The risk of malignancy in patients with secukinumab-treated psoriasis, psoriatic arthritis and ankylosing spondylitis: analysis of clinical trial and postmarketing surveillance data with up to five years of follow-up.

BACKGROUND: Data on the use of biologic therapy and malignancy risk are inconsistent due to limited long-term robust studies. OBJECTIVES: To assess the malignancy risk in patients with secukinumab-treated psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS). METHODS: This integrated safety analysis from both the secukinumab clinical trial programme and postmarketing safety surveillance data included any patient receiving at least one approved dose of secukinumab with a maximum of 5 years of follow-up. Safety analyses evaluated the rate of malignancy using exposure-adjusted incidence rates [EAIR; incidence rates per 100 patient treatment-years (PTY)]. Standardized incidence ratios (SIRs) were reported using the Surveillance, Epidemiology, and End Results Program (SEER) database as a reference population. Crude incidence of malignancy was also reported using postmarketing surveillance data. RESULTS: Safety data from 49 clinical trials with secukinumab-treated patients were included: 10 685 patients with psoriasis, 2523 with PsA and 1311 with AS. Across indications over a 5-year period, the EAIR of malignancy was 0·85 per 100 PTY [95% confidence interval (CI) 0·74-0·98] in secukinumab-treated patients, corresponding to 204 patients per 23 908 PTY. Overall, the observed vs. expected number of malignancies from secukinumab clinical trial data were comparable, as indicated by an SIR of 0·99 (95% CI 0·82-1·19) across indications. The estimated crude cumulative incidence reporting rate per 100 PTY for malignancy was 0·27 in the postmarketing surveillance data across indications with a cumulative exposure of 285 811 PTY. CONCLUSIONS: In this large safety analysis, the risk of malignancy was low for up to 5 years of secukinumab treatment. These data support the long-term use of secukinumab in these indications.

The risk of depression, suicidal ideation and suicide attempt in patients with psoriasis, psoriatic arthritis or ankylosing spondylitis.

BACKGROUND: Sparse information is available concerning mental health issues in psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients. OBJECTIVE: To estimate risk of depression, suicidal ideation and suicide attempt in patients with psoriasis, PsA and AS, respectively, compared with the general population. METHODS: This population-based cohort study analysed 36 214 psoriasis patients, 5138 PsA patients and 1878 AS patients who were frequency-matched with a general population cohort. Annual incidence rate of depression, suicidal ideation and suicide attempt was calculated separately for psoriasis, PsA and AS. RESULTS: There was an increased risk of depression in the three cohorts; adjusted IRR: psoriasis, 1.14 (95% CI, 1.11, 1.17); PsA, 1.22 (95% CI, 1.16, 1.29); AS, 1.34 (95% CI, 1.23, 1.47). There was no significantly increased risk for suicidal ideations or suicide attempt among psoriasis, PsA or AS patients. LIMITATIONS: Patients were not excluded if previously diagnosed with depression, suicidal ideation or suicide attempt. Suicide attempt and completed suicide analyses were not adjusted for presence of depression. Use of systemic psoriasis treatment to measure severe psoriasis could lead to psoriasis severity misclassification. CONCLUSION: The risk of depression, but not suicidal ideation or suicide attempt, was significantly increased in patients with psoriasis, PsA and AS.

A methodological comparison of two European primary care databases and replication in a US claims database: inhaled long-acting beta-2-agonists and the risk of acute myocardial infarction.

