The risk of acute infections in new users of antidepressants: An observational cohort study.

BACKGROUND: Preclinical studies suggested that drugs that functionally inhibit acid sphingomyelinase (FIASMA)may enhance immune cell longevity and potentially offer protection against infections. Many antidepressants have shown FIASMA activity. METHODS: We conducted a cohort study using primary-care data from the UK-based Clinical Practice Research Datalink (2000-2021). We assessed the association of composite diagnosed acute infections in new users of fluoxetine, sertraline, paroxetine, or venlafaxine aged 18-80 years compared to citalopram. We compared SARS-CoV-2 infections between groups in a secondary analysis. We estimated incidence rates (IR) and IR ratios (IRR) of acute infections in four pairwise comparisons using negative binomial regression. We applied propensity score (PS) fine stratification to control for confounding. RESULTS: In the PS-weighted cohorts, we included 353,138 fluoxetine, 222,463 sertraline, 69,963 paroxetine, 32,608 venlafaxine, and between 515,996 and 516,583 new citalopram users. PS-weighted IRs ranged between 76.8 acute infections /1000 person-years (py) (sertraline) and 98.9 infections/1000 py (citalopram). We observed PS-weighted IRRs around unity for paroxetine (0.97, 95 % CI, 0.95-1.00), fluoxetine (0.94, 95 % CI, 0.92-0.95), and venlafaxine (0.90, 95 % CI, 0.87-0.94) vs citalopram. Reduced IRR for sertraline vs citalopram (0.84, 95 % CI, 0.82-0.85), became null within subgroups by cohort entry date. In the analysis of SARS-CoV-2 infection, no statistically relevant risk reduction was seen. LIMITATIONS: Analysis not limited to patients with diagnosed depression, possible underestimation of infection incidence, and unclear FIASMA activity of citalopram. CONCLUSIONS: Fluoxetine, sertraline, paroxetine, and venlafaxine were not associated with a reduced risk of acute infection when compared with the presumably weak FIASMA citalopram.

Risk of skin cancer in new users of thiazides and thiazide-like diuretics: a cohort study using an active comparator group.

BACKGROUND: Case-control studies report a dose-dependent increased risk of skin cancer in users of hydrochlorothiazide (HCTZ) vs. nonusers. The degree to which other thiazides and thiazide-like diuretics (TZs) are associated with skin cancer is less certain. OBJECTIVES: To assess the risk of skin cancer in new users of different TZs compared with new users of calcium channel blockers (CCBs). METHODS: We conducted a cohort study using a UK primary-care database (1998-2017), including 271 154 new TZ users [87·6% bendroflumethiazide (BFT), 5·8% indapamide and 3·6% HCTZ] and 275 263 CCB users. The outcomes were basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). We estimated incidence rates (IRs) and IR ratios (IRRs) in short-term (< 20 prescriptions) and long-term (≥ 20 prescriptions) users of TZs and CCBs using negative binomial regression, and calculated rate differences (RDs) for selected results. We used fine stratification on the propensity score (PS) to control for 23 baseline covariates. RESULTS: Long-term use of HCTZ increased absolute and relative risks of SCC [PS-weighted IRR 1·95; 95% confidence interval (CI) 1·87-2·02; RD per 100 000 person-years 87.4], but not of BCC or CMM. Long-term use of indapamide was associated with an increased incidence of CMM (IRR 1·43; 95% CI 1·35-1·50). BFT was not meaningfully associated with the risk of any type of skin cancer. CONCLUSIONS: Our results corroborate the previously reported increased risk of SCC (but not of BCC or CMM) for long-term use of HCTZ. BFT may be a safer alternative for patients at increased risk of skin cancer.

Hyperlipidaemia and incident osteoarthritis of the hand: a population-based case-control study.

