The impact of consanguinity on the design of iPSC banks.

The effect of consanguinity on identifying universal induced pluripotent stem cell (iPSC) donors, i.e., homozygous for the major human leukocyte antigen (HLA) loci, is unknown. The discovery sample size was calculated in a consanguineous population using a method (1qF) based on the inbreeding coefficient. The result was orders of magnitude smaller compared to the standard method.

Intravenous Immunoglobulins Alone for the Desensitization of Lung Transplant Recipients with Preformed Donor Specific Antibodies and Negative Flow Cytometry Crossmatch.

BACKGROUND: The lack of evidence regarding optimal desensitization strategies for lung transplant candidates with preformed donor specific anti-human leukocyte antigen antibodies (DSAs) has led to varying approaches among centers towards this patient group. Our institution's desensitization protocol for recipients with preformed DSAs and negative flow cytometry crossmatch (FCXM) consists of intravenous immunoglobulin (IVIG) as the sole therapy. The study aimed to determine outcomes using this approach. METHODS: This retrospective study included adults who underwent lung-only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA-positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low-level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)-free times were compared between groups using Cox proportional hazards models. RESULTS: Thirty-six out of 167 eligible patients (22%) were DSA-positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55-1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34-1.52) in DSA-positive patients compared to patients with low-level/negative DSAs. Incidences of antibody-mediated rejection (p = 1.00) and serious thromboembolic events (p = 0.63) did not differ between study groups. CONCLUSION: We describe a single-center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols.

Derivation and validation of Transform equations to convert historical Enhanced liver fibrosis (ELF) scores to modern equivalents.

BACKGROUND AND AIMS: The Siemens Healthineers ELF™ Test was designed in 2004 with 2 algorithms to allow choice in histological alignment. Consequently, historical and modern algorithms are not fully harmonized, complicating comparisons involving early datasets. We derived transform equations to equate all ELF score versions, allowing historical data to be used in systematic reviews and meta-analyses. METHODS: Historical ELF equations were graphed pairwise versus their modern equivalent to assess correlation and derive four transforms. Transforms were validated using multiple datasets and evaluated for median absolute bias, number of samples reflecting clinically significant bias, number of discordant samples, bias at established cutoffs, and regression slope and y-intercept. RESULTS: Three transforms were validated equating Scheuer-aligned and/or age-included historical ELF equations (Immuno 1) to later equations aligned to Ishak and omitting age. A fourth transform corrected ADVIA Centaur® / Atellica® IM ELF scores miscalculated using the Scheuer Immuno 1 equation. Transformed data were well within allowable ELF bias limits. CONCLUSIONS: All transforms enabled accurate comparison of ELF scores generated by all historical algorithms to the current ADVIA Centaur / Atellica IM Analyzer ELF score. The transforms presented in this report should be used in systematic reviews and meta-analyses to facilitate comparisons to historical data.

Quality of Life Evaluation in Saudi Arabian Pediatric Patients with Primary Immunodeficiency Diseases Receiving 20% Subcutaneous IgG Infusions at Home.

BACKGROUND AND AIMS: Subcutaneous immunoglobulin (SCIG) home infusion is widely used as an alternative to intravenous immunoglobulin (IVIG). This study aimed to determine the quality of life (QoL) of patients with primary immunodeficiency (PID) after switching to home-based SCIG. METHODS: In this prospective open-label single-center study, QoL was determined using the validated Arabic version of the Child Health Questionnaire at baseline and 3 and 6 months after switching from IVIG to SCIG. RESULTS: Twenty-four patients were recruited from July 2018 to August 2021, including 14 females and 10 males. The median age of the patients was 5 years (range, 0-14 years). The patients' diagnoses included severe combined immunodeficiency, combined immunodeficiency, agammaglobulinemia, Omenn syndrome, immunodysregulation, hyper-IgE syndrome, common variable immunodeficiency, and bare lymphocyte syndrome. The median duration on IVIG before inclusion was 40 months (range, 5-125 months). The QoL score showed a significant improvement in the patients' global health at 3 and 6 months compared with those at baseline and a significant improvement in the patients' general health at 3 and 6 months compared with that at baseline. The mean baseline serum IgG trough level was 8.8 ± 2.1 g/L. The mean serum IgG level was significantly higher on SCIG at both 3 and 6 months (11.7 ± 2.3 and 11.7 ± 2.5 g/L, respectively). CONCLUSIONS: This is the first study involving an Arab population to show improvement in the QoL of patients with PID after switching from hospital-based IVIG to home-based 20% SCIG.

