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Background Early aggressive therapy can reduce the mortality associated with severe sepsis but this relies on prompt recognition, which is hindered by variation among published severity criteria. Our aim was to test the performance of different severity scores in predicting mortality among a cohort of hospital inpatients with sepsis. Methods We anonymously linked routine outcome data to a cohort of prospectively identified adult hospital inpatients with sepsis, and used logistic regression to identify associations between mortality and demographic variables, clinical factors including blood culture results, and six sets of severity criteria. We calculated performance characteristics, including area under receiver operating characteristic curves (AUROC), of each set of severity criteria in predicting mortality. Results Overall mortality was 19.4% (124/640) at 30 days after sepsis onset. In adjusted analysis, older age (odds ratio 5.79 (95% CI 2.87-11.70) for ≥80y versus 21d versus

The aim of the study was to evaluate the risks of hospitalisation and death due to hypersensitivity reactions associated with the NSAIDs naproxen and ibuprofen, using a record-linkage database for Tayside, Scotland (population 400,000). Cohorts of patients exposed to naproxen (n=54,038) and ibuprofen (n=79,513) were assembled. There were no deaths due to hypersensitivity. There was an increased risk of unvalidated hypersensitivity reactions during periods on-drug versus off-drug in patients exposed to naproxen and ibuprofen. However, after checking medical records, none of the three valid cases of hypersensitivity in the naproxen cohort and neither of the two in the ibuprofen cohort were judged to be due to NSAID exposure. A "worst-case" scenario gave an adjusted rate-ratio of on-drug with naproxen versus on-drug with ibuprofen of 1.63 (0.50, 5.29). The study shows that hypersensitivity reactions associated with NSAID use are rare, and provides no evidence that the risks of hypersensitivity reactions differ between naproxen and ibuprofen.

Aims To define the number of people in Tayside, Scotland (population 349 303) with Type 2 diabetes who use metformin, the incidence of contraindications to its continued use in these people and the proportion that discontinued metformin treatment following the development of a contraindication. Methods Retrospective cohort study of the incidence of contraindications to metformin in all patients with Type 2 diabetes using metformin from January 1993 to June 1995. The contraindications of acute myocardial infarction, cardiac failure, renal impairment and chronic liver disease were identified by: the regional diabetes information system, biochemistry database and hospital admissions database and a database of all encashed community prescriptions. Results One thousand eight hundred and forty seven subjects (26.3% of those with Type 2 diabetes) redeemed prescriptions for metformin. Of these, 3.5% were admitted with an acute myocardial infarction (71 episodes); 4.2% were admitted with cardiac failure (114 episodes); 21.0% received metformin and loop diuretics for cardiac failure concurrently; 4.8% developed renal impairment; and 2.8% developed chronic liver disease. The development of contraindications rarely resulted in discontinuation of metformin, for example only 17.5% and 25% stopped metformin after admission with acute myocardial infarction and development of renal impairment, respectively. In total, 24.5% of subjects receiving metformin, 6.4% of all people with Type 2 diabetes, had contraindications to its use. There was one episode of lactic acidosis in 4600 patient years. Conclusions This population-based study shows that 24.5% of patients prescribed metformin have contraindications to its use. Development of contraindications rarely results in discontinuation of metformin therapy. Despite this, lactic acidosis remains rare. Diabet. Med. 18, 483‐488 (2001)

End-stage renal disease is a complex, progressive and debilitating illness that affects patients' quality of life, physical and mental health, well-being, social functioning and emotional health. A cross-sectional survey was carried out in renal dialysis centres in Scotland to assess patients' health status and the impact of haemodialysis treatment on quality of life and well-being. Participants scored considerably lower than the UK general population in all domains of health-related quality of life, although mental health components were nearer to general population norms than physical health components. However, nearly half of the participants achieved a score on a general well-being questionnaire that was indicative of stress and anxiety. Increasing age was associated with better overall mental health but worse physical functioning. Increasing levels of hope and support were associated with improved general well-being.

Objectives: To investigate patterns of self monitoring of blood glucose concentration in diabetic patients who use insulin and to determine whether frequency of self monitoring is related to glycaemic control. Setting: Diabetes database, Tayside, Scotland. Subjects: Patients resident in Tayside in 1993-5 who were using insulin and were registered on the database and diagnosed with insulin dependent (type 1) or non-insulin dependent (type 2) diabetes before 1993. Main outcome measures: Number of glucose monitoring reagent strips dispensed (reagent strip uptake) derived from records of prescriptions. First recorded haemoglobin A1c concentration in the study period, and reagent strips dispensed in the previous 6 months. Results: Among 807 patients with type 1 diabetes, 128 (16%) did not redeem any prescriptions for glucose monitoring reagent strips in the 3 year study period. Only 161 (20%) redeemed prescriptions for enough reagent strips to test glucose daily. The corresponding figures for the 790 patients with type 2 diabetes who used insulin were 162 (21%; no strips) and 131 (17%; daily tests). Reagent strip uptake was influenced both by age and by deprivation category. There was a direct relation between uptake and glycaemic control for 258 patients (with recorded haemoglobin A1c concentrations) with type 1 diabetes. In a linear regression model the decrease in haemoglobin A1c concentration for every extra 180 reagent strips dispensed was 0.7%. For the 290 patients with type 2 diabetes who used insulin there was no such relation. Conclusions: Self monitoring of blood glucose concentration is associated with improved glycaemic control in patients with type 1 diabetes. Regular self monitoring in patients with type 1 and type 2 diabetes is uncommon. Key messages Several studies have indicated the importance of self monitoring of blood glucose concentration for prevention of complications in patients with diabetes Uptake of reagent strips for self monitoring of blood glucose among diabetic patients who used insulin was low, with only 20% of patients with type 1 diabetes and 17% of those with type 2 diabetes obtaining enough strips to test blood glucose concentration once daily Reagent strip uptake depends on characteristics such as age and social deprivation category, and patient groups with low uptake should be identified and targeted There was a direct association between strip uptake in the previous 6 months and glycaemic control in patients with type 1 diabetes but not in those with type 2 diabetes

To assess whether users of pancreatic-specific sulphonylureas are at reduced risk of mortality and cardiovascular mortality compared with users of non-specific sulphonylureas, we conducted a cohort study in the population of Tayside, Scotland. We identified 3331 patients with type 2 diabetes who were newly treated with sulphonylureas between 1994 and 2001 and categorized them into those treated with only pancreatic-specific sulphonylureas and those treated with only non-specific sulphonylureas. The risks of mortality and cardiovascular mortality were compared in a survival analysis. There were 2914 patients treated with pancreatic-specific sulphonylureas only, of which 683 (23.4%) died. Of 186 patients treated with non-specific drugs only, 40 (21.5%) died. After adjusting for confounding factors, the adjusted risk ratios (with 95% CI) for mortality and cardiovascular mortality were 0.84 (0.61 to 1.17) and 0.81 (0.59 to 1.11) among the non-specific users compared with the pancreatic-specific users. This provides no evidence that there are differences between the two sulphonylureas types.

