Evaluation of Serial Procalcitonin Levels for the Optimization of Antibiotic Use in Non-Critically Ill COVID-19 Patients.

BACKGROUND: Procalcitonin (PCT) has been used as a biomarker to guide antibiotic therapy in various patient populations. However, its role in optimizing antibiotic use in COVID-19 patients has not been well studied to date. Thus, we aimed to evaluate the use of serial PCT monitoring as an antimicrobial stewardship tool for COVID-19 patients. METHODS: This retrospective study included 240 COVID-19 patients who were admitted to a tertiary medical institution in Saudi Arabia between January 2020 and February 2022. Patients who received empiric antibiotic therapy for community-acquired pneumonia (CAP) and had serial procalcitonin levels were included. The patients were divided into two groups: the normal procalcitonin arm (PCT level < 0.5 ng/mL) and the elevated PCT arm (PCT level > 0.5 ng/mL). The primary and secondary outcomes were the effect of PCT monitoring on the duration of antibiotic exposure and the length of hospital stay, respectively. To measure the accuracy of PCT, the receiver-operating characteristic area under the curve (ROC-AUC) was determined. RESULTS: Among the included patients, 142 were in the normal procalcitonin arm (median PCT, 0.12 ng/mL), and 78 were in the elevated PCT arm (median PCT, 4.04 ng/mL). The baseline characteristics were similar between the two arms, except for the higher prevalence of kidney disease in the elevated PCT arm. There was no statistically significant difference in the duration of antibiotic exposure between the normal and elevated PCT arms (median duration: 7 days in both arms). However, the length of hospital stay was significantly shorter in the normal PCT arm (median stay, 9 days) than in the elevated PCT arm (median stay, 13 days; p = 0.028). The ROC-AUC value was 0.54 (95% CI: 0.503-0.595). CONCLUSIONS: Serial PCT monitoring did not lead to a reduction in the duration of antibiotic exposure in COVID-19 patients. However, it was associated with a shorter hospital stay. These findings suggest that PCT monitoring may be useful for optimizing antibiotic use and improving outcomes in COVID-19 patients. While PCT-guided algorithms have the potential to enable antibiotic stewardship, their role in the context of COVID-19 treatment requires further investigation.

Barriers to Mental Illness Treatment in Saudi Arabia: A Population-Based Cross-Sectional Study.

BACKGROUND: Mental illness is a disorder that can cause impairment and disability, affecting mood, thinking, and behavior; therefore, early intervention will reduce morbidity. This study aims to evaluate all the personal, family, societal, and medical barriers that prevent mental health patients from seeking consultation and treatment. METHODS: In Saudi Arabia, a cross-sectional study was conducted on 463 individuals aged 18 and above. Data were collected by face-to-face interviews using a validated questionnaire, which consisted of two parts. The first part included sociodemographic data, while the second part contained subsections of society/family, personal, and medical barriers. RESULTS: The results showed that 379 (81.9%) indicated that society and family barriers impacted them, whereas 325 (70.3%) believed that personal barriers hindered seeking help. However, 294 (63.5%) opted for medical barriers as a hindrance. Regarding the highest barriers, 120 of the total respondents (25.9%) saw psychiatric illness as a source of shame and stigma, 166 respondents (35.9%) said that the psychiatric patient is seen as crazy, 159 of them (34.3%) believed it is tough for anyone to talk about their feelings and emotions and 183 respondent (39.5%) feared that psychiatric illness would decrease the chance of marriage to the appropriate person. Our findings also indicated a low trust in hospital treatment, hence a loss of confidence in using medications. CONCLUSION: The findings of this study indicate that societal stigma is the most common barrier preventing people from seeking mental health consultation. Many barriers differ significantly between males and females.

Assessment of knowledge, attitude, and practices of acute kidney injury incidence with co-administration of piperacillin/tazobactam and vancomycin among healthcare workers: A cross-sectional study.

