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.

Efficacy of Prostacyclin Anticoagulation in Critically Ill Patients Requiring Extracorporeal Support: A Systematic Review and Meta-Analysis.

Extracorporeal support modalities are highly prothrombotic. Anticoagulation is frequently used for patients receiving Continuous Renal Replacement Therapy (CRRT), Molecular Adsorbent Recirculating System (MARS), and Extracorporeal Membrane Oxygenation (ECMO). The objective of this systematic review and meta-analysis is to determine if prostacyclin-based anticoagulation strategies are effective compared to other anticoagulation strategies, in critically ill children and adults who needs extracorporeal support, such as continuous renal replacement therapy. We conducted a systematic review and meta-analysis using multiple electronic databases and included studies from inception to June 1, 2022. Circuit lifespan, proportion of bleeding, thrombotic, and hypotensive events, and mortality were evaluated. Out of 2,078 studies that were screened, 17 studies (1,333 patients) were included. The mean circuit lifespan was 29.7 hours in the patients in the prostacyclin-based anticoagulation series and 27.3 hours in the patients in the heparin- or citrate-based anticoagulation series, with a mean difference of 2.5 hours (95%CI -12.0;16.9, p=0.74, I2=0.99, n=4,003 circuits). Bleeding occurred in 9.5% of the patients in the prostacyclin-based anticoagulation series and in 17.1% of the patients in the control series, which was a statistically significant decrease (LogOR -1.14 (95%CI -1.91;-0.37), p<0.001, I2=0.19, n=470). Thrombotic events occurred in 3.6% of the patients in the prostacyclin-based anticoagulation series and in 2.2% of the patients in the control series, which was not statistically different (LogOR 0.97 (95%CI -1.09;3.04), p=0.35, I2=0.0, n=115). Hypotensive events occurred in 13.4% of the patients in the prostacyclin-based anticoagulation series and in 11.0% of the patients in the control series, which was not statistically different (LogOR -0.56 (95%CI -1.87;0.74), p=0.40, I2=0.35, n=299). The mortality rate was 26.3% in the prostacyclin-based anticoagulation series, and 32.7% in the control series, which was not statistically different (LogOR -0.40 (95%CI -0.87;0.08), p=0.10, I2=0.00, n=390). The overall risk of bias was low to moderate. In this systematic review and meta-analysis of 17 studies, prostacyclin-based anticoagulation was associated with fewer bleeding events, but with similar circuit lifespans, thrombotic events, hypotensive events, and mortality rates. The potential benefits of prostacyclin-based anticoagulation should be explored in large randomized controlled trials.

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.

Utility of patient information leaflet and perceived impact of its use on medication adherence.

BACKGROUND: Although patients frequently use patient information leaflets (PILs) to obtain information about medicine, their confidence in using it may be diminished after reading it. This study aimed to assess the public perception of PIL's quality and the perceived impact of its use on medication adherence. METHODS: A community-based cross-sectional study of 1,138 adult individuals in Saudi Arabia, April-May 2020, was conducted via Survey Monkey using an anonymous validated e-questionnaire. Data were collected on personal characteristics, PIL readership and preferences, perception towards PIL quality and impact of its use on taking medication, and reasons for not reading PIL. In addition, logistic regression analysis was performed to identify the significant predictors of reading PIL. Significance was considered at p < 0.05. RESULTS: Nearly all participants (91.1%) reported reading PIL. The more read PIL's sections were directions of use (52.7%) and side effects (30.3%). Female gender (OR = 5.64, 95%CI: 3.53,9.02), age over 40 years (OR = 2.80, 95%CI: 1.69,4.64), and secondary education or more (OR = 1.74, 95%CI: 1.06,2.85) were the significant predictors of reading PIL. The majority of PIL readers reported their preference for verbal information (65.8%), hard copy presentation (77%), adding graphics (71.1%), and concise content of PIL (68.8%). In addition, most participants reported PIL always/usually adds to their knowledge of medicines (70.6%) and said that PIL reading positively impacted their medication adherence (64.9%). For only 8.8%, PIL reading negatively impacted their adherence, primarily because of reading information on medicine's side effects and complications (74.4%). More than one-half of participants perceived the PIL quality as good/excellent in terms of; font size (51.3%), language comprehensiveness (64.9%), paper quality (68.0%), and general appearance (64.9%). Getting sufficient information from doctors and pharmacists was the main reason for not reading the PIL (59.2%). Most participants (92.5%) agreed on standardizing how information is displayed in the PIL among all PILs of all companies. CONCLUSION: PIL is read by nearly all the study sample, especially females, older, and educated subjects. It was perceived as beneficial in upgrading medication adherence. Effective designing of PILs should focus on patients' literacy level and age. Standardization of the PIL structure in all pharmaceutical companies is recommended.

