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

Emergence of light-driven protometabolism on recruitment of a photocatalytic cofactor by a self-replicator

Establishing how life can emerge from inanimate matter is among the grand challenges of contemporary science. Chemical systems that capture life’s essential characteristics—replication, metabolism and compartmentalization—offer a route to understanding this momentous process. The synthesis of life, whether based on canonical biomolecules or fully synthetic molecules, requires the functional integration of these three characteristics. Here we show how a system of fully synthetic self-replicating molecules, on recruiting a cofactor, acquires the ability to transform thiols in its environment into disulfide precursors from which the molecules can replicate. The binding of replicator and cofactor enhances the activity of the latter in oxidizing thiols into disulfides through photoredox catalysis and thereby accelerates replication by increasing the availability of the disulfide precursors. This positive feedback marks the emergence of light-driven protometabolism in a system that bears no resemblance to canonical biochemistry and constitutes a major step towards the highly challenging aim of creating a new and completely synthetic form of life. [Figure not available: see fulltext.]

Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice

Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria, but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived. The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections; therefore, we have investigated the kinetics, duration and characteristics of the Plasmodium-specific memory B cell response in an infection of P. chabaudi in mice. Memory B cells and plasma cells specific for the C-terminal region of Merozoite Surface Protein 1 were detectable for more than eight months following primary infection. Furthermore, a classical memory response comprised predominantly of the T-cell dependent isotypes IgG2c, IgG2b and IgG1 was elicited upon rechallenge with the homologous parasite, confirming the generation of functional memory B cells. Using cyclophosphamide treatment to discriminate between long-lived and short-lived plasma cells, we demonstrated long-lived cells secreting Plasmodium-specific IgG in both bone marrow and in spleens of infected mice. The presence of these long-lived cells was independent of the presence of chronic infection, as removal of parasites with anti-malarial drugs had no impact on their numbers. Thus, in this model of malaria, both functional Plasmodium-specific memory B cells and long-lived plasma cells can be generated, suggesting that defects in generating these cell populations may not be the reason for generating short-lived antibody responses

Adherence with statins in a real-life setting is better when associated cardiovascular risk factors increase: a cohort study

<p>Abstract</p> <p>Background</p> <p>While the factors for poor adherence for treatment with statins have been highlighted, the impact of their combination on adherence is not clear.</p> <p>Aims</p> <p>To estimate adherence for statins and whether it differs according to the number of cardiovascular risk factors.</p> <p>Methods</p> <p>A cohort study was conducted using data from the main French national health insurance system reimbursement database. Newly treated patients with statins between September 1 and December 31, 2004 were included. Patients were followed up 15 months. The cohort was split into three groups according to their number of additional cardiovascular risk factors that included age and gender, diabetes mellitus and cardiovascular disease (using co-medications as a <it>proxy</it>). Adherence was assessed for each group by using four parameters: <it>(i) </it>proportion of days covered by statins, <it>(ii) </it>regularity of the treatment over time, <it>(iii) </it>persistence, and <it>(iv) </it>the refill delay.</p> <p>Results</p> <p>16,397 newly treated patients were identified. Of these statin users, 21.7% did not have additional cardiovascular risk factors. Thirty-one percent had two cardiovascular risk factors and 47% had at least three risk factors. All the parameters showed a sub-optimal adherence whatever the group: days covered ranged from 56% to 72%, regularity ranged from 23% to 33% and persistence ranged from 44% to 59%, but adherence was better for those with a higher number of cardiovascular risk factors.</p> <p>Conclusions</p> <p>The results confirm that long-term drug treatments are a difficult challenge, particularly in patients at lower risk and invite to the development of therapeutic education.</p

Capturing judgement strategies in risk assessments with improved quality of clinical information: How nurses' strategies differ from the ecological model

