To describe the process of the development of evidence-based guidelines on the assessment and clinical management of internal contamination with transuranic actinides (specifically plutonium, americium, and curium) in incidents where workers, emergency responders, and the public might uptake these radionuclides internally through inhalation, ingestion, or wound contamination.

The World Health Organization (WHO) set up a guidelines development group (GDG) that follows the protocol required for producing evidence-based recommendations as described elsewhere. The GRADE® approach was applied throughout the process, including developing research questions formulation, prioritization and rating the importance for the outcomes, assessing the certainty of the evidence, considering contextual factors, and making recommendations.

Through 3 working group meetings held 2023-2024, the GDG defined and rated patient-important health outcomes, and evidence gathered through systematic reviews and its certainty rating, working towards formulating the recommendations using an evidence-to-recommendation (EtR) framework.

The WHO protocol for developing health care management guidelines uses a transparent and robust evidence-based GRADE® approach. Once published, these guidelines will provide the first evidence-based recommendations for assessment and clinical management of internal contamination with transuranic actinides.

There is increasing emphasis on reducing the use and improving the safety of mechanical restraint (MR) in psychiatric settings, and on improving the quality of evidence for outcomes. To date, however, a systematic appraisal of evidence has been lacking.

We included studies of adults (aged 18–65) admitted to inpatient psychiatric settings. We included primary randomised or observational studies from 1990 onwards that reported patterns of MR and/or outcomes associated with MR, and qualitative studies referring to an index admission or MR episode. We presented prevalence data only for studies from 2010 onwards. The risk of bias was assessed using an adapted checklist for randomised/observational studies and the Newcastle-Ottawa scale for interventional studies.

We included 83 articles on 73 studies from 1990–2022, from 22 countries. Twenty-six studies, from 11 countries, 2010 onwards, presented data from on proportions of patients/admissions affected by MR. There was wide variation in prevalence (<1–51%). This appeared to be mostly due to variations in standard protocols between countries and regions, which dictated use compared to other restrictive practices such as seclusion. Indications for MR were typically broad (violence/aggression, danger to self or property). The most consistently associated factors were the early phase of admission, male sex, and younger age. Ward and staff factors were inconsistently examined. There was limited reporting of patient experience or positive effects.

MR remains widely practiced in psychiatric settings internationally, with considerable variation in rates, but few high-quality studies of outcomes. There was a notable lack of studies investigating different types of restraint, indications, clinical factors associated with use, the impact of ethnicity and language, and evidence for outcomes. Studies examining these factors are crucial areas for future research. In limiting the use of MR, some ward-level interventions show promise, however, wider contextual factors are often overlooked.

Stakeholders worldwide increasingly acknowledge the need to address coercive practices in mental healthcare. Options have been described and evaluated in several countries, as noted recently in major policy documents from the World Health Organization (WHO) and World Psychiatric Association (WPA). The WHO's QualityRights initiative promotes human rights and quality of care for persons with mental health conditions and psychosocial disabilities. A position statement from the WPA calls for implementation of alternatives to coercion in mental healthcare.

We describe the engagement of both the WHO and WPA in this work. We discuss their mutual aim to support countries in improving human rights and quality of care, as well as the differences between these two organisations in their stated goals related to coercion in mental healthcare: the WHO's approach to eliminate coercion and the WPA's goal to implement alternatives to coercion.

We outline and critically analyse the common ground between the two organisations, which endorse a similar range of rights-based approaches to promoting non-coercive practices in service provision, including early intervention in prevention and care and other policy and practice changes.

Advocacy and action based on an agreed need to find practical solutions and advances in this area have the power to build consensus and unify key actors.

We conclude that persons with lived experience, families, mental health professionals and policy makers are now coming together in several parts of the world to work toward the common goals of improving quality, promoting human rights and addressing coercion in mental health services.

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.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Families express a need for information to support people with severe anorexia nervosa.

To examine the impact of the addition of a skills training intervention for caregivers (Experienced Caregivers Helping Others, ECHO) to standard care.

Patients over the age of 12 (mean age 26 years, duration 72 months illness) with a primary diagnosis of anorexia nervosa and their caregivers were recruited from 15 in-patient services in the UK. Families were randomised to ECHO (a book, DVDs and five coaching sessions per caregiver) or treatment as usual. Patient (n=178) and caregiver (n=268) outcomes were measured at discharge and 6 and 12 months after discharge.

