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Journal of Clinical Medicine May 2019Breast density, a measure of dense fibroglandular tissue relative to non-dense fatty tissue, is confirmed as an independent risk factor of breast cancer. Although there... (Review)
Review
Breast density, a measure of dense fibroglandular tissue relative to non-dense fatty tissue, is confirmed as an independent risk factor of breast cancer. Although there has been an increasing interest in the quantitative assessment of breast density, no research has investigated the optimal technical approach of breast MRI in this aspect. Therefore, we performed a systematic review and meta-analysis to analyze the current studies on quantitative assessment of breast density using MRI and to determine the most appropriate technical/operational protocol. Databases (PubMed, EMBASE, ScienceDirect, and Web of Science) were searched systematically for eligible studies. Single arm meta-analysis was conducted to determine quantitative values of MRI in breast density assessments. Combined means with their 95% confidence interval (CI) were calculated using a fixed-effect model. In addition, subgroup meta-analyses were performed with stratification by breast density segmentation/measurement method. Furthermore, alternative groupings based on statistical similarities were identified via a cluster analysis employing study means and standard deviations in a Nearest Neighbor/Single Linkage. A total of 38 studies matched the inclusion criteria for this systematic review. Twenty-one of these studies were judged to be eligible for meta-analysis. The results indicated, generally, high levels of heterogeneity between study means within groups and high levels of heterogeneity between study variances within groups. The studies in two main clusters identified by the cluster analysis were also subjected to meta-analyses. The review confirmed high levels of heterogeneity within the breast density studies, considered to be due mainly to the applications of MR breast-imaging protocols and the use of breast density segmentation/measurement methods. Further research should be performed to determine the most appropriate protocol and method for quantifying breast density using MRI.
PubMed: 31137728
DOI: 10.3390/jcm8050745 -
ERJ Open Research Apr 2019Primary ciliary dyskinesia (PCD) is a genetic, heterogeneous disease caused by dysfunction of cilia. Evidence is sparse and reports of lung function in PCD patients... (Review)
Review
Primary ciliary dyskinesia (PCD) is a genetic, heterogeneous disease caused by dysfunction of cilia. Evidence is sparse and reports of lung function in PCD patients range from normal to severe impairment. This systematic review and meta-analysis of studies of lung function in PCD patients examines the spirometric indices of PCD patients and differences by age group and sex. We searched PubMed, Embase and Scopus for studies that described lung function in 10 or more patients with PCD. We performed meta-analyses and meta-regression to explain heterogeneity. We included 24 studies, ranging from 13 to 158 patients per study. The most commonly reported spirometric indices were forced expiratory volume in 1 s (FEV) and forced vital capacity presented as mean and standard deviation of percent predicted values. We found considerable heterogeneity for both parameters ( =94-96%). The heterogeneity remained when we stratified the analysis by age; however, FEV in adult patients was lower. Even after taking into account explanatory factors, the largest part of the between-studies variance remained unexplained. Heterogeneity could be explained by genetic differences between study populations, methodological factors related to the variability of study inclusion criteria or details on the performance and evaluation of lung function measurements that we could not account for. Prospective studies therefore need to use standardised protocols and international reference values. These results underline the possibility of distinct PCD phenotypes as in other chronic respiratory diseases. Detailed characterisation of these phenotypes and related genotypes is needed in order to better understand the natural history of PCD.
PubMed: 31111042
DOI: 10.1183/23120541.00231-2018 -
Plastic Surgery (Oakville, Ont.) May 2019Posterior interosseous nerve (PIN) resection in combination with proximal row carpectomy (PRC), is a preferred method in order to obtain rapid recovery. However, the...
BACKGROUND
Posterior interosseous nerve (PIN) resection in combination with proximal row carpectomy (PRC), is a preferred method in order to obtain rapid recovery. However, the contribution of such combination to results isn't known well.
OBJECTIVES
We performed a comparative study to evaluate the effects of PIN neurectomy for PRC and a systematic review of the literature was performed to identify whether such combination has an advantage.
