Comparison of the global prevalence and trend of human intestinal carriage of ESBL-producing Escherichia coli between healthcare and community settings: a systematic review and meta-analysis.

Objectives: The widespread intestinal carriage of ESBL-producing Escherichia coli (ESBL E. coli) among both patients and healthy individuals is alarming. However, the global prevalence and trend of this MDR bacterium in healthcare settings remains undetermined. To address this knowledge gap, we performed a comparative meta-analysis of the prevalence in community and healthcare settings. Methods: Our systematic review included 133 articles published between 1 January 2000 and 22 April 2021 and indexed in PubMed, EMBASE or Google Scholar. A random-effects meta-analysis was performed to obtain the global pooled prevalence (community and healthcare settings). Subgroup meta-analyses were performed by grouping studies using the WHO regions and 5 year intervals of the study period. Results: We found that 21.1% (95% CI, 19.1%-23.2%) of inpatients in healthcare settings and 17.6% (95% CI, 15.3%-19.8%) of healthy individuals worldwide carried ESBL E. coli in their intestine. The global carriage rate in healthcare settings increased 3-fold from 7% (95% CI, 3.7%-10.3%) in 2001-05 to 25.7% (95% CI, 19.5%-32.0%) in 2016-20, whereas in community settings it increased 10-fold from 2.6% (95% CI, 1.2%-4.0%) to 26.4% (95% CI, 17.0%-35.9%) over the same period. Conclusions: The global and regional human intestinal ESBL E. coli carriage is increasing in both community and healthcare settings. Carriage rates were generally higher in healthcare than in community settings. Key relevant health organizations should perform surveillance and implement preventive measures to address the spread of ESBL E. coli in both settings.

Comparison of renin-angiotensin-aldosterone system inhibitors with other antihypertensives in association with coronavirus disease-19 clinical outcomes.

BACKGROUND: Reports on the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting. We performed this meta-analysis to find conclusive evidence. METHODS: We searched published articles through PubMed, EMBASE and medRxiv from 5 January 2020 to 3 August 2020. Studies that reported clinical outcomes of patients with COVID-19, stratified by the class of antihypertensives, were included. Random and fixed-effects models were used to estimate pooled odds ratio (OR). RESULTS: A total 36 studies involving 30,795 patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR = 0.79, 95% CI: [0.67, 0.95]) compared with those receiving non-RAAS inhibitor antihypertensives. However, further sub-meta-analysis showed that specific RAAS inhibitors did not show a reduction of poor COVID-19 outcomes when compared with any class of antihypertensive except beta-blockers (BBs). For example, compared to calcium channel blockers (CCBs), neither angiotensin-I-converting enzyme inhibitors (ACEIs) (OR = 0.91, 95% CI: [0.67, 1.23]) nor angiotensin-II receptor blockers (ARBs) (OR = 0.90, 95% CI: [0.62, 1.33]) showed a reduction of poor COVID-19 outcomes. When compared with BBs, however, both ACEIs (OR = 0.85, 95% CI: [0.73, 0.99) and ARBs (OR = 0.72, 95% CI: [0.55, 0.94]) showed an apparent decrease in poor COVID-19 outcomes. CONCLUSIONS: RAAS inhibitors did not increase the risk of mortality or severity of COVID-19. Differences in COVID-19 clinical outcomes between different class of antihypertensive drugs were likely due to the underlying comorbidities for which the antihypertensive drugs were prescribed, although adverse effects of drugs such as BBs could not be excluded.

The global prevalence and trend of human intestinal carriage of ESBL-producing Escherichia coli in the community.

OBJECTIVES: Intestinal colonization by ESBL Escherichia coli and its association with community-acquired MDR infections is of great concern. This review determined the worldwide prevalence of human faecal ESBL E. coli carriage and its trend in the community over the past two decades. METHODS: A systematic literature search was conducted using PubMed, EMBASE and Google Scholar to retrieve articles published between 1 January 2000 and 13 February 2020 that contained data on the prevalence of faecal carriage of ESBL E. coli among healthy individuals. A cumulative (for the whole period) meta-analysis was used to estimate the global and regional pooled prevalence rates. Articles were grouped into study periods of 3 years, and subgroup meta-analyses were undertaken to examine the global pooled prevalence over time. RESULTS: Sixty-two articles covering 29 872 healthy persons were included in this meta-analysis. The cumulative (2003-18) global pooled prevalence of ESBL E. coli intestinal carriage in the community was 16.5% (95% CI 14.3%-18.7%; P  <  0.001). The pooled prevalence showed an upward trend, increasing from 2.6% (95% CI 1.6%-4.0%) in 2003-05 to 21.1% (95% CI 15.8%-27.0%) in 2015-18. Over the whole period, the highest carriage rate was observed in South-East Asia (27%; 95% CI 2.9%-51.3%), while the lowest occurred in Europe (6.0%; 95% CI 4.6%-7.5%). CONCLUSIONS: Globally, an 8-fold increase in the intestinal carriage rate of ESBL E. coli in the community has occurred over the past two decades. Prevention of its spread may require new therapeutic and public health strategies.

