Deviant Dosing: A Post hoc Analysis of Pharmacist Characteristics Related to Renal Dosing Decisions.

BACKGROUND: A recent study demonstrated that pharmacists presented with multiple estimating equations deviated from recommended dosing guidance more often than pharmacists who were presented with a single estimate on clinical vignettes. OBJECTIVES: To identify characteristics associated with an increased tendency to deviate from approved recommendations. METHODS: Participant data were split into 2 cohorts: pharmacists who chose a dose that was inconsistent with dosing recommendations on at least 1 of the 4 vignettes and pharmacists who did not deviate on a single case. Bivariate analysis of demographic- and practice-related variables were conducted between groups using the χ2, Mann-Whitney U, or Student t-test for nominal, ordinal, and continuous variables, respectively. Statistically different covariates between groups (P < 0.05) were assessed using multivariable linear regression. RESULTS: Survey data from 154 inpatient pharmacists, 71 of whom deviated on at least 1 clinical vignette, were analyzed. On univariate analysis, deviator pharmacists were more likely to have completed postgraduate residency training (68% vs 41%; P < 0.05) and board certification (39% vs 20%; P < 0.05). Deviator pharmacists were also more likely to have been presented with multiple renal estimates as opposed to a single estimate and had differing renal dosing practices at baseline (P < 0.05). Following multivariable regression, residency training, mismatched baseline renal practices, and multiple renal estimates remained independent predictors (P < 0.05) of dosing deviation. CONCLUSION AND RELEVANCE: Higher clinical training, practice variation, and multiple renal estimates may affect renal dosing practices. Prospective, statistically powered studies are needed to verify these hypotheses.

Impact of risk-stratified mycophenolate dosing in heart transplantation.

Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid, is a highly effective immunosuppressive agent in heart transplant therapy. While the FDA approved dose is 1500 mg twice daily, dosing is often reduced due to dose-dependent adverse effects. However, empiric MMF dose reductions may lead to sub-therapeutic dosing and impair clinical outcomes. Our single center protocolized a risk-stratified approach based on age and weight to dose 500 mg twice daily or 1000 mg twice daily to patients after heart transplantation. This retrospective single-center study analyzed 140 consecutive heart transplant patients who were initiated on our risk-stratified MMF protocol post-transplant. The analysis revealed that the composite rate of biopsy-proven rejection, graft loss, or mortality at 1-year post-transplantation was similar between the two groups. Incidence of neutropenia, thrombocytopenia, infection, cardiac allograft vasculopathy, or acute kidney injury by 1-year also showed similar results between the two groups. Risk-stratification of MMF dosing appears to be a safe and effective strategy after heart transplantation.

Medication Dosing Safety for Pediatric Patients: Recognizing Gaps, Safety Threats, and Best Practices in the Emergency Medical Services Setting. A Position Statement and Resource Document from NAEMSP.

BACKGROUND: Millions of patients receive medications in the Emergency Medical Services (EMS) setting annually, and dosing safety is critically important. The need for weight-based dosing in pediatric patients and variability in medication concentrations available in the EMS setting may require EMS providers to perform complex calculations to derive the appropriate dose to deliver. These factors can significantly increase the risk for harm when dose calculations are inaccurate or incorrect. METHODS: We conducted a scoping review of the EMS, interfacility transport and emergency medicine literature regarding pediatric medication dosing safety. A priori, the authors identified four research topics: (1) what are the greatest safety threats that result in significant dosing errors that potentially result in harm to patients, (2) what practices or technologies are known to enhance dosing safety, (3) can data from other settings be extrapolated to the EMS environment to inform dosing safety, and (4) what impact could standardization of medication formularies have on enhancing dosing safety. To address these topics, 17 PICO (Patient, Intervention, Comparison, Outcome) questions were developed and a literature search was performed. RESULTS: After applying exclusion criteria, 70 articles were reviewed. The methods for the investigation, findings from these articles and how they inform EMS medication dosing safety are summarized here. This review yielded 11 recommendations to improve safety of medication delivery in the EMS setting. CONCLUSION: These recommendations are summarized in the National Association of EMS Physicians® position statement: Medication Dosing Safety for Pediatric Patients in Emergency Medical Services.