OBJECTIVE: Preclinical evidence suggests that increased cholesterol levels might be involved in the pathophysiology of osteoarthritis of the hand (HOA), but evidence from observational studies remains scarce. We aimed to analyse the association between hyperlipidaemia and incident HOA. DESIGN: We conducted a matched (1:1) case-control study using the UK-based Clinical Practice Research Datalink (CPRD). Cases were patients aged 30-89 years with an incident diagnosis of HOA between 1995 and 2014. In multivariable conditional logistic regression analyses, we calculated odds ratios (OR) for incident HOA in patients with hyperlipidaemia, categorized by gender, age, previous duration of hyperlipidaemia, and recent statin treatment. RESULTS: Among 19,590 cases and 19,590 controls, we observed an increased risk of HOA in patients with hyperlipidaemia (OR 1.37, 95% confidence intervals (CI) 1.28-1.47), when compared to patients without hyperlipidaemia. Thus, of all HOA cases in our study population, 3.6% may have been attributable to the presence of hyperlipidaemia (population attributable risk). Most patients with HOA were elderly, but the strength of the association between HOA and hyperlipidaemia inversely correlated with increasing age, with the highest OR of 1.72 (95% CI 1.24-2.38) in patients aged 29-49 years. Categorization by previous hyperlipidaemia duration, as well as sub-classification of patients with hyperlipidaemia into those with and without recent statin use did not meaningfully change the effect estimate. CONCLUSIONS: Our results suggest that hyperlipidaemia may be an independent risk factor for new onset HOA.

Type II diabetes mellitus and incident osteoarthritis of the hand: a population-based case-control analysis.

OBJECTIVES: Emerging evidence suggests that diabetes may be a risk factor for osteoarthritis (OA). However, previous results on the association between diabetes and all OA were conflicting. We aimed to comprehensively analyse the association between type II diabetes mellitus (T2DM) and osteoarthritis of the hand (HOA) specifically. METHODS: We conducted a matched (1:1) case-control study using the UK-based Clinical Practice Research Datalink (CPRD) of cases aged 30-90 years with an incident diagnosis of HOA from 1995 to 2013. In multivariable conditional logistic regression analyses, we calculated odds ratios (OR) for incident HOA in patients with T2DM, categorized by T2DM severity (HbA1C), duration, and pharmacological treatment. We further performed sensitivity analyses in patients with and without other metabolic diseases (hypertension (HT), hyperlipidaemia (HL), obesity). RESULTS: Among 13,500 cases and 13,500 controls, we observed no statistically significant association between T2DM and HOA (OR 0.95, 95% confidence interval (CI) 0.87-1.04), regardless of T2DM severity, duration, or pharmacological treatment. Having HT did not change the OR. Although we observed slightly increased ORs in overweight T2DM patients with co-occurring HL with or without coexisting HT, none of these ORs were statistically significant. CONCLUSIONS: Our results provide evidence that T2DM is not an independent risk factor for HOA. Concurrence of T2DM with HT, HL, and/or obesity did not change this association significantly.

Previously diagnosed influenza infections and the risk of developing epilepsy.

Several epidemiological studies suggest a possible involvement of viral infection in the development of epilepsy. While recent research from in vitro studies increasingly supports the role of herpes simplex virus type 1 (HSV-1) in the pathogenesis of epilepsy, little is known about the role of other viral infections such as influenza. Using data from the Clinical Practice Research Datalink (CPRD), we conducted a matched case-control analysis to assess the association between GP-diagnosed influenza infections and the risk of developing an incident diagnosis of epilepsy. During the study period 11 244 incident epilepsy cases and 44 976 matched control patients were identified. Prior exposure to influenza was reported in 7·5% of epilepsy cases and 6·7% of controls [adjusted odds ratio (aOR) 1·12, 95% confidence interval (CI) 1·03-1·22]. Prior history of 'complicated influenza', i.e. influenza associated with a possible super-infection, was associated with a slightly increased epilepsy risk (aOR 1·64, 95% CI 1·10-2·46), particularly if recorded within the 2 months preceding the epilepsy diagnosis (aOR 6·03, 95% CI 1·10-33·2). Our findings suggest that prior influenza exposure does not appear to materially alter the risk of developing epilepsy. By contrast, influenza episodes accompanied by complications were associated with a slightly increased epilepsy risk.

