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Aims: The authors share their early experiences of developing and implementing a telehealth service for patients with chronic obstructive pulmonary disease (COPD), through a collaborative approach. The article will explore the process of implementing telehealth service in a local care community team, identifying opportunities for improving care delivery and person-centred care. Discussion: The initial feedback and thoughts of both patients and healthcare professionals were obtained. Such feedback included patient’s health insights, which helped improve risk assessment and personalised parameter settings. Conclusions: To-date, there has been a lack of robust evidence for the clinical benefits of telehealth. However, the feedback from staff and patients using telehealth was positive in several areas. Person-centred care plans also helped provide greater insight into patient’s health goals, thereby streamlining care.

The Met Office in the United Kingdom has developed a completely new probabilistic postprocessing system called IMPROVER to operate on outputs from its operational numerical weather prediction (NWP) forecasts and precipitation nowcasts. The aim is to improve weather forecast information to the public and other stakeholders while better exploiting the current and future generations of underpinning kilometer-scale NWP ensembles. We wish to provide seamless forecasts from nowcasting to medium range, provide consistency between gridded and site-specific forecasts, and be able to verify every stage of the processing. The software is written in a modern modular framework that is easy to maintain, develop, and share. IMPROVER allows forecast information to be provided with greater spatial and temporal detail and a faster update frequency than previous postprocessing. Independent probabilistic processing chains are constructed for each meteorological variable consisting of a series of processing stages that operate on predefined grids and blend outputs from several NWP inputs to give a frequently updated, probabilistic forecast solution. Probabilistic information is produced as standard, with the option of extracting a most likely or yes–no outcome if required. Verification can be performed at all stages, although it is only currently switched on for the most significant stages when run in real time. IMPROVER has been producing real-time output since March 2021 and became operational in spring 2022.

Childhood steroid-sensitive nephrotic syndrome is a frequently relapsing disease with significant short- and long-term complications, leading to high healthcare costs and reduced quality of life for patients. The majority of relapses are triggered by upper respiratory tract infections (URTIs) and evidence shows that daily low-dose prednisolone at the time of infection may reduce the risk of relapse.The aim of this study was to assess the cost effectiveness of a 6-day course of low-dose prednisolone at the start of a URTI when compared with placebo.A state-transition Markov model was developed to conduct a cost-utility analysis with the outcome measured in quality-adjusted life-years (QALYs). Resource use and outcome data were derived from the PREDNOS2 trial. The analysis was performed from a UK National Health Service perspective and the results were extrapolated to adulthood. Model parameter and structural uncertainty were assessed using sensitivity analyses.The base-case results showed that administering low-dose prednisolone at the time of a URTI generated more QALYs and a lower mean cost at 1 year compared with placebo. In the long-term, low-dose prednisolone was associated with a cost saving (£176) and increased effectiveness (0.01 QALYs) compared with placebo and thus remained the dominant treatment option. These findings were robust to all sensitivity analyses.A 6-day course of low-dose prednisolone at the time of a URTI in children with steroid-sensitive nephrotic syndrome has the potential to reduce healthcare costs and improve quality of life compared with placebo.

Background Most children with steroid-sensitive nephrotic syndrome have relapses that are triggered by upper respiratory tract infections. Four small trials, mostly in children already taking maintenance corticosteroid in countries of different upper respiratory tract infection epidemiology, showed that giving daily low-dose prednisone/prednisolone for 5–7 days during an upper respiratory tract infection reduces the risk of relapse. Objectives To determine if these findings were replicated in a large UK population of children with relapsing steroid-sensitive nephrotic syndrome on different background medication or none. Design A randomised double-blind placebo-controlled trial, including a cost-effectiveness analysis. Setting A total of 122 UK paediatric departments, of which 91 recruited patients. Participants A total of 365 children with relapsing steroid-sensitive nephrotic syndrome (mean age 7.6 ± 3.5 years) were randomised (1 : 1) according to a minimisation algorithm based on background treatment. Eighty children completed 12 months of follow-up without an upper respiratory tract infection. Thirty-two children were withdrawn from the trial (14 prior to an upper respiratory tract infection), leaving a modified intention-to-treat analysis population of 271 children (134 and 137 children in the prednisolone and placebo arms, respectively). Interventions At the start of an upper respiratory tract infection, children received 6 days of prednisolone (15 mg/m2) or an equivalent dose of placebo. Main outcome measures The primary outcome was the incidence of first upper respiratory tract infection-related relapse following any upper respiratory tract infection over 12 months. The secondary outcomes were the overall rate of relapse, changes in background treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, change in Achenbach Child Behaviour Checklist score and quality of life. Analysis was by intention-to-treat principle. The cost-effectiveness analysis used trial data and a decision-analytic model to estimate quality-adjusted life-years and costs at 1 year, which were then extrapolated over 16 years. Results There were 384 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the prednisolone arm, and 407 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms, respectively (adjusted risk difference –0.024, 95% confidence interval –0.14 to 0.09; p = 0.70). There was no evidence that the treatment effect differed when data were analysed according to background treatment. There were no significant differences in secondary outcomes between treatment arms. Giving daily prednisolone at the time of an upper respiratory tract infection was associated with increased quality-adjusted life-years (0.9427 vs. 0.9424) and decreased average costs (£252 vs. £254), when compared with standard care. The cost saving was driven by background therapy and hospitalisations after relapse. The finding was robust to sensitivity analysis. Limitations A larger number of children than expected did not have an upper respiratory tract infection and the sample size attrition rate was adjusted accordingly during the trial. Conclusions The clinical analysis indicated that giving 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of steroid-sensitive nephrotic syndrome in UK children. However, there was an economic benefit from costs associated with background therapy and relapse, and the health-related quality-of-life impact of having a relapse. Future work Further work is needed to investigate the clinical and health economic impact of relapses, interethnic differences in treatment response, the effect of different corticosteroid regimens in treating relapses, and the pathogenesis of individual viral infections and their effect on steroid-sensitive nephrotic syndrome. Trial registration Current Controlled Trials ISRCTN10900733 and EudraCT 2012-003476-39. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 3. See the NIHR Journals Library website for further project information.

Background Residual malaria transmission is the result of adaptive mosquito behavior that allows malaria vectors to thrive and sustain transmission in the presence of good access to bed nets or insecticide residual spraying. These behaviors include crepuscular and outdoor feeding as well as intermittent feeding upon livestock. Ivermectin is a broadly used antiparasitic drug that kills mosquitoes feeding on a treated subject for a dose-dependent period. Mass drug administration with ivermectin has been proposed as a complementary strategy to reduce malaria transmission. Methods A cluster randomized, parallel arm, superiority trial conducted in two settings with distinct eco-epidemiological conditions in East and Southern Africa. There will be three groups: human intervention, consisting of a dose of ivermectin (400 mcg/kg) administered monthly for 3 months to all the eligible population in the cluster (>15 kg, non-pregnant and no medical contraindication); human and livestock intervention, consisting human treatment as above plus treatment of livestock in the area with a single dose of injectable ivermectin (200 mcg/kg) monthly for 3 months; and controls, consisting of a dose of albendazole (400 mg) monthly for 3 months. The main outcome measure will be malaria incidence in a cohort of children under five living in the core of each cluster followed prospectively with monthly RDTs Discussion The second site for the implementation of this protocol has changed from Tanzania to Kenya. This summary presents the Mozambique-specific protocol while the updated master protocol and the adapted Kenya-specific protocol undergo national approval in Kenya. BOHEMIA will be the first large-scale trial evaluating the impact of ivermectin-only mass drug administration to humans or humans and cattle on local malaria transmission Trial registration ClinicalTrials.govNCT04966702. Registered on July 19, 2021. Pan African Clinical Trials Registry PACTR202106695877303.

Although guidelines can reduce postoperative opioid prescription, the problem of unused opioids persists. We assessed the pattern of opioid prescription and utilization after total hip arthroplasty (THA) and total knee arthroplasty (TKA). We hypothesized that opioid prescription patterns can influence opioid utilization.With institutional ethics approval, patients undergoing THA and TKA were enrolled prospectively. Surveys on opioid use were completed at two, six, and 12 weeks after surgery. Patients' age, sex, American Society of Anesthesiologists' Physical Status score, first 24-hr opioid consumption, quantity of opioid prescribed, and quantity of opioid utilized were analyzed to evaluate their effect on opioid consumption, unused opioid, and patient satisfaction.Patients received prescriptions ranging from 200 morphine milligram equivalents (MME) to 800 MME. Three hundred and thirty THA and 230 TKA patients completed the surveys. Opioid utilization was influenced by the amount of prescribed opioids for both THA and TKA. The percentage of prescribed opioids used (~55% in THA and ~75% in TKA) and the proportion of patients using all prescribed opioids (~22% in THA and ~50% in TKA) were higher after TKA vs THA (P0.001 for both). Patients who used opioids for two days or less accounted for most (~50%) of the unused opioid. Patient satisfaction remained high and was not influenced by the amount of prescribed opioid.This study showed that larger prescriptions are associated with higher opioid consumption. A wide variation in opioid consumption requires approaches to minimize the initial opioid prescription and to provide additional prescriptions for patients that require higher levels of analgesia.RéSUMé: OBJECTIF: Bien que les lignes directrices puissent réduire la prescription d’opioïdes postopératoires, le problème des opioïdes inutilisés persiste. Nous avons évalué les schémas de prescription et d’utilisation d’opioïdes après une arthroplastie totale de la hanche (ATH) et une arthroplastie totale du genou (ATG). Nous avons émis l’hypothèse que les schémas de prescription d’opioïdes pouvaient influencer l’utilisation des opioïdes. MéTHODE: Avec l’approbation du comité d’éthique de notre établissement, les patients bénéficiant d’une ATH et une ATG ont été recrutés de manière prospective. Les questionnaires sur la consommation d’opioïdes ont été complétés deux, six et 12 semaines après la chirurgie. L’âge, le sexe et le score de statut physique selon l’American Society of Anesthesiologists des patients, ainsi que la consommation d’opioïdes au cours des premières 24 heures postopératoires, la quantité d’opioïdes prescrits et la quantité d’opioïdes utilisés ont été analysés pour évaluer leur effet sur la consommation d’opioïdes, les opioïdes inutilisés et la satisfaction des patients. RéSULTATS: Les patients ont reçu des ordonnances allant de 200 équivalents de morphine en milligrammes (EMM) à 800 EMM. Trois cent trente patients bénéficiant d’une ATH et 230 patients d’une ATG ont répondu aux questionnaires. L’utilisation des opioïdes a été influencée par la quantité d’opioïdes prescrits pour l’ATH et l’ATG. Le pourcentage d’opioïdes prescrits utilisés (~55 % dans l’ATH et ~75 % dans l’ATG) et la proportion de patients utilisant tous les opioïdes prescrits (~22 % dans l’ATH et ~50 % dans l’ATG) étaient plus élevés après l’ATG vs l’ATH (P0,001 pour les deux). Les patients qui ont utilisé des opioïdes pendant deux jours ou moins étaient à l’origine de la plupart (~ 50%) des opioïdes inutilisés. La satisfaction des patients est demeurée élevée et n’a pas été influencée par la quantité d’opioïdes prescrits. CONCLUSION: Cette étude a démontré que les ordonnances plus élevées sont associées à une consommation plus élevée d’opioïdes. Une grande variation dans la consommation d’opioïdes nécessite des approches visant à minimiser la prescription initiale d’opioïdes et à fournir des ordonnances supplémentaires aux patients qui nécessitent des niveaux plus élevés d’analgésie.

Published online: 06 Oct 2021. Purpose: The Australian English Communicative Development Inventory (OZI) is a 558-item parent report tool for assessing language development at 12–30 months. Here, we introduce the short form (OZI-SF), a 100-item, picture-supported, online instrument with substantially lower time and literacy demands. Method: In tool development (Study 1), 95 items were drawn from the OZI to match its item distribution by age of acquisition and semantic categories. Five items were added from four other semantic categories, plus 12 gestures and six games/routines. Simulations computed OZI-SF scores from existing long-form OZI norm data, and OZI and projected OZI-SF scores were correlated. In an independent norming sample (Study 2), parents (n¼230) completed the OZI-SF for their children aged 12–30 months. Child scores were analysed by age and sex. Result: OZI-SF and OZI scores correlate highly across age and language development levels. Vocabulary scores (receptive, expressive) correlate with age and the median for girls is higher until 24 months. By 24 months, 50% of the sample combine words “often”. The median time to OZI-SF completion was 12 minutes. Conclusion: Fitted percentiles permit working guidelines for typical (median) performance and lower cut-offs for children who may be behind on age-based expectations and/or at risk for a communication difficulty. The OZI-SF is a short-form of the OZI that has promise for research and clinical/educational use with Australian families. This work was supported by the Australian Research Council Centre of Excellence for the Dynamics of Language (ARC CoEDL, CE140100041).

Characterizing older adult engagement is important to determine the effectiveness of interventions. Engagement refers to the occupying of oneself in external stimuli and is observable across multiple dimensions of behavior. Engagement of older adults is commonly investigated using a single behavioral dimension. There is a dearth of analytical methods that can simultaneously quantify both verbal and non-verbal forms of communication as proxies for engagement. In this article, we present a multidimensional technique to measure engagement of older adults using techniques appropriate for people with varying degrees of dementia. The new analytical approach measures facial movement, lexical use, and prosodic patterns of speech as indices of affective and behavioral outcomes of engagement. Contexts for engagement included a dyadic reminiscence therapy interview and a 12-week technology-driven group reminiscence therapy. Illustrative examples of the technique are described by two participants from two different groups in a naturalistic setting. Application of these analytical techniques can enhance measurement precision and further develop the science and evidence base, especially for, but not confined to, non-pharmacological interventions.

Credited with averting almost 68% of new cases between 2000 and 2015, insecticide-treated bednets (ITNs) are one of the most efficacious malaria-prevention tools. Their effectiveness, however, depends on if and how they are used, making 'compliance' (and the social factors affecting it) a key area of interest for research on malaria transmission. This article situates the notion of compliance with 'bednet use' within everyday practices in an area of south-west Burkina Faso with high malaria transmission. By drawing on ethnographic fieldwork conducted between 2017 and 2018, it critically describes the precarious micro-environments that foreground bednet use-from gender and age to the means of (re)production of social and labour conditions-and assesses the bednets' effectiveness and community uptake. Bednet use stems from concrete, ordinary dynamics that interweave only apparently at the margins of the time individuals most need to be protected by a net. This work conceptualises 'compliance' beyond binary indicators of intervention uptake and locates 'use' as the result of contingent assemblages.

