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Recently, changes in urinary albumin and in GFR have been recognized as risk factors for the development of end-stage kidney disease and mortality. Though most clinical epidemiology studies of chronic kidney disease (CKD) used renal function and proteinuria at baseline alone, definitive diagnosis of CKD with multiple measurements intensifies the differences in the risk for mortality between the CKD and non-CKD populations. We hypothesized that a transient diagnosis of proteinuria and reduced renal function each indicate a significantly higher mortality compared to definitive non-CKD as the negative control and lower mortality compared with definitive CKD as the positive control. The present longitudinal study evaluated a general-population cohort of 338,094 persons who received annual health checkups, with a median 4.3-year study period. There were 2,481 deaths, including 510 CVD deaths (20.6%) and 1,328 cancer deaths (53.5%), and mortality risk was evaluated for transient proteinuria and for transiently reduced renal function. The hazard ratios (HRs) for all-cause mortality and cancer mortality were not significant, but that for cardiovascular mortality was significantly higher for transient proteinuria (HR, 1.94 [95% confidence interval, 1.27–2.96] in men and 2.78 [1.50–5.16] in women). On the other hand, transiently reduced renal function was not significant for either cardiovascular mortality risk or cancer mortality risk. We surmise that this is the first study of the mortality risk of transient dipstick proteinuria in a large general-population cohort with cause-specific death registration. Transiently positive proteinuria appears to be a significant risk specifically for cardiovascular mortality compared with definitely negative for proteinuria. [ABSTRACT FROM AUTHOR]

Recently, the United States Food and Drug Administration approved a new oral dosage preparation of amlodipine besylate (AML) and celecoxib (CEL) for the management of hypertension and osteoarthritis. However, no simultaneous estimation procedures for these two analytes have been described. Hence, two simple, accurate, and precise ultraviolet spectroscopic procedures that manipulated the ratio spectra were established for concurrent quantification of AML and CEL using ethanol as a solvent. The first method involves determining the peak-to-trough amplitude difference of the ratio spectra of AML and CEL. The second method involves determining the peak amplitude of the ratio first derivative (Δλ 4 nm) spectra of AML and CEL at 334.2 nm and 254.2 nm, correspondingly. Both methods showed linearity in the range of 1–6 μg mL-1 for AML and 5–40 μg mL-1 for CEL with an excellent correlation coefficient (<0.999). The proposed procedures were validated by following the International Conference on Harmonization guidelines for accuracy, precision, selectivity, recovery, and stability studies. It is evident from the low %RSD and %RE that both analytical procedures were found to be accurate and precise, respectively. The percent recovery of AML and CEL from the formulation was found to be 99.79% and 99.34% using the ratio-difference method and 100.13% and 99.70% using the ratio first-derivative method, with a low percent relative standard deviation. Further, the proposed techniques permit concurrent quantification of AML and CEL in different concentration ratios without interference from each other; hence, these techniques can be adopted for regular quality-control studies. [ABSTRACT FROM AUTHOR]

Context: Xanthone derivatives have been reported to possess a wide range of biological properties. In effort to search new effective antihypertensive compounds, we have synthesizednovel xanthone derivatives (xanthonoxypropanolamines) and got patent for these compounds (The Patent Office, Government of India, S. No.: 011–016308, Patent No.: 250538). Objective: In the present work, we attempted to establish the antihypertensive activity, toxicity and molecular docking study forthese newly synthesized compounds (1a, 1b and 2). Materials and method: The preliminary antihypertensive screening was performed by administering synthesized compounds and standard drugs intraperitonially and orally into wistar rats. The change in systolic, diastolic and the mean blood pressure before and after the treatment of the drugs was measured on a Digital LE-S100 Blood Pressure Meter by Tail-cuff method non-invasively. Toxicity studies were carried out after oral administration of synthesized compounds to rats at doses of 25, 50, and 100mg/kg. The serum samples were tested for different toxicity parameters such as liver function test, kidney function test etc. The docking simulations of all the compounds were performed using Maestro, version 9.4 implemented from Schrodinger software suite. Results and discussion: The result showed that the compound 1a, 1b and 2 have greater antihypertensive activity with almost equal or less toxicity profile in comparison to standard drug Propranolol and Atenolol. The docking score for the compound 1b was found -9.1 while for compound 1a and 2 were found -8.7 and -8.6 respectively. Conclusion: These novel compounds i.e. 1a, 1b, and 2 have greater antihypertensive activity in comparison to standard drugs Propranolol and Atenolol. All these compounds do not have any toxicity. [ABSTRACT FROM AUTHOR]

Background: Uncontrolled high blood pressure (UBP) can lead to various cardiovascular complications causing an estimated nine million deaths per year worldwide. In Meknes, epidemiologic data on UBP are scarce, depriving programs from evidence-based information that would allow a better management of hypertension. Hence, we aimed to assess UBP prevalence in hypertensive patients treated in Meknes and identify UBP-associated risk factors. Methods: Between November and December 2017, we conducted a cross-sectional study enrolling 922 hypertensive patients managed at Meknes’s primary health care facilities using the multistage sampling method. We interviewed patients face to face to collect their socio-demographic-characteristics, lifestyle behaviours, clinical parameters and the triad care system-patient-physician. Another questionnaire was self-administered by physicians to characterize therapeutic inertia. A multivariate logistic regression analysis highlighted the risk factors associated with UBP. Results: UBP prevalence was 73% with a mean age of 61±11 years (mean±standard deviation) and a male/female ratio of 1/3. Risk factors associated with UBP were: therapeutic inertia (adjusted odds ratio to other variables (AOR) = 18.2, 95% CI [8.35–39.84]), drug non-adherence (AOR = 1.8, 95% CI [1.07–3.04]), obesity/overweight (AOR = 1.6, 95% CI [1.03–2.58]), unemployment (AOR = 1.9, 95% CI [1.09–3.01]), low income (AOR = 2.6, 95% CI [1.01–6.86]), family history of hypertension (AOR = 1.5, 95% CI [1.07–2.08]) and male sex (AOR = 1.6, 95% CI [1.04–2.58]). Conclusion: UBP prevalence is high in Meknes. Prevention should firstly focus on raised awareness of hypertensive patients’ self-care management. Secondly, health professionals should better comply to the guidelines of anti-hypertensive treatments. Lastly, health professionals should frequently be reminded to reach therapeutic goals to overcome therapeutic inertia. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is featured by increased plasma very low density lipoproteins (VLDL). The extent to which plasma apolipoprotein E (ApoE) levels are elevated in NAFLD is unclear. We determined whether plasma ApoE is elevated in subjects with suspected NAFLD. Plasma ApoE and genotypes were determined in 6,762 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. A Fatty Liver Index (FLI) ≥ 60 was used as a proxy of NAFLD. A total of 1,834 participants had a FLI ≥ 60, which coincided with increased triglycerides, non-HDL cholesterol, ApoB and ApoE (all P<0.001). In multivariable linear regression analysis, plasma ApoE levels were positively associated with an elevated FLI when taking account of ApoE genotypes and other clinical and laboratory covariates (fully adjusted model: β = 0.201, P<0.001). Stratified analysis for ApoE genotypes (ApoE ε3ε3 homozygotes, ApoE ε2 carriers, and ApoE ε3ε4 and ε4ε4 carriers combined), also showed positive associations of plasma ApoE levels with an elevated FLI in each group (all P<0.001). In conclusion, it is suggested that NAFLD is characterized by increased plasma ApoE levels, even when taking account of the various ApoE genotypes. Increased plasma ApoE may contribute to altered VLDL metabolism and to increased atherosclerosis susceptibility in NAFLD. [ABSTRACT FROM AUTHOR]

Background: Some experts have proposed combating rising drug prices by promoting brand-brand competition, a situation that is supposed to arise when multiple US Food and Drug Administration (FDA)-approved brand-name products in the same class are indicated for the same condition. However, numerous reports exist of price increases following the introduction of brand-name competition, suggesting that it may not be effective. We performed a systematic literature review of the peer-reviewed health policy and economics literature to better understand the interplay between new drug entry and intraclass drug prices.Methods and Findings: We searched PubMed and EconLit for original studies on brand-brand competition in the US market published in English between January 1990 and April 2019. We performed a qualitative synthesis of each study's data, recording its primary objective, methodology, and results. We found 10 empirical investigations, with 1 study each on antihypertensives, anti-infectives, central nervous system stimulants for attention deficit/hyperactivity disorder, disease-modifying therapies for multiple sclerosis, histamine-2 (H2) blockers, and tumor necrosis factor (TNF) inhibitors; 2 studies on cancer medications; and 2 studies on all marketed or new drugs. None of the studies reported that brand-brand competition lowers list prices of existing drugs within a class. The findings of 2 studies suggest that such competition may help restrain how new drug prices are set. Other studies found evidence that brand-brand competition was mediated by the relative quality of competing drugs and the extent to which they are marketed, with safer or more effective new drugs and greater marketing associated with higher intraclass list prices. Our investigation was limited by the studies' use of list rather than net prices and the age of some of the data.Conclusions: Our findings suggest that policies to promote brand-brand competition in the US pharmaceutical market, such as accelerating approval of non-first-in-class drugs, will likely not result in lower drug list prices absent additional structural reforms. [ABSTRACT FROM AUTHOR]

Introduction: Over the past few decades, the prevalence of hypertension has dramatically increased in Sub-Saharan Africa. Poor adherence has been identified as a major cause of failure to control hypertension. Scarce data are available in Africa. Aims: We assessed adherence to medication and identified socioeconomics, clinical and treatment factors associated with low adherence among hypertensive patients in 12 sub-Saharan African countries. Method: We conducted a cross-sectional survey in urban clinics of both low and middle income countries. Data were collected by physicians on demographics, treatment and clinical data among hypertensive patients attending the clinics. Adherence was assessed by questionnaires completed by the patients. Factors associated with low adherence were investigated using logistic regression with a random effect on countries. Results: There were 2198 individuals from 12 countries enrolled in the study. Overall, 678 (30.8%), 738 (33.6%), 782 (35.6%) participants had respectively low, medium and high adherence to antihypertensive medication. Multivariate analysis showed that the use of traditional medicine (OR: 2.28, 95%CI [1.79–2.90]) and individual wealth index (low vs. high wealth: OR: 1.86, 95%CI [1.35–2.56] and middle vs. high wealth: OR: 1.42, 95%CI [1.11–1.81]) were significantly and independently associated with poor adherence to medication. In stratified analysis, these differences in adherence to medication according to individual wealth index were observed in low-income countries (p<0.001) but not in middle-income countries (p = 0.17). In addition, 26.5% of the patients admitted having stopped their treatment due to financial reasons and this proportion was 4 fold higher in the lowest than highest wealth group (47.8% vs 11.4%) (p<0.001). Conclusion: This study revealed the high frequency of poor adherence in African patients and the associated factors. These findings should be useful for tailoring future programs to tackle hypertension in low income countries that are better adapted to patients, with a potential associated enhancement of their effectiveness. [ABSTRACT FROM AUTHOR]

