How Did COVID-19 Impact Smoking Habits in the Saudi Community?

Background/aims Most countries have gone through lockdowns to varying degrees during the COVID-19 pandemic to reduce the spread of the disease. The successive pandemic waves have impacted the health system, imposing restrictions set by the government. This changed people's daily life routines and they felt more socially isolated, which in turn had an impact on their mental health. Some factors were linked to the severity and outcome of COVID-19 on patients. One of these factors was smoking. This study was carried out to investigate the prevalence and impact of lockdown on smoking habits, as well as the changes in attitudes, behavior, and the rate of consumption before and after the government restrictions in the general population of Saudi Arabia. Materials and methods The present cross-sectional study was conducted on a sample of 921 participants from the general population of Saudi Arabia. Data were collected via an online questionnaire. A structured self-response questionnaire was given to the participants after institutional research ethical approval was obtained for the study. Results A total of 921 participants from the smoker population of Saudi Arabia were included in the study. The majority of participants were male (72.9%), and more than half were aged between 18 and 34 years (53.7%). Single individuals had a higher prevalence of increased smoking and a lower rate of quitting compared to married individuals. Participants with higher education levels were more likely to continue smoking at the same rate. While 40.5% of participants reported no change in their smoking rate during the pandemic, 15.4% reported a decrease, 39.0% reported an increase, and 5.1% reported quitting smoking. Participants who reported feeling more stressed during the pandemic had a higher prevalence of increased smoking. The majority of participants believed that smoking increased the risk of COVID-19 infection. Conclusion The study highlights the need for targeted smoking cessation interventions and support services during the pandemic, considering demographic factors, living arrangements, and psychological impact. Efforts should be made to raise awareness about the negative health consequences of smoking during the pandemic and provide resources for stress management and alternative coping strategies. These findings have important implications for public health interventions and policies in Saudi Arabia.

Medial Tibial Stress Syndrome (Shin Splint): Prevalence, Causes, Prevention, and Management in Saudi Arabia.

Background/aims Medial tibial stress syndrome (MTSS), also known as "shin splint", is most often described as exertional leg pain along the shinbone (tibia), which occurs due to the inflammation of the muscles, tendons, and bone tissue in this area. This study aims to assess the prevalence, risk factors, and their association with the development of MTSS, as well as the effective treatments that reduce pain and improve functions among the Saudi general population. Materials and method The present cross-sectional study was conducted on the general population of Saudi Arabia through an electronic survey over a period of three months. The study sample of 443 patients was deemed and considered. The study included participants from the general population in Saudi Arabia above the age of 18. A structured self-response questionnaire was given to the participants after institutional research ethical approval was obtained for the study. Results Among the 443 participants, the majority were male (n = 228, 51.5%), aged 18-29 (n = 227, 51.2%), and residing in the central region of Saudi Arabia (n = 398, 89.8%). Most participants reported engaging in sporting activities (n = 211, 47.6%), with high-intensity training being the most common (n = 93, 44.1%). Only a small proportion (n = 8, 1.8%) reported a previous diagnosis of MTSS. Analysis revealed associations between MTSS prevalence and certain demographic factors, including walking surface preferences and engagement in specific sports. Treatment strategies for MTSS included rest, ice application, physiotherapy, and pain-relieving medication, with varying degrees of satisfaction and recurrence rates among participants. Conclusion The study provides valuable insights into the prevalence, risk factors, management, and preventive measures related to MTSS among the Saudi general population. While certain demographic factors and exercise practices were associated with MTSS prevalence, effective treatment options such as rest, physiotherapy, and appropriate footwear were reported. Moreover, adherence to preventive measures such as stretching, proper footwear selection, and gradual training progression may help mitigate the risk of MTSS development.

Population pharmacokinetics of gentamicin in acute lymphoblastic leukemia pediatric patients compared to non-oncology patients.

