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Abstract Background Although global poverty rates have declined in the last decade, the fall in the Asia-Pacific region has been slow relative to the rest of the world. Poverty continues to be a major cause of poor maternal and newborn health, and a barrier to accessing timely antenatal care. Papua New Guinea has one of the highest poverty rates and some of the worst maternal and neonatal outcomes in the Asia-Pacific region. Few studies have investigated equity in antenatal care utilization in this setting. We explored equity in antenatal care utilization and the determinants of service utilization, which include a measure of multidimensional poverty in Papua New Guinea. Methods To explore the association between poverty and antenatal care utilization this study uses data from a ten-cluster randomized controlled trial. The poverty headcount, average poverty gap, adjusted poverty headcount, and multidimensional poverty index of antenatal clinic attendees are derived using the Alkire-Foster method. The distribution of service utilization is explored using the multidimensional poverty index, followed by multivariate regression analyses to evaluate the determinants of service utilization. Results The poverty headcount was 61.06%, the average poverty gap 47.71%, the adjusted poverty headcount 29.13% and the average multidimensional poverty index was 0.363. Further, antenatal care utilization was regressive with respect to poverty. The regression analyses indicated that older women; being a widow (small number of widows (n = 3) asserts interpreting result with caution); or formally employed increase the likelihood of accessing antenatal care more often in pregnancy. Travelling for over an hour to receive care was negatively associated with utilization. Conclusion This study indicated high levels of multidimensional poverty in PNG and that ANC utilization was regressive; highlighting the need to encourage pregnant women, especially those who are economically more vulnerable to visit clinics regularly throughout pregnancy.

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.

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

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.

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.

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.

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 Understanding factors associated with women's healthcare decision-making during and after pregnancy is important. While there is considerable evidence related to general determinants of women’s decision-making abilities or agency, there is little evidence on factors associated with women's decision-making abilities or agency with regards to health care (henceforth, health agency), especially for antenatal and postnatal care. We assessed women’s health agency during and after pregnancy in slums in Mumbai, India, and examined factors associated with increased participation in healthcare decisions. Methods Cross-sectional data were collected from 2,630 women who gave birth and lived in 48 slums in Mumbai. A health agency module was developed to assess participation in healthcare decision-making during and after pregnancy. Linear regression analysis was used to examine factors associated with increased health agency. Results Around two-thirds of women made decisions about perinatal care by themselves or jointly with their husband, leaving about one-third outside the decision-making process. Participation increased with age, secondary and higher education, and paid employment, but decreased with age at marriage and household size. The strongest associations were with age and household size, each accounting for about a 0.2 standard deviation difference in health agency score for each one standard deviation change (although in different directions). Similar differences were observed for those in paid employment compared to those who were not, and for those with higher education compared to those with no schooling. Conclusion Exclusion of women from maternal healthcare decision-making threatens the effectiveness of health interventions. Factors such as age, employment, education, and household size need to be considered when designing health interventions targeting new mothers living in challenging conditions, such as urban slums in low- and middle-income countries.

Abstract Background Paediatric patients being treated for long-term physical health conditions (LTCs) have elevated mental health needs. However, mental health services in the community are difficult to access in the usual course of care for these patients. The Lucy Project – a self-referral drop-in access point—was a program to address this gap by enrolling patients for low-intensity psychological interventions during their treatment for LTCs. In this paper, we evaluate the cost-effectiveness of the Lucy Project. Methods Using a pre-post design, we evaluate the cost-effectiveness of the intervention by calculating the base-case incremental cost-effectiveness ratio (ICER) using outcomes data and expenses recorded by project staff. The target population was paediatric patients enrolled in the program with an average age of 9 years, treated over a time horizon of 6 months. Outcome data were collected via the Paediatric Quality of Life Inventory, which was converted to health utility scores using an instrument found in the literature. The QALYs were estimated using these health utility scores and the length of the intervention. We calculate a second, practical-case incremental cost-effectiveness ratio using streamlined costing figures with maximum capacity patient enrolment within a one-year time horizon, and capturing lessons learned post-trial. Results The base-case model showed an ICER of £21,220/Quality Adjusted Life Years (QALY) gained, while the practical model showed an ICER of £4,359/QALY gained. The practical model suggests the intervention garners significant gains in quality of life at an average cost of £309 per patient. Sensitivity analyses reveal use of staff time was the greatest determinant of the ICER, and the intervention is cost-effective 75% of the time in the base-case model, and 94% of the time in the practical-case model at a cost-effectiveness threshold of £20,000/QALY gained. Conclusions We find the base-case intervention improves patient outcomes and can be considered cost-effective according to the National Institute for Health and Care Excellence (NICE) threshold of £20,000—£30,000/QALY gained, and the practical-case intervention is roughly four times as cost-effective as the base-case. We recommend future studies incorporate a control group to corroborate the effect size of the intervention.

