify, appraise, and synthesize the evidence on (1) the association of blood pressure measurement methods and future cardiovascular (CVD)-related outcomes, (2) thresholds for discussions of treatment initiation, and (3) patient acceptability of hypertension screening methods. For the review of blood pressure measurement methods and future CVD-related outcomes, we will perform a de novo review and search MEDLINE, Embase, CENTRAL, and APA PsycInfo for randomized controlled trials, prospective or retrospective cohort studies, nested case-control studies, and within-arm analyses of intervention studies. For the thresholds for discussions of treatment initiation review, we will perform an overview of reviews and update results from a relevant 2019 UK NICE review. We will search MEDLINE, Embase, APA PsycInfo, and Epistemonikos for systematic reviews. For the acceptability review, we will perform a de novo systematic review and search MEDLINE, Embase, and APA PsycInfo for randomized controlled trials, controlled clinical trials, and observational studies with comparison groups. Websites of relevant organizations, gray literature sources, and the reference lists of included studies and reviews will be hand-searched. Title and abstract screening will be completed by two independent reviewers. Full-text screening, data extraction, risk-of-bias assessment, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers. Results from included studies will be synthesized narratively and pooled via meta-analysis when appropriate. The GRADE approach will be used to assess the certainty of evidence for outcomes. DISCUSSION: The results of the evidence reviews will be used to inform Canadian recommendations on screening for hypertension in adults aged 18 years and older. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered on PROSPERO and is available on the Open Science Framework (osf.io/8w4tz).

Assessing the quality and value of metabolic chart data for capturing core outcomes for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

BACKGROUND: Generating rigorous evidence to inform care for rare diseases requires reliable, sustainable, and longitudinal measurement of priority outcomes. Having developed a core outcome set for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, we aimed to assess the feasibility of prospective measurement of these core outcomes during routine metabolic clinic visits. METHODS: We used existing cohort data abstracted from charts of 124 children diagnosed with MCAD deficiency who participated in a Canadian study which collected data from birth to a maximum of 11 years of age to investigate the frequency of clinic visits and quality of metabolic chart data for selected outcomes. We recorded all opportunities to collect outcomes from the medical chart as a function of visit rate to the metabolic clinic, by treatment centre and by child age. We applied a data quality framework to evaluate data based on completeness, conformance, and plausibility for four core MCAD outcomes: emergency department use, fasting time, metabolic decompensation, and death. RESULTS: The frequency of metabolic clinic visits decreased with increasing age, from a rate of 2.8 visits per child per year (95% confidence interval, 2.3-3.3) among infants 2 to 6 months, to 1.0 visit per child per year (95% confidence interval, 0.9-1.2) among those ≥ 5 years of age. Rates of emergency department visits followed anticipated trends by child age. Supplemental findings suggested that some emergency visits occur outside of the metabolic care treatment centre but are not captured. Recommended fasting times were updated relatively infrequently in patients' metabolic charts. Episodes of metabolic decompensation were identifiable but required an operational definition based on acute manifestations most commonly recorded in the metabolic chart. Deaths occurred rarely in these patients and quality of mortality data was not evaluated. CONCLUSIONS: Opportunities to record core outcomes at the metabolic clinic occur at least annually for children with MCAD deficiency. Methods to comprehensively capture emergency care received at outside institutions are needed. To reduce substantial heterogeneous recording of core outcome across treatment centres, improved documentation standards are required for recording of recommended fasting times and a consensus definition for metabolic decompensations needs to be developed and implemented.

SARS-CoV-2 transmission risk for common group activities and settings: a living scoping review.