The aim of this study was to investigate the association between H2-receptor antagonists and acute pancreatitis. The automated database of the Medicines Monitoring Unit (MEMO) was used to carry out a case-control study, supplemented with information on possible confounding factors from hospital and GP medical records. Cases were patients hospitalized with a computerized diagnosis of acute pancreatitis, and two sets of controls were drawn from (1) the study population and from (2) the same GP practice as the case. Current or 60-day exposure to cimetidine and ranitidine was analysed. In adjusted analyses, cimetidine exposure and ranitidine exposure were associated with an increased risk of hospitalization for acute pancreatitis, as were alcohol abuse and cholelithiasis. The risks were lower in unadjusted analyses, suggesting that the association is confounded, although they did not disappear completely. A possible explanation is that data on confounding were incomplete. This study cannot discount the existence of an association between H2-antagonists and acute pancreatitis, and highlights the difficulties involved in obtaining complete and accurate data on confounding factors that are not collected routinely. Copyright © 1998 John Wiley & Sons, Ltd.

Aim—To determine the appropriate size of risk windows in both exposed and unexposed sub-cohorts. Method—Data was taken from a previous study of upper gastrointestinal haemorrhage and perforation. The length of each prescription for NSAIDs was estimated. The risk was calculated for the duration of a prescription plus increments of −30, −25, …, +115, +120 (i.e. 31 increments). Ten unexposed groups were re-sampled for each increment (stratified for age and sex), using the same lengths of risk window as the exposed group. Mean risks and rate-ratios were calculated (per thousand person-years). Results—The NSAID risk rose from 3·52 at −30 days to a peak of 5·82 at −15 days, and then decreased gradually to 2·83 at +120 days. Unexposed risk was variable for the negative increments, and decreased gradually from 2·16 at +0 days to 1·54 at +120 days. The rate-ratio rose from 1·55 at −30 days to a peak of 2·85 at −5 days, and then decreased to 1·85 at +120 days. Conclusion—Risk windows should be the same as (or slightly less than) the calculated length of a prescription. Lengthy windows should not be used for unexposed comparator groups (the exposed windows may be randomly allocated). © 1998 John Wiley & Sons, Ltd.

Automated databases are increasingly being used for pharmacoepidemiological research and fieldwork is often carried out to supplement and validate information held within them. In MEMO's case-control studies, patients are identified using computerized ICD9 diagnosis codes, the original medical records are retrieved and checked, and only patients fulfilling case inclusion criteria are used. The 20-30% of patients for whom medical records cannot be found are usually excluded. The aim is to eliminate misclassification bias. However, selection bias may be introduced if availability of medical records is associated with exposure. This investigation was therefore carried out to assess the relative importance of misclassification and selection bias. Data from four previous case-control studies, investigating the associations between NSAIDs and hospitalization for colitis, acute renal failure, appendicitis and colorectal cancer, were used. To assess misclassification, odds ratios (with 95% CI) for recent exposure to NSAIDs were compared in repeated studies that used all patients identified by ICD9 codes, with studies using validated cases only. Selection bias was assessed by comparing results in studies using patients for whom records could and could not be found. Results were plotted and the graphs indicated that misclassification bias was relatively unimportant, but that selection bias could be introduced into a study in this way.

This cohort study examined the relationship between newly prescribed NSAIDs (none in the previous six months) and upper gastrointestinal hemorrhage and perforation in Tayside, Scotland. Exposure was classified by prescription duration. The study population consisted of the population of Tayside. A Comparator Group was chosen at random (within age and sex strata). Two hundred re-sampled comparator groups were created. Statistical analyses were carried out by Poisson regression (repeated for each of the re-samples). The analyses controlled for age, sex, prior hospitalization for upper gastrointestinal events, prior endoscopy, and the use of ulcer healing drugs. There were 78,191 subjects in the NSAID group, and 78,207 in each of the comparator groups. The increased risk with NSAIDs was only apparent for subjects without a history of upper gastrointestinal events; univariate rate ratio = 2.76 (1.90, 4.01). The final, re-sampled estimate of NSAID risk was rate ratio = 2.48 (1.87, 3.29).

This study assessed incidence of impaired glucose regulation (IGR) and progression to type 2 diabetes (T2D) in adults in one region of Scotland using routinely collected health-care data. Incidence of IGR was 2720 per 100,000 person years. Nine percent of IGR patients progressed to T2D in a mean time of 34 months.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very widely prescribed but they have a poor tolerability profile, with a range of potential adverse effects. NSAIDs that are used in topical formulations have been developed in the past 15 years and their use is increasing. The purpose is to achieve a high local concentration of the active ingredient at the affected site, with as low a plasma concentration as possible to minimise possible systemic adverse effects. The gastrointestinal and renal toxicity of topical NSAIDs has recently been highlighted in the medical literature. The elderly seem to be more sensitive to the adverse effects of NSAIDs than younger individuals, and this may also be true for topical NSAIDs. More formal epidemiological evaluation of the safety of topical NSAIDs is required in the postmarketing situation, as the main source of information regarding adverse drug reactions to topical NSAIDs in the UK has been spontaneous reporting data.

OBJECTIVE—To compare the mortality of people who were diagnosed with type 2 diabetes over 65 years of age with that of nondiabetic individuals. RESEARCH DESIGN AND METHODS—Using a population-based diabetes information system for an observational cohort study in Tayside, Scotland, people who were diagnosed with type 2 diabetes over the age of 65 years between 1993 and 2002 were identified. Nondiabetic comparators, matched for age and sex, were identified from the nondiabetic population. The two cohorts were followed up for mortality and cardiovascular mortality according to death certification records. RESULTS—There were 3,594 people with type 2 diabetes (48% male) and 7,188 matched comparators identified in the study. Over a mean follow-up period of 4.6 ± 2.9 years for 3,594 people with type 2 diabetes and 7,188 comparators, 909 (25.3%) patients in the diabetic cohort and 1,651 (23.0%) in the nondiabetic cohort died. The adjusted relative risk for mortality in the diabetic cohort compared with the nondiabetic cohort was 1.06 (95% CI 0.94–1.19) for men and 1.29 (1.15–1.45) for women. Cardiovascular deaths accounted for 49.4% of the deaths in people with and 45.2% in those without diabetes (adjusted relative risk 1.01 [0.93–1.10]). CONCLUSIONS—Men diagnosed with type 2 diabetes over the age of 65 years have no excess mortality compared with their nondiabetic counterparts, a finding that was not replicated for women.

