Appropriate training for community pharmacists may improve the quality of medication use. Few studies have reported the impact of such programs on medication management for patients with chronic ...kidney disease (CKD).
Multicenter, cluster-randomized, controlled trial.
Patients with CKD stage 3a, 3b, or 4 from 6 CKD clinics (Quebec, Canada) and their community pharmacies.
Each cluster (a pharmacy and its patients) was randomly assigned to either ProFiL, a training-and-communication network program, or the control group. ProFiL pharmacists completed a 90-minute interactive web-based training program on use of medications in CKD and received a clinical guide, patients’ clinical summaries, and facilitated access to the CKD clinic.
Drug-related problems (primary outcome), pharmacists’ knowledge and clinical skills, and patients’ clinical attributes (eg, blood pressure and glycated hemoglobin concentration).
Drug-related problems were evaluated the year before and after the recruitment of patients using a validated set of significant drug-related problems, the Pharmacotherapy Assessment in Chronic Renal Disease (PAIR) criteria. Pharmacists’ questionnaires were completed at baseline and after 1 year. Clinical attributes were documented at baseline and after 1 year using available information in medical charts.
207 community pharmacies, 494 pharmacists, and 442 patients with CKD participated. After 1 year, the mean number of drug-related problems per patient decreased from 2.16 to 1.60 and from 1.70 to 1.62 in the ProFiL and control groups, respectively. The difference in reduction of drug-related problems per patient between the ProFiL and control groups was −0.32 (95% CI, −0.63 to −0.01). Improvements in knowledge (difference, 4.5%; 95% CI, 1.6%-7.4%) and clinical competencies (difference, 7.4%; 95% CI, 3.5%-11.3%) were observed among ProFiL pharmacists. No significant differences in clinical attributes were observed across the groups.
High proportion of missing data on knowledge and clinical skills questionnaire (34.6%) and clinical attributes (11.1%).
Providing community pharmacists with essential clinical data, appropriate training, and support from hospital pharmacists with expertise in nephrology increases pharmacists’ knowledge and reduces drug-related problems in patients with CKD who are followed up in clinics incorporating a multidisciplinary health care team.
Background Explicit criteria for judging medication safety and use issues in patients with chronic kidney disease (CKD) are lacking. Study Design Quality improvement report. Setting & Participants ...Nephrologists (n = 4), primary care physicians (n = 2), hospital pharmacists with expertise in nephrology (n = 4), and community pharmacists (n = 2). The PAIR (Pharmacotherapy Assessment in Chronic Renal Disease) criteria were applied retrospectively to 90 patients with CKD in a randomized study. Quality Improvement Plan Development of an explicit set of criteria to enable rapid and systematic detection of drug-related problems (DRPs). Using a RAND method, experts judged the clinical significance of DRPs and the appropriateness of a community pharmacist intervention. The PAIR criteria include 50 DRPs grouped into 6 categories. Outcomes DRPs detected using the PAIR criteria compared with implicit clinical judgment by nephrology pharmacists. Measurements Prevalence of DRPs and reliability, validity, and responsiveness of the PAIR criteria. Results A mean of 2.5 DRPs/patient (95% CI, 2.0-3.1) was identified based on the PAIR criteria compared with 3.9 DRPs/patient (95% CI, 3.4-4.5) based on clinical judgment of nephrology pharmacists. Inter-rater reliability coefficients (κ) by PAIR category varied from 0.80-1.00, with an intraclass correlation coefficient (ICC) of 0.93 (95% CI, 0.89-0.95) for total DRPs per patient. Test-retest reliability coefficients by category varied from 0.74-1.00, with an ICC of 0.91 (95% CI, 0.82-0.96) for total DRPs per patient. During the study, the mean number of DRPs per patient did not change significantly when assessed using the PAIR criteria and clinical judgment. Limitation The prevalence of PAIR DRPs may be underestimated due to the retrospective nature of the validation. Conclusion The prevalence of DRPs requiring the intervention of community pharmacists is high in patients with CKD. The PAIR criteria are reliable, but their responsiveness remains to be shown.
