Causes of vancomycin dosing error; problem detection and practical solutions; a retrospective, single-center, cross-sectional study.

Vancomycindosing error and inappropriate monitoring is a common problem in hospital daily practice. In King Abdulaziz Medical City (KAMC) in Jeddah, a high percentage of abnormal vancomycin trough levels is still detected despite using the recommended dose. Therefore, the current research objective is to study the major causes of vancomycin dosing errors. This retrospective, single-center, cross-sectional study was carried out at KAMC hospital in Jeddah from January 1st until December 31st 2019. All adult patients (≥15 years) who received vancomycin and had an initial abnormal trough level at the measured steady-state were included in this study. 472 patients have met the study inclusion criteria. The current study evaluated the factors that play a role in causing vancomycin trough level abnormalities such as sampling time, vancomycin dosing, and patient's pharmacokinetic and pharmacodynamic variations. In this study, we found that pharmacokinetic and pharmacodynamic variability was attributed to 65% of vancomycin's abnormal trough level. Also, the result showed a significantly increased odds of the low trough in the non-elderly group (OR 6, 95% CI 2.48 - 14.9, P < 0.001) and febrile neutropenic patients (OR 2.21, 95% CI 1.119 - 4.365, P < 0.05). However, the odds of high trough levels were significantly elevated among patients who have CrCl < 50 ml/min (OR 5, 95% CI 1.262-20.539, P < 0.05). In addition, the present investigation revealed that the occurrence of abnormal vancomycin levels was not affected by daily duty time or working days (p > 0.05). The current study indicated that vancomycin dosing errors were common in KAMC patients; thus, there is an unmet need to evaluate the causes of vancomycin abnormal trough level and optimize a strategy that would enhance the therapeutic effectiveness and minimize the potential toxicity.

Acute Kidney Injury: Definition, Management, and Promising Therapeutic Target.

Acute kidney injury (AKI) is caused by a sudden loss of renal function, resulting in the build-up of waste products and a significant increase in mortality and morbidity. It is commonly diagnosed in critically ill patients, with its occurrence estimated at up to 50% in patients hospitalized in the intensive critical unit. Despite ongoing efforts, the death rate associated with AKI has remained high over the past half-century. Thus, it is critical to investigate novel therapy options for preventing the epidemic. Many studies have found that inflammation and Toll-like receptor-4 (TLR-4) activation have a significant role in the pathogenesis of AKI. Noteworthy, challenges in the search for efficient pharmacological therapy for AKI have arisen due to the multifaceted origin and complexity of the clinical history of people with the disease. This article focuses on kidney injury's epidemiology, risk factors, and pathophysiological processes. Specifically, it focuses on the role of TLRs especially type 4 in disease development.

Cost-efficiency analysis of conversion to biosimilar filgrastim for supportive cancer care and resultant expanded access analysis to supportive care and early-stage HER2+ breast cancer treatment in Saudi Arabia: simulation study.

AIMS: This study estimated, for Saudi Arabia, the cost-efficiency of converting patients from reference Neupogen and Neulastim to one of two filgrastim biosimilars (Nivestim, Zarzio); the budget-neutral expanded access to supportive care with biosimilar filgrastim and therapeutic care to ado-trastuzumab emtansine thus afforded; and the number-needed-to-convert (NNC) to provide supportive or therapeutic treatment to one patient. MATERIALS AND METHODS: Replicating prior studies, we modeled the cost-efficiencies gained from converting varying proportions of a hypothetical panel of 4,000 patients undergoing six cycles of cancer treatment from Neupogen or Neulastim to one of the two biosimilar G-CSF formulations, using national cost inputs. Cost-savings in USD were used to estimate the additional doses of biosimilar G-CSF and expanded access to ado-trastuzumab emtansine on a budget-neutral basis, and NNC to purchase one additional dose of supportive or therapeutic treatment. RESULTS: Savings from conversion from reference to a biosimilar filgrastim were $3,086,400 (Nivestim) and $3,460,800 (Zarzio). With reference pegfilgrastim, savings from conversion were $11,712,240 (Nivestim) and $12,086,640 (Zarzio). Biosimilar conversion from reference to biosimilar filgrastim enabled expanded access to ado-trastuzumab emtansine ranging from 61 patients (5 days, Nivestim) to 191 patients (14 days, Zarzio). For supportive care, biosimilar conversion enabled expanded access ranging from 8,244 patients (5 days, Nivestim) to 25,882 patients (14 days, Zarzio). For biosimilar conversion from daily filgrastim, the NNC for treatment with ado-trastuzumab emtansine decreased as days of injections increased [5 days: 395 (Nivestim), 352 (Zarzio); 14 days: 141(Nivestim), 126 (Zarzio)]. Alternately, for biosimilar conversion from single-injection pegfilgrastim to daily biosimilar filgrastim, the NNC for treatment with ado-trastuzumab emtansine rose as days of injections increased, being highest under the 14-day scenario (146, Nivestim; 130, Zarzio). CONCLUSION: This simulation study demonstrated significant potential cost-savings from biosimilar conversion. These savings provide budget-neutral increased access to supportive and therapeutic cancer care.

