Search

Introduction Antiviral drugs have shown limited effectiveness in treating patients with coronavirus disease 2019 (COVID-19). We aimed to assess the effects of a favipiravir and hydroxychloroquine combination on treating moderate-to-severe COVID-19 patients. Methods An investigator-initiated, multicenter, open-label, randomized trial at nine hospitals. Eligible patients were adults with moderate-to-severe COVID-19 defined as oxygen saturation (SaO2) of ≤ 94% while breathing ambient air or significant clinical symptoms with chest x-ray changes requiring hospital admission. Randomization was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The primary outcome was time to clinical improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population. Results From May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 to the treatment. The mean age was 52 (± 13) years, and 103 (41%) were women. At randomization, six patients were on invasive mechanical ventilation, 229 (90.15%) were requiring supplemental oxygen only (with or without non-invasive ventilation), and 19 (7.48%) were receiving neither. The time to clinical improvement was not significantly different between the groups: median of 9 days in the treatment group and 7 days in the control group (HR: 0.845; 95% CI 0.617–1.157; p-value = 0.29). The 28-day mortality was not significantly different between the groups (7.63% treatment) vs. (10.32% control); p-value = 0.45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group. Conclusion The combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19. Clinical Trial Registration ClinicalTrials.gov (NCT04392973). Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00496-6.

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.

Summary Background ChAdOx1-vectored vaccine candidates against several pathogens have been developed and tested in clinical trials and ChAdOx1 nCoV-19 has now been licensed for emergency use for COVID-19. We assessed the safety and immunogenicity of the ChAdOx1 MERS vaccine in a phase 1b trial in healthy Middle Eastern adults. Method MERS002 is an open-label, non-randomised, dose-escalation, phase 1b trial. Healthy Middle Eastern adults aged 18–50 years were included in the study. ChAdOx1 MERS was administered as a single intramuscular injection into the deltoid muscle of the non-dominant arm at three different dose groups: 5·0 × 109 viral particles in a low-dose group, 2·5 × 1010 viral particles in an intermediate-dose group, and 5·0 × 1010 viral particles in a high-dose group. The primary objective was to assess the safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited and unsolicited adverse events after vaccination for up to 28 days and occurrence of serious adverse events up to 6 months. The study is registered with ClinicalTrials.gov, NCT04170829. Findings Between Dec 17, 2019, and June 1, 2020, 24 participants were enrolled (six to the low-dose, nine to the intermediate-dose, and nine to the high-dose group) and received a dose; 23 were available for follow-up at 6 months. The one dose of ChAdOx1 MERS vaccine was well tolerated with no serious adverse event reported during the 6 months of follow-up. Most adverse events were mild (67, 74%) and moderate (17, 19%). Six (7%) severe adverse events were reported by two participants in the intermediate-dose group (two feverish, two headache, one joint pain, and one muscle pain). Pain at the injection site was the most common local and overall adverse event, reported by 15 (63%) of the 24 participants. The most common systemic adverse event was headache, reported by 14 (58%), followed by muscle pain reported by 13 (54%). The vaccine induced both antibody and T cell immune responses in all volunteers; antibodies peaked at day 28 and T cell responses peaked at day 14; and continued until the end of follow-up at 6 months. Interpretation The acceptable safety and immunogenicity data from this phase 1b trial of ChAdOx1 MERS vaccine candidate in Healthy Middle Eastern adults, combined with previous safety and immunogenicity data from a trial in the UK, support selecting the ChAdOx1 MERS vaccine for advancement into phase 2 clinical evaluation. Funding UK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research; and King Abdullah International Medical Research Center.

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.

