The intestinal microbiota plays a key role in the pathogenesis of acute graft-versus-host disease (aGVHD). High-dose conditioning regimens given prior to allogeneic hematopoietic stem cell ...transplantation (aHSCT) modulate the composition of gut microbiota and damage the gut epithelial barrier, resulting in increased systemic inflammation. We assessed whether gut decontamination with antibiotics (ATB) prior to aHSCT influenced the frequency of aGVHD and mortality in 500 patients from two Canadian centers between 2005 and 2012. The rate of grade II-IV aGVHD was higher in the ATB arm compared with the arm without ATB (42% vs 28%; p < 0.001). This difference was mainly driven by a 2-fold higher rate of grade II-IV gastrointestinal aGVHD (GI-GVHD) in the ATB arm compared with the arm without ATB (20.7% vs 10.8%; p = 0.003). Multivariate analyses adjusted for known aGVHD risk factors revealed that more patients in the ATB group developed clinically significant GI-GVHD and liver aGVHD; adjusted odds ratio (aOR) = 1.83; p = 0.023 and aOR = 3.56; p = 0.047, respectively. Importantly, median overall survival (OS) was significantly lower in the group receiving ATB and the OS at 10 y remained decreased in the ATB group; adjusted hazard ratio (aHR) = 1.61 (p < 0.001).
Without undermining the role of ATB prophylaxis to prevent infection in aHSCT, we have shown that the use of ATB that targets intestinal bacteria is associated with a more severe aGVHD that involves the GI organs and impacts OS. Prospective studies that evaluate the contribution of bacterial decontamination to aGVHD are warranted.
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.
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.
Introduction:
The impact of commensal bacteria harbored in the gastrointestinal tract known as the microbiota has long been recognized as a pivotal factor in allogeneic hematopoietic stem cell ...transplantation (aHSCT). The microbiota is at the origin of acute graft-versus-host disease (aGVHD) and infections, two important lethal complications in aHSCT. High-dose conditioning chemotherapy prior aHSCT disrupts the gut epithelial barrier allowing bacterial by-products to translocate into the peripheral blood and modulates T cell response and pro-inflammatory cytokines. Such observation led to an effort by certain transplant centers to eliminate bacterial colonization prior to aHSCT to decrease the risk of gram-negative bacterial translocation. In this study, we assessed whether patients' gut decontamination prior to allogeneic stem cell infusion influenced the frequency of aGVHD, pneumomatosis coli (PC) a significant complication of gastrointestinal (GI) GVHD and overall survival.
Methods:
We retrospectively reviewed the charts of 543 patients who had undergone a single myeloablative or nonmyeloabaltive aHSCT for hematological malignancies from two academic hospitals in the province of Quebec, Canada between January 2005 and December 2012. Exclusion criteria included prior aHSCT, syngeneic and haploidentical aHSCT. Each university hospital has implemented a different pre-transplant antibioprophylaxis guideline. At HMR hospital, ciprofloxacin or moxifloxacine were started at initiation of the conditioning regimen for gut decontamination, but were omitted in patients with fluoroquinolone or penicillin allergy and during nosocomial infections outbreak. On the other hand, in the CHU de Quebec patients were not prescribed prophylactic antibiotics (ATB). In addition, ATB used to treat infections before the stem cells infusion were considered. To determine the impact of ATB, we performed multivariable analyses adjusting for the following confounding factors: age, gender, stem cell origin (source), donor type/match, and conditioning regimens to compare the frequency of aGVHD, PC, leucocytes recovery at day+14 and overall survival (OS) in patients receiving or not ATB.
Results:
500 patients were included and a total of 240 (48%) patients received ATB at the time of conditioning regimen. Demographics were similar in both groups with mean age of 48 years. Frequency of grade II-IV aGVHD was more elevated in patients receiving ATB compared to the no ATB group (42% vs 28% respectively with adjusted OR (aOR)=1.53 (p<0.05). The severity of the aGVHD in the ATB group was driven by the GI-GVHD with a higher level of grade II-IV (20.7%) compared to no ATB group (10.8%) with aOR=2.00 (p<0.01). Severity of skin and liver GVHD were similar in both groups. Among the 12 patients that developed PC diagnosed on CT-scan, all received ciprofloxacin during conditioning and PC was associated with 80% mortality. The difference of aGVH frequency may have translated into survival as the ATB group was associated to lower 1 year survival compared to no ATB group (74% vs 88%, OR=0.36 and aOR=0.38 (p<0.05). This significant survival difference at 1 year persisted over time and median OS was 4 and 5 years respectively (p<0.05). Taking into consideration the entire follow-up period of 10 years, the hazard rates associated with ATB were estimated at 1.61(p<0.06) and 1.43 (p<0.05) after adjusting for clinical parameters. Interestingly, post-hoc analysis revealed independent impact of the ATB on D+14 neutrophils. This was reflected by a lower neutrophil count in patients on ATB that received stem cells from a match-related donor compared to no ATB counterpart with a ratio of 0.38 (p<0.05).
Discussion:
This retrospective study indicated that ATB were associated to a more severe aGVHD driven by digestive manifestations of the GVHD and higher incidence of PC even after multivariable analysis. These life-threatening complications may impact on the 1-year and OS that were lower in the ATB group. Without undermining the role of ATB prophylaxis to prevent infection in aHSCT setting, treatment with ATB impact on the commensal microbiota and diminishes its diversity. This imbalance created by the ATB may have contributed to the pathophysiology of GI-GVHD. This ultimately highlights the importance to reconsider antibioprophylaxis to preserve an intact flora and its benefits in aHSCT.
No relevant conflicts of interest to declare.
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