Correction: Alhasso et al. Development of a Nanoemulgel for the Topical Application of Mupirocin. Pharmaceutics 2023, 15, 2387.

Simon P [...].

A real-world exploration into clinical outcomes of direct oral anticoagulant therapy in people with chronic kidney disease: a large hospital-based study.

BACKGROUND: There is limited evidence to support definite clinical outcomes of direct oral anticoagulant (DOAC) therapy in chronic kidney disease (CKD). By identifying the important variables associated with clinical outcomes following DOAC administration in patients in different stages of CKD, this study aims to assess this evidence gap. METHODS: An anonymised dataset comprising 97,413 patients receiving DOAC therapy in a tertiary health setting was systematically extracted from the multidimensional electronic health records and prepared for analysis. Machine learning classifiers were applied to the prepared dataset to select the important features which informed covariate selection in multivariate logistic regression analysis. RESULTS: For both CKD and non-CKD DOAC users, features such as length of stay, treatment days, and age were ranked highest for relevance to adverse outcomes like death and stroke. Patients with Stage 3a CKD had significantly higher odds of ischaemic stroke (OR 2.45, 95% Cl: 2.10-2.86; p = 0.001) and lower odds of all-cause mortality (OR 0.87, 95% Cl: 0.79-0.95; p = 0.001) on apixaban therapy. In patients with CKD (Stage 5) receiving apixaban, the odds of death were significantly lowered (OR 0.28, 95% Cl: 0.14-0.58; p = 0.001), while the effect on ischaemic stroke was insignificant. CONCLUSIONS: A positive effect of DOAC therapy was observed in advanced CKD. Key factors influencing clinical outcomes following DOAC administration in patients in different stages of CKD were identified. These are crucial for designing more advanced studies to explore safer and more effective DOAC therapy for the population.

Antimicrobial consumption in an acute NHS Trust during the COVID-19 pandemic: intervention time series analysis.

Objective: To determine the impact of the COVID-19 pandemic on antimicrobial consumption and trends of therapeutic drugs for COVID-19 treatments, including corticosteroids, remdesivir and monoclonal antibodies (tocilizumab) from April 2017 to September 2022 in a secondary care NHS Trust in England. Methods: A retrospective intervention time series analysis was conducted for April 2017 to September 2022 at the Mid Yorkshire Teaching NHS Trust. Data were retrieved from the pharmacy dispensing system as defined daily doses (DDDs) monthly and reported per 1000 occupied bed days (OBDs). Antimicrobial consumption and COVID-19 treatment options were measured. DDDs were calculated according to the classification of antimicrobials for systemic use (J01) and for other drugs classification. Trends for antimicrobial consumption and other therapeutic drugs for treating COVID-19 were also determined in each wave in England. Results: During the pandemic: total antibiotic consumption decreased from 826.4 to 728.2 DDDs per 1000 OBDs (P = 0.0067); piperacillin/tazobactam use increased (P < 0.0001) and ciprofloxacin use decreased (P < 0.0001); there were no changes in Access, Watch, Reserve antibiotic use, and the proportion of antifungal consumption was consistent throughout the study. The use of total antibiotics (P = 0.024), levofloxacin (P = 0.0007), piperacillin/tazobactam (P = 0.0015) and co-amoxiclav (P = 0.0198) increased during wave one. Consumption of COVID-19 treatment drugs was highest during wave two, with 624.3 DDDs per 1000 OBDs for dexamethasone (P = 0.4441), 6.8 DDDs per 1000 OBDs for remdesivir (P < 0.0001) and 35.01 DDDs per 1000 OBDs for tocilizumab (P = 0.2544). Discussion: This study determined the consumption of antimicrobials trends before and during the pandemic. The individual wave antimicrobial consumption indicates maximum consumption in the first wave, advocating for antimicrobial stewardship and preparedness for future pandemics.

Direct oral anticoagulants and the risk of adverse clinical outcomes among patients with different body weight categories: a large hospital-based study.

