CD4 T-HELPER CELL COUNT IS AN ALTERNATIVE PROMISING MARKER FOR DOSING CYCLOSPORINE IN KIDNEY TRANSPLANT PATIENT

Objective: The study was aimed to find out the correlation between cyclosporine blood concentrations and (Clusters of Differentiation 4) CD4 T-helper cell count (percentage) in order to use the latter parameter as an alternative marker for cyclosporine dosing. Besides, the study was also aimed to find out the optimum dosing strategy for Iraqi patients requiring cyclosporine therapy in Iraqi hospitals using TDM approach.Methods: One hundred and twenty subjects participated in the study. The subjects are involved two groups; group A was 80 patients (53 males and 27 females) using cyclosporine twice daily (Sandimmune® oral solution containing cyclosporine 100 mg/ml) and they had kidney transplantation for more than one year. The ages of the patients were 15-45 y (mean±SD =31.962±8.8207); and. Group B included 40 healthy control subjects (24 males and 16 females) with ages of 15-45 y (mean±SD =31.666±8.1606). According to the condition and the need of the patients, they were administered cyclosporine dose range of 1-10 mg/kg/d. Ten ml blood samples were withdrawn from each patient after fasting for about 12 h for monitoring trough/minimum blood concentration (C0) of cyclosporine and for determination of (Clusters of Differentiation 4) CD4 T-helper cells count at C0. Other 10 ml of blood was then withdrawn after 2 h of cyclosporine administration to be used for monitoring maximum/peak cyclosporine blood cyclosporine (Cmax) after 2 h of drug intake (C2) and for determination of (Clusters of Differentiation 4) CD4 T-helper cells count at C2. Five ml of blood samples were withdrawn from each control subject for determination of (Clusters of Differentiation 4) CD4 T-helper cells count.Results: Good correlations were found between cyclosporine dose administered to each patient and the resulted C0 and C2. The majority of patients (66 patients=82.5%) had C0 of 150-200 ng/ml and C2 of 700-900 ng/ml, which are within the therapeutic range. The range of cyclosporine doses that produce therapeutic C0 and C2 was 4.1-9 mg/kg/d. The mean total lymphocyte count and percentage decreased significantly in all patients compared to the control subjects (1.26±0.60 vs.1.98±0.66 e3/uL) and (19.92±13.77 vs. 28.88±10.22), respectively. A similar trend was found for the total lymphocyte count and percentage of patients with cyclosporine C0, and C2 within the therapeutic range (66 patients) compared to the control subjects (1.34±0.57 vs. 1.98±0.66) and (18.98±10.93 vs. 28.88±10.22), respectively. Good negative correlations were found between lymphocyte count and percentage versus C0 for all patients and for patients with C0 within the therapeutic range. Similarly, good negative correlations were found between lymphocyte count and percentage versus C2 for all patients and for patients with C2 within the therapeutic range. The (Clusters of Differentiation 4) CD4 T-helper cell percentage at C0 decreased significantly in all patients and patients with cyclosporine blood concentrations within the therapeutic range (66 patients) compared to the control subjects (24.33±10.31 vs. 35.83±9.11) and (25.50±2.44 vs. 35.83±9.11), respectively. Similarly, (Clusters of Differentiation 4) CD4 T-helper cell percentage at C2 decreased significantly in all patients and patients with cyclosporine blood concentrations within the therapeutic range compared to the control subjects (22.60±9.28 vs. 35.83±9.11) and (21.50±2.16 vs. 35.83±9.11), respectively. The range of (Clusters of Differentiation 4) CD4 T-helper cell percentages at C0 for patients with cyclosporine blood levels above the therapeutic concentrations was 21.65-23.43; for patients with cyclosporine blood levels within the therapeutic concentrations, the range was 23.70-29.00; and for patients with cyclosporine blood levels below the therapeutic concentrations, the range was 29.80-34.60. Good negative correlations were found between (Clusters of Differentiation 4) CD4 T-helper cell percentage and C0 for all patients and for patients with blood concentrations of cyclosporine within the therapeutic range. The (Clusters of Differentiation 4) CD4 T-helper cell percentage range at C2 for patients with cyclosporine blood levels above the therapeutic concentrations was 13.40-18.20; for patients with cyclosporine blood levels within the therapeutic concentrations, the range was 18.50-22.23; and for patients with cyclosporine blood levels below the therapeutic concentrations, the range was 22.76-24.42. Identically, good negative correlations were found between (Clusters of Differentiation 4) CD4 T-helper cell percentage and C2 for all patients and for patients with blood concentrations of cyclosporine within the therapeutic range. For patients with cyclosporine blood levels above therapeutic concentrations; the minimum percentage of (Clusters of Differentiation 4) CD4 T-helper cell at C2 was 13.40, whereas, the maximum percentage of (Clusters of Differentiation 4) CD4 T-helper cell at C0 was 20.23. For patients with cyclosporine blood levels within therapeutic concentrations; the minimum percentage of (Clusters of Differentiation 4) CD4 T-helper cell at C2 was 18.50, whereas, the maximum percentage of (Clusters of Differentiation 4) CD4 T-helper cell at C0 was 29.00. For patients with cyclosporine blood levels below therapeutic concentrations; the minimum percentage of (Clusters of Differentiation 4) CD4 T-helper cell at C2 was 23.40, whereas, the maximum percentage of (Clusters of Differentiation 4) CD4 T-helper cell at C0 was 34.60.Conclusion: Good negative (reciprocal) correlations were demonstrated between cyclosporine blood concentrations at C0 and C2 versus The percentage of (Clusters of Differentiation 4) CD4 T-helper cell. Therefore, the percentage of (Clusters of Differentiation 4) CD4 T-helper cell may be used as an alternative or surrogate marker for optimum cyclosporine dosing than the traditional dosing strategy using TDM, since the former approach is direct for reflecting drug safety and efficacy, beside, it is the affordable, fast and simple approach. The range of cyclosporine doses that produce therapeutic C0 and C2 in Iraqi kidney transplant patients was 4.1-9 mg/kg/d

