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Notes on subgroup analyses and meta-regression
... Finally, effects of Ulva attached to Gracilaria (GU) were compared to effects of Gracilaria alone (G) across the three data sets in a single quantitative analysis. Hedges g was calculated, as a standardized effect size, for each matching pair of 'G vs GU' treatments (cf. the matching grey and black bars in Fig. 3.2, 3.4 and 3.6) as [(GU -G) / S] J, where S is the pooled standard deviation and J is a factor that corrects for bias associated with small sample sizes (see Borenstein et al. 2009). A standard meta-analysis was carried out on abundance and richness data separately, using weighted random effect models, assuming that summary statistics have both sampling error and a true random component of variation in effect sizes between studies ( Borenstein et al. 2009). ...
... Hedges g was calculated, as a standardized effect size, for each matching pair of 'G vs GU' treatments (cf. the matching grey and black bars in Fig. 3.2, 3.4 and 3.6) as [(GU -G) / S] J, where S is the pooled standard deviation and J is a factor that corrects for bias associated with small sample sizes (see Borenstein et al. 2009). A standard meta-analysis was carried out on abundance and richness data separately, using weighted random effect models, assuming that summary statistics have both sampling error and a true random component of variation in effect sizes between studies ( Borenstein et al. 2009). ...
The important role of indirect facilitation, like trophic cascade and keystone predation, in structuring communities have been documented over many decades and across ecosystems. By contrast, indirect facilitation mediated by habitat cascades (where ‘inhabitants’ organisms are facilitated through sequential habitat formation or modification) is less studied, and these processes are not covered in ecological text books or conservation practices. This could be because habitat cascades are ecologically unimportant, or, alternatively, highlights a major research gap.
In this thesis, I investigated the core hypothesis that habitat cascades can be key drivers of biodiversity in marine benthic ecosystems. To test this hypothesis, I combined descriptive and experimental field and laboratory studies aimed at improving our understanding of the mechanisms underpinning habitat cascades via three broad research objectives: (i) quantifing the variability in habitat cascades under different environmental conditions, (ii) testing mechanisms that increase or decrease habitat cascades, (i) testing how habitat cascades can be affected by human stressors.
In Chapter 2, I described two new habitat cascades from relatively ‘simple’ sedimentary estuarine shell beds, where small infaunal bivalves (Austrovenus stutchburyi, primary habitat former) provide substrate for large and form-functionally different seaweeds (Ulva sp. and Gracilaria chilensis, secondary habitat formers). To date, most research on habitat cascades has focused on interactions between a single primary and secondary habitat former studied on small spatio-temporal scales, thereby questioning if habitat cascades have broad ecological relevance. I tested if habitat cascades, when standardized by seaweed biomass, are stronger at high than low abundances of the secondary habitat former and when the secondary habitat former has high (Gracilaria) compared to low (Ulva) morphological complexity. I also tested if habitat cascades are stronger at higher latitudes, where intertidal desiccation stress is stronger, and when secondary habitat formers are alive compared to mimics. In contrast to my hypotheses, I found weaker habitat cascades at high abundances and for the coarsely branched habitat formers, and I found no patterns across latitudes; however, as expected I did find stronger habitat cascades for living than mimic of secondary habitat formers.
Chapter 3 described, from the same estuarine sedimentary system, a rare example of a ‘higher-level habitat cascade’. Virtually all habitat cascade studies have tested if and how two co-occurring habitat-forming species affect biodiversity compared to systems dominated by a single habitat-forming species. My aim here was to document a new ‘long habitat formation cascade’ where the primary bivalve Austrovenus provides attachment space for the secondary seaweed Gracilaria, that again provides substratum for the tertiary epiphytic seaweed Ulva. I tested if this long bivalve-seaweed-seaweed cascade affected mobile invertebrates and if it is a general process operating across Gracilaria biomasses, seasons, elevation levels, sites and estuaries. My study confirmed that Ulva increased invertebrate abundances and altered community structures, whereas increases in taxonomic richness only was observed under a smaller subset of environmental conditions. These positive effects were, however, not supported for non-living Ulva mimics, suggesting that common invertebrates graze on Ulva.
In Chapter 4 I described a new habitat cascade from a seagrass-dominated system where unattached seaweeds (Ulva, secondary habitat former) can become entrapped and entangled around seagrass leaves (Zostera muelleri, primary habitat former). I tested the hypotheses that (i) the presence of seaweeds entangled in estuarine seagrass beds modify biodiversity via cascading habitat formation, (ii) similar processes occur across a wide range of spatial and temporal conditions, and (iii) the biomass and the structural attributes of seaweeds (comparing living vs artificial mimics) modify the strength of habitat cascades. I found that entangled seaweeds, across latitudes, elevation levels and seasons, consistently increased the abundance and richness of invertebrates and I also found stronger facilitation of invertebrates in high than low seaweed biomass and by live than mimic seaweeds. Furthermore, an experiment, using different seaweed mimics showed consistent facilitation of invertebrates with increasing mimic biomass between estuaries and across latitudes, thereby supporting all three hypotheses in a single experiment. I concluded that entangled seaweeds, by adding biomass and different physical structures, can support strong habitat cascades in sedimentary estuarine seagrass beds.
In Chapter 5 I tested, again in a seagrass-dominated system, if and how anthropogenic stressors, like fertilization and enhanced sedimentation, affect seagrass performances and seagrass-seaweed habitat cascades. I found that fertilization had little impact whereas even low sedimentation levels had strong negative effects on both seagrass and fauna. Furthermore, I found strong negative effects of sediments, across seasons and elevation levels, but also that negative effects of sediments on invertebrates were elevated in the presence of the secondary habitat former. These results thereby provide rare evidence of how a habitat cascade can break down under high anthropogenic stress.
In Chapter 6, I studied habitat cascades from more diverse rocky intertidal shores. Primary habitat formers with different morphologies affect secondary habitat-forming epiphytes and epifauna differently. However, no studies have tested the opposite hypothesis; do morphologically ‘similar’ congeneric primary habitat formers support similar epiphytes with similar direct and indirect cascading effects on invertebrate communities? This hypothesis was tested by sampling co-existing congeneric habitat-forming fucoid seaweeds, Cystophora torulosa, C. scalaris, and C. retroflexa, with and without epiphytes across reefs and latitudes. The survey was then followed by field experiments, where defaunated Cystophora species and the morphologically different fucoid Hormosira banksii, with and without living and mimics of epiphytes, were out-transplanted to quantify the impact on colonizing gastropods. I found that the three Cystophora species supported different gastropod communities and had different cascading effects, and that these results can be, in part, explained by their physical structures. I also found that epiphytic biomass had strong positive effect on gastropods abundances, and that artificial mimics and live epiphytes were colonized by similar gastropod communities, suggesting that structural effects are more important than whether the habitat is ‘edible’.
In Chapter 7, I tested, again from rocky intertidal systems, if habitat cascades affect secondary (animal) production. Secondary production of small mobile invertebrates inhabiting Cystophora seaweed, with and without epiphytes, was estimated from published productivity models. More specifically, I tested if (i) the three Cystophora species support similar secondary production, (ii) finely branched epiphytes increase secondary production, (iii) production is greatest in warmer locations and seasons, and (iv) secondary production is higher on living epiphytes than non-living epiphyte mimics. The first two hypotheses were rejected as the three Cystophora species supported different secondary production and because epiphytes, when its biomass was taken into consideration, did not increase secondary production. Nevertheless, the two latter hypotheses were both supported, as production was highest in the northern location and in summer months and on living than mimic epiphytes. Thus, similar looking congeneric primary habitat formers supported different secondary production and epiphytes did not increase secondary production per seaweed-biomass, but will increase areal-based production when epiphytes enhance total standing plant biomass.
I conclude that poorly studied habitat cascades were ubiquitous in marine benthic systems on the South Island of New Zealand, modifying animal biodiversity across habitats, seasons, years, latitudes, sites and elevations levels. I also conclude that data on the abundances, morphologies and types (live or not) of co-existing habitat formers were strong mechanistic descriptors of habitat cascades. I finally suggest that habitat cascades, like other important indirect facilitation processes, should be covered in ecological text books and conservation practices.
... By the same logic, we cannot give too much weight to a very large study (the way we might in a fixed-effect analysis). Our goal was to estimate the mean effect in a range of studies, and we do not want that overall estimate to be overly influenced by any one of them (Borenstein et al., 2009). The effect size was computed by logarithmic transformation of the ratio (Nasrollahi et al., 2015), and mean (µ) difference was computed for each variable as follows: ...
... By the same logic, we cannot give too much weight to a very large study (the way we might in a fixed-effect analysis). Our goal was to estimate the mean effect in a range of studies, and we do not want that overall estimate to be overly influenced by any one of them (Borenstein et al., 2009). The effect size was computed by logarithmic transformation of the ratio (Nasrollahi et al., 2015), and mean (μ) difference was computed for each variable as follows: ...
A meta-analysis of the potential effect of forage provision on growth performance and rumen fermentation of dairy calves was conducted using published data from the literature (1998–2016). Meta-regression was used to evaluate the effect of different forage levels, forage sources, forage offering methods, physical forms of starter, and grain sources on the heterogeneity of the results. A total of 27 studies that reported the effects of forage provision to dairy calves were considered. Estimated effect sizes of forage were calculated on starter feed intake, average daily gain (ADG), feed efficiency (FE), body weight (BW), and rumen fermentation parameters. Intake of starter feed, ADG, BW, ruminal pH and rumen molar proportion of acetate increased when supplementing forage, but FE decreased. Heterogeneity (amount of variation among studies) was significant for intake of starter feed, ADG, FE, final BW, and rumen fermentation parameters. Improving overall starter feed intake was greater in calves offered alfalfa hay compared to those offered other types of forages. During the milk feeding and overall periods, improving ADG was greater for calves fed a high level of forage (> 10 % in DM) compared to those fed a low level of forage (≤ 10 % in DM) diets. The advantages reported in weight gain at a high level of forage could be due to increased gut fill. Improving overall ADG was lower for calves offered forages with textured starter feed compared to ground starter feed. The meta-regression analysis revealed that changes associated with forage provision affect differently FE for various forage sources and forage offering methods during the milk-feeding period. Forage sources also modulated the effect of feeding forage on ruminal pH during the milk-feeding period. In conclusion, forage has potential to affect starter feed intake and performance of dairy calves, but its effects depend on source, level, and method of forage feeding and physical form of starter feed independently of grain sources included in the starter feed.
... Sensitivity analyses were conducted by systematically excluding one study at a time to evaluate the heterogeneity and robustness of the pooled results. This approach facilitated the identification of any single study that disproportionately influenced the meta-analysis outcomes [30]. ...