Majed Al Jeraisy,1,2 Shaden Al Osaimi,1 Abdullah Al Hawas,1 Alanoud Muamar,1 Lamia Aleidi,3 Njoud Khonain,4 Mostafa A Abolfotouh2 1College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia; 2King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia; 3Unaizah College of Pharmacy, Qassim University, Riyadh, Saudi Arabia; 4College of Pharmacy, Princess Noura Bint Abdulrahman University, Riyadh, Saudi ArabiaCorrespondence: Mostafa A AbolfotouhKing Abdullah International Medical Research Center (KAIMRC)/King Saud bin-Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard- Health Affairs, P.O. Box 3660, Riyadh, 11426, Saudi ArabiaTel +966 11 429-4460; +966 503659204Fax +966 11 429-4440Email mabolfotouh@gmail.comBackground: 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.Keywords: flagging, drug allergy, allergy documentation, quality, Naranjo scale

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.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.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 (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.

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.

Background: Thiamine is a precursor of the essential coenzyme thiamine pyrophosphate (TPP) required for glucose metabolism; it improves the immune system function and has been shown to reduce the risk of several diseases. The role of thiamine in COVID-19 critically ill patients is still unclear, however, its role in the critically ill septic patient has been addressed in multiple studies. The objective of this study was to evaluate the use of thiamine as adjunctive therapy on the mortality in COVID 19 critically ill patients. Methods: This is a multicenter, non-interventional, retrospective cohort study for all critically ill patients admitted to intensive care units (ICUs) with a confirmed diagnosis of COVID19. All patients aged 18 years or older who were admitted to ICUs between March 1st to December 31st, 2020 with positive PCR COVID-19 were included in the study. We investigated the association between thiamine use as an adjunctive therapy and clinical outcomes in COVID -19 after propensity score matching using baseline severity scores, systemic use of corticosteroids and study centers. Results: A total of 738 critically ill patients with COVID-19 who had been admitted in ICUs at the two governmental hospitals included in the study. Among 166 patients matched using propensity score, 83 had received thiamine as adjunctive therapy. There was significant association between thiamine use with in-hospital mortality (OR=0.49; 95% CI = 0.25- 0.97; P=0.04) as well with 30-day ICU mortality (OR=0.45; 95% CI = 0.215- 0.935; P=0.03). Moreover, patients who received thiamine as an adjunctive therapy were less likely to have thrombosis during ICU stay by 81 % (OR (95%CI): 0.19 (0.040,0.884), p-value=0.034).Conclusion: Thiamine use as an adjunctive therapy may have potential survival benefits in critically ill patients with COVID-19.

IntroductionA 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 analysisWe 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 disseminationThe 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 numberNational Clinical Trial Registry (NCT04464408).

Mostafa A Abolfotouh,1– 3 Adel F Almutairi,1– 3 Ala’a Banimustafa,1– 3 Soheir A Hagras,4 Majed Al Jeraisy1– 3 1King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 2King Saud Bin-Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 3King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia; 4Inaya Medical College, Riyadh, Saudi ArabiaCorrespondence: Mostafa A AbolfotouhKing Abdullah International Medical Research Center (KAIMRC)/King Saud Bin-Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard- Health Affairs, Riyadh, 11426, Saudi ArabiaTel +966 (11) 429-4460; +966 503659204Fax +966 (11) 429-4440Email mabolfotouh@gmail.comBackground: 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.Keywords: SARS-CoV-2, lockdown, perception, behavior, compliance, preparedness, precautionary measures, self-quarantine

Objectives The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. Trial design This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm. Participants All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. Intervention and comparator The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief . Main outcomes The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization). Randomisation Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission. Blinding (masking) This is an Open label study and only the analyst will be blinded during the study conduct. Numbers to be randomised (sample size) Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group). Trial status Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020. Trial registration ClinicalTrials.gov Identifier: NCT04392973, 19 May 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Muath Fahmi Najjar,1,2 Syed Azhar Syed Sulaiman,2 Majed Al Jeraisy,1 Hashim Balubaid3 1King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Science, College of Pharmacy, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia; 2Pharmaceutical Sciences School, Clinical Pharmacy Discipline, Universiti Sains Malaysia, Penang, Malaysia; 3King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Science, College of Medicine, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia Background: There is a difference between evidence-based guidelines for geriatric patients and clinical practice of physicians. Prescribing potentially inappropriate medications (PIMs) can be attributed to the fact that many physicians are not aware of PIMs usage. Aim: The aim of this study was to assess the effectiveness of a combined intervention program comprising an educational and clinical pharmacist intervention to reduce the incidence of PIMs among hospitalized geriatric patients. Methods: This was a prospective pre-test versus post-test design study. The screening tool of older persons’ prescriptions, 2nd version, and 2015 American Geriatric Society Beers’ criteria were used to assess the appropriateness of medications prescribed for geriatric inpatients. The study was carried out in the medical wards of the Department of Medicine at King Abdulaziz Medical City in Riyadh, Saudi Arabia. Results: Four hundred geriatric patients were enrolled in the study: 200 in a pre-intervention group (control) and 200 in the intervention group. After the combined intervention, the incidence rate of PIMs decreased significantly from 61% to 29.5% (p

Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare autosomal recessive inborn errors of metabolism characterized by hyperammonemia due to N-acetylglutamate synthase (NAGS) dysfunction. Carglumic acid (Carbaglu®; Orphan Europe Ltd.) is approved by the US Food and Drug Administration (USFDA) for the treatment of hyperammonemia due hepatic NAGS deficiency. Here we report the rationale and design of a phase IIIb trial that is aimed at determining the long-term efficacy and safety of carglumic acid in the management of PA and MMA. This prospective, multicenter, open-label, randomized, parallel group phase IIIb study will be conducted in Saudi Arabia. Patients with PA or MMA (≤15 years of age) will be randomized 1:1 to receive twice daily carglumic acid (50 mg/kg/day) plus standard therapy (protein-restricted diet, L-carnitine, and metronidazole) or standard therapy alone for a 2-year treatment period. The primary efficacy outcome is the number of emergency room visits due to hyperammonemia. Safety will be assessed throughout the study and during the 1 month follow-up period after the study. Current guidelines recommend conservative medical treatment as the main strategy for the management of PA and MMA. Although retrospective studies have suggested that long-term carglumic acid may be beneficial in the management of PA and MMA, current literature lacks evidence for this indication. This clinical trial will determine the long-term safety and efficacy of carglumic acid in the management of PA and MMA. King Abdullah International Medical Research Center ( KAIMRC ): (RC13/116) 09/1/2014. Saudi Food and Drug Authority (SFDA) (33066) 08/14/2014. ClinicalTrials.gov (identifier: NCT02426775) 04/22/2015.

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.

Abstract The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b 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.

The threat of Antimicrobial Resistance (AMR) has attracted the highest level of attention after the United Nation (UN) General Assembly's High Level meeting on AMR in 2016. During that meeting a temporary committee, the inter agency coordination group (IACG) [1] was formulated, under the chairmanship of the Director General of the World Health Organization (DG-WHO) and the UN Deputy Secretary General. The IACG group was tasked to link, guide and advise on political steps needed to address and mitigate the emergence of AMR globally [2]. Efforts to combat AMR, however, have previously been developed prior to this initiative by several decades. Yet, the emergence of resistance continues to be on the rise. The Gulf Cooperation Council Center for Infection Control (GCC-IC) was been established in 2005 and has made major efforts to address all aspects related to human infection control in the member countries. Many of which have been reached. In 2015, the board was able to draft through its multidisciplinary meeting the first roadmap for the counties on this issue [3]. Two years later a follow-up meeting took place in Riyadh on April 2017. Regional and international experts joined in to share and contribute to the understanding of AMR and to advise on further steps needed for this initiative. We dedicated 3 papers on this meeting. The first paper is to provide an update on progress form the GCC countries and further steps that need to be taken, (in press). The second paper is part one out of two round table discussions. The first round table discussion paper, which is the current paper, addresses AMR and the "One Health" concept with a focus on leadership. The second round table discussion paper addresses AMR and the "One Health" concept with a focus on human health [4].

