Using electronic health records to inform trial feasibility in a rare autoimmune blistering skin disease in England.

BACKGROUND: Trials of novel agents are required to improve the care of patients with rare diseases, but trial feasibility may be uncertain due to concerns over insufficient patient numbers. We aimed to determine the size of the pool of potential participants in England 2015-2017 for trials in the autoimmune blistering skin disease bullous pemphigoid. METHODS: The size of the pool of potential participants was estimated using routinely collected healthcare data from linked primary care (Clinical Practice Research Datalink; CPRD) and secondary care (Hospital Episode Statistics; HES) databases. Thirteen consultant dermatologists were surveyed to determine the likelihood that a patient would be eligible for a trial based on the presence of cautions or contra-indications to prednisolone use. These criteria were applied to determine how they influenced the potential pool of participants. RESULTS: Extrapolated to the population of England, we would expect approximately 10,800 (point estimate 10,747; 95% CI 7191 to 17,239) new cases of bullous pemphigoid to be identified in a three-year period. For a future trial involving oral prednisolone (standard care), the application of cautions to its use as exclusion criteria would result in approximately 365 potential participants unlikely to be recruited, a further 5332 could be recruited with caution, and 5104 in whom recruitment is still possible. 11-17% of potential participants may have pre-existing dementia and require an alternative consent process. CONCLUSIONS: Routinely collected electronic health records can be used to inform the feasibility of clinical trials in rare diseases, such as whether recruitment is feasible nationally and how long recruitment might take to meet recruitment targets. Future trials of bullous pemphigoid in England may use the data presented to inform trial design, including eligibility criteria and consent processes for enrolling people with dementia.

Incidence, prevalence and mortality of bullous pemphigoid in England 1998-2017: a population-based cohort study.

BACKGROUND: A rising incidence and high mortality were found for bullous pemphigoid (BP) over a decade ago in the UK. Updated estimates of its epidemiology are required to understand the healthcare needs of an ageing population. OBJECTIVES: To determine the incidence, prevalence and mortality rates of BP in England from 1998 to 2017. METHODS: We conducted a cohort study of longitudinal electronic health records using the Clinical Practice Research Datalink and linked Hospital Episode Statistics. Incidence was calculated per 100 000 person-years and annual point prevalence per 100 000 people. Multivariate analysis was used to determine incidence rate ratios by sociodemographic factors. Mortality was examined in an age-, sex- and practice-matched cohort, using linked Office of National Statistics death records. Hazard ratios (HRs) were stratified by matched set. RESULTS: The incidence was 7·63 [95% confidence interval (CI) 7·35-7·93] per 100 000 person-years and rose with increasing age, particularly for elderly men. The annual increase in incidence was 0·9% (95% CI 0·2-1·7). The prevalence almost doubled over the observation period, reaching 47·99 (95% CI 43·09-53·46) per 100 000 people and 141·24 (95% CI 125·55-158·87) per 100 000 people over the age of 60 years. The risk of all-cause mortality was highest in the 2 years after diagnosis (HR 2·96; 95% CI 2·68-3·26) and remained raised thereafter (HR 1·54; 95% CI 1·36-1·74). CONCLUSIONS: We report a modest increase in the incidence rate of BP, but show that the burden of disease in the elderly population is considerable. Mortality is high, particularly in the first 2 years after diagnosis.

NHS Health Checks for people with mental ill-health 2013-2017: an observational study.