This research aimed to evaluate the impact of probiotic supplementation on the severity of psoriasis symptoms and its association with the risk of developing the disease. We analyzed the association between probiotic usage and psoriasis among 21,942 participants from the 2009–2014 NHANES, employing advanced machine learning techniques for data analysis. A separate meta-analysis was conducted to assess the effects of probiotics on the severity, life quality, and some related inflammation factors. Dichotomous data were analyzed using odds ratios (ORs) corresponding to the 95% confidence interval (CI). Analysis of NHANES data did not reveal a statistically significant association between probiotic intake and the risk of psoriasis. However, the meta-analysis indicated that probiotic supplementation significantly lowers Psoriasis Area and Severity Index (PASI) scores both for change in PASI score and post-data change, and enhances PASI 75 (OR = 4.80, 95% CI = 2.92–7.89) and clearance responses (OR = 3.14, 95% CI = 1.99–4.96), as well as reduced levels of inflammatory markers. While the improvement of life quality was only observed in the post-treatment data. While probiotic supplements do not appear to reduce the risk of psoriasis, they have a significant positive effect on reducing disease severity. Registered on PROSPERO: Registration number CRD42023484417.
... Meta-regression analyses were used to assess the association of different teaching methods and content of the intervention, with the effect size for each outcome. Since there was considerable heterogeneity in the reporting of biomedical outcomes, we also used full random effects analyses to combine studies within each subgroup (24). A random effects model is used to combine subgroups and yield the overall effect. ...
Background
Chronic disorders are highly prevalent and are a major contributor to death and disability worldwide. Evidence has shown that therapeutic patient education (TPE) interventions are effective in improving a range of biomedical and psychological outcomes for a variety of chronic disorders. This has been demonstrated in scores of randomized controlled and evidence-synthesis studies. However, no quantitative evidence has been published so far on the content and effective teaching strategies in TPE programs. The present systematic review and meta-analysis aim to bridge this gap by answering the who, what, and how of TPE programs.Methods
Using a pretested search strategy, we searched the Web of Science, MEDLINE, CINAHL, PsycINFO, and the COCHRANE databases, from inception to August 2019. The search strategy was based on four comprehensive search concepts (patient education, chronic diseases, study design, and outcomes). After a careful screening for eligible studies, two reviewers extracted qualitative and quantitative data from the randomized controlled trials on the TPE interventions. We also developed a taxonomy of curriculum skills and intervention delivery techniques to aid the extraction of data in these domains.ResultsWe found that these interventions were effective in improving biological outcomes (SMD = 0.48; 95% CI: 0.38–0.57), adherence to the treatment regimen (SMD = 0.73; 95% CI: 0.46–1.002), knowledge (SMD = 1.22; 95% CI: 0.79–1.65), self-efficacy (SMD = 0.43; 95% CI: 0.30–0.56), and psychological health (SMD = −0.41; 95% CI: −0.53 to −0.29). This effectiveness was consistent across different delivery formats (individual, group, and electronic) and delivery agents (non-specialists vs. specialists).Conclusion
The flexibility in the choice of mode of delivery and curriculum development gives stakeholders an opportunity to scale up TPE interventions in healthcare settings.Systematic review registrationIdentifier: CRD42019141294.
... We compared fingerprints across groups using both Pearson correlation and the Euclidean distance between each larva and its mean wild-type sibling fingerprint (Figure 1.6A). The statistical test used to compare effect sizes was a Z-test used for comparing two studies in meta-analysis (Borenstein et al., 2009). As a control, in the stable knockout experiment, the effect size between wild types and heterozygotes (Cohen's = 0.28) was significantly different (p = 0.04) than the effect size between wild types and homozygotes (Cohen's = 1.57). ...
To design prevention strategies and disease-modifying therapies in Alzheimer’s disease, we must discover biological processes which contribute to disease. Genomic studies can point to such causal processes, but their findings are rarely exploited in a systematic, hypothesis-free manner. In this thesis, we present a strategy in zebrafish to link disease-associated genes to likely causal processes. The first step is to inactivate each gene in zebrafish larvae. For this purpose, we developed a rapid CRISPR-Cas9 method capable of converting wild-type eggs directly into knockout larvae for any gene of interest. The method effectively cuts the experimental time from gene to knockout zebrafish from months to one day. The second step is to monitor the behaviour of the mutated larvae. As a case study, we targeted the three genes associated with early-onset Alzheimer’s disease. We found, for example, that larvae with loss-of-function mutations in presenilin 2 are less active during the day. The third step will be to use predictive pharmacology to identify drugs which cause the same phenotype in wild- type animals, thereby pointing to the defective process. This strategy is both scalable thanks to the knockout method and generalisable beyond Alzheimer’s disease. It can now be employed to screen tens or hundreds of genes associated with other conditions, such as schizophrenia or epilepsy.
... We compared fingerprints across groups using both Pearson correlation and the Euclidean distance between each larva and its mean wild-type sibling fingerprint ( Figure 6A). The statistical test used to compare effect sizes is a Z-test used for comparing two studies in meta-analysis (Borenstein et al., 2009). As a control, in the stable knockout experiment, the effect size between wild types and heterozygotes (Cohen's d = 0.28) was significantly different (p = 0.04) than the effect size between wild types and homozygotes (Cohen's d = 1.57). ...
Hundreds of human genes are associated with neurological diseases, but translation into tractable biological mechanisms is lagging. Larval zebrafish are an attractive model to investigate genetic contributions to neurological diseases. However, current CRISPR-Cas9 methods are difficult to apply to large genetic screens studying behavioural phenotypes. To facilitate rapid genetic screening, we developed a simple sequencing-free tool to validate gRNAs and a highly effective CRISPR-Cas9 method capable of converting >90% of injected embryos directly into F0 biallelic knockouts. We demonstrate that F0 knockouts reliably recapitulate complex mutant phenotypes, such as altered molecular rhythms of the circadian clock, escape responses to irritants, and multi-parameter day-night locomotor behaviours. The technique is sufficiently robust to knockout multiple genes in the same animal, for example to create the transparent triple knockout crystal fish for imaging. Our F0 knockout method cuts the experimental time from gene to behavioural phenotype in zebrafish from months to one week.
... Second, inadequate statistical power for subgroup analyses was noted. Most subgroups were composed of a small number of RCTs (<6), which may not have adequate power to detect a difference among subgroups (81,82); the results of such subgroup analyses should be interpreted cautiously. Third, some of the included RCTs (52,53,(59)(60)(61) in this meta-analysis had small sample sizes; thus, results of such RCTs that reported no significant treatment effect on muscle outcomes may contribute negative effect size to the overall result. ...
Objective
To investigate the effect of muscle strength exercise training (MSET) on lean mass (LM) gain and muscle hypertrophy in older patients with lower extremity osteoarthritis (OA).
Methods
A comprehensive search of online databases was performed on April 20, 2019. Randomized controlled trials (RCTs) that reported the effects of MSET on LM, muscle thickness, and cross‐sectional area (CSA) in older patients with OA were identified. A risk of bias assessment and meta‐analysis were performed for the included RCTs.
Results
We included 19 RCTs with a median Physiotherapy Evidence Database score of 6 of 10 (range 3–7). In total, data from 1,195 patients (65% women, 85% with knee OA) with a mean age of 62.1 years (range 40–86 years) were analyzed. MSET resulted in significantly higher LM gain (standardized mean difference [SMD] 0.49 [95% confidence interval (95% CI) 0.28, 0.71], P < 0.00001) than did the nonexercise controls. Meta‐analysis results revealed significantly positive effects of MSET on muscle thickness (SMD 0.82 [95% CI 0.20, 1.43], P = 0.009) and CSA (SMD 0.80 [95% CI 0.25, 1.35], P = 0.004) compared with nonexercise controls. No significant effects in favor of MSET were observed for any muscle outcome compared with exercise controls. Five RCTs reported nonsevere adverse events in response to MSET, whereas no RCTs reported severe events.
Conclusion
MSET is effective in increasing LM and muscle size in older adults with OA. Clinicians should incorporate MSET into their management of patients at risk of low muscle mass to maximize health status, particularly for older individuals with OA.
... When concentrating on only one covariate as effect modifier, one has to be aware that the problem of confounding may arise and therefore results have to be interpreted with care (Lipsey, 2003). According to Borenstein, Hedges, Higgins, and Rothstein (2009b), small studies, few studies, or a small covariate effect could lead to problems with low power in metaregression. Furthermore regressing on characteristics which do not differentiate substantially across trials may lead to higher biases, as could be seen in the results of the simulation study for the covariate range 0.4 -0.5. ...
Individualized therapies for patients with biomarkers are moving more and more into the focus of research interest when developing new treatments. Hereby, the term individualized (or targeted) therapy denotes a treatment specifically developed for biomarker‐positive patients. A network meta‐analysis model for a binary endpoint combining the evidence for a targeted therapy from individual patient data with the evidence for a non‐targeted therapy from aggregate data is presented and investigated. The biomarker status of the patients is either available at patient‐level in individual patient data or at study‐level in aggregate data. Both types of biomarker information have to be included. The evidence synthesis model follows a Bayesian approach and applies a meta‐regression to the studies with aggregate data. In a simulation study, we address three treatment arms, one of them investigating a targeted therapy. The bias and the root‐mean‐square error of the treatment effect estimate for the subgroup of biomarker‐positive patients based on studies with aggregate data are investigated. Thereby, the meta‐regression approach is compared to approaches applying alternative solutions. The regression approach has a surprisingly small bias even in the presence of few studies. By contrast, the root‐mean‐square error is relatively greater. An illustrative example is provided demonstrating implementation of the presented network meta‐analysis model in a clinical setting.
... Finally, inadequate statistical power for subgroup analyses was noted. Several subgroups (such as intervention durations for ALM) included a small number of RCTs (less than six), which may not have adequate power for detecting differences among subgroups [71,72]; the results of such subgroup analyses should be cautiously interpreted. ...
Aging and frailty are associated with a high risk of lean mass (LM) loss, which leads to physical disability and can be effectively alleviated by protein supplementation (PS) and muscle strengthening exercise (MSE). In this study, the associations between LM gain and PS + MSE efficacy (measured using physical outcomes) in elderly patients with a high risk of sarcopenia or frailty were identified. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) reporting the efficacy of PS + MSE in elderly patients with sarcopenia or frailty. The included RCTs were analyzed using meta-analysis and risk of bias assessment. We finally included 19 RCTs in this meta-analysis with a median (range/total) Physiotherapy Evidence Database score of 7/10 (5–9/10). The PS + MSE group exhibited significant improvements in the whole-body LM (standard mean difference (SMD) = 0.66; p < 0.00001), appendicular LM (SMD = 0.35; p < 0.00001), leg strength (SMD = 0.65; p < 0.00001), and walking capability (SMD = 0.33; p = 0.0006). Meta-regression analyses showed that changes in appendicular LM were significantly associated with the effect sizes of leg strength (β = 0.08; p = 0.003) and walking capability (β = 0.17; p = 0.04), respectively. Our findings suggest that LM gain after PS + MSE significantly contributes to the efficacy of the intervention in terms of muscle strength and physical mobility in elderly patients with a high risk of sarcopenia or frailty.
