Optimizing Vancomycin Dosing in Chronic Kidney Disease by Deriving and Implementing a Web-Based Tool Using a Population Pharmacokinetics Analysis.

Background: Chronic kidney disease (CKD) patients requiring intravenous vancomycin bear considerable risks of adverse outcomes both from the infection and vancomycin therapy itself, necessitating especially precise dosing to avoid sub- and supratherapeutic vancomycin exposure. Methods: In this retrospective study, we performed a population pharmacokinetic analysis to construct a vancomycin dose prediction model for CKD patients who do not require renal replacement therapy. The model was externally validated on an independent cohort of patients to assess its prediction accuracy. The pharmacokinetic parameter estimates and the equations were productized into a Web application (VancApp) subsequently implemented in routine care. The association between VancApp-based dosing and time-to-target concentration attainment, 30-day mortality, and nephrotoxicity were assessed postimplementation. Results: The model constructed from an initial cohort (n = 80) revealed a population clearance and volume of distribution of 1.30 L/h and 1.23 L/kg, respectively. External model validation (n = 112) demonstrated a mean absolute prediction error of 1.25 mg/L. Following 4 months of clinical implementation of VancApp as an optional alternative to usual care [VancApp (n = 22) vs. usual care (n = 21)], patients who had received VancApp-based dosing took a shorter time to reach target concentrations (median: 66 vs. 102 h, p = 0.187) and had fewer 30-day mortalities (14% vs. 24%, p = 0.457) compared to usual care. While statistical significance was not achieved, the clinical significance of these findings appear promising. Conclusion: Clinical implementation of a population pharmacokinetic model for vancomycin in CKD can potentially improve dosing precision in CKD and could serve as a practical means to improve vital clinical outcomes

Effectiveness and Content Analysis of Interventions to Enhance Oral Antidiabetic Drug Adherence in Adults with Type 2 Diabetes : Systematic Review and Meta-Analysis

We thank Frederic Bergeron, information scientist, for assistance in search strategies. We thank American Journal Experts for editing the text. Source of financial support: This study was funded by the Laval University Chair on Adherence to Treatments. This Chair is supported by nonrestricted grants from AstraZeneca Canada, Merck Canada, Sanofi Canada, and Pfizer Canada and from the Prends soin de toi program (a Quebec provincial program for the improvement of public health).Peer reviewedPostprin

Health locus of control in patients undergoing coronary artery surgery – changes and associated outcomes: a seven-year cohort study

Introduction: Health locus of control is a measure of an individual’s beliefs in factors that are thought to determine health experiences. Scores are generated and form a graduated linear scale from external to internal control, with respect to their views on health causality. Health locus of control has been considered to be a relatively stable entity. However, it is not clear if this status changes in the advent of serious health challenges, such as coronary artery bypass graft surgery. The aim of this study is to explore the variability of health locus of control and its association with postoperative health in this context. Methods: In a longitudinal cohort study of patients undergoing coronary artery bypass graft surgery, a purposive sample (n=215) were recruited from the waiting list and followed up postoperatively, at approximately one year and seven years later. Results: Patients undergoing coronary artery bypass graft surgery demonstrated marked fluctuations in health locus of control in their peri-operative and rehabilitative phases. Mean health locus of control became more external (often associated with poorer outcomes) peri-operatively, and more internal (generally associated with better health outcomes) in the rehabilitative period. Conclusions: Health locus of control scores were shown to be changeable during a major health care intervention, with possible consequences for patient outcomes and care needs. The significant health belief upheaval demonstrated in this cohort should be considered in assessing patients preoperatively, and managed as part of the patients’ clinical journey by both acute and rehabilitation staff. It is likely to have particular importance in individualised assessment and management of future prevention advice for patients

Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults

BackgroundThe measurement of severity and control of asthma in both children and adults can be based on subjective or objective measures. It has been advocated that fractional exhaled nitric oxide (FeNO) can be used to monitor airway inflammation as it correlates with some markers of asthma. Interventions for asthma therapies have been traditionally based on symptoms and/or spirometry.ObjectivesTo evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults.Search strategyWe searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was completed in February 2009.Selection criteriaAll randomised controlled comparisons of adjustment of asthma therapy based on exhaled nitric oxide compared to traditional methods (primarily clinical symptoms and spirometry/peak flow).Data collection and analysisResults of searches were reviewed against pre-determined criteria for inclusion. Relevant studies were independently selected in duplicate. Two authors independently assessed trial quality and extracted data. Authors were contacted for further information with response from one.Main resultsTwo studies have been added for this update, which now includes six (2 adults and 4 children/adolescent) studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels, the way in which FeNO was used to adjust therapy and duration of study. Of 1053 participants randomised, 1010 completed the trials. In the meta-analysis, there was no significant difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms, (mean difference -450 mcg; 95% CI -677 to 223 mcg budesonide equivalent/day). However, the total amount of inhaled corticosteroid used in one of the adult studies was 11% greater in the FeNO arm. In contrast, in the paediatric studies, there was a significant increase in inhaled corticosteroid dose in the FeNO strategy arm (mean difference of 140 mcg; 95% CI 29 to 251, mcg budesonide equivalent/day).Authors' conclusionsTailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the six studies and found only modest benefit at best and potentially higher doses of inhaled corticosteroids in children. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids cannot be routinely recommended for clinical practice at this stage and remains uncertain

Percutaneous transluminal angioplasty in patients with peripheral arterial disease does not affect circulating monocyte subpopulations

Monocytes are mononuclear cells characterized by distinct morphology and expression of CD14 and CD16 surface receptors. Classical, quiescent monocytes are positive for CD14 (lipopolysaccharide receptor) but do not express Fc gamma receptor III (CD16). Intermediate monocytes coexpress CD16 and CD14. Nonclassical monocytes with low expression of CD14 represent mature macrophage-like monocytes. Monocyte behavior in peripheral arterial disease (PAD) and during vessel wall directed treatment is not well defined. This observation study aimed at monitoring of acute changes in monocyte subpopulations during percutaneous transluminal angioplasty (PTA) in PAD patients. Patients with Rutherford 3 and 4 PAD with no signs of inflammatory process underwent PTA of iliac, femoral, or popliteal segments. Flow cytometry for CD14, CD16, HLA-DR, CD11b, CD11c, and CD45RA antigens allowed characterization of monocyte subpopulations in blood sampled before and after PTA (direct angioplasty catheter sampling). Patients were clinically followed up for 12 months. All 61 enrolled patients completed 12-month follow-up. Target vessel failure occurred in 12 patients. While absolute counts of monocyte were significantly lower after PTA, only subtle monocyte activation after PTA (CD45RA and β-integrins) occurred. None of the monocyte parameters correlated with long-term adverse clinical outcome. Changes in absolute monocyte counts and subtle changes towards an activation phenotype after PTA may reflect local cell adhesion phenomenon in patients with Rutherford 3 or 4 peripheral arterial disease

Current clinician perspective on non-vitamin K antagonist oral anticoagulant use in challenging clinical cases.

OBJECTIVE: The evolution of non-vitamin K antagonist anticoagulants (NOACs) has changed the horizon of stroke prevention in atrial fibrillation (SPAF). All 4 NOACs have been tested against dose-adjusted warfarin in well-designed, pivotal, phase III, randomized, controlled trials (RCTs) and were approved by regulatory authorities for an SPAF indication. However, as traditional RCTs, these trials have important weaknesses, largely related to their complex structure and patient participation, which was limited by strict inclusion and extensive exclusion criteria. In the real world, however, clinicians are often faced with complex, multimorbid patients who are underrepresented in these RCTs. This article is based on a meeting report authored by 12 scientists studying atrial fibrillation (AF) in diverse ways who discussed the management of challenging AF cases that are underrepresented in pivotal NOAC trials. METHODS: An advisory board panel was convened to confer on management strategies for challenging AF cases. The article is derived from a summary of case presentations and the collaborative discussions at the meeting. CONCLUSION: This expert consensus of cardiologists aimed to define management strategies for challenging cases with patients who underrepresented in pivotal trials using case examples from their routine practice. Although strong evidence is lacking, exploratory subgroup analysis of phase III pivotal trials partially informs the management of these patients. Clinical trials with higher external validity are needed to clarify areas of uncertainty. The lack of clear evidence about complex AF cases has pushed clinicians to manage patients based on clinical experience, including rare situations of off-label prescriptions