BACKGROUND: While the modes of transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are well studied, the risk of transmission in various group settings or activities is less clear. This living scoping review aims to summarize the risk factors of coronavirus disease 2019 (COVID-19) spread in common group activities (e.g. social gatherings) or settings (e.g. schools, hospitals, shared workplaces) to understand the drivers of transmission and to inform a risk assessment profile tool for use of rapid antigen detection tests. METHODS: We systematically searched electronic databases, MEDLINE and Embase, from January 2019 until February 2022. We included studies that evaluated the risk of SARS-CoV-2 transmission in activities and settings, deemed strategically important to government departments in Ireland, provided by the Department of Health (Ireland) Expert Advisory Group on Rapid Testing. RESULTS: After screening 14 052 records, data from 139 studies were narratively synthesized. The risk was consistently reported as 'high' for large social events (e.g. weddings) and indoor sports, working in healthcare settings and shared workplaces, working/living in residential settings and travelling via public transportation. Most studies were from healthcare settings, with common risk factors including close contact with COVID-19 cases, working in high-risk departments and inappropriate use of personal protective equipment. For other settings and activities, lack of infection prevention and control practices reportedly contributed to infection transmission. CONCLUSION: The heterogeneity across studies and lack of direct information on dominant variants, preventive measures, vaccination coverage necessitates further research on transmission risk within group activities to inform infection prevention and control measures.

Sex differences in schizophrenia-spectrum diagnoses: results from a 30-year health record registry.

This study investigated sociodemographic and clinical differences between the sexes in individuals affected by schizophrenia-spectrum disorders (SSD) who accessed outpatient mental health services. Within a retrospective cohort of 45,361 outpatients receiving care in Ferrara (Italy) from 1991 to 2021, those with a SSD diagnosis were compared between the sexes for sociodemographic and clinical characteristics before and after the index date (when the ICD-9: 295.*diagnosis was first recorded) to assess early trajectory, age and type of diagnosis, and severity of illness indicated by medication use, hospitalization, and duration of psychiatric care. Predictors of discharge were also investigated. Among 2439 patients, 1191 were women (48.8%). Compared to men, women were significantly older at first visit (43.7 vs. 36.8 years) and at index date (47.8 vs. 40.6) with peak frequency at age 48 (vs. 30). The most frequent last diagnosis recorded before the index date was delusional disorder (27.7%) or personality disorder (24.3%) in men and depression (24%) and delusional disorder (30.1%) in women. After the index date, long-acting antipsychotics and clozapine were more frequently prescribed to men (46.5% vs. 36.3%; 13.2% vs. 9.4%, p < 0.05) and mood stabilizers and antidepressants to women (24.3% vs. 21.1%; 50.1% vs. 35.5%; p < 0.05). Women had fewer involuntary admissions (10.1% vs. 13.6%) and were more likely to be discharged as the time under care increased (p = 0.009). After adjusting for covariates, sex was not a significant predictor of discharge. Our study confirmed that sex differences exist in clinical and sociodemographic characteristics of outpatients with SSD and that gender considerations might influence the rapidity of diagnosis and medications prescribed. These findings highlight the need to implement a women-tailored approach in specialist care programs for psychoses.

Serological markers and long COVID-A rapid systematic review.

BACKGROUND: Long COVID is highly heterogeneous, often debilitating, and may last for years after infection. The aetiology of long COVID remains uncertain. Examination of potential serological markers of long COVID, accounting for clinical covariates, may yield emergent pathophysiological insights. METHODS: In adherence to PRISMA guidelines, we carried out a rapid review of the literature. We searched Medline and Embase for primary observational studies that compared IgG response in individuals who experienced COVID-19 symptoms persisting ≥12 weeks post-infection with those who did not. We examined relationships between serological markers and long COVID status and investigated sources of inter-study variability, such as severity of acute illness, long COVID symptoms assessed and target antigen(s). RESULTS: Of 8018 unique records, we identified 29 as being eligible for inclusion in synthesis. Definitions of long COVID varied. In studies that reported anti-nucleocapsid (N) IgG (n = 10 studies; n = 989 participants in aggregate), full or partial anti-Spike IgG (i.e. the whole trimer, S1 or S2 subgroups, or receptor binding domain, n = 19 studies; n = 2606 participants), or neutralizing response (n = 7 studies; n = 1123 participants), we did not find strong evidence to support any difference in serological markers between groups with and without persisting symptoms. However, most studies did not account for severity or level of care required during acute illness, and other potential confounders. CONCLUSIONS: Pooling of studies would enable more robust exploration of clinical and serological predictors among diverse populations. However, substantial inter-study variations hamper comparability. Standardized reporting practices would improve the quality, consistency and comprehension of study findings.

