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.

Mitofusin 2 mutation drives cell proliferation in Charcot-Marie-Tooth 2A fibroblasts.

Dominant mutations in ubiquitously expressed mitofusin 2 gene (MFN2) cause Charcot-Marie-Tooth type 2A (CMT2A; OMIM 609260), an inherited sensory-motor neuropathy that affects peripheral nerve axons. Mitofusin 2 protein has been found to take part in mitochondrial fusion, mitochondria-endoplasmic reticulum tethering, mitochondrial trafficking along axons, mitochondrial quality control and various types of cancer, in which MFN2 has been indicated as a tumor suppressor gene. Discordant data on the mitochondrial altered phenotypes in patient-derived fibroblasts harboring MFN2 mutations and in animal models have been reported. We addressed some of these issues by focusing on mitochondria behavior during autophagy and mitophagy in fibroblasts derived from a CMT2AMFN2 patient with an MFN2650G > T/C217F mutation in the GTPase domain. This study investigated mitochondrial dynamics, respiratory capacity and autophagy/mitophagy, to tackle the multifaceted MFN2 contribution to CMT2A pathogenesis. We found that MFN2 mutated fibroblasts showed impairment of mitochondrial morphology, bioenergetics capacity, and impairment of the early stages of autophagy, but not mitophagy. Unexpectedly, transcriptomic analysis of mutated fibroblasts highlighted marked differentially expressed pathways related to cell population proliferation and extracellular matrix organization. We consistently found the activation of mTORC2/AKT signaling and accelerated proliferation in the CMT2AMFN2 fibroblasts. In conclusion, our evidence indicates that MFN2 mutation can positively drive cell proliferation in CMT2AMFN2 fibroblasts.

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.

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.

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.

Comparing the Effects of the EU- Versus the US-JUUL Pod in a Sample of UK Smokers: Nicotine Absorption, Satisfaction, and Other Nicotine-Related Subjective Effects.

INTRODUCTION: Pod Vaping Devices (PVD) such as JUUL have become extremely popular in the United States although their uptake and use in the United Kingdom remain lower. A key difference between the United States and the United Kingdom is the nicotine strength legally permitted, typically 59 mg/mL in the United States but capped at 20 mg/mL in the United Kingdom and European Union. This may limit the ability of EU vaping devices to deliver satisfactory nicotine levels. The primary aim was to compare the EU- (18 mg/mL nicotine strength) with the U.S.-JUUL (59 mg/mL) on daily smokers' subjective experiences, craving relief, and blood nicotine levels. AIMS AND METHODS: Double-blind, counterbalanced within-participants design with two conditions: 18 mg/mL versus 59 mg/mL. On two separate occasions, UK smokers (N =19, 10 males, 9 females) vaped ad libitum for 60 mins and provided blood samples at baseline 5, 15, 30, and 60 min. Subjective effects (incl. satisfaction) were measured at 10 and 60 min and, craving and withdrawal symptoms (WS) at baseline, 10 and 60 min. RESULTS: Satisfaction did not differ between conditions. There was a significant interaction between Time and Nicotine concentration for Nicotine Hit (p = .045). Mean self-report of Nicotine Hit increased under the use of the 59 mg/mL from 10 to 60 min and decreased under the 18 mg/mL. Participants reported higher Throat Hits following use of the 59 mg/mL (p = .017). There were no differences in other subjective effects including craving, WS relief (ps > .05). Liquid consumption was doubled under the 18 versus the 59 mg/mL (p = .001) and nicotine boost was significantly higher in the 59 mg/mL at all time-points (p ≤ .001). CONCLUSIONS: The results did not support our hypotheses that satisfaction, craving, and withdrawal reduction would be higher with the 59 mg/mL JUUL. This could be because of the doubling of liquid consumption in the 18 mg/mL. Whether satisfaction and craving relief persist over the longer-term outside of the lab remains to be determined. IMPLICATIONS: In a 60-min ad-lib vaping session, the EU-JUUL was found to produce comparable satisfaction, craving- and withdrawal relief as the U.S.-JUUL in this sample of UK smokers. These findings could suggest that the higher nicotine concentrations available in PVDs in the United States are not necessary for providing satisfaction and improving craving and WS. However, this was at the expense of a considerable increase in liquid consumption indicative of compensatory puffing.

