Healthcare Resource Utilization Associated with Intermittent Oral Corticosteroid Prescribing Patterns in Asthma.

Purpose: Oral corticosteroid (OCS) use for asthma is associated with considerable healthcare resource utilization (HCRU) and costs. However, no study has investigated this in relation to patterns of intermittent OCS prescription. Methods: This historical UK cohort study used primary care medical records, linked to Hospital Episode Statistics, from 2008 to 2019, of patients (≥4 years old) with asthma prescribed intermittent OCS. Patients were categorized by OCS prescribing pattern (one-off [single], less frequent [≥90-day gap] and frequent [<90-day gap]) and matched 1:1 (by sex, age and index date) with people never prescribed OCS with/without asthma. HCRU (reported as episodes, except for length of hospital stay [days] and any prescription [records]) and associated costs were compared between intermittent OCS and non-OCS cohorts, and among intermittent OCS prescribing patterns. Results: Of 149,191 eligible patients, 50.3% had one-off, 27.4% less frequent, and 22.3% frequent intermittent OCS prescribing patterns. Annualized non-respiratory HCRU rates were greater in the intermittent OCS versus non-OCS cohorts for GP visits (5.93 vs 4.70 episodes, p < 0.0001), hospital admissions (0.24 vs 0.16 episodes, p < 0.0001), and length of stay (1.87 vs 1.58 days, p < 0.0001). In the intermittent OCS cohort, rates were highest in the frequent prescribing group for GP visits (7.49 episodes; p < 0.0001 vs one-off), length of stay (2.15 days; p < 0.0001) and any prescription including OCS (25.22 prescriptions; p < 0.0001). Mean per-patient non-respiratory related and all-cause HCRU-related costs were higher with intermittent OCS than no OCS (£3902 vs £2722 and £8623 vs £4929, respectively), as were mean annualized costs (£565 vs £313 and £1526 vs £634, respectively). A dose-response relationship existed; HCRU-related costs were highest in the frequent prescribing cohort (p < 0.0001). Conclusion: Intermittent OCS use and more frequent intermittent OCS prescription patterns were associated with increased HCRU and associated costs. Improved asthma management is needed to reduce reliance on intermittent OCS in primary care.

Greenhouse gas emissions associated with suboptimal asthma care in the UK: the SABINA healthCARe-Based envirONmental cost of treatment (CARBON) study.

BACKGROUND: Poorly controlled asthma is associated with increased morbidity and healthcare resource utilisation (HCRU). Therefore, to quantify the environmental impact of asthma care, this retrospective, cohort, healthCARe-Based envirONmental cost of treatment (CARBON) study estimated greenhouse gas (GHG) emissions in the UK associated with the management of well-controlled versus poorly controlled asthma. METHODS: Patients with current asthma (aged ≥12 years) registered with the Clinical Practice Research Datalink (2008‒2019) were included. GHG emissions, measured as carbon dioxide equivalent (CO2e), were estimated for asthma-related medication use, HCRU and exacerbations during follow-up of patients with asthma classified at baseline as well-controlled (<3 short-acting ß2-agonist (SABA) canisters/year and no exacerbations) or poorly controlled (≥3 SABA canisters/year or ≥1 exacerbation). Excess GHG emissions due to suboptimal asthma control included ≥3 SABA canister prescriptions/year, exacerbations and any general practitioner and outpatient visits within 10 days of hospitalisation or an emergency department visit. RESULTS: Of the 236 506 patients analysed, 47.3% had poorly controlled asthma at baseline. Scaled to the national level, the overall carbon footprint of asthma care in the UK was 750 540 tonnes CO2e/year, with poorly controlled asthma contributing excess GHG emissions of 303 874 tonnes CO2e/year, which is equivalent to emissions from >124 000 houses in the UK. Poorly controlled versus well-controlled asthma generated 3.1-fold higher overall and 8.1-fold higher excess per capita carbon footprint, largely SABA-induced, with smaller contributions from HCRU. CONCLUSIONS: These findings suggest that addressing the high burden of poorly controlled asthma, including curbing high SABA use and its associated risk of exacerbations, may significantly alleviate asthma care-related carbon emissions.

Functional Consequences of Pathogenic Variants of the GJB2 Gene (Cx26) Localized in Different Cx26 Domains.

