External Validation of Obese/Critically Ill Vancomycin Population Pharmacokinetic Models in Critically Ill Patients Who Are Obese.

Obesity combined with critical illness might increase the risk of acquiring infections and hence mortality. In this patient population the pharmacokinetics of antimicrobials vary significantly, making antimicrobial dosing challenging. The objective of this study was to assess the predictive performance of published population pharmacokinetic models of vancomycin in patients who are critically ill or obese for a cohort of critically ill patients who are obese. This was a multi-center retrospective study conducted at 2 hospitals. Adult patients with a body mass index of ≥30 kg/m2 were included. PubMed was searched for published population pharmacokinetic studies in patients who were critically ill or obese. External validation was performed using Monolix software. A total of 4 models were identified in patients who were obese and 5 models were identified in patients who were critically ill. In total, 138 patients who were critically ill and obese were included, and the most accurate models for these patients were the Goti and Roberts models. In our analysis, models in patients who were critically ill outperformed models in patients who were obese. When looking at the most accurate models, both the Goti and the Roberts models had patient characteristics similar to ours in terms of age and creatinine clearance. This indicates that when selecting the proper model to apply in practice, it is important to account for all relevant variables, besides obesity.

Effectiveness, safety, and cost of vancomycin and linezolid in Kuwait: A retrospective cohort study.

Background: The effectiveness, safety, and cost of vancomycin and linezolid for managing gram-positive bacterial infections in Kuwait are unknown. This study assessed the effectiveness, safety, and cost of vancomycin, teicoplanin and linezolid for managing gram-positive bacterial infections in Kuwait. Research design and methods: This retrospective study included adult patients who were prescribed antibiotics (vancomycin, teicoplanin, and linezolid) for the treatment of gram-positive infections at five hospitals in Kuwait. Descriptive statistics were used to assess the effectiveness and safety outcomes. A cost analysis was performed on the patients hospitalised for gram-positive infections. Results: Among 116 patients, 42.2 % (n = 49) received glycopeptides (vancomycin [n = 45] and teicoplanin [n = 4]) or linezolid (n = 67). Clinical cure was achieved in 100 patients without significant intergroup differences (p = 0.34). Thrombocytopenia and acute kidney injury occurred in 19 and 20 patients (p = 0.82 and 0.96), respectively, and their incidence was similar with all the studied agents. The average cost per patient was USD 983.70. The estimated total direct medical costs were USD 894,570.6, the cost was highest for linezolid (USD 469,682.30) and vancomycin (USD 370,342.5), and lowest for teicoplanin (USD 20,799.9). Conclusions: Glycopeptides and linezolid were highly effective. Linezolid was the most frequently prescribed agent; its effectiveness and safety were similar according to the antibiotic class. However, treatment with linezolid and vancomycin were associated with considerable costs.

Population Pharmacokinetics of Topiramate in Patients with Epilepsy Using Nonparametric Modeling.

BACKGROUND: Topiramate (TPM) is used for the treatment of various epileptic seizures and the prevention of migraine. This study aimed to develop a population pharmacokinetic model and identify covariates that influence TPM behavior in patients with epilepsy in Kuwait. METHODS: Data were collected retrospectively from 108 patients (2 years old and above) with epilepsy who were treated with oral TPM and 174 TPM blood samples from 3 hospitals in Kuwait from 2009 to 2016. Data were randomly divided into 2 groups for model development and validation. The population pharmacokinetic model was built using the nonparametric modeling algorithm (Pmetrics). The model was evaluated internally through the visual predictive check method and externally using a new data set. RESULTS: A 1-compartment model with first-order elimination fitted the data well. Covariates showing a significant effect on the elimination rate constant were renal function and coadministration of carbamazepine (CBZ). The mean estimated clearance was 2.11 L/h; this was 50% higher for patients coadministered with CBZ. Age and sex were essential covariates for the volume of distribution (V). The visual predictive check of the final model could predict the measured concentrations. External validation further confirmed the favorable predictive performance of the model with low bias and imprecision for predicting the concentration in a particular population. CONCLUSIONS: TPM elimination was increased with CBZ coadministration and was affected by renal function. Meanwhile, age and sex were the main predictors for V. The predictive performance of the final model proved to be valid internally and externally.

