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This systematic review aimed to identify factors significantly associated with the occurrence of epilepsy in autistic individuals and to consider the impact of study quality on findings. Electronic databases were systematically searched on October 2nd, 2020 and records retrieved were limited to those published from 2000 onwards. Study quality was categorised as 'good', 'moderate' or 'weak'. Fifty-three studies were included and in studies where the prevalence of epilepsy was reported (n = 257,892), 18,254 (7%) had co-occurring epilepsy. Intellectual disability/cognitive impairment was the most commonly reported risk factor associated with occurrence of epilepsy in autistic individuals. The evidence supporting other, potentially relevant factors was weak and inconsistent and requires further evaluation. Only 9/53 studies were considered 'good' quality.

Abstract Monoclonal antibodies are an increasingly important tool for prophylaxis and treatment of acute virus infections like SARS-CoV-2 infection. However, their use is often restricted due to the time required for development, variable yields and high production costs, as well as the need for adaptation to newly emerging virus variants. Here we use the genetically modified filamentous fungus expression system Thermothelomyces heterothallica (C1), which has a naturally high biosynthesis capacity for secretory enzymes and other proteins, to produce a human monoclonal IgG1 antibody (HuMab 87G7) that neutralises the SARS-CoV-2 variants of concern (VOCs) Alpha, Beta, Gamma, Delta, and Omicron. Both the mammalian cell and C1 produced HuMab 87G7 broadly neutralise SARS-CoV-2 VOCs in vitro and also provide protection against VOC Omicron in hamsters. The C1 produced HuMab 87G7 is also able to protect against the Delta VOC in non-human primates. In summary, these findings show that the C1 expression system is a promising technology platform for the development of HuMabs in preventive and therapeutic medicine.

Last Thursday, Ursula von der Leyen, the new – and […]

Introduction As nearly two-thirds of women presenting at their first antenatal visit are either overweight or obese in urban South Africa, the preconception period is an opportunity to optimise health and offset transgenerational risk of both obesity and non-communicable diseases. This protocol describes the planned economic evaluation of an individually randomised controlled trial of a complex continuum of care intervention targeting women and children in Soweto, South Africa (Bukhali trial).Methods and analysis The economic evaluation of the Bukhali trial will be conducted as a within-trial analysis from both provider and societal perspectives. Incremental costs and health outcomes of the continuum of care intervention will be compared with standard care. The economic impact on implementing agencies (programme costs), healthcare providers, participants and their households will be estimated. Incremental cost-effectiveness ratios (ICERs) will be calculated in terms of cost per case of child adiposity at age years averted. Additionally, ICERs will also be reported in terms of cost per quality-adjusted life year gained. If Bukhali demonstrates effectiveness, we will employ a decision analytical model to examine the cost-effectiveness of the intervention over a child’s lifetime. A Markov model will be used to estimate long-term health benefits, healthcare costs and cost-effectiveness. Probabilistic sensitivity analyses will be conducted to explore uncertainty and ensure robust results. An analysis will be conducted to assess the equity impact of the intervention, by comparing intervention impact within quintiles of socioeconomic status.Ethics and dissemination The Bukhali trial economic evaluation has ethical approval from the Human Ethics Research Committee of the University of the Witwatersrand, Johannesburg, South Africa (M240162). The results of the economic evaluation will be disseminated in a peer-reviewed journal and presented at a relevant international conference.Trial registration number Pan African Clinical Trials Registry (PACTR201903750173871; https://pactr.samrc.ac.za).

Acute generalized exanthematous pustulosis (AGEP) is a rare, acute skin eruption characterized by the development of numerous nonfollicular sterile pustules. Most cases are caused by drug reactions, among which Diltiazem has been incriminated. Herein, we present an 83-year-old female who presented for evaluation of generalized skin rash 3 days after initiation of Diltiazem. She was eventually diagnosed with AGEP, Diltiazem was discontinued, and systemic steroids were administered with the resolution of symptoms. This case report has the objective of encouraging clinicians to include AGEP in the differential diagnosis of skin eruption following the initiation of Diltiazem.

