Systematic differences between Cochrane and non-Cochrane meta-analyses on the same topic: a matched pair analysis

BACKGROUND: Meta-analyses conducted via the Cochrane Collaboration adhere to strict methodological and reporting standards aiming to minimize bias, maximize transparency/reproducibility, and improve the accuracy of summarized data. Whether this results in differences in the results reported by meta-analyses on the same topic conducted outside the Cochrane Collaboration is an open question. METHODS: We conducted a matched-pair analysis with individual meta-analyses as the unit of analysis, comparing Cochrane and non-Cochrane reviews. Using meta-analyses from the cardiovascular literature, we identified pairs that matched on intervention and outcome. The pairs were contrasted in terms of how frequently results disagreed between the Cochrane and non-Cochrane reviews, whether effect sizes and statistical precision differed systematically, and how these differences related to the frequency of secondary citations of those reviews. RESULTS: Our search yielded 40 matched pairs of reviews. The two sets were similar in terms of which was first to publication, how many studies were included, and average sample sizes. The paired reviews included a total of 344 individual clinical trials: 111 (32.3%) studies were included only in a Cochrane review, 104 (30.2%) only in a non-Cochrane review, and 129 (37.5%) in both. Stated another way, 62.5% of studies were only included in one or the other meta-analytic literature. Overall, 37.5% of pairs had discrepant results. The most common involved shifts in the width of 95% confidence intervals that would yield a different statistical interpretation of the significance of results (7 pairs). Additionally, 20% differed in the direction of the summary effect size (5 pairs) or reported greater than a 2-fold difference in its magnitude (3 pairs). Non-Cochrane reviews reported significantly higher effect sizes (P < 0.001) and lower precision (P < 0.001) than matched Cochrane reviews. Reviews reporting an effect size at least 2-fold greater than their matched pair were cited more frequently. CONCLUSIONS: Though results between topic-matched Cochrane and non-Cochrane reviews were quite similar, discrepant results were frequent, and the overlap of included studies was surprisingly low. Non-Cochrane reviews report larger effect sizes with lower precision than Cochrane reviews, indicating systematic differences, likely reflective of methodology, between the two types of reviews that could generate different interpretations of the interventions under question

Systematic differences between Cochrane and non-Cochrane meta-analyses on the same topic: a matched pair analysis

BACKGROUND: Meta-analyses conducted via the Cochrane Collaboration adhere to strict methodological and reporting standards aiming to minimize bias, maximize transparency/reproducibility, and improve the accuracy of summarized data. Whether this results in differences in the results reported by meta-analyses on the same topic conducted outside the Cochrane Collaboration is an open question. METHODS: We conducted a matched-pair analysis with individual meta-analyses as the unit of analysis, comparing Cochrane and non-Cochrane reviews. Using meta-analyses from the cardiovascular literature, we identified pairs that matched on intervention and outcome. The pairs were contrasted in terms of how frequently results disagreed between the Cochrane and non-Cochrane reviews, whether effect sizes and statistical precision differed systematically, and how these differences related to the frequency of secondary citations of those reviews. RESULTS: Our search yielded 40 matched pairs of reviews. The two sets were similar in terms of which was first to publication, how many studies were included, and average sample sizes. The paired reviews included a total of 344 individual clinical trials: 111 (32.3%) studies were included only in a Cochrane review, 104 (30.2%) only in a non-Cochrane review, and 129 (37.5%) in both. Stated another way, 62.5% of studies were only included in one or the other meta-analytic literature. Overall, 37.5% of pairs had discrepant results. The most common involved shifts in the width of 95% confidence intervals that would yield a different statistical interpretation of the significance of results (7 pairs). Additionally, 20% differed in the direction of the summary effect size (5 pairs) or reported greater than a 2-fold difference in its magnitude (3 pairs). Non-Cochrane reviews reported significantly higher effect sizes (P < 0.001) and lower precision (P < 0.001) than matched Cochrane reviews. Reviews reporting an effect size at least 2-fold greater than their matched pair were cited more frequently. CONCLUSIONS: Though results between topic-matched Cochrane and non-Cochrane reviews were quite similar, discrepant results were frequent, and the overlap of included studies was surprisingly low. Non-Cochrane reviews report larger effect sizes with lower precision than Cochrane reviews, indicating systematic differences, likely reflective of methodology, between the two types of reviews that could generate different interpretations of the interventions under question