Understanding the pharmacokinetics of gentamicin is essential in special populations, such as pediatric patients with acute lymphoblastic leukemia (ALL), in light of previous studies indicating that ALL patients have a lower volume of distribution than non-ALL patients. Furthermore, validation of such results is needed to ensure their clinical application. Accordingly, this single-center, retrospective, cross-sectional study compares the pharmacokinetic parameters of volume of distribution and clearance (Cl) of gentamicin between ALL and non-ALL patients. Inclusion criteria were pediatric patients aged between 1 and 14 years with or without ALL and receiving intravenous gentamicin for treatment courses > 72 h. Patients' characteristics, such as age, sex, height, serum albumin, diagnosis, serum creatinine (Scr) concentration, dosing, and pharmacokinetic information, including peak and trough concentrations, were retrieved. The study scrutinized a total of 115 pediatric patients, comprising toddlers (15.7 %), children (76.5 %), and adolescents (7.8 %). All patients received gentamicin every 8 h, with an average dose of 2.50 (0.64) mg/kg. Patients were divided into two groups based on disease state, with 45.2 % (n = 52) in the non-ALL group and 54.8 % (n = 63) in the ALL group. Both groups had similar characteristics in terms of gender, weight, body surface area, and dose. The only significant covariates identified were weight and creatinine clearance (Clcr) for volume of distribution (Vd). A significant difference was found in Scr, Clcr, and blood urea nitrogen (BUN); however, no significant difference between ALL and non-ALL patients emerged in the volume of distribution or Cl. In conclusion, the study findings indicate that dosing requirements were similar between the two groups. Further prospective studies with larger sample sizes are warranted.

Evaluation of pharmacokinetic pharmacodynamic target attainment of meropenem in pediatric patients.

BACKGROUND: Meropenem is a widely used carbapenem for treating severe pediatric infections. However, few studies have assessed its pharmacokinetics/pharmacodynamics (PK/PD) in pediatric patients. This study aimed to evaluate the proportion of Saudi pediatric patients achieving the PK/PD target of meropenem. METHODS: A prospective observational study was conducted at King Saud University Medical City from July to September 2022. Pediatric patients receiving meropenem for suspected or proven infections were included in the study. The primary outcome was the percentage of patients achieving the recommended PK/PD target for critically ill or non-critically ill pediatric patients. RESULTS: The study included 30 patients (nine neonates and 21 older pediatric patients). All neonates were critically ill. Among them, 55 % achieved the PK/PD target of 100 % free time above the MIC. In older ICU pediatric patients, only 11 % attained this target, whereas 58 % of older pediatrics in the general wards achieved the PK/PD target of 50 % free time above the MIC. Augmented renal clearance (ARC) was identified in 57 % of our pediatric patient population, none of whom achieved the recommended PK/PD targets. The median trough concentrations in patients with and without ARC were 0.75 and 1.3 µg/mL, respectively (P < 0.05). CONCLUSIONS: The majority of patients in our cohort did not achieve the PK/PD target for meropenem. ARC emerged as a major risk factor for target attainment failure in both critically ill and non-critically ill pediatric patients.

Therapeutic Drug Monitoring of Voriconazole in Critically Ill Pediatric Patients: A Single-Center Retrospective Study.