AIMS: People living with serious mental ill-health experience adverse cardiovascular outcomes causing some of the greatest health inequality gaps in England, UK. We describe uptake of the NHS Health Check programme in people with mental ill-health, and rates of new diagnoses and management of cardiovascular risk factors in those who attend NHS Health Checks in comparison to those people without mental ill-health. METHODS: We used a large nationally representative database of people registered with general practitioners in England (QResearch). Between 2013 and 2017, we analysed attendance at NHS Health Checks and outcomes in the succeeding 12 months, in people with serious mental illness (SMI) including psychoses and in people prescribed long-term antidepressant medications (LTAD), with comparison to attendees who did not have these conditions. Hazard ratios (HR) were used to describe the association between outcomes and SMI and LTAD adjusting for sociodemographic variables. RESULTS: In those eligible for the NHS Health Check programme, we found a higher percentage of people with SMI attended an NHS Health Check (65 490, 19.8%) than those without SMI (524 728, 16.6%); adjusted HR 1.05 [95% confidence interval 1.02-1.08]. We also observed a higher percentage of attendance in people on LTAD (46 437, 20.1%) compared to people who were not prescribed LTAD (543 781, 16.7%); adjusted HR 1.10 (1.08-1.13). People with SMI were more likely to be identified with chronic kidney disease (CKD, HR 1.23, 1.12-1.34) and type 2 diabetes (HR 1.14, 1.03-1.25) within the 12 months following their NHS Health Check compared with those without SMI. People on LTAD were more likely to be identified with CKD (HR 1.55, 1.42-1.70) and type 2 diabetes (HR 1.45, 1.31-1.60) and also hypertension, cardiovascular disease, non-diabetic hyperglycaemia, familial hypercholesterolemia and dementia within the 12 months following their NHS Health Check. Statins were more likely to be prescribed to NHS Health Check attendees with SMI and those on LTAD than those without these conditions; HR 1.31 (1.25-1.38) and 1.91 (1.82-2.01), respectively. Antihypertensives were more likely to be prescribed to those on LTAD; HR 1.21 (1.14-1.29). CONCLUSIONS: We found evidence that people with SMI or on LTAD treatment were 5-10% more likely to access NHS Health Checks than people without these conditions. People with SMI or on LTAD treatment who attended NHS Health Checks had higher rates of diagnosis of CKD, type 2 diabetes and some other relevant co-morbidities and increased treatment with statins and also anti-hypertensive medication in people on LTAD. This is likely to contribute to equitable reduction in adverse cardiovascular events for people with mental ill-health.

Exposure to bisphosphonates and risk of common non-gastrointestinal cancers: series of nested case-control studies using two primary-care databases.

BACKGROUND: Bisphosphonates are the most commonly prescribed osteoporosis drugs but long-term effects are unclear, although antitumour properties are known from preclinical studies. METHODS: Nested case-control studies were conducted to investigate bisphosphonate use and risks of common non-gastrointestinal cancers (breast, prostate, lung, bladder, melanoma, ovarian, pancreas, uterus and cervical). Patients 50 years and older, diagnosed with primary cancers between 1997 and 2011, were matched to five controls using the UK practice-based QResearch and Clinical Practice Research Datalink (CPRD) databases. The databases were analysed separately and the results combined. RESULTS: A total of 91 556 and 88 845 cases were identified from QResearch and CPRD, respectively. Bisphosphonate use was associated with reduced risks of breast (odds ratio (OR): 0.92, 95% confidence interval (CI): 0.87-0.97), prostate (OR: 0.87, 95% CI: 0.79-0.96) and pancreatic (OR: 0.79, 95% CI: 0.68-0.93) cancers in the combined analyses, but no significant trends with duration. For alendronate, reduced risk associations were found for prostate cancer in the QResearch (OR: 0.81, 95% CI: 0.70-0.93) and combined (OR: 0.84, 95% CI: 0.75-0.93) analyses (trend with duration P-values 0.009 and 0.001). There were no significant associations from any of the other analyses. CONCLUSION: In this series of large population-based case-control studies, bisphosphonate use was not associated with increased risks for any common non-gastrointestinal cancers.

Use of a large general practice syndromic surveillance system to monitor the progress of the influenza A(H1N1) pandemic 2009 in the UK.

The Health Protection Agency/QSurveillance national surveillance system utilizes QSurveillance®, a recently developed general practitioner database covering over 23 million people in the UK. We describe the spread of the first wave of the influenza A(H1N1) pandemic 2009 using data on consultations for influenza-like illness (ILI), respiratory illness and prescribing for influenza from 3400 contributing general practices. Daily data, provided from 27 April 2009 to 28 January 2010, were used to give a timely overview for those managing the pandemic nationally and locally. The first wave particularly affected London and the West Midlands with a peak in ILI in week 30. Children aged between 1 and 15 years had consistently high consultation rates for ILI. Daily ILI rates were used for modelling national weekly case estimates. The system enabled the 'real-time' monitoring of the pandemic to a small geographical area, linking morbidity and prescribing for influenza and other respiratory illnesses.