Abstract BackgroundTwo-thirds of the 2.4 million newborn deaths that occurred in 2020 within the first 28 days of life might have been avoided by implementing existing low-cost evidence-based interventions for all sick and small newborns. An open-source digital quality improvement tool (Neotree) combining data capture with education and clinical decision support is a promising solution for this implementation gap. ObjectiveWe present results from a cost analysis of a pilot implementation of Neotree in 3 hospitals in Malawi and Zimbabwe. MethodsWe combined activity-based costing and expenditure approaches to estimate the development and implementation cost of a Neotree pilot in 1 hospital in Malawi, Kamuzu Central Hospital (KCH), and 2 hospitals in Zimbabwe, Sally Mugabe Central Hospital (SMCH) and Chinhoyi Provincial Hospital (CPH). We estimated the costs from a provider perspective over 12 months. Data were collected through expenditure reports, monthly staff time-use surveys, and project staff interviews. Sensitivity and scenario analyses were conducted to assess the impact of uncertainties on the results or estimate potential costs at scale. A pilot time-motion survey was conducted at KCH and a comparable hospital where Neotree was not implemented. ResultsTotal cost of pilot implementation of Neotree at KCH, SMCH, and CPH was US $37,748, US $52,331, and US $41,764, respectively. Average monthly cost per admitted child was US $15, US $15, and US $58, respectively. Staff costs were the main cost component (average 73% of total costs, ranging from 63% to 79%). The results from the sensitivity analysis showed that uncertainty around the number of admissions had a significant impact on the costs in all hospitals. In Malawi, replacing monthly web hosting with a server also had a significant impact on the costs. Under routine (nonresearch) conditions and at scale, total costs are estimated to fall substantially, up to 76%, reducing cost per admitted child to as low as US $5 in KCH, US $4 in SMCH, and US $14 in CPH. Median time to admit a baby was 27 (IQR 20-40) minutes using Neotree (n=250) compared to 26 (IQR 21-30) minutes using paper-based systems (n=34), and the median time to discharge a baby was 9 (IQR 7-13) minutes for Neotree (n=246) compared to 3 (IQR 2-4) minutes for paper-based systems (n=50). ConclusionNeotree is a time- and cost-efficient tool, comparable with the results from limited similar mHealth decision-support tools in low- and middle-income countries. Implementation costs of Neotree varied substantially between the hospitals, mainly due to hospital size. The implementation costs could be substantially reduced at scale due to economies of scale because of integration to the health systems and reductions in cost items such as staff and overhead. More studies assessing the impact and cost-effectiveness of large-scale mHealth decision-support tools are needed.

With its decision in Humpert and others v Germany of 14 December 2023, the European Court of Human Rights settled a long-standing debate: The ban on strikes for German Civil Servants does not violate the rights under the European Convention on Human Rights. This decision ends the strategic litigating efforts of the applicants and their union to obtain the right to strike for the approximately 1.7 million civil servants in Germany. The judgment is also the culmination of an extraordinarily intense dialogue between Strasbourg and Karlsruhe.

Introduction Feeding practices developed in early life can impact a child’s nutrition, growth, dental health, cognitive development and lifetime risk of chronic diseases. Substantial evidence suggests ethnic health inequalities, and non-recommended complementary infant feeding practices among UK’s South Asian (SA) population. Nurture Early for Optimal Nutrition aims to use women’s group participatory learning and action (PLA) cycles to optimise infant feeding, care and dental hygiene practices in SA infants

Hydraulic drives, which for the most part is multi-circuit and branched, are widely used in hydraulic drives of modern mobile equipment and technological equipment. The analysis of the conducted studies has shown that throttle flow dividers, as well as flow dividers-adders, are the most suitable for providing automatic control of multi-circuit systems. Dividers are used to separate one working fluid flow entering the divided into two independent streams with an arbitrary flow ratio independent of loads. If it is necessary to organize a larger number of threads, two-threaded DP and DSP are switched on sequentially, and then one additional thread divider must be installed to receive each subsequent stream. Thus, in order to obtain n threads, it is necessary to have (n-1) two-threaded thread dividers, which is quite expensive and technically unjustified. The article describes the designs of multithreaded choke dividers and flow dividers-adders and a comparative analysis of their basic properties is carried out.