Background: In atherosclerotic renal artery disease, the benefit of revascularization is controversial. A clinical decision-making process based on a multidisciplinary meeting was formalized in the Lyon university hospital. Objectives: To investigate whether this decisional process ensured a clinical benefit to patients assigned to renal revascularization. Methods: Single-centre retrospective cohort study, including patients diagnosed from April 2013 to February 2015 with an atherosclerotic renal artery disease with a peak systolic velocity >180cm/s. For each patient, the decision taken in multidisciplinary meeting (medical treatment or revacularization) was compared to the one guided by international guidelines. Blood pressure values, number of antihypertensive medications, presence of an uncontrolled or resistant hypertension, and glomerular filtration rate at one-year follow-up were compared to baseline values. Safety data were collected. Results: Forty-nine patients were included: 26 (53%) were assigned to a medical treatment and 23 (47%) to a renal revascularization. Therapeutic decision was in accordance with the 2013 American Health Association guidelines and with the 2017 European Society of Cardiology guidelines for 78% and 22% of patients who underwent revascularization, respectively. Patients assigned to revascularization presented a significant decrease in systolic blood pressure (-23±34mmHg, p = 0.007), diastolic blood pressure (-12±18mmHg, p = 0.007), number of antihypertensive medications (-1.00±1.03, p = 0.001), and number of uncontrolled or resistant hypertension (p = 0.022 and 0.031) at one-year follow-up. Those parameters were not modified among patients assigned to medical treatment alone. There was no grade 3 adverse event. Conclusion: Based on a multidisciplinary selection of revascularization indications, patients on whom a renal revascularization was performed exhibited a significant improvement of blood pressure control parameters with no severe adverse events. [ABSTRACT FROM AUTHOR]

Background: Antidepressants are frequently used in older patients with depression, but little is known about the comparative safety of individual agents. The objective of the study was to determine the comparative risk of death of antidepressants in older patients with depression. Methods and findings: We carried out a cohort study from 2004 to 2015 utilizing the German Pharmacoepidemiological Research Database, a population-based database supplied by statutory health insurance providers covering approximately 17% of the general population and all geographical regions. We included 376,846 patients aged 65+ years with a diagnosis of depression who initiated treatment with one of 13 antidepressants (ADs). In total 27,019 patients died during follow-up corresponding to a rate of 119.7 per 1,000 person years. We used proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the risk of death for twelve ADs compared to citalopram. In the primary analysis, we found an increased risk of death associated with the use of amitriptyline (HR 1.15, 95%CI: 1.10–1.20). However, opipramol, trimipramine, doxepin, mirtazapine, fluoxetine, paroxetine, duloxetine, venlafaxine, and St. John’s wort were found to be associated with a lower risk of death. The increased risk of amitriptyline diminished after exclusion of patients with a history of cancer (HR 0.88, 95%CI: 0.82–0.94) and after high-dimensional propensity score (HdPS) adjustment (HR 1.04, 95%CI: 0.95–1.14). In older patients and in those with dementia, differences in risk between most individual ADs and citalopram were smaller. After adjustment by HdPS, the decreased risks for fluoxetine, paroxetine, venlafaxine and mirtazapine compared to citalopram disappeared. Conclusions: This study suggests that ADs recommended as first-line treatment in patients with depression have a similar safety profile with regard to the risk of death, especially in very old patients and in those with dementia. Further research is needed to investigate the risk of death for individual ADs in specific subgroups such as patients with cancer or cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Heart rate variability (HRV) reflects the autonomous nervous system modulation on heart rate and is associated with several pathologies, including cardiac mortality. While mechanistic studies show that smoking is associated with lower HRV, population-based studies present conflicting results. Methods: We assessed the mutual effects of active smoking status, cumulative smoking history, and current smoking intensity, on HRV among 4751 adults from the Cooperative Health Research In South Tyrol (CHRIS) study. The HRV metrics standard deviation of normal-to-normal (NN) inter-beat intervals (SDNN), square root of the mean squared differences of consecutive NN intervals (RMSSD), total power (TP), low (LF) and high frequency (HF) power, and their ratio (LF/HF), were derived from 20-minute electrocardiograms. Smoking status, pack-years (PY), and tobacco grams/day from standardized questionnaires were the main exposures. We fitted linear mixed models to account for relatedness, non-linearity, and moderating effects, and including fractional polynomials. Results: Past smokers had higher HRV levels than never smokers, independently of PY. The association of HRV with current smoking became apparent when accounting for the interaction between smoking status and PY. In current smokers, but not in past smokers, we observed HRV reductions between 2.0% (SDNN) and 4.9% (TP) every 5 PY increase. Furthermore, current smokers were characterized by dose-response reductions of 9.8% (SDNN), 8.9% (RMSSD), 20.1% (TP), 17.7% (LF), and 19.1% (HF), respectively, every 10 grams/day of smoked tobacco, independently of common cardiometabolic conditions and HRV-modifying drugs. The LF/HF ratio was not associated with smoking status, history, or intensity. Conclusions: Smoking cessation was associated with higher HRV levels. In current smokers, heavier smoking intensity appears gradually detrimental on HRV, corroborating previous evidence. By affecting both the sympathetic and parasympathetic nervous system indexes, but not the LF/HF balance, smoking intensity seems to exert a systemic dysautonomic effect. [ABSTRACT FROM AUTHOR]

Introduction: Renin-angiotensin system inhibitors (RAS) drugs have a proteinuria-reducing effect that could prevent the progression of kidney disease in diabetic patients. Our study aimed to assess the budget impact based on healthcare payer perspective of increasing uptake of RAS drugs into the current treatment mix of standard anti-hypertensive treatments to prevent progression of kidney disease in patient’s comorbid with hypertension and diabetes. Methods: A Markov model of a Malaysian hypothetical cohort aged ≥30 years (N = 14,589,900) was used to estimate the total and per-member-per-month (PMPM) costs of RAS uptake. This involved an incidence and prevalence rate of 9.0% and 10.53% of patients with diabetes and hypertension respectively. Transition probabilities of health stages and costs were adapted from published data. Results: An increasing uptake of RAS drugs would incur a projected total treatment cost ranged from MYR 4.89 billion (PMPM of MYR 27.95) at Year 1 to MYR 16.26 billion (PMPM of MYR 92.89) at Year 5. This would represent a range of incremental costs between PMPM of MYR 0.20 at Year 1 and PMPM of MYR 1.62 at Year 5. Over the same period, the care costs showed a downward trend but drug acquisition costs were increasing. Sensitivity analyses showed the model was minimally affected by the changes in the input parameters. Conclusion: Mild impact to the overall healthcare budget has been reported with an increased utilization of RAS. The long-term positive health consequences of RAS treatment would reduce the cost of care in preventing deterioration of kidney function, thus offsetting the rising costs of purchasing RAS drugs. Optimizing and increasing use of RAS drugs would be considered an affordable and rational strategy to reduce the overall healthcare costs in Malaysia. [ABSTRACT FROM AUTHOR]

Under the Universal Coverage Scheme (UCS) with payment per capita for outpatient (OP) services, hospitals’ financial risks will rise if access to essential drugs increases. This study examined trends in access to and price of essential drugs for noncommunicable diseases (NCDs) and an overall purchasing price index (PPI) for an OP drug basket from public hospitals. To examine drug access, OP prescription data from 2010–2012 were obtained from the UCS. Access to thirteen drugs for diabetes, hypertension, and dyslipidemia was examined for trend using a time-series analysis. To calculate the PPI, drugs in the same dataset in 2010 that each contributed at least 0.2% of the total OP drug expenditure (N = 118 items) were selected together with drugs expected for near future growth (N = 48 items). The PPI was constructed from purchasing prices in 16 hospitals using a standard method developed by the International Labour Organization. Based on 166 drug items accounting for 75% of OP drug expenditures, the overall PPI continually declined by 6.8% from 2010 to 2012. Access to the 13 selected NCD drugs, accounting for 22% of the total OP drug expenditure increased from 22 to 30 per 1,000 population for antidiabetics, 27 to 47 for antihypertensive agents, and 32 to 53 for antilipidemics from 2010–2012. Growth in the study drug recipients was relatively higher than that in the population and diagnosed patients. Due to generic market competition, metformin, glipizide, amlodipine, losartan, simvastatin, atorvastatin, and fenofibrate prices decreased by 6–22%. Antiretrovirals and risperidone prices decreased by more than 10% due to price negotiation by the UCS. Access to essential drugs for diabetes, hypertension and dyslipidemia has increased. A decline in the PPI could contain essential drug expenditure when the demand for the drugs increased. Generic market competition and price negotiation by the UCS led to price reduction. [ABSTRACT FROM AUTHOR]

