Examining differences in real-world effectiveness of e-cigarettes for smoking cessation by source of purchase in England: an observational study of different contexts before and after the COVID-19 pandemic.

INTRODUCTION: The effectiveness of e-cigarettes for smoking cessation may differ by source of purchase. The changing influence of self-selection on purchase location caused by COVID-19 pandemic-related vape shop closures means we can examine the association between smoking abstinence e-cigarette use by purchase source and test for moderation of this association by the timing of the pandemic. METHODS: Repeat-cross-sectional nationally representative surveys, conducted between January-2017 and August-2023. Participants (N=1,284; ≥18y, 46.9% women) who made a past-year quit attempt, used an e-cigarette in their most recent attempt, currently vaping and provided data on the purchase source were included. The association between e-cigarette purchase source and continuous abstinence following the most recent quit attempt was assessed with adjusted regression, including an interaction between the timing of pandemic restrictions (March-2020 through January-2022). RESULTS: Overall, 48.1% usually purchasing their e-cigarettes from vape shops, declining from 53.6% pre-pandemic to 40.6% during the pandemic. There was inconclusive evidence that those purchasing from vape shops had greater odds of quitting smoking (ORadj=1.25, 95%CI 0.92-1.76). The association between purchase source and successful quitting did not depend upon whether purchasing occurred before or during the pandemic (F=0.08, pinteraction=0.774; pre-pandemic: ORadj=1.23, 0.79-1.91; and pandemic: ORadj=1.29, 0.81-2.06). CONCLUSIONS: More data are needed to conclusively determine whether purchasing from a specialist vape shop increases smoking cessation. Given the changing influence of self-selection on purchase location caused by the pandemic, the similar associations between purchase source and quit success across both periods suggests it is unlikely an artefact of unmeasured confounding. IMPLICATIONS: It is important to know if where e-cigarettes are purchased can increase their effectiveness for smoking cessation. While we found a positive association between purchasing from a specialist vape shop and abstinence rates, the results were inconclusive. Further studies are required to establish whether purchasing from specialist vape shops improves smoking cessation outcomes compared with other purchase sources.

Nicotine strength of e-liquids used by adult vapers in Great Britain: A population survey 2016 to 2024.

BACKGROUND AND AIMS: In March 2024, the UK government announced plans to introduce a Vaping Products Duty that will tax e-liquids based on their nicotine strength. This study examined trends in the nicotine strength of e-liquids used by adult vapers and differences in those currently used across relevant subgroups. DESIGN: Nationally-representative, cross-sectional household survey, July 2016 to January 2024. SETTING: Great Britain. PARTICIPANTS: 7981 adult vapers. MEASUREMENTS: Participants were asked whether the e-cigarette they mainly use contains nicotine (yes/no) and the e-liquid strength (no nicotine, >0-≤ 6, 7-11, 12-19 or ≥20 mg/ml). We also collected information on the main device type used (disposable/refillable/pod), age, gender, occupational social grade, history of ≥1 mental health conditions, smoking status and (among past-year smokers) level of cigarette addiction. FINDINGS: The proportion of vapers in England using high-strength (≥20 mg/ml) e-liquids increased from an average of 3.8% (95% confidence interval [CI] = 2.9-5.0) up to June 2021 to 32.5% (CI = 27.9-37.4) in January 2024 (the vast majority of whom [93.3% in January 2024] reported using exactly 20 mg/ml; the legal limit). This rise was most pronounced among those using disposable e-cigarettes, those aged 18-24 years and all smoking statuses (including never smokers) except long-term (≥1y) ex-smokers. Of those surveyed in 2022-2024 in Great Britain, overall, 89.5% (CI = 88.1-90.8) said they usually used e-cigarettes containing nicotine, 8.7% (CI = 7.5-10.0) used nicotine-free e-cigarettes, and 1.8% (CI = 1.2-2.4) were unsure. The proportion using ≥20 mg/ml was higher among those mainly using disposable (47.9%) compared with pod (16.3%) or refillable (11.5%) devices; never smokers (36.0%), current smokers (28.8%) or recent (<1y) ex-smokers (27.4%), compared with long-term ex-smokers (13.9%); and younger (16-24y; 44.2%) compared with older (≥25y; range 9.4-25.1%) age groups. There were no notable differences across other subgroups of interest. CONCLUSIONS: Use of high-strength nicotine e-liquids in England appears to have increased sharply in recent years. Most adult vapers in Great Britain appear to use e-cigarettes that contain nicotine but different subgroups use different strengths: nicotine strengths tend to be higher among those who mainly use disposable devices and those aged 16-24y, and lower among long-term ex-smokers.