METHODS
Patients with wrist diseases who underwent PRC were evaluated retrospectively. Patients without PIN neurectomy (group 1, n = 7) and with PIN neurectomy (group 2, n = 8) were compared in respect of mean age, follow-up, gender, Q-DASH, VAS, MAYO wrist scores, flexion-extension/radial-ulnar deviation range of motion at final follow-up. The MEDLINE database was searched for studies published between 2005 and 2015, as the second part of the study. The following keywords were used: "proximal," "row," "carpectomy." Studies, which met the inclusion criteria, were evaluated in terms of such combination.
RESULTS
There were no significant difference between the groups in regard with age ( = .463), follow-up period ( = .728), the ranges of flexion-extension ( = .431) and radio-ulnar deviation ( = .689), Q-DASH ( = .452), and MAYO scores ( = .728). In the second part of the study, 12 studies met the inclusion criteria and none of them was specifically evaluating such combination. Only one study had specific comments on PRC with PIN neurectomy.
CONCLUSION
According to our study (which, to our knowledge, was the first comparative study in the literature), we advocate not to combine PRC with PIN neurectomy for such an approach has no advantage.
PubMed: 31106170
DOI: 10.1177/2292550319826099 -
Critical Care (London, England) Feb 2019With the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
With the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in pulmonary disease diagnosis. We aimed to review and summarize lung fluid biomarkers associated with acute respiratory distress syndrome diagnosis and mortality.
METHODS
After searching PubMed, Embase, Web of Science, and the Cochrane Library for articles published prior to January 11, 2018, we performed a meta-analysis on biomarkers for acute respiratory distress syndrome diagnosis in at-risk patients and those related to disease mortality. From the included studies, we then extracted the mean and standard deviation of the biomarker concentrations measured in the lung fluid, acute respiratory distress syndrome etiologies, sample size, demographic variables, diagnostic criteria, mortality, and protocol for obtaining the lung fluid. The effect size was measured by the ratio of means, which was then synthesized by the inverse-variance method using its natural logarithm form and transformed to obtain a pooled ratio and 95% confidence interval.
RESULTS
In total, 1156 articles were identified, and 49 studies were included. Increases in total phospholipases A2 activity, total protein, albumin, plasminogen activator inhibitor-1, soluble receptor for advanced glycation end products, and platelet activating factor-acetyl choline were most strongly associated with acute respiratory distress syndrome diagnosis. As for biomarkers associated with acute respiratory distress syndrome mortality, interleukin-1β, interleukin-6, interleukin-8, Kerbs von Lungren-6, and plasminogen activator inhibitor-1 were significantly increased in the lung fluid of patients who died. Decreased levels of Club cell protein and matrix metalloproteinases-9 were associated with increased odds for acute respiratory distress syndrome diagnosis, whereas decreased levels of Club cell protein and interleukin-2 were associated with increased odds for acute respiratory distress syndrome mortality.
CONCLUSIONS
This meta-analysis provides a ranking system for lung fluid biomarkers, according to their association with diagnosis or mortality of acute respiratory distress syndrome. The performance of biomarkers among studies shown in this article may help to improve acute respiratory distress syndrome diagnosis and outcome prediction.
Topics: Antigens, Human Platelet; Biomarkers; Bronchoalveolar Lavage Fluid; Hepatocyte Growth Factor; Humans; Interleukin-8; Lung; Plasminogen Activator Inhibitor 1; Platelet Activating Factor; Receptor for Advanced Glycation End Products; Respiratory Distress Syndrome
PubMed: 30755248
DOI: 10.1186/s13054-019-2336-6 -
The Cochrane Database of Systematic... Jan 2019People with cancer with febrile neutropenia are at risk of severe infections and mortality and are thus treated empirically with broad-spectrum antibiotic therapy.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
People with cancer with febrile neutropenia are at risk of severe infections and mortality and are thus treated empirically with broad-spectrum antibiotic therapy. However, the recommended duration of antibiotic therapy differs across guidelines.
