Comparing risk of major bleeding between users of different oral anticoagulants in patients with nonvalvular atrial fibrillation.

AIMS: The introduction of direct oral anticoagulants (DOACs) has broadened the treatment arsenal for nonvalvular atrial fibrillation, but observational studies on the benefit-risk balance of DOACs compared to vitamin K antagonists (VKAs) are needed. The aim of this study was to characterize the risk of major bleeding in DOAC users using longitudinal data collected from electronic health care databases from 4 different EU-countries analysed with a common study protocol. METHODS: A cohort study was conducted among new users (≥18 years) of DOACs or VKAs with nonvalvular atrial fibrillation using data from the UK, Spain, Germany and Denmark. The incidence of major bleeding events (overall and by bleeding site) was compared between current use of DOACs and VKAs. Cox regression analysis was used to calculate hazard ratios and 95% confidence intervals (CI) and adjust for confounders. RESULTS/CONCLUSION: Overall, 251 719 patients were included across the 4 study cohorts (mean age ~75 years, % females between 41.3 and 54.3%), with overall hazard ratios of major bleeding risk for DOACs vs VKAs ranging between 0.84 (95% CI: 0.79-0.90) in Denmark and 1.13 (95% CI 1.02-1.25) in the UK. When stratifying according to the bleeding site, risk of gastrointestinal bleeding was increased by 48-67% in dabigatran users and 30-50% for rivaroxaban users compared to VKA users in all data sources except Denmark. Compared to VKAs, apixaban was not associated with an increased risk of gastrointestinal bleeding in all data sources and seemed to be associated with the lowest risk of major bleeding events compared to dabigatran and rivaroxaban.

Use of hydrochlorothiazide and risk of skin cancer in a large nested case-control study in Spain.

PURPOSE: Hydrochlorothiazide (HCTZ) use has been linked to skin cancer in northern European countries. We assessed the association between HCTZ exposure and risk of malignant melanoma (MM) and keratinocyte carcinoma (KC) in a European Mediterranean population. METHODS: Two parallel nested case-control studies were conducted in Spain using two electronic primary healthcare databases, each one providing data on both exposure and outcomes: SIDIAP and BIFAP. Cancer cases were matched to 10 controls by age and gender through risk-set sampling. The ORs and 95% CI for MM and KC associated with previous HCTZ use were estimated using conditional logistic regression. In BIFAP, KC cases were further identified as basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). RESULTS: In adjusted analyses, both ever and cumulative high (≥50,000 mg) use of HCTZ were associated with an increased risk of KC. The risk estimates for high use were 1.30 (1.26-1.34) in SIDIAP and 1.20 (1.12-1.30) in BIFAP, with a lower risk for BCC (1.11 [1.02-1.21]) than for SCC (1.71 [1.45-2.02]). A dose-response relationship was observed between cumulative doses of HCTZ and KC risk. Inconsistent results were found for high use of HCTZ and risk of MM: 1.25 (1.09-1.43) in SIDIAP and 0.85 (0.64-1.13) in BIFAP. CONCLUSIONS: In this European Mediterranean population, a high cumulative use of HCTZ was related to an increased risk of KC with a clear dose-response pattern.

Major bleeding in users of direct oral anticoagulants in atrial fibrillation: A pooled analysis of results from multiple population-based cohort studies.

OBJECTIVE: To establish the risk of major bleeding in direct oral anticoagulant (DOAC) users (overall and by class) versus vitamin K antagonist (VKA) users, using health care databases from four European countries and six provinces in Canada. METHODS: A retrospective cohort study was performed according to a similar protocol. First-users of VKAs or DOACs with a diagnosis of non-valvular atrial fibrillation (NVAF) were included. The main outcome of interest was major bleeding and secondary outcomes included gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Incidence rates of events per 1000 person years were calculated. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using a Cox proportional hazard regression model. Exposure and confounders were measured and analysed in a time-dependant way. Risk estimates were pooled using a random effect model. RESULTS: 421 523 patients were included. The risk of major bleeding for the group of DOACs compared to VKAs showed a pooled HR of 0.94 (95% CI: 0.87-1.02). Rivaroxaban showed a modestly increased risk (HR 1.11, 95% CI: 1.06-1.16). Apixaban and dabigatran showed a decreased risk of respectively HR 0.76 (95% CI: 0.69-0.84) and HR 0.85 (95% CI: 0.75-0.96). CONCLUSIONS: This study confirms that the risk of major bleeding of DOACs compared to VKAs is not increased when combining all DOACs. However, we observed a modest higher risk of major bleeding for rivaroxaban, whereas for apixaban and dabigatran lower risks of major bleeding were observed compared to VKAs.

Repetitive syncopal episodes in a child with documented ventricular tachycardia, early repolarization pattern in leads I an aVL, Brugada syndrome, and fever.

We present a small child with febrile peaks and syncopal episodes secundary to ventricular tachycardia, in whom it was eventually possible to demostrate the Brugada Syndrome with a special presentation in the ECG; early repolarization pattern in lead I and a aVL and Brugada pattern during fever in V1-V2. This is, to our knowledge, tha first case with this special ECG presentation in a small child.