Trends in cross-border and illicit tobacco purchases among people who smoke in England, 2019-2022.

OBJECTIVES: The last 5 years have seen substantial changes in England's social and economic landscape as a result of Brexit, the COVID-19 pandemic and cost of living crisis. We aimed to examine changes in cross-border and illicit tobacco purchasing over this period. DESIGN: Nationally representative monthly cross-sectional survey. SETTING: England, 2019-2022. PARTICIPANTS: 11 232 adults (≥18 years) who smoked in the past year. MAIN OUTCOME MEASURES: We estimated time trends in the proportion reporting purchasing tobacco from (1) cross-border and (2) illicit sources in the past 6 months. RESULTS: Between February 2019 and October 2022, there was a non-linear increase in the proportion of participants reporting cross-border tobacco purchases (from 5.2% to 16.1% overall; prevalence ratio (PR)=3.10, 95% CI 2.03-4.73). Prevalence first increased from 5.2% to 15.4% between February 2019 and April 2020, before falling to 7.8% between April 2020 and September 2021 during the COVID-19 pandemic, and then increasing again to 16.1% by the end of the period. Changes in cross-border tobacco purchasing were more pronounced among participants from more advantaged (from 6.6% to 23.3%; PR=3.52, 95% CI 2.05-5.91) compared with less advantaged (4.4% to 11.5%; PR=2.61, 95% CI 1.17-5.20) social grades (pinteraction=0.034). There was no overall change in the proportion reporting illicit tobacco purchases (from 9.2% to 8.5%; PR=0.92, 95% CI 0.70-1.21), nor any significant difference in trends by social grade (pinteraction=0.783). CONCLUSIONS: Despite a fall in cross-border tobacco purchasing during the first year of the COVID-19 pandemic among adults in England who smoke, the proportion reporting cross-border tobacco purchases is now three times higher than it was at the start of 2019. The proportion reporting illicit tobacco purchases has not changed substantially.

How can tuberculosis services better support patients with a diabetes co-morbidity? A mixed methods study in the Philippines.

BACKGROUND: People with diabetes mellitus (DM) have an estimated two- to three-times greater risk of adverse tuberculosis (TB) treatment outcomes compared to those without DM. Blood glucose control is a primary aim of managing DM during TB treatment, yet TB programmes are not generally adapted to provide DM services. The purpose of this study was to understand perceptions and the lived experiences of diabetic patients in TB treatment in the Philippines, with a view to informing the development of disease co-management strategies. METHODS: This mixed methods study was conducted within a prospective cohort of adults newly-starting treatment for drug-sensitive and drug-resistant TB at 13 public TB clinics in three regions of the Philippines. Within the subset of 189 diabetic persons who self-reported a prior DM diagnosis, or were diagnosed by screenings conducted through the TB clinic, longitudinal blood glucose data were used to ascertain individuals' glycaemic control (controlled or uncontrolled). Univariable logistic regression analyses exploring associations between uncontrolled glycaemia and demographic and clinical factors informed purposive sampling of 31 people to participate in semi-structured interviews. All audio-recorded data were transcribed and thematic analysis performed. RESULTS: Participants - both with controlled and uncontrolled blood glucose - were knowledgeable about diabetes and its management. However, a minority of participants were aware of the impact of DM on TB treatment and outcomes. Many participants newly-diagnosed with DM at enrolment in TB treatment had not perceived any diabetic symptoms prior and would have likely not sought clinical consult otherwise. Access to free glucose-lowering medications through TB clinics was a key enabling resource. However, participants expressed fear of side effects and interrupted access to glucose-lowering medications, and a preference for phytotherapy. Many participants felt that physical and financial impacts of TB and its treatment were challenges to DM management. CONCLUSIONS AND RECOMMENDATIONS: Results of this study indicate that public TB clinics can provide diabetic patients with additional health care resources and education to address co-morbidity. TB programmes might consider identifying patients with complicated DM, and offering diabetic monitoring and management, as DM and diabetic complications may compound the burden of TB and its treatment.

