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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.

Background To evaluate the adverse events profile of oral prednisolone among adult asthma patients in the UK. Methods 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). Results 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. Conclusion Oral prednisolone use is associated with infections, gastrointestinal, neuropsychiatric, ocular, cardiovascular, metabolic, and bone-related complications among adult asthma patients.

The objective of this study was to explore the association between use of metformin or other antidiabetic drugs, diabetes, and the risk of pancreatic cancer. We conducted a case-control study using the UK-based General Practice Research Database (GPRD). Cases had a first-time diagnosis of pancreatic cancer, and six controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD before the index date. Results were further adjusted in multivariate logistic regression analyses for potential confounders such as body mass index, smoking, alcohol consumption, and diabetes duration. In all, 2,763 case patients with a recorded diagnosis of pancreatic cancer were identified. Mean age ± s.d. was 69.5 ± 11.0 years. Long-term use (≥ 30 prescriptions) of metformin was not associated with a materially altered risk of pancreatic cancer (adjusted odds ratio (adj. OR): 0.87, 95% confidence interval (CI): 0.59-1.29), but there was a suggestion of effect modification by gender, as long-term use of metformin was linked to a decreased risk in women (adj. OR: 0.43, 95% CI: 0.23-0.80). Both use of sulfonylureas (≥ 30 prescriptions, adj. OR: 1.90, 95% CI: 1.32-2.74) and of insulin (≥ 40 prescriptions, adj. OR: 2.29, 95% CI: 1.34-3.92) were associated with an increased risk of pancreatic cancer. Use of metformin was associated with a decreased risk of pancreatic cancer in women only, whereas use of sulfonylureas and of insulin was associated with an increased risk of pancreatic cancer.

Subjective tinnitus is a common symptom with potentially negative impact on quality of life. More research is required to gain a deeper understanding of the disease and its clinical presentation. To estimate the incidence of tinnitus and to describe patient-related characteristics such as lifestyle factors and comorbidities. Using the Clinical Practice Research Datalink, we calculated incidence rates of first-time diagnosed tinnitus in an adult population between 2000 and 2016. We stratified incidence rates by sex, age, and year of diagnosis. Additionally, we performed a 1:1 matched case-control study comparing body mass index, lifestyle factors and selected comorbidities between patients with incident tinnitus and tinnitus-free controls. We identified 109 783 adults with a first-time diagnosis of tinnitus between 2000 and 2016, yielding an overall age-standardized incidence rate of 25.0 new tinnitus cases per 10,000 person-years (95% CI: 24.6-25.5). There was a steady increase in tinnitus incidence throughout the study period. Approximately 80% of tinnitus cases were diagnosed at age 40 years or older. We observed the highest incidence rate in individuals aged 60-69 years (41.2 per 10,000 person-years, 95% CI: 40.7-41.7). Smokers and alcohol drinkers were at lower risk of being diagnosed with tinnitus compared with non-smokers and non-drinkers, respectively. The occurrence of tinnitus was strongly associated with a recent diagnosis of several otological and vestibular disorders as well as head and neck disorders. The present observational study found an increasing incidence of tinnitus over time, emphasizing the continuously growing health burden. The findings on patient characteristics, lifestyle factors, and selected comorbidities contribute to a better understanding of risk factors for tinnitus.

Glucocorticoids, the class of steroids used in management of asthma, have been observed to be associated with adverse events such as increased coagulation and inhibition of fibrinolysis. This study evaluated the risk of VTE in relation to the use of glucocorticoids in patients with asthma. We conducted a nested case-control study among patients aged 20-59 years with asthma who received at least one glucocorticoid prescription during 1995-2015 in the UK-based Clinical Practice Research Datalink GOLD. We used descriptive analyses and conditional logistic regression to evaluate the risk of VTE associated with glucocorticoid use. The adjusted ORs (aORs) (95% CI) for VTE in patients exposed to glucocorticoids were 1.9 (1.6-2.3), 1.4 (1.1-1.8), and 1.2 (0.9-1.5) for current, recent, and past glucocorticoid users, respectively, compared to the unexposed. The aORs (95% CI) for VTE in patients exposed to systemic glucocorticoid and inhaled glucocorticoids, compared to the unexposed, were 3.5 (2.7-4.5) and 1.5 (1.3-1.8), respectively. Current and systemic glucocorticoid use was associated with a dose-response increased risk of incident idiopathic VTE.

