Results of a multicenter cluster-randomized controlled clinical trial testing the effectiveness of a bioinformatics-enabled pharmacist intervention in transplant recipients.

An ambulatory medication safety dashboard was developed to identify missing labs, concerning labs, drug interactions, nonadherence, and transitions in care. This system was tested in a 2-year, prospective, cluster-randomized, controlled multicenter study. Pharmacists at 5 intervention sites used the dashboard to address medication safety issues, compared with usual care provided at 5 control sites. A total of 2196 transplant events were included (1300 intervention vs 896 control). During the 2-year study, the intervention arm had a 11.3% (95% confidence interval, 7.1%-15.5%) absolute risk reduction of having ≥1 emergency department (ED) visit (44.2% vs 55.5%, respectively; P < .001, respectively) and a 12.3% (95% confidence interval, 8.2%-16.4%) absolute risk reduction of having ≥1 hospitalization (30.1% vs 42.4%, respectively; P < .001). In those with ≥1 event, the median ED visit rate (2 [interquartile range (IQR) 1, 5] vs 2 [IQR 1, 4]; P = .510) and hospitalization rate (2 [IQR 1, 3] vs 2 [IQR 1, 3]; P = .380) were similar. Treatment effect varied by comorbidity burden, previous ED visits or hospitalizations, and heart or lung recipients. A bioinformatics dashboard-enabled, pharmacist-led intervention reduced the risk of having at least one ED visit or hospitalization, predominantly demonstrated in lower risk patients.

A Randomized Control Trial Testing a Medication Safety Dashboard in Veteran Transplant Recipients.

INTRODUCTION: Medication errors, adverse events, and nonadherence in organ transplant recipients are common and can lead to suboptimal outcomes. A medication safety dashboard was developed to identify issues in medication therapy. RESEARCH QUESTIONS: Can a multicenter bioinformatics dashboard accurately identify clinically relevant medication safety issues in US military Veteran transplant recipients? DESIGN: The dashboard was tested through a 24-month, prospective, cluster-randomized controlled multicenter study. Pharmacists used the dashboard to identify and address potential medication safety issues, which was compared with usual care. RESULTS: Across the 10 sites (5 control sites and 5 intervention sites), 2012 patients were enrolled (1197 intervention vs 831 control). The mean age was 65 (10) years, 95% male, and 27% Black. The dashboard produced 18 132 alerts at a rate of 0.61(0.32) alerts per patient-month, ranging from 0.44 to 0.72 across the 5 intervention sites. Lab-based issues were most common (83.4%), followed by nonadherence (9.4%) and transitions in care (6.4%); 56% of alerts were addressed, taking an average of 43 (29) days. Common responses to alerts included those already resolved by another provider (N = 4431, 44%), the alert not clinically relevant (N = 3131, 31%), scheduling of follow-up labs (N = 591, 6%), and providing medication reconciliation/education (N = 99, 1%). Inaccurate flags significantly decreased over the study by a mean of -0.6% per month (95% CI -0.1 to -1.0; P = .0265), starting at 13.4% and ending at 2.6%. CONCLUSION: This multicenter cluster-randomized controlled trial demonstrated that a medication safety dashboard was feasibly deployable across the VA healthcare system, creating valid alerts.

The putative transporter MtUMAMIT14 participates in nodule formation in Medicago truncatula.

Transport systems are crucial in many plant processes, including plant-microbe interactions. Nodule formation and function in legumes involve the expression and regulation of multiple transport proteins, and many are still uncharacterized, particularly for nitrogen transport. Amino acids originating from the nitrogen-fixing process are an essential form of nitrogen for legumes. This work evaluates the role of MtN21 (henceforth MtUMAMIT14), a putative transport system from the MtN21/EamA-like/UMAMIT family, in nodule formation and nitrogen fixation in Medicago truncatula. To dissect this transporter's role, we assessed the expression of MtUMAMIT14 using GUS staining, localized the corresponding protein in M. truncatula root and tobacco leaf cells, and investigated two independent MtUMAMIT14 mutant lines. Our results indicate that MtUMAMIT14 is localized in endosomal structures and is expressed in both the infection zone and interzone of nodules. Comparison of mutant and wild-type M. truncatula indicates MtUMAMIT14, the expression of which is dependent on the presence of NIN, DNF1, and DNF2, plays a role in nodule formation and nitrogen-fixation. While the function of the transporter is still unclear, our results connect root nodule nitrogen fixation in legumes with the UMAMIT family.

