Association between quetiapine use and self-harm outcomes among people with recorded personality disorder in UK primary care: A self-controlled case series analysis.

BACKGROUND: Quetiapine is frequently prescribed to people with personality disorder diagnoses, but this is not supported by evidence or treatment guidelines. AIMS: To examine associations between periods of quetiapine prescribing and self-harm events in people with personality disorder. METHOD: Self-controlled case series using linked primary care and hospital records covering the period 2007-2017. We calculated incidence rates and incidence rate ratios (IRRs) for self-harm events during periods when people were prescribed (exposed to) quetiapine, as well as periods when they were unexposed or pre-exposed to quetiapine. RESULTS: We analysed data from 1,082 individuals with established personality disorder diagnoses, all of whom had at least one period of quetiapine prescribing and at least one self-harm episode. Their baseline rate of self-harm (greater than 12 months before quetiapine treatment) was 0.52 episodes per year. Self-harm rates were elevated compared to the baseline rate in the month after quetiapine treatment was commenced (IRR 1.85; 95% confidence interval (CI) 1.46-2.34) and remained raised throughout the year after quetiapine treatment was started. However, self-harm rates were highest in the month prior to quetiapine initiation (IRR 3.59; 95% CI 2.83-4.55) and were elevated from 4 months before quetiapine initiation, compared to baseline. CONCLUSION: Self-harm rates were elevated throughout the first year of quetiapine prescribing, compared to the baseline rate. However, rates of self-harm reduced in the month after patients commenced quetiapine, compared to the month before quetiapine was initiated. Self-harm rates gradually dropped over a year of quetiapine treatment. Quetiapine may acutely reduce self-harm. Longer-term use and any potential benefits need to be balanced with the risk of adverse events.

Prescribing of antipsychotics among people with recorded personality disorder in primary care: a retrospective nationwide cohort study using The Health Improvement Network primary care database.

OBJECTIVES: To investigate the extent of antipsychotic prescribing to people with recorded personality disorder (PD) in UK primary care and factors associated with such prescribing. DESIGN: Retrospective cohort study. SETTING: General practices contributing to The Health Improvement Network UK-wide primary care database, 1 January 2000-31 December 2016. PARTICIPANTS: 46 210 people registered with participating general practices who had a record of PD in their general practice notes. 1358 (2.9%) people with missing deprivation information were excluded from regression analyses; no other missing data. MAIN OUTCOME MEASURES: Prescriptions for antipsychotics in general practice records and length of time in receipt of antipsychotic prescriptions. RESULTS: Of 46 210 people with recorded PD, 15 562 (34%) were ever prescribed antipsychotics. Among the subgroup of 36 875 people with recorded PD, but no recorded severe mental illness (SMI), 9208 (25%) were prescribed antipsychotics; prescribing was lower in less deprived areas (adjusted rate ratio (aRR) comparing least to most deprived quintile: 0.56, 95% CI 0.48 to 0.66, p<0.001), was higher in females (aRR:1.25, 95% CI 1.16 to 1.34, p<0.001) and with a history of adverse childhood experiences (aRR:1.44, 95% CI 1.28 to 1.56, p<0.001). Median time prescribed antipsychotics was 605 days (IQR 197-1639 days). Prescribing frequency has increased over time. CONCLUSIONS: Contrary to current UK guidelines, antipsychotics are frequently and increasingly prescribed for extended periods to people with recorded PD, but with no history of SMI. An urgent review of clinical practice is warranted, including the effectiveness of such prescribing and the need to monitor for adverse effects, including metabolic complications.

Depression, depressive symptoms and treatments in women who have recently given birth: UK cohort study.