OBJECTIVES
To assess the safety of protocol-guided discontinuation of antibiotics regardless of neutrophil count, compared to continuation of antibiotics until neutropenia resolution in people with cancer with fever and neutropenia, in terms of mortality and morbidity. To assess the emergence of resistant bacteria in people with cancer treated with short courses of antibiotic therapy compared with people with cancer treated until resolution of neutropenia.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 10) in the Cochrane Library, MEDLINE, Embase, and LILACS up to 1 October 2018. We searched the metaRegister of Controlled Trials and the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov for ongoing and unpublished trials. We reviewed the references of all identified studies for additional trials and handsearched conference proceedings of international infectious diseases and oncology and haematology conferences.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared a short antibiotic therapy course in which discontinuation of antibiotics was guided by protocols regardless of the neutrophil count to a long course in which antibiotics were continued until neutropenia resolution in people with cancer with febrile neutropenia. The primary outcome was 30-day or end of follow-up all-cause mortality.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed all studies for eligibility, extracted data, and assessed risk of bias for all included trials. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) whenever possible. For dichotomous outcomes with zero events in both arms of the trials, we conducted meta-analysis of risk differences (RDs) as well. For continuous outcomes, we extracted means with standard deviations (SD) from the studies and computed mean difference (MD) and 95% CI. If no substantial clinical heterogeneity was found, trials were pooled using the Mantel-Haenszel fixed-effect model.
MAIN RESULTS
We included eight RCTs comprising a total of 662 distinct febrile neutropenia episodes. The studies included adults and children, and had variable design and criteria for discontinuation of antibiotics in both study arms. All included studies but two were performed before the year 2000. All studies included people with cancer with fever of unknown origin and excluded people with microbiological documented infections.We found no significant difference between the short-antibiotic therapy arm and the long-antibiotic therapy arm for all-cause mortality (RR 1.38, 95% CI 0.73 to 2.62; RD 0.02, 95% CI -0.02 to 0.05; low-certainty evidence). We downgraded the certainty of the evidence to low due to imprecision and high risk of selection bias. The number of fever days was significantly lower for people in the short-antibiotic treatment arm compared to the long-antibiotic treatment arm (mean difference -0.64, 95% CI -0.96 to -0.32; I² = 30%). In all studies, total antibiotic days were fewer in the intervention arm by three to seven days compared to the long antibiotic therapy. We found no significant differences in the rates of clinical failure (RR 1.23, 95% CI 0.85 to 1.77; very low-certainty evidence). We downgraded the certainty of the evidence for clinical failure due to variable and inconsistent definitions of clinical failure across studies, possible selection bias, and wide confidence intervals. There was no significant difference in the incidence of bacteraemia occurring after randomisation (RR 1.56, 95% CI 0.91 to 2.66; very low-certainty evidence), while the incidence of any documented infections was significantly higher in the short-antibiotic therapy arm (RR 1.67, 95% CI 1.08 to 2.57). There was no significant difference in the incidence of invasive fungal infections (RR 0.86, 95% CI 0.32 to 2.31) and development of antibiotic resistance (RR 1.49, 95% CI 0.62 to 3.61). The data on hospital stay were too sparse to permit any meaningful conclusions.
AUTHORS' CONCLUSIONS
We could make no strong conclusions on the safety of antibiotic discontinuation before neutropenia resolution among people with cancer with febrile neutropenia based on the existing evidence and its low certainty. Results of microbiological outcomes favouring long antibiotic therapy may be misleading due to lower culture positivity rates under antibiotic therapy and not true differences in infection rates. Well-designed, adequately powered RCTs are required that address this issue in the era of rising antibiotic resistance.
Topics: Adult; Anti-Bacterial Agents; Child; Drug Resistance, Bacterial; Febrile Neutropenia; Humans; Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome; Withholding Treatment
PubMed: 30605229
DOI: 10.1002/14651858.CD012184.pub2 -
The Cochrane Database of Systematic... Nov 2018Risky consumption of alcohol is a global problem. More than 3.3 million deaths annually are associated with risky use of alcohol, and global alcohol consumption... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Risky consumption of alcohol is a global problem. More than 3.3 million deaths annually are associated with risky use of alcohol, and global alcohol consumption continues to increase. People who have high alcohol consumption often require planned and emergency surgical procedures.Risky drinking is associated with increased postoperative complications such as infections, cardiopulmonary complications, and bleeding episodes. Alcohol causes disorders of the liver, pancreas, and nervous system. Stopping consumption of alcohol can normalize these organ systems to some degree and may reduce the occurrence of complications after surgery.This review was first published in 2012 and was updated in 2018.
