Adjuvant anti-PD1 immunotherapy of resected skin melanoma: an example of non-personalized medicine with no overall survival benefit.

Randomized clinical trials demonstrated a recurrence-free survival benefit with adjuvant anti-programmed death-1 (anti-PD1) inhibitors of resected stage IIB-IV melanoma. However, no improvement in overall survival has been observed thus far. Furthermore, there are no predictive markers for immunotherapy response in melanoma, therefore adjuvant treatment is offered to all comers based exclusively on the pathological and clinical stages. Additionally, one year of treatment duration and the risk of chronic immune-related adverse effects may negatively impact patients´ quality of life. In this review, we will try to answer whether the currently available data on adjuvant anti-PD1 therapy of stage IIB-IV resected melanoma is sufficient to make this strategy available to all patients. We will also discuss the economic impact of this therapy on healthcare system budgets. Recent studies suggest that the high cost of cancer drugs may affect access to these agents globally by raising questions of sustainability for patients and society.

Impact of intermediate to high doses of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation.

INTRODUCTION: In addition to respiratory support needs, patients' characteristics to guide indication or timing of corticosteroid treatment in COVID-19 patients are not completely established. This study aimed to evaluate the impact of methylprednisolone on mortality rate in patients with COVID-19 pneumonia-induced severe systemic inflammation (PI-SSI). METHODS: Between 9 March and 5 May 2020 (final follow-up on 2 July 2020), a retrospective cohort study was conducted in hospitalised patients with COVID-19 PI-SSI (≥2 inflammatory biomarkers [IBs]: temperature ≥38℃, lymphocyte ≤800 cell/µL, C-reactive protein ≥100 mg/L, lactate dehydrogenase ≥300 units/L, ferritin ≥1000 mcg/L, D-dimer ≥500 ng/mL). Patients received 0.5-1.0 mg/kg of methylprednisolone for 5-10 days or standard of care. The primary outcome was 28-day all-cause mortality. Secondary outcomes included ≥2 points improvement on a 7-item WHO-scale (Day 14), transfer to intensive care unit (ICU) (Day 28) and adverse effects. Kaplan-Meier method and Cox proportional hazard regression were implemented to analyse the time to event outcomes. RESULTS: A total of 142 patients (corticosteroid group n = 72, control group n = 70) were included. A significant reduction in 28-day all-cause mortality was shown with methylprednisolone in patients with respiratory support (HR: 0.15; 95% CI 0.03-0.71), with ≥3 (HR: 0.17; 95% CI 0.05-0.61) or ≥4 altered IB (HR: 0.15; 95% CI 0.04-0.54) and in patients with both respiratory support and ≥3 (HR: 0.11; 95% CI 0.02-0.53] or ≥4 altered IB (HR: 0.14; 95% CI 0.04-0.51). No significant differences were found in secondary outcomes. CONCLUSION: Intermediate to high doses of methylprednisolone, initiated between 5 and 12 days after symptom onset, was associated with a significant reduction in 28-day all-cause mortality in patients with COVID-19 pneumonia and ≥3 o ≥ 4 altered IB, independently of the need of respiratory support.

Patient and health professional satisfaction with an interdisciplinary patient safety program.

Background Measuring humanistic outcomes is an important component of valuating healthcare services. There is a paucity of data on satisfaction with pharmacist implemented clinical services in long-term care settings. Objective To evaluate patient and health professional (HP) satisfaction with an interdisciplinary patient safety program performed in elderly patients with polypharmacy admitted to a long-term care hospital (LTCH). Method An interventional, longitudinal, prospective study was conducted in a Spanish LTCH. Pharmacist conducted the pharmacotherapy follow-up (reconciliation, pharmacotherapeutic optimization and educational interviews). Two satisfaction surveys were designed on a 10-point Likert-type scale. The patient survey was administered at discharge. The HP survey included the following dimensions: knowledge and program importance, pharmacist skills and pharmacist contributions to the interdisciplinary team. A reliability analysis was performed. Results 123 surveys were completed and returned; 74 patient surveys (response rate 97.4%) and 49 HP surveys (response rate 98.0%). The overall mean score of the patient survey was 9.46 ± 0.87, resulting in 82.4% very satisfied and 17.6% satisfied. The overall mean score of the HP survey was 8.85 ± 1.42, resulting in 65.3% very satisfied and 30.6% satisfied. Conclusion Elderly patients with polypharmacy and HPs reported high levels of satisfaction with the interdisciplinary patient safety program implemented in an LTCH. This positive response supports the value of pharmacists for managing older high-risk populations.

Improvement on prescribing appropriateness after implementing an interdisciplinary pharmacotherapy quality programme in a long-term care hospital.