Lifetime prevalence and treatment of mental disorders in Saudi youth and adolescents.

Previous global and regional studies indicate that adolescents and young adults (i.e., youth) are affected by various mental disorders with lifelong consequences. However, there are no national estimates of mental disorders prevalent among Saudi youth. Using data from the Saudi National Mental Health Survey (SNMHS), we examined the lifetime prevalence, treatment, and socio-demographic correlates of mental disorders among Saudi youth (aged 15-30). A total of 4004 interviews were conducted using the adapted Composite International Diagnostic Interview (CIDI 3.0). Cross tabulations and logistic regression were used to generate estimates for the SNMHS youth sample (n = 1881). The prevalence of a mental disorder among Saudi youth was 40.10%, where anxiety disorders affected 26.84% of the sample, followed by disruptive behavior disorders (15.44%), mood disorders (9.67%), substance use disorders (4%) and eating disorders (7.06%). Sex, education, parental education, income, marital status, region, and family history of disorders were significant correlates of various classes of mental disorders. Only 14.47% of Saudi youth with any mental disorder received treatment for a lifetime disorder. Age, parental education, and family history of disorders emerged as significant correlates of mental health treatment. Lifetime mental disorders are highly prevalent among Saudi youth. There is an unmet need for culturally sensitive and age-appropriate treatment of lifetime mental disorders among youth in Saudi Arabia.

Chorioangioma: a single tertiary care center retrospective study.

OBJECTIVES: Chorioangioma represents a challenge due to the rarity of the condition, paucity of sufficient management guidelines, and controversies regarding the best invasive fetal therapy option; most of the scientific evidence for clinical treatment has been limited to case reports. The aim of this retrospective study was to review the natural antenatal history, maternal and fetal complications, and therapeutic modalities used in pregnancies complicated with placental chorioangioma at a single Center. METHODS: This retrospective study was conducted at King Faisal Specialist Hospital and Research Center (KFSH&RC) in Riyadh, Saudi Arabia. Our study population included all pregnancies with ultrasound features of chorioangioma, or histologically confirmed chorioangiomas, between January 2010 and December 2019. Data were collected from the patients' medical records, including the ultrasound reports and histopathology results. All subjects were kept anonymous; case numbers were used as identifiers. Data collected by the investigators were entered into Excel worksheets in an encrypted format. A MEDLINE database was used to retrieve 32 articles for literature review. RESULTS: Over a 10-year period between January 2010 and December 2019, 11 cases of chorioangioma were identified. Ultrasound remains the gold standard for diagnosis and follow-up of the pregnancy. Seven of the 11 cases were detected by ultrasound, allowing proper fetal surveillance and antenatal follow-up. Of the remaining six patients, one underwent radiofrequency ablation, two underwent intrauterine transfusion for fetal anemia due to placenta chorioangioma, one had vascular embolization with an adhesive material, and two were managed conservatively until term with ultrasound surveillance. CONCLUSIONS: Ultrasound remains the gold standard modality for prenatal diagnosis and follow-up of pregnancies with suspected chorioangiomas. Tumor size and vascularity play a significant role in the development of maternal-fetal complications and the success of fetal interventions. To determine the superior modality of fetal intervention mandates more data and research; nevertheless, Fetoscopic Laser Photocoagulation and embolization with adhesive material seem to be a lead choice, with reasonable fetal survival.

Efficacy of generic sofosbuvir with daclatasvir compared to sofosbuvir/ledipasvir in genotype 4 hepatitis C virus: A prospective comparison with historical control.

