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Epidemiology, aetiology, interventions and genomics in children with arthrogryposis multiplex congenita: protocol for a multisite registry

Por: Dahan-Oliel · N. · van Bosse · H. · Darsaklis · V. B. · Rauch · F. · Bedard · T. · Bardai · G. · James · M. · Raney · E. · Freese · K. · Hyer · L. · Altiok · A. · Pellett · J. · Giampietro · P. · Hall · J. · Hamdy · R. C.
Introduction

Arthrogryposis multiplex congenita (AMC) is an umbrella term including hundreds of conditions with the common clinical manifestation of multiple congenital contractures. AMC affects 1 in 3000 live births and is caused by lack of movement in utero. To understand the long-term needs of individuals diagnosed with a rare condition, it is essential to know the prevalence, aetiology and functional outcomes in a large sample. The development and implementation of a multicentre registry is critical to gather this data. This registry aims to improve health through genetic and outcomes research, and ultimately identify new therapeutic targets and diagnostics for treating children with AMC.

Methods and analysis

Participants for the AMC registry will be recruited from seven orthopaedic hospitals in North America. Enrollment occurs in two phases; Part 1 focuses on epidemiology, aetiology and interventions. For this part, retrospective and cross-sectional data will be collected using a combination of patient-reported outcomes and clinical measures. Part 2 focuses on core subset of the study team, including a geneticist and bioinformatician, identifying causative genes and linking the phenotype to genotype via whole genome sequencing to identify genetic variants and correlating these findings with pedigree, photographs and clinical information. Descriptive analyses on the sample of 400 participants and logistic regression models to evaluate relationships between outcomes will be conducted.

Ethics and dissemination

Ethical approval has been granted from corresponding governing bodies in North America. Dissemination of findings will occur via traditional platforms (conferences, manuscripts) for the scientific community. Other modalities will be employed to ensure that all stakeholders, including youth, families and patient support groups, may be provided with findings derived from the registry. Ensuring the findings are circulated to a maximum amount of interested parties will ensure that the registry can continue to serve as a platform for hypothesis-driven research and further advancement for AMC.

Use of equity-informed social media COVID-19 risk communication tools: a scoping review protocol

Por: Kothari · A. · Peter · N. · Donelle · L.
Introduction

Health agencies and community organisations play a crucial role in disseminating information to the public about COVID-19 risks and events, providing instructions on how to change behaviour to mitigate those risks, motivating compliance with health directives and addressing false information. Social media platforms are a critical tool in risk communication, providing a medium for rapid transmission of messages as well as providing the opportunity for engagement and immediate feedback. Access to health information, services and support are especially important for marginalised and underserved (‘equity-deserving’) populations who are disproportionately affected by COVID-19. This scoping review aims to review the breadth and depth of the academic and grey literature on equity-informed social media risk communication tools to provide guidance on promising practices and principles for reaching equity-deserving populations through social media.

Methods and analysis

Arksey and O’Malley’s (2005) framework guided the identification of the research question; identification and selection of relevant studies from electronic databases and hand-searches of discipline-specific journals; extraction and charting of the data; and collating and reporting of findings. The results of the screening process will be reported using the Preferred Reporting Items for Systematic Review and Meta-Analysis-Scoping Review guidelines.

Findings

We will identify reported facilitators and barriers to the development of risk communications that target equity-deserving communities. We will also identify recommendations for equity-informed risk communication for COVID-19.

Ethics and dissemination

This study does not require ethics approval. We intend to disseminate the results through publication in an open-access peer-reviewed journal, conference presentations, lay summaries (eg, checklists) for health organisations and messages to be shared through social media.

Access to HIV healthcare services by farm workers in sub-Saharan Africa (SSA): a systematic review protocol

Por: Mlangeni · N. · Adetokunboh · O. · Lembani · M. · Malotle · M. · Nyasulu · P.
Introduction

Sub-Saharan Africa (SSA) region harbours the highest burden of HIV infections in the world. Agricultural work has been reported as one of the occupations with a high prevalence of HIV. Farm workers generally have poor access to health services, which prevents them from receiving proper HIV prevention and care. Furthermore, poor policies and policy implementation, and lack of workplace programmes increases farm workers’ vulnerability to HIV infection. Thus, the aim of this study is to conduct a systematic review to assess HIV prevention and treatment services and national policies governing access to healthcare services by farm workers in SSA.

Methods and analysis

Our systematic review will include studies published from January 1990 to December 2021 within SSA countries. We will use a sensitive search strategy for electronic bibliographic databases and grey literature sources. Databases will include PubMed, CINAHL, Cochrane library, African Index Medicus and Scopus. The main outcomes to be reported will be HIV policy for farmworkers, availability of HIV prevention service(s), availability of treatment and support to farmworkers who are living with HIV, presence of referral structures for farmworkers through the health system and follow-up services for farmworkers who are on antiretroviral therapy. We will synthesise the main characteristics of included studies and use summary measures to describe study characteristics. In a situation where data are not sufficiently homogeneous to perform a quantitative synthesis, we will conduct a narrative synthesis. We will explore themes and relationships between included studies for qualitative data.