A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database.

OBJECTIVES: The aim of this study was to establish the relative safety and balance of risks for antidepressant treatment in older people. The study objectives were to (1) determine relative and absolute risks of predefined adverse events in older people with depression, comparing classes of antidepressant drugs [tricyclic and related antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and other antidepressants] and commonly prescribed individual drugs with non-use of antidepressant drugs; (2) directly compare the risk of adverse events for SSRIs with TCAs; (3) determine associations with dose and duration of antidepressant medication; (4) describe patterns of antidepressant use in older people with depression; and (5) estimate costs of antidepressant medication and primary care visits. DESIGN: A cohort study of patients aged 65 years and over diagnosed with depression. SETTING: The study was based in 570 general practices in the UK supplying data to the QResearch database. PARTICIPANTS: Patients diagnosed with a new episode of depression between the ages of 65 and 100 years, from 1 January 1996 to 31 December 2007. Participants were followed up until 31 December 2008. INTERVENTIONS: The exposure of interest was treatment with antidepressant medication. Antidepressant drugs were grouped into the major classes and commonly prescribed individual drugs were identified. MAIN OUTCOME MEASURES: There were 13 predefined outcome measures: all-cause mortality, sudden cardiac death, suicide, attempted suicide/self-harm, myocardial infarction, stroke/transient ischaemic attack (TIA), falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions and hyponatraemia. RESULTS: In total, 60,746 patients were included in the study cohort. Of these, 54,038 (89.0%) received at least one prescription for an antidepressant during follow-up. The associations with the adverse outcomes were significantly different between the classes of antidepressant drugs for seven outcomes. SSRIs were associated with the highest adjusted hazard ratios (HRs) for falls [1.66, 95% confidence interval (CI) 1.58 to 1.73] and hyponatraemia (1.52, 95% CI 1.33 to 1.75), and the group of other antidepressants was associated with the highest HRs for all-cause mortality (1.66, 95% CI 1.56 to 1.77), attempted suicide/self-harm (5.16, 95% CI 3.90 to 6.83), stroke/TIA (1.37, 95% CI 1.22 to 1.55), fracture (1.63, 95% CI 1.45 to 1.83) and epilepsy/seizures (2.24, 95% CI 1.60 to 3.15) compared with when antidepressants were not being used. TCAs did not have the highest HR for any of the outcomes. There were also significantly different associations between the individual drugs for seven outcomes, with trazodone, mirtazapine and venlafaxine associated with the highest rates for several of these outcomes. The mean incremental cost (for all antidepressant prescriptions) ranged between £51.58 (amitriptyline) and £641.18 (venlafaxine) over the 5-year post-diagnosis period. CONCLUSIONS: This study found associations between use of antidepressant drugs and a number of adverse events in older people. There was no evidence that SSRIs or drugs in the group of other antidepressants were associated with a reduced risk of any of the adverse outcomes compared with TCAs; however, they may be associated with an increased risk for certain outcomes. Among individual drugs trazodone, mirtazapine and venlafaxine were associated with the highest rates for some outcomes. Indication bias and residual confounding may explain some of the study findings. The risks of prescribing antidepressants need to be weighed against the potential benefits of these drugs. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Exposure to cyclooxygenase-2 inhibitors and risk of cancer: nested case-control studies.

