Objective Branched and fenestrated repair has been shown to be effective for treatment of complex aortic aneurysms. However, the long-term durability of branches is not well reported. Methods ...Prospective data collected for all patients enrolled in a physician-sponsored investigational device exemption trial for branched and fenestrated endografts were analyzed. Retrospective review of imaging studies and electronic records was used to supplement the dataset. Incidences of branch stent secondary intervention, stent fracture, migration, branch-related rupture, and death were calculated. A time-to-event analysis was performed for secondary intervention for any branch. Univariable and multivariable analyses were performed to identify related variables. Branch instability, a composite outcome of any branch event, was reported as a function of exponential decay to capture the loss of freedom from complications over time. Results Between the years 2001 and 2010, 650 patients underwent endovascular aortic repair with branched or fenestrated devices. Over 9 years of follow-up (mean standard deviation, 3 2.3 years), secondary procedures were performed for 0.6% of celiac, 4% of superior mesenteric artery (SMA), 6% of right renal artery, and 5% of left renal artery stents. Mean time to reintervention was 237 (354) days. The 30-day, 1-year, and 5-year freedom from branch intervention was 98% (95% confidence interval CI, 96%-99%), 94% (95% CI, 92%-96%), and 84% (95% CI, 78%-90%), respectively. Death from branch stent complications occurred in three patients, two related to SMA thrombosis and one due to an unstented SMA scallop. Multivariable analysis revealed no factors as independent predictors of need for branch reintervention. Conclusions Branches, after branched or fenestrated aortic repair, appear to be durable and are rarely the cause of patient death. The absence of long-term data on branch patency in open repair precludes comparison, yet the lower morbidity and mortality risk coupled with longer-term durability data will further alter the balance of repair options.
To assess the effects of vitamin D supplementation during pregnancy on obstetric outcomes and birth variables.
Systematic review and meta-analysis of randomized controlled trials (RCTs).
Not ...applicable.
Pregnant women and neonates.
PubMed and 5 other research databases were searched through March 2014 for RCTs evaluating vitamin D supplementation ± calcium/vitamins/ferrous sulfate vs. a control (placebo or active) during pregnancy.
Measures were: circulating 25-hydroxyvitamin D 25(OH)D levels, preeclampsia, gestational diabetes mellitus (GDM), small for gestational age (SGA), low birth weight, preterm birth, birth weight, birth length, cesarean section. Mantel-Haenszel fixed-effects models were used, owing to expected scarcity of outcomes. Effects were reported as relative risks and their 95% confidence intervals (CIs).
Thirteen RCTs (n = 2,299) were selected. Circulating 25(OH)D levels were significantly higher at term, compared with the control group (mean difference: 66.5 nmol/L, 95% CI 66.2-66.7). Birth weight and birth length were significantly greater for neonates in the vitamin D group; mean difference: 107.6 g (95% CI 59.9-155.3 g) and 0.3 cm (95% CI 0.10-0.41 cm), respectively. Incidence of preeclampsia, GDM, SGA, low birth weight, preterm birth, and cesarean section were not influenced by vitamin D supplementation. Across RCTs, the doses and types of vitamin D supplements, gestational age at first administration, and outcomes were heterogeneous.
Vitamin D supplementation during pregnancy was associated with increased circulating 25(OH)D levels, birth weight, and birth length, and was not associated with other maternal and neonatal outcomes. Larger, better-designed RCTs evaluating clinically relevant outcomes are necessary to reach a definitive conclusion.
Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially ...fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use.
MEDLINE, Embase, and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade ≥ 3 from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian-Laird random effects models. We compared incidences between PD-1 and PD-L1 inhibitors and between treatment naive and previously treated patients.
Nineteen trials (12 with PD-1 inhibitors n = 3,232 and 7 with PD-L1 inhibitors n = 1,806) were identified. PD-1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis compared with PD-L1 inhibitors (3.6%; 95% CI, 2.4%-4.9% vs 1.3%; 95% CI, 0.8%-1.9%, respectively; P = .001). PD-1 inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis (1.1%; 95% CI, 0.6%-1.7% vs 0.4%; 95% CI, 0%-0.8%; P = .02). Treatment naive patients had higher incidence of grade 1 through 4 pneumonitis compared with previously treated patients (4.3%; 95% CI, 2.4%-6.3% vs 2.8%; 95% CI, 1.7%- 4%; P = .03).
There was a higher incidence of pneumonitis with use of PD-1 inhibitors compared with PD-L1 inhibitors. Higher rate of pneumonitis was more common in treatment naive patients.
Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is ...associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI.