OBJECTIVE: Through predictable pharmacokinetics-including a convenient fixed-dose regimen, direct oral anticoagulants (DOACs) are preferred over previous treatments in anticoagulation for various indications. However, the association between higher body weight and the risk of adverse consequences is not well studied among DOAC users. We aim to explore the association of body weight and adverse clinical outcomes in DOAC users. METHODS: A total of 97,413 anonymised DOAC users in a tertiary care setting were identified following structured queries on the electronic health records (EHRs) to extract the feature-rich anonymised dataset. The prepared dataset was analysed, and the features identified with machine learning (ML) informed the adjustments of covariates in the multivariate regression analysis to examine the association. Kaplan-Meier analysis was performed to evaluate the mortality benefits of DOACs. RESULTS: Among DOAC users, the odds of adverse clinical outcomes, such as clinically relevant non-major bleeding (CRNMB), ischaemic stroke, all-cause mortality, and prolonged hospital stay, were lower in patients with overweight, obesity, or morbid obesity than in patients with normal body weight. The odds of ischaemic stroke (OR 0.42, 95% CI: 0.36-0.88, p = 0.001) and all-cause mortality (OR 0.87, 95% CI: 0.81-0.95, p = 0.001) were lower in patients with morbid obesity than in patients with normal body weight. In the Kaplan-Meier analysis, apixaban was associated with a significantly lower rate of mortality overall and in obesity and overweight subgroups than other DOACs (p < 0.001). However, rivaroxaban performed better than apixaban in the morbid obesity subgroup (p < 0.001). CONCLUSION: This study shows the positive effects of DOAC therapy on clinical outcomes, particularly in patients with high body weight. However, this still needs validation by further studies particularly among patients with morbid obesity.

Pharmacist-led interventions in optimising the use of oral anticoagulants in patients with atrial fibrillation in general practice in England: a retrospective observational study.

BACKGROUND: Oral anticoagulation (OAC) is the mainstay of treatment for the prevention of strokes in patients with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) account for increasing OAC in patients with AF. However, prescribing DOACs for patients with established AF poses various challenges and general practice pharmacists may have an important role in supporting their management. AIM: To investigate the effectiveness of pharmacist-led interventions in general practice in optimising the use of OAC therapies in AF. DESIGN & SETTING: A retrospective observational study in general practices in Bradford. METHOD: The data were collected retrospectively from 1 November 2018-31 December 2019 using electronic health record data. The data were analysed: 1) to identify patients with AF not on OAC; 2) to describe inappropriate DOAC prescriptions; and 3) to calculate HAS-BLED scores. RESULTS: Overall, 76.3% (n = 470) of patients with AF received OAC therapy, and of these, 63.4% received DOACs. Pharmacist-led interventions increased DOAC prescribing by 6.0% (P = 0.03). Inappropriate DOAC use was identified in 24.5% of patients with AF, with underdosed and overdosed identified in 9.7% and 14.8%, respectively. Post-intervention, inappropriate prescribing was reduced to 1.7%. The mean HAS-BLED score decreased from 3.00 to 2.22 (P<0.01). Successful transition from vitamin K antagonist (VKA) therapy to DOACs was achieved in 25.7% of patients. CONCLUSION: Pharmacist-led interventions have successfully improved the use of OAC therapies in patients with AF, and effectively managed the bleeding risks and transition from VKA to DOAC therapy, in line with guidelines.

Exploring drivers and challenges influencing antibiotic prescribing in outpatient settings and possible mitigation strategies in the United Arab Emirates: a qualitative study.

Objectives: Healthcare institutions implement antimicrobial stewardship (AMS) programmes to optimize the use of antibiotics. The focus is often on inpatient rather than outpatient settings. We aimed to explore perceptions of AMS stakeholders on effective interventions for appropriate antibiotic use in outpatient settings, and the role of clinical pharmacists in the AMS multidisciplinary team. Methods: A qualitative semi-structured interview study using thematic analysis by two researchers independently. Participants that practice AMS programmes were recruited from healthcare facilities in the United Arab Emirates (UAE). Interviews were conducted face to face or online and transcribed verbatim. Results: Four themes emerged: (i) Perceived factors leading to unnecessary or inappropriate antibiotic prescribing and their impact on patients and the community; (ii) current outpatient AMS activities and perceived barriers and facilitators for their sustainability; (iii) suggested outpatient AMS strategies to be implemented in outpatient settings; and (iv) perceived future AMS implementation barriers and suggested mitigation strategies. Conclusions: Several AMS interventions, together with the presence of a clinical pharmacist, may be effective in improving antibiotic use in UAE outpatient settings. Future research should investigate the most appropriate AMS strategy considering barriers and possible mitigation strategies to ensure sustainability.

