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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 -
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 -
The Cochrane Database of Systematic... Dec 2019Sepsis occurs when an infection is complicated by organ failure. Sepsis may be complicated by impaired corticosteroid metabolism. Thus, providing corticosteroids may... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sepsis occurs when an infection is complicated by organ failure. Sepsis may be complicated by impaired corticosteroid metabolism. Thus, providing corticosteroids may benefit patients. The original review was published in 2004 and was updated in 2010 and 2015 prior to this update.
OBJECTIVES
To examine the effects of corticosteroids on death in children and adults with sepsis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, ISRCTN, and the WHO Clinical Trials Search Portal, on 25 July 2019. In addition, we conducted reference checking and citation searching, and contacted study authors, to identify additional studies as needed.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of corticosteroids versus placebo or usual care (antimicrobials, fluid replacement, and vasopressor therapy as needed) in children and adults with sepsis. We also included RCTs of continuous infusion versus intermittent bolus of corticosteroids.
DATA COLLECTION AND ANALYSIS
All review authors screened and selected studies for inclusion. One review author extracted data, which was checked by the others, and by the lead author of the primary study when possible. We obtained unpublished data from the authors of some trials. We assessed the methodological quality of trials and applied GRADE to assess the certainty of evidence. Review authors did not contribute to assessment of eligibility and risk of bias, nor to data extraction, for trials they had participated in.
MAIN RESULTS
We included 61 trials (12,192 participants), of which six included only children, two included children and adults, and the remaining trials included only adults. Nine studies are ongoing and will be considered in future versions of this review. We judged 19 trials as being at low risk of bias. Corticosteroids versus placebo or usual care Compared to placebo or usual care, corticosteroids probably slightly reduce 28-day mortality (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.84 to 0.99; 11,233 participants; 50 studies; moderate-certainty evidence). Corticosteroids may result in little to no difference in long-term mortality (RR 0.97, 95% CI 0.91 to 1.03; 6236 participants; 7 studies; low-certainty evidence) and probably slightly reduce hospital mortality (RR 0.90, 95% CI 0.82 to 0.99; 8183 participants; 26 trials; moderate-certainty evidence). Corticosteroids reduced length of intensive care unit (ICU) stay for all participants (mean difference (MD) -1.07 days, 95% CI -1.95 to -0.19; 7612 participants; 21 studies; high-certainty evidence) and resulted in a large reduction in length of hospital stay for all participants (MD -1.63 days, 95% CI -2.93 to -0.33; 8795 participants; 22 studies; high-certainty evidence). Corticosteroids increase the risk of muscle weakness (RR 1.21, 95% CI 1.01 to 1.44; 6145 participants; 6 studies; high-certainty evidence). Corticosteroids probably do not increase the risk of superinfection (RR 1.06, 95% CI 0.95 to 1.19; 5356 participants; 25 studies; moderate-certainty evidence). Corticosteroids increase the risk of hypernatraemia (high-certainty evidence) and probably increase the risk of hyperglycaemia (moderate-certainty evidence). Moderate-certainty evidence shows that there is probably little or no difference in gastroduodenal bleeding, stroke, or cardiac events, and low-certainty evidence suggests that corticosteroids may result in little to no difference in neuropsychiatric events. Continuous infusion of corticosteroids versus intermittent bolus We are uncertain about the effects of continuous infusion of corticosteroids compared with intermittent bolus administration. Three studies reported data for this comparison, and the certainty of evidence for all outcomes was very low.
AUTHORS' CONCLUSIONS
Moderate-certainty evidence indicates that corticosteroids probably reduce 28-day and hospital mortality among patients with sepsis. Corticosteroids result in large reductions in ICU and hospital length of stay (high-certainty evidence). There may be little or no difference in the risk of major complications; however, corticosteroids increase the risk of muscle weakness and hypernatraemia, and probably increase the risk of hyperglycaemia. The effects of continuous versus intermittent bolus administration of corticosteroids are uncertain.
Topics: Adrenal Cortex Hormones; Adult; Child; Hospital Mortality; Humans; Length of Stay; Randomized Controlled Trials as Topic; Risk Factors; Sepsis; Time Factors
PubMed: 31808551
DOI: 10.1002/14651858.CD002243.pub4 -
PeerJ 2017The objective of this study is to conduct a systematic review of multi-scale HIV immunoepidemiological models to improve our understanding of the synergistic impact...
OBJECTIVE
The objective of this study is to conduct a systematic review of multi-scale HIV immunoepidemiological models to improve our understanding of the synergistic impact between the HIV viral-immune dynamics at the individual level and HIV transmission dynamics at the population level.
BACKGROUND
While within-host and between-host models of HIV dynamics have been well studied at a single scale, connecting the immunological and epidemiological scales through multi-scale models is an emerging method to infer the synergistic dynamics of HIV at the individual and population levels.
METHODS
We reviewed nine articles using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework that focused on the synergistic dynamics of HIV immunoepidemiological models at the individual and population levels.
RESULTS
HIV immunoepidemiological models simulate viral immune dynamics at the within-host scale and the epidemiological transmission dynamics at the between-host scale. They account for longitudinal changes in the immune viral dynamics of HIV+ individuals, and their corresponding impact on the transmission dynamics in the population. They are useful to analyze the dynamics of HIV super-infection, co-infection, drug resistance, evolution, and treatment in HIV+ individuals, and their impact on the epidemic pathways in the population. We illustrate the coupling mechanisms of the within-host and between-host scales, their mathematical implementation, and the clinical and public health problems that are appropriate for analysis using HIV immunoepidemiological models.
CONCLUSION
HIV immunoepidemiological models connect the within-host immune dynamics at the individual level and the epidemiological transmission dynamics at the population level. While multi-scale models add complexity over a single-scale model, they account for the time varying immune viral response of HIV+ individuals, and the corresponding impact on the time-varying risk of transmission of HIV+ individuals to other susceptibles in the population.
PubMed: 28970973
DOI: 10.7717/peerj.3877 -
Immunity, Inflammation and Disease Jan 2023Infections with fungi, such as Aspergillus species, have been found as common complications of viral pneumonia. This study aims to determine the risk factors of fungal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Infections with fungi, such as Aspergillus species, have been found as common complications of viral pneumonia. This study aims to determine the risk factors of fungal superinfections in viral pneumonia patients using meta-analysis.
OBJECTIVE
This study aims to determine the risk factors of fungal infection s in viral pneumonia patients using meta-analysis.
METHODS
We reviewed primary literature about fungal infection in viral pneumonia patients published between January 1, 2010 and September 30, 2020, in the Chinese Biomedical Literature, Chinese National Knowledge Infrastructure, Wanfang (China), Cochrane Central Library, Embase, PubMed, and Web of Science databases. These studies were subjected to an array of statistical analyses, including risk of bias and sensitivity analyses.
RESULTS
In this study, we found a statistically significant difference in the incidence of fungal infections in viral pneumonia patients that received corticosteroid treatment as compared to those without corticosteroid treatment (p < .00001). Additionally, regarding the severity of fungal infections, we observed significant higher incidence of invasive pulmonary aspergillosis (IPA) in patients with high Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p < .001), tumors (p = .005), or immunocompromised patients (p < .0001).
CONCLUSIONS
Our research shows that corticosteroid treatment was an important risk factor for the development of fungal infection in patients with viral pneumonia. High APACHE II scores, tumors, and immunocompromised condition are also important risk factors of developing IPA. The diagnosis of fungal infection in viral pneumonia patients can be facilitated by early serum galactomannan (GM) testing, bronchoalveolar lavage fluid Aspergillus antigen testing, culture, and biopsy.
Topics: Humans; Superinfection; Sensitivity and Specificity; Aspergillus; Invasive Pulmonary Aspergillosis; Risk Factors; Neoplasms
PubMed: 36705416
DOI: 10.1002/iid3.760 -
HIV Medicine Oct 2020The aim of the study was to systematically review current studies reporting on clinical outcomes in people living with HIV (PLHIV) infected with severe acute respiratory...
OBJECTIVES
The aim of the study was to systematically review current studies reporting on clinical outcomes in people living with HIV (PLHIV) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
METHODS
We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive literature search was conducted in Global Health, SCOPUS, Medline and EMBASE using pertinent key words and Medical Subject Headings (MeSH) terms relating to coronavirus disease 2019 (COVID-19) and HIV. A narrative synthesis was undertaken. Articles are summarized in relevant sections.
RESULTS
Two hundred and eighty-five articles were identified after duplicates had been removed. After screening, eight studies were analysed, totalling 70 HIV-infected patients (57 without AIDS and 13 with AIDS). Three themes were identified: (1) controlled HIV infection does not appear to result in poorer COVID-19 outcomes, (2) more data are needed to determine COVID-19 outcomes in patients with AIDS and (3) HIV-infected patients presenting with COVID-19 symptoms should be investigated for superinfections.
CONCLUSIONS
Our findings suggest that PLHIV with well-controlled disease are not at risk of poorer COVID-19 disease outcomes than the general population. It is not clear whether those with poorly controlled HIV disease and AIDS have poorer outcomes. Superimposed bacterial pneumonia may be a risk factor for more severe COVID-19 but further research is urgently needed to elucidate whether PLHIV are more at risk than the general population.
Topics: Acquired Immunodeficiency Syndrome; COVID-19; Coinfection; Disease Progression; Female; Humans; MEDLINE; Male; Medical Informatics Applications; Risk Factors
PubMed: 32671970
DOI: 10.1111/hiv.12911 -
Medicine Feb 2020This meta-analysis assessed the clinical efficacy and safety of cefoperazone-sulbactam for empiric therapy febrile neutropenia. (Meta-Analysis)
Meta-Analysis
PURPOSE
This meta-analysis assessed the clinical efficacy and safety of cefoperazone-sulbactam for empiric therapy febrile neutropenia.
METHODS
The PubMed, Web of Science, EBSCO, Cochrane Library, Ovid Medline, EMBASE, and ClinicalTrial.gov database were searched through May 10, 2019. Only clinical trials comparing cefoperazone-sulbactam with other antibiotics for empiric treatment of febrile neutropenia were included. The primary outcome was treatment success without modification, and the secondary outcomes were all-cause mortality and adverse events (AEs).
RESULTS
Ten randomized controlled trials (RCTs) and 1 retrospective cohort study were included. Overall, cefoperazone-sulbactam exhibited a treatment success rate similar to those of comparator drugs for the treatment of febrile neutropenia (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.85 to 1.24, I = 0%). A similar finding was noted in pooled analysis of 10 RCTs (OR, 1.07; 95% CI, 0.88 to 1.30, I = 0%). Subgroup analysis showed that cefoperazone-sulbactam had a treatment success rate similar to the rates of comparators for adults (OR, 1.10; 95% CI, 0.88 to 1.38, I = 0%) and children (OR, 0.96; 95% CI, 0.63 to 1.46, I = 0%). Cefoperazone-sulbactam did not differ significantly from comparators in the risks of all-cause mortality (OR, 0.96; 95% CI, 0.58 to 1.58, I = 0%) or common AEs, namely rash, nausea/vomiting, and superinfection.
CONCLUSION
The clinical efficacy and tolerability of cefoperazone-sulbactam are comparable to those of comparator drugs in the treatment of febrile neutropenia.
Topics: Anti-Bacterial Agents; Cefoperazone; Drug Therapy, Combination; Febrile Neutropenia; Humans; Sulbactam
PubMed: 32080150
DOI: 10.1097/MD.0000000000019321 -
BioMed Research International 2019To reevaluate the benefits and risks of corticosteroid treatment in adult patients with septic shock. This study was performed based on PRISMA guidelines. Randomized... (Meta-Analysis)
Meta-Analysis
To reevaluate the benefits and risks of corticosteroid treatment in adult patients with septic shock. This study was performed based on PRISMA guidelines. Randomized controlled trials (RCTs) of corticosteroids versus placebo were retrieved from PubMed, MEDLINE, EMBASE, Web of Science, the Cochrane Central RCTs, and ClinicalTrials.gov from January 1980 to April 2018. We also conducted a trial sequential analysis to indicate the possibility of type I or II errors and calculate the information size. Grading of Recommendations, Assessment, Development and Evaluation approach (GRADE) was applying to assess the certainty of evidence at the primary outcome level. Twenty-one RCTs were identified and analyzed. Patients treated with corticosteroid had a 7% reduction in relative risk in 28-day all-cause mortality compared to controls (RR 0.93, 95% CI 0.88 to 0.99). However, there were no significant differences for the intensive care unit (ICU) mortality (RR 0.97, 95% CI 0.86 to 1.09) or in-hospital mortality (RR 1.01, 95% CI 0.92 to 1.11). Corticosteroids shortened the length of ICU stay by 1.04 days (RR -1.04, 95% CI -1.72 to -0.36) and the length of hospital stay by 2.49 days (RR -2.49, 95% CI -4.96 to -0.02). Corticosteroids increased the risk of hyperglycemia (RR 1.11, 95% CI 1.06 to 1.16) but not gastroduodenal bleeding (RR 1.06, 95% CI 0.82 to 1.37) or superinfection (RR 1.04, 95% CI 0.94 to 1.15). However, some date on secondary outcomes were unavailable because they were not measured or not reported in the included studies which may cause a lack of power or selective outcome reporting. The information size was calculated at 10044 patients. Trial sequential analysis showed that the meta-analysis was conclusive and the risk of type 2 error was minimal. Corticosteroids are likely to be effective in reducing 28-day mortality and attenuating septic shock without increasing the rate of life-threatening complications. TSA showed that the risk of type II error in this meta-analysis was minimal and the result was conclusive.