Optimization of a Patient-Specific External Fixation Device for Lower Limb Injuries

From MDPI via Jisc Publications RouterHistory: accepted 2021-08-02, pub-electronic 2021-08-10Publication status: PublishedFunder: Engineering and Physical Sciences Research Council; Grant(s): EP/R01513/1Funder: King Saud University; Grant(s): RSP-2021/299The use of external fixation devices is considered a valuable approach for the treatment of bone fractures, providing proper alignment to fractured fragments and maintaining fracture stability during the healing process. The need for external fixation devices has increased due to an aging population and increased trauma incidents. The design and fabrication of external fixations are major challenges since the shape and size of the defect vary, as well as the geometry of the human limb. This requires fully personalized external fixators to improve its fit and functionality. This paper presents a methodology to design personalized lightweight external fixator devices for additive manufacturing. This methodology comprises data acquisition, Computer tomography (CT) imaging analysis and processing, Computer Aided Design (CAD) modelling and two methods (imposed predefined patterns and topology optimization) to reduce the weight of the device. Finite element analysis with full factorial design of experiments were used to determine the optimal combination of designs (topology optimization and predefined patterns), materials (polylactic acid, acrylonitrile butadiene styrene, and polyamide) and thickness (3, 4, 5 and 6 mm) to maximize the strength and stiffness of the fixator, while minimizing its weight. The optimal parameters were found to correspond to an external fixator device optimized by topology optimization, made in polylactic acid with 4 mm thickness

Change: A Leader’s Perspective

Change: A Leader\u27s Perspective represents the culmination of the Change Leadership course taught at Winona State University in the fall term of 2017. Leadership is a broad category with many facets. This book explores the subject and offers students of leadership and aspiring leaders current perspectives on leadership theories, the omnipresence of change, and personal reflections on the course material. Additional thoughts which resonate throughout this text are that leaders influence outcomes and that leadership manifests itself in change, whether by cause or effect.https://openriver.winona.edu/leadershipeducationbooks/1000/thumbnail.jp

Profitability of Commercial Banks Revisited: New Evidence from Oil and Non-Oil Exporting Countries in the MENA Region

This paper investigates the determinants of commercial bank profitability in oil and non-oil countries of the Middle East and North Africa (MENA) region using data from 11 countries over the period 2004–2014. Since banks are under no obligation to fill reports to Bankscope database, irregular reporting banks are omitted from the sample and the model is re-estimated using only regular reporting banks, and a comparative analysis between total banks’ sample and regular reporting banks’ sample is provided. Using the two-step system GMM and fixed effects models, the results indicate that credit risk is negative and highly significant when irregular reporting banks are omitted from the sample, particularly in the non-oil group, unlike the oil countries case, which indicates that adding irregular reporting banks to the sample could lead to bias in some estimated coefficients if they constitute a considerable percentage of the total banks’ sample. Diversification is a key determinant for profitability in oil countries. No enough evidence to support the impact of financial inclusion and financial openness on bank profitability. In addition, the global financial crisis has significantly affected bank profitability in oil countries. Several policy implications are provided to the bank management to follow based on each country group

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic

Background: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic. Methods: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients’ location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality. Results: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37–5.74) compared to HIC. Conclusions: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors

Implementing Basel II: an investigation of the UAE banks' Basel II preparations

Purpose – This study aims at exploring the UAE banks' Basel II preparations. It is essential for the UAE banks to make adequate preparations to ensure their compliance with international standards and practices in the field of banking. Design/methodology/approach – The author developed a modified version of the Ernst & Young questionnaire to examine the UAE banks' Basel II preparations. Five hypotheses have been formulated and tested. Findings – Based on the results of the analysis in this study, it is concluded that the UAE banks are ready for the implementation of Basel II. This conclusion is supported by the fact that the UAE banks have sufficient resources for the implementation of Basel II, which represents a prerequisite for the implementation. The readiness of the UAE banks for implementing Basel II is also supported by the common understanding of Basel II by the employees of the UAE banks and the satisfactory level of education on Basel II. The results also indicate that there is no difference between UAE national and foreign banks in their readiness for the implementation of Basel II, which gives a positive impression about the competitive advantage of the national banks. Finally, the results support the importance of training and education on Basel II as one of the requirements of the implementation. Practical implications – Improving the level of education on Basel II is still needed and this can be achieved because of the availability of the required resources and the awareness of the UAE banks of the benefits, the positive impact, and the challenges of the implementation of Basel II, as indicated by the results. The results also support the importance of training and education on Basel II as one of the requirements of the implementation. Originality/value – The paper is important for the decision makers of the UAE banks and the regulators as the main objective of the study is to increase their awareness of the implementation of Basel II. The results would help the UAE banks to know the level of their Basel II preparations and what are the necessary steps that should be taken in this regard. The results would also help the regulators regarding the required steps that should be taken by the UAE Central Bank in order to motivate or encourage the UAE banks in implementing Basel II properly.Banks, Regulation, Risk management, United Arab Emirates