Top 10 Signs and Symptoms of Psychotropic Adverse Drug Events to Monitor in Long-Term Care Residents.

OBJECTIVES: To produce a consensus list of the top 10 signs and symptoms suggestive of adverse drug events (ADEs) for monitoring in residents of long-term care facilities (LTCFs) who use antipsychotics, benzodiazepines, or antidepressants. DESIGN: A 3-round Delphi study. SETTING AND PARTICIPANTS: Geriatricians, psychiatrists, pharmacologists, general practitioners, pharmacists, nurses, and caregivers from 13 Asia Pacific, European, and North American countries. METHODS: Three survey rounds were completed between April and June 2023. In Round 1, participants indicated their level of agreement on a 9-point Likert scale on whether 41 signs or symptoms identified in a systematic review should be routinely monitored. Participants considered signs and symptoms that reduce quality of life or cause significant harm, are observable or measurable by nurses or care workers, and can be assessed at a single time point. Round 1 statements were included in a list for prioritization in Round 3 if ≥ 70% of participants responded ≥7 on the Likert scale. Statements were excluded if ≤ 30% of participants responded ≥7. In Round 2, participants indicated their level of agreement with statements that did not reach initial consensus, plus amended statements based on Round 1 participant feedback. Round 2 statements were included in Round 3 if ≥ 50% of the participants responded ≥7 on the Likert scale. In Round 3, participants prioritized the signs and symptoms. RESULTS: Forty-four participants (93.6%) completed all 3 rounds. Four of 41 signs and symptoms reached consensus for inclusion after Round 1, and 9 after Round 2. The top 10 signs and symptoms prioritized in Round 3 were recent falls, daytime drowsiness or sleepiness, abnormal movements (eg, shaking or stiffness), confusion or disorientation, balance problems, dizziness, postural hypotension, reduced self-care, restlessness, and dry mouth. CONCLUSIONS AND IMPLICATIONS: The top 10 signs and symptoms provide a basis for proactive monitoring for psychotropic ADEs.

Polypharmacy and risk of fractures in older adults: A systematic review.

BACKGROUND: Fractures have serious health consequences in older adults. While some medications are individually associated with increased risk of falls and fractures, it is not clear if this holds true for the use of many medications (polypharmacy). We aimed to identify what is known about the association between polypharmacy and the risk of fractures in adults aged ≥65 and to examine the methods used to study this association. METHODS: We conducted a systematic review with narrative synthesis of studies published up to October 2023 in PubMed, Embase, CINAHL, PsychINFO, Cochrane Library, Web of Science, and the grey literature. Two independent reviewers screened titles, abstracts, and full texts, then performed data extraction and quality assessment. RESULTS: Among the 31 studies included, 11 different definitions of polypharmacy were used and were based on three medication counting methods (concurrent use 15/31, cumulative use over a period 6/31, daily average 3/31, and indeterminate 7/31). Overall, polypharmacy was frequent and associated with higher fracture risk. A dose-response relationship between increasing number of medications and increased risk of fractures was observed. However, only seven studies adjusted for major confounders (age, sex, and chronic disease). The quality of the studies ranged from poor to high. CONCLUSIONS: Polypharmacy appears to be a relevant modifiable risk factor for fractures in older individuals that can easily be used to identify those at risk. The diversity of medication calculation methods and definitions of polypharmacy highlights the importance of a detailed methodology to understand and compare results.

Community Pharmacist Training-and-Communication Network and Drug-Related Problems in Patients With CKD: A Multicenter, Cluster-Randomized, Controlled Trial.

BACKGROUND: 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). STUDY DESIGN: Multicenter, cluster-randomized, controlled trial. SETTING & PARTICIPANTS: Patients with CKD stage 3a, 3b, or 4 from 6 CKD clinics (Quebec, Canada) and their community pharmacies. INTERVENTION: 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. OUTCOMES: Drug-related problems (primary outcome), pharmacists' knowledge and clinical skills, and patients' clinical attributes (eg, blood pressure and glycated hemoglobin concentration). MEASUREMENTS: 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. RESULTS: 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. LIMITATIONS: High proportion of missing data on knowledge and clinical skills questionnaire (34.6%) and clinical attributes (11.1%). CONCLUSIONS: 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.

Conversion of oral alfacalcidol to oral calcitriol in the treatment of secondary hyperparathyroidism in chronic hemodialysis patients.