OBJECTIVES: To investigate how depression is recognised in the year after child birth and treatment given in clinical practice. DESIGN: Cohort study based on UK primary care electronic health records. SETTING: Primary care. PARTICIPANTS: Women who have given live birth between 2000 and 2013. OUTCOMES: Prevalence of postnatal depression, depression diagnoses, depressive symptoms, antidepressant and non-pharmacological treatment within a year after birth. RESULTS: Of 206 517 women, 23 623 (11%) had a record of depressive diagnosis or symptoms in the year after delivery and more than one in eight women received antidepressant treatment. Recording and treatment peaked 6-8 weeks after delivery. Initiation of selective serotonin reuptake inhibitors (SSRI) treatment has become earlier in the more recent years. Thus, the initiation rate of SSRI treatment per 100 pregnancies (95% CI) at 8 weeks were 2.6 (2.5 to 2.8) in 2000-2004, increasing to 3.0 (2.9 to 3.1) in 2005-2009 and 3.8 (3.6 to 3.9) in 2010-2013. The overall rate of initiation of SSRI within the year after delivery, however, has not changed noticeably. A third of the women had at least one record suggestive of depression at any time prior to delivery and of these one in four received SSRI treatment in the year after delivery.Younger women were most likely to have records of depression and depressive symptoms. (Relative risk for postnatal depression: age 15-19: 1.92 (1.76 to 2.10), age 20-24: 1.49 (1.39 to 1.59) versus age 30-34). The risk of depression, postnatal depression and depressive symptoms increased with increasing social deprivation. CONCLUSIONS: More than 1 in 10 women had electronic health records indicating depression diagnoses or depressive symptoms within a year after delivery and more than one in eight women received antidepressant treatment in this period. Women aged below 30 and from the most deprived areas were at highest risk of depression and most likely to receive antidepressant treatment.

Prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the research conducted on prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries (LMICs) and to estimate the pooled prevalence of frailty and prefrailty in community-dwelling older adults in LMICs. DESIGN: Systematic review and meta-analysis. PROSPERO registration number is CRD42016036083. DATA SOURCES: MEDLINE, EMBASE, AMED, Web of Science, CINAHL and WHO Global Health Library were searched from their inception to 12 September 2017. SETTING: Low-income and middle-income countries. PARTICIPANTS: Community-dwelling older adults aged ≥60 years. RESULTS: We screened 7057 citations and 56 studies were included. Forty-seven and 42 studies were included in the frailty and prefrailty meta-analysis, respectively. The majority of studies were from upper middle-income countries. One study was available from low-income countries. The prevalence of frailty varied from 3.9% (China) to 51.4% (Cuba) and prevalence of prefrailty ranged from 13.4% (Tanzania) to 71.6% (Brazil). The pooled prevalence of frailty was 17.4% (95% CI 14.4% to 20.7%, I2=99.2%) and prefrailty was 49.3% (95% CI 46.4% to 52.2%, I2=97.5%). The wide variation in prevalence rates across studies was largely explained by differences in frailty assessment method and the geographic region. These findings are for the studies with a minimum recruitment age 60, 65 and 70 years. CONCLUSION: The prevalence of frailty and prefrailty appears higher in community-dwelling older adults in upper middle-income countries compared with high-income countries, which has important implications for healthcare planning. There is limited evidence on frailty prevalence in lower middle-income and low-income countries. PROSPERO REGISTRATION NUMBER: CRD42016036083.

Effectiveness and cost-effectiveness of a cardiovascular risk prediction algorithm for people with severe mental illness (PRIMROSE).

OBJECTIVES: To determine the cost-effectiveness of two bespoke severe mental illness (SMI)-specific risk algorithms compared with standard risk algorithms for primary cardiovascular disease (CVD) prevention in those with SMI. SETTING: Primary care setting in the UK. The analysis was from the National Health Service perspective. PARTICIPANTS: 1000 individuals with SMI from The Health Improvement Network Database, aged 30-74 years and without existing CVD, populated the model. INTERVENTIONS: Four cardiovascular risk algorithms were assessed: (1) general population lipid, (2) general population body mass index (BMI), (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those considered high risk (> 10%) were assumed to be prescribed statin therapy while others received usual care. PRIMARY AND SECONDARY OUTCOME MEASURES: Quality-adjusted life years (QALYs) and costs were accrued for each algorithm including no algorithm, and cost-effectiveness was calculated using the net monetary benefit (NMB) approach. Deterministic and probabilistic sensitivity analyses were performed to test assumptions made and uncertainty around parameter estimates. RESULTS: The SMI-specific BMI algorithm had the highest NMB resulting in 15 additional QALYs and a cost saving of approximately £53 000 per 1000 patients with SMI over 10 years, followed by the general population lipid algorithm (13 additional QALYs and a cost saving of £46 000). CONCLUSIONS: The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of an SMI-specific BMI algorithm (blood tests not required) makes it an attractive algorithm to implement in clinical settings.