The Tasmanian Atrial Fibrillation Study (TAFS): Differences in Stroke Prevention According to Sex.

Background: There are limited Australian data on sex differences in oral anticoagulant (OAC) prescribing in atrial fibrillation (AF) and ongoing debate regarding the optimal approach to stroke risk assessment and OAC prescribing in female patients with AF. Objective: The purpose of this study was to investigate sex differences in the prescribing of OACs in patients with AF stratified by stroke risk and in the rate of adverse outcomes. Methods: A retrospective analysis of patients admitted to the Royal Hobart Hospital (Tasmania, Australia) with nonvalvular AF between January 2011 and July 2015 was conducted. Rates of antithrombotic prescribing according to sex and stroke risk were assessed along with a multivariate analysis for predictors of OAC prescribing. Rates of thromboembolism, bleeding, and all-cause mortality were assessed according to sex. Results: A total of 2090 patients were included (44.7% female). Women with a CHA2DS2-VA score ≥2 were less likely to receive an OAC compared with men (56.7% vs 62.2%, P = 0.023). Female sex was an independent negative predictor of OAC prescribing (adjusted odds ratio = 0.83; 95% CI = 0.69-0.99; P = 0.041). There were no sex differences in the incidence rates of thromboembolism, bleeding, or all-cause mortality in patients newly commenced on antithrombotic therapy. Conclusion and Relevance: Female patients with a high stroke risk were less likely to receive guideline-recommended treatment. This study provides new information on prescribing trends within the Australian setting and highlights the opportunity to improve the management of female patients with AF and 1 or more additional stroke risk factors.

The Tasmanian atrial fibrillation study: Transition to direct oral anticoagulants 2011-2015.

INTRODUCTION: Contemporary Australian data regarding antithrombotic prescribing patterns following approval of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) are limited. AIM: The aim of this study was to assess antithrombotic prescribing patterns before, during, and after the clinical introduction of DOACs. METHODS: Using digital medical records, this retrospective cohort study included all patients with AF as a primary or secondary diagnosis who were admitted to the Royal Hobart Hospital, Tasmania, Australia, between January 2011 and July 2015. RESULTS: Antithrombotic agents were prescribed for 2078 (91.9%) of 2261 patients without documented contraindication to therapy. Higher rates of OAC prescribing were observed following government subsidization of DOACs in Quarter 3 (Q3) 2013 than anticoagulation rates in the prior quarters (54.4% in Q3, 2013, to 68.1% in Q2, 2015, P<.001), with the prescribing of warfarin and antiplatelet agents declining. DOACs, as a class, accounted for 18.4% of patients on antithrombotic therapy in 2011-2015; the proportion of patients receiving a DOAC steadily increased from 3.9% among OAC users in Q3, 2011, to 67.6% in Q2, 2015 (P<.001). In a subset of patients with newly diagnosed AF, patients commenced on DOACs were younger (70.4 vs 73.8 years, P=.04) and had lower stroke and bleeding risk scores (CHA2DS2-VASc 2.8 vs 3.3, P=.03, HAS-BLED 2 vs 3, P=.04) than patients who were newly prescribed warfarin. CONCLUSIONS: Direct oral anticoagulants rapidly became the most commonly prescribed class of antithrombotic medications in patients with AF soon after they became widely available. Warfarin and antiplatelet prescribing declined significantly, although a substantial proportion of patients continued to be prescribed antiplatelet therapy. Patients who were initiated on DOACs were typically younger with fewer comorbid conditions compared with those initiated on warfarin therapy.

Suboptimal Use of Oral Anticoagulants in Atrial Fibrillation: Has the Introduction of Direct Oral Anticoagulants Improved Prescribing Practices?

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) and the associated risk of stroke are emerging epidemics throughout the world. Suboptimal use of oral anticoagulants for stroke prevention has been widely reported from observational studies. In recent years, direct oral anticoagulants (DOACs) have been introduced for thromboprophylaxis. We conducted a systematic literature review to evaluate current practices of anticoagulation in AF, pharmacologic features and adoption patterns of DOACs, their impacts on proportion of eligible patients with AF who receive oral anticoagulants, persisting challenges and future prospects for optimal anticoagulation. LITERATURE SOURCE AND SELECTION CRITERIA: In conducting this review, we considered the results of relevant prospective and retrospective observational studies from real-world practice settings. PubMed (MEDLINE), Scopus (RIS), Google Scholar, EMBASE and Web of Science were used to source relevant literature. There were no date limitations, while language was limited to English. Selection was limited to articles from peer reviewed journals and related to our topic. RESULTS: Most studies identified in this review indicated suboptimal use of anticoagulants is a persisting challenge despite the availability of DOACs. Underuse of oral anticoagulants is apparent particularly in patients with a high risk of stroke. DOAC adoption trends are quite variable, with slow integration into clinical practice reported in most countries; there has been limited impact to date on prescribing practice. CONCLUSION: Available data from clinical practice suggest that suboptimal oral anticoagulant use in patients with AF and poor compliance with guidelines still remain commonplace despite transition to a new era of anticoagulation featuring DOACs.