Comparison of a metronome-guided prehospital medication infusion technique with standard calculation: a simulated randomized, controlled, cross-over study.

BACKGROUND: Limited research regarding administration of timed medication infusions in the prehospital environment has identified wide variability with accuracy, timing, and overall feasibility. This study was a quality improvement project that utilized a randomized, controlled, crossover study design to compare two different educational techniques for medication infusion administration. We hypothesized that the use of a metronome-based technique would decrease medication dosage errors and reduce time to administration for intravenous medication infusions. METHODS: Forty-two nationally registered paramedics were randomized to either a metronome-based technique versus a standard stopwatch-based technique. Each subject served as a control. Subjects were asked to establish an infusion of amiodarone at a dose of 150 mg administered over 10 min, simulating treatment of a hemodynamically stable patient with sustained monomorphic ventricular tachycardia. Descriptive statistics and a repeated measures mixed linear regression model were used for data analysis. RESULTS: When compared to a standard stopwatch-based technique, a metronome-based technique was associated with faster time to goal (median 34 s [IQR, 22-54] vs 50 s; [IQR 38-61 s], P = 0.006) and fewer mid-infusion adjustments. Ease of use was reported to be significantly higher for the metronome group (median ranking 5, IQR 4-5) compared to the standard group (median ranking 2, IQR 2-3; P < 0.001). CONCLUSIONS: Knowledge regarding a metronome technique may help EMS clinicians provide safe and effective IV infusions. Such a technique may be beneficial for learners and educators alike.

Nephrology comanagement and the quality of antibiotic prescribing in primary care for patients with chronic kidney disease: a retrospective cross-sectional study.

BACKGROUND: In primary care, patients with chronic kidney disease (CKD) are frequently prescribed excessive doses of antibiotics relative to their kidney function. We examined whether nephrology comanagement is associated with improved prescribing in primary care. METHODS: In a retrospective propensity score-matched cross-sectional study, we studied the appropriateness of antibiotic prescriptions by primary care physicians to Ontarians ≥66 years of age with CKD Stages 4 and 5 (estimated glomerular filtration rate <30 mL/min/1.73 m2 not receiving dialysis) from 1 April 2003 to 31 March 2014. Comanagement was defined as having at least one outpatient visit with a nephrologist within the year prior to antibiotic prescription date. We compared the rate of appropriately dosed antibiotics in primary care between 3937 patients who were comanaged by a nephrologist and 3937 patients who were not. RESULTS: Only 1184 (30%) of 3937 noncomanaged patients had appropriately dosed antibiotic prescriptions prescribed by a primary care physician. Nephrology comanagement was associated with an increased likelihood that an appropriately dosed prescription was prescribed by a primary care physician; however, the magnitude of the effect was modest [1342/3937 (34%); odds ratio 1.20 (95% confidence interval 1.09-1.32); P < 0.001]. CONCLUSION: The majority of antibiotics prescribed by primary care physicians are inappropriately dosed in CKD patients, whether or not a nephrologist is comanaging the patient. Nephrologists have an opportunity to increase awareness of appropriate dosing of medications in primary care through the patients they comanage.

A systematic review of clinical pharmacist interventions in paediatric hospital patients.