Background Previous studies suggested an elevated risk of venous thromboembolism (VTE) among patients with type 2 diabetes mellitus (T2DM), with a possible sex difference. The impact of glycemic control on the risk of VTE is unclear. Our objective was to analyze the association between glycemic control and the risk of unprovoked (idiopathic) VTE in men and women with T2DM. Methods We conducted a nested case–control analysis (1:4 matching) within a cohort of patients with incident T2DM between 1995 and 2019 using data from the CPRD GOLD. We excluded patients with known risk factors for VTE prior to onset of DM. Cases were T2DM patients with an unprovoked treated VTE. The exposure of interest was glycemic control measured as HbA1c levels. We conducted conditional logistic regression analyses adjusted for several confounders. Results We identified 2′653 VTE cases and 10′612 controls (53.1% females). We found no association between the HbA1c level and the risk of VTE in our analyses. However, when the most recent HbA1c value was recorded within 90 days before the index date, women with HbA1c levels > 7.0% had a 36–55% increased relative risk of VTE when compared to women with HbA1c > 6.5–7.0%. Conclusions Our study raises the possibility that female T2DM patients with HbA1c levels > 7% may have a slightly higher risk for unprovoked VTE compared to women with HbA1c levels > 6.5–7.0%. This increase may not be causal and may reflect differences in life style or other characteristics. We observed no effect of glycemic control on the risk of VTE in men.

Metformin is a commonly used oral antidiabetic agent that has been associated with decreased cancer risk. However, data regarding the association between metformin use and the risk of meningioma are unavailable. We conducted a matched case-control analysis using data from the U.K.-based Clinical Practice Research Datalink (CPRD) to analyse diabetes status, duration of diabetes, glycemic control, and use of metformin, sulfonylureas, and insulin in relation to the risk of meningioma. We conducted conditional logistic regression analyses to determine relative risks, estimated as odds ratios (ORs) with 95% confidence intervals (CIs) and adjusted for body mass index, smoking, history of arterial hypertension, myocardial infarction, and use of estrogens (among women). We identified 2,027 meningioma cases and 20,269 controls. For diabetes there was the suggestion of an inverse association with meningioma (OR = 0.89; 95%CI = 0.74-1.07), which was driven by an inverse relation among women (OR = 0.78; 95%CI = 0.62-0.98), in whom we also noted a suggestive inverse association with duration of diabetes (p-value for trend = 0.071). For metformin there was a suggestive positive relation, particularly after matching on duration of diabetes and HbA1c level (OR = 1.64; 95%CI = 0.89-3.04). Sulfonylureas showed no clear association (OR = 0.91; 95%CI = 0.46-1.80). For insulin there was the suggestion of an inverse relation, in particular when comparing a high vs. low number of prescriptions (OR = 0.58; 95%CI = 0.18-1.83). Further studies are needed to solidify a possible inverse association between diabetes and meningioma risk and to clarify the role of antidiabetics in this context.

