Primary Analysis Research Articles

Primary Quench Detection Analysis for the EU-DEMO Toroidal Field Coils

Primary Quench Detection Analysis for the EU-DEMO Toroidal Field Coils

Maternal Morbidity According to Mode of Delivery Among Pregnant Patients With Pulmonary Hypertension.

Patients with pulmonary hypertension have a high risk of maternal morbidity and mortality. It is unknown if a trial of labor carries a lower risk of morbidity in these patients compared to a planned cesarean delivery. The objective of this study was to examine the association of delivery mode with severe maternal morbidity events during delivery hospitalization among patients with pulmonary hypertension. This retrospective cohort study used the Premier inpatient administrative database. Patients delivering ≥25 weeks gestation from January 1, 2016, to September 30, 2020, and with pulmonary hypertension were included. The primary analysis compared intended vaginal delivery (ie, trial of labor) to intended cesarean delivery (intention to treat analysis). A sensitivity analysis was conducted comparing vaginal delivery to cesarean delivery (as treated analysis). The primary outcome was nontransfusion severe maternal morbidity during the delivery hospitalization. Secondary outcomes included blood transfusion (4 or more units) and readmission to the delivery hospital within 90 days from discharge from delivery hospitalization. The cohort consisted of 727 deliveries. In the primary analysis, there was no difference in nontransfusion morbidity between intended vaginal delivery and intended cesarean delivery groups (adjusted odds ratio [aOR], 0.75; 95% confidence interval [CI], 0.49-1.15). In secondary analyses, intended cesarean delivery was not associated with blood transfusion (aOR, 0.71; 95% CI, 0.34-1.50) or readmission within 90 days (aOR, 0.60; 95% CI, 0.32-1.14). In the sensitivity analysis, cesarean delivery was associated with a 3-fold higher risk of nontransfusion morbidity compared to vaginal delivery (aOR, 2.64; 95% CI, 1.54-3.93), a 3-fold higher risk of blood transfusion (aOR, 3.06; 95% CI, 1.17-7.99), and a 2-fold higher risk of readmission within 90 days (aOR, 2.20; 95% CI, 1.09-4.46) compared to vaginal delivery. Among pregnant patients with pulmonary hypertension, a trial of labor was not associated with a higher risk of morbidity compared to an intended cesarean delivery. One-third of patients who required an intrapartum cesarean delivery had a morbidity event, demonstrating the increased risk of adverse events in this group.

Comparative Efficacy, Tolerability, and Acceptability of Donanemab, Lecanemab, Aducanumab, Melatonin, and Aerobic Exercise for a Short Time on Cognitive Function in Mild Cognitive Impairment and Mild Alzheimer's Disease: A Systematic Review and Network Meta-Analysis.

The Food and Drug Administration (FDA) has approved lecanemab and aducanumab and is reviewing donanemab, but they have questionable efficacy, serious side effects and are costly, whereas melatonin administration and aerobic exercise for a short time may overcome these problems. We aim to compare the efficacy on cognitive function, tolerability and acceptability of melatonin administration and aerobic exercise for a short time with donanemab, lecanemab, and aducanumab in people with mild AD and MCI. We systematically reviewed relevant randomized placebo-controlled trials (RCTs) in PubMed, the Cochrane Library, CINHAL, and ClinicalTrials.gov and performed network meta-analyses. The analysis included 10 randomized placebo-controlled trials with 4,599 patients. Although melatonin and aerobic exercise for a short time were significantly more effective than donanemab, lecanemab, aducanumab and placebo in the primary analysis, there was significant heterogeneity. In the sensitivity analysis excluding exercise, melatonin was significantly more effective than donanemab, lecanemab, aducanumab and placebo, with no significant heterogeneity. Aerobic exercise for a short time was significantly less acceptable than donanemab, aducanumab and placebo. Donanemab, lecanemab, and aducanumab were significantly less tolerable than placebo and donanemab and lecanemab were significantly less acceptable than placebo. Melatonin may be a better potential disease-modifying treatment for cognitive decline in mild AD and MCI. Aerobic exercise for a short time might also be better than donanemab, lecanemab and aducanumab if continued, as it is well tolerated and more effective, although less valid due to heterogeneity. Another limitation is the small number of participants.

Maternal childhood trauma and observed maternal care behaviors with 4-month-old infants.