BACKGROUND AND OBJECTIVE: Voriconazole pharmacokinetics are highly variable in pediatric patients, and the optimal dosage has yet to be determined. The purpose of this study was to describe voriconazole pharmacokinetic and pharmacodynamic targets achieved and evaluate the efficacy and safety of voriconazole for critically ill pediatrics. METHODS: This is a single-center retrospective study conducted at a pediatric intensive care unit at a tertiary/quaternary hospital. Pediatrics admitted to the pediatric intensive care unit and who received voriconazole for a proven or suspected fungal infection with at least one measured trough concentration were included. The primary outcomes included the percentage of pediatric patients who achieved the pharmacokinetic and pharmacodynamic targets. Secondary outcomes included assessing the correlation between voriconazole trough concentrations and clinical/microbiological outcomes. All statistical analyses were performed using the R statistical software and Microsoft Excel. Multiple logistic regression was used to assess the predictors of both clinical and microbiologic cures. Multiple linear regression was used to determine significant factors associated with trough concentrations. RESULTS: A total of 129 voriconazole trough concentrations were measured from 71 participants at steady state after at least three doses of voriconazole. The mean (± standard deviation) of the first and second trough concentrations were 2.9 (4.2) and 2.3 (3.3) mg/L, respectively. Among the first trough concentrations, only 33.8% were within the therapeutic range (1-5 mg/L), 46.5% were below the therapeutic range, and 19.7% were above the therapeutic range. A clinical cure occurred in 78% of patients, while a microbiologic cure occurred in 80% of patients. CONCLUSIONS: Voriconazole trough concentrations vary widely in critically ill pediatric patients and only a third of the patients achieved therapeutic concentrations with initial doses.

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.

Interethnic differences in drug response: projected impact of genetic variations in the Saudi population.

Ethnicity is known to have an impact on drug responses. This is particularly important for drugs that have a narrow therapeutic window, nonlinearity in pharmacokinetics and are metabolized by enzymes that demonstrate genetic polymorphisms. However, most clinical trials are conducted among Caucasians, which might limit the usefulness of the findings of such studies for other ethnicities. The representation of participants from Saudi Arabia in global clinical trials is low. Therefore, there is a paucity of evidence to assess the impact of ethnic variability in the Saudi population on drug response. In this article, the authors assess the projected impact of genetic polymorphisms in drug-metabolizing enzymes and drug targets on drug response in the Saudi population.

Population pharmacokinetics of vancomycin in very low birth weight neonates.

Introduction: Vancomycin dosing in very low birth weight (VLBW) neonates is challenging. Compared with the general neonatal population, VLBW neonates are less likely to achieve the vancomycin therapeutic targets. Current dosing recommendations are based on studies of the general neonatal population, as only a very limited number of studies have evaluated vancomycin pharmacokinetics in VLBW neonates. The main aim of this study was to develop a vancomycin population pharmacokinetic model to optimize vancomycin dosing in VLBW neonates. Methods: This multicenter study was conducted at six major hospitals in Saudi Arabia. The study included VLBW neonates who received vancomycin and had at least one vancomycin serum trough concentration measurement at a steady state. We developed a pharmacokinetic model and performed Monte Carlo simulations to develop an optimized dosing regimen for VLBW infants. We evaluated two different targets: AUC0-24 of 400-600 or 400-800 µg. h/mL. We also estimated the probability of trough concentrations >15 and 20 µg/mL. Results: In total, we included 236 neonates, 162 in the training dataset, and 74 in the validation dataset. A one-compartment model was used, and the distribution volume was significantly associated only with weight, whereas clearance was significantly associated with weight, postmenstrual age (PMA), and serum creatinine (Scr). Discussion: We developed dosing regimens for VLBW neonates, considering the probability of achieving vancomycin therapeutic targets, as well as different toxicity thresholds. The dosing regimens were classified according to PMA and Scr. These dosing regimens can be used to optimize the initial dose of vancomycin in VLBW neonates.

Population Pharmacokinetics of Rivaroxaban in Real-World Patients.

