Mantel-Haenszel Relative Risk Research Articles

Effect of Pembrolizumab Monotherapy Versus Brentuximab Vedotin (BV) on Symptoms Associated with Health-Related Quality of Life (HRQoL) in Relapsed/Refractory (R/R) Classical Hodgkin Lymphoma (cHL) in the Randomized, Phase 3, Keynote-204 Study

Effect of Pembrolizumab Monotherapy Versus Brentuximab Vedotin (BV) on Symptoms Associated with Health-Related Quality of Life (HRQoL) in Relapsed/Refractory (R/R) Classical Hodgkin Lymphoma (cHL) in the Randomized, Phase 3, Keynote-204 Study

DOACs Versus VKAs in Older Adults Treated for Acute Venous Thromboembolism: Systematic Review and Meta-Analysis.

Four direct-acting oral anticoagulants (DOACs) are currently approved by the Food and Drug Administration for the treatment of venous thromboembolism (VTE). Limited efficacy and safety data are available for their use in older adults (aged ≥75 years). Medline, Cochrane Central Register of Controlled Trials, Embase, EBSCO, Web of Science, and CINAHL databases were searched for trials comparing DOACs with vitamin K antagonists (VKAs) for the treatment of VTE in older adults from inception through January 1, 2020. Meta-analysis was performed to assess the combined endpoint of recurrent VTE and related deaths and bleeding events (composite of major and clinically relevant nonmajor bleeding). The Mantel-Haenszel relative risk (RR) random effects model was used to pool results across studies. Six randomized controlled trials at low risk of bias met criteria for inclusion with a total of 3,665 patients aged 75 years and older with follow-up of 24 weeks or longer. Data for bleeding events were not available for dabigatran. Overall, DOACs had an improved efficacy over VKAs (RR = .56; 95% confidence interval [CI] = .38-.82). There was no statistically significant difference in the safety outcomes (RR = .77; 95% CI = .56-1.05). No significant heterogeneity was observed for efficacy outcome, and only moderate heterogeneity was observed for safety outcome. In older adults with VTE, DOACs appear to improve rates of recurrent VTE and VTE-related deaths compared with VKAs with similar bleeding outcomes.

Quantifying unmeasured confounding in three epidemiological studies associating myelodysplastic syndromes (MDS) with cardiovascular disease (CVD).

e19532 Background: Confounding occurs when an investigator studies the effect of an exposure on the occurrence of an outcome, but in the process measures the effect of another factor (a confounding variable). Knowledge of possible causal pathways assists an investigator to minimize confounding, but despite utmost attempts, errors are frequent. To assess role of a possible confounder (smoking), data from 3 studies (1. Herrera at al. 2019 2. Goldberg et al. 2010 and 3. Brunner et al. 2017) associating MDS (exposure) with CVD (outcome) was used to conduct sensitivity analysis. Methods: 2 x 2 tables were constructed with data from 3 studies (part 2 of table below). A vector defining the proportion of confounder (smoking) among exposed [prop (Smoking+|MDS+)], unexposed [prop (Smoking+|MDS-)] and risk ratio associating smoking status with CVD (part 1) using historical data was deduced. Extracted data was added to online bias analysis tool ( https://sites.google.com/site/biasanalysis/ ) to calculate crude as well as mantel-haenszel (MH) relative risk (RR) adjusted for smoking. Results: RRs unadjusted for smoking status for studies 1, 2 and 3 were 1.31, 1.34 and 2.21, respectively, signifying increased risk of CVD in MDS patients (part 3). Upon adjustment for smoking status, MH-RR for MDS-CVD relationship was 0.95, 0.97 for studies 1 and 2 respectively, signifying no increased CVD risk and 1.59 for study 3 signifying increased CVD risk but lower upon adjustment. Conclusions: Making inference of MDS-CVD association without accounting for smoking status can blur effects and at times result in false associations. Given ambiguity in results from these 3 studies, further evidence is needed to better assess MDS-CVD relationship. A simple online tool allows estimating nonrandom errors, assess magnitude and direction of biases, and help clinicians/researchers quantify these biases for better interpretation of observational data in a time efficient manner. Other bias analyses for these studies will be presented. [Table: see text]

Waning of Measured Influenza Vaccine Effectiveness Over Time: The Potential Contribution of Leaky Vaccine Effect.

Several observational studies have shown decreases in measured influenza vaccine effectiveness (mVE) during influenza seasons. One study found decreases of 6-11%/month during the 2011-2012 to 2014-2015 seasons. These findings could indicate waning immunity but could also occur if vaccine effectiveness is stable and vaccine provides partial protection in all vaccinees ("leaky") rather than complete protection in a subset of vaccinees. Since it is unknown whether influenza vaccine is leaky, we simulated the 2011-2012 to 2014-2015 influenza seasons to estimate the potential contribution of leaky vaccine effect to the observed decline in mVE. We used available data to estimate daily numbers of vaccinations and infections with A/H1N1, A/H3N2, and B viruses. We assumed that vaccine effect was leaky, calculated mVE as 1 minus the Mantel-Haenszel relative risk of vaccine on incident cases, and determined the mean mVE change per 30 days since vaccination. Because change in mVE was highly dependent on infection rates, we performed simulations using low (15%) and high (31%) total (including symptomatic and asymptomatic) seasonal infection rates. For the low infection rate, decreases (absolute) in mVE per 30 days after vaccination were 2% for A/H1N1 and 1% for A/H3N2and B viruses. For the high infection rate, decreases were 5% for A/H1N1, 4% for A/H3, and 3% for B viruses. The leaky vaccine bias could account for some, but probably not all, of the observed intraseasonal decreases in mVE. These results underscore the need for strategies to deal with intraseasonal vaccine effectiveness decline.

Comparative analysis of cerebrovascular events in transcatheter and surgical aortic valve replacement: a systematic review and meta-analysis of randomised trials

Transcatheter aortic valve replacement (TAVR) has become the procedure of choice for inoperable patients and a safe alternative to surgical aortic valve replacement (SAVR) among moderate-risk patients. We used meta-analysis to compare the incidence of cerebrovascular events amongst patients undergoing TAVR and SAVR in randomised controlled trials (RCT). Our search revealed five RCT published between 2011 and 2017 with a total of 5,414 patients. Data were summarised as Mantel-Haenszel relative risk (RR) and 95% confidence intervals (CI). The risk of major stroke (RR 0.89, 95% CI: 0.53-1.51), all strokes (RR 0.85, 95% CI: 0.59-1.22) and all cerebrovascular events (RR 0.94, 95% CI: 0.75-1.17) was comparable between patients undergoing TAVR and SAVR at 30 days of follow-up. The risk of all strokes (RR 0.92, 95% CI: 0.69-1.22), major stroke (RR 0.92, 95% CI: 0.62-1.37) and all cerebrovascular events (RR 1.03, 95% CI: 0.79-1.33) was comparable between TAVR and SAVR at one year of follow-up. The incidence of major stroke (RR 1.02, 95% CI: 0.64-1.61), all strokes (RR 1.12, 95% CI: 0.78-1.62) and all cerebrovascular events (RR 1.23, 95% CI: 0.91-1.66) was comparable between TAVR and SAVR between 30 days and one year of follow-up. In our meta-analysis of RCT comparing TAVR and SAVR, we showed comparable risk of major stroke, all stroke and all cerebrovascular events.

Safety and efficacy of cerebral protection devices in transcatheter aortic valve replacement: A clinical end-points meta-analysis.

Stroke after transcatheter aortic valve replacement (TAVR) occurs with an incidence of 4-11% and is a particularly devastating adverse event associated with the procedure. Several cerebral protection devices (CPD) have been developed to prevent cerebrovascular events during TAVR. While most studies have shown CPD to be associated with decreased number and volume of lesions on diffusion weighted magnetic resonance imaging, the clinical benefit of these devices remains uncertain. We aimed to use meta-analysis techniques to study the clinical safety and efficacy of these CPD in prospective randomized and non-randomized studies. Data was summarized as Mantel-Haenszel relative risk (RR) and 95% confidence intervals (CI). We used the Higgins' I2 statistic to evaluate heterogeneity. We found no evidence of difference between patients with and without CPD [RR 0.70 (95% CI 0.40-1.21)] for the primary composite outcome of stroke and mortality at 30 days. The two groups were also comparable in peri-procedural strokes [RR 0.53 (95% CI 0.27-1.07)], stroke at 30 days [RR 0.69(95% CI 0.38-1.26)], mortality [RR 0.59 (95% CI 0.22-1.59) at 30 days, AKI [RR 0.68(95% CI 0.28-1.62)], major bleeding [RR 0.56 (95% CI 0.26-1.18)], life threating bleeding [0.54 (95% CI 0.19-1.53)] and major vascular complications [RR 0.80 (95% CI 0.52-1.24)]. The risk of strokes within the first week of TAVR was significantly lower in the CPD group [0.56(95% CI 0.33-0.96)]. CPD are associated with a decreased incidence of strokes within 1 week of follow-up without showing any evidence of increased risk of other peri-procedural adverse events.

Clinical and Echocardiographic Outcomes Following Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement: Meta-Analysis and Meta-Regression.

Transcatheter aortic valve replacement has become the procedure of choice for inoperable, high-risk, and many intermediate-risk patients with aortic stenosis. Conduction abnormalities are a common finding after transcatheter aortic valve replacement and often result in permanent pacemaker (PPM) implantation. Data pertaining to the clinical impact of PPM implantation are controversial. We used meta-analysis techniques to summarize the effect of PPM implantation on clinical and echocardiographic outcomes after transcatheter aortic valve replacement. Data were summarized as Mantel-Haenszel relative risk (RR) and 95% confidence intervals (CIs) for dichotomous variables and as standardized mean difference and 95% CI for continuous variables We used the Higgins I2 statistic to evaluate heterogeneity. We found that patients with and without PPM have similar all-cause mortality (RR, 0.85; 95% CI, 0.70-1.03), cardiovascular mortality (RR, 0.84; 95% CI, 0.59-1.18), myocardial infarction (RR, 0.47; 95% CI, 0.20-1.11), and stroke (RR, 1.26; 95% CI, 0.70-2.26) at 30 days. The groups were also comparable in all-cause mortality (RR, 1.03; 95% CI, 0.92-1.16), cardiovascular mortality (RR, 0.69; 95% CI, 0.39-1.24), myocardial infarction (RR, 0.58; 95% CI, 0.30-1.13), and stroke (RR, 0.70; 95% CI, 0.47-1.04) at 1 year. We observed that the improvement in left ventricular ejection fraction was significantly greater in the patients without PPM (standardized mean difference, 0.22; 95% CI, 0.12-0.32). PPM implantation is not associated with increased risk of all-cause mortality, cardiovascular mortality, stroke, or myocardial infarction both at short- and long-term follow-up. However, PPM is associated with impaired left ventricular ejection fraction recovery post-transcatheter aortic valve replacement.

Screening for coronary artery disease in patients with type 2 diabetes: a meta-analysis and trial sequential analysis

ObjectiveTo evaluate the efficacy of coronary artery disease screening in asymptomatic patients with type 2 diabetes and assess the statistical reliability of the findings.MethodsElectronic databases (MEDLINE, EMBASE, Cochrane Library and...

The prognostic value of magnetic resonance imaging in moderate and severe traumatic brain injury: a systematic review and meta-analysis protocol.

BackgroundTraumatic brain injury (TBI) is a devastating condition with significant long-term mortality and morbidity. Despite current need for objective indicators to guide initial decision-making, few reliable acute phase prognostic factors have been identified. Early magnetic resonance imaging (MRI) has been investigated as a prognostic tool, but uncertainty remains in both its discriminative predictive value and which acute phase lesion patterns correlate with long-term outcome.MethodsWe will conduct a systematic review of observational cohort studies and randomized controlled trials of adult moderate or severe TBI patients who underwent MRI in the acute phase after trauma. A high sensitivity search strategy will be employed in MEDLINE, EMBASE, BIOSIS, and Cochrane CENTRAL to identify citations. Two reviewers will independently screen all identified references for eligibility and extract data into a standardized form. Data will be collected on study design, baseline demographics, trauma characteristics, magnetic resonance (MR) technical specifications, lesion patterns, and outcomes as related to acute MRI imaging. If meta-analysis is possible, quantitative data for each outcome will be pooled per type of lesion pattern using random effects models and expressed as Mantel-Haenszel relative risks in order to determine the prognostic value of lesions detected on acute MRI and their strength as discriminatory predictors of long-term outcome. Statistical heterogeneity will be evaluated with the I2 statistics, and risk of bias and reporting quality will be assessed with standardized scales. Subgroup analyses are planned as a function of TBI severity, MRI-timing post-TBI, MRI field strength, MRI sequence, timing of outcome assessment, and risk of bias.DiscussionWe expect significant clinical heterogeneity, as eligible studies will likely encompass different periods in evolving MRI technology in addition to significant variability of image sequence protocols and timing of acquisition between centers. Based on existing studies in TBI, we expect lesions detected in the brainstem to be of significant predictive value as MRI is particularly sensitive for imaging the brain’s posterior fossa. Our systematic review will allow clinicians to more accurately interpret MRI in the context of determining prognosis for moderate and severe TBI patients and inform researchers in this domain to improve the methodology of future studies.Systematic review registrationProspero CRD42015017074Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0184-x) contains supplementary material, which is available to authorized users.

Abstract 12540: High-Dose Statins Reduce the Risk of Contrast-Induced Nephropathy in Patients Undergoing Angiography: Meta-Analysis of 27 Randomized Controlled Trials

Introduction: Contrast-induced nephropathy (CIN) is a common complication of contrast administration during angiography. Short-term high-dose statins have been suggested for the prevention of CIN in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). Hypothesis: Multiple randomized controlled trials (RCT) have examined the role of statin in preventing CIN with conflicting results. We expanded on previous meta-analyses by including additional RCTs to provide a better outlook on the efficacy of statins in the prevention of CIN. Methods: We searched Pubmed, Medline, Embase, Cochrane, and conference abstracts for prospective RCTs that compared short-term high-dose statins to low-dose statins or placebo in patients undergoing CAG, PCI, computed tomography angiography, or peripheral angiography. High-dose statin was defined as Atorvastatin 40-80 mg, Simvastatin 40 mg, and Rosuvastatin 10-40 mg. Study quality was assessed using the Jadad score. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. Mantel Haenszel relative risk was calculated using the random effect model. Results: Twenty seven trials (N=9559) were included in the analysis. Eight of the included trials enrolled patients with acute coronary syndrome (ACS) exclusively. High-dose statin was associated with statistically significant reduction in the incidence of CIN (RR=0.56; 95% CI 0.46, 0.69; P<001) compared to low-dose statin or placebo. This protective effect remained significant upon looking on trials that enrolled patients with ACS only (RR=0.40; 95% CI 0.29, 0.56; P<001). Subgroup analysis based on the type of statin showed no significant difference between simvastatin, atorvastatin, or rosuvastatin. No heterogeneity was detected among the studied outcomes (I2=0%). Conclusions: Peri-procedural Short-term high-dose statin administration significantly reduces the incidence of CIN in patients undergoing angiography.

Dopamine Administration is a Risk Factor for Delirium in Patients Undergoing Coronary Artery Bypass Surgery

Delirium is an important morbidity following heart surgery. We sought to determine whether dopamine infusion is associated with increased risk of delirium in patients undergoing coronary artery bypass grafting. A total of 137 patients (mean age; 61.02±7.83, 105 males) were included in the study. Patients undergoing isolated coronary artery bypass grafting were considered eligible and those with preoperative neurological deficit or significant neurocognitive disorders, dementia or psychiatric disorders were excluded. Primary outcome measure was occurrence of delirium within 72 hours after operation. The diagnosis of delirium was made using confusion assessment method for the intensive care unit questionnaire. Both administration of dopamine as a dichotomised variable and the total amount of dopamine per kg body-weight were included in two different logistic regression models. Delirium occurred in 18 (13.1%) patients. Age adjusted Mantel-Haenszel relative risk for delirium with receiving dopamine was 4.62. Relative risk was 2.37 (0.18 to 31.28, 95% CI, p=0.51) in total doses over 10mg whereas it was 3.55 (1.16 to 10.89 95% CI, p=0.02) in total doses over 30 mg per kg body-weight. Older age (p=0.03), dopamine administration (OR: 9.227 95% CI, 2.688-32.022, p<0.001) and the amount of dopamine administered (OR: 1.072, 95% CI, 1.032-1.115, p<0.001) were independent predictors for delirium 72 hours after surgery. Along with older age, dopamine infusion--even in low doses but more probably in higher doses--emerged as an independent risk factor for delirium in patients undergoing CABG. Further study is needed to confirm the validity of results presented.

Comparison of the efficacy of Neethling lumpy skin disease virus and x10RM65 sheep-pox live attenuated vaccines for the prevention of lumpy skin disease – The results of a randomized controlled field study

Lumpy skin disease (LSD) is a viral disease of cattle and buffalo, caused by a Capripox virus. A field study was performed during an LSD epidemic which occurred in 2012–2013 in Israel, in order to assess the efficacy of two commercial vaccines for protection against LSD. Fifteen dairy herds, vaccinated 2–5 months prior to study onset with a single dose of 102.5 TCID50 of RM65 attenuated sheep-pox vaccine, and not affected previously, were enrolled in the study. 4694 cows were randomized to be either vaccinated with a 103.5 TCID50/dose of RM65 vaccine (x10RM65) or with a same dose of an attenuated Neethling LSD virus vaccine. A case of LSD was defined as the appearance of at least 5 lesions typical to LSD and a severe case was defined if this sign was accompanied by either fever (>39.5°C) or/and a 20% reduction in milk production. Deep lesion biopsies and blood samples were collected from 64.5% of the cases in an attempt to detect DNA of LSD virus by PCR and to differentiate between the wild strain and the vaccine Neethling strain. Seventy-six cows were affected by LSD in 8 herds with an incidence of 0.3–5.7%. Mantel–Haenszel relative risk (RRMH) for LSD morbidity at least 15 days after vaccination in x10RM65 vs. Neethling was 2.635 (CI95%=1.44–4.82) and 11.2 (2.3–54.7) for severe morbidity. RRMH for laboratory confirmed cases was 4.28 (1.59–11.53). An incidence of 0.38% (9/2356) of Neethling associated disease was observed among Neethling vaccinated cows while no such disease occurred in x10RM65 vaccinated cows. We conclude that the Neethling vaccine is significantly more effective than x10RM65 in preventing LSD morbidity, though it might cause a low incidence of Neethling associated disease. No transmission of the Neethling strain to non-Neethling vaccinated cows was observed in this study.

Enteral Immunomodulatory Diet (Omega-3 Fatty Acid, γ-Linolenic Acid and Antioxidant Supplementation) for Acute Lung Injury and Acute Respiratory Distress Syndrome: An Updated Systematic Review and Meta-Analysis.

Enteral immunomodulatory nutrition is considered as a promising therapy for the treatment of acute lung injury and acute respiratory distress syndrome (ALI/ARDS). However, there are still some divergences, and it is unclear whether this treatment should be recommended for patients with ALI/ARDS. Therefore, we conducted this systematic review and meta-analysis to assess the efficacy and safety of an enteral immunomodulatory diet on the clinical outcomes of ALI/ARDS patients. Methods: We retrieved potentially relevant clinical trials though electronic databases. All trials of enteral immunomodulatory diet for ALI/ARDS were included. Analyses of the overall all-cause mortality, 28-day ventilator-free days and 28-day intensive care unit (ICU) free days were conducted. Results: In total six controlled trials were evaluated. The pooled results did not show a significant reduction in the risk of all-cause mortality (M-H RR (the overall Mantel-Haenszel relative risk), 0.81 (95% CI, 0.50–1.31); p = 0.38; 6 trials, n = 717) in ALI/ARDS patients treated with the immunomodulatory diet. This treatment also did not extend the ventilator-free days and ICU-free days. However, patients with high mortality might benefit from this treatment. Conclusions: The enteral immunomodulatory diet could not reduce the severity of the patients with ALI/ARDS. Whereas, for ALI/ARDS patients with high mortality, this treatment might reduce the all-cause mortality, but its use should be treated with discretion.

Catheter Ablation for Atrial Fibrillation in Heart Failure Patients: A Meta-Analysis of Randomized, Controlled Trials

ObjectivesThe objective of the study was to compare rate control versus atrial fibrillation (AF) catheter ablation strategies in patients with AF and heart failure (HF). BackgroundRhythm control with antiarrhythmic drugs (AADs) is not superior to rate control in patients with HF and AF, but AF ablation may be more successful at achieving rhythm control than are AADs. However, risks for both ablation and AADs are probably higher and success rates lower in patients with HF. MethodsWe conducted a meta-analysis of trials that randomized HF patients (left ventricular ejection fraction [LVEF] <50%) with AF to a rate control or AF catheter ablation strategy and reported changes in LVEF, quality of life, 6-min walk test, or peak oxygen consumption. Study quality and heterogeneity were assessed through the use of Jadad scores and Cochran’s Q statistics, respectively. Mantel-Haenszel relative risks and mean differences were calculated through the use of random effect models. ResultsFour trials (N = 224) met inclusion criteria; 82.5% (n = 185) had persistent AF. AF ablation was associated with an increase in LVEF (mean difference, 8.5%; 95% confidence interval [CI]: 6.4% to 10.7%; p < 0.001) compared with rate control. AF ablation was superior in improving quality of life by Minnesota Living With Heart Failure (MLWHF) questionnaire scores (mean difference, –11.9; 95% CI: –17.2 to 6.6; p < 0.001). Peak oxygen consumption and 6-min walk distance increased in AF ablation compared with rate-control patients (mean difference, 3.2; 95% CI: 1.1 to 5.3; p = 0.003; mean difference, 34.8; 95% CI: 2.9 to 66.7; p = 0.03, respectively). In the persistent AF subgroup, LVEF and MLWHF were significantly improved with AF ablation. Major adverse event rates (risk ratio: 1.3; 95% CI: 0.4 to 3.9; p = 0.64) were not significantly different. No significant heterogeneity was evident. ConclusionsIn patients with HF and AF, AF catheter ablation is superior to rate control in improving LVEF, quality of life, and functional capacity. Before accepting a rate-control strategy in HF patients with persistent or drug-refractory AF, consideration should be given to AF ablation.

Patients Receiving Prebiotics and Probiotics Before Liver Transplantation Develop Fewer Infections Than Controls: A Systematic Review and Meta-Analysis

Among patients who have received liver transplants, infections increase morbidity and mortality and prolong hospital stays. Administration of antibiotics and surgical trauma create intestinal barrier dysfunction and microbial imbalances that allow enteric bacteria to translocate to the blood. Probiotics are believed to prevent bacterial translocation by stabilizing the intestinal barrier and stimulating proliferation of the intestinal epithelium, mucus secretion, and motility. We performed a meta-analysis to determine the effects of probiotics on infections in patients receiving liver transplants. We searched PubMed and EMBASE for controlled trials that evaluated the effects of prebiotics and probiotics on infections in patients who underwent liver transplantation. Heterogeneity was analyzed by the Cochran Q statistic. Pooled Mantel-Haenszel relative risks were calculated with a fixed-effects model. We identified 4 controlled studies, comprising 246 participants (123 received probiotics, 123 served as controls), for inclusion in the meta-analysis. In these studies, the intervention groups received enteric nutrition and fiber (prebiotics) with probiotics, and the control groups received only enteric nutrition and fiber without probiotics. The infection rate was 7% in groups that received probiotics vs 35% in control groups (relative risk [RR], 0.21; 95% confidence interval [CI], 0.11-0.41; P= .001). The number needed to treat to prevent 1 infection was 3.6. In subgroup analyses, only 2% of subjects in the probiotic groups developed urinary tract infections, compared with 16% of controls (RR, 0.14; 95% CI, 0.04-0.47; P < .001); only 2% of subjects in the probiotic groups developed intra-abdominal infections, compared with 11% of controls (RR, 0.27; 95% CI, 0.09-0.78; P= .02). Subjects receiving probiotics also had shorter stays in the hospital than controls (mean difference, 1.41 d; P < .001), as well as in the intensive care unit (mean difference, 1.41 d; P < .001), and duration of antibiotic use (mean difference, 3.89 d; P < .001). There was no difference in mortality between groups (RR, 0.97; 95% CI,0.21-4.47). There was no significant heterogeneity among studies. Based on the meta-analysis, giving patients a combination of probiotics and prebiotics before, or on the day of, liver transplantation reduces the rate of infection after surgery. These agents also reduced the amount of time spent in the hospital or intensive care unit and the duration of antibiotic use.

Primary prophylaxis to prevent obstetric complications in asymptomatic women with antiphospholipid antibodies: a systematic review.

Obstetric complications are common in patients with antiphospholipid syndrome. However, the impact of antiphosholipid antibodies (aPL) in the pregnancy outcomes of asymptomatic aPL carriers is uncertain. The aim of this systematic review is to assess whether primary prophylaxis is beneficial to prevent obstetric complications during pregnancy in asymptomatic women positive for aPL who have no history of recurrent pregnancy loss or intrauterine fetal death. Studies evaluating the effect of prophylactic treatment versus no treatment in asymptomatic pregnant aPL carriers were identified in an electronic database search. Design, population and outcome homogeneity of studies was assessed and meta-analysis was performed. The pooled Mantel-Haenszel relative risk of specific pregnancy outcomes was obtained using random effects models. Heterogeneity was measured with the I(2) statistic. All analyses were conducted using Review Manager 5.3. Data from five studies involving 154 pregnancies were included and three studies were meta-analysed. The risk ratio and 95% confidence interval (CI) of live birth rates, preterm birth, low birth weight and overall pregnancy complications in treated and untreated pregnancies were 1.14 (0.18-7.31); 1.71 (0.32-8.98); 0.98 (0.07-13.54) and 2.15 (0.63-7.33),respectively. Results from the meta-analysis revealed that prophylactic treatment with aspirin is not superior to placebo to prevent pregnancy complications in asymptomatic aPL carriers. This systematic review did not find evidence of the superiority of prophylactic treatment with aspirin compared to placebo or usual care to prevent unfavourable obstetric outcomes in otherwise healthy women with aPL during the first pregnancy.

Bilateral Versus Unilateral Stenting for Malignant Hilar Obstruction: A Meta-Analysis

Introduction: Malignant hilar biliary obstruction is a dreaded complication of various types of cancers including pancreatic cancer, cholangiocarcinoma, gallbladder carcinoma, and hepatocellular carcinoma. Palliative endoscopic biliary drainage plays an important role in resolving jaundice and cholangitis. The optimal stenting techniques remain to be definitely decided and the necessity to drain both liver lobes in hilar tumors remains uncertain. We report a meta-analysis of studies comparing unilateral versus bilateral stenting for malignant hilar biliary obstruction. Methods: We searched Pubmed, Medline, Embase, and Cochrane for controlled studies that compared unilateral versus bilateral stenting for malignant hilar biliary obstruction. Studies were excluded if they were non-controlled or included patients with non-malignant and non-hilar obstruction. Studies selection and data extraction were done by 2 reviewers. Disagreement was solved by a third reviewer. The quality for each included study was assessed by Consort system. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. Mantel Haenszel relative risk and mean difference were calculated with random effect for outcomes with significant heterogeneity; for all others the fixed effect method was used. Results: Seven studies met the inclusion criteria with a total of 634 patients. After the initial placement of stents, there was no significant difference in the occlusion rate between unilateral and bilateral stenting (odds ratio [OR]: 1.47; confidence interval [CI]: 0.68-3.19). There was moderate heterogeneity among results reported in the studies but the clinical characteristics of the patients and the method of outcome assessment were similar and did not change our inferences. A sensitivity analysis that sorted studies based on the use of metal versus plastic stents found no statistically significant difference in the occlusion rate. Therapeutic failure, defined as the lack of resolution of symptoms post stenting, was noted in 17% with unilateral stenting compared to 22% with bilateral stenting without a statistically significant difference (OR: 0.63; CI: 0.31-1.28). Bilateral stenting was associated with higher incidence of post-stenting cholangitis 22% compared to unilateral stenting 12% (OR 0.52; 95% CI 0.28-0.96). There was no evidence of publication bias among the reported outcomes. Conclusion: When compared to bilateral stenting, unilateral stenting performed for patients with malignant hilar strictures is associated with lower incidence of post-stenting cholangitis, similar success in symptom resolution and no difference in the post stenting occlusion rate. Therefore, in the majority of patients with malignant biliary obstruction, unilateral stenting provides similar outcome to bilateral stenting.

Early TIPS versus Endoscopic Treatment in Cirrhotics with Variceal Bleeding: A Meta-Analysis: Presidential Poster

