Improvement in Medication Adherence after Pharmacist Intervention Is Associated with Favorable Clinical Outcomes in Patients with Ulcerative Colitis.

Background/Aims: Although pharmacist intervention for patients with chronic diseases has been shown to improve medication adherence, few studies have evaluated its effects on the objective clinical outcomes. We investigated the impact of pharmacist intervention on medication adherence and clinical outcomes in patients with ulcerative colitis (UC). Methods: Patients with UC and low medication adherence were divided into two groups, based on pharmacist intervention. Their medication possession ratio and nonadherence rate for 6 months before and after the baseline were investigated. The partial Mayo score, flare-up incidence, and factors influencing flare-up events for 1 year after the baseline were analyzed. Results: Of 99 patients, 33 and 66 were included in the intervention and control groups, respectively. The nonadherence rate significantly declined in the intervention group 6 months after the baseline (60.6% before vs 30.3% after; p=0.013). The groups showed a significant difference regarding time-related partial Mayo scores (p=0.002). Intervention was significantly negatively correlated with time and the partial Mayo score (r2=0.035, p=0.013). A significant difference was observed in the flare-up incidence (33.3% in the intervention group vs 54.6% in the control group; p=0.046). Multivariate logistic regression indicated that pharmacist intervention (adjusted odds ratio, 0.370; 95% confidence interval, 0.145 to 0.945; p=0.038) independently reduced the flareup risk. Conclusions: Pharmacist intervention significantly decreased the nonadherence rate, improved the partial Mayo score, and reduced the flare-up incidence compared with the control group in a cohort of UC patients identified to have low medication adherence.

Broad-Spectrum Antibiotic Regimen Affects Survival in Patients Receiving Nivolumab for Non-Small Cell Lung Cancer.

Antibiotic-induced dysbiosis may affect the efficacy of immune checkpoint inhibitors. We investigated the impact of antibiotics on the clinical outcomes of nivolumab in patients with non-small cell lung cancer (NSCLC). Patients who received nivolumab for NSCLC between July 2015 and June 2018 and who were followed up until June 2020 were included in a retrospective cohort analysis. Of 140 eligible patients, 70 were on antibiotics. Overall survival (OS) was shorter in patients on antibiotics (ABX) compared to those not on antibiotics (NoABX) (p = 0.014). OS was negatively associated with piperacillin/tazobactam (PTZ) (HR = 3.31, 95% CI: 1.77-6.18), days of therapy (DOT) ≥ 2 weeks (HR = 2.56, 95% CI: 1.30-5.22) and DOT of PTZ. The defined daily dose (DDD) in PTZ (r = 0.27) and glycopeptides (r = 0.21) showed weak correlations with mortality. There was no difference in progression-free survival (PFS) between ABX and NoABX; however, PFS was negatively associated with the antibiotic class PTZ and DOT of PTZ. Therefore, the use of a broad-spectrum antibiotic, such as PTZ, the long-term use of antibiotics more than 2 weeks in total and the large amount of defined daily dose of specific antibiotics were associated with decreased survival in patients receiving nivolumab for NSCLC.

Differences in Colistin Administration and Bacterial and Treatment Outcomes in Critically Ill Patients.

The desired target steady-state average colistin concentration (Css,avg) to balance between therapeutic effectiveness and nephrotoxicity is largely unclear. The objective of this study was to evaluate the effect of the desired target colistin Css,avg on the effectiveness and safety of IV colistin therapy in critically ill patients. Overall, 153 critically ill patients (71% males) receiving IV colistin were retrospectively analyzed. The desired target colistin Css,avg was estimated based on the daily colistin dose and creatinine clearance of each patient. No significant predictor for clinical cure was identified. However, microbiological outcome was significantly associated with pneumonia compared to bacteremia (odds ratio [OR] 0.092, 95% confidence interval [CI] [0.033-0.251], P < 0.001) and the use of IV colistin loading dose (OR 2.783, 95% CI [1.126-6.880], P = 0.027). Colistin-associated nephrotoxicity was significantly less likely to occur in patients who received inhaled colistin close to the time of IV colistin therapy (OR 0.331, CI [0.119-0.925], P = 0.035). The desired target Css,avg of colistin was not associated with treatment outcomes or the risk of nephrotoxicity. Loading dose and inhaled colistin use near the time of IV colistin therapy may be considered to maximize therapeutic effectiveness and minimize the risk of colistin-associated nephrotoxicity, respectively.

Interprofessional Collaboration Between a Multidisciplinary Palliative Care Team and the Team Pharmacist on Pain Management.