Introduction:
Chronic kidney disease (CKD) patients are multimorbid elderly at high risk of drug‐related problems. A Web‐based training program was developed based on a list of significant ...drug‐related problems in CKD patients requiring a pharmaceutical intervention. The objectives were to evaluate the impact of the program on community pharmacists' knowledge and skills and their satisfaction with the training.
Methods:
Pharmacists were randomized to the training program or the control group. Training comprised a 60‐minute Web‐based interactive session supported by a clinical guide. Pharmacists completed a questionnaire on knowledge (10 multiple‐choice questions) and skills (2 clinical vignettes) at baseline and a second time within 1 month. Trained pharmacists completed a written satisfaction questionnaire. Semidirected telephone interviews were conducted with 8 trained pharmacists. Changes in knowledge and skills scores were compared between the groups.
Results:
Seventy pharmacists (training: 52; control: 18) were recruited; the majority were women with <15 years' experience. Compared with the control group, an adjusted incremental increase in the knowledge score (22%; 95% confidence interval CI: 16%–27%) and skills score (24%; 95% CI: 16%–33%) was observed in the training group. Most pharmacists (87%–100%) rated each aspect of the program “excellent'' or “very good.” Additional training and adding a discussion forum were suggested to complement the program.
Discussion:
Pharmacists like the Web‐based continuing education program. Over a short time span, the program improved their knowledge and skills. Its impact on their clinical practices and quality of medication use in CKD patients remains to be assessed.
During nervous system development, Sonic hedgehog (Shh) guides developing commissural axons toward the floor plate of the spinal cord. To guide axons, Shh binds to its receptor Boc and activates ...downstream effectors such as Smoothened (Smo) and Src-family-kinases (SFKs). SFK activation requires Smo activity and is also required for Shh-mediated axon guidance. Here we report that β-arrestin1 and β-arrestin2 (β-arrestins) serve as scaffolding proteins that link Smo and SFKs in Shh-mediated axon guidance. We found that β-arrestins are expressed in rat commissural neurons. We also found that Smo, β-arrestins and SFKs form a tripartite complex, with the complex formation dependent on β-arrestins. β-arrestin knockdown blocked the Shh-mediated increase in Src phosphorylation, demonstrating that β-arrestins are required to activate Src kinase downstream of Shh. β-arrestin knockdown also led to the loss of Shh-mediated attraction of rat commissural axons in axon turning assays. Expression of two different dominant negative β-arrestins, β-arrestin1 V53D which blocks the internalization of Smo and β-arrestin1 P91G-P121E which blocks its interaction with SFKs, also led to the loss of Shh-mediated attraction of commissural axons. In vivo , the expression of these dominant negative β-arrestins caused defects in commissural axon guidance in the spinal cord of chick embryos of mixed sexes. Thus we show that β-arrestins are essential scaffolding proteins that connect Smo to SFKs and are required for Shh-mediated axon guidance. Significance Statement The correct guidance of axons is important for the formation of the nervous system. Sonic hedgehog (Shh)-mediated axon guidance relies on the activation of Src family kinases (SFKs) downstream of the atypical G protein-coupled receptor (GPCR) Smoothened (Smo). How SFKs are activated downstream of Smo was unknown. In this study, we found that β-arrestin1 and 2 (β-arrestins) serve as scaffolding proteins between Smo and SFKs. We also found that β-arrestins are required for the activation of SFKs. Knocking down β-arrestins or expressing dominant negative β-arrestins caused loss of Shh-mediated attraction of commissural axons. In vivo, the expression of dominant negative β-arrestins caused commissural axon guidance defects. Our work identifies for the first time a role for β-arrestins in axon guidance.