Background and Aim: Management of genotype 4 hepatitis C virus (HCV) has shifted to interferon-free regimens with a high sustained virological response (SVR-12), especially with NS5B/NS5A inhibitor combinations such as sofosbuvir and ledipasvir (Sof-Led). The guidelines have recommended the combination of sofosbuvir and another NS5A inhibitor, daclatasvir, to manage HCV genotypes 1-3. However, its use was extended to genotype 4 HCV based on extrapolating evidence. Our aim is to assess the efficacy of generic sofosbuvir + branded daclatasvir (Sof-Dac) compared to the Sof-Led combination in treating genotype 4 HCV. Methods: This study is an open-label, 2-period, noninferiority study that compared patients receiving a combination of generic sofosbuvir 400 mg and daclatasvir 60 mg orally daily (Group 2) prospectively to a historical control (Group 1) that included patients who received a combination of sofosbuvir/ledipasvir 400/90 mg orally daily. The primary endpoint is the proportion of patients who achieved SVR-12. Results: The study included 111 patients in the (Sof-Led) Group 1 and 109 patients (Sof-Dac) Group 2. For the primary outcome, SVR-12 was achieved in 106 (95.5%) of the patients in Group 1 versus 108 (99.1%) in Group 2 (p = 0.2). In addition, all patients who achieved SVR-12 also achieved SVR-24. Conclusion: Generic sofosbuvir combined with branded daclatasvir was safe and effective for treating genotype 4 HCV compared to Sof-Led. This combination may significantly reduce the cost burden, enabling a larger pool of treated patients. Office of research affairs at KFSHRC RAC# 2171 036.

Adjunctive ketamine for sedation in critically ill mechanically ventilated patients: an active-controlled, pilot, feasibility clinical trial.

OBJECTIVE: Ketamine has been shown to decrease sedative requirements in intensive care unit (ICU). Randomized trials are limited on patient-centered outcomes. We designed this pilot trial to evaluate the feasibility of a large randomized controlled trial (RCT) testing the effect of ketamine as an adjunct analgosedative compared with standard of care alone as a control group (CG) in critically ill patients with mechanical ventilation (MV). We also provided preliminary evidence on clinically relevant outcomes to plan a larger trial. MATERIAL AND METHODS: Pilot, active-controlled, open-label RCT was conducted at medical, surgical, and transplant ICUs at a large tertiary and quaternary care medical institution (King Faisal Specialist Hospital and Research Center, Saudi Arabia). The study included adult patients who were intubated within 24 h, expected to require MV for the next calendar day, and had institutional pain and sedation protocol initiated. Patients were randomized in a 1:1 ratio to adjunct ketamine infusion 1-2 µg/kg/min for 48 h or CG alone. RESULTS: Of 437 patients screened from September 2019 through November 2020, 83 (18.9%) patients were included (43 in CG and 40 in ketamine) and 352 (80.5%) were excluded. Average enrollment rate was 3-4 patients/month. Consent and protocol adherence rates were adequate (89.24% and 76%, respectively). Demographics were balanced between groups. Median MV duration was 7 (interquartile range [IQR] 3-9.25 days) in ketamine and 5 (IQR 2-8 days) in CG. Median VFDs was 19 (IQR 0-24.75 days) in ketamine and 19 (IQR 0-24 days) in the CG (p = 0.70). More patients attained goal Richmond Agitation-Sedation Scale at 24 and 48 h in ketamine (67.5% and 73.5%, respectively) compared with CG (52.4% and 66.7%, respectively). Sedatives and vasopressors cumulative use, and hemodynamic changes were similar. ICU length-of-stay was 12.5 (IQR 6-21.2 days) in ketamine, compared with 12 (IQR 5.5-23 days) in CG. No serious adverse events were observed in either group. CONCLUSIONS: Ketamine as an adjunct analgosedative agent appeared to be feasible and safe with no negative impact on outcomes, including hemodynamics. This pilot RCT identified areas of improvement in study protocol before conducting a large, adequately powered, multicenter RCT which is likely justified to investigate ketamine association with patient-centered outcomes further. Trial registration ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020.

