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Journal of Thrombosis and Thrombolysis Oct 2022Arterial and venous thrombotic events in COVID-19 cause significant morbidity and mortality among patients. Although international guidelines agree on the need for... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients: a meta-analysis of multicenter randomized controlled trials.
Arterial and venous thrombotic events in COVID-19 cause significant morbidity and mortality among patients. Although international guidelines agree on the need for anticoagulation, it is unclear whether full-dose heparin anticoagulation confers additional benefits over prophylactic-dose anticoagulation. This systematic review and meta-analysis aimed to investigate the efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients. We searched Pubmed/Medline, EMBASE, Clinicaltrials.gov, medRxiv.org and Cochrane Central Register of clinical trials dated up to April 2022. Randomized controlled trials (RCTs) comparing full-dose heparin anticoagulation to prophylactic-dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients were included in our pooled analysis. The primary endpoint was the rate of major thrombotic events and the co-primary endpoint was the rate of major bleeding events. We identified 4 studies, all of them multicenter, randomizing 2926 patients. Major thrombotic events were 23/1524 (1.5%) in full-dose heparin anticoagulation versus 57/1402 (4.0%) in prophylactic-dose [relative risk (RR) 0.39; 95% confidence interval (CI) 0.25-0.62; p˂0.01; I = 0%]. Clinical relevant bleeding events occurred in 1.7% (26/1524) among patients treated with heparin full anticoagulation dose compared to 1.1% (15/1403) in prophylactic-dose group (RR 1.60; 95% CI 0.85-3.03; p = 0.15; I = 20%). Mortality was 6.6% (101/1524) versus 8.6% (121/1402) (RR 0.63; 95% CI 0.33-1.19; p = 0.15). In this meta-analysis of high quality multicenter randomized trials, full-dose anticoagulation with heparin was associated with lower rate of major thrombotic events without differences in bleeding risk and mortality in hospitalized non critically ill COVID-19 patients.Study registration PROSPERO, review no. CRD42022301874.
Topics: Anticoagulants; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Thrombosis; COVID-19 Drug Treatment
PubMed: 35922578
DOI: 10.1007/s11239-022-02681-x -
Frontiers in Public Health 2021Several studies suggest an association between serum 25-hydroxyvitamin D (25OHD) and the outcomes of Severe Acute Respiratory Syndrome Corona-Virus-2 (SARS-CoV-2)... (Meta-Analysis)
Meta-Analysis
Several studies suggest an association between serum 25-hydroxyvitamin D (25OHD) and the outcomes of Severe Acute Respiratory Syndrome Corona-Virus-2 (SARS-CoV-2) infection, in particular Coronavirus Disease-2019 (COVID-19) related severity and mortality. The aim of the present meta-analysis was to investigate whether vitamin D status is associated with the COVID-19 severity, defined as ARDS requiring admission to intensive care unit (ICU) or mortality (primary endpoints) and with the susceptibility to SARS-CoV-2 and COVID-19-related hospitalization (secondary endpoints). A search in PubMed, ScienceDirect, Web of Science, Google Scholar, Scopus, and preprints repositories was performed until March 31th 2021 to identify all original observational studies reporting association measures, or enough data to calculate them, between Vitamin D status (insufficiency <75, deficiency <50, or severe deficiency <25 nmol/L) and risk of SARS-CoV-2 infection, COVID-19 hospitalization, ICU admission, or death during COVID-19 hospitalization. Fifty-four studies (49 as fully-printed and 5 as pre-print publications) were included for a total of 1,403,715 individuals. The association between vitamin D status and SARS-CoV2 infection, COVID-19 related hospitalization, COVID-19 related ICU admission, and COVID-19 related mortality was reported in 17, 9, 27, and 35 studies, respectively. Severe deficiency, deficiency and insufficiency of vitamin D were all associated with ICU admission (odds ratio [OR], 95% confidence intervals [95%CIs]: 2.63, 1.45-4.77; 2.16, 1.43-3.26; 2.83, 1.74-4.61, respectively), mortality (OR, 95%CIs: 2.60, 1.93-3.49; 1.84, 1.26-2.69; 4.15, 1.76-9.77, respectively), SARS-CoV-2 infection (OR, 95%CIs: 1.68, 1.32-2.13; 1.83, 1.43-2.33; 1.49, 1.16-1.91, respectively) and COVID-19 hospitalization (OR, 95%CIs 2.51, 1.63-3.85; 2.38, 1.56-3.63; 1.82, 1.43-2.33). Considering specific subgroups (i.e., Caucasian patients, high quality studies, and studies reporting adjusted association estimates) the results of primary endpoints did not change. Patients with low vitamin D levels present an increased risk of ARDS requiring admission to intensive care unit (ICU) or mortality due to SARS-CoV-2 infection and a higher susceptibility to SARS-CoV-2 infection and related hospitalization.
