People suffering from common mental disorders (CMDs), such as depression and anxiety, are more likely to be inactive in the labor market. Psychological therapies are highly effective at treating CMDs, but less is known about their impact on long-term labor market outcomes.

Using national treatment program data in England, NHS Talking Therapies (NHSTT), with unique linkage to administration data on employment and census records, we estimated the effects of NHSTT on employment and earnings. We used an event study approach using individual fixed effects to capture time-invariant confounders and natural recovery.

Overall, completing treatment led to a maximum average increase of £17 in monthly earnings (year 2) and a likelihood of paid employment by 1.5 percentage points (year 7). Those 'Not working, seeking work' saw a maximum average increase in pay of £63 per month (year 7) and a likelihood of paid employment by 3.1 percentage points (year 4). Patients in the younger age groups (25-34 years) saw the largest effect on the likelihood of paid employment by 2.3 percentage points (year 7), followed by those aged 35-44 years with 2.0 percentage points (year 5).

Completion of psychological treatment for CMDs through the national NHSTT program leads to sustained increases in both employment and earnings up to 7 years after the start of treatment. Our findings demonstrate the economic benefits of treating CMDs and how investing in mental health can impact labor market participation.

Regular physical activity is an important treatment component for chronic pain. To unravel the neuronal influence of exercise on pain, we investigated the neuronal changes during exercise-induced hypoalgesia in endurance athletes and controls. Twenty-two athletes (mean age: 33.3 ± 10.8 years) and 20 non-athletes (mean age: 28.9 ± 9.0 years) underwent high-intensity interval training (HIIT) and pressure pain tests, while brain oxygenation was monitored using functional near-infrared spectroscopy to cover key regions of pain processing: the prefrontal cortex (PFC), sensorimotor cortices and posterior parietal cortex (PPC). During HIIT both groups exhibited a steady increase in PFC oxyhaemoglobin, with athletes showing a greater increase in the PPC area than non-athletes. As expected athletes showed a significant reduction in pain perception after HIIT, whereas non-athletes did not. In line with this athletes showed a significant decrease in oxyhaemoglobin levels in all brain areas post-HIIT, whereas non-athletes only showed a decrease in sensorimotor areas. Interestingly, in athletes, pain reduction correlated with the decrease in PFC oxyhaemoglobin during painful stimulation, whereas no significant correlation was observed in non-athletes. The pronounced HIIT-induced increase in oxyhaemoglobin in athletes may elevate baseline neural activity to a level where additional activation is limited, potentially reducing the salience of pain-related signals. This athlete-specific response may result from endurance training adaptations, such as enhanced microvascularization and oxygen delivery, promoting greater neural efficiency during high-intensity exercise. These findings highlight HIIT's potential as a targeted pain management strategy for athletes and the need for tailored approaches in non-athletes. KEY POINTS: Regular physical activity is known to reduce pain, but the brain mechanisms behind this effect are not well understood, especially in trained compared with untrained people. We studied how the brain responds to short bouts of very intense exercise and how this relates to pain perception in endurance athletes and non-athletes. During exercise athletes showed a stronger increase in oxygen supply in brain regions involved in attention and body awareness than non-athletes. Only athletes experienced reduced pain after exercise, which was linked to lower activity in the frontal brain regions during painful stimulation. These results suggest that long-term endurance training changes how the brain processes pain during and after exercise, which may help design more effective exercise-based pain treatments for different populations.