Clinical pharmacists provide beneficial services to adult patients, though their benefits for paediatric hospital patients are less defined. Five databases were searched using the MeSH terms 'clinical pharmacist', 'paediatric/paediatric', 'hospital', and 'intervention' for studies with paediatric patients conducted in hospital settings, and described pharmacist-initiated interventions, published between January 2000 and October 2017. The search strategy after full-text review identified 12 articles matching the eligibility criteria. Quality appraisal checklists from the Joanna Briggs Institute were used to appraise the eligible articles. Clinical pharmacist services had a positive impact on paediatric patient care. Medication errors intercepted by pharmacists included over- and under-dosing, missed doses, medication history gaps, allergies, and near-misses. Interventions to address these errors were positively received, and implemented by physicians, with an average acceptance rate of over 95%. Clinical pharmacist-initiated education resulted in improved medication understanding and adherence, improved patient satisfaction, and control of chronic medical conditions.Conclusion: This review found that clinical pharmacists in paediatric wards may reduce drug-related problems and improve patient outcomes. The benefits of pharmacist involvement appear greatest when directly involved in ward rounds, due to being able to more rapidly identify medication errors during the prescribing phase, and provide real-time advice and recommendations to prescribers. What is Known: • Complex paediatric conditions can require multiple pharmaceutical treatments, utilised in a safe manner to ensure good patient outcomes • The benefits of pharmacist interventions when using these treatments are well-documented in adult patients, though less so in paediatric patients What is New: • Pharmacists are adept at identifying and managing medication errors for paediatric patients, including incorrect doses, missed doses, and gaps in medication history • Interventions recommended by pharmacists are generally well-accepted by prescribing physicians, especially when recommendations can be made during the prescribing phase of treatment.

Pediatric Prehospital Medication Dosing Errors: A Mixed-Methods Study.

Prehospital dosing errors affect approximately 56,000 US children yearly. To decrease these errors, barriers, enablers and solutions from the paramedic (EMT-P) and medical director (MD) standpoint need to be understood. We conducted a mixed-methods study of EMT-P and MDs in Michigan utilizing focus groups (FG). FGs were held at EMS agencies and state EMS conferences. Questions focused on the drug dose delivery process, barriers and enablers to correct dosing and possible solutions to decrease errors. Responses were coded by the research team for themes and number of response mentions. Participants completed a pre-FG survey on pediatric experience and agency characteristics. There were 35 EMT-P and 9 MD participants: 43% of EMT-Ps had been practicing > 10 years, 11% had been practicing < 1 year; and 25% reported they had not administered a drug dose to a child in the last 12 months. EMT-Ps who were "very comfortable" with their ability to administer a correct drug dose to infants, toddlers, school-aged, and adolescents were: 5%, 7%, 10%, and 54%, respectively. FGs identified themes of: difficulty obtaining weight, infrequent pediatric encounters, infrequent/inadequate pediatric training, difficulties with drug packaging, drug bags that were not "EMS friendly," difficulty with drug calculations, and lack of dosing aids. Simplification of dose delivery, an improved length based tape for EMS, pediatric checklists, and dose cards in mL were given as solutions. This mixed-methods study identified barriers and potential solutions to reducing prehospital pediatric drug dosing errors. Solutions should be thoroughly tested prior to implementation.

A retrospective description of anesthetic medication dosing in overweight and obese children.

INTRODUCTION: Pediatric obesity is a major health concern in the United States and as many as 34% of those who require general anesthesia are overweight or obese (OW). The lack of data and recommendations for dosing medications in obese children leaves significant gaps in the understanding of correct dosing in the clinical setting. OBJECTIVE: To determine whether OW children were more likely to receive doses of medications outside the recommended range. METHODS: Following IRB approval, patient medical records were queried to identify children 2 through 17 years who underwent noncardiac surgeries and received at least one medication of interest. Children with hepatic disease, renal disease, neurological impairment, sleep-disordered breathing, or missing height or weight measurements were excluded. Children were stratified into weight categories based on age and gender percentiles as per CDC guidelines. Those ≥85th percentile were classified as overweight/obese. Ideal and lean weight (for age, gender) were calculated. Drug doses were stratified as under-dosed (>10% below minimum recommended dose), overdosed (>10% above maximum recommended dose), or within recommended dose (dose ± 10%). Actual doses were compared to recommended doses as per actual, ideal, or lean weight (as recommended for specific drugs) in the overweight/obese groups vs the control weight (CW) group. RESULTS: Ten thousand five hundred and nine doses were reviewed. Overweight/obese children were more likely to receive doses outside the recommended dose range than the CW group. CONCLUSIONS: Overweight/obese children were more likely to receive doses of common anesthetic medications outside the recommended doses potentially adding risk of adverse outcomes in these children.