The pharmacokinetics (PK) of rivaroxaban have been studied in different populations, and there were differences in the PK parameters. However, most of these studies were conducted on healthy subjects from different ethnic groups. Thus, this study aimed to investigate the PK of rivaroxaban in real-world patients to determine the covariates that may cause differences in the pharmacokinetics of rivaroxaban. This was a prospective observational study. Five blood samples were collected at different time points after starting the rivaroxaban dose. Plasma concentrations were analyzed, and population PK models were developed using Monolix version 4.4 software. In total, 100 blood samples from 20 patients (50% men/50% women) were analyzed. The patients' mean (±standard deviation) age was 53.1 (±15.5) years and their mean body weight was 81.7 (±27.2) kg. The PK of rivaroxaban were described by a 1-compartment model. The initial estimates for the absorption rate constant, apparent clearance (CL/F), and apparent volume of distribution were 1.8/h, 4.46 L/h, and 21.7 L, respectively. The interindividual variability for absorption rate constant, CL/F, and volume of distribution was 14%, 24%, and 29.3%, respectively. Covariates were tested for their influence on rivaroxaban pharmacokinetics. The aspartate aminotransferase, alanine aminotransferase, body mass index, and albumin concentrations had an effect on the CL/F of rivaroxaban. In this analysis, the population PK model of rivaroxaban found significant interindividual variability. Several covariates influenced the clearance of rivaroxaban and contributed to this variability. The results may provide a guide that can aid the clinician during the initiation and adjustment of therapeutic regimens.

Evaluation of vancomycin individualized model-based dosing approach in neonates.

BACKGROUND: Vancomycin is commonly used to treat methicillin-resistant staphylococcal infections in neonates. Consensus on its ideal dosing in neonates has not been achieved. Model-based dosing recently has evolved as an important tool to optimize vancomycin initial dosing. The aim of this is to evaluate a population pharmacokinetic model-based approach in achieving the vancomycin therapeutic target of an AUC0-24 400 as recommended by the recent IDSA treatment guidelines. This model was implemented as a simple Excel calculator to individualize and optimize vancomycin initial dosing in neonates. METHODS: An Excel calculator was developed using a previously published population pharmacokinetic model in neonates. It was evaluated using retrospectively retrieved data. For each patient, the initial empiric dose was calculated using the proposed Excel model and the most widely used neonatal dosing references. The probability of achieving the target AUC0-24 of >400 mg h/L using the model-based method was calculated and compared with that of the empiric doses using other references. RESULTS: This analysis included 225 neonates. The probability of achieving the target AUC0-24 >400 was 89% using our model-based approach compared with 11%-59% using tertiary neonatal dosing references (p < 0.01 for all comparisons). CONCLUSION: These innovative personalized dosing calculators are promising to improve vancomycin initial dosing in neonates and are easily applicable in routine practices.

Clinical pharmacokinetics of capecitabine and its metabolites in colorectal cancer patients.

Background: Capecitabine is one of the fluoropyrimidine anticancer agents which is extensively used in the management of colorectal cancer. We have noticed a discrepancy between the doses we are using in our patients and the recommended dosing regimen. Thus, this study aims to assess the pharmacokinetic parameters of capecitabine and its metabolites in colorectal cancer patients and report some clinical outcomes. Methods: This study is a prospective observational pharmacokinetic study. It was conducted at the Oncology Center at King Saud University Medical City. The study included adult patients who received capecitabine for any stage of colorectal cancer. Blood samples were collected following the oral administration of capecitabine. Capecitabine and its metabolites concentration in plasma were determined using HPLC and pharmacokinetic parameters were estimated using PKanalix software. Results: The study included 30 colorectal cancer patients with a mean age of 58 ± 9.5 years and ECOG Performance Status of 0-1. 60 % of the patients were in stage IV. The average total daily dose was 1265 ± 350 mg/m2/day. Cmax for capecitabine was 5.2 ± 1.3 µg/ mL and Tmax was 1 ± 0.25 h. AUClast for capecitabine was 28 ± 10 µg.h/ mL. Vdobs and Clobs for capecitabine were 186 ± 28 L and 775 ± 213 mL/min, respectively. Calculated half-life (t1/2) was 2.7 h. Half of our patients showed partial tumor response and 20% showed stable disease. Only two patients had to discontinue the treatment because of the toxicity. Conclusion: Despite using lower doses, capecitabine and its metabolites parameters were found to be similar to previous studies except for the longer half-life found in our patients. In addition, lower doses of capecitabine showed acceptable response rate which might indicate that higher doses are not always necessary to achieve desired therapeutic effect.

Successful treatment of Gustilo type 3C open tibial fracture with a massive muscles and soft tissues wasting: A case report.

