Effectiveness of Short-Acting Opioid Escalation vs Initiation of a Long-Acting Opioid in Nursing Home Residents.

OBJECTIVES: Modifications to opioid regimens for persistent pain are typically made after an initial period of short-acting opioid (SAO) use. Regimen changes may include an escalation of the SAO dosage or an initiation of a long-acting opioid (LAO) as a switch or add-on therapy. This study evaluates the comparative effectiveness between these alternative regimens/options in nursing home residents. DESIGN: A retrospective observational cohort analysis of US long-stay nursing home residents. SETTING AND PARTICIPANTS: Nursing home resident data were obtained from the national Minimum Dataset (MDS) version 3.0 and linked Medicare data, 2011-2016. METHODS: Opioid regimen changes were identified using Part D dispensing claims to identify dosage escalation of SAOs, initiation of an LAO, or a switch to an LAO. Outcomes included indices of pain occurrence, frequency, and severity reported on the earliest MDS assessment within 3 months following the opioid regimen change. Resident attributes were described by opioid regimen cohort. Prevalence ratios of pain and depression indices were quantified using doubly robust inverse probability of treatment (IPT)-weighted log-binomial regression. RESULTS: The study cohorts included 2072 SAO dose escalations, 575 LAO add-on initiations, and 247 LAO switch initiations. After IPT weighting, we observed comparable effects on pain and mood across the opioid regimen cohorts. A substantial number of residents continued to report frequent/constant pain (36% in SAO Escalation Cohort, 42% in LAO Add-on Cohort, 42% in the LAO Switch Cohort). The distribution of depressive symptoms was similar regardless of the opioid regimen change. CONCLUSIONS AND IMPLICATIONS: Initiation of an LAO as an add-on to SAO or a switch from SAO had comparable effects on pain and mood to SAO dose escalation without initiation of an LAO. Although fewer residents reported any pain after the regimen change, persistent pain was reported by most residents.

Development and validation of a performance-based palliative care assessment tool for student pharmacists.

INTRODUCTION: Integration of hospice and palliative care principles within pharmacy curricula is essential to fill the need of pharmacist training in this growing specialty. A formalized assessment tool to evaluate skill development does not exist for student pharmacists specific to palliative care. The objective of this study was to develop a valid and reliable, palliative care-focused, performance-based assessment tool for student pharmacists. METHODS: Eight academic palliative care (PC) pharmacists were recruited for the workgroup to perform domain development, validation, tool creation, and reliability testing for this performance-based assessment tool. Hospice and palliative care clinical pharmacist entrustable professional activities (EPAs) served as the framework. Content validity testing utilized content validity index and scale universal agreement (S-CVI/UA) to determine level of agreement for activities included in the tool. Student volunteers completed a standardized patient case and workgroup members served as raters during the reliability testing phase. Interrater reliability was measured through calculation of Fleiss Kappa scores for each activity. RESULTS: Out of 14 EPAs, nine were deemed "essential" to include in the tool. Thirty-four supporting activities for the nine essential EPAs were drafted. Two rounds of content validity testing were necessary to achieve S-CVI/UA of 0.9593. Consensus was reached from workgroup members for activities deemed necessary to include in the tool after questionnaire distribution utilizing a Fleiss Kappa cutoff >0.6. CONCLUSIONS: This validated tool will afford colleges and schools of pharmacy with PC curricula an opportunity to assess student achievement of PC-specific skills and evaluate curricular effectiveness.

Comparative safety of adding serotonin and norepinephrine reuptake inhibitors (SNRIs) versus nonsteroidal anti-inflammatory drugs (NSAIDs) to short-acting opioids for non-malignant pain in nursing homes.