Endometrial Cancer: A Pilot Study of the Tissue Microbiota.

BACKGROUND: The endometrium remains a difficult tissue for the analysis of microbiota, mainly due to the low bacterial presence and the sampling procedures. Among its pathologies, endometrial cancer has not yet been completely investigated for its relationship with microbiota composition. In this work, we report on possible correlations between endometrial microbiota dysbiosis and endometrial cancer. METHODS: Women with endometrial cancer at various stages of tumor progression were enrolled together with women with a benign polymyomatous uterus as the control. Analyses were performed using biopsies collected at two specific endometrial sites during the surgery. This study adopted two approaches: the absolute quantification of the bacterial load, using droplet digital PCR (ddPCR), and the analysis of the bacterial composition, using a deep metabarcoding NGS procedure. RESULTS: ddPCR provided the first-ever assessment of the absolute quantification of bacterial DNA in the endometrium, confirming a generally low microbial abundance. Metabarcoding analysis revealed a different microbiota distribution in the two endometrial sites, regardless of pathology, accompanied by an overall higher prevalence of pathogenic bacterial genera in cancerous tissues. CONCLUSIONS: These results pave the way for future studies aimed at identifying potential biomarkers and gaining a deeper understanding of the role of bacteria associated with tumors.

Electronic cigarettes and subsequent use of cigarettes in young people: An evidence and gap map.

BACKGROUND AND AIMS: The use of e-cigarettes may influence later smoking uptake in young people. Evidence and gap maps (EGMs) are interactive on-line tools that display the evidence and gaps in a specific area of policy or research. The aim of this study was to map clusters and gaps in evidence exploring the relationship between e-cigarette use or availability and subsequent combustible tobacco use in people aged < 30 years. METHODS: We conducted an EGM of primary studies and systematic reviews. A framework and an interactive EGM was developed in consultation with an expert advisory group. A systematic search of five databases retrieved 9057 records, from which 134 studies were included. Systematic reviews were appraised using AMSTAR-2, and all included studies were coded into the EGM framework resulting in the interactive web-based EGM. A descriptive analysis of key characteristics of the identified evidence clusters and gaps resulted in this report. RESULTS: Studies were completed between 2015 and 2023, with the first systematic reviews being published in 2017. Most studies were conducted in western high-income countries, predominantly the United States. Cohort studies were the most frequently used study design. The evidence is clustered on e-cigarette use as an exposure, with an absolute gap identified for evidence looking into the availability of e-cigarettes and subsequent cessation of cigarette smoking. We also found little evidence analysing equity factors, and little exploring characteristics of e-cigarette devices. CONCLUSIONS: This evidence and gap map (EGM) offers a tool to explore the available evidence regarding the e-cigarette use/availability and later cigarette smoking in people under the age of 30 years at the time of the search. The majority of the 134 reports is from high-income countries, with an uneven geographic distribution. Most of the systematic reviews are of lower quality, suggesting the need for higher-quality reviews. The evidence is clustered around e-cigarette use as an exposure and subsequent frequency/intensity of current combustible tobacco use. Gaps in evidence focusing on e-cigarette availability, as well as on the influence of equity factors may warrant further research. This EGM can support funders and researchers in identifying future research priorities, while guiding practitioners and policymakers to the current evidence base.

Glycemic control during TB treatment among Filipinos: The Starting Anti-Tuberculosis Treatment Cohort Study.