Surgical management of extrahepatic portal vein obstruction in children: advantages of MesoRex shunt compared with distal splenorenal shunt.

PURPOSE: To review surgical management of extrahepatic portal vein obstruction (EHPVO) at Red Cross War Memorial Children's Hospital and compare MesoRex shunt (MRS) with distal splenorenal shunt (DSRS). METHODS: This is a single-centre retrospective review documenting pre- and post-operative data in 21 children. Twenty-two shunts were performed, 15 MRS and 7 DSRS, over an 18-year period. Patients were followed up for a mean of 11 years (range 2-18). Data analysis included demographics, albumin, prothrombin time (PT), partial thromboplastin time (PTT), International normalised ratio (INR), fibrinogen, total bilirubin, liver enzymes and platelets before the operation and 2 years after shunt surgery. RESULTS: One MRS thrombosed immediately post-surgery and the child was salvaged with DSRS. Variceal bleeding was controlled in both groups. Significant improvements were seen amongst MRS cohort in serum albumin, PT, PTT, and platelets and there was a mild improvement in serum fibrinogen. The DSRS cohort showed only a significant improvement in the platelet count. Neonatal umbilic vein catheterization (UVC) was a major risk for Rex vein obliteration. CONCLUSION: In EHPVO, MRS is superior to DSRS and improves liver synthetic function. DSRS does control variceal bleeding but should only be considered when MRS is not technically feasible or as a salvage procedure when MRS fails.

The pre-surgical factors that determine the decision to proceed to resection in children diagnosed with high-risk neuroblastoma in a resource limited setting.

Surgical control has prognostic value in neuroblastoma (NB). Advanced NB is common at diagnosis in South Africa. We investigated the pre-surgery factors that influenced decisions to perform surgical resections. We included 204 patients with high-risk NB from a national retrospective study, who completed induction chemotherapy between 2000 and 2016.The median age was 32.4 months (IQR 15.1 - 53.5 months). Primary tumor resection was achieved in 76.9% of patients between 0-18 months of age, 51.8% between 18-60 months and 51.7% older than 60 months (p < 0.001). Only 43.2% of patients with distant metastatic disease had surgery done (p < 0.001). LDH was >750 U/L in 46.8% and ferritin >120 g/dL in 53.1% of those who had surgery (p = 0.005). The majority (80.4%), who had achieved post-induction metastatic complete remission (mCR), were operated, while 28.7% without mCR had surgery (p < 0.001). The long-term overall survival in patients with mCR and primary tumor resection was 36.5% compared to those with mCR without primary tumor resection (25.4%) and without mCR (≤3.0%)(p < 0.001). Age (p < 0.001), stage (p < 0.001), mCR (p < 0.001) and treatment setting (p < 0.001) were of prognostic significance. The tumor site and MYCN-amplification did not significantly predict resection rates. Post-induction mCR and stage were associated with surgical resection and five-year OS (p < 0.001) on multivariate analysis.Patients with high-risk NB who achieved mCR and had primary tumor resections are curable in limited resourced settings. Stage and post-induction mCR were significant variables that led to surgery. These variables should be included as indications in the management of metastatic NB in resource limited settings.