OBJECTIVES
To assess the effects of perioperative alcohol cessation interventions on rates of postoperative complications and alcohol consumption.
SEARCH METHODS
We searched the following databases up until 21 September 2018: Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; CINAHL via EBSCOhost; and two trials registers. We scanned the reference lists and citations of included trials and any identified relevant systematic reviews for further references to additional trials. When necessary, we contacted trial authors to ask for additional information.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) that evaluated the effects of perioperative alcohol cessation interventions on postoperative complications and alcohol consumption. We included participants with risky consumption of alcohol who were undergoing all types of elective or acute surgical procedures under general or regional anaesthesia or sedation, who were offered a perioperative alcohol cessation intervention or no intervention.We defined 'risky drinking' as alcohol consumption equivalent to more than 3 alcoholic units (AU)/d or 21 AU/week (with 1 AU containing 12 grams of ethanol) with or without symptoms of alcohol abuse or dependency. This corresponds to the amount of alcohol associated with increased postoperative complication rates in most clinical studies.
DATA COLLECTION AND ANALYSIS
We used guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions. We presented main outcomes as dichotomous variables in a meta-analysis. When data were available, we conducted subgroup and sensitivity analyses to explore the risk of bias. Primary outcome measures were postoperative complications and in-hospital and 30-day mortality. Secondary outcomes were successful quitting at the end of the programme, postoperative alcohol use, and length of hospital stay. We assessed the quality of evidence using the GRADE approach.
MAIN RESULTS
We included in this updated review one new study (70 participants), resulting in a total of three RCTs (140 participants who drank 3 to 40 AU/d). All three studies were of moderate to good quality. All studies evaluated the effects of intensive alcohol cessation interventions, including pharmacological strategies for alcohol withdrawal symptoms, patient education, and relapse prophylaxis. We identified one ongoing study.Overall, 53 of the 122 participants from three studies who underwent surgery developed any type of postoperative complication that required treatment. Of 61 participants in the intervention groups, 20 had complications, compared with 33 of 61 participants in the control groups (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.40 to 0.96). Results show differences between the three clinical studies regarding outcome measurement and intensity of the interventions. However, all alcohol cessation programmes were intensive and included pharmacological therapy. The overall quality of evidence for this outcome is moderate.In-hospital and 30-day postoperative mortality rates were low in the three studies. Researchers reported one death among 61 participants in the intervention groups, and three deaths among 61 participants in the control groups (RR 0.47, 95% CI 0.07 to 2.96). The quality of evidence for this outcome is low.Investigators describe more successful quitters at the end of the intervention programme than among controls. Forty-one out of 70 participants in the intervention groups successfully quit drinking compared with only five out of 70 participants in the control groups (RR 8.22, 95% CI 1.67 to 40.44). The quality of evidence for this outcome is moderate.All three studies reported postoperative alcohol consumption (grams of alcohol/week) at the end of the programme as median and range values; therefore it was not possible to estimate the mean and the standard deviation (SD). We performed no meta-analysis. All three studies reported length of stay, and none of these studies described a significant difference in length of stay. Data were insufficient for review authors to perform a meta-analysis. No studies reported on the prevalence of participants without risky drinking in the longer term.
AUTHORS' CONCLUSIONS
This systematic review assessed the efficacy of perioperative alcohol cessation interventions for postoperative complications and alcohol consumption. All three studies showed a significant reduction in the number of participants who quit drinking alcohol during the intervention period. Intensive alcohol cessation interventions offered for four to eight weeks to participants undergoing all types of surgical procedures to achieve complete alcohol cessation before surgery probably reduced the number of postoperative complications. Data were insufficient for review authors to assess their effects on postoperative mortality. No studies reported an effect on length of stay, and no studies addressed the prevalence of risky drinking in the longer term.Included studies were few and reported small sample sizes; therefore one should be careful about drawing firm conclusions based on these study results. All three studies were conducted in Denmark, and most participants were men. The included participants may represent a selective group, as they could have been more motivated and/or more interested in participating in clinical research or otherwise different, and effects may have been overestimated for both intervention and control groups in these studies. Trial results indicate that these studies are difficult to perform, that strong research competencies are necessary for future studies, and that further evaluation of perioperative alcohol cessation interventions in high-quality randomized controlled trials is needed. Once published and assessed, the one 'ongoing' study identified may alter the conclusions of this review.
