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The Cochrane Database of Systematic... Oct 2021The effect of antibiotics with potential antiviral and anti-inflammatory properties are being investigated in clinical trials as treatment for COVID-19. The use of... (Review)
Review
BACKGROUND
The effect of antibiotics with potential antiviral and anti-inflammatory properties are being investigated in clinical trials as treatment for COVID-19. The use of antibiotics follows the intention-to-treat the viral disease and not primarily to treat bacterial co-infections of individuals with COVID-19. A thorough understanding of the current evidence regarding effectiveness and safety of antibiotics as anti-viral treatments for COVID-19 based on randomised controlled trials (RCTs) is required.
OBJECTIVES
To assess the efficacy and safety of antibiotics compared to each other, no treatment, standard of care alone, placebo, or any other active intervention with proven efficacy for treatment of COVID-19 outpatients and inpatients. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (including MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, medRxiv, CENTRAL), Web of Science and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 14 June 2021.
SELECTION CRITERIA
RCTs were included that compared antibiotics with each other, no treatment, standard of care alone, placebo, or another proven intervention, for treatment of people with confirmed COVID-19, irrespective of disease severity, treated in the in- or outpatient settings. Co-interventions had to be the same in both study arms. We excluded studies comparing antibiotics to other pharmacological interventions with unproven efficacy.
DATA COLLECTION AND ANALYSIS
We assessed risk of bias of primary outcomes using the Cochrane risk of bias tool (ROB 2) for RCTs. We used GRADE to rate the certainty of evidence for the following primary outcomes: 1. to treat inpatients with moderate to severe COVID-19: mortality, clinical worsening defined as new need for intubation or death, clinical improvement defined as being discharged alive, quality of life, adverse and serious adverse events, and cardiac arrhythmias; 2. to treat outpatients with asymptomatic or mild COVID-19: mortality, clinical worsening defined as hospital admission or death, clinical improvement defined as symptom resolution, quality of life, adverse and serious adverse events, and cardiac arrhythmias.
MAIN RESULTS
We included 11 studies with 11,281 participants with an average age of 54 years investigating antibiotics compared to placebo, standard of care alone or another antibiotic. No study was found comparing antibiotics to an intervention with proven efficacy. All studies investigated azithromycin, two studies investigated other antibiotics compared to azithromycin. Seven studies investigated inpatients with moderate to severe COVID-19 and four investigated mild COVID-19 cases in outpatient settings. Eight studies had an open-label design, two were blinded with a placebo control, and one did not report on blinding. We identified 19 ongoing and 15 studies awaiting classification pending publication of results or clarification of inconsistencies. Of the 30 study results contributing to primary outcomes by included studies, 17 were assessed as overall low risk and 13 as some concerns of bias. Only studies investigating azithromycin reported data eligible for the prioritised primary outcomes. Azithromycin doses and treatment duration varied among included studies. Azithromycin for the treatment of COVID-19 compared to placebo or standard of care alone in inpatients We are very certain that azithromycin has little or no effect on all-cause mortality at day 28 compared to standard of care alone (risk ratio (RR) 0.98; 95% confidence interval (CI) 0.90 to 1.06; 8600 participants; 4 studies; high-certainty evidence). Azithromycin probably has little or no effect on clinical worsening or death at day 28 (RR 0.95; 95% CI 0.87 to 1.03; 7311 participants; 1 study; moderate-certainty evidence), on clinical improvement at day 28 (RR 0.96; 95% CI 0.84 to 1.11; 8172 participants; 3 studies; moderate-certainty evidence), on serious adverse events during the study period (RR 1.11; 95% CI 0.89 to 1.40; 794 participants; 4 studies; moderate-certainty evidence), and cardiac arrhythmias during the study period (RR 0.92; 95% CI 0.73 to 1.15; 7865 participants; 4 studies; moderate-certainty evidence) compared to placebo or standard of care alone. Azithromycin may increase any adverse events slightly during the study period (RR 1.20; 95% CI 0.92 to 1.57; 355 participants; 3 studies; low-certainty evidence) compared to standard of care alone. No study reported quality of life up to 28 days. Azithromycin for the treatment of COVID-19 compared to placebo or standard of care alone in outpatients Azithromycin may have little or no effect compared to placebo or standard of care alone on all-cause mortality at day 28 (RR 1.00 ; 95% CI 0.06 to 15.69; 876 participants; 3 studies; low-certainty evidence), on admission to hospital or death within 28 days (RR 0.94 ; 95% CI 0.57 to 1.56; 876 participants; 3 studies; low-certainty evidence), and on symptom resolution at day 14 (RR 1.03; 95% CI 0.95 to 1.12; 138 participants; 1 study; low-certainty evidence). We are uncertain whether azithromycin increases or reduces serious adverse events compared to placebo or standard of care alone (0 participants experienced serious adverse events; 454 participants; 2 studies; very low-certainty evidence). No study reported on adverse events, cardiac arrhythmias during the study period or quality of life up to 28 days. Azithromycin for the treatment of COVID-19 compared to any other antibiotics in inpatients and outpatients One study compared azithromycin to lincomycin in inpatients, but did not report any primary outcome. Another study compared azithromycin to clarithromycin in outpatients, but did not report any relevant outcome for this review.