BACKGROUND: Selective cyclooxygenase-2 (COX2) inhibitors are widely used as analgesics and it is unclear whether its long-term use affects cancer risk. METHODS: A series of nested case-control studies using the QResearch primary care database. Associations of COX2 inhibitor use with risk of all cancers and 10 common site-specific cancers were estimated using conditional logistic regression adjusted for comorbidities, smoking status, socioeconomic status, and use of non-steroidal anti-inflammatory drugs, aspirin and statins. RESULTS: A total of 88,125 cancers, diagnosed between 1998 and 2008, matched with up to five controls, were analysed. Use of COX2 inhibitors for more than a year was associated with a significantly increased risk of breast cancer (odds ratio (OR) 1.24, 95% confidence interval (CI) 1.08-1.42) and haematological malignancies (OR 1.38, 95% CI 1.12-1.69) and a decreased risk of colorectal cancer (OR 0.76, 95% CI 0.63-0.92). There were no other significant associations. CONCLUSION: Prolonged use of COX2 inhibitors was associated with an increased risk of breast and haematological cancers and decreased risk of colorectal cancer. These findings need to be confirmed using other data sources.

Early spread of the 2009 influenza A(H1N1) pandemic in the United Kingdom--use of local syndromic data, May-August 2009.

Following the confirmation of the first two cases of pandemic influenza on 27 April 2009 in the United Kingdom (UK), syndromic surveillance data from the Health Protection Agency (HPA)/QSurveillance and HPA/NHS Direct systems were used to monitor the possible spread of pandemic influenza at local level during the first phase of the outbreak. During the early weeks, syndromic indicators sensitive to influenza activity monitored through the two schemes remained low and the majority of cases were travel-related. The first evidence of community spread was seen in the West Midlands region following a school-based outbreak in central Birmingham. During the first phase several Primary Care Trusts had periods of exceptional influenza activity two to three weeks ahead of the rest of the region. Community transmission in London began slightly later than in the West Midlands but the rates of influenza-like illness recorded by general practitioners (GPs) were ultimately higher. Influenza activity in the West Midlands and London regions peaked a week before the remainder of the UK. Data from the HPA/NHS Direct and HPA/QSurveillance systems were mapped at local level and used alongside laboratory data and local intelligence to assist in the identification of hotspots, to direct limited public health resources and to monitor the progression of the outbreak. This work has demonstrated the utility of local syndromic surveillance data in the detection of increased transmission and in the epidemiological investigation of the pandemic and has prompted future spatio-temporal work.

Value of syndromic surveillance in monitoring a focal waterborne outbreak due to an unusual Cryptosporidium genotype in Northamptonshire, United Kingdom, June - July 2008.

The United Kingdom (UK) has several national syndromic surveillance systems. The Health Protection Agency (HPA)/NHS Direct syndromic surveillance system uses pre-diagnostic syndromic data from a national telephone helpline, while the HPA/QSurveillance national surveillance system uses clinical diagnosis data extracted from general practitioner (GP)-based clinical information systems. Data from both of these systems were used to monitor a local outbreak of cryptosporidiosis that occurred following Cryptosporidium oocyst contamination of drinking water supplied from the Pitsford Reservoir in Northamptonshire, United Kingdom, in June 2008. There was a peak in the number of calls to NHS Direct concerning diarrhoea that coincided with the incident. QSurveillance data for the local areas affected by the outbreak showed a significant increase in GP consultations for diarrhoea and gastroenteritis in the week of the incident but there was no increase in consultations for vomiting. A total of 33 clinical cases of cryptosporidiosis were identified in the outbreak investigation, of which 23 were confirmed as infected with the outbreak strain. However, QSurveillance data suggest that there were an estimated 422 excess diarrhoea cases during the outbreak, an increase of about 25% over baseline weekly levels. To our knowledge, this is the first time that data from a syndromic surveillance system, the HPA/QSurveillance national surveillance system, have been able to show the extent of such a small outbreak at a local level. QSurveillance, which covers about 38% of the UK population, is currently the only GP database that is able to provide data at local health district (primary care trust) level. The Cryptosporidium contamination incident described demonstrates the potential usefulness of this information, as it is unusual for syndromic surveillance systems to be able to help monitor such a small-scale outbreak.

Performance of the QRISK cardiovascular risk prediction algorithm in an independent UK sample of patients from general practice: a validation study.