PURPOSE: Results from observational studies on inhaled long-acting beta-2-agonists (LABA) and acute myocardial infarction (AMI) risk are conflicting, presumably due to variation in methodology. We aimed to evaluate the impact of applying a common study protocol on consistency of results in three databases. METHODS: In the primary analysis, we included patients from two GP databases (Dutch-Mondriaan, UK-CPRD GOLD) with a diagnosis of asthma and/or COPD and at least one inhaled LABA or a "non-LABA inhaled bronchodilator medication" (short-acting beta-2-agonist or short-/long-acting muscarinic antagonist) prescription between 2002 and 2009. A claims database (USA-Clinformatics) was used for replication. LABA use was divided into current, recent (first 91 days following the end of a treatment episode), and past use (after more than 91 days following the end of a treatment episode). Adjusted hazard ratios (AMI-aHR) and 95 % confidence intervals (95 % CI) were estimated using time-dependent multivariable Cox regression models stratified by recorded diagnoses (asthma, COPD, or both asthma and COPD). RESULTS: For asthma or COPD patients, no statistically significant AMI-aHRs (age- and sex-adjusted) were found in the primary analysis. For patients with both diagnoses, a decreased AMI-aHR was found for current vs. recent LABA use in the CPRD GOLD (0.78; 95 % CI 0.68-0.90) and in Mondriaan (0.55; 95 % CI 0.28-1.08), too. The replication study yielded similar results. Adjusting for concomitant medication use and comorbidities, in addition to age and sex, had little impact on the results. CONCLUSIONS: By using a common protocol, we observed similar results in the primary analysis performed in two GP databases and in the replication study in a claims database. Regarding differences between databases, a common protocol facilitates interpreting results due to minimized methodological variations. However, results of multinational comparative observational studies might be affected by bias not fully addressed by a common protocol.

Seasonal changes in prescribing of long-acting beta-2-agonists-containing drugs.

BACKGROUND: For patients with asthma, COPD, or asthma-COPD overlap syndrome (ACOS), inter-country comparisons of seasonal changes in drug prescriptions are scarce or missing. Hence, we aimed to compare seasonal changes in prescription rates of long-acting beta-2-agonist (LABA) in four European countries. METHODS: A common study protocol was applied to six health care databases (Germany, Spain, the Netherlands (2), and the UK (2)) to calculate age- and sex-standardized point prevalence rates (PPRs) of LABA-containing prescriptions by the 1st of March, June, September, and December of each year during the study period 2002-2009. Seasonal variation of PPRs was quantified using seasonal indexes (SIs; based on the ratio-to-moving-average-method) and SIs averaged over the study period (aSI) stratified by sex, age, and indication (asthma, COPD, or ACOS). RESULTS: There was a moderate seasonal change in LABA-containing prescriptions which was more pronounced in asthma or COPD patients compared to ACOS patients. For asthma and ACOS patients, highest seasonal variation was found for patients living in Spain (aSI: 87.3-110.7, aSI: 93.2-103.1) whereas for COPD highest seasonal variation was revealed for the NPCRD database (the Netherlands) (aSI: 92.2-105.6). Regarding age and sex, highest seasonal variation was found in Spanish boys under 10 years of age having a diagnosis of asthma. CONCLUSIONS: By applying a common analysis in six databases, we could observe moderate overall seasonal changes in LABA-containing prescription rates in patients with asthma, COPD, or ACOS.

Ethnic inequalities in access to and outcomes of healthcare: analysis of the Health Survey for England.

BACKGROUND: Ethnic/racial inequalities in access to and quality of healthcare have been repeatedly documented in the USA. Although there is some evidence of inequalities in England, research is not so extensive. Ethnic inequalities in use of primary and secondary health services, and in outcomes of care, were examined in England. METHODS: Four waves of the Health Survey for England were analysed, a representative population survey with ethnic minority oversamples. Outcome measures included use of primary and secondary healthcare services and clinical outcomes of care (controlled, uncontrolled and undiagnosed) for three conditions - hypertension, raised cholesterol and diabetes. RESULTS: Ethnic minority respondents were not less likely to use GP services. For example, the adjusted odds ratios for Indian, Pakistani and Bangladeshi versus white respondents were 1.29 (95% confidence intervals 1.07 to 1.54), 1.32 (1.10 to 1.58) and 1.35 (1.10 to 1.65) respectively. Similarly, there were no ethnic inequalities for the clinical outcomes of care for hypertension and raised cholesterol, and, on the whole, no inequalities in outcomes of care for diabetes. There were ethnic inequalities in access to hospital services, and marked inequalities in use of dental care. CONCLUSION: Ethnic inequalities in access to healthcare and the outcomes of care for three conditions (hypertension, raised cholesterol and diabetes), for which treatment is largely provided in primary care, appear to be minimal in England. Although inequalities may exist for other conditions and other healthcare settings, particularly internationally, the implication is that ethnic inequalities in healthcare are minimal within NHS primary care.