... Fifth, inadequate statistical power for subgroup analyses was noted. Several subgroups (such as participant types for lean body mass) included a small number of RCTs less than six, which may not have adequate power for detecting a difference among subgroups [89,90]; the results of such subgroup analyses should be cautiously interpreted. Finally, there may have been sex differences for changes in body composition in response to PS plus exercise training [20,[91][92][93]. ...
Aging poses a high risk of lean mass loss, which can be effectively improved through resistance exercise training (RET), or multicomponent exercise training (MET) as well as nutrition supplementation, such as protein supplementation (PS). This study investigated the effects of PS plus exercise training on frail older individuals. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) that reported the efficacy of PS combined with RET or MET in frail older individuals. The included RCTs were analyzed through a meta-analysis and risk-of-bias assessment. We finally included 22 RCTs in the meta-analysis, with a mean (range/total) Physiotherapy Evidence Database score of 6.7 (4–9/10). PS plus exercise training significantly improved the frailty status (odds ratio = 2.77; p = 0.006), lean mass (standard mean difference (SMD) = 0.52; p < 0.00001), leg strength (SMD = 0.37; p < 0.00001), and walking speed (SMD = 0.32; p = 0.002). Subgroup analyses revealed that PS plus MET exert significant effects on frailty indices, whereas PS plus RET further improves lean mass. Our findings suggest that PS plus RET as well as MET is effective in improving frailty status, lean mass, muscle strength, and physical mobility in frail older individuals.
... Then, multivariate meta-regression analyses were performed to identify effective BCTs and intervention features associated with HbA1c level. Following the recommendation by Borenstein et al., 69 BCTs were added in the subgroup and meta-regression analyses if they were included in at least two studies. ...
Background: Digital interventions may assist patients with type 2 diabetes in improving glycemic control. We aimed to synthesize effect sizes of digital interventions on glycated hemoglobin (HbA1c) levels and to identify effective features of digital interventions targeting patients with poorly controlled type 2 diabetes.
Materials and Methods: MEDLINE, ISI Web of Science, and PsycINFO were searched for randomized controlled trials (RCTs) comparing the effects of digital interventions with usual care. Two reviewers independently assessed studies for eligibility and determined study quality, using the Cochrane Risk of Bias Assessment Tool. The Behavioral Change Technique Taxonomy V1 (BCTTv1) was used to identify BCTs used in interventions. Mean HbA1c differences were pooled using analysis of covariance to adjust for baseline differences and pre–post correlations. To examine effective intervention features and to evaluate differences in effect sizes across groups, meta-regression and subgroup analyses were performed.
Results: Twenty-three arms of 21 RCTs were included in the meta-analysis (n = 3787 patients, 52.6% in intervention arms). The mean HbA1c baseline differences ranged from −0.2% to 0.64%. The pooled mean HbA1c change was statistically significant (−0.39 {95% CI: [−0.51 to −0.26]} with substantial heterogeneity [I2 statistic, 80.8%]) and a significant HbA1c reduction was noted for web-based interventions. A baseline HbA1c level above 7.5%, β = −0.44 (95% CI: [−0.81 to −0.06]), the BCTs “problem solving,” β = −1.30 (95% CI: [−2.05 to −0.54]), and “self-monitoring outcomes of behavior,” β = −1.21 (95% CI: [−1.95 to −0.46]) were significantly associated with reduced HbA1c levels.
Conclusions: Digital interventions appear effective for reducing HbA1c levels in patients with poorly controlled type 2 diabetes.
... Then, multivariate meta-regression analyses were performed to identify effective BCTs and intervention features associated with HbA1c level. Following the recommendation by Borenstein et al., 69 BCTs were added in the subgroup and meta-regression analyses if they were included in at least two studies. ...
Objective: Digital interventions may assist patients with type 2 diabetes with improving glycaemic control. We aimed to synthesize effect sizes of digital interventions on glycated hemoglobin (HbA1c) levels and to identify effective features of digital interventions targeting patients with poorly controlled type 2 diabetes.
Research Design and Methods: MEDLINE, ISI Web of Science and PsycInfo were searched for randomized controlled trials (RCTs) comparing the effects of digital interventions with usual care. Two reviewers independently assessed studies for eligibility and determined study quality, using the Cochrane risk of bias assessment tool. The Behavioural Change Technique Taxonomy v1 was employed to identify behavior change techniques (BCTs) employed in interventions. Mean HbA1c differences were pooled using Analysis of Covariance to adjust for baseline differences and pre-post correlations. To examine effective intervention features and to evaluate differences in effects sizes across groups, meta-regression and subgroup analyses were performed.
Results: Twenty three arms of 21 RCTs were included in the meta-analysis (n= 3787 patients, 52.6% in intervention arms). The mean HbA1c baseline differences ranged from -0.2% to 0.64%. The pooled mean HbA1c change was statistically significant (-0.39 (95% CI: [-0.51, -0.26]) with substantial heterogeneity (I-squared statistic, 80.8%)) and a significant HbA1c reduction was noted for web-based interventions. A baseline HbA1c level above 7.5%, β=-0.44 (95% CI: [-0.81, -0.06]) and the BCTs ’problem solving’, β=-1.30(95% CI: [-2.05, -0.54]) and ’self-monitoring outcomes of behavior’, β=-1.21 (95% CI: [-1.95, -0.46]) were significantly associated with reduced HbA1c levels.
Conclusions: Digital interventions appear effective for reducing HbA1c levels in patients with poorly controlled type 2 diabetes.
... T 2 was first computed within subgroups and then pooled across subgroups. 14 Additional univariate metaregression analyses according to both achieved SBP and DBP values under the random-effects model (Method of Moments) were performed for those adverse events reported in ≥10 total subgroups of included RCTs, according to the rule of thumb for metaregression analysis, 15 to evaluate a possible moderating effect of finally achieved BP values (during the follow-up period) on the aforementioned events. Final, an additional univariate ...
Current recommendations do not specifically address the optimal blood pressure (BP) reduction for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a systematic review and metaregression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized controlled clinical trials of secondary stroke prevention. For all reported events during each eligible study period, we calculated the corresponding risk ratios to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. On the basis of the reported BP values, we performed univariate metaregression analyses according to the achieved BP values under the random-effects model (Method of Moments) for those adverse events reported in ≥10 total subgroups of included randomized controlled clinical trials. In pairwise meta-analyses, antihypertensive treatment lowered the risk for recurrent stroke (risk ratio, 0.73; 95% confidence interval, 0.62-0.87; P<0.001), disabling or fatal stroke (risk ratio, 0.71; 95% confidence interval, 0.59-0.85; P<0.001), and cardiovascular death (risk ratio, 0.85; 95% confidence interval, 0.75-0.96; P=0.01). In metaregression analyses, systolic BP reduction was linearly related to the lower risk of recurrent stroke (P=0.049), myocardial infarction (P=0.024), death from any cause (P=0.001), and cardiovascular death (P<0.001). Similarly, diastolic BP reduction was linearly related to a lower risk of recurrent stroke (P=0.026) and all-cause mortality (P=0.009). Funnel plot inspection and Egger statistical test revealed no evidence of publication bias. The extent of BP reduction is linearly associated with the magnitude of risk reduction in recurrent cerebrovascular and cardiovascular events. Strict and aggressive BP control seems to be essential for effective secondary stroke prevention.
... We assumed the between-study variance (tau-squared) to be the same for all subgroups. Tausquared was first computed within subgroups and then pooled across subgroups [12]. We assessed heterogeneity between studies with the Cochran Q and I 2 statistics. ...
Background:
Although Fingolimod (FGD) and Natalizumab (NTZ) appear to be effective in relapsing-remitting multiple sclerosis (RRMS), they have never been directly compared in a randomized clinical trial (RCT).
Methods and findings:
We evaluated the comparative efficacy of FGD vs. NTZ using a meta-analytical approach. Data from placebo-controlled RCTs was used for indirect comparisons and observational data was utilized for head-to-head comparisons. We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). NTZ was associated with a greater reduction in the 2-year annualized relapse rate (ARR; SMDindirect = -0.24;95% CI: from -0.44 to -0.04; p = 0.005) and with the probability of no disease activity at 2 years (ORindirect:1.82, 95% CI: from 1.05 to 3.15) compared to FGD, while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect = 1.20;95% CI: from 0.84 to 1.71) and those with disability progression (ORindirect = 0.76;95% CI: from 0.48 to 1.21) at 2 years. In the analysis of observational data, we found no significant differences between NTZ and FGD in the 2-year ARR (SMD = -0.05; 95% CI: from -0.26 to 0.16), and 2-year disability progression (OR:1.08;95% CI: from 0.77 to 1.52). However, NTZ-treated patients were more likely to remain relapse-free at 2-years compared to FGD (OR: 2.19;95% CI: from 1.15 to 4.18; p = z0.020).
Conclusions:
Indirect analyses of RCT data and head-to-head comparisons of observational findings indicate that NTZ may be more effective than FGD in terms of disease activity reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation.
... Statistical significance of between subgroup differences was evaluated by meta-regression. 17 Publication bias was evaluated with funnel plots to check symmetrical distribution and convergence toward the pooled effect, along with Egger tests. Further, sensitivity analyses were performed (1) excluding relatively small studies (with fewer than 80 participants per randomization group) and (2) restricting analyses to studies of high quality. ...
Control of blood pressure (BP) remains a major challenge in primary care. Innovative interventions to improve BP control are therefore needed. By updating and combining data from 2 previous systematic reviews, we assess the effect of pharmacist interventions on BP and identify potential determinants of heterogeneity.
Randomized controlled trials (RCTs) assessing the effect of pharmacist interventions on BP among outpatients with or without diabetes were identified from MEDLINE, EMBASE, CINAHL, and CENTRAL databases. Weighted mean differences in BP were estimated using random effect models. Prediction intervals (PI) were computed to better express uncertainties in the effect estimates. Thirty-nine RCTs were included with 14 224 patients. Pharmacist interventions mainly included patient education, feedback to physician, and medication management. Compared with usual care, pharmacist interventions showed greater reduction in systolic BP (-7.6 mm Hg, 95% CI: -9.0 to -6.3; I(2)=67%) and diastolic BP (-3.9 mm Hg, 95% CI: -5.1 to -2.8; I(2)=83%). The 95% PI ranged from -13.9 to -1.4 mm Hg for systolic BP and from -9.9 to +2.0 mm Hg for diastolic BP. The effect tended to be larger if the intervention was led by the pharmacist and was done at least monthly.
