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ImportanceUncombable hair syndrome (UHS) is a rare hair shaft anomaly that manifests during infancy and is characterized by dry, frizzy, and wiry hair that cannot be combed flat. Only about 100 known cases have been reported so far.ObjectiveTo elucidate the genetic spectrum of UHS.Design, Setting, and ParticipantsThis cohort study includes 107 unrelated index patients with a suspected diagnosis of UHS and family members who were recruited worldwide from January 2013 to December 2021. Participants of all ages, races, and ethnicities were recruited at referral centers or were enrolled on their own initiative following personal contact with the authors. Genetic analyses were conducted in Germany from January 2014 to December 2021.Main Outcomes and MeasuresClinical photographs, Sanger or whole-exome sequencing and array-based genotyping of DNA extracted from blood or saliva samples, and 3-dimensional protein modeling. Descriptive statistics, such as frequency counts, were used to describe the distribution of identified pathogenic variants and genotypes.ResultsThe genetic characteristics of patients with UHS were established in 80 of 107 (74.8%) index patients (82 [76.6%] female) who carried biallelic pathogenic variants in PADI3, TGM3, or TCHH (ie, genes that encode functionally related hair shaft proteins). Molecular genetic findings from 11 of these 80 individuals were previously published. In 76 (71.0%) individuals, the UHS phenotype were associated with pathogenic variants in PADI3. The 2 most commonly observed PADI3 variants account for 73 (48.0%) and 57 (37.5%) of the 152 variant PADI3 alleles in total, respectively. Two individuals carried pathogenic variants in TGM3, and 2 others carried pathogenic variants in TCHH. Haplotype analyses suggested a founder effect for the 4 most commonly observed pathogenic variants in the PADI3 gene.Conclusions and RelevanceThis cohort study extends and gives an overview of the genetic variant spectrum of UHS based on molecular genetic analyses of the largest worldwide collective of affected individuals, to our knowledge. Formerly, a diagnosis of UHS could only be made by physical examination of the patient and confirmed by microscopical examination of the hair shaft. The discovery of pathogenic variants in PADI3, TCHH, and TGM3 may open a new avenue for clinicians and affected individuals by introducing molecular diagnostics for UHS.

BACKGROUND Adolescents and young adults have health needs which are distinctly different from children and adults. A lack of education and training is reported by clinicians to be one of the main barriers to providing comprehensive developmentally appropriate care to young people, including the provision of confidential healthcare and taking a holistic approach. AIM This study documents the current provision of care to young people on an adult inpatient medical ward at a large tertiary teaching hospital in Auckland. METHODS Forty-three staff and 40 patients aged 16-24 years on an adult medical ward completed surveys, which were based on the Northern Regional Alliance, Northern Regional Youth Health Network Standards for Quality Care for Adolescents and Young Adults in Secondary or Tertiary Care. RESULTS Few staff (12%) had completed any specific training in looking after adolescent and young adult (AYA) patients. Confidentiality was not routinely discussed with young people by 50% of clinicians, and only 23% of staff reported that they see a young person alone as part of their consultation or admission. Less than half of young people reported receiving a comprehensive psychosocial assessment that included sexual health, mental health and suicide, and safety. CONCLUSIONS Key components of comprehensive developmentally appropriate healthcare were not regularly carried out by staff on an adult medical ward. These findings suggest that further education and training, and service improvements are needed in tertiary adult hospital settings. This article is protected by copyright. All rights reserved.

BACKGROUND Lack of validated and responsive outcome measures in the management of Frontal Fibrosing Alopecia (FFA) significantly limits our ability to assess disease progression and treatment response over time. OBJECTIVES The aim of this study was to understand how FFA extent and progression is currently assessed in UK specialist centres, validate components of the International FFA Cooperative Group (IFFACG) statement on FFA assessment, and identify pragmatic advice to improve FFA management in clinic. METHODS Consultant Dermatologists with a specialist interest in hair loss (n=17) were invited to take part. Preferred FFA assessment methods were explored using questionnaires and clinical scenarios. Participants were asked to identify and mark the current hairline in 10 frontal and 10 temporal hairline images, with assessment repeated 3 months later (to assess intra-individual variability) and 12 months later (to test whether inter-individual accuracy could be improved with simple instruction). RESULTS All 17 clinicians (100%) completed the questionnaire at each time interval. We identified a wide variation in assessment techniques between our experts. Measurements were perceived as the most accurate method of assessing frontal recession whereas photography was preferred for temporal recession. Inter-rater reliability between clinicians measuring the frontal hairline scenarios indicated a moderate strength of agreement (ICC 0.613; 95% CI: 0.398 to 0.848), yet intra-rater reliability was found to be poor with wide limits of agreement (-8.71mm to 9.92mm) on follow-up. Importantly, when clear guidance was provided on how the hairline should be identified (questionnaire 3), inter-rater reliability improved significantly, with an ICC 0.702 suggesting moderate agreement (95% CI: 0.508 to 0.890; p

Objective To determine men's satisfaction with and the potential acceptability of 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) when used for 28 days as an experimental, once-daily, oral hormonal male contraceptive (HMC). Study design We surveyed participants from a double-blind, randomized, placebo-controlled, phase 1 clinical trial, examining their experience with and willingness to use daily oral 11β-MNTDC for male contraception. Results Of 42 trial participants, 40 (30 11β-MNTDC, 10 placebo) completed baseline and end-of-treatment surveys. Based on a 28-day experience, few cited any baseline concerns about safety and drug adherence. Following treatment, nearly three-quarters (72.5%) of participants reported satisfaction with the study drug and nearly all (92.5%) would recommend the method to others. More than half of participants would be willing to pay for the study drug (62.5%) and indicated that the method exceeded initial expectations (53.9%). Nearly 90% reported that taking the pill was easy to remember and did not interfere with their daily routines. Approximately one-third of participants reported bothersome side effects (37% 11β-MNTDC vs. 20% placebo, p = 0.45). Given the option, 42% of participants would prefer a daily HMC pill over injectable regimens or a daily topical gel. Conclusion A majority of participants in this short-term trial of daily oral 11β-MNTDC reported satisfaction with the regimen, would recommend it to others, and would pay to use the drug as HMC despite some bothersome side effects. Implications Oral 11β-MNTDC would be an acceptable and preferable method among men desiring reversible hormonal male contraception (HMC). These data support further trials of novel oral HMCs such as 11β-MNTDC.

IntroductionWomen from ethnic minority groups are at more risk of adverse outcomes in pregnancy compared with those from white British groups; suboptimal care may contribute to this increased risk. This study aimed to examine serious clinical incidents at two maternity units to explore causative factors for women from ethnic minorities and determine whether these differed from white women.MethodsA retrospective review was conducted of all serious incidents (n=36) occurring in a large National Health Service maternity provider (~14 000 births per annum) between 2018 and 2020. Data were collected from case records for variables which could mediate the association between ethnicity and adverse outcome. The incident reviews were blinded and reviewed by two independent investigators and data regarding root causes and contributory factors were extracted.ResultsFourteen of the 36 incidents (39%) occurred in women from minority ethnic groups, which is comparable to the maternity population. Women involved in serious clinical incidents frequently had pre-existing medical or obstetric complications. Booking after 12 weeks’ gestation occurred more frequently in women from minority ethnic groups than in the background population. There were differences in root causes of serious incidents between groups, a lack of situational awareness was the most frequent cause in white women and staff workload was most frequent in women from minority ethnic groups. Communication issues and detection of deterioration were similar between the two groups.DiscussionAlthough there was no difference in the proportion of serious incidents between the groups, there were differences in medical and pregnancy-related risk factors between groups and in the root causes identified. Efforts are needed to ensure equity of early access to antenatal care and to ensure that there is adequate staffing to ensure that women’s needs are met; this is particularly cogent when there are complex medical or social needs.