Purpose: Research on fiscal implications of the bundled care (BC) model exist; however, patient-perceived experiences are less well known. As BC expands in Ontario, this study aims to examine these experiences with physiotherapy care within the total knee replacement (TKR) BC program. Methods: Qualitative cross-sectional study design. Semi-structured one-on-one telephone interviews were conducted with eight patients four to six weeks post-TKR. Thematic analysis was used. Results: This exploratory study identified three themes across the care journey that patients perceived as influencing their physiotherapy experiences: timely access to physiotherapy care, quality of physiotherapy care, and patient outcomes. Communication, clinical support, and social support were sub-themes. Conclusions: Patients’ overall experiences with BC physiotherapy were positive. Areas for improvement included coordination of postoperative physiotherapy and return-to-work support. Patients valued group settings and were interested in meeting previous TKR patients. Health system planners are advised to consider incorporating patient experiences when evaluating and developing BC programs to achieve patient-centred outcomes.

BackgroundThe 2013 WHO guidelines for nutritional rehabilitation of malnourished infants under six months (u6m) focus on inpatient re-establishment of exclusive breastfeeding and recommends discharge when infant is gaining weight on breastmilk alone. Guided by a breastfeeding support tool, breastfeeding peer supporters (BFPS) can support implementation of these guideline by providing continuous individualised breastfeeding counselling to mothers of malnourished infants u6m. Recording and sharing information plays an important role in shaping in-patient care but little is known about recording practices for inpatient nutrition rehabilitation of infants u6m or how such practices affect care. We set out to explore introduction of BFPS into hospitals, and how it shaped the recording and practices of care for acutely malnourished infants u6m.MethodsWe applied a descriptive, exploratory design involving a pre and during intervention audit of the infant u6m inpatient records in two hospitals in Kenya, as well as pre- and post-intervention in-depth interviews with health workers involved in the care of admitted infants u6m. We developed an audit tool and used it to extract routine data on patient information from hospital records. Data were entered into a REDCap database and analyzed using STATA 17.0 software. We conducted thirty in-depth interviews with health workers exploring their care practices and their perceived effect of the presence of the BFPS on health workers treatment practices. We analysed interview data using thematic framework approach.ResultsA total of 170 and 65 inpatient files were available for the audit during the pre- and post-intervention period respectively. The presence of the BFPS seemed to have encouraged the recording of (i) breastfeeding status upon admission, (ii) breastfeeding management plan and (iii) reporting of its implementation and progress during treatment. The breastfeeding peer support intervention had a positive impact on breastfeeding recording and reporting practices. Health workers reported that the BFPS facilitated the recording of observed breastfeeding data and how their records influenced final inputs of breastfeeding support provided in the inpatient file.ConclusionsGuideline implementation tools facilitate effective application of guidelines and should accompany any guideline formulation process and have their effectiveness at recording and monitoring progress evaluated.

The epidemic that was a result of the Coronavirus (Cupples, 2019) began in China towards the end of 2019 and has quickly spread throughout the world. To minimize the spread of the virus and keep it as contained as possible, many countries have required residents to quarantine. This epidemic has been a major concern for students of all ages, especially college students. Students that attend universities have been affected more profoundly due to the close quarters of dorms, fraternities, sororities, and close classroom contact. Due to the contagiousness of the virus and the fact that many who are positive can be asymptomatic hundreds can be affected quickly. The pandemic has forced many students to quarantine themselves. This requires that they not leave their homes, rooms, and apartment for a period of up to 14 days. The purpose of this research was to assess how COVID has affected college students and how it has affected their eating habits and lifestyle habits.

Aims Sudden cardiac death (SCD) is the most common mode of death in paediatric hypertrophic cardiomyopathy (HCM). This study describes the implant and programming strategies with clinical outcomes following implantable cardioverter-defibrillator (ICD) insertion in a well-characterized national paediatric HCM cohort. Methods and results Data from 90 patients undergoing ICD insertion at a median age 13 (±3.5) for primary (n = 67, 74%) or secondary prevention (n = 23, 26%) were collected from a retrospective, longitudinal multi-centre cohort of children ( Conclusion In a large national cohort of paediatric HCM patients with an ICD, device and programming strategies varied widely. No particular strategy was associated with inappropriate therapies, missed/delayed therapies, or lead complications.

Many Aboriginal and Torres Strait Islander children are affected by chronic middle ear infection or otitis media from infancy that has a negative impact on development of listening and communicatio...

This article is the fourth in a series introducing the reader to methods and theories relevant to advancing socio‐legal research. They are written for the curious rather than the expert reader and provide illustrations of how the theories, methods, and frameworks have been employed and might be used in your work. This article explores the use of case biography methods for socio‐legal studies. Drawing on ‘paths to justice’ studies, network analysis, and legal archaeology, we develop a case study of AC v.Berkshire West Primary Care Trust. We show how the judicial determination of the case suppressed a transgender rights narrative construction of the dispute in favour of one about health care law. Our case biography analysis explores how competing narratives can be traced not only through legal argument and literature, but also through the personnel involved, in ways that are obscured by formal records. Paying attention to biographical features leads to a richer understanding of cases, including the importance of pre‐ and post‐judicial decision‐making aspects.

Recessive mutations in diacylglycerol kinase epsilon (DGKE) display genetic pleiotropy, with pathological features reported as either thrombotic microangiopathy or membranoproliferative glomerulonephritis (MPGN), and clinical features of atypical hemolytic uremic syndrome (aHUS), nephrotic syndrome or both. Pathophysiological mechanisms and optimal management strategies have not yet been defined. In prospective and retrospective studies of aHUS referred to the United Kingdom National aHUS service and prospective studies of MPGN referred to the National Registry of Rare Kidney Diseases for MPGN we defined the incidence of DGKE aHUS as 0.009/million/year and so-called DGKE MPGN as 0.006/million/year, giving a combined incidence of 0.015/million/year. Here, we describe a cohort of sixteen individuals with DGKE nephropathy. One presented with isolated nephrotic syndrome. Analysis of pathological features reveals that DGKE mutations give an MPGN-like appearance to different extents, with but more often without changes in arterioles or arteries. In 15 patients presenting with aHUS, ten had concurrent substantial proteinuria. Identified triggering events were rare but coexistent developmental disorders were seen in six. Nine with aHUS experienced at least one relapse, although in only one did a relapse of aHUS occur after age five years. Persistent proteinuria was seen in the majority of cases. Only two individuals have reached end stage renal disease, 20 years after the initial presentation, and in one, renal transplantation was successfully undertaken without relapse. Six individuals received eculizumab. Relapses on treatment occurred in one individual. In four individuals eculizumab was withdrawn, with one spontaneously resolving aHUS relapse occurring. Thus we suggest that DGKE-mediated aHUS is eculizumab non-responsive and that in individuals who currently receive eculizumab therapy it can be safely withdrawn. This has important patient safety and economic implications., Graphical abstract

The tumor microenvironment plays a critical role in the proliferation and chemoresistance of cancer cells. Growth factors (GFs) are known to interact with the extracellular matrix (ECM) via heparin binding sites, and these associations influence cell behavior. In the present study, we demonstrate the ability to define signals presented by the scaffold by pre-mixing growth factors, such as epidermal growth factor, into the heparin-based (HP-B) hydrogel prior to gelation. In the 3D biomimetic microenvironment, breast cancer cells formed spheroids within 24 hours of initial seeding. Despite higher number of proliferating cells in 2D cultures, 3D spheroids exhibited a higher degree of chemoresistance after 72 hours. Further, our RNA sequencing results highlighted the phenotypic changes influenced by solid-phase GF presentation. Wnt/beta-catenin and TGF-beta signaling were upregulated in the cells grown in the hydrogel, while apoptosis, IL2-STAT5 and PI3K-AKT-mTOR signaling were downregulated. With emerging technologies for precision medicine in cancer, this nature of fine-tuning the microenvironment is paramount for cultivation and downstream characterization of primary cancer cells and rare circulating tumor cells (CTCs), and effective screening of chemotherapeutic agents. National Institute of General Medical Sciences of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R35GM133610] We would like to thank Carla Finkielstein for her thoughtful discussions on experimental design and RNA seq data analysis. Research reported in this publication was supported by The National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM133610.