Topics: COVID-19; Humans; RNA, Viral; SARS-CoV-2; Vitamin D; Vitamin D Deficiency
PubMed: 35004568
DOI: 10.3389/fpubh.2021.736665 -
Dermatology and Therapy Oct 2020To investigate the associations of alopecia areata (AA) with serum vitamin D and calcium levels. (Review)
Review
INTRODUCTION
To investigate the associations of alopecia areata (AA) with serum vitamin D and calcium levels.
METHODS
A systematic review of all relevant articles published up to February 2020 in PubMed, Embase, and Cochrane Library databases was conducted. Primary endpoints were serum 25-hydroxyvitamin D [25(OH)D] levels and vitamin D deficiency, and the secondary endpoint was serum calcium level. Odds ratio (OR) and standardized mean difference (SMD) with 95% CI across studies were analyzed.
RESULTS
Data on 1585 patients with AA and 1114 controls from 16 case-control studies and three cross-sectional studies were included in this meta-analysis. A pooled meta-analysis was conducted using the random-effects model because of inter-study heterogeneity (vitamin D level, I = 87.90%; vitamin D deficiency, I = 81.10%; serum calcium level, I = 83.80%). A combined analysis revealed that patients with AA had significantly lower mean serum 25(OH)D level compared with control (WMD - 9.08, 95% CI - 11.65, - 6.50, p < 0.001), and were more likely to have vitamin D deficiency (OR 4.14, 95% CI 2.34, 7.35, p < 0.001). However, the pooled analysis revealed that patients with AA did not have significantly lower serum calcium levels compared with control (WMD - 0.17, 95% CI - 0.40, 0.06, p = 0.143). Subgroup analysis suggested that matched control, mean age, and country might contribute to the heterogeneity of serum vitamin D level, while study design, matched control, and country might contribute to the heterogeneity of vitamin D deficiency.
CONCLUSION
Deficiency of serum 25(OH)D level, rather than calcium level, was present in patients with AA. Screening for vitamin D deficiency and vitamin D supplementation may be beneficial in the treatment of patients with AA.
PubMed: 32772238
DOI: 10.1007/s13555-020-00433-4 -
Annals of Thoracic and Cardiovascular... Dec 2022The best treatment strategy for primary spontaneous pneumothorax is controversial and varies widely in practice. (Meta-Analysis)
Meta-Analysis
PURPOSE
The best treatment strategy for primary spontaneous pneumothorax is controversial and varies widely in practice.
METHODS
Literatures were searched from databases till 24 August 2021. A Bayesian network meta-analysis was conducted to compare the outcomes of various treatments with the following endpoints: recurrence rate, postoperative chest tube duration, postoperative air leakage duration, length of hospital stay, and complications rate.
RESULTS
In all, 7210 patients of 20 randomized controlled trials and 17 cohort studies were included. Surgery had a significantly lower recurrence rate compared to other treatments. Besides, bullectomy (BT) combined with chemical pleurodesis (CP), mechanical pleurodesis, or staple line coverage (SLC) can reduce the recurrence rate compared to BT alone, but none of them were statistically significant. In terms of reducing chest tube duration, BT with tubular Neoveil outperformed BT + pleural abrasion (mean difference [MD], 95% confidence interval [CI]: -2.5 [-4.63, -0.35]) and BT + apical pleurectomy (MD, 95% CI: -2.72 [-5.16, -0.27]).
CONCLUSIONS
Surgical methods were superior to manual aspiration (MA), chest tube drainage (CTD), and conservative treatment in terms of recurrence reduction. There was no significant difference between MA and CTD in reducing the recurrence rate. Among surgical methods, CP is more effective than mechanical pleurodesis and SLC among the additional procedures based on BT.