Background: The prevalence of stillbirth in many high income countries like Australia has remained unchanged for over 30 years. The 2018 Australian government Senate Select Committee on Stillbirth Research and Education highlighted the need for a public health campaign to encourage public conversations and increase awareness. However, there is little evidence about the community's knowledge and perceptions towards pregnancy and stillbirth, nor their aspirations for a public health campaign. Aims: To assess the general knowledge, perceptions, myths and attitudes towards stillbirth to inform future public health campaigns. Methods: Australian participants (n = 344; predominately women n = 294 (85.5%)) were recruited via Facebook.com. They completed a cross-sectional online survey designed to assess their knowledge of pregnancy and stillbirth, with additional questions on socio-demographic characteristics. Results: Stillbirth knowledge and awareness of incidence was low in this sample. Prominent myths, such as baby runs out of room in the uterus (n = 112, 33%) and baby slows down when preparing for labour (n = 24, 27%) were endorsed. Only 25% (n = 85) knew the prevalence of stillbirth in Australia (six per day). Almost two-thirds (n = 205; 62%) agreed that there needs to be a public health campaign, however one in five (n = 65; 20%) were concerned that talking about stillbirth with pregnant women may cause them to worry. Discussion and conclusion: Our findings reinforce the need for a targeted campaign, which educates the general population about the definition and prevalence of stillbirth, stillbirth risks and modifiable health behaviours. Appropriate messaging should target pregnant women during antenatal care as well as their support and care systems (family, friends, and care providers).53 Refereed/Peer-reviewed

Background We previously reported the Alopecia Areata Consensus of Experts study, which presented results of an international expert opinion on treatments for alopecia areata. Objective To report the results of the Alopecia Areata Consensus of Experts international expert opinion on diagnosis and laboratory evaluation for alopecia areata. Methods Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Consensus threshold was set at greater than or equal to 66%. Results Of 148 questions, expert consensus was achieved in 82 (55%). Round 1 consensus was achieved in 10 of 148 questions (7%). Round 2 achieved consensus in 47 of 77 questions (61%). The final face-to-face achieved consensus in 25 of 32 questions (78%). Consensus was greatest for laboratory evaluation (12 of 14 questions [86%]), followed by diagnosis (11 of 14 questions [79%]) of alopecia areata. Overall, etiopathogenesis achieved the least category consensus (31 of 68 questions [46%]). Limitations The study had low representation from Africa, South America, and Asia. Conclusion There is expert consensus on aspects of epidemiology, etiopathogenesis, clinical features, diagnosis, laboratory evaluation, and prognostic indicators of alopecia areata. The study also highlights areas where future clinical research could be directed to address unresolved hypotheses in alopecia areata patient care.

Background. Patients with chronic obstructive pulmonary disease (COPD) typically experience multidimensional symptoms throughout the course of their disease, with burdensome physical symptoms, social isolation, and additional psychological suffering. COVID-19 lockdown resulted in restrictions on chronic care delivery at primary healthcare (PHC) facilities, and it is not known what the care experiences of patients with COPD were during this time.Objectives. To describe patient experiences of the impact of the lockdown on their needs and their experiences of the primary care received for their COPD.Methods. The data reported in this paper are from a cohort of 49 patients with COPD receiving primary care, recruited in February and March 2020, before recruitment was paused for COVID-19 lockdown, for a feasibility stepped-wedge hybrid type II design randomised controlled trial of integrated person-centred palliative care in primary care for patients with COPD in Cape Town, South Africa. Data are open-text responses from participants who responded to a single question on a validated measure of primary care consultation empathy (CARE), and describe patient experiences of the impact of the lockdown on the primary care received for their COPD, prior to crossover to trial intervention.Results. Thirty-two patients with COPD gave between 1 and 9 responses each to the open-ended question between March and December 2020. The average age of the participants was 58.6 years, and 53.1% (n=17) were female. Inductive analysis of the open-text data identified four main themes. Participants described decreased access to chronic care and a desire for more person-centred care in interactions with healthcare professionals. The socioeconomic ramifications of the COVID-19 lockdown added to the burden they experienced.Conclusion. The COVID-19 lockdown PHC service restrictions caused a disruption to the continuity of care for patients with COPD, with associated worry, anxiety and disappointment. Medication access was largely supported by the home delivery of chronic medication. We suggest that there are opportunities for providing more sustained support for patients with COPD through referrals to community health workers, and also through telephonic patient follow-up by primary care teams

BackgroundPerson-centred care (PCC) is being internationally recognised as a critical attribute of high-quality healthcare. The International Alliance of Patients Organisations defines PCC as care that is focused and organised around people, rather than disease. Focusing on delivery, we aimed to review and evaluate the evidence from interventions that aimed to deliver PCC for people with serious physical illness and identify models of PCC interventions.MethodsSystematic review of literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched AMED, CINAHL, Cochrane Library, Embase, Medline, PsycINFO, using the following key concepts: patient/person-centred care, family centred care, family based care, individualised care, holistic care, serious illness, chronic illness, long-term conditions from inception to April 2022. Due to heterogeneity of interventions and populations studied, narrative synthesis was conducted. Study quality was appraised using the Joanna Briggs checklist.ResultsWe screened n=6156 papers. Seventy-two papers (reporting n=55 different studies) were retained in the review. Most of these studies (n=47) were randomised controlled trials. Our search yielded two main types of interventions: (1) studies with self-management components and (2) technology-based interventions. We synthesised findings across these two models:Self-management component: the interventions consisted of training of patients and/or caregivers or staff. Some studies reported that interventions had effect in reduction hospital admissions, improving quality of life and reducing costs of care.Technology-based interventions: consisted of mobile phone, mobile app, tablet/computer and video. Although some interventions showed improvements for self-efficacy, hospitalisations and length of stay, quality of life did not improve across most studies.DiscussionPCC interventions using self-management have some effects in reducing costs of care and improving quality of life. Technology-based interventions improves self-efficacy but has no effect on quality of life. However, very few studies used self-management and technology approaches. Further work is needed to identify how self-management and technology approaches can be used to manage serious illness.PROSPERO registration numberCRD42018108302.

BackgroundThe health disadvantages faced by Australian Aboriginal peoples are evidenced in early life, although few studies have focused on the reasons for population-level inequalities in more severe adverse outcomes. This study aimed to examine the scale of disparity in severe neonatal morbidity (SNM) and mortality between Aboriginal and non-Aboriginal births and quantify the relative contributions of important maternal and infant factors.MethodA retrospective cohort study with singleton live births (≥32 weeks’ gestation) was conducted using Western Australia linked whole population datasets, from 1999 to 2015. Aboriginal status was determined based on the mothers’ self-reported ethnic origin. An Australian validated indicator was adapted to identify neonates with SNM. The Oaxaca-Blinder method was employed to calculate the contribution of each maternal and infant factor to the disparity in SNM and mortality.ResultsAnalyses included 425 070 births, with 15 967 (3.8%) SNM and mortality cases. The disparity in SNM and mortality between Aboriginal and non-Aboriginal births was 2.9 percentage points (95% CI 2.6 to 3.2). About 71% of this gap was explained by differences in modelled factors including maternal area of residence (23.8%), gestational age (22.2%), maternal age (7.5%) and antenatal smoking (7.2%).ConclusionsThere is a considerable disparity in SNM and mortality between Aboriginal and non-Aboriginal births in Western Australia with the majority of this related to differences in maternal sociodemographic factors, antenatal smoking and gestational age. Public health programmes targeting these factors may contribute to a reduction in early life health differentials and benefit Aboriginal population health through the life course.

