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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.

There is evidence that training for strength and balance prevents decline in physical function in old age when the training is personally instructed. It is an open question whether interventions that deliver training via up-to-date technologies can achieve long-term effects. This study examined the effects of an 8-month fitness training program delivered via information and communication technology (ICT) on lower-body strength and balance in female home care users (n = 72) aged 75 years on average. For statistical analysis, the test group was divided into two subgroups, one who used the program at least 8 times per month (n = 26) and another one who used the program less often (n = 17) compared with a control group that received no exercise program (n = 29). It was found that regular ICT-exercisers exhibited positive effects over time on lower-body strength and balance compared to a decrease in both indicators in irregular exercisers and the control group. The authors see potential in offering exercise programs to people of advanced age via ICT to counteract physical decline in old age.

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.

Improvements in oral health are changing the requirements for oral health care provision. This study assessed the frequency and major reason of dental visits and personal oral hygiene measures in Switzerland, and temporal trends in visit frequency. The number of dental visits in the previous twelve months, the reason for these visits, and the prevalence of oral hygiene measures were quantified from weighted data from the 2012 Swiss Health Survey. The frequency of dental visits in 2012 was compared with previous surveys (1992–2007). Almost two thirds of subjects reported visiting a dentist and almost half had visited a dental hygienist in the previous twelve months. Voluntary (33%) or recall check-ups (25%) were the most common reasons for the last dental visit across age groups. Treatment needs including caries/filling/endodontic treatment (10%), crowns/FDP/RDP/implants (8%), toothache (5%), extraction (5%), periodontal complaints (2%), or orthodontic appliances (2%) were more heterogeneously distributed across age groups. One in ten subjects had dental implants; prevalence increased with increasing age as did the number of missing teeth. Use of interdental cleaning devices and frequent tooth brushing were more common among subjects with few or no missing teeth and among subjects with higher versus lower income or education. Oral health awareness varied with a higher awareness in women than in men and in subjects with higher versus lower income or education. The prevalence of dental implants and dental hygienist’s visits has increased in Switzerland since 2002, but oral hygiene measures remained stable.

Objective When questionnaires are used for pain assessment, the order effect must be taken into consideration; that is, whether the answer to a pain item is influenced by answers given to previous items. This study aimed to evaluate possible order effects in children and adolescents when answering pain items. Furthermore, the possible influence of sex on order effects was analyzed. Method Three pain items (worst, at movement, and at rest) were given in 6 different orders. Two hundred and 46 postoperative hospitalized children and adolescents (age range of 11-18 years, mean of 14.4 years; female: 41%, duration of surgery range of 2-274 min) participated in this study. Each item order was answered by 40-43 children and adolescents. Results While there were no general order effects, we observed a sex-specific order effect. The position of pain at rest (p = .034) and pain on movement (p = .036) items had different influences on worst pain values in female patients compared to male patients. A sex-specific influence on pain at rest values was only caused by the position of pain on movement items (p = .036). Conclusion The fact that male and female pediatric patients are differently influenced by the order of pain items has to be considered in planning a questionnaire. As more specific items (pain on movement) are less influenced by the item order effect, they should be preferred.

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.

Summary Background Ocular toxicity was described in the late 1950s for some anti-malarial drugs, but only limited information is available on the comparison of ocular toxicity of different anti-malarials. Methods We conducted a follow-up study with a nested case-control analysis using the General Practice Research Database to compare the risk of developing a first-time diagnosis of an eye disorder during exposure of mefloquine, chloroquine and/or proguanil or atovaquone/proguanil use to non-users. We calculated incidence rates with 95% confidence intervals (CI) and odds ratios using multivariate conditional logistic regression analyses. Results We included 83,148 patients and identified 652 cases with an incident eye disorder. The incidence rates with 95% CI of all eye disorders combined in users of mefloquine, chloroquine and/or proguanil, atovaquone/proguanil or travellers not using anti-malarials were 5.3 (4.3–6.5), 7.1 (5.0–9.9), 6.3 (5.6–7.2) and 5.1 (4.6–5.7), per 1000 person-years, respectively. As compared to non-users of anti-malarials, the adjusted odds ratio with 95% CI in the nested case-control analysis for users of mefloquine, chloroquine and/or proguanil, or atovaquone/proguanil were 1.33 (1.01–1.75), 1.61 (1.06–2.45), and 1.25 (1.03–1.52), respectively. Conclusions The study provides evidence that there was an increased risk of eye disorders in users of all anti-malarials compared to non-users of anti-malarials.