Cardiovascular medication, physical activity and mortality: cross-sectional population study with ongoing mortality follow-up.

OBJECTIVE: To establish physical activity levels in relation to cardiovascular medication and to examine if physical activity is associated with benefit independently of medication among people with no diagnosis of cardiovascular disease (CVD). DESIGN: Cross-sectional surveys in 1998 and 2003 with continuing mortality follow-up. SETTING: Household-based interviews in England and Scotland. PARTICIPANTS: Population samples of adults aged >or=35 living in households, respondents of the Scottish Health Survey and the Health Survey for England. MAIN OUTCOME MEASURE: Moderate to vigorous physical activity (MVPA) levels and CVD mortality. RESULTS: 15% (n = 3116) of the 20 177 respondents (8791 men) were prescribed at least one cardiovascular drug. Medicated respondents were less likely than those unmedicated to meet the physical activity recommendations (OR = 0.89, 95% CI 0.81 to 0.99, p = 0.028). The mean (SD) follow-up was 6.6 (2.3) years. There were 1509 any-cause deaths and 427 CVD deaths. Increased physical activity was associated with all-cause and CVD mortality among both unmedicated (all-cause mortality hazard ratio (HR) for those with >or=150 min/week of MVPA compared with those who reported no MVPA): HR = 0.58, 95% CI 0.48 to 0.69, p<0.001); CVD mortality: 0.65, 0.46 to 0.91, p = 0.036) and medicated respondents (all-cause death: 0.54, 0.40 to 0.72, p<0.001; CVD death: 0.46 (0.27 to 0.78, p = 0.008). CONCLUSIONS: Although physical activity protects against premature mortality among both medicated and unmedicated adults, cardiovascular medication is linked with lower uptake of health-enhancing physical activity. These results highlight the importance of physical activity in the primary prevention of CVD over and above medication.

Overweight and obesity trends from 1974 to 2003 in English children: what is the role of socioeconomic factors?

AIMS: To examine the childhood overweight and obesity prevalence trends between 1974 and 2003 and to assess whether these trends relate to parental social class and household income. METHODS: A school based and a general population health survey: the National Study of Health and Growth in 1974, 1984, and 1994, and the Health Survey for England, yearly from 1996 to 2003. Participants were 14,587 white boys and 14,014 white girls aged 5-10 years. Overweight and obesity prevalence were calculated using UK specific as well as international body mass index (kg/m2) cut-offs. Socioeconomic status was measured using the Registrar General's social class; household income (1997 onwards only) was adjusted for household size. RESULTS: The prevalence of obesity (UK specific definition) in boys increased from 1.2% in 1984 to 3.4% in 1996-97 and 6.0% in 2002-03. In girls, obesity increased from 1.8% in 1984 to 4.5% in 1996-97 and 6.6% in 2002-03. Obesity prevalence has been increasing at accelerating rates in the more recent years. Children from manual social classes had marginally higher odds (OR 1.14, 95% CI 0.98 to 1.33) and children from higher income households had lower odds (OR 0.74, 95% CI 0.61 to 0.89) to be obese than their peers from non-manual class, and lower income households, respectively. CONCLUSION: Childhood obesity is increasing rapidly into the 2000s in England and these increases are more marked among children from lower socioeconomic strata. There is an urgent need for action to prevent further increase in obesity among children.

Guidelines and risk factor management.

Efforts to reduce the death rate from cardiovascular disease in the UK are beginning to make a difference.

Lipid levels and the use of lipid-lowering agents in England and Scotland.