Development and Refinement of a Matrix Competency Framework, with Associated Entrustable Professional Activities, to Support Initial Pharmacy Education in Kuwait.

The development of competency frameworks serves as the foundation for the development of competency-based education. It is vital to develop a country-specific framework to address the specific needs of the local population for pharmacy services. This study aimed to describe the development process of a competency framework for undergraduate pharmacy education in Kuwait with a unique matrix structure. The process started with the development of guiding principles for curriculum revision and implementation, as well as the identification of global educational outcomes. This process was followed by: (A) a needs assessment with key stakeholders; (B) development of the initial competency framework; and (C) refinement of the framework. Qualitative data were thematically analyzed to identify the main competency domains that students need to perform the identified entrustable professional activities (EPAs). Five population needs were identified by the needs assessment, with 17 EPAs suggested to fulfill those needs. In addition, 11 competency domains were identified. The initial competency framework was created as a 3 × 8 matrix, with 3 professional and 8 transversal competency domains. Refinement of the framework resulted in the removal of redundancies and the development of a global behavior competency profile. The development of a matrix competency framework and associated EPAs for Kuwait serves as a foundation for preparing pharmacists to fulfill local population needs and expanding the scope of practice in the country.

Practices, Knowledge, and Attitudes of Nephrologists Towards Prescribing and Monitoring Vancomycin at Dialysis Centers.

BACKGROUND: Vancomycin dosing protocols are varied in the literature for hemodialysis patients. This study sought to determine nephrologists' practices, knowledge, attitudes, and barriers toward prescribing and monitoring vancomycin at dialysis centers. METHODS: A cross-sectional and multi-center study was conducted in Kuwait using a validated self-administered questionnaire among 168 nephrologists. Descriptive and comparative analyses were performed using SPSS (version 28). RESULTS: The response rate was 75% (n = 126). Over half of nephrologists frequently prescribed a vancomycin loading dose of 1000 mg (53.2%) and a maintenance dose of 500 mg (51.6%) to all patients. Their overall median (IQR) percentage knowledge about the therapeutic monitoring of vancomycin was 66.7% (33.3) and was found to be higher in nephrologists aged ≤ 40 years and in registrars/senior registrars (p < 0.05). Their overall median (IQR) attitude score was 4.0 (1.0) [positive attitude]. Nephrologists with > 15 years of practice experience expressed higher attitudes (p < 0.05). The top two perceived barriers were a lack of clear local hospital/national guidelines (60.3%) for vancomycin dosing in dialysis and inconsistencies among different dosing references and guidelines (51.6%). CONCLUSION: Findings showed that nephrologists have varying practices, moderate knowledge, and positive attitudes toward prescribing and monitoring vancomycin and highlight the need for interventions to overcome the perceived barriers.

Transforming pharmacy practice in Kuwait.

In the last few decades, pharmacy services have expanded to fulfil the need for more complex health needs from population worldwide. Moving from 'product-centred' to a 'patient-centred' profession, pharmacists are required to master more professional competencies to deliver high quality pharmaceutical services to their patients and community. In Kuwait pharmacy practice has long been identified as a sector yet to be developed. With the announcement of the 'new Kuwait vision 2035' planning for pharmacy practice and workforce development and improvement has become imperative. Academic, professional, and regulatory bodies have collaborated to shape the future of pharmacy profession in the country. The approach described here reflects the initial steps for transforming and advancing the pharmacy profession in Kuwait.

Awareness, perception, and barriers of healthcare providers toward the revised consensus guideline for therapeutic monitoring of vancomycin.