Pharmacist interventions - alone or in collaboration with other healthcare professionals - improved BP management. Nevertheless, pharmacist interventions had differential effects on BP, from very large to modest or no effect; and determinants of heterogeneity could not be identified. Determining the most efficient, cost-effective, and least time-consuming intervention should be addressed with further research.
Importance
The associations of sodium glucose cotransporter-2 inhibitors (SGLT2is) with reduction in mortality and hospitalization rates in patients with heart failure (HF) are well established. However, their association with improving functional capacity and quality of life (QOL) has been variably studied and less reported.
Objective
To provide evidence on the extent to which SGLT2is are associated with improvement on objective measures of functional capacity and QOL in patients living with HF.
Data Sources
The MEDLINE, EMBASE, and Cochrane databases were systematically searched for relevant articles on July 31, 2023.
Study Selection
Randomized, placebo-controlled clinical trials reporting the effect of SGLT2i on functional outcomes of exercise capacity (peak oxygen consumption [peak VO 2 ] or 6-minute walk distance [6MWD]) and/or QOL using validated questionnaires for patients with HF were included.
Data Extraction and Synthesis
Data were extracted by 2 authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, and a meta-analysis using the restricted maximum likelihood random-effects model was conducted.
Main Outcomes and Measures
Outcomes of interest included changes in peak VO 2 , 6MWD, and Kansas City Cardiomyopathy Questionnaire-12 total symptom score (KCCQ-TSS), clinical summary score (KCCQ-CSS), and overall summary score (KCCQ-OSS).
Results
In this meta-analysis of 17 studies, 23 523 patients (mean [range] age, 69 [60-75] years) were followed over a period ranging from 12 to 52 weeks. Four studies included peak VO 2 as an outcome, 7 studies included 6MWD, and 10 studies reported KCCQ scores. Mean (SD) left ventricular ejection fraction was 43.5% (12.4%). Compared with controls, patients receiving SGLT2i treatment experienced significant increases in peak VO 2 (mean difference [MD], 1.61 mL/kg/min; 95% CI, 0.59-2.63 mL/kg/min; P = .002) and 6MWD (MD, 13.09 m; 95% CI, 1.20-24.97 m; P = .03). SGLT2i use was associated with increased KCCQ-TSS (MD, 2.28 points; 95% CI, 1.74-2.81 points; P < .001), KCCQ-CSS (MD, 2.14 points; 95% CI, 1.53-2.74 points; P < .001), and KCCQ-OSS (MD, 1.90 points; 95% CI, 1.41-2.39 points; P < .001) scores. Subgroup analysis and meta-regression demonstrated almost all improvements were consistent across ejection fraction, sex, and the presence of diabetes.
Conclusions and Relevance
These findings suggest that in addition to known clinical associations with mortality and hospitalization outcomes, SGLT2i use is associated with improvement in outcomes of interest to patients’ everyday lives as measured by objective assessments of maximal exercise capacity and validated QOL questionnaires, regardless of sex or ejection fraction.
Objective
Hearing loss (HL) has been postulated to be linked to cardiovascular diseases (CVDs) via vascular mechanisms, but epidemiological associations remain unclear. The study aims to clarify the association between HL and stroke, coronary artery disease (CAD), and any CVD.
Data Sources
PubMed, Embase, and SCOPUS from inception until April 27, 2022.
Review Methods
Three blinded reviewers selected observational studies reporting stroke, CAD, and any CVD in patients with HL, compared to individuals without HL. We extracted data, evaluated study bias using the Newcastle‐Ottawa scale, following Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines and a PROSPERO‐registered protocol (CRD42022348648). We used random‐effects inverse variance meta‐analyses to pool the odds ratios (ORs) for the association of HL with stroke, CAD, and any CVD.
Results
We included 4 cohort studies (N = 940,771) and 6 cross‐sectional studies (N = 680,349). Stroke, CAD, and any CVD were all strongly associated with HL. The overall pooled OR of the association between HL and stroke was 1.26 (95% confidence interval [CI] = 1.16‐1.37, I ² = 78%), and was 1.33 (95% CI = 1.12‐1.58) and 1.29 (95% CI = 1.14‐1.45) for low‐ and high‐frequency HL, respectively. Minimal publication bias was observed, with minimal change to pooled effect size following trim and fill. Similarly, the pooled OR of the association between HL and CAD was 1.36 (95% CI = 1.13‐1.64, I ² = 96%), while that between HL and any CVD was 1.38 (95% CI = 1.07‐1.77, I ² = 99%).
Conclusion
Our findings suggest that HL and CVD are closely related. Physicians treating patients with HL should be cognizant of this association and view HL in the broader context of general health and aging.
Extreme weather events (EWEs; for example, heatwaves, cold spells, storms, floods and droughts) and non-native species invasions are two major threats to global biodiversity and are increasing in both frequency and consequences. Here we synthesize 443 studies and apply multilevel mixed-effects metaregression analyses to compare the responses of 187 non-native and 1,852 native animal species across terrestrial, freshwater and marine ecosystems to different types of EWE. Our results show that marine animals, regardless of whether they are non-native or native, are overall insensitive to EWEs, except for negative effects of heatwaves on native mollusks, corals and anemone. By contrast, terrestrial and freshwater non-native animals are only adversely affected by heatwaves and storms, respectively, whereas native animals negatively respond to heatwaves, cold spells and droughts in terrestrial ecosystems and are vulnerable to most EWEs except cold spells in freshwater ecosystems. On average, non-native animals displayed low abundance in terrestrial ecosystems, and decreased body condition and life history traits in freshwater ecosystems, whereas native animals displayed declines in body condition, life history traits, abundance, distribution and recovery in terrestrial ecosystems, and community structure in freshwater ecosystems. By identifying areas with high overlap between EWEs and EWE-tolerant non-native species, we also provide locations where native biodiversity might be adversely affected by their joint effects and where EWEs might facilitate the establishment and/or spread of non-native species under continuing global change.
Technologies and teaching practices can provide a rich log data, which enables learning analytics (LA) to bring new insights into the learning process for ultimately enhancing student success. This type of data has been used to discover student online learning patterns, relationships between online learning behaviors and assessment performance. Previous studies have provided empirical evidence that not all log variables were significantly associated with student academic achievement and the relationships varied across courses. Therefore, this study employs a systematic review with meta‐analysis method to provide a comprehensive review of the log variables that have an impact on student academic achievement. We searched six databases and reviewed 88 relevant empirical studies published from 2010 to 2021 for an in‐depth analysis. The results show different types of log variables and the learning contexts investigated in the reviewed studies. We also included four moderating factors to do moderator analyses. A further significance test was performed to test the difference of effect size among different types of log variables. Limitations and future research expectations are provided subsequently.
Practitioner notes
What is already known about this topic Significant relationship between active engagement in online courses and academic achievement was identified in a number of previous studies.
Researchers have reviewed the literature to examine different aspects of applying LA to gain insights for monitoring student learning in digital environments (eg, data sources, data analysis techniques).
What this paper adds Presents a new perspective of the log variables, which provides a reliable quantitative conclusion of log variables in predicting student academic achievement.
Conducted subgroup analysis, examined four potential moderating variables and identified their moderating effect on several log variables such as regularity of study interval, number of online sessions, time‐on‐task, starting late and late submission.
Compared the effect of generic and course‐specific, basic and elaborated log variables, and found significant difference between the basic and elaborated.
Implications for practice and/or policy A depth of understanding of these log variables may enable researchers to build robust prediction models.
It can guide the instructors to timely adjust teaching strategies according to their online learning behaviors.
Objective:
Few reviews and no meta-analyses have explored the utility of investigations, such as laboratory tests, among patients presenting with psychiatric symptoms, and none has explored the yield of history and physical examination. A meta-analysis of studies exploring the utility of "medical clearance" among adult psychiatric patients was conducted.
Methods:
PubMed, PsycInfo, and Web of Science were systematically searched from inception until February 15, 2021. Primary outcome was detection by investigations (e.g., bloodwork and imaging), history, or physical examination of an illness that caused or aggravated psychiatric symptoms or was comorbid and that resulted in change in the patient's diagnosis or management ("yield"). A mixed-effects meta-analysis with inverse-variance weighting was used to pool results.
Results:
Twenty-five cross-sectional studies were included. Pooled yield of investigations was 1.1% (95% confidence interval [CI]=0.5%-2.2%), although yield was relatively higher among disoriented, agitated, or older patients. Yield was higher in the inpatient setting, compared with the emergency room, with similar results by approach (protocolized versus nonprotocolized). Compared with investigations, yield of history and physical examination was higher (15.6%, 95% CI=9.1%-25.6%; and 14.9%, 95% CI=8.1%-25.9%, respectively), with nonsignificant differences by evaluator (psychiatrist versus nonpsychiatrist) for physical examination.
Conclusions:
Investigations were of relatively low yield, especially when weighed against cost and potential harm, and they should not be routinely conducted for patients presenting with primarily psychiatric complaints, although certain subgroups may benefit. History and physical examination, by contrast, should be undertaken for all patients, ideally with participation of the consulting psychiatrist.
Context
Whether proton pump inhibitors (PPI) can improve glycemic control among individuals with diabetes or decrease the risk of incident diabetes in the general population is unclear.
Objective
To evaluate the impact of PPI therapy on glycemic control among individuals with diabetes and the risk of diabetes among those without diabetes.
Results
PubMed, Embase, Scopus, and ClinicalTrials.gov were searched from inception to November 21, 2020. We included studies comparing glycosylated hemoglobin (HbA1c) or fasting blood glucose (FBG) among individuals with diabetes treated with and without PPI therapy as an add-on to standard therapy. Studies evaluating the risk of incident diabetes among individuals taking PPI were assessed. We performed dual independent review, data extraction, and quality assessment. Weighted mean differences between groups or relative risks were imputed using random-effects models.
Results
Seven studies (n = 342) for glycemic control and 5 studies (n = 244 439) for risk of incident diabetes were included. Compared with standard therapy, add-on PPI was associated with a significant decrease in HbA1c (WMD, −0.36 %; 95% CI, −0.68 to −0.05; P = 0.025) and FBG (WMD, −10.0 mg/dL; 95% CI, −19.4 to −0.6; P = 0.037). PPI use did not reduce the risk of incident diabetes (pooled RR, 1.10; 95% CI, 0.89 to 1.34; P = 0.385).
Conclusion
Add-on PPI improved glycemic indices among individuals with diabetes but did not alter the risk of incident diabetes. The effects of PPI on glycemic control should be considered when prescribing antacids to patients with diabetes.
Objective
The purpose of this study was to review the effects of robot-assisted therapy (RT) for improving poststroke upper extremity motor impairment.