Aim To investigate self-monitoring of blood glucose (SMBG) behaviour among non-insulin treated patients with type 2 diabetes mellitus, and to evaluate associations with glycaemic control. Methods Eligible patients in 23 GP practices in Tayside, Scotland, were identified (18–75 years, no insulin treatment, SMBG reagent strips dispensed in 2009). Consenting patients were administered questionnaires addressing SMBG behaviour: these primary data were record-linked to clinical data (including HbA1c) from a validated population-based diabetes clinical information system, then anonymised. Results Among 629 eligible patients, 207 were interviewed and analysed. Mean SMBG reagent strips dispensed in 12 months was 268. In response to a perceived high test result, 80 (38.8%) patients took no action or simply checked later with most of them (61.3%) indicating they did not know what action to take. Of the 126 (61.2%) patients who took some action, 101 made changes to diet, 12 increased physical activity, 10 made changes to medication and 12 mad a HCP appointment. A high score on a Diabetes Knowledge Test was a statistically significant predictor of taking action (odds ratio: 2.07). However, neither taking action nor increased SMBG frequency was associated with improved glycaemic control. Conclusions Responding to SMBG test results and increased testing frequency were not associated with improved glycaemic control in the short-term. There is a lack of knowledge surrounding SMBG in non-insulin treated patients.

This paper considers socioeconomic inequalities in self-assessed health amongst people with and without a history of cancer using representative data from Scotland.A cross-sectional analysis using the Scottish Health Survey was done. Cancer survivors were identified using linked Cancer Registry data. Bivariate and multivariate analysis was used to compare and contrast self-assessed health amongst those with a history of cancer to those without.Of the 17,505 survey participants, 432 (2.5 %) had a history of cancer. After taking into account potential confounders, those in the lowest socioeconomic group were more likely to report poor health than those in the highest group amongst those with a history of cancer [odds ratio, 2.96; confidence interval (CI), 1.82-4.80] and those with no history of cancer (odds ratio, 2.45; CI, 2.21-2.71). Those in the lowest socioeconomic group with no history of cancer had a greater propensity to report poor health than any of the highest groups that did have a history of cancer (p 0.01). Differences in propensities to indicate poor health were particularly marked amongst those 4 years or more post-cancer diagnosis.Findings underline the scale of socioeconomic gradients in health. That disparities were so wide amongst those most temporally distant from initial diagnosis is particularly a concern given improving survival after a cancer diagnosis.Socioeconomic circumstances have a considerable influence on health and well-being. Practitioners and policy makers should consider socioeconomic circumstances in considering approaches to health and social care of cancer survivors.

Background Due to improvements in cancer survival the number of people of working age living with cancer across Europe is likely to increase. UK governments have made commitments to reduce the number of working days lost to ill-health and to improve access to vocational rehabilitation (VR) services. Return to work for people with cancer has been identified as a priority. However, there are few services to support people to remain in or return to work after cancer and no associated trials to assess their impact. A pilot randomised controlled trial among women with breast cancer has been designed to assess the feasibility of a larger definitive trial of VR services for people with cancer. Methods Patients are being recruited from three clinical sites in two Scottish National Health Service (NHS) Boards for 6 months. Eligible patients are all women who are: (1) aged between 18 and 65 years; (2) in paid employment or self-employed; (3) living or working in Lothian or Tayside, Scotland, UK; (4) diagnosed with an invasive breast cancer tumour; (5) treated first with surgery. Patients are randomly allocated to receive referral to a VR service or usual care, which involves no formal employment support. The primary outcome measure is self-reported sickness absence in the first 6 months following surgery. Secondary outcome measures include changes in quality of life (FACT-B), fatigue (FACIT-Fatigue) and employment status between baseline and 6- and 12-months post-surgery. A post-trial evaluation will be conducted to assess the acceptability of the intervention among participants and the feasibility of a larger, more definitive, trial with patients with lung and prostate cancer. Discussion To our knowledge this is the first study to determine the feasibility of a randomised controlled trial of the effectiveness of VR services to enable people with cancer to remain in or return to employment. The study will provide evidence to assess the relevance and feasibility of a larger future trial involving patients with breast, prostate or lung cancer and inform the development of appropriate VR services for people living with cancer. Trial Registration ISRCTN: ISRCTN29666484 Registration date: 07/10/10; Randomisation of first patient: 03/12/10

Background: For many regularly used drugs, evidence for safe use in pregnancy has not been established. Despite this, international studies have identified high levels of drug prescribing among pregnant women. Objective: To investigate the patterns of prescribing of drugs to women who gave birth in Tayside, Scotland, in 2007. Methods: Scottish maternity records were linked to dispensed prescribing data for all women who gave birth in Tayside in 2007. Drugs prescribed were coded according to the US FDA classification for risks of drugs in pregnancy. Patterns of prescribing were investigated during the 3 trimesters of pregnancy and the 3 months prior to conception. Results: Prescribing in pregnancy was common, with 21 093 prescriptions dispensed to 3356 (85.2%) of the 3937 women. The most frequently prescribed drugs were antacids, antibacterials, oral iron, folic acid preparations and analgesics. Category A drugs (positive evidence of safety in pregnancy) and Category B drugs (some evidence of safety in pregnancy) accounted for 19.6% and 26.9% of all prescriptions dispensed, respectively. Prescribing of Category X drugs (evidence of risk to the fetus; use contraindicated in women who are or may become pregnant) during pregnancy was rare, with 112 prescriptions dispensed to 68 women (1.7%). Most of these were oral contraceptives or sex hormones. Prescribing of Category X drugs fell markedly during the first trimester and remained very low thereafter. Category D drugs (evidence of risk to the fetus but benefits of therapy may outweigh the potential risk) [432] were dispensed to 166 women (4.2%) during pregnancy. The most commonly prescribed Category D drugs were anxiolytics, nicotine replacement therapy and antiepileptic drugs. The frequency of prescribing of Category D drugs reduced in the third trimester. Prescribing of Category C drugs (insufficient evidence to know whether they are harmful) was common. Thirty percent of women received a total of 3641 Category C prescriptions, which accounted for 17.3% of all prescriptions issued during pregnancy. Prescribing of Category C drugs showed only a very modest decline during pregnancy. No FDA code was available for 4035 prescriptions issued (87 different items), the majority of which were for antacids and preparations for indigestion. More than 40% of women received such medications. Conclusions: Prescribing of drugs during pregnancy was very common, but the levels of prescribing of drugs that are known to be harmful were low. Much of the prescribing was for drugs related to the pregnancy. While this study provides some evidence that primary-care prescribers in Tayside are prescribing potentially harmful drugs appropriately and with caution during pregnancy, safety data during pregnancy are unavailable for many drugs that are commonly prescribed.

Summary Aims The influence of socio-economic status on the prevalence of Type 1 and Type 2 diabetes mellitus, and on obesity, was explored using routinely collected healthcare data for the population of Tayside, Scotland. Methods Among 366 849 Tayside residents, 792 and 5474 patients with Type 1 and Type 2 diabetes, respectively, were identified from a diabetes register. The Carstairs Score was used as a proxy for socio-economic status. This is a material deprivation measure derived from the UK census, using postcode data for four key variables. Odds ratios for diabetes prevalence, adjusted for age, were determined for each of six deprivation categories (1 – least deprived, 6/7 – most deprived). The mean body mass index (BMI) in each group was also determined, and the effect of deprivation category explored by analysis of covariance, adjusting for age and sex. Results The prevalence of Type 2 diabetes, but not Type 1 diabetes, varied by deprivation. People in deprivation category 6 and 7 were 1.6-times (95% confidence interval 1.4–1.8) more likely to have Type 2 diabetes than those least deprived. There was no relationship between deprivation and BMI in Type 1 diabetes (P = 0.36), but there was an increase in BMI with increasing deprivation in Type 2 diabetes (P

Problem: System-wide improvement of chronic disease care is challenging because it requires collaboration and communication across organisational and professional boundaries. Managed clinical networks are one potential solution, but there is little evidence of their effectiveness. Design and setting: Retrospective, mixed-methods evaluation of the form and impact of quality improvement in the Tayside Diabetes Managed Clinical Network (MCN) 1998–2005. Strategies for change: Progressive implementation of multiple quality improvement strategies predominately directed at individuals and clinical teams (guideline development and dissemination, education, clinical audit, encouragement of multidisciplinary team working, task redesign). Information technology played an important role in supporting QI activity, but participants identified it as facilitative rather than delivering QI by itself. More important was achieving widespread clinical engagement through persuasion and appeal to shared professional values by clinical leaders. Effects of change: Simple process measures such as glycated haemoglobin measurement rapidly improved. More complex process measures such as eye screening improved more slowly, and were more dependent on redesign of the care pathway. Improvement was greater for type 2 than type 1 diabetes. Significant shifts of care for type 2 diabetes into primary care were achieved, but were harder to achieve without additional resources. Lessons learnt: Delivering better care to whole populations across organisational and professional boundaries required sustained work over long periods, and at all levels of the system of care. Past network focus on clinical collaboration has been effective at improving clinical process and outcome, and the network is now prioritising work with managers and patients to support future redesign.

Whether there was an increased prevalence of cancer associated with insulin use was questioned in the early twentieth century (Marble, 1934), and there is a growing body of evidence suggesting that diabetes increases the risk of the incidence and mortality from certain cancers. These include pancreatic and liver cancer, colorectal cancer, breast cancer, bladder cancer, cancer of the kidney and endometrial cancer (Wideroff et al, 1997; Coughlin et al, 2004; Rousseau et al, 2006; Kuriki et al, 2007). However, the results of studies of diabetes and cancer have been very mixed with many not distinguishing between type 1 and type 2 diabetes (Wideroff et al, 1997), or have defined groups according to treatment (Swerdlow et al, 2005). In some studies, the basis for diabetes diagnosis is self-report (Coughlin et al, 2004), in others it is clinical (Saydah et al, 2003). Studies have been both retrospective (Kuriki et al, 2007) and prospective, with some prospective studies following up from diagnosis of diabetes (Ragozzino et al, 1982); another followed up a cross-sectional sample of patients (Swerdlow et al, 2005). In this study, we present the risks of different cancers following diagnosis of type 2 diabetes in Tayside, Scotland, using a standardised methodology.

BackgroundGrowing evidence suggests that perinatal depression is associated with disrupted mother–infant interactions and poor infant outcomes. Antenatal depression may play a key role in this cycle by disrupting the development of a maternal response to infant stimuli. The current study therefore investigated the impact of depressive symptoms on the basic cognitive processing of infant stimuli at the beginning of pregnancy.MethodA total of 101 women were recruited by community midwives and tested at an average gestation of 11 weeks. An established computerized paradigm measured women's ability to disengage attention from infant and adult faces displaying negative positive and neutral emotions. Depressive symptoms were measured using a computerized interview (the Clinical Interview Schedule).ResultsThe effect of infant emotion on women's ability to disengage from infant faces was found to be influenced by depressive symptoms. Non-depressed pregnant women took longer to disengage attention from distressed compared with non-distressed infant faces. This bias was not, however, seen in women experiencing depressive symptoms. There was a difference of −53 (s.d.=0.7) ms (95% confidence interval −90 to −14, p=0.007) between those with and without depressive symptoms in this measure of attentional bias towards distressed infant faces.ConclusionsOur results suggest that depressive symptoms are already associated with differential attentional processing of infant emotion at the very beginning of childbearing. The findings have potential implications for our understanding of the impact of depressive symptoms during pregnancy on the developing mother–infant relationship.

Background: It has been suggested that diabetes is under-recorded on death certificates. Methods: We examined the death certificates of 1,872 people with type 2 diabetes in Tayside, Scotland, to determine how frequently diabetes was recorded. Results: Diabetes was mentioned on the certificates of 42.8% and was the underlying cause of death for 6.4%. There was mention of diabetes for 51.3% of the 811 people for whom cardiovascular disease was the underlying cause of death. Being male was associated with less frequent mention of diabetes, with more frequent mention associated with increasing duration of diabetes, increasing age and underlying cardiovascular cause of death. Conclusions: This study highlights the limitations of using routine mortality data for monitoring the burden of diabetes in populations.

To develop and test a set of measures of quality of care in the process of sepsis management, to determine the inter-rater reliability of case-note review in assessment of these measures and to assess our current standard of care.Five measures of process of care and one of outcome were identified from the literature review and previous experience. Failure modes and effects analysis was used by a multidisciplinary team to validate these measures and prioritize them in terms of associated risk. Forty sets of case notes were reviewed by two independent teams and the inter-rater reliability was determined using observed percentage agreement and the kappa statistic. We used the data to calculate the proportion of patients in whom we are currently meeting targets for good quality of care.The multidisciplinary team did not identify any additional areas of concern and assigned the highest risk priority to a delay of over 4 h from recognition of sepsis to antibiotic administration. The inter-rater agreement was80% for four of the measures, but was only 62.5% for appropriateness of antibiotic therapy. Room for improvement in practice exists, for example, antibiotic administration within 4 h was not achieved in 40% of patients.Four of our five measures of care are suitable for use in assessing the effect of interventions aimed at improving sepsis management, with at least moderate inter-rater reliability. Specific areas where increased clarity should improve agreement further have been identified.