Background The housing stock of rural sub-Saharan Africa is changing rapidly. With millions of new homes required over the coming decades, there is an opportunity to protect residents by screening homes from malaria mosquitoes. This study, undertaken in the Upper River Region of The Gambia, explores local perceptions of what a good house should provide for its inhabitants and responses to living in a house that has been modified as part of a randomized control trial designed to assess whether improved housing provided additional protection against clinical malaria in children (the RooPfs trial). Methods This descriptive, exploratory study was undertaken over 22 months using mixed-methods (informal conversations, observations, focus group discussions, photovoice, and a questionnaire survey) in a parallel convergent design. Analysis was conducted across the data sets using a framework approach. Following coding, the textual data were charted by a priori and emerging themes. These themes were compared with the quantitative survey results. The nature and range of views about housing and the RooPfs study modifications and the relationships among them were identified and described. Results The data were derived from a total of 35 sets of observations and informal conversations in 10 villages, 12 discussions with the photovoice photographers, 26 focus group discussions (across 13 villages) and 391 completed questionnaires. The study participants described a ‘good house’ as one with a corrugate-metal roof, cement walls (preferably cement block, but mud block covered with cement plaster was also an acceptable and cheaper substitute) and well-fitting doors. These features align with local perceptions of a modern house that provides social status and protection from physical harms. The RooPfs modifications were largely appreciated, although poor workmanship caused concerns that houses had become insecure. However, the long-term trusting relationship with the implementing institution and the actions taken to rectify problems provided reassurance and enhanced acceptability. Conclusion In developing housing to address population needs in Africa, attention should be paid to local perceptions of what is required to make a house secure for its inhabitants, as well as providing a healthy environment.

Key Points Question In children with relapsing corticosteroid-sensitive nephrotic syndrome, does daily low-dose corticosteroid given at the time of upper respiratory tract infection prevent upper respiratory tract infection–related relapse? Findings In this randomized clinical trial of 365 children, daily low-dose corticosteroid therapy resulted in no difference in the frequency of upper respiratory tract infection–related relapses compared with placebo. Meaning Results of this study suggest that low-dose corticosteroid treatment is not beneficial as a strategy to prevent upper respiratory tract infection–related relapses., Importance In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an upper respiratory tract infection reduced the risk of relapse, but the generalizability of their findings is limited by location of the studies and selection of study population. Objective To investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection–related relapses. Design, Setting, and Participants This double-blind, placebo-controlled randomized clinical trial (Prednisolone in Nephrotic Syndrome [PREDNOS] 2) evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. Data from the modified intention-to-treat population were analyzed from July 1, 2020, to December 31, 2020. Interventions At the start of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater. Main Outcomes and Measures The primary outcome was the incidence of first upper respiratory tract infection–related relapse. Secondary outcomes included overall rate of relapse, changes in background immunosuppressive treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, and quality of life. Results The modified intention-to-treat analysis population comprised 271 children (mean [SD] age, 7.6 [3.5] years; 174 [64.2%] male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection–related relapse was 56 of 131 (42.7%) in the prednisolone arm and 58 of 131 (44.3%) in the placebo arm (adjusted risk difference, −0.02; 95% CI, −0.14 to 0.10; P = .70). No evidence was found that the treatment effect differed according to background immunosuppressive treatment. No significant differences were found in secondary outcomes between the treatment arms. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40-1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81-1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P = .09). Conclusions and Relevance The results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK. Further work is needed to investigate interethnic differences in treatment response. Trial Registration isrctn.org Identifier: ISRCTN10900733; EudraCT 2012-003476-39, This randomized clinical trial investigates whether a low daily dose of prednisolone in children with relapsing steroid-sensitive nephrotic syndrome prevents upper respiratory tract infection–related relapse.

BACKGROUND Characterising older adult engagement is important to determine the effectiveness of interventions. Engagement is the occupying of oneself in external stimuli and is observable across multiple dimensions of behaviour. Engagement of older adults is commonly investigated on a single behavioural dimension. OBJECTIVE In this article, we present a multidisciplinary approach for measuring and characterising engagement of older adults using techniques appropriate for people with varying degrees of dementia. METHODS Contexts for engagement included a dyadic reminiscence therapy interview and a 12-week technology driven group reminiscence therapy. Participants were older adults (8 female, 1 male, mean age: 79) who attended a day respite facility. Audio-visual recordings of the sessions were processed to analyse facial movement, lexical use, and prosodic patterns of speech. Facial movement was processed using OpenFace to measure the presence and intensity of facial movement. Lexical use was processed using the Linguistic Enquiry and Word Count to measure personal pronoun use, affective word use, and emotional tone of words in speech. Prosodic patterns of speech were processed using custom scripts written in Praat and Python, to measure mean duration of utterances, mean words per utterance, articulation rate and variability of F0. Mixed-effects modelling was used to assess effects of treatment conditions on dependent variable outcomes. RESULTS Results indicate measuring engagement through a multidimensional approach can sensitively capture older adults’ engagement. CONCLUSIONS Application of this method can enhance a researcher’s ability to measure older adult engagement, provide means to compare across interventions and contextual environments, and further develop the science of psychosocial intervention research.

Supplemental Digital Content is available in the text., Background: Purkinje fibers (PFs) control timing of ventricular conduction and play a key role in arrhythmogenesis in heart failure (HF) patients. We investigated the effects of HF on PFs. Methods: Echocardiography, electrocardiography, micro-computed tomography, quantitative polymerase chain reaction, immunohistochemistry, volume electron microscopy, and sharp microelectrode electrophysiology were used. Results: Congestive HF was induced in rabbits by left ventricular volume- and pressure-overload producing left ventricular hypertrophy, diminished fractional shortening and ejection fraction, and increased left ventricular dimensions. HF baseline QRS and corrected QT interval were prolonged by 17% and 21% (mean±SEMs: 303±6 ms HF, 249±11 ms control; n=8/7; P=0.0002), suggesting PF dysfunction and impaired ventricular repolarization. Micro-computed tomography imaging showed increased free-running left PF network volume and length in HF. mRNA levels for 40 ion channels, Ca2+-handling proteins, connexins, and proinflammatory and fibrosis markers were assessed: 50% and 35% were dysregulated in left and right PFs respectively, whereas only 12.5% and 7.5% changed in left and right ventricular muscle. Funny channels, Ca2+-channels, and K+-channels were significantly reduced in left PFs. Microelectrode recordings from left PFs revealed more negative resting membrane potential, reduced action potential upstroke velocity, prolonged duration (action potential duration at 90% repolarization: 378±24 ms HF, 249±5 ms control; n=23/38; P

The UK Inshore Waters Forecast predicts wind speeds, sea states, weather conditions and visibilities for marine areas within 12 nautical miles of the UK coast. In addition to the now-common web-based outlets of most public forecast products, this very high profile forecast product is also broadcast by the BBC on national radio and television. It is the enviable task of Operational Meteorologists, based at UK Met Office sites in Exeter and Aberdeen, to issue these forecasts every six hours for the vitally important purpose of protecting lives in the coastal waters surrounding the UK. Currently, the production process involves a marine forecaster comprehensively inspecting deterministic model fields, prior to manual text generation. However, direct utilisation of an ensemble model-based product has the potential to make this task considerably more efficient and possibly make the forecast more accurate.Raw output from the Met Office Global and Regional Ensemble Prediction System (MOGREPS) is used routinely throughout the Met Office to assist forecasters. Furthermore, a recent project to develop and improve the techniques used to statistically post-process this data (IMPROVER) is now employed to further reduce identified errors within MOGREPS data.This session describes the latest work to exploit both raw MOGREPS and post-processed data for the generation of the wind component to the Inshore Waters Forecast. This component is verified against post-processed nowcast analysis fields to determine its accuracy and the results are compared against the equivalent performance currently achieved by Operational Maritime Meteorologists. The outcome of this assessment will help to determine whether either of these data-sources are suitable as a guide for the production of this high-profile forecast product.

