Healthcare staff use coercive measures to manage patients at acute risk of harm to self or others, but their effect on patients’ mental health is underexplored. This nationwide Swiss study emulated a trial to investigate the effects of coercive measures on the mental health of psychiatric inpatients at discharge.

We analysed retrospective longitudinal data from all Swiss adult psychiatric hospitals that provided acute care (2019–2021). The primary exposure was any coercive measure during hospitalization; secondary exposures were seclusion, restraint and forced medication. Our primary outcome was Health of the Nations Outcome Scale (HoNOS) score at discharge. We used inverse probability of treatment weighting to emulate random assignment to the exposure.

Of 178,369 hospitalizations, 9.2% (n = 18,800) included at least one coercive measure. In patients exposed to coercive measures, mental health worsened a small but statistically significant amount more than in non-exposed patients. Those who experienced at least one coercive measure during hospitalization had a significantly higher HoNOS score (1.91-point, p < .001, 95% confidence interval [CI]: 1.73; 2.09) than those who did not experience any coercive measure. Results were similar for seclusion (1.60-point higher score, p < .001, 95% CI: 1.40; 1.79) and forced medication (1.97-point higher score, p < .001, 95% CI: 1.65; 2.30). Restraint had the strongest effect (2.83-point higher score, p < .001, 95% CI: 2.38; 3.28).

Our study presents robust empirical evidence highlighting the detrimental impact of coercive measures on the mental health of psychiatric inpatients. It underscores the importance of avoiding these measures in psychiatric hospitals and emphasized the urgent need for implementing alternatives in clinical practice.

Exposure to second-generation antipsychotics (SGAs) carries a risk of type 2 diabetes, but questions remain about the diabetogenic effects of SGAs.

To assess the diabetes risk associated with two frequently used SGAs.

This was a retrospective cohort study of adults with schizophrenia, bipolar I disorder or severe major depressive disorder (MDD) exposed during 2008–2013 to continuous monotherapy with aripiprazole or olanzapine for up to 24 months, with no pre-period exposure to other antipsychotics. Newly diagnosed type 2 diabetes was quantified with targeted minimum loss-based estimation; risk was summarised as the restricted mean survival time (RMST), the average number of diabetes-free months. Sensitivity analyses were used to evaluate potential confounding by indication.

Aripiprazole-treated patients had fewer diabetes-free months compared with olanzapine-treated patients. RMSTs were longer in olanzapine-treated patients, by 0.25 months [95% CI: 0.14, 0.36], 0.16 months [0.02, 0.31] and 0.22 months [0.01, 0.44] among patients with schizophrenia, bipolar I disorder and severe MDD, respectively. Although some sensitivity analyses suggest a risk of unobserved confounding, E-values indicate that this risk is not severe.

Using robust methods and accounting for exposure duration effects, we found a slightly higher risk of type 2 diabetes associated with aripiprazole compared with olanzapine monotherapy regardless of diagnosis. If this result was subject to unmeasured selection despite our methods, it would suggest clinician success in identifying olanzapine candidates with low diabetes risk. Confirmatory research is needed, but this insight suggests a potentially larger role for olanzapine in the treatment of well-selected patients, particularly for those with schizophrenia, given the drug's effectiveness advantage among them.

While past research suggested that living arrangements are associated with suicide death, no study has examined the impact of sustained living arrangements and the change in living arrangements. Also, previous survival analysis studies only reported a single hazard ratio (HR), whereas the actual HR may change over time. We aimed to address these limitations using causal inference approaches.

Multi-point data from a general Japanese population sample were used. Participants reported their living arrangements twice within a 5-year time interval. After that, suicide death, non-suicide death and all-cause mortality were evaluated over 14 years. We used inverse probability weighted pooled logistic regression and cumulative incidence curve, evaluating the association of time-varying living arrangements with suicide death. We also studied non-suicide death and all-cause mortality to contextualize the association. Missing data for covariates were handled using random forest imputation.

A total of 86,749 participants were analysed, with a mean age (standard deviation) of 51.7 (7.90) at baseline. Of these, 306 died by suicide during the 14-year follow-up. Persistently living alone was associated with an increased risk of suicide death (risk difference [RD]: 1.1%, 95% confidence interval [CI]: 0.3–2.5%; risk ratio [RR]: 4.00, 95% CI: 1.83–7.41), non-suicide death (RD: 7.8%, 95% CI: 5.2–10.5%; RR: 1.56, 95% CI: 1.38–1.74) and all-cause mortality (RD: 8.7%, 95% CI: 6.2–11.3%; RR: 1.60, 95% CI: 1.42–1.79) at the end of the follow-up. The cumulative incidence curve showed that these associations were consistent throughout the follow-up. Across all types of mortality, the increased risk was smaller for those who started to live with someone and those who transitioned to living alone. The results remained robust in sensitivity analyses.