To examine the relationship between maternal childhood trauma and early maternal caregiving behaviors (MCB). Participants included 74 mother-infant dyads (maternal age 20-45 years; ethnicity 64.9% Latina) from a longitudinal pregnancy cohort study. Maternal childhood trauma was assessed during pregnancy with the childhood trauma questionnaire (CTQ). Observed mother-infant interactions at infant age 4 months were coded utilizing modified Ainsworth's MCB rating scales that assessed a range of behaviors (e.g., acceptance, soothing, and delight) which we analyze grouped together and will summarize using the term "maternal sensitivity." Linear regressions tested the associations between maternal childhood trauma and MCB. Primary analyses examined the relationships of MCB with (a) any maternal childhood trauma (moderate or greater exposure to physical abuse, sexual abuse, emotional abuse, physical neglect, and/or emotional neglect) and (b) cumulative childhood trauma. Secondary analyses examined the relationships between each type of childhood trauma and MCB. Exposure to childhood trauma was not associated with MCB (p = .88). Cumulative childhood trauma score was associated with lower scores on MCB (β = -1.88, p < .05). Emotional abuse and emotional neglect were individually associated with lower scores on MCB (β = -1.78, p = .04; β = -1.55, p = .04, respectively). Physical abuse, sexual abuse, and physical neglect were not associated with MCB. Many mothers exposed to childhood trauma may be resilient to negative effects on parenting behaviors, while specific experiences of childhood trauma (emotional abuse, emotional neglect, and cumulative childhood trauma) may predict less sensitive early parenting behaviors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Enabling pandemic‐resilient healthcare: Narrowband Internet of Things and edge intelligence for real‐time monitoring

AbstractThe Internet of Things (IoT) in deploying robotic sprayers for pandemic‐associated disinfection and monitoring has garnered significant attention in recent research. The authors introduce a novel architectural framework designed to interconnect smart monitoring robotic devices within healthcare facilities using narrowband Internet of Things (NB‐IoT) technology. The core objective is establishing a seamless data transmission pipeline that bridges these devices with the nearest base station. The associated data is routed directly from the edge computing infrastructure to the Cloud storage. The proposed architecture increases data security and optimises system performance by avoiding dependencies on central data centres. The critical components of this system allow the edge node to transmit data to the cloud, where primary data processing and analysis occur. The selection of NB‐IoT as the underlying protocol facilitates real‐time data collection and monitoring in healthcare with boosted capacity and coverage, extended battery life, and cost efficiency.

Association of lipid-modifying therapy with risk of obstructive sleep apnea: A drug-target mendelian randomization study

BackgroundObstructive sleep apnea (OSA) is considered to be an important contributor of dyslipidemia. However, there lacks observational studies focusing on the potential effect of lipid management on OSA risk. Thus, we aimed to investigate the genetic association of lipid-modifying therapy with risk of OSA. MethodsA drug-target mendelian randomization (MR) study using both cis-variants and cis-expression quantitative trait loci (eQTLs) of lipid-modifying drug targets was performed. The MR analyses used summary-level data of genome wide association studies (GWAS). Primary MR analysis was conducted using inverse-variance-weighted (IVW) method. Sensitivity analysis was performed using weighted median (WM) and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. ResultsGenetically proxied low-density lipoprotein cholesterol (LDL-C)-lowering effect of cholesteryl ester transfer protein (CETP) was associated with reduced risk of OSA (odds ratio [OR] =0.75, 95% confidence interval [CI]: 0.60–0.94, false discovery rate [FDR] q value = 0.046). A significant MR association with risk of OSA was observed for CETP expression in subcutaneous adipose tissue (OR = 0.94, 95%CI: 0.89–1.00, FDR q value = 0.049), lung (OR = 0.94, 95%CI: 0.89–1.00, FDR q value = 0.049) and small intestine (OR = 0.96, 95%CI: 0.93–1.00, FDR q value = 0.049). No significant effects of high-density lipoprotein cholesterol (HDL-C)-raising effect of CETP inhibition, LDL-C-lowering and triglycerides-lowering effect of other drug targets on OSA risk were observed. ConclusionsThe present study presented genetic evidence supporting the association of LDL-C-lowering therapy by CETP inhibition with reduced risk of OSA. These findings provided novel insights into the role of lipid management in patients with OSA and encouraged further clinical validations and mechanistic investigations.