Background: As the burden of noncommunicable diseases grows, access to safe medical therapy is increasing in importance. The aim of this study was to develop a method for evaluating the quality of antihypertensive drugs and to examine whether this prevalence varies by socioeconomic variables. Methods: We conducted a cross-sectional survey of registered pharmacies in 6 local government areas (LGAs) in Lagos State, Nigeria. In each LGA, we sampled 17 pharmacies from a list of all registered pharmacies derived from the Pharmacists Council of Nigeria. We assessed drug quality based on (1) the level of active pharmaceutical ingredients (APIs), which identified falsely labeled drug samples; and (2) the amount of impurities, which revealed substandard drug samples in accordance with the international pharmacopoeia guidelines. Good-quality drugs met specifications for both API and impurity. Results: Of the 102 drug samples collected, 30 (29.3%) were falsely labeled, 76 (74.5%) were substandard,78 (76.5%) were of poor quality and 24 (23.5%) were of good quality.Among the falsely labeled drugs, 2 samples met standards set for purity while 28 did not. Among the 76 substandard drug samples, 28 were also falsely labeled. Of the falsely labeled drugs, 17 (56.7%) came from LGAs with low socioeconomic status, and 40 (52.6%) of the substandard drug samples came from LGAs with high socioeconomic status. Most of the good-quality drug samples, 14 (58.3%), were from LGAs with low socioeconomic status. Eighteen (60%) of the falsely labeled samples, 37 (48.7%) of the substandard samples, and 15 (62.5%) of the good-quality drug samples were from manufacturers based in Asia. The average price was 375.67 Nigerian naira (NGN) for falsely labeled drugs, 383.33 NGN for substandard drugs, and 375.67 NGN for good-quality drugs. The prevalence of falsely labeled and substandard drug samples did not differ by LGA-level socioeconomic status (P = .39) or region of manufacturer (P = .24); however, there was a trend for a difference by price (P = .06). Conclusion: The prevalence of falsely labeled and substandard drug samples was high in Lagos. Treatment of noncommunicable diseases in this setting will require efforts to monitor and assure drug quality. [ABSTRACT FROM AUTHOR]

Background: Studies using health administrative databases (HAD) may lead to biased results since information on potential confounders is often missing. Methods that integrate confounder data from cohort studies, such as multivariate imputation by chained equations (MICE) and two-stage calibration (TSC), aim to reduce confounding bias. We provide new insights into their behavior under different deviations from representativeness of the cohort. Methods: We conducted an extensive simulation study to assess the performance of these two methods under different deviations from representativeness of the cohort. We illustrate these approaches by studying the association between benzodiazepine use and fractures in the elderly using the general sample of French health insurance beneficiaries (EGB) as main database and two French cohorts (Paquid and 3C) as validation samples. Results: When the cohort was representative from the same population as the HAD, the two methods are unbiased. TSC was more efficient and faster but its variance could be slightly underestimated when confounders were non-Gaussian. If the cohort was a subsample of the HAD (internal validation) with the probability of the subject being included in the cohort depending on both exposure and outcome, MICE was unbiased while TSC was biased. The two methods appeared biased when the inclusion probability in the cohort depended on unobserved confounders. Conclusion: When choosing the most appropriate method, epidemiologists should consider the origin of the cohort (internal or external validation) as well as the (anticipated or observed) selection biases of the validation sample. [ABSTRACT FROM AUTHOR]

Background: Obesity increases mortality, and is linked to cardiovascular diseases and metabolic syndrome (MetS). Therefore, the purpose of this study was to analyze the ability of different adiposity indices to identify subjects with MetS among people with intermediate cariovascular risk. Materials and methods: The cross-sectional study involved 2478 subjects, recruited by the MARK study. Adiposity measures: general adiposity by body mass index (BMI), central adiposity by waist-to-height ratio (WHtR), fat mass percent by the Clínica Universidad de Navarra—body adiposity estimator (CUN-BAE), percentage of body fat and of visceral adipose tissue by body roundness index (BRI) and visceral obesity and general adiposity with body shape index (ABSI). The diagnosis of MetS was made in accordance with the criteria established in the international consensus of the Joint Scientific Statement National Cholesterol Education Program III. Results: The highest correlation coefficients were obtained by the glycemic components (HbA1c and FPG) of the MetS and ranged from 0.155 to 0.320. The exception was ABSI, which showed lower values in the global analysis and in the males. Values of the area under the ROC curve with the adiposity indices ranged from 0.773 with the BMI in males to 0.567 with ABSI in males. In the logistic regression analysis, all adiposity factors, except ABSI, showed similar OR values of MetS after adjusting for possible confounding factors. In the global analysis, the adiposity index that showed a highest OR of MetS was CUN-BAE (OR 5.50; 95% CI 4.27–7.09). In the analysis by gender, the highest ORs were BMI in males (OR 5.98; 95% CI 4.70–7.60) and both WHtR and BRI in females (OR 4.15; 95% CI 3.09–5.58). Conclusion: All adiposity indices, except for ABSI, show an association with MetS and similar ability to detect subjects with MetS among people with intermediate cariovascular risk. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system. Given the chronic and heterogenous nature of the disease, treatment with various therapies is a frequent scenario in clinical practice. In persons with chronic morbidity such as MS patients, polypharmacy can give rise to considerable health problems. Objectives: The aim of the present study was to examine the frequency of polypharmacy among relapsing-remitting (RR) MS patients as well as to analyse sociodemographic and clinical factors, which might be associated with polypharmacy (use of five or more medications). Differences in medication between MS patients with and without secondary illnesses (PwSI and Pw/oSI), between men and women and between patients with and without polypharmacy (PwP and Pw/oP) were examined. Methods: For 145 RRMS outpatients, we prospectively collected data by means of anamnesis, patient records, clinical examination and a structured patient interview. This was followed by comparative analyses of various patient subgroups (PwP vs. Pw/oP, PwSI vs. Pw/oSI, men vs. women). Results: The proportion of included MS patients with polypharmacy (use of ≥5 medications) was 30.3%. PwP were significantly older than Pw/oP (45.9 vs. 41.7 years), had a lower level of education and showed a significantly higher median EDSS score (3.0 vs. 2.0). Comorbidities (p<0.001; odds ratio [OR] = 6.293) and higher EDSS scores (p = 0.029; OR = 1.440) were associated with a higher risk of polypharmacy. The proportion of polypharmacy among PwSI was approximately four times higher than among Pw/oSI (46.8% vs. 11.8%). Particularly in the use of antihypertensives, gastrointestinal drugs and dietary supplements, there were differences between Pw/oP and PwP. Conclusion: We found a high burden of polypharmacy in patients with RRMS. This particularly applies to more severely disabled MS patients who suffer from comorbidities. [ABSTRACT FROM AUTHOR]

Background: Syncope could be related to high risk of falls and injury in adults, but documentation is sparse. We examined the association between syncope and subsequent fall-related injuries in a nationwide cohort. Methods: By cross-linkage of nationwide registers, all residents ≥18 years with a first-time diagnosis of syncope were identified between 1997–2012. Syncope patients were matched 1:1 with individuals from the general population. The absolute one-year risk of fall-related injuries, defined as fractures and traumatic head injuries requiring hospitalization, was calculated using Aalen-Johansen estimator. Ratios of the absolute one-year risk of fall-related injuries (ARR) were assessed by absolute risk regression analysis. Results: We identified 125,763 patients with syncope: median age 65 years (interquartile range 46–78). At one year, follow-up was complete for 99.8% where a total of 8394 (6.7%) patients sustained a fall-related injury requiring hospitalization, of which 1606 (19.1%) suffered hip fracture. In the reference group, 4049 (3.2%) persons had a fall-related injury. The one-year ARR of a fall-related injury was 1.79 (95% confidence interval 1.72–1.87, P<0.001) in patients with syncope compared with the reference group; however, increased ARR was not exclusively in older patients. Factors independently associated with increased ARR of fall-related injuries in the syncope population were: injury in past 12 months, 2.39 (2.26–2.53, P<0.001), injury in relation to the syncope episode, 1.62 (1.49–1.77, P<0.001), and depression, 1.37 (1.30–1.45, P<0.001) Conclusion: Patients with syncope were at 80% increased risk of severe fall-related injuries within the year following discharge. Notably, increased risk was not exclusively in older patients. [ABSTRACT FROM AUTHOR]

Background: The blood pressure (BP) variability (BPV) is a predictor of cardiovascular disease, independently of the BP itself. In addition, visceral fat accumulation can trigger atherosclerotic disease through various mechanisms. Methods and results: We examined the association between fat accumulation and day-to-day BPV in 61 adult hypertensive patients. Visceral fat area (VFA) was measured using the dual bioelectrical impedance analysis method. Participants were divided into three groups based on VFA. The standard deviation (SD) in home systolic BP (SBP) for 7 consecutive days was significantly lower in the high VFA tertile (low VFA, 8.40±4.15 mmHg; intermediate VFA, 8.47±2.80 mmHg; and high VFA, 5.84±2.37 mmHg, p of One-way ANOVA = 0.017, p for trend = 0.0126). A similar association was observed between the coefficient of variance (CV) of home SBP and the VFA tertile. Multiple-regression analysis adjusted for age, sex, antihypertensive drug, diabetes, habitual drinking, and SBP level also showed a significant association between the VFA tertile and the SD or CV of home SBP. The adjusted coefficient of regression for the SD of home SBP was -3.28 (95%CI: -5.60 to -0.97, p = 0.008) and the CV of home SBP was -2.51 (95%CI: -4.31 to -0.71, p = 0.008) for the highest VFA tertile as compared to the lowest VFA tertile. Conclusions: These results show for the first time negative correlation between VFA and day-to-day BPV. The degree of obesity should be taken into account when evaluating the value of BPV. [ABSTRACT FROM AUTHOR]