Type I interferon autoantibodies in hospitalized patients with Middle East respiratory syndrome and association with outcomes and treatment effect of interferon beta-1b in MIRACLE clinical trial.

Background: Type I interferons (IFNs) are essential antiviral cytokines induced upon respiratory exposure to coronaviruses. Defects in type I IFN signaling can result in severe disease upon exposure to respiratory viral infection and are associated with worse clinical outcomes. Neutralizing autoantibodies (auto-Abs) to type I IFNs were reported as a risk factor for life-threatening COVID-19, but their presence has not been evaluated in patients with severe Middle East respiratory syndrome (MERS). Methods: We evaluated the prevalence of type I IFN auto-Abs in a cohort of hospitalized patients with MERS who were enrolled in a placebo-controlled clinical trial for treatment with IFN-ß1b and lopinavir-ritonavir (MIRACLE trial). Samples were tested for type I IFN auto-Abs using a multiplex particle-based assay. Results: Among the 62 enrolled patients, 15 (24.2%) were positive for immunoglobulin G auto-Abs for at least one subtype of type I IFNs. Auto-Abs positive patients were not different from auto-Abs negative patients in age, sex, or comorbidities. However, the majority (93.3%) of patients who were auto-Abs positive were critically ill and admitted to the ICU at the time of enrollment compared to 66% in the auto-Abs negative patients. The effect of treatment with IFN-ß1b and lopinavir-ritonavir did not significantly differ between the two groups. Conclusion: This study demonstrates the presence of type I IFN auto-Abs in hospitalized patients with MERS.

Heterogeneity of treatment effect of interferon-ß1b and lopinavir-ritonavir in patients with Middle East respiratory syndrome by cytokine levels.

Animal and human data indicate variable effects of interferons in treating coronavirus infections according to inflammatory status and timing of therapy. In this sub-study of the MIRACLE trial (MERS-CoV Infection Treated with a Combination of Lopinavir-Ritonavir and Interferon ß-1b), we evaluated the heterogeneity of treatment effect of interferon-ß1b and lopinavir-ritonavir versus placebo among hospitalized patients with MERS on 90-day mortality, according to cytokine levels and timing of therapy. We measured plasma levels of 17 cytokines at enrollment and tested the treatment effect on 90-day mortality according to cytokine levels (higher versus lower levels using the upper tertile (67%) as a cutoff point) and time to treatment (≤ 7 days versus > 7 days of symptom onset) using interaction tests. Among 70 included patients, 32 received interferon-ß1b and lopinavir-ritonavir and 38 received placebo. Interferon-ß1b and lopinavir-ritonavir reduced mortality in patients with lower IL-2, IL-8 and IL-13 plasma concentrations but not in patients with higher levels (p-value for interaction = 0.09, 0.07, and 0.05, respectively) and with early but not late therapy (p = 0.002). There was no statistically significant heterogeneity of treatment effect according to other cytokine levels. Further work is needed to evaluate whether the assessment of inflammatory status can help in identifying patients with MERS who may benefit from interferon-ß1b and lopinavir-ritonavir. Trial registration: This is a sub-study of the MIRACLE trial (ClinicalTrials.gov number, NCT02845843).

Effect of melatonin in children with neurodevelopmental disabilities and sleep disorders.