Results of the Stop the Spread Ottawa (SSO) cohort study: a Canadian urban-based prospective evaluation of antibody responses and neutralisation efficiency to SARS-CoV-2 infection and vaccination.

BACKGROUND: Predictors of COVID-19 vaccine immunogenicity and the influence of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require elucidation. METHODS: Stop the Spread Ottawa is a prospective cohort of individuals at-risk for or who have been infected with SARS-CoV-2, initially enrolled for 10 months beginning October 2020. This cohort was enriched for public-facing workers. This analysis focuses on safety and immunogenicity of the initial two doses of COVID-19 vaccine. RESULTS: Post-vaccination data with blood specimens were available for 930 participants. 22.8% were SARS-CoV2 infected prior to the first vaccine dose. Cohort characteristics include: median age 44 (IQR: 22-56), 66.6% women, 89.0% white, 83.2% employed. 38.1% reported two or more comorbidities and 30.8% reported immune compromising condition(s). Over 95% had detectable IgG levels against the spike and receptor binding domain (RBD) 3 months post second vaccine dose. By multivariable analysis, increasing age and high-level immune compromise predicted diminishing IgG spike and RBD titres at month 3 post second dose. IgG spike and RBD titres were higher immediately post vaccination in those with SARS-CoV-2 infection prior to first vaccination and spike titres were higher at 6 months in those with wider time intervals between dose 1 and 2. IgG spike and RBD titres and neutralisation were generally similar by sex, weight and whether receiving homogeneous or heterogeneous combinations of vaccines. Common symptoms post dose 1 vaccine included fatigue (64.7%), injection site pain (47.5%), headache (27.2%), fever/chills (26.2%) and body aches (25.3%). These symptoms were similar with subsequent doses. CONCLUSION: The initial two COVID-19 vaccine doses are safe, well-tolerated and highly immunogenic across a broad spectrum of vaccine recipients including those working in public facing environments.

Protocol for a living evidence synthesis on variants of concern and COVID-19 vaccine effectiveness.

BACKGROUND: It is evident that COVID-19 will remain a public health concern in the coming years, largely driven by variants of concern (VOC). It is critical to continuously monitor vaccine effectiveness as new variants emerge and new vaccines and/or boosters are developed. Systematic surveillance of the scientific evidence base is necessary to inform public health action and identify key uncertainties. Evidence syntheses may also be used to populate models to fill in research gaps and help to prepare for future public health crises. This protocol outlines the rationale and methods for a living evidence synthesis of the effectiveness of COVID-19 vaccines in reducing the morbidity and mortality associated with, and transmission of, VOC of SARS-CoV-2. METHODS: Living evidence syntheses of vaccine effectiveness will be carried out over one year for (1) a range of potential outcomes in the index individual associated with VOC (pathogenesis); and (2) transmission of VOC. The literature search will be conducted up to May 2023. Observational and database-linkage primary studies will be included, as well as RCTs. Information sources include electronic databases (MEDLINE; Embase; Cochrane, L*OVE; the CNKI and Wangfang platforms), pre-print servers (medRxiv, BiorXiv), and online repositories of grey literature. Title and abstract and full-text screening will be performed by two reviewers using a liberal accelerated method. Data extraction and risk of bias assessment will be completed by one reviewer with verification of the assessment by a second reviewer. Results from included studies will be pooled via random effects meta-analysis when appropriate, or otherwise summarized narratively. DISCUSSION: Evidence generated from our living evidence synthesis will be used to inform policy making, modelling, and prioritization of future research on the effectiveness of COVID-19 vaccines against VOC.

Expansion of non-invasive prenatal screening to the screening of 10 types of chromosomal anomalies: a cost-effectiveness analysis.