Topics: Alcohol Abstinence; Alcohol Drinking; Elective Surgical Procedures; Female; Hospital Mortality; Humans; Male; Perioperative Care; Postoperative Complications; Preoperative Care; Randomized Controlled Trials as Topic; Secondary Prevention; Substance Withdrawal Syndrome; Surgical Procedures, Operative
PubMed: 30408162
DOI: 10.1002/14651858.CD008343.pub3 -
PloS One 2018Mitochondria are energy-producing structure of the cell and help to maintain redox environment. In cardiovascular disease, the number of mitochondrial DNA (mtDNA) will... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mitochondria are energy-producing structure of the cell and help to maintain redox environment. In cardiovascular disease, the number of mitochondrial DNA (mtDNA) will changes accordingly compare to normal condition. Some investigators ask whether it has a clear association between mtDNA and cardiovascular disease with its adverse events. Thus, we conduct the meta-analysis to assess the role of circulating mtDNA in evaluating cardiovascular disease.
METHODS
The meta-analysis was conducted in accordance with a predetermined protocol following the recommendations of Cochrane Handbook of Systematic Reviews. We searched the Pubmed, Embase, the Cochrane Central Register of Controlled Trials and World Health Organization clinical trials registry center to identify relevant studies up to the end of October 2017. Data were analyzed using STATA. Besides, publication bias and meta-regression analysis were also conducted.
RESULTS
We collected results from 5 articles for further analyses with 8,252 cases and 20,904 control. The normalized mtDNA copy number level is lower in cardiovascular disease (CVD) than the control groups with a pooled standard mean difference (SMD) of -0.36(95%CI,-0.65 to -0.08); The pooled odds ratio (OR) for CVD proportion associated with a 1-SD (standard deviation) decrease in mtDNA copy number level is 1.23 (95% CI,1.06-1.42); The OR for CVD patients with mtDNA copy number lower than median level is 1.88(95% CI,1.65-2.13); The OR for CVD patients with mtDNA copy number located in the lowest quartile part is 2.15(95% CI, 1.46-3.18); the OR between mtDNA copy number and the risk of sudden cardiac death (SCD) is 1.83(95% CI, 1.22-2.74).
CONCLUSION
Although inter-study variability, the overall performance test of mtDNA for evaluating CVD and SCD revealed that the mtDNA copy number presented the potential to be a biomarker for CVD and SCD prediction. Given that, the fewer copies of mtDNA, the higher the risk of CVD.
Topics: Cardiovascular Diseases; Case-Control Studies; DNA, Mitochondrial; Death, Sudden, Cardiac; Gene Dosage; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Odds Ratio; Publication Bias; Risk Factors
PubMed: 30403687
DOI: 10.1371/journal.pone.0206003 -
Campbell Systematic Reviews 2018This Campbell systematic review examines the impact of class size on academic achievement. The review summarises findings from 148 reports from 41 countries. Ten studies...
UNLABELLED
This Campbell systematic review examines the impact of class size on academic achievement. The review summarises findings from 148 reports from 41 countries. Ten studies were included in the meta-analysis. Included studies concerned children in grades kindergarten to 12 (or the equivalent in European countries) in general education. The primary focus was on measures of academic achievement. All study designs that used a well-defined control group were eligible for inclusion. A total of 127 studies, consisting of 148 papers, met the inclusion criteria. These 127 studies analysed 55 different populations from 41 different countries. A large number of studies (45) analysed data from the Student Teacher Achievement Ratio (STAR) experiment which was for class size reduction in grade K-3 in the US in the eighties. However only ten studies, including four of the STAR programme, could be included in the meta-analysis. Overall, the evidence suggests at best a small effect on reading achievement. There is a negative, but statistically insignificant, effect on mathematics. For the non-STAR studies the primary study effect sizes for reading were close to zero but the weighted average was positive and statistically significant. There was some inconsistency in the direction of the primary study effect sizes for mathematics and the weighted average effect was negative and statistically non-significant. The STAR results are more positive, but do not change the overall finding. All reported results from the studies analysing STAR data indicated a positive effect of smaller class sizes for both reading and maths, but the average effects are small.