Topics: Adrenal Cortex Hormones; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Publication Bias; Randomized Controlled Trials as Topic; Respiration, Artificial; Risk Factors; Shock, Septic
PubMed: 31281831
DOI: 10.1155/2019/3175047 -
Le Infezioni in Medicina Mar 2020Evaluation of serum procalcitonin (PCT) levels has been suggested for diagnosis of infection, precise medical decision making and guidance for prescribing antibiotics in... (Meta-Analysis)
Meta-Analysis
Effectiveness of procalcitonin-guided antibiotic therapy to shorten treatment duration in critically-ill patients with bloodstream infections: a systematic review and meta-analysis.
Evaluation of serum procalcitonin (PCT) levels has been suggested for diagnosis of infection, precise medical decision making and guidance for prescribing antibiotics in critically-ill patients. The aim of this study was to assess the effectiveness of PCT to shorten antibiotic treatment in critically-ill patients with bloodstream infections. Furthermore, the mortality and ICU length of stay (LOS) in such patients were secondary outcomes. Medline/PubMed, EMBASE, Scopus and Cochrane Databases were searched from January 1, 2007 to September 1, 2018. Randomized controlled trials (RCTs) on using PCT to guide antibiotic therapy compared with routine treatments for administration of antibiotics in critically-ill adult patients published in English were included. Two reviewers assessed the methodology of the studies included and extracted their data using the CONSORT checklist. Inverse-variance weighting and fixed and random effects meta-analyses were performed using the length of antibiotic treatment, LOS in an intensive care unit (ICU) and all-cause mortality. No significant reduction was found in the length of antibiotic treatment: although the cut-off point of 0.25
Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Bacteremia; Biomarkers; Cause of Death; Critical Illness; Humans; Intensive Care Units; Length of Stay; Procalcitonin; Time Factors
PubMed: 32172259
DOI: No ID Found -
The Journal of International Medical... Jul 2018Objective This meta-analysis with trial sequential analysis (TSA) was performed to determine whether low-dose corticosteroids (LDCs) can improve survival or shock... (Meta-Analysis)
Meta-Analysis
Objective This meta-analysis with trial sequential analysis (TSA) was performed to determine whether low-dose corticosteroids (LDCs) can improve survival or shock reversal from septic shock in adults. Methods A literature search was performed using several databases (Medline, Cochrane Library, Embase, and Chinese Biological Medical Database) until 23 October 2017. The systematic review was registered in PROSPERO. Results Nine randomized controlled trials (RCTs) (n = 1182) were included. LDC intervention improved 7-day shock reversal compared with the control group (relative risk, 1.36; TSA-adjusted 95% confidence interval, 1.20-1.54). LDCs had no statistically significant effects on gastrointestinal bleeding or superinfection. LDCs did not reduce 28-day mortality from septic shock (relative risk, 0.96; TSA-adjusted 95% confidence interval, 0.74-1.24). The TSA indicated that RCTs of about 3000 patients would be needed to draw definitive conclusions; similar results were obtained in a subgroup analysis of nonresponders. Conclusions LDCs improve 7-day shock reversal. However, whether LDCs improve 28-day survival from septic shock in adults remains unclear. The results of well-designed larger RCTs are needed.
Topics: Adult; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Shock, Septic
PubMed: 29911468
DOI: 10.1177/0300060518774985