Limited Sampling Strategy Using End of Infusion and Six-Hour Concentrations Overestimates Intravenous Busulfan Clearance Compared With Standard Six-Point Sampling in Hematopoietic Stem Cell Transplant Patients.

BACKGROUND: Therapeutic drug monitoring for busulfan (Bu) is important to improve outcomes of hematopoietic stem cell transplantation. However, standard therapeutic drug monitoring requires multiple samples and is inconvenient, labor-intensive, and costly. Accordingly, a limited sampling strategy (LSS) was evaluated, using 2-point sampling at end of infusion and at 6 hours, and the area-under-the-curve and Bu clearances (CLs) were compared with the results obtained from the standard sampling strategy (SSS) using 5-6 samples. METHOD: The analysis was based on retrospective clinical data from 202 patients receiving intravenous Bu before hematopoietic stem cell transplantation for malignant or nonmalignant conditions. Bu plasma concentrations were measured via liquid chromatography tandem-mass spectrometry, and pharmacokinetic parameters were calculated using the PKCNA package in R program. RESULT: A total of 502 doses were analyzed by applying SSS and LSS. Using the modified Bland-Altman plot, the mean percentage difference in CL between the SSS and LSS estimates of Bu 6-hourly regimen was -41% (Limits: -53% and -30%). In the once daily regimen, the mean difference in CL between the 2 strategies on the modified Bland-Altman plot was -22% (Limits: -66% and +22%). CONCLUSIONS: The Bu CL values estimated based on the BU concentration at end of infusion and at 6 hours postinfusion were significantly higher than the values obtained via the SSS.

Impact of Glutathione S-Transferase Polymorphisms on Busulfan Pharmacokinetics and Outcomes of Hematopoietic Stem Cell Transplantation.

BACKGROUND: Busulfan (Bu) is an alkylating drug used in many preparative regimens before hematopoietic stem cell transplantation (HSCT). It is conjugated in the liver mainly by glutathione S-transferase isoenzyme A1-1 ( GSTA1 ). Genetic polymorphisms in these isoenzymes may affect the pharmacokinetics of Bu and the clinical outcomes of HSCT. This study aimed to assess the impact of glutathione S-transferase ( GST ) genetic polymorphisms on the clearance of Bu and the clinical outcomes of patients undergoing HSCT. METHODS: This single-center retrospective study included patients who received IV Bu before HSCT at Sultan Qaboos University Hospital (SQUH), Oman from January 2003 to October 2016. Genotyping for polymorphisms was performed for GSTM1 , GSTT1 , GSTA1 , and GSTP1 . Each GST polymorphism was analyzed for its impact on Bu clearance and HSCT outcomes. RESULTS: A total of 135 patients were included. The mean Bu clearance was 3.7 ± 0.98 mL/min/kg. Patients with GSTA1 A-513G heterozygosity (AG) were found to have a higher incidence of graft loss ( P = 0.006). Homozygous double null of GSTM1 and GSTT1 was associated with a higher incidence of acute graft versus host disease ( P = 0.04). Double non-null GSTM1 and GSTT1 and non-null GSTM1 increased the risk of mortality ( P = 0.034 and 0.021, respectively). CONCLUSIONS: GST genotyping before HSCT may predict HSCT outcomes. The results of this preliminary retrospective study need to be confirmed in a larger prospective study.

Analysis of COVID-19 Vaccine Adverse Drug Reactions Reported Among Sultan Qaboos University Hospital Staff.

Objectives: This study aimed to report any suspected adverse drug reactions (ADRs) experienced by all vaccinated staff and students in a tertiary teaching hospital following COVID-19 vaccination. Methods: This retrospective study was conducted during the COVID-19 vaccination campaign at Sultan Qaboos University and Hospital in Muscat, Oman, from August to September 2021. An online survey was generated and sent to all staff and students via email and text messages. An announcement was made on the hospital website with a link to the survey. Results: A total of 8,421 individuals reported being vaccinated at least once with a total of 11,468 doses administered from January to July 2021; 8,014 staff and students received the Pfizer-Biotech vaccine while 3,454 staff and students received the Oxford-AstraZeneca vaccine. The survey received a total of 3,275 responses (response rate = 38.8%). Of these, 741 individuals (22.6%) experienced an ADR after vaccination and 67.2% (n = 498) were females (P <0.001). The majority of the ADRs reported were fever and chills (19.7%) followed by localised pain and swelling at the injection site (18.8%). Other ADRs such as hair loss (0.5%) were reported, and one staff/student reported a clot in the right leg. Among the responders, 27.0% considered their ADRs as mild while 25.0% considered them as severe. Conclusions: In the study cohort, mild symptoms of COVID-19 vaccines were reported. Females experienced more ADRs compared to males. Long-term observation of ADRs to the vaccines and follow-up monitoring should be done on subjects to preclude any unwanted effects.

Vancomycin Therapeutic Drug Monitoring (TDM) and Its Association with Clinical Outcomes: A Retrospective Cohort.