The climate crisis has detrimental impacts on the mental health and wellbeing of children and young people. Psychological effects include feelings of fear, overwhelm, worry, distress, hopelessness and anger; PTSD; depression; anxiety; phobias; panic disorder; sleep disturbances; attachment disorders; learning difficulties; substance abuse; shock and trauma symptoms; adjustment problems; behavioural problems; and, suicidal thinking. First Nations' children and young people are particularly at risk due to loss of place, identity, culture, land and customs informed by kinship relationships with the Earth; while sustainable land use practices and connection to Country and community can enhance climate resilience. In Western Australia (WA), some young people engage in climate activism - including striking from school - to demand government action to address the causes of climate change, including colonisation and capitalism. Climate activism can promote resilience, particularly when children and young people can emotionally engage in the climate crisis; when mental health is systemically supported; when climate communication is transparent and comprehensive; and, when activism is informed by the knowledges and wisdoms of First Nations peoples and grounded on Country. This article is co-authored by WA young people, Aboriginal and non-Aboriginal academics, activists and practitioners engaged in youth, mental health and climate justice spaces. We argue for structural change to address the causes of the climate crisis, alongside enhanced evidence and approaches to appropriately support the mental health of children and young people. Furthermore, we support the call of Aboriginal peoples to ensure culturally appropriate, place-based responses based in caring for Country.

Quantification of stillbirth risk has potential to support clinical decision-making. Studies that have attempted to quantify stillbirth risk have been hampered by small event rates, a limited range of predictors that typically exclude obstetric history, lack of validation, and restriction to a single classifier (logistic regression). Consequently, predictive performance remains low, and risk quantification has not been adopted into antenatal practice. The study population consisted of all births to women in Western Australia from 1980 to 2015, excluding terminations. After all exclusions there were 947,025 livebirths and 5,788 stillbirths. Predictive models for stillbirth were developed using multiple machine learning classifiers: regularised logistic regression, decision trees based on classification and regression trees, random forest, extreme gradient boosting (XGBoost), and a multilayer perceptron neural network. We applied 10-fold cross-validation using independent data not used to develop the models. Predictors included maternal socio-demographic characteristics, chronic medical conditions, obstetric complications and family history in both the current and previous pregnancy. In this cohort, 66% of stillbirths were observed for multiparous women. The best performing classifier (XGBoost) predicted 45% (95% CI: 43%, 46%) of stillbirths for all women and 45% (95% CI: 43%, 47%) of stillbirths after the inclusion of previous pregnancy history. Almost half of stillbirths could be potentially identified antenatally based on a combination of current pregnancy complications, congenital anomalies, maternal characteristics, and medical history. Greatest sensitivity is achieved with addition of current pregnancy complications. Ensemble classifiers offered marginal improvement for prediction compared to logistic regression.

IntroductionPerson-centred care (PCC) is internationally recognised as a critical component of high-quality healthcare. However, PCC evolved in a few high-income countries and there are limited data exploring this concept across the vast majority of countries which are low- and middle-income. This study aimed to appraise and adapt a PCC model across three serious physical conditions in three middle-income countries and generate an evidence-based framework and recommendations for globally relevant PCC.MethodsCross-national, cross-sectional qualitative study. In depth, semistructured interviews conducted with: advanced cancer patients in Jordan (n=50), their caregivers (n=20) and healthcare professionals (HCPs) (n=20); chronic obstructive pulmonary disease patients in South Africa (n=22), their caregivers (n=19) and HCPs (n=22); heart failure patients in Thailand (n=14), their caregivers (n=10) and HCPs (n=12). Data were analysed using framework analysis. Santana et al’s PCC model (2018) and Giusti et al’s systematic review (2020) were used to construct an a priori coding frame for deductive analysis, with additional inductive coding for coding that did not fit the frame.ResultsThe findings both reveal specific practical actions that contribute towards delivering PCC and highlight new cross-national domains of person-centredness: interdependency and collectivism; bringing care into the home and community; equity and non-discrimination; addressing health and illness within the context of limited resources; and workforce well-being.ConclusionThe data suggest that PCC requires particular structural features of the healthcare system to be in place, such as professional education in PCC values and partnerships with community-based workers. These structures may better enable PCC processes, including tailored information sharing and providing genuine opportunities for patients to do the things that matter to them, such as making informed care decisions and sustaining social relationships. PCC must also accommodate a collectivist perspective and support the well-being of the workforce.

There is scant literature about antepartum stillbirth management but guidelines usually recommend reserving caesarean sections for exceptional circumstances. However, little is known about caesarean section rates following antepartum stillbirth in Australia.We aimed to describe the onset of labour, mode of birth, and use of analgesia and anaesthesia following antepartum stillbirth and to identify factors associated with caesarean section.In this retrospective cohort study, we used a population-based dataset of all singleton antepartum stillbirths ≥20 weeks gestation in Western Australia between 2010-2015. The overall, primary and repeat caesarean section rates for antepartum stillbirths were calculated and multivariable Poisson regression analyses were performed to identify associated factors, and to calculate relative risks (RRs) and 95% confidence intervals (CIs).This study included 634 antepartum stillbirths. Labour was spontaneous for 134 (21.1%), induced for 457 (72.1%), and 43 (6.8%) had a prelabour caesarean section. The overall, primary and repeat caesarean section rates were 8.5%, 4.6% and 23.0% respectively and increased with gestation (P trends all0.01). Other factors associated with an increased caesarean section risk included: any placenta praevia or placental abruption, birth at a metropolitan private hospital, large-for-gestational-age birthweight, and any maternal chronic condition. During labour, the most frequently used types of analgesia were systemic narcotics (46.0%) and regional blocks (34.7%) while among those who had a caesarean section, 40.7% had a general anaesthetic.In Western Australia between 2010-2015, the caesarean section rates among women with antepartum stillbirths were low, in line with current guidelines.

It is known that a previous preterm birth increases the risk of a subsequent preterm birth, but a limited number of studies have examined this beyond two consecutive pregnancies.This study aimed to assess the risk and patterns of (recurrent) preterm birth up to the fourth pregnancy.We used Western Australian routinely linked population health datasets to identify women who had two or more consecutive singleton births (≥20 weeks gestation) from 1980 to 2015. A log-binomial model was used to calculate risk ratios (RRs) and 95% confidence interval (CIs) for preterm birth risk in the third and fourth deliveries by the combined outcomes of previous pregnancies.We analysed 255 435 women with 651 726 births. About 7% of women had a preterm birth in the first delivery, and the rate of continuous preterm birth recurrence was 22.9% (second), 44.9% (third) and 58.5% (fourth) deliveries. The risk of preterm birth at the third delivery was highest for women with two prior indicated preterm births (RR 12.5, 95% CI: 11.3, 13.9) and for those whose first pregnancy was 32-36 weeks gestation, and second pregnancy was less than 32 weeks gestation (RR 11.8, 95% CI: 10.3, 13.5). There were similar findings for the second and fourth deliveries.Our findings demonstrate that women with any prior preterm birth were at greater risk of preterm birth in subsequent pregnancies compared with women with only term births, and the risk increased with shorter gestational length, and the number of previous preterm deliveries, especially sequential ones.