Objective: This study evaluates the actual blood pressure control rate and its estimation by general practitioners, the use of single-pill or free combinations, and the attitude towards single-pill combinations in primary care. Methods: Cross-sectional observational survey in primary care between January 2015 and September 2016 in Belgium and Luxembourg. The participating general practitioners enrolled hypertensive patients taking at least 2 antihypertensive molecules (as fixed or free associations). Results: 742 general practitioners included a total of 8,006 patients, with a mean age of 66 ± 12 years. Systolic blood pressure and diastolic blood pressure were respectively 141 ± 17 mmHg and 82 ± 10 mmHg (means ± SD). These patients had a blood pressure control rate of 45%, whereas it was estimated by general practitioners to be 60%. General practitioners with 11–25 years’ experience performed better than general practitioners with 36–51 years’ experience in the evaluation of blood pressure control. Combinations used were free in 39%, single-pill in 34% and mixed in 27% of the patients. Patients receiving single-pill combinations were younger than those treated with free combinations (63 ± 12 vs. 68 ± 12 years, p < 0.001), with fewer comorbidities (39 vs. 55%, p < 0.001). In patients treated solely with free pill associations, 66% of patient cases, general practitioners were willing to switch to a single-pill combination. The main reasons were improved adherence (76%) and better blood pressure control (64%). Conclusion: In patients requiring at least two antihypertensive drugs, blood pressure control rate remains low and is overestimated by general practitioners. Free combinations remain largely used although many general practitioners seem willing to shift to single-pill combinations. Treatment simplification could improve adherence and blood pressure control rate, which has been shown to lead to reduced morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Antihypertensive treatments have been shown to reduce the risk of Alzheimer’s disease (AD). The renin-angiotensin system (RAS) has been implicated in AD, and thus RAS-acting AHTs (angiotensin converting enzyme inhibitors (ACEIs), and angiotensin-II receptor blockers (ARBs)) may offer differential and additional protective benefits against AD compared with other AHTs, in addition to hypertension management. Methods: In a retrospective cohort design, we examined the medical and pharmacy claims of a 20% sample of Medicare beneficiaries from 2007 to 2013, and compared rates of AD diagnosis for 1,343,334 users of six different AHT drug treatments, 65 years of age or older (4,215,338 person-years). We compared AD risk between RAS and non-RAS AHT drug users, and between ACEI users and ARB users, by sex and race/ethnicity. Models adjusted for age, socioeconomic status, underlying health, and comorbidities. Findings: RAS-acting AHTs were slightly more protective against onset of AD than non-RAS-acting AHTs for males, (male OR = 0.931 (CI: 0.895–0.969)), but not so for females (female OR = 0.985 (CI: 0.963–1.007)). Relative to other AHTs, ARBs were superior to ACEIs for both men (male ARB OR = 0.834 (CI: 0.788–0.884); male ACEI OR = 0.978 (CI: 0.939–1.019)) and women (female ARB OR = 0.941 (CI: 0.913–0.969); female ACEI OR = 1.022 (CI: 0.997–1.048)), but only in white men and white and black women. No association was shown for Hispanic men and women. Conclusion: Hypertension management treatments that include RAS-acting ARBs may, in addition to lowering blood pressure, reduce AD risk, particularly for white and black women and white men. Additional studies and clinical trials that include men and women from different racial and ethnic groups are needed to confirm these findings. Understanding the potentially beneficial effects of certain RAS-acting AHTs in high-risk populations is of great importance. [ABSTRACT FROM AUTHOR]

Backgrounds: Few studies have investigated the therapeutic effects of metformin in patients with type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD). We compared the risk of all-cause mortality between metformin users and nonusers. Methods: We conducted a retrospective cohort study for patients with T2DM and COPD who were enrolled between January 1, 2000 and June 30, 2012. Individuals with exacerbated symptoms who were hospitalized or sent to the emergency department (ED) were identified as having exacerbated COPD; outpatient claims were identified as having stable COPD. A total of 40,597 metformin users and 39,529 nonusers comprised the cohort of stable COPD; 14,001 metformin users and 21,613 nonusers comprised the cohort of exacerbated COPD. Users and nonusers were matched using propensity score (1:1). Our primary outcome was all-cause mortality. Results: A total of 19,505 metformin users were matched to 19,505 nonusers in the cohort of diabetes with stable COPD. The mean follow-up time was 3.91 years. All-cause mortality was reported in 1326 and 1609 metformin users and nonusers, respectively. After multivariate adjustment, metformin users had lower risk of mortality (adjusted hazard ratio [aHR] = 0.84, p < 0.0001). Metformin users had significantly lower risk of noncardiovascular death (aHR = 0.86, p = 0.0008). A total of 7721 metformin users were matched to 7721 nonusers in the cohort of diabetes with exacerbated COPD. The mean follow-up time was 3.18 years. All-cause mortality was reported in 1567 and 1865 metformin users and nonusers, respectively. After multivariate adjustment, metformin users had significantly lower risk of mortality (aHR = 0.89, p = 0.002) and cardiovascular death (aHR = 0.70, p = 0.01). Conclusion: This large-series, nationwide cohort study demonstrated that metformin use could significantly lower the risk of all-cause mortality in patients with T2DM and either stable or exacerbated COPD. [ABSTRACT FROM AUTHOR]

Although physicians learn about new medical technologies from their peers, the magnitude and source of peer influence is unknown. We estimate the effect of peer adoption of three first-in-class medications (dabigatran, sitigliptin, and aliskiren) on physicians’ own adoption of those medications. We included 11,958 physicians in Pennsylvania prescribing anticoagulant, antidiabetic, and antihypertensive medications. We constructed 4 types of peer networks based on shared Medicare and Medicaid patients, medical group affiliation, hospital affiliation, and medical school/residency training. Instrumental variables analysis was used to estimate the causal effect of peer adoption (fraction of peers in each network adopting the new drug) on physician adoption (prescribing at least the median number prescriptions within 15 months of the new drug’s introduction). We illustrate how physician network position can inform targeting of interventions to physicians by computing a social multiplier. Dabigatran was adopted by 25.2%, sitagliptin by 24.5% and aliskiren by 8.3% of physicians. A 10-percentage point increase in peer adoption in the patient-sharing network led to a 5.90% (SE = 1.50%, p<0.001) increase in physician adoption of dabigatran, 8.32% (SE = 1.51%, p<0.001) increase in sitagliptin, and 7.84% increase in aliskiren adoption (SE = 2.93%, p<0.001). Peer effects through shared hospital affiliation were positive but not significant, and medical group and training network effects were not reliably estimated. Physicians in the top decile of patient-sharing network peers were estimated to have nearly 2-fold stronger influence on their peers’ adoption compared to physicians in the top decile of prescribing volume. Limitations include lack of detailed clinical information and pharmaceutical promotion, variables which may influence physician adoption but which are unlikely to bias our peer effect estimates. Peer adoption, especially by those with whom physicians share patients, strongly influenced physician adoption of new drugs. Our study shows the potential for using information on physician peer networks to improve technology diffusion. [ABSTRACT FROM AUTHOR]

Background and purpose: A multi-country European study using data from six healthcare databases from four countries was performed to evaluate in a large study population (>32 million) the risk of ischemic stroke (IS) associated with individual NSAIDs and to assess the impact of risk factors of IS and co-medication. Methods: Case-control study nested in a cohort of new NSAID users. For each case, up to 100 sex- and age-matched controls were selected and confounder-adjusted odds ratios for current use of individual NSAIDs compared to past use calculated. Results: 49,170 cases of IS were observed among 4,593,778 new NSAID users. Use of coxibs (odds ratio 1.08, 95%-confidence interval 1.02–1.15) and use of traditional NSAIDs (1.16, 1.12–1.19) were associated with an increased risk of IS. Among 32 individual NSAIDs evaluated, the highest significant risk of IS was observed for ketorolac (1.46, 1.19–1.78), but significantly increased risks (in decreasing order) were also found for diclofenac, indomethacin, rofecoxib, ibuprofen, nimesulide, diclofenac with misoprostol, and piroxicam. IS risk associated with NSAID use was generally higher in persons of younger age, males, and those with a prior history of IS. Conclusions: Risk of IS differs between individual NSAIDs and appears to be higher in patients with a prior history of IS or transient ischemic attack (TIA), in younger or male patients. Co-medication with aspirin, other antiplatelets or anticoagulants might mitigate this risk. The small to moderate observed risk increase (by 13–46%) associated with NSAIDs use represents a public health concern due to widespread NSAID usage. [ABSTRACT FROM AUTHOR]

Background: Previous research has been highly suggestive that patients of African ancestry are less responsive to beta-blockers and angiotensin converting enzyme inhibitors. However, clinical practice within Ethiopia has continued to recommend all drugs for treatment of hypertension despite the lack of evidentiary support. Therefore this study aims to compare the effectiveness of the three major antihypertensive drugs currently prescribed in an Ethiopian health care setting to further the potential for evidence based prescribing practices. Methods: A prospective, randomized, open label comparative study was used to determine the mean reduction in blood pressure (primary outcome) and assess cardiovascular events (secondary outcomes) among patients receiving one or more of three common antihypertensive drugs (i.e., nifedipine, hydrochlorothiazide, and enalapril) in routine clinical practice between November 2016 and April 2017. Patients were followed for three months. Analysis was based on an intention-to-treat approach. One way analysis of covariance was used to compare the difference in therapeutic effectiveness in reducing blood pressure. Result: A total of 141 patients were randomized to one of three recipient groups—nifedipine (n = 47), enalapril (n = 47) or hydrochlorothiazide (n = 47). Three months after randomization, 44 patients in each group completed the follow-up. Patients randomized to nifedipine had significantly higher mean reduction in systolic blood pressure than those randomized to enalapril(p = 0.003) or hydrochlorothiazide(p = 0.036). The mean reduction in systolic blood pressure was -37.35(CI:-40, -34.2) in the nifedipine group; -30.3(CI: -33.5, -27.1) in patients receiving enalapril; and -32.1(CI:-35, -29.3) in patients assigned hydrochlorothiazide. However, nifedipine did not have a significance difference in reduction of mean diastolic blood pressure compared than those receiving enalapril (p = 0.57) or hydrochlorthiazide (p = 0.99). Conclusion: This study revealed that amongst the three drugs nifedipine was found to be the most effective drug in reduction of systolic blood pressure. Hydrochlorothiazide and enalapril did not show a difference in reduction of mean blood pressure. Further, long term randomized trials are highly recommended to inform revision of Ethiopia-centric hypertension treatment guidelines. [ABSTRACT FROM AUTHOR]

Background: Anticoagulant therapy is recommended in patients with atrial fibrillation (AF) but remains underused. The proper use of anticoagulants has been encouraged in guidelines frequently published over the past two decades. Materials and methods: In this study, we used insurance claims data collected from 2005 to 2014 to investigate the prevalence and incidence of non-valvular AF (NVAF) patients aged 20 to 74 years standardized to the Japanese population in 2012 and subdivided by stroke prevention drug type. We estimated the frequency of coagulation monitoring in patients with incident NVAF undergoing warfarin therapy in 2011 and later. Results: From 2005 to 2014, the standardized prevalence of NVAF increased from 117/100,000 to 278/100,000 and the proportion of anticoagulant users increased from 38.4% to 58.0%, while that of antiplatelet monotherapy decreased from 32.3% to 12.0%. The standardized incidence of NVAF was stable at ~40/100,000 patient-years. The proportion of those patients who started anticoagulant soon after the initial diagnosis increased from 19.9% to 49.1% from 2006 to 2013. Among patients who started warfarin, switchers to DOAC had more frequent coagulation monitoring than non-switchers. Conclusion: The use of anticoagulant therapy has gradually increased in patients with NVAF in Japan during the study period from 2005 to 2014. [ABSTRACT FROM AUTHOR]

Background: Guideline-adherent prescribing for treatment of multiple risk factors in type 2 diabetes (T2D) patients is expected to improve clinical outcomes. However, the relationship to Health-Related Quality of Life (HRQoL) is not straightforward since guideline-adherent prescribing can increase medication burden. Objectives: To test whether guideline-adherent prescribing and disease-specific medication burden are associated with HRQoL in patients with T2D. Methods: Cross-sectional study including 1,044 T2D patients from the e-VitaDM/ZODIAC study in 2012 in the Netherlands. Data from the diabetes visit, such as laboratory and physical examinations and prescribed medication, and from two HRQoL questionnaires, the EuroQol 5 Dimensions 3 Levels (EQ5D-3L) and the World Health Organization Well-Being Index (WHO-5) were collected. Twenty indicators assessing prescribing of recommended glucose lowering drugs, statins, antihypertensives and renin-angiotensin-aldosterone system (RAAS)-inhibitors and potentially inappropriate drugs from a validated diabetes indicator set were included. Disease-specific medication burden was assessed using a modified version of the Medication Regimen Complexity Index (MRCI). Associations were tested with regression models, adjusting for age, gender, diabetes duration, comorbidity, body mass index and smoking. Results: The mean MRCI was 7.1, the median EQ5D-3L-score was 0.86 and the mean WHO-5 score was 72. Seven indicators included too few patients and were excluded from the analysis. The remaining thirteen indicators focusing on recommended start, intensification, current and preferred use of glucose lowering drugs, statins, antihypertensives, RAAS inhibitors, and on inappropriate prescribing of glibenclamide and dual RAAS blockade were not significantly associated with HRQoL. Finally, also the MRCI was not associated with HRQoL. Conclusions: We found no evidence for associations between guideline-adherent prescribing or disease-specific medication burden and HRQoL in T2D patients. This gives no rise to refrain from prescribing intensive treatment in T2D patients as recommended, but the interpretation of these results is limited by the cross-sectional study design and the selection of patients included in some indicators. [ABSTRACT FROM AUTHOR]

Background: The high burden of chronic communicable diseases such as HIV/AIDS, and an escalating rise of non-communicable diseases (NCDs) in Malawi and other sub-Saharan African countries, calls for a shift in how health care services are designed and delivered. Patient-centred care and patient self-management are critical elements in chronic care, and are advocated as universal strategies. In sub-Saharan Africa, there is need for more evidence around the practice of patient self-management, and how to best support patients with chronic conditions in the African context. Our study explored self-management practices of patients with different chronic conditions, and their strategies to overcome care challenges in a resource-constrained setting in Malawi. Methods: This is primarily a qualitative study, involving patients with different chronic conditions from one rural district in Malawi. Data are drawn from semi-structured questions of a survey with 129 patients (from the third of four-part data collection series), 14 in-depth interviews, and four focus-group discussions with patients (n = 31 respondents). A framework approach was used for qualitative analysis, and descriptive statistical analysis was performed on survey data. Results: Patients demonstrated ability to self-manage their conditions, though this varied between conditions, and was influenced by individual and external factors. Factors included: 1) ability to acquire appropriate disease knowledge; 2) poverty level; 3) the presence of support from family caregivers and community-based support initiatives; 4) the nature of one’s social relations; and 5) the ability to deal with stressors and stigma. NCD and HIV comorbid patients were more disadvantaged in their access to care, as they experienced frequent drug stock-outs and incurred additional costs when referred. These barriers contributed to delayed care, poorer treatment adherence, and likelihood of poorer treatment outcomes. Patients proved resourceful and made adjustments in the face of (multiple) care challenges. Conclusion: Our findings complement other research on self-management experiences in chronically ill patients with its analysis on factors and barriers that influence patient self-management capacity in a resource-constrained setting. We recommend expanding current peer-patient and support group initiatives to patients with NCDs, and further investments in the decentralisation of integrated health services to primary care level in Malawi. [ABSTRACT FROM AUTHOR]

Inadequate care of chronic kidney disease (CKD) is common and may be associated with adverse outcomes after dialysis. The nationwide pre-end-stage renal disease pay for performance program (P4P) has been implemented in Taiwan to improve quality of CKD care. However, the effectiveness of the P4P program in improving the outcomes of pre-dialysis care and dialysis is uncertain. We conducted a longitudinal cohort study. Patients who newly underwent long-term dialysis (≥3 mo) between 2007 and 2009 were identified from the Taiwan National Health Insurance Research Database. Based on the patient enrolment of the P4P program, they were categorized into P4P or non-P4P groups. We analysed pre-dialysis care, healthcare expenditures, and mortality between two groups. Among the 26 588 patients, 25.5% participated in the P4P program. The P4P group received significantly better quality of care, including a higher frequency of glomerular filtration rate measurement and CKD complications survey, a higher rate of vascular access preparation, and more frequent use of arteriovenous fistulas than the non-P4P group did. The P4P group had a 68.4% reduction of the 4-year total healthcare expenditure (excluding dialysis fee), which is equivalent to US$345.7 million, and a significant 22% reduction in three-year mortality after dialysis (hazard ratio 0.78, 95% confidence interval: 0.75–0.82, P < 0.001) compared with the non-P4P group. P4P program improves quality of pre-dialysis CKD care, and provide survival benefit and a long-term cost saving for dialysis patients. [ABSTRACT FROM AUTHOR]

Huntington’s disease (HD) age of onset (AO) is mainly determined by the length of the CAG repeat expansion in the huntingtin gene. The remaining AO variability has been attributed to other little-known factors. A factor that has been associated with other neurodegenerative diseases is arterial hypertension (AHT). The aim of this study is to evaluate the contribution of AHT to the AO of HD. We used data from a cohort of 630 European HD patients with adult onset collected by the REGISTRY project of the European Huntington’s Disease Network. Multiple linear regression and ANOVA, controlling for the CAG repeat number of the expanded allele (CAGexp) of each patient, were performed to assess the association between the AHT condition and the AO of the motor symptoms (mAO). The results showed a significant association between AHT and mAO, especially when we only considered the patients diagnosed with AHT prior to manifesting any HD signs (pre-HD AHT). Remarkably, despite the low number of cases, those patients developed motor symptoms 5–8 years later than normotensive patients in the most frequent CAGexp range (40–44). AHT is an age-related condition and consequently, the age of the patient at the time of data collection could be a confounder variable. However, given that most pre-HD AHT patients included in our study had started treatment with antihypertensive drugs prior to the onset of HD, and that antihypertensive drugs have been suggested to confer a neuroprotective effect in other neurodegenerative diseases, raises the interest in elucidating the impact of AHT and/or AHT treatment in HD age of onset in further studies. A confirmation of our results in a larger sample set would open the possibility to significantly improve HD management. [ABSTRACT FROM AUTHOR]

Background: Controlling blood pressure (BP) leads to significant reduction in cardiovascular risks and associated deaths. In Ethiopia, data is scarce about the level and determinants of optimal BP control among hypertensive patients. This study aimed to assess the prevalence and associated factors of optimal BP control among hypertensive patients attending at a district hospital. Methods: A hospital-based, cross-sectional study was conducted among 392 hypertensive patients who were on treatment and follow-up at a district hospital. A structured questionnaire adopted from WHO approach was prepared to collect the data. Medication adherence was measured by the four-item Morisky Green Levine Scale, with a score ≥3 defined as “good adherence”. Blood pressure was measured, and optimal BP control was 0DEFined as systolic BP < 140 mmHg and diastolic BP<90 mmHg. Both binary and multivariable logistic regressions models were fitted to identify correlates of optimal BP control. All statistical tests were two-sided and a p values <0.05 was considered for statistical significance. Results: The mean age of the participants was 58 years (SD±13 years). Over half (53.8%) were females. Three quarters (77.3%) of the participants were adherent to their medications. The overall proportion of participants with optimally controlled BP was 42.9%.Female sex (Adjusted Odd Ratio(AOR) = 1.94, 95% CI: 1.15, 3.26), age older than 60 years (AOR = 2.95, 95% CI: 1.18, 7.40), consumption of vegetables on most days of the week (AOR = 2.16, 95% CI: 1.25, 3.73), physical activity (AOR = 4.85, 95% CI: 2.39, 9.83), and taking less than three drugs per day (AOR = 3.04, 95% CI: 1.51, 6.14) were positively associated with optimally controlled BP. Poor adherence to medications (AOR = 0.18, 95% CI: 0.09, 0.35), having asthma comorbidity (AOR = 0.33, 95% CI:0.12, 0.88) and use of top added salt on a plate (AOR = 0.20, 95% CI:0.11, 0.36) were negatively associated with optimal BP control. Conclusion: A higher proportion of hypertensive patients remain with un-controlled BP. Modifiable risk factors including poor adherence to medications, lack of physical exercise, adding salt into meals, being on multiple medications and comorbidities were significantly and independently associated with poor BP control. Evidence-based, adherence-enhancing and healthy life style interventions should be implemented. [ABSTRACT FROM AUTHOR]

Aim: Among the three adiponectin isoforms, a lower ratio of high molecular weight (HMW) adiponectin to total adiponectin (TA) is well known to cause insulin resistance and type 2 diabetes (T2D). However, how the levels of other adiponectin isoforms, such as the middle molecular weight (MMW) and low molecular weight (LMW) isoforms, and their relative ratio to TA change in T2D subjects has not been determined. Therefore, we investigated the association of these adiponectin-related parameters with T2D. Methods: We examined the associations between adiponectin-related parameters and diabetes in a group of 394 T2D subjects and 374 controls (1st group) randomly selected from among the participants in our previous study. The associations between these parameters and the HOMA-IR in a 2nd group, consisting of the subjects remaining in the 1st group after the exclusion of subjects receiving diabetic medication, were also examined. Result: In the 1st group, after adjusting for confounding factor, the levels of all the adiponectin isoforms and the HMW/TA ratio were significantly lower among the diabetic subjects than among the controls (all P values < 0.01). On the contrary, the LMW/TA ratio was significantly higher among the diabetic subjects (P < 0.01) and was positively associated with T2D (odds ratio = 8.64, P < 0.01). In the 2nd group, the HMW/TA ratio was inversely associated with the HOMA-IR; however, the LMW/TA ratio was positively associated with the HOMA-IR (β for LMW/TA ratio = 0.89, SE = 0.24, P < 0.001), similar to the association with T2D. The MMW/TA ratio was not associated with T2D or the HOMA-IR. Conclusion: The current investigation demonstrated that, unlike the reduction in the levels of all the adiponectin isoforms and the HMW/TA ratio, an increased LMW/TA ratio was associated with T2D through its relation to insulin resistance. [ABSTRACT FROM AUTHOR]

Background: Recent studies show that placebo response has grown significantly over time in clinical trials for antidepressants, ADHD medications, antiepileptics, and antidiabetics. Contrary to expectations, trial outcome measures and success rates have not been impacted. This study aimed to see if this trend of increasing placebo response and stable efficacy outcome measures is unique to the conditions previously studied or if it occurs in trials for conditions with physiologically-measured symptoms, such as hypertension. Method: For this reason, we evaluated the efficacy data reported in the US Food and Drug Administration Medical and Statistical reviews for 23 antihypertensive programs (32,022 patients, 63 trials, 142 treatment arms). Placebo and medication response, effect sizes, and drug-placebo differences were calculated for each treatment arm and examined over time using meta-regression. We also explored the relationship of sample size, trial duration, baseline blood pressure, and number of treatment arms to placebo/drug response and efficacy outcome measures. Results: Like trials of other conditions, placebo response has risen significantly over time (R2 = 0.093, p = 0.018) and effect size (R2 = 0.013, p = 0.187) drug-placebo difference (R2 = 0.013, p = 0.182) and success rate (134/142, 94.4%) have remained unaffected, likely due to a significant compensatory increase in antihypertensive response (R2 = 0.086, p<0.001). Treatment arms are likely overpowered with sample sizes increasing over time (R2 = 0.387, p<0.0001) and stable, large effect sizes (0.78 ±0.37). The exploratory analysis of sample size, trial duration, baseline blood pressure, and number of treatment arms yielded mixed results unlikely to explain the pattern of placebo response and efficacy outcomes over time. The magnitude of placebo response had no relationship to effect size (p = 0.877), antihypertensive-placebo differences (p = 0.752), or p-values (p = 0.963) but was correlated with antihypertensive response (R2 = 0.347, p<0.0001). Conclusions: As hypothesized, this study shows that placebo response is increasing in clinical trials for hypertension without any evidence of this increase impacting trial outcomes. Attempting to control placebo response in clinical trials for hypertension may not be necessary for successful efficacy outcomes. In exploratory analysis, we noted that despite finding significant relationships, none of the trial or patient characteristics we examined offered a clear explanation of the rise in placebo and stability in outcome measures over time. Collectively, these data suggest that the phenomenon of increasing placebo response and stable efficacy outcomes may be a general trend, occurring across trials for various psychiatric and medical conditions with physiological and non-physiological endpoints. [ABSTRACT FROM AUTHOR]

Objectives: Shiga-toxin producing O157:H7 Entero Haemorrhagic E. coli [STEC/EHEC] are the most common cause of Haemolytic Uraemic Syndrome [HUS] related to infectious haemorrhagic colitis. Nearly all recommendations on long term treatment of EHEC infections refer to this strain. The 2011 outbreak in Northern Europe was the first of this dimension to be caused by the serotype O104:H4. We report on the 3.5 year follow up of 61 patients diagnosed with symptomatic EHEC O104:H4 infection in spring 2011. Methods: Patients with EHEC O104 infection were followed in a monocentric, prospective observational study at four time points: 4, 12, 24 and 36 months. These data include the patients’ histories, clinical findings, and complications. Results: Sixty-one patients suffering from EHEC O104:H4 associated enterocolitis participated in the study at the time of hospital discharge. The mean age of patients was 43 ± 2 years, 37 females and 24 males. 48 patients participated in follow up 1 [FU 1], 34 patients in follow up 2 [FU 2], 23 patients in follow up 3 [FU 3] and 18 patients in follow up 4 [FU 4]. Out of 61 patients discharged from the hospital and included in the study, 54 [84%] were examined at least at one additional follow up. Serum creatinine decreased significantly between discharge and FU 1 from 1.3 ± 0.1 mg/dl to 0.7 ± 0.1 mg/dl [p = 0.0045]. From FU 1 until FU 4, no further change in creatinine levels could be observed. The patients need of antihypertensive medications decreased significantly [p = 0.0005] between discharge and FU 1 after four months. From FU 1 until FU 3, 24 months later, no further significant change in antihypertensive treatment was observed. Conclusions: Our findings suggest that patients free of pathological findings at time of discharge do not need a specific follow up. Patients with persistent health problems at hospital discharge should be clinically monitored over four months to evaluate chronic organ damage. Progressive or new emerging renal damage could not be observed over time in any patient. [ABSTRACT FROM AUTHOR]

Objective: In order to search for metabolic biomarkers of antihypertensive drug responsiveness, we measured >600 biochemicals in plasma samples of subjects participating in the GENRES Study. Hypertensive men received in a double-blind rotational fashion amlodipine, bisoprolol, hydrochlorothiazide and losartan, each as a monotherapy for one month, with intervening one-month placebo cycles. Methods: Metabolomic analysis was carried out using ultra high performance liquid chromatography-tandem mass spectrometry. Full metabolomic signatures (the drug cycles and the mean of the 3 placebo cycles) became available in 38 to 42 patients for each drug. Blood pressure was monitored by 24-h recordings. Results: Amlodipine (P values down to 0.002), bisoprolol (P values down to 2 x 10−5) and losartan (P values down to 2 x 10−4) consistently decreased the circulating levels of long-chain acylcarnitines. Bisoprolol tended to decrease (P values down to 0.002) the levels of several medium- and long-chain fatty acids. Hydrochlorothiazide administration was associated with an increase of plasma uric acid level (P = 5 x 10-4) and urea cycle metabolites. Decreases of both systolic (P = 0.06) and diastolic (P = 0.04) blood pressure after amlodipine administration tended to associate with a decrease of plasma hexadecanedioate, a dicarboxylic fatty acid recently linked to blood pressure regulation. Conclusions: Although this systematic metabolomics study failed to identify circulating metabolites convincingly predicting favorable antihypertensive response to four different drug classes, it provided accumulating evidence linking fatty acid metabolism to human hypertension. [ABSTRACT FROM AUTHOR]

Objective: It was shown that sodium can promote auto-immunity through the activation of the Th17 pathway. We aimed to compare sodium intake in patients with rheumatoid arthritis (RA) vs. matched controls. Methods: This case-control study included 24 patients with RA at diagnosis and 24 controls matched by age, gender and body mass index. Sodium intake was evaluated by 24-hr urinary sodium excretion. Results: Sodium excretion was greater for patients with early RA (2,849±1,350 vs. 2,182±751.7mg/day, p = 0.039) than controls. This difference remained significant after adjustment for smoking and the use of anti-hypertensive and nonsteroidal anti-inflammatory drugs (p = 0.043). Patients with radiographic erosion at the time of diagnosis had a higher sodium excretion than those without (p = 0.028). Conclusion: Patients with early RA showed increased sodium excretion which may have contributed to autoimmunity. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess whether a standard intervention package of cardiovascular disease (CVD) care was being delivered effectively, and if it was associated with improved lifestyle and biomedical indicators. Methods: In rural China, we implemented a pragmatic cluster randomized controlled trial for 12 months, randomized at the township hospital level, and compared with usual care. Intervention case management guideline, training and performance monitoring meeting and patient support activities were designed to fit within the job description of family doctors in the township hospitals and comprised: 1) prescription of a standardised package of medicines targeted at those with hypertension or diabetes; 2) advice about specific lifestyle interventions; and 3) advice about medication adherence. Participants were 50–74 years old, had hypertension and CVD risk scores >20% or diabetes, but were excluded if a history of severe CVD events. We also randomly selected 100 participants from six selected clusters per arm as a panel to collect intermediate biomedical indicators over time. Results: A total of 28,130 participants, in 33 intervention and 34 control township hospitals, were recruited. Compared with the control arm, participants in the intervention arm had substantially improved prescribing rates of anti-hypertensives, statins and aspirin (P<0.001), and had higher medication taking rates of aspirin and statins (P<0.001). Mean systolic and diastolic blood pressures were similar across both arms (0.15 mmHg, P = 0.79, and 0.52 mmHg, P = 0.05, respectively). In the panel, (950) rates of smoking (OR = 0.23, P = 0.02) and salt intake (OR = 2.85, P = 0.03) were significantly reduced in the intervention versus control arms, but there were no statistically significant improvement over the 12 month follow-up period in biomedical indicators (P>0.05). Conclusion: Implementation of the package by family doctors was feasible and improved prescribing and some lifestyle changes. Additional measures such as reducing medication costs and patient education are required. Trial registration: Current Controlled Trials [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association of psychotropic drug use with falls among older adults in Germany based on data from the National Health Interview and Examination Survey for Adults 2008–2011 (DEGS1). Methods: DEGS1 collected data on drug use in the past 7 days and on falls occurred in the last 12 months. Study participants were older adults aged 65–79 years with complete data on drug use and falls (N = 1,833). Odds ratio (OR) and 95% confidence intervals (95% CI) were derived from logistic regression models adjusting for potential confounders including socio-demographic characteristics, health-related behaviors (alcohol drinking), body mass index and health conditions (frailty, vision impairment, disability, polypharmacy, blood pressure) as well as use of potential falls-risk-increasing drugs. SPSS complex sample methods were used for statistical analysis. Results: Compared to people without falls, people with falls (n = 370) had a higher psychotropic drug use (33.1% vs. 20.7%, p < .001). After adjusting for potential confounders, use of psychotropic drugs overall was associated with a higher risk of falls (OR 1.64, 95% CI 1.14–2.37). This was particularly true for the use of synthetic psychotropic drugs (1.57, 1.08–2.28), antidepressants overall (2.88, 1.63–5.09) or synthetic antidepressants (2.66, 1.50–4.73), specifically, selective serotonin reuptake inhibitors (SSRIs) (6.22, 2.28–17.0). Similar results were found for recurrent falls. Conclusions: Use of psychotropic drugs overall, especially synthetic antidepressants like SSRIs, is associated with higher risks of falls and recurrent falls among community dwelling older adults aged 65–79 years in Germany. [ABSTRACT FROM AUTHOR]

