The objective of the current study was to investigate the associations between lifetime classic psychedelic use and cardiometabolic diseases. Using data from the National Survey on Drug Use and Health (2005–2014), the present study examined the associations between lifetime classic psychedelic use and two types of cardiometabolic disease: heart disease and diabetes. Respondents who reported having tried a classic psychedelic at least once in their lifetime had lower odds of heart disease in the past year (adjusted odds ratio (aOR) = 0.77 (0.65–0.92), p = .006) and lower odds of diabetes in the past year (adjusted odds ratio (aOR) = 0.88 (0.78–0.99), p = .036). Classic psychedelic use might be beneficial for cardiometabolic health, but more research is needed to investigate potential causal pathways of classic psychedelics on cardiometabolic diseases.
Age-specific estimates of mean testosterone (T) concentrations appear to vary by year of observation and by birth cohort, and estimates of longitudinal declines in T typically outstrip cross-sectional decreases. These observations motivate a hypothesis of a population-level decrease in T over calendar time, independent of chronological aging. We observe a substantial age-independent decline in T that does not appear to be attributable to observed changes in explanatory factors, including health and lifestyle characteristics such as smoking and obesity. The estimated population-level declines are greater in magnitude than the cross-sectional declines in T typically associated with age.
The emergency use authorization of two mRNA vaccines in less than a year since the emergence of SARS-CoV-2 represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers vaccinated with the Pfizer-BioNTech mRNA vaccine. Vaccination resulted in robust production of neutralizing antibodies (nAbs) against the parent Wuhan strain and, to a lesser extent, the B.1.351 strain, and significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a strikingly enhanced innate immune response compared to primary vaccination, evidenced by a greater: (i) frequency of CD14+CD16+ inflammatory monocytes; (ii) concentration of plasma IFN-g; (iii) transcriptional signature of innate antiviral immunity. Consistent with these observations, single-cell transcriptomics analysis demonstrated a ~100-fold increase in the frequency of a myeloid cell cluster, enriched in interferon-response transcription factors (TFs) and reduced in AP-1 TFs, following secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and nAb responses, and show that a monocyte-related signature correlates with the nAb response against the B.1.351 variant strain. Collectively, these data provide insights into immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response following booster immunization.
Summary Background Emerging evidence suggests that living near major roads might adversely affect cognition. However, little is known about its relationship with the incidence of dementia, Parkinson's disease, and multiple sclerosis. We aimed to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada. Methods In this population-based cohort study, we assembled two population-based cohorts including all adults aged 20–50 years (about 4·4 million; multiple sclerosis cohort) and all adults aged 55–85 years (about 2·2 million; dementia or Parkinson's disease cohort) who resided in Ontario, Canada on April 1, 2001. Eligible patients were free of these neurological diseases, Ontario residents for 5 years or longer, and Canadian-born. We ascertained the individual's proximity to major roadways based on their residential postal-code address in 1996, 5 years before cohort inception. Incident diagnoses of dementia, Parkinson's disease, and multiple sclerosis were ascertained from provincial health administrative databases with validated algorithms. We assessed the associations between traffic proximity and incident dementia, Parkinson's disease, and multiple sclerosis using Cox proportional hazards models, adjusting for individual and contextual factors such as diabetes, brain injury, and neighbourhood income. We did various sensitivity analyses, such as adjusting for access to neurologists and exposure to selected air pollutants, and restricting to never movers and urban dwellers. Findings Between 2001, and 2012, we identified 243 611 incident cases of dementia, 31 577 cases of Parkinson's disease, and 9247 cases of multiple sclerosis. The adjusted hazard ratio (HR) of incident dementia was 1·07 for people living less than 50 m from a major traffic road (95% CI 1·06–1·08), 1·04 (1·02–1·05) for 50–100 m, 1·02 (1·01–1·03) for 101–200 m, and 1·00 (0·99–1·01) for 201–300 m versus further than 300 m ( p for trend=0·0349). The associations were robust to sensitivity analyses and seemed stronger among urban residents, especially those who lived in major cities (HR 1·12, 95% CI 1·10–1·14 for people living