We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS) and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies 112 randomized controlled trials (RCTs); 64 cohort studies with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0-10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria 7.0% (6.0-8.0%), 6.7% (5.0-8.0%), 5.9% (4.0-7.0%), respectively. The prevalence of SI in RCTs was significantly lower compared with cohort studies 4.9% (4.0-6.0%) vs. 17% (14-19%). The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately 18% (14-21%), 8.2% (6.0-10%), 9.1% (6.0-11%), respectively. Statin lipid solubility did not affect the prevalence of SI 4.0% (2.0-5.0%) vs. 5.0% (4.0-6.0%). Age odds ratio (OR) 1.33, P = 0.04, female gender (OR 1.47, P = 0.007), Asian and Black race (P < 0.05 for both), obesity (OR 1.30, P = 0.02), diabetes mellitus (OR 1.26, P = 0.02), hypothyroidism (OR 1.37, P = 0.01), chronic liver, and renal failure (P < 0.05 for both) were significantly associated with SI in the meta-regression model. Antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose were also associated with a higher risk of SI.
Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI.
Abstract
Background
We systematically assessed benefits and harms of the use of ivermectin (IVM) in patients with coronavirus disease 2019 (COVID-19).
Methods
Published and preprint randomized ...controlled trials (RCTs) assessing the effects of IVM on adult patients with COVID-19 were searched until 22 March 2021 in 5 engines. Primary outcomes were all-cause mortality rate, length of hospital stay (LOS), and adverse events (AEs). Secondary outcomes included viral clearance and severe AEs (SAEs). The risk of bias (RoB) was evaluated using the Cochrane Risk of Bias 2.0 tool. Inverse variance random effect meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods.
Results
Ten RCTs (n = 1173) were included. The controls were the standard of care in 5 RCTs and placebo in 5. COVID-19 disease severity was mild in 8 RCTs, moderate in 1, and mild and moderate in 1. IVM did not reduce all-cause mortality rates compared with controls (relative risk RR, 0.37 95% confidence interval, .12–1.13; very low QoE) or LOS compared with controls (mean difference, 0.72 days 95% confidence interval, −.86 to 2.29 days; very low QoE). AEs, SAEs, and viral clearance were similar between IVM and control groups (low QoE for all outcomes). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality rates in 3 RCTs at high RoB were reduced with IVM.
Conclusions
Compared with the standard of care or placebo, IVM did not reduce all-cause mortality, LOS, or viral clearance in RCTs in patients with mostly mild COVID-19. IVM did not have an effect on AEs or SAEs and is not a viable option to treat patients with COVID-19.
Our systematic review of randomized controlled trials showed that ivermectin (vs control) did not reduce all-cause mortality, hospital stays, or viral clearance in patients with mostly mild coronavirus disease 2019 (COVID-19). Ivermectin is not a viable treatment option for COVID-19.
Meta-Analysis Hernandez, Adrian V.; Marti, Katherine M.; Roman, Yuani M.
Chest,
July 2020, 2020-07-00, 20200701, Letnik:
158, Številka:
1
Journal Article
Recenzirano
Odprti dostop
When a review is performed following predefined steps (ie, systematically) and its results are quantitatively analyzed, it is called meta-analysis. Publication of meta-analyses has increased ...exponentially in pubmed.gov; using the key word “meta-analysis,” 1,473 titles were yielded in 2007 and 176,704 on January 2020. Well-designed and reported meta-analyses provide valuable information for clinicians, researchers, and policymakers. The aim of this study was to provide CHEST peer reviewers, as well as authors and researchers in training, with tools that can help to improve the quality and timeliness of journal reviews, as well as the quality of the meta-analyses submitted. This article also is intended to be a practical guide to inform authors about the key features of meta-analyses to be considered when producing their review.
Efficacy and safety of treatments for hospitalized COVID-19 are uncertain. We systematically reviewed efficacy and safety of remdesivir for the treatment of COVID-19.
Studies evaluating remdesivir in ...adults with hospitalized COVID-19 were searched in several engines until August 21, 2020. Primary outcomes included all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAEs). Inverse variance random effects meta-analyses were performed.