One of the most common forms of genetic deafness has been predominantly associated with pathogenic variants in the GJB2 gene, encoding transmembrane protein connexin 26 (Cx26). The Cx26 molecule consists of an N-terminal domain (NT), four transmembrane domains (TM1-TM4), two extracellular loops (EL1 and EL2), a cytoplasmic loop, and a C-terminus (CT). Pathogenic variants in the GJB2 gene, resulting in amino acid substitutions scattered across the Cx26 domains, lead to a variety of clinical outcomes, including the most common non-syndromic autosomal recessive deafness (DFNB1A), autosomal dominant deafness (DFNA3A), as well as syndromic forms combining hearing loss and skin disorders. However, for rare and poorly documented variants, information on the mode of inheritance is often lacking. Numerous in vitro studies have been conducted to elucidate the functional consequences of pathogenic GJB2 variants leading to amino acid substitutions in different domains of Cx26 protein. In this work, we summarized all available data on a mode of inheritance of pathogenic GJB2 variants leading to amino acid substitutions and reviewed published information on their functional effects, with an emphasis on their localization in certain Cx26 domains.

Greenhouse Gas Emissions from Respiratory Treatments: Results from the SABA CARBON International Study.

INTRODUCTION: Healthcare systems are looking to reduce their carbon impact. Short-acting ß2-agonist (SABA) overuse (≥ 3 canisters/year) is common in asthma and linked to poor outcomes; however, its environmental impact remains unknown. As part of the CARBON programme, this study retrospectively quantified the carbon footprint of SABA and controller inhalers across all respiratory indications and SABA overuse in asthma in lower-middle-income countries (LMICs), upper-middle-income countries and high-income countries across Africa, Asia Pacific, Latin America and the Middle East. METHODS: Two data sources were utilised to evaluate the carbon contribution of inhalers to respiratory care. To quantify greenhouse gas (GHG) emissions associated with total inhaler use across all respiratory indications, inhaler sales data were obtained from IQVIA MIDAS® (Q4/2018-Q3/2019) and compared by dose to prevent confounding from differences in canister actuation counts. GHG emissions associated with SABA overuse in asthma were evaluated using prescription and self-reported over-the-counter purchase data from the SABA use IN Asthma (SABINA) III study (2019-2020). Inhaler-related GHG emissions were quantified using published data and product life cycle assessments. RESULTS: SABA accounted for > 50% of total inhaler use and inhaler-related emissions in most countries analysed. The total SABA-related emissions were estimated at 2.7 million tonnes carbon dioxide equivalents, accounting for 70% of total inhaler-related emissions. Among the countries, regions and economies analysed, per capita SABA use and associated emissions were higher in Australia, the Middle East and high-income countries. Most SABA prescriptions for asthma (> 90%) were given to patients already overusing SABA. CONCLUSIONS: Globally, SABA use/overuse is widespread and is the greatest contributor to the carbon footprint of respiratory treatment, regardless of the economic status of countries. Implementing evidence-based treatment recommendations, personalising treatment and reducing healthcare inequities, especially in LMICs, may improve disease control and patient outcomes, thereby reducing SABA overuse and associated carbon emissions beyond SABA use alone.

The healthcare sector is a large emitter of greenhouse gases (GHGs); therefore, healthcare systems will need to reduce their carbon footprint to meet their carbon reduction targets. In respiratory care, the environmental impact of controller inhalers has received considerable attention due to the global warming potential of the propellants used in metered-dose inhalers. In contrast, little is known about the contribution made by short-acting ß₂-agonist (SABA) relievers globally, which are often the only inhaled medication used by many patients with milder asthma. The SABA use IN Asthma (SABINA) programme reported that SABA overuse (3 or more SABA canisters/year) is common and associated with an increased risk of asthma attacks. Since all inhalers have a carbon footprint, SABA overuse may result in an avoidable excess carbon footprint. Therefore, to provide a complete picture of the carbon footprint of respiratory care, we examined the contribution of SABA relievers and their potential overuse. The total SABA-related GHG emissions accounted for 70% of total inhaler-related GHG emissions, and > 90% of prescriptions for SABA relievers for asthma were given to patients who were already overusing their SABA. Overall, SABA use/overuse is commonly observed worldwide and is likely a significant contributor to the carbon footprint of respiratory treatment. Therefore, there is an urgent need for healthcare providers to follow the latest international treatment guidelines to reduce high SABA use in respiratory care and improve patient outcomes. This, in turn, will enable healthcare systems to reduce their carbon footprint from both treatment and patient interactions.