Development of a Nanoemulgel for the Topical Application of Mupirocin.

Mupirocin (MUP) is an effective topical antibiotic with poor skin permeability; however, its skin permeability can be improved by a nanoemulsion formulation based on eucalyptus oil or eucalyptol. Despite this improvement, the nanoemulsion has limitations, such as low viscosity, low spreadability, and poor retention on the skin. To overcome these limitations, the aim of this study was to develop a nanoemulgel formulation that would enhance its rheological behaviour and physicochemical properties. The MUP nanoemulgel was prepared by incorporating a preprepared MUP nanoemulsion into Carbopol gel at a concentration of 0.75% in a 1:1 ratio. The nanoemulgel formulations were characterised and evaluated for their physicochemical and mechanical strength properties, rheological behaviour, and in vitro skin permeation and deposition, as well as antibacterial studies. Both nanoemulgels exhibited stability at temperatures of 4 and 25 °C for a period of 3 months. They had a smooth, homogenous, and consistent appearance and displayed non-Newtonian pseudoplastic behaviour, with differences in their viscosity and spreadability. However, both nanoemulgels exhibited lower skin permeability compared to the marketed control. The local accumulation efficiency of MUP from nanoemulgel after 8 h was significantly higher than that of the control, although there was no significant difference after 24 h. Micro-CT scan imaging allowed visualisation of these findings and interpretation of the deposited drug spots within the layers of treated skin. While there were no significant differences in the antibacterial activities between the nanoemulgels and the control, the nanoemulgels demonstrated superiority over the control due to their lower content of MUP. These findings support the potential use of the nanoemulgel for targeting skin lesions where high skin deposition and low permeability are required, such as in the case of topical antibacterial agents.

Comparative Evaluation of the Powder and Tableting Properties of Regular and Direct Compression Hypromellose from Different Vendors.

Hypromellose, a widely used polymer in the pharmaceutical industry, is available in several grades, depending on the percentage of substitution of the methoxyl and hydroxypropyl groups and molecular weight, and in various functional forms (e.g., suitable for direct compression tableting). These differences can affect their physicomechanical properties, and so this study aims to characterise the particle size and mechanical properties of HPMC K100M polymer grades from four different vendors. Eight polymers (CR and DC grades) were analysed using scanning electron microscopy (SEM) and light microscopy automated image analysis particle characterisation to examine the powder's particle morphology and particle size distribution. Bulk density, tapped density, and true density of the materials were also analysed. Flow was determined using a shear cell tester. Flat-faced polymer compacts were made at five different compression forces and the mechanical properties of the compacts were evaluated to give an indication of the powder's capacity to form a tablet with desirable strength under specific pressures. The results indicated that the CR grades of the polymers displayed a smaller particle size and better mechanical properties compared to the DC grade HPMC K100M polymers. The DC grades, however, had better flow properties than their CR counterparts. The results also suggested some similarities and differences between some of the polymers from the different vendors despite the similarity in substitution level, reminding the user that care and consideration should be given when substitution is required.

Exploring thresholds and interaction effects among antibiotic usage, covariates, and their effect on antibiotic resistance using an extended-spectrum ß-Lactamase-producing Klebsiella pneumoniae case.

BACKGROUND: This study was aimed to explore thresholds with interaction effects among antibiotic usage, covariates (alcohol-based hand rub (ABHR)), and their effect on extended-spectrum ß-lactamase-producing Klebsiella pneumoniae (ESBL-producing K. pneumoniae) in hospitalized patients. METHODS: Multivariate Adaptive Regression Spline models were used. These considered second-order interactions among antibiotic use and ABHR in addition to potential thresholds that further improve explained variance in the ESBL-producing K. pneumoniae response. The study involved collecting monthly hospital-level data for January 2017-December 2021. RESULTS: Analysis of the main effects showed that third-generation cephalosporins above 2.00 DDD/100 occupied bed days (OBD) generally increased ESBL-producing K. pneumoniae incidence (cases/100 OBD). Levels of ABHR above 6.61 L/100 OBD were shown to generally decrease ESBL-producing K. pneumoniae incidence. Second-order interactions revealed that when third-generation cephalosporin use was greater than 3.71 DDD/100 OBD, and ABHR was greater than 6.6 L/100 OBD (same as main effect threshold), ABHR partially lost effectiveness in its ability to reduce ESBL-producing K. pneumoniae incidence. This demonstrates the importance of not exceeding the identified thresholds of 3.71 DDD/100 OBD for third-generation cephalosporin use. CONCLUSION: The main-effect thresholds in third-generation cephalosporins and ABHR, and the identified interaction between third-generation cephalosporins and ABHR can inform effective hospital antimicrobial stewardship.