25-Hydroxylase vitamin D deficiency in 27 Saudi Arabian subjects: a clinical and molecular report on CYP2R1 mutations.

Vitamin D deficiency remains a major cause of rickets worldwide. Nutritional factors are the major cause and less commonly, inheritance causes. Recently, CYP2R1 has been reported as a major factor for 25-hydroxylation contributing to the inherited forms of vitamin D deficiency. We conducted a prospective cohort study at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia, to review cases with 25-hydroxylase deficiency and describe their clinical, biochemical, and molecular genetic features. We analyzed 27 patients from nine different families who presented with low 25-OH vitamin D and not responding to usual treatment. Genetic testing identified two mutations: c.367+1G>A (12/27 patients) and c.768dupT (15/27 patients), where 18 patients were homozygous for their identified mutation and 9 patients were heterozygous. Both groups had similar clinical manifestations ranging in severity, but none of the patients with the heterozygous mutation had hypocalcemic manifestations. Thirteen out of 18 homozygous patients and all the heterozygous patients responded to high doses of vitamin D treatment, but they regressed after decreasing the dose, requiring lifelong therapy. Five out of 18 homozygous patients required calcitriol to improve their biochemical data, whereas none of the heterozygous patients and patients who carried the c.367+1G>A mutation required calcitriol treatment. To date, this is the largest cohort series analyzing CYP2R1-related 25-hydroxylase deficiency worldwide, supporting its major role in 25-hydroxylation of vitamin D. It is suggested that a higher percentage of CYP2R1 mutations might be found in the Saudi population. We believe that our study will help in the diagnosis, treatment, and prevention of similar cases in the future.

Epidemiology of Pancreatic Cancer in Saudi Arabia: A Retrospective Analysis of Pancreatic Cancer Diagnosed in Saudi Arabia Between 2004 and 2015.

PURPOSE: Over the last decades, the incidence of pancreatic cancer has increased, particularly in countries with a higher socioeconomic status. The present work aimed to provide detailed epidemiological data on the incidence of pancreatic cancer in Saudi Arabia. PATIENTS AND METHODS: In this retrospective descriptive study, the epidemiological data on pancreatic cancer cases diagnosed in 13 administrative regions of Saudi Arabia between January 2004 and December 2015 were extracted from the Saudi Cancer Registry. The frequency, the crude incidence rate (CIR), and the age-standardized incidence rate (ASIR), stratified by geographical region, gender, and the year of diagnosis, were analyzed. RESULTS: From January 2004 to December 2015, a total of 2338 cases of pancreatic cancer were registered, including 1443 males and 895 females. The overall CIR was 1.28/100,000 among males and 0.80/100,000 in females, with an overall ASIR of 2.26 and 1.41/100,000 for males and females, respectively. Higher ASIR and CIR were observed among males than females (ratio 1.6). In both genders, the ASIR of pancreatic cancer increased with increasing age, with the highest incidence in patients aged 70 years or more. The ASIR in the Eastern Region (3.2/100,000) and the regions of Riyadh (3.0/100,000) and Tabuk (2.6/100,000) proved to be significantly higher than in the other regions of the country. Among women, the ASIR was significantly higher in Riyadh (2.3/100,000), the northern region (2.2/100,000), and Tabuk (2.0/100,000). CONCLUSION: This study revealed a slight increase of the CIR and ASIR of pancreatic cancer among males and females of the Saudi population. Eastern region, Riyadh, and Tabuk had the highest overall ASIRs of pancreatic cancer among males, Riyadh, Northern region, and Tabuk among Saudi females. The area least affected by pancreatic cancer was observed in Jazan among male and female Saudis. The rates of pancreatic cancer in Saudi Arabia were significantly higher among males compared with female Saudis. Further analytical studies are needed to identify the potential risk factors for pancreatic cancer among the Saudi population.

Performance Assessment of a Multifaceted Unfractionated Heparin Dosing Protocol in Adult Patients on Extracorporeal Membrane Oxygenator.