Topics: Humans; Pneumothorax; Network Meta-Analysis; Bayes Theorem; Treatment Outcome; Recurrence; Pleurodesis; Thoracic Surgery, Video-Assisted
PubMed: 36002271
DOI: 10.5761/atcs.oa.22-00113 -
Advances in Radiation Oncology 2023Although the frequency of noninferiority trials is increasing, the consistency of the reporting of these trials can vary. The aim of this systematic review was to assess... (Review)
Review
PURPOSE
Although the frequency of noninferiority trials is increasing, the consistency of the reporting of these trials can vary. The aim of this systematic review was to assess the reporting quality of radiation therapy noninferiority trials.
METHODS AND MATERIALS
The PubMed, Embase, and Cochrane databases were queried for randomized controlled radiation therapy trials with noninferiority hypotheses published in English between January 2000 and July 2022, and this was performed by an information scientist. Descriptive statistics were used to summarize data.
RESULTS
Of 423 records screened, 59 (14%) were included after full-text review. All were published after 2003 and open label. The most common primary cancer type was breast (n = 15, 25%). Altered radiation fractionation (n = 26, 45%) and radiation de-escalation (n = 11, 19%) were the most common types of interventions. The most common primary endpoints were locoregional control (n = 17, 29%) and progression-free survival (n = 14, 24%). Fifty-three (90%) reported the noninferiority margin, and only 9 (17%) provided statistical justification for the margin. The median absolute noninferiority margin was 9% (interquartile range, 5%-10%), and the median relative margin was 1.51 (interquartile range, 1.33-2.04). Sample size calculations and confidence intervals were reported in 54 studies (92%). Both intention-to-treat and per-protocol analyses were reported in 27 studies (46%). In 31 trials (53%), noninferiority of the primary endpoint was reached.
CONCLUSIONS
There was variability in the reporting of key components of noninferiority trials. We encourage consideration of additional statistical reasoning such as guidelines or previous trials in the selection of the noninferiority margin, reporting both absolute and relative margins, and the avoidance of statistically vague or misleading language in the reporting of future noninferiority trials.
PubMed: 36852015
DOI: 10.1016/j.adro.2023.101178 -
Cancer Treatment Reviews Nov 2023To analyze changes in recurrent/refractory osteosarcoma phase II trials over time to inform future trials in this population with poor prognosis. (Review)
Review
BACKGROUND/OBJECTIVE
To analyze changes in recurrent/refractory osteosarcoma phase II trials over time to inform future trials in this population with poor prognosis.
METHODS
A systematic review of trials registered on trial registries between 01/01/2017-14/02/2022. Comparison of 98 trials identified between 2003 and 2016. Publication search/analysis for both periods, last update on 01/12/2022.
RESULTS
Between 2017 and 2022, 71 phase-II trials met our selection criteria (19 osteosarcoma-specific trials, 14 solid tumor trials with and 38 trials without an osteosarcoma-specific stratum). The trial number increased over time: 13.9 versus 7 trials/year (p = 0.06). Monotherapy remained the predominant treatment (62% vs. 62%, p = 1). Targeted therapies were increasingly evaluated (66% vs. 41%, P = 0.001). Heterogeneity persisted in the trial characteristics. The inclusion criteria were measurable disease (75%), evaluable disease (14%), and surgical remission (11%). 82% of the trials included pediatric or adolescent patients. Biomarker-driven trials accounted for 25% of the total trials. The survival endpoint use (rather than response) slightly increased (40% versus 31%), but the study H/H hypotheses remained heterogeneous. Single-arm designs predominated over multiarm trials (n = 7). Available efficacy data on 1361 osteosarcoma patients in 58 trials remained disappointing, even though 21% of these trials were considered positive, predominantly those evaluating multi-targeted kinase inhibitors.
CONCLUSION
Despite observed changes in trial design and an increased number of trials investigating new therapies, high heterogeneity remained with respect to patient selection, study design, primary endpoints, and statistical hypotheses in recently registered phase II trials for osteosarcoma. Continued optimization of trial design informed by a deeper biological understanding should strengthen the development of new therapies.
PubMed: 37738712
DOI: 10.1016/j.ctrv.2023.102625 -
European Journal of Anaesthesiology Sep 2023Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively. (Meta-Analysis)
Meta-Analysis
The postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve and field blocks: A systematic review and meta-analysis, with trial sequential analysis.