Introduction. The paper submits the analysis of existing design solutions of flow dividers used to synchronize hydraulic drives of working bodies of technological and mobile machines. The market demands for multithreaded throttle flow dividers without valves with the controlled division ratio, such as multi-axle vehicle chassis, are identified. The objective of the work was to analyze the possibility and rationale for developing a throttle four-way flow divider without valves with sensing elements of the Venturi tube type. The solution should provide the synchronicity of movement (rotation) of more than three working bodies of technological and mobile machines.Materials and Methods. A patent search for the designs of hydraulic flow dividers is carried out, and systems that require the division of the hydraulic fluid flow into more than two executive bodies are considered. An upgrade option, which allows dividing the flow into four branches, is proposed for the design of a three-channel throttle flow divider without valves.Results. The urgency of developing a multithreaded throttle flow divider without valves for application in industrial and mobile machines is validated. Two types of four-flow dividers are considered, their weaknesses are indicated. It is noted that the development of a multithreaded throttle flow divider based on the designs created in 1989 and 1991 will reduce the number of hydraulic pumps and get rid of the series connection of double-flow dividers. In this way, it is possible to reduce pressure losses in the hydraulic system and implement adaptive control of hydraulic motors of multi-motor mobile machines. The possibility to obtain a divider/combiner into four flows by adding an outlet chamber connected to the membrane chamber through a channel entering the Venturi nozzle on the basis of a three-flow throttle divider is shown. The principle of operation of such equipment is described.Discussion and Conclusions. The principles of construction of throttle flow dividers without valves are considered. An upgrade option is proposed to increase the number of division channels from three to four. However, to validate the operability of this design, a numerical analysis of the various modes of operation of the divider is required — calculation of the reduced volumetric stiffness of its working cavities. The information obtained can be used to modernize the hydraulic units of technological and mobile machines, increase their reliability, manufacturability, and efficiency. The issues that need to be solved in further research are identified.

Background: The main aim of this study was to evaluate whether selected polymorphic variants in genes from the inflammatory pathway can be predictors of pulmonary or digestive manifestation of cystic fibrosis, as well as of severity of lung disease. Materials and methods: Using pyrosequencing and sequencing we have genotyped 12 variants in TNF (rs361525, rs1800629), CXCL8 (rs4073, rs2227306, rs2227307, rs188378669), IL1B (rs16944, rs1143634, rs1142639, rs1143627), IL6 (rs1800795) and IL10 (rs1800896) genes in a cohort of 55 Polish patients with diagnosed cystic fibrosis and controls. In our study group, a pulmonary manifestation of disease revealed 44 of subjects (80%), and digestive symptoms dominated in 11 (20%) of analyzed individuals. Severe lung dysfunction has occurred in 20 (36.4%) of patients. Results: We proved, that two promoter variants of IL1B, rs1143627 (c.-118G > A) and rs16944 (c.-598T > C) are presented significantly more often in patients with severe character of lung disease compared to mild (82.5% vs. 62.8%, p-value 0.030, and 87.5% vs. 64.3%, p-value 0.008, respectively) in cystic fibrosis course. Haplotype AC formed by both changes had also a higher frequency (80%) in patients with severe course compared to the mild character (61.4%) of disease. However, the frequency of promoter variant TNF c.-308C > T (rs1800629) was presented at a significantly lower level in the patient’s group compared to healthy controls (2.7% vs. 15%, p-value 0.001). Furthermore, the presence of methicillin-resistant Staphylococcus aureus significantly correlated with the lower FEV1% in patients (p-value 0.01). Conclusions: Genetic variants, rs1143627 and rs16944, of IL1B are promising candidates as predictors of the severe character of lung disease in Polish patients with cystic fibrosis.