IntroductionIntervention strategies that seek to improve early childhood development outcomes are often targeted at the primary caregivers of children, usually mothers. The interventions require mothers to assimilate new information and then act upon it by allocating sufficient physical resources and time to adopt and perform development promoting behaviours. However, women face many competing demands on their resources and time, returning to familiar habits and behaviours. In this study, we explore mothers' allocation of time for caregiving activities for children under the age of 2, nested within a cluster randomised controlled trial of a nutrition and care for development intervention in rural Haryana, India.MethodsWe collected quantitative maternal time use data at two time points in rural Haryana, India, using a bespoke survey instrument. Data were collected from 704 mothers when their child was 12 months old, and 603 mothers when their child was 18 months old. We tested for significant differences in time spent by mothers on different activities when children are 12 months of age vs. 18 months of age between arms as well as over time, using linear regression. As these data were collected within a randomised controlled trial, we adjusted for clusters using random effects when testing for significant differences between the two time points.ResultsAt both time points, no statistically significant difference in maternal time use was found between arms. On average, mothers spent most of their waking time on household chores (over 6 h and 30 min) at both time points. When children were aged 12 months, approximately three and a half hours were spent on childcare activities for children under the age of 2 years. When children were 18 months old, mothers spent more time on income generating activities (30 min) than when the children were 12 years old, and on leisure (approximately 4 h and 30 min). When children were 18 months old, less time was spent on feeding/breastfeeding children (30 min less) and playing with children (15 min). However, mothers spent more time talking or reading to children at 18 months than at 12 months.ConclusionWe find that within a relatively short period of time in early childhood, maternal (or caregiver) time use can change, with time allocation being diverted away from childcare activities to others. This suggests that changing maternal time allocation in resource poor households may be quite challenging, and not allow the uptake of new and/or optimal behaviours.

IntroductionAlmost 250 million children fail to achieve their full growth or developmental potential, trapping them in a cycle of continuing disadvantage. Strong evidence exists that parent-focussed face to face interventions can improve developmental outcomes; the challenge is delivering these on a wide scale. SPRING (Sustainable Programme Incorporating Nutrition and Games) aimed to address this by developing a feasible affordable programme of monthly home visits by community-based workers (CWs) and testing two different delivery models at scale in a programmatic setting. In Pakistan, SPRING was embedded into existing monthly home visits of Lady Health Workers (LHWs). In India, it was delivered by a civil society/non-governmental organisation (CSO/NGO) that trained a new cadre of CWs.MethodsThe SPRING interventions were evaluated through parallel cluster randomised trials. In Pakistan, clusters were 20 Union Councils (UCs), and in India, the catchment areas of 24 health sub-centres. Trial participants were mother-baby dyads of live born babies recruited through surveillance systems of 2 monthly home visits. Primary outcomes were BSID-III composite scores for psychomotor, cognitive and language development plus height for age z-score (HAZ), assessed at 18 months of age. Analyses were by intention to treat.Results1,443 children in India were assessed at age 18 months and 1,016 in Pakistan. There was no impact in either setting on ECD outcomes or growth. The percentage of children in the SPRING intervention group who were receiving diets at 12 months of age that met the WHO minimum acceptable criteria was 35% higher in India (95% CI: 4–75%, p = 0.023) and 45% higher in Pakistan (95% CI: 15–83%, p = 0.002) compared to children in the control groups.DiscussionThe lack of impact is explained by shortcomings in implementation factors. Important lessons were learnt. Integrating additional tasks into the already overloaded workload of CWs is unlikely to be successful without additional resources and re-organisation of their goals to include the new tasks. The NGO model is the most likely for scale-up as few countries have established infrastructures like the LHW programme. It will require careful attention to the establishment of strong administrative and management systems to support its implementation.

BackgroundThe majority of post-neonatal deaths in children under 5 are due to malaria, diarrhoea and pneumonia (MDP). The WHO recommends integrated community case management (iCCM) of these conditions using community-based health workers (CHW). However iCCM programmes have suffered from poor implementation and mixed outcomes. We designed and evaluated a technology-based (mHealth) intervention package 'inSCALE' (Innovations At Scale For Community Access and Lasting Effects) to support iCCM programmes and increase appropriate treatment coverage for children with MDP.MethodsThis superiority cluster randomised controlled trial allocated all 12 districts in Inhambane Province in Mozambique to receive iCCM only (control) or iCCM plus the inSCALE technology intervention. Population cross-sectional surveys were conducted at baseline and after 18 months of intervention implementation in approximately 500 eligible households in randomly selected communities in all districts including at least one child less than 60 months of age where the main caregiver was available to assess the impact of the intervention on the primary outcome, the coverage of appropriate treatment for malaria, diarrhoea and pneumonia in children 2-59months of age. Secondary outcomes included the proportion of sick children who were taken to the CHW for treatment, validated tool-based CHW motivation and performance scores, prevalence of cases of illness, and a range of secondary household and health worker level outcomes. All statistical models accounted for the clustered study design and variables used to constrain the randomisation. A meta-analysis of the estimated pooled impact of the technology intervention was conducted including results from a sister trial (inSCALE-Uganda).FindingsThe study included 2740 eligible children in control arm districts and 2863 children in intervention districts. After 18 months of intervention implementation 68% (69/101) CHWs still had a working inSCALE smartphone and app and 45% (44/101) had uploaded at least one report to their supervising health facility in the last 4 weeks. Coverage of the appropriate treatment of cases of MDP increased by 26% in the intervention arm (adjusted RR 1.26 95% CI 1.12-1.42, pInterpretationThe inSCALE intervention led to an improvement in appropriate treatment of common childhood illnesses when delivered at scale in Mozambique. The programme will be rolled out by the ministry of health to the entire national CHW and primary care network in 2022-2023. This study highlights the potential value of a technology intervention aimed at strengthening iCCM systems to address the largest causes of childhood morbidity and mortality in sub-Saharan Africa.

