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Background and Purpose. Gentamicin (GEN) is a broad-spectrum antibiotic that cannot be prescribed freely because of its toxicity. Thymoquinone (THQ), a phytochemical, has antibacterial, antioxidant, and toxicity-reducing properties. However, its hydrophobicity and light sensitivity make it challenging to utilize. This incited the idea of co-encapsulating GEN and THQ in liposomes (Lipo-GEN-THQ). Method. Lipo-GEN-THQ were characterized using the zeta-potential, dynamic light scattering, Fourier transform infrared spectroscopy, and transmission electron microscope (TEM). The liposomes' stability was evaluated under different storage and biological conditions. Lipo-GEN-THQ's efficacy was investigated by the minimum inhibitory/bactericidal concentrations (MICs-MBCs), time–kill curves, and antibiofilm and antiadhesion assays. Bacterial interactions with the empty and GEN-THQ-loaded liposomes were evaluated using TEM. Results. The Lipo-GEN-THQ were spherical, monodispersed, and negatively charged. The Lipo-GEN-THQ were relatively stable and released GEN sustainably over 24 h. The liposomes exhibited significantly higher antibacterial activity than free GEN, as evidenced by the four-fold lower MIC and biofilm eradication in resistant E. coli strain (EC-219). TEM images display how the empty liposomes fused closely to the tested bacteria and how the loaded liposomes caused ultrastructure damage and intracellular component release. An antiadhesion assay showed that the Lipo-GEN-THQ and free GEN (0.125 mg/L) similarly inhibited Escherichia coli (EC-157) adhesion to the A549 cells (68% vs. 64%). Conclusions. The Lipo-THQ-GEN enhanced GEN by combining it with THQ within the liposomes, reducing the effective dose. The reduction in the GEN dose after adding THQ may indirectly reduce the toxicity and aid in developing an enhanced and safer form of GEN. [ABSTRACT FROM AUTHOR]

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‐β1b 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‐β1b 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. [ABSTRACT FROM AUTHOR]

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (,15 years) =39%. Around 55% complained of respiratory tract infections, 25% urinary tract infections (UTIs), and 20% others. Broad-spectrum coverage ATBs were prescribed for 76% of the cases. Before the prescription, 82% of pediatrics had their weight taken, while 18% had their weight estimated. Allergy checking was done in 8% only. Prevalence of inappropriate ATB prescriptions with at least one type of error was 46.2% (pediatrics =58% and adults =39%). Errors were in ATB selection (2%), dosage (22%), frequency (4%), and duration (29%). Dosage and duration errors were significantly predominant among pediatrics (P,0.001 and P,0.0001, respectively). Selection error was higher among adults (P=0.001). Age stratification and binary logistic regression were applied. Significant predictors of inappropriate prescriptions were associated with: 1) cephalosporin prescriptions (adults: P,0.001, adjusted odds ratio [adj OR] =3.31) (pediatrics: P,0.001, adj OR =4.12) compared to penicillin; 2) UTIs (adults: P,0.001, adj OR =2.78) (pediatrics: P=0.039, adj OR =0.73) compared to respiratory tract infections; 3) obtaining weight for pediatrics before the prescription of ATB (P,0.001, adj OR =1.83) compared to those whose weight was estimated; and 4) broad-spectrum ATBs in adults (P=0.002, adj OR =0.67). Conclusion: Prevalence of ATB prescription errors in this emergency department was generally high and was particularly common with cephalosporin, narrow-spectrum ATBs, and UTI infections. [ABSTRACT FROM AUTHOR]

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 <0.001). Out of 317 recommendations given by the clinical pharmacist, the physicians accepted a total of 196 (61.83%) recommendations. The most common PIMs to avoid regardless of diagnosis of geriatric patients before interventions were first-generation antihistamines (46%), sliding scale insulin (18.5%), antipsychotics (6.5%), benzodiazepines (9.5%), and antiarrhythmic drugs (15%)., Conclusion: Using a combined intervention program that comprises an educational intervention of updated evidence-based guidelines and clinical pharmacist intervention would add a significant value to improve prescribing patterns in hospitalized geriatric patients., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: To compare sedation outcomes for chloral hydrate (CH) and midazolam (MD) as sedative agents for diagnostic procedures in children., Methods: A prospective, randomized, double-blinded study conducted between July 2005 and October 2006, at the Pediatric Day Care Unit (DCU), King Abdulaziz Medical City, Riyadh, Saudi Arabia. After meeting the inclusion criteria and getting informed consent, patients were randomized, given the study drug, and monitored for sedation outcomes., Results: Two hundred and seventy-five patients who had 292 sedation sessions for diagnostic procedures were included in the study. Due to missing data, 286 sedations were included in the final analysis; 144 in the CH and 142 in the MD group. Both groups were comparable with respect to demographic and baseline characteristics. The CH compared to MD group, had a higher sedation success rate, shorter time to achieve sedation, shorter length of stay in DCU, and longer sedation duration. In both study groups, patients who required a second dose tended to be older and heavier. No major side effects were encountered. The CH group had a significantly higher mean sedation scores at 15, 30, 45, and 60 minutes., Conclusion: Chloral hydrate compared to MD, had a shorter time to achieve sedation, a higher success rate, less need for a second dose, and decreased the time spent in the DCU. Older and heavier patients are more likely to require a second dose of the study drug to be sedated.

Objective: To identify the pediatric age group and most affected gender by asthma, and to determine the significant predictors of severity of asthma, and assess the appropriateness of asthma medication administration., Methods: This cross-sectional study was carried out at Emergency Department (ED) of children's Hospital at King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia from January to March 2009. Interviews were carried out with the parents of 185 children, who presented to the Hospital with asthma exacerbation more than once over the last 6 months, to collect data of possible risk factors, and appropriateness of medication administration technique., Results: Most patients were males 71.9%, aged 1-6 years (58.9%), and 8.1% of them presented to the ED because of asthma exacerbation more than once over the last 6 months. Approximately two-thirds (65.9%) of the parents explained the way of meter dose inhaler administration correctly. Infants were significantly the least affected group (p=0.02). Severity was significantly higher among appropriate users of medications (p=0.046)., Conclusion: Appropriateness of medications administration was significantly associated with severity. However, this may not be considered a valid predictor of severity, as parents of children with recurrent attacks may have a better chance of being taught how to use medications.