Background: A revised consensus guideline published in 2020 recommended transitioning vancomycin monitoring to the area under the concentration-time curve over 24 h to minimum inhibitory concentration (AUC24/MIC). The decision to transition to AUC24/MIC monitoring or to continue trough-based monitoring is made at the institutional level and is influenced by several factors, including healthcare providers and system-related factors. Changing current practices is expected to be difficult, and it is important to understand healthcare providers' perceptions and potential barriers before the transition. This study assessed the awareness and perception of physicians and pharmacists toward the revised guideline and identified barriers to their implementation in Kuwait. Methods: A cross-sectional survey that employed a self-administered questionnaire was used. A random sample of physicians (n = 390), clinical microbiologists (n = 37), and clinical pharmacists (n = 48) across six Kuwaiti public hospitals were surveyed. Descriptive and comparative statistical analyses were performed. Factors associated with awareness and perceptions among the participants were identified. Results: The response rate was 85.3% (n = 431). Participants had a high (median = 75%) awareness score for the updated vancomycin guideline, as well as a positive perception (median = 5). The main factor identified to affect the awareness and perception of participants following the group analysis was the years of experience. The main barriers identified were a lack of training to perform vancomycin AUC24 calculations, a lack of accurate documentation sample time, and a long turnaround time for serum levels, which might hinder the implementation of the updated guideline. Conclusion: Physicians, clinical microbiologists, and pharmacists working in Kuwait public hospitals were aware of the 2020 vancomycin monitoring guidelines with positive perceptions. Participants agreed on the several barriers to transitioning to the AUC24/MIC approach, which should be considered by stakeholders before implementation.

Pharmacy practice in hospital settings in GCC countries: Dispensing and administration.

Purpose: To outline dispensing and administration practices in hospital pharmacy across the Gulf Cooperation Councils (GCC) countries' hospitals. Paucity of data in appraising hospital pharmacy practice in GCC regions motivated us to conduct this study. Methods: A modified survey questionnaire was prepared from the American Society of Health-System Pharmacist (ASHP) survey questions. Three major domains of questions for general characteristics of the medication use process for dispensing and administration were identified. These were, (1) medication distribution system, and medication distribution technology, (2) technology used to compound sterile preparations, compounding I.V. medication and method of compounding nutrition support preparations, (3) medication administration practices, medication orders, medication administration records (MARs), and technician activities. A list of hospitals was obtained from the Ministry of Health of the targeted GCC countries. A secure invitation link containing a survey questionnaire was sent to the participants directly. Results: Sixty-four hospitals responded to this survey. The overall response rate was 52%. Most surveyed hospitals have centralized inpatient medications distribution system (75.0%). About 37.5% of hospitals used automated dispensing cabinets (ADCs) in their patient care areas. Compounding sterile preparations in the pharmacy, barcode verification technology, workflow management technology, and robotic technology were used by 17.2%, 15.6%, and 4.7% of hospitals, respectively. In using safety technology for medication administration, almost all hospitals have partially or completely implemented an electronic health record (EHR). About 40.6% of hospitals used electronic medication administration records (e-MARs), 20.3% used bar-code-assisted medication administration (BCMA), and 35.9% used smart infusion pumps. Conclusion: The results of this survey revealed an opportunity to improve the medication use management process on dispensing and administration practices in hospitals in GCC countries.

Knowledge, Confidence, and Perception Toward Therapeutic Drug Monitoring Among Physicians and Pharmacists in Kuwait.