Infants HIV-exposed and uninfected (IHEU) who are born to women living with HIV are at an increased risk of preterm birth (PTB). Antenatal exposure to certain maternal antiretroviral therapy (ART) ...regimens has been associated with PTB, although existing studies in this domain are limited and report discordant findings. We determined odds of PTB among IHEU by antenatal ART regimens and timing of exposure, adjusting for maternal risk factors.
We retrospectively studied IHEU born in British Columbia (BC), Canada between 1990 and 2012 utilizing provincial health administrative databases. We included data from a control group of infants HIV-unexposed and uninfected (IHUU) matched ~3:1 for each IHEU on age, sex and geocode.
A total of 411 IHEU and 1224 IHUU were included in univariable analysis. PTB was more frequent among IHEU (20%) compared with IHUU (7%). IHEU were more often antenatally exposed to alcohol, tobacco, as well as prescription, nonprescription, and illicit drugs (IHEU: 36%, 8% and 35%; vs. IHUU: 3%, 1% and 9%, respectively). After adjusting for maternal substance use and smoking exposure, IHEU remained at increased odds of PTB adjusted odds ratio (aOR) (95% CI): 2.66; (1.73, 4.08) compared with matched IHUU controls. ART-exposed IHEU (excluding those with NRTIs only ART) had lower adjusted odds of PTB compared with IHEU with no maternal ART exposure, regardless of regimen aOR range: 0.16-0.29 (0.02-0.95). Odds of PTB between IHEU exposed to ART from conception compared with IHEU exposed to ART postconception did not differ aOR: 0.91 (0.47, 1.76); however, both groups experienced lower odds of PTB compared with IHEU with no maternal ART preconception: aOR: 0.28 (0.08, 0.89); postconception: aOR 0.30 (0.11, 0.83).
BC IHEU were over twice as likely to be born preterm compared with demographically matched controls. Maternal substance use in pregnancy modulated this risk; however, we found no adverse associations of PTB with exposure to antenatal ART.
OBJECTIVES:To assess and compare neurodevelopmental disorders in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children in British Columbia, Canada. To determine associations ...between these outcomes and in-utero exposure to antiretroviral drugs.
DESIGN:Retrospective controlled cohort study.
METHODS:Data were collected on 446 HEU children and 1323 HUU children (matched ∼1 : 3 for age, sex, and geocode) born between 1990 and 2012. Multivariable logistic regressions determined odds ratios of neurodevelopmental disorder diagnoses.
RESULTS:HEUs had three times higher odds of being born preterm (P < 0.0001), and a more than two-fold increase in odds for autism, disturbance of emotions, hyperkinetic syndrome, and developmental delay compared with matched HUUs (P < 0.02) in unadjusted analysis. This association was reduced adjusted neurodevelopmental disorder odds ratio (AOR) = 1.67; 95% confidence interval1.12–2.48; P = 0.011 after adjusting for maternal substance use and/or smoking (children born after April 2000). Regardless of antiretroviral exposure type (i.e. none, treatment with one or multiple drug classes), HEUs had higher odds of any neurodevelopmental disorders compared with matched HUUs; however, there was no evidence suggesting any specific classes of antiretroviral drugs or exposure durations increased their likelihood of neurodevelopmental disorders.
CONCLUSION:The results suggest no adverse associations between antiretroviral drugs and neurodevelopmental disorders within antiretroviral-exposed HEU children in our cohort. Prevalence of neurodevelopmental disorders is higher in HEUs; however, maternal substance use plays a role, as could other environmental factors not captured. These findings highlight a need for holistic support for pregnant women as well as careful developmental monitoring of HEUs past infancy, and access to early interventions, particularly among those born preterm and those exposed to addictive substances.
Compared with children who are HIV-unexposed and uninfected (CHUU), children who are HIV-exposed and uninfected (CHEU) experience more clinical complications. We investigated hospitalizations among ...CHEU by antenatal antiretroviral therapy (ART) exposure, in British Columbia, Canada.