Objectives Ginger extracts gingerol and paradol exhibit anti-platelet aggregation properties. Prior studies have shown a reduction in platelet aggregation; however, results remain inconclusive due to heterogeneity of the used methods i.e. different dose regimen, ginger formulation, and study participants. The main aim of the study was to evaluate the effect of ginger consumption on platelet aggregation upon healthy participants. Methods Forty healthy male and female participants were randomized (1:1) to consume ginger tea four gram once daily vs. twice daily for five consecutive days. The primary outcome was inhibition in platelet aggregation which was assessed at baseline and at day five post ginger intake using agonists Adenosine Diphosphonate, Arachidonic Acid, Collagen, Ristocetin and Epinephrine. Results Complete blood count, platelet aggregation and platelets morphology at baseline were not statistically different between study groups. Taking ginger four gram once daily did not show an effect on the platelet aggregation using Adenosine Diphosphonate, Arachidonic Acid, Collagen and Ristocetin, except Epinephrine where reduction in platelet aggregation had been observed (p = 0.032). Dose increment to ginger 4 g twice daily does not influence the platelet aggregation using any of the agonists. Females have shown increase in platelet aggregation inhibition compared to males in response to Arachidonic Acid (p = 0.01). Conclusion Results showed that ginger 4 g daily had an impact on platelet aggregation using Epinephrine only, with no change observed after dose increment. Platelet aggregation inhibition was higher among females using Arachidonic Acid only.

ObjectivesClinical 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.DesignCross-sectional.SettingThe 2016 Al Jenadriyah cultural/heritage festival in Riyadh, KSA.ParticipantsParticipating booths and exhibition halls, as well as festival visitors, were approached to participate in the study.Primary and secondary outcome measuresKnowledge of and attitudes toward CTs.ResultsThe 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.ConclusionsThe 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.

Background It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. Methods The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. Discussion This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. Trial registration ClinicalTrials.gov, ID: NCT02845843. Registered on 27 July 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2427-0) contains supplementary material, which is available to authorized users.

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.

Background Little is known about the perceived attitude, barriers and facilitators of Saudi Pharmacists about practice based research. We aimed to measure the attitude, barriers, and facilitators of Saudi hospital pharmacists towards pharmacy practice research. Method A cross-sectional survey of hospital pharmacists (n = 216) working in King Abdulaziz Medical Cities in Central, Eastern and Western region hospitals was conducted during first week of September, 2013. The survey instrument comprised of six different sections that explored pharmacists previous participation in research, items regarding attitude, perception and willingness to participate, motivators, barriers, different areas of interest for doing research and patient demographics. Quantitative data collected was initially explored using frequency distribution, and descriptive analysis was carried out. Mann-Whitney U and independent samples t-test were used to explore the differences between the study variables. Results One hundred and eighty two pharmacists completed the survey yielding a response rate of 84 %. Fifty-nine percent of pharmacists have prior research experience. Pharmacists with research experience were more confident in reading and evaluating research papers (p = 0.01), and designing a research study (p = 0.001). Pharmacists with previous research experience were also more likely to participate in future research opportunities (p = 0.004) and were confident in their research skills (p = 0.003). No differences were observed about the perceived value of research, facilitators and barriers to participate in research, between pharmacists with prior research experience and pharmacists who have no prior experience to do research. Conclusion Pharmacists in this study were unanimous about the importance of research but showed considerable differences in their confidence to carry out research. There is a need to provide additional support to enable Saudi pharmacists in conducting practice based research. Electronic supplementary material The online version of this article (doi:10.1186/s40545-016-0052-z) contains supplementary material, which is available to authorized users.

