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EClinicalMedicine Jul 2023The optimal isolation duration for patients with COVID-19 remains unclear. To support an update of World Health Organization (WHO)'s Living Clinical management...
BACKGROUND
The optimal isolation duration for patients with COVID-19 remains unclear. To support an update of World Health Organization (WHO)'s Living Clinical management guidelines for COVID-19 (https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2022.2), this rapid systematic review and modelling study addresses the effects of different isolation periods for preventing onward transmission leading to hospitalisation and death among secondary cases.
METHODS
We searched the WHO COVID-19 database for studies up to Feb 27, 2023. We included clinical studies of any design with COVID-19 patients confirmed by PCR test or rapid antigen test addressing the impact of any isolation strategy on preventing the spread of COVID-19. There were no restrictions on publication language, publication status, age of patients, severity of COVID-19, variants of SARS-COV-2, comorbidity of patients, isolation location, or co-interventions. We performed random-effects meta-analyses to summarise testing rates of persistent test positivity rates after COVID-19 infection. We performed pre-specified subgroup analyses by symptom status and meta-regression analyses for the proportion of fully vaccinated patients. We developed a model to compare the effects of three isolation strategies on onward transmission leading to hospitalisation and death. The three isolation strategies were (1) 5-day isolation, with no test to release; (2) removal of isolation based on a negative test; and (3) 10-day isolation, with no test to release. The model incorporates estimates of test positivity rates, effective reproduction number, isolation adherence, false negative rate, and hospitalisation rates or case fatality rates. To assess the impact of varying isolation adherence and false negative rates on rapid antigen testing, we conducted some sensitivity analyses. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess certainty of evidence. The protocol is registered with PROSPERO (CRD42022348626).
FINDINGS
Fifteen studies addressing persistent test positivity rates including 4188 patients proved eligible. Asymptomatic patients (27.1%, 95% CI: 15.8%-40.0%) had a significantly lower rapid antigen test positive rate than symptomatic patients (68.1%, 95% CI: 40.6%-90.3%) on day 5. The rapid antigen test positive rate was 21.5% (95% CI: 0-64.1%; moderate certainty) on day 10. Our modelling study suggested that the risk difference (RD) for asymptomatic patients between 5-day isolation and 10-day isolation in hospitalisations (23 more hospitalisations of secondary cases per 10,000 patients isolated, 95% uncertainty interval (UI) 14 more to 33 more) and mortality (5 more per 10,000 patients, 95% UI 1 to 9 more) of secondary cases proved very small (very low certainty). For symptomatic patients, the potential impact of 5- versus 10-day isolation was much greater in hospitalisations (RD 186 more per 10,000 patients, 95% UI 113 more to 276 more; very low certainty) and mortality (RD 41 more per 10,000 patients, 95% UI 11 more to 73 more; very low certainty). There may be little or no difference between removing isolation based on a negative antigen test and 10-day isolation in the onward transmission leading to hospitalisation or death, but the average isolation period (mean difference -3 days) will be shorter for the removal of isolation based on a negative antigen test (moderate certainty).
INTERPRETATION
5 days versus 10 days of isolation in asymptomatic patients may result in a small amount of onward transmission and negligible hospitalisation and mortality; however, in symptomatic patients, the level of onward transmission is concerning and may lead to high hospitalisation and death rates. The evidence is, however, very uncertain.
FUNDING
This work was done in collaboration with WHO.
PubMed: 37360963
DOI: 10.1016/j.eclinm.2023.102058 -
Open Life Sciences 2023Cell-free circulating tumor DNA (ctDNA) is synthesized by tumor cells, including metastatic tumors, and circulates in the bloodstream. Evidence suggests that ctDNA is a... (Review)
Review
Cell-free circulating tumor DNA (ctDNA) is synthesized by tumor cells, including metastatic tumors, and circulates in the bloodstream. Evidence suggests that ctDNA is a potential predictive and prognostic biomarker for colorectal cancer (CRC), but its predictive efficacy in detecting CRC liver metastasis (CLM) remains unclear. Additionally, its utility in the clinical setting needs further investigation. We conducted a meta-analysis to determine the utility of ctDNA as a biomarker for predicting the prognosis of CLM and investigate the relationship between CLM and ctDNA positivity. A literature search was performed in electronic databases to identify relevant studies published up to March 19, 2022. We retrieved data on overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) for both ctDNA-positive and ctDNA-negative colorectal liver metastasis (CLM) patients from the selected articles. Hazard ratios (HRs) were also calculated for these survival outcomes analysis was also performed. The stability of the combined meta-analysis was verified by sensitivity analysis and publication bias evaluation. Ten trials were included, and 615 patients were evaluated. In patients with CLM, pooled HRs revealed a substantial link between ctDNA positivity and RFS/DFS. Subgroup analysis revealed that ctDNA had a prospective detection value. Sensitivity analysis and publication bias evaluation indicated stable results. Although the results on pooled HR for OS suggested that ctDNA-positive patients had a shorter survival time, their pooled HRs had a relatively evident heterogeneity, and sensitivity analysis and publication bias evaluation indicated that pooled HRs were extremely unstable. In conclusion, our results demonstrate that ctDNA appears to be a prognostic biomarker for resectable CLM patients.
PubMed: 37250841
DOI: 10.1515/biol-2022-0615 -
Metabolism: Clinical and Experimental Jun 2021Disease severity and mortality rates due to COVID-19 infection are greater in the elderly and chronically ill patients, populations at high risk for vitamin D... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Disease severity and mortality rates due to COVID-19 infection are greater in the elderly and chronically ill patients, populations at high risk for vitamin D deficiency. Vitamin D plays an important role in immune function and inflammation. This systematic review and meta-analysis assesses the impact of vitamin D status and supplementation on COVID-19 related mortality and health outcomes.
METHODS
We searched four databases until December 18th 2020, and trial registries until January 20th 2021. Two reviewers screened the studies, collected data, assessed the risk of bias, and graded the evidence for each outcome across studies, independently and in duplicate. Pre-specified outcomes of interest were mortality, ICU admission, invasive and non-invasive ventilation, hospitalization, time of hospital stay, disease severity and SARS-CoV-2 positivity. We only included data from peer-reviewed articles in our primary analyses.
RESULTS
We identified 31 peer-reviewed observational studies. In our primary analysis, there was a positive trend between serum 25(OH)D level <20 ng/ml and an increased risk of mortality, ICU admission, invasive ventilation, non-invasive ventilation or SARS-CoV-2 positivity. However, these associations were not statistically significant. Mean 25(OH)D levels was 5.9 ng/ml (95% CI [-9.5, -2.3]) significantly lower in COVID-19 positive, compared to negative patients. The certainty of the evidence was very low. We identified 32 clinical trial protocols, but only three have published results to-date. The trials administer vitamin D doses of 357 to 60,000 IU/day, from one week to 12 months. Eight megatrials investigate the efficacy of vitamin D in outpatient populations. A pilot trial revealed a significant decrease in ICU admission with calcifediol, compared to placebo (OR = 0.003), but the certainty of the evidence was unclear. Another small trial showed that supplementation with cholecalciferol, 60,000 IU/day, decreased fibrinogen levels, but did not have an effect on D-dimer, procalcitonin and CRP levels, compared to placebo. The third trial did not find any effect of vitamin D supplementation on COVID-19 related health outcomes.
CONCLUSION
While the available evidence to-date, from largely poor-quality observational studies, may be viewed as showing a trend for an association between low serum 25(OH)D levels and COVID-19 related health outcomes, this relationship was not found to be statistically significant. Calcifediol supplementation may have a protective effect on COVID-19 related ICU admissions. The current use of high doses of vitamin D in COVID-19 patients is not based on solid evidence. It awaits results from ongoing trials to determine the efficacy, desirable doses, and safety, of vitamin D supplementation to prevent and treat COVID-19 related health outcomes.
Topics: COVID-19; Dietary Supplements; Humans; Nutritional Status; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 33774074
DOI: 10.1016/j.metabol.2021.154753 -
Clinical and Experimental Rheumatology Jun 2022Studies report that autoimmune thyroid disease and elevated levels of thyroid autoantibodies are associated with fibromyalgia and widespread chronic pain. The aim of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Studies report that autoimmune thyroid disease and elevated levels of thyroid autoantibodies are associated with fibromyalgia and widespread chronic pain. The aim of this meta-analysis was to investigate the relationship between fibromyalgia and thyroid autoimmunity. Clinical symptoms and depression associated with fibromyalgia were also investigated in relation to the presence of thyroid autoantibodies.
METHODS
A literature search was conducted on PubMed and Embase for studies published between January, 1980 and February, 2020 on thyroid autoimmunity in fibromyalgia patients. Two reviewers independently screened and assessed the quality of the articles. Meta-analysis was performed to analyse the difference in frequency of thyroid autoantibody positivity between fibromyalgia patients and healthy controls. Clinical symptoms and depression were also analysed according to the presence of thyroid autoantibodies.
RESULTS
Data from 10 original studies were included in the systematic review, and 5 case-control studies that satisfied the selection criteria were subjected to meta-analysis. Thyroid autoantibody positivity was more common in fibromyalgia patients compared to healthy controls (thyroid peroxidase antibody: OR 3.41, 95% CI 1.97-5.90; thyroglobulin antibody: OR 2.23, 95% CI 1.23-4.01). The frequency of postmenopausal status was significantly higher in fibromyalgia patients with thyroid autoantibodies (OR 1.95, 95% CI 1.23-3.08). However, the severity of disease (pain and fatigue level, fibromyalgia impact questionnaire score, and disease duration) and prevalence of depression did not show a statistically significant difference according to thyroid autoantibody positivity.
CONCLUSIONS
Thyroid autoimmunity should be considered in fibromyalgia patients. The percentage of women in menopause was higher in thyroid autoantibody positive fibromyalgia patients.
Topics: Autoantibodies; Autoimmunity; Causality; Female; Fibromyalgia; Humans; Thyroid Gland
PubMed: 34369360
DOI: 10.55563/clinexprheumatol/y3gfva -
ACS Environmental Au Sep 2023Documenting the occurrence of viruses on fomites is crucial in determining the significance of fomite-mediated transmission and the potential use of fomites for... (Review)
Review
Documenting the occurrence of viruses on fomites is crucial in determining the significance of fomite-mediated transmission and the potential use of fomites for environmental disease surveillance. We conducted a systematic review and meta-analysis to compile information on the occurrence of human viruses on fomites in the environment; we identified 134 peer-reviewed papers. We compiled sampling and measurement methods, results, quality control information, and whether virus data were compared with community health data from the papers. We conducted univariate and multivariate analyses to investigate if presence of virus on fomites was associated with virus type (enveloped, nonenveloped), sampling location (healthcare setting, nonhealthcare temporary setting, nonhealthcare nontemporary setting), and area of fomite swabbed (<50, 50-100, >100 cm). Across 275 data sets from the 134 papers, there was the most data available for Coronaviridae and from fomites at hospitals. Positivity rates, defined as the percent positive fomite samples, were low (median = 6%). Data were available on viruses from 16 different viral families, but data on viruses from 9 families had few ( < 5) data sets. Many human virus families were not identified in this review (11 families). Less than 15% of the data sets reported virus concentrations in externally valid units (viruses per area of surface), and 16% provided a quantitative comparison between virus and health data. Virus type and area swabbed were significant predictors of virus presence on fomites, and the positivity rate of data sets collected from healthcare settings and nonhealthcare nontemporary settings (e.g., individual housing) were significantly higher than those collected in nonhealthcare temporary settings (e.g., restaurants). Data from this review indicates that viruses may be present on fomites, that fomite-mediated virus transmission may occur, and that fomites may provide information on circulation of infectious diseases in the community. However, more quantitative data on diverse viruses are needed, and method reporting needs significant improvements.
PubMed: 37743950
DOI: 10.1021/acsenvironau.3c00025 -
PloS One 2022To review the diagnostic accuracy of contrast-enhanced computed tomography (CT) in differentiating abscesses from cellulitis in patients with neck infections, using... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To review the diagnostic accuracy of contrast-enhanced computed tomography (CT) in differentiating abscesses from cellulitis in patients with neck infections, using surgical findings as the reference standard.
MATERIALS AND METHODS
Previous studies in the last 32 years were searched from PubMed and Embase. Because of partial verification bias (only positive abscess findings are usually verified surgically), sensitivity and specificity estimates are unreliable, and we focused on positive predictive value (PPV). For all studies, PPV was calculated as the proportion of true positives out of all positives on imaging. To estimate pooled PPV, we used both the median with an interquartile range and a model-based estimate. For narrative purposes, we reviewed the utility of common morphological CT criteria for abscesses, such as central hypodensity, the size of the collection, bulging, rim enhancement, and presence of air, as well as sensitivity and specificity values reported by the original reports.
RESULTS
23 studies were found reporting 1453 patients, 14 studies in children (771 patients), two in adults (137 patients), and seven including all ages (545 patients). PPV ranged from 0.67 to 0.97 in individual studies, had a median of 0.84 (0.79-0.87), and a model-based pooled estimate of 0.83 (95% confidence interval 0.80-0.85). Most morphological CT criteria had considerable overlap between abscesses and cellulitis.
CONCLUSIONS
The pooled estimate of PPV is 0.83 for diagnosing neck abscesses with CT. False positives may be due to limited soft tissue contrast resolution. Overall, none of the morphological criteria seem to be highly accurate for differentiation between abscess and cellulitis.
Topics: Child; Adult; Humans; Abscess; Predictive Value of Tests; Cellulitis; Tomography, X-Ray Computed; Sensitivity and Specificity
PubMed: 36288374
DOI: 10.1371/journal.pone.0276544 -
Rheumatology and Therapy Mar 2021The diagnosis of antiphospholipid syndrome (APS) requires the presence of thrombosis and/or recurrent miscarriages along with one or more anti-phospholipid antibodies... (Review)
Review
BACKGROUND
The diagnosis of antiphospholipid syndrome (APS) requires the presence of thrombosis and/or recurrent miscarriages along with one or more anti-phospholipid antibodies (aPL). The role of aPL has been largely investigated in systemic lupus erythematosus (SLE) with minimal data on other autoimmune rheumatic diseases. In this review, we aim to assess the prevalence of aPL in patients with inflammatory and autoimmune rheumatic and musculoskeletal diseases (RMDs) other than SLE, and their association with thrombosis.
RESULTS
A total of 20 studies, including 3242 patients, measured aPL in different inflammatory and autoimmune RMDs. The overall median percentage of aPL-positive patients was 14.05% (from 0 to 57.5%). For systemic sclerosis (SSc) patients, the median positivity was 14.05% for aPL, with IgG aCL being detected in up to 35.48% of all SSc aPL-positive patients. Only six studies (30%) performed an antibody confirmation test after 12 weeks, with the median prevalence being 10.88% (from 0 to 29.79%). Only six studies also assessed the number of double or triple aPL-positive patients. A total of eight (40%) studies including 1071 patients investigated the association between aPL and thrombotic events, namely five for SSc, one for SS, one for ANCA associated vasculitides (AAV), and one for RA. A median of 18.75% (7.69-71.43%) of aPL-positive patients experienced an arterial event in comparison to a median of 13.66% (7.69-31.25%) who underwent venous thrombotic event. Taking into consideration only the studies that performed a confirmation test, a median value of 34.36% (12.9-71.43%) of aPL-positive patients underwent an arterial event and a median value of 16.32% (9.68-25%) of aPL-positive patients underwent a venous event.
CONCLUSIONS
Anti-phospholipid antibodies can be detected in up to a third of patients with inflammatory and autoimmune RMDs, especially in SSc. However, there was a large heterogeneity among the retrieved studies. Available data supporting a general screening for aPL in all inflammatory and autoimmune RMDs are still insufficient. Screening for aPL in selected scenarios (e.g., pregnancy planning) could be considered.
PubMed: 33420626
DOI: 10.1007/s40744-020-00273-w -
Journal of Personalized Medicine Dec 2021Recently, checkpoint inhibitors have been investigated in metastatic prostate cancer, however their overall effect is unclear and needs to be further investigated. (Review)
Review
UNLABELLED
Recently, checkpoint inhibitors have been investigated in metastatic prostate cancer, however their overall effect is unclear and needs to be further investigated.
OBJECTIVES
The aim of this systematic review is to investigate the oncological response of metastatic castration-resistant prostate cancer patients to immune checkpoint inhibitors.
METHODS
Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, a systematic review of the literature was conducted through online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. Eligible publications were selected after a staged screening and selection process. RevMan 5.4 software was employed to run the quantitative analysis and forest plots. Risk of bias assessment was conducted using the Cochrane tool and Newcastle-Ottawa Scale for the randomized and non-randomized trials, respectively.
RESULTS
From the 831 results retrieved, 8 studies including 2768 patients were included. There was no significant effect on overall survival (OS) (overall response (OR) = 0.98; Z = 0.42; = 0.67). Meanwhile, progression-free survival (PFS) was significantly better with immune checkpoint inhibitors administration (OR = 0.85; Z = 3.9; < 0.0001). The subgroup analysis for oncological outcomes based on programmed death ligand 1 (PD-L1) positivity status displayed no significant effect, except on prostate-specific antigen response rate (PSA RR) (OR = 3.25; Z = 2.29; = 0.02). Based on DNA damage repair (DDR), positive patients had a significantly better PFS and a trend towards better OS and overall response rate (ORR); the ORR was 40% in positive patients compared to 20% in the negative patients (OR = 2.46; Z = 1.3; = 0.19), while PSA RR was 23.5% compared to 14.3% (OR = 1.88; Z = 0.88; = 0.38). Better PFS was clearly associated with DDR positivity (OR = 0.70; Z = 2.48; = 0.01) with a trend towards better OS in DDR positive patients (OR = 0.71; Z = 1.38; = 0.17). Based on tumor mutation burden (TMB), ORR was 46.7% with high TMB versus 8.8% in patients with low TMB (OR = 11.88; Z = 3.0; = 0.003).
CONCLUSIONS
Checkpoint inhibitors provide modest oncological advantages in metastatic castration-resistant prostate cancer. There are currently no good predictive indicators that indicate a greater response in some patients.
PubMed: 35055323
DOI: 10.3390/jpm12010008 -
Biological Psychology Mar 2009The magnitude of the cortisol awakening response, a relatively new indicator of hypothalamic-pituitary-adrenocortical (HPA) axis activation, has been related to a number... (Review)
Review
The magnitude of the cortisol awakening response, a relatively new indicator of hypothalamic-pituitary-adrenocortical (HPA) axis activation, has been related to a number of psychosocial factors. But findings have been inconsistent across studies. We systematically reviewed previous studies investigating the association between the cortisol awakening response and psychosocial factors. 147 eligible studies from 62 articles were identified. Separate analyses were carried out on the increase in cortisol following waking (CARi), and the integrated volume of cortisol released over the waking period (CARauc). We found that the CARi was positively associated with job stress and general life stress. It was negatively associated with fatigue, burnout, or exhaustion. There were less reliable negative associations between the CARi and positive affects. The CARauc was positively related to general life stress and negatively related to posttraumatic stress syndrome. This review concludes that different psychosocial factors are associated with an enhanced or reduced cortisol awakening response.
Topics: Animals; Databases, Bibliographic; Humans; Hydrocortisone; Meta-Analysis as Topic; Psychology; Wakefulness
PubMed: 19022335
DOI: 10.1016/j.biopsycho.2008.10.004 -
Gastrointestinal Endoscopy Aug 2022Current adenoma detection rate (ADR) benchmarks for colonoscopy in individuals positive for a fecal immunochemical test (FIT) are ≥45% in men and ≥35% in women.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Current adenoma detection rate (ADR) benchmarks for colonoscopy in individuals positive for a fecal immunochemical test (FIT) are ≥45% in men and ≥35% in women. These are based on weak, low-quality evidence. We performed a meta-analysis to ascertain the pooled ADR in FIT-positive colonoscopy.
METHODS
Major databases like PubMed, EMBASE, and Web of Science were searched in October 2021 for studies reporting on ADR of colonoscopy in a FIT-positive population. Meta-analysis was performed by standard methodology using the random-effects model. Heterogeneity was assessed by I and 95% prediction interval statistics.
RESULTS
Thirty-four high-quality studies that included more than 6 million asymptomatic average-risk individuals were analyzed; 2,655,345 individuals completed a screening FIT test. The pooled FIT screening rate was 69.8% (95% CI, 62.8-76.1), the pooled FIT positivity rate was 5.4% (95% CI, 4.3-6.9), and the colonoscopy completion rate was 85% (95% CI, 82.8-86.9). The pooled ADR was 47.8% (95% CI, 44.1-51.6), pooled advanced ADR was 25.3% (95% CI, 22-29), and the pooled colorectal cancer detection rate was 5.1% (95% CI, 4.4-5.9). The pooled ADR in men was 58.3% (95% CI, 52.8-63.6) and in women was 41.9% (95% CI, 36.4-47.6). The pooled ADR with qualitative FIT assessment was 67.7% (95% CI, 50.7-81), with 1-stool sample FIT was 52.8% (95% CI, 48.8-56.8), and at a cutoff threshold of 100 ng hemoglobin/mL was 52.1% (95% CI, 47-57.1). Based on time-period cumulative analysis, the ADR improved over time from 30.5% (95% CI, 24.6-37.2) to 47.8% (95% CI, 44.1-51.6).
CONCLUSIONS
This meta-analysis supports the current ADR benchmarks for colonoscopy in FIT-positive individuals. Excellent pooled ADR parameters were demonstrated with qualitative assessment of 1 stool sample at a test cutoff value of 100 ng hemoglobin/mL, and ADR per endoscopist improved over time.
Topics: Adenoma; Colonoscopy; Colorectal Neoplasms; Early Detection of Cancer; Female; Hemoglobins; Humans; Male
PubMed: 35413330
DOI: 10.1016/j.gie.2022.04.004