Background: No studies have identified a link between acute kidney injury (AKI) incidence due to the co-administration of vancomycin and piperacillin/tazobactam (VPT) and healthcare providers' knowledge, attitudes, and practices. We aimed to (1) assess the knowledge, attitudes, and practices towards AKI due to VPT co-administration among healthcare providers in Saudi Arabia, and (2) examine the relationship between healthcare providers' knowledge and attitudes about AKI due to VPT co-administration and their practices. Methods: This cross-sectional study was conducted between February 2022 and April 2022. Healthcare providers, including physicians, pharmacists, and nurses, were included in the study population. The correlation coefficient assessed the relationship between knowledge, attitude, and practice. Spearman's rho was used as a test statistic. Results: Of the invited healthcare providers, 192 responded to the survey. A significant difference in knowledge was found among healthcare providers for two variables: the definition of AKI (p < 0.001) and appropriate management of AKI due to VPT (p = 0.002). Physicians were found to rely less on the most common causative organisms of infection to guide empirical antibiotic therapy (p < 0.001). In addition, physicians were less likely to switch piperacillin/tazobactam to cefepime or meropenem in combination with vancomycin with AKI incidence (p = 0.001). A positive attitude towards the perceived AKI risk with VPT was positively correlated with avoiding using VPT unless no alternatives were available (Rho = 0.336) and taking protective measures when using VPT (Rho = 0.461). Conclusion: Deviation has been observed in the knowledge, attitudes, and practices of AKI incidence with the co-administration of piperacillin/tazobactam and vancomycin among healthcare workers. Interventions at the organizational level are recommended to guide best practices.

Prevalence and Associations of Type 2 Diabetes Risk and Sociodemographic Factors in Saudi Arabia: A Web-Based Cross-Sectional Survey Study.

Type 2 diabetes mellitus (T2DM) is a chronic disease with ever-increasing prevalence worldwide. In our study, we evaluated the prevalence of the risk of developing T2DM in Saudi Arabia and investigated associations between that risk and various sociodemographic characteristics. To those ends, a web-based cross-sectional survey of Saudi nationals without diabetes, all enrolled using snowball sampling, was conducted from January 2021 to January 2022. The risk of developing T2DM was evaluated using a validated risk assessment questionnaire (ARABRISK), and associations of high ARABRISK scores and sociodemographic variables were explored in multivariable logistic regression modeling. Of the 4559 participants, 88.1% were 18 to 39 years old, and 67.2% held a college or university degree. High ARABRISK scores were observed in 7.5% of the sample. Residing in a midsize city versus a large city was associated with a lower ARABRISK risk score (p = 0.007), as were having private instead of governmental insurance (p = 0.005), and being unemployed versus employed (p < 0.001). By contrast, being married (p < 0.001), divorced or widowed (p < 0.001), and/or retired (p < 0.001) were each associated with a higher ARABRISK score. A large representative study is needed to calculate the risk of T2DM among Saudi nationals.

Echinocandin exposures in obese patients: A scoping review and clinical perspectives.

PURPOSE: Echinocandins are favored drugs for the treatment of fungal infections. There is growing evidence that obese patients treated with echinocandins have lower exposures due to pharmacokinetic (PK) alterations. We conducted a scoping review to characterize, evaluate, and summarize the available evidence on echinocandins exposures in obese patients. SUMMARY: A comprehensive search of PubMed, Embase, and Cochrane Library for studies on echinocandins published from database inception to October 28, 2022, was conducted using PRISMA-ScR methodology. A total of 25 studies comprising more than 3,174 subjects (8 micafungin studies, 7 caspofungin studies, 9 anidulafungin studies, and 1 rezafungin study) were included in this review. Seventeen studies reported lower echinocandins exposures in overweight and obese individuals compared with normal-weight individuals; the authors of these studies recommended dose adjustments. Conversely, 8 studies did not find significant differences in echinocandin exposure among subjects in varying body weight categories. Clinicians may consider dose adjustments of echinocandins in obese patients; however, there is limited evidence on the ideal dose adjustment strategy to overcome the low echinocandins exposures in obese patients. CONCLUSION: This scoping review shed light on a growing body of evidence indicating that obese patients have lower echinocandin exposures relative to targeted PK indices, which may lead to negative therapeutic implications. Currently, a lack of high-quality evidence impedes reaching consensus on recommendations for echinocandin dosing adjustment in obese patients. Future research evaluating the optimal echinocandin dosing strategy for obese patients is needed.

