Cardiovascular co-medication among users of antiobesity drugs: a population-based study

Aim The purpose of this study was to investigate to what extent patients using prescription antiobesity drugs (orlistat, sibutramine and rimonabant) used cardiovascular and antidiabetic drugs. An additional aim was to investigate whether such co-medication differed according to gender, age and amount of antiobesity drugs used. Method Data were retrieved from the Norwegian Prescription Database (NorPD). All patients who had an antiobesity drug (ATC code A08A) dispensed from a Norwegian pharmacy between January 2004 and December 2007 were included in the study. Results During the 4-year study period 83,717 patients had antiobesity drugs dispensed. One in three patients using antiobesity drugs had at least on one occasion used a cardiovascular and/or an antidiabetic drug concomitantly. A significantly higher percentage of men used antihypertensives (40.4 vs. 27.2%, P < 0.0005), lipid modifying agents (24.4 vs. 11.9%, P < 0.0005) and drugs used in diabetes (12.7 vs. 6.4%, P < 0.0005) concomitantly with antiobesity drugs when compared to women. The percentage of patients who had concomitant drug use increased markedly with age. One in four patients had antiobesity drugs dispensed only once during the period 2004–2007. Conclusion Use of cardiovascular and antidiabetic drugs among patients using antiobesity drugs was extensive, especially among men and elderly patients. Overall, there was a high degree of polypharmacy among users of antiobesity drugs. Also, many patients dispensed antiobesity drugs in amounts that indicated use less than the recommended daily dose, and many dispensed antiobesity drugs only once. When prescribing antiobesity drugs to patients the potential benefits of antiobesity drugs should be considered in relation to the patients other chronic diseases and to the total complexity of the patients drug regimen

Association between adherence to calcium-channel blocker and statin medications and likelihood of cardiovascular events among US managed care enrollees

<p>Abstract</p> <p>Background</p> <p>Prior studies have found that patients taking single-pill amlodipine/atorvastatin (SPAA) have greater likelihood of adherence at 6 months than those taking 2-pill calcium-channel blocker and statin combinations (CCB/statin). This study examines whether this adherence benefit results in fewer cardiovascular (CV) events.</p> <p>Methods</p> <p>A retrospective cohort study was conducted using administrative claims data from the IMS LifeLink: US Health Plan Claims database, identifying adults already taking CCB or statin (but not both) who had an index event of either initiating treatment with SPAA or adding CCB to statin (or vice versa) between April 1, 2004 to August 31, 2005. Inclusion criteria included age 18+ years, continuously enrolled for minimum of 6 months prior and 18 months following treatment initiation, >1 diagnosis of hypertension, and no prescription claims for SPAA or added CCB or statin for 6 months prior. Exclusion criteria included >1 claim with missing or invalid days supplied, age 65+ years and not enrolled in Medicare Advantage, or history of prior CV events, cancer diagnosis, or chronic renal failure. The primary outcome measure was the rate of CV events (myocardial infarction, heart failure, angina, other ischemic heart disease, stroke, peripheral vascular disease, or revascularization procedure) from 6 to 18 months following index date, analyzed at three levels: 1) all adherent vs. non-adherent patients, 2) SPAA vs. dual-pill patients (regardless of adherence level), and 3) adherent SPAA, adherent dual-pill, and non-adherent SPAA patients vs. non-adherent dual-pill patients.</p> <p>Results</p> <p>Of 1,537 SPAA patients, 56.5% were adherent at 6 months, compared with 21.4% of the 17,910 CCB/statin patients (p < 0.001). Logistic regression found SPAA patients more likely to be adherent (OR = 4.7, p < 0.001) than CCB/statin patients. In Cox proportional hazards models, being adherent to either regimen was associated with significantly lower risk of CV event (HR = 0.77, p = 0.003). A similar effect was seen for SPAA vs. CCB/statin patients (HR = 0.68, p = 0.02). In a combined model, the risk of CV events was significantly lower for adherent CCB/statin patients (HR = 0.79, p = 0.01) and adherent SPAA patients (HR = 0.61, p = 0.03) compared to non-adherent CCB/statin patients.</p> <p>Conclusions</p> <p>Patients receiving SPAA rather than a 2-pill CCB/statin regimen are more likely to be adherent. In turn, adherence to CCB and statin medications is associated with lower risk of CV events in primary prevention patients.</p

Deep-Ocean dissolved organic matter reactivity along the Mediterranea Sea: does size matter?