Objectives: The aim of this study is to assess the efficacy and side effects of melatonin use in a population of children with neurodevelopmental disabilities who had sleep disorders. Methods: This is a cross-sectional study conducted in the pediatric neurology clinic at King Abdulaziz Medical City. A designed questionnaire was given to the parents to inquire about the sleep characteristics of their children before and after using melatonin. The patients' demographic data were collected and different parameters before and after starting melatonin were compared. Categorical variables were summarized and reported in terms of frequency and percent (n%). Continuous variables were reported in terms of mean and standard deviation. Results: A total of 23 patients were enrolled in our study, of which 15 (65.22%) were male. The mean age was 5.83 ± 3.07 years. For melatonin dose, 9 (39.13%) received 1 mg, 8 (34.78%) received 2 mg, and 6 (26.09%) received over 3 mg. Regarding melatonin duration of use, 7 (30.43%) received melatonin for 0 to 6 months, 7 (30.43%) received it for 7 to 12 months, and 9 (39.13%) received it for over a year. Significant differences were observed in time taken to fall asleep (P =0.046), the number of times the child woke up at night (P =0.071), total sleep time within 24 hours (P =.011), and time taken to wake up (P =.007), while no significant difference was observed in the number of naps taken during the daytime (P =.801). There were no major side effects reported. Conclusion: Melatonin had a significant impact on total sleep time and quality during the pre and post assessment of children with neurodevelopmental disabilities and sleep disorders.

Patterns of adverse drug reactions (ADRs) in Saudi Arabia.

BACKGROUND: Pharmacovigilance enhances post-market drug safety. However, analytical reports of a pattern of adverse drug reactions (ADRs) experienced by patients in Saudi Arabia are demanded. OBJECTIVE: To describe patterns of ADRs submitted to the Saudi Central National Pharmacovigilance and Drug Safety Center (NPC), Saudi Food and Drug Administration (SFDA), from its inception in 2015 until the end of 2017 to understand the pattern of ADR reporting in Saudi Arabia. METHODS: In this retrospective study, data from cases reported to the NPC were used to determine ADRs and identify the most common associated drug classes based on anatomical therapeutic chemical (ATC) classification system. RESULT: A total of 17,730 ADR cases were reported during study period. An annual increase in ADRs was clearly evident. Approximately 54% of the total ADRs reported were serious. Most commonly reported ATC drug classes were anti-infective agents for systemic use (22.27%), antineoplastic and immunomodulating agents (21.49%), alimentary tract and metabolism (15.48 %), cardiovascular system (11.11%) and nervous system (10.23%). Vancomycin (2.7%), ceftiraxone (1.8%), fingolimod (1.4%) and paracetamol (1.4%) were the most common drugs associated with serious ADRs. CONCLUSION: This study provide valuable insights in hypothesis generation for future studies on drug-event interactions and amplification studies. The NPC educational programs and awareness campaigns to promote systematic reporting of ADRs among healthcare professionals and general public should be continued.

Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial.

OBJECTIVE: To evaluate whether favipiravir reduces the time to viral clearance as documented by negative RT-PCR results for severe acute respiratory syndrome coronavirus 2 in mild cases of coronavirus disease 2019 (COVID-19) compared to placebo. METHODS: In this randomized, double-blinded, multicentre, and placebo-controlled trial, adults with PCR-confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day 1 followed by 800 mg twice daily (n = 112) or a matching placebo (n = 119) for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, intensive care unit admissions, adverse events, and 28-day mortality. RESULTS: Two hundred thirty-one patients were randomized and began the study (median age, 37 years; interquartile range (IQR): 32-44 years; 155 [67%] male), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board recommended stopping enrolment because of futility at the interim analysis. The median time to viral clearance was 10 days (IQR: 6-12 days) in the favipiravir group and 8 days (IQR: 6-12 days) in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571-1.326; p = 0.51). The median time to clinical recovery was 7 days (IQR: 4-11 days) in the favipiravir group and 7 days (IQR: 5-10 days) in the placebo group. There was no difference between the two groups in the secondary outcome of hospital admission. There were no drug-related severe adverse events. CONCLUSION: In this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment.

