Breast cancer is a major global health issue, especially among women. Previous research has indicated a possible association between psychiatric conditions, particularly schizophrenia, and an increased risk of breast cancer. However, the specific risk of breast cancer in women with schizophrenia, compared with those with other psychiatric disorders and the general population, remains controversial and needs further clarification.

To estimate the risk of breast cancer among people with schizophrenia compared with people with other psychiatric disorders and people in the general population.

We utilised medical claims data of women aged 18 to 80 years in the Korean National Health Information Database from 2007 to 2018. Individuals with schizophrenia were defined as women with ICD-10 codes F20 or F25 (n = 224 612). The control groups were defined as women with other psychiatric disorders (n = 224 612) and women in the general Korean population (n = 449 224). Cases and controls were matched by index date and age, in a 1:1:2 ratio. We estimated the hazard of breast cancer using the Cox proportional hazards model, adjusting for insurance premiums and medical comorbidities. Among the people with schizophrenia, we used the landmark method to estimate the association between duration of antipsychotic medication use and the incidence of breast cancer.

In multivariable Cox regression models, the hazard rate of breast cancer was 1.26 times higher in the people with schizophrenia than in the general population (95% CI: 1.20–1.32). In comparison with the psychiatric patient group, the hazard ratio was 1.17 (95% CI: 1.11–1.28). Among women with schizophrenia, the hazard of breast cancer was greater among those who took antipsychotic medications for 1 year or more compared with those who took antipsychotics for less than 6 months.

Women with schizophrenia have an elevated risk of breast cancer, and long-term use of antipsychotics is associated with an increased risk of breast cancer.

The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established.

To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system.

Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders.

Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76–0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69–0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses.

These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.

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.

This study serves as an exemplar to demonstrate the scalability of a research approach using survival analysis applied to general practice electronic health record data from multiple sites. Collection of these data, the subsequent analysis, and the preparation of practice-specific reports were performed using a bespoke distributed data collection and analysis software tool.

Statins are a very commonly prescribed medication, yet there is a paucity of evidence for their benefits in older patients. We examine the relationship between statin prescriptions for general practice patients over 75 and all-cause mortality.

We carried out a retrospective cohort study using survival analysis applied to data extracted from the electronic health records of five Australian general practices.

The data from 8025 patients were analysed. The median duration of follow-up was 6.48 years. Overall, 52 015 patient-years of data were examined, and the outcome of death from any cause was measured in 1657 patients (21%), with the remainder being censored. Adjusted all-cause mortality was similar for participants not prescribed statins versus those who were (HR 1.05, 95% CI 0.92–1.20, P = 0.46), except for patients with diabetes for whom all-cause mortality was increased (HR = 1.29, 95% CI: 1.00–1.68, P = 0.05). In contrast, adjusted all-cause mortality was significantly lower for patients deprescribed statins compared to those who were prescribed statins (HR 0.81, 95% CI 0.70–0.93, P < 0.001), including among females (HR = 0.75, 95% CI: 0.61–0.91, P < 0.001) and participants treated for secondary prevention (HR = 0.72, 95% CI: 0.60–0.86, P < 0.001). This study demonstrated the scalability of a research approach using survival analysis applied to general practice electronic health record data from multiple sites. We found no evidence of increased mortality due to statin-deprescribing decisions in primary care.

The hazard ratio (HR) is a commonly used summary statistic when comparing time to event (TTE) data between trial arms, but assumes the presence of proportional hazards (PH). Non-proportional hazards (NPH) are increasingly common in NICE technology appraisals (TAs) due to an abundance of novel cancer treatments, which have differing mechanisms of action compared with traditional chemotherapies. The goal of this study is to understand how pharmaceutical companies, evidence review groups (ERGs) and appraisal committees (ACs) test for PH and report clinical effectiveness in the context of NPH.

A thematic analysis of NICE TAs concerning novel cancer treatments published between 1 January 2020 and 31 December 2021 was undertaken. Data on PH testing and clinical effectiveness reporting for overall survival (OS) and progression-free survival (PFS) were obtained from company submissions, ERG reports, and final appraisal determinations (FADs).

NPH were present for OS or PFS in 28/40 appraisals, with log-cumulative hazard plots the most common testing methodology (40/40), supplemented by Schoenfeld residuals (20/40) and/or other statistical methods (6/40). In the context of NPH, the HR was ubiquitously reported by companies, inconsistently critiqued by ERGs (10/28), and commonly reported in FADs (23/28).

There is inconsistency in PH testing methodology used in TAs. ERGs are inconsistent in critiquing use of the HR in the context of NPH, and even when critiqued it remains a commonly reported outcome measure in FADs. Other measures of clinical effectiveness should be considered, along with guidance on clinical effectiveness reporting when NPH are present.

Obsessive-compulsive disorder (OCD) and schizophrenia are often reported as co-morbid conditions. However, the evidence of an association between OCD and the risk of schizophrenia is limited. This study investigated the risk of schizophrenia in patients newly diagnosed with OCD using a nationally representative sample cohort in South Korea.

Data were obtained from the 2002–2013 Korean National Health Insurance Service-National Sample Cohort of the National Health Insurance Service. Using propensity score matching, 2509 patients with OCD and a control group of 7527 patients were included in the analysis. Chi-squared tests were used to investigate and compare the general characteristics of the study population. The risk of schizophrenia was analysed using the Cox proportional hazard model.

The incidence rate was 45.79/10 000 person-year for patients with OCD and 4.19/10 000 person-year for patients without OCD. Patients with OCD had a higher risk of schizophrenia compared to the control group after adjusting for covariates (hazard ratio = 10.46, 95% confidence interval = 6.07–18.00).

This study identified an association between the diagnosis of OCD and the risk of schizophrenia in a South Korean national representative cohort. Further research using a prospective design to clarify the causality of OCD in schizophrenia in a controlled environment should be conducted to validate these findings.

Suicide risk is complex and nuanced, and how place impacts suicide risk when considered alongside detailed individual risk factors remains uncertain. We aimed to examine suicide risk in Denmark with both individual and neighbourhood level risk factors.

We used Danish register-based data to identify individuals born in Denmark from 1972, with full parental information and psychiatric diagnosis history. We fitted a two-level survival model to estimate individual and neighbourhood determinants on suicide risk.

We identified 1723 cases of suicide in Denmark during the follow-up period from 1982 to 2015. Suicide risk was explained mainly by individual determinants. Parental comorbidities, particularly maternal schizophrenia [incidence rate ratio (IRR): 2.29, 95% CI 1.56–3.16] and paternal death (2.29, 95% CI 1.31–3.72) partly explained suicide risk when adjusted for all other determinants. The general contextual effect of suicide risk across neighbourhoods showed a median incidence rate ratio (MRR) of 1.13 (1.01–1.28), which was further reduced with full adjustment. Suicide risk increased in neighbourhoods with a higher proportion of manual workers (IRR: 1.08; 1.03–1.14), and decreased with a higher population density (IRR: 0.89; 0.83–0.96).

Suicide risk varies mainly between individuals, with parental comorbidities having the largest effect on suicide risk. Suicide risk was less impacted by neighbourhood, though, albeit to a lesser extent than individual determinants, some characteristics were associated with suicide risk. Suicide prevention policies might consider targeting interventions towards individuals more vulnerable due to particular parental comorbidities, whilst taking into account that some neighbourhood characteristics might exacerbate this risk further.