Mycorrhiza-mediated potassium transport in Medicago truncatula can be evaluated by using rubidium as a proxy.

Arbuscular mycorrhizal (AM) fungi considerably improve plant nutrient acquisition, particularly phosphorus and nitrogen. Despite the physiological importance of potassium (K+) in plants, there is increasing interest in the mycorrhizal contribution to plant K+ nutrition. Yet, methods to track K+ transport are often costly and limiting evaluation opportunities. Rubidium (Rb+) is known to be transported through same pathways as K+. As such our research efforts attempt to evaluate if Rb+ could serve as a viable proxy for evaluating K+ transport in AM symbiosis. Therefore, we examined the transport of K+ in Medicago truncatula colonized by the AM fungus Rhizophagus irregularis isolate 09 having access to various concentrations of Rb+ in custom-made two-compartment systems. Plant biomass, fungal root colonization, and shoot nutrient concentrations were recorded under sufficient and limited K+ regimes. We report that AM plants displayed higher shoot Rb+ and K+ concentrations and a greater K+:Na+ ratio relative to non-colonized plants in both sufficient and limited K+ conditions. Consequently, our results indicate that Rb+ can be used as a proxy to assess the movement of K+ in AM symbiosis, and suggest the existence of a mycorrhizal uptake pathway for K+ nutrition in M. truncatula.

Discontinuation of Proton Pump Inhibitors in Patients With Chronic Kidney Disease.

Purpose: Proton pump inhibitors (PPIs) are commonly used medications and are historically well tolerated. Recent studies have linked PPI use to the development of chronic kidney disease (CKD) and end-stage renal disease. This study investigated the impact of discontinuing PPIs on renal function in patients with CKD. Methods: We conducted a retrospective chart review of patients with established CKD, defined as 2 eGFR (estimated glomerular filtration rate) measurements of less than 60 mL/min/1.73 m2 at least 90 days apart, who were on a PPI from January 1, 2014 to December 31, 2014, with a medication possession ratio greater than or equal to 70%. We compared baseline eGFR to a final eGFR after at least 6 months of discontinuation or continuation of a PPI. After power analysis, we targeted an enrollment of 200 patients (100 in each group) to achieve a power of 0.80 and an alpha of 0.05. Summary: A total of 97 patients in the PPI discontinuation group and 100 patients in the PPI continuation group met the study inclusion criteria. Baseline eGFR in the PPI continuation group was 47.9 mL/min/1.73 m2 and 50.7 mL/min/1.73 m2 in the discontinuation group. Final eGFR in the PPI continuation group was significantly higher than baseline at 51.1 mL/min/1.73 m2 (+3.25 ± 12.8, P = .01). Final eGFR in the PPI discontinuation group was 51.8 mL/min/1.73 m2 (+1.09 ± 12.8, P = .3). The average time between baseline and final eGFRs was 270 days in the PPI continuation group and 301 days in the discontinuation group. There was no statistically significant difference in the change in eGFRs between groups (95% confidence interval [CI] = -5.48-2.03, P = .37). Conclusions: Proton pump inhibitor discontinuation after prolonged continuous use in patients with CKD was not associated with a significant change in renal function after 1 year.

Sevelamer Carbonate and Lanthanum Usage Evaluation and Cost Considerations at a Veteran's Affairs Medical Center.

