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Drug development for pulmonary arterial hypertension: unleashing the potential of single‐patient studies using continuous monitoring
Get PDFBandung, State-making, and Citizenship in South Asia
Get PDFThe Final Communiqué of the Bandung conference included a set of ten principles that emphasized “respect for the sovereignty and territorial integrity of all nations” and “abstention from intervention or interference in the internal affairs of another country.” In this essay, I examine the impact of these emphases on the domestic law of one of the Bandung states, specifically the law of citizenship in India. Given the significance of state sovereignty and the demarcation of the domestic and international spheres, international law has only generated partial and uneasy responses to questions of citizenship and the intentional creation of statelessness through state policy. Using the Indian case study, I argue that Bandung’s focus on borders has facilitated the disenfranchisement of religious minorities, requiring a rethink of the nation-state as the basis of the international order
Effect of Advertising Exposure on Responses of Young Non‐e‐Cigarette Users to Banning Flavors in China: A Cross‐Sectional Study
Get PDFBackground
E-cigarettes, particularly those with flavors, have become increasingly popular among young people. Many countries have implemented flavor bans, though limited research has explored how non-users react to flavor bans. This research investigates the influence of advertising exposure on changes in intention to use e-cigarettes among young Chinese non-users in response to a hypothetical flavor ban.
Methods
A probability-based online survey conducted from September to November 2021 included 2989 participants aged 20−34. We assessed the association between advertising exposure and change in intention to use e-cigarettes after a hypothetical flavor ban. We used propensity score weighting (PSW) to reduce potential selection bias.
Results
The intention to use e-cigarettes next year among young non-users was rated highly (3.99 out of 5 points), with the flavor ban, this intention decreased by 5.8%. Females showed a greater decline in intention than males (p = 0.011). After adjusting for covariates, young adults with higher advertising exposure exhibited a more pronounced decline in their intention to try e-cigarettes. The interaction between advertising exposure and sex was statistically significant (B = 0.217, p < 0.05), suggesting that females are more likely than males to initiate e-cigarette use with increased advertising exposure.
Conclusions
A flavor ban may have the potential to significantly reduce young people's intention to use e-cigarettes, particularly among females and those exposed to more advertising. These findings highlight the need for sex-specific approaches in tobacco control policies
E-Cigarette Sales to School-Uniformed Adolescents in China: A Randomized Clinical Trial
Get PDFImportance: Electronic cigarettes (e-cigarettes) are appealing to adolescents, but sale of e-cigarettes to individuals younger than 18 years is prohibited in China. The effect of school uniforms on e-cigarette sales to adolescents has not been explored.
Objective: To study e-cigarette sales to adolescents wearing school uniforms compared with those wearing casual attire.
Design, Setting, and Participants: This 2-arm randomized clinical trial involved adolescent mystery shoppers wearing school uniforms or casual attire who attempted to purchase e-cigarettes. The trial was conducted across 36 major metropolitan areas in China from July 29 to September 3, 2023. Adolescent buyers aged 18 to 19 years were randomly assigned to wear 1 of the 2 attire types. A 1:1 matching of e-cigarette and cigarette stores was also performed.
Intervention: Adolescent buyers attempting to purchase e-cigarettes while wearing school uniforms were the intervention group, and those in casual attire served as the control group.
Main Outcomes and Measures: The primary outcome was successful purchase of e-cigarettes. Secondary outcomes assessed whether sellers verbally inquired about the buyer’s age, requested an identification (ID) card for age verification, or dissuaded the buyers from using e-cigarettes. Multivariable logistic regression models identified factors associated with outcomes by attire type, adjusted for buyer, seller, and store characteristics.