BackgroundDisturbances of copper (Cu) homeostasis can lead to hypertrophic cardiac phenotypes (eg, Wilson’s disease). We previously identified abnormal Cu homeostasis in patients with hypertrophic cardiomyopathy (HCM) and, therefore, hypothesised that Cu2+–selective chelation with trientine dihydrochloride may slow or reverse disease progression in HCM. The aim of this study was, therefore to explore the clinical efficacy, safety and tolerability of trientine in HCM.MethodsIn this medicines and healthcare products regulatory agency (MHRA) registered open-label pilot study, we treated 20 HCM patients with trientine for 6 months. Patients underwent a comprehensive assessment schedule including separate cardiac magnetic resonance imaging (CMR) and CMR 31P-spectroscopy at baseline and end of therapy. Predefined end points included changes in left ventricular mass (LVM), markers of LV fibrosis, markers of LV performance and myocardial energetics. Ten matched patients with HCM were studied as controls.ResultsTrientine treatment was safe and tolerated. Trientine caused a substantial increase in urinary copper excretion (0.42±0.2 vs 2.02±1.0, p=0.001) without affecting serum copper concentrations. Treatment was associated with significant improvements in total atrial strain and global longitudinal LV strain using both Echo and CMR. LVM decreased significantly in the treatment arm compared with the control group (−4.2 g v 1.8 g, p=0.03). A strong trend towards an absolute decrease in LVM was observed in the treatment group (p=0.06). These changes were associated with a significant change in total myocardial volume driven by a significant reduction in extracellular matrix (ECM) volume (43.83±18.42 mL vs 41.49±16.89 mL, p=0.04) as opposed to pure cellular mass reduction and occurred against a background of significant ECM volume increase in the control group (44.59±16.50 mL vs 47.48±19.30 mL, p=0.02). A non-significant 10% increase in myocardial phosphocreatine/adenosine triphosphate (PCr/ATP) ratio with trientine therapy (1.27±0.44 vs 1.4±0.39) was noted.ConclusionsCu2+–selective chelation with trientine in a controlled environment is safe and a potential future therapeutic target. A phase 2b trial is now underway.

To achieve universal health coverage, health system strengthening (HSS) is required to support the of delivery of high-quality care. The aim of the National Institute for Health Research Global Research Unit on HeAlth System StrEngThening in Sub-Saharan Africa (ASSET) is to address this need in a four-year programme, with three healthcare platforms involving eight work-packages. Key to effective health system strengthening (HSS) is the pre-implementation phase of research where efforts focus on applying participatory methods to embed the research programme within the existing health system. To conceptualise the approach, we provide an overview of the key methods applied across work-package to address this important phase of research conducted between 2017 and 2021. Work-packages are being undertaken in publicly funded health systems in rural and urban areas in Ethiopia, Sierra Leone, South Africa, and Zimbabwe. Stakeholders including patients and their caregivers, community representatives, clinicians, managers, administrators, and policymakers are the main research participants. In each work-package, initial activities engage stakeholders and build relationships to ensure co-production and ownership of HSSIs. A mixed-methods approach is then applied to understand and address determinants of high-quality care delivery. Methods such as situation analysis, cross-sectional surveys, interviews and focus group discussions are adopted to each work-package aim and context. At the end of the pre-implementation phase, findings are disseminated using focus group discussions and participatory Theory of Change workshops where stakeholders from each work package use findings to select HSSIs and develop a programme theory. ASSET places a strong emphasis of the pre-implementation phase in order to provide an in-depth and systematic diagnosis of the existing heath system functioning, needs for strengthening and stakeholder engagement. This common approach will inform the design and evaluation of the HSSIs to increase effectiveness across work packages and contexts, to better understand what works, for whom, and how.

The mission of the Tear Film & Ocular Surface Society (TFOS) is to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Fundamental to fulfilling this mission is the TFOS Global Ambassador program. TFOS Ambassadors are dynamic and proactive experts, who help promote TFOS initiatives, such as presenting the conclusions and recommendations of the recent TFOS DEWS II™, throughout the world. They also identify unmet needs, and propose future clinical and scientific solutions, for management of ocular surface diseases in their countries. This meeting report addresses such needs and solutions for 25 European countries, as detailed in the TFOS European Ambassador meeting in Rome, Italy, in September 2019.

Importance A recent expert consensus exercise emphasized the importance of developing a global network of patient registries for alopecia areata to redress the paucity of comparable, real-world data regarding the effectiveness and safety of existing and emerging therapies for alopecia areata. Objective To generate core domains and domain items for a global network of alopecia areata patient registries. Evidence Review Sixty-six participants, representing physicians, patient organizations, scientists, the pharmaceutical industry, and pharmacoeconomic experts, participated in a 3-round eDelphi process, culminating in a face-to-face meeting at the World Congress of Dermatology, Milan, Italy, June 14, 2019. Findings Ninety-two core data items, across 25 domains, achieved consensus agreement. Twenty further noncore items were retained to facilitate data harmonization in centers that wish to record them. Broad representation across multiple stakeholder groups was sought; however, the opinion of physicians was overrepresented. Conclusions and Relevance This study identifies the domains and domain items required to develop a global network of alopecia areata registries. These domains will facilitate a standardized approach that will enable the recording of a comprehensive, comparable data set required to oversee the introduction of new therapies and harness real-world evidence from existing therapies at a time when the alopecia areata treatment paradigm is being radically and positively disrupted. Reuse of similar, existing frameworks in atopic dermatitis, produced by the Treatment of Atopic Eczema (TREAT) Registry Taskforce, increases the potential to reuse existing resources, creates opportunities for comparison of data across dermatology subspecialty disease areas, and supports the concept of data harmonization.

Background: The South African National Policy Framework and Strategy on Palliative Care (NPFSPC) recommends that when integrating palliative care (PC) into the health system, a PC indicators tool should be used to guide clinicians to recognise a patient who should receive PC. The policy document recommends ‘a simple screening tool developed for use in South Africa that would assist healthcare professionals (HCPs) to recognise patients who may have unmet palliative care needs’.Aim: This research study sought to develop South African consensus on indicators for PC to assist clinicians to recognise a patient in need of PC.Setting: The South African healthcare setting.Methods: A Delphi study was considered suitable as a methodology to develop consensus. The methodology was based on the Conducting and REporting of DElphi studies (CREDES) guidance on Delphi studies to ensure rigour and transparency in conducting and reporting. Six different Delphi rounds were used to develop consensus. Each round allowed participants to anonymously rate statements with predefined rating scales.Results: Cognisant of the disparities in healthcare provision and access to equitable healthcare in South Africa, the expert advisory group recommended, especially for South Africa, that ‘this tool is for deteriorating patients with an advanced life-limiting illness where all available and appropriate management for underlying illnesses and reversible complications has been offered’. The expert advisory group felt that disease-specific indicators should be described before the general indicators in the South African indicators tool, so all users of the tool orientate themselves to the disease categories first. This study included three new domains to address the South African context: trauma, infectious diseases and haematological diseases. General indicators for PC aligned with the original Supportive and Palliative Care Indicators Tool (SPICT) tool.Conclusion: The Supportive and Palliative Care Indicators Tool for South Africa (SPICTTM-SA) is a simple screening tool for South Africa that may assist HCPs to recognise patients who may have unmet PC needs.

IntroductionThe burden of chronic kidney disease (CKD) is growing rapidly around the world. However, there is limited information on the overall regional prevalence of CKD, as well as the variations in national prevalence within Asia. We aimed to consolidate available data and quantify estimates of the CKD burden in this region.MethodsWe systematically searched MEDLINE, Embase and Google Scholar for observational studies and contacted national experts to estimate CKD prevalence in countries of Asia (Eastern, Southern and South Eastern Asia). CKD was defined as estimated glomerular filtration rate (eGFR) 2 or the presence of proteinuria. For countries without reported data, we estimated CKD prevalence using agglomerative average-linkage hierarchical clustering, based on country-level risk factors and random effects meta-analysis within clusters. Published CKD prevalence data were obtained for 16 countries (of the 26 countries in the region) and estimates were made for 10 countries.ResultsThere was substantial variation in overall and advanced (eGFR 2) CKD prevalence (range: 7.0%–34.3% and 0.1%–17.0%, respectively). Up to an estimated 434.3 million (95% CI 350.2 to 519.7) adults have CKD in Asia, including up to 65.6 million (95% CI 42.2 to 94.9) who have advanced CKD. The greatest number of adults living with CKD were in China (up to 159.8 million, 95% CI 146.6 to 174.1) and India (up to 140.2 million, 95% CI 110.7 to 169.7), collectively having 69.1% of the total number of adults with CKD in the region.ConclusionThe large number of people with CKD, and the substantial number with advanced CKD, show the need for urgent collaborative action in Asia to prevent and manage CKD and its complications.