Introduction and importance: Gustilo-Anderson type 3 open tibial fractures are commonly accompanied by extensive damage and serious complications, especially in types 3B and 3C. Case presentation: A 25-year-old male was transferred after motor vehicle accident and the emergent choice was an above-knee amputation in other two hospital. A left open distal tibial fracture (Gustilo type 3C) with a wide and contaminated soft tissues defect, that extended from the knee to the midfoot, is accompanied by wasting of the anterior compartment muscles and ruptured of the anterior tibial artery. We did irrigation and debridement and then we placed an anteriomedial external fixation system type AO with pins. A cross-leg flap and free skin grafts from the opposite limb was performed three weeks after a daily irrigation and debridement, povidon and ozone cream bandages, and antibiotics. After twelve months of follow-up, the fracture was healed and the external fixator was removed. Discussion/conclusion: Gustilo-Anderson type 3 open fractures remain a veritable orthopedic challenge, even for surgeons with greater experience, because of neurovascular damages, high amputation rate, and vast soft tissue injuries. The collaboration of the multidisciplinary surgical team led to preserve the limb with good result after one year. It is reasonable to judge and attempt a limb preservation even with wide open tibial fractures.

Can First-Dose Therapeutic Drug Monitoring Predict the Steady State Area Under the Blood Concentration-Time Curve of Busulfan in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation?

Busulfan has high intra-individual variability and possible time-dependent changes in clearance, which complicates therapeutic drug monitoring (TDM), as first dose sampling may not predict the steady state concentrations. In this study, we aimed to use Bayesian pharmacokinetic parameters estimated from the first dose to predict the steady state AUC for busulfan. This observational study was conducted among pediatric patients at King Abdullah Specialist Children's Hospital. From each patient, we collected six blood samples (2, 2.25, 2.5, 3, 4, and 6 h after the start of IV infusion of the first dose). A subset of patients were also sampled at the steady state. First, we modeled the data using only the first dose. The model was used to estimate the empirical Bayesian estimates of clearance for each individual patient, then we used the empirical Bayesian estimates of clearance to predict the AUC0-tau at steady state (i.e., predicted AUC0-tau). Steady state AUC0-tau was also calculated for patients sampled at steady state using the trapezoidal method using raw time concentration data; this was considered the reference AUC0-tau.. Then, we compared the AUC0-tau predicted using the Bayesian approach with the reference AUC0-tau values. We calculated bias and precision to assess predictability. In total we had 33 patients sampled after first dose and at steady state. Using the Bayesian approach to predict the AUC0-tau, bias was -2.8% and precision was 33%. This indicates that first dose concentrations cannot accurately predict steady state busulfan concentrations; therefore, follow-up TDM may be required for optimal dosing.

Early Bactericidal Activity of Delpazolid (LCB01-0371) in Patients with Pulmonary Tuberculosis.

Delpazolid, an oxazolidinone, has been studied in non-clinical studies of efficacy and toxicity and Phase 1 clinical studies. Delpazolid has in vitro activity against Gram-positive bacteria, including Mycobacterium tuberculosis. This study evaluated the bactericidal activity, safety, and pharmacokinetics of delpazolid in patients with pulmonary tuberculosis (TB). Seventy-nine subjects, aged 19 to 75 years with newly diagnosed smear-positive TB with no prior treatment for the current episode and no confirmed resistance to rifampin or isoniazid, were randomized to receive delpazolid 800 mg once a day (QD), 400 mg twice a day (BID), 800 mg BID or 1,200 mg QD or an active control of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) or linezolid 600 mg BID. The primary endpoint was the average daily reduction in log transformed bacterial load, assessed on 7H11 solid-media culture, from days 0 to 14. The average daily decline in log-CFU was 0.044 ± 0.016, 0.053 ± 0.017, 0.043 ± 0.016, and 0.019 ± 0.017, for the delpazolid 800 mg QD, 400 mg BID, 800 mg BID, and the 1,200 mg QD groups, respectively. The average daily decline in log-CFU was 0.192 ± 0.028 for the HRZE group and 0.154 ± 0.023 for the linezolid 600 mg BID group. Three serious adverse events (SAE) were reported, one each in the delpazolid 400 mg BID group (death due to worsening of TB at day 2), the HRZE group (hospitalization due to pleural effusion) and the linezolid group (hyperkalemia); none of the SAEs were assessed as related to study drugs. This study has been registered at ClinicalTrials.gov with registration number NCT02836483.

