Objectives
To explore the risk of developing Alzheimer's disease (AD) in individuals with diabetes mellitus treated with metformin or other antidiabetic drugs.
Design
Case–control study.
Setting
The ...United Kingdom–based General Practice Research Database (GPRD), a well‐established primary care database.
Participants
Seven thousand eighty‐six individuals aged 65 and older with an incident diagnosis of AD identified between 1998 and 2008 and the same number of matched controls without dementia. Matching criteria were age, sex, general practice, calendar time, and years of history in the database.
Measurements
Comparison of previous use of metformin or other antidiabetic drugs between cases and controls and calculation of corresponding odds ratios (ORs) with 95% confidence intervals (CIs), using conditional logistic regression. Risk estimates were stratified according to duration of use and adjusted for potential confounders.
Results
As compared with nonusers, long‐term users of 60 or more metformin prescriptions were at greater risk of developing AD (adjusted OR (AOR) = 1.71, 95% CI = 1.12–2.60), but there was no consistent trend with increasing number of prescriptions. Long‐term use of other antidiabetic drugs such as sulfonylureas (AOR = 1.01, 95% CI = 0.72–1.42), thiazolidinediones (AOR = 0.87, 95% CI = 0.31–2.40), or insulin (AOR = 1.01, 95% CI = 0.58–1.73) was not related to an altered risk of developing AD.
Conclusion
Long‐term use of sulfonylureas, thiazolidinediones, or insulin was not associated with an altered risk of developing AD. There was a suggestion of a slightly higher risk of AD in long‐term users of metformin.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening mucocutaneous diseases. SJS/TEN mostly manifest as a reaction to new drug use, but little is known ...about their incidence and epidemiology. We conducted a large observational study on the epidemiology of SJS/TEN using data from the UK-based Clinical Practice Research Datalink. Among 551 validated SJS/TEN patients, we calculated an incidence rate of 5.76 SJS/TEN cases per million person-years between 1995 and 2013, which was consistent throughout the study period and was highest in patients aged 1–10 years and 80 years or older. Within a 1:4 matched case-control analysis, black and Asian patients were at a 2-fold risk of SJS/TEN when compared with white patients. Among patients with epilepsy and gout, odds ratios for SJS/TEN were significantly increased only in the presence of recent new drug treatment with antiepileptics or allopurinol, respectively. We observed statistically significant associations between SJS/TEN and pre-existing depression, lupus erythematosus, recent pneumonia, chronic kidney disease, and active cancer, but confounding by drug use needs to be followed up. This large and longitudinal observational study on the epidemiology of SJS/TEN contributes to the understanding of this still underinvestigated severe skin disease in a European and largely white study population.
Abstract
Context
Diabetes mellitus (DM) has been associated with an increased risk of fractures. However, the effect of glycemic control on the risk of fracture is not well understood.
Objective
To ...evaluate the association between glycemic control and the risk of low-trauma fractures in patients with type 1 DM (T1DM) and type 2 DM (T2DM).
Design
Nested case-control analysis.
Setting
UK-based Clinical Practice Research Datalink.
Patients or Other Participants
The study population was patients whose T1DM or T2DM had been newly diagnosed between 1995 and 2015. The cases were patients with a low-trauma fracture after DM onset. We matched four controls to each case by age, sex, general practice, fracture date, and DM type and duration.
Statistical Analysis
Conditional logistic regression analyses were performed, adjusted for covariates, including body mass index, smoking, DM complications and medications.
Results
The study population included 3329 patients with T1DM and 44,275 patients with T2DM. The median duration between DM onset and fracture date was 4.5 years for both T1DM and T2DM. The risk of fracture was increased in the patients with T1DM with a mean hemoglobin A1c >8.0% (adjusted OR, 1.39; 95% CI, 1.06 to 1.83) compared with those patients with T1DM and a mean hemoglobin A1c ≤7.0%. No such effect was found in the patients with T2DM. Independently of glycemic control, the risk of fracture was elevated in patients with T2DM and the current use of rosiglitazone and pioglitazone.