Incidence of direct oral anticoagulant use in patients with nonvalvular atrial fibrillation and characteristics of users in 6 European countries (2008-2015): A cross-national drug utilization study.

AIMS: To estimate the incidence of direct oral anticoagulant drug (DOAC) use in patients with nonvalvular atrial fibrillation and to describe user and treatment characteristics in 8 European healthcare databases representing 6 European countries. METHODS: Longitudinal drug utilization study from January 2008 to December 2015. A common protocol approach was applied. Annual period incidences and direct standardisation by age and sex were performed. Dose adjustment related to change in age and by renal function as well as concomitant use of potentially interacting drugs were assessed. RESULTS: A total of 186 405 new DOAC users (age ≥18 years) were identified. Standardized incidences varied from 1.93-2.60 and 0.11-8.71 users/10 000 (2011-2015) for dabigatran and rivaroxaban, respectively, and from 0.01-8.12 users/10 000 (2012-2015) for apixaban. In 2015, the DOAC incidence ranged from 9 to 28/10 000 inhabitants in SIDIAP (Spain) and DNR (Denmark) respectively. There were differences in population coverage among the databases. Only 1 database includes the total reference population (DNR) while others are considered a population representative sample (CPRD, BIFAP, SIDIAP, EGB, Mondriaan). They also varied in the type of drug data source (administrative, clinical). Dose adjustment ranged from 4.6% in BIFAP (Spain) to 15.6% in EGB (France). Concomitant use of interacting drugs varied between 16.4% (SIDIAP) and 70.5% (EGB). Cardiovascular comorbidities ranged from 25.4% in Mondriaan (The Netherlands) to 82.9% in AOK Nordwest (Germany). CONCLUSION: Overall, apixaban and rivaroxaban increased its use during the study period while dabigatran decreased. There was variability in patient characteristics such as comorbidities, potentially interacting drugs and dose adjustment. (EMA/2015/27/PH).

Metabolic syndrome and insulin resistance are associated with frailty in older adults: a prospective cohort study.

Background: diabetes increases the risk of frailty that is a leading cause of disability and premature mortality in older people. Metabolic syndrome (MS) and insulin resistance (IR) are strong risk factors for diabetes and could, thus, lead to frailty. However, the association between MS or IR and frailty has barely been investigated. Methods: data were obtained from a cohort of 1,499 community-dwelling individuals aged ≥60, who were free of diabetes at 2008-10 and were followed up for 3.5 years. At baseline, MS was ascertained according to the harmonised definition, and IR with the Homoeostatic Model Assessment for IR index (HOMA-IR). Frailty was defined as having three or more of the Fried's criteria: exhaustion, low physical activity, slow walking, unintentional weight loss and low grip strength. Statistical analyses were performed with logistic regression, and adjusted for the main confounders. Results: in 2012, 84 cases of incident frailty were identified. Compared with subjects without MS, those with MS showed increased risk of frailty (multivariate odds ratio [OR]: 1.85; 95% confidence interval [CI] 1.12-3.05). The association persisted after further adjustment for fibrinogen and C-reactive protein. When the frailty criteria were considered individually, low grip strength was the criterion that showed a stronger association with MS (OR: 1.67; 95% CI: 1.25-2.21). Higher HOMA-IR values were also associated with higher risk of frailty. Conclusion: MS and IR were associated with increased risk of frailty. This work extends the spectrum of harmful consequences of MS, and suggests that preventing or controlling MS may serve to delay frailty.

[Application of a social capital scale in older women attending public primary care clinics]. / Capital social de las mujeres mayores usuarias de la red pública de la Atención Primaria de Salud.

BACKGROUND: Social capital is an economical idea that refers to connections between individuals and entities that can be economically valuable. AIM: To establish the relationship of social capital as a health care asset, with sociodemographic variables of older women attending public health care services. MATERIAL AND METHODS: Chen’s Personal Social Capital scale was applied to 113 women aged between 64 and 80 years during 2014. Cronbach’s alpha of the instrument was calculated. RESULTS: The Cronbach’s alpha of the instrument was 0.86. The average score for social capital was 23.9 points of a maximum of 50. Bridging capital scores had the higher disparity, specifically in participation in community organizations and the representation of their interest in them. Bonding capital decreased along with a higher age of interviewed women (r = -0,43, p < 0,01). Higher territorial roots were associated with a lower perception of social community resource availability (r = -0,42, p < 0,01). CONCLUSIONS: The social capital scores in these women were low. Their better support networks were close relationships and relatives. The sensation of solitude increased with age.

Major dietary patterns and risk of frailty in older adults: a prospective cohort study.