Study Partner Type and Adverse Event Reporting in Mild-to-Moderate Alzheimer's Disease Clinical Trials.

In randomized clinical trials (RCTs), monitoring adverse events (AEs) and serious AEs (SAEs) is critical. All Alzheimer's disease (AD) RCTs require participants to enroll with a study partner. We examined AE reporting rates in mild-to-moderate AD trials and their associations with study partner type. We estimated AE reporting rates using placebo data from seven independent RCTs conducted by the Alzheimer's Disease Cooperative Study. We assessed the heterogeneity of reporting rates as a function of visits using generalized estimating equations. In the primary analysis, we tested the hypotheses that the rates of reporting differed by study partner type and time they spent with the participant weekly using Poisson regression with robust variance estimation. In all regression models, log-transformed total patient years was included. The estimated reporting rates were 2.83 (95% CI: 2.66, 3.02), 1.18 (95% CI: 1.09, 1.28), 0.23 (95% CI: 0.19, 0.27), and 0.28 (95% CI: 0.24, 0.33) events per participant year for grade 1-3 AEs and SAEs, respectively. We estimated that greater number of visits per year was associated with increased reporting for grade 1-2 AEs and SAEs. We did not find evidence to suggest that AE reporting differed by study partner type or by time the study partner spent with the participant. Study partner type and time the study partner spent with the participant did not appear to impact AE reporting. Estimated reporting rates may be useful to evaluate safety in future studies, particularly those with no control arm and similar visit frequencies.

Association between non-scarring alopecia and hypothyroidism: a bidirectional two-sample Mendelian randomization study.

Non-scarring alopecia is typically represented by two main types: alopecia areata (AA) and androgenetic alopecia (AGA). While previous observational studies have indicated a link between non-scarring alopecia and hypothyroidism, the precise causal relationship remains uncertain. To determine the potential links between non-scarring alopecia and hypothyroidism, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis. We used independent genetic instruments from the FinnGen consortium for AA (682 cases, 361,140 controls) and AGA (195 cases, 201,019 controls) to investigate the association with hypothyroidism in the UK Biobank study (22,687 cases, 440,246 controls). The primary analysis was performed using the inverse variance-weighted method. Complementary approaches were employed to evaluate the pleiotropy and heterogeneity. Genetically predicted AA exhibited a positive causal effect on hypothyroidism (odds ratio [OR], 1.0017; 95% confidence interval [CI], 1.0004-1.0029; P = 0.0101). Additionally, hypothyroidism was found to be strongly correlated with an increase in the risk of AA (OR, 45.6839; 95% CI, 1.8446-1131.4271, P = 0.0196). However, no causal relationship was demonstrated between AGA and hypothyroidism. A sensitivity analysis validated the integrity of these causal relationships. This MR study supports a bidirectional causal link between AA and hypothyroidism. Nevertheless, additional research is needed to gain a more thorough comprehension of the causal relationship between non-scarring alopecia and hypothyroidism.

Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC-1 study design.

Cancer cachexia is a multifactorial metabolic wasting syndrome characterized by anorexia, unintentional loss of weight involving both skeletal muscle and adipose tissues, progressive functional impairment and reduced survival. Therapeutic strategies for this serious condition are very limited. Growth differentiation factor 15 (GDF-15) is a cytokine that is implicated in cancer cachexia and may represent both a biomarker of cancer cachexia and a potential therapeutic target. Ponsegromab is a potent and selective humanized monoclonal antibody that inhibits GDF-15-mediated signalling. Preclinical and preliminary phase 1 data suggest that ponsegromab-mediated inactivation of circulating GDF-15 may lead to improvement in key characteristics of cachexia. The primary objective of this phase 2 study is to assess the effect of ponsegromab on body weight in patients with cancer, cachexia and elevated GDF-15 concentrations. Secondary objectives include assessing physical activity, physical function, actigraphy, appetite, nausea and vomiting, fatigue and safety. Exploratory objectives include evaluating pharmacokinetics, pharmacodynamics, immunogenicity, lumbar skeletal muscle index and Response Evaluation Criteria in Solid Tumors. Approximately 168 adults with non-small-cell lung, pancreatic or colorectal cancers who have cachexia and elevated GDF-15 concentrations will be randomized in a double-blind, placebo-controlled study (NCT05546476). Participants meeting eligibility criteria will be randomized 1:1:1:1 to one of three dose groups of ponsegromab (100, 200 or 400mg) or matching placebo administered subcutaneously every 4weeks for an initial 12-week treatment period. This is followed by optional open-label treatment with ponsegromab of 400mg administered every 4weeks for up to 1year. The primary endpoint is mean change from baseline in body weight at Week 12. A mixed model for repeated measures followed by a Bayesian Emax model will be used for the primary analysis. Secondary endpoints include physical activity, physical function and actigraphy measured by remote digital sensors; patient-reported appetite-related symptoms assessed by Functional Assessment of Anorexia-Cachexia Therapy subscale scores; anorexia/appetite, nausea and vomiting, and fatigue evaluated according to questions from the Cancer-Related Cachexia Symptom Diary; and incidence of adverse events, safety laboratory tests, vital signs and electrocardiogram abnormalities. Cancer-related cachexia is an area of significant unmet medical need. This study will support the clinical development of ponsegromab as a novel inhibitor of GDF-15, which may ameliorate key pathologies of cancer cachexia to improve patient symptoms, functionality and quality of life. ClinicalTrials.gov ID: NCT05546476.

Association between 19 medication use and risk of common cancers: A cross-sectional and Mendelian randomisation study.

Previous studies have yielded inconsistent results concerning drug use and the risk of cancers. We conducted a large-scale cross-sectional study and a two-sample Mendelian randomisation (MR) study to reveal the causal effect between the use of 19 medications and the risk of four common cancers (breast, lung, colorectal, and prostate). We obtained information on medication use and cancer diagnosis from National Health and Nutrition Examination Survey participants. After propensity score matching, we conducted survey-weighted multivariate logistic regression and restricted cubic spline analysis to assess the observed correlation between medication use and cancer while adjusting for multiple covariates. We also performed MR analysis to investigate causality based on summary data from genome-wide association studies on medication use and cancers. We performed sensitivity analyses, replication analysis, genetic correlation analysis, and reverse MR analysis to improve the reliability of MR findings. We found that the use of agents acting on the renin-angiotensin system was associated with reduced risk of prostate cancer (odds ratio (OR) = 0.42; 95% confidence interval (CI) = 0.27-0.63, P < 0.001), and there was a nonlinear association of 'decrease-to-increase-to-decrease' (P < 0.0001). The random-effects inverse variance weighted (IVW) model-based primary MR analysis (OR = 0.94, 95% CI = 0.91-0.97, P = 0.0007) and replication MR analysis (OR = 0.90, 95% CI = 0.85-0.96, P = 0.0006) both provided robust evidence of the causality of genetic liability for the use of agents acting on the renin-angiotensin system on a decreased risk of prostate cancer. Our study provides robust evidence that the use of drugs acting on the renin-angiotensin system can reduce prostate cancer risk. Given the high prevalence of prostate cancer, these findings have important implications for drug selection and prostate cancer prevention in patients with cardiovascular disease.

Diagnostic Utility of Glial Fibrillary Acidic Protein Beyond 12 Hours After Traumatic Brain Injury: A TRACK-TBI Study.

Blood levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) within 12h of suspected traumatic brain injury (TBI) have been approved by the Food and Drug administration to aid in determining the need for a brain computed tomography (CT) scan. The current study aimed to determine whether this context of use can be expanded beyond 12h post-TBI in patients presenting with Glasgow Coma Scale (GCS) 13-15. The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled TBI participants aged ≥17 years who presented to a United States Level 1 trauma center and received a clinically indicated brain CT scan within 24h post-injury, a blood draw within 24h and at 14 days for biomarker analysis. Data from participants with emergency department arrival GCS 13-15 and biomarker values at days 1 and 14 were extracted for the primary analysis. A subgroup of hospitalized participants with serial biomarkers at days 1, 3, 5, and 14 were analyzed, including plasma GFAP and UCH-L1, and serum neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B). The primary analysis compared biomarker values dichotomized by head CT results (CT+/CT-). Area under receiver-operating characteristic curve (AUC) was used to determine diagnostic accuracy. The overall cohort included 1142 participants with initial GCS 13-15, with mean age 39.8 years, 65% male, and 73% Caucasian. The GFAP provided good discrimination in the overall cohort at days 1 (AUC = 0.82) and 14 (AUC = 0.72), and in the hospitalized subgroup at days 1 (AUC = 0.84), 3 (AUC = 0.88), 5 (AUC = 0.82), and 14 (AUC = 0.74). The UCH-L1, NSE, and S100B did not perform well (AUC = 0.51-0.57 across time points). This study demonstrates the utility of GFAP to aid in decision-making for diagnostic brain CT imaging beyond the 12h time frame in patients with TBI who have a GCS 13-15.