Comparative analysis of the growth and biological activity of a respiratory and atheroma isolate of reveals strain-dependent differences in inflammatory activity and innate immune evasion

En el año 2010, como contraparte de los festejos del centenario de la Revolución mexicana, el poeta Jorge Esquinca invitó a treinta y cuatro poetas a participar en una antología titulada País de sombra y fuego. La relevancia de este ejercicio poético proviene de la pregunta que lo estructura: ¿Existe todavía en el vocablo Patria un núcleo generador de significado?A través del análisis de estos poemas y de los tópicos que prevalecen en ellos, es posible conocer el doloroso México que perciben los poetas mexicanos y la forma en que la poesía mexicana contemporánea del siglo XXI lo nombra.In 2010, as a counterpart to the festivities related to the 100th anniversary of the Mexican Revolution, the poet Jorge Esquinica invited thirty-four poets to participate in an anthology titled País de sombra y fuego. The relevance of this poetic exercise stems from the very question which gives it structure. Is the word Motherland still relevant in today's world?Through an analysis of these poems and the themes that prevail in them, it is possible to discover how these anthologized Mexican poets view their country nowadays and how they address its main issues.A l’any 2010, com a contrapart dels festejos del centenari de la Revolució mexicana, el poeta Jorge Esquinca va convidar trenta-quatre poetes a participar en una antologia titulada País de sombra y fuego. La rellevància d’aquest exercici poètic prové de la pregunta que l’estructura: existeix encara en el terme Pàtria un nucli generador de significat? A través de l’anàlisi d’aquests poemes i dels tòpics que prevalen en ells, és possible conèixer el dolorós Mèxic que perceben els poetes mexicans i la forma en què la poesia mexicana contamporània del segle XXI ho nombra

The Association of Obesity with Walking Independent of Knee Pain: The Multicenter Osteoarthritis Study

Practice guidelines recommend addressing obesity for people with knee OA, however, the association of obesity with walking independent of pain is not known. We investigated this association within the Multicenter Osteoarthritis Study, a cohort of older adults who have or are at high risk of knee OA. Subjects wore a StepWatch to record steps taken over 7 days. We measured knee pain from a visual analogue scale and obesity by BMI. We examined the association of obesity with walking using linear regression adjusting for pain and covariates. Of 1788 subjects, the mean steps/day taken was 8872.9 ± 3543.4. Subjects with a BMI ≥35 took 3355 fewer steps per day independent of knee pain compared with those with a BMI ≤25 (95% CI −3899, −2811). BMI accounted for 9.7% of the variability of walking while knee pain accounted for 2.9%. BMI was associated with walking independent of knee pain

Randomized clinical trials to identify optimal antibiotic treatment duration

Background Antibiotic resistance is a major barrier to the continued success of antibiotic treatment. Such resistance is often generated by overly long durations of antibiotic treatment. A barrier to identifying the shortest effective treatment duration is the cost of the sequence of clinical trials needed to determine shortest optimal duration. We propose a new method to identify the optimal treatment duration of an antibiotic treatment regimen. Methods Subjects are randomized to varying treatment durations and the cure proportions of these durations are linked using a logistic regression model, making effective use of information across all treatment duration groups. In this paper, Monte Carlo simulation is used to evaluate performance of such a model. Results Using a hypothetical dataset, the logistic regression model is seen to provide increased precision in defining the point estimate and confidence interval (CI) of the cure proportion at each treatment duration. When applied to the determination of non-inferiority, the regression model allows identification of the shortest duration meeting the predefined non-inferiority margin. Conclusions This analytic strategy represents a practical way to develop shortened regimens for tuberculosis and other infectious diseases. Application of this strategy to clinical trials of antibiotic therapy could facilitate decreased antibiotic usage, reduce cost, minimize toxicity, and decrease the emergence of antibiotic resistance

Cartilage markers and their association with cartilage loss on magnetic resonance imaging in knee osteoarthritis: the Boston Osteoarthritis Knee Study