Results: The final analytical sample included 1089 visits to e-cigarette stores (543 by adolescents in school uniforms and 546 by those in casual attire) and 1059 visits to cigarette stores. Of the e-cigarette stores visited, 85.4% (95% CI, 80.3%-89.4%) posted external advertising, 39.4% (95% CI, 35.9%-43.0%) were located in shopping malls, 90.8% (95% CI, 87.7%-93.2%) displayed age-of-sale signs, and only 15.0% (95% CI, 9.7%-22.5%) exhibited health warnings specifically for e-cigarettes. The overall success rate of adolescents purchasing e-cigarettes without age verification was 78.3% (95% CI, 75.8%-80.6%), significantly lower than the 94.5% (95% CI, 91.3%-96.6%) success rate for purchasing cigarettes without age verification. Adolescents wearing school uniforms had significantly lower odds of successfully purchasing e-cigarettes (adjusted odds ratio [AOR], 0.39; 95% CI, 0.23-0.66) than those in casual attire and were more likely to be asked about their age (AOR, 9.18; 95% CI, 6.46-13.06), requested to show an ID card (AOR, 6.68; 95% CI, 4.53-9.87), and dissuaded from using e-cigarettes (AOR, 1.79; 95% CI, 1.30-2.47). Additionally, when sellers requested ID cards, the probability of successful e-cigarette purchases was significantly lower than when they did not (AOR, 0.02; 95% CI, 0.01-0.03).
Conclusions and Relevance: In this randomized clinical trial of e-cigarette sales, e-cigarettes remained widely sold to adolescents without age verification in China, but wearing a school uniform appeared to reduce adolescents’ ability to purchase e-cigarettes.
Trial Registration: ClinicalTrials.gov Identifier: NCT0596241
Shape vs flow: a 2D statistical shape analysis of the projection of common iliac veins in patients with deep vein thrombosis
Get PDFDeep vein thrombosis (DVT) of the lower limb is characterised by the formation of abnormal blood clots in deep veins of lower extremity. Changes in blood flow have been associated with an increased risk of thrombus development. Understanding the relationship between variable venous anatomy and haemodynamics can reveal insights to support clinical decision-making processes. The purpose of this study was to combine statistical shape modelling (SSM)- to analyse venous shape- and computational fluid dynamics (CFD)- to estimate blood flowin the common iliac vein to demonstrate the feasibility of a combined framework to support the treatment of DVT. Principal geodesic analysis was used to extract dominant shape modes from a set of 24 venous shapes in 2D: 8 patient-specific extracted from standard angiograms and 16 synthetic complementing the set. Steady-state CFD simulations were run on the associated 3D geometries. Low wall shear stress distributions below three thresholds (< 0.15,< 0.10,< 0.05Pa) were the haemodynamic risk metrics of choice. The distribution of CFD output metrics was evaluated using the three most dominant shape modes from PGA and compared to the three modes that showed the strongest correlation with the CFD metrics, illustrating that they are not the same. The study demonstrated the feasibility of combining SSM and CFD to examine the importance of shape variability and inflow in a local region of the venous circulation. It will serve as a basis for extended work on a larger set of venous shapes extracted from standard medical image
Service delivery, behavioural, and self-management interventions for adults with epilepsy
No full textBACKGROUND: Epilepsy is a common condition, affecting around 660 per 100,000 people worldwide. Despite treatment with anti-seizure medications, one-third of people do not achieve seizure control. There is a need to focus on models of service delivery and therapies that target cognitive, psychological, and behavioural aspects to improve seizure control and quality of life. OBJECTIVES: To assess the effects of service delivery, behavioural, and self-management inventions on seizure control and health-related quality of life in adults with epilepsy. SEARCH METHODS: We used the Cochrane Register of Studies, MEDLINE, and two other databases, together with reference checking and contact with study authors, to identify the studies included in the review. The latest search date was 21 August 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs of any design (double/single-blinded, unblinded; parallel, cross-over, or cluster) involving participants with a mean age of 16 or older. Eligible interventions included behavioural, self-management, or service-delivery approaches. Behavioural and self-management interventions had to report seizure control as an outcome. DATA COLLECTION AND ANALYSIS: Our primary outcome was seizure frequency. Our secondary outcomes were: seizure severity, health-related quality of life (HRQoL), medication usage, knowledge, general health, social and psychological function, and adverse events. We classified outcomes as short-term (up to six months) or long-term (over six months). At least two review authors independently screened all papers, extracted data, assessed the risk of bias, and analysed data. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 36 studies with 5834 randomised participants. Twenty-six studies included participants with a diagnosis of epilepsy, six studies included participants with severe or drug-resistant epilepsy, and four studies included participants with epilepsy and another comorbidity, including depression, psychosocial problems, or learning disabilities. We rated 16 studies as having an overall low risk of bias, 11 studies as high risk, and nine studies with an unclear risk of bias. Twenty-one studies were conducted in high-income countries, seven in upper-middle-income countries, and eight in lower-middle-income countries. We categorised interventions into psycho-behavioural, mind-body, self-management, physical exercise, nurse-led service delivery, and other service delivery interventions. Seizure frequency Two studies showed that psycho-behavioural interventions likely reduce seizure frequency at three to six months (mean seizure frequency reduction 4.42 per month, 95% confidence interval (CI) 6.41 per month lower to 2.43 per month lower; 64 participants; moderate-certainty evidence). However, this intervention may not improve seizure frequency immediately post-intervention. Three studies showed that mind-body interventions may reduce seizure frequency slightly at six to eight weeks (mean seizure frequency reduction 3.28 per month, 95% CI 6.36 per month lower to 0.20 per month lower; 148 participants; low-certainty evidence). However, evidence from two studies suggests that such interventions have no effect on seizure control. Evidence from three studies suggests that self-management interventions may not reduce seizure frequency between 20 weeks and six months (mean seizure frequency was 1.61 per month higher, 95% CI 6.08 per month lower to 9.29 per month higher; 222 participants; low-certainty evidence). However, three studies showed these interventions are likely to increase seizure freedom. In the short term, the effect of physical exercise on seizure control is very uncertain. Evidence from one study suggests that a nurse-led service delivery intervention does not improve seizure frequency. No data were available for other service-based interventions. The long-term data (> six months) for psycho-behavioural, self-management, and service-based interventions are limited. There are no long-term data available for mind-body, physical exercise, or nurse-led service delivery interventions. Health-related quality of life One study reported that psycho-behavioural interventions likely result in no difference in Quality of Life in Epilepsy Inventory (QOLIE)-10 total score at six months (mean total score was 0.89 higher, 95% CI 1.06 lower to 2.84 higher; 120 participants; moderate-certainty evidence). Overall, there is very uncertain evidence of the short- and long-term effect of psycho-behavioural interventions on HRQoL outcomes. One study showed that mind-body interventions may result in no difference in QOLIE-31-P (31-item questionnaire with patient-weighted scoring system) total scores at six weeks (mean total score was 0.75 higher, 95% CI 5.49 lower to 6.99 higher; 60 participants; low-certainty evidence). Two studies showed that self-management interventions probably do not improve the mean QOLIE-31 or QOLIE-31-P total scores at six months (mean scores 2.42 higher, 95% CI 2.58 lower to 7.42 higher; 393 participants; moderate-certainty evidence). However, one study showed that these interventions are likely to result in a slight improvement in QOLIE-10 total scores. Four studies showed that this intervention probably does not improve HRQoL outcomes. We are very uncertain about the effect of this intervention on long-term outcomes. Three studies showed that physical exercise may result in no difference to HRQoL outcomes in the short term. Two studies showed that nurse-led service delivery interventions probably do not improve outcomes in the short or long term. One study showed that a service delivery-based intervention likely results in an improvement in HRQoL in the long term. Other outcomes Evidence for improvements in epilepsy knowledge, medication usage, general health, social and psychological function was very limited and showed no consistent differences between interventions and controls. There were no reported adverse events related to the interventions. AUTHORS' CONCLUSIONS: There is no high-certainty evidence that service delivery, behavioural, and self-management interventions improve seizure control or quality of life outcomes for adults with epilepsy. There were wide variations in the size of the effect estimate, depending on how outcomes were measured. Furthermore, there was significant clinical heterogeneity amongst the populations studied, types of interventions delivered, study setting, and study design, which limit interpretation of the currently available evidence and its overall applicability. Further research is needed from well-designed studies using validated measures to assess long-term improvement in outcomes important to adults with epilepsy
Estimating the lifetime costs and benefits of the incredible years teacher classroom management intervention using data from 30 months follow-up of the supporting teachers and children in schools trial
Get PDFObjectives: The Incredible Years Teacher® Classroom Management (IY-TCM) intervention is associated with short-term improvements in mental health difficulties in young people. The aim was to estimate the long-term impact and cost-effectiveness of the IY-TCM intervention compared with no intervention.