PLAIN LANGUAGE SUMMARY
Reducing class size is seen as a way of improving student performance. But larger class sizes help control education budgets. The evidence suggests at best a small effect on reading achievement. There is a negative, but statistically insignificant, effect on mathematics, so it cannot be ruled out that some children may be adversely affected. Increasing class size is one of the key variables that policy makers can use to control spending on education.But the consensus among many in education research is that smaller classes are effective in improving student achievement which has led to a policy of class size reductions in a number of US states, the UK, and the Netherlands. This policy is disputed by those who argue that the effects of class size reduction are only modest and that there are other more cost-effective strategies for improving educational standards.Despite the important policy and practice implications of the topic, the research literature on the educational effects of class-size differences has not been clear.This review systematically reports findings from relevant studies that measure the effects of class size on academic achievement. Included studies concerned children in grades kindergarten to 12 (or the equivalent in European countries) in general education. The primary focus was on measures of academic achievement. All study designs that used a well-defined control group were eligible for inclusion.A total of 127 studies, consisting of 148 papers, met the inclusion criteria. These 127 studies analysed 55 different populations from 41 different countries. A large number of studies (45) analysed data from the Student Teacher Achievement Ratio (STAR) experiment which was for class size reduction in grade K-3 in the US in the eighties. However only ten studies, including four of the STAR programme, could be included in the meta-analysis. Overall, the evidence suggests at best a small effect on reading achievement. There is a negative, but statistically insignificant, effect on mathematics.For the non-STAR studies the primary study effect sizes for reading were close to zero but the weighted average was positive and statistically significant. There was some inconsistency in the direction of the primary study effect sizes for mathematics and the weighted average effect was negative and statistically non-significant.The STAR results are more positive, but do not change the overall finding. All reported results from the studies analysing STAR data indicated a positive effect of smaller class sizes for both reading and maths, but the average effects are small. There is some evidence to suggest that there is an effect of reducing class size on reading achievement, although the effect is very small. There is no significant effect on mathematics achievement, though the average is negative meaning a possible adverse impact on some students cannot be ruled out.The overall reading effect corresponds to a 53 per cent chance that a randomly selected score of a student from the treated population of small classes is greater than the score of a randomly selected student from the comparison population of larger classes. This is a very small effect.Class size reduction is costly. The available evidence points to no or only very small effect sizes of small classes in comparison to larger classes. Moreover, we cannot rule out the possibility that small classes may be counterproductive for some students. It is therefore crucial to know more about the relationship between class size and achievement in order to determine where money is best allocated. The review authors searched for studies published up to February 2017. This Campbell systematic review was published in 2018.
EXECUTIVE SUMMARY/ABSTRACT
Increasing class size is one of the key variables that policy makers can use to control spending on education. Reducing class size to increase student achievement is an approach that has been tried, debated, and analysed for several decades. Despite the important policy and practice implications of the topic, the research literature on the educational effects of class-size differences has not been clear.The consensus among many in education research, that smaller classes are effective in improving student achievement has led to a policy of class size reductions in a number of U.S. states, the United Kingdom, and the Netherlands. This policy is disputed by those who argue that the effects of class size reduction are only modest and that there are other more cost-effective strategies for improving educational standards. The purpose of this review is to systematically uncover relevant studies in the literature that measure the effects of class size on academic achievement. We will synthesize the effects in a transparent manner and, where possible, we will investigate the extent to which the effects differ among different groups of students such as high/low performers, high/low income families, or members of minority/non-minority groups, and whether timing, intensity, and duration have an impact on the magnitude of the effect. Relevant studies were identified through electronic searches of bibliographic databases, internet search engines and hand searching of core journals. Searches were carried out to February 2017. We searched to identify both published and unpublished literature. The searches were international in scope. Reference lists of included studies and relevant reviews were also searched. The intervention of interest was a reduction in class size. We