Monitoring of alcohol consumption in primary care among adults with bipolar disorder: A cross-sectional and retrospective cohort study.

BACKGROUND: Screening for alcohol use disorders is an important priority in the healthcare of people with bipolar disorder, incentivised in UK primary care since 2011, through the Quality and Outcomes Framework (QOF). The extent of alcohol monitoring in primary care, and impact of QOF, is unknown. The aim was to examine recording of alcohol consumption in primary care. METHODS: Poisson regression of biennial alcohol recording rates between 2000 and 2013 among 14,051 adults with bipolar disorder and 90,023 adults without severe mental illness (SMI), from 484 general practices contributing to The Health Improvement Network UK-wide primary care database. RESULTS: Alcohol recording rates among people with bipolar disorder increased from 88.6 records per 1000 person-years (95% confidence interval 81.2-96.6) in 2000/2002 to 837.4 records per 1000 person-years (817.4-858.0) in 2011/2013; a more than nine-fold increase, mainly occurring after the introduction of the QOF incentive in 2011. In 2000/2002 alcohol recording levels among people with bipolar disorder were not statistically significantly different from those without SMI (adjusted rate ratio 0.96, 0.88-1.05). By 2011/2013, people with bipolar disorder were over four times as likely to have an alcohol record: adjusted rate ratio 4.45 (4.15-4.77). LIMITATIONS: The routinely collected data may be incomplete. Alcohol data entered as free-text was not captured. CONCLUSIONS: The marked rise in alcohol consumption recording highlights what can be achieved. It is most likely attributable to QOF, suggesting that QOF, or similar schemes, can be powerful tools in promoting aspects of healthcare.

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.

IMPORTANCE: People 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. OBJECTIVE: To develop and validate a risk model exclusive to predicting CVD events in people with SMI incorporating established cardiovascular risk factors and additional variables. DESIGN, SETTING, AND PARTICIPANTS: We 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. MAIN OUTCOMES AND MEASURES: Ten-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. RESULTS: We 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. CONCLUSIONS AND RELEVANCE: The 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.

Socio-demographic variation in chest pain incidence and subsequent coronary heart disease in primary care in the United Kingdom.

BACKGROUND: We know little about socio-demographic differences in chest pain presenting to primary care and subsequent coronary heart disease (CHD) diagnosis. METHODS: We conducted a cohort study with 198,209 patients aged 30 years and over with a first episode of chest pain, using data from 339 general practices in The Health Improvement Network (THIN) primary care database during 1997-2007. We calculated incidence of chest pain and subsequent CHD by age, gender and quintiles of Townsend area deprivation score. RESULTS: Chest pain incidence was 19.6/1000 person years at risk (PYAR, 95% CI 19.5-19.7). Incidence rose with age and increasing deprivation, with minimal gender differences. The incidence of CHD in the year following chest pain in primary care was 96.6/1000 PYAR (95% CI 95.1-98.0). There were significant interactions with age/deprivation and gender/deprivation on subsequent CHD diagnosis. The effect of deprivation was less for those over 60 years, and greater for younger women. Women in their 30s with chest pain in deprived areas had 8.77 times (95% CI 3.34-23.06) the CHD incidence compared to those in the most affluent areas. The absolute risk difference was small (8/1000 PYAR, 95% CI 4.5-11.5/1000 PYAR). CONCLUSIONS: There was a modestly greater incidence of chest pain in primary care in more deprived areas compared to the least deprived areas. There were interactions between age, gender and deprivation on subsequent CHD diagnosis, with the greatest effect of deprivation on CHD diagnosis seen in younger women. This observation suggests the need for targeting health promotion and CHD prevention among younger women in deprived areas.

Recording of severe mental illness in United Kingdom primary care, 2000-2010.