The Bayesian-Based Area under the Curve of Vancomycin by Using a Single Trough Level: An Evaluation of Accuracy and Discordance at Tertiary Care Hospital in KSA.

The AUC0-24 is the most accurate way to track the vancomycin level while the Cmin is not an accurate surrogate. Most hospitals in Saudi Arabia are under-practicing the AUC-guided vancomycin dosing and monitoring. No previous work has been conducted to evaluate such practice in the whole kingdom. The current study objective is to calculate the AUC0-24 using the Bayesian dosing software (PrecisePK), identify the probability of patients who receive the optimum dose of vancomycin, and evaluate the accuracy and precision of the Bayesian platform. This retrospective study was conducted at King Abdulaziz medical city, Jeddah. All adult patients treated with vancomycin were included. Pediatric patients, critically ill patients requiring ICU admission, patients with acute renal failure or undergoing dialysis, and febrile neutropenic patients were excluded. The AUC0-24 was predicted using the PrecisePK platform based on the Bayesian principle. The two-compartmental model by Rodvold et al. in this platform and patients' dose data were utilized to calculate the AUC0-24 and trough level. Among 342 patients included in the present study, the mean of the estimated vancomycin AUC0-24 by the posterior model of PrecisePK was 573 ± 199.6 mg, and the model had a bias of 16.8%, whereas the precision was 2.85 mg/L. The target AUC0-24 (400 to 600 mg·h/L) and measured trough (10 to 20 mg/L) were documented in 127 (37.1%) and 185 (54%), respectively. Furthermore, the result demonstrated an increase in odds of AUC0-24 > 600 mg·h/L among trough level 15-20 mg/L group (OR = 13.2, p < 0.05) as compared with trough level 10-14.9 mg/L group. In conclusion, the discordance in the AUC0-24 ratio and measured trough concentration may jeopardize patient safety, and implantation of the Bayesian approach as a workable alternative to the traditional trough method should be considered.

Altered Pharmacokinetics Parameters of Vancomycin in Patients with Hematological Malignancy with Febrile Neutropenia, a Bayesian Software Estimation.

The pharmacokinetics of vancomycin vary significantly between specific groups of patients, such as critically ill patients and patients with hematological malignancy (HM) with febrile neutropenia (FN). Recent evidence suggests that the use of the usual standard dose of antibiotics in patients with FN may not offer adequate exposure due to pharmacokinetic variability (PK). Therefore, the purpose of this study is to assess the effect of FN on AUC0-24 as a key parameter for vancomycin monitoring, as well as to determine which vancomycin PK parameters are affected by the presence of FN using Bayesian software PrecisePK in HM with FN. This study was carried out in King Abdulaziz Medical City. All adult patients who were admitted to the Princess Norah Oncology Center PNOC between 1 January and 2017 and 31 December 2020, hospitalized and received vancomycin with a steady-state trough concentration measured before the fourth dose, were included. During the trial period, 297 patients received vancomycin during their stay at the oncology center, 217 of them meeting the inclusion criteria. Pharmacokinetic parameters were estimated for the neutropenic and non-FN patients using the precise PK Bayesian platform. The result showed that there was a significant difference (p < 0.05) in vancomycin clearance Clvan, the volume of distribution at a steady-state Vdss, the volume of distribution for peripheral compartment Vdp, half-life for the elimination phase t½ß, and the first-order rate constant for the elimination process ß in FN compared to non-FN patients. Furthermore, AUC0-24 was lower for FN patients compared to non-FN patients, p < 0.05. FN has a significant effect on the PK parameters of vancomycin and AUC0-24, which may require specific consideration during the treatment initiation.