Background: Intra-dialytic hypertension (IDH) is emerging as an important issue in hemodialysis patients. Its risk factors and clinical outcomes are unclear. Methods: A total of 73 prevalent hemodialysis patients were enrolled. They included 14 (19.2%) patients with baseline IDH and 59 patients without IDH. Their clinical parameters, laboratory parameters, and mortality were investigated over 78 months. Results: The risks factor of IDH included low serum potassium levels, low ultrafiltration, and low arm muscle area. Lower median survival was evident in the IDH group compared to the non-IDH group, but was not significantly different. After adjusting for relevant confounders for age, the IDH group displayed 2.846 times higher mortality rate than the non-IDH Group (adjusted hazard ratio: 2.846; 95% confidence interval: 1.081–7.490; P = 0.034). Conclusion: IDH is associated with high mortality in hemodialysis patients. Clinicians should be aware of the risk factors. Future research studies are needed to explore the mechanisms involved in the association between IDH and mortality. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that anti-hypertensive medications may worsen leg ischemia in peripheral artery disease (PAD) patients. We undertook a meta-analysis to assess the effect of anti-hypertensive medications on measures of leg ischemia including maximum walking distance (MWD), pain free walking distance (PFWD) and ankle brachial pressure index (ABPI). A meta-regression was performed to evaluate whether the effect of the anti-hypertensive medications on mean arterial pressure (MAP) was associated with changes in ABPI, MWD or PFWD. Method: A systematic literature search was performed to identify placebo controlled randomized control trials (RCT) testing anti-hypertensive medications, which reported baseline and follow-up measurements of: MAP and MWD, PFWD or ABPI in patients with intermittent claudication (IC) due to PAD. Result: A meta-analysis was performed on 5 RCTs comprising a total of 180 and 127 patients receiving anti-hypertensive medications and placebo respectively. This analysis suggested that anti-hypertensive medication did not significantly affect MWD, PFWD or ABPI. In contrast, the meta-regression analysis showed that the reduction in MAP due to the anti-hypertensive drugs was positively correlated with increased MWD during follow-up (β = 8.371, p = 0.035). Heterogeneity across studies, as assessed by I2, was high. The follow-up period within the included trials was generally short with 3 out of 5 studies having a follow-up period of ≤ 6 weeks. Conclusion: This study suggests that anti-hypertensive treatment does not worsen but may improve leg ischemia in PAD patients. Larger multicenter trials with longer anti-hypertensive treatment periods are required to clarify the effect of anti-hypertensives on leg ischemia in PAD patients. [ABSTRACT FROM AUTHOR]

Background: The significant rise in the prevalence of obesity coincides with the considerable increase in the prevalence of metabolic syndrome (MS) currently being observed worldwide. The components of MS are not static and their dynamics, such as the order of their occurrence, or the time of exposure to them are, as yet, unknown but could well be clinically relevant. Our objective was to study the dynamic behaviour of MS and its components in a large population-based cohort from a Mediterranean region. Methods and findings: Our study employed a retrospective cohort (between January 1, 2005 and December 31, 2012) made up of individuals from the general population in a region in the northeast of Catalonia, Spain. Given that most of the explicative variables of the risk of having MS were time dependent and, therefore, the risk was not proportional, we used the Andersen-Gill (AG) model to perform a multivariate survival analysis and inferences were performed using a Bayesian framework. Thirty-nine percent of the participants developed MS; 44.6% of them with a single limited episode. Triglycerides and low HDL cholesterol, together with obesity, are components associated with the first occurrence of MS. Components related to the metabolism of glucose are associated with a medium risk of having a first episode of MS, and those related to blood pressure are associated with a lower risk. When the components related to blood pressure and the metabolism of glucose appear first, they determine the appearance of the first episode of MS. The variables concerning the persistence of MS are those that correspond to clinical conditions that do not have well-established drug treatment criteria. Conclusions: Our results suggest that the components related to the metabolism of glucose and to high blood pressure appear early on and act as biomarkers for predicting MS, while the components related to obesity and dyslipidaemia, although essential for the development of MS, appear later. Making lifestyle changes reduces the conditions associated with the persistence of MS. [ABSTRACT FROM AUTHOR]

Background: While body mass index (BMI) is the most widely used anthropometric measure, its association with all-cause mortality is generally J-shaped or U-shaped. A body shape index (ABSI) is a recently formulated anthropometric measure that shows linear relationship to all-cause mortality, especially in Caucasian cohorts. We aimed to address the relationship between ABSI and all-cause mortality in Asians and to assess the influence of sex difference and of chronic kidney disease (CKD) on this relationship. Methods: This was a longitudinal cohort study assessing the association of ABSI, BMI, waist circumference (WC), and waist-to-height ratio (WHtR) with all-cause mortality in a Japanese nationwide Specific Health Checkup database. The study enrolled 160,625 participants followed-up between 2008 and 2012. We calculated the all-cause mortality risk associated with a 1-standard deviation increase (+1SD) in ABSI, BMI, WC, or WHtR in cohorts stratified by sex and the presence of CKD. Results: During the 4-year follow up, 1.3% of participants died. In men, ABSI (+1SD) significantly increased the risk for all-cause mortality after adjusting for other known risk factors including CKD; hazard ratio (HR) and 95% confidence intervals (CI) of non-CKD cohort, 1.30 (1.18 to 1.43), p<0.01; HR and 95%CI of CKD cohort, 1.16 (1.01 to 1.34), p = 0.04. In women, ABSI (+1SD) did not show significant association with all-cause mortality, especially in the CKD cohort; HR and 95% CI of non-CKD cohort, 1.07 (0.99 to 1.17), p = 0.09; HR and 95%CI of CKD cohort, 0.98 (0.84 to 1.14), p = 0.78. Conversely, BMI (+1SD) was associated with significantly lower risk in men, although minimal association was found in women. WC and WHtR showed little association with all-cause mortality. On stratification per ABSI quartiles, mortality risk increased linearly and significantly with ABSI in men, but not in women with CKD. Both BMI and WC showed significant but U-shaped association with mortality in the non-CKD cohort and in men with CKD. WHtR also showed significant U-shaped association with mortality in men. Conclusions: In the Japanese population, ABSI showed significant and linear correlation with mortality risk in men but not in women, especially in the presence of CKD. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups. Methods: 281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjögren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls. Results: Median age was 49 (IQR 36–59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB (40%) positive patients, had more plaques than their respective controls (23% vs. 11%, p = 0.008). Notably, patients with nephritis were younger than other SLE patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we performed an age-matched nested case-control analysis, which demonstrated that patients with nephritis had twice as often plaques (23%) as both non-nephritis patients (11%, p = 0.038) and controls (12%, p = 0.035). Conclusions: In SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis. This subgroup had plaques twice as often as age-matched non-nephritis SLE patients and population controls. Non-nephritis SLE patients, including the aPL positive subgroup, which has a high CVD risk, had similar prevalence of plaques as controls. To prevent later CVD events, this novel observation calls for risk factor screening and initiation of anti-atherosclerotic treatment selectively in SLE nephritis patients. Preferably at nephritis onset, which is often at a young age. In a general perspective this study demonstrates the importance to perform careful clinical subgroup analyses when investigating heterogeneous, hitherto not clearly defined, conditions like SLE. [ABSTRACT FROM AUTHOR]

Background: Effect of prediabetes and normal glucose on arterial stiffness remains controversial. The primary aim of this study was to investigate the relationship of fasting plasma glucose (FPG), postprandial glucose (PG) and glycosylated haemoglobin (HbA1c) with brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) in Caucasian adults. The secondary aim was to analyse this relationship by glycaemic status. Methods: Cross-sectional study. Setting: Primary care. Participants: 2,233 subjects, 35–74 years. Measures: FPG (mg/dL) and HbA1c (%) of all subjects were measured using standard automated enzymatic methods. PG (mg/dL) was self-measured at home two hours after meals (breakfast, lunch and dinner) for one day using an Accu-chek ® glucometer. CAVI was measured using a VaSera VS-1500® device (Fukuda Denshi), and baPWV was calculated using a validated equation. Results: CAVI and baPWV values were significantly higher in subjects with diabetes mellitus than in glucose normal and prediabetes groups (p<0.001). FPG, PG and HbA1c were positively associated with CAVI and baPWV. The β regression coefficient for: HbA1c was 0.112 (CI 95% 0.068 to 0.155) with CAVI, 0.266 (CI 95% 0.172 to 0.359) with baPWV; for PG was 0.006 (CI 95% 0.004 to 0.009 and for FPG was 0.005 (CI 95% 0.002 to 0.008) with baPWV; and for PG was 0.002 (CI 95% 0.001 to 0.003) and 0.003 (CI 95% 0.002 to 0.004) with CAVI (p<0.01 in all cases). When analysing by hyperglycaemic status, FPG, PG and HbA1c were positively associated with CAVI and baPWV in subjects with type 2 diabetes mellitus. Conclusion: FPG, PG and HbA1c show a positive association with CAVI and baPWV, in Caucasian adults with intermediate cardiovascular risk factors. When analysing by hyperglycaemic status, the association is only maintained in subjects with type 2 diabetes mellitus. Trial registration: Clinical Trials.gov Identifier: . Registered 2 September 2011. Retrospectively registered. Last updated September 8, 2016. [ABSTRACT FROM AUTHOR]