BACKGROUND: The use of extracorporeal membrane oxygenator (ECMO) support devices are associated with complications, including bleeding and thrombosis. Unfractionated heparin (UFH) is the gold standard anticoagulant in ECMO patients. Clinically, UFH is monitored through activated clotting time (ACT), activated partial thromboplastin time (aPTT), and anti-factor Xa assay. It is unknown which assay best predicts anticoagulation effects in adults. OBJECTIVE: To assess the correlation of UFH dosing and monitoring using an established protocol. METHODS: A pilot, prospective cohort, historically controlled study was conducted at a tertiary care hospital. Patients ≥18 years-old who received ECMO on the multifaceted anticoagulation protocol were included and compared with those on the conventional method of anticoagulation. The primary end point was to assess the correlation between UFH dose and different monitoring methods throughout 72 hours using the new protocol guided by ACT and anti-factor Xa assay. RESULTS: In each arm, 20 patients were enrolled. The study revealed that anti-factor Xa assay had the largest number of "strong" correlations 11/20 (55%), followed by both aPTT and aPTT ratio 10/20 (50%), and, finally, ACT 2/20 (10%). Concordance between anti-factor Xa assay and the other monitoring parameters in the prospective arm was generally low: 31% with aPTT ratio, 26% with ACT, and 23% with aPTT. CONCLUSION AND RELEVANCE: The adaption of a multifaceted anticoagulation protocol using anti-factor Xa assay may provide a better prediction of heparin dosing in adults ECMO patients compared with the conventional ACT-based protocol. Further studies are needed to assess the safety and different monitoring modalities.

Pride and Prejudice during the COVID-19 Pandemic: The Misfortune of Inappropriate Clinical Trial Design.

Coronavirus Disease 2019 (COVID-19) is a rapidly evolving global pandemic for which more than a thousand clinical trials have been registered to secure therapeutic effectiveness, expeditiously. Most of these are single-center non-randomized studies rather than multi-center, randomized controlled trials. Single-arm trials have several limitations and may be conducted when spontaneous improvement is not anticipated, small placebo effect exists, and randomization to a placebo is not ethical. In an emergency where saving lives takes precedence, it is ethical to conduct trials with any scientifically proven design, however, safety must not be compromised. A phase II or III trial can be conducted directly in a pandemic with appropriate checkpoints and stopping rules. COVID-19 has two management paradigms- antivirals, or treatment of its complications. Simultaneous assessment of two different treatments can be done using 2 × 2 factorial schema. World Health Organization's SOLIDARITY trial is a classic example of the global research protocol which can evaluate the preferred treatment to combat COVID-19 pandemic. Short of that, a trial design must incorporate the practicality of the intervention used, and an appropriate primary endpoint which should ideally be a clinical outcome. Collaboration between institutions is needed more than ever to successfully execute and accrue in randomized trials.

Comparing the utility of 30- and 60-minute cortisol levels after the standard short synacthen test to determine adrenal insufficiency: A retrospective cross-sectional study.

Short Synacthen test (SST) involves measuring the baseline, 30-, and 60-minute serum cortisol levels, after injecting 250 µg of synthetic adrenocorticotropic hormone or Synacthen (ACTH). This study aimed to review the current clinical practice of performing SST to establish a standardized test protocol and to additionally test the hypothesis regarding performing the 60-minute cortisol test alone and the dependence of overall SST result on baseline cortisol level.Patients >14 years who underwent SST from January 2010 to December 2017 were included. Pearson's chi-square cross-tabulation was used to identify individuals with inconsistent 30- and 60-minute serum cortisol test results. Logistic regression analysis was performed to predict normal responses based on the baseline cortisol value.Of the 965 patients identified from pharmacy, medical, and laboratory records, 849 were included. Mean baseline, 30-, and 60-minute cortisol levels after ACTH injection were 394 ±â€Š286.58, 722 ±â€Š327.11, and 827 ±â€Š369.30 nmol/L, respectively. Overall, 715 (84%) and 134 (16%) patients had normal and abnormal responses, respectively. Primary and secondary adrenal insufficiency was diagnosed in 10% and 35%, respectively, while ACTH levels were not measured in 55% of the patients. Overall, 9.49% (n = 72) of the patients had a suboptimal response at 30 minutes, but reached the threshold value of 550 nmol/L at 60 minutes. This particular subgroup's mean change (240 nmol/L) in cortisol level from baseline to 30-minute was higher than that observed in patients with abnormal response at both time-points (mean change, 152 nmol/L). No patient with 30-minute optimal responses had 60-minute suboptimal responses. The baseline serum cortisol threshold of ≥226 nmol/L had 80% sensitivity, 71% specificity, and 93% positive predictive value for detecting a normal SST (P-value < .0001).Relying on a 60-minute cortisol level can identify all normal and abnormal responses, while relying on 30-minute cortisol level alone may produce false-positives. Additionally, a baseline cortisol level of ≥226 nmol/L is a reliable threshold for determining adequate adrenal function, particularly with a low pretest hypoadrenalism probability.