Abstract Background Papua New Guinea (PNG) has one of the highest burdens of HIV and syphilis in pregnancy in the Asia-Pacific region. Timely and effective diagnosis can alleviate the burden of HIV and syphilis and improve maternal and newborn health. Supply-side factors related to implementation and scale up remain problematic, yet few studies have considered their impact on antenatal testing and treatment for HIV and syphilis. This study explores health service availability and readiness for antenatal HIV and/or syphilis testing and treatment in PNG. Methods Using data from two sources, we demonstrate health service availability and readiness. Service availability is measured at a province level as the average of three indicators: infrastructure, workforce, and antenatal clinic utilization. The readiness score comprises 28 equally weighted indicators across four domains; and is estimated for 73 health facilities. Bivariate and multivariate robust linear regressions explore associations between health facility readiness and the proportion of antenatal clinic attendees tested and treated for HIV and/or syphilis. Results Most provinces had fewer than one health facility per 10 000 population. On average, health worker density was 11 health workers per 10 000 population per province, and approximately 22% of pregnant women attended four or more antenatal clinics. Most health facilities had a composite readiness score between 51% and 75%, with urban health facilities faring better than rural ones. The multivariate regression analysis, when controlling for managing authority, catchment population, the number of clinicians employed, health facility type and residence (urban/rural) indicated a weak positive relationship between health facility readiness and the proportion of antenatal clinic attendees tested and treated for HIV and/or syphilis. Conclusion This study adds to the limited evidence base for the Asia-Pacific region. There is a need to improve antenatal testing and treatment coverage for HIV and syphilis and reduce healthcare inequalities faced by rural and urban communities. Shortages of skilled health workers, tests, and medicines impede the provision of quality antenatal care. Improving service availability and health facility readiness are key to ensuring the effective provision of antenatal care interventions.

Abstract Introduction The Nurture Early for Optimal Nutrition (NEON) study is a multiphase project that aims to optimize feeding, care and dental hygiene practices in South Asian children

Abstract Background Globally, nearly half of all deaths among children under the age of 5 years can be attributed to malaria, diarrhoea, and pneumonia. A significant proportion of these deaths occur in sub-Saharan Africa. Despite several programmes implemented in sub-Saharan Africa, the burden of these illnesses remains persistently high. To mobilise resources for such programmes it is necessary to evaluate their costs, costs-effectiveness, and affordability. This study aimed to estimate the provider costs of treating malaria, diarrhoea, and pneumonia among children under the age of 5 years in routine settings at the health facility level in rural Uganda and Mozambique. Methods Service and cost data was collected from health facilities in midwestern Uganda and Inhambane province, Mozambique from private and public health facilities. Financial and economic costs of providing care for childhood illnesses were investigated from the provider perspective by combining a top-down and bottom-up approach to estimate unit costs and annual total costs for different types of visits for these illnesses. All costs were collected in Ugandan shillings and Mozambican meticais. Costs are presented in 2021 US dollars. Results In Uganda, the highest number of outpatient visits were for children with uncomplicated malaria and of inpatient admissions were for respiratory infections, including pneumonia. The highest unit cost for outpatient visits was for pneumonia (and other respiratory infections) and ranged from $0.5 to 2.3, while the highest unit cost for inpatient admissions was for malaria ($19.6). In Mozambique, the highest numbers of outpatient and inpatient admissions visits were for malaria. The highest unit costs were for malaria too, ranging from $2.5 to 4.2 for outpatient visits and $3.8 for inpatient admissions. The greatest contributors to costs in both countries were drugs and diagnostics, followed by staff. Conclusions The findings highlighted the intensive resource use in the treatment of malaria and pneumonia for outpatient and inpatient cases, particularly at higher level health facilities. Timely treatment to prevent severe complications associated with these illnesses can also avoid high costs to health providers, and households. Trial registration: ClinicalTrials.gov, identifier: NCT01972321.