Poor TB treatment outcomes are observed in patients with type 2 diabetes mellitus (DM) comorbidity and glycemic control throughout treatment may play a role. The objective of this study was to investigate glycemic control longitudinally among Filipino adults undergoing TB treatment using mixed-effects linear and logistic regression. Analyses were conducted in 188 DM-TB patients out of 901 enrolled in the Starting Anti-TB Treatment (St-ATT) cohort, with a median baseline glycosylated hemoglobin (HbA1c) of 8.2% (range 4.5-13.3%). Previous versus new DM diagnosis was associated with higher mean HbA1c (worse glycemic control) during treatment, with a smaller effect amongst those with central obesity (coefficient 0.80, 95% confidence interval [CI] 0.26, 1.57, P = 0.043) than amongst those without central obesity (coefficient 3.48, 95% CI 2.16, 4.80, P<0.001). In those with a new DM diagnosis, central obesity was associated with higher blood glucose (coefficient 1.62, 95% CI 0.72, 2.53, P = 0.009). Of 177 participants with ≥2 HbA1c results, 40% had uncontrolled glycemia (≥2 HbA1c results ≥8%). Of 165 participants with ≥3 HbA1c results, 29.9% had consistently-controlled glycemia, 15.3% had initially-uncontrolled glycemia, and 18.6% had consistently-uncontrolled glycemia. Previous versus new DM diagnosis and glucose-lowering medication use versus no use were associated with having uncontrolled versus controlled glycemia (adjusted odds ratio [aOR] 2.50 95%CI 1.61, 6.05, P = 0.042; aOR 4.78 95% CI 1.61,14.23, P<0.001) and more likely to have consistently-uncontrolled versus consistently-controlled glycemia (adjusted relative risk ratio [aRRR] 5.14 95% CI 1.37, 19.20, P = 0.015; aRRR 10.24 95% CI 0.07, 0.95, P = 0.003). Relapse cases of TB were less likely than new cases to have uncontrolled (aOR 0.20 95%CI 0.06, 0.63, P = 0.031) or consistently-uncontrolled (aRRR 0.25 95%CI 0.07, 0.95, P = 0.042) versus controlled glycemia. Those with long-term DM, suggested by previous diagnosis, glucose-lowering medication use and possibly central obesity, may require additional support to manage blood glucose during TB treatment.

Characterising smoking and nicotine use behaviours among women of reproductive age: a 10-year population study in England.

BACKGROUND: Tobacco smoking affects women's fertility and is associated with substantial risks of adverse pregnancy outcomes. This study explored trends by socioeconomic position in patterns of smoking, use of non-combustible nicotine products, and quitting activity among women of reproductive age in England. METHODS: Data come from a nationally representative monthly cross-sectional survey. Between October 2013 and October 2023, 197,266 adults (≥ 18 years) were surveyed, of whom 44,052 were women of reproductive age (18-45 years). Main outcome measures were current smoking, vaping, and use of nicotine replacement therapy (NRT), heated tobacco products (HTPs), and nicotine pouches; mainly/exclusively smoking hand-rolled cigarettes and level of dependence among current smokers; past-year quit attempts among past-year smokers; and success of quit attempts among those who tried to quit. We modelled time trends in these outcomes, overall and by occupational social grade (ABC1 = more advantaged/C2DE = less advantaged). RESULTS: Smoking prevalence among women of reproductive age fell from 28.7% [95%CI = 26.3-31.2%] to 22.4% [19.6-25.5%] in social grades C2DE but there was an uncertain increase from 11.7% [10.2-13.5%] to 14.9% [13.4-16.6%] in ABC1. By contrast, among all adults and among men of the same age, smoking prevalence remained relatively stable in ABC1. Vaping prevalence among women of reproductive age more than tripled, from 5.1% [4.3-6.0%] to 19.7% [18.0-21.5%], with the absolute increase more pronounced among those in social grades C2DE (reaching 26.7%; 23.3-30.3%); these changes were larger than those observed among all adults but similar to those among men of the same age. The proportion of smokers mainly/exclusively smoking hand-rolled cigarettes increased from 40.5% [36.3-44.9%] to 61.4% [56.5-66.1%] among women of reproductive age; smaller increases were observed among all adults and among men of the same age. Patterns on other outcomes were largely similar between groups. CONCLUSIONS: Among women of reproductive age, there appears to have been a rise in smoking prevalence in the more advantaged social grades over the past decade. Across social grades, there have been substantial increases in the proportion of women of reproductive age who vape and shifts from use of manufactured to hand-rolled cigarettes among those who smoke. These changes have been more pronounced than those observed in the general adult population over the same period.

Evaluation of cytokine profiles related to Mycobacterium tuberculosis latent antigens using a whole-blood assay in the Philippines.

Introduction: There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens. Materials and methods: Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay. Results: A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups. Conclusion: The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.

Mitochondrial and Nuclear DNA Variants in Amyotrophic Lateral Sclerosis: Enrichment in the Mitochondrial Control Region and Sirtuin Pathway Genes in Spinal Cord Tissue.