Increasing numbers of young people are seeking gender-affirming healthcare in Aotearoa New Zealand, and although international studies report health and wellbeing benefits of early medical intervention, we have no published reports on the impact of health services in this country.Transgender young people accessing a specialist service providing medical gender-affirming healthcare were invited to take part in a survey about their health and wellbeing.High or very high psychological distress levels were reported by 74% of respondents, with 39% being unable to access mental health support when needed.Although the proportion of transgender young people with high or very high levels of psychological distress was five times greater (74%) than for the general population of young people (14.5%) in Aotearoa New Zealand, it was not as large as the proportion found for transgender young people in a community study (86%) in which an unmet need for hormones was reported by 29%. This highlights the need for clear referral pathways to access specialist gender-affirming healthcare services in order to reduce disparities in mental health outcomes.

The carotid intimal media thickness (CIMT) is a validated measure of subclinical atherosclerosis. Human immunodeficiency virus (HIV) is a risk factor for cardiovascular disease (CVD) and has been associated with CIMT in North America and Europe; however, there are limited data from Sub-Saharan Africa (SSA). In this cross-sectional study, we measured CIMT in a cohort of 262 people living with HIV (PLHIV) on antiretroviral therapy (ART) for ≥6 months and HIV-negative adults in western Kenya. Using linear regression, we examined the associations between CVD risk factors and CIMT, both overall and stratified according to the HIV status. Among the PLHIV, we examined the association between CIMT and HIV-related factors. Of 262 participants, approximately half were women. The HIV-negative group had a higher prevalence of age ≥55 years (P = .002), previously diagnosed hypertension (P = .02), treatment for hypertension (P = .03), and elevated blood pressure (BP) (P = .01). Overall prevalence of carotid plaques was low (15/262 [6.0%]). HIV-positive status was not significantly associated with a greater mean CIMT (P = .19). In multivariable regression models, PLHIV with elevated blood pressure or treatment for hypertension had a greater mean CIMT (P = .002). However, the CD4 count, viral load, and ART regimen were not associated with differences in CIMT. In the HIV-negative group, older age (P = .006), high total cholesterol levels (P = .01), and diabetes (P = .02) were associated with a greater mean CIMT. In this cross-sectional study of Kenyan adults, traditional CVD risk factors were found to be more prevalent among HIV-negative participants. After multivariable regression analysis, we found no association between HIV status and CIMT, and PLHIV had fewer CVD risk factors associated with CIMT than HIV-negative participants did. HIV-specific factors were not associated with the CIMT.

Journal Pre-proof, The mission of the Tear Film & Ocular Surface Society (TFOS) is to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Fundamental to fulfilling this mission is the TFOS Global Ambassador program. TFOS Ambassadors are dynamic and proactive experts, who help promote TFOS initiatives, such as presenting the conclusions and recommendations of the recent TFOS DEWS IITM, throughout the world. They also identify unmet needs, and propose future clinical and scientific solutions, for management of ocular surface diseases in their countries. This meeting report addresses such needs and solutions for 25 European countries, as detailed in the TFOS European Ambassador meeting in Rome, Italy, in September 2019., TFOS - Tear Film and Ocular Surface Society(undefined)

Background A systematic review failed to identify any systemic therapy used in alopecia areata (AA) where use is supported by robust evidence from high-quality randomized controlled trials. Objective To produce an international consensus statement on the use and utility of various treatments for AA. Methods Fifty hair experts from 5 continents were invited to participate in a 3-round Delphi process. Agreement of 66% or greater was considered consensus. Results In the first round, consensus was achieved in 22 of 423 (5%) questions. After a face-to-face meeting in round 3, overall, consensus was achieved for only 130 (33%) treatment-specific questions. There was greater consensus for intralesional treatment of AA (19 [68%]) followed by topical treatment (25 [43%]). Consensus was achieved in 45 (36%) questions pertaining to systemic therapies in AA. The categories with the least consensus were phototherapy and nonprescription therapies. Limitations The study included a comprehensive list of systemic treatments for AA but not all treatments used. Conclusion Despite divergent opinions among experts, consensus was achieved on a number of pertinent questions. The concluding statement also highlights areas where expert consensus is lacking and where an international patient registry could enable further research.

It is critical that health service evaluation frameworks include Aboriginal people and their cultural worldviews from design to implementation. During a large participatory action research study, Elders, service leaders and Aboriginal and non-Aboriginal researchers co-designed evaluation tools to test the efficacy of a previously co-designed engagement framework. Through a series of co-design workshops, tools were built using innovative collaborative processes that foregrounded Aboriginal worldviews. The workshops resulted in the development of a three-way survey that records the service experiences related to cultural safety from the perspective of Aboriginal clients, their carer/s, and the service staff with whom they work. The surveys centralise the role of relationships in client-service interactions, which strongly reflect their design from an Aboriginal worldview. This paper provides new insights into the reciprocal benefits of engaging community Elders and service leaders to work together to develop new and more meaningful ways of servicing Aboriginal families. Foregrounding relationships in service evaluations reinstates the value of human connection and people-centred engagement in service delivery which are central to rebuilding historically fractured relationships between mainstream services and Aboriginal communities. This benefits not only Aboriginal communities, but also other marginalised populations expanding the remit of mainstream services to be accessed by many. Refereed/Peer-reviewed

Background Perinatal mortality rates are typically higher in Aboriginal than non-Aboriginal populations of Australia. Objectives This study aimed to examine the pattern of stillbirth and neonatal mortality rate disparities over time in Western Australia, including an evaluation of these disparities across gestational age groupings. Methods All singleton births (>= 20 weeks gestation) in Western Australia between 1980 and 2015 were included. Linked data were obtained from core population health datasets of Western Australia. Stillbirth and neonatal mortality rates and percentage changes in the rates over time were calculated by Aboriginal status and gestational age categories. Results From 1980 to 2015, data were available for 930 926 births (925 715 livebirths, 5211 stillbirths and 2476 neonatal deaths). Over the study period, there was a substantial reduction in both the Aboriginal (19.6%) and non-Aboriginal (32.3%) stillbirth rates. These reductions were evident in most gestational age categories among non-Aboriginal births and in Aboriginal term births. Concomitantly, neonatal mortality rates decreased in all gestational age windows for both populations, ranging from 32.1% to 77.5%. The overall stillbirth and neonatal mortality rate differences between Aboriginal and non-Aboriginal birth decreased by 0.6 per 1000 births and 3.9 per 1000 livebirths, respectively, although the rate ratios (RR 2.51, 95% CI 2.14, 2.94) and (RR 2.94, 95% CI 2.24, 3.85), respectively reflect a persistent excess of Aboriginal perinatal mortality across the study period. Conclusions Despite steady improvements in perinatal mortality rates in Western Australia over 31/2 decades, the gap between Aboriginal and non-Aboriginal rates remains unchanged in relative terms. There is a continuing, pressing need to address modifiable risk factors for preventable early mortality in Aboriginal populations.

Objective To assess the feasibility of a family meal intervention to address indicators of parent and adolescent nutrition and well-being and household food security. Methods Nine adolescents and a parent/caregiver were recruited from a youth health clinic. Families were provided with meal plans, recipes, and ingredients for 5 meals weekly for 4 weeks. Participants completed baseline and follow-up surveys and open-ended interviews. Results Overall, fidelity to the intervention was high among families; the frequency of family meals increased by approximately 2 meals/wk. Both parent/caregivers and adolescents reported improvements to nutrition (4 of 9 increased vegetable consumption for both) and most reported improvements to mental well-being. Household food insecurity also reduced during the intervention (means of 8.2 and 0.2 at baseline and follow-up, respectively). Conclusions and Implications Providing families with meal plans, recipes, and ingredients is an acceptable way to increase weekly frequency of family meals. Future research may consider the family meal as a way to engage with families about broader concerns.