PURPOSE: The optimal vitamin D3 therapy for the treatment of secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients is still controversial. Recent studies suggest that uremia in end-stage renal disease is associated with enzymatic hepatic dysfunction altering 25-hydroxylation of vitamin D3. The goal of our study was to compare the efficacy of calcitriol, the fully hydroxylated active form of vitamin D3, to alfacalcidol which needs 25-hydroxylation to be effective, for the treatment of SHPT in chronic hemodialysis patients. METHODS: We retrospectively reviewed 45 chronic hemodialysis patients who were switched from oral alfacalcidol to oral calcitriol for the treatment of SHPT. Parathyroid hormone (PTH), serum calcium and serum phosphorus levels were compared pre- and post-conversion using paired Student's t tests. RESULTS: The mean dose of active vitamin D3 decreased from 3.50 mcg/week at baseline to 2.86 mcg (P < 0001) after the switch from alfacalcidol to calcitriol. PTH significantly decreased from 94.4 to 82.6 pmol/L (-11.8 pmol/L, P = 0.02). The mean corrected calcium increased from 2.17 to 2.25 mmol/L (+0.08 mmol/L, P < 0.001) without any clinically significant hypercalcemia, and phosphorus levels were stable. Results were similar in a subgroup of patients (n = 17) for whom the medication was administrated during the hemodialysis session, ensuring a complete compliance. CONCLUSIONS: According to our study, calcitriol in equal dosage is more effective than alfacalcidol in lowering serum PTH level in chronic hemodialysis patients. This suggests that calcitriol may be the optimal active vitamin D3 for the treatment of SHPT in chronic hemodialysis patients.

New drugs to prevent and treat hyperkalemia.

PURPOSE OF REVIEW: Hyperkalemia is frequent, but occurs mostly in patients with chronic kidney disease and is often the cause of discontinuation or omission of renin-angiotensin-aldosterone system inhibitors in patients with diabetes, chronic kidney disease and heart failure. RECENT FINDINGS: Without much evidence in the literature on its efficacy, sodium polystyrene sulfonate is being used frequently in the clinical setting to treat hyperkalemia. In the last few years, two new promising agents have been developed to treat hyperkalemia - patiromer and sodium zirconium cyclosilicate 9 (ZS-9). Both patiromer and ZS-9 have been shown to decrease potassium in patients with hyperkalemia and then to maintain normokalemia. Gastrointestinal adverse events were more frequent with patiromer, and edema occurred in patients using high doses of ZS-9, possibly due to its high sodium content. SUMMARY: Although patiromer and ZS-9 are very promising in terms of safety and efficacy, many questions remain, mostly in terms of selection of patients, long-term effects and costs.

Randomized Clinical Trial of Sodium Polystyrene Sulfonate for the Treatment of Mild Hyperkalemia in CKD.

BACKGROUND AND OBJECTIVES: Hyperkalemia affects up to 10% of patients with CKD. Sodium polystyrene sulfonate has long been prescribed for this condition, although evidence is lacking on its efficacy for the treatment of mild hyperkalemia over several days. This study aimed to evaluate the efficacy of sodium polystyrene sulfonate in the treatment of mild hyperkalemia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 33 outpatients with CKD and mild hyperkalemia (5.0-5.9 mEq/L) in a single teaching hospital were included in this double-blind randomized clinical trial. We randomly assigned these patients to receive either placebo or sodium polystyrene sulfonate of 30 g orally one time per day for 7 days. The primary outcome was the comparison between study groups of the mean difference of serum potassium levels between the day after the last dose of treatment and baseline. RESULTS: The mean duration of treatment was 6.9 days. Sodium polystyrene sulfonate was superior to placebo in the reduction of serum potassium levels (mean difference between groups, -1.04 mEq/L; 95% confidence interval, -1.37 to -0.71). A higher proportion of patients in the sodium polystyrene sulfonate group attained normokalemia at the end of their treatment compared with those in the placebo group, but the difference did not reach statistical significance (73% versus 38%; P=0.07). There was a trend toward higher rates of electrolytic disturbances and an increase in gastrointestinal side effects in the group receiving sodium polystyrene sulfonate. CONCLUSIONS: Sodium polystyrene sulfonate was superior to placebo in reducing serum potassium over 7 days in patients with mild hyperkalemia and CKD.

Pharmacist Web-based training program on medication use in chronic kidney disease patients: impact on knowledge, skills, and satisfaction.

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.

Development and validation of the PAIR (Pharmacotherapy Assessment in Chronic Renal Disease) criteria to assess medication safety and use issues in patients with CKD.

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.