BACKGROUND: The comparative safety of serotonin and norepinephrine reuptake inhibitors (SNRIs) as adjuvants to short-acting opioids in older adults is unknown even though SNRIs are commonly used. We compared the effects of SNRIs versus nonsteroidal anti-Inflammatory drugs (NSAIDs) on delirium among nursing home residents when SNRIs or NSAIDs were added to stable regimens of short-acting opioids. METHODS: Using 2011-2016 national Minimum Data Set (MDS) 3.0 and Medicare claims data to implement a new-user design, we identified a cohort of nursing home residents receiving short-acting opioids who initiated either an SNRI or an NSAID. Delirium was defined from the Confusion Assessment Method in MDS 3.0 assessments and ICD9/10 codes using Medicare hospitalization claims. Propensity score matching balanced underlying differences for initiating treatments on 39 demographic and clinical characteristics (nSNRIs = 5350; nNSAIDs = 5350). Fine and Gray models provided hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for the competing risk of death. RESULTS: Hydrocodone was the most commonly used short-acting opioid (48%). Residents received ~23 mg daily oral morphine equivalent at the time of SNRIs/NSAIDs initiation. The majority were women, non-Hispanic White, and aged ≥75 years. There were no differences in any of the confounders after propensity matching. Over 1 year, 10.8% of SNRIs initiators and 8.9% of NSAIDs initiators developed delirium. The rate of delirium onset was similar in SNRIs and NSAID initiators (HR(delirium in nursing home or hospitalization for delirium):1.10; 95% CI: 0.97-1.24; HR(hospitalization for delirium): 1.06; 95% CI: 0.89-1.25), and were similar regardless of baseline opioid daily dosage. CONCLUSIONS: Among nursing home residents, adding SNRIs to short-acting opioids does not appear to increase risk of delirium relative to initiating NSAIDs. Understanding the comparative safety of pain regimens is needed to inform clinical decisions in a medically complex population often excluded from clinical research.

Comparative Safety Analysis of Opioid Agonist Treatment in Pregnant Women with Opioid Use Disorder: A Population-Based Study.

INTRODUCTION AND OBJECTIVE: Receipt of opioid agonist treatment during early and late pregnancy for opioid use disorder may relate to varying perinatal risks. We aimed to assess the effect of time-varying prenatal exposure to opioid agonist treatment using buprenorphine or methadone on adverse neonatal and pregnancy outcomes. METHODS: We conducted a retrospective cohort study of pregnant women with opioid use disorder using Rhode Island Medicaid claims data and vital statistics during 2008-16. Time-varying exposure was evaluated in early (0-20 weeks) and late (≥ 21 weeks) pregnancy. Marginal structural models with inverse probability of treatment weighting were applied. RESULTS: Of 400 eligible pregnancies, 85 and 137 individuals received buprenorphine and methadone, respectively, during early pregnancy. Compared with 152 untreated pregnancies with opioid use disorders, methadone exposure in both periods was associated with an increased risk of preterm birth (adjusted odds ratio [aOR]: 2.52; 95% confidence interval [CI] 1.07-5.95), low birth weight (aOR: 2.99; 95% CI 1.34-6.66), neonatal intensive care unit admission (aOR, 5.04; 95% CI 2.49-10.21), neonatal abstinence syndrome (aOR: 11.36; 95% CI 5.65-22.82), respiratory symptoms (aOR, 2.71; 95% CI 1.17-6.24), and maternal hospital stay > 7 days (aOR, 14.51; 95% CI 7.23-29.12). Similar patterns emerged for buprenorphine regarding neonatal abstinence syndrome (aOR: 10.27; 95% CI 4.91-21.47) and extended maternal hospital stay (aOR: 3.84; 95% CI 1.83-8.07). However, differences were found favoring the use of buprenorphine for preterm birth versus untreated pregnancies (aOR: 0.17; 95% CI 0.04-0.77), and for several outcomes versus methadone. CONCLUSIONS: Methadone and buprenorphine prescribed for the treatment of opioid use disorder during pregnancy are associated with varying perinatal risks. However, buprenorphine may be preferred in the setting of pregnancy opioid agonist treatment. Further research is necessary to confirm our findings and minimize residual confounding.

Survival and recovery modeling of acute kidney injury in critically ill adults.