Ethics and dissemination

The study will use publicly available data and ethics exemption has been obtained from Human Research Ethics Committees, Faculty of Medicine & Health Sciences, Stellenbosch University. The results of this study will be disseminated through peer-reviewed journals, conference presentations and seminars.

PROSPERO registration number

CRD42021277528.

Studies of prevalence: how a basic epidemiology concept has gained recognition in the COVID-19 pandemic

Por: Buitrago-Garcia · D. · Salanti · G. · Low · N.
Background

Prevalence measures the occurrence of any health condition, exposure or other factors related to health. The experience of COVID-19, a new disease caused by SARS-CoV-2, has highlighted the importance of prevalence studies, for which issues of reporting and methodology have traditionally been neglected.

Objective

This communication highlights key issues about risks of bias in the design and conduct of prevalence studies and in reporting them, using examples about SARS-CoV-2 and COVID-19.

Summary

The two main domains of bias in prevalence studies are those related to the study population (selection bias) and the condition or risk factor being assessed (information bias). Sources of selection bias should be considered both at the time of the invitation to take part in a study and when assessing who participates and provides valid data (respondents and non-respondents). Information bias appears when there are systematic errors affecting the accuracy and reproducibility of the measurement of the condition or risk factor. Types of information bias include misclassification, observer and recall bias. When reporting prevalence studies, clear descriptions of the target population, study population, study setting and context, and clear definitions of the condition or risk factor and its measurement are essential. Without clear reporting, the risks of bias cannot be assessed properly. Bias in the findings of prevalence studies can, however, impact decision-making and the spread of disease. The concepts discussed here can be applied to the assessment of prevalence for many other conditions.

Conclusions

Efforts to strengthen methodological research and improve assessment of the risk of bias and the quality of reporting of studies of prevalence in all fields of research should continue beyond this pandemic.

Transitioning care in youth-onset type 1 and type 2 diabetes: a scoping review protocol using the socio-ecological model framework

Por: Ude · A. O. · De Baca · T. C. · Dixon · S. A. · Arboine · S.-A. · Terry · N. L. · Chung · S. T.
Introduction

The transition from paediatric to adult diabetes care in youth-onset diabetes (type 1 diabetes mellitus, Y-T1DM and type 2 diabetes mellitus, Y-T2DM) is associated with worsening glycaemic control, missed clinical visits, decreased medication adherence and the emergence of cardiometabolic complications. The socio-ecological challenges that influence transitioning to adult diabetes care may be distinct between Y-T1DM and Y-T2DM. The goal of this scoping review is to map the state of the literature on transitioning care in Y-T2DM compared with Y-T1DM and to identify the main sources and types of evidence available. The objectives are : (1) to identify the factors within the socio-ecological framework (individual, relationship, community, societal) associated with transitioning to adult care in Y-T2DM compared with Y- T1DM, and (2) to identify knowledge gaps related to transitioning to adult care.

Methods

The scoping review protocol and reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews guidelines. A systematic search of scientific databases (PubMed, Embase, Cumulative Index to Nursing and Allied Health, Scopus and APA PsycNet will be undertaken for articles between 1 January 1990 and 30 September 2022. Study designs will include peer-reviewed experimental and quasi-experimental published studies without language or country-specific restrictions. We will exclude articles on other diabetes subtypes and will exclude non-peer reviewed articles such as opinion papers, anecdotal reports or supplementary commentaries.

Analysis

References will be collated, sorted and extracted using Covidence. Factors associated with transition from paediatric to adult diabetes care in Y-T1DM and Y-T2DM will be identified using the socio-ecological framework and results will be presented in narrative format, tables, and summary graphs.

Ethics and dissemination

Ethical approval will not be applicable for this review.

Trial registration number

https://osf.io/k2pwc.

Calibrating a network meta-analysis of diabetes trials of sodium glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor analogues and dipeptidyl peptidase-4 inhibitors to a representative routine population: a systematic review protocol

Por: Butterly · E. · Wei · L. · Adler · A. I. · Almazam · S. A. M. · Alsallumi · K. · Blackbourn · L. A. K. · Dias · S. · Hanlon · P. · Hughes · K. · Lewsey · J. · Lindsay · R. · McGurnaghan · S. · Petrie · J. · Phillippo · D. · Sattar · N. · Tomlinson · L. A. · Welton · N. · Wild · S. · McAlli
Introduction

Participants in randomised controlled trials (trials) are generally younger and healthier than many individuals encountered in clinical practice. Consequently, the applicability of trial findings is often uncertain. To address this, results from trials can be calibrated to more representative data sources. In a network meta-analysis, using a novel approach which allows the inclusion of trials whether or not individual-level participant data (IPD) is available, we will calibrate trials for three drug classes (sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) receptor analogues and dipeptidyl peptidase-4 (DPP4) inhibitors) to the Scottish diabetes register.

Methods and analysis

Medline and EMBASE databases, the US clinical trials registry (clinicaltrials.gov) and the Chinese Clinical Trial Registry (chictr.org.cn) will be searched from 1 January 2002. Two independent reviewers will apply eligibility criteria to identify trials for inclusion. Included trials will be phase 3 or 4 trials of SGLT2 inhibitors, GLP1 receptor analogues or DPP4 inhibitors, with placebo or active comparators, in participants with type 2 diabetes, with at least one of glycaemic control, change in body weight or major adverse cardiovascular event as outcomes. Unregistered trials will be excluded.