Pharmacokinetics of meropenem in critically ill patients in Saudi Arabia.

BACKGROUND: Meropenem is commonly used in the ICU to treat gram-negative infections. Due to various pathophysiological changes, critically ill patients are at higher risk of having subtherapeutic concentrations and hence have a higher risk of treatment failure-especially in regions where gram-negative drug resistance is increasing, such as Saudi Arabia. No studies have evaluated the pharmacokinetics of meropenem in critically ill patients in Saudi Arabia. Our primary objective is to assess the percentage of patients achieving the therapeutic target for meropenem. METHODS: This prospective observational study was conducted in the ICUs of King Khalid University Hospital. Patient were included if >18 years-of-age and received meropenem for a clinically suspected or proven bacterial infection. The primary outcome was to assess the percentage of patients who achieved the pharmacokinetic/pharmacodynamic (PKPD) therapeutic target of a free trough concentration four times the MIC. The secondary outcome was to estimate the pharmacokinetics of meropenem. Pharmacokinetic analysis was performed using Monolix Suite 2020R1 (Lixoft, France). RESULTS: Trough concentrations were highly variable and ranged from <0.5 µg/mL to 39 µg/mL, with a mean ± SD trough concentration of 8.5 ± 8 µg/mL. Only 46% of patients achieved the therapeutic target. The only significant predictor of failing to achieve the PKPD target was augmented renal clearance. CONCLUSION: In conclusion, more than half of our patients did not achieve the PKPD target. Thus, there is a need for better dosing strategies of meropenem in critically ill patients in Saudi Arabia such as extended and continuous infusion.

Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation.

Micafungin is widely used for invasive candidiasis, especially in critically ill patients and those with cancer, and for empirical antifungal therapy in patients with neutropenic fever. This is the first study to investigate the pharmacokinetics and disposition parameters of micafungin in patients with cancer. In this observational pharmacokinetic study, blood samples were collected and analyzed using high-performance liquid chromatography. Pharmacokinetic parameters were estimated using Monolix 4.4 software. The plasma micafungin concentrations were measured in a total of 133 samples from 19 patients. In the final two-compartment model with linear elimination, the estimated micafungin clearance (CL) was significantly higher in patients with cancer than in those without cancer (1.2 vs. 0.6 L/h, p = 0.012), whereas other parameters did not significantly differ between the two groups. Aspartate and alanine transaminases and body weight significantly influenced micafungin CL in patients, with and without cancer. Overall, the probability of target attainment increased with increasing doses and decreased with higher MICs in both groups. In simulations, the patients without cancer achieved higher pharmacokinetic/pharmacodynamic targets with a 90% probability for all simulated doses, compared to the patients with cancer. Micafungin demonstrated dose-proportional linear pharmacokinetics in both the patients with and those without cancer. The estimated micafungin CL was significantly higher in patients with cancer, suggesting a need for increased dosage, especially for Candida spp. with high MICs, in these patients. Further studies should assess the efficacy and optimum dosage of micafungin for the treatment and prevention of febrile neutropenia (FN) in patients with cancer.

Dorsalis pedis artery pseudoaneurysm: A rare entity in the field of vascular surgery.