Elicitation of Health Utilities in Oncology in the Kingdom of Saudi Arabia.

PURPOSE: Health utilities (HUs) are quantitative measures of quality of life that are used to derive outcomes such as quality-adjusted life years in cost-effectiveness analyses. In the Kingdom of Saudi Arabia, there are no HUs for cancer. This study aimed to generate HU estimates for various health states associated with cancer in the Kingdom of Saudi Arabia. METHODS: Adult citizens of the Kingdom of Saudi Arabia, patients with cancer, and patients without cancer were recruited to participate in an online version of the Time Trade-Off (TTO) survey, a direct method that asks participants to indicate the amount of time they are willing to trade off in return for full health. The time horizon was 10 years. Patients were surveyed on their own health state; patients without cancer were presented with a scenario describing stage III colon cancer and were asked to act as proxies. RESULTS: Mean HU score was 0.398 (n = 398), 0.315 for patients with cancer (n = 199), and 0.482 for patients without cancer (n = 199). Among patients, the largest subgroup with colorectal cancer (n = 105), had a mean HU of 0.296; the subgroup with the lowest mean HU was patients with hepatocellular cancer (n = 3; 0.047), and the subgroup with the highest mean HU was patients with cholangiocarcinoma (n = 5; 0.508). Overall, the initial stage I subgroup (n = 7) had a mean HU of 0.456; initial stage II (n = 25), 0.240; stage II (n = 67), 0.319; and initial stage IV (n = 77), 0.320. CONCLUSION: To our knowledge, this is the first study of this size to elicit HU scores for cancer in the Kingdom of Saudi Arabia. Patients may have had clinically worse disease than the patients in the scenario that was presented to patients without cancer. Further analyses are warranted for specific types of cancer. These HUs can in turn be applied in cost-utility analyses.

National Survey about awareness of Primary Immunodeficiency Disorders among Primary Care Physicians in Saudi Arabia: Protocol and Challenges.

INTRODUCTION: Primary Health Care Centers (PHCC) are the first contact health facility to which patients in Saudi Arabia can go to seek help. Primary Immunodeficiency Disorders (PIDD) are of various types and severities, and they are associated with a delay in diagnosis. Early diagnosis of PIDD helps to improve the quality of life of affected children and prevent permanent consequences such as organ damage and disability. In this study, we present a protocol of a national survey that assesses awareness among PHCC physicians about diagnosing PIDD and the challenges associated with the execution of this protocol. METHODS: This cross-sectional survey used stratified multistage sampling and systematic random selection of PHCC from a list of PHCC affiliated centers under the Ministry of Health (MOH) in Saudi Arabia. The survey was conducted through phone calls to the selected physicians. Data collection started in April 2020, and it is still ongoing. CONCLUSION: In Saudi Arabia, this study will provide baseline data about PHCC physicians' levels of awareness of the diagnosis of PIDD. This will help policy-makers in designing educational courses or programs to increase awareness levels among physicians. The protocol could be used to study other health outcomes at a national level.

Empirical Monetary Valuation of a Quality-Adjusted Life-Year in the Kingdom of Saudi Arabia: A Willingness-to-Pay Analysis.

