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Objectives To evaluate the potential of blood glucose levels and weight change before the onset of diabetes as predictors of pancreatic cancer among subjects with new-onset diabetes, that is, cancer-related diabetes versus normal type 2 diabetes. Methods We conducted a case-control study among subjects with new diabetes in the United Kingdom-based Clinical Practice Research Datalink. Cases were pancreatic cancer subjects with diabetes for ≤2 years before the cancer diagnosis (i.e., cancer-related diabetes). Controls were cancer-free, type 2 diabetic subjects matched to cases on age, sex, and diabetes duration. We calculated adjusted odds ratios (aORs) for pancreatic cancer as a function of both weight change and blood glucose before the onset of diabetes. Results Weight loss of 10.0%–14.9% at diabetes onset was associated with an aOR for pancreatic cancer of 3.58 (95% CI 2.31–5.54), loss of ≥15.0%, with an aOR of 4.56 (95% CI 2.82–7.36), compared with stable weight. Blood glucose levels of ≤5.1 mmol/L or 5.2–5.6 mmol/L before diabetes onset were associated with an increased risk of a pancreatic cancer diagnosis, with aORs of 2.42 (95% CI 1.60–3.66) and 2.20 (95% CI 1.45–3.35), respectively, when compared with blood glucose levels ≥6.3 mmol/L within >2–3 years before cancer detection. Conclusions Weight loss as well as blood glucose levels in the normal range (and thus rapid development of hyperglycemia) before diabetes onset may be predictive of pancreatic cancer-related diabetes and may help target which subjects with new diabetes to refer for pancreatic cancer screening examinations.

Background Statins are effective lipid-lowering drugs for the prevention of cardiovascular disease, but muscular adverse events can limit their use. Hydrophilic statins (pravastatin, rosuvastatin) may cause less muscular events than lipophilic statins (e.g. simvastatin, atorvastatin) due to lower passive diffusion into muscle cells. Objective To compare the risk of muscular events between statins at comparable lipid-lowering doses and to evaluate if hydrophilic statins are associated with a lower muscular risk than lipophilic statins. Design/Setting Propensity score-matched cohort study using data from the United Kingdom-based Clinical Practice Research Datalink (CPRD) GOLD. Patients New statin users. Cohort 1: pravastatin 20-40 mg (hydrophilic) vs simvastatin 10-20 mg (lipophilic), cohort 2: rosuvastatin 5-40 mg (hydrophilic) vs atorvastatin 10-80 mg (lipophilic), and cohort 3: simvastatin 40-80 mg vs atorvastatin 10-20 mg. Main Measures The outcome was a first record of a muscular event (myopathy, myalgia, myositis, rhabdomyolysis) during a maximum follow-up of 1 year. Key Results The propensity score-matched cohorts consisted of 1) 9,703, 2) 7,032, and 3) 37,743 pairs of statin users. Comparing the risk of muscular events between low-intensity pravastatin vs low-intensity simvastatin yielded a HR of 0.86 (95% CI 0.64-1.16). In the comparison of moderate- to high-intensity rosuvastatin vs equivalent doses of atorvastatin, we observed a HR of 1.17 (95% CI 0.88-1.56). Moderate- to high-intensity simvastatin was associated with a HR of 1.33 (95% CI 1.16-1.53), when compared with atorvastatin at equivalent doses. Limitations We could not conduct other pairwise comparisons of statins due to small sample size. In the absence of a uniform definition on the comparability of statin doses, the applied dose ratios may not fully match with all literature sources. Conclusions Our results do not suggest a systematically lower risk of muscular events for hydrophilic statins when compared to lipophilic statins at comparable lipid-lowering doses.

Unexplained iron-deficiency anemia is an important marker for colorectal cancer (CRC). Our objectives were as follows: (a) to assess whether the association between anemia and CRC can be detected on the 'Clinical Practice Research Datalink', (b) to evaluate the timing between laboratory changes and CRC detection, and (c) to analyze its association with survival. We conducted a case-control study on patients with an incident CRC diagnosis during 2008-2012 and a 1 : 1-matched control group. We compared anemia markers serum ferritin (SF), hemoglobin (Hb), mean corpuscular volume (MCV), and red blood cell count between cases and controls using conditional logistic regression. We assessed survival in CRC cases. SF values up to 20 ng/ml were associated with an odds ratio [OR (95% confidence interval)] of 10.66 (6.88-16.51) compared with SF values of 101-300 ng/ml when restricted to measurements up to 180 days before the CRC diagnosis. For measurements taken at 1 year or earlier before the diagnosis, the OR was 2.02 (1.57-2.61). For Hb values less than 9 g/dl compared with Hb values of 13.0-15.9 g/dl the corresponding ORs were 74.25 (34.69-158.91) and 2.19 (1.31-3.67), respectively. The corresponding ORs for MCV values up to 80 fl compared with MCV values of 86-95 fl were 13.94 (10.31-18.85) and 1.89 (1.51-2.36), respectively. Low levels of these markers were only weakly associated with survival. Hb, MCV, and SF levels substantially dropped only shortly before the CRC diagnosis. Although slightly more cases had anemia markers compared with controls at 1 year or earlier before the diagnosis, most cases still had normal values. The Clinical Practice Research Datalink is well-suited to detect associations between low Hb, MCV, and SF levels and CRC.