Background: Vascular risk factors have been proposed as important targets for the prevention of dementia. As lipid fractions represent easily modifiable targets, we examined the longitudinal relationship of baseline lipid fractions with 13-y incident dementia and its subtypes (Alzheimer disease [AD] and mixed or vascular dementia) in older community-dwelling persons.Methods and Findings: Non-institutionalized persons aged 65+ y (n = 9,294) were recruited for the Three-City Study (3C Study), a population-based cohort study from the electoral rolls of the cities of Dijon, Bordeaux, and Montpellier, France, between March 1999 and March 2001. Follow-up examinations were performed every 2 y after the baseline assessment. The final study sample comprised 7,470 participants from the 3C Study (mean age ± standard deviation [SD] 73.8 ± 5.3 y, 61.0% women) who were prospectively followed up for up to 13 y. Fasting lipid fractions (triglycerides [TGs], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC]) were studied as continuous variables, and results are reported per SD increase of each lipid fraction. Incident dementia and its subtypes were studied as censored variables using Cox models with age as time scale. Analyses were adjusted for sex, study center, and educational level, as well as vascular risk factors and apolipoprotein E (APOE) ε4 genotype. We corrected for multiple testing, yielding a significance threshold of 0.0169. p-Values above the significance threshold but less than 0.05 were considered nominally significant. During a mean (± SD) follow-up period of 7.9 ± 3.6 y, 779 participants developed incident dementia (n = 532 AD and n = 154 mixed or vascular dementia). Higher LDL-C and TC concentrations at baseline were associated with an increased risk of AD (hazard ratio [HR] per SD increase = 1.13 [95% CI 1.04-1.22], p = 0.0045, and HR = 1.12 [1.03-1.22], p = 0.0072, respectively). These associations were largely unchanged after adjustment for vascular risk factors and were attenuated after adjustment for APOEε4 (HR per SD increase = 1.12 [1.03-1.23], p = 0.0110, and HR = 1.12 [1.02-1.23], p = 0.0171, respectively). Higher TG concentrations at baseline were associated with an increased risk of all dementia (HR per SD increase = 1.11 [1.03-1.19], p = 0.0044) and mixed or vascular dementia (HR = 1.21 [1.04-1.41], p = 0.0163). However, these associations disappeared after adjusting for vascular risk factors (HR = 1.07 [0.98-1.17], p = 0.1374, and HR = 1.17 [0.96-1.42], p = 0.1206, respectively). Main limitations of the study include interval censoring of incident dementia cases, potential selective survival bias, and the fact that variation in lipid concentrations during follow-up could not be accounted for in the analyses.Conclusions: In a large population-based sample of older community-dwelling persons with up to 13 y of follow-up, we observed that higher LDL-C and TC concentrations were associated with an increased risk of AD. This result was independent of vascular risk factors and was attenuated after adjustment for APOEε4 carrier status. TG and HDL-C concentrations were not associated with risk of incident dementia or its subtypes after accounting for vascular risk factors. [ABSTRACT FROM AUTHOR]

Objective: The effects of seasonality on blood pressure (BP) and cardiovascular (CV) events are well established, while the influence of seasonality and other environmental factors on arterial stiffness and wave reflection has never been analyzed. This study evaluated whether seasonality (daily number of hours of light) and acute variations in outdoor temperature and air pollutants may affect carotid-femoral pulse wave velocity (PWV) and pressure augmentation. Design and method: 731 hypertensive patients (30–88 years, 417 treated) were enrolled in a cross-sectional study during a 5-year period. PWV, central BP, Augmentation Index (AIx) and Augmentation Pressure (AP) were measured in a temperature-controlled (22–24°C) room. Data of the local office of the National Climatic Data Observatory were used to estimate meteorological conditions and air pollutants (PM10, O3, CO, N2O) exposure on the same day. Results: PWV (mean value 8.5±1.8 m/s) was related to age (r = 0.467, p<0.001), body mass index (r = 0.132, p<0.001), central systolic (r = 0.414, p<0.001) and diastolic BP (r = 0.093, p = 0.013), daylight hours (r = -0.176, p<0.001), mean outdoor temperature (r = -0.082, p = 0.027), O3 (r = -0.135, p<0.001), CO (r = 0.096, p = 0.012), N2O (r = 0.087, p = 0.022). In multiple linear regression analysis, adjusted for confounders, PWV remained independently associated only with daylight hours (β = -0.170; 95% CI: -0.273 to -0.067, p = 0.001). No significant correlation was found between pressure augmentation and daylight hours, mean temperature or air pollutants. The relationship was stronger in untreated patients and women. Furthermore, a positive, independent association between O3 levels and PWV emerged in untreated patients (β: 0.018; p = 0.029; CI: 0.002 to 0.034) and in women (β: 0.027; p = 0.004; CI: 0.009 to 0.045). Conclusions: PWV showed a marked seasonality in hypertensive patients. Environmental O3 levels may acutely reduce arterial stiffness in hypertensive women and in untreated patients. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: To develop a prediction model that can predict HbA1c levels after six years in the non-diabetic general population, including previously used readily available predictors. Methods: Data from 5,762 initially non-diabetic subjects from three population-based cohorts (Hoorn Study, Inter99, KORA S4/F4) were combined to predict HbA1c levels at six year follow-up. Using backward selection, age, BMI, waist circumference, use of anti-hypertensive medication, current smoking and parental history of diabetes remained in sex-specific linear regression models. To minimize overfitting of coefficients, we performed internal validation using bootstrapping techniques. Explained variance, discrimination and calibration were assessed using R2, classification tables (comparing highest/lowest 50% HbA1c levels) and calibration graphs. The model was externally validated in 2,765 non-diabetic subjects of the population-based cohort METSIM. Results: At baseline, mean HbA1c level was 5.6% (38 mmol/mol). After a mean follow-up of six years, mean HbA1c level was 5.7% (39 mmol/mol). Calibration graphs showed that predicted HbA1c levels were somewhat underestimated in the Inter99 cohort and overestimated in the Hoorn and KORA cohorts, indicating that the model’s intercept should be adjusted for each cohort to improve predictions. Sensitivity and specificity (95% CI) were 55.7% (53.9, 57.5) and 56.9% (55.1, 58.7) respectively, for women, and 54.6% (52.7, 56.5) and 54.3% (52.4, 56.2) for men. External validation showed similar performance in the METSIM cohort. Conclusions/interpretation: In the non-diabetic population, our DIRECT-DETECT prediction model, including readily available predictors, has a relatively low explained variance and moderate discriminative performance, but can help to distinguish between future highest and lowest HbA1c levels. Absolute HbA1c values are cohort-dependent. [ABSTRACT FROM AUTHOR]

Objectives: The purposes of this study were to assess the adherence to medication of hypertensive patients visiting community health stations in a rural area in Vietnam, to examine the relationship between levels of adherence and cardiovascular risk among hypertensive patients and to further understand factors influencing adherence. Methods: This study is part of a prospective one-year study conducted on hypertension management in a population aged 35 to 64 years. Data on age, sex, blood pressure and blood test results were collected at baseline. Cardiovascular risk was based on the Cardiovascular Risk Prediction Model for populations in Asia. To calculate medication adherence, the number of days the drug was taken was divided by the number of days since the first day of the prescription. A threshold of 80% was applied to differentiate between adherence and non-adherence. In-depth interviews were conducted among 18 subjects, including subjects classified as adherent and as non-adherent. Results: Among 315 patients analyzed, 49.8% of the patients were adherent. Qualitative investigation revealed discrepancies in classification of adherence and non-adherence based on quantitative analysis and interviews. No significant difference in medication compliance between two cardiovascular disease risk groups (<10% vs. >10% risk) was found, also not after controlling for age, sex, and ethnicity (adjusted odds ratio at 1.068; 95% CI: 0.614 to 1.857). The odds of medication adherence in females was 1.531 times higher than in males but the difference was not statistically significant (95% CI: 0.957 to 2.448). Each one-year increase in age resulted in patients being 1.036 times more likely to be compliant (95% CI: 1.002 to 1.072). Awareness of complications related to hypertension was given as the main reason for adherence to therapy. Conclusions: Medication adherence rate was relatively low among hypertensive subjects. The data suggest that rather than risk profile, the factor of age should be considered for guiding the choice on who to target for improving medication adherence. [ABSTRACT FROM AUTHOR]

Background: Changes during the puerperium are still unclear, particularly in women with hypertension. The choice of antihypertensives, both to control very high blood pressure episodes and to keep blood pressure stable, also requires further elucidation. Currently, there are no clear data to guide the decision for the choice of postpartum antihypertensives. Captopril plays an important role in the treatment of very high blood pressure episodes and may be used postpartum. Clonidine has been used as an alternative in pregnant or postpartum women with contraindications to captopril, with satisfactory effect. The objective of the present study was to evaluate the effectiveness and safety of clonidine compared to captopril for treating severe postpartum hypertension. Methods and findings: A randomized, drug-controlled, triple-blind clinical trial evaluating postpartum women receiving captopril or clonidine. Inclusion criteria consisted of: women with hypertensive disorders of pregnancy systolic blood pressure (SBP) ≥180 mmHg and/or diastolic blood pressure (DBP) ≥110 mmHg], requiring magnesium sulfate. Exclusion criteria were: heart disease, smoking, illicit drug use, contraindications to captopril, clonidine or oral medication, and having used captopril/clonidine previously. The primary outcome was the frequency of very high blood pressure episodes while in the obstetric intensive care unit. A total of 90 postpartum women met the study inclusion criteria, with 45 randomized to each group. There were fewer very high blood pressure episodes during hospitalization (2.1 ± 2.1 vs. 3.5 ± 4.7, p = 0.08), greater percentage reduction in SBP (14.0% ± 8.6% vs. 10.8% ± 8.8%, p = 0.08) and fewer women requiring sodium nitroprusside (2.3% vs. 13.3%; RR: 0.17; 95%CI: 0.02–1.39; p = 0.06) in the clonidine group compared to the captopril group; however, these differences were not significant. The groups were similar regarding daily mean SBP or DBP; however, on the third postpartum day, mean SBP was lower in the clonidine compared to the captopril group (151.9 ± 11.8 mmHg vs. 158.1 ± 13.6 mmHg, p = 0.02). Although not statistically significant, adverse reactions were more common in the captopril group (28.8%) compared to the clonidine group (18.6%). Conclusion: Clonidine and captopril represent safe, effective treatments for severe postpartum hypertension. Trial registration: clinicaltrials.gov: , . [ABSTRACT FROM AUTHOR]

Background: Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients. Objectives: To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations. Methods: A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR. Results: Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66–2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations. Conclusion: BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment. [ABSTRACT FROM AUTHOR]