BACKGROUND: No willingness-to-pay (WTP) per quality-adjusted life-year (QALY) value exists for the Kingdom of Saudi Arabia (KSA). OBJECTIVE: The primary objective of this study was to determine the WTP for a QALY in the KSA. METHODS: Adult citizens of the KSA, patients with cancer, or members of the general public (MGP) were recruited to participate in a time trade-off survey to elicit health utilities. Cancer was chosen as the disease of interest for patients and the MGP, with a scenario describing stage 3 colorectal cancer, because it is a disease condition that impacts on both quality of life and survival time. In a second step, respondents were asked about their WTP to move from the estimated health state to a state of perfect health for 1 year (QALY). Finally, that amount was processed to generate the WTP for a full QALY. The second step was repeated with a 5-year horizon. Sensitivity analyses were performed without outliers. RESULTS: From 400 participants, data from 378 subjects were obtained and usable: 177 patients, 201 MGP; 278 male, 100 female subjects; 231 aged 26-65 years. Demographic distribution varied widely between the two subgroups for age, education level, and employment status, but with less variation in sex and income. Elicited health utilities were 0.413 (0.472 after adjustment) for the overall group, 0.316 (0.416) for patients, and 0.499 (0.508) for MGP. Overall WTP for a QALY was $US25,600 (adjusted $US32,000) for the 1-year horizon and $US19,200 (adjusted $US22,720) for the 5-year horizon. CONCLUSION: This was the first empirical attempt to estimate the WTP per QALY for the KSA. Results are comparable to those in some other countries and to gross domestic product figures for the KSA. Further research in a country-wide sample is warranted.

Adjunct low-dose ketamine infusion vs standard of care in mechanically ventilated critically ill patients at a Tertiary Saudi Hospital (ATTAINMENT Trial): study protocol for a randomized, prospective, pilot, feasibility trial.

BACKGROUND: A noticeable interest in ketamine infusion for sedation management has developed among critical care physicians for critically ill patients. The 2018 Pain, Agitation/sedation, Delirium, Immobility, and Sleep disruption guideline suggested low-dose ketamine infusion as an adjunct to opioid therapy to reduce opioid requirements in post-surgical patients in the intensive care unit (ICU). This was, however, rated as conditional due to the very low quality of evidence. Ketamine has favorable characteristics, making it an especially viable alternative for patients with respiratory and hemodynamic instability. The Analgo-sedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU patients (ATTAINMENT) trial aims to assess the effect and safety of adjunct low-dose continuous infusion of ketamine as an analgo-sedative compared to standard of care in critically ill patients on mechanical ventilation (MV) for ≥ 24 h. METHODS/DESIGN: This trial is a prospective, randomized, active controlled, open-label, pilot, feasibility study of adult ICU patients (> 14 years old) on MV. The study will take place in the adult ICUs in the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia, and will enroll 80 patients. Patients will be randomized post-intubation into two groups: the intervention group will receive an adjunct low-dose continuous infusion of ketamine plus standard of care. Ketamine will be administered over a period of 48 h at a fixed infusion rate of 2 µg/kg/min (0.12 mg/kg/h) in the first 24 h followed by 1 µg/kg/min (0.06 mg/kg/h) in the second 24 h. The control group will receive standard of care in the ICU (propofol and/or fentanyl and/or midazolam) according to the KFSH&RC sedation and analgesia protocol as clinically appropriate. The primary outcome is MV duration until ICU discharge, death, extubation, or 28 days post-randomization, whichever comes first. DISCUSSION: The first patient was enrolled on 1 September 2019. As of 10 October 2019, a total of 16 patients had been enrolled. We expect to complete the recruitment by 31 December 2020. The findings of this pilot trial will likely justify further investigation for the role of adjunct low-dose ketamine infusion as an analgo-sedative agent in a larger, multicenter, randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020.

Coping with the COVID-19 Pandemic's Unique Challenges Associated with Medical Research: A Saudi Institution Approach.

