Michael King

Cardiovascular risk prediction models for people with severe mental illness: results from the prediction and management of cardiovascular risk in people with severe mental illnesses (PRIMROSE) research program

IMPORTANCEnPeople with severe mental illness (SMI), including schizophrenia and bipolar disorder, have excess rates of cardiovascular disease (CVD). Risk prediction models validated for the general population may not accurately estimate cardiovascular risk in this group.nnnOBJECTIVEnTo develop and validate a risk model exclusive to predicting CVD events in people with SMI incorporating established cardiovascular risk factors and additional variables.nnnDESIGN, SETTING, AND PARTICIPANTSnWe used anonymous/deidentified data collected between January 1, 1995, and December 31, 2010, from the Health Improvement Network (THIN) to conduct a primary care, prospective cohort and risk score development study in the United Kingdom. Participants included 38,824 people with a diagnosis of SMI (schizophrenia, bipolar disorder, or other nonorganic psychosis) aged 30 to 90 years. During a median follow-up of 5.6 years, 2324 CVD events (6.0%) occurred.nnnMAIN OUTCOMES AND MEASURESnTen-year risk of the first cardiovascular event (myocardial infarction, angina pectoris, cerebrovascular accidents, or major coronary surgery). Predictors included age, sex, height, weight, systolic blood pressure, diabetes mellitus, smoking, body mass index (BMI), lipid profile, social deprivation, SMI diagnosis, prescriptions for antidepressants and antipsychotics, and reports of heavy alcohol use.nnnRESULTSnWe developed 2 CVD risk prediction models for people with SMI: the PRIMROSE BMI model and the PRIMROSE lipid model. These models mutually excluded lipids and BMI. In terms of discrimination, from cross-validations for men, the PRIMROSE lipid model D statistic was 1.92 (95% CI, 1.80-2.03) and C statistic was 0.80 (95% CI, 0.76-0.83) compared with 1.74 (95% CI, 1.63-1.86) and 0.78 (95% CI, 0.75-0.82) for published Cox Framingham risk scores. The corresponding results in women were 1.87 (95% CI, 1.76-1.98) and 0.79 (95% CI, 0.76-0.82) for the PRIMROSE lipid model and 1.58 (95% CI, 1.48-1.68) and 0.77 (95% CI, 0.73-0.81) for the Cox Framingham model. Discrimination statistics for the PRIMROSE BMI model were comparable to those for the PRIMROSE lipid model. Calibration plots suggested that both PRIMROSE models were superior to the Cox Framingham models.nnnCONCLUSIONS AND RELEVANCEnThe PRIMROSE BMI and lipid CVD risk prediction models performed better in SMI compared with models that include only established CVD risk factors. Further work on the clinical effectiveness and cost-effectiveness of the PRIMROSE models is needed to ascertain the best thresholds for offering CVD interventions.

Relative incidence of common cancers in people with severe mental illness. Cohort study in the United Kingdom THIN primary care database

BACKGROUNDnA recent United Kingdom (UK) report found that breast and colorectal cancers were more common in people with severe mental illness (SMI) and recommended targeted screening. Epidemiological evidence is however inconsistent.nnnOBJECTIVESnTo estimate relative incidence rates for colorectal, breast and lung cancer, and the overall incidence of the commonest other UK cancers, in people with SMI compared with people without SMI.nnnMETHODnCohort study in the UK using The Health Improvement Network (THIN) primary care database between 1990 and June 2008. Poisson regression was used to obtain adjusted incidence rate ratios (IRRs) for cancer, comparing two cohorts of people over 18; with and without a diagnosis of SMI.nnnRESULTSnWe identified 20,632 people with SMI and 116,152 people without, with median follow up of over 6years. No significant associations were observed between SMI and cancers of the breast (adjusted IRR 1.17; 95% confidence interval 0.95-1.45), colon (0.70; 0.46-1.05), rectum (1.05; 0.65-1.69) or lung (0.84; 0.65-1.10). The adjusted IRR for an aggregate cancer outcome in SMI was 0.95; 0.85-1.06. Results were similar for schizophrenia and bipolar disorder.nnnCONCLUSIONSnIn a cohort analysis within a large UK primary care database, the incidence of colo-rectal, breast and lung cancer, and of all common cancers, did not differ significantly in people with SMI, including schizophrenia, compared with people without SMI. Our results do not support enhanced screening procedures for cancer in people with SMI.