The impact of the COVID-19 pandemic on antibiotic consumption and prevalence of pathogens in primary and secondary healthcare settings in Northern Ireland.

AIM: To evaluate the impact of the COVID-19 pandemic on the patterns of antimicrobial use and the incidence of pathogens in primary and secondary healthcare settings in Northern Ireland. METHODS: Data were collected on antibiotic use and Gram-positive and Gram-negative pathogens from primary and secondary healthcare settings in Northern Ireland for the period before (January 2015-March 2020) and during (April 2020-December 2021) the pandemic. Time series intervention analysis methods were utilized. RESULTS: In the hospital setting, the mean total hospital antibiotic consumption during the pandemic was 1864.5 defined daily doses (DDDs) per 1000 occupied-bed days (OBD), showing no significant change from pre-pandemic (P = .7365). During the pandemic, the use of second-generation cephalosporins, third-generation cephalosporins, co-amoxiclav and levofloxacin increased, there was a decrease in the percentage use of the hospital Access group (P = .0083) and an increase in the percentage use of Watch group (P = .0040), and the number of hospital Klebsiella oxytoca and methicillin-susceptible Staphylococcus aureus cases increased. In primary care, the mean total antibiotic consumption during the COVID-19 pandemic was 20.53 DDDs per 1000 inhabitants per day (DID), compared to 25.56 DID before the COVID-19 pandemic (P = .0071). During the pandemic, there was a decrease in the use of several antibiotic classes, an increase in the percentage use of the Reserve group (P = .0032) and an increase in the number of community-onset Pseudomonas aeruginosa cases. CONCLUSION: This study provides details of both changes in antibiotic consumption and the prevalence of infections in hospitals and primary care before and during the COVID-19 pandemic that emphasize the importance of antimicrobial stewardship in pandemic situations.

Personalised 3D-Printed Mucoadhesive Gastroretentive Hydrophilic Matrices for Managing Overactive Bladder (OAB).

Overactive bladder (OAB) is a symptomatic complex condition characterised by frequent urinary urgency, nocturia, and urinary incontinence with or without urgency. Gabapentin is an effective treatment for OAB, but its narrow absorption window is a concern, as it is preferentially absorbed from the upper small intestine, resulting in poor bioavailability. We aimed to develop an extended release, intragastric floating system to overcome this drawback. For this purpose, plasticiser-free filaments of PEO (polyethylene oxide) and the drug (gabapentin) were developed using hot melt extrusion. The filaments were extruded successfully with 98% drug loading, possessed good mechanical properties, and successfully produced printed tablets using fused deposition modelling (FDM). Tablets were printed with varying shell numbers and infill density to investigate their floating capacity. Among the seven matrix tablet formulations, F2 (2 shells, 0% infill) showed the highest floating time, i.e., more than 10 h. The drug release rates fell as the infill density and shell number increased. However, F2 was the best performing formulation in terms of floating and release and was chosen for in vivo (pharmacokinetic) studies. The pharmacokinetic findings exhibit improved gabapentin absorption compared to the control (oral solution). Overall, it can be concluded that 3D printing technology is an easy-to-use approach which demonstrated its benefits in developing medicines based on a mucoadhesive gastroretentive strategy, improving the absorption of gabapentin with potential for the improved management of OAB.

Development of Nanoemulsions for Topical Application of Mupirocin.