Metformin and the risk of head and neck cancer: a case-control analysis.

AIMS: Metformin use has been associated with a decreased risk of some cancers, although data on head and neck cancer (HNC) are scarce. We explored the relation between the use of antidiabetic drugs and the risk of HNC. METHODS: We conducted a case-control analysis in the UK-based Clinical Practice Research Datalink (CPRD) of people with incident HNC between 1995 and 2013 below the age of 90 years. Six controls per case were matched on age, sex, calendar time, general practice and number of years of active history in the CPRD prior to the index date. Other potential confounders including body mass index (BMI), smoking, alcohol consumption and comorbidities were also evaluated. The final analyses were adjusted for BMI, smoking and diabetes mellitus (or diabetes duration in a sensitivity analysis). Results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Use of metformin was neither associated with a statistically significant altered risk of HNC overall (1-29 prescriptions: adjusted OR 0.87, 95% CI 0.61-1.24 and ≥ 30 prescriptions adjusted OR 0.80, 95% CI 0.53-1.22), nor was long-term use of sulphonylureas (adjusted OR 0.87, 95% CI 0.59-1.30), or any insulin use (adjusted OR 0.92, 95% CI 0.63-1.35). However, we found a (statistically non-significant) decreased risk of laryngeal cancer associated with long-term metformin use (adjusted OR 0.41, 95% CI 0.17-1.03). CONCLUSIONS: In this population-based study, the use of antidiabetic drugs was not associated with a materially altered risk of HNC. Our data suggest a protective effect of long-term metformin use for laryngeal cancer.

Epidemiology of basal cell carcinoma in the United Kingdom: incidence, lifestyle factors, and comorbidities.

BACKGROUND: Little is known about the epidemiology of basal cell carcinoma (BCC). METHODS: Using the Clinical Practice Research Datalink, we calculated annual incidence rates. In a case-control analysis, we examined lifestyle factors and comorbidities. RESULTS: Incidence rose significantly between 2000 and 2011. Basal cell carcinoma risk was increased in alcohol drinkers (slightly) and immunocompromised patients, but reduced in smokers and individuals with abnormal weight. CONCLUSIONS: Basal cell carcinoma places a growing public health burden. Lifestyle factors do not play a major role in pathogenesis, but immunosuppression is important.

Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK--a nested case-control analysis.

AIMS: To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs. METHODS: Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders. RESULTS: Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 ± 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [≥ 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia. CONCLUSIONS: Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas.

Sun protective behaviour of vacationers spending holidays in the tropics and subtropics.

BACKGROUND: The development of malignant melanoma has been associated with intense episodic sun exposure, as it typically occurs during holidays in high ultraviolet (UV)-index countries. OBJECTIVES: To investigate sun protective behaviour and sunburn experience of vacationers spending holidays in the tropics or subtropics. METHODS: Using standardized face-to-face interviews, we conducted cross-sectional surveys among air passengers waiting in the departure or the baggage claim area at the Airport Basel-Mulhouse (Switzerland/France), and among vacationers waiting for pretravel health advice at a travel clinic in Basel (Switzerland). RESULTS: We completed 533, 324 and 308 interviews with departing air passengers, returning air passengers and vacationers at the travel clinic, respectively. The interviews revealed widespread misconceptions about how to prepare the skin for the sun before holidays (e.g. pretanning in the solarium). At the holiday destination, almost all respondents used sunscreen, whereas wearing protective clothing and seeking shade were less practised. Among the returning air passengers, 44% had got sunburnt during their holiday stay. CONCLUSIONS: The sunburn rate among returning vacationers was alarmingly high. Skin cancer prevention campaigns and pretravel health advice should tackle misconceptions regarding the preparation of the skin for the sun, and emphasize the significance of covering up and seeking shade.

Antihypertensive drugs and the risk of incident rosacea.