OBJECTIVES: To determine the cost-effectiveness of the addition of chromosomal anomalies detectable by non-invasive prenatal screening (NIPS), in a prenatal screening programme targeting common aneuploidies. DESIGN, SETTING AND PARTICIPANTS: A simulation study was conducted to study the addition of chromosomal anomalies detectable by NIPS (sex chromosome aneuploidies, 22q11.2 deletion syndrome, large deletion/duplication >7 Mb and rare autosomal trisomies) to five basic strategies currently aiming the common trisomies: three strategies currently offered by the public healthcare systems in Canada, whose first-tier test is performed with biochemical markers, and two programmes whose first-tier test consists of NIPS-based methods. OUTCOME MEASURES: The total number of cases of chromosomal anomalies detected and the costs related to the consumption of medical services. RESULTS: The most effective and the most cost-effective option in almost all prenatal screening strategies is the option that includes all targeted additional conditions. In the strategies where NIPS is used as first-tier testing, the cost per additional case detected by adding all possible additional anomalies to a programme that currently targets only common trisomies is $C25 710 (95% CI $C25 489 to $C25 934) for massively parallel shotgun sequencing and $C57 711 (95% CI $C57 141 to $C58 292) for targeted massively parallel sequencing, respectively. The acceptability curves show that at a willingness-to-pay of $C50 000 per one additional case detected, the expansion of NIPS-based methods for the detection of all possible additional conditions has a 90% probability of being cost-effective. CONCLUSION: From an economic perspective, in strategies that use NIPS as a first-tier screening test, expanding the programmes to detect any considered chromosomal anomalies other than the three common trisomies would be cost-effective. However, the potential expansion of prenatal screening programmes also requires consideration of societal issues, including ethical ones.

Establishment of a Public Mental Health Database for Research Purposes in the Ferrara Province: Development and Preliminary Evaluation Study.

Background: The immediate use of data exported from electronic health records (EHRs) for research is often limited by the necessity to transform data elements into an actual data set. Objective: This paper describes the methodology for establishing a data set that originated from an EHR registry that included clinical, health service, and sociodemographic information. Methods: The Extract, Transform, Load process was applied to raw data collected at the Integrated Department of Mental Health and Pathological Addictions in Ferrara, Italy, from 1925 to February 18, 2021, to build the new, anonymized Ferrara-Psychiatry (FEPSY) database. Information collected before the first EHR was implemented (ie, in 1991) was excluded. An unsupervised cluster analysis was performed to identify patient subgroups to support the proof of concept. Results: The FEPSY database included 3,861,432 records on 46,222 patients. Since 1991, each year, a median of 1404 (IQR 1117.5-1757.7) patients had newly accessed care, and a median of 7300 (IQR 6109.5-9397.5) patients were actively receiving care. Among 38,022 patients with a mental disorder, 2 clusters were identified; the first predominantly included male patients who were aged 25 to 34 years at first presentation and were living with their parents, and the second predominantly included female patients who were aged 35 to 44 years and were living with their own families. Conclusions: The process for building the FEPSY database proved to be robust and replicable with similar health care data, even when they were not originally conceived for research purposes. The FEPSY database will enable future in-depth analyses regarding the epidemiology and social determinants of mental disorders, access to mental health care, and resource utilization.

Exploring COVID-19 education to support vaccine confidence amongst the general adult population with special considerations for healthcare and long-term care staff: A scoping review.