Patients with caregivers in the ECHO group had reduced eating disorder psychopathology (EDE-Q) and improved quality of life (WHO-Quol; both effects small) and reduced in-patient bed days (7–12 months post-discharge). Caregivers in the ECHO group had reduced burden (Eating Disorder Symptom Impact Scale, EDSIS), expressed emotion (Family Questionnaire, FQ) and time spent caregiving at 6 months but these effects were diminished at 12 months.

Small but sustained improvements in symptoms and bed use are seen in the intervention group. Moreover, caregivers were less burdened and spent less time providing care. Caregivers had most benefit at 6 months suggesting that booster sessions, perhaps jointly with the patients, may be needed to maintain the effect. Sharing skills and information with caregivers may be an effective way to improve outcomes. This randomised controlled trial (RCT) was registered with Current Controlled Trials ISRCTN06149665.

The Patient Health Questionnaire (PHQ) is the most commonly used measure to screen for depression in primary care but there is still lack of clarity about its accuracy and optimal scoring method.

To determine via meta-analysis the diagnostic accuracy of the PHQ-9-linear, PHQ-9-algorithm and PHQ-2 questions to detect major depressive disorder (MDD) among adults.

We systematically searched major electronic databases from inception until June 2015. Articles were included that reported the accuracy of PHQ-9 or PHQ-2 questions for diagnosing MDD in primary care defined according to standard classification systems. We carried out a meta-analysis, meta-regression, moderator and sensitivity analysis.

Overall, 26 publications reporting on 40 individual studies were included representing 26 902 people (median 502, s.d.=693.7) including 14 760 unique adults of whom 14.3% had MDD. The methodological quality of the included articles was acceptable. The meta-analytic area under the receiver operating characteristic curve of the PHQ-9-linear and the PHQ-2 was significantly higher than the PHQ-9-algorithm, a difference that was maintained in head-to-head meta-analysis of studies. Our best estimates of sensitivity and specificity were 81.3% (95% CI 71.6–89.3) and 85.3% (95% CI 81.0–89.1), 56.8% (95% CI 41.2–71.8) and 93.3% (95% CI 87.5–97.3) and 89.3% (95% CI 81.5–95.1) and 75.9% (95% CI 70.1–81.3) for the PHQ-9-linear, PHQ-9-algorithm and PHQ-2 respectively. For case finding (ruling in a diagnosis), none of the methods were suitable but for screening (ruling out non-cases), all methods were encouraging with good clinical utility, although the cut-off threshold must be carefully chosen.

The PHQ can be used as an initial first step assessment in primary care and the PHQ-2 is adequate for this purpose with good acceptability. However, neither the PHQ-2 nor the PHQ-9 can be used to confirm a clinical diagnosis (case finding).

Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.

To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.

The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.

In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.

This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.

To quantify the association of dietary quality with prospective changes in adiposity.

Children participating in the QUALITY (QUebec Adipose and Lifestyle InvesTigation in Youth) study underwent examination at baseline and at 2-year follow-up. Dietary quality was assessed by the Diet Quality Index–International (DQII) using three non-consecutive 24 h diet recalls at baseline. The DQII has four main categories: dietary adequacy, variety, moderation and overall balance. Fat mass index (FMI; [fat mass (kg)]/[height (m)]2), central FMI (CFMI; [trunk fat mass (kg)]/[height (m)]2), percentage body fat (%BF; [total fat mass (kg)]/[total mass (kg)]) and percentage central BF (%CBF; [trunk fat mass (kg)]/[total mass (kg)]) were assessed through dual-energy X-ray absorptiometry.

Children were selected from schools in the greater Montreal, Sherbrooke and Quebec City metropolitan areas between 2005 and 2008, Quebec, Canada.

A total of 546 children aged 8–10 years, including 244 girls and 302 boys.

Regression analysis adjusting for age, sex, energy intake, physical activity and Tanner stage revealed that every 10-unit improvement in overall DQII score was associated with lower gain in CFMI (β=−0·08; 95 % CI −0·17, −0·003) and %BF (β=−0·55; 95 % CI −1·08, −0·02). Each unit improvement in dietary adequacy score was associated with lower gain in FMI (β=−0·05; 95 % CI −0·08, −0·008), CFMI (β=−0·03; 95 % CI −0·05, −0·007), %BF (β=−0·15; 95 % CI −0·28, −0·03) and %CBF (β=−0·09; 95 % CI −0·15, −0·02).

Promotion of dietary quality and adequacy may reduce weight gain in childhood and prevent chronic diseases later in life.