Methods
The PubMed, EMBASE, Medline, and Web of Science databases were searched from inception to April 8, 2020. Randomized controlled trials that were conducted to evaluate the effects of RT on upper extremity motor impairment poststroke and that used Fugl-Meyer Assessment Upper Extremity (FMA-UE) scores as an outcome were included. Two authors independently screened articles, extracted data, and assessed the methodological quality of the included studies using the Physiotherapy Evidence Database (PEDro) scale. A random-effects meta-analysis was performed to pool the effect sizes across the studies.
Results
Forty-one randomized controlled trials with 1916 stroke patients were included. Compared with dose-matched conventional rehabilitation, RT significantly improved the FMA-UE scores of the patients with stroke, with a small effect size (Hedges g = 0.25; 95% CI = 0.11 to 0.38; I2 = 45.9%). The subgroup analysis revealed that the effects of unilateral RT, but not that of bilateral RT, was superior to conventional rehabilitation (Hedges g = 0.32; 95% CI = 0.15 to 0.50; I2 = 55.9%). Regarding the type of robot devices, the effects of the end effector device (Hedges g = 0.22; 95% CI = 0.09 to −0.36; I2 = 35.4%), but not the exoskeleton device, were superior to conventional rehabilitation. Regarding the stroke stage, the between-group difference (ie, RT vs convention rehabilitation) was significant only for people with late subacute or chronic stroke (Hedges g = 0.33; 95% CI = 0.16 to 0.50; I2 = 34.2%).
Conclusion
RT might be superior to conventional rehabilitation in improving upper extremity motor impairment in people after stroke with notable upper extremity hemiplegia and limited potential for spontaneous recovery.
Objective:
To investigate the effect of interpregnancy interval (IPI) on preterm birth (PTB) according to whether the previous birth was preterm or term.
Design:
Cohort study.
Setting:
USA (California), Australia, Finland, Norway (1980-2017).
Population:
Women who gave birth to first and second (n = 3 213 855) singleton livebirths.
Methods:
Odds ratios (ORs) for PTB according to IPIs were modelled using logistic regression with prognostic score stratification for potential confounders. Within-site ORs were pooled by random effects meta-analysis.
Outcome measure:
PTB (gestational age <37 weeks).
Results:
Absolute risk of PTB for each IPI was 3-6% after a previous term birth and 17-22% after previous PTB. ORs for PTB differed between previous term and preterm births in all countries (P-for-interaction ≤ 0.001). For women with a previous term birth, pooled ORs were increased for IPI <6 months (OR 1.50, 95% CI 1.43-1.58); 6-11 months (OR 1.10, 95% CI 1.04-1.16); 24-59 months (OR 1.16, 95% CI 1.13-1.18); and ≥ 60 months (OR 1.72, 95%CI 1.60-1.86), compared with 18-23 months. For previous PTB, ORs were increased for <6 months (OR 1.30, 95% CI 1.18-1.42) and ≥60 months (OR 1.29, 95% CI 1.17-1.42), but were less than ORs among women with a previous term birth (P < 0.05).
Conclusions:
Associations between IPI and PTB are modified by whether or not the previous pregnancy was preterm. ORs for short and long IPIs were higher among women with a previous term birth than a previous PTB, which for short IPI is consistent with the maternal depletion hypothesis. Given the high risk of recurrence and assuming a causal association between IPI and PTB, IPI remains a potentially modifiable risk factor for women with previous PTB.
Tweetable abstract:
Short versus long interpregnancy intervals associated with higher ORs for preterm birth (PTB) after a previous PTB.
While both methodological and applied work on Bayesian meta-analysis have flourished, Bayesian modeling of differences between groups of studies remains scarce in meta-analyses in psychology, education, and the social sciences. On rare occasions when Bayesian approaches have been used, non-informative prior distributions have been chosen. However, more informative prior distributions have recently garnered popularity. We propose a group-specific weakly informative prior distribution for the between-studies standard-deviation parameter in meta-analysis. The proposed prior distribution incorporates a frequentist estimate of the between-studies standard deviation as the noncentrality parameter in a folded noncentral t distribution. This prior distribution is then separately modeled for each subgroup of studies, as determined by a categorical factor. Use of the new prior distribution is shown in two extensive examples based on a published meta-analysis on psychological interventions aimed at increasing optimism. We compare the folded noncentral t prior distribution to several non-informative prior distributions. We conclude with discussion, limitations, and avenues for further development of Bayesian meta-analysis in psychology and the social sciences.
Background
Infections with multidrug resistant (MDR) bacteria in hospital settings have substantial implications in terms of clinical and economic outcomes. However, due to clinical and methodological heterogeneity, estimates about the attributable economic and clinical effects of healthcare-associated infections (HAI) due to MDR microorganisms (MDR HAI) remain unclear. The objective was to review and synthesize the evidence on the impact of MDR HAI in adults on hospital costs, length of stay, and mortality at discharge.
Methods and findings
Literature searches were conducted in PubMed/MEDLINE, and Google Scholar databases to select studies that evaluated the impact of MDR HAI on economic and clinical outcomes. Eligible studies were conducted in adults, in order to ensure homogeneity of populations, used propensity score matched cohorts or included explicit confounding control, and had confirmed antibiotic susceptibility testing. Risk of bias was evaluated, and effects were measured with ratios of means (ROM) for cost and length of stay, and risk ratios (RR) for mortality. A systematic search was performed on 14th March 2019, re-run on the 10th of June 2019 and extended the 3rd of September 2019. Small effect sizes were assessed by examination of funnel plots. Sixteen articles (6,122 patients with MDR HAI and 8,326 patients with non-MDR HAI) were included in the systematic review of which 12 articles assessed cost, 19 articles length of stay, and 14 mortality. Compared to susceptible infections, MDR HAI were associated with increased cost (ROM 1.33, 95%CI [1.15; 1.54]), prolonged length of stay (ROM 1.27, 95%CI [1.18; 1.37]), and excess in-hospital mortality (RR 1.61, 95%CI [1.36; 1.90]) in the random effects models. Risk of publication bias was only found to be significant for mortality, and overall study quality good.
Conclusions
MDR HAI appears to be strongly associated with increases in direct cost, prolonged length of stay and increased mortality. However, further comprehensive studies in this setting are warranted.
Trial registration
PROSPERO (CRD42019126288).
Background: Vascular complications (VCs) after transcatheter aortic valve implantation (TAVI) are associated with impaired outcome. We performed a meta-analysis to determine in-hospital/30-day major VCs rate after transfemoral-TAVI adjudicated by an independent clinical-event-committee, and to compare the major VCs rate with regard to consecutive generations of balloon-expandable and self-expanding platforms, device profile, experience and patient risk-profile.
Methods: A systematic, computerized search with predefined criteria was performed in PubMed, Embase and Cochrane on March 27, 2018. The overall pooled proportion of VC was calculated using a random-effects model. Subgroups were examined based on sheath size (low (≤ 16 French); high-profile (> 16French)), STS-score (high (STS>8%); intermediate-risk (STS 4-8%) studies) and start-date of inclusion (early (< January 2012); late-phase (≥January 2012) studies).
Results: A total of 24 unique studies with 14308 patients were included. The pooled major VCs rate was 7.71% and was lower in low-profile vs. high-profile device studies (5.51% vs. 8.46%, p=0.0015). Major VCs rate decreased significantly with transition to newer generation balloon-expandable valves ((Sapien vs. SapienXT (15.18% vs. 8.48%, p<0.00001); SapienXT vs Sapien3 (8.48% vs. 4.48%, p= 0.005)) and there was a tendency towards fewer major VCs in EvolutR vs. CoreValve (5.98% vs. 7.97%, p=0.094). Major VC rate was lower in late-phase vs. early-phase studies (5.82% vs 7.84%, p=0.048) and a tendency towards a lower rate was seen in intermediate vs. high-risk studies (7.09% vs. 9.62%, p=0.059).
Conclusion: The pooled rate of independently adjudicated major VCs after transfemoral-TAVI was 7.71%. Experience and device profile are associated with fewer major VCs.
Purpose:
Run-in periods are used to identify placebo-responders and washout. Our aim was to assess the association of run-in periods with clinical outcomes of antipsychotics in dementia.
Methods:
We searched randomized placebo-controlled trials of conventional and atypical antipsychotics for neuropsychiatric symptoms (NPS) in dementia in electronic sources and references of selected articles. We extracted (a) the presence of a run-in period, use of placebo/investigated drug during run-in (versus washout only), and run-in duration (1 week or more) and (b) the reduction in NPS, number of participants with somnolence, extrapyramidal symptoms (EPS), and deaths per treatment group. We pooled clinical outcomes comparing antipsychotic and placebo groups in trials with and without run-in.
Results:
We identified 35 trials. Twenty-nine trials used run-in. The pooled standardized mean difference in the reduction of NPS was -0.170 (95% CI, -0.227 to -0.112) in trials with run-in and -0.142 (95% CI, -0.331 to 0.047) in trials without run-in. The pooled odds ratio for somnolence was 2.8 (95% CI, 2.3-3.5) in trials with run-in and 3.5 (95% CI, 1.2-10.7) in trials without run-in; for EPS, these ORs were 1.8 (95% CI, 1.4-2.2) and 2.0 (95% CI, 1.3-3.1) respectively, and for mortality 1.4 (95% CI, 1.0-2.0) and 1.6 (95% CI, 0.7-3.4). The use of placebo/investigated drug during run-in and run-in duration did not affect the estimates in a consistent way.
Conclusions:
The use of run-in in trials might have led to overestimated efficacy and especially underestimated risks of side effects of antipsychotics compared with placebo for NPS in dementia.
Importance
Bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, remains one of the major and most common complications of very preterm birth. Insight into factors associated with the pathogenesis of BPD is key to improving its prevention and treatment.
Objective
To perform a systematic review, meta-analysis, and metaregression of clinical studies exploring the association between chorioamnionitis (CA) and BPD in preterm infants.
Data Sources
PubMed and Embase were searched without language restriction (last search, October 1, 2018). Key search terms included bronchopulmonary dysplasia, chorioamnionitis, and risk factors.
Study Selection
Included studies were peer-reviewed studies examining preterm (<37 weeks’ gestation) or very low-birth-weight (<1500 g) infants and reporting primary data that could be used to measure the association between exposure to CA and the development of BPD.
Data Extraction and Synthesis
The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. Data were independently extracted by 2 researchers. A random-effects model was used to calculate odds ratios (ORs) and 95% CIs. Heterogeneity in effect size across studies was studied using multivariate, random-effects metaregression analysis.
Main Outcomes and Measures
The primary outcome was BPD, defined as supplemental oxygen requirement on postnatal day 28 (BPD28) or at the postmenstrual age of 36 weeks (BPD36). Covariates considered as potential confounders included differences between CA-exposed and CA-unexposed infants in gestational age, rates of respiratory distress syndrome (RDS), exposure to antenatal corticosteroids, and rates of early- and late-onset sepsis.
Results
A total of 3170 potentially relevant studies were found, of which 158 met the inclusion criteria (244 096 preterm infants, 20 971 CA cases, and 24 335 BPD cases). Meta-analysis showed that CA exposure was significantly associated with BPD28 (65 studies; OR, 2.32; 95% CI, 1.88-2.86; P < .001; heterogeneity: I² = 84%; P < .001) and BPD36 (108 studies; OR, 1.29; 95% CI, 1.17-1.42; P < .001; heterogeneity: I² = 63%; P < .001). The association between CA and BPD remained significant for both clinical and histologic CA. In addition, significant differences were found between CA-exposed and CA-unexposed infants in gestational age, birth weight, odds of being small for gestational age, exposure to antenatal corticosteroids, and early- and late-onset sepsis. Chorioamnionitis was not significantly associated with RDS (48 studies; OR, 1.10; 95% CI, 0.92-1.34; P = .24; heterogeneity: I² = 90%; P < .001), but multivariate metaregression analysis with backward elimination revealed that a model combining the difference in gestational age and the odds of RDS was associated with 64% of the variance in the association between CA and BPD36 across studies.
Conclusions and Relevance
The results of this study confirm that among preterm infants, exposure to CA is associated with a higher risk of developing BPD, but this association may be modulated by gestational age and risk of RDS.
Reactivation of latent tuberculosis following solid organ transplantation has serious consequences for the recipient. The most useful diagnostic test for latent TB is not clear. We conducted a systematic review and meta‐analysis to assess the relative test performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) in people undergoing solid organ transplantation. The clinical or radiological risk factors were used as the proxy reference standard. Test performance was expressed as an odd ratio (OR). We identified 24 studies (N=7811), 12 studies compared IGRAs with TST directly, 9 studies evaluated only TST and 3 studies only IGRAs. Direct comparison between tests and clinical risk factors indicated both tests were strongly associated with the presence of clinical risk factors for TB (TST: OR 3.17; 95%CI 1.55‐6.48, IGRA: OR 2.78; 95%CI 1.55‐5.01), and radiological evidence of past TB (TST: OR 3.26; 95%CI 1.85‐5.73, IGRA: OR 3.85; 95%CI 2.16‐6.86). Relative comparison indicated IGRAs positivity was more strongly associated with presence of radiological evidence of TB than TST (relative OR: 3.24; 95%CI 1.10‐9.56). While there is no strong evidence in supporting use of IGRAs over TST for diagnosing latent TB, IGRAs positivity is more associated with presence of radiological evidence of previous TB. This article is protected by copyright. All rights reserved.
Background:
Although many studies have shown that low zinc status is associated with diabetes, the putative effects of zinc supplementation on glycemic control are inconclusive.
Objectives:
The aim of this meta-analysis of randomized controlled trials was to assess the effects of zinc supplementation in preventing and managing diabetes.
Methods:
PubMed, Embase, and the Cochrane Library were searched for articles that were published through February 10, 2019 and contained estimates for the outcomes of interest. The pooled results were then analyzed with the use of a random-effects model.
Results:
Thirty-two placebo-controlled interventions were extracted from 36 publications, involving a total of 1700 participants in 14 countries. Overall, compared with their respective control groups, the subjects in the zinc-supplementation group had a statistically significant reduction in fasting glucose [FG, weighted mean difference (WMD): -14.15 mg/dL; 95% CI: -17.36, -10.93 mg/dL], 2-h postprandial glucose (WMD: -36.85 mg/dL; 95% CI: -62.05, -11.65 mg/dL), fasting insulin (WMD: -1.82 mU/L; 95% CI: -3.10, -0.54 mU/L), homeostasis model assessment for insulin resistance (WMD: -0.73; 95% CI: -1.22, -0.24), glycated hemoglobin (WMD: -0.55%; 95% CI: -0.84, -0.27%), and high-sensitivity C-reactive protein (WMD: -1.31 mg/L; 95% CI: -2.05, -0.56 mg/L) concentrations. Moreover, subgroup analyses revealed that the effects of zinc supplementation on FG are significantly influenced by diabetic status and the formulation of the zinc supplement.
Conclusions:
Our analysis revealed that several key glycemic indicators are significantly reduced by zinc supplementation, particularly the FG in subjects with diabetes and in subjects who received an inorganic zinc supplement. Together, these findings support the notion that zinc supplementation may have clinical potential as an adjunct therapy for preventing or managing diabetes. This trial was registered at PROSPERO as CRD42018111838.
Background:
Various mechanisms link higher total homocysteine to higher insulin resistance (IR) and risk of type 2 diabetes (T2D). Folate supplementation is recognized as a way to lower homocysteine. However, randomized controlled trials (RCTs) show inconsistent results on IR and T2D outcomes.
Objective:
The aim of this study was to examine the effect of folate supplementation on IR and T2D outcomes.
Design:
We conducted a systematic literature search in PubMed, Web of Science, and EMBASE and prior systematic reviews and meta-analyses and identified 29 RCTs (22,250 participants) that assessed the effect of placebo-controlled folate supplementation alone or in combination with other B vitamins on fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), or risk of T2D. The meta-analysis was conducted using both random- and fixed-effects models to calculate weighted mean differences (WMDs) or risk ratios with 95% CIs. Subgroup analyses were conducted based on intervention type (folate alone or in combination with other B vitamins), as well as analysis based on population characteristics, duration, dose, and change in homocysteine.
Results:
When compared with placebo, folate supplementation lowered fasting insulin (WMD: -13.47 pmol/L; 95% CI: -21.41, -5.53 pmol/L; P < 0.001) and HOMA-IR (WMD: -0.57 units; 95% CI: -0.76, -0.37 units; P < 0.0001), but no overall effects were observed for fasting glucose or HbA1c. Heterogeneity was low in all meta-analyses, and subgroup analysis showed no signs of effect modification except for change in homocysteine, with the most pronounced effects in trials with a change of >2.5 µmol/L. Changes in homocysteine after folate supplementation correlated with changes in fasting glucose (β = 0.07; 95% CI: 0.01, 0.14; P = 0.025) and HbA1c (β = 0.46; 95% CI: 0.06, 0.85; P = 0.02). Only 2 studies examined folate supplementation on risk of T2D, and they found no change in RR (pooled RR: 0.91; 95% CI: 0.80, 1.04; P = 0.16).
Conclusion:
Folate supplementation might be beneficial for glucose homeostasis and lowering IR, but at present there are insufficient data to conclusively determine the effect on development of T2D. This trial was registered on the Prospero database as CRD42016048254.
Objective:
This meta-analysis synthesized the literature regarding the effect of therapist experience on internalizing client outcomes to evaluate the utility of lay providers in delivering treatment and to inform therapist training.
Method:
The analysis included 22 studies, contributing 208 effect sizes. Study and client characteristics were coded to examine moderators. We conducted subgroup meta-analyses examining the relationship of therapist experience across a diverse set of internalizing client outcomes.
Results:
Results demonstrated a small, but significant relationship between therapist experience and internalizing client outcomes. There was no relationship between therapist experience and outcomes in clients with primary anxiety disorders. In samples of clients with primary depressive disorders and in samples of clients with mixed internalizing disorders, there was a significant relationship between experience and outcomes. The relationship between therapist experience and outcomes was stronger when clients were randomized to therapists, treatment was not manualized, and for measures of client satisfaction and "other" outcomes (e.g., dropout).
Conclusions:
It appears that therapist experience may matter for internalizing clients under certain circumstances, but this relationship is modest. Continuing methodological concerns in the literature are noted, as well as recommendations to address these concerns.
Diffusion tensor imaging quantifies the asymmetry (fractional anisotropy; FA) and amount of water diffusion (mean diffusivity/apparent diffusion coefficient; MD/ADC) and has been used to assess white matter damage following traumatic brain injury (TBI). In healthy brains, diffusion is constrained by the organization of axons, resulting in high FA and low MD/ADC. Following a TBI, diffusion may be altered; however the exact nature of these changes has yet to be determined. A meta-analysis was therefore conducted to determine the location and extent of changes in DTI following adult TBI. The data from 44 studies that compared the FA and/or MD/ADC data from TBI and Control participants in different regions of interest (ROIs) were analyzed. The impact of injury severity, post-injury interval (acute: ≤ 1 week, subacute: 1 week-3 months, chronic: > 3 months), scanner details and acquisition parameters were investigated in subgroup analyses, with the findings indicating that mild TBI should be examined separately to that of moderate to severe injuries. Lower FA values were found in 88% of brain regions following mild TBI and 92% following moderate-severe TBI, compared to Controls. MD/ADC was higher in 95% and 100% of brain regions following mild and moderate-severe TBI, respectively. Moderate to severe TBI resulted in larger changes in FA and MD/ADC than mild TBI. Overall, changes to FA and MD/ADC were widespread, reflecting more symmetric and a higher amount of diffusion, indicative of white matter damage.
Metformin and insulin differently affect the risk of colon cancer in type 2 diabetic patients, however their effects on colon adenoma is not clear. PubMed, ISI, Scopus and Cochrane databases were searched for studies reporting. The outcomes were total adenoma; advanced adenoma and recurrent adenoma. Traditional and Bayesian metaanalysis were conducted via random-effects models. Odds ratios (OR) with 95% confidence intervals (CIs)/or credible intervals (CrI) were used to describe the ratio of different events. A random-effects model described by DerSimonian and Laird was performed, when significant between-study heterogeneity existed. Alternatively, an inverse variance fixed effects model was used, when there was no significant heterogeneity across studies. The potential publication bias was assessed with funnel plot, Egger and Begg's regression asymmetry tests. Moreover, “trim and fill” procedure was used to assess the possible effect of publication bias. For metformin intake, 11 studies (51991 patients) were included. The results showed that metformin significantly decreased the risk of advance adenoma (OR= 0.51, p< 0.001). The risk of total adenoma was not associated with metformin use (OR= 0.86, p=0.274), and metformin did not affect the risk of adenoma recurrence (OR= 0.89, p=0.137). Five studies (2678 patients) were included in the analysis to determine the effect of insulin therapy. Insulin significantly increased the risk of colorectal adenoma (OR= 1.43, p=0.002). These findings indicate that metformin has no protective effect on total and recurrent adenoma, whilst it significantly reduces the risk of advanced adenoma, but insulin increases the risk of total adenoma. © 2018, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.
Objectives:
The objective of this study was to evaluate the association between salivary and plaque arginine levels/ADS activities with dental caries.