BACKGROUND: There is emerging evidence of the role of certain nutrients as risk factors for frailty. However, people eat food, rather than nutrients, and no previous study has examined the association between dietary patterns empirically derived from food consumption and the risk of frailty in older adults. METHODS: This is a prospective cohort study of 1,872 non-institutionalized individuals aged ≥60 years recruited between 2008 and 2010. At baseline, food consumption was obtained with a validated diet history and, by using factor analysis, two dietary patterns were identified: a 'prudent' pattern, characterized by high intake of olive oil and vegetables, and a 'Westernized' pattern, with a high intake of refined bread, whole dairy products, and red and processed meat, as well as low consumption of fruit and vegetables. Participants were followed-up until 2012 to assess incident frailty, defined as at least three of the five Fried criteria (exhaustion, weakness, low physical activity, slow walking speed, and unintentional weight loss). RESULTS: Over a 3.5-year follow-up, 96 cases of incident frailty were ascertained. The multivariate odds ratios (95% confidence interval) of frailty among those in the first (lowest), second, and third tertile of adherence to the prudent dietary pattern were 1, 0.64 (0.37-1.12), and 0.40 (0.2-0.81), respectively; P-trend = 0.009. The corresponding values for the Westernized pattern were 1, 1.53 (0.85-2.75), and 1.61 (0.85-3.03); P-trend = 0.14. Moreover, a greater adherence to the Westernized pattern was associated with an increasing risk of slow walking speed and weight loss. CONCLUSIONS: In older adults, a prudent dietary pattern showed an inverse dose-response relationship with the risk of frailty while a Westernized pattern had a direct relationship with some of their components. Clinical trials should test whether a prudent pattern is effective in preventing or delaying frailty.

Sleep quality and the metabolic syndrome: the role of sleep duration and lifestyle.

BACKGROUND: This study examined the association between sleep quality and the metabolic syndrome and whether if it is independent of sleep duration and if it can be explained by lifestyles linked to sleep quality. METHODS: Cross-sectional study conducted from 2008 to 2010 with 10 342 individuals representative of the population aged ≥18 years in Spain. Poor sleep quality was ascertained through self-reported difficulty falling asleep, difficulty maintaining sleep and sleeping pill consumption. Metabolic syndrome was defined according to the recent harmonized definition. Analyses were conducted with logistic regression and adjusted for the main confounders. RESULTS: Difficulty falling asleep was associated with higher frequency of metabolic syndrome after adjustment for sociodemographic variables, lifestyle and diagnosed morbidity [odds ratio (OR) = 1.25; 95% confidence interval (CI) = 1.06-1.47]. The association was slightly attenuated after further adjusting for sleep duration (OR = 1.23; 95% CI = 1.04-1.46) and held after additional adjustment for energy intake, adherence to a Mediterranean dietary pattern, energy spent in physical activity and time watching TV (OR = 1.20; 95% CI = 1.01-1.42). No associations were found between metabolic syndrome and other sleep quality indicators. Difficulty falling asleep was associated with high blood pressure in the fully adjusted analyses (OR = 1.17; 95% CI = 1.00-1.37) but not with the rest of components of metabolic syndrome. CONCLUSIONS: Difficulty falling asleep is associated with metabolic syndrome and, in particular, with high blood pressure. This association is independent of sleep duration and is not due to lifestyles related to poor sleep. This finding should be replicated in prospective studies using objective sleep measures; also, the influence of antihypertensive and lipid-lowering drug treatment on this association should be further studied.

Binge drinking in Spain, 2008-2010.

BACKGROUND: Most alcohol-related research has focused on northern and eastern Europe and the United States. Data on Mediterranean countries point to drinking patterns approaching the sporadic and excessive patterns found in northern and eastern Europe. This is the first study to estimate the prevalence of binge drinking (BD) and the joint distribution of BD, regular heavy alcohol consumption, and alcohol abuse or dependence (AAD) in a nationally representative sample of the adult population of Spain. METHODS: Cross-sectional study conducted in 2008 to 2010 with 9,130 persons aged 18 to 64 years. BD was defined as intake of ≥80 g of alcohol in men (≥60 g in women) during any drinking occasion in the previous month, with ≥3 BD episodes discriminating between frequent and sporadic BD. Regular alcohol consumption was measured with a validated diet history, and the threshold between moderate and heavy drinking was ≥40 g of alcohol/d in men (≥24 g in women). AAD was defined by a CAGE score ≥2. RESULTS: BD prevalence was 10% (95% confidence interval [CI]: 8.8 to 11.2) in men and 4.2% (95% CI: 3.5 to 4.8) in women, and proved highest among 18- to 24-year-olds (19.5% in men and 10.3% in women). During the latest BD episode, men consumed a mean of 114 g of alcohol versus 85.3 g in women; spirits accounted for 65.2 and 66.2% of total intake, respectively. The mean number of monthly BD episodes was 2.3 in men and 2 in women. Among binge drinkers, 61% were 18- to 34-year-olds, over 80% had regular moderate drinking, 25% reported frequent BD, and 22.8% reported AAD. In multivariate analyses, sporadic BD and frequent BD were associated with AAD independently of regular alcohol intake. CONCLUSIONS: Prevalence of BD in Spain is moderately high. Prevention interventions should consider that the majority of binge drinkers are young men with regular moderate consumption and no AAD traits.