The southwest monsoon rains in 2019 were the heaviest over India in a quarter of a century. The 2019 seasonal JJAS precipitation over the whole country was 110 % of its long period average (LPA) of 880mm. Precipitation is a cumulative field driven by many atmospheric processes both within nature and numerical prediction. It’s a weather variable that impacts everyone’s life and hence is used routinely to assess the skill of modelling systems. In this study, we have analyzed the 2019 JJAS seasonal precipitation forecast skill of two global ensemble models: (1) the UK Met Office GloSea5 and (2) the National Center for Medium Range Weather Forecasting (NCMRWF) Global Ensemble Prediction System (NEPS-G). The Integrated Multi-satellite Retrievals for Global Precipitation Measurement (IMERG-GPM) rainfall and ERA5 winds with high spatial resolution and temporal data are used for verification of the model forecasts across a seamless range of time scales. In order to compare a seamless range of time scales, we have summed forecast fields over time windows of forecast lead time from 1 day to 2 weeks. We also computed the actual skill and potential skill of the model ensemble forecasts at different lead windows. Our results for both models show large precipitation biases and reduced precipitation skills with forecast lead windows. We also found that the models’ actual and potential skill are sensitive to the number of ensemble members and type of ensemble generation. Moreover, the GloSea5 model actual skill is higher than the NEPS-G model over Indian homogeneous regions. To use the GloSea5 NWP forecast model ensemble members for more quantitative applications in downstream hazard and/or impact-based modelling and applications the between-ensemble-member bias introduced by the lagging needs to be addressed.

Cytomegalovirus (CMV) reactivation remains a serious complication after allogeneic hematopoietic cell transplantation (HCT) occurring in approximately 60-70% of CMV-seropositive HCT recipients. CMV reactivation leads to adverse outcomes including end-organ damage, graft-versus-host disease, and graft failure.Ganciclovir was administered pretransplant at 5 mg/kg twice daily intravenously from the start of conditioning to Day T-2 to CMV-seropositive patients receiving their first allogeneic HCT. CMV DNA was monitored weekly until at least Day 100 posttransplant.A total of 109 consecutive patients were treated, median age 57 (range 20-73) years. Of these, 36 (33%) patients had a CMV reactivation within the first 105 days posttransplant with a median time of reactivation of 52.5 (range 36-104) days posttransplant. The cumulative incidence of CMV reactivation at Day 105 posttransplant was 33.1% (95% confidence interval: 24.4-42.0). One patient developed CMV disease.The use of pretransplant ganciclovir was associated with low incidence of CMV reactivation and disease. These data suggest that pretransplant ganciclovir with preemptive therapy for viral reactivation may be a useful strategy to reduce CMV reactivation. Future prospective trials are needed to compare strategies for CMV prophylaxis.

Introduction Sudden cardiac death is the most common cause of mortality in childhood onset hypertrophic cardiomyopathy. Identifying individuals at highest risk is therefore an essential part of clinical care but remains challenging. The 12 lead electrocardiogram (ECG) has been proposed as a useful tool for risk stratification and an ECG risk score has been proposed. However, this has not been independently validated and the ECG phenotype of childhood HCM has not been previously described. The aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. Methods Participants with an available baseline resting 12-lead ECG were identified from a large, international, multi-centre, retrospective cohort of patients aged less than 16 years fulfilling the diagnostic criteria for HCM (n=1029). Resting baseline ECG was evaluated and ECG variables were extracted. In addition, the ECG risk score based on 8 parameters (deviation in QRS axis, pathological T-wave inversion in limb or precordial leads, ST-segment depression, dominant S-wave in V4, limb-lead amplitude sum, 12-lead amplitude duration product and QTc) was calculated as previously described. The primary study endpoint was a composite outcome of major cardiac events (MACE) defined as SCD, resuscitated cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia (VT) with haemodynamic compromise. The discriminatory performance of using an ECG risk score >5 to identify patients at increased risk of MACE at 5 years was determined using Harrell’s C-index. Results Of 356 patients with childhood HCM (68.9% male, mean age at presentation 10.1 ± 4.5 years), 347 (97.5%) had baseline ECG abnormalities such as: repolarization abnormalities (n=277, 77.8%), left ventricular hypertrophy (n=240. 67.6%), abnormal QRS axis (n=126, 35.4%) or QT prolongation (n=131, 36.8%). Over a median follow up of 3.9 years (IQR 2.0-7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93-2.04). No ECG variables were associated with 5-year MACE on univariable or multivariable Cox regression analysis. Of the 164 participants with an ECG score >5, 153 (93.3%) did not have a MACE within 5 years. Harrell’s C-index (the probability of correctly distinguishing between high and low risk patients using an ECG risk score threshold of >5) was 0.60 (95% CI 0.484-0.715) at 5 years. The corresponding positive and negative predictive values were 6.7% (95% CI 4.7 – 9.4%) and 96.9% (95% CI 94.2 – 98.4%). Conclusions In a large, international, multi-centre cohort of children with HCM, ECG abnormalities are common. No ECG characteristic, either in isolation or combined in the ECG risk score, was associated with 5-year MACE risk. This suggests that the role of the baseline ECG phenotype in improving risk stratification in childhood HCM is limited. Conflict of Interest None

In order to meet the unique needs of local populations, health and care providers need to come together as a collective. A model of integration in line with the NHS Long Term Plan will support transformation, sustainability and meeting the increasing demands on the NHS. Due the complexity and variety of services in care communities, it is vital that organisations and the third sector acknowledge and understand one another with greater depth. Primary care networks (PCNs) support this by dissolving organisational boundaries, with services wrapping around each other and moving forward as one system. This article describes how one PCN in Wirral committed to appreciating each service's roles. By engaging regularly in different ways, members of the PCN were able build on professional relationships. The refocusing and reconnecting regularly as a collective team enabled a more streamlined approach to proactive, place-based patient care while providing professionals with improved working relationships, skill-sharing and increased job satisfaction.

Continuing professional learning is vital to early childhood professionals, and the use of digital technology can potentially reduce costs and improve access. In this study, 74 educators across 17 early childhood services in Australian urban and regional locations completed a questionnaire about their personal and professional uses of digital technology to find resources. The results indicate most early childhood educators use digital technology to construct their own professional knowledge bases, and though they make some use of formal resources around national standards, they make greater use of informal resources and discussion groups. They tend to seek practical information and activity ideas and ways to connect with other professionals, although this varies somewhat by years of professional experience, age and the socioeconomic context they work in. Results highlight early childhood educators’ professional learning desires and the potential value of mobile learning for providing access to professional learning for early childhood educators working in resource-limited and geographically limited settings.