Individuals who persistently live alone have an increased risk of suicide death as well as non-suicide death and all-cause mortality, whereas this impact is weaker for those who change their living arrangements.

Theories propose that judgment of and reactivity to inner experiences are mediators of the effect of mindfulness-based interventions on generalized anxiety disorder (GAD). However, no study has tested such theories using brief, mindfulness ecological momentary intervention (MEMI). We thus tested these theories using a 14-day MEMI versus self-monitoring app (SM) control for GAD.

Participants (N = 110) completed self-reports of trait mindfulness (Five Facet Mindfulness Questionnaire), GAD severity (GAD-Questionnaire-IV), and trait perseverative cognitions (Perseverative Cognitions Questionnaire) at prerandomization, posttreatment, and 1-month follow-up (1MFU). Counterfactual mediation analyses with temporal precedence were conducted.

Improvement in pre–post mindfulness domains (acceptance of emotions, describing feelings accurately, acting with awareness, judgment of inner experience, and reactivity to inner experience) predicted pre-1MFU reduction in GAD severity and pre-1MFU reduction in trait perseverative cognitions from MEMI but not SM. MEMI reduced pre–post reactivity to inner experiences (but not other mindfulness domains) significantly more than SM. Only reduced pre–post reactivity significantly mediated stronger efficacy of MEMI over SM on pre-1MFU reductions in GAD severity (indirect effect: β = −2.970 [−5.034, −0.904], p = .008; b path: β = −3.313 [−6.350, −0.276], p = .033; percentage mediated: 30.5%) and trait perseverative cognitions (indirect effect: β = −0.153 [−0.254, −0.044], p = .008; b path: β = −0.145 [−0.260, −0.030], p = .014; percentage mediated: 42.7%). Other trait mindfulness domains were non-significant mediators.

Reactivity to inner experience might be a mindfulness-based intervention change mechanism and should be targeted to optimize brief MEMIs for GAD.

The United States Congress passed the 21st Century Cures Act mandating the development of Food and Drug Administration guidance on regulatory use of real-world evidence. The Forum on the Integration of Observational and Randomized Data conducted a meeting with various stakeholder groups to build consensus around best practices for the use of real-world data (RWD) to support regulatory science. Our companion paper describes in detail the context and discussion of the meeting, which includes a recommendation to use a causal roadmap for study designs using RWD. This article discusses one step of the roadmap: the specification of a sensitivity analysis for testing robustness to violations of causal model assumptions.

We present an example of a sensitivity analysis from a RWD study on the effectiveness of Nifurtimox in treating Chagas disease, and an overview of various methods, emphasizing practical considerations on their use for regulatory purposes.

Sensitivity analyses must be accompanied by careful design of other aspects of the causal roadmap. Their prespecification is crucial to avoid wrong conclusions due to researcher degrees of freedom. Sensitivity analysis methods require auxiliary information to produce meaningful conclusions; it is important that they have at least two properties: the validity of the conclusions does not rely on unverifiable assumptions, and the auxiliary information required by the method is learnable from the corpus of current scientific knowledge.

Prespecified and assumption-lean sensitivity analyses are a crucial tool that can strengthen the validity and trustworthiness of effectiveness conclusions for regulatory science.

Chronic pain has been extensively explored as a risk factor for opioid misuse, resulting in increased focus on opioid prescribing practices for individuals with such conditions. Physical disability sometimes co-occurs with chronic pain but may also represent an independent risk factor for opioid misuse. However, previous research has not disentangled whether disability contributes to risk independent of chronic pain.

Here, we estimate the independent and joint adjusted associations between having a physical disability and co-occurring chronic pain condition at time of Medicaid enrollment on subsequent 18-month risk of incident opioid use disorder (OUD) and non-fatal, unintentional opioid overdose among non-elderly, adult Medicaid beneficiaries (2016–2019).

We find robust evidence that having a physical disability approximately doubles the risk of incident OUD or opioid overdose, and physical disability co-occurring with chronic pain increases the risks approximately sixfold as compared to having neither chronic pain nor disability. In absolute numbers, those with neither a physical disability nor chronic pain condition have a 1.8% adjusted risk of incident OUD over 18 months of follow-up, those with physical disability alone have an 2.9% incident risk, those with chronic pain alone have a 3.6% incident risk, and those with co-occurring physical disability and chronic pain have a 11.1% incident risk.

These findings suggest that those with a physical disability should receive increased attention from the medical and healthcare communities to reduce their risk of opioid misuse and attendant negative outcomes.