Methods: An existing health economic model (LifeSim 1.0) was used to translate short-term changes in the Strength and Difficulties Questionnaire (SDQ), based on the Supporting Teachers and childRen in Schools cluster randomized controlled trial of the IY-TCM intervention in schools, into estimated medium- and long-term effects using multiple longitudinal data sets. LifeSim 1.0 was adapted to incorporate teacher-reported SDQ and account for individual heterogeneity. Cost-effectiveness analyses were conducted using the trial-based intervention cost with subgroup analyses on deprivation, conduct scores and parental depression in the simulated baseline population.
Results: Regression analyses show significant predictor variables for intervention effectiveness, including deprivation and baseline SDQ. LifeSim results indicate small gains in long-term outcomes, and cost-effective analyses estimated that the IY-TCM intervention could be cost-effective, but there was a large amount of uncertainty (net monetary benefit = £10, Estimated CI = −£134, £156). Benefits and certainty of cost-effectiveness were greater for some subgroups, such as those with high conduct scores at baseline (net monetary benefit = £206, Estimated CI = £26, £318).
Conclusions: IY-TCM could be cost-effective, but there was a large amount of uncertainty around costs and benefits. Greater benefits for pupils with difficulties at baseline suggest that the intervention may be more cost-effective for schools in more deprived areas with high levels of conduct problems
Amplifying Insights:How Logarithmic Bayesianism can Validate Causation in Participatory Policymaking Methods
No full textAssessing the role of anoxia as a potential extinction driver in the shallow marine Neotethys during the Permian-Triassic mass extinction
Get PDFAnoxia has been hypothesised as a major kill mechanism for marine ecosystems during the Permian-Triassic mass extinction, but its importance is increasingly debated for shallow marine settings. For the Neotethys Ocean, in particular, geochemical data that is suitable to verify a local anoxic signal is lacking. Here, we investigated two shallow marine successions from the Antalya Nappes, Türkiye, for their redox sensitive metal and rare earth element and Yttrium (REY) composition to reconstruct local redox changes before, during and after the Permian-Triassic mass extinction. The investigated sections recorded reoccurring enrichments in the redox sensitive trace metals Re, U and Mo, supporting dynamic local redox conditions cycling between oxic and anoxic throughout the investigated Permian interval. No clear changes in redox conditions compared to the pre-extinction interval nor evidence of anoxic upwelling coinciding with the extinction event could be identified, questioning the role of anoxia as a local extinction driver. Above the extinction horizon, the sections were generally characterised by low redox sensitive metal enrichments and negative Ce anomalies revealing that post-extinction sediments were deposited in a consistently oxic environment. Hence, local anoxia within the shallow marine ecosystem of the Antalya Nappes appears not persistent enough around the extinction, and did not occur during the recovery, rendering it unlikely to explain biodiversity changes. Therefore, alternative environmental factor(s) should be considered as potential drivers of biodiversity changes for shallow marine ecosystems of the western Neotethys during the Permian-Triassic mass extinction and its recovery
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