Conclusions
The effect of glycemic control on the risk of low-trauma fracture differs between patients with T1DM and T2DM. Poor glycemic control increased the risk of fractures in patients with T1DM but not in those with T2DM.
The effect of glycemic control on fracture risk differed between patients with T1DM and T2DM with short-term disease. Poor glycemic control increased the risk of fracture in T1DM but not T2DM.
Summary
Objective
Older antiepileptic drugs (AEDs) are known to cause Stevens‐Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, evidence for newer AED is sparse. We quantified risks ...of SJS/TEN in association with use of all AEDs in the United Kingdom.
Methods
In a matched case‐control study of 480 previously validated SJS/TEN cases (1995–2013) we used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and calculated absolute risks of SJS/TEN within separate cohorts of new users of 28 AEDs. We assessed causality between drugs and SJS/TEN in each exposed case, using an adapted version of the algorithm of drug causality for epidermal necrolysis (ALDEN) score.
Results
We observed a strong association between SJS/TEN and new use of carbamazepine (OR 92.57, 95% CI 19.89–∞), phenytoin (OR 49.96, 95% CI 10.13–∞), and lamotrigine (OR 26.90, 95% CI 4.88–∞), where causality, according to the ALDEN score, was very probable or probable for most exposed cases. Absolute risks for SJS/TEN were highest for phenytoin (45.86 cases/100,000 exposed), lamotrigine (44.17 cases/100,000 exposed), and carbamazepine (20.38 cases/100,000 exposed). Despite increased ORs for valproate (40,941 exposed), gabapentin (116,037 exposed), pregabalin (59,967 exposed), and clobazam (4,300 exposed), ALDEN suggested no causal association. There were no observed cases of SJS/TEN among new users of levetiracetam (n = 96,77), clonazepam (n = 18,075), or topiramate (n = 11,307).
Significance
The results of our study are consistent with those of previous studies of SJS/TEN, which found increased risks of SJS/TEN in new use of carbamazepine, phenytoin, and lamotrigine. Despite frequent use, no ALDEN‐score confirmed cases were observed in new users of valproate, gabapentin, pregabalin, levetiracetam, topiramate, or clonazepam.
Antidepressants and the risk of suicidal behaviors Jick, Hershel; Kaye, James A; Jick, Susan S
JAMA : the journal of the American Medical Association,
07/2004, Letnik:
292, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The relation between use of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and suicidal ideation and behaviors has received considerable public attention recently. The ...use of such drugs among teenagers has been of particular concern.
To estimate the relative risks (RRs) of nonfatal suicidal behavior in patients starting treatment with 1 of 3 antidepressant drugs compared with patients starting treatment with dothiepin.
Matched case-control study of patients treated in UK general practices using the UK General Practice Research Database for 1993-1999.
The base population included 159,810 users of the 4 antidepressant drugs. Participants could have used only 1 of these antidepressants and had to have received at least 1 prescription for the study antidepressant within 90 days before their index date (the date of suicidal behavior or ideation for cases and the same date for matched controls).
Frequency of first-time exposure to amitriptyline, fluoxetine, paroxetine, and dothiepin of patients with a recorded diagnosis of first-time nonfatal suicidal behavior or suicide compared with comparable patients who did not exhibit suicidal behavior.
After controlling for age, sex, calendar time, and time from first antidepressant prescription to the onset of suicidal behavior, the relative risks for newly diagnosed nonfatal suicidal behavior in 555 cases and 2062 controls were 0.83 (95% confidence interval, CI 0.61-1.13) for amitriptyline, 1.16 (95% CI, 0.90-1.50) for fluoxetine, and 1.29 (95% CI, 0.97-1.70) for paroxetine compared with those using dothiepin. The RR for suicidal behavior among patients first prescribed an antidepressant within 1 to 9 days before their index date was 4.07 (95% CI, 2.89-5.74) compared with patients who were first prescribed an antidepressant 90 days or more before their index date. Time since first antidepressant prescription was not, however, a confounder of the relation between specific antidepressants and suicidal behavior since its relation to suicidal behavior was not materially different among users of the 4 study drugs. Similarly for fatal suicide, the RR among patients who were first prescribed an antidepressant within 1 to 9 days before their index date was 38.0 (95% CI, 6.2-231) compared with those who were first prescribed an antidepressant 90 days or more before their index date. There were no significant associations between the use of a particular study antidepressant and the risk of suicide.