Purpose: In cirrhotics, acute variceal hemorrhage is associated with high morbidity and mortality. The most recent (2007) practice guideline co-developed by the American College of Gastroenterology and the American Association for the Study of Liver Disease recommends endoscopic/pharmacologic treatment for prevention of recurrent hemorrhage. Transjugular intrahepatic portosystemic shunt (TIPS) is not advocated, except for endoscopic/pharmacologic failures. Several small studies suggest higher success in prevention of re-bleeding, as well as improved survival without excess hepatic encephalopathy in patients who receive TIPS within the first week after bleeding. We report a meta-analysis of randomized controlled trials (RCTs) of early TIPS vs. endoscopic/pharmacologic treatment. Methods: We searched Pubmed, Medline, Embase, and Cochrane database for studies that compared endoscopic therapy to TIPS within the first week after acute variceal bleeding. We only included randomized control trials (RCTs). Studies selection and data extraction were done by two reviewers. The quality of trials was assessed using methodology obtained from The Cochrane Reviewers' Handbook. Heterogeneity of the studies was analyzed by Cochran's Q statistics. Mantel Haenszel relative risk was calculated with fixed effect model to combine studies. Results: Thirty-five studies were evaluated; 26 were rejected because of different study end-points, no control group, non-randomization, or TIPS performed more than a week post-variceal bleeding. This left nine trials, which included 563 cirrhotic patients with Child-Pugh class A, B, and C. Early TIPS was associated with a significant risk reduction in the one-year incidence of variceal re-bleeding (Relative risk [RR] 0.28; 95% confidence interval [CI] 0.20-0.39; P <0.001). Significantly lower one-year mortality was observed in patients who underwent early TIPS, compared to endoscopic therapy (RR, 0.70; 95% CI 0.50-1.00; P= 0.05). No significant difference in the incidence of hepatic encephalopathy was observed between the two treatment groups. (RR 1.06; 95% CI 0.63; 1.76; P= 0.83). However, there was moderate heterogeneity among the hepatic encephalopathy results reported in the studies (I2= 60%). Conclusion: TIPS performed within a week of major esophageal variceal hemorrhage is superior to pharmacologic/endoscopic treatment in reducing subsequent bleeding. It is associated with superior one-year survival, and does not result in higher degrees of encephalopathy. Clinical practice guideline recommendations may need to be modified to reflect clear and compelling new data, reflecting the value of early TIPS in appropriately selected patients.

Safety of formoterol in asthma clinical trials: an update

Use of long-acting β-agonists (LABAs) in asthma remains controversial, and large safety trials are in progress. We have previously reported safety outcomes with formoterol in 117 AstraZeneca asthma trials (78,339 patients, 92% using inhaled corticosteroids) completed by December 2006, and have now added 32 trials with formoterol (26,124 patients, 100% using inhaled corticosteroids) completed by December 2011. The primary dataset of 79 randomised controlled trials includes 94,684 patients, 67,380 of whom were exposed to formoterol, while the complete dataset comprises 149 trials and 104,463 patients. There were no new asthma-related deaths in the expanded primary dataset, with eight asthma-related deaths among formoterol-randomised patients and two among non-LABA-randomised patients (relative risk 1.13, 95% CI 0.23-10.9), and 15 versus nine cardiac-related deaths (relative risk 0.47, 95% CI 0.19-1.22). Nonfatal asthma-related serious adverse events were significantly reduced with formoterol (relative risk 0.63, 95% CI 0.53-0.75), as were discontinuations due to adverse events. Examining 40 trials with direct formoterol versus non-LABA comparisons, Mantel-Haenszel relative risk for asthma-related death was 2.75 (95% CI 0.52-14.4) and for serious adverse events 0.83 (95% CI 0.68-1.02). We conclude that this enlarged dataset indicates no increased risk of asthma-related deaths among patients exposed to formoterol compared with non-LABA treatments, although the wide confidence interval precludes certainty.

Efficacy of Emergency Department-Initiated Tobacco Control--Systematic Review and Meta-analysis of Randomized Controlled Trials

Systematic review and meta-analysis of randomized controlled trials evaluating the efficacy of emergency department-initiated tobacco control (ETC). Literature search in 7 databases and gray literature sources. Point prevalence tobacco abstinence at 1-, 3-, 6-, and/or 12-month follow-up was abstracted from each study. The proportionate effect (relative risk) of ETC on tobacco abstinence was calculated separately for each study and follow-up time and pooled, at different follow-up times, by Mantel-Haenszel relative risks. The effects of ETC on combined point prevalence tobacco abstinence across all follow-up times were calculated using generalized linear mixed models. Seven studies with overall 1,986 participants were included. The strongest effect of ETC on point prevalence tobacco abstinence was found at 1 month: Relative risk (RR) = 1.47 (3 studies) (95% confidence interval [CI]: 1.06-2.06), while the effect at 3, 6, and 12 months was RR = 1.24 (6 studies) (95% CI: 0.93-1.65); 1.13 (5 studies) (95% CI: 0.86-1.49); and 1.25 (1 study) (95% CI: 0.91-1.72). The benefit on combined point prevalence tobacco abstinence was RR = 1.33 (7 studies) (95% CI: 0.96-1.83), p = .08; with RR = 1.33 (95% CI: 0.92-1.92), p = .10, for the 5 studies combining motivational interviewing and booster phone calls. ETC combining motivational interviewing and booster phone calls showed a trend toward increased episodically measured tobacco abstinence up to 12 months. More methodologically rigorous trials are needed to effectively evaluate the impact of ETC.