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American Journal of Infection Control Jan 2021To collate the evidence on the accuracy parameters of all available diagnostic methods for detecting SARS-CoV-2. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To collate the evidence on the accuracy parameters of all available diagnostic methods for detecting SARS-CoV-2.
METHODS
A systematic review with meta-analysis was performed. Searches were conducted in Pubmed and Scopus (April 2020). Studies reporting data on sensitivity or specificity of diagnostic tests for COVID-19 using any human biological sample were included.
RESULTS
Sixteen studies were evaluated. Meta-analysis showed that computed tomography has high sensitivity (91.9% [89.8%-93.7%]), but low specificity (25.1% [21.0%-29.5%]). The combination of IgM and IgG antibodies demonstrated promising results for both parameters (84.5% [82.2%-86.6%]; 91.6% [86.0%-95.4%], respectively). For RT-PCR tests, rectal stools/swab, urine, and plasma were less sensitive while sputum (97.2% [90.3%-99.7%]) presented higher sensitivity for detecting the virus.
CONCLUSIONS
RT-PCR remains the gold standard for the diagnosis of COVID-19 in sputum samples. However, the combination of different diagnostic tests is highly recommended to achieve adequate sensitivity and specificity.
Topics: Antibodies, Viral; COVID-19; COVID-19 Nucleic Acid Testing; COVID-19 Serological Testing; COVID-19 Testing; Coronavirus Envelope Proteins; Coronavirus RNA-Dependent RNA Polymerase; Humans; Immunoglobulin G; Immunoglobulin M; Lung; SARS-CoV-2; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 32659413
DOI: 10.1016/j.ajic.2020.07.011 -
The Cochrane Database of Systematic... Jan 2018Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness.
OBJECTIVES
To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD.
SEARCH METHODS
We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles.
SELECTION CRITERIA
We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non-cyclophosphamide-containing therapies for at least six months, with follow-up of at least 12 months from the start of treatment.
DATA COLLECTION AND ANALYSIS
We imported studies identified by the search into a reference manager database. We retrieved the full-text versions of relevant studies, and two review authors independently extracted data. Primary outcomes were change in lung function (change in forced vital capacity (FVC) % predicted and diffusing capacity of the lung for carbon monoxide (DLCO) % predicted), adverse events, and health-related quality of life measures. Secondary outcomes included all-cause mortality, dyspnoea, cough, and functional exercise testing. When appropriate, we performed meta-analyses and subgroup analyses by severity of lung function, connective tissue disease diagnosis, and radiological pattern of fibrosis. We assessed the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and created 'Summary of findings' tables.
MAIN RESULTS
We included in the analysis four trials with 495 participants (most with systemic sclerosis). We formed two separate comparisons: cyclophosphamide versus placebo (two trials, 195 participants) and cyclophosphamide versus mycophenolate (two trials, 300 participants). We found evidence to be of low quality, as dropout rates were high in the intervention groups, and as we noted a wide confidence interval around the effect with small differences, which affected the precision of results.The data demonstrates significant improvement in lung function with cyclophosphamide compared with placebo (post-treatment FVC % mean difference (MD) 2.83, 95% confidence interval (CI) 0.80 to 4.87; P = 0.006) but no significant difference in post-treatment DLCO (% MD -1.68, 95% CI -4.37 to 1.02; P = 0.22; two trials, 182 participants).Risk of adverse effects was increased in the cyclophosphamide treatment groups compared with the placebo groups, in particular, haematuria, leukopenia, and nausea, leading to a higher rate of withdrawal from cyclophosphamide treatment. The data demonstrates statistically significant improvement in one-measure of quality of life in one trial favouring cyclophosphamide over placebo and clinically and statistically significant improvement in breathlessness in one trial favouring cyclophosphamide compared with placebo, with no significant impact on mortality.Trialists reported no significant impact on lung function when cyclophosphamide was used compared with mycophenolate at 12 months (FVC % MD -0.82, 95% CI -3.95 to 2.31; P = 0.61; two trials, 149 participants; DLCO % MD -1.41, 95% CI -10.40 to 7.58; P = 0.76; two trials, 149 participants).Risk of side effects was increased with cyclophosphamide versus mycophenolate, in particular, leukopenia and thrombocytopenia.The data demonstrates no significant impact on health-related quality of life, all-cause mortality, dyspnoea, or cough severity in the cyclophosphamide group compared with the mycophenolate group. No trials reported outcomes associated with functional exercise tests.We performed subgroup analysis to determine whether severity of lung function, connective tissue disease diagnosis, or radiological pattern had any impact on outcomes. One trial reported that cyclophosphamide protected against decreased FVC in individuals with worse fibrosis scores, and also showed that cyclophosphamide may be more effective in those with worse lung function. No association could be made between connective tissue disease diagnosis and outcomes.