BACKGROUND: There is increasing emphasis on primary care services for individuals with severe mental illnesses (SMI), including schizophrenia, bipolar disorder, and other non-organic psychotic disorders. However we lack information on how many people receive these different diagnoses in primary care. Primary care databases offer an opportunity to explore the recording of new SMI diagnoses in representative general practices. METHODS: We used data from The UK Health Improvement Network (THIN) primary care database including longitudinal patient records for individuals aged over 16 years from 437 general practices. We determined the annual GP recorded rate of first diagnosis of SMI by age, gender, social deprivation and urbanicity between 2000 and 2010. RESULTS: We identified 10,520 individuals with a first record of schizophrenia, bipolar disorder or other non-organic psychosis among 4,164,794 patients. This corresponded to a rate of first diagnosis of 46.4 per 100,000 person years at risk (PYAR) (95% CI 45.4 to 47.4) in the 16-65 age group. The rate of first record of schizophrenia was 9.2 per 100,000 PYAR (95% CI 8.7 to 9.6) in this age group, bipolar disorder was 15.0 per 100,000 PYAR (95% CI 14.4 to 15.5) and other non-organic psychotic disorder was 22.3 per 100,000 PYAR (95% CI 21.6 to 23.0). CONCLUSIONS: The rates of GP recorded SMI in primary care records were broadly comparable to incidence rates from previous epidemiological studies of SMI and show similar patterns by socio-demographic characteristics. However there were some differences by specific diagnoses. GPs may be recording rates that are higher than those used to commission services.

Rising adiposity curbing decline in the incidence of myocardial infarction: 20-year follow-up of British men and women in the Whitehall II cohort.

Aims To estimate the contribution of risk factor trends to 20-year declines in myocardial infarction (MI) incidence in British men and women. Methods and results From 1985 to 2004, 6379 men and 3074 women in the Whitehall II cohort were followed for incident MI and risk factor trends. Over 20 years, the age-sex-adjusted hazard of MI fell by 74% (95% confidence interval 48-87%), corresponding to an average annual decline of 6.5% (3.2-9.7%). Thirty-four per cent (20-76%) of the decline in MI hazard could be statistically explained by declining non-HDL cholesterol levels, followed by increased HDL cholesterol (17%, 10-32%), reduced systolic blood pressure (13%, 7-24%), and reduced cigarette smoking prevalence (6%, 2-14%). Increased fruit and vegetable consumption made a non-significant contribution of 7% (-1-20%). In combination, these five risk factors explained 56% (34-112%). Rising body mass index (BMI) was counterproductive, reducing the scale of the decline by 11% (5-23%) in isolation. The MI decline and the impact of the risk factors appeared similar for men and women. Conclusion In men and women, over half of the decline in MI risk could be accounted for by favourable risk factor time trends. The adverse role of BMI emphasizes the importance of addressing the rising population BMI.

Social class differences in secular trends in established coronary risk factors over 20 years: a cohort study of British men from 1978-80 to 1998-2000.

BACKGROUND: Coronary heart disease (CHD) mortality in the UK since the late 1970s has declined more markedly among higher socioeconomic groups. However, little is known about changes in coronary risk factors in different socioeconomic groups. This study examined whether changes in established coronary risk factors in Britain over 20 years between 1978-80 and 1998-2000 differed between socioeconomic groups. METHODS AND FINDINGS: A socioeconomically representative cohort of 7735 British men aged 40-59 years was followed-up from 1978-80 to 1998-2000; data on blood pressure (BP), cholesterol, body mass index (BMI) and cigarette smoking were collected at both points in 4252 survivors. Social class was based on longest-held occupation in middle-age. Compared with men in non-manual occupations, men in manual occupations experienced a greater increase in BMI (mean difference = 0.33 kg/m(2); 95%CI 0.14-0.53; p for interaction = 0.001), a smaller decline in non-HDL cholesterol (difference in mean change = 0.18 mmol/l; 95%CI 0.11-0.25, p for interaction≤0.0001) and a smaller increase in HDL cholesterol (difference in mean change = 0.04 mmol/l; 95%CI 0.02-0.06, p for interaction≤0.0001). However, mean systolic BP declined more in manual than non-manual groups (difference in mean change = 3.6; 95%CI 2.1-5.1, p for interaction≤0.0001). The odds of being a current smoker in 1978-80 and 1998-2000 did not differ between non-manual and manual social classes (p for interaction = 0.51). CONCLUSION: Several key risk factors for CHD and type 2 diabetes showed less favourable changes in men in manual occupations. Continuing priority is needed to improve adverse cardiovascular risk profiles in socially disadvantaged groups in the UK.