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.

Objectives The aim of this study was to characterize the role of glycemic control and weight change as markers for pancreatic cancer (PaC) in patients with long-standing diabetes. Methods We conducted case-control analyses in patients with long-standing diabetes (>2 years) in the United Kingdom-based Clinical Practice Research Datalink. Cases were patients with PaC matched to control subjects on variables including age, sex, and diabetes duration. We compared glycated hemoglobin (HbA1c) levels, blood glucose levels, and weight change before cancer detection (matched date) between cases and control subjects to assess associations between the potential markers and PaC. Results Cases were more likely than control subjects to have high HbA1c levels. The adjusted odds ratio (aOR) was 4.94 (95% confidence interval [CI], 3.52-6.94) for HbA1c of 64.0 mmol/mol or greater compared with HbA1c of 47.5 mmol/mol or less within 6 months before cancer detection and within >1 to 2 years, 2.66 (95% CI, 2.00-3.54). Weight loss was also more common in cases, with an aOR of 15.40 (95% CI, 10.65-22.26) for loss of 15.0% body weight or greater compared with stable weight. The aOR for patients with both weight loss of 15.0% or greater and high HbA1c at 2 years or less before diagnosis was 60.97 (95% CI, 35.87-103.65), compared with patients with neither. Conclusions Poor glycemic control and weight loss, particularly in combination, may be useful early markers for PaC in patients with long-standing diabetes.

The demographic change and ageing in Europe will lead to a growing number of people suffering from dementia. Consequently, costs for public health will increase because people become more and more reliant on care and gradually lose their independence and mobility. In the case of dementia, remedial measures could be provided by assistive technology to support independent living at home for as long as possible. Current assistance systems are often limited to actively raising an alert (i.e., electronic panic buttons) or location tracking. Due to this small range of functions these systems are poorly accepted by the target group. Thus, this paper reports on a selection process for a spatial data collection device allowing the development of a new so-called mobility safeguarding assistance system for people with dementia which combines features of different systems. In particular, the wearability as an everyday object is a key issue when it comes to identifying an adequate gadget for elderly people. The proposed methodology considers user requirements as well as technical requirements when it comes to finding a suitable device. Based on these requirements, several different devices were reviewed and tested in order to find most suitable potential device as part of the selection process. The device selected shows that the proposed process on how to choose the right device performed well.

While the time trends in oral health are favourable, differences still persist in dental status and in prosthetic dental restorations (PDR) between population subgroups. This study aimed to identify changes in oral health in Switzerland over two decades and to describe their relationship to sociodemographic factors in 2012. Swiss Health Surveys were conducted in 1992, 2002, and 2012. The mean number of missing teeth and the prevalence of PDR were calculated at each time point. Logistic regression analysis was performed to assess associations between the prevalence of PDR and sociodemographic factors. The mean number of missing teeth decreased from five in 1992 to three in 2012. Dental status - as indicated by the number of teeth present - improved across all sociodemographic groups, with the greatest improvements being found in obese participants and in participants with the lowest incomes and educational levels. The prevalence of implant-based restorations increased from 3.2% in 2002 to 9.8% in 2012, and the shift from fixed to removable restorations occurred in the age group being 10 years older. The overall prevalence of PDR decreased in middle-aged people. In conclusion, over the two decades of the study, the oral health of the Swiss population substantially improved. Although sociodemographic differences persisted, they decreased considerably in terms of the number of missing teeth and percentage of the population with a functional dentition.