Objective: Mortality among adults of all ages diagnosed with impaired glucose regulation (IGR) in Tayside, Scotland, UK, was evaluated using routinely collected healthcare data sets. Research design and methods: Using recordlinked data in 2003–2008, all instances of blood glucose testing in the population defined 2 cohorts of patients aged 18+years: those with IGR (whether impaired fasting glucose or impaired glucose tolerance (IGT)) according to the WHO criteria, and those who were normoglycemic. They were followed in survival analyses for mortality or cardiovascular mortality (censoring deaths that occurred within a 30-day period of testing), to derive HRs (with 95% CI) for IGR status using Cox regression, adjusted for age, sex, and an area measure of deprivation. Results: There were 2 372 712 tests for 214 094 patients, with 196 799 patients in the non-IGR cohort and 50 080 in the IGR cohort. During follow-up, 19 147 (9.7%) and 8397 (16.8%) patients died in 2 cohorts, respectively, with mortality rates of 33.2/1000 patient-years and 70.7/1000 patient-years. In multivariable analyses, the overall adjusted risk of mortality for IGR was 1.16 (95% CI 1.13 to 1.20). However, it was 2.59 (95% CI 2.17 to 3.10) for people aged

Aims/hypothesis We examined incidence, prevalence and mortality from type 2 diabetes mellitus in a Scottish population over 12 years, and evaluated the effects on prevalence of increasing incidence and decreasing mortality. Materials and methods We used a diabetes clinical information system in Tayside (population 387,908), Scotland, to identify new cases of type 2 diabetes between 1993 and 2004 and to calculate incidence rates and mid-year prevalence. We defined mortality rates as the number of deaths of diabetic people divided by mid-year prevalence. We used logistic and Poisson regression to analyse trends. We then modelled the increase in prevalence for each year for three scenarios, based on whether mortality or incidence rates remained unchanged from 1993. Results There was a doubling in incidence and prevalence of type 2 diabetes in Tayside over the 12 years, with statistically significant increasing trends of 6.3 and 6.7% per year respectively. The mortality rate decreased. If incidence and mortality had remained at 1993 levels, there would have been an increase in prevalence of 855 per 100,000 in 2003, accounting for 60.1% of the actual increase of 1,423 per 100,000. If there had been no mortality decrease, prevalence in 2003 would have been very similar to the actual prevalence observed. Conclusions/interpretation Decreasing mortality rates in Tayside had less effect on the increase in prevalence than did increasing incidence. Even if incidence and mortality remain unchanged, prevalence will increase by over 20% in the next decade.

Objectives To review all published observational studies reporting on all-cause mortality in patients with type 2 diabetes to determine the degree of increased mortality when diagnosed at an older age. Design Systematic literature search. Setting The review included studies carried out in populations from Germany, United Kingdom, United States, Japan, Italy, Western Australia, Netherlands and Sweden. Measurements Medline, CINAHL, EMBASE, National Research Register and Cochrane Reviews were systematically searched from 1975 to 2004. We identified observational studies that reported overall mortality for people diagnosed with type 2 diabetes when they were over the age of 60, compared with a non-diabetic population. Outcome measures were expressed as risk ratios or relative risks. Results Among 14 eligible studies, one study reported reduced mortality for patients diagnosed with type 2 diabetes over the age of 60, whereas another found virtually no increased risk of mortality. However, 7 of the 14 studies reported increased mortality in all patients diagnosed when older, and 5 studies for certain subgroups only. A meta-analysis showed the combined relative risks (with 95% CI) of increased mortality for men diagnosed between the ages of 60 and 70 to be 1.38 (1.08-1.76) and 1.13 (0.88-1.45) for men diagnosed aged 70 years or older. A similar pattern was found for the same age groups for women, with combined relative risks of 1.40 (1.10-1.79) and 1.19 (0.93-1.52) respectively. Conclusion Increased mortality associated with a diagnosis of type 2 diabetes at an older age is lower than that reported for the general older diabetic population.

Background A recent case-control study reported an association between non-steroidal anti-inflammatory drug (NSAID) use and acute appendicitis. This association was investigated in a case-control study of patients, aged 30 years and over, admitted as an emergency to hospitals in Tayside between 1989 and 1992, who had appendicectomy for acute appendicitis. Methods A record-linkage database containing records of dispensed prescriptions and hospital admissions was used. A total of 223 patients were identified. The medical records of 161 were checked, of which 138 were valid cases, and information on white cell count and NSAID exposure was recorded. Community and hospital controls were generated. Results Some 9.0 per cent of patients were prescribed NSAIDs within 90 days of hospitalization, compared with 7.6 per cent of community controls and 11.5 per cent of hospital controls. The odds ratio was 1.21 (95 per cent confidence interval 0.73–2.01) and 0.75 (0.43–1.32) respectively. There was no significant difference in white cell count between exposed and non-exposed cases. No increased risk of appendicectomy was associated with aspirin use: odds ratio 1.67 (052–5.30) and 0.37 (0.12–1.13) using community and hospital controls respectively. Conclusion Appendicectomy for acute appendicitis is not associated with increased prior use of NSAIDs.

The aim of this study was to evaluate the risk of adverse cardiovascular outcomes in patients with type 2 diabetes newly treated with sulfonylureas and metformin.The Diabetes Audit and Research in Tayside Scotland (DARTS) diabetes information system and the Medicines Monitoring Unit (MEMO) dispensed prescribing database for the population of Tayside, Scotland (400,000 people) were employed. Patients newly prescribed with oral hypoglycaemic agents between 1994 and 2001 were classified into five study cohorts according to the treatment received: metformin only, sulfonylureas only, sulfonylureas added to metformin, metformin added to sulfonylureas, and both drugs simultaneously. In Cox regression analyses, we estimated relative risks for all-cause mortality, cardiovascular mortality and cardiovascular hospital admission for patients in the five study cohorts, with metformin monotherapy as the reference group.Of the 5,730 study patients, 1,000 died during a maximum of 8 years follow-up. Patients in the sulfonylureas only cohort had increased risks of mortality and cardiovascular mortality, with unadjusted relative risks of 3.12 (95% CI 2.54-3.84) and 3.71 (95% CI 2.64-5.22), respectively. After adjusting for differences between groups (age, sex, duration of diabetes, blood pressure, cholesterol, HbA(1c), smoking, previous hospital admission, treatment with cardiovascular medication), these relative risks were 1.43 (95% CI 1.15-1.77) and 1.70 (95% CI 1.18-2.45), respectively. Patients in the combination cohorts had significantly increased risks of cardiovascular hospital admission, as well as increased risks of mortality and cardiovascular mortality.In this cohort study of patients newly treated with oral hypoglycaemic agents, those treated with sulfonylureas only, or combinations of sulfonylureas and metformin, were at higher risk of adverse cardiovascular outcomes than those treated with metformin alone.