We used data from a longitudinal observation study to determine whether markers of cartilage turnover could serve as predictors of cartilage loss on magnetic resonance imaging (MRI). We conducted a study of data from the Boston Osteoarthritis of the Knee Study (BOKS), a completed natural history study of knee osteoarthritis (OA). All subjects in the study met American College of Rheumatology criteria for knee OA. Baseline and follow-up knee magnetic resonance images were scored for cartilage loss by means of the WORMS (Whole Organ Magnetic Resonance Imaging Score) semiquantitative grading scheme. Within the BOKS population, 80 subjects who experienced cartilage loss and 80 subjects who did not were selected for the purposes of this nested case control study. We assessed the baseline levels of cartilage degradation and synthesis products by means of assays for type I and II cleavage by collagenases (Col2:3/4Cshort or C1,2C), type II cleavage only with Col2:3/4Clongmono (C2C), type II synthesis (C-propeptide), the C-telopeptide of type II (Col2CTx), aggrecan 846 epitope, and cartilage oligomeric matrix protein (COMP). We performed a logistic regression to examine the relation of levels of each biomarker to the risk of cartilage loss in any knee. All analyses were adjusted for gender, age, and body mass index (BMI); results stratified by gender gave similar results. One hundred thirty-seven patients with symptomatic knee OA were assessed. At baseline, the mean (standard deviation) age was 67 (9) years and 54% were male. Seventy-six percent of the subjects had radiographic tibiofemoral OA (Kellgren & Lawrence grade of greater than or equal to 2) and the remainder had patellofemoral OA. With the exception of COMP, none of the other biomarkers was a statistically significant predictor of cartilage loss. For a 1-unit increase in COMP, the odds of cartilage loss increased 6.09 times (95% confidence interval [CI] 1.34 to 27.67). After the analysis of COMP was adjusted for age, gender, and BMI, the risk for cartilage loss was 6.35 (95% CI 1.36 to 29.65). Among subjects with symptomatic knee OA, a single measurement of increased COMP predicted subsequent cartilage loss on MRI. The other biochemical markers of cartilage synthesis and degradation do not facilitate prediction of cartilage loss. With the exception of COMP, if changes in cartilage turnover in patients with symptomatic knee OA are associated with cartilage loss, they do not appear to affect systemic biomarker levels

Hubble Space Telescope Observations of Element Abundances in Low-redshift Damped Lyman-alpha Galaxies and Implications for the Global Metallicity-Redshift Relation

Most models of cosmic chemical evolution predict that the mass-weighted mean interstellar metallicity of galaxies should rise with time from a low value $\sim 1/30$ solar at $z \sim 3$ to a nearly solar value at $z = 0$. In the absence of any selection effects, the damped Lyman-alpha absorbers (DLAs) in quasar spectra are expected to show such a rise in global metallicity. However, it has been difficult to determine whether or not DLAs show this effect, primarily because of the very small number of DLA metallicity measurements at low redshifts. In an attempt to put tighter constraints on the low-redshift end of the DLA metallicity-redshift relation, we have observed Zn II and Cr II lines in four DLAs at $0.09 < z < 0.52$, using the Space Telescope Imaging Spectrograph (STIS) onboard the Hubble Space Telescope (HST). These observations have provided the first constraints on Zn abundances in DLAs with $z < 0.4$. In all the three DLAs for which our observations offer meaningful constraints on the metallicity, the data suggest that the metallicities are much lower than the solar value. These results are consistent with recent imaging studies indicating that these DLAs may be associated with dwarf or low surface brightness galaxies. We combine our results with higher redshift data from the literature to estimate the global mean metallicity-redshift relation for DLAs. We find that the global mean metallicity shows at most a slow increase with decreasing redshift. ...(Please see the paper for the complete abstract).Comment: 56 pages, including 13 figures. Accepted for publication in the Astrophysical Journa