To analyze the risk of incident cataract (diagnosis or extraction) in patients with or without diabetes focusing on other comorbid conditions, antidiabetic drug use, and diabetes duration. The study population comprised newly diagnosed diabetes patients (≥40 years) from the UK-based Clinical Practice Research Datalink (CPRD) between 2000 and 2015, and a random sample of the general population matched for age, sex, general practice, and year of diabetes diagnosis. We assessed cataract incidence rates (IRs) and performed a nested case-control analysis in the diabetic cohort to assess potential risk factors for a cataract. There were 56,510 diabetes patients included in the study. IRs of cataract were 20.4 (95% CI 19.8–20.9) per 1000 person-years (py) in patients with diabetes and 10.8 (95% CI 10.5–11.2) per 1000 py in the general population. IRs increased considerably around the age of 80 years and with a concomitant diagnosis of macular edema. The incidence rate ratio (IRR) was highest in patients of the age group of 45–54 years. In the nested case-control study, we identified 5800 patients with cataract. Risk of cataract increased with increasing diabetes duration (adj. OR 5.14, 95% CI 4.19–6.30 diabetes for ≥10 years vs. diabetes

Background: The non-interventional study CONIFER was designed to assess the safety and clinical practicability of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome (MDS) patients. Methods: Patients included in the study were diagnosed with MDS and received at least 1 treatment with deferasirox. The observation period covered the time from the initial visit until the last follow-up. Results: The data of 99 patients with MDS scored mainly as International Prognostic Scoring System (IPSS) low and intermediate 1 were evaluated. The mean age of the participants was 75 years and 58% of the patients were male. Iron overload was assessed by serum ferritin level (mean baseline serum ferritin 2,080 ± 1,244 µg/l). Patients were treated for a mean duration of 16 months (mean daily dose at baseline 11.8 ± 7.0 mg/kg). Stratification of serum ferritin levels by deferasirox dose showed a reduction at the higher but no reduction at the lower dose (< 15 mg/kg vs. ≥ 15 mg/kg and < 20 mg/kg vs. ≥ 20 mg/kg). The majority of patients (81%) were affected by at least 1 adverse event, with decreased renal creatinine clearance being the most frequent. Conclusion: Higher doses (≥ 15 mg/kg) of deferasirox effectively and safely reduced serum ferritin levels in MDS patients with transfusional iron overload.

Previous large epidemiological studies reporting on the association between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases mainly focussed on prevalent diseases rather than on the incidence of newly diagnosed cardiovascular outcomes. We used the UK-based General Practice Research Database (GPRD) to assess the prevalence and incidence of cardiovascular diseases in COPD patients aged 40-79 between 1995 and 2005, and we randomly matched COPD-free comparison patients to COPD patients. In nested-case control analyses, we compared the risks of developing an incident diagnosis of cardiac arrhythmias, venous thromboembolism, myocardial infarction, or stroke between patients with and without COPD, stratifying the analyses by COPD-severity, using COPD-treatment as proxy for disease severity. We identified 35,772 patients with COPD and the same number of COPD-free patients. Most cardiovascular diseases were more prevalent among COPD patients than among the comparison group of COPD-free patients. The relative risk estimates of developing an incident diagnosis of cardiac arrhythmia (OR 1.19, 95% CI 0.98-1.43), deep vein thrombosis (OR 1.35, 95% CI 0.97-1.89), pulmonary embolism (OR 2.51, 95% CI 1.62-3.87), myocardial infarction (OR 1.40, 95% CI 1.13-1.73), or stroke (OR 1.13, 95% CI 0.92-1.38), tended to be increased for patients with COPD as compared to COPD-free controls. The findings of this large observational study provide further evidence that patients with COPD are at increased risk for most cardiovascular diseases.

OBJECTIVE In pregnancy women experience metabolic and hemodynamic changes of potential long term impact. Conflicting evidence exists on the impact on blood pressure (BP). We investigated the association between parity and BP in the Swiss Study on Air Pollution And Lung and Heart Disease In Adults cohort. METHODS Multilevel linear and logistic regression analyses were performed in 2837 women aged 30 73 years with data on parity number of births BP and doctor diagnosed hypertension adjusting for potential confounders. Hypertension was defined as at least 140/90?mmHg doctor diagnosed or taking relevant treatment. Stratified analyses were performed by age (

Peptic ulcer disease, gastro-oesophageal reflux disease (GORD) and weight loss have been associated with chronic obstructive pulmonary disease (COPD). Many studies, especially on peptic ulcer and weight loss, are cross-sectional or were done back in the 1960s or 1970s. Our purpose was to learn more about GORD, ulcer, and weight loss in relation to COPD during long-term follow-up in recent years. We conducted a case-control and a follow-up study using the UK-based General Practice Research Database to assess and compare the prevalence and incidence of GORD, peptic ulcer and weight loss in patients with COPD and in COPD-free patients during the period 1995-2005. We identified 35,772 patients with COPD and the same number of COPD-free patients. Incidence rates of GORD, peptic ulcer and weight loss in COPD patients were 59.2, 14.8 and 134.0 per 10,000 person years, respectively. The risk of weight loss was increased in patients with COPD compared to COPD-free patients (1.81, 95% CI 1.61-2.02), while the risk of GORD (OR 1.19, 95% CI 1.00-1.40) or peptic ulcer (OR 1.24, 95% CI 0.92-1.66) were similar in both groups. The results provide further evidence that COPD is associated with weight loss, while there is no materially increased risk for ulcer or GORD associated with COPD.