Ethno-linguistic and cultural interaction on the Russian-Chinese borderland

INTRODUCTION. Problems of dialogue of cultures and dialogue of languages on the Russian -Chinese borderland are currently actively attracting researchers. In the process of interaction b etween ethnic groups on the eastern section of the border between Russia and China, an exchange of information inevitably occurs, which is contained in political statements, media texts, works of science, technology, fiction, as well as through spontaneous information flows during informal communication between communication participants. The purpose of the study is to describe the interaction of languages on the Russian-Chinese borderland.MATERIALS AND METHODS. The material consists of recordings of speech of residents of the Far East. The main method is descriptive, which includes procedures for collecting material, its primary analysis, presentation of the results obtained and their characteristics. Elements of the comparative method are also used when comparing data from the Russian and Chinese languages.RESULTS AND DISCUSSION. It is necessary to separate concepts such as “regiolect” and “regionalism”. There is no special regionalect in the Far East, but the peculiarities of the speech of the inhabitants of the Outer Manchuria and Primorye regions include regionalisms, which are always represented in dialects, sociolects, and urban speech throughout the territories of distribution of the Russian language.CONCLUSION. The main interaction between the cultures and languages of the Russian and Chinese peoples occurs on the eastern section of the border between the countries, where more than 80 million people live. In the Russian-Chinese borderland, Chineseisms are noted in Russian linguistic culture and Russianisms in Chinese. Russian and Chinese onyms of all categories are widely represented in the speech of residents on both sides of the border, which function in dialect, urban speech and are included by writers in literary texts about the lives of people on both sides of the border.

A population-based time-series analysis of opioid agonist treatment dispensed during pregnancy.

Identifying effective opioid treatment options during pregnancy is a high priority due to the growing prevalence of opioid use disorder across North America. We assessed the temporal impact of three population-level interventions on the use of opioid agonist treatment (OAT) during pregnancy in Ontario, Canada. This was a population-based time-series analysis to identify trends in the monthly prevalence of pregnant people dispensed methadone and buprenorphine. The impact of adding buprenorphine/naloxone to the public drug formulary, the release of pregnancy-specific guidance and the start of the COVID-19 pandemic were assessed. The study was conducted in Ontario, Canada between 1 July 2013 and 31 March 2022, comprising people who delivered a live or stillbirth in any Ontario hospital during the study period. We identified any prescription for methadone or buprenorphine dispensed between the estimated conception date and delivery date and calculated the monthly prevalence of OAT-exposed pregnancies among all pregnant people in Ontario. Overall, rates of OAT during pregnancy have declined since mid-2018. Methadone-exposed pregnancies decreased from 0.46% of all pregnancies in Ontario in 2015 to a low of 0.16% in 2022. In the primary analysis, none of the interventions had a statistically significant impact on overall OAT rates; however, in the stratified analyses, there was a small increase in buprenorphine after the formulary change [0.006%, 95% confidence interval (CI) = 0.0032-0.0081, P < 0.0001] and a decrease in buprenorphine after the release of the 2017 guidelines (-0.005%, 95% CI = -0.0080 to -0.0020, P = 0.001) and the start of the COVID-19 pandemic (-0.003%, 95% CI = -0.0054 to -0.0006, P = 0.015). Despite changes in guidance and funding, opioid agonist treatment during pregnancy has been declining in Ontario, Canada since 2018.

I-Poems: A Window Into the Personal Experiences of Family Caregivers of People Living With Advanced Cancer.