Background: Despite the demonstrated efficacy of approved COVID-19 vaccines, high levels of hesitancy were observed in the first few months of the COVID-19 vaccines' rollout. Factors contributing to vaccine hesitancy are well-described in the literature. Among the various strategies for promoting vaccine confidence, educational interventions provide a foundationally and widely implemented set of approaches for supporting individuals in their vaccine decisions. However, the evidence around the measurable impact of various educational strategies to improve vaccine confidence is limited. We conducted a scoping review with the aim of exploring and characterizing educational interventions delivered during the pandemic to support COVID-19 vaccine confidence in adults. Methods: We developed a search strategy with a medical information scientist and searched five databases, including Ovid MEDLINE and Web of Science, as well as grey literature. We considered all study designs and reports. Interventions delivered to children or adolescents, interventions on non-COVID-19 vaccines, as well as national or mass vaccination campaigns without documented interaction(s) between facilitator(s) and a specific audience were excluded. Articles were independently screened by three reviewers. After screening 4602 titles and abstracts and 174 full-text articles across two rounds of searches, 22 articles met our inclusion criteria. Ten additional studies were identified through hand searching. Data from included studies were charted and results were described narratively. Results: We included 32 studies and synthesized their educational delivery structure, participants (i.e., facilitators and priority audience), and content. Formal, group-based presentations were the most common type of educational intervention in the included studies (75%). A third of studies (34%) used multiple strategies, with many formal group-based presentations being coupled with additional individual-based interventions (29%). Given the novelty of the COVID-19 vaccines and the unique current context, studies reported personalized conversations, question periods, and addressing misinformation as important components of the educational approaches reviewed. Conclusions: Various educational interventions were delivered during the COVID-19 pandemic, with many initiatives involving multifaceted interventions utilizing both formal and informal approaches that leveraged community (cultural, religious) partnerships when developing and facilitating COVID-19 vaccine education. Train-the-trainer approaches with recognized community members could be of value as trust and personal connections were identified as strong enablers throughout the review.

An in-depth qualitative study of health care providers' experiences of performance-based financing program as a nation-wide adopted policy in Cameroon: A principal-agent perspective.

OBJECTIVES: The study applies the principal-agent approach to explore providers' experiences before and after the introduction of performance-based financing (PBF) in Cameroon, challenges and facilitators in the implementation process, and mechanisms in place to ensure sustainability. METHODS: The study was an in-depth qualitative study whose goal was to provide multiple descriptions of experiences and insights from a principal-agent analysis perspective. Purposive sampling was used to identify the key characteristics of the participants relevant to the study. A snowballing technique was used to further identify eligible participants. Only healthcare providers who were exposed to the previous system and could reflect on and provide meaningful data that captured the everyday experiences before and after the implementation of PBF were included. Data were collected from three districts in the Southwest region of Cameroon from May 2021 to August 2021. Data were transcribed and analyzed using MaxQDA. RESULTS: A total of 17 interviews and 3 focus group discussions (24 participants) were conducted with healthcare providers and key stakeholders involved in PBF. The respondents described a range of changes that they had experienced since the introduction of PBF. Each of these changes was categorized as either positive or negative. Positive changes were framed into 14 dominant categories: motivation, negotiations, innovation, resource allocation, autonomy, decentralization, transparency, improved quality of care, separation of function, performance, equity considerations, opportunity to recruit, participation in decision-making, and improved access to and utilization of maternal health services. The main challenges (negative experiences) reported were framed into nine categories: management of change, retention issues, conflict of interest, poor understanding of the PBF concept, resistance to change, verification challenges, delays in payment of PBF incentives, data entry and documentation, and challenges in meeting the equity considerations of the poor and vulnerable. Despite the challenges, providers preferred the decentralized approach to the centralized system. CONCLUSION: PBF is a national strategy for achieving universal health coverage in Cameroon, and the experiences of providers provide a vital guide to refine national policy. The introduction of PBF has provided positive changes to providers' quality of care when compared to the previous system. Addressing the delays in PBF payments will help to overcome the challenges to implementation and provide opportunities for health facilities to be more efficient and improve their performance. Despite the limitations of delay in payment, PBF helps to align the incentives of the health workers (agent) with those of the Ministry of Health (principal).

Performance of different rapid antigen testing strategies for SARS-CoV-2: A living rapid review.