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02., Frontal fibrosing alopecia (FFA) features lichenoid cutaneous inflammation and scarring hair loss. Here, Tziotzios et al. identify four genetic loci associated with FFA by GWAS followed by Bayesian fine-mapping, co-localisation and HLA imputation which highlights HLA-B*07:02 as a risk factor.

Objectives Artificial intelligence (AI), including predictive analytics, has great potential to improve the care of common chronic conditions with high morbidity and mortality. However, there are still many challenges to achieving this vision. The goal of this project was to develop and apply methods for enhancing chronic disease care using AI.Methods Using a dataset of 27,904 patients with diabetes, an analytical method was developed and validated for generating a treatment pathway graph which consists of models that predict the likelihood of alternate treatment strategies achieving care goals. An AI-driven clinical decision support system (CDSS) integrated with the electronic health record (EHR) was developed by encapsulating the prediction models in an OpenCDS Web service module and delivering the model outputs through a SMART on FHIR (Substitutable Medical Applications and Reusable Technologies on Fast Healthcare Interoperability Resources) web-based dashboard. This CDSS enables clinicians and patients to review relevant patient parameters, select treatment goals, and review alternate treatment strategies based on prediction results.Results The proposed analytical method outperformed previous machine-learning algorithms on prediction accuracy. The CDSS was successfully integrated with the Epic EHR at the University of Utah.Conclusion A predictive analytics-based CDSS was developed and successfully integrated with the EHR through standards-based interoperability frameworks. The approach used could potentially be applied to many other chronic conditions to bring AI-driven CDSS to the point of care.

Funder: GlaxoSmithKline; funder-id: http://dx.doi.org/10.13039/100004330, Introduction: Delayed graft function (DGF) following renal transplantation is a manifestation of acute kidney injury (AKI) leading to poor long-term outcome. Current treatments have limited effectiveness in preventing DGF. Interleukin-18 (IL18), a biomarker of AKI, induces interferon-γ expression and immune activation. GSK1070806, an anti-IL18 monoclonal antibody, neutralizes activated (mature) IL18 released from damaged cells following inflammasome activation. This phase IIa, single-arm trial assessed the effect of a single dose of GSK1070806 on DGF occurrence post donation after circulatory death (DCD) kidney transplantation. Methods: The 3 mg/kg intravenous dose was selected based on prior studies and physiologically based pharmacokinetic (PBPK) modeling, indicating the high likelihood of a rapid and high level of IL18 target engagement when administered prior to kidney allograft reperfusion. Utilization of a Bayesian sequential design with a background standard-of-care DGF rate of 50% based on literature, and confirmed via extensive registry data analyses, enabled a statistical efficacy assessment with a minimal sample size. The primary endpoint was DGF frequency, defined as dialysis requirement ≤7 days post transplantation (except for hyperkalemia). Secondary endpoints included safety, pharmacokinetics and pharmacodynamic biomarkers. Results: GSK1070806 administration was associated with IL18-GSK1070806 complex detection and increased total serum IL18 levels due to IL18 half-life prolongation induced by GSK1070806 binding. Interferon-γ−induced chemokine levels declined or remained unchanged in most patients. Although the study was concluded prior to the Bayesian-defined stopping point, 4/7 enrolled patients (57%) had DGF, exceeding the 50% standard-of-care rate, and an additional two patients, although not reaching the protocol-defined DGF definition, demonstrated poor graft function. Six of seven patients experienced serious adverse events (SAEs), including two treatment-related SAEs. Conclusion: Overall, using a Bayesian design and extensive PBPK dose modeling with only a small sample size, it was deemed unlikely that GSK1070806 would be efficacious in preventing DGF in the enrolled DCD transplant population. Trial registration: NCT02723786.

INTRODUCTION Retrospective studies have reported an association between a single episode of significantly increased fetal movements (IFMs) and stillbirth after 28 weeks' gestation. This prospective study aimed to report the outcome of pregnancies associated with maternal perception of IFMs and determine whether this symptom is associated with adverse pregnancy outcome, a pathological intrauterine environment or placental dysfunction. MATERIAL AND METHODS Women reporting IFMs after 28 weeks' gestation were recruited from St Mary's Hospital, Manchester and Liverpool Women's Hospital, UK, between 1 November 2017 and 1 May 2019. Demographic and clinical information were obtained and an ultrasound scan was performed to assess fetal biometry, liquor volume and umbilical artery Doppler. Maternal serum samples were collected for analysis of placentally derived biomarkers using ELISA. After delivery, maternal and fetal outcome data were collected and placentas and umbilical cord blood were obtained for analysis using immunohistochemistry and ELISA, respectively. Placental and serum samples were matched by gestation and maternal characteristics to participants with normal fetal activity. RESULTS Seventy-seven women presented with IFM, representing 0.45% of the maternity population; 64 women consented to participate in the study, of which 7 (10.9%) experienced adverse pregnancy outcome: birthweight

Soil-transmitted helminths (STH) are endemic and widespread across Sub-Saharan Africa. A community wide soil-transmitted helminth (STH) prevalence survey was performed on the island of Bubaque in Guinea-Bissau using both Kato-katz microscopy and qPCR methodology. Predictors of infection and morbidity indicators were identified using multivariable logistic regression, and diagnostic methods were compared using k statistics. Among 396 participants, prevalence of STH by microscopy was 23.2%, hookworm was the only species identified by this method and the mean infection intensity was 312 eggs per gram. qPCR analysis revealed an overall prevalence of any STH infection of 47.3%, with the majority A. duodenale (32.3%), followed by N. americanus (15.01%) and S. stercoralis (13.2%). A. lumbricoides, and T. trichiura infections were negligible, with a prevalence of 0.25% each. Agreement between diagnostic tests was k = 0.22, interpreted as fair agreement, and infection intensity measured by both methods was only minimally correlated (Rs = -0.03). STH infection overall was more common in females and adults aged 31–40. STH infection was associated with open defaecation, low socio-economic status and further distance to a water-source. The prevalence of anaemia (defined as a binary outcome by the WHO standards for age and sex) was 69.1%, and 44.2% of children were malnourished according to WHO child growth standards. Hookworm infection intensity by faecal egg count showed no statistically significant association with age (Rs 0.06) but S. Stercoralis infection intensity by qPCR cycle threshold was higher in pre-school aged children (Rs = 0.30, p-value 0.03) There was no statistically significant association between STH infection and anaemia (OR 1.0 p = 0.8), stunting (OR 1.9, p-value 0.5) and wasting (OR 2.0, p-value 0.2) in children. This study reveals a persistent reservoir of STH infection across the community, with high rates of anaemia and malnutrition, despite high-coverage of mebendazole mass-drug administration in pre-school children. This reflects the need for a new strategy to soil-transmitted helminth control, to reduce infections and ultimately eliminate transmission., Author summary To date, the overall aim of the WHO policy of STH control through periodic mass-drug administration (MDA) has been morbidity control through a reduction in infection intensity in school-aged children. The main limitation of this approach is the rapid re-infection rate, both from the environment in areas with poor sanitation, and the persistent reservoir in adults who are not included in the MDA programme. As a consequence of this limitation, there have been calls to change the overall aim from morbidity control to the elimination of STH infection altogether by breaking the transmission cycle through community-wide deworming. However, there is a dearth of epidemiological data pertaining to adults in relation to STH and in addition, most surveys exclude the helminth Strongyloides stercoralis, due to limitations of the diagnostic methods used. Our study aims to provide up-to-date epidemiological data of STH prevalence, individual and household risk-factors for infection and the association with anaemia and malnutrition in children under 5 years. From 396 participants who provided a stool sample, we found a high prevalence of STH infection, predominantly the hookworm Ancylostoma duodenale, across all age-groups and both sexes. There was a clear association between STH infection and open defaecation in this study, with use of a protected pit latrine protective against infection. There were high rates of anaemia and malnutrition which had no statistically significant association with STH infection, and are likely multifactorial. This study uncovered an ongoing reservoir of STH infection despite high coverage with mebendazole MDA, high rates of morbidity alongside the STH infection and a clear association between STH infection and inadequate sanitation. This reflects the need for further interventional research to assess the optimum strategy to alleviate morbidity and break the STH transmission cycle in this population.