AIM: To assess the performance of the QRISK score for predicting cardiovascular disease (CVD) in an independent UK sample from general practice and compare with the Framingham score. DESIGN: Prospective open cohort study. SETTING: UK general practices contributing to the THIN and QRESEARCH databases. COHORT: The THIN validation cohort consisted of 1.07 million patients, aged 35-74 years registered at 288 THIN practices between 1 January 1995 and 1 April 2006. The QRESEARCH validation cohort consisted of 0.61 million patients from 160 practices (one-third of the full database) with data until 1 January 2007. Patients receiving statins, those with diabetes or CVD at baseline were excluded. END POINT: First diagnosis of CVD (myocardial infarction, coronary heart disease (CHD), stroke and transient ischaemic attack) recorded on the clinical computer system during the study period. EXPOSURES: Age, sex, smoking status, systolic blood pressure, total/high-density lipoprotein cholesterol ratio, body mass index, family history of premature CHD, deprivation and antihypertensive medication. RESULTS: Characteristics of both cohorts were similar, except that THIN patients were from slightly more affluent areas and had lower recording of family history of CHD. QRISK performed better than Framingham for every discrimination and calibration statistic in both cohorts. Framingham overpredicted risk by 23% in the THIN cohort, while QRISK underpredicted risk by 12%. CONCLUSION: This analysis demonstrated that QRISK is better calibrated to the UK population than Framingham and has better discrimination. The results suggest that QRISK is likely to provide more appropriate risk estimates than Framingham to help identify patients at high risk of CVD in the UK.

Uptake of pneumococcal polysaccharide vaccine in at-risk populations in England and Wales 1999-2005.

The UK has had a pneumococcal polysaccharide vaccination (PPV) programme for groups at higher risk of invasive disease since 1992. This paper presents data from a sample of primary-care practices (Q-RESEARCH) of PPV uptake in patients according to their risk status. Of 2.9 million registered patients in 2005, 2.1% were vaccinated with PPV in the preceding 12 months and 6.5% in the preceding 5 years. Twenty-nine per cent of the registered population fell into one or more risk groups. The proportion of each risk group vaccinated in the previous 5 years ranged from 69% (cochlear implants), 53.4% (splenic dysfunction), 36.5% (chronic heart disease), 34.7% (diabetes), 22.9% (immunosuppressed), 28.7% (chronic renal disease), 15.9% (sickle cell disease) to 12.6% (chronic respiratory disease). Uptake was lower in areas where the non-white proportion of population was >10%. In conclusion, there remain large gaps in the uptake of PPV in several high-risk populations in the United Kingdom. Effective strategies need to be developed to address these deficiencies.

Quality of diabetes care in patients with schizophrenia and bipolar disorder: cross-sectional study.

AIMS: To determine whether patients with severe mental illness receive poorer health care for diabetes than patients without. METHODS: This population-based cross-sectional survey used electronic general practice records from 481 UK general practices contributing to the QRESEARCH database. The records of 11 043 patients with diabetes, drawn from a database population of over 9 million patients, were extracted. Unadjusted and adjusted odds ratios were calculated using unconditional logistic regression for each of 17 quality indicators for diabetes care from the new General Medical Services contract for general practitioners. RESULTS: The presence of severe mental illness did not reduce the quality of care received; the only significant difference between groups showed that such patients were more likely to have glycated haemoglobin < 7.5%[adjusted odds ratio = 1.45 (99% confidence interval 1.20-1.76)]. Increasing age was associated with better care [adjusted odds ratios from 1.06 (1.02-1.11) to 1.61 (1.52-1.70)], but other confounding variables had no consistent effect across indicators. Overall, performance against government targets was good. CONCLUSIONS: The hypothesis of poorer diabetes care for those with severe mental illness is disproved, perhaps surprisingly, in the light of other recent UK studies showing inequalities in care for the mentally ill. The study does not reveal who is providing this good care (general practitioners, psychiatrists or diabetologists) or take account of the estimated 600 000 people in the UK with undiagnosed diabetes.

Inequalities in hospital admission rates for unintentional poisoning in young children.