A retrospective study of cardiotoxicities induced by 5-fluouracil (5-FU) and 5-FU based chemotherapy regimens in Pakistani adult cancer patients at Shaukat Khanum Memorial Cancer Hospital & Research Center.

OBJECTIVE: To study cardiotoxicities, especially bradycardia in cancer patients treated with 5-Fluouracil and 5-Fluouracil based chemotherapy regimens in Pakistani population. METHODS: Data was extracted from the medical records of all diagnosed cancer patients at Shaukat Khanum Memorial Cancer Hospital and Research Center registered between January 2002 and December 2004 receiving 5- Fluouracil based chemotherapy regimens. The data was analysed retrospectively, including electrocardiogram and cardiac markers. Pearson's Correlation coefficient was calculated to see any possible correlation between 5-Fluouracil alone and 5-Fluouracil based regimens and cardiotoxicity, and other variables. RESULTS: Symptomatic cardiotoxicity was observed in 60 (19.93%) out of 301 patients whose cases were part of the study. Bradycardia was the most common cardiotoxicity and was observed in 36 (11.96%) patients. Nine (2.99%) mortalities were also observed. The incidence of cardiotoxicity was not significantly different between the patients with and without pre-existing cardiovascular disease (p = 0.095) and having negative correlation - 0.305. Cardiotoxicities were more common with Continuous Infusion (CI) of 5-Fluouracil, radiotherapy concurrent with 5-Fluouracil and when 5-Fluouracil was used in combination with Cisplatinum (CDDP). CONCLUSION: Cardiotoxicities were more prevalent when 5-Fluouracil was used along with concurrent radiotherapy and with Cisplatinum and when administered in continuous infusion pattern. Hence, 5-Fluouracil and 5-Fluouracil based chemotherapy regimens cause cardiotoxicities, especially bradycardia, in a significant number of cancer patients in Pakistani population.

The Overriding of Computerized Physician Order Entry (CPOE) Drug Safety Alerts Fired by the Clinical Decision Support (CDS) Tool: Evaluation of Appropriate Responses and Alert Fatigue Solutions.

Introduction Most computerized physician order entry (CPOE) software come with clinical decision-support components (CDS) that provide prescribers assistance and notify them about adverse drug reactions. An excessive number of alerts in a repeated and non-relevant manner leads to alert fatigue and enforces physicians and pharmacists to alert overrides. King Abdulaziz Medical City (KAMC) in Jeddah still reports a higher percentage of drug alerts overridden by clinicians and pharmacists. Thus, this study was conducted to evaluate CDS alerts overriding and to determine which alerts are clinically irrelevant and need modifications. Methods The study was carried out in the inpatient setting at KAMC in Jeddah, from September 1, 2020, to December 31, 2020. It was designed as a retrospective chart review study that included all red alerts that required comments and were overridden by a physician and pharmacist. Results Among 11350 red alerts, potential drug-drug interaction (pDDI), dose, and allergy alerts represent 57%, 41%, and 2%, respectively, of the total alerts. The most common drug-drug interactions (DDIs) in category X were proton pump inhibitors and clopidogrel (9.9%). The appropriate response by prescribers and pharmacists toward allergy alerts was associated with the highest odds compared with the other alerts (p < 0.05) while there is a significant decrease in the odds of appropriate action being taken by both prescribers and pharmacists in the dose screen alerts (p < 0.05). Among all clinical specialties, there is an increased odds of appropriate action being taken by residents and fellows for allergy and dose alerts, respectively, compared to other groups (p < 0.05). For diminishing the unnecessary alerts, we provided 14 alert refinements strategies and advised turning off four alerts. Applying this will terminate 32% of irrelevant alerts. Conclusion Our study's findings indicated that a substantial number of alerts are ignored, and the rate of appropriateness varies significantly by alert type and prescriber level.