AUTHORS' CONCLUSIONS
We are certain that risk of death in hospitalised COVID-19 patients is not reduced by treatment with azithromycin after 28 days. Further, based on moderate-certainty evidence, patients in the inpatient setting with moderate and severe disease probably do not benefit from azithromycin used as potential antiviral and anti-inflammatory treatment for COVID-19 regarding clinical worsening or improvement. For the outpatient setting, there is currently low-certainty evidence that azithromycin may have no beneficial effect for COVID-19 individuals. There is no evidence from RCTs available for other antibiotics as antiviral and anti-inflammatory treatment of COVID-19. With accordance to the living approach of this review, we will continually update our search and include eligible trials to fill this evidence gap. However, in relation to the evidence for azithromycin and in the context of antimicrobial resistance, antibiotics should not be used for treatment of COVID-19 outside well-designed RCTs.
Topics: Anti-Bacterial Agents; COVID-19; Cause of Death; Humans; Middle Aged; Respiration, Artificial; SARS-CoV-2
PubMed: 34679203
DOI: 10.1002/14651858.CD015025 -
Canadian Journal of Surgery. Journal... May 2020In medical and surgical departments around the world, morbidity and mortality conferences (MMC) serve dual roles: they are cornerstones of quality-improvement programs...
BACKGROUND
In medical and surgical departments around the world, morbidity and mortality conferences (MMC) serve dual roles: they are cornerstones of quality-improvement programs and provide timely opportunities for education within the urgent context of clinical care. Despite the widespread adoption of MMCs, adverse events and preventable errors remain high or incompletely characterized, and opportunities to learn from and adjust to these events are frequently lost. This review examines the published literature on strategies to improve surgical MMCs.
METHODS
We searched OVID Medline, PubMed, Embase and CENTRAL. We defined our combination of search terms using a PICO (population, intervention, comparison, outcome) model, focusing on the use of MMCs in general surgery.
RESULTS
The MMC literature focused on 5 themes: educational value, error analysis, case selection and representation, attendance and dissemination. Strategies used to increase educational value included limiting case presentation time to 15-20 minutes, mandatory brief literature reviews, increasing audience interaction, and standardizing presentations using a PowerPoint template or SBAR (situation, background, assessment, recommendation) format. Interventions to improve error analysis included focused discussion on causative factors and taxonomic error analysis. Case selection was improved by using an electronic clinical registry, such as the National Surgery Quality Improvement Program, to better capture incidence of morbidity and mortality. Attendance was improved with teleconferencing. Dissemination strategies included MMC newsletters, incorporating MMCs into plan-do-check-act cycles, and surgeon report cards.
CONCLUSION
Greater standardization of best practices may increase the quality improvement and educational impact of MMCs and provide a baseline to measure the effect of new MMC format innovations on the clinical and educational performance of surgical systems.