We have identified a target population from the population-based Scottish diabetes register. The chosen cohort comprises people in Scotland with type 2 diabetes who either (1) require further treatment due to poor glycaemic control where any of the three drug classes may be suitable, or (2) who have adequate glycaemic control but are already on one of the three drug classes of interest or insulin.

Ethics and dissemination

Ethical approval for IPD use was obtained from the University of Glasgow MVLS College Ethics Committee (Project: 200160070). The Scottish diabetes register has approval from the Scottish A Research Ethics Committee (11/AL/0225) and operates with Public Benefit and Privacy Panel for Health and Social Care approval (1617-0147).

PROSPERO registration number

CRD42020184174.

Disruptions to the procurement of medical abortion medicines during COVID-19: a scoping review

Por: Cassinath · N. · Titulaer · P. · Läser · L. · Lavelanet · A. · Ahsan · S. · Kwankam Toedtli · F. · Mawa · S. · Rehnstrom Loi · U.
Objectives

This scoping review aimed to systematically search, retrieve and map the extent and characteristics of available literature on the evidenced disruptions to medical abortion (MA) medicine procurement caused by the COVID-19 outbreak.

Design

Scoping review using Arksey and O’Malley’s methodology and Levac et al’s methodological enhancement with adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews.

Data sources

PubMed, Embase, PMC, Science Direct, the Cochrane Library and Google Scholar were searched from January 2020 to April 2022.

Eligibility criteria

We included articles in English that: (1) contained information on MA medicines; (2) included descriptions of procurement disruptions, including those with examples, characteristics and/or statistics; (3) documented events during the COVID-19 pandemic; and (4) presented primary data.

Data extraction and synthesis

Two reviewers independently screened search results, performed a full-text review of preliminarily included articles and completed data extraction in a standard Excel spreadsheet. Extracted data from was compared for validation and synthesised qualitatively.

Results

The two articles included are unpublished grey literature demonstrating evidence of short-lived disruptions in sexual and reproductive health commodity procurement, including MA medicines, in sub-Saharan Africa during the early months of the pandemic. Findings from the two included grey literature articles show that in sub-Saharan contexts, emergency preparedness, stockpiling, adaptations and flexibility of key actors, including donors, alleviated COVID-19 disruptions allowing for resumption of services within weeks.

Conclusion

There is a need for increased empirical evidence of MA procurement challenges to understand which barriers to MA procurement may persist and impact continuity of supply while others can fuel resilience and preparedness efforts at the country and subregional levels. The lack of evidence from social marketing organisations and their networks is a significant gap as these actors constitute a vital artery in the distribution of MA commodities in low-income and middle-income countries.

Cohort profile: the Swedish Maternal Microbiome project (SweMaMi) - assessing the dynamic associations between the microbiome and maternal and neonatal adverse events

Por: Fransson · E. · Gudnadottir · U. · Hugerth · L. W. · Itzel · E. W. · Hamsten · M. · Boulund · F. · Pennhag · A. · Du · J. · Schuppe-Koistinen · I. · Brusselaers · N. · Engstrand · L.
Purpose

The Swedish Maternal Microbiome (SweMaMi) project was initiated to better understand the dynamics of the microbiome in pregnancy, with longitudinal microbiome sampling, shotgun metagenomics, extensive questionnaires and health registry linkage.

Participants

Pregnant women were recruited before the 20th gestational week during 2017–2021 in Sweden. In total, 5439 pregnancies (5193 unique women) were included. For 3973 pregnancies (73%), samples were provided at baseline, and for 3141 (58%) at all three timepoints (second and third trimester and postpartum). In total, 38 591 maternal microbiome samples (vaginal, faecal and saliva) and 3109 infant faecal samples were collected. Questionnaires were used to collect information on general, reproductive and mental health, diet and lifestyle, complemented by linkage to the nationwide health registries, also used to follow up the health of the offspring (up to age 10).

Findings to date

The cohort is fairly representative for the total Swedish pregnant population (data from 2019), with 41% first-time mothers. Women with university level education, born in Sweden, with normal body mass index, not using tobacco-products and aged 30–34 years were slightly over-represented.

Future plans

The sample and data collection were finalised in November 2021. The next steps are the characterisation of the microbial DNA and linkage to the health and demographic information from the questionnaires and registries. The role of the microbiome on maternal and neonatal outcomes and early-childhood diseases will be explored (including preterm birth, miscarriage) and the role and interaction of other risk factors and confounders (including endometriosis, polycystic ovarian syndrome, diet, drug use). This is currently among the largest pregnancy cohorts in the world with longitudinal design and detailed and standardised microbiome sampling enabling follow-up of both mothers and children. The findings are expected to contribute greatly to the field of reproductive health focusing on pregnancy and neonatal outcomes.