Metformin, widely given to patients with type 2 diabetes, works by targeting the enzyme AMPK (AMP activated protein kinase), which induces muscles to take up glucose from the blood. A recent breakthrough has found the upstream regulator of AMPK to be a protein kinase known as LKB1.1 2 LKB1 is a well recognised tumour suppressor. Activation of AMPK by metformin and exercise requires LKB1, and this would also explain why exercise is beneficial in the primary and secondary prevention of certain cancers.3 We hypothesise that metformin use in patients with type 2 diabetes may reduce their risk of cancer. We tested this hypothesis using record linkage databases developed in Tayside, Scotland: a diabetes clinical information system (DARTS) and a database of dispensed prescriptions (MEMO).4 We did a pilot case-control study using previously validated methods.5 From 314 127 people who were resident (or died) in Tayside in …

Aim The DARTS diabetes register was used to determine incidence rates of diabetes and related complications in 1997. Methods The diabetes register records detailed clinical information for all patients diagnosed with diabetes in Tayside, Scotland. The study population included patients who were alive and registered with a Tayside GP for the duration of 1997 or who died in Tayside during this time. Patients who had diabetes prior to 1997, those who developed diabetes in 1997, and those who developed diabetic complications in 1997, were identified. Results In the Tayside population of 385 774 at the start of 1997, there were 942 and 6632 patients with Type 1 and Type 2 diabetes, with a further 29 and 744 patients diagnosed in 1997. The incidence rates (with 95% confidence intervals) of diabetic complications per 1000 patients with Type 1 and Type 2 diabetes, respectively, were: angina 8.8 (4.5–17.3) and 38.4 (33.4–44.2); myocardial infarction 8.6 (4.4–16.9) and 21.9 (18.4–25.9); cerebrovascular accident 1.1 (0.3–6.0) and 14.2 (11.6–17.5); lower extremity amputation 3.2 (1.2–9.4) and 3.1 (2.1–4.8); peripheral vascular disease 5.5 (2.4–12.8) and 13.6 (11.0–16.8); registered blindness 1.1 (0.3–5.9) and 1.6 (0.9–2.9); end-stage renal failure 6.4 (3.0–13.8) and 5.0 (3.6–7.0). Mortality was 14.6 per 1000 (9.6–25.7) in Type 1 diabetes and 50.0 per 1000 (45.1–55.3) in Type 2 diabetes. Conclusion This study provides baseline figures for rates of diabetic complications for Type 1 and Type 2 diabetes, and confirms the increased burden of macrovascular disease in Type 2 diabetes.

To compare the mortality of people who were diagnosed with type 2 diabetes over 65 years of age with that of nondiabetic individuals.Using a population-based diabetes information system for an observational cohort study in Tayside, Scotland, people who were diagnosed with type 2 diabetes over the age of 65 years between 1993 and 2002 were identified. Nondiabetic comparators, matched for age and sex, were identified from the nondiabetic population. The two cohorts were followed up for mortality and cardiovascular mortality according to death certification records.There were 3,594 people with type 2 diabetes (48% male) and 7,188 matched comparators identified in the study. Over a mean follow-up period of 4.6 +/- 2.9 years for 3,594 people with type 2 diabetes and 7,188 comparators, 909 (25.3%) patients in the diabetic cohort and 1,651 (23.0%) in the nondiabetic cohort died. The adjusted relative risk for mortality in the diabetic cohort compared with the nondiabetic cohort was 1.06 (95% CI 0.94-1.19) for men and 1.29 (1.15-1.45) for women. Cardiovascular deaths accounted for 49.4% of the deaths in people with and 45.2% in those without diabetes (adjusted relative risk 1.01 [0.93-1.10]).Men diagnosed with type 2 diabetes over the age of 65 years have no excess mortality compared with their nondiabetic counterparts, a finding that was not replicated for women.

Aim To investigate whether patients require insulin as a result of poor adherence to oral hypoglycaemic agents (OHAs) in Type 2 diabetes. Methods A diabetes information system and a database of drugs dispensed for the study period 1993–1996 were used in Tayside, Scotland (population 400 000). Patients aged over 34 years with Type 2 diabetes who had at least 6 months exclusive therapy with OHAs (sulphonylureas or metformin) prior to insulin treatment were identified. Intended duration of every OHA prescription was calculated from prescription details. Adherence was estimated by dividing total intended duration of OHA therapy by study time for each patient, and compared between those who did and did not convert to insulin. Results There were 2537 patients on sulphonylureas (51% male, mean age 67 years). There was improved adherence in the 262 patients who commenced insulin, who had mean adherence of 88.3% (95% confidence interval (CI) 85.9–90.6%) compared with the remaining 2275 patients whose mean adherence was 87.4% (95% CI 86.7–88.2%). In a logistic regression analysis, the adjusted odds ratio (OR) for commencing insulin was 1.20 (95% CI 1.07–1.35) for a quartile increase in adherence. There were 1519 patients on metformin (49% male, mean age 64 years). Mean adherence was 79.7% (95% CI 76.4–83.1%) and 83.1% (95% CI 82.0–84.1%) in 169 patients who did and 1350 who did not commence insulin, respectively, with an adjusted OR for a quartile increase in adherence of 0.91 (95% CI 0.78–1.07). Conclusion Despite suboptimal adherence to OHAs in Type 2 diabetes, this is not associated with subsequent requirement for insulin. Diabet. Med. 19, 685–688 (2002)

Record-linkage refers to the linking together of data relating to the same individual from separate source files. In this paper, we discuss ways in which the technique can enhance observational prescribing research in large populations. We draw upon the work of the Medicines Monitoring Unit (MEMO), University of Dundee, to illustrate its contribution to prescribing research.

Problem Antibiotic administration to inpatients developing sepsis in general hospital wards was frequently delayed. We aimed to reproduce improvements in sepsis management reported in other settings. Context Ninewells Hospital, an 860-bed teaching hospital with quality improvement (QI) experience, in Scotland, UK. The intervention wards were 22 medical, surgical and orthopaedic inpatient wards. Design A multifaceted intervention, informed by baseline process data and questionnaires and interviews with junior doctors, evaluated using segmented regression analysis of interrupted time series (ITS) data. Measures for improvement Primary outcome measure: antibiotic administration within 4 hours of sepsis onset. Secondary measures: antibiotics within 8 hours; mean and median time to antibiotics; medical review within 30 min for patients with a standardised early warning system score ≥4; blood cultures taken before antibiotic administration; blood lactate level measured. Strategies for change The intervention included printed and electronic clinical guidance, educational clinical team meetings including baseline performance data, audit and monthly feedback on performance. Effects of change Performance against all study outcome measures improved postintervention but differences were small and ITS analysis did not attribute the observed changes to the intervention. Lessons learnt Rigorous analysis of this carefully designed improvement intervention could not confirm significant effects. Statistical analysis of many such studies is inadequate, and there is insufficient reporting of negative studies. In light of recent evidence, involving senior clinical team members in verbal feedback and action planning may have made the intervention more effective. Our focus on rigorous intervention design and evaluation was at the expense of iterative refinement, which likely reduced the effect. This highlights the necessary, but challenging, requirement to invest in all three components for effective QI.