Nintedanib is a disease-modifying agent licensed for the treatment of IPF. Data on Polish experience with nintedanib in IPF are lacking. The present study aimed to describe the safety and efficacy profiles of nintedanib in a large real-world cohort of Polish patients with IPF. This was a multicenter, retrospective, observational study of IPF patients treated with nintedanib between March 2018 and October 2021. Data collection included baseline clinical characteristics, results of pulmonary function tests (PFTs), and a six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), and treatment persistence were also retrieved. A total of 501 patients (70% male) with a median age of 70.9 years (IQR 65–75.7) were included in this study. Patients were followed on treatment for a median of 15 months (7–25.5). The majority of patients (66.7%) were treated with the full recommended dose of nintedanib and 33.3% of patients were treated with a reduced dose of a drug. Intermittent dose reductions or drug interruptions were needed in 20% of patients. Over up to 3 years of follow-up, pulmonary function remained largely stable with the minority experiencing disease progression. The most frequent ADRs included diarrhea (45.3%), decreased appetite (29.9%), abdominal discomfort (29.5%), weight loss (32.1%), nausea (20.8%), fatigue (19.2%), increased liver aminotransferases (15.4%), and vomiting (8.2%). A total of 203 patients (40.5%) discontinued nintedanib treatment due to diverse reasons including ADRs (10.2%), death (11.6%), disease progression (4.6%), patient’s request (6.6%), and neoplastic disease (2.2%). This real-world study of a large cohort of Polish patients with IPF demonstrates that nintedanib therapy is safe, and is associated with acceptable tolerance and disease stabilization. These data support the findings of previously conducted clinical trials and observational studies on the safety and efficacy profiles of nintedanib in IPF.

Abstract Background Cystic fibrosis (CF) is one of the most common autosomal recessive diseases. Factors contributing to disease exacerbations and survival rate of CF patients are type of mutation in the CFTR gene, poor nutritional status, lung failure, and infection development by Pseudomonas aeruginosa. The study aimed to evaluate the relationship between the severity of mutation, nutritional status, lung function, and Pseudomonas aeruginosa prevalence and survival rate in adult patients with cystic fibrosis. Methods A study of 124 (68 ♀ and 56 ♂) adults with CF aged 18–51 years were evaluated for (a) type of mutation in the CFTR gene, (b) nutritional status (BMI), (c) lung function (FEV1%), and (d) Pseudomonas aeruginosa prevalence. For statistical calculations, Kaplan-Meier analysis of survival, chi-squared test for multiple samples, and logistic regression were used. Results The type of mutation (χ 2 = 12.73, df = 3, p = 0.005), FEV1% (χ 2 = 15.20, df = 2, p = 0.0005), Pseudomonas aeruginosa prevalence (χ 2 = 11.48, df = 3, p = 0.009), and BMI (χ 2 = 31.08, df = 4, p < 0.000) significantly differentiated the probability of survival of patients with CF. The shortest life expectancy was observed in patients with a severe type of mutation on both alleles, FEV1% < 40, subjects in whom Pseudomonas culture was extensively drug-resistant or pandrug-resistant, and patients whose BMI was lower than 18.5 kg/m2. The period from 30 to 40 years of age was the most critical in CF adults’ lifespan. The risk of adults with CF death doubled with Pseudomonas aeruginosa prevalence (OR = 2.06, 95% CI 1.29; 2.28) and eightfold when the bacteria acquired antibiotic resistance (OR = 8.11, 95% CI 1.67; 38.15). Conclusions All factors included in the study were significantly related to the survival rate of patients with cystic fibrosis.

Abstract Background Inappropriate dispensing of antibiotics at community pharmacies is an important driver of antimicrobial resistance (AMR), particularly in low- and middle-income countries. Thus, a better understanding of dispensing practices is crucial to inform national, regional, and global responses to AMR. This requires careful examination of the interactions between vendors and clients, sensitive to the context in which these interactions take place. Methods In 2019, we conducted a qualitative study to examine antibiotic dispensing practices and associated drivers in Indonesia, where self-medication with antibiotics purchased at community pharmacies and drug stores is widespread. Data collection involved 59 in-depth interviews with staff at pharmacies and drug stores (n = 31) and their clients (n = 28), conducted in an urban (Bekasi) and a semi-rural location (Tabalong) to capture different markets and different contexts of access to medicines. Interview transcripts were analysed using thematic content analysis. Results A common dispensing pattern was the direct request of antibiotics by clients, who walked into pharmacies or drug stores and asked for antibiotics without prescription, either by their generic/brand name or by showing an empty package or sample. A less common pattern was recommendation to use antibiotics by the vendor after the patient presented with symptoms. Drivers of inappropriate antibiotic dispensing included poor knowledge of antibiotics and AMR, financial incentives to maximise medicine sales in an increasingly competitive market, the unintended effects of health policy reforms to make antibiotics and other essential medicines freely available to all, and weak regulatory enforcement. Conclusions Inappropriate dispensing of antibiotics in community pharmacies and drug stores is the outcome of complex interactions between vendors and clients, shaped by wider and changing socio-economic processes. In Indonesia, as in many other LMICs with large and informal private sectors, concerted action should be taken to engage such providers in plans to reduce AMR. This would help avert unintended effects of market competition and adverse policy outcomes, as observed in this study.