BACKGROUND: Therapeutic drug monitoring (TDM) helps ensure an efficient and safe therapeutic outcome. This study assessed physicians' and pharmacists' knowledge, confidence, and perception regarding clinical pharmacokinetics and TDM. METHODS: A cross-sectional survey that used a self-administered questionnaire was used. A stratified random sample of 322 physicians and pharmacists across 3 Kuwait public hospitals was surveyed. Descriptive and comparative statistical analyses were performed during data analysis. A multivariate logistic regression model was used to identify factors associated with low levels of knowledge and confidence and negative perceptions among the subjects. RESULTS: The response rate was 88%. Overall, the respondents' mean total knowledge score percentage was low (50.3%), with no significant difference between the physicians' and pharmacists' scores ( P > 0.5); 60.4% of the participants (95% confidence interval: 54.9-65.6) felt confident when using TDM in their practice. Most participants expressed positive perceptions (90.1%; 95% confidence interval: 86.3-92.9) toward TDM. There was high agreement internally that pharmacists require some knowledge of TDM, should be asked by physicians in general for recommendations on the appropriate use of TDM, and should be able to provide relevant information regarding the appropriate use of TDM. CONCLUSIONS: Physicians and pharmacists in this study had high confidence in-and the positive perceptions of-TDM and its clinical implications. The present study's findings indicate an urgent need for professional education and training in clinical pharmacokinetics and TDM and its clinical implications through continuous professional development programs and its integration within the curricula of medical and pharmacy schools.

Introduction of an Ambulatory Care Medication Reconciliation Service in Dialysis Patients: Positive Impact on Medication Prescribing and Economic Benefit.

OBJECTIVE: The aim of the study was to assess the implementation of medication reconciliation (MedRec) and medication-related costs in dialysis-dependent patients. METHODS: Completed best possible medication history and reconciliation forms were collected within 6 months from 77 patients' file at the dialysis center. Outcome measures were number and types of medication discrepancies, medication-related problems (MRPs), and their potential to cause harm, in addition to the type and number of interventions conducted during MedRec and the resulted medication costs reduction. RESULTS: The mean number of medications was 11 ± 4, which was reduced to 8 ± 3 (P < 0.0001) after MedRec. Medication discrepancies accounted for 55, and MRPs were raised by pharmacists 216 times, and 55% had the potential to cause moderate patient discomfort. Mediations were held in 1.2%, discontinued in 21.2%, and changed in 5.4%, which led to €75.665 (U.S. $85.33) and €459.93 (U.S. $511.979) reduction in medication costs per patient for 1 and 6 months, respectively. CONCLUSIONS: Several discrepancies and MRPs were identified in the present study that put patients undergoing dialysis at risk for potential harm and adverse drug events. Regularly performing ambulatory MedRec and involving pharmacists in the model of care can improve the quality of healthcare delivered to dialysis-dependent patients and reduce cost.

Pharmacy practice in hospital settings in GCC countries: Prescribing and transcribing.

PURPOSE: To outline hospital pharmacy practices across the Gulf Cooperation Councils (GCC) countries' hospitals. METHODS: A modified survey questionnaire was prepared from the original 2019 American Society of Health-System Pharmacist (ASHP) survey questions. Survey details were discussed with some pharmacy directors for clarity and relevance. A list of hospitals were obtained from the Ministry of Health of each of the targeted GCC countries. A secure invitation link containing a survey questionnaire was sent to the participants directly. RESULTS: Sixty four hospitals responded to this survey. The overall response rate was 52%. About 47% of the surveyed hospitals considered their drug formularies as closed, and strict. Additionally, only 44% of hospitals compare the effectiveness of products, when taking formulary decisions for drug inclusion. Forty-four percent of hospitals have computerized prescriber order entry (CPOE / EHR) system functionality for formulary system management. At about 39.1% hospitals, pharmacists have the responsibility for managing medication therapies, majority were engaged in providing anticoagulation therapies. About 61% of hospital pharmacies in GCC countries receive medication orders electronically, through CPOE/EHR. Majority (66%) of the hospitals in GCC countries have an active Antimicrobial Stewardship Program (ASP) while only 40% of pharmacists have a key role in providing clinical support. About 57.8% of hospital pharmacy directors reported that pharmacists do not provide ambulatory care clinical pharmacy services in their hospitals. CONCLUSION: In GCC countries' hospitals, there are major areas for improvement to patient care of which pharmacists are uniquely qualified as the medication experts to have the most meaningful outcomes in all of the domains of safe medication use, medication therapy management, antimicrobial stewardship program and participation in outpatient clinics.