BACKGROUND: Therapeutic drug monitoring (TDM) has proven effectiveness in maintaining efficacy and reducing toxicities associated with vancomycin. A trough level of (15-20 mg/L) for MRSA serious infections is recommended. Therapeutic failure is of concern due to suboptimal routine vancomycin utilization in clinical practice. This study aims to identify factors of vancomycin TDM practice potentially associated with vancomycin-induced nephrotoxicity and therapeutic failure measured by the need to restart vancomycin therapy within 28-days and all-cause mortality in a tertiary hospital in Oman. METHODS: A single-center retrospective cohort was conducted in a tertiary care hospital that included all adult patients aged ≥ 18 years treated with IV vancomycin for> 72 h. RESULTS: Vancomycin therapeutic level was not achieved in 16.8% of the patients, and 47.5% had high levels (>20 mg/L). Vancomycin-induced nephrotoxicity occurred in 31.7% of the patients, it was restarted within 28-days in 18.8% of the patient, and 25.2% of the patients died during the same hospitalization. Univariate analysis showed old age (p < 0.01), higher baseline creatinine reading (p = 0.03), high vancomycin level (p = 0.03), and vancomycin-induced nephrotoxicity (p < 0.01) were associated with increased all-cause mortality. Multivariate analysis identified overweight and vancomycin-induced nephrotoxicity were independent factors associated with increased all-cause mortality (OR:1.04; p = 0.043; 95% CI 1.00-1.08) and (OR:1.96; p = 0.049; 95% CI 1.00-21.61) respectively. CONCLUSION: Failure to achieve the recommended therapeutic vancomycin level (15-20 mg/L) is common in clinical practice and associated with poor health outcomes; hence, appropriate TDM practice is an essential exercise to improve efficacy, prevent failure and reduce serious toxicities associated with vancomycin therapy.

Maternal and Neonatal Outcomes of Operative Vaginal Deliveries at a Single Tertiary Center.

OBJECTIVES: Our study sought to assess the maternal and neonatal outcomes of operative vaginal deliveries (OVDs) at Sultan Qaboos University Hospital (SQUH). We assessed the proportion of OVDs along with the proportion of maternal and neonatal outcomes of kiwi OmniCup vacuum, metal cup vacuum, and forceps deliveries. METHODS: We conducted a retrospective cohort study in the Obstetrics and Gynecology Department at SQUH from June 2015 to March 2018. The hospital information system was utilized to obtain records of all women who delivered at SQUH by vacuum or forceps during the study period. We collected data on maternal demographics, maternal and neonatal outcomes, and total number of deliveries. RESULTS: During the study period, 3.8% of deliveries were OVDs. The most common instrument used was the Kiwi OmniCup vacuum device. No significant difference was found between the type of tears and instrument used except perineal tears (p = 0.003), which was seen more in the vacuum group, particularly Kiwi OmniCup. Neonatal birth weight (p = 0.046) was significantly higher in the metallic vacuum cup group. Thirty-one neonates (6.6%) were admitted to the neonatal intensive care unit, and most were born using Kiwi OmniCup vacuum (67.7%). CONCLUSIONS: OVD is an ideal alternative to cesarean section with fewer maternal and neonatal complications in women who cannot deliver spontaneously if performed by a well-trained obstetrician.

Medication use during pregnancy in Omani women.

OBJECTIVE: The aim of this study was to evaluate medication use pattern in a university tertiary hospital in the Sultanate of Oman. SETTING: The study was conducted at the Sultan Qaboos University Hospital (SQUH) and the SQUH Family and Community Medicine clinic (FAMCO), Muscat, Sultanate of Oman during 7th to 25th June 2008. METHOD: The medication use pattern was evaluated in women attending FAMCO and the standard antenatal clinics at the hospital. Women were interviewed in different gestational ages using a structured questionnaire. The Electronic Patient Record (EPR) was reviewed to acquire additional information on medication use. Medications were classified according to the US FDA risk classification. MAIN OUTCOME MEASURE: Medication used including prescribed medications, OTC medications, or herbal treatment during the current pregnancy and 3 months prior to conception. RESULTS: The study included a total of 139 pregnant mothers with an overall mean age of 28 ± 5 years ranging from 19 to 45 years. There was a slight overall reduction in the medication use including prescribed medications. However, there was a significant increase in utilization of vitamins and supplements (84-95% vs. 12% in the 3-months prior, P < 0.001) as well as herbal preparations (16-19% vs. 7% in the 3-months prior, P = 0.011) throughout pregnancy (P < 0.010). The use of category A medications increased in all trimester (43-52% vs. 13% in the 3 months prior, P < 0.010) while a reduction in the use of category C (for first and third trimester, P < 0.050) and D medications was seen. A reduction in the use of teratogenic drugs in all trimesters (P < 0.010) was also observed. CONCLUSION: The prescribing of vitamins and minerals was optimal. However, the common use of herbal supplements observed warrants special attention due to their unknown risks. The conclusions should be interpreted in light of the study's limitations.