Classic psychedelics such as psilocybin, lysergic acid diethylamide (LSD), and 5-methoxy-dimethyltryptamine (5-MeO-DMT) have shown promising effects in the treatment of certain mental health conditions. Enthusiastic claims about their therapeutic potential have led to overly optimistic reactions in the media and the public, subsequently resulting in increased use outside of clinical contexts and a heightened rate of psychedelic-related complications. As psychedelics exhibit low toxicity and hardly any habit-forming potential, the typical risks and harms of these substances are often overlooked by mental health professionals and under-assessed in psychedelic research. Similar to the medical history of other psychoactive substances introduced as medicines such as opioids, cocaine, and benzodiazepines, awareness for psychedelic-related complications has emerged with delay. Psychedelics are characterized by a wide range of acute effects on the human psyche and by a particular temporal dynamic in which these effects unfold, including acute, subacute, and long-term effects. Knowledge of how psychedelic effects unfold is not only essential for their use in therapy but also for the understanding and management of risks and complications.Here we provide an overview of complications that may be associated with the use of classic psychedelics, drawing on historical and current classification approaches and using the typical temporal dynamics of drug effects as a guiding thread. We will also discuss to what extent psychedelic-related disorders can be causally and specifically attributed to psychedelic use. Finally, considerations regarding the placement of psychedelic-related disorders within nosological-diagnostic classification systems will be discussed. The increasing interest in using psychedelics within the framework of psychotherapy and the rise of non-medical use underscore the need for a more nuanced classification of psychedelic-related risks and harms. The suggested classification can be used as a comprehensive starting point for the assessment of psychedelic-related complications, contributing to maximizing benefits and minimizing risks of these substances in research, therapy, and beyond.

Substance use has been associated with blunted brain responses to non-drug rewards, but findings in people who use cannabis are mixed. Adolescents may be uniquely vulnerable to cannabis-related disruption to reward processing due to ongoing neuromaturation, but longitudinal research is lacking. In this longitudinal fMRI study, we compared brain measures of reward anticipation in 46 adolescents (16-17 years) and adults (26-29 years) who used cannabis (1-7 days/week) and 50 age-matched controls with the Monetary Incentive Delay task at baseline and 12-month follow-up. Region of interest (ROI) analyses adjusted for cigarette/roll-up use, depression, and risk-taking found that reward anticipation activity decreased in the right (p = 0.05, η_p² = 0.04) and left (p = 0.02, η_p² = 0.05) ventral striatum from baseline to follow-up in participants who used cannabis compared with control participants. These effects remained in unadjusted models and when including only participants who consistently used or abstained from cannabis during the study period. There were no significant interactions between the cannabis user-group and age-group, or between the user-group, age-group, and time. There were also no cannabis user-group main or interaction effects in full sample ROI analyses for the thalamus, insula, or supplementary motor area, or in exploratory whole-brain analyses. The current results suggest that cannabis use may be associated with reductions in non-drug reward anticipation activity in the ventral striatum, a key part of the brain's reward system. However, there was no evidence of adolescent resilience or vulnerability to cannabis-related changes in brain reward anticipation activity.

Jack Jumper ant (JJA) venom immunotherapy (VIT) is highly efficacious but the lowest effective dose is unknown. Delta-inulin adjuvant (Advax) is known to enhance honeybee VIT immunogenicity.

This phase 1/2 single-blind, randomised controlled trial aimed to compare the efficacy and safety of JJA VIT with different doses of venom ± Advax.

Adults aged 18-65 with a history of immediate systemic reaction (SR) to JJA stings were randomised to receive JJA VIT at a maintenance dose of 25 mcg or 50 mcg ± Advax; participants were blinded to treatment allocation. Primary outcomes were the response to sting challenges after 12 months and venom-specific IgE and IgG4 responses to treatment.