Accuracy of Antibiotic Allergy Documentation and the Validity of Physicians' Decision in a Pediatric Tertiary Care Setting.

BACKGROUND: Patients allergic to antibiotics are at higher risk of receiving treatment with a broader spectrum, more harmful, and expensive agents. The aims of this study were (1) to assess the quality of documentation of antibiotics allergies in the electronic medical records (EMR) in a Pediatric tertiary care setting, and (2) to determine the validity of physicians' decision to hold antibiotics prescriptions. METHODS: This is a retrospective cohort study at King Abdullah Specialized Children Hospital, Riyadh, Saudi Arabia. A review of the EMR and all Adverse Drug Reaction (ADR) reports of pediatric patients 1-14 years old, with a documented allergy to antibiotics from June 2016 until June 2019. The quality of documentation of antibiotics allergy was assessed based on the presence of four parameters: 1) allergy alert notification, 2) allergy severity classification, 3) setting notes, and 4) symptoms' description. In addition, all physicians' reports of allergy to antibiotics were cross-classified according to their corresponding ADR reports, and the validity of physicians' documentation of allergy was assessed. RESULTS: Of a total of 105 Pediatric patients' EMR, documentation of antibiotics allergy was available in 98 (93.3%), with the presence of symptoms description (83%), allergy notes (87%), severity (67%), and signs of alert (50.8%). Overall documentation quality was good for only 23.5% of patients, while it was poor for 35.7%. Physicians' documentation of antibiotics allergy was 0.82 sensitive [with 0.18 risk of allergy] and 0.60 specific [with 0.40 unnecessary restrictions of prescriptions]. Of all children with possible/actual allergies, only 38.9% were referred to the immunology clinic. CONCLUSION: The quality of documentation of antibiotic allergy in children and the validity of physicians' decisions are less than satisfactory. Therefore, improving communications between all healthcare providers regarding patients' allergy status and follow-up for further assessment of the reaction is recommended to improve patient care.

Evaluation of thiamine as adjunctive therapy in COVID-19 critically ill patients: a two-center propensity score matched study.

BACKGROUND: Thiamine is a precursor of the essential coenzyme thiamine pyrophosphate required for glucose metabolism; it improves the immune system function and has shown to reduce the risk of several diseases. The role of thiamine in critically ill septic patient has been addressed in multiple studies; however, it's role in COVID-19 patients is still unclear. The aim of this study was to evaluate the use of thiamine as an adjunctive therapy on mortality in COVID-19 critically ill patients. METHODS: This is a two-center, non-interventional, retrospective cohort study for critically ill patients admitted to intensive care units (ICUs) with a confirmed diagnosis of COVID19. All patients aged 18 years or older admitted to ICUs between March 1, 2020, and December 31, 2020, with positive PCR COVID-19 were eligible for inclusion. We investigated thiamine use as an adjunctive therapy on the clinical outcomes in critically ill COVID-19 patients after propensity score matching. RESULTS: A total of 738 critically ill patients with COVID-19 who had been admitted to ICUs were included in the study. Among 166 patients matched using the propensity score method, 83 had received thiamine as adjunctive therapy. There was significant association between thiamine use with in-hospital mortality (OR = 0.39; 95% CI 0.19-0.78; P value = 0.008) as well as the 30-day mortality (OR = 0.37; 95% CI 0.18-0.78; P value = 0.009). Moreover, patients who received thiamine as an adjunctive therapy were less likely to have thrombosis during ICU stay [OR (95% CI) 0.19 (0.04-0.88), P value = 0.03]. CONCLUSION: Thiamine use as adjunctive therapy may have potential survival benefits in critically ill patients with COVID-19. Additionally, it was associated with a lower incidence of thrombosis. Further interventional studies are required to confirm these findings.