Objectives: Acute kidney injury is common among the critically ill. However, the incidence, medication use, and outcomes of acute kidney injury have been variably described. We conducted a single-center, retrospective cohort study to examine the risk factors and correlates associated with acute kidney injury in critically ill adults with a particular focus on medication class usage. Methods: We reviewed the electronic medical records of all adult patients admitted to an intensive care unit between 1 February and 30 August 2020. Acute kidney injury was defined by the 2012 Kidney Disease: Improving Global Outcomes guidelines. Data included were demographics, comorbidities, symptoms, laboratory parameters, interventions, and outcomes. The primary outcome was acute kidney injury incidence. A Least Absolute Shrinkage and Selection Operator regression model was used to determine risk factors associated with acute kidney injury. Secondary outcomes including acute kidney injury recovery and intensive care unit mortality were analyzed using a Cox regression model. Results: Among 226 admitted patients, 108 (47.8%) experienced acute kidney injury. 37 (34.3%), 39 (36.1%), and 32 patients (29.6%) were classified as acute kidney injury stages I-III, respectively. Among the recovery and mortality cohorts, analgesics/sedatives, anti-infectives, and intravenous fluids were significant (p-value < 0.05). The medication classes IV-fluid electrolytes nutrition (96.7%), gastrointestinal (90.2%), and anti-infectives (81.5%) were associated with an increased odds of developing acute kidney injury, odd ratios: 1.27, 1.71, and 1.70, respectively. Cox regression analyses revealed a significantly increased time-varying mortality risk for acute kidney injury-stage III, hazard ratio: 4.72 (95% confidence interval: 1-22.33). In the recovery cohort, time to acute kidney injury recovery was significantly faster in stage I, hazard ratio: 9.14 (95% confidence interval: 2.14-39.06) cohort when compared to the stage III cohort. Conclusion: Evaluation of vital signs, laboratory, and medication use data may be useful to determine acute kidney injury risk stratification. The influence of particular medication classes further impacts the risk of developing acute kidney injury, necessitating the importance of examining pharmacotherapeutic regimens for early recognition of renal impairment and prevention.

Drug-Induced QTc Prolongation: What We Know and Where We Are Going.

Drug-induced QTc prolongation is a concerning electrocardiogram (ECG) abnormality. This cardiac disturbance carries a 10% risk of sudden cardiac death due to the malignant arrhythmia, Torsades de Pointes. The Arizona Center for Education and Research on Therapeutics (AzCERT) has classified QTc prolonging therapeutic classes, such as antiarrhythmics, antipsychotics, anti-infectives, and others. AzCERT criteria categorize medications into three risk categories: "known," "possible," and "conditional risk" of QTc prolongation and Torsades de Pointes. The list of QTc prolonging medications continues to expand as new drug classes are approved and studied. Risk factors for QTc prolongation can be delineated into modifiable or non-modifiable. A validated risk scoring tool may be utilized to predict the likelihood of prolongation in patients receiving AzCERT classified medication. The resultant risk score may be applied to a clinical decision support system, which offers mitigation strategies. Mitigation strategies including discontinuation of possible offending agents with a selection of an alternative agent, assessment of potential drug interactions or dose adjustments through pharmacokinetic and pharmacodynamic monitoring, and initiation of both ECG and electrolyte monitoring are essential to prevent a drug-induced arrhythmia. The challenges presented by the COVID-19 pandemic have led to the development of innovative continuous monitoring technology, increasing protection for both patients and healthcare workers. Early intervention strategies may reduce adverse events and improve clinical outcomes in patients identified to be at risk of QTc prolongation.

An analysis of the management and incidence of postoperative nausea and vomiting.

BACKGROUND: Postoperative nausea and vomiting significantly increases recovery time, reduces patient satisfaction, and increases time to discharge. Consensus guidelines for the management of postoperative nausea and vomiting highlight effective methods for prophylaxis and treatment. Implications of adherence to these guidelines include both improved patient outcomes and reduced healthcare costs. OBJECTIVE: This study aimed to assess the incidence, contributing factors, and current prescribing practices for prophylaxis and treatment of postoperative nausea and vomiting. METHODS: Electronic medical records were assessed for adult patients who had an elective gastrointestinal or gynaecologic surgical procedure over a one-year period. Patient demographics and perioperative data were collected to assess risk factors and the incidence of postoperative nausea and vomiting. The appropriateness of prophylaxis and treatment was assessed according to current guidelines. RESULTS: The incidence of postoperative nausea and vomiting was consistent with previously noted findings. The average time spent under anaesthesia was significantly higher in patients who experienced postoperative nausea and vomiting. Appropriate evidence-based rescue therapy was administered in a minority of the cohort experiencing postoperative nausea and vomiting. CONCLUSION: There is substantial opportunity for provider education and adherence to best prescribing practices. Enhanced adherence to evidence-based rescue therapy prescribing may improve patient outcomes and satisfaction.