To date, there is little understanding of how caring during advanced cancer can be a transformational experience for personal becoming for family caregivers (FCGs). FCGs experience personal becoming as they create their own meaning of health and illness and choose patterns relating to the self-identity of the past while reaching forward into the unknowns. Gaining greater insight into a potentially positive aspect of cancer caregiving can contribute to family caregiver well-being and quality of life. This paper identifies I-Poems within cancer caregiver narratives and explores them for themes of personal becoming. The narrative environment created space for FCGs to construct and share their voices; at the same time, the analytic method of poetic inquiry provided the voice of the FCGs to be seen, heard, and contextually explored. As a secondary analysis, we used five cancer caregiver narrative texts obtained from the primary study to create individual I-Poems. Each of the I-statements within the cancer caregiver narrative texts was lifted and repositioned into a poem format while retaining the chronological order and voice of the participant. We then explored the I-Poems for converging themes of personal becoming as emerged from the primary narrative-thematic analysis. I-Poems were created from each of the five participants caregivers' narratives and then explored for themes of personal becoming. Each of the participant stories is briefly introduced, followed by their I-Poem. We found that the I-Poems converged with emergent themes and provided a first-person representation of their caring journey and transformation of being. I-Poems are a postmodern form of poetic inquiry that can be used alongside thematic analysis to explore personal meaning of caring for someone with advanced cancer and how FCGs experience personal transformation of self. While we found I-Poems to be a meaningful and useful form of analysis for some narrative data, we propose an evolved genre of poetic inquiry-We-Poems-to be used in dyadic nursing research and with FCGs who are in partnered relationships.

An Exploration of Low Back Beliefs of Male Pre-Professional and Professional Dancers.

Globally, male dancers are affected by low back pain (LBP) up to 2.5 times more than female dancers. While female dancers' beliefs around LBP and dance-specific low back movements exist, no research has explored male dancers' beliefs. This study aimed to (1) examine the low back beliefs of Australian male professional and pre-professional dancers, and (2) determine if beliefs toward common low back movements and lifting differed when current LBP or history of disabling LBP (DLBP) were considered. 40 male dancers (mean age [SD] 26.9 years [7.9]) from a range of dance backgrounds (all participating in ballet) were recruited to complete a cross-sectional survey comprising a beliefs questionnaire considering dance-specific movement and lifting tasks, the Back Pain Attitudes Questionnaire (Back-PAQ) and the Athletic Fear Avoidance Questionnaire (AFAQ). Primary analysis included initial descriptives, a repeated measures ANOVA for movement-specific beliefs and visual thematic analysis for written responses within the belief's questionnaire. Secondary subgroup analysis included independent T-tests for those with/without current LBP and those with/without a history of DLBP. Fourteen dancers reported current LBP and 30 reported a history of DLBP. Dancers held generally negative beliefs toward the low back (Back-PAQ mean 123.1 ± 9.7) with neither subgroup demonstrating significant between-group difference (P < .05). Dance-specific flexion movements were seen as safer than extension movements (P < .05), and more extended-spine lifting was seen as safer than more flexed-spine lifting (P < .05). Dancers experiencing current LBP held less positive beliefs surrounding some dance-specific movements. Dancers hold negative general beliefs toward the low back irrespective of current or historical DLBP, however their beliefs surrounding dance-specific movements were relatively positive. Dancers' beliefs surrounding some movements were affected by the presence of current LBP, in particular an arabesque and a fish dive.

Text message-based Cessation Intervention for People who Smoked or Used Smokeless Tobacco in India: a Feasibility Randomised Controlled Trial.