The risk of suicidal behavior after starting antidepressant treatment is similar among users of amitriptyline, fluoxetine, and paroxetine compared with the risk among users of dothiepin. The risk of suicidal behavior is increased in the first month after starting antidepressants, especially during the first 1 to 9 days. A possible small increase in risk (bordering statistical significance) among those starting the newest antidepressant, paroxetine, is of a magnitude that could readily be due to uncontrolled confounding by severity of depression. Based on limited information, we also conclude that there is no substantial difference in effect of the 4 drugs on people aged 10 to 19 years.
An increased risk of multiple sclerosis among smokers has been found in several prospective epidemiological studies. The association between smoking and progression of multiple sclerosis has not been ...examined. We identified patients who had a first multiple sclerosis diagnosis recorded in the General Practice Research Database (GPRD) between January 1993 and December 2000. Their diagnosis and date of first symptoms were confirmed through examination of medical records. Smoking status was obtained from the computer records. To assess the association between smoking and risk of multiple sclerosis, we conducted a case–control study nested in the GPRD. Up to 10 controls per case were randomly selected, matched on age, sex, practice, date of joining the practice and availability of smoking data. To assess the association between smoking and progression of multiple sclerosis, we conducted a cohort study of multiple sclerosis cases with a relapsing–remitting onset. Our nested case–control study included 201 cases of multiple sclerosis and 1913 controls. The odds ratio 95% confidence interval (CI) of multiple sclerosis was 1.3 (1.0–1.7) for ever smokers compared with never smokers. Our cohort study included 179 cases with a mean (median) length of follow-up of 5.3 (5.3) years. The hazard ratio of secondary progression was 3.6 (95% CI 1.3–9.9) for ever smokers compared with never smokers. These results support the hypothesis that cigarette smoking is associated with an increased risk of multiple sclerosis, and suggest that smoking may be a risk factor for transforming a relapsing–remitting clinical course into a secondary progressive course.
To evaluate the adverse events profile of oral prednisolone among adult asthma patients in the UK.
Using data from the UK-based Clinical Practice Research Datalink, we conducted a series of cohort ...studies to quantify incidence rates and incidence rate ratios, and a series of nested case-control analyses to estimate crude and adjusted odds ratios, of 11 different potential corticosteroid-related adverse events (bone-related conditions, hypertension, peptic ulcer, severe infections, herpes zoster, diabetes mellitus type 2, cataract, glaucoma, chronic kidney disease, affective disorders, and cardiovascular events).
Between 165,900 and 269,368 asthma patients were included in each of the 11 cohorts, of whom between 836 and 16,192 developed an outcome of interest. Incidence rates per 1000 person-years of potential corticosteroid-related adverse events in patients with new current use of oral prednisolone ranged from 1.4 (95% confidence interval CI, 1.0-1.8) for peptic ulcer to 78.0 (95% CI, 74.8-81.2) for severe infections. After adjusting for confounding, current oral prednisolone use was most strongly associated with an increased risk of severe infection, compared with non-use of prednisolone; OR 2.16 (95% CI, 2.05-2.27). There were smaller elevated risks of peptic ulcer, affective disorders, and cataract at higher doses, and marginally increased risks of herpes zoster, cardiovascular events, diabetes mellitus type 2, and bone related conditions, compared with non-use of prednisolone. We did not observe an association between oral prednisolone use and glaucoma, chronic kidney disease, or hypertension.
Oral prednisolone use is associated with infections, gastrointestinal, neuropsychiatric, ocular, cardiovascular, metabolic, and bone-related complications among adult asthma patients.
COPD and the Risk of Depression SCHNEIDER, Cornelia; JICK, Susan S; BOTHNER, Ulrich ...