Are weekend handovers of adequate quality for the on-call general medical team?

Weekend handover is vital for patient safety--poor handover is a cause of avoidable adverse events. This study evaluated whether the quality of information handed over for patients requiring weekend review was adequate. Two external doctors imagined themselves as the doctor on-call and judged whether the handed-over information was adequate for each case. Of the 1,130 handovers evaluated, 867 were handed over using a computerised proforma and discussed at the handover meeting, 148 using the computerised proforma but not discussed, 30 handovers were handwritten. Of handovers of patient details and background information, 87.3% were judged of adequate quality by the first auditor and 86.0% by the second. Similarly 70.6% and 75.8% of handovers of action plans were of adequate quality. Use of computerised proforma and discussion at a handover meeting gave the highest percentage of handovers of adequate quality, however, there was room for improvement. Training in handover may improve communication.

Trends in longer-term survival following an acute myocardial infarction and prescribing of evidenced-based medications in primary care in the UK from 1991: a longitudinal population-based study.

BACKGROUND: Both the incidence of myocardial infarction (MI) and short-term case fatality have declined in the UK. However, little is known about trends in longer-term survival following an MI. The aim of the study was to investigate trends in longer-term survival, alongside trends in medication prescribing in primary care. METHODS: Data came from 218 general practices contributing to the Health Improvement Network, a UK-wide primary care database. 3-year survival and medication use were determined for 6,586 men and 3,766 women who had an MI between 1991 and 2002 and had already survived 3 months. RESULTS: Adjusting for age and gender, the 3-year post-MI case-fatality rate among 3-month survivors fell by 28% (95% CI 13 to 40), from 83 deaths per 1000 person-years for MI occurring in 1991-2 to 61 deaths per 1000 person-years for MI in 2001-2. Relative declines in the case-fatality rate of 37% (20 to 50) and 14% (-11 to 34) were observed for men and women, respectively (p=0.06 for interaction). Prescribing in the 3 months following the MI of lipid-regulating drugs increased from 3% of patients in 1991 to 79% in 2002, prescribing of beta-blockers increased from 26% to 68%, prescribing of ACE inhibitors increased from 11% to 71% and prescribing of anti-platelet medication increased from 46% to 86%. CONCLUSION: There has been a moderate improvement in longer-term survival following an MI, distinct from improvements in short-term survival, although men may have benefited more than women. Increased medication prescribing in primary care may be a contributing factor.

Explaining variation in referral from primary to secondary care: cohort study.

OBJECTIVES: To determine the extent to which referral for defined symptoms from primary care varies by age, sex, and social deprivation and whether any sociodemographic variations in referral differ according to the presence of national referral guidance and the potential of the symptoms to be life threatening. DESIGN: Cohort study using individual patient data from the health improvement network database in primary care. SETTING: United Kingdom. PARTICIPANTS: 5492 patients with postmenopausal bleeding, 23 121 with hip pain, and 101 212 with dyspepsia from 326 general practices, 2001-7. MAIN OUTCOME MEASURES: Multivariable associations between odds of immediate referral for postmenopausal bleeding and age and social deprivation; hazard rates of referral for hip pain or dyspepsia and age, sex, and social deprivation. Analyses for dyspepsia were stratified for people aged less than and more than 55 years because referral guidance differs by age. RESULTS: 61.4% (3374/5492) of patients with postmenopausal bleeding, 17.4% (4019/23 121) with hip pain, and 13.8% (13 944/101 212) with dyspepsia were referred. The likelihood of referral for postmenopausal bleeding declined with increasing age: the adjusted odds ratio for patients aged 85 or more compared with those aged 55-64 was 0.39 (95% confidence interval 0.31 to 0.49). Patients aged 85 or more with hip pain were also less likely to be referred than those aged 55-64 (0.68, 0.57 to 0.81). Women were less likely than men to be referred for hip pain (hazard ratio 0.90, 95% confidence interval 0.84 to 0.96). More deprived patients with hip pain or dyspepsia (if aged <55) were less likely to be referred. Adjusted hazard ratios for those in the most deprived Townsend fifth compared with the least deprived were 0.72 (95% confidence interval 0.62 to 0.82) and 0.76 (0.68 to 0.85), respectively. No socioeconomic gradient was evident in referral for postmenopausal bleeding. CONCLUSIONS: Inequalities in referral associated with socioeconomic circumstances were more likely to occur in the absence of both explicit guidance and potentially life threatening conditions, whereas inequalities with age were evident for all conditions.