High-risk neuroblastoma that achieved post-induction chemotherapy metastatic remission and have undergone resection, is curable, even in limited resource settings.Achieving metastatic complete remission was the only factor that significantly predicated if surgery was done.The age at diagnosis, stage and hospitals with expertise in neuroblastoma surgery were of prognostic significance in South Africa.If a patient with high-risk neuroblastoma achieves metastatic complete remission in a resource limited setting, it should be an indication for resection of the primary tumor.

Association of postnatal severe acute malnutrition with pancreatic exocrine and endocrine function in children and adults: a systematic review.

Severe acute malnutrition may lead both concurrently and subsequently to malabsorption and impaired glucose metabolism from pancreatic dysfunction. We conducted a systematic review to investigate the associations of current and prior postnatal wasting malnutrition with pancreatic endocrine and exocrine functions in humans. We searched PubMed, Google Scholar, Web of Science and reference lists of retrieved articles, limited to articles in English published before 1 February 2022. We included sixty-eight articles, mostly cross-sectional or cohort studies from twenty-nine countries including 592 530 participants, of which 325 998 were from a single study. Many were small clinical studies from decades ago and rated poor quality. Exocrine pancreas function, indicated by duodenal fluid or serum enzymes, or faecal elastase, was generally impaired in malnutrition. Insulin production was usually low in malnourished children and adults. Glucose disappearance during oral and intravenous glucose tolerance tests was variable. Upon treatment of malnutrition, most abnormalities improved but frequently not to control levels. Famine survivors studied decades later showed ongoing impaired glucose tolerance with some evidence of sex differences. The similar findings from anorexia nervosa, famine survivors and poverty- or infection-associated malnutrition in low- and middle-income countries (LMIC) lend credence to results being due to malnutrition itself. Research using large, well-documented cohorts and considering sexes separately, is needed to improve prevention and treatment of exocrine and endocrine pancreas abnormalities in LMIC with a high burden of malnutrition and diabetes.

Evidence-based surgical guidelines for treating children with Wilms tumor in low-resource settings.

BACKGROUND: Survival of Wilms tumor (WT) is > 90% in high-resource settings but < 30% in low-resource settings. Adapting a standardized surgical approach to WT is challenging in low-resource settings, but a local control strategy is crucial to improving outcomes. OBJECTIVE: Provide resource-sensitive recommendations for the surgical management of WT. METHODS: We performed a systematic review of PubMed and EMBASE through July 7, 2020, and used the GRADE approach to assess evidence and recommendations. RECOMMENDATIONS: Initiation of treatment should be expedited, and surgery should be done in a high-volume setting. Cross-sectional imaging should be done to optimize preoperative planning. For patients with typical clinical features of WT, biopsy should not be done before chemotherapy, and neoadjuvant chemotherapy should precede surgical resection. Also, resection should include a large transperitoneal laparotomy, adequate lymph node sampling, and documentation of staging findings. For WT with tumor thrombus in the inferior vena cava, neoadjuvant chemotherapy should be given before en bloc resection of the tumor and thrombus and evaluation for viable tumor thrombus. For those with bilateral WT, neoadjuvant chemotherapy should be given for 6-12 weeks. Neither routine use of complex hilar control techniques during nephron-sparing surgery nor nephron-sparing resection for unilateral WT with a normal contralateral kidney is recommended. When indicated, postoperative radiotherapy should be administered within 14 days of surgery. Post-chemotherapy pulmonary oligometastasis should be resected when feasible, if local protocols allow omission of whole-lung irradiation in patients with nonanaplastic histology stage IV WT with pulmonary metastasis without evidence of extrapulmonary metastasis. CONCLUSION: We provide evidence-based recommendations for the surgical management of WT, considering the benefits/risks associated with limited-resource settings.

Inequalities in Smoking and Quitting-Related Outcomes Among Adults With and Without Children in the Household 2013-2019: A Population Survey in England.

INTRODUCTION: Smoking among those who live with children is an important influence on smoking initiation among children. This study assessed socioeconomic inequalities in smoking and quitting-related outcomes among all adults with and without children in the household. AIMS AND METHODS: Monthly repeat cross-sectional household survey of adults (16+) from 2013-2019 in England (N = 138 583). We assessed the association between cigarette smoking and quitting-related outcomes and having children in the household, and whether these relationships were moderated by occupational social grade (categories AB-E from most to least advantaged). Trends in smoking prevalence among adults with and without children in the household were explored. RESULTS: In adjusted analysis, the association of having children in the household with smoking prevalence depended on social grade: smoking prevalence was between 0.71 (95% confidence interval 0.66-0.77) and 0.93 (0.88-0.98) times lower among social grades AB-D with children in the household relative to those without. Conversely, it was 1.11 (1.05-1.16) times higher among social grade E. Yearly prevalence declined similarly among those with and without children (both prevalence ratio: 0.98, 95% confidence interval 0.97-0.99). Motivation to stop smoking was higher among those with children than those without, but lower among disadvantaged than more advantaged groups. Social grades D-E had greater heavy smoking, but higher prevalence of past-month quit attempts. CONCLUSIONS: Among the most disadvantaged social grade in England, smoking prevalence was higher in those with children in the household than without. To attenuate future smoking-related inequalities, there is an urgent need to target support and address barriers to quitting and promote longer-term quit success. IMPLICATIONS: In the most disadvantaged occupational social grade, having children in the household was associated with higher smoking prevalence compared with not having children. This contrasts with all other social grades in which there was lower comparative smoking prevalence among those with than without children in the household. Without attention this disparity could exacerbate existing and future health inequalities related to smoking.

Exploring changes in temporary abstinence in increasing and higher risk drinkers in England and Dry January participation in users of the Try Dry app in the UK between 2020 and 2021.

BACKGROUND: We looked at changes in the prevalence of increasing and higher risk drinkers reporting a reduction attempt motivated by temporary abstinence and changes in prevalence of use of the official app accompanying Dry January between 2020 vs 2021, following the onset of the COVID-19 pandemic. We also explored potential shifts in the sociodemographic composition of both groups. METHODS: We analysed data from: i) 1863 increasing and higher risk drinkers (defined as ≥ 8 on the AUDIT) responding to a nationally representative survey of adults in England in January and February 2020 and 2021, and ii) 104,598 users of the 'Try Dry' app, the official aid to those participating in Dry January 2020 and 2021 in the UK. We used logistic regression to examine shifts in the prevalence of increasing and higher risk drinkers reporting a reduction attempt motivated by temporary abstinence and explored whether there were shifts in the characteristics of this group in terms of AUDIT score, number of last year reduction attempts, smoking status, living alone, living with children, reducing alcohol consumption due to future health motives, age, sex, and occupational social grade between 2020 and 2021. We used t-tests and chi-squared tests to compare the prevalence of users of the 'Try Dry' app in 2020 and 2021 and examine whether the two groups differed in terms of age and sex. RESULTS: The proportion of increasing and higher risk drinkers reporting a reduction attempt motivated by temporary abstinence increased from 4% in 2020 to 8% in 2021 (OR = 2.07, 95% CI = 1.38-3.11, p < .001) with no changes detected in sociodemographic composition. The number of Try Dry app users in 2021 increased by 34.8% relative to 2020. App users in 2021 were two years older on average [p < .001, d = .02], with a 2% increase in the proportion of female app users [p < .001, vs. < .01]. CONCLUSIONS: Higher participation in Dry January 2021 relative to 2020 indicates increased engagement with a period of temporary abstinence following the COVID-19 related lockdowns in England and the UK, which is positive in the wider context of increasing alcohol consumption throughout the pandemic.

A cross-sectional survey of smoking and cessation support policies in a sample of homeless services in the United Kingdom.