Evolving to Objective Structured Clinical Exams (OSCE): Transitional experience in an undergraduate pharmacy program in Kuwait.

BACKGROUND: Objective Structured Clinical Exams (OSCEs) can assess professional competencies in a structured manner and facilitate objective evaluation of clinical performance. With limited data from the Eastern Mediterranean region, this study aims to describe the development, implementation, and evaluation of OSCEs for final year pharmacy students in Kuwait. The study also aims to compare students' performance in two academic years (2015-2016 and 2016-2017). METHODS: The design, implementation, and evaluation of the competency-based OSCE followed a 3-phase systematic evidence-based approach. The development phase involved establishing an OSCE working group to develop a blueprint and scoring rubrics and to organise assessors and standardised patient/physician training. The implementation phase involved conducting formative and summative OSCEs. The evaluation phase involved undertaking student and staff perception surveys. RESULTS: The overall students' OSCE scores for the academic years 2015-2016 and 2016-2017 were (median (interquartile range)) (71.6%, 32.2) and (60.0% (30.7)) and respectively (p < 0.0001). The average students' performance score was high in stations covering 'patient consultation and diagnosis' competency (71.4% (95% CI: 66.7-73.3)) and lower in stations covering 'monitoring of medicine therapy' competency (50.0% (95% CI: 33.3-66.7)). Students perceived stations covering 'monitoring medicines therapy' and 'assessment of medicine' as difficult. However, staff perceived stations related to 'patient consultation and diagnosis' competency as the easiest. Students reported that the OSCE was a positive experience as it provided them an opportunity to practice real life scenarios in a safe learning environment. CONCLUSION: The OSCE helped to identify the level of competency of students prior to graduation and areas to improve in the curriculum.

The impact of omeprazole on mycophenolate pharmacokinetics in kidney transplant recipients.

BACKGROUND: The absorption rates of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) may be influenced by the concomitant use of omeprazole. METHODS: One hundred kidney transplant patients were recruited during their outpatient visits, including 50 on MMF and 50 on EC-MPS. At the clinic, a predose mycophenolic acid (MPA) sample (C0) was collected; subsequently, the participants received the proton-pump inhibitor omeprazole along with either MMF or EC-MPS. Two more blood samples were collected at 1.5 and 3.5 hours and used to estimate an area under the curve (AUC) from zero to 12 hours [AUC (0-12)]. RESULTS: The mean number of months after transplant was 92 months. The median AUC (0-12) and C0 results were 62.2 mg·h/L and 2.0 mg/L for the MMF group and 71.9 mg·h/L and 1.8 mg/L for the EC-MPS group (P = 0.160 and 0.225, respectively). Interestingly, 54% of the MMF group and 62% of the EC-MPS group showed AUCs above the target values. The correlation between MPA C0 and the predicted AUC was poor in both groups. CONCLUSION: Omeprazole can be safely co-administered with either MMF or EC-MPS, as it did not compromise the MPA exposure. Unexpectedly, however, a high percentage of patients presented MPA AUCs exceeding the target value, highlighting the importance of periodically assessing MPA level.

Monitoring Tacrolimus Trough Concentrations During the First Year After Kidney Transplantation: A National Retrospective Cohort Study.