Clinical and cost-effectiveness of an intervention for reducing cholesterol and cardiovascular risk for people with severe mental illness in English primary care: a cluster randomised controlled trial

BACKGROUNDnPeople with severe mental illnesses, including psychosis, have an increased risk of cardiovascular disease. We aimed to evaluate the effects of a primary care intervention on decreasing total cholesterol concentrations and cardiovascular disease risk in people with severe mental illnesses.nnnMETHODSnWe did this cluster randomised trial in general practices across England, with general practices as the cluster unit. We randomly assigned general practices (1:1) with 40 or more patients with severe mental illnesses using a computer-generated random sequence with a block size of four. Researchers were masked to allocation, but patients and general practice staff were not. We included participants aged 30-75 years with severe mental illnesses (schizophrenia, bipolar disorder, or psychosis), who had raised cholesterol concentrations (5·0 mmol/L) or a total:HDL cholesterol ratio of 4·0 mmol/L or more and one or more modifiable cardiovascular disease risk factors. Eligible participants were recruited within each practice before randomisation. The Primrose intervention consisted of appointments (≤12) with a trained primary care professional involving manualised interventions for cardiovascular disease prevention (ie, adhering to statins, improving diet or physical activity levels, reducing alcohol, or quitting smoking). Treatment as usual involved feedback of screening results only. The primary outcome was total cholesterol at 12 months and the primary economic analysis outcome was health-care costs. We used intention-to-treat analysis. The trial is registered with Current Controlled Trials, number ISRCTN13762819.nnnFINDINGSnBetween Dec 10, 2013, and Sept 30, 2015, we recruited general practices and between May 9, 2014, and Feb 10, 2016, we recruited participants and randomly assigned 76 general practices with 327 participants to the Primrose intervention (n=38 with 155 patients) or treatment as usual (n=38 with 172 patients). Total cholesterol concentration data were available at 12 months for 137 (88%) participants in the Primrose intervention group and 152 (88%) participants in the treatment-as-usual group. The mean total cholesterol concentration did not differ at 12 months between the two groups (5·4 mmol/L [SD 1·1] for Primrose vs 5·5 mmol/L [1·1] for treatment as usual; mean difference estimate 0·03, 95% CI -0·22 to 0·29; p=0·788). This result was unchanged by pre-agreed supportive analyses. Mean cholesterol decreased over 12 months (-0·22 mmol/L [1·1] for Primrose vs -0·36 mmol/L [1·1] for treatment as usual). Total health-care costs (£1286 [SE 178] in the Primrose intervention group vs £2182 [328] in the treatment-as-usual group; mean difference -£895, 95% CI -1631 to -160; p=0·012) and psychiatric inpatient costs (£157 [135] vs £956 [313]; -£799, -1480 to -117; p=0·018) were lower in the Primrose intervention group than the treatment-as-usual group. Six serious adverse events of hospital admission and one death occurred in the Primrose group (n=7) and 23, including three deaths, occurred in the treatment-as-usual group (n=18).nnnINTERPRETATIONnTotal cholesterol concentration at 12 months did not differ between the Primrose and treatment-as-usual groups, possibly because of the cluster design, good care in the treatment-as-usual group, short duration of the intervention, or suboptimal focus on statin prescribing. The association between the Primrose intervention and fewer psychiatric admissions, with potential cost-effectiveness, might be important.nnnFUNDINGnNational Institute of Health Research Programme Grants for Applied Research.

Attitudes to suicide following the suicide of a friend or relative: a qualitative study of the views of 429 young bereaved adults in the UK