INTRODUCTION: Dorsalis pedis artery aneurysms (PDAA) and pseudoaneurysms are rare conditions of lower limb vasculature. The rarity of the disease increases in the pediatric age group where only 4 cases of pediatric patients with PDAA. PRESENTATION OF THE CASE: We present A case of a 2-year-old baby girl who was diagnosed with dorsalis pedis pseudoaneurysm, which was treated successfully with pseudoaneurysm dissection and anastomosis. CLINICAL DISCUSSION: The dorsalis pedis pseudoaneurysm in this case has a rare anatomical location in addition to the unusual onset at this age group. Due to the rarity of this condition among all age groups, there is not a well-structured approach. CONCLUSION: DPAA/pseudoaneurysm is a rare entity in the field of vascular surgery. Medical treatment is not suitable for DPAA/pseudoaneurysm to avoid the future risk of thrombosis or ischemia. The surgical approach is the Mainstay of treatment.

Estimation of Tacrolimus Clearance in Saudi Adult Kidney Transplant Recipients.

Tacrolimus is commonly used in adult kidney transplant patients. Only few studies have so far described the pharmacokinetics of tacrolimus in the Saudi population. Thus, the goal of this study is to determine the population pharmacokinetics of tacrolimus in Saudi adult kidney transplant recipients and to identify the factors that explain variability. We performed a retrospective chart review of adult patients who received oral tacrolimus at two centers. We developed the population pharmacokinetic models using Monolix 4.4. The factors screened for influence on these parameters were weight, age, gender, liver function tests, and creatinine clearance. The analysis included a total of 149 tacrolimus plasma concentrations from 139 patients. A one-compartment open model with linear absorption and elimination adequately described the data. The average parameter estimates for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 9.1 L/h and 912 L, respectively. The interindividual variabilities (coefficients of variation) in CL/F and V/F were 20% and 18%, respectively. Aspartate aminotransferase was identified to be the main covariate that influences tacrolimus CL/F. In conclusion, the population pharmacokinetic model of tacrolimus was established and a significant covariate of the model was identified. These findings offer a rationale for the personalization of tacrolimus dosing regimens. Further studies are required to understand the factors that may influence the pharmacokinetics of tacrolimus and assist in drug dosage decisions.

Radiological Outcomes and Complications of Vertical Expandable Titanium Rib Instrumentation in Congenital Scoliosis With or Without Rib Fusion: A Retrospective Study.

INTRODUCTION: In congenital anomalies of the thoracic spine, fusion in situ and hemi-epiphysiodesis are unsuitable surgical options, because three-dimensional thoracic deformity and insufficiency are uncorrectable. We aimed to evaluate the radiological outcome of vertical expandable titanium rib (VEPTR) application after follow-up in children with congenital scoliosis with or without rib fusion. METHODS: In our study, we included 58 patients with congenital scoliosis with or without fused ribs; all treated with VEPTR from 2005 to 2015 at our institute. There were 19 males and 39 females. For each patient, we collected information about age at the index surgery (VEPTR application) and the total number of VEPTR lengthening procedures. Also, Cobb angle, kyphotic angle, thoracic height, and spinal height were measured on preoperative radiographs, immediately post-operative, two years post-operative, and at final follow-up. RESULTS: The mean duration of follow-up was five years (range, 2-12 years). Twenty-eight patients had rib-to-pelvis type VEPTR, 20 patients had rib-to-rib type VEPTR, and 10 patients had a rib to pedicle/lamina type of VEPTR implant. Post-VEPTR, 63.8% of our patients reported one or more complications. The immediate post-VEPTR application showed that the mean Cobb angle decreased to 43.56° with a percentage change of 22.8% (p<0.001). The mean increase in thoracic height between VEPTR application surgery and final follow-up was 32 mm with a 19.3% increase (p<0.001). Similarly, the mean increase in the spinal height between the VEPTR application surgery and final follow-up was 46.6 mm, with a 23% increase (p<0.001). CONCLUSIONS: VEPTR instrumentation for congenital scoliosis, with or without rib fusion, successfully corrects the coronal Cobb angle in the majority of patients. It also allows the thoracic (T1-T12) and spinal (T1-S1) growth to approach normal for a particular age.