Is the recent rise in type 2 diabetes incidence from 1984 to 2007 explained by the trend in increasing BMI?: evidence from a prospective study of British men.

OBJECTIVE: To estimate the extent to which increasing BMI may explain the rise in type 2 diabetes incidence in British men from 1984 to 2007. RESEARCH DESIGN AND METHODS: A representative cohort ratio of 6,460 British men was followed-up for type 2 diabetes incidence between 1984 (aged 45-65 years) and 2007 (aged 67-89 years). BMI was ascertained at regular intervals before and during the follow-up. RESULTS: Between 1984-1992 and 1999-2007, the age-adjusted hazard of type 2 diabetes more than doubled (hazard ratio 2.33 [95% CI 1.75-3.10]). Mean BMI rose by 1.42 kg/m(2) (95% CI 1.10-1.74) between 1984 and 1999; this could explain 26% (95% CI 17-38) of the type 2 diabetes increase. CONCLUSIONS: An appreciable portion of the rise in type 2 diabetes can be attributed to BMI changes. A substantial portion remains unexplained, possibly associated with other determinants such as physical activity. This merits further research.

Assessing the impact of medication use on trends in major coronary risk factors in older British men: a cohort study.

AIMS: To investigate the role of medication in 20-year trends in blood pressure (BP) and blood lipids in older British men. METHODS AND RESULTS: BP and lipids were measured in 4231 men from a representative cohort at baseline (1978-1980, aged 40-59 years) and after 20 years (1998-2000). Cohort-wide age-adjusted 20-year mean changes were as follows: systolic BP -7.6 mmHg (95% confidence interval: -9.7 to -5.4); diastolic BP +3.3 mmHg (+2.2 to +4.5); non-high-density lipoprotein (HDL)-cholesterol -0.4 mmol/l (-0.5 to -0.2); HDL-cholesterol +0.16 mmol/l (+0.13 to +0.19). Much (79%) of the systolic BP fall occurred only among 1561 men (37%) reporting the use of BP-lowering medication during the follow-up; systolic BP changed by -12.3 mmHg (-14.7 to -9.9) and -1.6 mmHg (-3.7 to +0.5) among medication users and men not using medication, respectively (P<0.001 for medication-time interaction). One-third of the non-HDL-cholesterol fall occurred only among 302 men (8%) reporting the use of lipid-regulating drugs; non-HDL-cholesterol changed by -1.8 mmol/l (-2.0 to -1.6) and -0.2 mmol/l (-0.4 to -0.1) among medication users and men not using medication, respectively (P<0.001 for interaction). The HDL-cholesterol increase was not associated with lipid-regulating drug use (P=0.15 for interaction). CONCLUSION: Decreases in BP were largely confined to medication users and overall changes in non-HDL-cholesterol were modest, suggesting the need for greater efforts to reduce BP and cholesterol among the general population. HDL-cholesterol increased among all men, likely reflecting cohort-wide improvements in associated health behaviours.

Sociodemographic variations in the contribution of secondary drug prevention to stroke survival at middle and older ages: cohort study.

OBJECTIVES: To determine the extent to which secondary drug prevention for patients with stroke in routine primary care varies by sex, age, and socioeconomic circumstances, and to quantify the effect of secondary drug prevention on one year mortality by sociodemographic group. DESIGN: Cohort study using individual patient data from the health improvement network primary care database. SETTING: England. PARTICIPANTS: 12 830 patients aged 50 or more years from 113 general practices who had a stroke between 1995 and 2005 and who survived the first 30 days after the stroke. MAIN OUTCOME MEASURES: Multivariable associations between odds of receiving secondary prevention after a stroke, and sex, age group, and socioeconomic circumstances; hazard ratios for all cause mortality from 31 days after the stroke and within the first year among patients receiving treatment and by social group; and probabilities of one year mortality for social factors of interest and treatment. RESULTS: Only 25.6% of men and 20.8% of women received secondary prevention. Receipt of secondary prevention did not vary by socioeconomic circumstances or by sex. Older patients were, however, substantially less likely to receive treatment. The adjusted odds ratio for 80-89 year olds compared with 50-59 year olds was 0.53 (95% confidence interval 0.41 to 0.69). This was because older people were less likely to receive lipid lowering drugs-for example, the adjusted odds ratio for 80-89 year olds compared with 50-59 year olds was 0.44 (95% confidence interval 0.33 to 0.59). Secondary prevention was associated with a 50% reduction in mortality risk (adjusted hazard ratio 0.50, 95% confidence interval 0.42 to 59). On average, mortality within the first year was 5.7% for patients receiving treatment compared with 11.1% for patients not receiving treatment. There was little evidence that the effect of treatment differed between the social groups examined. CONCLUSION: Under-treatment among older people with stroke in routine primary care cannot be justified given the lack of evidence on variations in effectiveness of treatment by age.

How much of the recent decline in the incidence of myocardial infarction in British men can be explained by changes in cardiovascular risk factors? Evidence from a prospective population-based study.

BACKGROUND: The incidence of myocardial infarction (MI) in Britain has fallen markedly in recent years. Few studies have investigated the extent to which this decline can be explained by concurrent changes in major cardiovascular risk factors. METHODS AND RESULTS: The British Regional Heart Study examined changes in cardiovascular risk factors and MI incidence over 25 years from 1978 in a cohort of 7735 men. During this time, the age-adjusted hazard of MI decreased by 3.8% (95% confidence interval 2.6% to 5.0%) per annum, which corresponds to a 62% decline over the 25 years. At the same time, after adjustment for age, cigarette smoking prevalence, mean systolic blood pressure, and mean non-high-density lipoprotein (HDL) cholesterol decreased, whereas mean HDL cholesterol, mean body mass index, and physical activity levels rose. No significant change occurred in alcohol consumption. The fall in cigarette smoking explained the greatest part of the decline in MI incidence (23%), followed by changes in blood pressure (13%), HDL cholesterol (12%), and non-HDL cholesterol (10%). In combination, 46% (approximate 95% confidence interval 23% to 164%) of the decline in MI could be explained by these risk factor changes. Physical activity and alcohol consumption had little influence, whereas the increase in body mass index would have produced a rise in MI risk. CONCLUSIONS: Modest favorable changes in the major cardiovascular risk factors appear to have contributed to considerable reductions in MI incidence. This highlights the potential value of population-wide measures to reduce exposure to these risk factors in the prevention of coronary heart disease.

Continuous monitoring of long-term outcomes with application to hip prostheses.

The CUSUM continuous monitoring method could be a valuable tool in evaluating the performance (revision experience) of prostheses used in hip replacement surgery. The dilemma when applying the CUSUM in this context is the choice of statistical model for the outcome (revision). The Bernoulli model is perhaps the most straightforward approach but the Poisson model is a plausible, and could be argued, preferable alternative for long-term outcomes such as this, provided the rate of revision with time from surgery can be assumed to be constant. However, a rate (or hazard) varying according to the Weibull distribution appears to be a better representation of a prosthesis lifetime. We show how to adapt the Poisson approach to allow for the hazard to vary according to the Weibull model as well as other parametric survival models. Application to data on a known poorly performing prosthesis shows both the Poisson and Weibull CUSUMs could have given early warning of the poor performance, with the Weibull chart alerting before the Poisson. Simulation work to investigate the robustness of the Poisson and Weibull CUSUM to departures from the underlying survival model highlights the need for correct specification of the model for the outcome.