Analyses of human clinical HIV-1 vaccine trials and preclinical vaccine studies performed in rhesus macaque (RM) models have identified associations between non-neutralizing Fc Receptor (FcR)-dependent antibody effector functions and reduced risk of infection. Specifically, antibody-dependent phagocytosis (ADP) has emerged as a common correlate of reduced infection risk in multiple RM studies and the human HVTN505 trial. This recurrent finding suggests that antibody responses with the capability to mediate ADP are most likely a desirable component of vaccine responses aimed at protecting against HIV-1 acquisition. As use of RM models is essential for development of the next generation of candidate HIV-1 vaccines, there is a need to determine how effectively ADP activity observed in RMs translates to activity in humans. In this study we compared ADP activity of human and RM monocytes and polymorphonuclear leukocytes (PMN) to bridge this gap in knowledge. We observed considerable variability in the magnitude of monocyte and PMN ADP activity across individual humans and RM that was not dependent on FcR alleles, and only modestly impacted by cell-surface levels of FcRs. Importantly, we found that for both human and RM phagocytes, ADP activity of antibodies targeting the CD4 binding site was greatest when mediated by human IgG3, followed by RM and human IgG1. These results demonstrate that there is functional homology between antibody and FcRs from these two species for ADP. We also used novel RM IgG1 monoclonal antibodies engineered with elongated hinge regions to show that hinge elongation augments RM ADP activity. The RM IgGs with engineered hinge regions can achieve ADP activity comparable to that observed with human IgG3. These novel modified antibodies will have utility in passive immunization studies aimed at defining the role of IgG3 and ADP in protection from virus challenge or control of disease in RM models. Our results contribute to a better translation of human and macaque antibody and FcR biology, and may help to improve testing accuracy and evaluations of future active and passive prevention strategies.

ObjectiveHypertrophic cardiomyopathy (HCM) is an important predictor of long-term outcomes in Friedreich’s ataxia (FA), but the clinical spectrum and survival in childhood is poorly described. This study aimed to describe the clinical characteristics of children with FA-HCM.Design and settingRetrospective, longitudinal cohort study of children with FA-HCM from the UK.Patients78 children (InterventionAnonymised retrospective demographic and clinical data were collected from baseline evaluation and follow-up.Main outcome measuresThe primary study end-point was all-cause mortality (sudden cardiac death, atrial arrhythmia-related death, heart failure-related death, non-cardiac death) or cardiac transplantation.ResultsThe mean age at diagnosis of FA-HCM was 10.9 (±3.1) years. Diagnosis was within 1 year of cardiac referral in 34 (65.0%) patients, but preceded the diagnosis of FA in 4 (5.3%). At baseline, 65 (90.3%) had concentric left ventricular hypertrophy and 6 (12.5%) had systolic impairment. Over a median follow-up of 5.1 years (IQR 2.4–7.3), 8 (10.5%) had documented supraventricular arrhythmias and 8 (10.5%) died (atrial arrhythmia-related n=2; heart failure-related n=1; non-cardiac n=2; or unknown cause n=3), but there were no sudden cardiac deaths. Freedom from death or transplantation at 10 years was 80.8% (95% CI 62.5 to 90.8).ConclusionsThis is the largest cohort of childhood FA-HCM reported to date and describes a high prevalence of atrial arrhythmias and impaired systolic function in childhood, suggesting early progression to end-stage disease. Overall mortality is similar to that reported in non-syndromic childhood HCM, but no patients died suddenly.

Background and Aims At least 80% of children with steroid sensitive nephrotic syndrome (SSNS) have relapses and many are triggered by upper respiratory tract infections (URTIs). Previous small studies (4 studies, 232 patients in total), mostly in children already taking maintenance corticosteroid in countries where URTI epidemiology is different to Europe, showed that giving daily low-dose prednisolone for 5-7 days during an URTI reduces the risk of relapse. The objective of the PREDNOS 2 trial was to determine if these findings were replicated in a large UK population of children with relapsing SSNS on different background medication or none. Method A randomised, double-blind, placebo-controlled trial, including a model-based economic evaluation was carried out in 122 UK paediatric departments. Between February 2013 and January 2019, 365 children with relapsing SSNS (mean age: 7.6 ± 3.5 y) were recruited from 91 sites and randomised (1:1) according to a minimisation algorithm based on background treatment (no background treatment; low-dose prednisolone only; low-dose prednisolone and other immunosuppression; other immunosuppression only). At the start of an URTI, children received 6 days of prednisolone 15 mg/m2 or matching preparation of placebo. Those already taking alternate day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 or their alternate-day dose, whichever was the greater. The primary outcome was the incidence of first URTI-related relapse (URR) following any URTI over 12 months. Secondary outcomes were the overall rate of relapse, changes in background treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, change in Achenbach Child Behaviour Checklist score and quality of life. Analysis was by intention to treat. The economic evaluation used trial data and a decision-analytic model to estimate Quality-Adjusted-Life-Years (QALYs) and costs at 1-year, which were then extrapolated over 16 years. Results 80 children completed 12 m follow-up without an URTI. Consent was withdrawn for 32 children, 14 prior to an URTI, leaving a modified intention to treat analysis population of 271 children (134 and 137 in prednisolone and placebo arms respectively). There were 384 URTIs and 82 URRs in the prednisolone arm, and 407 URTIs and 82 URRs in the placebo arm. The number of patients experiencing a URR was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms respectively (adjusted risk difference: -0.024, 95% CI: -0.14 to 0.095; P=0.7). There was no evidence that the treatment effect differed when data were analysed according to background treatment. There were no significant differences in secondary outcomes between treatment arms. A post-hoc subgroup analysis assessing primary outcome in 58 children of South Asian ethnicity (RR 0.66, 95% CI: 0.396 to 1.105) versus 213 of other ethnicity (RR 1.11, 95% CI: 0.806 to 1.535) showed possible efficacy of intervention in those of South Asian ethnicity (test for interaction P=0.09). Giving daily prednisolone at the time of an URTI was found to increase QALYs and decrease overall costs, when compared to standard care, a finding that was robust to sensitivity analysis. Conclusion In a large and methodologically-robust study, PREDNOS 2 has shown that giving 6 days of daily low-dose prednisolone at the time of an URTI does not reduce the risk of relapse of nephrotic syndrome in UK children, but could offer a cost-effective use of health care resources. Further work is needed to investigate inter-ethnic differences in treatment response, and the pathogenesis of individual viral infections and their effect on nephrotic syndrome.

Overlapping clinical features promoted the discussion of whether Kawasaki disease (KD) and PIMS-TS share pathophysiological features and disease outcomes. Medical records from English patients with KD (2015-02/20, N = 27) and PIMS-TS (02/2020-21, N = 34) were accessed to extract information. Children with PIMS-TS were older and more frequently of minority ethnicity background. They patients more commonly exhibited cytopenias and hyperferritinemia, which associated with diffuse cardiac involvement and functional impairment. In some PIMS-TS cases, cardiac pathology developed late, but outcomes were more favorable. In both, KD and PIMS-TS, baseline coronary diameter was a predictor of outcomes. PIMS-TS treatment more frequently included respiratory and cardiovascular support, and corticosteroids with IVIG. Cardiac involvement in PIMS-TS may be the result of a cytokine storm. Though more severe and diffuse when compared to KD, cardiac involvement of PIMS-TS has a more favorable prognosis, which may, after recovery, mitigate the need for long-term follow up.

