Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).

Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.

Although research has highlighted that suicidal imagery (SuiMI) and experiential avoidance (EA) are important in understanding suicidality, there is a need to understand how they potentially interact. Previous research has highlighted that EA potentially leads to increased cognitive intrusions, but it not known whether EA leads to increased SuiMI.

The purpose of this study was to explore the influence of SuiMI and EA on suicidality (i.e. encompassing thoughts, behaviour and suicide attempts). It was hypothesised that greater frequency of SuiMI would be associated with greater EA. It was also hypothesised that greater SuiMI would be associated with greater suicidality, and that EA would moderate this relationship.

Hypotheses were tested by surveying 197 general university students who completed self-report measures that assessed suicide-related mental imagery (i.e. Suicidal Imagery Questionnaire, SIQ), experiential avoidance (i.e. Multi-dimensional Experiential Avoidance Questionnaire, MEAQ) and suicidality (i.e. Suicidal Behaviours Questionnaire-Revised, SBQ-R).

Frequency of SuiMI was positively correlated with the tendency to engage in EA. SuiMI was a significant predictor of both suicidality and EA. Exploratory analysis found that voluntary SuiMI explained greater variance in suicidality than intrusive, involuntary SuiMI, and that SuiMI only predicted EA in low-risk participants and not for those at high risk of suicide. EA did not predict suicidality and it also did not show any moderating effect on the relationship between SuiMI and suicidality.

There is evidence to suggest that suicide-related mental imagery may play an important role in suicide risk and more specifically imagery that is voluntarily engaged with. Future research is needed to explore the different types of imagery in relation to suicidal ideation in populations at higher risk of suicide.

Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.5% of people due to concerns about clozapine-associated myocarditis (CAM). The opportunity for clozapine rechallenge is important for people with TRS and CAM, due to limited alternative treatments. However, there is a lack of consensus regarding the optimal process, monitoring, and dose titration to achieve successful clozapine rechallenge. The study aimed to review the process, monitoring, and dose titration within cases of clozapine rechallenge after CAM, to identify features associated with successful rechallenge.

A systematic review of clozapine rechallenge cases following CAM was conducted. PubMed, EMBASE, Cinahl, and PsycINFO were searched for cases. Reference lists of retrieved articles and field experts were consulted to identify additional studies.

Forty-five cases were identified that described clozapine rechallenge, 31 of which were successful. Successful rechallenge cases generally used a slower dose titration regime with more frequent monitoring than standard clozapine initiation protocols; however, this data was not always completely recorded within cases. Six cases referred to published rechallenge protocols to guide their rechallenge.

The process, monitoring, and dose titration of clozapine rechallenge are inconsistently reported in the literature. Despite this, 69% of case reports detailed a successful rechallenge post CAM; noting limitations associated with reliance on case data. Ensuring published clozapine rechallenge cases report standardised data, including titration speed and monitoring frequencies, is required to guide the development and validation of guidelines for clozapine rechallenge.

Autistic women are at high risk of developing restrictive eating disorders (REDs), such as anorexia nervosa.

This study provides an overview of the clinical characteristics of autistic women with REDs to (i) enhance understanding of increased risk, and (ii) support the identification of autistic women in eating disorder services.

We compared self-reported autistic and disordered eating characteristics of: autistic participants with REDs (Autism + REDs; n = 57); autistic participants without REDs (Autism; n = 69); and women with REDs who are not autistic (REDs; n = 80). We also included a group of women with high autistic traits (HATs) and REDs, but no formal autism diagnosis (HATs + REDs; n = 38).

Autism + REDs participants scored similarly to Autism participants in terms of autistic characteristics and to REDs participants in terms of experiencing traditional disordered eating symptoms. Autism + REDs participants were distinguished from both groups by having more restricted and repetitive behaviours and autism-specific eating behaviours related to sensory processing, flexibility and social differences. HATs + REDs participants showed a similar pattern of scores to Autism + REDs participants, and both also presented with high levels of co-occurring mental health difficulties, particularly social anxiety.

The presentation of autistic women with REDs is complex, including both traditional disordered eating symptoms and autism-related needs, as well as high levels of co-occurring mental health difficulties. In eating disorder services, the REDs presentation of autistic women and those with HATs should be formulated with reference to autism-specific eating behaviours and co-occurring difficulties. Treatment adaptations should be offered to accommodate autistic characteristics and related needs.

To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up.

Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo.

Community settings and care homes in 26 UK centers.

People with probable or possible Alzheimer’s disease and agitation.

Primary outcome included incremental cost of participants’ health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants’ and unpaid carers’ gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives.

One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment.

On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.

Heart attacks (HAs) present clinically with varying symptoms, which are not always described by patients as chest pain (CP) or chest discomfort (CD). Emergency Medical Dispatchers (EMDs) select the CP/CD dispatch protocol for non-chest pain HA symptoms or classic HA complaint of CP/CD. Nevertheless, it is still unknown how often callers report HA symptoms other than CP/CD.

The objective of this study was to characterize the caller’s descriptions of the primary HA symptoms, descriptions of the other HA symptoms, and the use of a case entry (CE) question clarifier.

A retrospective descriptive study analyzed randomly selected EMD audios (where CD/CD protocol was used) from five accredited emergency communication centers in the United States. Several Quality Performance Review (QPR) experts reviewed the audios and recorded callers’ initial problem descriptions, the use of and responses to the CE question clarifier, including the EMD-assigned final determinant code.

A total of 1,261 audios were reviewed. The clarifier was used only 8.5% of the time. The CP/CD symptoms were mentioned alone or with other problems 87.0% of the time. Overall, CP symptom was mentioned alone 70.8%, HA alone 4.0%, and CD symptom alone 1.4% of the time.

9-1-1 callers report potential HA cases using a variety of terms and descriptions—most commonly CP. Other less-common symptoms associated with a HA may be mentioned. Therefore, EMDs must be well-trained to be prepared to probe the caller with a clarifying query to elicit more specific information when “having a heart attack” is the only complaint initially mentioned.

The COVID-19 pandemic has created a high demand on personal protective equipment, including disposable N95 masks. Given the need for mask reuse, we tested the feasibility of vaporized hydrogen peroxide (VHP), ultraviolet light (UV), and ethanol decontamination strategies on N95 mask integrity and the ability to remove the infectious potential of SARS-CoV-2.

Disposable N95 masks, including medical grade (1860, 1870+) and industrial grade (8511) masks, were treated by VHP, UV, and ethanol decontamination. Mask degradation was tested using a quantitative respirator fit testing. Pooled clinical samples of SARS-CoV-2 were applied to mask samples, treated, and then either sent immediately for real-time reverse transcriptase–polymerase chain reaction (RT-PCR) or incubated with Vero E6 cells to assess for virucidal effect.

Both ethanol and UV decontamination showed functional degradation to different degrees while VHP treatment showed no significant change after two treatments. We also report a single SARS-CoV-2 virucidal experiment using Vero E6 cell infection in which only ethanol treatment eliminated detectable SARS-CoV-2 RNA.

We hope our data will guide further research for evidenced-based decisions for disposable N95 mask reuse and help protect caregivers from SARS-CoV-2 and other pathogens.

UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.

Describe the development, implementation and results of this questionnaire.

An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.

A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.

The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.

UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.

An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.

An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.

157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.

The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.

G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.