The spread of COVID-19 has become a significant threat to economic activity throughout the world, and it has made life particularly difficult for research institutions. According to a report published by Spain's largest public research body, Cybermetrics Labs, King Faisal Specialist Hospital and Research Centre (KFSH&RC) is ranked first among the leading hospitals in the Arab world, and it has instituted a wide range of policy changes to accommodate researchers by providing them with additional flexibility. The aim of this project was to highlight the most prevalent COVID-related global challenges facing research institutions and describe how research protocol at KFSH&RC has been adjusted to minimize the disruption experienced by its researchers.

The Risk Of Seizure-Related Hospitalization Among Older Adults On Levetiracetam Monotherapy: A Retrospective Comparative Cohort Study.

BACKGROUND: Antiepileptic drug monotherapy is the mainstay of treatment for epilepsy; however, the efficacy of different antiepileptic drugs in reducing the incidence of seizure-related hospitalization among older adults, who are at higher risk of developing epilepsy compared to their younger counterparts, has not been examined. PURPOSE: The objective of the present study was to compare the rate of seizure-related hospitalization among older adults on levetiracetam compared to different antiepileptic drugs (AEDs). PATIENTS AND METHODS: This was a retrospective cohort study of older adults (≥60 years) in two tertiary care hospitals. Patients who are 60 years of age and older, have a confirmed diagnosis of epilepsy, and are taking a single and the same antiepileptic drug for at least 36 months were included. The patients were followed up for 24 months after 12 months of treatment with no incidence of seizure-related hospitalization via their health records. Multiple Poisson regression with robust error variance was used to estimate the relative risk of hospitalization for patients on levetiracetam compared to different antiepileptic drugs controlling for age, gender, number of prescription medications, dosage strengths, and Charlson Comorbidity Index (CCI) score. RESULTS: One hundred and thirty-six patients met the inclusion criteria and were included in the study. The recruited patients were on one of the following four antiepileptic drugs: carbamazepine (n=44), levetiracetam (n=39), phenytoin (n=31), and valproic acid (n=22). Patients on levetiracetam were more than twice as likely to be hospitalized due to seizures within the 24 months of follow-up compared to their counterparts on other AEDs (RR=2.76, 95% CI=1.16-6.53, P=0.021). CONCLUSION: This study suggests that older adults on old generation AEDs such as phenytoin, carbamazepine, and valproic acid appear to have a lower risk of seizure-related hospitalization compared to their counterparts on levetiracetam.

Assessment of Late Thromboembolic Complications Post-Fontan Procedure in Relation to Different Antithrombotic Regimens: 30-Years' Follow-up Experience.

Background: The current CHEST guidelines recommend the use of antithrombotic therapy, either aspirin or warfarin, as a primary thromboembolic complications (TECs) prophylaxis in patients who undergo Fontan procedure, without specification on drug selection or duration of therapy. Objective: To investigate the incidence rate of late TECs, occurring after 1-year post-Fontan procedure and to assess the difference in rate of late TECs between warfarin and aspirin. Methods: A retrospective cohort study included patients who had Fontan procedures between 1985-2010 at our institution. Patients were stratified according to the antithrombotic regimen-warfarin, aspirin, or no therapy-at the time of TECs. Results: We screened 499 patients who underwent Fontan procedures; 431 procedures met the inclusion criteria. Over a median follow-up of 13.6 years (IQR= 8.7), freedom from late TECs at 5, 10, 15, and 20 years was 97.54%, 96.90%, 90.78%, and 88.07%, respectively. There was no difference in late TEC incidence rates per 1000 patient-years between warfarin and aspirin: 7.82 and 5.83 events, respectively; rate ratio= 1.34 (95% CI= 0.68-2.60). Warfarin was associated with a higher major bleeding incidence rate per 1000 patient-years: 3.70 versus 2.91 events with aspirin; rate ratio= 1.27 (95% CI= 0.49 to 3.29). Conclusion and Relevance: The incidence rate of late clinical TECs post-Fontan procedure in our population is low. Warfarin was not superior to aspirin for prevention of late TECs. Yet warfarin was associated with a higher rate of bleeding. This finding suggests a simpler antithrombotic regimen for prevention of TEC after 1-year post-Fontan procedure.