OBJECTIVES: To determine the prevalence of inappropriate prescribing in elderly patients with polypharmacy admitted to a long-term care hospital (LTCH) and to evaluate the impact of an interdisciplinary pharmacotherapy quality programme on improvement of prescribing appropriateness. METHODS: An interventional, longitudinal, prospective study was conducted in a Spanish LTCH (October 2013 to July 2014) including 162 elderly (≥70 years) patients with polypharmacy (≥5 medications). Pharmacists conducted the pharmacotherapy follow-up of patients with medication reconciliation, pharmacotherapeutic optimisation and educational interviews from admission to discharge. Reconciliation errors, potentially inappropriate medications (PIMs), potentially prescribing omissions (PPOs) and significant drug interactions rates were calculated. The impact of the programme was evaluated considering the difference between the inappropriateness score per patient (total number of reconciliation errors, PIMs, PPOs and significant drug interactions) before and after implementing pharmacotherapy recommendations. RESULTS: At admission, 163 reconciliation errors (median(range), 1(1-6)) in 92 (56.8%) patients (65.6% drug omissions), 335 PIMs (2(1-6)) in 147 (90.7%) patients (39.3% use ≥2 anticholinergic drugs), 43 PPOs (1(1-3)) in 32 (19.8%) patients (48.5% statin omission) and 594 significant drug interactions (4(1-19)) in 130 (80.2%) patients were detected. After implementing pharmacotherapy recommendations, statistically significant reductions in admission reconciliation errors (8.3% to 0.1%), PIMs (17.0% to 12.2%), PPOs (2.2% to 0.7%) and significant drug interactions (30.2% to 26.8%) rates were found. The programme achieved a 31% improvement in prescribing appropriateness, with a statistically significant reduction in the inappropriateness score (6(IQR:4-9) to 4(IQR:2-7)). CONCLUSION: Reconciliation errors, PIMs and drug interactions are highly prevalent in elderly patients with polypharmacy admitted to an LTCH. This interdisciplinary pharmacotherapy quality programme seems to be a useful approach in the improvement of prescribing appropriateness in a high-risk older population.

Clinical impact of an interdisciplinary patient safety program for managing drug-related problems in a long-term care hospital.

Background Medication reviews intended to identify drug-related problems (DRPs) have been researched in primary care, acute care and nursing homes rather than in long-term care hospitals (LTCHs). Objectives To assess the clinical impact of an interdisciplinary pharmacotherapy quality improvement and patient safety program in elderly patients with polypharmacy admitted to an LTCH. Setting An interventional, longitudinal, prospective study was conducted in a Spanish LTCH Method A total of 162 elderly (≥ 70 years) patients with polypharmacy (≥ 5 medications) were included. Pharmacist conducted the pharmacotherapy follow-up of patients (reconciliation, pharmacotherapeutic optimization, educational interviews) from admission to discharge. Demographic, clinical and treatment-related variables were recorded. Main outcome measured Clinical impact of the program by DRP-based effectiveness and drug-related morbidity (DRM)-based safety indicators. Results 895 DRPs (median of 5 (1-23)) were identified in 153 (94.4%) patients. The most common DRPs were unnecessary drug (25.3%), dosage too high (24.9%) and a need for additional drug (24.8%). The most frequent pharmacotherapy recommendations were individualizing the dosage regimen (29.6%) and stopping (27.3%) or starting (21.9%) a drug. The mean implementation rate of pharmacotherapy recommendations was 90.9%. The effectiveness indicator revealed a 94.9% of prevented or resolved DRPs. The safety indicator showed an 89.3% of prevented or resolved DRM. Therefore, the program prevented or resolved 92.5% of adverse effects and 91.7% of suboptimal responses or therapeutic failures. Conclusion This interdisciplinary patient safety program seems to be a valuable approach to identify, prevent and resolve the high number of DRPs and potential DRM that elderly patients with polypharmacy admitted to an LTCH present.

Comparative cost-effectiveness of bevacizumab-irinotecan-fluorouracil versus irinotecan-fluorouracil in first-line metastatic colorectal cancer.

PURPOSE: To evaluate the cost-effectiveness of the addition of bevacizumab to the irinotecan-fluorouracil (Douillard regimen-CPT-FUFA-) in first-line treatment of metastatic colorectal cancer in a single-institution population. METHODS: Controlled, nonrandomized retrospective observational study. Treatment-naïve metastatic colorectal cancer patients received CPT-FUFA (January 2000-December 2003; control group) and bevacizumab_CPT-FUFA (January 2007-December 2010; study group). Variables related to: patient, clinical response (number of disease progression or death events, progression-free survival) and treatment (antineoplastic dose reduction, incremental cost/treated patient associated with the addition of bevacizumab). STATISTICAL ANALYSIS: median progression-free survival (Kaplan-Meier method), and hazard ratio (Cox regression). Survival curves were compared (Mantel-Haenszel test). RESULTS: In all, 69 patients were included: 32 (57.2 years -95%CI: 54.0-60.5-, 65.6% men) in CPT-FUFA group and 37 (68.1 years - 95%CI: 65.5-70.7-, 78.4% men) in bevacizumab_CPT-FUFA group. The disease progression or death events were 29 (90.6%) in CPT-FUFA group and 34 (91.9%) in bevacizumab_CPT-FUFA group. Median progression-free survival was 10.1 months (95%CI: 7.1-12.2) in CPT-FUFA and 11.0 months (95%CI: 7.6-12.6) in bevacizumab_CPT-FUFA (hazard ratio = 1.22; 95%CI: 0.7-2.1). Dose reductions: irinotecan and fluorouracil 11% (range: 4-20) in 5/32 (15.6%) CPT-FUFA patients and 25% (range: 8-35) in 18/37 (48.6%) bevacizumab_CPT-FUFA patients; Bevacizumab 30% (range: 4-50) in 20/37 (54.1%) bevacizumab_CPT-FUFA patients. The incremental cost associated with the addition of bevacizumab was 12,696.5 (IC95%:10,860.8-14,532.1) euros/patient. CONCLUSION: The addition of bevacizumab to the irinotecan-fluorouracil regimen, does not improve progression-free survival in our study population but increases costs per treated patient. These results potentially compromise the cost-effectiveness of the Bevacizumab_CPT-FUFA regimen.