Summary Background The risk of individuals having adverse effects from drug use (eg, alcohol) generally depends on the frequency of use and potency of the drug used. We aimed to investigate how frequent use of skunk-like (high-potency) cannabis in south London affected the association between cannabis and psychotic disorders. Methods We applied adjusted logistic regression models to data from patients aged 18–65 years presenting to South London and Maudsley NHS Foundation Trust with first-episode psychosis and population controls recruited from the same area of south London (UK) to estimate the effect of the frequency of use, and type of cannabis used on the risk of psychotic disorders. We then calculated the proportion of new cases of psychosis attributable to different types of cannabis use in south London. Findings Between May 1, 2005, and May 31, 2011, we obtained data from 410 patients with first-episode psychosis and 370 population controls. The risk of individuals having a psychotic disorder showed a roughly three-times increase in users of skunk-like cannabis compared with those who never used cannabis (adjusted odds ratio [OR] 2·92, 95% CI 1·52–3·45, p=0·001). Use of skunk-like cannabis every day conferred the highest risk of psychotic disorders compared with no use of cannabis (adjusted OR 5·4, 95% CI 2·81–11·31, p=0·002). The population attributable fraction of first-episode psychosis for skunk use for our geographical area was 24% (95% CI 17–31), possibly because of the high prevalence of use of high-potency cannabis (218 [53%] of 410 patients) in our study. Interpretation The ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies. Funding UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, SLaM and the Institute of Psychiatry at King's College London, Psychiatry Research Trust, Maudsley Charity Research Fund, and th European Community's Seventh Framework Program grant (agreement No. HEALTH-F2-2009-241909 [Project EU-GEI]).
Background The COVID-19 pandemic created the need for very large scale, rapid testing to prevent and contain transmission of the SARS-CoV-2 virus. Lateral flow device (LFD) immunoassays meet this need by indicating the presence of SARS-CoV-2 antigen from nose/throat swab washings in 30 minutes without laboratory processing, and can be manufactured quickly at low cost. Since March 2021, UK schools have asked pupils without symptoms to test twice weekly. Pupils have posted on social media about using soft drinks to create positive results. The aim of this study was to systematically test a variety soft drinks to determine whether they can cause false false positive LFD results. Methods This study used 14 soft drinks and 4 artificial sweeteners to determine the outcome of misusing them as analyte for the Innova SARS-CoV-2 antigen rapid qualitative LFD. The pH value, sugar content and ingredients of each sample are described. The LFD results were double read and a subset was repeated using the same devices and fake analytes but differently sourced. Findings One sample (1/14; 7%), spring water, produced a negative result. Ten drinks (10/14; 71%) produced a positive or weakly positive result. Three samples (3/14; 21%) produced void results, mostly the fruit concentrate drinks. There was no apparent correlation between the pH value (pH 5.0 in 13/14, 93%; pH 6.5 in 1/14; 7%) or the sugar content (range 0-10.7 grams per 100mls) of the drinks and their LFD result. The 4 artificial sweeteners all produced negative results. A subset of the results was fully replicated with differently sourced materials. Interpretation Several soft drinks can be misused to give false positive SARS-CoV-2 LFD results. Daily LFD testing should be performed first thing in the morning, prior to the consumption of any food or drinks, and supervised where feasible. Funding This work was self-funded by author LO and the LFD were gifted for use in this study.
Animals across phyla can detect early cues of infection in conspecifics, thereby reducing the risk of contamination. It is unknown, however, if humans can detect cues of sickness in people belonging to communities with whom they have limited or no experience. To test this, we presented Western faces photographed 2 h after the experimental induction of an acute immune response to one Western and five non-Western communities, including small-scale hunter–gatherer and large urban-dwelling communities. All communities could detect sick individuals. There were group differences in performance but Western participants, who observed faces from their own community, were not systematically better than all non-Western participants. At odds with the common belief that sickness detection of an out-group member should be biased to err on the side of caution, the majority of non-Western communities were unbiased. Our results show that subtle cues of a general immune response are recognized across cultures and may aid in detecting infectious threats.