Topics: Global Health; Humans; Medical Errors; Morbidity; Orthopedic Procedures; Quality Improvement; Survival Rate
PubMed: 32386469
DOI: 10.1503/cjs.009219 -
Journal of General Internal Medicine Jul 2020The number of preventable inpatient deaths in the USA is commonly estimated as between 44,000 and 98,000 deaths annually. Because many inpatient deaths are believed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The number of preventable inpatient deaths in the USA is commonly estimated as between 44,000 and 98,000 deaths annually. Because many inpatient deaths are believed to be preventable, mortality rates are used for quality measures and reimbursement. We aimed to estimate the proportion of inpatient deaths that are preventable.
METHODS
A systematic literature search of Medline, Embase, Web of Science, and the Cochrane Library through April 8, 2019, was conducted. We included case series of adult patients who died in the hospital and were reviewed by physicians to determine if the death was preventable. Two reviewers independently performed data extraction and study quality assessment. The proportion of preventable deaths from individual studies was pooled using a random-effects model.
RESULTS
Sixteen studies met inclusion criteria. Eight studies of consecutive or randomly selected cohorts including 12,503 deaths were pooled. The pooled rate of preventable mortality was 3.1% (95% CI 2.2-4.1%). Two studies also reported rates of preventable mortality limited to patients expected to live longer than 3 months, ranging from 0.5 to 1.0%. In the USA, these estimates correspond to approximately 22,165 preventable deaths annually and 7150 deaths for patients with greater than 3-month life expectancy.
DISCUSSION
The number of deaths due to medical error is lower than previously reported and the majority occur in patients with less than 3-month life expectancy. The vast majority of hospital deaths are due to underlying disease. Our results have implications for the use of hospital mortality rates for quality reporting and reimbursement.
STUDY REGISTRATION
PROSPERO registration number CRD42018095140.
Topics: Adult; Hospital Mortality; Hospitals; Humans; Inpatients; Life Expectancy; Medical Errors
PubMed: 31965525
DOI: 10.1007/s11606-019-05592-5 -
BMJ Open Aug 2022In this study, we aim to analyse the relationship between educational attainment and all-cause mortality of adults in the high-income Asia Pacific region. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
In this study, we aim to analyse the relationship between educational attainment and all-cause mortality of adults in the high-income Asia Pacific region.
DESIGN
This study is a comprehensive systematic review and meta-analysis with no language restrictions on searches. Included articles were assessed for study quality and risk of bias using the Joanna Briggs Institute critical appraisal checklists. A random-effects meta-analysis was conducted to evaluate the overall effect of individual level educational attainment on all-cause mortality.
SETTING
The high-income Asia Pacific Region consisting of Japan, South Korea, Singapore and Brunei Darussalam.
PARTICIPANTS
Articles reporting adult all-cause mortality by individual-level education were obtained through searches conducted from 25 November 2019 to 6 December 2019 of the following databases: PubMed, Web of Science, Scopus, EMBASE, Global Health (CAB), EconLit and Sociology Source Ultimate.
PRIMARY AND SECONDARY OUTCOME MEASURES
Adult all-cause mortality was the primary outcome of interest.
RESULTS
Literature searches resulted in 15 345 sources screened for inclusion. A total of 30 articles meeting inclusion criteria with data from the region were included for this review. Individual-level data from 7 studies covering 222 241 individuals were included in the meta-analyses. Results from the meta-analyses showed an overall risk ratio of 2.40 (95% CI 1.74 to 3.31) for primary education and an estimate of 1.29 (95% CI 1.08 to 1.54) for secondary education compared with tertiary education.
CONCLUSION
The results indicate that lower educational attainment is associated with an increase in the risk of all-cause mortality for adults in the high-income Asia Pacific region. This study offers empirical support for the development of policies to reduce health disparities across the educational gradient and universal access to all levels of education.
PROSPERO REGISTRATION NUMBER
CRD42020183923.
Topics: Adult; Asia; Health Inequities; Humans; Japan; Mortality; Republic of Korea; Singapore
PubMed: 35940840
DOI: 10.1136/bmjopen-2021-059042 -
BMC Pregnancy and Childbirth Nov 2023To quantify the extent of incompleteness and misclassification of maternal and pregnancy related deaths, and to identify general and context-specific factors associated... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To quantify the extent of incompleteness and misclassification of maternal and pregnancy related deaths, and to identify general and context-specific factors associated with incompleteness and/or misclassification of maternal death data.