BACKGROUND: Rapid antigen detection tests (RADTs) for SARS-CoV-2 testing offer several advantages over molecular tests, but there is little evidence supporting an ideal testing algorithm. We aimed to examine the diagnostic test accuracy (DTA) and the effectiveness of different RADT SARS-CoV-2 testing strategies. METHODS: Following PRISMA DTA guidance, we carried out a living rapid review and meta-analysis. Searches were conducted in Ovid MEDLINE® ALL, Embase and Cochrane CENTRAL electronic databases until February 2022. Results were visualized using forest plots and included in random-effects univariate meta-analyses, where eligible. RESULTS: After screening 8010 records, 18 studies were included. Only one study provided data on incidence outcomes. Seventeen studies were DTA reports with direct comparisons of RADT strategies, using RT-PCR as the reference standard. Testing settings varied, corresponding to original SARS-CoV-2 or early variants. Strategies included differences in serial testing, the individual collecting swabs and swab sample locations. Overall, specificity remained high (>98%) across strategies. Although results were heterogeneous, the sensitivity for healthcare worker-collected samples was greater than for self-collected samples. Nasal samples had comparable sensitivity when compared to paired RADTs with nasopharyngeal samples, but sensitivity was much lower for saliva samples. The limited evidence for serial testing suggested higher sensitivity if RADTs were administered every 3 days compared to less frequent testing. CONCLUSIONS: Additional high-quality research is needed to confirm our findings; all studies were judged to be at risk of bias, with significant heterogeneity in sensitivity estimates. Evaluations of testing algorithms in real-world settings are recommended, especially for transmission and incidence outcomes.

A scoping review establishes need for consensus guidance on reporting health equity in observational studies.

OBJECTIVES: To evaluate the support from the available guidance on reporting of health equity in research for our candidate items and to identify additional items for the Strengthening Reporting of Observational studies in Epidemiology-Equity extension. STUDY DESIGN AND SETTING: We conducted a scoping review by searching Embase, MEDLINE, CINAHL, Cochrane Methodology Register, LILACS, and Caribbean Center on Health Sciences Information up to January 2022. We also searched reference lists and gray literature for additional resources. We included guidance and assessments (hereafter termed "resources") related to conduct and/or reporting for any type of health research with or about people experiencing health inequity. RESULTS: We included 34 resources, which supported one or more candidate items or contributed to new items about health equity reporting in observational research. Each candidate item was supported by a median of six (range: 1-15) resources. In addition, 12 resources suggested 13 new items, such as "report the background of investigators". CONCLUSION: Existing resources for reporting health equity in observational studies aligned with our interim checklist of candidate items. We also identified additional items that will be considered in the development of a consensus-based and evidence-based guideline for reporting health equity in observational studies.

A systematic review of the effect of performance-based financing interventions on out-of-pocket expenses to improve access to, and the utilization of, maternal health services across health sectors in sub-Saharan Africa.

Background: Performance-based financing (PBF) assumes that subsidizing user fees for maternal health services to reduce out-of-pocket expenses will expand coverage and reduce inequities in access to maternal health services. It is usually associated with process changes, and the idea that increasing a facility's resources from PBF interventions can improve the availability of equipment, drugs, and medical supplies at the facility, has an indirect effect on out-of-pocket expenses. Assessment of complex interventions such as PBF requires consideration of specific underlying assumption or theories of change. Such assessment will allow a better and broader understanding of the system's strengths and weaknesses, where the gaps lie, whether the theory of change is sound, and will inform policy design and implementation. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) checklist, we performed a systematic review and a critical appraisal of selected studies using the risk-of-bias criteria developed by the Cochrane Effective Practice and Organisation of Care. We used the Grading of Recommendation and Evaluation, Development and Assessment framework for assessing the overall strength of the evidence. Results: After the abstract screening (n = 9873), we deemed 302 as relevant for full-text screening and assessed 85 studies for review eligibility. Finally, we included 17 studies in the review. We could not conduct a meta-analysis, so we report a narrative synthesis. As an add-on to an existing payment mechanism, PBF may facilitate the removal of operational barriers to enhance utilization of certain maternal health services in some contexts, especially in public facilities. Conclusions: PBF strategies may potentially decrease out-of-pocket expenses for specific maternal health services, especially in settings that have already instituted some form of user fee exemption policies on maternal health services. The implementation of PBF can be considered a potential access instrument in reducing out-of-pocket expenses to stimulate demand for maternal services. However, the implementation approaches employed will determine utilization, taking into consideration existing equitable and inequitable access characteristics which vary by context. Registration: PROSPERO CRD42020222893.