Mupirocin (MUP) is a topical antibacterial agent used to treat superficial skin infections but has limited application due to in vivo inactivation and plasma protein binding. A nanoemulsion formulation has the potential to enhance the delivery of mupirocin into the skin. MUP-loaded nanoemulsions were prepared using eucalyptus oil (EO) or eucalyptol (EU), Tween® 80 (T80) and Span® 80 (S80) as oil phase (O), surfactant (S) and cosurfactant (CoS). The nanoemulsions were characterised and their potential to enhance delivery was assessed using an in vitro skin model. Optimised nanoemulsion formulations were prepared based on EO (MUP-NE EO) and EU (MUP-NE EU) separately. MUP-NE EO had a smaller size with mean droplet diameter of 35.89 ± 0.68 nm and narrower particle size index (PDI) 0.10 ± 0.02 nm compared to MUP-NE EU. Both nanoemulsion formulations were stable at 25 °C for three months with the ability to enhance the transdermal permeation of MUP as compared to the control, Bactroban® cream. Inclusion of EU led to a two-fold increase in permeation of MUP compared to the control, while EO increased the percentage by 48% compared to the control. Additionally, more MUP was detected in the skin after 8 h following MUP-NE EU application, although MUP deposition from MUP-NE EO was higher after 24 h. It may be possible, through choice of essential oil to design nanoformulations for both acute and prophylactic management of topical infections.

Public knowledge of antibiotics, self-medication, and household disposal practices in Jordan.

BACKGROUND: This study aimed to assess public understanding of antibiotics, self-medication, and drug disposal practices. METHODS: A cross-sectional self-administered online survey was undertaken in Jordan. RESULTS: The study was completed by 1,105 participants. When asked about their knowledge of antibiotics, rational antibiotic use, and disposal practices, 16% percent believed they should discontinue antibiotics once they felt better, and 12% agreed to take the same antibiotics prescribed to others for the same illness. Self-medication with antibiotics was practiced by 44% of the participants. Prior experience, healthcare costs, and pharmacy location were all major determinants of self-medication. Only 6.4% of unneeded antibiotics were returned to the pharmacy, 60% were kept at home, and 26.6% were disposed of at home. Almost half of those who kept the antibiotics said they would use them again, and one-third said they would give them to friends and family. Respondents who had used antibiotics within the previous 6 months (p = 0.052) and relied on medication leaflets (p = 0.031) and physician recommendations (p = 0.001) were less likely to self-medicate with antibiotics. CONCLUSIONS: The study highlighted areas of inappropriate use of antibiotics, self-medication and the improper antibiotic disposal that can inform antimicrobial stewardship.

Challenges and Possible Solutions to Direct-Acting Oral Anticoagulants (DOACs) Dosing in Patients with Extreme Bodyweight and Renal Impairment.

This article aims to highlight the dosing issues of direct oral anticoagulants (DOACs) in patients with renal impairment and/or obesity in an attempt to develop solutions employing advanced data-driven techniques. DOACs have become widely accepted by clinicians worldwide because of their superior clinical profiles, more predictable pharmacokinetics, and hence more convenient dosing relative to other anticoagulants. However, the optimal dosing of DOACs in extreme bodyweight  patients and patients with renal impairment is difficult to achieve using the conventional dosing approach. The standard dosing approach (fixed-dose) is based on limited data from clinical studies. The existing formulae (models) for determining the appropriate doses for these patient groups leads to suboptimal dosing. This problem of mis-dosing is worsened by the lack of standardized laboratory parameters for monitoring the exposure to DOACs in renal failure and extreme bodyweight patients. Model-informed precision dosing (MIPD) encompasses a range of techniques like machine learning and pharmacometrics modelling, which could uncover key variables and relationships as well as shed more light on the pharmacokinetics and pharmacodynamics of DOACs in patients with extreme bodyweight or renal impairment. Ultimately, this individualized approach-if implemented in clinical practice-could optimise dosing for the DOACs for better safety and efficacy.

Antibiotic use and resistance: Information sources and application by dentists in Jordan.

INTRODUCTION: The availability of evidence-based information sources for dentists is essential to influence antibiotic prescribing practices and we need to understand how dentists interact with such sources and how this influences their practice. The present study aimed to evaluate dentists' preferred sources of information and their awareness of available information and initiatives on prudent antibiotic prescribing practices in Jordan. METHODOLOGY: An online cross-sectional questionnaire was administered to dentists between July to September 2021. It was an adapted version of the European Centre for Disease Prevention and Control (ECDC) survey for antibiotic use and resistance. RESULTS: A total of 204 dentists responded to the survey. The main sources of information regarding avoiding unnecessary antibiotic prescribing were published guidelines (35.5%), the dental professional body (20.0%), colleagues or peers (18.6%), and scientific organizations (17.2%), with the influence of these sources on changing prescribers' views being 40.7%, 9.8%, 10.3%, and 14.2%, respectively. Of the surveyed dentists, 9.3%, 33.8%, and 56.9% were aware, unaware, and unsure of the presence of national action plans on antimicrobial resistance, respectively. Dentists reported their desire to receive more information about resistance to antibiotics (57.8%), medical conditions for which antibiotics are used (52.9%), how to use antibiotics (41.2%), prescribing of antibiotics (39.7%), and links between the health of humans, animals, and the environment (26.0%). CONCLUSIONS: The study provided insights into the information available to and used by dentists, which can inform effective antimicrobial stewardship strategies for improving antibiotic prescribing.