AUTHORS' CONCLUSIONS
This review, which is based on studies of varying methodological quality, demonstrates that overall, in this population, small benefit may be derived from the use of cyclophosphamide in terms of mean difference in % FVC when compared with placebo, but not of the difference in % DLCO, or when compared with mycophenolate. Modest clinical improvement in dyspnoea may be noted with the use of cyclophosphamide. Clinical practice guidelines should advise clinicians to consider individual patient characteristics and to expect only modest benefit at best in preserving FVC. Clinicians should carefully monitor for adverse effects during treatment and in the years thereafter.Further studies are required to examine the use of cyclophosphamide; they should be adequately powered to compare outcomes within different subgroups, specifically, stratified for extent of pulmonary infiltrates on high-resolution computed tomography (HRCT) and skin involvement in SSc. Studies on other forms of connective tissue disease are needed. Researchers may consider comparing cyclophosphamide (a potent immunosuppressant) versus antifibrotic agents, or comparing both versus placebo, in particular, for those with evidence of rapidly progressive fibrotic disease, who may benefit the most.
Topics: Connective Tissue Diseases; Cyclophosphamide; Humans; Immunosuppressive Agents; Lung; Lung Diseases, Interstitial; Quality of Life; Randomized Controlled Trials as Topic; Scleroderma, Systemic; Vital Capacity
PubMed: 29297205
DOI: 10.1002/14651858.CD010908.pub2 -
The Lancet. Infectious Diseases Jan 2018In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In February, 2017, the US Food and Drug Administration approved the blood infection marker procalcitonin for guiding antibiotic therapy in patients with acute respiratory infections. This meta-analysis of patient data from 26 randomised controlled trials was designed to assess safety of procalcitonin-guided treatment in patients with acute respiratory infections from different clinical settings.
METHODS
Based on a prespecified Cochrane protocol, we did a systematic literature search on the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase, and pooled individual patient data from trials in which patients with respiratory infections were randomly assigned to receive antibiotics based on procalcitonin concentrations (procalcitonin-guided group) or control. The coprimary endpoints were 30-day mortality and setting-specific treatment failure. Secondary endpoints were antibiotic use, length of stay, and antibiotic side-effects.
FINDINGS
We identified 990 records from the literature search, of which 71 articles were assessed for eligibility after exclusion of 919 records. We collected data on 6708 patients from 26 eligible trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided patients than in control patients (286 [9%] deaths in 3336 procalcitonin-guided patients vs 336 [10%] in 3372 controls; adjusted odds ratio [OR] 0·83 [95% CI 0·70 to 0·99], p=0·037). This mortality benefit was similar across subgroups by setting and type of infection (p>0·05), although mortality was very low in primary care and in patients with acute bronchitis. Procalcitonin guidance was also associated with a 2·4-day reduction in antibiotic exposure (5·7 vs 8·1 days [95% CI -2·71 to -2·15], p<0·0001) and a reduction in antibiotic-related side-effects (16% vs 22%, adjusted OR 0·68 [95% CI 0·57 to 0·82], p<0·0001).
INTERPRETATION
Use of procalcitonin to guide antibiotic treatment in patients with acute respiratory infections reduces antibiotic exposure and side-effects, and improves survival. Widespread implementation of procalcitonin protocols in patients with acute respiratory infections thus has the potential to improve antibiotic management with positive effects on clinical outcomes and on the current threat of increasing antibiotic multiresistance.
FUNDING
National Institute for Health Research.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Length of Stay; Male; Middle Aged; Procalcitonin; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Survival Analysis
PubMed: 29037960
DOI: 10.1016/S1473-3099(17)30592-3 -
Clinical Infectious Diseases : An... Jul 2022Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD)... (Meta-Analysis)
Meta-Analysis
Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Virus Infections in Lung Transplant Recipients: A Systematic Review of Outcomes and Treatment Strategies.
BACKGROUND
Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin.
METHODS
Relevant databases were queried and study outcomes extracted using a standardized method and summarized.
RESULTS
Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0-3%), but CLAD progression 180-360 days postinfection was substantial (pooled incidences 19-24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27-1.18]), although results were highly variable between studies.
CONCLUSIONS
RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections.
Topics: Humans; Lung; Metapneumovirus; Parainfluenza Virus 1, Human; Parainfluenza Virus 2, Human; Paramyxoviridae Infections; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Retrospective Studies; Ribavirin; Transplant Recipients
PubMed: 35022697
DOI: 10.1093/cid/ciab969 -
BMC Infectious Diseases May 2019Chlorhexidine gluconate (CHG) bathing of hospitalized patients may have benefit in reducing hospital-acquired bloodstream infections (HABSIs). However, the magnitude of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chlorhexidine gluconate (CHG) bathing of hospitalized patients may have benefit in reducing hospital-acquired bloodstream infections (HABSIs). However, the magnitude of effect, implementation fidelity, and patient-centered outcomes are unclear. In this meta-analysis, we examined the effect of CHG bathing on prevention of HABSIs and assessed fidelity to implementation of this behavioral intervention.
METHODS
We undertook a meta-analysis by searching Medline, EMBASE, CINAHL, Scopus, and Cochrane's CENTRAL registry from database inception through January 4, 2019 without language restrictions. We included randomized controlled trials, cluster randomized trials and quasi-experimental studies that evaluated the effect of CHG bathing versus a non-CHG comparator for prevention of HABSIs in any adult healthcare setting. Studies of pediatric patients, of pre-surgical CHG use, or without a non-CHG comparison arm were excluded. Outcomes of this study were HABSIs, patient-centered outcomes, such as patient comfort during the bath, and implementation fidelity assessed through five elements: adherence, exposure or dose, quality of the delivery, participant responsiveness, and program differentiation. Three authors independently extracted data and assessed study quality; a random-effects model was used.
RESULTS
We included 26 studies with 861,546 patient-days and 5259 HABSIs. CHG bathing markedly reduced the risk of HABSIs (IRR = 0.59, 95% confidence interval [CI]: 0.52-0.68). The effect of CHG bathing was consistent within subgroups: randomized (0.67, 95% CI: 0.53-0.85) vs. non-randomized studies (0.54, 95% CI: 0.44-0.65), bundled (0.66, 95% CI: 0.62-0.70) vs. non-bundled interventions (0.51, 95% CI: 0.39-0.68), CHG impregnated wipes (0.63, 95% CI: 0.55-0.73) vs. CHG solution (0.41, 95% CI: 0.26-0.64), and intensive care unit (ICU) (0.58, 95% CI: 0.49-0.68) vs. non-ICU settings (0.56, 95% CI: 0.38-0.83). Only three studies reported all five measures of fidelity, and ten studies did not report any patient-centered outcomes.
CONCLUSIONS
Patient bathing with CHG significantly reduced the incidence of HABSIs in both ICU and non-ICU settings. Many studies did not report fidelity to the intervention or patient-centered outcomes. For sustainability and replicability essential for effective implementation, fidelity assessment that goes beyond whether a patient received an intervention or not should be standard practice particularly for complex behavioral interventions such as CHG bathing.
TRIAL REGISTRATION
Study registration with PROSPERO CRD42015032523 .
Topics: Anti-Infective Agents, Local; Chlorhexidine; Cross Infection; Fungi; Gram-Negative Bacteria; Humans; Incidence; Intensive Care Units
PubMed: 31088521
DOI: 10.1186/s12879-019-4002-7 -
Heart, Lung & Circulation Jan 2020Mycotic coronary aneurysms (MCA) are rare but often lead to significant morbidity and mortality. Evidence on the topic is limited to case reports and small case series....
BACKGROUND
Mycotic coronary aneurysms (MCA) are rare but often lead to significant morbidity and mortality. Evidence on the topic is limited to case reports and small case series. A systematic review was performed to improve understanding of this challenging diagnosis. A case report prompting this review is also included.
METHODS
Relevant articles were identified by searching databases Medline and Google Scholar for terms 'mycotic coronary aneurysm'. Manual searching from article references identified further case reports.
RESULTS
Ninety-seven (97) published cases of MCA were identified between 1812 and 2017; 80 cases since the introduction of percutaneous coronary intervention (PCI) with stents in 1986. The most common associations were PCI (40.0%) and infective endocarditis (IE) (40.0%). Complications including aneurysm rupture (28.9%), pericardial effusion (37.3%) and myocardial infarction (39.8%) were frequent. Short-term mortality was high at 42.6%. The most common treatment was surgical resection of the aneurysm with bypass grafting.
CONCLUSIONS
We present a case and the largest systematic review to date of this rare diagnosis, identifying 97 published case reports. Clinical scenarios in which to consider MCA include febrile illness after recent PCI, febrile illness (particularly infective endocarditis) with evidence of coronary ischaemia, and purulent pericarditis. Given the high rate of complications and mortality, immediate surgical referral is recommended.
Topics: Aneurysm, Infected; Coronary Aneurysm; Endocarditis; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Pericardial Effusion
PubMed: 30686642
DOI: 10.1016/j.hlc.2018.12.004 -
European Respiratory Review : An... Sep 2023A proportion of coronavirus disease 2019 (COVID-19) survivors experience persistent dyspnoea without measurable impairments in lung function. We performed a systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A proportion of coronavirus disease 2019 (COVID-19) survivors experience persistent dyspnoea without measurable impairments in lung function. We performed a systematic review and meta-analysis to determine relationships between dyspnoea and imaging abnormalities over time in post-COVID-19 patients.
METHODS
Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we analysed studies published prior to 15 September 2022 and indexed by Google Scholar, PubMed and LitCOVID which assessed chest imaging in adults ≥3 months after COVID-19. Demographic, chest imaging, spirometric and post-COVID-19 symptom data were extracted. The relationships between imaging abnormalities and dyspnoea, sex and age were determined using a random effects model and meta-regression.
RESULTS
47 studies were included in the meta-analysis (n=3557). The most prevalent computed tomography (CT) imaging abnormality was ground-glass opacities (GGOs) (44.9% (95% CI 37.0-52.9%) at any follow-up time-point). Occurrence of reticulations significantly decreased between early and late follow-up (p=0.01). The prevalence of imaging abnormalities was related to the proportion of patients with dyspnoea (p=0.012). The proportion of females was negatively correlated with the presence of reticulations (p=0.001), bronchiectasis (p=0.001) and consolidations (p=0.025). Age was positively correlated with imaging abnormalities across all modalities (p=0.002) and imaging abnormalities present only on CT (p=0.001) (GGOs (p=0.004) and reticulations (p=0.001)). Spirometric values improved during follow-up but remained within the normal range at all time-points.
CONCLUSIONS
Imaging abnormalities were common 3 months after COVID-19 and their occurrence was significantly related to the presence of dyspnoea. This suggests that CT imaging is a sensitive tool for detecting pulmonary abnormalities in patients with dyspnoea, even in the presence of normal spirometric measurements.
Topics: Adult; Female; Humans; COVID-19; SARS-CoV-2; Lung; Dyspnea; Lung Diseases
PubMed: 37558261
DOI: 10.1183/16000617.0253-2022 -
Journal of Infection in Developing... Nov 2021Leprosy and tuberculosis are endemic in several countries. The aim of this study was to describe factors associated with co-infection among both diseases. A systematic...
Leprosy and tuberculosis are endemic in several countries. The aim of this study was to describe factors associated with co-infection among both diseases. A systematic review was carried out, following the Quality of Reporting of Meta-analyses, with the PubMed and Biblioteca Virtual em Saúde (BVS) portals as sources, under eligibility criteria: cross-sectional, cohort, case-control studies or case reports, published in Portuguese, English, French and Spanish, from 2015 to 2020. Studies that dealt with leprosy and tuberculosis not in the context of co-infection were excluded. The initial phase resulted in 1079 articles; 13 went on to a final stage. All were case reports. Thirteen (72.2%) participants were male, aged between 17 and 72 years. Life habits were found in 8 (44.4%) of the articles: 1 (12.5%) reported chronic alcoholism, 1 (12.5%) reported chronic smoking and alcoholism and 1(12.5%) reported chronic smoking, alcoholism and use of illicit drugs. Pathological history was mentioned by 14 (77.8%) patients; 1 (7.1%) reported HIV/AIDS. Three patients (16.6%) described previous history of tuberculosis and/or leprosy. Seven (38.9%) participants reported vaccination with Bacillus Calmette-Guérin. The pulmonary form of tuberculosis predominated and one third of the patients presented resistance to, at least, one tuberculostatic. All cases had multibacillary leprosy. The study did not highlight any comorbidity, and there was no change in the course of the conditions owing to co-infection.
Topics: Adolescent; Adult; Aged; Coinfection; Female; Humans; Leprosy; Male; Middle Aged; Tuberculosis, Pulmonary; Young Adult
PubMed: 34898480
DOI: 10.3855/jidc.14308 -
International Journal of Molecular... May 2023The pulmonary endothelium is a highly regulated organ that performs a wide range of functions under physiological and pathological conditions. Since endothelial... (Review)
Review
The pulmonary endothelium is a highly regulated organ that performs a wide range of functions under physiological and pathological conditions. Since endothelial dysfunction has been demonstrated to play a direct role in sepsis and acute respiratory distress syndrome, its role in COVID-19 has also been extensively investigated. Indeed, apart from the COVID-19-associated coagulopathy biomarkers, new biomarkers were recognised early during the pandemic, including markers of endothelial cell activation or injury. We systematically searched the literature up to 10 March 2023 for studies examining the association between acute and long COVID-19 severity and outcomes and endothelial biomarkers.
Topics: Humans; COVID-19; Post-Acute COVID-19 Syndrome; Vascular Diseases; Lung; Biomarkers
PubMed: 37175942
DOI: 10.3390/ijms24098237 -
Respiratory Research Apr 2023Pulmonary fibrosis is an emerging complication of SARS-CoV-2 infection. In this study, we speculate that patients with COVID-19 and idiopathic pulmonary fibrosis (IPF)... (Review)
Review
BACKGROUND
Pulmonary fibrosis is an emerging complication of SARS-CoV-2 infection. In this study, we speculate that patients with COVID-19 and idiopathic pulmonary fibrosis (IPF) may share aberrant expressed microRNAs (miRNAs) associated to the progression of lung fibrosis.
OBJECTIVE
To identify miRNAs presenting similar alteration in COVID-19 and IPF, and describe their impact on fibrogenesis.
METHODS
A systematic review of the literature published between 2010 and January 2022 (PROSPERO, CRD42022341016) was conducted using the key words (COVID-19 OR SARS-CoV-2) AND (microRNA OR miRNA) or (idiopathic pulmonary fibrosis OR IPF) AND (microRNA OR miRNA) in Title/Abstract.
RESULTS
Of the 1988 references considered, 70 original articles were appropriate for data extraction: 27 studies focused on miRNAs in COVID-19, and 43 on miRNAs in IPF. 34 miRNAs were overlapping in COVID-19 and IPF, 7 miRNAs presenting an upregulation (miR-19a-3p, miR-200c-3p, miR-21-5p, miR-145-5p, miR-199a-5p, miR-23b and miR-424) and 9 miRNAs a downregulation (miR-17-5p, miR-20a-5p, miR-92a-3p, miR-141-3p, miR-16-5p, miR-142-5p, miR-486-5p, miR-708-3p and miR-150-5p).
CONCLUSION
Several studies reported elevated levels of profibrotic miRNAs in COVID-19 context. In addition, the balance of antifibrotic miRNAs responsible of the modulation of fibrotic processes is impaired in COVID-19. This evidence suggests that the deregulation of fibrotic-related miRNAs participates in the development of fibrotic lesions in the lung of post-COVID-19 patients.
Topics: Humans; MicroRNAs; COVID-19; SARS-CoV-2; Idiopathic Pulmonary Fibrosis; Lung
PubMed: 37061683
DOI: 10.1186/s12931-023-02413-6