Effect of the COVID-19 pandemic on maternal healthcare indices in Southern Iran: an interrupted time series analysis

Por: Yadollahi · P. · Zangene · N. · Heiran · A. · Sharafi · M. · Heiran · K. N. · Hesami · E. · Saffari · M. · Azima · S. · Mirahmadizadeh · A.
Objectives

Epidemics are anticipated to influence the coverage of health services. We assessed the impact of the COVID-19 pandemic on maternal healthcare indices and care providers’ performance.

Setting

1801 maternal healthcare centres under the auspices of Shiraz University of Medical Sciences, Shiraz, Southern Iran.

Participants

Approximately 63 000 pregnant women.

Primary and secondary outcome measures

In this prospective ecological study, interrupted time series analysis was used to model and compare the trend of maternal healthcare indices before and after the COVID-19 pandemic announcement.

Results

The results showed a significant drop in count of preconception healthcare visits, first routine laboratory tests, first trimester prenatal care, first trimester sonography, prenatal screening for birth defects at weeks 11–13, prenatal care visits at weeks 16–20, second routine laboratory tests, second trimester sonography, prenatal care visits at weeks 24–30, prenatal care visits at weeks 31–34, postpartum care visits at days 10–15 and postpartum care visits at days 30–42 with the start of the COVID-19 pandemic (–50% (95% CI –48.68% to –51.36%), –19.67% (95% CI –22.12% to –17.15%), –25.88% (95% CI –28.46% to –23.21%), –23.84% (95% CI –26.26% to –21.34%), –20.16% (95% CI –23.01% to –17.20%), –18.53% (95% CI –21.25% to –15.71%), –28.63% (95% CI –31.03% to –26.14%), –27.48% (95% CI –30.07% to –24.79%), –31.08% (95% CI –33.43% to –28.61%), –31.84% (95% CI –34.35% to –29.23%), 32.55% (95% CI –35.12% to –29.89%) and –39.28% (95% CI –41.59% to –36.88%), respectively). Nevertheless, the trend in coverage of these services showed recovery in the subsequent months (8.36%, 10.55%, 5.74%, 8.01%, 4.40%, 5.06%, 11.20%, 7.58%, 7.38%, 7.80%, 9.59% and 9.61% per month, respectively).

Conclusions

Using ecological data during the COVID-19 pandemic era, we observed a ‘level change and slope change’ as the major pattern of interruption of maternal healthcare coverage, indicating a possible indirect effect rather than a causative relationship. Such relative predictability might assist with future pandemic planning.

Acceptability and feasibility of an online information linker service for caregivers who have a child with genetic epilepsy: a mixed-method pilot study protocol

Por: Robertson · E. G. · Kelada · L. · Best · S. · Goranitis · I. · Grainger · N. · Le Marne · F. · Pierce · K. · Nevin · S. M. · Macintosh · R. · Beavis · E. · Sachdev · R. · Bye · A. · Palmer · E. E.
Introduction

Developmental and epileptic encephalopathies (DEEs) are rare epilepsy conditions that collectively impact 1 in 2000 children. They are highly genetically heterogeneous, resulting in significant barriers to accurate and adequate information for caregivers. This can lead to increased distress and dissatisfaction with the healthcare system. To address this gap, we developed ‘GenE Compass’ to provide caregivers with the highest-quality possible, understandable and relevant information in response to specific questions about their child’s DEE. Using a mixed-method design, we will now pilot GenE Compass to evaluate the acceptability to caregivers and clinicians, feasibility and impact to caregivers.

Methods and analysis

We will recruit 88 caregivers (estimated final sample of 50 at follow-up) who have a child under 18 years of age with a suspected or confirmed DEE diagnosis. Following consent and a baseline questionnaire (questionnaire 1 (Q1)), participants will be able to submit questions to GenE Compass over a 3-month period. After 3 months, participants will complete a follow-up questionnaire (Q2) and an optional telephone interview to answer the research questions. Primary outcomes are acceptability of GenE Compass and feasibility of delivering the intervention (eg, cost of the intervention, number of questions submitted and time taken to respond to questions). Secondary outcomes include the impact of GenE Compass on caregivers’ quality of life, information searching behaviours, perceptions of their child’s illness and activation.

Ethics and discussion

The study protocol (V.2, dated 16 September 2021) has been approved by the Sydney Children’s Hospitals Network Human Research Ethics Committee (ETH11277). The results will be disseminated in peer-reviewed journals and at scientific conferences. A lay summary will be disseminated to all participants.

Trial registration number

ACTRN12621001544864.

Challenges and ways of coping of parturient women with chronic hepatitis B in Ghana during COVID-19 pandemic: a qualitative inquiry

Por: Lanyo · T. N. · Ani-Amponsah · M. · Adjei · C. A.
Objective

To explore the psychosocial concerns and ways of coping of pregnant women with chronic hepatitis B infection in Ghana.

Setting

Participants were selected from public health facilities in the Tema Metropolis.

Design

Exploratory descriptive qualitative design was employed.

Participants

Fourteen pregnant women were purposively selected to participate in face-to-face interviews. The data were analysed using the content analysis procedure.