Materials and methods:
A systematic search was performed as per PRISMA statement using PubMed, Scopus, Cochrane Library, and Web of Science. Published studies that investigated adults and children (P) with caries-active status (E) and caries-free status (C), whereby arginine levels/ADS activity (O) was measured in saliva/plaque to analyze exposure-outcome association compared to the control group were deemed eligible for inclusion. Quality assessment was performed using combined Newcastle-Ottawa Scale and Modified RTI Item Bank scale. Meta-analysis was performed for effect size, precision estimation, and subgroup effects analysis.
Results:
Of 233 records identified, seven (κ = 1.00) were included for qualitative synthesis (systematic review) and four for quantitative synthesis (meta-analysis). No specific bias could be identified in five studies assessed as per the Modified RTI Item Bank scale. Two studies received lower scores on the Newcastle Ottawa scale. Plaque ADS activity in adults (effect size = 0.93, p = 0.008), salivary ADS activity in adults and children (effect size = 0.85, p < 0.001), and salivary ADS activity in adults (effect size = 0.87, p < 0.001) identified a statistically significant effect size. Subgroup analysis demonstrated non-significant variance (Q value = 0.042, p = 0.838) between saliva and plaque ADS activities of adults.
Conclusions:
The results of this review suggest the salivary and plaque ADS activities appear to be promising caries risk indicators for adults, while results remain inconclusive in children.
Clinical relevance:
Measuring ADS activities (saliva or plaque) can be a potential caries risk indicator in adults. The protocol was registered on PROSPERO database: CRD42017060701.
PurposeEvidence suggests anti-estrogen endocrine therapy (ET) is associated with adverse cognitive effects; however, findings are based on small samples and vary in the cognitive abilities affected. We conducted a meta-analysis to quantitatively synthesize the evidence. Methods
Electronic databases were searched in November 2016. Fourteen studies totaling 911 BC patients on aromatase inhibitors (AIs) or tamoxifen (TAM) and 911 controls (i.e., non-cancer controls and BC controls not using ET) were included. Neuropsychological tests were categorized into six domains. Effect sizes were computed to compare (1) ET patients versus controls and (2) TAM patients versus AI patients. ResultsIn cross-sectional comparisons, ET patients performed worse than control groups on verbal learning/memory, visual learning/memory, frontal executive function, and processing speed, but did not differ on psychomotor efficiency or visuospatial function. Subgroup analyses revealed that verbal learning/memory was the only domain where ET patients performed worse than both non-cancer and BC controls. In other domains, ET patients and BC controls performed equivalently. Regarding change from pre-treatment performance, ET patients did not differ from controls on any domain. TAM and AI patients did not from one another differ overall; however, subgroup analyses indicated that TAM patients performed better than non-steroidal AI patients on several domains, but showed few performance differences relative to steroidal AI patients. Conclusions
Verbal learning/memory was the only domain where ET patients performed worse than both non-cancer and BC controls, suggesting specific adverse effects on this domain. Additional studies assessing change from pre-treatment performance and differences between steroidal and non-steroidal AIs are warranted.
Context:
Late-preterm infants born at 34 to 36 weeks' gestation have increased risks of various health problems. Health service utilization (HSU) of late-preterm infants has not been systematically summarized before.
Objectives:
To summarize the published literature on short- and long-term HSU by late-preterm infants versus term infants from infancy to adulthood after initial discharge from the hospital.
Data sources:
We searched Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, and PsycINFO.
Study selection:
Cohort and case-control studies that compared HSU (admissions, emergency department visits, etc) between late-preterm infants and term infants were included.
Data extraction:
Data extracted included study design, setting, population, HSU, covariates, and effect estimates.
Results:
Fifty-two articles were included (50 cohort and 2 case-control studies). Meta-analyses with random effect models that used the inverse-variance method found that late-preterm infants had higher chances of all-cause admissions than term infants during all the time periods. The magnitude of the differences decreased with age from the neonatal period through adolescence, with adjusted odds ratios from 2.34 (95% confidence intervals 1.19-4.61) to 1.09 (1.05-1.13) and adjusted incidence rate ratios from 2.62 (2.52-2.72) to 1.14 (1.11-1.18). Late-preterm infants had higher rates of various cause-specific HSU than term infants for jaundice, infection, respiratory problems, asthma, and neurologic and/or mental health problems during certain periods, including adulthood.
Limitations:
Considerable heterogeneity existed and was partially explained by the variations in the adjustment for multiple births and gestational age ranges of the term infants.
Conclusions:
Late-preterm infants had higher risks for all-cause admissions as well as for various cause-specific HSU during the neonatal period through adolescence.
Vividness is an aspect of consciousness related to mental imagery and prospective episodic memory. Despite being harshly criticized in the past for failing to demonstrate robust correlations with behavioral measures, currently this construct is attracting a resurgent interest in cognitive neuroscience. Therefore, an updated examination of the validity of this construct is timely. A corpus of peer-reviewed literature was analyzed through meta-analysis, which compared the two main formats used to measure vividness [trial-by-trial vividness ratings (VR) and the Vividness of Visual Imagery Questionnaire (VVIQ)]. These two formats were compared in relation to all available behavioral/cognitive (BC) and neuroscience (NS) measures in Phase 1 (3542 statistical observations representing 393 journal articles); and then in relation to all available BC, EEG and fMRI literature in Phase 2 (3624 observations representing 402 articles). Both Phases observed significantly larger effect size estimates (ESEs) for VR than VVIQ, and larger ESEs for NS than BC measures. ESEs for EEG and fMRI were not significantly different in Phase 2, but were greater than BC ESEs. These data suggest VR are a more reliable self-report measure than VVIQ, and may reflect a more direct route of reportability than the latter. Furthermore, both VR and VVIQ are more strongly associated with the neural, than the cognitive and behavioural correlates of imagery. If one establishes neuroscience measures as the criterion variable, then self-reports of vividness show higher construct validity than behavioural/cognitive measures of imagery. We discuss how the present findings contribute to current issues on measurement of reportability; and how this study advances our understanding of vividness as a phenomenological characteristic of imagery, and other forms of conscious experience which do not necessarily involve imagery.
Objective:
To integrate long-term measures of disease-modifying drug efficacy and risk to guide selection of first-line treatment of multiple sclerosis.
Methods:
We created a Markov decision model to evaluate disability worsening and progressive multifocal leukoencephalopathy (PML) risk in patients receiving natalizumab (NTZ), fingolimod (FGL), or glatiramer acetate (GA) over 30 years. Leveraging publicly available data, we integrated treatment utility, disability worsening, and risk of PML into quality-adjusted life-years (QALYs). We performed sensitivity analyses varying PML risk, mortality and morbidity, and relative risk of disease worsening across clinically relevant ranges.
Results:
Over the entire reported range of NTZ-associated PML risk, NTZ as first-line therapy is predicted to provide a greater net benefit (15.06 QALYs) than FGL (13.99 QALYs) or GA (12.71 QALYs) treatment over 30 years, after accounting for loss of QALYs due to PML or death (resulting from all causes). NTZ treatment is associated with delayed worsening to an Expanded Disability Status Scale score ≥6.0 vs FGL or GA (22.7, 17.0, and 12.4 years, respectively). Compared to untreated patients, NTZ-treated patients have a greater relative risk of death in the early years of treatment that varies according to PML risk profile.
Conclusions:
NTZ as a first-line treatment is associated with the highest net benefit across full ranges of PML risk, mortality, and morbidity compared to FGL or GA. Integrated modeling of long-term treatment risks and benefits informs stratified clinical decision-making and can support patient counseling on selection of first-line treatment options.
Aims:
Several authors claimed that expression of suicidal ideation is one of the most important predictors of completed suicide. However, the strength of the association between suicidal ideation and subsequent completed suicide has not been firmly established in different populations. Furthermore, the absolute suicide risk after expression of suicidal ideation is unknown. In this meta-analysis, we examined whether the expression of suicidal ideation predicted subsequent completed suicide in various populations, including both psychiatric and non-psychiatric populations.
Methods:
A meta-analysis of cohort and case-control studies that assessed suicidal ideation as determinant for completed suicide in adults. Two independent reviewers screened 5726 articles for eligibility and extracted data of the 81 included studies. Pooled risk ratios were estimated in a random effects model stratified for different populations. Meta-regression analysis was used to determine suicide risk during the first year of follow-up.
Results:
The risk for completed suicide was clearly higher in people who had expressed suicidal ideation compared with people who had not, with substantial variation between the different populations: risk ratio ranging from 2.35 (95% confidence interval (CI) 1.43-3.87) in affective disorder populations to 8.00 (95% CI 5.46-11.7) in non-psychiatric populations. In contrast, the suicide risk after expression of suicidal ideation in the first year of follow-up was higher in psychiatric patients (risk 1.40%, 95% CI 0.74-2.64) than in non-psychiatric participants (risk 0.23%, 95% CI 0.10-0.54). Past suicide attempt-adjusted risk ratios were not pooled due to large underreporting.
Conclusions:
Assessment of suicidal ideation is of priority in psychiatric patients. Expression of suicidal ideation in psychiatric patients should prompt secondary prevention strategies to reduce their substantial increased risk of suicide.
Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous hematopoietic stem cell transplantation (AHSCT) using BEAM or cyclophosphamide (CY) based conditioning regimens. Patients were followed for clinical and immunological parameters for two years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL, and increased A1 gene expression when compared with healthy counterparts. In the BEAM-group, BAK, BIK, BIMEL, FAS, FASL, A1, BCL2, BCLXL, CFLIPL and CIAP2 genes were upregulated after AHSCT. With exception of BIK, BIMEL and A1, all genes reached levels similar to controls at D+720 post-transplantation. Furthermore, in these patients, we observed increased CD8+Fas+ T-cell frequencies after AHSCT, when compared to baseline. In the CY-group, we observed increased BAX, BCLW, CFLIPL, CIAP1, and decreased BIK and BID gene expressions after transplantation. At D+720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLXL and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At one year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the reestablishment of immune tolerance during the first two years post-transplantation. This article is protected by copyright. All rights reserved.
Purpose:
Sedentary behavior, characterized by a sitting or reclining posture and low-energy expenditure, has been recognized as an independent health risk factor. We conducted a systematic review and meta-analysis to examine the association between sedentary behavior and sleep problems.
Method:
Keyword and reference search were performed in PubMed, Cochrance Library, and Web of Science databases to identify relevant studies. The methodological quality of each study was assessed by standardized tools. The pooled estimates on the relationship between sedentary behavior and sleep problems were calculated in meta-analysis. Subgroup analyses were conducted for studies examining alternative sedentary behavior types, using self-reported or objective measures of sedentary behavior, different age groups, and assessed with different study quality levels.
Results:
Sixteen eligible studies were identified through a literature search. Meta-analysis found sedentary behavior to be associated with an increased risk of insomnia (pooled odds ratio [POR] = 1.176, 95% confidence interval [CI] = 1.014-1.364) and sleep disturbance (POR = 1.381, 95% CI = 1.282-1.488). No association between sedentary behavior and daytime sleepiness and/or poor sleep quality was observed. Except for study quality levels, no significant differences in sleep disturbance were observed across alternative sedentary behavior types, sedentary behavior measures, and age groups in subgroup analyses.