Recent trends in asthma diagnosis, preschool wheeze diagnosis and asthma exacerbations in English children and adolescents: a SABINA Jr study.

BACKGROUND: Asthma-related burden remains poorly characterised in children in the UK. We quantified recent trends in asthma prevalence and burden in a UK population-based cohort (1‒17-year-olds). METHODS: The Clinical Practice Research Datalink Aurum database (2008‒2018) was used to assess annual asthma incidence and prevalence in 1‒17-year-olds and preschool wheeze in 1‒5-year-olds, stratified by sex and age. During the same period, annual asthma exacerbation rates were assessed in those with either a diagnosis of preschool wheeze or asthma. RESULTS: Annual asthma incidence rates decreased by 51% from 1403.4 (95% CI 1383.7 to 1423.2) in 2008 to 688.0 (95% CI 676.3 to 699.9) per 105 person-years (PYs) in 2018, with the most pronounced decrease observed in 1‒5-year olds (decreasing by 65%, from 2556.9 (95% CI 2509.8 to 2604.7) to 892.3 (95% CI 866.9 to 918.3) per 105 PYs). The corresponding decreases for the 6‒11- and 12‒17-year-olds were 36% (1139.9 (95% CI 1110.6 to 1169.7) to 739.9 (95% CI 720.5 to 759.8)) and 20% (572.3 (95% CI 550.4 to 594.9) to 459.5 (95% CI 442.9 to 476.4)) per 105 PYs, respectively. The incidence of preschool wheeze decreased over time and was slightly more pronounced in the 1‒3 year-olds than in the 4-year-olds. Prevalence of asthma and preschool wheeze also decreased over time, from 18.0% overall in 2008 to 10.2% in 2018 for asthma. Exacerbation rates increased over time from 1.33 (95% CI 1.31 to 1.35) per 10 PYs in 2008 to 1.81 (95% CI 1.78 to 1.83) per 10 PYs in 2018. CONCLUSION: Paediatric asthma incidence decreased in the UK since 2008, particularly in 1-5-year-olds; this was accompanied by a decline in asthma prevalence. Preschool wheeze incidence also decreased in this age group. However, exacerbation rates have been increasing.

Insight into the Natural History of Pathogenic Variant c.919-2A>G in the SLC26A4 Gene Involved in Hearing Loss: The Evidence for Its Common Origin in Southern Siberia (Russia).

Pathogenic variants in the SLC26A4 gene leading to nonsyndromic recessive deafness (DFNB4), or Pendred syndrome, are some of the most common causes of hearing loss worldwide. Earlier, we found a high proportion of SLC26A4-related hearing loss with prevailing pathogenic variant c.919-2A>G (69.3% among all mutated SLC26A4 alleles that have been identified) in Tuvinian patients belonging to the indigenous Turkic-speaking Siberian people living in the Tyva Republic (Southern Siberia, Russia), which implies a founder effect in the accumulation of c.919-2A>G in Tuvinians. To evaluate a possible common origin of c.919-2A>G, we genotyped polymorphic STR and SNP markers, intragenic and flanking SLC26A4, in patients homozygous for c.919-2A>G and in healthy controls. The common STR and SNP haplotypes carrying c.919-2A>G were revealed, which convincingly indicates the origin of c.919-2A>G from a single ancestor, supporting a crucial role of the founder effect in the c.919-2A>G prevalence in Tuvinians. Comparison analysis with previously published data revealed the identity of the small SNP haplotype (~4.5 kb) in Tuvinian and Han Chinese carriers of c.919-2A>G, which suggests their common origin from founder chromosomes. We assume that c.919-2A>G could have originated in the geographically close territories of China or Tuva and subsequently spread to other regions of Asia. In addition, the time intervals of the c.919-2A>G occurrence in Tuvinians were roughly estimated.

Short-acting ß2-agonists and exacerbations in children with asthma in England: SABINA Junior.