Insulin Status and Vascular Responses to Weight Loss in Obesity

ObjectivesThe aim of this study was to determine whether the effects of weight loss on arterial function are differentially modified by insulin status.BackgroundClinical studies suggest that plasma insulin levels may predict the extent of cardiovascular benefit achieved with weight loss in obese individuals, but mechanisms are currently unknown.MethodsWe prospectively followed 208 overweight or obese patients (body mass index [BMI] ≥25 kg/m2) receiving medical/dietary (48%) or bariatric surgical (52%) weight-loss treatment during a median period of 11.7 months (interquartile range: 4.6 to 13 months). We measured plasma metabolic parameters and vascular endothelial function using ultrasound at baseline and following weight-loss intervention and stratified analyses by median plasma insulin levels.ResultsPatients age 45 ± 1 years, with BMI 45 ± 9 kg/m2, experienced 14 ± 14% weight loss during the study period. In individuals with higher baseline plasma insulin levels (above median >12 μIU/ml; n = 99), ≥10% weight loss (compared with <10%) significantly improved brachial artery macrovascular flow-mediated vasodilation and microvascular reactive hyperemia (p < 0.05 for all). By contrast, vascular function did not change significantly in the lower insulin group (≤12 μIU/ml; n = 109) despite a similar degree of weight loss. In analyses using a 5% weight loss cut point, only microvascular responses improved in the higher insulin group (p = 0.02).ConclusionsInsulin status is an important determinant of the positive effect of weight reduction on vascular function with hyperinsulinemic patients deriving the greatest benefit. Integrated improvement in both microvascular and macrovascular function was associated with ≥10% weight loss. Reversal of insulin resistance and endothelial dysfunction may represent key therapeutic targets for cardiovascular risk reduction in obesity

Assessment of the item selection and weighting in the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis

Objective To assess the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) with respect to its selection and weighting of items. Methods This study used the BVAS/WG data from the Wegener's Granulomatosis Etanercept Trial. The scoring frequencies of the 34 predefined items and any “other” items added by clinicians were calculated. Using linear regression with generalized estimating equations in which the physician global assessment (PGA) of disease activity was the dependent variable, we computed weights for all predefined items. We also created variables for clinical manifestations frequently added as other items, and computed weights for these as well. We searched for the model that included the items and their generated weights yielding an activity score with the highest R 2 to predict the PGA. Results We analyzed 2,044 BVAS/WG assessments from 180 patients; 734 assessments were scored during active disease. The highest R 2 with the PGA was obtained by scoring WG activity based on the following items: the 25 predefined items rated on ≥5 visits, the 2 newly created fatigue and weight loss variables, the remaining minor other and major other items, and a variable that signified whether new or worse items were present at a specific visit. The weights assigned to the items ranged from 1 to 21. Compared with the original BVAS/WG, this modified score correlated significantly more strongly with the PGA. Conclusion This study suggests possibilities to enhance the item selection and weighting of the BVAS/WG. These changes may increase this instrument's ability to capture the continuum of disease activity in WG.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60211/1/23707_ftp.pd

The Smoking Paradox in the Development of Psoriatic Arthritis among Psoriasis Patients – A Population-Based Study

Objectives: Smoking is strongly associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among psoriasis patients. We sought to clarify the possible methodologic mechanisms behind this paradox. Methods: Using 1995-2015 data from The Health Improvement Network, we performed survival analysis to examine the association between smoking and incident PsA in the general population and among psoriasis patients. We clarified the paradox using mediation analysis and conducted bias sensitivity analyses to evaluate the potential impact of index event bias and quantify its magnitude from uncontrolled/unmeasured confounders. Results: Of 6.65 million subjects without PsA at baseline, 225,213 participants had psoriasis and 7,057 developed incident PsA. Smoking was associated with an increased risk of PsA in the general population (RR, 1.27; 95% CI, 1.19-1.36), but with a decreased risk among psoriasis patients (RR 0.91; 95% CI, 0.85-0.99). Mediation analysis showed that the effect of smoking on the risk of PsA was mediated almost entirely through its effect on psoriasis. Bias sensitivity analyses indicated that even when the relation of uncontrolled confounders to either smoking or PsA was modest (both RRs = ~1.50), it could reverse the biased estimate of effect of smoking among psoriasis patients (RR=0.9). Conclusions: In this large cohort representative of the UK general population, smoking was positively associated with PsA risk in the general population, but negatively associated among psoriasis patients. Conditioning on a causal intermediate variable (psoriasis) can reverse the association between smoking and PsA, explaining the smoking paradox for the risk of PsA among psoriasis patients