Original research paperDespite of the major role ascribed to marine dissolved organic matter (DOM) in the global carbon cycle, the reactivity of this pool in the dark ocean is still poorly understood. Present hypotheses, posed within the size-reactivity continuum (SRC) and the microbial carbon pump (MCP) conceptual frameworks, need further empirical support. Here, we provide field evidence of the soundness of the SRC model. We sampled the high salinity core-of-flow of the Levantine Intermediate Water along its westward route through the entire Mediterranean Sea. At selected sites, DOM was size-fractionated in apparent high (aHMW) and low (aLMW) molecular weight fractions using an efficient ultrafiltration cell. A percentage decline of the aHMW DOM from 68–76% to 40–55% was observed from the Levantine Sea to the Strait of Gibraltar in parallel with increasing apparent oxygen utilization (AOU). DOM mineralization accounted for 30±3% of the AOU, being the aHMW fraction solely responsible for this consumption, verifying the SRC model in the field. We also demonstrate that, in parallel to this aHMW DOM consumption, fluorescent humic-like substances accumulate in both fractions and protein-like substances decline in the aLMW fraction, thus indicating that not only size matters and providing field support to the MCP modelHOTMIX (grant number CTM2011–30010-C02 01-MAR and 02-MAR) and the project FERMIO (MINECO, CTM2014-57334-JIN), both co-financed with FEDER funds; (reference BES-2012- 056175) from the Spanish Ministry of Economy, Industry and Competitivenes; the project MODMED from CSIC (PIE, 201730E020) and CSIC Program “Junta para la Ampliación de Estudios” co-financed by the ESF (reference JAE DOC 040)Versión del editor2,92

The @RISK Study: Risk communication for patients with type 2 diabetes: design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients with type 2 diabetes mellitus (T2DM) have an increased risk to develop severe diabetes related complications, especially cardiovascular disease (CVD). The risk to develop CVD can be estimated by means of risk formulas. However, patients have difficulties to understand the outcomes of these formulas. As a result, they may not recognize the importance of changing lifestyle and taking medication in time. Therefore, it is important to develop risk communication methods, that will improve the patients' understanding of risks associated with having diabetes, which enables them to make informed choices about their diabetes care.</p> <p>The aim of this study is to investigate the effects of an intervention focussed on the communication of the absolute 10-year risk to develop CVD on risk perception, attitude and intention to change lifestyle behaviour in patients with T2DM. The conceptual framework of the intervention is based on the Theory of Planned Behaviour and the Self-regulation Theory.</p> <p>Methods</p> <p>A randomised controlled trial will be performed in the Diabetes Care System West-Friesland (DCS), a managed care system. Newly referred T2DM patients of the DCS, younger than 75 years will be eligible for the study. The intervention group will be exposed to risk communication on CVD, on top of standard managed care of the DCS. This intervention consists of a simple explanation on the causes and consequences of CVD, and possibilities for prevention. The probabilities of CVD in 10 year will be explained in natural frequencies and visualised by a population diagram. The control group will receive standard managed care. The primary outcome is appropriateness of risk perception. Secondary outcomes are attitude and intention to change lifestyle behaviour and illness perception. Differences between baseline and follow-up (2 and 12 weeks) between groups will be analysed according to the intention-to-treat principle. The study was powered on 120 patients in each group.</p> <p>Discussion</p> <p>This innovative risk communication method based on two behavioural theories might improve patient's appropriateness of risk perception and attitude concerning lifestyle change. With a better understanding of their CVD risk, patients will be able to make informed choices concerning diabetes care.</p> <p>Trail registration</p> <p>The trial is registered as NTR1556 in the Dutch Trial Register.</p

Adherence to cardioprotective medications and mortality among patients with diabetes and ischemic heart disease