Despite the high burden of tobacco use in India, users do not have access to adequate help. This pilot trial aimed to evaluate the feasibility and acceptability of a text messaging intervention for tobacco cessation, generate preliminary estimates of its impact, and fine-tune procedures for a definitive trial. Parallel two-arm single blind individually randomised controlled pilot trial with nested qualitative study. Participants included adult current tobacco users (smoked and smokeless). Eligible and consenting participants were randomised to receive either (a) text messaging intervention (ToQuit) which covered specific content areas such as psychoeducation about consequences of tobacco use and benefits of quitting and tobacco avoidance strategies or (b) information about tobacco cessation helplines such as the helpline number and the languages in which tobacco cessation support was available (control). Feasibility data included screening and consent rates, treatment dropouts and outcome ascertainment. The primary abstinence outcome was self-reported abstinence from tobacco in the past seven days at three months post-randomisation. In-depth interviews were conducted with a sub-sample of participants primarily to collect acceptability data. The primary abstinence analysis used a chi-squared test and logistic regression (complete-case), and qualitative data analysed using thematic analysis. Ninety eight participants were randomised into the two trial arms; 77 (79%) completed outcome evaluation. No between-arm differences in abstinence were found though findings favoured the intervention (7-day abstinence: ToQuit 23%, control 19%; adjusted odds ratio 1.23, 95% confidence interval 0.38, 3.97). Participants appreciated the language, comprehensibility, and relevance of the messages; and reported overall satisfaction with and positive impact from the intervention on their lives. The findings indicate the acceptability and feasibility of ToQuit and if found effective, it could be a potentially scalable first-line response to tobacco use in low resource settings. Our pilot RCT provides sufficient findings supporting the acceptability and feasibility of an intervention for tobacco cessation which is suitable for a context which has a shortage of healthcare workers and for individuals who use smoked or smokeless tobacco. This is critical on a background of limited contextually relevant interventions for a problem with a high burden in low- and middle- income countries such as India.

Do Flavour Descriptions Influence Subjective Ratings of Flavoured and Unflavoured E-Liquids among Non-Smoking and Non-Vaping UK Adolescents?

Youth use of electronic cigarettes (e-cigarettes) is rising globally and is associated with health harms. Flavour descriptions on e-liquid packaging may contribute to the appeal of e-cigarettes among youth. This study compared subjective ratings of e-liquid packaging flavour descriptions among non-smoking and non-vaping UK adolescents. This was an online observational study in a UK sample of non-smoking and non-vaping adolescents aged 11-17 years. The primary analyses compared flavoured versus unflavoured descriptions and the secondary analyses compared candy/sweet flavour versus fruit flavour descriptions. Outcomes were packaging appraisal, packaging receptivity, perceived harm, and perceived audience. The survey was completed by 120 participants (74% female). Packaging appraisal ratings were higher for e-liquids with flavoured descriptions than unflavoured descriptions (mean difference 5.9, 95% CI 4.2 to 7.6, p<.001). Similarly, packaging receptivity ratings were higher for e-liquids with flavoured descriptions than unflavoured descriptions (mean difference 4.2, 95% CI 2.8 to 5.6, p<.001). Participants also perceived e-liquids with flavoured (versus unflavoured) descriptions as less 'grown-up' (mean difference -5.2, 95% CI -7.3 to -3.1, p<.001). However, ratings of perceived harm were similar for flavoured and unflavoured descriptions (mean difference -1.0, 95% CI -2.6 to 0.5, p=.189). Although this study found differences in subjective ratings of e-liquids with flavoured and unflavoured descriptions, non-smoking and non-vaping UK adolescents generally had low appraisal and receptivity for e-liquids and they perceived them as being 'grown-up' and harmful. Youth use of electronic cigarettes (e-cigarettes) is increasing globally, leading to concerns about health harms. This study compared adolescents' ratings of e-liquids with flavoured versus unflavoured descriptions and e-liquids with candy/sweet flavour versus fruit flavour descriptions. This study adds to previous studies that have compared adolescents' ratings of e-liquids with tobacco flavour versus non-tobacco flavour descriptions. Although packaging appraisal and receptivity ratings were higher (more positive) for e-liquids with flavoured versus unflavoured descriptions, overall, adolescents who do not smoke or vape had low appraisal and receptivity for e-liquids, and they perceived them as being 'grown-up' and harmful.

Is thyroid function associated with polycystic ovary syndrome? A bidirectional Mendelian randomization study.