OBJECTIVE: Utilization and costs of prescription drugs were investigated in diabetic and nondiabetic patients. RESEARCH DESIGN AND METHODS: The study was carried out in Tayside, Scotland, U.K. A validated population-based diabetes register was used to identify patients with type 1 and type 2 diabetes, and a database of all prescriptions dispensed in the community was used to investigate drug utilization in 1995. RESULTS: In a population of 406,526, there were 974 (0.2%) with type 1 diabetes and 6,869 (1.7%) with type 2 diabetes. The mean dispensed prescribing rates for all drugs (excluding antidiabetic medication) were higher across all age-groups for diabetic patients. After adjusting for age, patients with type 1 diabetes were 2.07 times (95% CI 2.03-2.11) more likely and patients with type 2 diabetes were 1.70 times (1.69-1.71) more likely to be dispensed a drug item than people without diabetes. This likelihood was increased in every drug category, even those not directly related to diabetes, and the proportion and cost of drug items dispensed to diabetic patients was therefore higher than expected given the prevalence of diabetes. Upon projecting these results to the U.K. population, it was discovered that nearly 8% of the U.K. drug budget (Pound Sterling 350 million) is accounted for by patients with diabetes (90% of that by patients with type 2 diabetes). CONCLUSIONS: This study highlights the increased usage and cost of prescription drugs in diabetes, with type 2 diabetes constituting a particular burden. It was discovered that 1.4% of drug usage in the entire population can be accounted for by the increased prescribing rate of diabetic patients compared with that of nondiabetic patients.

Record-linkage is the linkage of patient-specific information that is stored separately. Recent advances in computerization have meant that record-linkage techniques in medical research are increasingly being used and refined. In particular, they have made a significant contribution to pharmacovigilance, which involves linking drug exposure to outcomes data. In this article, the contribution of record-linkage in Scotland to medical research is described. The two organizations that utilize record-linkage techniques are the Medicines Monitoring Unit (MEMO) of the University of Dundee and the Information and Statistics Division (ISD) of the NHS in Scotland. Pharmacovigilance is MEMO's main concern (using data from the Tayside region of Scotland), while ISD link health care datasets for Scotland for general health care research. The experience of the two groups is now being combined to carry out drug safety studies in the entire population of Scotland.

OBJECTIVE To evaluate the association between the use of ACE inhibitors and hospital admission for severe hypoglycemia and to explore the effects of potential confounding variables on this relationship. RESEARCH DESIGN AND METHODS The association between the use of ACE inhibitors and the incidence of hypoglycemia is controversial. A recent study reported that 14% of all hospital admissions for hypoglycemia might be attributable to ACE inhibitors. We performed a nested case-control study, using a cohort of 6,649 diabetic patients taking insulin or oral antidiabetic drugs, on the Diabetes Audit and Research in Tayside, Scotland (DARTS) database. From 1 January 1993 to 30 April 1994, we identified 64 patients who had been admitted to Tayside hospitals with hypoglycemia and selected 440 control patients from the same cohort. RESULTS Hypoglycemia was associated with the use of ACE inhibitors (odds ratio [OR] 3.2, 95% CI 1.2–8.3, P = 0.023), whereas use of β-blockers and calcium antagonists was not associated with an increased risk of hospitalization for hypoglycemia with ORs of 0.9 (95% CI 0.3–3.3) and 1.7 (95% CI 0.2–2.1), respectively. There were significant differences between case and control patients in type of diabetes treatment, diabetes duration, place of routine diabetes care, and congestive cardiac failure. These differences did not confound the relationship between ACE inhibitors and hypoglycemia (adjusted OR 4.3, 95% CI 1.2–16.0). CONCLUSIONS The results show that the association between ACE inhibitor therapy and hospital admission for severe hypoglycemia is not explained by these confounding factors. Although ACE inhibitors have distinct advantages over other antihypertensive drugs in diabetes, the risk of hypoglycemia should be considered.

BACKGROUND: To evaluate the relation between non-steroidal anti-inflammatory drugs (NSAIDs) and colitis due to inflammatory bowel disease. METHODS: A case-control study was conducted using a prospectively constructed, record linkage database containing hospital event and dispensed drug data (1989-93). The study population consisted of 319,465 people resident in Tayside in January 1989, and still resident (or dead) in October 1994. RESULTS: Of the 785 patients admitted to hospital as emergencies with colitis between July 1989 and June 1993, 200 fulfilled the case criterion of colitis due to inflammatory bowel disease. A further 1198 persons were used as community controls. Odds ratios were calculated for three exposure periods (current, recent, and past exposure). The overall odds ratios (with 95% confidence intervals) for current and recent exposure to NSAIDs were 1.77 (1.01 to 3.10) and 1.93 (1.20 to 3.09) respectively. Current and recent exposure to NSAIDs was also associated for incident cases, with odds ratios of 2.96 (1.32 to 6.64) and 2.51 (1.13 to 5.55). There was a trend for recent exposure among non-incident cases. CONCLUSION: The use of NSAIDs may be associated with an increased risk of emergency admission to hospital for colitis due to inflammatory bowel disease, particularly among patients with no previous history.