Background: Nurses' risk assessments of patients at risk of deterioration are sometimes suboptimal. Advances in clinical simulation mean higher quality information can be used as an alternative to traditional paper-based approaches as a means of improving judgement. This paper tests the hypothesis that nurses' judgement strategies and policies change as the quality of information used by nurses in simulation changes. Methods: Sixty-three student nurses and 34 experienced viewed 25 paper-case based and 25 clinically simulated scenarios, derived from real cases, and judged whether the (simulated) patient was at 'risk' of acute deterioration. Criteria of judgement "correctness" came from the same real cases. Information relative weights were calculated to examine judgement policies of individual nurses. Group comparisons of nurses and students under both paper and clinical simulation conditions were undertaken using non parametric statistical tests. Judgment policies were also compared to the ecological statistical model. Cumulative relative weights were calculated to assess how much information nurses used when making judgements. Receiver operating characteristic (ROC) curves were generated to examine predictive accuracy amongst the nurses. Results: There were significant variations between nurses' judgement policies and those optimal policies determined by the ecological model. Nurses significantly underused the cues of consciousness level, respiration rate, and systolic blood pressure than the ecological model requires. However, in clinical simulations, they tended to make appropriate use of heart rate, with non-significant difference in the relative weights of heart rate between clinical simulations and the ecological model. Experienced nurses paid substantially more attention to respiration rate in the simulated setting compared to paper cases, while students maintained a similar attentive level to this cue. This led to a non-significant difference in relative weights of respiration rate between experienced nurses and students. Conclusions: Improving the quality of information by clinical simulations significantly impacted on nurses' judgement policies of risk assessments. Nurses' judgement strategies also varied with the increased years of experience. Such variations in processing clinical information may contribute to nurses' suboptimal judgements in clinical practice. Constructing predictive models of common judgement situations, and increasing nurses' awareness of information weightings in such models may help improve judgements made by nurses

Cholesterol treatment with statins: Who is left out and who makes it to goal?

<p>Abstract</p> <p>Background</p> <p>Whether patient socio-demographic characteristics (age, sex, race/ethnicity, income, and education) are independently associated with failure to receive indicated statin therapy and/or to achieve low density lipoprotein cholesterol (LDL-C) therapy goals are not known. We examined socio-demographic factors associated with a) eligibility for statin therapy among those not on statins, and b) achievement of statin therapy goals.</p> <p>Methods</p> <p>Adults (21-79 years) participating in the United States (US) National Health and Nutrition Examination Surveys, 1999-2006 were studied. Statin eligibility and achievement of target LDL-C was assessed using the US Third Adult Treatment Panel (ATP III) on Treatment of High Cholesterol guidelines.</p> <p>Results</p> <p>Among 6,043 participants not taking statins, 10.4% were eligible. Adjusted predictors of statin eligibility among statin non-users were being older, male, poorer, and less educated. Hispanics were less likely to be eligible but not using statins, an effect that became non-significant with adjustment for language usually spoken at home. Among 537 persons taking statins, 81% were at LDL-C goal. Adjusted predictors of goal failure among statin users were being male and poorer. These risks were not attenuated by adjustment for healthcare access or utilization.</p> <p>Conclusion</p> <p>Among person's not taking statins, the socio-economically disadvantaged are more likely to be eligible and among those on statins, the socio-economically disadvantaged are less likely to achieve statin treatment goals. Further study is needed to identify specific amenable patient and/or physician factors that contribute to these disparities.</p

Phylodynamics and movement of Phycodnaviruses among aquatic environments

Phycodnaviruses have a significant role in modulating the dynamics of phytoplankton, thereby influencing community structure and succession, nutrient cycles and potentially atmospheric composition because phytoplankton fix about half the carbon dioxide (CO2) on the planet, and some algae release dimethylsulphoniopropionate when lysed by viruses. Despite their ecological importance and widespread distribution, relatively little is known about the evolutionary history, phylogenetic relationships and phylodynamics of the Phycodnaviruses from freshwater environments. Herein we provide novel data on Phycodnaviruses from the largest river system on earth—the Amazon Basin—that were compared with samples from different aquatic systems from several places around the world. Based on phylogenetic inference using DNA polymerase (pol) sequences we show the presence of distinct populations of Phycodnaviridae. Preliminary coarse-grained phylodynamics and phylogeographic inferences revealed a complex dynamics characterized by long-term fluctuations in viral population sizes, with a remarkable worldwide reduction of the effective population around 400 thousand years before the present (KYBP), followed by a recovery near to the present time. Moreover, we present evidence for significant viral gene flow between freshwater environments, but crucially almost none between freshwater and marine environments