Forty-nine of 50 screened subjects met inclusion criteria and were randomised; 44 started treatment (25 mcg n = 12; 25 mcg + Advax n = 13; 50mcg n = 12, 50 mcg + Advax n = 12). Subsequently, two withdrew due to SRs to treatment, and two withdrew due to unrelated factors. The higher JJA venom maintenance dose was associated with reduced likelihood of SRs (OR 0.53 (95% CI, 0.28-0.98)), while Advax did not have an effect (OR 1.17 (95% CI, 0.59-2.32)). Forty proceeded to sting challenge, with six developing SRs. There was no difference between groups for sting challenge outcome (p = 0.98), and the ORs for 25 mcg vs. 50 mcg venom dose (0.89, 95% CI, 0.38-2.09) and Advax vs. no Advax (0.99, 95% CI 0.42-2.33) indicated no effect. There were no differences between groups for venom sIgE (p = 0.78), sIgG4 (p = 0.25), sIgE/IgG4 ratio (p = 0.42), intradermal (p = 0.77), and basophil activation test (BAT) (p = 0.69) responses to treatment. Subjects with high baseline BAT sensitivity, which reduced markedly in response to treatment, were less likely to have a positive sting challenge (p = 0.006).

Challenge outcomes were similar for all groups, with no significant difference found between 25 and 50 mcg maintenance dose or between treatment with and without Advax. Further research of low dose JJA VIT is warranted to confirm its efficacy and tolerability.

NCT03066986.

The last 40 years have seen a substantial improvement in overall survival from cancer in children and young people. There is limited information on psychiatric wellbeing in female survivors of cancer at a young age.

In this 40-year population-based linkage study, we set out to determine the incidence of first psychiatric admission compared with a non-exposed age-matched control.

Scottish cancer registry records from 1981 to 2012 were linked to psychiatric admissions, maternity and death records from January 1981 to September 2018 using the unique personal Community Health Index number allocated to each person in Scotland. For each exposed subject, three age and deprivation matched controls from the population were selected. The primary exposed group was all females with a cancer diagnosis at age <25 years and no previous pregnancy and no psychiatric admission before cancer diagnosis. The main outcome measure is admission to a psychiatric hospital with a mental health diagnosis.

Female cancer survivors had a significantly lower cumulative incidence of first psychiatric admissions than matched controls over the 38 years of follow-up for the cohort (p<0.05). The relative risk of a first psychiatric admission at 25 years from cancer diagnosis was 0.72 (0.56-0.89).

Overall, we have shown that young cancer survivors are less likely than age-matched controls to have a psychiatric admission after cancer diagnosis. In particular, psychiatric admissions for mood disorders, neuroses, personality disorders and substance use are significantly less likely in the cancer survivors.

The experience of cancer treatment and survival in young females may reduce the risk of psychiatric admission in later life.

Dynapenia-loss of muscle strength despite preserved muscle mass-is a clinical concern linked to functional decline in older adults. Diabetes may contribute to dynapenia; however, few studies have examined whether this association varies by sex and age. Clarifying these differences may help inform targeted prevention strategies. This study investigated the association between diabetes and dynapenia in community-dwelling older adults in Japan, focusing on sex- and age-specific differences.

We conducted a cross-sectional analysis using pooled data from four geriatric cohorts in Japan. Participants were classified into three groups: (1) established diabetes (treatment or HbA1c ≥ 6.5%), (2) prediabetes (HbA1c 5.7%-6.4%, no treatment), and (3) non-diabetes (HbA1c < 5.7%, no treatment). Dynapenia was defined per Asian Working Group for Sarcopenia 2019 cutoffs as low grip strength with preserved muscle mass. Sex-stratified logistic regression examined the association between diabetes status and dynapenia, adjusting for age, body fat, comorbidities, lifestyle factors, and cohort. Analyses were also stratified by age group (65-74 and ≥ 75 years).

Among 3085 participants (34.8% men; median age: 70 years), the prevalence of dynapenia was 13.0% in both sexes. In women, dynapenia prevalence increased with glycemic status; adjusted ORs were 1.32 (95% CI: 0.97-1.78) for prediabetes and 1.86 (1.27-2.71) for established diabetes. Stratified analyses showed significant associations in men aged 65-74 and women aged ≥ 75.

Diabetes was associated with dynapenia, with distinct patterns by sex and age. Targeted strategies may be needed for younger-old men and older-old women with diabetes.