Amyotrophic Lateral Sclerosis (ALS) is a progressive disease with prevalent mitochondrial dysfunctions affecting both upper and lower motor neurons in the motor cortex, brainstem, and spinal cord. Despite mitochondria having their own genome (mtDNA), in humans, most mitochondrial genes are encoded by the nuclear genome (nDNA). Our study aimed to simultaneously screen for nDNA and mtDNA genomes to assess for specific variant enrichment in ALS compared to control tissues. Here, we analysed whole exome (WES) and whole genome (WGS) sequencing data from spinal cord tissues, respectively, of 6 and 12 human donors. A total of 31,257 and 301,241 variants in nuclear-encoded mitochondrial genes were identified from WES and WGS, respectively, while mtDNA reads accounted for 73 and 332 variants. Despite technical differences, both datasets consistently revealed a specific enrichment of variants in the mitochondrial Control Region (CR) and in several of these genes directly associated with mitochondrial dynamics or with Sirtuin pathway genes within ALS tissues. Overall, our data support the hypothesis of a variant burden in specific genes, highlighting potential actionable targets for therapeutic interventions in ALS.

Intersection of gambling with smoking and alcohol use in Great Britain: a cross-sectional survey in October 2022.

OBJECTIVES: Gambling is associated with cigarette smoking and alcohol consumption. We explored the intersection of gambling across all risk levels of harm with smoking and alcohol use among adults in Great Britain. DESIGN: A nationally representative cross-sectional survey in October 2022. SETTING: Great Britain. PARTICIPANTS: A weighted total of 2398 adults (18+ years). OUTCOME MEASURES: We examined the prevalence of past-year gambling and, among those reporting gambling, assessed the associations between the outcome of any risk of harm from gambling (scoring >0 on the Problem Gambling Severity Index) and the binary predictor variables of current cigarette smoking and higher risk alcohol consumption (AUDIT-C score≥4). We also explored data on weekly expenditure on gambling with smoking and alcohol use among those categorised at any-risk of harm from gambling. RESULTS: Overall, 43.6% (95% CI 41.2% to 45.9%) of adults gambled in the past year. Among these, 7.3% (95% CI 5.3% to 9.3%) were classified at any-risk of harm from gambling, 16.0% (95% CI 13.2% to 18.8%) were currently smoking and 40.8% (95% CI 37.2% to 44.4%) were drinking at increasing and higher risk levels. There were no associations between any risk of harm from gambling and current smoking (OR adjusted=0.80, 95% CI 0.35 to 1.66) or drinking at increasing and higher risk levels (OR adjusted=0.94, 95% CI 0.52 to 1.69), respectively. Analyses using Bayes factors indicated that these data were insensitive to distinguish no effect from a range of associations (OR=95% CI 0.5 to 1.9). The mean weekly spend on gambling was £7.69 (95% CI £5.17 to £10.21) overall, £4.80 (95% CI £4.18 to £5.43) among those classified as at no risk and £45.68 (95% CI £12.07 to £79.29) among those at any risk of harm from gambling. CONCLUSIONS: Pilot data in a population-level survey on smoking and alcohol use yielded similar estimates to other population-level surveys on gambling participation and at-risk gambling. Further data are needed to elucidate the intersections more reliably between gambling, smoking and alcohol use and inform population-level approaches to reduce harm.

Smoking prevalence and purchasing of menthol cigarettes since the menthol flavour ban in Great Britain: a population-based survey between 2020 and 2023.

BACKGROUND: Menthol cigarettes have been banned in Great Britain (GB) since May 2020. Still, menthol accessories and unlabelled cigarettes perceived as mentholated are available, and people can buy menthol cigarettes overseas or illicitly. This study assessed: trends in smoking menthol cigarettes among all adults and 18-24-year-olds in GB between October 2020 and March 2023; trends in and differences between England, Scotland and Wales during the same period and purchase sources among people smoking menthol versus non-flavoured cigarettes. METHODS: Population-weighted data were from a monthly cross-sectional survey of adults in GB. Among people smoking cigarettes, we calculated the proportion smoking menthol cigarettes across all adults and 18-24-year-olds, and prevalence ratios (PR) between the first and last quarter. We also calculated the proportions of people smoking menthol/non-flavoured cigarettes by purchase source (including illicit sources). RESULTS: In the first quarter, 16.2% of adults smoking cigarettes reported menthol cigarette smoking with little to no decline throughout the study (PR 0.85, 95% CI 0.71 to 1.01), while it declined among 18-24-year-olds (PR 0.75, 95% CI 0.63 to 0.89). The prevalence of menthol cigarette smoking fell by two-thirds in Wales (PR 0.36, 95% CI 0.19 to 0.62) but remained relatively stable in England (PR 0.88, 95% CI 0.72 to 1.06) and Scotland (PR 0.94, 95% CI 0.59 to 1.53). The main purchasing sources were licit (93.9%), 14.8% reported illicit sources and 11.5% cross-border purchases, without notable differences from people smoking non-flavoured cigarettes. CONCLUSIONS: Roughly one million adults in GB still smoke menthol cigarettes and, with the exception of Wales and young people, there were no noteworthy changes in the post-ban period. There was no indication that the overall persistence of menthol smoking was driven by illicit purchases.