PURPOSE: The purpose of the study was to evaluate the impact on pain management by multidisciplinary palliative care team (mPCT) and the team pharmacist. METHODS: Patients who were admitted to palliative care unit (PCU) for at least 7 days between April 2014 and December 2015 were included. The mPCT consisted of a physician, a pharmacist, nurses, and non-clinical support staff. The team was on charge of pain management of patients who were admitted to PCU. Pain intensity was assessed at 3 time points in each patient; 1 week before PCU admission (day -7), on the day of admission (day 0), and 1 week after admission (day 7) using 0 to 10 numerical rating scale (NRS). Analgesic use was evaluated with 6 categories based on National Comprehensive Cancer Network and Korean pain management guidelines. Pain intensity and analgesic use appropriateness were compared at day -7, day 0, and day 7 for the patients who were admitted to the PCU. RESULTS: Pain intensity decreased significantly on day 7 of PCU admission compared to it on day 0 (NRS: 4.05 vs 2.66, P < .001). A significant negative correlation was found between pain intensity and the proper use of analgesics ( r = -0.407; P < .001, r = -0.309; P = .001, r = -0.241; P = .009, on day -7, day 0, day 7, respectively). CONCLUSION: The mPCT contributed to the reduction of inappropriate use of analgesics and improved pain control. Pharmacist intervention appeared to have improved pain control in patients under palliative care. Each team member's role should be individualized and developed further.

Risk factors of colistin safety according to administration routes: Intravenous and aerosolized colistin.

BACKGROUND: Nephrotoxicity of intravenous (IV) colistin has impeded its clinical use; aerosolized (AS) colistin may be an alternative, but safety data are lacking. Therefore, this study aimed to evaluate the incidence of acute kidney injury (AKI) and risk factors associated with IV and AS colistin administration. METHODS: A retrospective study was performed in a tertiary referral hospital. Data were collected before and after colistin administration between October 2012 and April 2016. Exclusion criteria were as follows: age less than 18 years, previous colistin administration, concurrent use of IV and AS colistin, dialysis before colistin use, and colistin use for less than 3 days. We compared AKI incidence following administration of IV versus AS colistin and analyzed risk factors for colistin-associated nephrotoxicity. RESULTS: A total of 464 patients were enrolled (n = 311, IV group; n = 153, AS group). Incidence of AKI was significantly higher in the IV group (IV vs AS, 20.26% vs 7.84%, p-value < 0.001). Duration of colistin use (OR 1.033, 95% CI 1.009-1.058, p-value 0.008) and presence of chronic kidney disease (OR 2.710, 95% CI 1.348-5.448, p-value 0.005) were associated with nephrotoxicity. There were no significant risk factors associated with AS colistin. CONCLUSIONS: Although AS colistin was not associated with any significant risk factors for nephrotoxicity, duration of colistin use and baseline kidney function may affect AS colistin-associated nephrotoxicity.

Dose Optimization Based on Population Pharmacokinetic Modeling of High-Dose Cyclosporine, a P-glycoprotein Inhibitor, in Combination with Systemic Chemotherapy in Pediatric Patients with Retinoblastoma.

PURPOSE: Retinoblastoma is a childhood malignancy of the retina. To increase the exposures of systemic chemotherapy, high-dose cyclosporine, as a P-glycoprotein modulating agent, has been combined with a standard chemotherapy. However, the effective and safe dose of cyclosporine has not been well evaluated. This study is to optimize cyclosporine dose using population pharmacokinetic modeling. METHODS: Clinical data were obtained from 161 systemic chemotherapy cycles of 34 pediatric retinoblastoma patients between December 2006 and April 2015. Total 15 scenarios were simulated by 5 different doses (12, 14, 15, 17, and 20 mg/kg) of cyclosporine in 3 different weight groups (5-10, 10-15, and 15-20 kg). Numerical success ratio was obtained after assessing the simulated target cyclosporine concentration in the range of 2,000-2,500 ng/mL using NONMEM version 7.3 software. RESULTS: A final model was built based on a 1-compartment model with weight-normalized allometric scaling to minimize the variability of pediatric size. In simulations, numeric success ratio with 15 mg/kg/day and the above were higher than that of traditional doses in all of the scenario groups. No significant adverse responses were reported. Conclusion and Relevance: High-dose cyclosporine regimen as a P-gp modulator is required to improve the efficacy of systemic chemotherapy with caution in pediatric patients with retinoblastoma. Clearance, volume of distribution, and body weight are important parameters to consider in selecting adequate dosing regimen.