OBJECTIVE: Preventing cardiovascular events with lipid-lowering drugs has been established in several trials reported since 1994. Consequently national guidelines recommend statins for those with established cardiovascular disease (CVD) and those at high risk of developing CVD. We evaluated blood lipid levels, and compare treatment and control of dyslipidaemia in English and Scottish adults with national recommendations for lipid lowering. DESIGN AND METHODS: In 1998 the nationally-representative Health Survey for England and the Scottish Health Survey included valid cholesterol results for 9631 (England) and 6065 (Scotland) adults aged 16-74. Mean blood levels of total, high-density lipoproteins (HDL-), and total:HDL-cholesterol ratio; prevalence of elevated total cholesterol levels, and total:HDL-cholesterol ratios; prevalence of use of lipid-lowering agents in high risk subgroups; and lipid levels of those on treatment were calculated. RESULTS: Levels of dyslipidaemia, treatment and control were not significantly different between Scotland and England. Combining these data, mean total cholesterol levels were 5.43 and 5.48 mmol/l in men and women respectively; and mean HDL-cholesterol levels were 1.29 and 1.56 mmol/l. Overall 64.6% of adults had a total cholesterol > or =5 mmol/l, 24.6% had a total:HDL ratio > or =5 and 2.3% reported taking lipid-lowering drugs. Treatment rates among those with a total cholesterol >5 mmol/l and a history of coronary heart disease or stroke, hypertension, or diabetes, were 27.3%, 15.4% and 17.8% respectively, and control rates (total cholesterol <5 mmol/l) among those treated were 45.3%, 38.5% and 32.7%. CONCLUSIONS: Low treatment rates with lipid-lowering drugs existed overall, among high-risk patients suitable for primary prevention, and among those with established cardiovascular disease.

Prediction equations for normal and low lung function from the Health Survey for England.

The aim of this study was to derive new spirometric reference equations for the English population, using the 1995/1996 Health Survey for England, a large nationally representative cross-sectional study. The measurements used were the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of a sample of 6,053 "healthy" (nonsmokers with no reported diagnosis of asthma or respiratory symptoms) White people aged > or = 16 yrs. Multiple regression analysis, with age and height as predictors, was carried out to estimate prediction equations for mean FEV1, FVC and FEV1/FVC, separately for males and females. A method based on smoothing multiple estimates of the fifth percentiles of residuals was used to derive prediction equations for the lower limit of normal lung function. The new equations fit the current English adult population considerably better than the European Coal and Steel Community equations, and the proportions of people with "low" (below the fifth percentile) lung function are closer to those expected throughout the whole adult age range (16 to > 75 yrs). For the age ranges the studies share in common, the new equations give estimates close to those derived from other nonlinear equations in recent studies. It is, therefore, suggested that these newly developed prediction equations be used for the White English population in both epidemiological studies and clinical practice.

Passive smoking in the home: plasma cotinine concentrations in non-smokers with smoking partners.

BACKGROUND: Risks of lung cancer and of heart disease attributable to passive smoking have been evaluated mainly in non-smokers married to smokers, but there has been little quantitative assessment of the extent of exposure in marriage partners as indicated by markers of inhaled smoke dose. OBJECTIVE: To relate plasma cotinine concentrations in non-smoking English adults to the smoking behaviour of their partners and to demographic and other factors. DATA: Population survey. Data from two years (1994 and 1996) of the Health Survey for England. MAIN OUTCOME MEASURES: Plasma cotinine concentrations in non-smoking adults married to or cohabiting with a partner. RESULTS: There was a strong dose-response relation between cotinine concentrations in non-smoking adults and the smoking behaviour of their partners, rising from a geometric mean of 0.31 ng/ml in those with non-smoking partners to 1.99 ng/ml in those whose partners smoked 30 or more cigarettes per day. In addition, exposure was greater in men, in the autumn and winter, and in those living in more disadvantaged circumstances, and there was an increasing gradient of exposure from the south to the north of the country. On average, cotinine concentrations in non-smokers with a smoking partner were 0.6-0.7% of those in cigarette smokers. CONCLUSIONS: If cotinine is taken as a measure of risk relevant dose, the implied increase in risk of lung cancer in non-smokers with smoking partners is consistent with the risk observed in epidemiological studies. Smoking by partners in the home is a major source of non-smoking adults' exposure to passive smoking.

Improved hypertension management and control: results from the health survey for England 1998.