Reported adverse effects following COVID-19 vaccination at a tertiary care hospital, focus on cerebral venous sinus thrombosis (CVST).

Objectives: Several cases of unusual thrombotic events with thrombocytopenia were reported in several countries, in association with AstraZeneca's COVID-19 vaccine. The European medicines agency conducted a detailed review and concluded that there was no evidence to suggest an association of thrombotic events with the use of COVID-19 vaccine AstraZeneca.Methods: King Abdulaziz Medical City is a 1500 bed tertiary care hospital in Riyadh, Saudi Arabia; this study describes spontaneously reported vaccine adverse effects received through the hospital's internal electronic safety reporting system from December 2020 to 13 April 2021.We assessed each report for causality association utilizing the world health organization's (WHO) causality assessment of an adverse event following immunization (AEFI) classification 2nd Edition 2019.Results: The majority of the reported events were mild to moderate, there were five serious events, one reported cardiac arrest, two cerebral venous sinus thrombosis, and two pulmonary embolism. Clinical and laboratory summary of the five patients are presented in detail.Conclusions: Efforts of pharmacovigilance in mediating the rare risk of thrombosis associated with COVID-19 vaccine are crucial in providing awareness on the possible risk factors and signs/symptoms that should raise red flags.

Multicentre randomised double-blinded placebo-controlled trial of favipiravir in adults with mild COVID-19.

INTRODUCTION: A novel coronavirus, designated SARS-CoV-2, caused an international outbreak of a respiratory illness, termed COVID-19 in December 2019. There is a lack of specific therapeutic agents based on evidence for this novel coronavirus infection; however, several medications have been evaluated as a potential therapy. Therapy is required to treat symptomatic patients and decrease the virus carriage duration to limit the communitytransmission. METHODS AND ANALYSIS: We hypothesise that patients with mild COVID-19 treated with favipiravir will have a shorter duration of time to virus clearance than the control group. The primary outcome is to evaluate the effect of favipiravir on the timing of the PCR test conversion from positive to negative within 15 days after starting the medicine.Adults (>18 years, men or nonpregnant women, diagnosed with mild COVID-19 within 5 days of disease onset) are being recruited by physicians participating from the Ministry of National Guard Health Affairs and the Ministry of Health ethics committee approved primary healthcare centres. This double-blind, randomised trial comprises three significant parts: screening, treatment and a follow-up period. The treating physician and patients are blinded. Eligible participants are randomised in a 1:1 ratio to either the therapy group (favipiravir) or a control group (placebo) with 1800 mg by mouth two times per day for the first day, followed by 800 mg two times per day for 4-7 days. Serial nasopharyngeal/oropharyngeal swab samples are obtained on day 1 (5 days before therapy). On day5±1 day, 10±1 day, 15±2 days, extra nasopharyngeal/oropharyngeal PCR COVID-19 samples are requested.The primary analysis population for evaluating both the efficacy and safety outcomes will be a modified intention to treat population. Anticipating a 10% dropout rate, we expect to recruit 288 subjects per arm. The results assume that the hazard ratio is constant throughout the study and that the Cox proportional hazard regression is used to analyse the data. ETHICS AND DISSEMINATION: The study was approved by the King Abdullah International Medical Research Centre Institutional Review Board (28 April 2020) and the Ministry of Health Institutional Review Board (1 July 2020). Protocol details and any amendments will be reported to https://clinicaltrials.gov/ct2/show/NCT04464408. The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: National Clinical Trial Registry (NCT04464408).

Behavior Responses and Attitude of the Public to COVID-19 Pandemic During Movement Restrictions in Saudi Arabia.