Background: Prescription of three or more short-acting ß2-agonist (SABA) canisters per year in adult and adolescent asthma populations is associated with a risk of severe exacerbations; however, evidence in children aged <12 years is limited. Methods: This study analysed data on children and adolescents with asthma in three age cohorts: 1‒5 years, 6‒11 years and 12‒17 years from the Clinical Practice Research Datalink Aurum database for the period 1 January 2007 to 31 December 2019. Associations between SABA prescriptions (three or more versus fewer than three canisters per year) at baseline, defined as 6 months after an asthma diagnosis as a binary exposure variable, and the rate of future asthma exacerbations, defined as oral corticosteroid burst therapy, an emergency department visit or hospital admission, were assessed by multilevel negative binomial regression, adjusted for relevant demographic and clinical confounders. Results: Overall 48 560, 110 091 and 111 891 paediatric patients with asthma were aged 1‒5, 6‒11 and 12‒17 years, respectively. During the baseline period, 22 423 (46.2%), 42 137 (38.3%) and 40 288 (36.0%) in these three age cohorts, respectively, were prescribed three or more SABA canisters per year. Across all age ranges, the rate of future asthma exacerbations in those prescribed three or more versus fewer than three SABA canisters per year was at least two-fold higher. >30% of patients across all age cohorts were not prescribed inhaled corticosteroids (ICS), and the median proportion of days covered was only 33%, suggesting inadequate prescribing of ICS. Conclusion: In children, higher SABA prescriptions at baseline were associated with increased future exacerbation rates. These findings highlight the need for monitoring prescription of three or more SABA canisters per year to identify children with asthma at risk of exacerbations.

Application of an algorithm to analyze patterns of intermittent oral corticosteroid use in asthma.

An algorithm to describe patterns of intermittent oral corticosteroid use in the UK (n = 476,167) found that one-third of patients receiving intermittent oral corticosteroids for asthma only had short gaps (<90 days) between oral corticosteroid prescriptions sometime during follow-up. The increasing frequency pattern was more likely in patients with greater asthma severity and with more short-acting ß2-agonist use at baseline. Our approach may provide a clinically relevant representation of intermittent oral corticosteroid use in asthma.

Healthcare costs associated with short-acting ß2-agonists in asthma: observational UK SABINA study.

BACKGROUND: Poor asthma control is associated with high short-acting ß2-agonist (SABA) use. AIM: To assess asthma-related healthcare resource utilisation (HCRU) and medication costs associated with high versus low SABA prescriptions in the UK. DESIGN & SETTING: Analysis of SABINA I (SABA use IN Asthma I), a retrospective longitudinal study using UK electronic health records (Clinical Practice Research Datalink GOLD 2008-2019 and Hospital Episode Statistics database). METHOD: Eligible patients were ≥12 years old with SABA prescriptions in the past year. SABA prescriptions (number of canisters per year) were defined as high (≥3) or low (1-2). Association of SABA prescriptions with HCRU was assessed by negative binominal model adjusted for covariates. The UK unit costs from the NHS were applied to estimate total healthcare costs (2020). Medication costs were based on the annual average number of canisters per year per patient. RESULTS: Overall, 186 061 patients with SABA prescriptions were included, of whom 51% were prescribed high SABA. Total annual average costs (HCRU and medication) were 52% higher in the high SABA group versus the low SABA group (£2 256 091 per 1000 patients/year versus £1 480 640 per 1000 patients/year). Medication costs accounted for the majority of asthma-related costs. Across both groups, most HCRU costs were for non-exacerbation-related primary care or hospital outpatient visits. The annual average HCRU cost difference for high SABA versus low SABA was the greatest for hospitalisations (+230%; £15 521 per 1000 patients/year versus £4697 per 1000 patients/year) and exacerbation-related primary care visits (+162%; £18 770 per 1000 patients/year versus £7160 per 1000 patients/year). Asthma-related HCRU extrapolated to the broader UK asthma population was £108.5 million per year higher with high SABA versus low SABA. CONCLUSION: High SABA versus low SABA prescriptions are associated with higher asthma-related HCRU costs.

Observational UK cohort study to describe intermittent oral corticosteroid prescribing patterns and their association with adverse outcomes in asthma.

INTRODUCTION: Oral corticosteroids (OCS) for asthma are associated with increased risks of developing adverse outcomes (adverse outcomes); no previous study has focused exclusively on intermittent OCS use. METHODS: This historical (2008-2019) UK cohort study using primary care medical records from two anonymised, real-life databases (OPCRD and CPRD) included patients aged≥4 years with asthma receiving only intermittent OCS. Patients were indexed on their first recorded intermittent OCS prescription for asthma and categorised by OCS prescribing patterns: one-off (single), less frequent (≥90 day gap) and frequent (<90 day gap). Non-OCS patients matched 1:1 on gender, age and index date served as controls. The association of OCS prescribing patterns with OCS-related AO risk was studied, stratified by age, Global Initiative for Asthma (GINA) 2020 treatment step, and pre index inhaled corticosteroid (ICS) and short-acting ß2-agonist (SABA) prescriptions using a multivariable Cox-proportional hazard model. FINDINGS: Of 476 167 eligible patients, 41.7%, 26.8% and 31.6% had one-off, less frequent and frequent intermittent OCS prescribing patterns, respectively. Risk of any AO increased with increasingly frequent patterns of intermittent OCS versus non-OCS (HR; 95% CI: one-off 1.19 (1.18 to 1.20), less frequent 1.35 (1.34 to 1.36), frequent 1.42 (1.42 to 1.43)), and was consistent across age, GINA treatment step and ICS and SABA subgroups. The highest risks of individual OCS-related adverse outcomes with increasingly frequent OCS were for pneumonia and sleep apnoea. CONCLUSION: A considerable proportion of patients with asthma receiving intermittent OCS experienced a frequent prescribing pattern. Increasingly frequent OCS prescribing patterns were associated with higher risk of OCS-related adverse outcomes. Mitigation strategies are needed to minimise intermittent OCS prescription in primary care.

Selection of Diagnostically Significant Regions of the SLC26A4 Gene Involved in Hearing Loss.

Screening pathogenic variants in the SLC26A4 gene is an important part of molecular genetic testing for hearing loss (HL) since they are one of the common causes of hereditary HL in many populations. However, a large size of the SLC26A4 gene (20 coding exons) predetermines the difficulties of its complete mutational analysis, especially in large samples of patients. In addition, the regional or ethno-specific prevalence of SLC26A4 pathogenic variants has not yet been fully elucidated, except variants c.919-2A>G and c.2168A>G (p.His723Arg), which have been proven to be most common in Asian populations. We explored the distribution of currently known pathogenic and likely pathogenic (PLP) variants across the SLC26A4 gene sequence presented in the Deafness Variation Database for the selection of potential diagnostically important parts of this gene. As a result of this bioinformatic analysis, we found that molecular testing ten SLC26A4 exons (4, 6, 10, 11, 13−17 and 19) with flanking intronic regions can provide a diagnostic rate of 61.9% for all PLP variants in the SLC26A4 gene. The primary sequencing of these SLC26A4 regions may be applied as an initial effective diagnostic testing in samples of patients of unknown ethnicity or as a subsequent step after the targeted testing of already-known ethno- or region-specific pathogenic SLC26A4 variants.

Short-acting ß2 -agonist use and asthma exacerbations in Swedish children: A SABINA Junior study.

BACKGROUND: In adults and adolescents with asthma, use of ≥3 short-acting ß2 -agonist (SABA) canisters/year is associated with increased exacerbation risk. Whether this association is present in younger children remains unknown. In this SABA use IN Asthma (SABINA) Junior study, we assessed the association of SABA collection with exacerbation risk in the general Swedish pediatric asthma population. METHODS: This population-based cohort study utilized linked data from the Swedish national healthcare registries involving patients with asthma (<18 years) treated in secondary care between 2006-2015. Exacerbation risk, by baseline SABA collection (0-2 vs. ≥3 canisters, further examined as ordinal/continuous variable) and stratified on comorbid atopic disease (allergic rhinitis, dermatitis and eczema, and food/other allergies), was assessed for 1-year follow-up using negative binomial regression. RESULTS: Of 219,561 patients assessed, 45.4%, 31.7%, and 26.5% of patients aged 0-5, 6-11, and 12-17 years, respectively, collected ≥3 SABA canisters during the baseline year (high use). Collection of ≥3 SABA canisters (vs. 0-2) was associated with increased exacerbation risk during follow-up (incidence rate ratios [95% confidence interval]: 1.35 [1.29-1.42], 1.22 [1.15-1.29], and 1.26 [1.19-1.34] for 0-5-, 6-11-, and 12-17-year-olds, respectively); the association persisted with SABA as a continuous variable and was stronger among patients without atopic diseases (32%-44% increased risk versus. 14%-21% for those with atopic disease across groups). CONCLUSIONS: High SABA use was associated with increased asthma exacerbation risk in children, particularly in those without comorbid atopic diseases, emphasizing the need for asthma medication reviews and reformative initiatives by caregivers and healthcare providers on SABA use.