COVID-19 Mixed Impact on Hospital Antimicrobial Stewardship Activities: A Qualitative Study in UK-Based Hospitals.

Antimicrobial resistance (AMR) is a well-known global threat due to the subsequent increase in antimicrobial usage. Several antimicrobial stewardship (AMS) strategies have been implemented to curb irrational prescribing and reduce the AMR burden. However, since the beginning of the COVID-19 pandemic, it has enormously impacted the healthcare system and jeopardized public health, causing millions of deaths globally. Our semi-structured qualitative study aimed to explore the impact of COVID-19 on AMS activities in the UK hospitals. Seventeen interviews were conducted with health care professionals who were part of AMS teams (consultant medical microbiologists, infectious disease consultants, antimicrobial pharmacists). Interviews were audio-recorded and transcribed. An inductive thematic framework was adopted to analyse and create the themes. After agreement of the hierarchical framework definition, all transcripts were coded accordingly. Four main themes and 15 sub-themes were identified. These main themes were: (1) AMS activities or strategies before and during the pandemic; (2) challenges to implementing AMS activities before and during the pandemic; (3) information from public authorities on AMS during the pandemic; and (4) new AMS activities/strategies adopted during the pandemic. Staff vacancies, redeploying of AMS staff to other duties and meeting the burden related to the COVID-19 and lack of resources were the most frequently identified contributing factors to withheld AMS activities during the pandemic. However, modifications to the hybrid working environment, i.e., remote or flexible working, allowed for resumption of AMS activities including virtual ward rounds, virtual meetings and other activities. Further research needs to assess the impact of the hybrid delivery system on AMS activities.

Knowledge, Attitude, and Behavior about Antimicrobial Use and Resistance among Medical, Nursing and Pharmacy Students in Jordan: A Cross Sectional Study.

The present study aimed to survey medical, nursing and pharmacy students' knowledge, attitude and practice regarding antimicrobial use and resistance. Additionally, the study assessed the teaching and assessment activities received regarding antibiotic use. A cross sectional online survey was distributed to undergraduate students currently in clinical studies in their degree program. A total of 716 medicine, nursing and pharmacy undergraduate students were included. Respondents scored more than 76% on knowledge on effective use, unnecessary use and associated side effects of antibiotics, and 65.2% regarding knowledge on the spread of antibiotic resistance. Some participants (21.0%) agreed or strongly agreed that there has been good promotion of prudent antimicrobial use. Students were aware (13.1%), unaware (29.1%), or unsure (57.8%) that there is a national action plan relating to antimicrobial resistance. A total of 62.8% of the respondents strongly agreed or agreed that they have a key role in helping control antibiotic resistance. Participants reported that they require more information about resistance to antibiotics (53.9%), medical conditions for which antibiotics are used (51.7%) and how to use antibiotics (51.0%). Discussion of clinical cases and vignettes and small group teaching were reported as very useful or useful teaching strategies (79.9% and 74.2%, respectively). The findings from this study determined the current situation in relation to education on prudent antimicrobial use for undergraduates and highlighted areas for informing better curriculum design.

Exploring Antimicrobial Stewardship Influential Interventions on Improving Antibiotic Utilization in Outpatient and Inpatient Settings: A Systematic Review and Meta-Analysis.