BACKGROUND: Despite scarce evidence, use of calcium channel blockers is discouraged in patients with rosacea, whereas beta-blockers are recommended as an off-label treatment for erythematotelangiectatic rosacea. OBJECTIVES: To study the association of the use of calcium channel blockers, beta-blockers and other antihypertensive drugs with incident rosacea. METHODS: We conducted a matched case-control study of antihypertensive drugs and incident rosacea, using the U.K.-based General Practice Research Database. Cases had an incident diagnosis of rosacea recorded between 1995 and 2009. Each case was matched to one control on age, sex, general practice and years of history on the database before the index date. Drug use was stratified by timing (≤ or > 180 days before the index date) and duration (number of prescriptions) of drug exposure, in a multivariate conditional logistic regression model. RESULTS: Among 53 927 cases and 53 927 controls, we observed odds ratios (ORs) around unity for calcium channel blockers across all strata, with a slightly decreased OR of 0·77 (95% CI 0·69-0·86) for current users of dihydropyridine calcium channel blockers with ≥ 40 prescriptions. Among beta-blockers, atenolol and bisoprolol yielded slightly decreased ORs across all exposure strata, whereas propranolol revealed ORs around 1·0, irrespective of timing and duration of exposure. Neither angiotensin-converting-enzyme inhibitors nor angiotensin receptor blockers altered the relative rosacea risk. CONCLUSIONS: Our data contradict the prevailing notion that calcium channel blockers increase the risk of rosacea. Beta-blocker use was associated with a slightly decreased risk of rosacea, but the effect may be somewhat stronger in patients with erythematotelangiectatic rosacea.

The association between psychiatric diseases, psychotropic drugs and the risk of incident rosacea.

BACKGROUND: Psychological conditions, such as traumatic events or stress, have been discussed controversially as aetiological factors for rosacea. OBJECTIVES: To assess the association between diagnosed depression, other affective disorders or schizophrenia and subsequent incident rosacea. We further aimed at evaluating the possible role of various psychotropic drugs within this association. METHODS: We conducted a matched case-control study of psychiatric diseases and incident rosacea, stratified by exposure to various psychotropic drugs, using the UK-based General Practice Research Database. Cases had a first diagnosis of rosacea recorded between 1995 and 2009. Each case was matched to one control on age, sex, general practice and years of history on the database. RESULTS: A history of depression or other affective disorders was not associated with an increased risk of developing rosacea; lithium was the only antidepressant drug that significantly altered this association. Current long-term use of lithium was associated with a decreased odds ratio (OR) of 0·58 [95% confidence interval (CI) 0·38-0·88] among people without a schizophrenia diagnosis (with or without affective disorders), compared with people not exposed to lithium. Patients with diagnosed schizophrenia revealed a decreased rosacea risk (OR 0·71, 95% CI 0·60-0·91), independent of antipsychotic drug use. CONCLUSIONS: Depression or other affective disorders were not associated with incident rosacea, whereas patients with schizophrenia were at a decreased risk of this skin disease in our study population. The materially decreased risk of rosacea among people with chronic lithium exposure may lead to new insights into the pathomechanism of rosacea.

Effect of ibandronate on spontaneous osteonecrosis of the knee: a randomized, double-blind, placebo-controlled trial.