A survey in 1994 showed that among the 20% of the adult English population who were identified as hypertensive, approximately 30% had their blood pressures controlled to <160 mm Hg systolic and <95 mm Hg diastolic. The 1998 Health Survey for England data update the 1994 findings in light of new thresholds and targets for treatment outlined in recent national and international guidelines. This cross-sectional survey is analyzed to describe the prevalence, awareness, treatment, and control of hypertension in a random, nationally representative sample of 11 529 English adults (>/=16 years) living in noninstitutional households in 1998 and to compare these rates with those from 1994. In 1998, 20% and 37% of adults were hypertensive according to the old (systolic >/=160 mm Hg or diastolic >/=95 mm Hg) and new (systolic >/=140 mm Hg or diastolic >/=90 mm Hg) definitions, respectively. Corresponding values in 1994 were 20% and 38%. Treatment and control rates among hypertensive adults (new definition) improved from 26% to 32% and from 6% to 9%, respectively, although 60% of those on treatment received only 1 antihypertensive drug in both years. Among persons with controlled hypertension, 59% reported having received nonpharmacological advice from their physicians in 1998 compared with 30% in 1994. Rates of hypertension treatment and control have increased significantly (P=0.05 and P<0.01, respectively) since 1994 but remain low by international standards. The 1998 data suggest that improved detection, greater use of nonpharmacological measures, and increased use of >1 antihypertensive agent per patient would produce greater success in achieving target levels. This could lead to major reductions in fatal and nonfatal cardiovascular events.

Association between smoking and blood pressure: evidence from the health survey for England.

Cigarette smoking causes acute blood pressure (BP) elevation, although some studies have found similar or lower BPs in smokers compared with nonsmokers. Cross-sectional data from 3 years (1994 to 1996) of the annual Health Survey for England were used to investigate any difference in BP between smokers and nonsmokers in a nationally representative sample of adults (>/=16 years old). Randomly selected adults (33 860; 47% men) with valid body mass index (BMI) and BP measurements provided data on smoking status (never, past, or current) and were stratified into younger (16 to 44 years old) and older (>/=45 years old) age groups. Analyses provided between 89% and 94% power to detect a difference of 2 mm Hg systolic BP between smokers and nonsmokers in the 4 age/gender strata (alpha=0.05). Older male smokers had higher systolic BP adjusted for age, BMI, social class, and alcohol intake than did nonsmoking men. No such differences were seen among younger men or for diastolic blood pressure in either age group. Among women, light smokers (1 to 9 cigarettes/d) tended to have lower BPs than heavier smokers and never smokers, significantly so for diastolic BP. Among men, a significant interaction between BMI and the BP-smoking association was observed. In women, BP differences between nonsmokers and light smokers were most marked in those who did not drink alcohol. These data show that any independent chronic effect of smoking on BP is small. Differences between men and women in this association are likely to be due to complex interrelations among smoking, alcohol intake, and BMI.

Nicotine yield from machine-smoked cigarettes and nicotine intakes in smokers: evidence from a representative population survey.

BACKGROUND: The relevance of nicotine yields from machine-smoked cigarettes for quantifying smokers' nicotine intakes and exposure to cigarette toxins has been called into question. However, most studies of the relationship between nicotine yield and nicotine intake have been on relatively small and unrepresentative samples and have included few smokers of "ultra-low" brands (i.e., those yielding around 1 mg of tar and 0.1 mg of nicotine). METHODS: We examined the relationship between salivary cotinine (a major metabolite of nicotine) concentrations and nicotine yields of machine-smoked cigarettes in a nationally representative sample of 2031 adult smokers of manufactured cigarettes surveyed in the 1998 Health Survey for England. We used standard linear regression techniques to examine associations and two-sided tests of statistical significance. RESULTS: Cotinine concentrations varied widely between smokers at any level of nominal brand nicotine yield. On average, cotinine levels were slightly lower in smokers of lower nicotine-yielding brands, but these smokers differed in terms of sex, socioeconomic profile, and cigarette consumption. After we controlled for potential confounders, nicotine yield from the brand smoked accounted for only 0.79% of the variation in saliva cotinine concentrations. Nicotine intake per cigarette smoked, as estimated from salivary cotinine level, did not correspond with machine-smoked yields at any level of nicotine yield. Nicotine intake per cigarette was about eight times greater than machine-smoked yields at the lowest deliveries (1.17 mg estimated nicotine intake per cigarette from brands averaging 0.14-mg delivery from machine smoking) and 1.4 times greater for the highest yield cigarettes (1.31-mg estimated nicotine intake per cigarette from brands averaging 0.91 mg from machine smoking). CONCLUSIONS: Smokers' tendency to regulate nicotine intake vitiates potential health gains from lower tar and nicotine cigarettes. Current approaches to characterizing tar and nicotine yields of cigarettes provide a simplistic guide to smokers' exposure that is misleading to consumers and regulators alike and should be abandoned.