Background One of the most unfortunate events toddlers may encounter during their early years of curiosity and experimentation is substance poisoning. The aim of the study was to evaluate the poison severity score and its associated factors among toddlers with orally ingested substances at a pediatrics emergency department (ED), central Saudi Arabia. Methods A cross-sectional, poisoning report review between 2009&2011 was conducted. Exposures were patient characteristics (sex, age, body mass index, medical history) and incident characteristics (substance type, amount, form, witnessed or not, home remedy, arrival time to ED). Outcome was Poison Severity Score (PSS) that rates signs/symptoms of 11 body aspects on scale 0–4 (none, minor, moderate, severe, fatal). Inclusion criteria: age (1–3 years), previously healthy and oral exposure route. Bivariate analysis and multi-linear regression were conducted. Significance at p

Menyfah Q Alanazi,1 Majed I Al-Jeraisy,2,3 Mahmoud Salam2 1Drug Policy and Economic Center, 2King Abdullah International Medical Research Center (KAIMRC), 3King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia Background: Inappropriate antibiotic (ATB) prescriptions are a threat to patients, leading to adverse drug reactions, bacterial resistance, and subsequently, elevated hospital costs. Our aim was to evaluate ATB prescriptions in an emergency department of a tertiary care facility. Methods: A cross-sectional study was conducted by reviewing charts of patients complaining of infections. Patient characteristics (age, sex, weight, allergy, infection type) and prescription characteristics (class, dose, frequency, duration) were evaluated for appropriateness based on the AHFS Drug Information and the Drug Information Handbook. Descriptive and analytic statistics were applied. Results: Sample with equal sex distribution constituted of 5,752 cases: adults (15 years) =61% and pediatrics (

Background Poison management guidelines recommend contacting or visiting poison centers directly after exposure. However, some parents initiated non-medical interventions on their children before visiting these centers. Aim was to evaluate the clinical and hospital outcomes of such practices among toddlers with orally ingested medication or chemical substances at a tertiary care facility. Methods Retrospective cohort, based on four-arm outcome analysis. Exposures were gender, age, body mass index, arrival time to facility (hours) presented in Median [Interquartile range]. Clinical outcomes were vital signs, physical examination, diagnostic tests; Hospital outcomes were in-hospital admission, length of hospital stay (hours) presented in Median [Interquartile range], hospital cost ($US). Bivariate analysis (nonparametric tests), binary logistic/linear regression were conducted. Significance at p

OBJECTIVES To determine: 1) the range and magnitude of vancomycin trough cerebrospinal fluid (CSF) concentrations following intraventricular (IVT) vancomycin; 2) any correlation between patient demographic and CSF vancomycin concentrations; and 3) eradication and complications rates following IVT vancomycin. METHODS Medical records of pediatric patients with shunt infection who received IVT vancomycin during a 12 month period were reviewed. Demographic, microbiological data, IVT/intravenous (IV) vancomycin dosing, concomitant antibiotics, CSF and serum vancomycin concentrations, and CSF drainage output were recorded. RESULTS Seventeen patients ages 4 months to 17 years were hospitalized for shunt infection. Staphylococcus epidermidis (n=12) was the predominant organism. Sixteen patients received 10 mg, and one patient received 5 mg of IVT vancomycin for 3–23 days. All but one received concurrent IV vancomycin. The mean maximum trough CSF vancomycin concentration noted for 16 patients who recieved 10 mg of IVT vancomycin was 18.4±21.8 μg/mL (range: between 0.4 to 187.3 μg/mL). All four adolescents ≥25 kg had CSF vancomycin concentrations ≤5 μg/mL, three of four infants/children between 10.1 and 24.9 kg had trough CSF vancomycin concentrations between 10–20 μg/mL, and five of nine infants 20 μg/mL. All organisms were successfully eradicated. One patient developed chronic eosinophilia presumed related to elevated CSF vancomycin concentrations (187 μg/mL). CONCLUSIONS –The combination of IVT and IV vancomycin effectively eradicated CSF shunt infections. CSF vancomycin concentrations are highly variable and poorly correlated with age and CSF output. Following a 10 mg IVT vancomycin dose, CSF concentrations appear to be lower in older children and elevated in infants/young children. One infant experienced a complication related to an elevated CSF vancomycin concentration; hence, therapy must be individualized, using CSF trough vancomycin concentrations.