Paper I: Heterogeneous use of registry data for participant identification and primary outcome ascertainment is found in registry-based randomized controlled trials: A scoping review.

OBJECTIVES: Registry-based randomized controlled trials (RRCTs) have potential to address limitations of traditional clinical trials. To describe their current use, information on planned and published RRCTs was identified and synthesized. STUDY DESIGN AND SETTING: A scoping review of published RRCT protocols and reports was conducted. Articles published between 2010 and 2021 identified from electronic database searching, a recent review of RRCTs, and targeted searching for recent RRCT protocols (2018-2021) were screened. Data on trial data sources, types of primary outcomes, and how these primary outcomes were described, selected, and reported were extracted. RESULTS: Ninety RRCT articles (77 reports; 13 protocols) were included. Forty nine (54%) used or planned to rely on registry data for their trial, 26 (29%) used both registry and additional data, and 15 (17%) used the registry solely for recruitment. Primary outcomes were routinely collected from the registry for 66 articles (73%). Only 28 articles (31%) described any methods to promote outcome data quality during or after data collection. Core outcome sets were not used in any of the trials. CONCLUSION: With improvements in registry design, outcome selection, measurement, and reporting, future RRCTs may deliver on promises of efficient, high-quality trials that address clinically relevant questions.

Paper II: thematic framework analysis of registry-based randomized controlled trials provided insights for designing trial ready registries.

OBJECTIVES: Registry-based randomized controlled trials (RRCTs) are increasingly used, promising to address challenges associated with traditional randomized controlled trials. We identified strengths and limitations reported in planned and completed RRCTs to inform future RRCTs. STUDY DESIGN AND SETTING: We conducted an environmental scan of literature discussing conceptual or methodological strengths and limitations of using registries for trial design and conduct (n = 12), followed by an analysis of RRCT protocols (n = 13) and reports (n = 77) identified from a scoping review. Using framework analysis, we developed and refined a conceptual framework of RRCT-specific strengths and limitations. We mapped and interpreted strengths and limitations discussed by authors of RRCT articles using framework codes and quantified the frequencies at which these were mentioned. RESULTS: Our conceptual framework identified six main RRCT strengths and four main RRCT limitations. Considering implications for RRCT conduct and design, we formulated ten recommendations for registry designers, administrators, and trialists planning future RRCTs. CONCLUSION: Consideration and application of empirically underpinned recommendations for future registry design and trial conduct may help trialists utilize registries and RRCTs to their full potential.

Health equity considerations in guideline development: a rapid scoping review.

BACKGROUND: Systematic guidance for considering health equity in guidelines is lacking. This scoping review aims to synthesize current best practices for integrating health equity into guideline development and the benefits or drawbacks of these practices. METHODS: We searched Ovid MEDLINE ALL and Embase Classic+Embase on the Ovid platform, CINAHL on EBSCO, and Web of Science (Core Collection) from 2010 to 2022. We searched grey literature from 2015 to 2022, using the Canadian Agency for Drugs and Technologies in Health Grey Matters checklist and searches of potentially relevant websites. Articles were screened independently by 1 reviewer. Proposed best practices, advantages and disadvantages, and tools were extracted independently by 1 reviewer and qualitatively synthesized based on the relevant steps of a comprehensive checklist covering the stages of guideline development. RESULTS: We included 26 articles that proposed best practices for incorporating health equity within the guideline development process. These practices were organized under different stages of the development process, including guideline planning, evidence review, guideline development and dissemination. Included studies provided best practices from guideline producers, articles discussing health equity in current guidelines, articles addressing strategies to increase equity in the guideline implementation process, and literature reviews of promising health equity practices. INTERPRETATION: Our scoping review identified best practices to incorporate health equity considerations at each phase of guideline development. Identified practices may be used to inform equity-promoting strategies with the guideline development process; however, guideline producers should carefully consider the advantages and disadvantages of best practices when integrating health equity.