OBJECTIVE: To determine the relationship between deprivation and hospital admission rates for unintentional poisoning, by poisoning agent in children aged 0-4 years. DESIGN: Cross sectional study of routinely collected hospital admissions data. SETTING: East Midlands, UK. PARTICIPANTS: 1469 admissions due to unintentional poisoning over two years. MAIN OUTCOME MEASURE: Hospital admission rates for unintentional poisoning. Incidence rate ratios (IRRs) comparing hospital admission rates for poisoning in the most and least deprived electoral wards. RESULTS: Children in the most deprived wards had admission rates for medicinal poisoning that were 2-3 times higher than those in the least deprived wards (IRR 2.49, 95% CI 1.87 to 3.30). Admission rates for non-medicinal poisoning were about twice as high in the most compared to the least deprived wards (IRR 1.77, 95% CI 1.19 to 2.64). Deprivation gradients were particularly steep for benzodiazepines (IRR 5.63, 95% CI 1.72 to 18.40), antidepressants (IRR 4.58, 95% CI 1.80 to 11.66), cough and cold remedies (IRR 3.93, 95% CI 1.67 to 9.24), and organic solvents (IRR 3.69, 95% CI 1.83 to 7.44). CONCLUSIONS: There are steep deprivation gradients for admissions to hospital for childhood poisoning, with particularly steep gradients for some psychotropic medicines. Interventions to reduce these inequalities should be directed towards areas of greater deprivation.

Clinical pathways for patients with newly diagnosed hepatitis C - what actually happens.

Management of hepatitis C virus (HCV)-infected individuals requires referral to specialist care. To determine whether patients newly diagnosed as anti-HCV positive are appropriately referred for further investigation and management, and if not, to determine why not. We studied patients tested for antibodies to HCV by Nottingham Public Health Laboratory in a 2-year period (2000-2002). The progress of newly diagnosed anti-HCV positive patients into specialist clinics for further management was documented. For patients not referred for specialist care, a questionnaire was sent to the clinician requesting the initial anti-HCV test, to identify reasons for nonreferral. Eleven thousand one hundred and seventy-seven patients were tested for anti-HCV. Two hundred and fifty-six (2.3%) were newly diagnosed as being anti-HCV positive. Two per cent of samples sent from primary care were anti-HCV positive, compared to 18.8, 18.9 and 1.3% sent from prison, drug and alcohol units, and secondary care, respectively. About 64.3% of positive patients diagnosed in primary care were referred to specialist care, compared to 18.4, 42.4 and 62.6% of patients diagnosed in the other three settings. One hundred and twenty-five (49%) newly diagnosed patients were referred appropriately for further management. 68 of these attended clinic, 45 underwent liver biopsy and 26 (10%) began treatment. One hundred and thirty-one patients (51%) were not referred. In 54 cases, there was no evidence that the anti-HCV positive result reached the patient. In 15, referral was considered but rejected, and 20 patients were referred to non-HCV-specialists (their general practitioners or to genito-urinary medicine). Hence less than 50% of newly diagnosed anti-HCV positive patients are referred to an appropriate clinic for further investigation and management. Reasons for this are multifarious and complex, reflecting both systems failure and patient choice. Unless these are understood and addressed, the Department of Health Hepatitis C Strategy (2002) and Action Plan for England (2004) will fail to achieve their intended objectives.

Effect of statins on the mortality of patients with ischaemic heart disease: population based cohort study with nested case-control analysis.