Adequacy of nicotine replacement and success quitting tobacco in clinical populations: An observational study.

BACKGROUND: Nicotine replacement therapy (NRT) for smoking cessation is an effective intervention that reduces urges to smoke by substituting a safer source of nicotine. NRT dosing is imprecise, however, and there is some evidence that patients and providers are reluctant to use the larger doses that may be appropriate for some people who smoke. In this analysis, we assess the relationship between cigarettes smoked and NRT prescribed, and between adequacy of nicotine replacement and cessation success. METHODS: We analyzed data from 84,667 patients and 492 clinics participating in a province-wide NRT-based smoking cessation program. We evaluated the association between cigarettes per day (CPD) and NRT dose using descriptive methods, and used mixed-effects logistic regression to identify associations between dose and outcome. We used fractional polynomials to fit non-linear associations and multiple imputation to address missing data. RESULTS: Prescribed NRT doses increased much less than proportionately with CPD, with a median for higher CPD levels of about 1 mg/CPD at baseline. Doses did not increase at subsequent visits for people who continued to smoke daily. Dose-response curves derived from our model showed that initial doses below about 2 mg/CPD/day were associated with poorer outcomes. CONCLUSIONS: Under-dosing of NRT, both at treatment initiation and subsequent clinical contacts, is likely to contribute to the poorer treatment outcomes seen among people who smoke heavily. Improved communication with providers and patients is probably needed to overcome reluctance to use larger doses.

Patient-Specific Sedation Management via Deep Reinforcement Learning.

Introduction: Developing reliable medication dosing guidelines is challenging because individual dose-response relationships are mitigated by both static (e. g., demographic) and dynamic factors (e.g., kidney function). In recent years, several data-driven medication dosing models have been proposed for sedatives, but these approaches have been limited in their ability to assess interindividual differences and compute individualized doses. Objective: The primary objective of this study is to develop an individualized framework for sedative-hypnotics dosing. Method: Using publicly available data (1,757 patients) from the MIMIC IV intensive care unit database, we developed a sedation management agent using deep reinforcement learning. More specifically, we modeled the sedative dosing problem as a Markov Decision Process and developed an RL agent based on a deep deterministic policy gradient approach with a prioritized experience replay buffer to find the optimal policy. We assessed our method's ability to jointly learn an optimal personalized policy for propofol and fentanyl, which are among commonly prescribed sedative-hypnotics for intensive care unit sedation. We compared our model's medication performance against the recorded behavior of clinicians on unseen data. Results: Experimental results demonstrate that our proposed model would assist clinicians in making the right decision based on patients' evolving clinical phenotype. The RL agent was 8% better at managing sedation and 26% better at managing mean arterial compared to the clinicians' policy; a two-sample t-test validated that these performance improvements were statistically significant (p < 0.05). Conclusion: The results validate that our model had better performance in maintaining control variables within their target range, thereby jointly maintaining patients' health conditions and managing their sedation.

Clinical Decision Support System Based on Hybrid Knowledge Modeling: A Case Study of Chronic Kidney Disease-Mineral and Bone Disorder Treatment.

Clinical decision support systems (CDSSs) represent the latest technological transformation in healthcare for assisting clinicians in complex decision-making. Several CDSSs are proposed to deal with a range of clinical tasks such as disease diagnosis, prescription management, and medication ordering. Although a small number of CDSSs have focused on treatment selection, areas such as medication selection and dosing selection remained under-researched. In this regard, this study represents one of the first studies in which a CDSS is proposed for clinicians who manage patients with end-stage renal disease undergoing maintenance hemodialysis, almost all of whom have some manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD). The primary objective of the system is to aid clinicians in dosage prescription by levering medical domain knowledge as well existing practices. The proposed CDSS is evaluated with a real-world hemodialysis patient dataset acquired from Kyung Hee University Hospital, South Korea. Our evaluation demonstrates overall high compliance based on the concordance metric between the proposed CKD-MBD CDSS recommendations and the routine clinical practice. The concordance rate of overall medication dosing selection is 78.27%. Furthermore, the usability aspects of the system are also evaluated through the User Experience Questionnaire method to highlight the appealing aspects of the system for clinicians. The overall user experience dimension scores for pragmatic, hedonic, and attractiveness are 1.53, 1.48, and 1.41, respectively. A service reliability for the Cronbach's alpha coefficient greater than 0.7 is achieved using the proposed system, whereas a dependability coefficient of the value 0.84 reveals a significant effect.