Some observational studies have suggested the association between thyroid function and polycystic ovary syndrome (PCOS). However, it remains to be determined whether these associations are causal or not. The aim of this study was to investigate the underlying causal association between different thyroid function status and PCOS. Bidirectional Mendelian randomization (MR) analysis was conducted to explore the impact of different thyroid function statuses on PCOS. The study included 10,074 individuals with PCOS and 103,164 controls for the primary analysis, with validation analysis repeated in the FinnGen R9 and EstBB PCOS cohorts. Female-specific thyroid function GWAS data were obtained from European population, including Hyperthyroidism (22,383 cases and 54,288 controls) and Hypothyroidism (27,383 cases and 54,288 controls) from the UK Biobank, and TSH (54,288 cases and 72,167 controls) and FT4 (49,269 cases and 72,167 controls) within the reference range from the ThyroidOmics Consortium. Inverse variance weighting (IVW) was chosen as the principal method, and sensitivity analysis was conducted to test for the presence of horizontal pleiotropy or heterogeneity. The IVW analysis indicated nominal significance between normal TSH levels and PCOS after adjusted for age and BMI [OR (95% CI) = 0.78(0.62,0.97), P = 0.029], suggesting that maintaining normal TSH levels might act as a protective factor against the pathogenesis of PCOS. Besides, in order to increase the statistical power, we pooled PCOS GWAS above together by meta-analysis and found PCOS contributed to the occurrence of hyperthyroidism [OR(95%CI) = 1.37(0.73,2.57), P = 0.012]. However, no causal relationship was found after Bonferroni correction (P-value < 0.0031). Although the MR analysis didn't indicate genetic causal association between thyroid function and PCOS after Bonferroni correction. Further efforts are needed to interpret the potential causal relationship between thyroid function and PCOS in different age and BMI subgroup.

Relationships between obesity and functional outcome after ischemic stroke: a Mendelian randomization study.

Most previous studies suggested obesity deteriorates the functional outcome after ischemic stroke. But there are researches claiming that obesity is associated with lower mortality, recurrence, and readmission rates, which is known as the obesity paradox. Our current research aimed to investigate the correlation between genetically obesity and the post-stroke outcome with the Mendelian randomization (MR) method. The UK Biobank and the GIANT consortium provided instrumental variables for body mass index (BMI, 806,834 individuals) and waist-to-hip ratio (WHR, 697,734 individuals). Data of functional outcome after ischemic stroke were obtained from the Genetics of Ischemic Stroke Functional Outcome network (6012 individuals). Inverse-variance weighted approach was utilized as the primary analyses. Sensitivity analyses involved the utilization of different MR methods. The heterogeneity among genetic variants was assessed by I2 and Q value statistics. In univariable analysis, there was a significant connection between genetic susceptibility to WHR and worse functional outcome (modified Rankin Scale 3) after ischemic stroke (OR [95%CI] = 1.47 [1.07, 2.02], P = 0.016). Genetic liability to BMI and was not associated with post-stroke functional outcome (all P > 0.05). The overall patterns between genetic liability to WHR and functional outcome post-ischemic outcome no longer existed in the multivariable MR analysis after adjusting for BMI (OR [95%CI] = 1.26[0.76,1.67], P = 0.56). The current MR study provided evidence that WHR was correlated to unfavorable outcome post-ischemic stroke. Exploring interventions against obesity may potentially improve recovery after ischemic stroke.

The association between tinnitus and risk of cardiovascular events and all-cause mortality: insight from the UK Biobank

Background The potential influence of tinnitus on cardiovascular disease (CVD) and all-cause mortality has yet to be explored. We aim to examine the correlations between tinnitus and the risk of cardiovascular events and all-cause mortality. Methods We conducted a prospective cohort study utilising data from the UK Biobank. The presence of tinnitus was evaluated through a questionnaire. The primary outcome was defined as a composition of cardiovascular events, including myocardial infarction (MI), stroke, and mortality from CVD, as well as all-cause mortality. Cox proportional hazard models were employed to examine the associations between tinnitus and both the primary outcome and its individual components. Sensitivity analyses were conducted to evaluate the robustness of the primary analysis. Results A total of 140,146 participants were included in the study. The presence of tinnitus was found to be associated with a higher incident rate of the primary outcome (HR = 1.057, 95%CI: 1.017–1.099, p = 0.005), MI (HR = 1.139, 95%CI: 1.061–1.222, p < 0.001) and all-cause mortality (HR = 1.053, 95%CI: 1.003–1.105, p = 0.038) after adjusting for confounders. However, there was no significant association between tinnitus and stroke or mortality from CVD. Subgroup analysis revealed that the association between tinnitus and the primary outcome was significant in females, participants with abnormal BMI, and those without hearing difficulty, depression or anxiety. Sensitivity analyses yielded consistent results. Conclusion The findings from this study contribute to the existing body of evidence suggesting an association between tinnitus and an increased risk of cardiovascular events and all-cause mortality.