Results

The participants' psychosocial concerns and coping strategies were diverse. A significant number of the participants were concerned about the impact their hepatitis B seropositivity would have on their relationships, finances, and general well-being. Specifically, they feared that their social network, especially their spouses, would perceive them as having led a promiscuous lifestyle in the past to acquire hepatitis B infection. Also, fear of transmitting the infection to their infants and the effects of the infection on their infants later in life were identified as major concerns by nearly all participants. The participants further reported feelings of distress and diminished self-esteem. These psychosocial afflictions reported were attributed to lack of pre-test counselling during the antenatal care period. However, the participants coped using different strategies, including avoidance/denial, spirituality, and alternative treatment use.

Conclusion

To achieve optimal psychological and social well-being of pregnant women with chronic hepatitis B, it is important that their unique challenges are considered in their care and treatment cascade. Explicitly, protocols for supportive care addressing the specific needs of pregnant women with chronic hepatitis B should be implemented in the study setting

Canadian infants presenting with Brief Resolved Unexplained Events (BRUEs) and validation of clinical prediction rules for risk stratification: a protocol for a multicentre, retrospective cohort study

Por: Nama · N. · Hosseini · P. · Lee · Z. · Picco · K. · Bone · J. N. · Foulds · J. L. · Gagnon · J. A. · Sehgal · A. · Quet · J. · Drouin · O. · Luu · T. M. · Vomiero · G. · Kanani · R. · Holland · J. · Goldman · R. D. · Kang · K. T. · Mahant · S. · Jin · F. · Tieder · J. S. · Gill · P. J. · the C
Introduction

Brief Resolved Unexplained Events (BRUEs) are a common presentation among infants. While most of these events are benign and self-limited, guidelines published by the American Academy of Pediatrics inaccurately identify many patients as higher-risk of a serious underlying aetiology (positive predictive value 5%). Recently, new clinical prediction rules have been derived to more accurately stratify patients. This data were however geographically limited to the USA, with no large studies to date assessing the BRUE population in a different healthcare setting. The study’s aim is to describe the clinical management and outcomes of infants presenting to Canadian hospitals with BRUEs and to externally validate the BRUE clinical prediction rules in identified cases.

Methods and analysis

This is a multicentre retrospective study, conducted within the Canadian Paediatric Inpatient Research Network (PIRN). Infants (

The primary outcome will be the presence of a serious underlying illness. Secondary outcomes will include BRUE recurrence and length of hospital stay. We will describe the rates of hospital admissions and whether hospitalisation was associated with an earlier diagnosis or treatment. Variation across Canadian hospitals will be assessed using intraclass correlation coefficient. To validate the newly developed clinical prediction rule, measures of goodness of fit will be evaluated. For this validation, a sample size of 1182 is required to provide a power of 80% to detect patients with a serious underlying illness with a significance level of 5%.

Ethics and dissemination

Ethics approval has been granted by the UBC Children’s and Women’s Research Board (H21-02357). The results of this study will be disseminated as peer-reviewed manuscripts and presentations at national and international conferences.

Safety, tolerability, pharmacokinetics and preliminary antitumour activity of an antisense oligonucleotide targeting STAT3 (danvatirsen) as monotherapy and in combination with durvalumab in Japanese patients with advanced solid malignancies: a phase 1 stu

Por: Nishina · T. · Fujita · T. · Yoshizuka · N. · Sugibayashi · K. · Murayama · K. · Kuboki · Y.
Objectives

We assessed the safety, tolerability, pharmacokinetics, preliminary antitumour activity and pharmacodynamics of danvatirsen, an antisense oligonucleotide targeting signal transducer and activator of transcription 3 (STAT3), monotherapy and danvatirsen plus durvalumab, an antiprogrammed cell death ligand 1 monoclonal antibody, in patients with advanced solid malignancies.

Design

Phase 1, open-label study with two cohorts.

Setting

Two centres in Japan.

Participants

Japanese individuals aged ≥20 years, with histologically confirmed solid malignancies, except for hepatocellular carcinoma, refractory to standard therapy.

Interventions

In cohort 1, patients received danvatirsen monotherapy; in cohort 2, patients received danvatirsen plus durvalumab combination therapy.

Primary and secondary outcome measures

The primary endpoint was safety and tolerability based on adverse events (AEs). Secondary endpoints were pharmacokinetics, immunogenicity, antitumour activity and pharmacodynamics.

Results

Eleven patients were assigned to treatment and included in the analysis. Danvatirsen dose reductions were only required in cohort 2 for hepatic function abnormal (alanine aminotransferase (ALT)/ aspartate aminotransferase (AST)/gamma-glutamyl transferase (GT) increased), neutrophil count decreased and platelet count decreased. One patient experienced grade 3 ALT/AST increased and new appearance of eosinophilia as a dose-limiting toxicity. AEs were reported in 90.9% (10/11) patients. Commonly reported AEs causally related to the danvatirsen were platelet count decreased (60% (3/5)) and ALT/AST/GT increased (50% (3/6)) in cohorts 1 and 2, respectively; none was causally related to durvalumab. One serious AE occurred in cohort 1 (pancreatitis; unrelated to study treatment). One case of ALT/AST/GT increased occurred in cohort 2, leading to discontinuation. No AEs led to death. Danvatirsen did not accumulate in plasma after multiple dosing. In cohort 2, three patients had disease control at 12 weeks and one had unconfirmed partial response. STAT3 expression tended to decrease regardless of monotherapy or combination therapy.