BACKGROUND: Smoking is extremely common amongst adults experiencing homelessness. To date, there is no nationally representative data on how tobacco dependence is treated and if and how smoking cessation is supported across the homeless sector. The aim of this study was to document smoking and e-cigarette policies of UK homeless services and identify areas of good practice and where improvements could be made. METHODS: A cross-sectional survey with homeless centre staff was conducted between June 2020-December 2020 totalling 99 homeless centres. Quotas were stratified based on population and service type across Scotland, Northern Ireland, Wales, and England. Interviews were conducted over the phone or online in a minority of cases. Survey questions were themed to assess, i) onsite smoking and e-cigarette (vaping) policies ii) screening and recording of smoking status, iii) cessation training and resources available to staff, iv) cessation support for service users. RESULTS: 92% accounted for smoking within their policies in some form (stand-alone policy (56%) or embedded within another health and safety policy (36%)). 84% allowed smoking in at least some (indoor and outdoor) areas. In areas where smoking was not allowed, vaping was also disallowed in 96% of cases. Staff smoking rates were 23% and 62% of centres reported staff smoked with service users. Just over half (52%) reported screening and recording smoking status and 58% made referrals to Stop Smoking Services (SSS), although established links with SSS were low (12%) and most centres did not provide staff training on supporting smoking cessation. Areas of good practice included regular offers of smoking cessation support embedded in routine health reviews or visits from SSS and offering tangible harm reduction support. Areas for improvement include staff training, staff smoking with service users and skipping routine screening questions around smoking. CONCLUSIONS: Smoking is accounted for across different policy types and restricted in some areas within most settings. Smoking cessation support is not routinely offered across the sector and there is little involvement with the SSS.

Surgical implications of HIV infection.

According to the joint United Nations Programme on HIV/AIDS (UNAIDS), 37.7 million adults and children worldwide were estimated to be living with HIV or acquired immune deficiency syndrome (AIDS) at the end of 2020 [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. Most reside in low- and middle-income countries, with approximately 67% in sub-Saharan Africa (SSA). At the end of 2020, the total number of children less than 15 years of age living with HIV infection was 2.6 million, of whom 2.3 million (88%) were living in SSA. Aggressive interventions have reduced the annual number of incident (new) HIV infections among children to around 150,000 [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. However, paediatric HIV infection remains a pandemic affecting children predominantly in SSA but is also seen in Asia and sporadically elsewhere particularly in areas of civil strife such as is currently the case in Ukraine [War in Ukraine. (2022). https://www.unaids.org/en/War-Ukraine-special . Accessed Apr 2022]. New HIV infections among children declined by more than half (54%) from 2010 to 2020, due mainly to the increased provision of antiretroviral therapy to pregnant and breastfeeding women living with HIV [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. These programmes include early identification of HIV infection in pregnant or breastfeeding women through routine HIV testing, provision of antiretroviral therapy (ART) to all HIV-infected women who are pregnant or breastfeeding, provision of antiretroviral prophylaxis to their newborn infants during the first 6-12 weeks of life, delivery by elective Caesarean section when indicated, promotion of exclusive breastfeeding, early infancy screening for HIV infection, and initiation of ART in infants with HIV infection. HIV-infected children may require surgery either as an emergency to deal with a life-threatening incidental condition unrelated to HIV infection or for a complication of the disease such as tuberculosis or an aggressive soft tissue infection like necrotising fasciitis. Non-emergency surgical procedures may be required to assist in the diagnosis of an HIV-related condition or to correct a routine surgical problem electively. Surgical conditions associated with HIV infection are described under categories of soft tissue or organ-specific infections requiring drainage or debridement; gastrointestinal tract disease and complications; infections in the perineal area; malignancies and HIV-associated vasculitis. Although surgical outcomes are less favourable in HIV-infected children, pre-operative treatment of coinfections, administration of cotrimoxazole prophylaxis, nutritional support and antiretroviral therapy, together with peri-operative antibiotic prophylaxis have resulted in excellent short-term outcomes [World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: Recommendations for a public health approach, June 201 http://www.apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf?ua=1 ; World Health Organization Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV, September 2015. http://www.apps.who.int/iris/bitstream/10665/186275/1/9789241509565_eng.pdf?ua=1;Eley et al. in BMC Infect Dis 2:3, 2002;Karpelowsky et al. in Pediatr Surg Int 28:1007-1014, 2012;].

