Abstract Purpose The goal of this review was to synthesize existing evidence regarding outcomes (mortality) for patients who present to the emergency department, are administered antibiotics ...immediately (within 1 hour) or later (>1 hour), and are diagnosed with sepsis. Methods A search of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL, using the MeSH descriptors “sepsis,” “systemic inflammatory response syndrome,” “mortality,” “emergency,” and “antibiotics,” was performed to identify studies reporting time to antibiotic administration and mortality outcome in patients with sepsis. The included studies (published in English between 1990 and 2016) listed patient mortality based on time to antibiotic administration. Studies were evaluated for methodologic quality, and data were extracted by using a data extraction form tailored to this study. From an initial pool of 582 potentially relevant studies, 11 studies met our inclusion criteria, 10 of which had quantitative data for meta-analysis. Three different models (a random effects model, a bias-adjusted quality-effects synthetic bias model, and an inverse variance heterogeneity model) were used to perform the meta-analysis. Findings The pooled results suggest a significant 33% reduction in mortality odds for immediate (within 1 hour) compared with later (>1 hour) antibiotic administration (OR, 0.67 95% CI, 0.59–0.75) in patients with sepsis. Implications Immediate antibiotic administration (<1 hour) seemed to reduce patient mortality. There was some minor negative asymmetry suggesting that the evidence may be biased toward the direction of effect. Nevertheless, this study provides strong evidence for early, comprehensive, sepsis management in the emergency department.
Abstract Background Electroconvulsive therapy (ECT) guidelines, across various regulatory bodies, lack consensus as to the optimal frequency of treatment for individual patients. Some authors ...postulate that twice weekly ECT may have a similar efficacy to thrice weekly, and may have a lower risk of adverse cognitive outcomes. We did a systematic review and a meta-analysis to assess the strength of associations between ECT frequency and depression scores, duration of treatment, number of ECTs, and remission rates. Methods We searched on Medline, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials (to December 2009), and searched reports to identify comparative studies of frequency of ECT. We did both random-effects (RE) and quality effect (QE) meta-analyses to determine the risk of various outcomes associated with lesser frequency as compared to the thrice weekly frequency. Results We analysed 8 datasets (7 articles), including 214 subjects. Twice-weekly frequency of ECT was associated with a similar change in depression score (QE model SMD - 0.11 - 0.55–0.33 and RE model SMD - 0.17 - 0.77–0.43) as compared to thrice weekly ECT. The number of real ECT's trended towards fewer in the twice weekly group. There was a statistically significant longer duration of treatment with a twice weekly protocol (QE model 6.48 days 4.99–7.97 and RE model 4.78 days 0.74–8.82). There was a statistically significant greater efficacy for thrice weekly ECT compared to once weekly ECT (QE model SMD 1.25 - 0.62–1.9 and RE model SMD 1.31 0.6–2.02). Conclusions Twice weekly ECT is associated with similar efficacy to thrice weekly ECT, may require fewer treatments and may be associated with longer treatment duration when compared to thrice weekly. These epidemiological observations support the routine use of twice weekly ECT in acute courses, though choice of frequency should take into account individual patient factors. These observations have implications for resource utilisation e.g. costs of duration of admission vs cost of provision of ECT, as well as issues of access to inpatient beds and anaesthetist time.
Abstract
We report on sensitive dual-frequency (1.7 and 5 GHz) European very long baseline interferometry Network observations of the central region of nine Seyfert galaxies. These sources are among ...the faintest and least luminous members of a complete sample of nearby (d < 22 Mpc) low-luminosity active galactic nuclei. We detect radio emission on milliarcsecond scale in the nuclei of four galaxies, while for the other five sources we set an upper limit of <∼ 100 μJy. In three sources, namely NGC 3227, NGC 3982 and NGC 4138, radio emission is detected at both 1.7 and 5 GHz and it is resolved in two or more components. We describe the structural and spectral properties of these features; we find that in each of these three nuclei there is one component with high brightness temperature (typically T
B > 107.5 K) and flat/intermediate spectral index (0.3 ≤ α ≤ 0.6, S(ν) ∼ ν−α), accompanied by secondary steep spectrum extended components. In these cases, non-thermal emission from jets or outflows is thus the most natural explanation. A faint feature is detected in NGC 4477 at 5 GHz; keeping in mind the modest significance of this detection (∼5 σ), we propose the hot corona as the origin of non-thermal emission, on the basis of the unrealistic magnetic field values required by synchrotron self-absorption. Finally, the five non-detected nuclei remain elusive and further observations on intermediate scales will be necessary to investigate their nature.