OBJECTIVE: To measure the effect of statins on mortality for community based patients with ischaemic heart disease and determine whether the likely benefits are similar for women, the elderly, and patients with diabetes. DESIGN: Open prospective cohort study with nested case-control analysis. SETTING: 1.18 million patients registered with 89 practices spread across 23 strategic health authority areas within the UK. All practices had a minimum of eight years of longitudinal data and were contributing to the UK QRESEARCH database. SUBJECTS: All patients with a first diagnosis of ischaemic heart disease between January 1996 and December 2003. OUTCOMES: Adjusted hazard ratio with 95% confidence intervals (CIs) for all cause mortality (cohort analysis) and odds ratio (OR) with 95% CI (case-control analysis) for current use of statins. Adjustments were made for current use of aspirin, beta blockers, and angiotensin converting enzyme inhibitors, co-morbidity (myocardial infarction, diabetes, hypertension, congestive cardiac failure), smoking, body mass index, and quintile of deprivation. RESULTS: 13,029 patients had a first diagnosis of ischaemic heart disease in the study period giving an incidence rate of 3.38/1000 person years. 2266 patients with ischaemic heart disease died during the 43,460 person years of observation giving an overall mortality rate of 52.1/1000 person years (95% CI 50.0 to 54.3). In the case-control analysis, patients taking statins had a 39% lower risk of death than did patients not taking statins (adjusted OR 0.61, 95% CI 0.52 to 0.72) after use of other medication, co-morbidity, smoking, body mass index, and deprivation were taken into account. The benefits found in this study compared favourably with those found in the randomised controlled trials, although the current study population is at higher overall risk. The benefits extend to women, patients with diabetes, and the elderly and can be seen within two years of treatment. Longer duration of usage was associated with lower OR for risk of death with a 19% reduction in risk of death with each additional year of treatment (adjusted OR 0.81, 95% CI 0.77 to 0.86 per year). Mortality was similarly reduced among patients prescribed atorvastatin (adjusted OR 0.62, 95% CI 0.48 to 0.79) and simvastatin (adjusted OR 0.62, 95% CI 0.50 to 0.76). CONCLUSIONS: The benefits of statins found in randomised controlled trials extend to unselected community based patients. The benefits can be seen within the first two years of treatment and continue to accrue over time. Since patients in the community are likely to be at higher risk than those in trials, the potential benefits from statins are likely to be greater than expected.

Smoking cessation treatment in primary care: prospective cohort study.

OBJECTIVE: To compare the characteristics of smokers who do and do not receive smoking cessation treatment in primary care. DESIGN: Prospective cohort study using practices registered with the pilot QRESEARCH database. SETTING: 156,550 patients aged 18 years and over from 39 general practices located within four strategic health authorities, representing the former Trent Region, UK. SUBJECTS: Patients registered with practices between 1 April 2001 and 31 March 2003 aged 18 years and over who were identified as smokers before the two year study period. OUTCOME: Prescription for smoking cessation treatment (nicotine replacement therapy (NRT) or bupropion) in the two year study period. VARIABLES: Age, sex, deprivation score, co-morbidity. RESULTS: Of the 29,492 patients recorded as current smokers at the start of the study period 1892 (6.4%) were given prescriptions for smoking cessation treatment during the subsequent two years. Of these, 1378 (72.8%) were given NRT alone, 406 (21.5%) bupropion alone, and 108 (5.7%) both treatments. Smokers were more likely to receive smoking cessation treatment if they lived in the most deprived areas (odds ratio (OR) for the most relative to the least deprived fifth, adjusted for sex, age, and co-morbidity, 1.50, 95% confidence interval (CI) 1.26 to 1.78), and if they were aged 25-74 years compared to 18-24 years or 75 and over. Smokers with co-morbidity were also more likely to receive smoking cessation treatment. Smokers were less likely to receive smoking cessation treatment if they were male (adjusted OR 0.68, 95% CI 0.62 to 0.75). CONCLUSION: The low proportion of smokers being prescribed these products strongly suggests that a major public health opportunity to prevent smoking related illness is being missed.

Assessing the accuracy of a computerized decision support system for digoxin dosing in primary care: an observational study.