BACKGROUND
Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively.
OBJECTIVES
To compare the postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve or field blocks.
DESIGN
A systematic review and meta-analysis with trial sequential analysis.
DATA SOURCES
MEDLINE, Embase and Web of Science, among others, up to June 2022.
ELIGIBILITY CRITERIA
We retrieved randomised controlled trials comparing liposomal bupivacaine versus bupivacaine, levobupivacaine or ropivacaine for peripheral nerve and field blocks after all types of surgery. Our primary endpoint was rest pain score (analogue scale 0 to 10) at 24 h. Secondary endpoints included rest pain score at 48 and 72 h, and morphine consumption at 24, 48 and 72 h.
RESULTS
Twenty-seven trials including 2122 patients were identified. Rest pain scores at 24 h were significantly reduced by liposomal bupivacaine with a mean difference (95% CI) of -0.9 (-1.4 to -0.4), I2 = 87%, P < 0.001. This reduction in pain scores persisted at 48 h and 72 h with mean differences (95% CI) of -0.7 (-1.1 to -0.3), I2 = 82%, P = 0.001 and -0.7 (-1.1 to -0.3), I2 = 80%, P < 0.001, respectively. There were no differences in interval morphine consumption at 24 h ( P = 0.15), 48 h ( P = 0.15) and 72 h ( P = 0.07). The quality of evidence was moderate.
CONCLUSIONS
There is moderate level evidence that liposomal bupivacaine reduces rest pain scores by 0.9 out of 10 units, when compared with long-acting local anaesthetics at 24 hours after surgery, and by 0.7 up to 72 hours after surgery.
Topics: Humans; Anesthetics, Local; Pain, Postoperative; Bupivacaine; Analgesics; Morphine; Peripheral Nerves; Analgesics, Opioid
PubMed: 37038770
DOI: 10.1097/EJA.0000000000001833 -
Journal of Vascular Surgery Mar 2023The objective of this study was to evaluate the application of the Global Anatomic Staging System (GLASS) in the endovascular treatment of chronic limb-threatening... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of this study was to evaluate the application of the Global Anatomic Staging System (GLASS) in the endovascular treatment of chronic limb-threatening ischemia (CLTI).
METHODS
We performed systematic research between June 2019 and February 2022, including articles investigating the relationship of GLASS classification with the outcomes of endovascular interventions in the treatment of CLTI. Data from the included studies were pooled and meta-analyzed. The primary endpoints were limb-based patency (LBP) at 1-year follow-up and immediate technical failure (ITF). Secondary endpoints included major amputation. We performed subgroup analysis between studies that reported on calcium modifier inclusion during GLASS classification and studies that did not.
RESULTS
Eleven studies, including 1816 patients (1975 limbs) met the inclusion criteria. The pooled ITF rates for GLASS stages I, II, and III are 5.52% (95% confidence interval [CI], 3.74%-8.07%), 7.39% (95% CI, 5.32%-10.18%), and 21.07% (95% CI, 13.48%-31.39%) respectively. The pooled LBP for GLASS stages I, II, and III are 68.43% (95% CI, 53.44%-80.37%), 41.52% (95% CI, 18.91%-68.37%), and 38.64% (95% CI, 19.83%-61.57%). The relative risk (RR) for ITF regarding composite GLASS I and II stages vs GLASS III is 3.96 (95% CI, 1.96-7.98). The RR for LBP of GLASS I and II versus GLASS stage III is 1.51 (95% CI, 0.86-2.64). Pooled major amputation rates for the composite GLASS I, II and GLASS III stages are 7.62% (95% CI, 5.44%-10.58%) and 15.43% (95% CI, 11.72%-20.05%) respectively, whereas the RR between GLASS I, II, and GLASS III stages is 1.84 (95% CI, 1.18-2.87).
CONCLUSIONS
Our study demonstrated that patients with CLTI undergoing endovascular interventions classified as GLASS stage III had almost a four-fold risk increase for ITF and 1.84 times the risk of major amputation compared with stages I and II. Additionally, GLASS classification correctly predicted ITF for all three stages, whereas it failed to predict stage I and II LBP outcomes. Safe conclusions regarding LBP cannot be drawn due to the low quality and small number of the included studies, necessitating further research. Furthermore, we displayed the importance of calcium moderator inclusion in the accurate classification of GLASS.