Depression and its associated factors among people with multidrug-resistant tuberculosis in Myanmar.

BACKGROUND: Depression is an important potential comorbidity in persons with tuberculosis (TB), yet data in many settings are scarce. OBJECTIVE: To estimate the prevalence and risk factors of depression in persons with multidrug-resistant tuberculosis (MDR-TB) in Myanmar. METHODS: A cross-sectional survey among MDR-TB participants at Aung San MDR-TB treatment centre in Yangon during routine clinic follow-up visits. Patients Health Questionnaire-9 (PHQ-9) in the local language was used to screen for depression and structured questionnaires conducted. Univariable and multivariable logistic regression models were performed to identify associations. RESULTS: Three-hundred and twenty-nine participants were enrolled between 19th December 2019 and 31st January 2020; 33% (111/329) in the intensive treatment phase. The prevalence of depressive symptoms (PHQ-9 ≥ 10) was (34/329) 10.33%. Multivariable analysis indicated financial hardship as a result of MDR-TB symptoms/treatment (aOR = 2.63, 95%CI: 1.12-6.67), suffering ≥1 respiratory symptoms (aOR = 6.72, 95%CI: 2.41-18.76), high education level (aOR = 4.26, 95%CI: 1.70-10.70), reported diabetes (aOR = 3.05, 95%CI: 1.16-7.99) as associated with depressive symptoms, with weak evidence of an association in females (aOR = 2.09, 95%CI: 0.94-4.65). CONCLUSION: Depressive symptoms are more common in those with comorbidities/TB symptoms. Further research is required to determine the effects of interventions to support persons with depressive symptoms identified using simple, standardised validated tools like PHQ-9.

The Time Course of Compensatory Puffing With an Electronic Cigarette: Secondary Analysis of Real-World Puffing Data With High and Low Nicotine Concentration Under Fixed and Adjustable Power Settings.

INTRODUCTION: In a secondary analysis of our published data demonstrating compensatory vaping behavior (increased puff number, puff duration, and device power) with e-cigarettes refilled with low versus high nicotine concentration e-liquid, here we examine 5-day time course over which compensatory behavior occurs under fixed and adjustable power settings. AIMS AND METHODS: Nineteen experienced vapers (37.90 ± 10.66 years, eight females) vaped ad libitum for 5 consecutive days under four counterbalanced conditions (ie, 20 days in total): (1) low nicotine (6 mg/mL)/fixed power (4.0 V/10 W); (2) low nicotine/adjustable power; (3) high nicotine (18 mg/mL)/fixed power; (4) high nicotine/adjustable power (at 1.6 Ohm). Puff number, puff duration, and power settings were recorded by the device. For each day, total daily puffing time was calculated by multiplying daily puff number by mean daily puff duration. RESULTS: A significant day × setting interaction revealed that whilst puffing compensation (daily puffing time) continued to increase over 5 days under fixed power, it remained stable when power settings were adjustable. Separate analysis for puff number and puff duration suggested that the puffing compensatory behavior was largely maintained via longer puff duration. CONCLUSIONS: Under fixed power conditions (4.0 V/10 W), vapers appear to compensate for poor nicotine delivery by taking longer puffs and this compensatory puffing appears to be maintained over time. IMPLICATIONS: Studies in smokers suggest that when switching to lower nicotine levels, compensation for poorer nicotine delivery is transient. Our novel findings suggest that vapers show a different pattern of compensation which is influenced by both nicotine strength and device power settings. When power is fixed (4.0 V; 10 W), compensation (via more intensive puffing) appears prolonged, persisting up to 5 days. Under adjustable settings when power is increased, puffing patterns remain stable over time. Implications of such compensatory behaviors for product safety and user satisfaction need further exploration.