UNLABELLED: Based on this double-blind, placebo-controlled study, ibandronate has no beneficial effect on clinical and radiological outcome in patients with spontaneous osteonecrosis of the knee over and above anti-inflammatory medication. INTRODUCTION: Observational studies suggest beneficial effects of bisphosphonates in spontaneous osteonecrosis (ON) of the knee. We investigated whether ibandronate would improve clinical and radiological outcome in newly diagnosed ON. METHODS: In this randomized, double-blind, placebo-controlled trial, 30 patients (mean age, 57.3 ± 10.7 years) with ON of the knee were assigned to receive either ibandronate (cumulative dose, 13.5 mg) or placebo intravenously (divided into five doses 12 weeks). All subjects received additional treatment with oral diclofenac (70 mg) and supplementation with calcium carbonate (500 mg) and vitamin D (400 IU) to be taken daily for 12 weeks. Patients were followed for 48 weeks. The primary outcome was the change in pain score after 12 weeks. Secondary endpoints included changes in pain score, mobility, and radiological outcome (MRI) after 48 weeks. RESULTS: At baseline, both treatment groups (IBN, n = 14; placebo, n = 16) were comparable in relation to pain score and radiological grading (bone marrow edema, ON). After 12 weeks, mean pain score was reduced in both ibandronate- (mean change, -2.98; 95% CI, -4.34 to -1.62) and placebo- (-3.59; 95% CI, -5.07 to -2.12) treated subjects (between-group comparison adjusted for age, sex, and osteonecrosis type, p = ns). Except for significant decrease in bone resorption marker (CTX) in ibandronate-treated subjects (p < 0.01), adjusted mean changes in all functional and radiological outcome measures were comparable between treatment groups after 24 and 48 weeks. CONCLUSIONS: In patients with spontaneous osteonecrosis of the knee, bisphosphonate treatment (i.e., IV ibandronate) has no beneficial effect over and above anti-inflammatory medication.

Outdoor workers' sun-related knowledge, attitudes and protective behaviours: a systematic review of cross-sectional and interventional studies.

Sun protection is a major concern for outdoor workers as they are particularly exposed to solar ultraviolet radiation and therefore at increased risk of developing some forms of skin cancer, cataract and ocular neoplasm. In order to provide an overview of outdoor workers' sun-related knowledge, attitudes and protective behaviours as reported in the literature and to evaluate the effectiveness of sun-safety education programmes in outdoor occupational settings, we conducted a systematic review of the literature by searching three electronic databases (PubMed, Embase, PsycINFO) from their inception up to 25 April 2012. An extensive hand search complemented the database searches. We identified 34 relevant articles on descriptive studies and 18 articles on interventional studies. Considerable numbers of outdoor workers were found to have sun-sensitive skin types; sunburn rates per season ranged from 50% to 80%. Data concerning outdoor workers' sun-related knowledge and attitudes were scarce and controversial. The reported sun-protective behaviours were largely inadequate, with many workers stating that they never or only rarely wore a long-sleeved shirt (50-80%), sun-protective headgear (30-80%) and sunscreen (30-100%) while working in the sun. However, there is growing evidence that occupational sun-safety education is effective in increasing outdoor workers' sun-protection habits and presumably in decreasing sunburn rates. Occupational sun-safety education programmes offer great potential for improving outdoor workers' largely insufficient sun-protective behaviours. It is hoped that, in the future, committed support from healthcare authorities, cancer foundations, employers and dermatologists will open the way for rapid and uncomplicated implementation of sun-safety education programmes.

A study on the epidemiology of rosacea in the U.K.

BACKGROUND: Rosacea is a chronic facial skin disease of unclear origin. Epidemiological data are scarce and controversial, with reported prevalences ranging from 0·09% to 22%. To our knowledge, incidence rates have not been quantified before. OBJECTIVES: In this observational study we quantified incidence rates of diagnosed rosacea in the U.K. and described demographic characteristics and the prevalence of ocular symptoms in patients with rosacea. We compared lifestyle factors such as smoking and alcohol consumption between patients with rosacea and controls. METHODS: Using the U.K.-based General Practice Research Database, we identified patients with an incident diagnosis of rosacea between 1995 and 2009 and matched them (1:1) to rosacea-free control patients. We assessed person-time of all patients at risk and assessed incidence rates of rosacea, stratified by age, sex, year of diagnosis and region. RESULTS: We identified 60,042 rosacea cases and 60,042 controls (61·5% women). The overall incidence rate for diagnosed rosacea in the U.K. was 1·65 per 1000 person-years. Rosacea was diagnosed in some 80% of cases after the age of 30 years. Ocular symptoms were recorded in 20·8% of cases at the index date. We observed a significantly reduced relative risk of developing rosacea among current smokers (odds ratio 0·64, 95% confidence interval 0·62-0·67). Alcohol consumption was associated with a marginal risk increase. CONCLUSIONS: We quantified incidence rates and characteristics of patients with rosacea diagnosed in clinical practice in a large epidemiological study using primary care data from the U.K. Smoking was associated with a substantially reduced risk of developing rosacea.