Priority-Setting to Address the Geriatric Pharmacoparadox for Pain Management: A Nursing Home Stakeholder Delphi Study.

BACKGROUND: Evidence to guide clinical decision making for pain management in nursing home residents is scant. OBJECTIVE: Our objective was to explore the extent of consensus among expert stakeholders regarding what analgesic issues should be prioritized for comparative-effectiveness studies of beneficial and adverse effects of analgesic regimens in nursing home residents. METHODS: Two stakeholder panels (nurses only and a mix of clinicians/researchers) were engaged (n = 83). During a three-round online modified Delphi process, participants rated and commented on the need for new evidence on nonopioid analgesic regimens and opioid regimens, short-term adverse effects, long-term adverse effects, comorbid conditions, and other factors in the nursing home setting (9-point scale; 1 = not essential to 9 = very essential to obtain new evidence). The quantitative data were analyzed to determine the existence of consensus using an approach from the RAND/UCLA Appropriateness Method User's Manual. The qualitative data, consisting of participant explanations of their numeric ratings, were thematically analyzed by an experienced qualitative researcher. RESULTS: For nursing home residents, evidence generation was deemed essential for opioids, gabapentin (alone or with serotonin norepinephrine reuptake inhibitors [SNRIs]), and nonsteroid anti-inflammatory drugs with SNRIs. Experts prioritized the following outcomes as essential: long-term adverse effects, including delirium, cognitive decline, and decline in activities of daily living (ADLs). Kidney disease and depression were deemed essential conditions to consider in studies of pain medications. Coprescribing analgesic regimens with benzodiazepines, sedating medications, serotonergic medications, and non-SNRI antidepressants were considered essential areas of study. Experts noted that additional study was essential in residents with moderate/severe cognitive impairment and limitations in ADLs. CONCLUSIONS: Stakeholder priorities for more evidence reflect concerns related to treating medically complex residents with complex drug regimens and included long-term adverse effects, coprescribing, and sedating medications. Carefully conducted observational studies are needed to address the vast evidence gap for nursing home residents.

A retrospective analysis of the impact of disabling item review on item performance on computerized fixed-item tests in a doctor of pharmacy program.

OBJECTIVE: The decision to disable item review, or 'backward navigation,' during computerized-fixed item tests proved controversial among faculty at our institution. We sought to determine the effect of disabling backward navigation on performance of individual exam items and overall exam performance across multiple courses within a doctor of pharmacy program. METHODS: Exam items that were administered unchanged and without error or adjustment of scoring between 2016 and 2017 were eligible for inclusion. Included items were evaluated for change in difficulty index, point biserial, and discrimination index for the year when backward navigation was enabled to the year after the function was disabled. Performance on matching exam pairs in each time frame was compared for any changes. RESULTS: We screened 2033 items and identified 576 which met study inclusion criteria. There were no significant differences in overall item difficulty index, point biserial, discrimination index or performance of the 27% lowest-scoring students. There was a decrease of 0.95% for the highest-scoring students (z = -2.93, p = 0.003). We identified 15 pairs of exams that contained at least 30% identical items from 2016 to 2017. No difference was found in the percent score minimum, maximum, mean, median, or standard deviation. CONCLUSIONS: Although there was a statistically significant decrease in item performance for students with the highest scores on the exam, we were unable to demonstrate that disabling backward navigation had a significant impact on overall item performance or exam results.

Chemotherapy-Induced Peripheral Neuropathy: Causative Agents, Preventative Strategies, and Treatment Approaches.