Background The treatment of inborn errors of metabolism (IEM) has seen significant advances over the last decade. Many medicines have been developed and the survival rates of some patients with IEM have improved. Dosages of drugs used for the treatment of various IEM can be obtained from a range of sources but tend to vary among these sources. Moreover, the published dosages are not usually supported by the level of existing evidence, and they are commonly based on personal experience. Methods A literature search was conducted to identify key material published in English in relation to the dosages of medicines used for specific IEM. Textbooks, peer reviewed articles, papers and other journal items were identified. The PubMed and Embase databases were searched for material published since 1947 and 1974, respectively. The medications found and their respective dosages were graded according to their level of evidence, using the grading system of the Oxford Centre for Evidence-Based Medicine. Results 83 medicines used in various IEM were identified. The dosages of 17 medications (21%) had grade 1 level of evidence, 61 (74%) had grade 4, two medications were in level 2 and 3 respectively, and three had grade 5. Conclusions To the best of our knowledge, this is the first review to address this matter and the authors hope that it will serve as a quickly accessible reference for medications used in this important clinical field.

With its rapid introduction in 2009, concerns about the safety of the H1N1 vaccines have been raised. Data were especially limited on the pediatric safety of H1N1 vaccine in Saudi Arabia.The objectives of this study were to investigate the safety of the H1N1 vaccine (Pandemrix(®)) in children and examine the feasibility of obtaining information on possibly associated adverse reactions using mobile telephone contact with child caregivers.A cohort study was conducted in Riyadh, Saudi Arabia. Patients were included if they were aged between 6 and 18 years and had received one dose of the H1N1 vaccine. A control group involved children from the same school system who had not received the vaccine. Six months following vaccination, a clinical pharmacist called the caregiver of the child to ask about hospitalization, emergency room visits and events related to H1N1 vaccine administration using a standardized questionnaire.Caregivers of 372 school-age children were contacted. The response rate was 97% (n = 359). A total of 169 children who received at least one dose of the H1N1 vaccine were compared with 190 children in the control group who had not received the vaccine. Controlling for age, sex, education and use of medications, the odds ratio (OR) of hospitalization or emergency room visits for children within the 6 months after vaccination relative to the unvaccinated children was 1.25 (95% CI 0.47, 3.35). The risk of influenza-like symptoms was significantly reduced in vaccinated children compared with unvaccinated children (OR 0.63; 95% CI 0.41, 0.99).School-age children in Saudi Arabia who received the H1N1 vaccine did not have an increased risk of hospitalization or emergency room visits. Larger studies are needed to confirm these results. Proactive pharmacovigilance is important in assessing the safety of vaccines and other medications. It is feasible to collect information on adverse drug reactions using mobile telephones, a method that can be of benefit in both developed and developing countries.

Background Medication errors (MEs) are among the most common types of medical errors and one of the most common and preventable causes of iatrogenic injuries. The aims of the present study were; (i) to determine the incidence and types of medication prescribing errors (MPEs), and (ii) to identify some potential risk factors in a pediatric inpatient tertiary care setting in Saudi Arabia. Findings A five-week retrospective cohort study identified medication errors in the general pediatric ward and pediatric intensive care unit (PICU) at King Abdulaziz Medical City (KAMC) through the physical inspection of physician medication orders and reviews of patients' files. Out of the 2,380 orders examined, the overall error rate was 56 per 100 medication orders (95% CI: 54.2%, 57.8%). Dose errors were the most prevalent (22.1%). These were followed by route errors (12.0%), errors in clarity (11.4%) and frequency errors (5.4%). Other types of errors were incompatibility (1.9%), incorrect drug selection (1.7%) and duplicate therapy (1%). The majority of orders (81.8%) had one or more abbreviations. Error rates were highest in prescriptions for electrolytes (17.17%), antibiotics (13.72%) and bronchodilators (12.97%). Medication prescription errors occurred more frequently in males (64.5%), infants (44.5%) and for medications with an intravenous route of administration (50.2%). Approximately one third of the errors occurred in the PICU (33.9%). Conclusions The incidence of MPEs was significantly high. Large-scale prospective studies are recommended to determine the extent and outcome of medication errors in pediatric hospitals in Saudi Arabia.