METHODS
We conducted a systematic review of incompleteness and/or misclassification of maternal and pregnancy-related deaths. We conducted a narrative synthesis to identify methods used to capture and classify maternal deaths, as well as general and context specific factors affecting the completeness and misclassification of maternal death recording. We conducted a meta-analysis of proportions to obtain estimates of incompleteness and misclassification of maternal death recording, overall and disaggregated by income and surveillance system types.
FINDINGS
Of 2872 title-abstracts identified, 29 were eligible for inclusions in the qualitative synthesis, and 20 in the meta-analysis. Included studies relied principally on record linkage and review for identifying deaths, and on review of medical records and verbal autopsies to correctly classify cause of death. Deaths to women towards the extremes of the reproductive age range, those not classified by a medical examiner or a coroner, and those from minority ethnic groups in their setting were more likely misclassified or unrecorded. In the meta-analysis, we found maternal death recording to be incomplete by 34% (95% CI: 28-48), with 60% sensitivity (95% CI: 31-81.). Overall, we found maternal mortality was under-estimated by 39% (95% CI: 30-48) due to incompleteness and/or misclassification. Reporting of deaths away from the intrapartum, due to indirect causes or occurring at home were less complete than their counterparts. There was substantial between and within group variability across most results.
CONCLUSION
Maternal deaths were under-estimated in almost all contexts, but the extent varied across settings. Countries should aim towards establishing Civil Registration and Vital Statistics systems where they are not instituted. Efforts to improve the completeness and accuracy of maternal cause of death recording, such as Confidential Enquiries into Maternal Deaths, are needed even where CRVS is considered to be well-functioning.
Topics: Pregnancy; Humans; Female; Maternal Death; Maternal Mortality; Reproduction; Family; Ethnicity; Cause of Death
PubMed: 37968585
DOI: 10.1186/s12884-023-06077-4 -
Journal of Preventive Medicine and... Jun 2021The ongoing novel coronavirus disease 2019 (COVID-19) is the leading cause of morbidity and mortality due to its contagious nature and absence of vaccine and treatment.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The ongoing novel coronavirus disease 2019 (COVID-19) is the leading cause of morbidity and mortality due to its contagious nature and absence of vaccine and treatment. Although numerous primary studies reported extremely variable case fatality rate (CFR) of COVID-19, no review study attempted to estimate the CFR of COVID-19. The current systematic review and meta-analysis were aimed to assess the pooled CFR of COVID-19.
METHODS
Electronic databases: PubMed, Science Direct, Scopus, and Google Scholar were searched to retrieve the eligible primary studies that reported CFR of COVID-19. Keywords: ("COVID-19"OR "COVID-2019" OR "severe acute respiratory syndrome coronavirus 2"OR "severe acute respiratory syndrome coronavirus 2" OR "2019-nCoV" OR "SARS-CoV-2" OR "2019nCoV" OR (("Wuhan" AND ("coronavirus" OR "coronavirus")) AND (2019/12[PDAT] OR 2020[PDAT]))) AND ("mortality "OR "mortality" OR ("case" AND "fatality" AND "rate") OR "case fatality rate") were used as free text and MeSH term in searching process. A random-effects model was used to estimate the CFR in this study. I statistics, Cochran's Q test, and T were used to assess the functional heterogeneity between included studies.
RESULTS
The overall pooled CFR of COVID 19 was 10.0%(95% CI: 8.0-11.0); P < 0.001; I = 99.7). The pooled CFR of COVID-19 in general population was 1.0% (95% CI: 1.0-3.0); P < 0.001; I = 94.3), while in hospitalized patients was 13.0% (95% CI: 9.0-17.0); P < 0.001, I = 95.6). The pooled CFR in patients admitted in intensive care unit (ICU) was 37.0% (95% CI: 24.0-51.0); P < 0.001, I = 97.8) and in patients older than 50 years was 19.0% (95% CI: 13.0-24.0); P < 0.001; I = 99.8).
CONCLUSION
The present review results highlighted the need for transparency in testing and reporting policies and denominators used in CFR estimation. It is also necessary to report the case's age, sex, and the comorbidity distribution of all patients, which essential in comparing the CFR among different segments of the population.
Topics: COVID-19; Comorbidity; Female; Humans; Male; SARS-CoV-2; Survival Rate
PubMed: 34604571
DOI: 10.15167/2421-4248/jpmh2021.62.2.1627 -
European Heart Journal Sep 2022The effect of the COVID-19 pandemic on care and outcomes across non-COVID-19 cardiovascular (CV) diseases is unknown. A systematic review and meta-analysis was performed... (Meta-Analysis)
Meta-Analysis
AIMS
The effect of the COVID-19 pandemic on care and outcomes across non-COVID-19 cardiovascular (CV) diseases is unknown. A systematic review and meta-analysis was performed to quantify the effect and investigate for variation by CV disease, geographic region, country income classification and the time course of the pandemic.
METHODS AND RESULTS
From January 2019 to December 2021, Medline and Embase databases were searched for observational studies comparing a pandemic and pre-pandemic period with relation to CV disease hospitalisations, diagnostic and interventional procedures, outpatient consultations, and mortality. Observational data were synthesised by incidence rate ratios (IRR) and risk ratios (RR) for binary outcomes and weighted mean differences for continuous outcomes with 95% confidence intervals. The study was registered with PROSPERO (CRD42021265930). A total of 158 studies, covering 49 countries and 6 continents, were used for quantitative synthesis. Most studies (80%) reported information for high-income countries (HICs). Across all CV disease and geographies there were fewer hospitalisations, diagnostic and interventional procedures, and outpatient consultations during the pandemic. By meta-regression, in low-middle income countries (LMICs) compared to HICs the decline in ST-segment elevation myocardial infarction (STEMI) hospitalisations (RR 0.79, 95% confidence interval [CI] 0.66-0.94) and revascularisation (RR 0.73, 95% CI 0.62-0.87) was more severe. In LMICs, but not HICs, in-hospital mortality increased for STEMI (RR 1.22, 95% CI 1.10-1.37) and heart failure (RR 1.08, 95% CI 1.04-1.12). The magnitude of decline in hospitalisations for CV diseases did not differ between the first and second wave.
CONCLUSIONS
There was substantial global collateral CV damage during the COVID-19 pandemic with disparity in severity by country income classification.
Topics: COVID-19; Cardiovascular Diseases; Hospital Mortality; Hospitalization; Humans; Pandemics; ST Elevation Myocardial Infarction
PubMed: 36044988
DOI: 10.1093/eurheartj/ehac227 -
International Journal of Public Health 2022This study aims to summarize how child mortality-a Sustainable Development Goal stated by the United Nations-has been explicitly addressed in the context of... (Review)
Review
This study aims to summarize how child mortality-a Sustainable Development Goal stated by the United Nations-has been explicitly addressed in the context of innovations. A scoping review following the PRISMA-ScR Statement was performed analysing indexed and non-indexed literature. Empirical and non-disruptive innovation in the context of process targeting under-five mortality rate was the main subset of literature included in this article. The increment of literature on innovation in the context of SDGs over the last years denotes its growing importance and even though innovation aiming to reduce child mortality is currently being done, a significant part of it is not published in indexed databases but as grey literature. Empirical, disruptive innovation under a structural approach and empirical, non-disruptive innovation under a project point of view are the main types of innovation addressed in the literature and would be of utmost potential to reduce child mortality rate. A systematic review of the methods used for the measures of evaluation of applied innovations, their quality and results would be of great importance in the future.
Topics: Child; Child Mortality; Humans; Sustainable Development; United Nations
PubMed: 36046259
DOI: 10.3389/ijph.2022.1604815 -
International Journal of Surgery... Apr 2023Postoperative mortality is an important indicator for evaluating surgical safety. Postoperative mortality is influenced by hospital volume; however, this association is... (Meta-Analysis)
Meta-Analysis
Association between hospital surgical case volume and postoperative mortality in patients undergoing gastrectomy for gastric cancer: a systematic review and meta-analysis.
BACKGROUND
Postoperative mortality is an important indicator for evaluating surgical safety. Postoperative mortality is influenced by hospital volume; however, this association is not fully understood. This study aimed to investigate the volume-outcome association between the hospital surgical case volume for gastrectomies per year (hospital volume) and the risk of postoperative mortality in patients undergoing a gastrectomy for gastric cancer.
METHODS
Studies assessing the association between hospital volume and the postoperative mortality in patients who underwent gastrectomy for gastric cancer were searched for eligibility. Odds ratios were pooled for the highest versus lowest categories of hospital volume using a random-effects model. The volume-outcome association between hospital volume and the risk of postoperative mortality was analyzed. The study protocol was registered with Prospective Register of Systematic Reviews (PROSPERO).
RESULTS
Thirty studies including 586 993 participants were included. The risk of postgastrectomy mortality in patients with gastric cancer was 35% lower in hospitals with higher surgical case volumes than in their lower-volume counterparts (odds ratio: 0.65; 95% CI: 0.56-0.76; P <0.001). This relationship was consistent and robust in most subgroup analyses. Volume-outcome analysis found that the postgastrectomy mortality rate remained stable or was reduced after the hospital volume reached a plateau of 100 gastrectomy cases per year.
CONCLUSIONS
The current findings suggest that a higher-volume hospital can reduce the risk of postgastrectomy mortality in patients with gastric cancer, and that greater than or equal to 100 gastrectomies for gastric cancer per year may be defined as a high hospital surgical case volume.
Topics: Humans; Stomach Neoplasms; Hospitals, High-Volume; Hospital Mortality; Gastrectomy
PubMed: 36917144
DOI: 10.1097/JS9.0000000000000269 -
JAMA Pediatrics Dec 2021Childhood adversity (CA) is a powerful determinant of long-term physical and mental health that is associated with elevated risk for chronic disease and psychopathology....
IMPORTANCE
Childhood adversity (CA) is a powerful determinant of long-term physical and mental health that is associated with elevated risk for chronic disease and psychopathology. However, the degree to which CA contributes to mortality as a preventable driver of ill-health and death is unknown.
OBJECTIVE
To estimate the contribution of CA to health behaviors, including smoking and sedentary behavior, as well as the annual mortality attributable to CA in the US through influences on leading causes of death (eg, cardiovascular disease).
EVIDENCE REVIEW
For this systematic review, the PsycINFO and MEDLINE databases were searched on November 15, 2019. The databases were searched for publications from inception (1806 for PsycINFO, 1946 for MEDLINE) to November 15, 2019. Meta-analyses of the associations between CA and morbidity outcomes were included. The population attributable fraction (PAF) was calculated from these associations along with the estimated US prevalence of CA. The PAF was then applied to the number of annual deaths associated with each cause of death to estimate the number of deaths that are attributable to CA. Additionally, the PAF was applied to the incidence of health behaviors to derive the number of cases attributable to CA. Exposure to 1 or more experiences of adversity before the age of 18 years was analyzed, including abuse, neglect, family violence, and economic adversity.
FINDINGS
A total of 19 meta-analyses with 20 654 832 participants were reviewed. Childhood adversity accounted for approximately 439 072 deaths annually in the US, or 15% of the total US mortality in 2019 (2 854 838 deaths), through associations with leading causes of death (including heart disease, cancer, and suicide). In addition, CA was associated with millions of cases of unhealthy behaviors and disease markers, including more than 22 million cases of sexually transmitted infections, 21 million cases of illicit drug use, 19 million cases of elevated inflammation, and more than 10 million cases each of smoking and physical inactivity. The greatest proportion of outcomes attributable to CA were for suicide attempts and sexually transmitted infections, for which adversity accounted for up to 38% and 33%, respectively.
CONCLUSIONS AND RELEVANCE
The results of this systematic review suggest that CA is a leading contributor to morbidity and mortality in the US and may be considered a preventable determinant of mortality. The prevention of CA and the intervention on pathways that link these experiences to elevated disease risk should be considered a critical public health priority.
Topics: Adult; Adverse Childhood Experiences; Female; Humans; Male; Morbidity; Mortality; United States
PubMed: 34605870
DOI: 10.1001/jamapediatrics.2021.2320