Researchers' experiences of the design and conduct challenges associated with parallel-group cluster-randomised trials and views on a novel open-cohort design.

BACKGROUND: Two accepted designs exist for parallel-group cluster-randomised trials (CRTs). Closed-cohort designs follow the same individuals over time with a single recruitment period before randomisation, but face challenges in settings with high attrition. (Repeated) cross-sectional designs recruit at one or more timepoints before and/or after randomisation, collecting data from different individuals present in the cluster at these timepoints, but are unsuitable for assessment of individual change over time. An 'open-cohort' design allows individual follow-up with recruitment before and after cluster-randomisation, but little literature exists on acceptability to inform their use in CRTs. AIM: To document the views and experiences of expert trialists to identify: a) Design and conduct challenges with established parallel-group CRT designs,b) Perceptions of potential benefits and barriers to implementation of open-cohort CRTs,c) Methods for minimising, and investigating the impact of, bias in open-cohort CRTs. METHODS: Qualitative consultation via two expert workshops including triallists (n = 24) who had worked on CRTs over a range of settings. Workshop transcripts were analysed using Descriptive Thematic Analysis utilising inductive and deductive coding. RESULTS: Two central organising concepts were developed. Design and conduct challenges with established CRT designs confirmed that current CRT designs are unable to deal with many of the complex research and intervention circumstances found in some trial settings (e.g. care homes). Perceptions of potential benefits and barriers of open cohort designs included themes on: approaches to recruitment; data collection; analysis; minimising/investigating the impact of bias; and how open-cohort designs might address or present CRT design challenges. Open-cohort designs were felt to provide a solution for some of the challenges current CRT designs present in some settings. CONCLUSIONS: Open-cohort CRT designs hold promise for addressing the challenges associated with standard CRT designs. Research is needed to provide clarity around definition and guidance on application.

Trends in Harm Perceptions of E-Cigarettes vs Cigarettes Among Adults Who Smoke in England, 2014-2023.

Importance: Electronic cigarettes (e-cigarettes) are less harmful to users than combustible cigarettes. However, public health and media reporting have often overstated the potential risks of e-cigarettes, and inaccurate perceptions of the harms of vaping relative to smoking are pervasive. Objective: To examine time trends in harm perceptions of e-cigarettes compared with combustible cigarettes among adults who smoke. Design, Setting, and Participants: This nationally representative monthly cross-sectional survey study was conducted from November 2014 to June 2023 in England. Participants were adults who currently smoke. Main Outcomes and Measures: Participants were asked whether they thought e-cigarettes were less harmful, equally harmful, or more harmful than cigarettes, or did not know, with the proportion responding less harmful (vs all other responses) as the primary outcome. Logistic regression was used to test associations between survey wave and participants' perceptions of the harms of e-cigarettes. Results: Data were collected from 28 393 adults who smoke (mean [SD] age, 43.5 [17.3] years; 13 253 [46.7%] women). In November 2014, 44.4% (95% CI, 42.0%-46.8%) thought e-cigarettes were less harmful than cigarettes, 30.3% (95% CI, 28.2%-32.6%) thought e-cigarettes were equally harmful, 10.8% (95% CI, 9.4%-12.3%) thought they were more harmful, and 14.5% (95% CI, 12.9%-16.4%) did not know. However, by June 2023, the proportion who thought e-cigarettes were less harmful had decreased by 40% (prevalence ratio, 0.60; 95% CI, 0.55-0.66), and the proportion who thought e-cigarettes were more harmful had more than doubled (prevalence ratio, 2.16; 95% CI, 1.84-2.54). Changes over time were nonlinear: late 2019 saw a sharp decline in the proportion who thought e-cigarettes were less harmful and increases in the proportions who thought they were equally or more harmful. These changes were short-lived, returning to pre-2019 levels by the end of 2020. However, perceptions worsened again from 2021 up to the end of the study period: the proportion who thought e-cigarettes were more harmful increased to a new high, and the proportion who thought e-cigarettes were less harmful decreased to levels comparable to those in late 2019. As a result, in June 2023, the perception that e-cigarettes were equally as harmful as cigarettes was the most commonly held view among adults who smoke (33.7%; 95% CI, 31.4%-36.1%), with roughly similar proportions perceiving e-cigarettes to be less (26.7%; 95% CI, 24.6%-28.9%) and more (23.3%; 95% CI, 21.1%-25.7%) harmful. Conclusions and Relevance: This survey study of adults who smoke in England found that harm perceptions of e-cigarettes have worsened substantially over the last decade, such that most adults who smoked in 2023 believed e-cigarettes to be at least as harmful as cigarettes. The timing of the 2 most notable changes in harm perceptions coincided with the e-cigarette, or vaping product, use-associated lung injury outbreak in 2019 and the recent increase in youth vaping in England since 2021.

Comparing disease specific catastrophic cost estimates using longitudinal and cross-sectional designs: The example of tuberculosis.

BACKGROUND: There has been an increasing interest in assessing disease-specific catastrophic costs incurred by affected households as part of economic evaluations and to inform joint social/health policies for vulnerable groups. Although the longitudinal study design is the gold standard for estimating disease-specific household costs, many assessments are implemented with a cross-sectional design for pragmatic reasons. We aimed at identifying the potential biases of a cross-sectional design for estimating household cost, using the example of tuberculosis (TB), and exploring optimal approaches for sampling and interpolating cross-sectional cost data to estimate household costs. METHODS: Data on patient incurred costs, household income and coping strategies were collected from TB patients in Negros Occidental and Cebu in the Philippines between November 2018 and October 2020. The data collection tools were developed by adapting WHO Tuberculosis Patient Cost Surveys: A Handbook into a longitudinal study design. TB-specific catastrophic cost estimates were compared between longitudinal and simulated cross-sectional designs using different random samples from different times points in treatment (intensive and continuation phases). RESULTS: A total of 530 adult TB patients were enrolled upon TB diagnosis in this study. Using the longitudinal design, the catastrophic cost estimate for TB-affected households was 69 % using the output approach. The catastrophic cost estimates with the simulated cross-sectional design were affected by the reduction and recovery in household income during the episode of TB care and ranged from 40 to 55 %. CONCLUSION: Using longitudinally collected costs incurred by TB-affected households, we illustrated the potential limitations and implications of estimating household costs using a cross-sectional design. Not capturing changes in household income at multiple time points during the episode of the disease and estimating from inappropriate samples may result in biases that underestimates catastrophic cost.

OPA1 mutation affects autophagy and triggers senescence in autosomal dominant optic atrophy plus fibroblasts.

In several cases of mitochondrial diseases, the underlying genetic and bioenergetic causes of reduced oxidative phosphorylation (OxPhos) in mitochondrial dysfunction are well understood. However, there is still limited knowledge about the specific cellular outcomes and factors involved for each gene and mutation, which contributes to the lack of effective treatments for these disorders. This study focused on fibroblasts from a patient with Autosomal Dominant Optic Atrophy (ADOA) plus syndrome harboring a mutation in the Optic Atrophy 1 (OPA1) gene. By combining functional and transcriptomic approaches, we investigated the mitochondrial function and identified cellular phenotypes associated with the disease. Our findings revealed that fibroblasts with the OPA1 mutation exhibited a disrupted mitochondrial network and function, leading to altered mitochondrial dynamics and reduced autophagic response. Additionally, we observed a premature senescence phenotype in these cells, suggesting a previously unexplored role of the OPA1 gene in inducing senescence in ADOA plus patients. This study provides novel insights into the mechanisms underlying mitochondrial dysfunction in ADOA plus and highlights the potential importance of senescence in disease progression.

Kidney and urine cell transcriptomics in IgA nephropathy and lupus nephritis: a narrative review.