Conclusions

Danvatirsen was well tolerated by Japanese patients with advanced solid tumours as monotherapy and combined with durvalumab. No new safety signals arose.

Trial registration number

NCT03394144; ClinicalTrials.gov.

Cohort profile: the ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS)

Por: LeWinn · K. Z. · Karr · C. J. · Hazlehurst · M. · Carroll · K. · Loftus · C. · Nguyen · R. · Barrett · E. · Swan · S. H. · Szpiro · A. A. · Paquette · A. · Moore · P. · Spalt · E. · Younglove · L. · Sullivan · A. · Colburn · T. · Byington · N. · Sims Taylor · L. · Moe · S. · Wang · S. · Cord
Purpose

Exposures early in life, beginning in utero, have long-term impacts on mental and physical health. The ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS) was established to examine the independent and combined impact of pregnancy and childhood chemical exposures and psychosocial stressors on child neurodevelopment and airway health, as well as the placental mechanisms underlying these associations.

Participants

The ECHO-PATHWAYS consortium harmonises extant data from 2684 mother–child dyads in three pregnancy cohort studies (CANDLE [Conditions Affecting Neurocognitive Development and Learning in Early Childhood], TIDES [The Infant Development and Environment Study] and GAPPS [Global Alliance to Prevent Prematurity and Stillbirth]) and collects prospective data under a unified protocol. Study participants are socioeconomically diverse and include a large proportion of Black families (38% Black and 51% White), often under-represented in research. Children are currently 5–15 years old. New data collection includes multimodal assessments of primary outcomes (airway health and neurodevelopment) and exposures (air pollution, phthalates and psychosocial stress) as well as rich covariate characterisation. ECHO-PATHWAYS is compiling extant and new biospecimens in a central biorepository and generating the largest placental transcriptomics data set to date (N=1083).

Findings to date

Early analyses demonstrate adverse associations of prenatal exposure to air pollution, phthalates and maternal stress with early childhood airway outcomes and neurodevelopment. Placental transcriptomics work suggests that phthalate exposure alters placental gene expression, pointing to mechanistic pathways for the developmental toxicity of phthalates. We also observe associations between prenatal maternal stress and placental corticotropin releasing hormone, a marker of hormonal activation during pregnancy relevant for child health. Other publications describe novel methods for examining exposure mixtures and the development of a national spatiotemporal model of ambient outdoor air pollution.

Future plans

The first wave of data from the unified protocol (child age 8–9) is nearly complete. Future work will leverage these data to examine the combined impact of early life social and chemical exposures on middle childhood health outcomes and underlying placental mechanisms.

Experience and response to a randomised controlled trial of extended-release injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone for opioid use disorder: protocol for a mixed-methods evaluation

Por: Lowry · N. · Cowden · F. · Day · E. · Gilvarry · E. · Johnstone · S. · Murray · R. · Kelleher · M. · Mitcheson · L. · Marsden · J.
Introduction

Opioid use disorder (OUD) is a debilitating and persistent disorder. The standard-of-care treatment is daily maintenance dosing of sublingual buprenorphine (BUP-SL) or oral methadone (MET). Monthly, extended-release, subcutaneous injectable buprenorphine (BUP-XR) has been developed to enhance treatment effectiveness. This study aims to investigate the experiences of participants who have been offered BUP-XR (evaluation 1), health-related quality-of-life among participants who have opted to receive BUP-XR longer term (evaluation 2) and the experiences of participants allocated to receive BUP-XR or BUP-SL or MET with the offer of adjunctive personalised psychosocial intervention (evaluation 3).

Methods and analysis

Three qualitative–quantitative (mixed-methods) evaluations embedded in a five-centre, head-to-head, randomised controlled trial of BUP-XR versus BUP-SL and MET in the UK. Evaluation 1 is a four-centre interview anchored on an OUD-related topic guide and conducted after the 24-week trial endpoint. Evaluation 2 is a two-centre interview anchored on medications for opioid use disorder-specific quality-of-life topic guide conducted among participants after 12–24 months. Evaluation 3: single-centre interview after the 24-week trial endpoint. All evaluations include selected trial clinical measures, with evaluation 2 incorporating additional questionnaires. Target participant recruitment for evaluations 1 and 2 is 15 participants per centre (n=60 and n=30, respectively). Recruitment for evaluation 3 is 15 participants per treatment arm (n=30). Each evaluation will be underpinned by theory, drawing on constructs from the behavioural model for health service use or the health-related quality-of-life model. Qualitative data analysis will be by iterative categorisation.

Ethics and dissemination

Study protocol, consent materials and questionnaires were approved by the London-Brighton and Sussex research ethics committee (reference: 19/LO/0483) and the Health Research Authority (IRAS project number 255522). Participants will be provided with information sheets and informed written consent will be obtained for each evaluation. Study findings will be disseminated through peer-reviewed scientific journals.

Trial registration number

2018-004460-63.