NSAID use and risk of Parkinson disease: a population-based case-control study.

BACKGROUND: Previous epidemiologic studies have produced inconsistent findings regarding the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease (PD). METHODS: We conducted a case-control analysis using the General Practice Research Database. Cases (≥40 years) had a new diagnosis of PD between 1994 and 2009. We matched four controls to each PD case on age, sex, general practice, and index date. Use of NSAIDs, aspirin, and acetaminophen was stratified by exposure timing and duration for both cases and controls. We calculated odds ratios (OR) using conditional logistic regression. For additional analyses, the index date was brought backward 1, 2, and 3 years, respectively. RESULTS: We identified 4026 cases with an incident idiopathic PD diagnosis and 15,969 matched controls. Compared with patients without any previous prescription for NSAIDs, those with prior use had no increased risk of a PD diagnosis (OR 1.07, 95% CI 0.99-1.16). Long-term use (≥15 prescriptions) was associated with a slightly lower PD risk (adjusted OR 0.94, 95% CI 0.83-1.07). The relative PD risks of the use of aspirin or acetaminophen were not materially higher (PD risk of long-term use: adjusted ORs 1.16, 95% CI 1.03-1.30 and 1.15, 95% CI 1.02-1.30, respectively) compared with those for non-users. The risk estimate diminished toward the null in subsequent analyses with shifted index dates. CONCLUSION: In this large observational study with data from the UK primary care, the long-term use of NSAIDs, aspirin, or acetaminophen was not associated with a substantially altered risk of developing PD.

Risk of incident depression in patients with Parkinson disease in the UK.

BACKGROUND: Non-motor symptoms are not widely recognized in patients with Parkinson disease (PD). We sought to assess the incidence rate as well as the risk of depression in newly diagnosed patients with PD and to compare it to PD-free controls. METHODS: We conducted a population-based follow-up study with a nested case-control analysis based on data from the UK-based General Practice Research Database (GPRD). We included PD patients ≥ aged 40 years with a first PD diagnosis between 1994 and 2005, and a matched comparison group free of PD. We assessed incidence rates (IRs) and relative risk estimates (odds ratios [ORs] with 95% confidence intervals [CI]). RESULTS: The IR of depression in newly diagnosed PD in the UK community was 26.0 (95% CI 22.9-29.5) per 1000 person-years. The risk of developing depression was increased almost twofold in patients with PD when compared to patients without PD (adj. OR 1.89; 95% CI 1.49-2.40). The increased relative risk was most pronounced in women and in individuals 40-69 years of age. Long-term users of levodopa had an increased depression risk when compared to short-term users. CONCLUSIONS: Patients with PD are at an approximately twofold increased risk of being diagnosed with depression compared to the PD-free population.

Risk of gynecological cancers in users of estradiol/dydrogesterone or other HRT preparations.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Risk of cardiovascular outcomes in users of estradiol/dydrogesterone or other HRT preparations.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Thiazolidinediones and skeletal health]. / Thiazolidinediones et ostéoporose.

The insulin-sensitizing thiazolidinediones are effective drugs to achieve glycemic control in patients with type 2 diabetes. Results from preclinical studies have demonstrated that activation of PPAR-gamma inhibits primarily bone formation by diverting mesenchymal stem cells to the adipocytic rather than to the osteogenic lineage. In humans studies demonstrated accelerated bone loss, impaired bone mineral density as well as an increased fracture risk for thiazolidinedione users, mostly for women. As a consequence of these observations, clinicians have to carefully assess the fracture risk in patients with type 2 diabetes before starting a therapy with thiazolidinediones.