BACKGROUND: This study was carried out as part of a European Union funded project (PharmDIS-e+), to develop and evaluate software aimed at assisting physicians with drug dosing. A drug that causes particular problems with drug dosing in primary care is digoxin because of its narrow therapeutic range and low therapeutic index. OBJECTIVES: To determine (i) accuracy of the PharmDIS-e+ software for predicting serum digoxin levels in patients who are taking this drug regularly; (ii) whether there are statistically significant differences between predicted digoxin levels and those measured by a laboratory and (iii) whether there are differences between doses prescribed by general practitioners and those suggested by the program. METHODS: We needed 45 patients to have 95% Power to reject the null hypothesis that the mean serum digoxin concentration was within 10% of the mean predicted digoxin concentration. Patients were recruited from two general practices and had been taking digoxin for at least 4 months. Exclusion criteria were dementia, low adherence to digoxin and use of other medications known to interact to a clinically important extent with digoxin. RESULTS: Forty-five patients were recruited. There was a correlation of 0.65 between measured and predicted digoxin concentrations (P < 0.001). The mean difference was 0.12 microg/L (SD 0.26; 95% CI 0.04, 0.19, P = 0.005). Forty-seven per cent of the patients were prescribed the same dose as recommended by the software, 44% were prescribed a higher dose and 9% a lower dose than recommended. CONCLUSION: PharmDIS-e+ software was able to predict serum digoxin levels with acceptable accuracy in most patients.

Do rates of hospital admission for falls and hip fracture in elderly people vary by socio-economic status?

OBJECTIVE: To determine the relationship between hospital admissions for falls and hip fracture in elderly people and area characteristics such as socio-economic deprivation. STUDY DESIGN: Ecological study of routinely collected hospital admissions data for falls and hip fracture in people aged 75 years or over for 1992-1997, linked at electoral ward level with characteristics from census data. METHODS: In total, 42,293 and 17,390 admissions were identified for falls and hip fracture, respectively, from 858 electoral wards in Trent. Rate ratios (RRs) for hospital admissions for falls and hip fracture were calculated by the electoral wards' Townsend score divided by quintiles. RRs were estimated by negative binomial regression and adjusted for the ward characteristics of age, gender, ethnicity, rurality, proportion of elderly people living alone and distance from hospital. RESULTS: There was a small but statistically significant association at electoral ward level between hospital admissions for falls and the Townsend score, with the most deprived wards having a 10% higher admission rate for falls compared with the most affluent wards (adjusted RR 1.10, 95% CI 1.01-1.19). No association was found between hospital admission for hip fracture and deprivation (adjusted RR 1.05, 95% CI 0.95-1.16). CONCLUSION: There is some evidence of an association at electoral ward level between hospital admissions for falls and socio-economic deprivation, with higher rates in deprived areas. No such association was found for hip fracture. Further work is required to assess the impact of interventions on reducing inequalities in hospital admission rates for falls in elderly people.

Prevalence, care, and outcomes for patients with diet-controlled diabetes in general practice: cross sectional survey.

BACKGROUND: Tight glycaemic control reduces microvascular complications in patients with type 1 and type 2 diabetes. We aimed to establish the proportion with type 2 diabetes treated through diet only and to determine levels of complications and quality of care received compared with patients on hypoglycaemic medication. METHODS: We undertook a cross-sectional study of 7870 patients with type 2 diabetes from a population of 253,618 patients from 42 general practices in the UK. Our primary outcome was process of care measures and diabetes-related complications. FINDINGS: 31.3% of all patients with type 2 diabetes are being managed with diet only (1% of the total population). More than four-fold variation between practices exists (range 15.6-73.2%). Patients treated with diet only are much less likely to have HbA1c (glycosylated haemoglobin) measurements, blood pressure, cholesterol, smoking, microalbuminuria testing, or screening for foot pulses recorded. 38.4% of patients with type 2 diabetes on medication have a HbA(1c) above 7.5% compared with 17.3% of those treated with diet only. Compared with those on medication, patients treated by diet only are more likely to have raised blood pressure and less likely to be on anti-hypertensive medication; they are 45% more likely to have raised cholesterol and less likely to be prescribed lipid-lowering medication. Although fewer of those treated by diet (68%) have diabetes-related complications compared with those on medication (80%), the rate is much higher than for the population without diabetes. INTERPRETATION: Diabetics treated by diet only have significant rates of complications and are less likely than those on medication to be adequately monitored. There is great scope for improved management within general practice.