The DENOVA score was developed to support risk stratification for infective endocarditis (IE) in patients with Enterococcus faecalis bacteremia (EfB) and to guide echocardiographic evaluation; external validation remains, however, limited. The objective of this study was to externally validate the DENOVA score in a large prospective international cohort of patients with EfB.

Prospective multicenter cohort study (2019-2024) conducted across 23 centers in six countries (Italy, Spain, Israel, Brazil, Switzerland, and Romania), including adult patients with monomicrobial EfB who underwent at least one echocardiographic evaluation as part of the study protocol. Definite IE was defined according to the 2023 Duke criteria. The DENOVA score was externally validated; discrimination was assessed by the area under the receiver operating characteristic curve (AUC), calibration by observed versus predicted risk plots, and clinical utility by decision curve analysis (DCA) at the predefined threshold (DENOVA ≥3). Performance of the NOVA score was evaluated as a secondary analysis.

Among 543 patients, 125/543 (23.0%) were diagnosed with IE. When evaluated as a continuous variable, the DENOVA score showed an AUC of 0.871 (95%CI 0.835-0.906). At the predefined threshold (DENOVA ≥3), sensitivity was 79.2% (95%CI 71.0-85.9) and specificity was 83.0% (95% CI 79.1-86.5). Decision curve analysis showed that DENOVA ≥3 was associated with positive net clinical benefit across most threshold probabilities, with a reduction in unnecessary TEEs.

The study demonstrated that DENOVA supports risk stratification for IE in patients with EfB, informing clinical decision-making and use of TEE.

Leprosy, caused by Mycobacterium leprae, can pose diagnostic challenges in non-endemic regions because of its low frequency and possible atypical presentations.

This case describes the unusual clinical manifestations of leprosy in a 52-year-old Indian woman who immigrated to Italy: she presented with a granulomatous nasal plaque and hypopigmented abdominal lesion, without evidence of sensory loss or peripheral neuropathy. Initial evaluations were inconclusive, causing a significant diagnostic delay. Definitive diagnosis was achieved by molecular test for Mycobacterium leprae from respiratory and skin samples. After 12 months of multidrug therapy, the nasal lesion resolved completely.

This case highlights the imperative for health care providers in nonendemic settings to always consider leprosy in the differential diagnosis of chronic dermatologic conditions, especially in individuals with relevant epidemiologic background, even in absence of typical manifestations, emphasizing the need for high clinical suspicion and multidisciplinary collaboration.

Obsessive-compulsive disorder (OCD) is associated with impaired executive function and altered activity in associated neural circuits, contributing to reduced goal-directed behavior. To investigate neural activation during executive funtion, we conducted a mega-analysis in the ENIGMA-OCD consortium pooling individual participant data from 475 individuals with OCD and 345 healthy controls across 15 fMRI tasks collected worldwide.

Individual participant data was uniformly processed using HALFpipe to construct voxelwise statistical images of executive processing and task load contrasts. Parameter estimates extracted from regions of interest were entered into multilevel Bayesian models to examine regional and whole-brain effects of diagnosis, and, within OCD, the influence of medication status, symptom severity, and age of onset on task activation.

We observed a robust task activation pattern across individuals with OCD and control participants in executive processing regions across tasks. Relative to controls, individuals with OCD showed moderate to very strong evidence of weaker activation of the dorsolateral prefrontal cortex, precuneus, frontal eye fields, and inferior parietal lobule during executive function (all positive posterior probabilities [P+]<0.1). Individuals with OCD also showed stronger activation in regions of the default mode network during executive function relative to controls. We found little evidence for differential activation during executive function in task-positive regions related to disease onset, severity and medication status.

In the first mega-analysis of fMRI studies of executive function in OCD, we found strong evidence of weaker frontoparietal activation during executive function tasks. Our findings also suggest a failure of default mode network regions to appropriately disengage during task performance in OCD.