Parenteral Protein Decision Support System Improves Protein Delivery in Preterm Infants: A Randomized Clinical Trial.

BACKGROUND: Management of neonatal parenteral protein intake for preterm infants is challenging and requires daily modifications of the dose to account for the infant's postnatal age, birth weight, current weight, and the volume and protein concentration of concurrent enteral nutrition. The objective of this study was to create and evaluate the Parenteral Protein Calculator (PPC), a clinical decision support system to improve the accuracy of protein intake for preterm infants who require parenteral nutrition (PN). MATERIALS AND METHODS: We integrated the PPC into the computerized provider order entry system and tested it in a randomized controlled trial (routine or PPC). Infants were eligible if they were ≤3 days old, had a birth weight ≤1500 g, and had no inborn error of metabolism. The primary outcome was the appropriate total protein intake, defined as target protein dose ±0.5 g/kg. RESULTS: We randomly allocated 42 infants for 221 PN days in the control group and 211 in the PPC group. Total protein intake in the PPC group was more accurate as compared with the control group (appropriate protein dosing: odds ratio = 5.8; 95% CI, 2.7-12.4). Absolute deviation from protein target was 0.41 g/kg (0.24-0.58) lower in the PPC group. CONCLUSION: The PPC improved appropriate protein dosing for premature infants receiving PN. Further studies are needed to test whether clinical decision support systems will reduce uremia and improve growth and to replicate similar findings in the cases of other PN nutrients.

Pharmacist-Led Drug Therapy Problem Management in an Interprofessional Geriatric Care Continuum: A Subset of the PIVOTS Group.

BACKGROUND: Drug therapy problems, which are adverse events involving medications that can ultimately interfere with a patient's therapeutic goals, occur frequently in older adults. If not identified, resolved, and prevented through clinical decision-making, drug therapy problems may negatively affect patient health outcomes. OBJECTIVE: To quantify the impact of pharmacist interventions on the care of older adults by identifying the most common drug therapy problems, the medications most often involved in these problems, and the actions taken by pharmacists to resolve these problems. METHODS: This retrospective chart review included individuals seen by a geriatric pharmacist in one geriatric practice, where 4 pharmacists provide continuous, comprehensive medication management across 2 outpatient geriatric clinics, skilled-nursing facilities, and assisted-living facilities. The individuals were seen between August 2014 and November 2015. For all patient care encounters during this time frame, pharmacists used the Assurance System to document each drug therapy problem, the medications involved, the patient's care setting (ie, outpatient clinic, assisted-living facility, skilled-nursing facility), the actions taken to resolve any drug therapy problems, and the estimated 90-day impact on the patient and the healthcare system. RESULTS: A total of 3100 drug therapy problems were identified during 3309 patient-pharmacist encounters for 452 patients (mean age, 81.4 years), 48.7% of whom were seen in the skilled-nursing facility. The most common drug therapy problem was dose too low, followed by dose too high, and warfarin was the most common drug associated with drug therapy problems. Pharmacists provided 4921 interventions, often more than 1 intervention per drug therapy problem, for 275 different medications. Laboratory monitoring and dose change were the most common interventions, with an estimated annual financial savings between $268,690 and $270,591. CONCLUSION: Older patients are a vulnerable patient population who often receive unsafe medication regimens, which can result in adverse drug reactions and other critical problems. When integrated into interprofessional geriatric care teams, pharmacists' interventions provide an invaluable qualitative and monetary resource to the medication-based management of patients with well-recognized, high-risk geriatric syndromes as they transition to and through various levels of care.