We included four randomized controlled trials (RCTs) (n = 2296) two vs. placebo (n = 1299) and two comparing 5-day vs. 10-day regimens (n = 997), and two case series (n = 88). Studies used intravenous remdesivir 200mg the first day and 100mg for four or nine more days. One RCT (n = 236) was stopped early due to AEs; the other three RCTs reported outcomes between 11 and 15 days. Time to recovery was decreased by 4 days with remdesivir vs. placebo in one RCT (n = 1063), and by 0.8 days with 5-days vs. 10-days of therapy in another RCT (n = 397). Clinical improvement was better for 5-days regimen vs. standard of care in one RCT (n = 600). Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28, I2 = 43%) and need for invasive ventilation (RR 0.57, 95%CI 0.23 to 1.42, I2 = 60%) vs. placebo at 14 days but had fewer SAEs; 5-day decreased need for invasive ventilation and SAEs vs. 10-day in one RCT (n = 397). No differences in all-cause mortality or SAEs were seen among 5-day, 10-day and standard of care. There were some concerns of bias to high risk of bias in RCTs. Heterogeneity between studies could be due to different severities of disease, days of therapy before outcome determination, and how ordinal data was analyzed.
There is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in hospitalized COVID-19 patients. Until stronger evidence emerges, we cannot conclude that remdesivir is efficacious for treating COVID-19.
Antibiotic exposure is the most important risk factor for Clostridium difficile infection (CDI). Most evaluations of antimicrobial risk factors have been conducted in healthcare settings. The ...objective of this meta-analysis was to evaluate the association between antibiotic exposure and community-associated CDI (CA-CDI) (i.e. symptom onset in the community with no healthcare facility admission within 12 weeks) and to determine the classes of antibiotics posing the greatest risk.
We searched four electronic databases for subject headings and text words related to CA-CDI and antibiotics. Studies that investigated the risk of CA-CDI associated with antibiotic usage were considered eligible. Data from the identified studies were combined using a random-effects model and ORs were calculated.
Of 910 citations identified, eight studies (n = 30 184 patients) met our inclusion criteria. Antibiotic exposure was associated with an increased risk of CA-CDI (OR 6.91, 95% CI 4.17-11.44, I(2) = 95%). The risk was greatest with clindamycin (OR 20.43, 95% CI 8.50-49.09) followed by fluoroquinolones (OR 5.65, 95% CI 4.38-7.28), cephalosporins (OR 4.47, 95% CI 1.60-12.50), penicillins (OR 3.25, 95% CI 1.89-5.57), macrolides (OR 2.55, 95% CI 1.91-3.39) and sulphonamides/trimethoprim (OR 1.84, 95% CI 1.48-2.29). Tetracyclines were not associated with an increased CDI risk (OR 0.91, 95% CI 0.57-1.45).
Antibiotic exposure was an important risk factor for CA-CDI, but the risk was different amongst different antibiotic classes. The risk was greatest with clindamycin followed by fluoroquinolones and cephalosporins, whereas tetracyclines were not associated with an increased risk.
Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.
To conduct a systematic review of the benefits and ...adverse events (AEs) of cannabinoids.
Twenty-eight databases from inception to April 2015.
Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome.
Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis.
Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs.
A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio OR, 3.82 95% CI, 1.55-9.42; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 95% CI, 0.99-2.00; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference WMD, -0.46 95% CI, -0.80 to -0.11; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, -0.36 95% CI, -0.69 to -0.05; 7 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination.
There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.
This study was undertaken to evaluate the association between components defining insulin resistance and breast cancer in women.
We conducted a systematic review of four databases (PubMed-Medline, ...EMBASE, Web of Science, and Scopus) for observational studies evaluating components defining insulin resistance in women with and without breast cancer. A meta-analysis of the association between insulin resistance components and breast cancer was performed using random effects models.
Twenty-two studies (n = 33,405) were selected. Fasting insulin levels were not different between women with and without breast cancer (standardized mean difference, SMD -0.03, 95%CI -0.32 to 0.27; p = 0.9). Similarly, non-fasting/fasting C-peptide levels were not different between the two groups (mean difference, MD 0.07, -0.21 to 0.34; p = 0.6). Using individual odds ratios (ORs) adjusted at least for age, there was no higher risk of breast cancer when upper quartiles were compared with the lowest quartile (Q1) of fasting insulin levels (OR Q2 vs. Q1 0.96, 0.71 to 1.28; OR Q3 vs. Q1 1.22, 0.91 to 1.64; OR Q4 vs. Q1 0.98, 0.70 to 1.38). Likewise, there were no differences for quartiles of non-fasting/fasting C-peptide levels (OR Q2 vs. Q1 1.12, 0.91 to 1.37; OR Q3 vs. Q1 1.20, 0.91 to 1.59; OR Q4 vs. Q1 1.40, 1.03 to 1.92). Homeostatic model assessment (HOMA-IR) levels in breast cancer patients were significantly higher than in people without breast cancer (MD 0.22, 0.13 to 0.31, p<0.00001).
Higher levels of fasting insulin or non-fasting/fasting C-peptide are not associated with breast cancer in women. HOMA-IR levels are slightly higher in women with breast cancer.
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