Background Recent studies suggest an increased risk of malignancy in patients with inflammatory bowel disease (IBD), although the findings were inconsistent. We used data from the clinical practice research datalink (CPRD) to further examine this association. Methods Patients with a first-time diagnosis of IBD were randomly matched to an equally sized IBD-free comparison group. Multivariable adjusted hazard ratios (AHRs) for cancer risk were estimated using Cox’s proportional hazard regression. A nested case–control analysis comprising IBD patients only was then conducted using conditional logistic regression to estimate the risk of cancer development according to IBD severity, disease duration and IBD therapy. Results We identified 1077 cancers among 39,294 IBD or IBD-free patients followed between 1995 and 2012. There was no association between IBD and overall risk of cancer [AHR 1.11, 95 % confidence interval (CI) 0.98–1.25], but a borderline increase in the risk of lymphoproliferative malignancies was observed in patients with IBD (AHR 1.49, 95 % CI 1.00–2.23). Aminosalicylate use was significantly associated with reduced risk of all cancers [adjusted odds ratio (AOR), 0.72, 95 % CI 0.54–0.96], of intestinal cancer (AOR 0.33, 95 % 0.12–0.89) and of prostate cancer (AOR 0.32, 95 % 0.13–0.80). Conclusions There was no increased risk of cancer overall in individuals with IBD compared to IBD-free individuals. Consistent with previous findings, a reduction in cancer risk was observed in IBD patients using aminosalicylates, with a substantial reduction in prostate cancer risk. Further large-scale studies examining the relationship between IBD therapy and cancer risk appear to be warranted.

Validation studies of the Clinical Practice Research Datalink (CPRD) Aurum database in the UK are critical for making decisions about its suitability and validity for research purposes. To examine data source agreement of myocardial infarction (MI) diagnoses recorded in CPRD Aurum compared with linked Hospital Episode Statistics (HES) data. This comparison provides information on CPRD Aurum data correctness (accuracy, validity) and completeness (presence, missingness). Patients with MI diagnoses recorded in either data source were selected from a random sample of 50,000 patients in CPRD Aurum with HES linkage (1997-2017). Correctness was defined as the proportion of MI cases in CPRD Aurum with a concordant MI diagnosis recorded in HES or with strong supporting evidence in either data source. Completeness was defined as the proportion of patients with primary HES-coded MIs with strong supporting evidence that were also present in CPRD Aurum. There were 1260 patients with MI recorded in the CPRD Aurum sample. The overall correctness of the recorded MI diagnoses was 94%: 986 patients (78%) had concordant diagnoses in HES within 90 days; 123 (10%) were concordant with HES, but with an inconclusive date and another 71 (6%) had strong supporting evidence for being a true MI case. There were 1125 patients with MI recorded in HES primary diagnosis fields with strong supporting evidence in either data source. Of these, 880 (78%) were present in CPRD Aurum, with completeness somewhat higher in more recent years. MI diagnoses recorded in CPRD Aurum were highly likely to be correct, supporting its use in clinical research studies. Completeness was lower, indicating the need for data linkage for some studies.

Assessments of strengths and limitations of new data sources are critical for making decisions about suitability for specific research questions. For some studies, it is necessary to capture a drug's indication for use. To assess the presence of indications for prescription use in Clinical Practice Research Datalink (CPRD) Aurum (January 1988-June 2021) by describing the proportion of men in CPRD Aurum who had a recorded indication for use of prescriptions for 5-alpha reductase inhibitors (5-ARI), alpha blockers (AB), or tadalafil, which have multiple indications. From a random sample of 154 practices of CPRD Aurum data, we selected 85,597 male patients with a prescription for a 5-ARI, an AB, or tadalafil. Among these patients, we described presence of codes indicating whether the patient had benign prostatic hyperplasia, hypertension, erectile dysfunction, or alopecia using three indication definitions: narrow (specific diagnoses recorded within one year before and up to 90 days after the prescription), broad (specific diagnoses or supporting clinical codes in the time period described above), and widest (diagnoses or supporting codes recorded at any time before the prescription and up to 90 days after the prescription). Using the narrow indication definition limited to diagnoses only, 39,861 (46.6%) patients' records contained an indication for use. The broad definitions, which additionally included supporting codes, captured indications for 62,912 (73.5%) patients and the widest definition, which additionally included supporting codes and all available data before the first prescription date, captured indications for 71,478 (83.5%) patients. Indications were present more often for prescriptions in 2005 and later (85.9%). The findings of this assessment suggest that CPRD Aurum can be used for studies that require information on treatment indications for BPH and potentially for treatments of other chronic diseases managed in the primary care setting.