Conclusions:
Prolonged sedentary behavior tends to be associated with an elevated risk of insomnia and sleep disturbance in the existing literature. Future studies with experimental study design and longer follow-up periods are warranted to demonstrate the long-term causal impact of sedentary behavior on sleep problems.
Background and purpose:
Endovascular intervention for emergent large-vessel occlusion (ELVO) has evolved rapidly during the past decade. The question of whether pretreatment with intravenous thrombolysis (IVT) has a significant impact on the functional outcome of patients with ELVO still remains unanswered.
Methods:
We conducted a systematic review and meta-analysis of all available randomized controlled trials evaluating the efficacy of endovascular therapy (ET) for acute ischemic stroke. We performed a mixed-effects subgroup analysis of the reported odds ratios on the association of ET (versus standard therapy) with 3-month functional outcome, stratified by pretreatment with IVT.
Results:
Six randomized controlled trials were included, comprising 1916 total patients (49.1% receiving ET with IVT pretreatment and 5.6% receiving ET without IVT pretreatment). In the subgroup analysis, ET was associated with a higher likelihood of better 3-month functional outcome in both the subgroup of patients with (odds ratio=1.83; 95% confidence interval, 1.37-2.44; P<0.001) and without (odds ratio=2.47; 95% confidence interval, 1.32-4.63; P=0.001) pretreatment with IVT. We documented no significant effect of IVT pretreatment on the 3-month functional outcome of patients with ELVO undergoing ET, suggesting that ET is effective in all patients with ELVO. Heterogeneity was documented in the IVT pretreatment subgroup (I(2)=68.3%; P for Cochran Q=0.014), but not in the subgroup that did not receive IVT pretreatment (I(2)=0%, P for Cochran Q=0.927). The risk of bias was considered to be generally low in the qualitative assessment of the included trials.
Conclusions:
Our observation provides evidence and further reassurance to stroke clinicians regarding the efficacy of ET in ELVO independent of pretreatment with IVT.
Aim:
Both oral and intravenous proton pump inhibitors (PPIs) are equipotent in raising gastric pH, however, whether oral PPI can replace intravenous PPI in patients with bleeding peptic ulcers is unknown.
Methods:
We conducted a systematic review and meta-analysis of randomized controlled trials to compare oral and intravenous PPIs among patients with peptic ulcer bleeding. A search for all major databases and relevant journals from inception to April 2015 without restriction on languages was performed.
Results:
A total of 859 patients from seven randomized controlled trials were included in the meta-analysis. Similar pooled outcome was demonstrated in terms of oral PPI versus intravenous PPI in the rate of recurrent bleeding within a 30-day of follow-up period (risk ratio = 0.90; 95%CI: 0.58, 1.39; P = 0.62; I(2) = 0%). In terms of the rate of mortality, both oral and intravenous PPIs showed similar outcomes, and the pooled risk ratio was 0.88 (95%CI: 0.29, 2.71; P = 0.82; I(2) = 0%). Likewise, no significant difference was detected in blood transfusion and hospital stay, and the pooled mean differences were -0.14 (95%CI: -0.39, 0.12; P = 0.29; I(2) = 32%) and -0.60 (95%CI: -1.42, 0.23; P = 0.16; I(2) = 79%) respectively.
Conclusions:
Our results suggest that the effectiveness of oral PPI is a feasible, safe alternative to intravenous PPI in patients with bleeding peptic ulcers. Oral PPI may be able to replace intravenous PPI as the treatment of choice in peptic ulcer bleeding. This article is protected by copyright. All rights reserved.
There is an urgent need to treat individuals with high blood pressure (BP) with effective dietary strategies. Previous studies suggest a small, but significant decrease in BP after lactotripeptides (LTP) ingestion, although the data are inconsistent. The study aim was to perform a comprehensive meta-analysis of data from all relevant randomised controlled trials (RCT). Medline, Cochrane library, EMBASE and Web of Science were searched until May 2014. Eligibility criteria were RCT that examined the effects of LTP on BP in adults, with systolic BP (SBP) and diastolic BP (DBP) as outcome measures. Thirty RCT met the inclusion criteria, which resulted in 33 sets of data. The pooled treatment effect for SBP was -2.95 mmHg (95% CI: -4.17, -1.73; p < 0.001), and for DBP was -1.51 mmHg (95% CI: -2.21, -0.80; p < 0.001). Sub-group analyses revealed that reduction of BP in Japanese studies was significantly greater, compared with European studies (p = 0.002 for SBP and p < 0.001 for DBP). The 24-h ambulatory BP (AMBP) response to LTP supplementation was statistically non-significant (p = 0.101 for SBP and p = 0.166 for DBP). Both publication bias and "small-study effect" were identified, which shifted the treatment effect towards less significant SBP and non-significant DBP reduction after LTP consumption. LTP may be effective in BP reduction, especially in Japanese individuals; however sub-group, meta-regression analyses and statistically significant publication biases suggest inconsistencies.
It is hypothesized that prenatal and early postnatal exposure to n-3 long-chain polyunsaturated fatty acids (LCPUFAs) is negatively associated with adiposity later in life. We conducted a systematic review and meta-analysis to evaluate whether maternal n-3 LCPUFA supplementation in pregnancy and/or lactation exerts a beneficial effect on adiposity status in childhood. We searched six electronic databases till 20 May 2014 for randomized controlled trials (RCTs) of n-3 LCPUFA supplementation to pregnant and/or lactating women that reported data on body mass index (BMI), waist circumference, sum of skinfold thicknesses or body fat mass in children. Adiposity measures were grouped into three age categories: preschool children (<5 years), school-aged children (6-12 years), and adolescents (>13 years). Trial quality was assessed. We conducted fixed-effect and random-effects meta-analyses to combine study-specific estimates of differences between the supplemented and control groups. A total of 6 RCTs (9 publications) involving 2847 participants were included. Summary estimates showed no effect of maternal supplementation on BMI in preschool (standardized mean difference (SMD)=0.07, 95% confidence interval (CI)=-0.22, 0.36, P=0.65) and school-aged children (SMD=0.12, 95% CI=-0.06, 0.30, P=0.20). Because of sparse data, it was not possible to pool study results relating to other adiposity measures. There is currently no evidence to support that n-3 LCPUFA supplementation during pregnancy and/or lactation favourably affects child adiposity. Further high-quality trials are needed.European Journal of Clinical Nutrition advance online publication, 13 August 2014; doi:10.1038/ejcn.2014.158.
Alveolar ridge preservation strategies are indicated to minimize the loss of ridge volume that typically follows tooth extraction. The aim of this systematic review was to determine the effect that socket filling with a bone grafting material has on the prevention of postextraction alveolar ridge volume loss as compared with tooth extraction alone in nonmolar teeth. Five electronic databases were searched to identify randomized clinical trials that fulfilled the eligibility criteria. Literature screening and article selection were conducted by 3 independent reviewers, while data extraction was performed by 2 independent reviewers. Outcome measures were mean horizontal ridge changes (buccolingual) and vertical ridge changes (midbuccal, midlingual, mesial, and distal). The influence of several variables of interest (i.e., flap elevation, membrane usage, and type of bone substitute employed) on the outcomes of ridge preservation therapy was explored via subgroup analyses. We found that alveolar ridge preservation is effective in limiting physiologic ridge reduction as compared with tooth extraction alone. The clinical magnitude of the effect was 1.89 mm (95% confidence interval [CI]: 1.41, 2.36; p < .001) in terms of buccolingual width, 2.07 mm (95% CI: 1.03, 3.12; p < .001) for midbuccal height, 1.18 mm (95% CI: 0.17, 2.19; p = .022) for midlingual height, 0.48 mm (95% CI: 0.18, 0.79; p = .002) for mesial height, and 0.24 mm (95% CI: -0.05, 0.53; p = .102) for distal height changes. Subgroup analyses revealed that flap elevation, the usage of a membrane, and the application of a xenograft or an allograft are associated with superior outcomes, particularly on midbuccal and midlingual height preservation.
Traumatic spinal cord injury (SCI) is a devastating event with huge personal and societal costs. A limited number of treatments exist to ameliorate the progressive secondary damage that rapidly follows the primary mechanical impact. Mesenchymal stem or stromal cells (MSCs) have anti-inflammatory and neuroprotective effects and may thus reduce secondary damage after administration. We performed a systematic review with quantitative syntheses to assess the evidence of MSCs versus controls for locomotor recovery in rat models of traumatic SCI, and identified 83 eligible controlled studies comprising a total of 1,568 rats. Between-study heterogeneity was large. Fifty-three studies (64%) were reported as randomised, but only four reported adequate methodologies for randomisation. Forty-eight studies (58%) reported the use of a blinded outcome assessment. A random-effects meta-analysis yielded a difference in behavioural Basso-Beattie-Bresnahan (BBB) locomotor score means of 3.9 (95% confidence interval [CI] 3.2 to 4.7; P<0.001) in favour of MSCs. Trial sequential analysis confirmed the findings of the meta-analyses with the upper monitoring boundary for benefit being crossed by the cumulative Z-curve before reaching the diversity-adjusted required information size. Only time from intervention to last follow-up remained statistically significant after adjustment using multivariate random-effects meta-regression modeling. Lack of other demonstrable explanatory variables could be due to insufficient meta-analytic study power. MSCs would seem to demonstrate a substantial beneficial effect on locomotor recovery in a widely-used animal model of traumatic SCI. However, the animal results should be interpreted with caution concerning the internal and external validity of the studies in relation to the design of future clinical trials.
The explanation of heterogeneity plays an important role in meta-analysis. The random effects meta-regression model allows the inclusion of trial-specific covariates which may explain a part of the heterogeneity. We examine the commonly used tests on the parameters in the random effects meta-regression with one covariate and propose some new test statistics based on an improved estimator of the variance of the parameter estimates. The approximation of the distribution of the newly proposed tests is based on some theoretical considerations. Moreover, the newly proposed tests can easily be extended to the case of more than one covariate. In a simulation study, we compare the tests with regard to their actual significance level and we consider the log relative risk as the parameter of interest. Our simulation study reflects the meta-analysis of the efficacy of a vaccine for the prevention of tuberculosis originally discussed in Berkey et al. The simulation study shows that the newly proposed tests are superior to the commonly used test in holding the nominal significance level.
Controlling the risk of spurious findings from metaregression
- J P T Higgins
- S Thompson
Higgins, J.P.T., & Thompson, S.G (2004). Controlling the risk of spurious findings from metaregression. Statistics in Medicine 23,1663-1682.