BackgroundPeople bereaved by suicide are at increased risk of suicide attempt and suicide, but explanations for these associations remain theoretical. It is possible that the experience of suicide bereavement modifies personal attitudes towards suicide, but the nature of these changes remains unexplored. There is a need to understand personal attitudes to suicide following suicide bereavement, as this may inform the development of suicide prevention interventions. Our aim was to explore the attitudes of young adults bereaved by suicide towards their own likelihood of dying by suicide.MethodsWe conducted a cross-sectional study of staff and students aged 18–40 at 37 United Kingdom (UK) higher educational institutions in 2010. Ethical approval was granted by the UCL Research Ethics Committee. Qualitative responses to a question probing attitudes to own suicide were provided by 429 respondents who had experienced bereavement by the suicide of a close contact. We identified key themes in this dataset using thematic analysis.ResultsAnalysis identified four main themes: suicide as a more tangible option (whether feared or not); identification with the deceased and awareness of shared vulnerabilities to suicide; personal determination to avoid suicide; and beliefs regarding safeguards against suicide. These themes reflected a broad split in participantsxa0views regarding own likelihood of dying by suicide, influenced by the degree to which own suicide was feared and the extent to which they felt in control of determining a suicide death. Whilst the majority described an aversion to the idea of attempting suicide themselves, largely through an awareness of the impact on others, a minority described their experiences as having normalised suicide as a personal option.ConclusionsThe views of a sample of UK-based adults bereaved by suicide suggest that exposure to the suicide of a close friend or relative can influence attitudes to suicide in ways that could influence own risk of suicide attempt. The normalising attitudes to suicide observed in a minority of respondents could contribute to the observed association between suicide bereavement and suicide attempt.

The stigma associated with bereavement by suicide and other sudden deaths: A qualitative interview study

Quantitative studies have found that suicide bereavement is associated with suicide attempt, and is perceived as the most stigmatising of sudden losses. Their findings also suggest that perceived stigma may explain the excess suicidality. There is a need to understand the nature of this stigma and address suicide risk in this group. We aimed to describe and compare the nature of the experiences of stigma reported by people bereaved by suicide, sudden unnatural death, and sudden natural death, and identify any commonalities and unique experiences. We conducted a population-based cross-sectional survey of 659,572 staff and students at 37 British higher educational institutions in 2010, inviting those aged 18–40 who had experienced sudden bereavement of a close contact since the age of 10 to take part in an on-line survey and to volunteer for an interview to discuss their experiences. We used maximum variation sampling from 1398 volunteer interviewees to capture a range of experiences, and conducted individual face-to-face semi-structured interviews to explore perceptions of stigma and support. We continued sampling until no new themes were forthcoming, reaching saturation at nu202f=u202f27 interviews (11 participants bereaved by suicide). We employed thematic analysis to identify any distinct dimensions of reported stigma, and any commonalities across the three groups. We identified two key themes: specific negative attitudes of others, and social awkwardness. Both themes were common to interviewees bereaved by suicide, sudden unnatural death, and sudden natural death. All interviewees reported the experience of stigmatising social awkwardness, but this may have been experienced more acutely by those bereaved by suicide due to self-stigma. This study provides evidence of a persistent death taboo in relation to sudden deaths. There is potential for anti-stigma interventions to reduce the isolation and social awkwardness perceived by people bereaved suddenly, particularly after suicide loss.

Relative risks of cardiovascular disease in people prescribed olanzapine, risperidone and quetiapine

Antipsychotics may confer long term benefits and risks, including cardiovascular disease (CVD) risk. Several studies using routine clinical data have reported associations between antipsychotics and CVD but potential confounding factors and unclear classification of drug exposure limits their interpretation.nnnMETHODnWe used data from The Health Improvement Network, a large UK primary care database to determine relative risks of (CVD) comparing similar groups of people only prescribed olanzapine versus either risperidone or quetiapine. We included participants over 18 between 1995 and 2011. To assess confounding factors we created propensity scores for being prescribed each antipsychotic. We used propensity score matching and Poisson regression to calculate the CVD incidence rate ratios for olanzapine versus the other two drugs.nnnRESULTSnWe identified 18,319 people who received a single antipsychotic during follow-up (n=5090 risperidone, 7797 olanzapine and 4613 quetiapine). In unmatched analyses, the CVD incidence rate ratio (IRR) for olanzapine versus risperidone was 0.63 (0.51-0.77) but the propensity score matched IRR was 0.78 (0.61-1.02). In the unmatched olanzapine versus quetiapine analysis the IRR adjusted for age and sex for olanzapine was 1.52 (1.16-1.98) but the propensity score matched analysis gave an IRR of 1.08 (0.79-1.46).nnnCONCLUSIONSnAfter propensity score matching, we found no statistical differences in CVD incidence between olanzapine and either risperidone or quetiapine. Analyses which did not account for confounding factors produced very different results. Researchers must address confounding factors when designing observational studies to assess adverse outcomes of drugs, including antipsychotics.