Chemotherapy-induced peripheral neuropathy (CIPN) is a chronic symptom associated with chemotherapy treatment. Symptoms and severity vary based on chemotherapeutic agent used and dose. At present, effective options for the prevention and treatment of CIPN are inadequate and clinical guidance is limited. Unknown mechanism of action, lack of efficacy in many traditional neuropathic pain medications, and inconsistent evidence in regard to drug therapy have further complicated evaluation of therapeutic options. Twenty-five studies were identified and evaluated for CIPN prevention and treatment potential. Findings for CIPN pharmacological prevention were inconclusive as literature was largely conflicting. Exercise may be an effective non-pharmacological CIPN prevention method with limited adverse effects, however additional supporting data is still required. For treatment of CIPN, pharmacological agents duloxetine and topical combination product containing baclofen, amitriptyline, and ketamine have data supporting use. Early stage trials have shown initial promise for non-pharmacological therapies Scrambler Therapy and Photobiomodulation. Significant research is required as CIPN symptoms can lead to decreased quality of life, chemotherapy dose reduction, and discontinuation of drug therapy.

Comparison of multimodal, sliding scale acute pain protocols with traditional prescribing in non-surgical patients.

Objective: Our institution implemented six multimodal, sliding scale protocols for managing pain in non-surgical inpatients. The purpose of this study was to compare the use of these acute pain protocols with traditional prescribing in regard to pain management efficacy and safety measures.Methods: This retrospective cohort study evaluated hospital in-patients who were prescribed one of the protocols during the first 6 months following implementation, admitted to the hospitalist service, and had received at least two doses of PRN analgesic medication within a 24-hour period. Data collected included baseline demographics, verbal pain rating scores to determine time to achieve analgesia, total opioid use in oral morphine equivalent doses (MEDs), and safety measures. A sample of patients admitted during the same time frame, meeting inclusion/exclusion criteria, but who received traditional analgesic prescribing served as controls.Results: Forty-six adult, non-surgical patients were included in the analysis, and 46 served as controls. The average baseline pain scores were similar between groups (7.26 in protocol, 7.43 in control, p = 0.684). Protocol patients required significantly less time to achieve meaningful analgesia (average 507.52 min) compared to the control group (894.33 min, p = 0.045). Patients in the protocol group used an average of 35.81 MEDs per day compared to 65.77 MEDs in controls (p = 0.019). Patients in the protocol group used significantly fewer PRN analgesic doses (12.70 vs. 24.02, p < 0.0001).Conclusion: Analysis of the implementation of acute pain management protocols indicates that using standardized pain management protocols of opioids, non-opioids, and medications to prevent opioid-related adverse events is more effective than traditional analgesic prescribing for our patient population.

Mechanism of action of HTX-011: a novel, extended-release, dual-acting local anesthetic formulation for postoperative pain.

BACKGROUND AND OBJECTIVES: Obtaining consistent efficacy beyond 12-24 hours with local anesthetics, including extended-release formulations, has been a challenging goal. Inflammation resulting from surgery lowers the pH of affected tissues, reducing neuronal penetration of local anesthetics. HTX-011, an investigational, nonopioid, extended-release dual-acting local anesthetic combining bupivacaine and low-dose meloxicam, was developed to reduce postsurgical pain through 72 hours using novel extended-release polymer technology. Preclinical studies and a phase II clinical trial were conducted to confirm the mechanism of action of HTX-011. METHODS: In a validated postoperative pain pig model and a phase II bunionectomy trial, the analgesic effects of HTX-011, oral meloxicam (preclinical only), liposomal bupivacaine (preclinical only) and saline placebo were evaluated. The optimal meloxicam:bupivacaine ratio for HTX-011 and the effect of HTX-011 on incisional tissue pH were also evaluated preclinically. RESULTS: Preclinical data demonstrate the ability of HTX-011 to address local tissue inflammation as demonstrated by a less acidic tissue pH, which was associated with potentiated and prolonged analgesic activity. In the phase II bunionectomy study, HTX-011 achieved superior and sustained pain relief through 72 hours after surgery compared with each component in the polymer. CONCLUSIONS: Preclinical animal and clinical results confirm that the low-dose meloxicam in HTX-011 normalizes the local pH in the incision, resulting in superior and synergistic analgesic activity compared with extended-release bupivacaine. HTX-011 represents an extended-release local anesthetic with a dual-acting mechanism of action that may provide an important advancement in the treatment of postoperative pain. TRIAL REGISTRATION NUMBER: NCT02762929.

Health Care Burden Associated with Outpatient Opioid Use Following Inpatient or Outpatient Surgery.

BACKGROUND: The treatment of postsurgical pain with prescription opioids has been associated with persistent opioid use and increased health care utilization and costs. OBJECTIVE: To compare the health care burden between opioid-naive adult patients who were prescribed opioids after a major surgery and opioidnaive adult patients who were not prescribed opioids. METHODS: Administrative claims data from the IBM Watson Health MarketScan Research Databases for 2010-2016 were used. Opioid-naive adult patients who underwent major inpatient or outpatient surgery and who had at least 1 year of continuous enrollment before and after the index surgery date were eligible for inclusion. Cohorts were defined based on an opioid pharmacy claim between 7 days before index surgery and 1 year after index surgery (opioid use during surgery and inpatient use were not available). To ensure an opioid-naive population, patients with opioid claims between 365 and 8 days before surgery were excluded. Acute medical outcomes, opioid utilization, health care utilization, and costs were measured during the post-index period (index surgery hospitalization and day of index outpatient surgery not included). Predicted costs were estimated from multivariable log-linked gamma-generalized linear models. RESULTS: The final sample consisted of 1,174,905 opioid-naive patients with an inpatient surgery (73% commercial, 20% Medicare, 7% Medicaid) and 2,930,216 opioid-naive patients with an outpatient surgery (74% commercial, 23% Medicare, and 3% Medicaid). Opioid use after discharge was common among all 3 payer types but was less common among Medicare patients (63% inpatient/43% outpatient) than patients with commercial (80% inpatient/75% outpatient) or Medicaid insurance (86% inpatient/81% outpatient). Across all 3 payers, opioid users were younger, were more likely to be female, and had a higher preoperative comorbidity burden than nonopioid users. In unadjusted analyses, opioid users tended to have more hospitalizations, emergency department visits, and pharmacy claims. Adjusted predicted 1-year post-period total health care costs were significantly higher (P< 0.001) for opioid users than nonopioid users for commercial insurance (inpatient: $22,209 vs. $14,439; outpatient: $13,897 vs. $8,825), Medicare (inpatient: $31,721 vs. $26,761; outpatient: $24,529 vs. $15,225), and Medicaid (inpatient: $13,512 vs. $9,204; outpatient: $11,975 vs. $8,212). CONCLUSIONS: Filling an outpatient opioid prescription (vs. no opioid prescription) in the 1 year after inpatient or outpatient surgery was associated with increased health care utilization and costs across all payers. DISCLOSURES: Funding for this study was provided by Heron Therapeutics, which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Brummett is a paid consultant for Heron Therapeutics and Recro Pharma and reports receipt of research funding from MDHHS (Sub K Michigan Open), NIDA (Centralized Pain Opioid Non-Responsiveness R01 DA038261-05), NIH0DHHS-US-16 PAF 07628 (R01 NR017096-05), NIH-DHHS (P50 AR070600-05 CORT), NIH-DHHS-US (K23 DA038718-04), NIH-DHHS-US-16-PAF06270 (R01 HD088712-05), NIH-DHHS-US-17-PAF02680 (R01 DA042859-05), and UM Michigan Genomics Initiative and holding a patent for peripheral perineural dexmedetomidine. Oderda is a paid consultant for Heron Therapeutics. Pawasauskas is a paid consultant to Heron Therapeutics and Mallinckrodt Pharmaceuticals. England and Evans-Shields are employees of Heron Therapeutics. Kong, Lew, Zimmerman, and Henriques are employees of IBM Watson Health, which was compensated by Heron Therapeutics for conducting this research. Portions of this work were presented as a poster at the AMCP Managed Care and Specialty Pharmacy Annual Meeting 2019; March 25-28, 2019; San Diego, CA.

Multicentered Study Evaluating Pharmacy Students' Perception of Palliative Care and Clinical Reasoning Using Script Concordance Testing.

INTRODUCTION: As the role of the pharmacist on the transdisciplinary palliative care team grows, the need for adequate instruction on palliative care and clinical reasoning skills in schools of pharmacy grows accordingly. METHODS: This study evaluates second- and third-year pharmacy students from 6 accredited schools of pharmacy that participated in surveys before and after the delivery of a didactic palliative care elective. The survey collected student demographics, perceptions of the importance of and student skill level in palliative care topics. The script concordance test (SCT) was used to assess clinical decision-making skills on patient cases. Student scores on the SCT were compared to those of a reference panel of experts. RESULTS: A total of 89 students completed the pre-/postsurveys and were included in data analysis. There was no statistically significant difference in student perceived importance of palliative care skills before and after the elective. Students from all 6 institutions showed significant increase in confidence in their palliative care skills at the end of the course. There was also a significant improvement across all institutions in clinical reasoning skills in most of the SCT questions used to assess these skills. CONCLUSIONS: Students choosing an elective in palliative care likely do so because they already have an understanding of the importance of these topics in their future practice settings. Delivery of a palliative care elective in the pharmacy curriculum significantly increases both student confidence in their palliative care skills and their clinical reasoning skills in these areas.

Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects.

BACKGROUND AND OBJECTIVE: Several features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine. METHODS: In this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals. Comparisons of plasma pharmacokinetic profiles were conducted before, during, and after opioid co-administrations. RESULTS: Twenty-two subjects were included in the pharmacokinetic analysis. Observed paracetamol peak concentration (C max) and area under the plasma concentration-time curve over the dosing interval (AUC0-6) were reduced when oral paracetamol was co-administered with morphine (reduced from 11.6 to 7.25 µg/mL and from 31.00 to 25.51 µg·h/mL, respectively), followed by an abruptly increased C max and AUC0-6 upon discontinuation of morphine (to 13.5 µg/mL and 52.38 µg·h/mL, respectively). There was also a significantly prolonged mean time to peak plasma concentration (T max) after the 4th dose of oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However, pharmacokinetic parameters of paracetamol were not impacted when intravenous paracetamol was co-administered with morphine. CONCLUSIONS: Morphine co-administration significantly impacted the pharmacokinetics of oral but not intravenous paracetamol. The abrupt release of accumulated paracetamol at the end of morphine-mediated gastrointestinal inhibition following oral but not intravenous administration of paracetamol suggests that intravenous paracetamol provides a better option for the management of postoperative pain. CLINICALTRIALS. GOV IDENTIFIER: NCT02848729.

Adverse Drug Reactions in Palliative Care.

Adverse drug reactions (ADRs) have an impact on patient morbidity and mortality. Palliative care patients constitute a vulnerable population due to the complexity of their care and treatments. This study sought to identify ADRs in palliative care, assess their severity and preventability, and identify specific medications most commonly involved. This retrospective cohort study included patients who received a consult by the hospital's palliative care service over a 1-year period. Records were reviewed to identify ADR occurrences, causative and resulting events, and variables used to determine preventability and severity. Of the 430 patients who met inclusion criteria, 247 patients experienced an ADR (57.4%). In total, 440 ADRs were documented, with 45.7% of patients experiencing more than one. Patients with repeated hospitalizations, increased medication usage, documented drug allergies, and cancer diagnoses were more likely to experience an ADR. No associations were found between occurrences of ADR with gender or Charlson comorbidity scores. The majority of ADRs were of moderate severity (64.6%) and considered potentially preventable (81.5%). Organ systems most commonly affected by ADRs were gastrointestinal (32.7%) and neurological (15.9%). Antimicrobials, opioids, and anticoagulants were the most common causative agents. ADRs are commonly experienced in palliative care patients and are often preventable. Identification of risk factors for ADRs may prevent occurrences in the complex palliative care patient.

Opioid rotation: A case example using methadone in spinal cord injury.

Opioid rotation is a practice used when patients with chronic pain have insufficient analgesia, experience unwanted opioid-related adverse reactions, or other pharmacologic challenges with their current opioid. Methadone is an opioid with unique pharmacological properties, which render it clinically distinct from other opioids. The drug's potential clinical benefits in treating nociceptive and neuropathic pain are coupled with risks of serious, life-threatening adverse reactions. Its unique pharmacokinetic profile contributes added complexity; therefore, clinicians should be experienced with its dosing and monitoring. This report discusses the successful use of methadone during opioid rotation for chronic pain secondary to spinal cord injury.