Meta-analysis Of Prior Studies Research Articles

Time savings associated with lights and siren use by ambulances: a scoping review

PurposeMany studies have suggested the use of lights and siren by ambulances has the potential to save time, which can be clinically beneficial for certain patients. However, other studies suggest lights and siren use increases an emergency vehicle’s crash risk. In the absence of a comprehensive multi-center trial, a meta-analysis of prior studies can offer insight into this topic. Thus, we conducted a meta-analysis to evaluate the extent to which the use of lights and siren decreases response and transport times nationally.Design/methodology/approachWe searched PUBMED, EBSCO Academic Search Ultimate, Google Scholar and the premier EMS journals for potential articles identifying time savings associated with lights and siren use and augmented the search results with other relevant studies. Studies were included if they compared time involved with driving a given route using lights and siren with the time required to drive the same route without lights and siren.FindingsNine studies were included. Across these studies, lights and siren use was associated with a weighted average time savings of 159 s or 2.7 min (95% CI: 100–219 s, p < 0.0001).Originality/valueOur analysis of the previously-published literature reveals that lights and siren use is associated with time savings across geographies; however, the precise difference may only be beneficial to certain patients. Most studies are small and relatively dated, so individual EMS systems ought to study their specific geography to inform policies that maximize the beneficial impact of lights and siren use and minimize unnecessary risk.

A Systematic Survey of Just-in-Time Software Defect Prediction

Recent years have experienced sustained focus in research on software defect prediction that aims to predict the likelihood of software defects. Moreover, with the increased interest in continuous deployment, a variant of software defect prediction called Just-in-Time Software Defect Prediction (JIT-SDP) focuses on predicting whether each incremental software change is defective. JIT-SDP is unique in that it consists of two interconnected data streams, one consisting of the arrivals of software changes stemming from design and implementation, and the other the (defective or clean) labels of software changes resulting from quality assurance processes. We present a systematic survey of 67 JIT-SDP studies with the objective to help researchers advance the state of the art in JIT-SDP and to help practitioners become familiar with recent progress. We summarize best practices in each phase of the JIT-SDP workflow, carry out a meta-analysis of prior studies, and suggest future research directions. Our meta-analysis of JIT-SDP studies indicates, among other findings, that the predictive performance correlates with change defect ratio, suggesting that JIT-SDP is most performant in projects that experience relatively high defect ratios. Future research directions for JIT-SDP include situating each technique into its application domain, reliability-aware JIT-SDP, and user-centered JIT-SDP.

EPID-06. QUANTIFYING THE POTENTIAL PUBLIC HEALTH IMPACT OF VARICELLA ZOSTER VIRUS (VZV) VACCINATION ON GLIOMA INCIDENCE

Abstract BACKGROUND Varicella zoster virus (VZV) is a neurotropic a-herpesvirus that causes chickenpox and establishes latency in the dorsal root ganglion. Live attenuated VZV vaccine was approved for use in 1995, with the CDC estimating 95% of teens had been vaccinated in 2014. Prior epidemiological literature suggests an association between VZV infection and glioma risk. METHODS We conducted a systematic review and meta-analysis of prior studies on the association between VZV infection and glioma risk. We also identified genetic instruments for VZV infection from prior GWAS and tested these for association with glioma risk in TCGA and GliomaScan (2244 cases, 4914 controls). RESULTS In six previous studies, individuals with positive chickenpox history or anti-VZV IgG seropositivity had 1.8-fold lower odds of glioma (ORmeta=0.55, 95%Cl=0.39–0.77), with similar effects by grade. GWAS hits for personal history of chickenpox (HLA-A Gly107 and rs9266089) and shingles (HLA-AArg97, HLA-DRB1 PheSerHis13, rs2523591, rs41316748 and rs7047299) were not associated with glioma risk, nor were polygenic scores (P &amp;gt;0.05). DISCUSSION Prior VZV infection is associated with reduced glioma risk and, based on analysis of genetic instruments, this appears to be an acquired protection caused by VZV infection rather than innate immunologic differences. VZV infection in known to elicit a broader antibody response than vaccination, but it is unknown whether VZV vaccination provides comparable protection against glioma. Because 89% of U.S. adults have had chickenpox, the “prevented fraction” of glioma due to chickenpox is ~29% of annual incidence. If VZV vaccination confers an equivalent 1.8-fold reduction in glioma risk, this prevented fraction could increase to 32%. However, if VZV vaccination is less protective, it could decrease to just 2%. This potentially drastic increase in glioma incidence in coming decades merits mechanistic studies comparing the neuro-immunologic consequences of VZV vaccination versus chickenpox infection and warrants early public health attention.