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.

BACKGROUND: Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed. OBJECTIVES: The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies. METHODS: To measure the risk of HFF among adult users of BZDs during 2001-2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands). Four different models (A-D) with increasing levels of adjustment were analyzed. The risk according to duration and type of BZD was also explored. Adjusted hazard ratios (cohort), odds ratios (NCC), and their 95% confidence intervals were estimated. RESULTS: Adjusted hazard ratios (Model C) were 1.34 (1.23-1.47) in BIFAP, 1.66 (1.54-1.78) in CPRD, and 2.22 (1.55-3.29) in Mondriaan in cohort studies. Adjusted odds ratios (Model C) were 1.28 (1.16-1.42) in BIFAP, 1.60 (1.49-1.72) in CPRD, and 1.48 (0.89-2.48) in Mondriaan in NCC studies. A short-term effect was suggested in Mondriaan, but not in CPRD or BIFAP. All DBs showed an increased risk with the concomitant use of anxiolytic and hypnotic drugs. CONCLUSIONS: Applying similar study methods to different populations and DBs showed an increased risk of HFF in BZDs users but differed in the magnitude of the risk, which may be because of inherent differences between DBs. Copyright © 2015 John Wiley & Sons, Ltd.

Summary Background: The ‘Confidence’ smartphone application aims to support elderly people’s independence as long as possible. Objective: This paper presents first findings on the impact of the system on elderlies’ lives. Methods: 41 end-users tested ‘Confidence’ for six weeks in their daily routine. Before and after the test period the participants assessed their quality of life (QoL). These assessments were analyzed together with additional QoL statements and the usage of ‘Confidence’ which were collected with questionnaires. Results: Six participants assessed their QoL after the trial better than before and six participants assessed it as worse. Five individuals felt that ‘Confidence’ positively influenced their life and these five testers had a positive attitude towards ‘Confidence’ from the start of the trial. After the trial 38 % of the participants said that they felt safer, 37 % communicated more with others, 27 % forgot less, 13 % felt better oriented outside, and 7 % were more on the move due to ‘Confidence’. Three percent said that they were less on the move, two percent felt more unsafe and two percent were less outside. Conclusion: ‘Confidence’ has the potential to affect elderly users’ lives. However, within this analysis positive or negative effects of its usage were not correlated with the QoL assessment. A connection between positive attitude towards technology prior use and a positive impact afterwards was found. Citation: Willner V, Schneider C, Feichtenschlager M. Effects of an assistance service on the quality of life of elderly users. Appl Clin Inform 2015; 6: 429–442http://dx.doi.org/10.4338/ACI-2015-03-RA-0033

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 (

Summary Background Case reports and epidemiological studies have associated the use of mefloquine with neuropsychiatric adverse events. Methods We used the General Practice Research Database to conduct a follow-up study with a nested case–control analysis. We assessed the risk of developing first-time anxiety, stress-related disorders/psychosis, depression, epilepsy or peripheral neuropathies in patients using mefloquine, chloroquine and/or proguanil, or atovaquone/proguanil for malaria chemoprophylaxis, as compared to unexposed travelers. Results Compared to non-users of antimalarials, the adjusted odds ratio in the nested case–control analysis for users of mefloquine, chloroquine and/or proguanil, or atovaquone/proguanil were 0.71 (95% CI 0.56–0.90), 1.04 (95% CI 0.74–1.46), and 0.73 (95% CI 0.61–0.86) for anxiety or stress-related disorders combined, 0.54 (95% CI 0.41–0.71), 1.06 (95% CI 0.71–1.59), and 0.75 (95% CI 0.62–0.91) for depression, 0.69 (95% CI 0.35–1.36), 1.41 (95% CI 0.54–3.67), and 0.75 (95% CI 0.42–1.36) for epilepsy, and 1.22 (95% CI 0.50–2.99), 1.59 (95% CI 0.41–6.15), and 1.05 (95% CI 0.54–2.03) for neuropathies, respectively. The risk of all outcomes was higher in females than in males across all exposure categories. Conclusions The risk of neuropsychiatric disorders was similar for users and for non-users of anti-malarial chemoprophylaxis, with evidence for elevated risks in some subgroups.