Chest,
02/2010, Letnik:
137, Številka:
2
Journal Article
Recenzirano
Background: Chronic comorbidities are often associated with depression. Most previous studies exploring the association between COPD
and depression were rather small and based on a cross-sectional ...study design. We conducted a large population-based study
on the risk of developing an incident depression diagnosis in association with a previous COPD diagnosis.
Methods: We used the UK-based General Practice Research Database to assess and compare the prevalence of a history of depression and
to quantify the risk of developing incident depression in patients with COPD and patients without COPD between 1995 and 2005.
We conducted a nested case-control analysis, matching up to four patients who did not develop depression for each case patient
with depression, to further analyze the impact of COPD severity.
Results: In a study population of 35,722 patients with COPD and 35,722 patients without COPD, the prevalence of diagnosed depression
prior to the first COPD diagnosis was higher in the population with COPD (23.1%) than among patients without COPD (16.8%).
The incidence rate of a new-onset diagnosis of depression after the first COPD diagnosis was 16.2/1,000 person-years (py)
in the COPD group, whereas it was only 9.4/1,000 py in the COPD-free comparison group. In the nested case-control analysis,
patients with severe COPD had the highest risk of developing depression (odds ratio, 2.01; 95% CI, 1.45-2.78).
Conclusion: This large observational study provides further evidence that patients with COPD are at an increased risk of developing depression.
OBJECTIVE: To evaluate whether use of oral hypoglycemic agents is associated with an altered breast cancer risk in women. RESEARCH DESIGN AND METHODS: Using the U.K.-based General Practice Research ...Database, we conducted a nested case-control analysis among 22,621 female users of oral antidiabetes drugs with type 2 diabetes. We evaluated whether they had an altered risk of breast cancer in relation to use of various types of oral hypoglycemic agents. Case and control patients with a recorded diagnosis of type 2 diabetes were matched on age, calendar time, and general practice, and the multivariate conditional logistic regression analyses were further adjusted for use of oral antidiabetes drugs, insulin, estrogens, smoking BMI, diabetes duration, and HbA1c (A1C). RESULTS: We identified 305 case patients with a recorded incident diagnosis of breast cancer. The mean ± SD age was 67.5 ± 10.5 years at the time of the cancer diagnosis. Long-term use of ≥40 prescriptions (>5 years) of metformin, based on 17 exposed case patients and 120 exposed control patients, was associated with an adjusted odds ratio of 0.44 (95% CI 0.24-0.82) for developing breast cancer compared with no use of metformin. Neither short-term metformin use nor use of sulfonylureas or other antidiabetes drugs was associated with a materially altered risk for breast cancer. CONCLUSIONS: A decreased risk of breast cancer was observed in female patients with type 2 diabetes using metformin on a long-term basis.
Objective
Use of diuretics has been associated with an increased risk of gout. Data on different types of diuretics are scarce. We undertook this study to investigate the association between use of ...loop diuretics, thiazide or thiazide‐like diuretics, and potassium‐sparing agents and the risk of developing incident gout.
Methods
We conducted a retrospective population‐based case–control analysis using the General Practice Research Database established in the UK. We identified case patients who were diagnosed as having incident gout between 1990 and 2010. One control patient was matched to each case patient for age, sex, general practice, calendar time, and years of active history in the database. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), and we adjusted for potential confounders.
Results
We identified 91,530 incident cases of gout and the same number of matched controls. Compared to past use of diuretics from each respective drug class, adjusted ORs for current use of loop diuretics, thiazide diuretics, thiazide‐like diuretics, and potassium‐sparing diuretics were 2.64 (95% CI 2.47–2.83), 1.70 (95% CI 1.62–1.79), 2.30 (95% CI 1.95–2.70), and 1.06 (95% CI 0.91–1.23), respectively. Combined use of loop diuretics and thiazide diuretics was associated with the highest relative risk estimates of gout (adjusted OR 4.65 95% CI 3.51–6.16). Current use of calcium channel blockers or losartan slightly attenuated the risk of gout in patients who took diuretics.
Conclusion
Use of loop diuretics, thiazide diuretics, and thiazide‐like diuretics was associated with an increased risk of incident gout, although use of potassium‐sparing agents was not.
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