Generic Substitutions and Therapeutic Interchanges in Hospital Pharmacies: A Qualitative Study from Western Saudi Arabia.

Background: The aim of the present study was to understand hospital pharmacists' views and practices regarding generic substitution and therapeutic interchange. Method: This was a qualitative study involving pharmacists from three Western Saudi governorates: Taif, Makkah, and Jeddah. It included respondents from the Ministry of Health (MoH), military and private hospitals. Pharmacists were selected using a convenient sampling technique and data were collected using a structured face-to-face interview. Results: Fifty-seven pharmacists agreed to participate in this study. In MoH and private hospitals, generic substitution is a pharmacist-initiated act, while therapeutic interchange requires physician approval. Medication unavailability, side effects, patient characteristics, outcomes, and economic status justified most substitution decisions. In military hospitals, both types of substitutions are controlled by an auto-switch policy and physicians should be informed. In all hospitals, there are policies regulating substitution. Medications eligible for interchange mentioned by pharmacists from different hospitals were comparable to some extent. Pharmacists from the private sector considered substitution a supportive economic measure for both hospitals and patients. Most pharmacists highlighted that patient convenience and physician approval are the most challenging situations in substitution practice. Conclusions: An enhanced understanding of substitution and knowledge about medications included in the hospital formulary will be valuable support to the implementation of substitution practice which responds to the patients' needs to improve their outcomes.

Impact of Ursodeoxycholic Acid in Critically Ill Patients With Sepsis: A Retrospective Study.

Background: Using ursodeoxycholic acid (UDCA) in critically ill patients as adjunctive therapy for sepsis/septic shock in neonates and children is controversial, while it has not been extensively investigated in adults. This study aims to assess the effect of UDCA use on the early resolution of sepsis/septic shock in critically ill adult patients. Method: A retrospective study of critically ill adult patients in the intensive care unit (ICU) admitted with sepsis/septic shock at King Abdulaziz Medical City. Based on their usage of UDCA, patients were categorized into two groups. A total of 88 patients were included for analysis after matching, based on severity of illness scores within 24-hours of ICU admission. The primary outcome was to assess the effect of UDCA on the severity and resolution of shock at day three of ICU admission. The secondary outcomes were 30-day in-hospital mortality, mechanical ventilation (MV) duration, and ICU length of stay (LOS). Results: Out of the 88 patients matched, 44 patients (50%) received UDCA during the study period. Using UDCA was neither associated with improvement in Sequential Organ Failure Assessment (SOFA) score (p-value: 0.32), inotropes/vasopressors requirement (p-value: 0.79), Glasgow Coma Scale (GCS) (p-value: 0.59) nor total bilirubin levels (p-value: 0.79) at day three compared with the control. There was a significant association between using UDCA and improvement in PaO2/FiO2 ratio (p-value: 0.01) and early extubation at day three (p-value: 0.04). Conclusion: Using UDCA in critically ill patients with sepsis/septic shock was not associated with improvement in shock severity and resolution. However, patients who received UDCA were more likely to be extubated and not require MV on day three of ICU admission.

The impact of HMG-CoA reductase inhibitors use on the clinical outcomes in critically ill patients with COVID-19: A multicenter, cohort study.

Background: The cardiovascular complications of Coronavirus Disease 2019 (COVID-19) may be attributed to the hyperinflammatory state leading to increased mortality in patients with COVID-19. HMG-CoA Reductase Inhibitors (statins) are known to have pleiotropic and anti-inflammatory effects and may have antiviral activity along with their cholesterol-lowering activity. Thus, statin therapy is potentially a potent adjuvant therapy in COVID-19 infection. This study investigated the impact of statin use on the clinical outcome of critically ill patients with COVID-19. Methods: A multicenter, retrospective cohort study of all adult critically ill patients with confirmed COVID-19 who were admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on the statin use during ICU stay and were matched with a propensity score based on patient's age and admission APACHE II and SOFA scores. The primary endpoint was in-hospital mortality, while 30 day mortality, ventilator-free days (VFDs) at 30 days, and ICU complications were secondary endpoints. Results: A total of 1,049 patients were eligible; 502 patients were included after propensity score matching (1:1 ratio). The in-hospital mortality [hazard ratio 0.69 (95% CI 0.54, 0.89), P = 0.004] and 30-day mortality [hazard ratio 0.75 (95% CI 0.58, 0.98), P = 0.03] were significantly lower in patients who received statin therapy on multivariable cox proportional hazards regression analysis. Moreover, patients who received statin therapy had lower odds of hospital-acquired pneumonia [OR 0.48 (95% CI 0.32, 0.69), P < 0.001], lower levels of inflammatory markers on follow-up, and no increased risk of liver injury. Conclusion: The use of statin therapy during ICU stay in critically ill patients with COVID-19 may have a beneficial role and survival benefit with a good safety profile.

