Evidence for public health on novel psychoactive substance use: a mixed-methods study

Background: Novel psychoactive substances (NPSs) contribute to the public health impact of substance misuse. This report provides research evidence addressing 11 research questions related to NPSs, covering types, patterns and settings of use; supply sources; and implications for policy and practice. Methods: The study used a conceptually linked three-phase mixed-methods design with a shared conceptual framework based on multiple-context risk and protective factors. Phase 1 was a quantitative phase involving secondary data analysis of the longitudinal Belfast Youth Development Study (BYDS), a latent class analysis using the 2039 BYDS participants. Phase 2 was an extensive qualitative analysis via narrative interviews with participants, sampled from BYDS, drug/alcohol services and prisons, to explore NPS use trajectories. Phase 3 was the final quantitative phase; generalisability of the shared risk factor part of the model was tested using the manual three-step approach to examine risk factors associated with latent class membership. The quantitative and qualitative analyses were integrated, thus allowing emerging findings to be further explored. Results: The data suggest that NPSs have a place within a range of polydrug use trajectories. Models showed no distinctive NPS class, with no clear evidence of differential risks for NPS use compared with the use of other substances. From the qualitative analysis, a taxonomy of groups was derived that explored how and where NPSs featured in a range of trajectories. This taxonomy was used to structure the analysis of factors linked to use within a risk and protective framework. Drivers for use were considered alongside knowledge, perceptions and experience of harms. Suggestions about how interventions could best respond to the various patterns of use – with special consideration of synthetic cannabinoids (SCs), including how they relate to the use of heroin and the potential for NPSs to operate as a ‘snare’ to more problem use – were also presented. Limitations: The study was conducted during 2016/17; generalisability beyond this sample and time point is limited. The level of missing data for some of the BYDS analysis was a limitation, as was the fact that the BYDS data were collected in 2011, so in a different context from the data collected during the narrative interviews. The Psychoactive Substances Act 2016 (Great Britain. Psychoactive Substances Act 2016. London: The Stationery Office; 2016) came into force during qualitative fieldwork and, although not particularly influential in this study, may be influential in future work. It is acknowledged that many of the data related to SCs and mephedrone. Although drug use was measured by self-report, the strength of rapport within interviews, reflective diaries and methodological acceptability checks helped to mitigate self-report bias. Conclusions: NPSs continue to present significant challenges for legislation and monitoring, researching and developing interventions. Understanding of usage patterns remains poor, with most information based on populations and settings where problems have already occurred. This research contributes to the evidence base by providing much needed further empirical data on the lived experiences of NPS users across a range of settings. In the light of these data, implications for policy and practice are discussed. Future work: Future research must generate improved epidemiological data on the extent, patterns and motivations for use longitudinally. The uniqueness of the information concerning SC use points to a specific set of findings not evidenced in other literature (e.g. intensity of SC withdrawal). Future research should focus on the symbiotic link between SC and heroin use

Positive mindset and exercise capacity in school-aged children and adolescents with congenital heart disease

IntroductionPatients with congenital heart disease (CHD) have variable degrees of peak oxygen consumption (VO2) that can be improved with supervised fitness training. The ability to exercise is affected by anatomy, hemodynamics, and motivation. Motivation is in part related to mindset, or personal attitudes and beliefs, and a more positive mindset around exercise has been associated with better outcomes. It is unknown whether variations in measured peak VO2 in patients with CHD are related to having a positive mindset.MethodsPatient's ages 8–17 years with CHD were administered quality of life and physical activity questionnaires at the time of their routine cardiopulmonary exercise test. Those with severe hemodynamic burden were excluded. Patients were grouped based on disease classification. Mindset was evaluated via validated questionnaires including a PROMIS Meaning and Purpose (MaP) survey and an Anxiety survey. Pearson correlation coefficients were calculated to estimate the magnitude of the association between percent predicted peak oxygen consumption (pppVO2) and questionnaire scores overall and within CHD subgroups.ResultsEighty-five patients participated; median age was 14.7 years, 53% were female, 66% had complex CHD, 20% had simple CHD, and 14% had single ventricle heart disease. Mean MaP scores were significantly lower in all CHD groups compared to population norms (p < 0.001). As a group, MaP scores were positively associated with the amount of reported physical activity (p = 0.017). In patients with simple CHD, MaP scores were positively associated with pppVO2 (p = 0.015). The association was even stronger for MaP:Anxiety, with worse ratios associated with lower pppVO2 (p = 0.005). Patients with complex and single ventricle CHD did not show a similar association.ConclusionsPatients with CHD, regardless of severity, had lower meaning and purpose scores than the general population, and these scores were associated with amount of reported physical activity. In the simple CHD subset, having a more positive mindset was associated with higher peak VO2 and a more negative mindset with lower peak VO2. This relationship was not seen with more significant CHD. While underlying CHD diagnoses are not modifiable, mindset and peak VO2 are, and consideration should be given to measuring both as each may be a target for intervention

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc