Methadone and Corrected QT Prolongation in Pain and Palliative Care Patients: A Case–Control Study

Background: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients. Objective: Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool. Design: We performed a case–control study of adult inpatients receiving ME for pain management. Settings/Subjects: Adult inpatients receiving ME with a QTc \u3e470 msec (males) and \u3e480 msec (females) were matched 1:2 according to age, history of QTc prolongation, and gender with ME patients who did not have a prolonged QTc interval. QTc prolongation risk factors were collected for both groups. Covariates were analyzed using conditional logistic regression. Classification and regression tree analysis was used to identify the ME dose associated with QTc prolongation. Results: Predictors of QTc prolongation included congestive heart failure (CHF) (OR: 11.9; 95% CI: 3.7–38.2; p \u3c 0.00), peptic ulcer disease (PUD) (odds ratio [OR]: 8.3; 95% confidence interval [95% CI]: 2.4–28.9; p \u3c 0.00), hypokalemia (OR: 6.5; 95% CI: 1.5–28.2; p \u3c 0.01), rheumatologic diseases (OR: 4.7; 95% CI: 1.6–13.9; p \u3c 0.00), taking medications with a known torsades de pointes (TdP) risk (OR: 4.4; 95% CI: 1.8–10.7; p \u3c 0.01), malignancy (OR: 3.3; 95% CI: 1.2–9.3; p \u3c 0.03), hypocalcemia (OR: 2.1; 95% CI: 0.9–4.8; p \u3c 0.07), and ME doses \u3e45 mg per day (OR: 1.9; 95% CI: 0.8–4.8; p \u3c 0.16). Mild liver disease was protective against QTc prolongation (OR: 0.05; 95% CI: 0.0–0.46; p \u3c 0.01). Conclusions: Predictors of QTc prolongation in our multivariate conditional logistic regression model included CHF, PUD, hypokalemia, rheumatologic disorders, use of medications with a known TdP risk, malignancy, hypocalcemia, and ME doses \u3e45 mg per day

Morphine and Hydromorphone-Induced Hyperalgesia in a Hospice Patient

Opioids including morphine and hydromorphone are widely used for control of moderate to severe pain and dyspnea in hospice and palliative care patients. Accumulation of the active morphine-3-glucuronide (M3G) and hydromorphone-3-glucuronide (H3G) metabolites is one proposed mechanism for the development of neuroexcitatory effects including allodynia and opioid-induced hyperalgesia (OIH). We report the case of a 43-year-old female hospice patient with metastatic non-small cell lung cancer who initially developed allodynia following morphine administration and again following administration of hydromorphone. The allodynia resolved both times following the discontinuation of the opioid and rotation to a different opioid regimen. Potential opioid-induced neuroexcitatory treatment options include opioid rotation to an agent with inactive metabolites, use of adjuvant pain medications for opioid-sparing effects, management of undesired symptoms (e.g., myoclonus), or increasing opioid clearance with intravenous (IV) fluids. Although the incidence is not well defined in the literature, hospice and palliative care clinicians should suspect OIH in patients with allodynia and/or hyperalgesia, especially when repeated dose escalations do not improve analgesia or pain escalates following opioid dose titration

The Crossroads of Interprofessionalism: Four Avenues of Collaboration at the Wegmans School of Pharmacy

Objective: The utilization of interprofessional education and collaborative practice delivers optimal health services and improves patient outcomes. Training future healthcare providers in an integrated environment promotes a “collaborative practice-ready” workforce. The aim of this study was to identify ongoing specific interprofessional collaborative projects and promote their awareness among faculty at the St. John Fisher College Wegmans School of Pharmacy. Methods: Faculty members were surveyed to identify the ongoing interprofessional collaborative initiatives among pharmacy faculty. Results: A total of four collaborative practices were identified among faculty: ambulatory care, assisted-living, didactic, and assessment. The ambulatory care setting at an osteoporosis clinic provides patient-centered care with a clinical component. Each patient with a new diagnosis or change in medication therapy receives education/counseling from a pharmacist, a registered nurse for medication administration and a physician for a physical exam. In the assisted-living setting, pharmacy and nursing students are paired to conduct a high-level health assessment in their respective disciplines. Didactic interprofessional efforts are being conducted to create a flexible and comprehensive pain education curriculum. Physicians, dentists, nurses, pharmacists, psychologists, chiropractors, and oriental medicine practitioners will develop the curriculum. The pain module will be adaptable for interprofessional education activities. Finally, recognizing the similarities in accreditation standards for communication and professionalism, the School of Pharmacy and the NY Chiropractic School are sharing strategies and rubrics for assessing these outcomes. Implications: The survey revealed a broader range of interprofessional collaborations than was originally suspected. The school will continue to foster and support interprofessional education and collaborative practice

Associations of Polypharmacy and Inappropriate Medications with Adverse Outcomes in Older Adults with Cancer: A Systematic Review and Meta-Analysis

© AlphaMed Press 2019 Background: Polypharmacy (PP) and potentially inappropriate medications (PIM) are highly prevalent in older adults with cancer. This study systematically reviews the associations of PP and/or PIM with outcomes and, through a meta-analysis, obtains estimates of postoperative outcomes associated with PP in this population. Materials and Methods: We searched PubMed, Embase, Web of Science, and Cochrane Register of Clinical Trials using standardized terms for concepts of PP, PIM, and cancer. Eligible studies included cohort studies, cross-sectional studies, meta-analyses, and clinical trials which examined outcomes associated with PP and/or PIM and included older adults with cancer. A random effects model included studies in which definitions of PP were consistent to examine the association of PP with postoperative complications. Results: Forty-seven articles met the inclusion criteria. PP was defined as five or more medications in 57% of the studies. Commonly examined outcomes included chemotherapy toxicities, postoperative complications, functional decline, hospitalization, and overall survival. PP was associated with chemotherapy toxicities (4/9 studies), falls (3/3 studies), functional decline (3/3 studies), and overall survival (2/11 studies). A meta-analysis of four studies indicated an association between PP (≥5 medications) and postoperative complications (overall odds ratio, 1.3; 95% confidence interval [1.3–2.8]). PIM was associated with adverse outcomes in 3 of 11 studies. Conclusion: PP is associated with postoperative complications, chemotherapy toxicities, and physical and functional decline. Only three studies showed an association between PIM and outcomes. However, because of inconsistent definitions, heterogeneous populations, and variable study designs, these associations should be further investigated in prospective studies. Implications for Practice: Polypharmacy and potentially inappropriate medications (PIM) are prevalent in older adults with cancer. This systematic review summarizes the associations of polypharmacy and PIM with health outcomes in older patients with cancer. Polypharmacy and PIM have been associated with postoperative complications, frailty, falls, medication nonadherence, chemotherapy toxicity, and mortality. These findings emphasize the prognostic importance of careful medication review and identification of PIM by oncology teams. They also underscore the need to develop and test interventions to address polypharmacy and PIM in older patients with cancer, with the goal of improving outcomes in these patients

Methadone and Corrected QT Prolongation in Pain and Palliative Care Patients: A Case–Control Study

Background: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients. Objective: Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool. Design: We performed a case–control study of adult inpatients receiving ME for pain management. Settings/Subjects: Adult inpatients receiving ME with a QTc \u3e470 msec (males) and \u3e480 msec (females) were matched 1:2 according to age, history of QTc prolongation, and gender with ME patients who did not have a prolonged QTc interval. QTc prolongation risk factors were collected for both groups. Covariates were analyzed using conditional logistic regression. Classification and regression tree analysis was used to identify the ME dose associated with QTc prolongation. Results: Predictors of QTc prolongation included congestive heart failure (CHF) (OR: 11.9; 95% CI: 3.7–38.2; p \u3c 0.00), peptic ulcer disease (PUD) (odds ratio [OR]: 8.3; 95% confidence interval [95% CI]: 2.4–28.9; p \u3c 0.00), hypokalemia (OR: 6.5; 95% CI: 1.5–28.2; p \u3c 0.01), rheumatologic diseases (OR: 4.7; 95% CI: 1.6–13.9; p \u3c 0.00), taking medications with a known torsades de pointes (TdP) risk (OR: 4.4; 95% CI: 1.8–10.7; p \u3c 0.01), malignancy (OR: 3.3; 95% CI: 1.2–9.3; p \u3c 0.03), hypocalcemia (OR: 2.1; 95% CI: 0.9–4.8; p \u3c 0.07), and ME doses \u3e45 mg per day (OR: 1.9; 95% CI: 0.8–4.8; p \u3c 0.16). Mild liver disease was protective against QTc prolongation (OR: 0.05; 95% CI: 0.0–0.46; p \u3c 0.01). Conclusions: Predictors of QTc prolongation in our multivariate conditional logistic regression model included CHF, PUD, hypokalemia, rheumatologic disorders, use of medications with a known TdP risk, malignancy, hypocalcemia, and ME doses \u3e45 mg per day

Folic Acid Improves Parkin-Null Phenotypes and Transiently Reduces Vulnerable Dopaminergic Neuron Mitochondrial Hydrogen Peroxide Levels and Glutathione Redox Equilibrium

Loss-of-function parkin mutations cause oxidative stress and degeneration of dopaminergic neurons in the substantia nigra. Several consequences of parkin mutations have been described; to what degree they contribute to selective neurodegeneration remains unclear. Specific factors initiating excessive reactive oxygen species production, inefficient antioxidant capacity, or a combination are elusive. Identifying key oxidative stress contributors could inform targeted therapy. The absence of parkin causes selective degeneration of a dopaminergic neuron cluster that is functionally homologous to the substantia nigra. By comparing observations in these to similar non-degenerating neurons, we may begin to understand mechanisms by which parkin loss of function causes selective degeneration. Using mitochondrially targeted redox-sensitive GFP2 fused with redox enzymes, we observed a sustained increased mitochondrial hydrogen peroxide levels in vulnerable dopaminergic neurons of parkin-null flies. Only transient increases in hydrogen peroxide were observed in similar but non-degenerating neurons. Glutathione redox equilibrium is preferentially dysregulated in vulnerable neuron mitochondria. To shed light on whether dysregulated glutathione redox equilibrium primarily contributes to oxidative stress, we supplemented food with folic acid, which can increase cysteine and glutathione levels. Folic acid improved survival, climbing, and transiently decreased hydrogen peroxide and glutathione redox equilibrium but did not mitigate whole-brain oxidative stress

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit