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Medicine May 2021Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus disease 2019 (COVID-19). The purpose of this systematic review and meta-analysis of current literature was to investigate the clinical outcomes associated with corticosteroid treatment of COVID-19.
METHODS
We systematically searched PubMed, medRxiv, Web of Science, and Scopus databases through March 10, 2021 to identify randomized controlled trials (RCTs) that evaluated the effects of corticosteroid therapies for COVID-19 treatment. Outcomes of interest were mortality, need for mechanical ventilation, serious adverse events (SAEs), and superinfection.
RESULTS
A total of 7737 patients from 8 RCTs were included in the quantitative meta-analysis, of which 2795 (36.1%) patients received corticosteroids plus standard of care (SOC) while 4942 (63.9%) patients received placebo and/or SOC alone. The odds of mortality were significantly lower in patients that received corticosteroids as compared to SOC (odds ratio [OR] = 0.85 [95% CI: 0.76; 0.95], P = .003). Corticosteroid treatment reduced the odds of a need for mechanical ventilation as compared to SOC (OR = 0.76 [95% CI: 0.59; 0.97], P = .030). There was no significant difference between the corticosteroid and SOC groups with regards to SAEs and superinfections.
CONCLUSION
Corticosteroid treatment can reduce the odds for mortality and the need for mechanical ventilation in severe COVID-19 patients.
Topics: Adrenal Cortex Hormones; COVID-19; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34011029
DOI: 10.1097/MD.0000000000025719 -
Acta Gastro-enterologica Belgica Jun 2013Hydatidosis is not uncommon in Western Europe, mainly due to the presence of immigrants from endemic countries, and hepato-gastroenterologist must then be able to manage... (Review)
Review
Hydatidosis is not uncommon in Western Europe, mainly due to the presence of immigrants from endemic countries, and hepato-gastroenterologist must then be able to manage this infectious disease. The hepatic hydatidosis is due to development in the liver of the larvae of Echinococcus granulosus that causes liver cysts. It can grow in size throughout the years and can give rise to complications, mainly pain, super-infection or cyst rupture. Recent progresses in imaging modalities play an important role in diagnosis, classification and evaluation of response to treatment of the cysts. Imaging techniques led to both Gharbi's and WHO's classifications. Those can provide markers of cyst activity and can help to determine the best therapeutic strategy. By combining two immunodiagnostic techniques, the diagnostic accuracy of laboratory tests is excellent. During the last decade, treatment has improved : the main therapeutic modality in the past was surgery, until the discovery of PAIR procedure (Puncture, Aspiration, Injection, Re-aspiration). Albendazole also plays an important role in the treatment of hydatid cysts either alone or as a pre-procedure or post procedure prophylaxis. This review will cover the major aspects of the disease emphasizing the recent diagnostic and therapeutic advances.
Topics: Animals; Diagnosis, Differential; Disease Management; Echinococcosis, Hepatic; Echinococcus; Gastroenterology; Global Health; Humans; Incidence; Liver; Practice Guidelines as Topic
PubMed: 23898558
DOI: No ID Found -
The Cochrane Database of Systematic... Nov 2010Several beta-lactams are recommended as single agents for the treatment of febrile neutropenia. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several beta-lactams are recommended as single agents for the treatment of febrile neutropenia.
OBJECTIVES
To compare the effectiveness of different anti-pseudomonal beta-lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta-lactams.
SEARCH STRATEGY
We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing an antipseudomonal beta-lactam to another antipseudomonal beta-lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients.
DATA COLLECTION AND ANALYSIS
Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all-cause mortality. Risk of bias was assessed using a domain-based evaluation and its effect of results was assessed through sensitivity analyses.
MAIN RESULTS
Forty-four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin-tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double-blinded. The risk for all-cause mortality was significantly higher with cefepime compared to other beta-lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non-significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin-tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all-cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile.
AUTHORS' CONCLUSIONS
Current evidence supports the use of piperacillin-tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic-associated and Clostridium difficile-associated diarrhea. There is a high level of evidence that all-cause mortality is higher with cefepime compared to other beta-lactams and it should not be used as monotherapy for patients with febrile neutropenia.
Topics: Anti-Bacterial Agents; Cefepime; Ceftazidime; Cephalosporins; Fever; Humans; Imipenem; Meropenem; Neutropenia; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Thienamycins; beta-Lactams
PubMed: 21069685
DOI: 10.1002/14651858.CD005197.pub3 -
Current Opinion in Critical Care Feb 2022We conducted a systematic literature review to summarize the available evidence regarding the incidence, risk factors, and clinical characteristics of...
PURPOSE OF REVIEW
We conducted a systematic literature review to summarize the available evidence regarding the incidence, risk factors, and clinical characteristics of ventilator-associated pneumonia (VAP) in patients undergoing mechanical ventilation because of acute respiratory distress syndrome secondary to SARS-CoV-2 infection (C-ARDS).
RECENT FINDINGS
Sixteen studies (6484 patients) were identified. Bacterial coinfection was uncommon at baseline (<15%) but a high proportion of patients developed positive bacterial cultures thereafter leading to a VAP diagnosis (range 21-64%, weighted average 50%). Diagnostic criteria varied between studies but most signs of VAP have substantial overlap with the signs of C-ARDS making it difficult to differentiate between bacterial colonization versus superinfection. Most episodes of VAP were associated with Gram-negative bacteria. Occasional cases were also attributed to herpes virus reactivations and pulmonary aspergillosis. Potential factors driving high VAP incidence rates include immunoparalysis, prolonged ventilation, exposure to immunosuppressants, understaffing, lapses in prevention processes, and overdiagnosis.
SUMMARY
Covid-19 patients who require mechanical ventilation for ARDS have a high risk (>50%) of developing VAP, most commonly because of Gram-negative bacteria. Further work is needed to elucidate the disease-specific risk factors for VAP, strategies for prevention, and how best to differentiate between bacterial colonization versus superinfection.
Topics: COVID-19; Humans; Overdiagnosis; Pneumonia, Ventilator-Associated; Respiration, Artificial; Respiratory Distress Syndrome; SARS-CoV-2
PubMed: 34932525
DOI: 10.1097/MCC.0000000000000908 -
International Journal of Infectious... Sep 2021To date, there is no effective treatment for the new coronavirus disease (COVID-19). We aimed to systematically review the literature on the association between the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To date, there is no effective treatment for the new coronavirus disease (COVID-19). We aimed to systematically review the literature on the association between the combination of tocilizumab (TCZ) and systemic corticosteroid therapy (SCT) on outcomes of COVID-19 patients.
METHODS
We searched MEDLINE, Cochrane Central, and preprints, for studies in which health outcomes were compared between adults with severe COVID-19 who received TCZ and SCT and those who received standard of care without TCZ. Record screening, data extraction, and risk of bias assessment were performed in duplicate. Random effect models were used when pooling crude numbers and adjusted effect estimates of study outcomes.
RESULTS
Our search identified seventeen studies. The pooled crude mortality rate was lower in the combination arm (relative risk, RR=0.62, 95% confidence interval [CI]=0.42 - 0.91; I=60%). The adjusted mortality rates were also lower in the combination arm (RR=0.58, 95% CI=0.42 - 0.81; I=71%). The rate of superinfections did not differ between the two interventions.
CONCLUSIONS
The findings of this study show that combination of TCZ and SCT compared to SOC has lower mortality rates. There is an urgent need for well-designed randomized trials to assess the safety and efficacy of this combination in subjects with severe COVID-19.
Topics: Adrenal Cortex Hormones; Adult; Antibodies, Monoclonal, Humanized; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34273515
DOI: 10.1016/j.ijid.2021.07.021 -
Critical Care Medicine Apr 2024This systematic review and Bayesian network meta-analysis evaluated the efficacy and safety of hydrocortisone combined with fludrocortisone or hydrocortisone alone,... (Meta-Analysis)
Meta-Analysis
Do We Need to Administer Fludrocortisone in Addition to Hydrocortisone in Adult Patients With Septic Shock? An Updated Systematic Review With Bayesian Network Meta-Analysis of Randomized Controlled Trials and an Observational Study With Target Trial Emulation.
OBJECTIVES
This systematic review and Bayesian network meta-analysis evaluated the efficacy and safety of hydrocortisone combined with fludrocortisone or hydrocortisone alone, compared with placebo in adult patients with septic shock.
DATA SOURCES
By extending a prior Cochrane review, databases, including PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov , along with other relevant websites, were searched until August 31, 2023.
STUDY SELECTION
Randomized controlled trials (RCTs) and observational studies using target trial emulation were included.
DATA EXTRACTION
The primary outcome was short-term mortality with an emphasis on 28- or 30-day mortality as the main measure and in-hospital or ICU mortality as the nearest surrogate of this measure. Three of the most common adverse events, namely, gastroduodenal bleeding, superinfection, and hyperglycemia, were also considered.
DATA SYNTHESIS
A total of 19 studies involving 95,841 patients were included. Hydrocortisone plus fludrocortisone showed the lowest short-term mortality versus placebo (odds ratio [OR]: 0.79; 95% credible interval [CrI], 0.64-0.99; number needed to treat [NNT]: 21, range: 12-500; low certainty of evidence) in terms of informative priors. The surface under the cumulative ranking curve values for hydrocortisone plus fludrocortisone, hydrocortisone alone, and placebo were 0.9469, 0.4542, and 0.0989, respectively. Consistent results were observed in RCTs alone and those using a daily 200-mg dose of hydrocortisone. Although gastroduodenal bleeding or superinfection showed no clear increase, hyperglycemia risk increased. The ORs were 0.53 for placebo versus hydrocortisone plus fludrocortisone and 0.64 for placebo versus hydrocortisone alone, with very low certainty of evidence.
CONCLUSIONS
In adults with septic shock, hydrocortisone plus fludrocortisone improved short-term survival with minimal adverse events compared with hydrocortisone alone or placebo. However, these findings are not definitive due to the limited certainty of evidence and wide NNT range. Additional large-scale, placebo-controlled RCTs are needed to provide conclusive evidence.
Topics: Adult; Humans; Hydrocortisone; Fludrocortisone; Shock, Septic; Network Meta-Analysis; Superinfection; Randomized Controlled Trials as Topic; Hyperglycemia; Observational Studies as Topic
PubMed: 38156911
DOI: 10.1097/CCM.0000000000006161 -
Clinical Microbiology and Infection :... Aug 2022A significant increased risk of complications and mortality in immunocompromised patients affected by COVID-19 has been described. However, the impact of COVID-19 in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A significant increased risk of complications and mortality in immunocompromised patients affected by COVID-19 has been described. However, the impact of COVID-19 in solid organ transplant (SOT) recipients is an issue still under debate, due to conflicting evidence that has emerged from different observational studies.
OBJECTIVES
We performed a systematic review with a meta-analysis to assess the clinical outcome in SOT recipients with COVID-19 compared with the general population.
DATA SOURCES
PubMed-MEDLINE and Scopus were independently searched until 13 October 2021.
STUDY ELIGIBILITY CRITERIA
Prospective or retrospective observational studies comparing clinical outcome in SOT recipients versus general populations affected by COVID-19 were included. The primary endpoint was 30-day mortality.
PARTICIPANTS
Participants were patients with confirmed COVID-19.
INTERVENTIONS
Interventions reviewed were SOTs.
METHODS
The quality of the included studies was independently assessed with the Risk of Bias in Non-randomized Studies of Interventions tool for observational studies. The meta-analysis was performed by pooling ORs retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity.
RESULTS
A total of 3501 articles were screened, and 31 observational studies (N = 590 375; 5759 SOT recipients vs. 584 616 general population) were included in the meta-analyses. No difference in 30-day mortality rate was found in the primary analysis, including studies providing adjustment for confounders (N = 17; 3752 SOT recipients vs. 159 745 general population; OR: 1.13; 95% CI, 0.94-1.35; I = 33.9%). No evidence of publication bias was reported. A higher risk of intensive care unit admission (OR: 1.56; 95% CI, 1.03-2.63) and occurrence of acute kidney injury (OR: 2.50; 95% CI, 1.81-3.45) was found in SOT recipients.
CONCLUSIONS
No increased risk in mortality was found in SOT recipients affected by COVID-19 compared with the general population when adjusted for demographic and clinical features and COVID-19 severity.
Topics: COVID-19; Humans; Organ Transplantation; Prospective Studies; Retrospective Studies; Transplant Recipients
PubMed: 35289294
DOI: 10.1016/j.cmi.2022.02.039 -
Revista Brasileira de Terapia Intensiva 2021The Sociedade Portuguesa de Cuidados Intensivos and the Infection and Sepsis Group have previously issued health service and management recommendations for critically...
Update of the recommendations of the Sociedade Portuguesa de Cuidados Intensivos and the Infection and Sepsis Group for the approach to COVID-19 in Intensive Care Medicine.
INTRODUCTION
The Sociedade Portuguesa de Cuidados Intensivos and the Infection and Sepsis Group have previously issued health service and management recommendations for critically ill patients with COVID-19. Due to the evolution of knowledge, the panel of experts was again convened to review the current evidence and issue updated recommendations.
METHODS
A national panel of experts who declared that they had no conflicts of interest regarding the development of the recommendations was assembled. Operational questions were developed based on the PICO methodology, and a rapid systematic review was conducted by consulting different bibliographic sources. The panel determined the direction and strength of the recommendations using two Delphi rounds, conducted in accordance with the principles of the GRADE system. A strong recommendation received the wording "is recommended", and a weak recommendation was written as "is suggested."
RESULTS
A total of 48 recommendations and 30 suggestions were issued, covering the following topics: diagnosis of SARS-CoV-2 infection, coinfection and superinfection; criteria for admission, cure and suspension of isolation; organization of services; personal protective equipment; and respiratory support and other specific therapies (antivirals, immunomodulators and anticoagulation).
CONCLUSION
These recommendations, specifically oriented to the Portuguese reality but that may also apply to Portuguese-speaking African countries and East Timor, aim to support health professionals in the management of critically ill patients with COVID-19. They will be continuously reviewed to reflect the progress of our understanding and the treatment of this pathology.
Topics: COVID-19; Critical Care; Humans; Intensive Care Units; SARS-CoV-2; Sepsis
PubMed: 35081236
DOI: 10.5935/0103-507X.0103-507X-rbti-20210080 -
The Lancet. Microbe Feb 2023HIV-1 infections initiated by multiple founder variants are characterised by a higher viral load and a worse clinical prognosis than those initiated with single founder... (Meta-Analysis)
Meta-Analysis
BACKGROUND
HIV-1 infections initiated by multiple founder variants are characterised by a higher viral load and a worse clinical prognosis than those initiated with single founder variants, yet little is known about the routes of exposure through which transmission of multiple founder variants is most probable. Here we used individual patient data to calculate the probability of multiple founders stratified by route of HIV exposure and study methodology.
METHODS
We conducted a systematic review and meta-analysis of studies that estimated founder variant multiplicity in HIV-1 infection, searching MEDLINE, Embase, and Global Health databases for papers published between Jan 1, 1990, and Sept 14, 2020. Eligible studies must have reported original estimates of founder variant multiplicity in people with acute or early HIV-1 infections, have clearly detailed the methods used, and reported the route of exposure. Studies were excluded if they reported data concerning people living with HIV-1 who had known or suspected superinfection, who were documented as having received pre-exposure prophylaxis, or if the transmitting partner was known to be receiving antiretroviral treatment. Individual patient data were collated from all studies, with authors contacted if these data were not publicly available. We applied logistic meta-regression to these data to estimate the probability that an HIV infection is initiated by multiple founder variants. We calculated a pooled estimate using a random effects model, subsequently stratifying this estimate across exposure routes in a univariable analysis. We then extended our model to adjust for different study methods in a multivariable analysis, recalculating estimates across the exposure routes. This study is registered with PROSPERO, CRD42020202672.
FINDINGS
We included 70 publications in our analysis, comprising 1657 individual patients. Our pooled estimate of the probability that an infection is initiated by multiple founder variants was 0·25 (95% CI 0·21-0·29), with moderate heterogeneity (Q=132·3, p<0·0001, I=64·2%). Our multivariable analysis uncovered differences in the probability of multiple variant infection by exposure route. Relative to a baseline of male-to-female transmission, the predicted probability for female-to-male multiple variant transmission was significantly lower at 0·13 (95% CI 0·08-0·20), and the probabilities were significantly higher for transmissions in people who inject drugs (0·37 [0·24-0·53]) and men who have sex with men (0·30 [0·33-0·40]). There was no significant difference in the probability of multiple variant transmission between male-to-female transmission (0·21 [0·14-0·31]), post-partum transmission (0·18 [0·03-0·57]), pre-partum transmission (0·17 [0·08-0·33]), and intra-partum transmission (0·27 [0·14-0·45]).
INTERPRETATION
We identified that transmissions in people who inject drugs and men who have sex with men are significantly more likely to result in an infection initiated by multiple founder variants, and female-to-male infections are significantly less probable. Quantifying how the routes of HIV infection affect the transmission of multiple variants allows us to better understand how the evolution and epidemiology of HIV-1 determine clinical outcomes.
FUNDING
Medical Research Council Precision Medicine Doctoral Training Programme and a European Research Council Starting Grant.
Topics: Humans; Male; Female; HIV Infections; HIV-1; Homosexuality, Male; Sexual and Gender Minorities; Anti-HIV Agents; HIV Seropositivity
PubMed: 36642083
DOI: 10.1016/S2666-5247(22)00327-5 -
BMJ (Clinical Research Ed.) May 2003To compare the effectiveness of beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in the treatment of patients with fever and neutropenia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the effectiveness of beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in the treatment of patients with fever and neutropenia.
DATA SOURCES
Medline, Embase, Lilacs, the Cochrane Library, and conference proceedings to 2002. References of included studies and contact with authors. No restrictions on language, year of publication, or publication status.
STUDY SELECTION
All randomised trials of beta lactam monotherapy compared with beta lactam-minoglycoside combination therapy as empirical treatment for patients with fever and neutropenia.
DATA SELECTION
Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. An intention to treat approach was used. Relative risks were pooled with the random effect model.
MAIN OUTCOME MEASURE
All cause fatality.
RESULTS
Forty seven trials with 7807 patients met inclusion criteria. Nine trials compared the same beta lactam. There was no significant difference in all cause fatality (relative risk 0.85, 95% confidence interval 0.72 to 1.02). For success of treatment there was a significant advantage with monotherapy (0.92, 0.85 to 0.99), though there was considerable heterogeneity among trials. There was no significant difference between monotherapy and combination treatment in trials that compared the same beta lactam, whereas there was major advantage with monotherapy in trials that compared different beta lactams (0.87, 0.80 to 0.93). Rates of superinfection were similar. Adverse events, including those associated with severe morbidity, were significantly more common in the combination treatment group. Detected flaws in methods did not affect results.
CONCLUSIONS
For patients with fever and neutropenia there is no clinical advantage in treatment with beta lactam-aminoglycoside combination therapy. Broad spectrum beta lactams as monotherapy should be regarded as the standard of care for such patients.
Topics: Aminoglycosides; Anti-Bacterial Agents; Cause of Death; Drug Therapy, Combination; Fever; Humans; Neutropenia; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Superinfection; Treatment Failure; beta-Lactams
PubMed: 12763980
DOI: 10.1136/bmj.326.7399.1111