Background There is a paucity of methodologically robust vocational rehabilitation (VR) intervention trials. This study assessed the feasibility and acceptability of a VR trial of women with breast cancer to inform the development of a larger interventional study. Methods Women were recruited in Scotland and randomised to either a case management VR service or to usual care. Data were collected on eligibility, recruitment and attrition rates to assess trial feasibility, and interviews conducted to determine trial acceptability. Sick leave days (primary outcome) were self-reported via postal questionnaire every 4 weeks during the first 6 months post-surgery and at 12 months. Secondary outcome measures were change in employment pattern, quality of life and fatigue. Results Of the 1,114 women assessed for eligibility, 163 (15%) were eligible. The main reason for ineligibility was age (>65 years, n = 637, 67%). Of those eligible, 111 (68%) received study information, of which 23 (21%) consented to participate in the study. Data for 18 (78%) women were analysed (intervention: n = 7; control: n = 11). Participants in the intervention group reported, on average, 53 fewer days of sick leave over the first 6 months post-surgery than those in the control group; however, this difference was not statistically significant (p = 0.122; 95% confidence interval −15.8, 122.0). No statistically significant differences were found for secondary outcomes. Interviews with trial participants indicated that trial procedures, including recruitment, randomisation and research instruments, were acceptable. Conclusions Conducting a pragmatic trial of effectiveness of a VR intervention among cancer survivors is both feasible and acceptable, but more research about the exact components of a VR intervention and choice of outcomes to measure effectiveness is required. VR to assist breast cancer patients in the return to work process is an important component of cancer survivorship plans. Trial registration ISRCTN29666484

Non-steroidal anti-inflammatory drugs (NSAIDs) have been implicated in the aetiology of acute renal failure (ARF), but epidemiological studies examining this association have produced disparate results. We conducted a case-control study using a purpose-built record-linkage database for a population of 420,600 patients, resident in Tayside since May 1990. Patients (n = 207) hospitalized with a diagnostic code for ARF between 1990 and 1992 had their diagnosis validated by a renal physician. Six community controls and two hospital controls, matched for age and sex, were generated for each of these cases. Exposure to dispensed oral NSAIDs, topical NSAIDs and aspirin during the 90 days prior to the index date were investigated (recent exposure), as was exposure at any time since January 1989 (previous exposure). The most significant associations were modelled using conditional logistic regression. When community controls were used, recent exposure to NSAIDs and previous exposure to aspirin were independently associated with hospitalization for ARF, with adjusted odds ratios of 2.20 (1.49-3.25) and 2.19 (1.46-3.30), respectively. Only recent exposure to oral NSAIDs was associated when hospital controls were used: 1.84 (1.14-2.93). No significant interactions were present with previous chronic renal failure, other possible causes of ARF or whether the diagnosis was primary or secondary. There is an approximate doubling of the risk of hospitalization for ARF with use of oral NSAIDs.

Objective: To evaluate the relation between topically applied non-steroidal anti-inflammatory drugs and upper gastrointestinal bleeding and perforation. Design: A case-control study with 1103 patients admitted to hospital for upper gastrointestinal bleeding or perforation between January 1990 and December 1992 (cases). Two different control groups were used, with six community controls and with two hospital controls for each case. Previous exposure to topical and oral non-steroidal anti-inflammatory drugs and ulcer healing drugs was assessed. Study population--The population of 319465 people who were resident in Tayside and were registered with a Tayside general practitioner between January 1989 and October 1994. A record linkage database containing all data on hospital events and dispensed drugs between 1989 and 1992 was used for this population. Main outcome measures: Unadjusted and adjusted odds ratios of exposure in those admitted to hospital compared with controls. Results: Significant unadjusted associations were detected between all three classes of drug and upper gastrointestinal complications. The significant association detected for topical non-steroidal anti-inflammatory drugs was no longer evident in analyses which adjusted for the confounding effect of concomitant exposure to oral anti-inflammatories and ulcer healing drugs (odds ratio=1.45; 95% confidence interval 0.84 to 2.50 with community controls; 1.06; 0.60 to 1.88 with hospital controls). Conclusion: In this study topical non-steroidal anti-inflammatory drugs were not significantly associated with upper gastrointestinal bleeding and perforation after adjustment for the confounding effects of concomitant use of oral anti-inflammatories and ulcer healing drugs.

Many health promotion programmes for physical activity are targeted during childhood and adolescence, as these life stages are seen to be important for the development of health behaviours. The underlying assumption is that physical activity will become habitual or “track” (ie will be a stable aspect of behaviour between different ages). Given the considerable variation between studies in the extent to which physical activity demonstrates tracking, this systematic review examined studies that provided data on the tracking of physical …

To the Editor: In a recent letter to Diabetologia [1], D. Raccah questions the value of several recent observational studies, discussed by J. A. Tayek [2], that have identified increased cardiovascular mortality among type 2 diabetic patients treated with sulphonylureas compared with patients prescribed other therapies (such as metformin). He argues that prospective, randomised clinical trials are necessary to establish whether sulphonylureas are linked with excess mortality. We would like to clarify some of his misunderstandings surrounding our own observational study [3]. We used the databases of the Diabetes Audit and Research in Tayside, Scotland (DARTS)/the Medicines Monitoring Unit (MEMO) Collaboration, which contain comprehensive clinical data for all patients with type 2 diabetes in this region. Our study was retrospective only in the sense that it used ‘historical’ data collected (at the time) for patients from 1993 onwards. In fact, our study was a prospective cohort study that was specifically designed to evaluate cardiovascular risk (in contrast to Raccah’s assertion). We acknowledge that, in observational research, the distribution of confounding factors may vary between different comparison groups. In our study, patients in the sulphonylurea cohort did appear to have an increased cardiovascular risk at baseline compared with the other patients. However, there are statistical techniques that deal with such issues of confounding. We found increased cardiovascular risks associated with sulphonylurea use even after adjusting for confounding (as did others). We feel that Raccah has not made this sufficiently clear in his letter. Observational research can be difficult to interpret, particularly where there is concern as to whether these differences have been sufficiently adjusted for. However, it is essential that we do not disregard the signals generated by the observational studies that Raccah has described. Unfortunately, it would now be difficult to conduct further clinical trials in high-risk patient groups on a drug that is so widely used. This is why well-conducted observational studies (like our own) are essential to keep the debate alive.

To compare risks of cardiovascular outcomes between patients with type 2 diabetes and patients with established coronary heart disease.Cross sectional study and cohort study using routinely collected datasets.Tayside, Scotland (population 400 000) during 1988-95.In the cross sectional study, among patients aged 45-64, 1155 with type 2 diabetes were compared with 1347 who had had a myocardial infarction in the preceding 8 years. In the cohort study 3477 patients of all ages with newly diagnosed type 2 diabetes were compared with 7414 patients who had just had a myocardial infarction.Risk ratios for death from all causes, cardiovascular death, and hospital admission for myocardial infarction were calculated by Cox proportional hazards analysis and adjusted for age and sex.In the cross sectional study the adjusted risk ratio for death from all causes for patients who had myocardial infarction compared with those with diabetes was 1.33 (95% confidence interval 1.14 to 1.55) [corrected], and the risk ratio for hospital admission for myocardial infarction was 2.27 (1.82 to 2.83) [corrected]. In the cohort study, patients who had just had a myocardial infarction had a higher risk of death from all causes (adjusted risk ratio 1.35 (1.25 to 1.44)), cardiovascular death (2.93 (2.54 to 3.41)), and hospital admission for myocardial infarction (3.10 (2.57 to 3.73)).Patients with type 2 diabetes were at lower risk of cardiovascular outcomes than patients with established coronary heart disease.