BACKGROUND: The behavior of the general public and the adoption of precautionary measures during a pandemic determine the fate of the country in the absence of any specific cure. This study aimed to determine the public attitude and behavior responses to the COVID-19 pandemic in Saudi Arabia during movement restrictions, and the predictors of behavioral responses. METHODS: A community-based cross-sectional study of 2470 adult individuals in Saudi Arabia, 17-29 April 2020 was conducted via Survey Monkey, using an anonymous validated e-questionnaire. Data were collected on demographic characteristics, COVID-19-related attitudes, and behavioral responses in terms of; precautionary measures, preparedness, and self-quarantine activities, to be responded to by 4-point Likert scales. Multiple linear regression analyses were performed to identify the significant predictors of compliance with different behaviors. Significance was considered at p<0.05. RESULTS: Participants reported positive attitudes towards governmental actions (95%), self-hygiene (93.2%), social distancing (97.1%) and choice of healthy food (89.6%), and negative attitudes towards the current worldwide situation of the pandemic (81.0%) and hearing someone tested positive (77.8%) or died from COVID-19 (83.7%). High rates of compliance to behavior were reported by only 55.8% of participants in terms of precautionary measures (71.3%), preparedness (38.4%), and self-quarantine activities (46.1%). After adjusting for all possible confounders, the total attitude score was a significant predictor of the total scores of precautionary measures (t=12.01, p<0.001), preparedness (t=9.29, p<0.001), self-quarantine activities (t=12.05, p<0.001), and overall behavior response (t=14.09, p<0.001). Other significant predictors of higher overall behavior response scores were female gender (t=7.22, p<0.001) and non-Saudi nationality (t=3.40, p<0.001). CONCLUSION: This study provides baseline data on the behavioral response to the national COVID-19 pandemic in Saudi Arabia. The levels of compliance to behavior response and attitude to COVID-19 pandemic were less than satisfactory. Socio-demographics influence public behavior and protective health measures. COVID-19 awareness programs are recommended.

Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome.

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).

Efficacy of scopolamine transdermal patch in children with sialorrhea in a pediatric tertiary care hospital.

BACKGROUND: Drooling is common in children with neurological disorders, but its management is very challenging, Scopolamine transdermal patch (STP) appears to be useful in controlling drooling, although it is not approved for this indication and there are limited clinical studies about its effectiveness. This study aimed (1) to assess the impact of STP use on the severity of drooling and on the frequency of emergency department (ED) and hospital readmission (RA) visits related to drooling, and (2) to determine the level of family satisfaction with STP when used in children with neurological disorders. METHODS: This is a retrospective cohort study of all pediatric patients aged 3-14 years, with non-progressive neurodevelopmental disability, who used STP for more than one year during the period between April 2015 and July 2018 (n = 44). Data on demographics, clinical status, comorbidities, STP dose and duration, other medications, ED and RA visits were collected. Follow-up phone-call interviews with parents/caregivers were performed using a parent-reported frequency and severity rating scale of sialorrhea. Absolute and relative risk reductions were calculated to assess the impact of STP on ED and RA visits. Significance was considered at p-value of ≤ 0.05. RESULTS: STP use showed significant reduction in severity of drooling (p < 0.001), wiping of the child's mouth (p < 0.001), bibs or clothing changes (p < 0.001), choking and aspiration of saliva (p = 0.001). The Relative Risk Reduction of the drooling-related ED and RA visits were 86% and 67% respectively. Nearly two-thirds (60%) of caregivers were satisfied with using STP. CONCLUSIONS: This is the first study of its kind done in Saudi Arabia demonstrating favorable impact of STP use by children on the consequences associated with drooling and with the frequency of ER and RA visits due to drooling. Development of a medication use protocol is recommended to standardize STP treatment in order to optimize its effectiveness. This study serves as baseline information for future prospective interventional studies.

Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-ß1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial.

The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-ß1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-ß1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.

An Evaluation Of Antibiotics Prescribing Patterns In The Emergency Department Of A Tertiary Care Hospital In Saudi Arabia.