Protocol for a multicentre prospective observational study of families with full-term infants on postnatal wards and in the community to capture feeding practices across the first year of life: the Mother Infant Lactation Questionnaire (MILQ) study

Por: Gould · J. F. · Yelland · L. N. · Gibson · R. A. · McPhee · A. J. · Varghese · J. · Grivell · R. · Makrides · M.
Introduction

Breastmilk is considered the gold standard for infant nutrition. Breast feeding is recommended as the sole source of nutrition between birth until around 6 months of age and should be continued beyond this age as complementary foods are introduced. While breast feeding initiation is generally high in developed countries, continuation of breast feeding appears to drop rapidly. This is a prospective observational study of life that aims to characterise a current picture of infant feeding practices across the first year, and motivations for feeding practices, and to identify barriers and enablers for breast feeding.

Methods and analysis

Caregivers with newborn singleton infants of normal birth weight are approached on the postnatal units of three hospitals in South Australia, or through targeted online advertising campaigns promoting the study. Caregivers are asked to complete surveys when their infant reaches 3, 5 and 7 weeks’, and at 3, 4, 5, 6, 9 and 12 months of age. Initially, baseline characteristics, intentions and preferences for infant milk feeds, as well as reasons for preferences are captured. Latter surveys query how infants are being fed, difficulties or barriers to breast feeding, as well as any enablers (if breast feeding). Once infants reach 5 months of age, surveys capture complementary feeding. A large opportunistic sample from the Adelaide community with a minimum of 1000 mother–infant pairs will be enrolled. The data will be analysed descriptively and using regression models.

Ethics and dissemination

Women’s and Children’s Health Network Human Research Ethics Committee reviewed and approved the study (approval no HREC/19/WCHN/140, approval date: 22 November 2019). Study results will be disseminated through academic meetings, peer-reviewed journals, in-services for postnatal healthcare services, results letters for participants and social media.

Trial registration number

ACTRN12620000529943.

Characterising methamphetamine use to inform health and social policies in Manitoba, Canada: a protocol for a retrospective cohort study using linked administrative data

Por: Nickel · N. C. · Enns · J. E. · Freier · A. · McCulloch · S. C. · Chartier · M. · Casidsid · H. J. M. · Balogun · O. D. · Mulhall · D. · Dragan · R. · Sarkar · J. · Bolton · J. · Konrad · G. · Phillips-Beck · W. · Sanguins · J. · Shimmin · C. · McDonald · N. · Mignone · J. · Hinds · A. · M
Introduction

Rising use of methamphetamine is causing significant public health concern in Canada. The biological and behavioural effects of methamphetamine range from wakefulness, vigour and euphoria to adverse physical health outcomes like myocardial infarction, haemorrhagic stroke, arrhythmia and seizure. It can also cause severe psychological complications such as psychosis. National survey data point to increasing rates of methamphetamine use, as well as increasing ease of access and serious methamphetamine-related harms. There is an urgent need for evidence to address knowledge gaps, provide direction to harm reduction and treatment efforts and inform health and social policies for people using methamphetamine. This protocol describes a study that aims to address this need for evidence.

Methods

The study will use linked, whole population, de-identified administrative data from the Manitoba Population Research Data Repository. The cohort will include individuals in the city of Winnipeg, Manitoba, who came into contact with the health system for reasons related to methamphetamine use from 2013 to 2021 and a comparison group matched on age, sex and geography. We will describe the cohort’s sociodemographic characteristics, calculate incidence and prevalence of mental disorders associated with methamphetamine use and examine rates of health and social service use. We will evaluate the use of olanzapine pharmacotherapy in reducing adverse emergency department outcomes. In partnership with Indigenous co-investigators, outcomes will be stratified by First Nations and Métis identity.

Ethics and dissemination

The study was approved by the University of Manitoba Health Research Ethics Board, and access datasets have been granted by all data providers. We also received approval from the First Nations Health and Social Secretariat of Manitoba’s Health Information Research Governance Committee and the Manitoba Métis Federation. Dissemination will be guided by an ‘Evidence 2 Action’ group of public rightsholders, service providers and knowledge users who will ensure that the analyses address the critical issues.

Perceived quality of care among households ever enrolled in a community-based health insurance scheme in two districts of northeast Ethiopia: a community-based, cross-sectional study

Por: Hussien · M. · Azage · M. · Bayou · N. B.
Objectives

To examine how clients perceived the quality of healthcare they received and identify associated factors both at the individual and facility levels.

Design

A community-based, cross-sectional study.

Setting

Two rural districts of northeast Ethiopia, Tehulederie and Kallu.

Participants

1081 rural households who had ever been enrolled in community-based health insurance and visited a health centre at least once in the previous 12 months. Furthermore, 194 healthcare providers participated in the study to provide cluster-level data.

Outcome measures

The outcome variable of interest was the perceived quality of care, which was measured using a 17-item scale. Respondents were asked to rate the degree to which they agreed on 5-point response items relating to their experiences with healthcare in the outpatient departments of nearby health centres. A multilevel linear regression analysis was used to identify predictors of perceived quality of care.