Background: There is a lack of data in the literature on the evaluation of tacrolimus (TAC) dosage regimen and monitoring after kidney transplantation (KT) in Kuwait. The aim of the present study was to evaluate TAC dosing in relation to the hospital protocol, the achievement of target TAC trough concentration (C0), the prevalence of TAC side effects (SEs), namely, posttransplant diabetes mellitus (PTDM), denovo hypertension (HTN), and dyslipidemia, and factors associated with the occurrence of these SEs among KT recipients. Methods: A retrospective study was conducted among 298 KT recipients receiving TAC during the first year of PT. Descriptive and multivariate logistic regression analyses were used. Results: The initial TAC dosing as per the local hospital protocol was prescribed for 28.2% of patients. The proportion of patients who had C0 levels within the target range increased from 31.5 to 60.3% during week 1 through week 52. Among patients who did not have HTN, DM, or dyslipidemia before using TAC, 78.6, 35.2, and 51.9% of them were prescribed antihypertensive, antidiabetic, and antilipidemic medications during the follow-up period. Age of ≥40 years was significantly associated with the development of de novo HTN, dyslipidemia, and PTDM (p < 0.05). High TAC trough concentration/daily dose (C0/D) ratio was significantly associated with the development of PTDM (p < 0.05). Conclusion: Less than two-fifths of patients achieved target TAC C0 levels during the first month of PT. Side effects were more common in older patients. These findings warrant efforts to implement targeted multifaceted interventions to improve TAC prescribing and monitoring after KT.

Saudi lung cancer prevention and screening guidelines.

BACKGROUND: While lung cancer is the leading cancer cause of death, it is largely preventable. Furthermore, early diagnosis enhances the chance of cure. Therefore, we developed guidelines for lung cancer prevention and early detection. METHODS: A multidisciplinary team of experts in lung cancer representing different health-care sectors was assembled based on the National Cancer Center request and in coordination with the Saudi Lung Cancer Association of Saudi Thoracic Society. The team reviewed various reliable international guidelines and the data and experience in the Kingdom and formulated guidelines that address the primary and secondary prevention approaches in lung cancer, including tobacco control, early diagnosis, and lung cancer screening. RESULTS: The team developed guidelines to assist healthcare professionals in the Kingdom manage the different aspects of lung cancer prevention. Primary prevention through tobacco control: the recommendations encourage all healthcare professionals in all practice settings to screen their patients for smoking and to provide counseling and if needed referral to smoking cessation programs for current smokers. For early diagnosis of patients with symptoms suspicions of lung cancer, it is expected standard of care to investigate, work up, and refer the patients appropriately. Mass screening of patients at high risk for developing lung cancer: the recommendations listed the program requirements, eligible patients, and algorithm to manage findings. However, the team does not recommend that national screening program be mandated or implemented for lung cancer at this stage until more data and studies provide stronger evidence to justify adopting a national program. CONCLUSIONS: Physicians can play an important role in preventing lung cancer by tobacco control and also detect lung cancer at earlier presentation. However, national mass screening programs require further study.

Influence of multiple courses of therapy on aminoglycoside clearance in adult patients with cystic fibrosis.

OBJECTIVES: To investigate factors affecting aminoglycoside clearance in adult patients with cystic fibrosis who received multiple courses of antibiotic therapy over a period of up to 15 years. METHODS: Aminoglycoside concentration-time data and relevant clinical characteristics were collated from clinical pharmacokinetic databases established in Glasgow, Scotland and The Hague, The Netherlands. Data from Glasgow (1993-2009) were used for population model development; data from The Hague (2002-11) were used for model validation. NONMEM was used to determine structural and covariate models, with a particular focus on between-occasion variability and changes in aminoglycoside handling over multiple courses of therapy. RESULTS: The Glasgow dataset comprised 1075 courses of aminoglycoside therapy (96% tobramycin and 4% gentamicin) in 166 patients and included 2238 concentration measurements. The data were best described by a two-compartment model with creatinine clearance and height influencing aminoglycoside clearance, and height influencing volume of distribution. Between-subject and between-occasion variabilities in clearance were low, at 18% and 11%, respectively; between-subject variability was 12% for volume of distribution. Internal and external model validations were satisfactory. Multiple courses of therapy (ranging from 2 to 28 courses per patient) were not associated with any systematic changes in aminoglycoside clearance. CONCLUSIONS: Height was a better descriptor of aminoglycoside pharmacokinetics than weight in adult patients with cystic fibrosis. No changes in clearance were observed over time, even in patients who had received multiple courses of therapy over several years.