Lipid concentrations and the use of lipid lowering drugs: evidence from a national cross sectional survey.

OBJECTIVE: To evaluate the prevalence of the use of lipid lowering agents and its relation to blood lipid concentrations in English adults. DESIGN: Cross sectional survey. SETTING: England, 1998. PARTICIPANTS: Nationally representative sample of 13 586 adults (aged >/=16 years) living in non-institutional households. MAIN OUTCOME MEASURES: Mean blood concentrations of total cholesterol and high density lipoprotein (HDL) cholesterol, and the ratio of total cholesterol to HDL cholesterol, in participants classified by age and sex; prevalence of raised total cholesterol concentrations and increased ratio of total to HDL cholesterol; prevalence of use of lipid lowering agents and the lipid concentrations of people taking them. RESULTS: Mean total cholesterol concentrations were 5.47 (SE 0. 02) mmol/l in men and 5.59 (0.02) mmol/l in women. Mean HDL cholesterol concentrations were 1.28 (0.01) mmol/l in men and 1.55 (0.01) mmol/l in women. Overall, of 10 569 adults who had a valid cholesterol measurement taken 7133 (67.5%; 95% confidence interval 66.5% to 68.4%) had a total cholesterol concentration >/=5 mmol/l, 2804 (26.5%; 25.7% to 27.4%) had a ratio of total cholesterol to HDL cholesterol >/=5 mmol/l, and 237 (2.2%; 1.9% to 2.5%) reported taking lipid lowering drugs. Of 117 participants with no history of cardiovascular disease but whose estimated 10 year risk of coronary heart disease was >/=30% and whose total cholesterol concentration was >/=5 mmol/l, four (3%) were taking lipid lowering drugs. Of 385 adults aged 16-75 with a history of coronary heart disease and eligible for lipid lowering treatment, 114 (30%; 25% to 34%) were taking lipid lowering drugs, of whom only 50 (44%; 35% to 53%) had a total cholesterol concentration <5 mmol/l. CONCLUSIONS: Despite the high prevalence of dyslipidaemia in English adults, the proportion of adults taking lipid lowering drugs in 1998 was only 2.2%. Rates of treatment were low among high risk patients eligible for primary prevention with lipid lowering drugs, and less than one third of patients with established cardiovascular disease received such treatment.

Blood pressure levels and hypertension status among ethnic groups in England.

The prevalence of cardiovascular disease and hypertension show wide variability among different ethnic groups in the UK. We combined data collected annually between 1991-1996 in the Health Surveys for England--nationwide surveys that provide information on the health status in a representative sample of the population living in England, to compare blood pressure (BP) levels, hypertension rates (systolic BP > or = 160 mm Hg or diastolic BP > or = 95 mm Hg, or those on antihypertensive medication), hypertension treatment and control rates in people of white, black (combining black-Caribbean, black-African and black-other), and South Asian origin (combining Indians, Pakistanis and Bangladeshis). Analyses were stratified into two age groups, 16-39 (younger) and > or = 40 years (older), but were focused on older adults (30,619 whites, 295 blacks and 529 South Asians). Age-adjusted mean BP levels and hypertension rates of older adults were highest among blacks, while South Asian men showed BP levels and hypertension rates similar to black men and South Asian women had mean BP levels and hypertension rates similar to white women. After controlling for age, BMI, smoking, alcohol consumption, and social class the odds ratio (OR) of being hypertensive among older adults was higher in black men (OR 2.0; 95% CI 1.4, 2.9; P < 0.001); black women (OR 1.7; 95% CI 1.2, 2.5; P < 0.01); and South Asian men (1.9; CI 1.4, 2.4; P < 0.001), than in their white counterparts. Among those studied with hypertension, treatment rates were highest among black men and women. Among those on antihypertensive medication, the odds of having BP controlled (SBP < 160 mm Hg and DBP < 95 mm Hg) did not differ among the three groups of older men but was reduced in older South Asian women, compared with white women.

Blood lead and blood pressure: evidence from the Health Survey for England 1995.