Sample size calculations for noninferiority trials for time-to-event data using the concept of proportional time

Noninferiority trials intend to show that a new treatment is ‘not worse' than a standard-of-care active control and can be used as an alternative when it is likely to cause fewer side effects compared to the active control. In the case of time-to-event endpoints, existing methods of sample size calculation are done either assuming proportional hazards between the two study arms, or assuming exponentially distributed lifetimes. In scenarios where these assumptions are not true, there are few reliable methods for calculating the sample sizes for a time-to-event noninferiority trial. Additionally, the choice of the non-inferiority margin is obtained either from a meta-analysis of prior studies, or strongly justifiable ‘expert opinion', or from a ‘well conducted' definitive large-sample study. Thus, when historical data do not support the traditional assumptions, it would not be appropriate to use these methods to design a noninferiority trial. For such scenarios, an alternate method of sample size calculation based on the assumption of Proportional Time is proposed. This method utilizes the generalized gamma ratio distribution to perform the sample size calculations. A practical example is discussed, followed by insights on choice of the non-inferiority margin, and the indirect testing of superiority of treatment compared to placebo.

Abstract 16300: Efficacy and Safety of Anticoagulation Following Bioprosthetic Aortic Valve Replacement: A Meta-analysis

Background: The American College of Cardiology (ACC) guidelines recommend three months of anticoagulation (AC) after replacement of the aortic valve with a bioprosthesis (BP). However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether AC in the setting of a new BP was associated with improved outcomes and/or greater risk of bleeding. Methods: We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed AC with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks (TIA) and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa scale and random effects was used to pool the data from the available studies. I2 testing was done to assess the heterogeneity of the included studies. Results: After screening through 170 papers, a total of 13 studies (cases=6431, controls=18210) were included in the final analyses. Use of warfarin use was associated with a significantly increased risk of overall bleeding (OR= 1.96, 95% CI 1.25-3.08, P&lt;0.0001) or bleeding risk at 3 months (OR= 1.92, 95% CI 1.10-3.34), P&lt;0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke or TIA) at 3 months, no significant difference was seen with warfarin (OR= 1.13, 95% CI 0.82-1.56, P=0.67). Moreover AC was also not shown to improve outcomes at time interval &gt;3 months (OR= 1.12, 95% CI 0.80-1.58, P=0.79). Conclusion: Contrary to the current guidelines, a meta-analysis of prior studies suggests that AC in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable impact on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.

Abstract WP210: Prothrombin G20210A Mutation and Ischemic Stroke Risk in European Ancestry: The Genetics of Early Onset Stroke Study and Meta-Analysis of 2304 Young-Onset Stroke Cases

Background: Although the prothrombin G20210A mutation has been implicated in increased risk for venous thrombosis, its role in arterial ischemic stroke is unclear, particularly among young adults. To address this issue, we examined the association between prothrombin G20210A and ischemic stroke in Caucasian participants of the Genetics of Early Onset Stroke (GEOS) Study (n=396 cases) and also performed a meta-analysis of 17 case-control studies (n=2304 cases) examining the effect of prothrombin G20210A on ischemic stroke risk in young adults (&lt;55 years). Methods: A population-based case-control study identified 396 cases of women and men 15 to 49 years of age of European ancestry with first-ever ischemic stroke and 426 matched controls. Logistic regression was used to calculate odds ratios for the entire population and for subgroups stratified by gender, oral contraceptive use, smoking status, and age category. Results: In the GEOS study, the prothrombin G20210A mutation was associated with a large but non-significant increase in ischemic stroke risk (OR=2.4, 95% CI: 0.9-6.5, p=0.08). However, among adults aged 15-42 (younger than the median age), cases were significantly more likely to have the prothrombin mutation than controls (OR=5.9, 95% CI: 1.1-28.5, p=0.03), whereas adults ages 42-49 were not (OR 1.1, 95% CI 0.3-4.4, p=0.94). In the meta-analysis of prior studies, the prothrombin G20210A mutation was significantly associated with stroke risk (OR 1.4, 95% CI: 1.1-1.9, p=0.02) with these results increasing in precision with addition of the GEOS results (OR=1.5, 95% CI: 1.1-2.0, p=0.005). Conclusion: The prothrombin mutation is associated with ischemic stroke in young adults. The GEOS data suggests that, within the young adult age range, the prothrombin G20210A mutation may have an even stronger association among those with the earliest onset strokes. The finding of a stronger association in the ‘younger’ young adult population requires replication in other studies.

Cancer incidence in California flight attendants (United States).

To examine unusual exposure opportunities to flight crews from chemicals, cosmic radiation, and electric and magnetic fields. This project evaluated the incidence of cancers of the breast and other sites among Association of Flight Attendants (AFA) members residing in California. AFA membership files were matched to California's statewide cancer registry to identify a total of 129 newly diagnosed invasive cancers among AFA members with California residential histories between 1988 and 1995. Compared to the general population, female breast cancer incidence was over 30% higher than expected, and malignant melanoma incidence was roughly twice that expected. Both of these are cancers that are associated with higher socioeconomic status and have been suggestively associated with various sources of radiation. Consistent with the results from Nordic studies of cabin crews and a recent meta-analysis of prior studies, these data suggest that follow-up investigations should focus on the potential relative contribution of workplace exposures and lifestyle characteristics to the higher rates of disease for these two cancers.