This retrospective controlled cohort study used administrative health data from 1990 to 2012. CHEU and CHUU were matched 1:3 for age, sex and maternal geographical area of residence. We determined adjusted odds ratios (aORs) via conditional logistic regression, adjusting for maternal risk factors.
A total of 446 CHEU and 1333 CHUU were included. Compared with CHUU, more CHEU experienced one or more lifetime hospitalization (47.3% vs. 29.8%), one or more neonatal hospitalization (40.4% vs. 27.6%), and any intensive care unit admission (28.5% vs. 9.2%). In adjusted analyses, CHEU experienced higher odds of any lifetime hospitalization (aOR 2.30, 95% confidence interval 1.81-2.91) and neonatal hospitalization (aOR 2.14, 95% confidence interval 1.68-2.73), compared with CHUU. There was, however, no difference in infection-related hospitalizations (9.0% vs. 7.5%), which were primarily respiratory tract infections among both CHEU and CHUU. CHEU whose mothers-initiated ART preconception showed lower odds of infection-related hospitalizations than children whose mothers initiated ART during pregnancy or received no ART.
CHEU experienced increased odds of hospitalization relative to CHUU. A substantial number of CHEU hospitalizations occurred within the neonatal period and were ICU admissions. Initiating ART preconception may reduce the risk of infection-related hospitalizations. These findings reinforce the benefit of ART in pregnancy and the need for ongoing pediatric care to reduce hospitalizations.
Obesity is associated with systemic inflammation and elevated levels of TNFα, leading to impaired glucose tolerance. In humans, obesity is also associated with reduced nutrient-stimulated secretion ...of the intestinal incretin hormone, glucagon-like peptide-1 (GLP-1). We hypothesized that TNFα plays a direct role in the impairment of GLP-1 secretion from the enteroendocrine L-cell and that blocking TNFα can restore both GLP-1 secretion and glucose homeostasis. Expression of the TNFα receptor subytpe-1 was detected in the human NCI-H716 and murine GLUTag L-cell models and in mouse ileal sections. Although TNFα acutely increased GLP-1 release from NCI-H716 cells (P < .05–.001), preincubation with TNFα for 24 hours reduced proglucagon mRNA (P < .05) and GLP-1 cellular (P < .05) levels without affecting cell viability. Furthermore, both NCI-H716 and GLUTag cells pretreated with TNFα for 24 hours no longer responded to known GLP-1 secretagogues, an effect that was reversed by coincubation with the Nuclear Factor Kappa B inhibitor, 5-aminosalicylic acid, in the NCI-H716 cells. Mice given a high-fat diet (HFD) for 12 weeks developed impaired glucose tolerance, hyperinsulinemia, and increased TNFα mRNA expression in fat and ileal tissue. Hyperglycemia and hyperinsulinemia were reduced in HFD mice treated with the anti-TNFα biological, etanercept, for 2 weeks. In primary intestinal cultures from these animals, HFD control mice had impaired GLP-1 secretion, and this was not observed in the HFD etanercept-derived cultures (P < .05). In conclusion, chronic exposure to TNFα directly impairs GLP-1 secretion at the level of the intestinal L-cell, an effect that is reversed by anti-TNFα therapy in association with improved glucose tolerance.
Vaccines have led to a significant decrease in rates of vaccine-preventable diseases and have made a significant impact on the health of children. However, some parents express concerns about vaccine ...safety and the necessity of vaccines. The concerns of parents range from hesitancy about some immunizations to refusal of all vaccines. This clinical report provides information about the scope and impact of the problem, the facts surrounding common vaccination concerns, and the latest evidence regarding effective communication techniques for the vaccine conversation. After reading this clinical report, readers can expect to: Understand concepts and underlying determinants of vaccine uptake and vaccine hesitancy.Understand the relationship between vaccine hesitancy and costs of preventable medical care.Recognize and address specific concerns (eg, vaccine safety) with caregivers when hesitancy is present.
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