This narrative review sheds light on the use of transcriptomics in the analysis of kidney biopsies and urinary cell samples from patients with immunoglobulin A nephropathy or lupus nephritis. The conventional methods of examining kidney biopsy through light microscopy, immunofluorescence and electron microscopy provide valuable clinical information for diagnosis and prognosis but have some limitations that transcriptomics can address. Some recent studies have reported that kidney transcriptomics has uncovered new molecular biomarkers implicated in the inflammatory process induced by the deposition of circulating immune complexes in the investigated kidney diseases. In addition, transcriptomics applied to urinary cells mirrors the inflammatory process that occurs in the kidney. This means that we can study urinary cell transcriptomics in clinical practice to diagnose the stage of the inflammatory process. Furthermore, the transcriptomics of urinary cells can be used to make therapy decisions during patient follow-up to avoid the stress of a second kidney biopsy. The studies analyzed in this review have a significant limitation. Biomarkers have been identified in small cohorts of patients but none of them has been validated in independent external cohorts. Further prospective studies in large cohorts of patients are necessary for accurate and complete validation. Only after that can these biomarkers be widely used in clinical practice.

Costs incurred by people with co-morbid tuberculosis and diabetes and their households in the Philippines.

OBJECTIVE: Diabetes is a risk factor for TB mortality and relapse. The Philippines has a high TB incidence with co-morbid diabetes. This study assessed the pre- and post-TB diagnosis costs incurred by people with TB and diabetes (TB-DM) and their households in the Philippines. METHODS: Longitudinal data was collected for costs, income, and coping mechanisms of TB-affected households in Negros Occidental and Cebu, the Philippines. Data collection was conducted four times during TB treatment. The data collection tools were developed by adapting WHO's cross-sectional questionnaire in the Tuberculosis Patient Cost Surveys: A Handbook into a longitudinal study design. Demographic and clinical characteristics, self-reported household income, number of facility visits, patient costs, the proportion of TB-affected households facing catastrophic costs due to TB (>20% of annual household income before TB), coping mechanisms, and social support received were compared by diabetes status at the time of TB diagnosis. RESULTS: 530 people with TB were enrolled in this study, and 144 (27.2%) had TB-DM based on diabetes testing at the time of TB diagnosis. 75.4% of people with TB-DM were more than 45 years old compared to 50.3% of people with TB-only (p<0.001). People with TB-DM had more frequent visits for TB treatment (120 vs 87 visits, p = 0.054) as well as for total visits for TB-DM treatment (129 vs 88 visits, p = 0.010) compared to those with TB-only. There was no significant difference in the proportion of TB-affected households facing catastrophic costs between those with TB-DM (76.3%) and those with TB-only (68.7%, p = 0.691). CONCLUSION: People with TB-DM in the Philippines face extensive health service use. However, this does not translate into substantial differences in the incidence of catastrophic cost. Further study is required to understand the incidence of catastrophic costs due to diabetes-only in the Philippines.

Prevalence and characteristics of co-occurrence of smoking and increasing-and-higher-risk drinking: A population survey in England.

BACKGROUND: Smoking and drinking alcohol both significantly contribute to mortality and morbidity, and there is a need to characterise the sociodemographic and health-related characteristics (e.g. mental distress) of people who do both in order to target resources. This study reports the prevalence and characteristics of adults in the general population in England who both drink alcohol at increasing-and-higher-risk levels and smoke. METHODS: We used cross-sectional data from a monthly, nationally representative survey of adults in England (n = 37,258; April 2020-March 2022). Weighted data were used to report prevalence and unweighted data were used to report descriptive statistics for sociodemographic and health-related characteristics. RESULTS: The prevalence of both smoking and increasing-and-higher-risk drinking was 4.6% (95% CI = 4.4-4.9; n = 1,574). They smoked a mean of 10.4 (SD = 8.86) cigarettes per day and had a mean AUDIT score of 12.8 (SD = 5.18). Nearly half (48.2%, n = 751) were trying to cut down on their smoking and 28.0% (n = 441) on their drinking. A quarter (25.3%, n = 397) had received General Practitioner advice on smoking while 8.7% (n = 76) had received advice on their drinking. Nearly half (48.6%, n = 745) reported experiencing psychological distress in the past month and 44.6% (n = 529) had a diagnosed mental health condition, both of which were higher than among all adults (28.1% and 29.1%, respectively). CONCLUSION: In England, from April 2020 to March 2022, the prevalence of both smoking and increasing-and-higher-risk drinking was 4.6%. This group appears to experience high rates of mental health problems and targeted support is needed.