Results

The mean perceived quality of care was 70.28 (SD=8.39). Five dimensions of perceived quality of care were extracted from the factor analysis, with the patient-provider communication dimension having the highest mean score (M=77.84, SD=10.12), and information provision having the lowest (M=64.67, SD=13.87). Wealth status, current insurance status, perceived health status, presence of chronic illness and time to a recent health centre visit were individual-level variables that showed a significant association with the outcome variable. At the cluster level, the work experience of healthcare providers, patient volume and an interaction term between patient volume and staff job satisfaction also showed a significant association.

Conclusions

Much work remains to improve the quality of care, especially on information provision and access to care quality dimensions. A range of individual-level and cluster-level characteristics influence the perceived quality of care. For a better quality of care, it is vital to optimise the patient-provider ratio and enhance staff job satisfaction.

Using primary care data to assess comparative effectiveness and safety of apixaban and rivaroxaban in patients with nonvalvular atrial fibrillation in the UK: an observational cohort study

Por: Jaksa · A. · Gibbs · L. · Kent · S. · Rowark · S. · Duffield · S. · Sharma · M. · Kincaid · L. · Ali · A. K. · Patrick · A. R. · Govil · P. · Jonsson · P. · Gatto · N.
Objective

To compare real-world effectiveness and safety of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AFib) for prevention of stroke.

Study design and setting

A comparative cohort study in UK general practice data from The Health Improvement Network database.

Participants and interventions

Before matching, 5655 patients ≥18 years with nonvalvular AFib who initiated at least one DOAC between 1 July 2014 and 31 December 2020 were included. DOACs of interest included apixaban, rivaroxaban, edoxaban and dabigatran, with the primary comparison between apixaban and rivaroxaban. Initiators of DOACs were defined as new users with no record of prescription for any DOAC during 12 months before index date.

Primary and secondary outcome measures

The primary outcome was stroke (ischaemic or haemorrhagic). Secondary outcomes included the occurrence of all-cause mortality, myocardial infarction (MI), transient ischaemic attacks (TIA), major bleeding events and a composite angina/MI/stroke (AMS) endpoint.

Results

Compared with rivaroxaban, patients initiating apixaban showed similar rates of stroke (HR: 0.93; 95% CI 0.64 to 1.34), all-cause mortality (HR: 1.03; 95% CI 0.87 to 1.22), MI (HR: 0.95; 95% CI 0.54 to 1.68), TIA (HR: 1.03; 95% CI 0.61 to 1.72) and AMS (HR: 0.96; 95% CI 0.72 to 1.27). Apixaban initiators showed lower rates of major bleeding events (HR: 0.60; 95% CI 0.47 to 0.75).

Conclusions

Among patients with nonvalvular AFib, apixaban was as effective as rivaroxaban in reducing rate of stroke and safer in terms of major bleeding episodes. This head-to-head comparison supports conclusions drawn from indirect comparisons of DOAC trials against warfarin and demonstrates the potential for real-world evidence to fill evidence gaps and reduce uncertainty in both health technology assessment decision-making and clinical guideline development.

Sexual harassment before and during the COVID-19 pandemic among adolescent girls and young women (AGYW) in Nairobi, Kenya: a cross-sectional study

Por: Bevilacqua · K. G. · Williams · A. · Wood · S. N. · Wamue-Ngare · G. · Thiongo · M. · Gichangi · P. · Decker · M. R.
Objectives

Sexual harassment among adolescent girls and young women (AGYW) is a prevalent and understudied form of gender-based violence (GBV) with negative impacts on health and well-being. The COVID-19 pandemic raised global concern about GBV within homes; less is known about how it affected GBV in public spaces.

Methods

Present analyses use cross-sectional data from a cohort of adolescents and young adults residing in Nairobi, Kenya, restricted to female participants. Data were collected August–October 2020 via phone after implementation of COVID-19 restrictions. Prevalence of past-year sexual harassment and harassment relative to COVID-19 restrictions were calculated for overall sample, and by individual, household, and pandemic-related factors. Multivariate negative binomial regression models examine correlates of (1) past-year sexual harassment and (2) increases in sexual harassment relative to COVID-19 restrictions.

Results

Overall, 18.1% of AGYW experienced past-year sexual harassment at the 2020 survey. Among this group, 14.6% experienced sexual harassment pre-COVID-19 only, 18.8% after only and 66.6% at both time points. Among the latter group, 34.9% reported more occurrences following COVID-19 restrictions, 20.5% reported less occurrences and 44.7% reported no change in occurrence. Overall, 42.0% of AGYW experienced an increase in sexual harassment while 58.0% experienced no increase since COVID-19. In adjusted models, past-year sexual harassment was associated with higher educational attainment (adjusted risk ratio, aRR 2.11; 95% CI 1.27 to 3.52) and inability to meet basic financial needs (aRR 1.67; 95% CI 1.05 to 2.66). Increased sexual harassment since COVID-19 was associated with having full control to leave the home (aRR 1.69; 95% CI 1.00 to 2.90).

Conclusions

Sexual harassment among AGYW in Nairobi, Kenya was prevalent before and during COVID-19 restrictions. Safety in public spaces remains a highly gendered issue that impacts women’s safety and ability to participate in public life. Prevention and support services to address sexual harassment remain an important element in ensuring safe, sustainable public spaces.

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