Different antihypertensive drug classes may alter risk for atrial fibrillation. Some studies suggest that drugs that interfere with the renin-angiotensin system may be favorable because of their effect on atrial remodeling.; To assess and compare the relative risk for incident atrial fibrillation among hypertensive patients who receive antihypertensive drugs from different classes.; Nested case-control analysis.; The United Kingdom-based General Practice Research Database, a well-validated primary care database comprising approximately 5 million patient records.; 4661 patients with atrial fibrillation and 18,642 matched control participants from a population of 682,993 patients treated for hypertension.; A comparison of the risk for atrial fibrillation among hypertensive users of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), or beta-blockers with the reference group of users of calcium-channel blockers. Patients with clinical risk factors for atrial fibrillation were excluded.; Current exclusive long-term therapy with ACE inhibitors (odds ratio [OR], 0.75 [95% CI, 0.65 to 0.87]), ARBs (OR, 0.71 [CI, 0.57 to 0.89]), or beta-blockers (OR, 0.78 [CI, 0.67 to 0.92]) was associated with a lower risk for atrial fibrillation than current exclusive therapy with calcium-channel blockers.; Blood pressure changes during treatment courses could not be evaluated, and risk for bias by indication cannot be fully excluded in an observational study.; In hypertensive patients, long-term receipt of ACE inhibitors, ARBs, or beta-blockers reduces the risk for atrial fibrillation compared with receipt of calcium-channel blockers.; None.

Use of postmenopausal hormone replacement therapy (HRT) has been associated with an elevated risk of gynecological cancers. There is evidence that the effect differs with the type of hormone used. Dydrogesterone is pharmacologically very similar to progesterone.We used the UK-based General Practice Research Database (GPRD) to conduct a follow-up study with a nested case-control analysis. We assessed and compared the risk of developing breast, ovarian, endometrial/uterine or cervical cancer in estradiol/dydrogesterone (E/D) users, users of other HRT, or non-users of HRT.The breast cancer incidence rates were 2.41 (95% confidence interval (CI) 1.81-3.15), 3.28 (95% CI 3.01-3.55) and 3.16 (95% CI 2.92-3.42) per 1000 person-years for E/D users, users of other HRT or non-users, respectively. In a direct comparison, the breast cancer risk for E/D users was lower than for users of other HRT (odds ratio 0.76, 95% CI 0.56-1.05). The incidence rates of other gynecological cancers were similar or also slightly lower for E/D users than for users of other HRT.This study provides evidence that the risk of developing gynecological cancers with E/D use of several months to a few years is similar to the risks of developing gynecological cancer without HRT or use of other HRT.

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.

Use of postmenopausal hormone replacement therapy (HRT) used to be promoted to reduce the risk of ischemic cardiovascular diseases, a concept which has been challenged by results of the large Women's Health Initiative trial in users of estrogen and progestin. It is postulated that the type of progestin used in HRT affects the cardiovascular risk.We used the UK-based General Practice Research Database to conduct a follow-up study with a nested case-control analysis. We assessed and compared the risk of developing myocardial infarction, thrombotic stroke or venous thromboembolism in estradiol/dydrogesterone users, users of other HRT, or non-users of HRT.The incidence rates of myocardial infarction, thrombotic stroke and venous thromboembolism in estradiol/dydrogesterone users were 0.40 (95% confidence interval (CI) 0.18-0.76), 0.27 (95% CI 0.10-0.58) and 0.31 (95% CI 0.13-0.64) per 1000 person-years, respectively. As compared to non-users of HRT, the adjusted relative risk estimates (odds ratios) in the nested case-control analysis for estradiol/dydrogesterone users or users of other HRT were 1.06 (95% CI 0.48-2.36) and 1.12 (95% CI 0.84-1.51) for myocardial infarction, 0.50 (95% CI 0.21-1.22) and 1.18 (95% CI 0.94-1.48) for thrombotic stroke, and 0.84 (95% CI 0.37-1.92) and 1.42 (95% CI 1.10-1.82) for venous thromboembolism, respectively.The study provides evidence that estradiol/dydrogesterone use of several months to a few years is not associated with a higher risk of cardiovascular events than use of other HRT.