Abstract Background Timely and appropriate health care during pregnancy and childbirth are the pillars of better maternal health outcomes. However, factors such as poverty and low education levels, long distances to a health facility, and high costs of health services may present barriers to timely access and utilisation of maternal health services. Despite antenatal care (ANC), delivery and postnatal care being free at the point of use in Burundi, utilisation of these services remains low: between 2011 and 2017, only 49% of pregnant women attended at least four ANC visits. This study explores the socio-economic determinants that affect utilisation of maternal health services in Burundi. Methods We use data from the 2016–2017 Burundi Demographic and Health Survey (DHS) collected from 8941 women who reported a live birth in the five years that preceded the survey. We use multivariate regression analysis to explore which individual-, household-, and community-level factors determine the likelihood that women will seek ANC services from a trained health professional, the number of ANC visits they make, and the choice of assisted childbirth. Results Occupation, marital status, and wealth increase the likelihood that women will seek ANC services from a trained health professional. The likelihood that a woman consults a trained health professional for ANC services is 18 times and 16 times more for married women and women living in partnership, respectively. More educated women and those who currently live a union or partnership attend more ANC visits than non-educated women and women not in union. At higher birth orders, women tend to not attend ANC visits. The more ANC visits attended, and the wealthier women are; the more likely they are to have assisted childbirth. Women who complete four or more ANC visits are 14 times more likely to have an assisted childbirth. Conclusions In Burundi, utilisation of maternal health services is low and is mainly driven by legal union and wealth status. To improve equitable access to maternal health services for vulnerable population groups such as those with lower wealth status and unmarried women, the government should consider certain demand stimulating policy packages targeted at these groups.

Background: The main aim of this study was to evaluate whether selected polymorphic variants in genes from the inflammatory pathway can be predictors of pulmonary or digestive manifestation of cystic fibrosis, as well as of severity of lung disease. Materials and methods: Using pyrosequencing and sequencing we have genotyped 12 variants in TNF (rs361525, rs1800629), CXCL8 (rs4073, rs2227306, rs2227307, rs188378669), IL1B (rs16944, rs1143634, rs1142639, rs1143627), IL6 (rs1800795) and IL10 (rs1800896) genes in a cohort of 55 Polish patients with diagnosed cystic fibrosis and controls. In our study group, a pulmonary manifestation of disease revealed 44 of subjects (80%), and digestive symptoms dominated in 11 (20%) of analyzed individuals. Severe lung dysfunction has occurred in 20 (36.4%) of patients. Results: We proved, that two promoter variants of IL1B, rs1143627 (c.-118G > A) and rs16944 (c.-598T > C) are presented significantly more often in patients with severe character of lung disease compared to mild (82.5% vs. 62.8%, p-value 0.030, and 87.5% vs. 64.3%, p-value 0.008, respectively) in cystic fibrosis course. Haplotype AC formed by both changes had also a higher frequency (80%) in patients with severe course compared to the mild character (61.4%) of disease. However, the frequency of promoter variant TNF c.-308C > T (rs1800629) was presented at a significantly lower level in the patient’s group compared to healthy controls (2.7% vs. 15%, p-value 0.001). Furthermore, the presence of methicillin-resistant Staphylococcus aureus significantly correlated with the lower FEV1% in patients (p-value 0.01). Conclusions: Genetic variants, rs1143627 and rs16944, of IL1B are promising candidates as predictors of the severe character of lung disease in Polish patients with cystic fibrosis.

Transport is one of the most burdensome negative sources affecting the natural environment. Long-term exposure of the body to exhaust pollution can cause health problems and, in the worst case, even lead to death. In addition to exhaust emissions, traffic noise is another equally important issue. Due to its nature, variability over time or the design diversity of vehicles in the traffic flow, it is a phenomenon difficult to define. Like exhaust pollution, it affects people's health and quality of life. In addition to its direct impact on the human physical system, it can also cause psychosomatic disorders, which is why a detailed analysis of road noise taking into account the real operation of the vehicle is so important. The paper presents the basic concepts related to the problem of traffic noise in the world, determines the sources of noise in vehicles and the methodology of conducting acoustic road tests. At the final stage of the scientific paper, methods of reducing excessive noise levels in large urban agglomerations were also presented, and the effectiveness of using noise barriers on selected parts of the city road network using proprietary acoustic tests was assessed.