We report our intensive, high angular resolution radio monitoring observations of the jet in M 87 with the VLBI Exploration of Radio Astrometry (VERA) and the European VLBI Network (EVN) from 2011 ...February to 2012 October, together with contemporaneous high-energy (100 MeV < E < 100 GeV) gamma -ray light curves obtained by the Fermi Large Area Telescope. We detected a remarkable (up to ~70%) increase of the radio flux density from the unresolved jetbase (radio core) with VERA at 22 and 43 GHz coincident with the VHE activity. These results in the radio bands strongly suggest that the VHE gamma -ray activity in 2012 originates in the jet base within 0.03 pc or 56 Schwarzschild radii (the VERA spatial resolution of 0.4 mas at 43 GHz) from the central supermassive black hole. This indicates that a new radio-emitting component was created near the black hole in the period of the VHE event, and then propagated outward with progressively decreasing synchrotron opacity.
Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative evidence is required to justify ...large-scale deworming programmes. A recent Cochrane systematic review, which influences Global Burden of Disease (GBD) estimates for STH, has again called into question the evidence for deworming benefit on morbidity due to STH. In this narrative review, we investigate in detail what the shortfalls in evidence are.
We systematically reviewed recent literature that used direct measures to investigate morbidity from STH and we critically appraised systematic reviews, particularly the most recent Cochrane systematic review investigating deworming impact on morbidity. We included six systematic reviews and meta-analyses, 36 literature reviews, 44 experimental or observational studies, and five case series. We highlight where evidence is insufficient and where research needs to be directed to strengthen morbidity evidence, ideally to prove benefits of deworming.
Overall, the Cochrane systematic review and recent studies indicate major shortfalls in evidence for direct morbidity. However, it is questionable whether the systematic review methodology should be applied to STH due to heterogeneity of the prevalence of different species in each setting. Urgent investment in studies powered to detect direct morbidity effects due to STH is required.
An association between type 2 diabetes mellitus (DM) and cancer has long been postulated, but the biological mechanism responsible for this association has not been defined. In part one of this ...review, we discussed the epidemiological evidence for increased risk of cancer, decreased cancer survival, and decreased rates of cancer screening in diabetic patients. Here we review the risk factors shared by cancer and DM and how DM medications play a role in altering cancer risk. Hyperinsulinemia stands out as a major factor contributing to the association between DM and cancer, and modulation of circulating insulin levels by DM medications appears to play an important role in altering cancer risk. Drugs that increase circulating insulin, including exogenous insulin, insulin analogs, and insulin secretagogues, are generally associated with an increased cancer risk. In contrast, drugs that regulate insulin signaling without increasing levels, especially metformin, appear to be associated with a decreased cancer risk. In addition to hyperinsulinemia, the effect of DM medications on other shared risk factors including hyperglycemia, obesity, and oxidative stress as well as demographic factors that may influence the use of certain DM drugs in different populations are described. Further elucidation of the mechanisms behind the association between DM, cancer, and the role of DM medications in modulating cancer risk may aid in the development of better prevention and treatment options for both DM and cancer. Additionally, incorporation of DM medication use into cancer prediction models may lead to the development of improved risk assessment tools for diabetic patients.
Dose-response meta-analysis has been widely employed in evidence-based decision-making. Currently, the most popular approach is the one or two-stage generalized least squares for trend model. This ...approach however has some drawbacks, and therefore, we compare the latter with a one-stage robust error meta-regression (REMR) model, based on inverse variance weighted least squares regression and cluster robust error variances for dealing with the synthesis of correlated dose-response data from different studies.
We apply both methods to three examples (alcohol and lung cancer, alcohol and colorectal cancer, and BMI and renal cancer). The analysis of the three datasets reveals that the one-stage REMR approach may result in better error estimation and a better visual fit to the data than the generalized least squares approach with the added benefit of not needing to impute covariances from the data.