The bacterial pathogen responsible for causing Lyme disease, Borrelia burgdorferi, is an atypical Gram-negative spirochete that is transmitted to humans via the bite of an infected Ixodes tick. In diderms, peptidoglycan (PG) is sandwiched between the inner and outer membrane of the cell envelope. In many other Gram-negative bacteria, PG is bound by protein(s), which provide both structural integrity and continuity between envelope layers. Here, we present evidence of a peptidoglycan-associated protein (PAP) in B. burgdorferi. Using an unbiased proteomics approach, we identified Neutrophil Attracting Protein A (NapA) as a PAP. Interestingly, NapA is a Dps homologue, which typically functions to bind and protect cellular DNA from damage during times of stress. While B. burgdorferi NapA is known to be involved in the oxidative stress response, it lacks the critical residues necessary for DNA binding. Biochemical and cellular studies demonstrate that NapA is localized to the B. burgdorferi periplasm and is indeed a PAP. Cryo-electron microscopy indicates that mutant bacteria, unable to produce NapA, have structural abnormalities. Defects in cell-wall integrity impact growth rate and cause the napA mutant to be more susceptible to osmotic and PG-specific stresses. NapA-linked PG is secreted in outer membrane vesicles and augments IL-17 production, relative to PG alone. Using microfluidics, we demonstrate that NapA acts as a molecular beacon—exacerbating the pathogenic properties of B. burgdorferi PG. These studies further our understanding of the B. burgdorferi cell envelope, provide critical information that underlies its pathogenesis, and highlight how a highly conserved bacterial protein can evolve mechanistically, while maintaining biological function., Author summary Diderms typically produce peptidoglycan-associated proteins (PAPs) to enhance structural integrity and continuity within the cell envelope. We have identified a PAP in B. burgdorferi with structural and sequence homology to the near ubiquitous bacterial protein Dps (DNA binding protein from starved bacteria). The B. burgdorferi Dps paralogue is incapable of binding DNA. Instead, it bolsters the protective properties of the PG layer, while playing an important role in host immune modulation. Collectively, our findings highlight the plasticity of bacterial proteins in that they may change how they perform a task despite maintaining the same basic biological function.

The concepts of purity and contamination preoccupied early modern Europeans fundamentally, structuring virtually every aspect of their lives, not least how they created and experienced works of art and the built environment. In an era that saw a great number of objects and people in motion, the meteoric rise of new artistic and building technologies, and religious upheaval exert new pressures on art and its institutions, anxieties about the pure and the contaminated – distinctions between the clean and unclean, sameness and difference, self and other, organization and its absence – took on heightened importance. In this series of geographically and methodologically wide-ranging essays, thirteen leading historians of art and architecture grapple with the complex ways that early modern actors negotiated these concerns, covering topics as diverse as Michelangelo’s unfinished sculptures, Venetian plague hospitals, Spanish-Muslim tapestries, and emergency currency. The resulting volume offers surprising new insights into the period and into the modern disciplinary routines of art and architectural history.

Aims The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. Methods and results Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0–7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93–2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of >5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484–0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7% Conclusion In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.

The care of older patients with cancer is becoming increasingly complex. Common challenges for this population include management of comorbidities, safe transitions of care, and appropriate medication use. In particular, polypharmacy—generally defined as the regular use of five or more medications—and inappropriate medication use can lead to adverse effects and poor outcomes in older adults with cancer, including falls, hospital readmissions, cognitive impairment, poor adherence to essential medications, chemotherapy toxicity, and increased mortality. Managing polypharmacy across different cancer care settings is often challenging. Providers face barriers to safe and successful medication management that may include lack of time, absence of reimbursement, underappreciation of the scale of polypharmacy-related harm, lack of ownership of deprescribing efforts, and poor communication across care settings. Existing literature on managing inappropriate medication use and polypharmacy in older adults with cancer has often focused on ideal state settings in which resources are plentiful and time is purposefully allocated for medication interventions. This paper presents a narrative, rather than a systematic review, of studies published in the past decade that provided detailed information on medication management and polypharmacy across cancer care settings. This review aims to also summarize different healthcare provider roles in taking action against inappropriate medication use and polypharmacy in older adults with cancer.

Background The 2013 updated guidelines on management of severe acute malnutrition in infants and children recommends the support of exclusive breastfeeding. These guidelines are inconsistently applied in low and middle income countries (LMICs) due to barriers including unclear implementation guides, technical support and epidemiological factors. Peer support strategies have been used to offer psychological support to families with infants in NICU and improve mental health outcomes. Breastfeeding peer supporters (BFPS) have been shown to be effective in improving breastfeeding outcomes in community settings however, their success within hospital settings in LMICs is unknown. We conducted a scoping review to explore implementation of breastfeeding peer support strategies as have been applied to hospitalized infants globally and highlight their implementation strategies in order to guide future research and practice. Methods A scoping review of the literature was conducted using the Arksey and O’Malley framework. A search was conducted in five online databases (PubMed, Cochrane library, Hinari, Google Scholar and Open Grey library). Data were extracted and charted in data extraction tables to capture general characteristics, modes of peer support delivery, implementation details and evaluation procedures. Results From the online search 276 articles were identified, however only 18 met the inclusion criteria for the study. The majority of these articles were reports on in-patient breastfeeding peer support interventions applied in Europe and the United States of America and only two were from LMICs. The articles described peer supporters’ identification, training (n = 13) and supervision (n = 14). The majority of the BFPS were employed (n = 10) compared to volunteers (n = 3) and support was mainly one-to-one (n = 11) rather than group support. Process and impact evaluation (n = 13) reported positive breastfeeding outcomes associated with breastfeeding peer support. Conclusion Breastfeeding peer support strategies are applied in different hospital settings and can be used to improve breastfeeding outcomes. However, to achieve integration, scalability and comparability of impact and outcomes, there is a need to standardize training, develop consistent implementation and supervision plans of in-patient peer supporters’ strategies. Further research to assess sustainability and evaluate cost-effectiveness of in-patient breastfeeding peer support strategies will improve uptake and scalability of these potentially lifesaving interventions.

Iontophoresis employs low-intensity electrical voltage and continuous constant current to direct a charged drug into a tissue. Iontophoretic drug delivery has recently been used as a novel method for cancer treatment in vivo. There is an urgent need to precisely model the low-intensity electric fields in cell culture systems to optimize iontophoretic drug delivery to tumors. Here, we present an iontophoresis-on-chip (IOC) platform to precisely quantify carboplatin drug delivery and its corresponding anti-cancer efficacy under various voltages and currents. In this study, we use an in vitro heparin-based hydrogel microfluidic device to model the movement of a charged drug across an extracellular matrix (ECM) and in MDA-MB231 triple-negative breast cancer (TNBC) cells. Transport of the drug through the hydrogel was modeled based on diffusion and electrophoresis of charged drug molecules in the direction of an oppositely charged electrode. The drug concentration in the tumor extracellular matrix was computed using finite element modeling of transient drug transport in the heparin-based hydrogel. The model predictions were then validated using the IOC platform by comparing the predicted concentration of a fluorescent cationic dye (Alexa Fluor 594 (R)) to the actual concentration in the microfluidic device. Alexa Fluor 594 (R) was used because it has a molecular weight close to paclitaxel, the gold standard drug for treating TNBC, and carboplatin. Our results demonstrated that a 50 mV DC electric field and a 3 mA electrical current significantly increased drug delivery and tumor cell death by 48.12% +/- 14.33 and 39.13% +/- 12.86, respectively (n = 3, p-value