The potential role of adjunctive ascorbic acid in the prevention of colistin-induced nephrotoxicity in critically ill patients: A retrospective study.

Background: Colistin is considered a valuable and last-resort therapeutic option for MDR gram-negative bacteria. Nephrotoxicity is the most clinically pertinent adverse effect of colistin. Vivo studies suggest that administering oxidative stress-reducing agents, such as ascorbic acid, is a promising strategy to overcome colistin-induced nephrotoxicity (CIN). However, limited clinical data explores the potential benefit of adjunctive ascorbic acid therapy for preventing CIN. Therefore, this study aims to assess the potential nephroprotective role of ascorbic acid as adjunctive therapy against CIN in critically ill patients. Method: This was a retrospective cohort study at King Abdulaziz Medical City (KAMC) for all critically ill adult patients who received IV colistin. Eligible patients were classified into two groups based on the ascorbic acid use as concomitant therapy within three days of colistin initiation. The primary outcome was CIN odds after colistin initiation, while the secondary outcomes were 30-day mortality, in-hospital mortality, ICU, and hospital LOS. Propensity score (PS) matching was used (1:1 ratio) based on the patient's age, SOFA score, and serum creatinine. Results: A total of 451 patients were screened for eligibility; 90 patients were included after propensity score matching based on the selected criteria. The odds of developing CIN after colistin initiation were similar between patients who received ascorbic acid (AA) as adjunctive therapy compared to patients who did not (OR (95 %CI): 0.83 (0.33, 2.10), p-value = 0.68). In addition, the 30-day mortality, in-hospital mortality, ICU, and hospital LOS were similar between the two groups. Conclusion: Adjunctive use of Ascorbic acid during colistin therapy was not associated with lower odds of CIN. Further studies with a larger sample size are required to confirm these findings.

Evaluation of zinc sulfate as an adjunctive therapy in COVID-19 critically ill patients: a two center propensity-score matched study.

BACKGROUND: Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The role of zinc in critically ill patients with COVID-19 remains unclear. This study aims to evaluate the efficacy and safety of zinc sulfate as adjunctive therapy in critically ill patients with COVID-19. METHODS: Patients aged ≥ 18 years with COVID-19 who were admitted to the intensive care unit (ICU) in two tertiary hospitals in Saudi Arabia were retrospectively assessed for zinc use from March 1, 2020 until March 31, 2021. After propensity score matching (1:1 ratio) based on the selected criteria, we assessed the association of zinc used as adjunctive therapy with the 30-day mortality. Secondary outcomes included the in-hospital mortality, ventilator free days, ICU length of stay (LOS), hospital LOS, and complication (s) during ICU stay. RESULTS: A total of 164 patients were included, 82 patients received zinc. Patients who received zinc sulfate as adjunctive therapy have a lower 30-day mortality (HR 0.52, CI 0.29, 0.92; p = 0.03). On the other hand, the in-hospital mortality was not statistically significant between the two groups (HR 0.64, CI 0.37-1.10; p = 0.11). Zinc sulfate use was associated with a lower odds of acute kidney injury development during ICU stay (OR 0.46 CI 0.19-1.06; p = 0.07); however, it did not reach statistical significance. CONCLUSION: The use of zinc sulfate as an additional treatment in critically ill COVID-19 patients may improve survival. Furthermore, zinc supplementation may have a protective effect on the kidneys.

Single versus multiple doses of Tocilizumab in critically ill patients with coronavirus disease 2019 (COVID-19): A two-center, retrospective cohort study.

PURPOSE: To evaluate the effectiveness and safety of the optimal tocilizumab dosing regimen. METHODS: A two-center, retrospective cohort study, for COVID19 critically ill patients admitted to the intensive care units (ICUs). We included critically ill patients aged 18 years or older who received tocilizumab during ICU stay. Patients were divided into two groups based on the number of the received tocilizumab doses. The primary outcome was the in-hospital and 30-day mortality. Propensity score (PS) matching was used (1:1 ratio) based on the selected criteria. RESULTS: A total of 298 patients were included in the study; 70.4% (210 patients) received a single dose of tocilizumab. After adjusting for possible confounders, the 30-day mortality (HR 0.79 95% CI 0.43-1.45 P = 0.44) and in-hospital mortality (HR 0.81; 95% CI 0.46-1.49; P = 0.53) were not significantly different between the two groups. On the flip side, patients who received multiple doses had higher pneumonia odds than a single dose (OR 3.81; 95% CI 1.79-8.12 P = 0.0005). CONCLUSION: Repeating tocilizumab doses were not associated with a mortality benefit in COVID-19 critically ill patients, but it was associated with higher odds of pneumonia compared to a single dose.