Antimicrobial stewardship interventions are targeted efforts by healthcare organizations to optimize antimicrobial use in clinical practice. The study aimed to explore effective interventions in improving antimicrobial use in hospitals. Literature was systemically searched for interventional studies through PubMed, CINAHL, and Scopus databases that were published in the period between January 2010 to April 2022. A random-effects model was used to pool and evaluate data from eligible studies that reported antimicrobial stewardship (AMS) interventions in outpatient and inpatient settings. Pooled estimates presented as proportions and standardized mean differences. Forty-eight articles were included in this review: 32 in inpatient and 16 in outpatient settings. Seventeen interventions have been identified, and eight outcomes have been targeted. AMS interventions improved clinical, microbiological, and cost outcomes in most studies. When comparing non-intervention with intervention groups using meta-analysis, there was an insignificant reduction in length of stay (MD: -0.99; 95% CI: -2.38, 0.39) and a significant reduction in antibiotics' days of therapy (MD: -2.73; 95% CI: -3.92, -1.54). There were noticeable reductions in readmissions, mortality rates, and antibiotic prescriptions post antimicrobial stewardship multi-disciplinary team (AMS-MDT) interventions. Studies that involved a pharmacist as part of the AMS-MDT showed more significant improvement in measured outcomes than the studies that did not involve a pharmacist.

Risk Factors Associated with Mortality in COVID-19 Hospitalized Patients: Data from the Middle East.

This study aimed to assess the risk factors for COVID-19 mortality among hospitalized patients in Jordan. All COVID-19 patients admitted to a tertiary hospital in Jordan from September 20, 2020, to August 8, 2021, were included in this study. Demographics, clinical characteristics, comorbidities, and laboratory results were extracted from the patients' electronic records. Multivariable logistic and machine learning (ML) methods were used to study variable importance. Out of 1,613 COVID-19 patients, 1,004 (62.2%) were discharged from the hospital (survived), while 609 (37.8%) died. Patients who were of elderly age (>65 years) (OR, 2.01; 95% CI, 1.28-3.16), current smokers (OR, 1.61; 95%CI, 1.17-2.23), and had severe or critical illness at admission ((OR, 1.56; 95%CI, 1.05-2.32) (OR, 2.94; 95%CI, 2.02-4.27); respectively), were at higher risk of mortality. Comorbidities including chronic kidney disease (OR, 2.90; 95% CI, 1.90-4.43), deep venous thrombosis (OR, 2.62; 95% CI, 1.08-6.35), malignancy (OR, 2.22; 95% CI, 1.46-3.38), diabetes (OR, 1.31; 95% CI, 1.04-1.65), and heart failure (OR, 1.51; 95% CI, 1.02-2.23) were significantly associated with increased risk of mortality. Laboratory abnormalities associated with mortality included hypernatremia (OR, 11.37; 95% CI, 4.33-29.81), elevated aspartate aminotransferase (OR, 1.81; 95% CI, 1.42-2.31), hypoalbuminemia (OR, 1.75; 95% CI, 1.37-2.25), and low platelets level (OR, 1.43; 95% CI, 1.05-1.95). Several demographic, clinical, and laboratory risk factors for COVID-19 mortality were identified. This study is the first to examine the risk factors associated with mortality using ML methods in the Middle East. This will contribute to a better understanding of the impact of the disease and improve the outcome of the pandemic worldwide.

A Threshold Logistic Modelling Approach for Identifying Thresholds between Antibiotic Use and Methicillin-Resistant Staphylococcus aureus Incidence Rates in Hospitals.

The aim of this study was to demonstrate the utility of threshold logistic modelling, an innovative approach in identifying thresholds and risk scores in the context of population antibiotic use associated with methicillin-resistant Staphylococcus aureus (MRSA) incidence rates in hospitals. The study also aimed to assess the impact of exceeding those thresholds that resulted in increased MRSA rates. The study was undertaken in a 700-bed hospital in England between January 2015 and December 2021 (84 monthly observations). By employing the threshold logistic modelling approach, we: (i) determined the cut-off percentile value of MRSA incidence that defines a critical level of MRSA; (ii) identified thresholds for fluoroquinolone and co-amoxiclav use that would accelerate MRSA incidence rates and increase the probability of reaching critical incidence levels; (iii) enabled a better understanding of the effect of antibiotic use on the probability of reaching a critical level of resistant pathogen incidence; (iv) developed a near real-time performance monitoring feedback system; (v) provided risk scores and alert signals for antibiotic use, with the ability to inform hospital policies, and control MRSA incidence; and (vi) provided recommendations and an example for the management of pathogen incidence in hospitals. Threshold logistic models can help hospitals determine quantitative targets for antibiotic usage and can also inform effective antimicrobial stewardship to control resistance in hospitals. Studies should work toward implementing and evaluating the proposed approach prospectively, with the aim of determining the best counter-measures to mitigate the risk of increased resistant pathogen incidence in hospitals.