Re‐establishment and maintenance of exclusive breastfeeding (EBF) is recommended by the World Health Organization for the nutritional rehabilitation of malnourished infants under 6 months; however, there is no explicit guidance on how this should be achieved. The IBAMI study—a pilot study conducted in Kilifi, Kenya—implemented these recommendations using an intervention for hospitalized infants and their mothers that included ward‐based breastfeeding peer supporters. This paper explores how the challenges of maintaining EBF are recontextualized after infant hospitalization for malnutrition. Four weeks after discharge, semistructured interviews on experiences of trying to maintain EBF in a postdischarge home setting were conducted with a total of 20 mothers. Although most stated the aspiration of maintaining EBF for 6 months, a range of challenges were reported and not all had successfully maintained EBF post discharge. Reported challenges include the stress of household chores, food insecurity, technical difficulties and social stigma of expressing breast milk, pressure from neighbours and family members to introduce mixed feeding, and needing more community‐based awareness and support. Most of these challenges were specific to the home setting and were not easily surmountable, despite the breastfeeding practices mothers had learned in the ward. Indeed, in some cases, challenges were exacerbated by the overmedicalized nature of the breastfeeding practices taught in the ward. In order to aid the transition from ward to home, there may be a need to further translate ward‐based education and promotional messaging for EBF into a community setting, targeting other caregivers as well.

Background Detection of tuberculosis (TB) in children in Kenya is sub-optimal. Xpert MTB/RIF® assay (Xpert®) has the potential to improve speed of TB diagnosis due to its sensitivity and fast turnaround for results. Significant effort and resources have been put into making the machines widely available in Kenya, but use remains low, especially in children. We set out to explore the reasons for the under-detection of TB and underuse of Xpert® in children, identifying challenges that may be relevant to other newer diagnostics in similar settings. Methods This was an exploratory qualitative study with an embedded case study approach. Data collection involved semi-structured interviews; small-group discussions; key informant interviews; observations of TB trainings, sensitisation meetings, policy meetings, hospital practices; desk review of guidelines, job aides and policy documents. The Capability, Opportunity and Motivation (COM-B) framework was used to interpret emerging themes. Results At individual level, knowledge, skill, competence and experience, as well as beliefs and fears impacted on capability (physical & psychological) as well as motivation (reflective) to diagnose TB in children and use diagnostic tests. Hospital level influencers included hospital norms, processes, patient flows and resources which affected how individual health workers attempted to diagnose TB in children by impacting on their capability (physical & psychological), motivation (reflective & automatic) and opportunity (physical & social). At the wider system level, community practices and beliefs, and implementation of TB programme directives impacted some of the decisions that health workers made through capability (psychological), motivation (reflective & automatic) and opportunity (physical). Conclusion We used comprehensive approaches to identify influencers of TB case detection and use of TB diagnostic tests in children in Kenya. These results are being used to design a contextually-appropriate intervention to improve TB diagnosis, which may be relevant to similar low-resource, high TB burden countries and can be feasibly implemented by the National TB programme.

Background Exclusive breastfeeding up to 6 months of age is recommended by the World Health Organization as the optimal mode of infant feeding, providing adequate nutrition for the baby and protection against infectious diseases. Breastfeeding can be adversely affected by individual, cultural and socio-economic factors. The study aimed to explore barriers of exclusive breastfeeding in the first 6 months of life among first-time mothers in rural Kenya. Methods An observational longitudinal design aimed to provide rich data on breastfeeding behaviour. Twenty pregnant first-time mothers were recruited through antenatal clinics and snowballing. Mothers were visited nine times at home from late pregnancy, at 1 week and 2 weeks post-delivery, then monthly until the baby was aged 6 months. Visits were conducted between November 2016 and April 2018. At the first visit, participants were asked about breastfeeding intentions and infant feeding education received. At each postnatal visit, direct observation of breastfeeding, a recorded semi-structured interview on feeding, mother’s and baby’s health was performed. Interviews were transcribed, checked, content was grouped into categories and analyzed using a qualitative descriptive approach. Results Most participants were adolescent (75%) and unmarried (65%). All 20 mothers intended to and did breastfeed, however additional fluids and semi-solids were commonly given. Only two mothers exclusively breastfed from birth up to 6 months of age. Prelacteal feeds, home remedies and traditional medicine were given by over a third of mothers in the first week of life. Concern over babies’ bowel habits and persistent crying perceived as abdominal colic led to several mothers receiving advice to give gripe water and traditional remedies. Early introduction of maize porridge from 3 months of age because of perceived hunger of the child was recommended by other family members. Breastfeeding observation showed persistent problems with positioning and attachment of infants. Conclusions Exclusive breastfeeding from birth to 6 months was uncommon. Prioritization of capacity to detect mothers with breastfeeding problems and provide breastfeeding education and support is necessary, particularly during the antenatal and early postnatal period. It is important to engage with other women resident in the household who may offer conflicting feeding advice.

In the context of stalling progress against malaria, resistance of mosquitoes to insecticides, and residual transmission, mass drug administration (MDA) of ivermectin, an endectocide used for neglected tropical diseases (NTDs), has emerged as a promising complementary vector control method. Ivermectin reduces the life span of Anopheles mosquitoes that feed on treated humans and/or livestock, potentially decreasing malaria parasite transmission when administered at the community level. Following the publication by WHO of the preferred product characteristics for endectocides as vector control tools, this roadmap provides a comprehensive view of processes needed to make ivermectin available as a vector control tool by 2024 with a completely novel mechanism of action. The roadmap covers various aspects, which include 1) the definition of optimal dosage/regimens for ivermectin MDA in both humans and livestock, 2) the risk of resistance to the drug and environmental impact, 3) ethical issues, 4) political and community engagement, 5) translation of evidence into policy, and 6) operational aspects of large-scale deployment of the drug, all in the context of a drug given as a prevention tool acting at the community level. The roadmap reflects the insights of a multidisciplinary group of global health experts who worked together to elucidate the path to inclusion of ivermectin in the toolbox against malaria, to address residual transmission, counteract insecticide resistance, and contribute to the end of this deadly disease.

This article reports on a systematic review of English language, peer-reviewed publications from 13 empirical studies with donor-conceived children and adults regarding their experiences and perceptions of donor conception. A total of 19 articles that met the inclusion criteria were reviewed. These were identified by means of a bibliographic search of four electronic databases for the period 1990-2011 and supplemented by the authors' personal knowledge of work in this field. No reports from such studies appeared prior to 2000, and more than half have been published since 2008, demonstrating the relative novelty of research in this field. Much of the reviewed research evidence concerns individuals conceived through sperm donation conducted under a regime promoting both anonymity and nondisclosure. Consequently, there is little research that pertains to individuals conceived through other forms of collaborative reproduction, nor to those conceived under arrangements and regimes in which early parental disclosure is both advocated and practised and the identity of the donor and of other genetic relatives may be accessible to donor-conceived individuals. The studies consistently report that most donor-conceived people have an interest in securing information about their genetic and biographical heritage - more information than most of them have been able to obtain. Although a number of methodological limitations in the research base are identified, the authors conclude that the evidence is sufficiently robust to promote the implementation of policies and practices that promote transparency and openness in collaborative reproduction, thus reflecting the importance of maximising future choices and opportunities for donor-conceived people.