Importance Inadequate management of elevated blood pressure is a significant contributing factor to maternal deaths. The role of blood pressure self-monitoring in pregnancy in improving clinical outcomes for the pregnant individual and infant is unclear. Objective To evaluate the effect of blood pressure self-monitoring, compared with usual care alone, on blood pressure control and other related maternal and infant outcomes, in individuals with pregnancy hypertension. Design, Setting, and Participants Unblinded, randomized clinical trial that recruited between November 2018 and September 2019 in 15 hospital maternity units in England. Individuals with chronic hypertension (enrolled up to 37 weeks’ gestation) or with gestational hypertension (enrolled between 20 and 37 weeks’ gestation). Final follow-up was in May 2020. Interventions Participants were randomized to either blood pressure self-monitoring using a validated monitor and a secure telemonitoring system in addition to usual care (n = 430) or to usual care alone (n = 420). Usual care comprised blood pressure measured by health care professionals at regular antenatal clinics. Main Outcomes and Measures The primary maternal outcome was the difference in mean systolic blood pressure recorded by health care professionals between randomization and birth. Results Among 454 participants with chronic hypertension (mean age, 36 years; mean gestation at entry, 20 weeks) and 396 with gestational hypertension (mean age, 34 years; mean gestation at entry, 33 weeks) who were randomized, primary outcome data were available from 444 (97.8%) and 377 (95.2%), respectively. In the chronic hypertension cohort, there was no statistically significant difference in mean systolic blood pressure for the self-monitoring groups vs the usual care group (133.8 mm Hg vs 133.6 mm Hg, respectively; adjusted mean difference, 0.03 mm Hg [95% CI, −1.73 to 1.79]). In the gestational hypertension cohort, there was also no significant difference in mean systolic blood pressure (137.6 mm Hg compared with 137.2 mm Hg; adjusted mean difference, −0.03 mm Hg [95% CI, −2.29 to 2.24]). There were 8 serious adverse events in the self-monitoring group (4 in each cohort) and 3 in the usual care group (2 in the chronic hypertension cohort and 1 in the gestational hypertension cohort). Conclusions and Relevance Among pregnant individuals with chronic or gestational hypertension, blood pressure self-monitoring with telemonitoring, compared with usual care, did not lead to significantly improved clinic-based blood pressure control. Trial Registration ClinicalTrials.gov Identifier: NCT03334149

ObjectivesTo assess the scale of ethnic inequalities in severe maternal morbidity (SMM) rates and quantify the contribution of maternal characteristics to these disparities.DesignRetrospective cohort study.SettingWhole-of-population linked administrative data from 2002 to 2015 in Western Australia.ParticipantsWomen with 410 043 birth events (includes all births from the same pregnancy) of 20 weeks’ or more gestation, including terminations for congenital anomalies.Primary and secondary outcome measuresWomen with SMM were identified based on a composite indicator of SMM using diagnosis and procedure codes developed for use in routinely collected data. Mothers were classified into seven ethnic groups, based on their reported ethnic origin. The associations between maternal ethnic origin and SMM were examined using a log-binomial model, which estimates risk ratios (RRs) and 95% CIs. The Blinder-Oaxaca decomposition technique was employed to partition the disparity in SMM between Aboriginal and Caucasian populations into ‘explained’ and ‘unexplained’ components.ResultsDuring the study period, 9378 SMM cases were documented. In the adjusted model, Aboriginal (RR 1.73, 95% CI 1.59 to 1.87), African (RR 1.64, 95% CI 1.43 to 1.89) and ‘other’ ethnicity (RR 1.49, 95% CI 1.37 to 1.63) women were at significantly higher risk of SMM compared with Caucasian women. Teenage and older mothers and socioeconomically disadvantaged women were also at greater risk of SMM. Differences in sociodemographic characteristics explained 33.2% of the disparity in SMM between Aboriginal and Caucasian women.ConclusionsThere are distinct disparities in SMM by ethnicity in Western Australia, with a greater risk among Aboriginal and African women. While improvements in SES and a reduction in teenage pregnancy can potentially support a sizeable reduction in SMM rate inequalities, future research should investigate other potential pathways and targeted interventions to close the ethnicity disparity.

Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) concentration n 3250) of Australian Aboriginal and Torres Strait Islander adults aged ≥18 years. We used data from the 2012–2013 Australian Aboriginal and Torres Strait Islander Health Survey (AATSIHS). Serum 25(OH)D concentrations were measured by liquid chromatography-tandem MS. Survey-weighted logistic regression models were used to determine the independent predictors of vitamin D deficiency. Approximately 27 % of adult AATSIHS participants were vitamin D deficient. Vitamin D deficiency was more prevalent in remote areas (39 %) than in non-remote areas (23 %). Independent predictors of vitamin D deficiency included assessment during winter (men, adjusted OR (aOR) 5·7; 95 % CI 2·2, 14·6; women, aOR 2·2; 95 % CI 1·3, 3·8) and spring (men, aOR 3·3; 95 % CI 1·4, 7·5; women, aOR 2·6; 95 % CI 1·5, 4·5) compared with summer, and obesity (men, aOR 2·6; 95 % CI 1·2, 5·4; women, aOR 4·3; 95 % CI 2·8, 6·8) compared with healthy weight. Statistically significant associations were evident for current smokers (men only, aOR 2·0; 95 % CI 1·2, 3·4), remote-dwelling women (aOR 2·0; 95 % CI 1·4, 2·9) and university-educated women (aOR 2·4; 95 % CI 1·2, 4·8). Given the high prevalence of vitamin D deficiency in this population, strategies to maintain adequate vitamin D status through safe sun exposure and dietary approaches are needed.