BACKGROUND: Hyperphosphatemia is a common problem in patients with chronic kidney disease (CKD). Calcium-containing phosphate binders are typically used as first-line therapy, primarily due to cost considerations. Non-calcium phosphate binders such as sevelamer and lanthanum may be considered in the appropriate setting. It is hypothesized that lanthanum is less costly and has a lower pill burden compared to sevelamer carbonate. OBJECTIVE: Determine the difference in cost (outcome 1) and tablet burden (outcome 2) between sevelamer carbonate and lanthanum within the Veteran population. METHODS: Patients with an active prescription for lanthanum or sevelamer carbonate on October 22, 2014 were evaluated. Chi-square analysis was used to analyze categorical data, and 2-sided t test was used for continuous data. An α of 0.05 determined significance. RESULTS: One hundred fifty patients were included in the evaluation. Patients were predominately male (96%) and had a diagnosis of end stage renal disease (ESRD; 78%). The combined rate of non-dialysis CKD (ND-CKD) stage 5 and ESRD was similar between lanthanum and sevelamer carbonate groups. Both groups achieved similar phosphorus control (56% vs 65%, with phosphorus level less than or equal to 5.5 mg/dL, respectively; P = .23). Lanthanum prescriptions required significantly fewer tablets per day (4 lanthanum tablets daily vs 7 sevelamer carbonate tablets daily; P < .001). A potential prescription cost savings of approximately $4,500 monthly or $54,000 annually was seen when considering conversion of patients in this study population from sevelamer carbonate to lanthanum therapy, with appreciable savings beginning at sevelamer daily doses of at least 4,800 mg. CONCLUSIONS: Compared to sevelamer carbonate, lanthanum use was associated with reduced pill burden and lower absolute drug cost while maintaining similar phosphorus control.

Diuretics for hypertension: Hydrochlorothiazide or chlorthalidone?

Thiazide diuretics are the cornerstone of treatment of hypertension in most patients. Hydrochlorothiazide is the most commonly used thiazide diuretic in the United States, but interest in chlorthalidone is increasing. The authors summarize the literature comparing these two agents.

A pharmacist based intervention to improve the care of patients with CKD: a pragmatic, randomized, controlled trial.

BACKGROUND: Primary care providers do not routinely follow guidelines for the care of patients with chronic kidney disease (CKD). Multidisciplinary efforts may improve care for patients with chronic disease. Pharmacist based interventions have effectively improved management of hypertension. We performed a pragmatic, randomized, controlled trial to evaluate the effect of a pharmacist based quality improvement program on 1) outcomes for patients with CKD and 2) adherence to CKD guidelines in the primary care setting. METHODS: Patients with moderate to severe CKD receiving primary care services at one of thirteen community-based Veterans Affairs outpatient clinics were randomized to a multifactorial intervention that included a phone-based pharmacist intervention, pharmacist-physician collaboration, patient education, and a CKD registry (n = 1070) or usual care (n = 1129). The primary process outcome was measurement of parathyroid hormone (PTH) during the one year study period. The primary clinical outcome was blood pressure (BP) control in subjects with poorly controlled hypertension at baseline. RESULTS: Among those with poorly controlled baseline BP, there was no difference in the last recorded BP or the percent at goal BP during the study period (42.0% vs. 41.2% in the control arm). Subjects in the intervention arm were more likely to have a PTH measured during the study period (46.9% vs. 16.1% in the control arm, P <0.001) and were on more classes of antihypertensive medications at the end of the study (P = 0.02). CONCLUSIONS: A one-time pharmacist based intervention proved feasible in patients with CKD. While the intervention did not improve BP control, it did improve guideline adherence and increased the number of antihypertensive medications prescribed to subjects with poorly controlled BP. These findings can inform the design of quality improvement programs and future studies which are needed to improve care of patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01290614.

Polypharmacy in the elderly: focus on drug interactions and adherence in hypertension.

Polypharmacy is highly prevalent in the elderly due to an increased number of co-morbid disease states that accompany aging. Hypertension is one common disease that can be challenging to treat in the elderly due to the body's physiologic changes, potential risks for side effects, medication interactions, and decreased medication adherence. A thorough medication assessment for each patient is essential when determining pharmacotherapeutic options in the elderly.