Objective To study the function of syndecan-1 (SDC1) and its potential regulator miR-10b in endometriosis. Design Experimental laboratory study. Setting University medical center. Patient(s) Not applicable. Intervention(s) The human endometriotic cell line 12Z was transiently transfected with SDC1 small interfering RNA or miR-10b precursors and investigated for changes in cell behavior and gene expression. 12Z and primary eutopic endometrial stroma cells of two American Society for Reproductive Medicine class III endometriosis patients were transfected with miR-10b precursors to investigate posttranscriptional regulation of SDC1. Main Outcome Measure(s) Quantitative polymerase chain reaction, Western blotting, flow cytometry, 3′ untranslated region luciferase assays, and zymography were used to measure miR-10b–dependent targeting of SDC1 and SDC1-dependent expression changes of proteases and interleukin-6. Altered cell behavior was monitored by Matrigel invasion assays, cell viability assays, and mitogen-activated protein kinase activation blots. Result(s) Knockdown of SDC1 inhibited Matrigel invasiveness by >60% but did not affect cell viability. Interleukin-6 secretion, matrix metalloproteinase-9 expression, and matrix metalloproteinase-2 activity were reduced, whereas plasminogen activator inhibitor-1 protein expression was up-regulated. miR-10b overexpression significantly down-regulated SDC1, reduced Matrigel invasiveness by 20% and cell viability by 14%, and decreased mitogen-activated protein kinase activation in response to hepatocyte growth factor. Conclusion(s) Syndecan-1, a target of miR-10b, inhibits epithelial endometriotic cell invasiveness through down-regulation of metalloproteinase activity and interleukin-6.

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.

Objective To study the function of miR-145, known to be dysregulated in endometriosis, and to identify its target genes in an in vitro endometriosis model. Design Experimental laboratory study. Setting University medical centers. Patient(s) Primary endometrial stroma cells were derived from eutopic endometrium of three American Society for Reproductive Medicine stage III endometriosis patients and from ectopic lesions of four patients with deep infiltrating endometriosis. Intervention(s) The human endometriotic cell line 12Z and primary eutopic and ectopic endometrial stroma cells were transiently transfected with miR-145 precursors or anti–miR-145 inhibitors and investigated for posttranscriptional regulation of predicted target genes and changes in cell behavior. Main Outcome Measure(s) Predicted target expression was measured by quantitative reverse transcription–polymerase chain reaction and Western blotting, and altered cell behavior was monitored by cell proliferation assays. The 12Z cells were additionally investigated by Matrigel invasion assays, cell cycle analysis, side population analysis, and aldehyde dehydrogenase activity assays. Result(s) In all cells investigated, miR-145 overexpression inhibited cell proliferation and induced down-regulation of FASCIN-1, SOX2, and MSI2 . In 12Z cells miR-145 upregulation increased Matrigel invasiveness and reduced side population and aldehyde dehydrogenase-1 activity. Additional down-regulated targets in 12Z cells included OCT4, KLF4, PODXL, JAM-A , and SERPINE1/PAI-1. ACTG2 and TAGLN were up-regulated upon pre–miR-145 transfection. JAM-A, FASCIN-1, and PAI-I down-regulation in 12Z cells were confirmed by Western blotting. Conclusion(s) miR-145 inhibits endometriotic cell proliferation, invasiveness, and stemness by targeting multiple pluripotency factors, cytoskeletal elements, and protease inhibitors.