Background In the absence of treatment, endometrial hyperplasia (EH) can progress to endometrial cancer, particularly in the presence of histologic nuclear atypia. The development of EH results from exposure of the endometrium to oestrogen unopposed by progesterone. Oral progestogens have been used as treatment for EH without atypia, and in some cases of EH with atypia in women who wish to preserve fertility or who cannot tolerate surgery. EH without atypia is associated with a low risk of progression to atypia and cancer; EH with atypia is where the cells are structurally abnormal, and has a higher risk of developing cancer. Oral progestogen is not always effective at reversing the hyperplasia, can be associated with side effects, and depends on patient adherence. The levonorgestrel-intrauterine system (LNG-IUS) is an alternative method of administration of progestogen and may have some advantages over non-intrauterine progestogens. Objectives To evaluate the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in women with endometrial hyperplasia (EH) with or without atypia compared to medical treatment with non-intrauterine progestogens, placebo, surgery or no treatment. Search methods We searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO, and conference proceedings of 10 relevant organisations. We handsearched references in relevant published studies. We also searched ongoing trials in ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, and other trial registries. We performed the final search in May 2020. Selection criteria Randomised controlled trials (RCTs) and cross-over trials of women with a histological diagnosis of endometrial hyperplasia with or without atypia comparing LNG-IUS with non-intrauterine progestogens, placebo, surgery or no treatment. Data collection and analysis Two review authors independently performed study selection, risk of bias assessment and data extraction. Our primary outcome measures were regression of EH and adverse effects associated with the LNG-IUS device (such as pelvic inflammatory disease, device expulsion, uterine perforation) when compared to treatment with non-intrauterine progestogens, placebo, surgery or no treatment. Secondary outcomes included hysterectomy, hormone-related adverse effects (such as bleeding/spotting, pelvic pain, breast tenderness, ovarian cysts, weight gain, acne), withdrawal from treatment due to adverse effects, satisfaction with treatment, and cost or resource use. We rated the overall quality of evidence using GRADE methods. Main results Thirteen RCTs (1657 women aged 22 to 75 years) met the inclusion criteria. Two studies had insufficient data for meta-analysis, thus the quantitative analysis included 11 RCTs. All trials evaluated treatment duration of six months or less. The evidence ranged from very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding and poor reporting of study methods), inconsistency and imprecision. LNG-IUS versus non-intrauterine progestogens Primary outcomes Regression of endometrial hyperplasia The LNG-IUS probably improves regression of EH compared with non-intrauterine progestogens at short-term follow-up (up to six months) (OR 2.94, 95% CI 2.10 to 4.13; I² = 0%; 10 RCTs, 1108 participants; moderate-quality evidence). This suggests that if regression of EH following treatment with a non-intrauterine progestogen is assumed to be 72%, regression of EH following treatment with LNG-IUS would be between 85% and 92%. Regression of EH may be improved by LNG-IUS compared with non-intrauterine progestogens at long-term follow-up (12 months) (OR 3.80, 95% CI 1.75 to 8.23; 1 RCT, 138 participants; low-quality evidence), Adverse effects associated with LNG-IUS There was insufficient evidence to determine device-related adverse effects; only one study reported on expulsion with insufficient data for analysis. Secondary outcomes The LNG-IUS may be associated with fewer hysterectomies (OR 0.26, 95% CI 0.15 to 0.46; I² = 19%; 4 RCTs, 452 participants; low-quality evidence), fewer withdrawals from treatment due to hormone-related adverse effects (OR 0.41, 95% CI 0.12 to 1.35; I² = 0%; 4 RCTs, 360 participants; low-quality evidence) and improved patient satisfaction with treatment (OR 5.28, 95% CI 2.51 to 11.10; I² = 0%; 2 RCTs, 202 participants; very low-quality evidence) compared to non-intrauterine progestogens. The LNG-IUS may be associated with more bleeding/spotting (OR 2.13, 95% CI 1.33 to 3.43; I² = 78%; 3 RCTs, 428 participants) and less nausea (OR 0.52, 95% CI 0.28 to 0.95; I² = 0%; 3 RCTs, 428 participants) compared to non-intrauterine progestogens. Data from single trials for mood swings and fatigue had a similar direction of effect as for bleeding/spotting, nausea and weight gain. There was insufficient evidence to determine cost or resource use. LNG-IUS versus no treatment Regression of endometrial hyperplasia One study demonstrated that the LNG-IUS is associated with regression of EH without atypia (OR 78.41, 95% CI 22.86 to 268.97; I² = 0%; 1 RCT, 190 participants; moderate-quality evidence) compared with no treatment. This study did not report on any other review outcome. Authors' conclusions There is moderate-quality evidence that treatment with LNG-IUS used for three to six months is probably more effective than non-intrauterine progestogens at reversing EH in the short term (up to six months) and long term (up to two years). Adverse effects (device-related and hormone-related) were poorly and incompletely reported across studies. Very low quality to low-quality evidence suggests the LNG-IUS may reduce the risk of hysterectomy, and may be associated with more bleeding/spotting, less nausea, less withdrawal from treatment due to adverse effects, and increased satisfaction with treatment, compared to non-intrauterine progestogens. There was insufficient evidence to reach conclusions regarding device-related adverse effects, or cost or resource use.

Evidence about the association between maternal mental health disorders and stillbirth and infant mortality is limited and conflicting. We aimed to examine whether maternal prenatal mental health disorders are associated with stillbirth and/or infant mortality. MEDLINE, Embase, PsycINFO, and Scopus were searched for studies examining the association of any maternal prenatal (occurring before or during pregnancy) mental health disorder(s) and stillbirth or infant mortality. A random-effects meta-analysis was used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). The between-study heterogeneity was quantified using the I

Background and Purpose: Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the CYP2C19 gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function CYP2C19 alleles and outcome by treatment group in POINT. Methods: Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for CYP2C19 *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death. Results: Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09–1.21]; P =0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32–1.34]; P =0.25) among noncarriers. There was no significant interaction by genotype for major ischemia ( P =0.36) or stroke ( P =0.33). Conclusions: This substudy of POINT found no significant interaction with CYP2C19 loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00991029.

IntroductionMaternal mental health disorders such as anxiety and depression are major public health concerns. Evidence shows a link between maternal mental health disorders and preterm birth and low birth weight. However, the impacts of maternal mental health disorders on stillbirth and infant mortality have been less investigated and inconsistent findings have been reported. Thus, using the available literature, we plan to examine whether prenatal maternal mental health disorders impact the risk of stillbirth and infant mortality.Methods and analysisThis systematic review and meta-analysis will adhere to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and will be registered with the International Prospective Register of Systematic Reviews. Systematic searches will be conducted (from database inception to December 2019) in Medline, Embase, PsycINFO and Scopus for studies examining the association of prenatal mental health disorders and stillbirth and infant mortality. The search will be limited to studies published in English language and in humans only, with no restriction on the year of publication. Two independent reviewers will evaluate records and assess the quality of individual studies. The Newcastle–Ottawa scales and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach will be used to assess the methodological quality and bias of the included studies. In addition to a narrative synthesis, a random-effects meta-analysis will be conducted when sufficient data are available. I2 statistics will be used to assess between-study heterogeneity in the estimated effect size.Ethics and disseminationAs it will be a systematic review and meta-analysis based on previously published evidence, there will be no requirement for ethical approval. Findings will be published in a peer-reviewed journal and will be presented at various conferences.PROSPERO registration number159834.

We present the case of a patient admitted to hospital in septic shock. He had a history of tricuspid valve infective endocarditis (IE) 6 months prior and regularly injected intravenous drugs. A bedside echo on arrival confirmed vegetations on his tricuspid valve, torrential tricuspid regurgitation and signs of significantly raised right-sided pressures. The admission chest radiograph showed consolidative changes in the lungs, suggestive of septic pulmonary emboli. He was commenced on antibiotics and treated in the high-dependency unit. He subsequently developed an acutely ischaemic right foot and nasal tip. Suspicions were raised of a paradoxical septic embolus through a right-to-left shunt, subsequently confirmed on bubble echo which showed passage of agitated saline between the atria. This was not apparent clinically or on echocardiogram during his previous episode of tricuspid valve IE, raising the possibility of the development of an acquired inter-atrial communication since his previous episode.

Background A combination of safety concerns and labeling changes impacted use of erythropoiesis-stimulating agents (ESAs) in renal anemia. Data regarding contemporary utilization in pre-dialysis chronic kidney disease (CKD) are lacking. Methods Electronic healthcare records and medical claims data of pre-dialysis CKD patients were aggregated from a large US managed care provider (2011–13). ESA use patterns, characteristics, and outcomes of ESA-treated/untreated patients were quantified. Results At baseline, 109/32,308 patients (0.3%) were ESA users. Treated patients were older, had more advanced CKD (58.8% vs 5.4% with stage 4/5 vs 3) and greater prevalence of comorbid diabetes, hypertension, heart failure, and peripheral vascular disease. An additional 266 patients initiated ESA: hemoglobin at initiation was 8–10 g/dL in 193 of these and >10 g/dL in the remainder; 61.7% had stage 4/5 CKD; prevalence of cardiovascular disease was high (50.8% heart failure; 25.2% prior myocardial infarction; 24.1% prior stroke). During follow-up, rates of death and cardiovascular events were higher in baseline ESA users and ESA naives versus non-users. Conclusions ESA use in pre-dialysis CKD patients was exceedingly rare and directed disproportionately to older, sicker patients; these patients had high rates of death and cardiovascular events. These data provide context for contemporary use of ESA in pre-dialysis CKD. Electronic supplementary material The online version of this article (10.1186/s12882-018-0925-2) contains supplementary material, which is available to authorized users.