Considerations for Medication Management and Anticoagulation During Continuous Renal Replacement Therapy.

Providing safe and high-quality care to critically ill patients receiving continuous renal replacement therapy (CRRT) includes adequate drug dosing and evaluation of patients' response to medications during therapy. Pharmacokinetic drug studies in acute kidney injury and CRRT are limited, considering the number of medications used in critical care. Therefore, it is important to understand the basic principles of drug clearance during CRRT by evaluating drug properties, CRRT modalities, and how they affect medication clearance. Few published studies have addressed drug disposition and clinical response during CRRT. Additionally, clotting in the CRRT circuit is a concern, so a few options for anticoagulation strategies are presented. This article reviews (1) the CRRT system and drug property factors that affect medication management, (2) the evidence available to guide drug dosing, and (3) anticoagulation strategies for critically ill patients receiving CRRT.

The impact of real-time alerting on appropriate prescribing in kidney disease: a cluster randomized controlled trial.

BACKGROUND: Patients with kidney disease are at risk for adverse events due to improper medication prescribing. Few randomized controlled trials of clinical decision support (CDS) utilizing dynamic assessment of patients' kidney function to improve prescribing for patients with kidney disease have been published. METHODS: We developed a CDS tool for 20 medications within a commercial electronic health record. Our system detected scenarios in which drug discontinuation or dosage adjustment was recommended for adult patients with impaired renal function in the ambulatory and acute settings - both at the time of the initial prescription ("prospective" alerts) and by monitoring changes in renal function for patients already receiving one of the study medications ("look-back" alerts). We performed a prospective, cluster randomized controlled trial of physicians receiving clinical decision support for renal dosage adjustments versus those performing their usual workflow. The primary endpoint was the proportion of study prescriptions that were appropriately adjusted for patients' kidney function at the time that patients' conditions warranted a change according to the alert logic. We employed multivariable logistic regression modeling to adjust for glomerular filtration rate, gender, age, hospitalized status, length of stay, type of alert, time from start of study, and clustering within the prescribing physician on the primary endpoint. RESULTS: A total of 4068 triggering conditions occurred in 1278 unique patients; 1579 of these triggering conditions generated alerts seen by physicians in the intervention arm and 2489 of these triggering conditions were captured but suppressed, so as not to generate alerts for physicians in the control arm. Prescribing orders were appropriate adjusted in 17% of the time vs 5.7% of the time in the intervention and control arms, respectively (odds ratio: 1.89, 95% confidence interval, 1.45-2.47, P < .0001). Prospective alerts had a greater impact than look-back alerts (55.6% vs 10.3%, in the intervention arm). CONCLUSIONS: The rate of appropriate drug prescribing in kidney impairment is low and remains a patient safety concern. Our results suggest that CDS improves drug prescribing, particularly when providing guidance on new prescriptions.

Optimal medication dosing in patients with diabetes mellitus and chronic kidney disease.

Diabetes mellitus is the leading cause of chronic kidney disease (CKD) in Canada. As rates of diabetes rise, so does the prevalence of CKD. Diabetes and CKD are chronic diseases that require multiple medications for their management. Many of the anticipated effects of these medications are altered by the physiologic changes that occur in CKD. Failure to individualize drug dosing in this population may lead to toxicity or decreased therapeutic response, leading to treatment failure. At times this can be challenging for a multitude of reasons, including the limitations of available calculations for estimating renal function, inconsistent dosing recommendations and the lack of dosing recommendations for some medications. Clinicians caring for these patients need to consider an approach of individualized drug therapy that will ensure optimal outcomes. The better understanding that clinicians have of these challenges, the more effective they will be at using the available information as a guide together with their own professional judgement to make appropriate dosing changes. This article discusses the following: 1) physiologic changes that occur in CKD and its impact on drug dosing; 2) advantages and disadvantages of various calculations used for estimating renal function; 3) pharmacokinetic and pharmacodynamic changes of some commonly used medications in diabetes, and finally, 4) an approach to individualized drug dosing for this patient population.