A comparison of three thromboprophylaxis regimens in critically ill COVID-19 patients: An analysis of real-world data.

Introduction: Thrombotic complications of coronavirus disease 2019 (COVID-19) have received considerable attention. Although numerous conflicting findings have compared escalated thromboprophylaxis doses with a standard dose to prevent thrombosis, there is a paucity of literature comparing clinical outcomes in three different anticoagulation dosing regimens. Thus, we investigated the effectiveness and safety profiles of standard, intermediate, and high-anti-coagulation dosing strategies in COVID-19 critically ill patients. Methodology: This retrospective multicenter cohort study of intensive care unit (ICU) patients from the period of April 2020 to August 2021 in four Saudi Arabian centers. Inclusion criteria were age ≥ 18 years, diagnosis with severe or critical COVID-19 infection, and receiving prophylactic anticoagulant dose within 24-48 h of ICU admission. The primary endpoint was a composite of thrombotic events, with mortality rate and minor or major bleeding serving as secondary endpoints. We applied survival analyses with a matching weights procedure to control for confounding variables in the three arms. Results: A total of 811 patient records were reviewed, with 551 (standard-dose = 192, intermediate-dose = 180, and high-dose = 179) included in the analysis. After using weights matching, we found that the standard-dose group was not associated with an increase in the composite thrombotic events endpoint when compared to the intermediate-dose group {19.8 vs. 25%; adjusted hazard ratio (aHR) =1.46, [95% confidence of interval (CI), 0.94-2.26]} or when compared to high-dose group [19.8 vs. 24%; aHR = 1.22 (95% CI, 0.88-1.72)]. Also, there were no statistically significant differences in overall in-hospital mortality between the standard-dose and the intermediate-dose group [51 vs. 53.4%; aHR = 1.4 (95% CI, 0.88-2.33)] or standard-dose and high-dose group [51 vs. 61.1%; aHR = 1.3 (95% CI, 0.83-2.20)]. Moreover, the risk of major bleeding was comparable in all three groups [standard vs. intermediate: 4.8 vs. 2.8%; aHR = 0.8 (95% CI, 0.23-2.74); standard vs. high: 4.8 vs. 9%; aHR = 2.1 (95% CI, 0.79-5.80)]. However, intermediate-dose and high-dose were both associated with an increase in minor bleeding incidence with aHR = 2.9 (95% CI, 1.26-6.80) and aHR = 3.9 (95% CI, 1.73-8.76), respectively. Conclusion: Among COVID-19 patients admitted to the ICU, the three dosing regimens did not significantly affect the composite of thrombotic events and mortality. Compared with the standard-dose regimen, intermediate and high-dosing thromboprophylaxis were associated with a higher risk of minor but not major bleeding. Thus, these data recommend a standard dose as the preferred regimen.

Tocilizumab effectiveness in mechanically ventilated COVID-19 patients (T-MVC-19 Study): a multicenter real-world evidence.