Local Flexibility of a New Single-Ring Chaperonin Encoded by Bacteriophage AR9 Bacillus subtilis.

Chaperonins, a family of molecular chaperones, assist protein folding in all domains of life. They are classified into two groups: bacterial variants and those present in endosymbiotic organelles of eukaryotes belong to group I, while group II includes chaperonins from the cytosol of archaea and eukaryotes. Recently, chaperonins of a prospective new group were discovered in giant bacteriophages; however, structures have been determined for only two of them. Here, using cryo-EM, we resolved a structure of a new chaperonin encoded by gene 228 of phage AR9 B. subtilis. This structure has similarities and differences with members of both groups, as well as with other known phage chaperonins, which further proves their diversity.

The role of prenatal vitamin D on the development of childhood asthma and wheeze: An umbrella review of systematic reviews and meta-analyses.

BACKGROUND & OBJECTIVE: It has been suggested that prenatal vitamin D plays a role in the development of childhood asthma and wheeze. Several systematic reviews have been conducted, but the results are inconsistent, and the methodological quality has not been studied. Therefore, the objective of this umbrella review was to assess the internal validity of the evidence base and the evidence for an association between prenatal vitamin D and asthma or wheezing in the offspring. METHODS: We searched the electronic databases Embase, PubMed, and Cochrane Library for studies on prenatal vitamin D using search words such as vitamin D, 25-hydroxyvitamin D, calcidiol, fetal, and neonatal. The search was conducted in June 2020, and the databases were searched from their date of establishment. We included systematic reviews and/or meta-analyses of experimental and observational studies assessing the association between prenatal vitamin D or asthma and wheeze. We excluded narrative reviews, commentaries, and other umbrella reviews. The methodological quality of systematic reviews was assessed using AMSTAR 2 tool. PROSPERO reg. no. CRD42020151329. RESULTS: We identified 22 eligible systematic reviews (17 on asthma and 20 on wheeze). Using the AMSTAR 2 quality assessment tool, the methodological quality was rated as critically low in 21 out of 22 systematic reviews, suggesting that previous reviews and meta-analyses did not provide accurate and comprehensive summaries of the included studies and that conclusions reached were potentially flawed. The majority of the included reviews reported that prenatal vitamin D reduces the risk of wheeze in the offspring. CONCLUSION: Prior to informing public guidelines, high-quality systematic reviews of the current evidence are greatly warranted.

Environmental Sustainability in Respiratory Care: An Overview of the healthCARe-Based envirONmental Cost of Treatment (CARBON) Programme.

INTRODUCTION: Faced with the challenges of climate change, countries are seeking to decarbonise their economies. A greater understanding of what comprises the carbon footprint of care in healthcare systems will identify potential strategies for reduction of greenhouse gas (GHG) emissions. In respiratory care, the focus has been on preventer inhalers, thereby omitting contributions from other aspects such as healthcare resource utilisation (HCRU) and reliever inhaler use. The healthCARe-Based envirONmental cost of treatment (CARBON) programme aims to provide a broader understanding of the carbon footprint associated with respiratory care. METHODS: CARBON will quantify the carbon footprint of medications and HCRU among approximately 2.5 million patients with respiratory diseases from seven ongoing studies spanning more than 40 countries. Across studies, to obtain the carbon footprint of all inhaled, oral, and injectable medications, SimaPro life cycle assessment software modelling resource and energy consumption data, in addition to Ecoinvent® data sets and certified published studies, will be used. The carbon footprint of HCRU in the United Kingdom will be estimated by applying the methodology and data obtained from the Sustainable Healthcare Coalition Care Pathway Guidance. PLANNED OUTCOMES: In asthma, CARBON studies will quantify GHG emissions associated with well-controlled versus not well-controlled asthma, the contribution of short-acting ß2-agonist (SABA) reliever inhalers (and their potential overuse) to the carbon footprint of care, and how implementation of treatment guidelines can drive improved outcomes and footprint reduction. In chronic obstructive pulmonary disease (COPD), CARBON studies will assess the impact of exacerbation history on GHG emissions associated with HCRU and SABA use in subsequent years and estimate the carbon footprint associated with all aspects of COPD care. CONCLUSION: CARBON aims to show that the principle of evidence-led care focused on improvement of clinical outcomes has the potential to benefit patients and the environment.