Response to COVID-19 Pandemic: Managing Inpatient Pharmacy Services at King Abdulaziz Medical City - Jeddah.

Since early December 2019, the coronavirus disease 2019 (COVID-19) has been relentlessly spread worldwide and has hit the healthcare systems with terrible force. Pharmacists play a vital role in the healthcare system in providing medicines, therapeutics, vaccines, clinical services, and other pharmaceutical care services to patients. Therefore, to ensure all these services continued at King Abdulaziz Medical City - Jeddah during the COVID-19 pandemic, the Department of Pharmaceutical Care initiated a departmental crisis preparedness plan, as a part of general hospital preparedness plan. It started with adjusting medication dosing time, instituting a daily medication refill process, working remotely, expanding the use of automation, and modifying employee schedules. Other actions included the following: handling drug shortages, placing restrictions on some medications, using personal protective equipment, changing routine practices of pharmacy aides, revising the medication delivery process, starting a contingency training program, and restricting pneumatic tube operation. We took guidance from the Ministry of Health, our own institute's experience, World Health Organization recommendations, updated scientific research, and the American Society of Health-System Pharmacists regulatory updates. This article aims to describe how health services, policies, and systems were applied and adapted to address a specific problem while maintaining all pharmacy employees' safety. This article reviews the inpatient pharmacy's particular needs and responses to these needs to meet the COVID-19 pandemic challenges.

A Methodological Assessment of Pharmacist Therapeutic Intervention Documentation (TID) in a Single Tertiary Care Hospital in Jeddah, Kingdom of Saudi Arabia.

Pharmacist intervention has valuable input to the healthcare system by reducing medication errors, costs of treatment and improving therapeutic outcomes. This study aimed to analyze pharmacists' interventions during the verification of computerized physician order entry and to determine the association between prescribers' level and type of prescribing errors. In this cross-sectional, observational study, data collection was carried out over three months starting from 1 January 2020 to 31 March 2020. Included were 2405 interventions documented by 52 different pharmacists. The prevalence of prescribing order entry errors was 9.1%. The most identifiable type of intervention was incorrect dilution (40.2%) followed by dose substitution (27.7%). The drug category associated with a high percentage of interventions was perfusion solutions (41%), followed by antibacterial (35%). The number of junior physician orders that required pharmacist intervention was higher than other prescribers (45.2%), followed by specialist and senior physicians, (31.4% and 15.5%, respectively). Prescriber ordering time and types of prescribing errors were shown to have a significant (p < 0.05) association. Internal medicine physicians entered the highest percentage of prescribing errors, representing 22.7%. The current study concluded that TID has significant potential to reduce drug-related problems; TID fatigue is a real problem that might be under-reported and addressing this point in future studies would be of great value.

In vitro and in vivo biocompatibility study of polyacrylate TiO2@Ag coated nanoparticles for the radiation dose enhancement.

To enhance the efficacy of radiation therapy, functionalised core-shell nanoparticles (CS NPs) are used as a radiosensitizer. These NPs can act as a therapeutic agent and carrier for other therapeutic agents. In this study, the first poly-acrylic acid modified silver-coated titanium dioxide NPs were fabricated to evaluate the radiation dose enhancement within the human tissue equivalent polymer gel after investigating the biocompatibility. Macrophage cell line and rats model were used for in vitro and in vivo study respectively. Two different beam qualities were applied to quantify the radiation dose enhancement with different concentrations of NPs in the polymer gel. The dose enhancement factors (DEFs) indicated that these biocompatible CS NPs are more effective for the radiation dose enhancement at low energy x-rays (80 kV) as compared to the high energy gamma (1.25 MeV Co60). These results suggested that functionalised core-shell silver-coated titanium dioxide NPs have great potential as a radiosensitizer in radiation therapy.