The one-stage REMR approach is easily executed in Stata with codes given in this article. We therefore recommend that REMR models be considered for dose-response meta-analysis and suggest further comparison of these two methods in future studies to conclusively determine the benefits and pitfalls of each.
Detection of publication and related biases remains suboptimal and threatens the validity and interpretation of meta-analytical findings. When bias is present, it usually differentially affects small ...and large studies manifesting as an association between precision and effect size and therefore visual asymmetry of conventional funnel plots. This asymmetry can be quantified and Egger's regression is, by far, the most widely used statistical measure for quantifying funnel plot asymmetry. However, concerns have been raised about both the visual appearance of funnel plots and the sensitivity of Egger's regression to detect such asymmetry, particularly when the number of studies is small. In this article, we propose a new graphical method, the Doi plot, to visualize asymmetry and also a new measure, the LFK index, to detect and quantify asymmetry of study effects in Doi plots. We demonstrate that the visual representation of asymmetry was better for the Doi plot when compared with the funnel plot. We also show that the diagnostic accuracy of the LFK index in discriminating between asymmetry due to simulated publication bias versus chance or no asymmetry was also better with the LFK index which had areas under the receiver operating characteristic curve of 0.74-0.88 with simulations of meta-analyses with five, 10, 15, and 20 studies. The Egger's regression result had lower areas under the receiver operating characteristic curve values of 0.58-0.75 across the same simulations. The LFK index also had a higher sensitivity (71.3-72.1%) than the Egger's regression result (18.5-43.0%). We conclude that the methods proposed in this article can markedly improve the ability of researchers to detect bias in meta-analysis.
Summary
A genetic variant of the killer immunoglobulin‐like receptor 3DL1 (KIR3DL1) has been found in patients with systemic lupus erythematosus (SLE). Herein, we investigated the presence of ...autoantibodies to KIR3DL1 in a cohort of patients with SLE. We tested sera from 28 patients with SLE, 11 patients with rheumatoid arthritis (RA) and 17 healthy control subjects for anti‐KIR3DL1 activity by an enzyme‐linked immunosorbent assay (ELISA) using recombinant KIR3DL1‐enhanced green fluorescent protein (EGFP) and EGFP proteins. Anti‐KIR3DL1 antibodies were detected in 22 (79%) of the 28 patients with SLE, whereas they were present in only three (27%) of the 11 patients with RA examined. Notably, 10 (91%) of the 11 samples from patients with SLE prior to therapy had anti‐KIR3DL1 antibodies. None of the samples from healthy donors were positive for the antibodies. Here, we report the presence of anti‐KIR3DL1 antibodies in the sera of patients with SLE for the first time. Anti‐KIR3DL1 autoantibodies may be involved in the pathogenesis of autoimmune diseases.
Autoantibodies to KIR3DL1 are present in the sera of patients with SLE, which could be a applied as a novel diagnostic marker of SLE.
In order to examine the prevalence of overweight and obesity in childhood within the Indian subcontinent, a meta‐analysis of studies was conducted. Within the data sets analyzed, six homogeneous ...statistical subgroups were observed and three levels of prevalence were discernible (low, intermediate, and high). The pooled estimates of the prevalence of overweight and obesity in children were 2% (95% confidence interval CI, 2–3%) to 6% (95% CI, 6–7%) for the low‐prevalence group, 11% (95% CI, 11–12%) to 18% (95% CI, 17–18%) for the intermediate‐prevalence group, and 23% (95% CI, 22–24%) to 36% (95% CI, 34–37%) for the high‐prevalence group. Data on subjects in the low‐prevalence group were obtained from national‐level data and from data sets in which urban and rural subjects were combined. Neither the intermediate‐ nor the high‐prevalence category contained any data from the rural or national level. The intermediate group largely included urban children, whereas the high‐prevalence group generally included affluent children within major urban centers. Most of the data sets reported the prevalence of overweight and obesity among children in the 10−18‐year age range. The prevalence of overweight and obesity was higher among boys than girls, and had increased among urban dwellers during the last decade.
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