Background We investigated whether a public health intervention—a three-part documentary called Man Up which explored the relationship between masculinity and mental health, well-being and suicidality—could increase men’s intentions to seek help for personal and emotional problems. Methods We recruited men aged 18 years or over who were not at risk of suicide to participate in a double-blind randomised controlled trial. Participants were randomly assigned (1:1) via computer randomisation to view Man Up (the intervention) or a control documentary. We hypothesised that 4 weeks after viewing Man Up participants would report higher levels of intention to seek help than those who viewed the control documentary. Our primary outcome was assessed using the General Help Seeking Questionnaire, and was analysed for all participants. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001169437, Universal Trial Number: U1111-1186-1459) and was funded by the Movember Foundation. Results Three hundred and fifty-four men were assessed for eligibility for the trial and randomised to view Man Up or the control documentary. Of these, 337 completed all stages (nine participants were lost to follow-up in the intervention group and eight in the control group). Linear regression analysis showed a significant increase in intentions to seek help in the intervention group, but not in the control group (coef.=2.06, 95% CI 0.48 to 3.63, P=0.01). Conclusions Our trial demonstrates the potential for men’s health outcomes to be positively impacted by novel, media-based public health interventions that focus on traditional masculinity. Trial registration number ACTRN12616001169437, Results.
BACKGROUND: Pre-pregnancy diabetes is a strong risk factor for congenital heart defects (CHDs), suggesting a role for glucose in the causal pathway. Oral corticosteroids may cause hyperglycemia and maternal use could affect embryonic heart development. The objective of this study was to determine the association between maternal intake of oral corticosteroids 0-8 weeks after conception and CHDs in offspring. METHODS: A register-based nationwide prevalence study including all live singleton births in Denmark, 1996-2016, was conducted. In total, 1 194 687 individuals and their mothers were identified and linked with information on offspring CHDs and the mothers' use of oral corticosteroids in early pregnancy. Corticosteroid use was defined as a filled prescription for maternal use of oral corticosteroid 0-8 weeks after conception. CHDs were identified through International Classification of Diseases codes. The association was estimated by prevalence (odds) ratios using logistic regression and propensity score-matched analyses. RESULTS: Among 1 194 687 live births, 2032 had a mother who had used oral corticosteroids 0-8 weeks from conception. Of these offspring, 32 had a heart defect. Among the offspring of never-users of oral corticosteroids, 10 534 had a heart defect. The adjusted prevalence ratio was 1.29 (95% confidence interval, 0.90-1.84) comparing offspring prevalence of heart defects in oral corticosteroid users with that in oral corticosteroid never-users. Propensity score-matched analysis yielded similar results (prevalence ratio 1.38; 95% confidence interval, 0.95-2.02). CONCLUSIONS: This study supports that there is no association between maternal use of oral corticosteroids in the first 8 weeks after conception and CHDs.
BACKGROUND: Distal forearm fractures are common in children. The reference standard to diagnose these fractures is by conventional radiography, which exposes these patients to harmful radiation. Ultrasound (US) seems to be a good alternative. However, emergency physicians (EPs) in the Netherlands have limited experience in using US for diagnosing fractures in children. OBJECTIVE: The primary objective was to determine the accuracy of US, performed by a Dutch EP, compared with conventional radiography, in diagnosing distal forearm fractures in children. As a secondary objective, differences in pain scores during the performance of both US and plain radiography were determined. METHODS: Children, aged between 0 and 14 years old, suspected of having a distal forearm fracture were enrolled at the Emergency Department. US and radiographic findings were compared. Statistics for accuracy were calculated. Pain scores were recorded during US and radiography and compared as well. All participating operators received an hour-long pretrial training. RESULTS: 100 patients were enrolled. The mean age was 9.5 years (SD, 3.6), and 50% were women. Overall diagnostic accuracy was 92% (95% CI 85%-96%). The sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios for US were 95% (95% CI 87% to 99%), 86% (95% CI 71% to 95%), 92% (95% CI 83% to 97%), 91% (95% CI 76% to 98%), 6.86 (95% CI 3.04 to 15.51) and 0.05 (95% CI 0.02 to 0.17), respectively. The pain scores during US and radiographic imaging were 3.3 and 4.6, respectively (p