OBJECTIVES: To examine the relationship between blood lead and blood pressure (BP) and to estimate the possible effects of a decrease in blood lead on BP. METHODS: A 2-ml blood sample was collected from a sub-sample of those included in the Health Survey for England 1995, a cross-sectional survey of a nationally representative sample of the adult English population. Blood lead concentration was measured by atomic absorption spectrometry and three BP readings were taken under standardised conditions using the Dinamap 8100 monitor. Analyses were carried out using data on 2563 men and 2763 women aged 16 and over. RESULTS: In stepwise multiple regression analyses adjusting for various confounders--age, body mass index, smoking status, social class, region of residence and alcohol intake--blood lead was found to be significantly and positively associated with diastolic BP, and not systolic BP in men, but not in women. These findings were unaffected by the inclusion or exclusion of those on antihypertensive medication, by whether mean or median BP was used in the regression, or by the adjustment for alcohol consumption. A halving of currently prevalent blood lead levels is estimated to be associated with a decrease of between 0.8 to 1.1 mm Hg diastolic BP in men. CONCLUSION: These findings in the context of other published data are consistent with a small pressor effect of environmental lead levels on BP. They support recommendations for further efforts to reduce lead in the environment.

Inguinal hernia repair: incidence of elective and emergency surgery, readmission and mortality.

BACKGROUND: Inguinal hemia repair is one of the most common operations undertaken in routine surgical practice. It generally carries a very low risk of major adverse sequelae. We analysed profiles, separately, for elective and emergency operations to report on the incidence and major adverse outcomes of inguinal hernia repair in a geographically defined population. METHODS: Age- and sex-specific hospital admission rates, emergency readmission rates within 30 days of discharge, and mortality rates, separately for elective and emergency operations, were calculated for the period 1976-1986 in the Oxford Record Linkage Study (ORLS) area. RESULTS: In all, 30,675 inguinal hernia repairs were performed in the area, an all-ages annual incidence of 13 per 10,000 population. Some 9% of patients underwent operation in an emergency admission. Elective operation rates remained constant over time. Emergency repairs decreased significantly over time in males. Patients who underwent emergency repair were older, had higher emergency readmission rates than those undergoing elective repair, and had significantly elevated postoperative mortality rates. In those who died it was uncommon for inguinal hernia to be recorded on their death certificates. Of the operations, 91% were undertaken on males; age-specific rates were highest in infants and the elderly; and emergency operation rates rose exponentially with age in people > 50 years. CONCLUSIONS: The lifetime 'risk' of inguinal hernia repair is high: at currently prevailing rates we estimate it at 27% for men and 3% for women. There is significant elevation of mortality after emergency operations. Elective repair of inguinal hernia should be undertaken soon after the diagnosis is made to minimize the risk of adverse outcomes.

Crohn's disease and ulcerative colitis in England and the Oxford record linkage study area: a profile of hospitalized morbidity.

BACKGROUND: Crohn's disease and ulcerative colitis are chronic relapsing conditions. National hospital statistics in England only provide episode-based admission rates and cannot be used to identify multiple admissions per person. We used record linkage to provide a person-based profile of admission rates. METHODS: Age-standardized admission rates were calculated from the computer tapes of the Hospital In-patient Enquiry (HIPE) for 1970-1985 and the Oxford Record Linkage Study (ORLS) for the period 1970-1986. In addition, annual hospitalized prevalence, first hospital admission rates (as a proxy for incidence) and readmission rates were calculated for the Oxford population. Predictors of relapses were assessed by logistic regression models. RESULTS: Episode-based admission rates for Crohn's disease increased over time, both nationally and in Oxford. In Oxford, hospitalized incidence rates showed no increase for Crohn's disease. Neither episode-based nor person-based rates increased for ulcerative colitis. Relapses resulting in hospital admission were more common for Crohn's disease than for ulcerative colitis. They increased over time. We showed the influence of some sociodemographic characteristics (age, social class, district of residence, operations) on relapses. CONCLUSIONS: Data on episodes of hospital care for Crohn's disease showed an increase over time while data related to individuals in receipt of care showed no increase over time. Unlinked episodes of hospital care are of limited value when studying temporal trends for chronic conditions with multiple admissions.