Josie Evans

Metformin and reduced risk of cancer in diabetic patients

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.nnWe 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.5nnFrom 314 127 people who were resident (or died) in Tayside in …

Effect of Metformin on Mortality in Patients With Heart Failure and Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (DM) plus chronic heart failure (CHF) is a common but lethal combination and therapeutic options are limited. Metformin is perceived as being relatively contraindicated in this context, although mounting evidence indicates that it may be beneficial. This study was carried out to investigate the use of metformin therapy for treating patients with DM and CHF in a large population-based cohort study. The Health Informatics Centre-dispensed prescribing database for the population of Tayside, Scotland (population ∼400,000) was linked to the Diabetes Audit and Research in Tayside Scotland (DARTS) information system. Patients with DM and incident CHF from 1994 to 2003 receiving oral hypoglycemic agents but not insulin were identified. Cox regression was used to assess differences in all-cause mortality rates between patients prescribed metformin and patients prescribed sulfonylureas with adjustment for co-morbidities and other therapies. Four hundred twenty-two study subjects (mean ± SD 75.4 ± 0.5 years of age, 46.2% women) were identified: metformin monotherapy (n = 68, mean age 75.5 ± 1.1 years, 48.5% women), sulfonylurea monotherapy (n = 217, mean age 76.7 ± 0.7 years, 45.2% women), and combination (n = 137, mean age, 73.4 ± 0.7 years, 46.7% women). Fewer deaths occurred in metformin users, alone or in combination with sulfonylureas, compared to the sulfonylurea monotherapy cohort at 1 year (0.59, 95% confidence interval 0.36 to 0.96) and over long-term follow up (0.67, 95% confidence interval 0.51 to 0.88). In conclusion, this large observational data suggest that metformin may be beneficial in patients with CHF and DM. These findings need to be verified by a prospective clinical trial.

Comparison of cardiovascular risk between patients with type 2 diabetes and those who had had a myocardial infarction: cross sectional and cohort studies

Abstract Objective: To compare risks of cardiovascular outcomes between patients with type 2 diabetes and patients with established coronary heart disease. Design: Cross sectional study and cohort study using routinely collected datasets. Setting: Tayside, Scotland (population 400 000) during 1988-95. Subjects: 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. Main outcome measures: 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. Results: In the cross sectional study the adjusted risk ratio for death from all causes was 2.27 (95% confidence interval 1.82 to 2.83) for patients who had had myocardial infarction compared with those with diabetes, and the risk ratio for hospital admission for myocardial infarction was 1.33 (1.14 to 1.55). 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)). Conclusions: Patients with type 2 diabetes were at lower risk of cardiovascular outcomes than patients with established coronary heart disease. What is already known on this topic A recent influential study suggested that patients with type 2 diabetes without established cardiovascular disease have as high a risk of cardiovascular events and death as non-diabetic patients who have had a myocardial infarction Some clinicians therefore advocate aggressive treatment of cardiovascular risk factors in the presence of diabetes What this study adds Patients with type 2 diabetes are at lower risk of death from all causes or cardiovascular causes and of hospital admission for myocardial infarction than patients with established coronary heart disease

Non-steroidal anti-inflammatory drugs are associated with emergency admission to hospital for colitis due to inflammatory bowel disease.

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.

Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study

Abstract 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.

Prevalence and outcomes of use of potentially inappropriate medicines in older people: cohort study stratified by residence in nursing home or in the community

Objectives To compare the prevalence of use of potentially inappropriate medicines (PIMs) between older patients living in their own homes versus those living in nursing or residential homes, and to test the association between exposure to PIMs and mortality. Design Cohort study stratified by place of residence. Setting Tayside, Scotland. Participants All people aged between 66 and 99u2005years who were resident or died in Tayside from 2005 to 2006. Main outcome measures The exposure variable was PIM use as defined by Beers Criteria. All cause mortality was the main outcome measure. Results 70u2008299 people were enrolled in the cohort of whom 96% were exposed to any medicine and 31% received a PIM. Place of residence was not associated with overall risk of receiving PIMs, adjusted OR 0.94, 95% CI 0.87 to 1.01. Exposure to five of the PIMs (including long-acting benzodiazepines) was significantly higher in nursing homes whereas exposure to five other PIMs (including amitriptyline and NSAIDs) was significantly lower. Exposure to PIMs was similar (20–46%) across all 71 general practices in Tayside and was not associated with increased risk of mortality after adjustment for age, gender and polypharmacy (adjusted OR 0.98, 95% CI 0.92 to 1.05). Conclusions The authors question the validity of the full list of PIMs as an indicator of safety of medicines in older people because one-third of the population is exposed with little practice variation and no significant impact on mortality. Future studies should focus on management of a shorter list of genuinely high-risk medicines.

Factors influencing the use of complementary and alternative medicine and whether patients inform their primary care physician

OBJECTIVESnUse of complementary and alternative medicines (CAMs) is widespread. Several studies have explored why individuals chose to use CAM but there are fewer data to explain how its use dovetails with conventional medicine. This study aimed to determine the prevalence of CAM use in the adult population in Australia and the proportion that seek advice or tell their primary care physician after CAM use, and also to investigate which demographic characteristics, health behaviours and health status are associated with CAM use and disclosure.nnnDESIGNnA cross sectional survey.nnnMETHODSna random sample of 1261 adults was interviewed as part of 2010 Queensland Social Survey, which contained questions about CAM use, frequency of use, types of CAM used, reasons for use, discussing and reporting CAM use with the doctor and confidence in CAM use. Relationships were explored using bivariate and multiple logistic regression.nnnMAIN OUTCOME MEASURESnuse of CAM; sought advice from doctor before CAM use; informed doctor after CAM use.nnnRESULTSn61.7% of respondents had used self-prescribed CAM or visited a CAM practitioner. Being female and being younger predicted CAM use. Being male and in better health predicted seeking advice from the doctor before and also after CAM use.nnnCONCLUSIONnOur results confirm the relatively high use of CAM in Queensland, Australia and found that a significant proportion of people did not seek advice from their primary care physician before using CAM, or disclose its use afterwards. These factors should be taken into account in the doctor-patient consultation.

A 12-year follow-up study of all-cause and cardiovascular mortality among 10 532 people newly diagnosed with Type 2 diabetes in Tayside, Scotland

Diabet. Med. 27, 1124–1129 (2010)

Adherence to oral hypoglycaemic agents prior to insulin therapy in Type 2 diabetes

Aim To investigate whether patients require insulin as a result of poor adherence to oral hypoglycaemic agents (OHAs) in Type 2 diabetes.

Drugs dispensed in primary care during pregnancy: a record-linkage analysis in Tayside, Scotland.

AbstractBackground: 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.n Objective: To investigate the patterns of prescribing of drugs to women who gave birth in Tayside, Scotland, in 2007.n 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.n 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.n 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.