BACKGROUND: Antibiotic prescriptions at emergency departments (ED) could be a primary contributing factor to the overuse of antimicrobial agents and subsequently antimicrobial resistance. The aim of this study was to describe the pattern of antibiotic prescriptions at an emergency department of a tertiary care hospital in Saudi Arabia. METHODS: A cross-sectional study, based on a review of antibiotic prescriptions was conducted. All cases who visited the emergency department over a three-month period with a complaint of infection were analyzed in terms of patient characteristics (age, sex, infection type, and number of visits) and prescription characteristics (antibiotic category, spectrum, course and costs). The World Health Organization and International Network of Rational Use of Drugs prescribing indicators were presented. Descriptive and analytic statistics were applied. RESULTS: A total of 36,069 ED visits were recorded during the study period, of which 45,770 drug prescriptions were prescribed, including 6,354 antibiotics. The average number of drugs per encounter was 1.26, while the percentage of encounters with a prescribed antibiotic was 17.6%. Among antibiotic prescriptions, the percentage of encounters with injection antibiotics was 15.2%. Almost 77% of antibiotics were prescribed by their generic names, and the percentage of antibiotics prescribed from the essential list was 100%. CONCLUSION: The average number of drugs per encounter in general and antibiotics per encounter in specific at this setting was lower than the standard value. However, the percentage of antibiotics prescribed by its generic name was less than optimal.

Implementation of an ACPE-Accredited PharmD Curriculum at a Saudi College of Pharmacy.

Objective. To establish an academic curricular collaboration between the newly established college of pharmacy at King Saud Bin Abdulaziz Saudi University for Health Sciences (KSAU-HS) and a US college of pharmacy accredited by the Accreditation Council for Pharmacy Education, and assess measures of success. Methods. Criteria for selecting a college for collaboration were established. A systematic approach was followed in negotiating legal, logistical, and financial issues with the selected collaborating institution. Course materials were transferred and implemented and minimal changes were made to the alignment and sequencing of lectures. The faculty at KSAU-HS developed and implemented research and seminar courses. Pharmacy practice experiences were designed and rubrics were developed. Results. All courses were implemented successfully. The PharmD students scored significantly higher in all academic levels in a benchmarked progress test than did students in other programs. Students' evaluation of 43 first-, second-, and third-year courses in 2017-2018 using a survey that assessed numerous aspects of each course showed significantly higher overall satisfaction than the institutional averages. Also, female students indicated significantly higher satisfaction with the PharmD program than did male students. Conclusion. The transfer and implementation of an accredited PharmD curriculum to the KSAU-HS College of Pharmacy went smoothly and the program was launched on time. Learning and teaching success was facilitated by the KSAU-HS faculty. Program outcomes were verified by students' high scores on a benchmarked examination and by their satisfaction with the courses.

Knowledge of and attitudes toward clinical trials in Saudi Arabia: a cross-sectional study.

OBJECTIVES: Clinical trials (CTs) are considered an important method for developing new treatments and providing access to potentially effective drugs that are still under investigation. Measuring the public's knowledge of and attitudes toward CTs is important for assessing their readiness for and acceptance of human drug testing, which has previously not been assessed in the Kingdom of Saudi Arabia (KSA). The objective of this study is to explore the Saudi public's knowledge of and attitudes toward CTs as well as participation in trials to test new or approved drugs. DESIGN: Cross-sectional. SETTING: The 2016 Al Jenadriyah cultural/heritage festival in Riyadh, KSA. PARTICIPANTS: Participating booths and exhibition halls, as well as festival visitors, were approached to participate in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Knowledge of and attitudes toward CTs. RESULTS: The final number of participants was 938. The responses were converted to a percentage mean score (out of 100) for each knowledge-related response and attitude. The total mean knowledge score was 56.8±24.8 and the attitude-related score was 61.5±28.0. Although most of the participants supported testing approved or off-label and new drugs on adult and paediatric patients, only a third (30.5%) agreed that new drugs could be tested on healthy volunteers. The results indicated that gender, educational level, income, medical background, age and health insurance were independently associated with the level of knowledge of CTs. In terms of attitudes toward CTs, the factors that were independently associated were gender, educational level and medical background. CONCLUSIONS: The Saudi public has a low level of knowledge and a moderately positive attitude toward CTs. There is a moderate positive correlation between the two factors such that as knowledge of CTs increases, the Saudi public will hold more positive attitudes toward CTs.