BACKGROUND: This study aimed to evaluate the effectiveness of tocilizumab in mechanically ventilated patients with coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: This retrospective multicenter study included adults (≥18 years) diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab, and requiring invasive mechanical ventilation during admission. Survival analyses with inverse propensity score treatment weighting (IPTW) and propensity score matching (PSM) were conducted. To account for immortal bias, we used Cox proportional modeling with time-dependent covariance. Competing risk analysis was performed for the extubation endpoint. RESULTS: A total of 556 (tocilizumab = 193, control = 363) patients were included. Males constituted the majority of the participants (69.2% in tocilizumab arm,74.1% in control arm). Tocilizumab was not associated with a reduction in mortality with hazard ratio [(HR) = 0.82,95% confidence interval (95%CI): 0.62-1.10] in the Inverse propensity score weighting (IPTW) analysis and (HR = 0.86,95% CI: 0.64-1.16) in the PSM analysis. However, tocilizumab was associated with an increased rate of extubation (33.6%) compared to the control arm (11.9%); subdistributional hazards (SHR) = 3.1, 95% CI: 1.86-5.16). CONCLUSIONS: Although tocilizumab was not found to be effective in reducing mortality, extubation rate while on mechanical ventilation was higher among tocilizumab treated group.

Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis.

INTRODUCTION: Favipiravir is a repurposed drug to treat coronavirus 2019 (COVID-19). Due to a lack of available real-world data, we assessed its effectiveness and safety in moderately to critically ill COVID-19 patients. METHODS: This retrospective study was conducted in two public/specialty hospitals in Saudi Arabia. We included patients ≥18 years) admitted April-August 2020 with confirmed SARS-CoV-2 diagnosed by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab. Patients received either favipiravir (1800 mg or 1600 mg twice daily loading dose, followed by 800 mg or 600 mg twice daily) or supportive-care treatment. Patients were excluded if they were outside the study period, classified as having a mild form of the disease per WHO criteria, or had an incomplete patient file. Kaplan-Meier (KM) models were used to estimate median time to discharge. Discharge ratios, progression to mechanical ventilation, and mortality outcomes were estimated across the severity spectrum using Cox proportional-hazards models. As a sensitivity analysis, we performed propensity score-matching (PSM) analysis. RESULTS: Overall, median time to discharge was 10 days (95%CI = 9-10) in the favipiravir arm versus 15 days (95%CI = 14-16) in the supportive-care arm. The accelerated discharge benefit was seen across the COVID-19 spectrum of severity. The adjusted discharge ratio was 1.96 (95%CI = 1.56-2.46). Progression to mechanical ventilation was slower with favipiravir (HRadj = 0.10, 95%CI = 0.04-0.29). There was no significant effect on mortality (HRadj = 1.56, 95%CI = 0.73-3.36). There was a statistically non-significant trend toward worse outcomes in the critical category (HRadj = 2.80, 95%CI = 0.99-7.89). Age was an independent risk factor for mortality in mechanically ventilated patients. PSM analyses confirmed these findings. CONCLUSION: Favipiravir was associated with clinical benefits, including accelerated discharge rate and less progression to mechanical ventilation; however, no overall mortality benefits were seen across the severity spectrum.

Mortality, Severity, and Hospital Admission among COVID-19 Patients with ACEI/ARB Use: A Meta-Analysis Stratifying Countries Based on Response to the First Wave of the Pandemic.

BACKGROUND: The use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) is controversial for treating COVID-19 patients. We aimed to estimate pooled risks of mortality, disease severity, and hospitalization associated with ACEI/ARB use and stratify them by country and country clusters. METHODS: We conducted a search in various databases through 4 July 2020 and then applied random-effects models to estimate pooled risks (ORp) across stratifications by country cluster. Clusters were chosen to reflect outbreak times (China followed by Korea/Italy, others subsequently) and mobility restrictions (China and Denmark/France/Spain with stricter lockdowns than the UK/US). RESULTS: Overall analysis showed no increase in mortality; however, a statistical increase in mortality was seen in the US/UK cluster with ORp = 1.28 [95% CI = 1.04; 1.56] and a decrease in China with ORp = 0.65 [95% CI = 0.43; 0.96] and France with OR = 0.31 [95% CI = 0.14; 0.69]. Severity and hospitalization were not statistically significant in the analysis; however, several associations were seen in specific countries but not in country clusters. CONCLUSION: The country-cluster meta-analysis provided a reasonable explanation for COVID-19 mortality among ACEI/ARB users. The analysis did not explain differences in severity and suggested the involvement of other factors. Hospitalization findings among ACEI/ARB users may be considered informative as they may have been subjected to clinical decisions and hospital-bed availability.