Topics: Humans; Chronic Limb-Threatening Ischemia; Endovascular Procedures; Treatment Outcome; Calcium; Risk Factors; Limb Salvage; Ischemia; Peripheral Arterial Disease; Retrospective Studies; Chronic Disease
PubMed: 35953002
DOI: 10.1016/j.jvs.2022.07.183 -
BJA Open Dec 2022The use of high-flow nasal oxygen (HFNO) has the potential to improve patient safety by limiting hypoxaemia during gastrointestinal endoscopy. The degree of benefit is... (Review)
Review
BACKGROUND
The use of high-flow nasal oxygen (HFNO) has the potential to improve patient safety by limiting hypoxaemia during gastrointestinal endoscopy. The degree of benefit is not adequately established.
METHODS
English language literature searches of PubMed, Scopus, Web of Science, and Cochrane Library electronic databases were performed to identify randomised controlled trials comparing HFNO and conventional oxygen therapy (COT) for patients undergoing gastrointestinal endoscopy under deep sedation. The primary endpoint was the incidence of hypoxic events observed during endoscopic procedures. The secondary endpoints were the incidence of recourse to rescue manoeuvres, procedure interruption, and adverse events. A meta-analysis and a trial sequence analysis were performed.
RESULTS
A total of 2867 patients from six randomised controlled trials were considered. Desaturation was observed in 5.2% and 27.2% of patients receiving HFNO and COT, respectively. Desaturation <90% was observed in 1.8% and 12.6% of the patients receiving HFNO and COT, respectively. In the subgroup analysis, desaturation occurrence was lower during HFNO than during COT in non-obese patients (2.2% 25.2%) and obese patients (22.9% 43.3%). Desaturation occurrence was lower during maximum (3.6% 26.9%) and minimum (15.9% 29.8%) HFNO therapy than during COT. HFNO showed a lower recurrence to rescue manoeuvres rate (4.7% 34.3%), a lower procedure interruption rate (0.4% 6.7%), and a lower adverse events rate (18.7% 21%) than COT. A high level of heterogeneity between the studies precluded confidence in drawing inference from the meta-analysis.
CONCLUSIONS
The evidence reviewed suggests that compared with COT, HFNO has fewer hypoxaemic events during gastrointestinal endoscopy, but this may not apply to all patients and clinical scenarios.
PubMed: 37588780
DOI: 10.1016/j.bjao.2022.100098 -
BMC Surgery May 2021Entero-colovesical fistula is a rare complication of various benign and malignant diseases. The diagnosis is prominently based on clinical symptoms; imaging studies are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Entero-colovesical fistula is a rare complication of various benign and malignant diseases. The diagnosis is prominently based on clinical symptoms; imaging studies are necessary not only to confirm the presence of the fistula, but more importantly to demonstrate the extent and the nature of the fistula. There is still a lack of consensus regarding the if, when and how to repair the fistula. The aim of the study is to review the different surgical treatment options, focus on surgical indications, and explore cumulative recurrence, morbidity, and mortality rates of entero-vesical and colo-vesical fistula patients.
METHODS
A systematic review of the literature was conducted according to PRISMA guidelines. Random effects meta-analyses of proportions were developed to assess primary and secondary endpoints. I statistic and Cochran's Q test were computed to assess inter-studies' heterogeneity.
RESULTS
Twenty-two studies were included in the analysis with a total of 861 patients. Meta-analyses of proportions pointed out 5, 22.2, and 4.9% rates for recurrence, complications, and mortality respectively. A single-stage procedure was performed in 75.5% of the cases, whereas a multi-stage operation in 15.5% of patients. Palliative surgery was performed in 6.2% of the cases. In 2.3% of the cases, the surgical procedure was not specified. Simple and advanced repair of the bladder was performed in 84.3% and 15.6% of the cases respectively.
CONCLUSIONS
Although burdened by a non-negligible rate of complications, surgical repair of entero-colovesical fistula leads to excellent results in terms of primary healing. Our review offers opportunities for significant further research in this field. Level of Evidence Level III according to ELIS (SR/MA with up to two negative criteria).
Topics: Colon; Humans; Intestinal Fistula; Prevalence; Urinary Bladder Fistula
PubMed: 34044862
DOI: 10.1186/s12893-021-01272-6