Association between cigarette smoking status and voting intentions: Cross sectional surveys in England 2015-2020.

BACKGROUND AND AIMS: Cigarette smoking takes place within a cultural and social context. Political views and practices are an important part of that context. To gain a better understanding of smoking, it may be helpful to understand its association with voting patterns as an expression of the political views and practices of the population who smoke. This study aimed to assess the association between cigarette smoking and voting intentions and to examine how far any association can be explained by sociodemographic factors and alcohol use. METHODS: Pooled monthly representative repeat cross-sectional household surveys of adults (16+) in England (N = 55,482) between 2015 and 2020 were used to assess the association between cigarette smoking status and voting intentions, and whether this was accounted for by age, occupational grade, gender, region and alcohol use. Voting intention was measured by asking 'How would you vote if there were a General Election tomorrow?' Respondents chose from a list of the major English political parties or indicated their intention not to vote. RESULTS: In adjusted multinomial regression, compared with intending to vote Conservative (majority party of government during the period), being undecided (aOR1.22 [1.13-1.33] <0.001), intending to vote Labour (aOR1.27 [1.16-1.36] <0.001), to vote "Other" (aOR1.54 [1.37-1.72] <0.001), or not to vote (aOR1.93 [1.77-2.11] <0.001) was associated with higher odds of current relative to never smoking rates. Intending to vote for the Liberal Democrats was associated with a significant lower odds of current smoking prevalence (aOR0.80 [0.70-0.91] <0.001) compared with intending to vote Conservative. CONCLUSIONS: Controlling for a range of other factors, current as compared with never-smokers appear more likely to intend not to vote, to be undecided, to vote for Labour or a non-mainstream party, and less likely to vote for the Liberal Democrats, compared with the Conservative party.

Prevalence and characteristics of ever regular use of non-combustible nicotine for 1 year or more: a population survey in England.

INTRODUCTION: Up-to-date monitoring of non-combustible nicotine products (e.g. e-cigarettes, nicotine replacement therapies (NRT), heated tobacco products (HTP); NNP) is important to assess their impact. To date, there is little evidence on the association between ever regular use (defined here as 1 year or more) of NNP and current smoking status. AIMS/METHODS: The purpose of this study was to examine the prevalence, and sociodemographic, alcohol and smoking status correlates, of ever regular use of NNP in England in 2020. A cross-sectional survey of adults in England was conducted between February and June 2020. RESULTS: A total of 8486 adults were surveyed; 94.9% (8055) were complete cases. The weighted prevalence of ever regular NNP use was 5.4% (n = 436; 95% CI 5.0-6.0), of which 82% (n = 360; 95% CI 78.7-85.8) was single and 18% (n = 79; 95% CI 14.8-22) multiple product use. Amongst ever regular NNP users, the prevalence of ever regular NRT, e-cigarette and HTP use was 64.7% (95% CI 60.1-69), 43.4% (95% CI 38.8-48) and 2.5% (95% CI 1.4-4.5), respectively. In adjusted analysis, ever regular NNP use was associated with smoking status, being significantly higher among current (22.3%; adjusted OR (aOR) 34.9, 95% CI 24.0-50.8) and ex-smokers (12.7%, aOR 19.8, 95% CI 11.1-14.4) than among never-smokers (0.6%). More advantaged occupational grade (aOR, 1.27 95% CI 1.02-1.57) and at least hazardous alcohol use (aOR, 1.38 95% CI 1.06-1.78) were associated with greater prevalence of ever regular NNP use. CONCLUSIONS: Ever regularly using NNP was highest among smokers and ex-smokers and rare among never-smokers. Among people who have ever regularly used NNP, NRT is the most popular.