BACKGROUND: Patients with diabetes and ischemic heart disease (IHD) are at high risk for adverse cardiac outcomes. Clinical practice guidelines recommend multiple cardioprotective medications to reduce recurrent events. We evaluated the association between cardioprotective medication adherence and mortality among patients with diabetes and IHD. METHODS: In a retrospective cohort study of 3,998 patients with diabetes and IHD, we evaluated use of ACE inhibitors or angiotensin receptor blockers, β-blockers, and statin medications. Receipt of cardioprotective medications was based on filled prescriptions. Medication adherence was calculated as the proportion of days covered (PDC) for filled prescriptions. The primary outcome of interest was all-cause mortality. RESULTS: The majority of patients (92.8%) received at least 1 cardioprotective medication. Patients receiving any medications had lower unadjusted mortality rates compared to patients not receiving any medications (7.9% vs. 11.5%; p = 0.03). In multivariable analysis, receipt of any cardioprotective medication remained associated with lower all-cause mortality (OR 0.65; 95% CI 0.43–0.99). Among patients receiving cardioprotective medications, the majority (80.3%) were adherent (PDC ≥ 0.80). Adherent patients had lower unadjusted mortality rates (6.7% vs. 12.1%; p < 0.01). In multivariable analysis, medication adherence remained associated with lower all-cause mortality (OR 0.52; 95% CI 0.39–0.69) compared to non-adherence. In contrast, there was no mortality difference between patients receiving cardioprotective medications who were non-adherent compared to patients not receiving any medications (OR 1.01; 95% CI 0.64–1.61). CONCLUSION: In conclusion, medication adherence is associated with improved outcomes among patients with diabetes and IHD. Quality improvement interventions are needed to increase medication adherence in order for patients to maximize the benefit of cardioprotective medications

Does inequality erode generalized trust? Evidence from Romanian youths

Generalized trust is a critical component of liberal democratic citizenship. We evaluate the extent to which exposure to socioeconomic inequality erodes trust among Romanian youths. Using national survey data of Romanian eighth-grade and high school students, we evaluate this effect as a product of socioeconomic diversity within the classroom, controlling for the social status of the students as well as socioeconomic inequality within the community where the school is located. Our analysis shows that generalized trust is higher for students in higher grades. However, despite this maturing effect, students exposed to greater levels of socioeconomic diversity have significantly lower levels of trust. The effect is particularly acute for students in the ninth grade. This finding holds when controlling for socioeconomic diversity and polarization in the community. The result reinforces the idea that generalized trust develops early in one’s life and is quite stable, although a major life transformation, such as entering high school, may alter trust depending on the social context

Mining protein loops using a structural alphabet and statistical exceptionality

<p>Abstract</p> <p>Background</p> <p>Protein loops encompass 50% of protein residues in available three-dimensional structures. These regions are often involved in protein functions, e.g. binding site, catalytic pocket... However, the description of protein loops with conventional tools is an uneasy task. Regular secondary structures, helices and strands, have been widely studied whereas loops, because they are highly variable in terms of sequence and structure, are difficult to analyze. Due to data sparsity, long loops have rarely been systematically studied.</p> <p>Results</p> <p>We developed a simple and accurate method that allows the description and analysis of the structures of short and long loops using structural motifs without restriction on loop length. This method is based on the structural alphabet HMM-SA. HMM-SA allows the simplification of a three-dimensional protein structure into a one-dimensional string of states, where each state is a four-residue prototype fragment, called structural letter. The difficult task of the structural grouping of huge data sets is thus easily accomplished by handling structural letter strings as in conventional protein sequence analysis. We systematically extracted all seven-residue fragments in a bank of 93000 protein loops and grouped them according to the structural-letter sequence, named structural word. This approach permits a systematic analysis of loops of all sizes since we consider the structural motifs of seven residues rather than complete loops. We focused the analysis on highly recurrent words of loops (observed more than 30 times). Our study reveals that 73% of loop-lengths are covered by only 3310 highly recurrent structural words out of 28274 observed words). These structural words have low structural variability (mean RMSd of 0.85 Å). As expected, half of these motifs display a flanking-region preference but interestingly, two thirds are shared by short (less than 12 residues) and long loops. Moreover, half of recurrent motifs exhibit a significant level of amino-acid conservation with at least four significant positions and 87% of long loops contain at least one such word. We complement our analysis with the detection of statistically over-represented patterns of structural letters as in conventional DNA sequence analysis. About 30% (930) of structural words are over-represented, and cover about 40% of loop lengths. Interestingly, these words exhibit lower structural variability and higher sequential specificity, suggesting structural or functional constraints.</p> <p>Conclusions</p> <p>We developed a method to systematically decompose and study protein loops using recurrent structural motifs. This method is based on the structural alphabet HMM-SA and not on structural alignment and geometrical parameters. We extracted meaningful structural motifs that are found in both short and long loops. To our knowledge, it is the first time that pattern mining helps to increase the signal-to-noise ratio in protein loops. This finding helps to better describe protein loops and might permit to decrease the complexity of long-loop analysis. Detailed results are available at <url>http://www.mti.univ-paris-diderot.fr/publication/supplementary/2009/ACCLoop/</url>.</p