Impact of Non-Tailored One-Way Automated Short Messaging Service (OASMS) on Glycemic Control in Type 2 Diabetes: A Retrospective Feasibility Study.

Short message service (SMS) is easily accessible and potentially an ideal platform for delivering patient-targeted messages. However, an effective SMS dosing strategy is not well established. Our purpose was to evaluate the impact of diabetes self-care promoting messages via non-tailored one-way automated SMS (OASMS) on glycemic control in type 2 diabetes (T2DM). The change in hemoglobin A1c (HbA1c) was compared between patients who received the service and those who did not. This retrospective quasi-experimental pre-post feasibility study was conducted at an academic medical center endocrinology clinic. English-speaking adults (≥18 years) with uncontrolled T2DM (HbA1c ≥ 8%) were included. A total of 69 patients (intervention n = 34; control n = 35) met the inclusion criteria. The mean (±SD) baseline HbA1c values were 10.2% (±1.9%) and 9.9% (±1.7%) in the intervention and control arms, respectively. Median follow-up was 3.3 months (IQR = 3-4.2). An ANCOVA model adjusted for baseline HbA1c and age showed an estimated HbA1c reduction difference of -0.97% (95% CI, -1.73 to -0.20%, p = 0.014), favoring the intervention arm. Inverse propensity score weighting confirmed the ANCOVA results. Our study suggests that adding diabetes self-care promoting messages via non-tailored OASMS to usual care improves glycemic control in poorly controlled T2DM. Larger and longer studies are needed to evaluate different features of the non-tailored OASMS strategy.

Pharmacists' Knowledge About the Impact of Augmented Renal Clearance on Antimicrobial Dosing in Critically Ill Patients: A Cross-Sectional Study.

BACKGROUND: Broad-spectrum antibiotics are commonly prescribed in critically ill patients. While it is commonly believed that only patients with impaired renal function need dose adjustment, augmented renal clearance (ARC) is a phenomenon that warrants dose adjustment as well. In critically ill patients ARC is often undetectable because it is associated with a normal or decreased serum creatinine concentration (SCr). This study's objective was to assess pharmacists' knowledge about ARC identification, risk factors, affected antimicrobials, and dosing of antibiotics in patients with ARC. METHODS: In January 2020, we carried out a cross-sectional study by sending out an online survey to the Saudi Pharmaceutical Society, Kuwait Pharmaceutical Association, and Oman Pharmaceutical Society. Due to the expected low response rate, we administered an electronic questionnaire to pharmacists attending Dubai International Pharmaceuticals and Technologies Conference and Exhibition 2020 (DUPHAT). RESULTS: Data were collected from 288 respondents. However, only 134 were included in the final analysis following the exclusion of incomplete responses, no experience working in in-patient settings, and respondents who chose "no" universal ARC definition. Those who chose "yes" or "I do not know" regarding the universal definition of ARC were asked about SCr status in ARC. Elevation in SCr was chosen by 67/134 (50%) compared to those who chose decreased or normal (48/134, 35.8%). Regarding risk factors, only 1/134 (0.7%) respondent selected all risk factors. Two/134 (1.4%) respondents chose all hydrophilic antibiotics that are likely to be affected by ARC. Concerning the appropriate dose and frequency of piperacillin-tazobactam and meropenem, they were selected by 60.4% and 30.5%, respectively. CONCLUSION: Pharmacists' knowledge about ARC was limited. Implementation of educational programs targeting hospital pharmacists, especially those practicing in critical care settings, and developing antimicrobial institutional guidelines are important.