Different Rates of the SLC26A4-Related Hearing Loss in Two Indigenous Peoples of Southern Siberia (Russia).

Hereditary hearing loss (HL) is known to be highly locus/allelic heterogeneous, and the prevalence of different HL forms significantly varies among populations worldwide. Investigation of region-specific landscapes of hereditary HL is important for local healthcare and medical genetic services. Mutations in the SLC26A4 gene leading to nonsyndromic recessive deafness (DFNB4) and Pendred syndrome are common genetic causes of hereditary HL, at least in some Asian populations. We present for the first time the results of a thorough analysis of the SLC26A4 gene by Sanger sequencing in the large cohorts of patients with HL of unknown etiology belonging to two neighboring indigenous Turkic-speaking Siberian peoples (Tuvinians and Altaians). A definite genetic diagnosis based on the presence of biallelic SLC26A4 mutations was established for 28.2% (62/220) of all enrolled Tuvinian patients vs. 4.3% (4/93) of Altaian patients. The rate of the SLC26A4-related HL in Tuvinian patients appeared to be one of the highest among populations worldwide. The SLC26A4 mutational spectrum was characterized by the presence of Asian-specific mutations c.919-2A>G and c.2027T>A (p.Leu676Gln), predominantly found in Tuvinian patients, and c.2168A>G (p.His723Arg), which was only detected in Altaian patients. In addition, a novel pathogenic variant c.1545T>G (p.Phe515Leu) was found with high frequency in Tuvinian patients. Overall, based on the findings of this study and our previous research, we were able to uncover the genetic causes of HL in 50.5% of Tuvinian patients and 34.5% of Altaian patients.

Factors Associated with Infant Feeding Choices Among Women with HIV in Botswana.

INTRODUCTION: In resource-constrained settings, infant feeding decisions among women with HIV (WHIV) must balance the risk of infant HIV acquisition from breastfeeding with increased mortality associated with formula feeding. WHO guidelines recommend countries principally promote a single feeding method for WHIV, either breastfeeding or formula feeding. In 2016, Botswana revised its policy of formula feeding for infants born to WHIV, instead promoting exclusive breastfeeding during the first 6 months of life. METHODS: We sought to understand factors influencing infant feeding choices among WHIV by administering a questionnaire to pregnant and postpartum WHIV (2013-2015) participating in a clinical trial in Botswana (the Mpepu Study). Logistic regression analyses were used to identify factors associated with infant feeding choices. RESULTS: Of 810 surveyed participants, 24.0% chose breastfeeding and 76.0% chose formula feeding. Women were more likely to choose formula feeding if advised by a health worker to formula feed (aOR 1.90; 95% CI 1.02-3.57) or if they harboured doubts about the potency of antiretroviral treatment (ART) to prevent infant HIV acquisition (aOR 9.06; 95% CI 4.78-17.17). Women who reported lack of confidence in preparing infant formula safely (aOR 0.09; 95% CI 0.04-0.19) or low concerns about infant HIV acquisition (aOR 0.35; 95% CI 0.22-0.55) were significantly less likely to formula feed. DISCUSSION: Perceptions about ART effectiveness, social circumstances and health worker recommendations were key influencers of infant feeding choices among WHIV. Health system factors and maternal education interventions represent ideal targets for any programmatic actions aiming to shape informed decision-making towards HIV-free survival of infants.

Problems of the formation of youth changeable personal identity in postmodern conditions.

The relevance of the subject matter is connected with the necessity to study the specifics of identification of modern student youth. The purpose of the article is to study modern self-identity. The leading method for studying this problem is the method of analysing the standard paradigm of the theoretical description of this phenomenon that has developed in the modern scientific discourse. During the study, the authors analyzed the self-identity structure. Also, were researched. It was concluded that the standard paradigm for the study of mutable identity, without resorting to the deep socioeconomic factors of the modern self-identity crisis, provides a fragmented, superficial and socio-abstract picture of variable identity, which, in essence, is a philosophical apology, a mask of identity dehumanization in the postmodern world.