included children in grades kindergarten to 12 (or the equivalent in European countries) in general education. The primary focus was on measures of academic achievement. All study designs that used a well-defined control group were eligible for inclusion. Studies that utilized qualitative approaches were not included. The total number of potential relevant studies constituted 8,128 hits. A total of 127 studies, consisting of 148 papers, met the inclusion criteria and were critically appraised by the review authors. The 127 studies analysed 55 different populations from 41 different countries.A large number of studies (45) analysed data from the STAR experiment (class size reduction in grade K-3) and its follow up data.Of the 82 studies not analysing data from the STAR experiment, only six could be used in the data synthesis. Fifty eight studies could not be used in the data synthesis as they were judged to have too high risk of bias either due to confounding (51), other sources of bias (4) or selective reporting of results (3). Eighteen studies did not provide enough information enabling us to calculate an effects size and standard error or did not provide results in a form enabling us to use it in the data synthesis.Meta-analysis was used to examine the effects of class size on student achievement in reading and mathematics. Random effects models were used to pool data across the studies not analysing STAR data. Pooled estimates were weighted using inverse variance methods, and 95% confidence intervals were estimated. Effect sizes were measured as standardised mean differences (SMD). It was only possible to perform a meta-analysis by the end of the treatment year (end of the school year).Four of the studies analysing STAR data provided effect estimates that could be used in the data synthesis. The four studies differed in terms of both the chosen comparison condition and decision rules in selecting a sample for analysis. Which of these four studies' effect estimates should be included in the data synthesis was not obvious as the decision rule (concerning studies using the same data set) as described in the protocol could not be used. Contrary to usual practice we therefore report the results of all four studies and do not pool the results with the studies not analysing STAR data except in the sensitivity analysis. We took into consideration the ICC in the results reported for the STAR experiment and corrected the effect sizes and standard errors using ρ = 0.22. No adjustment due to clustering was necessary for the studies not analysing STAR data.Sensitivity analysis was used to evaluate whether the pooled effect sizes were robust across components of methodological quality, in relation to inclusion of a primary study result with an unclear sign, inclusion of effect sizes from the STAR experiment and to using a one-student reduction in class size in studies using class size as a continuous variable. All studies, not analysing STAR data, reported outcomes by the end of the treatment (end of the school year) only. The STAR experiment was a four year longitudinal study with outcomes reported by the end of each school year. The experiment was conducted to assess the effectiveness of small classes compared with regular-sized classes and of teachers' aides in regular-sized classes on improving cognitive achievement in kindergarten and in the first, second, and third grades. The goal of the STAR experiment was to have approximately 100 small classes with 13-17 students (S), 100 regular classes with 22-25 students (R), and 100 regular with aide classes with 22-25 students (RA).Of the six studies not analysing STAR, only five were used in the meta-analysis as the direction of the effect size in one study was unclear. The studies were from USA, the Netherlands and France, one was a RCT and five were NRS. The grades investigated spanned kindergarten to 3. Grade and one study investigated grade 10. The sample sizes varied; the smallest study investigated 104 students and the largest study investigated 11,567 students. The class size reductions varied from a minimum of one student in four studies, a minimum of seven students in another study to a minimum of 8 students in the last study.All outcomes were scaled such that a positive effect size favours the students in small classes, i.e. when an effect size is a class size reduction improves the students' achievement.Primary study effect sizes for reading lied in the range -0.08 to 0.14. Three of the study-level effects were statistically non-significant. The weighted average was positive and statistically significant. The random effects weighted standardised mean difference was 0.11 (95% CI 0.05 to 0.16) which may be characterised as small. There is some inconsistency in the direction of the effect sizes between the primary studies. Primary study effect sizes for mathematics lies in the range -0.41 to 0.11. Two of the study-level effects were statistically non-significant. The weighted average was negative and statistically non-significant. The random effects weighted standardised mean difference was -0.03 (95% CI -0.22 to 0.16). There is some inconsistency in the direction as well as the magnitude of the effect sizes between the primary studies.All reported results from the four studies analysing STAR data indicated a positive effect favouring the treated; all of the study-level effects were statistically significant. The study-level effect sizes for reading varied between 0.17 and 0.34 and the study-level effect sizes for mathematics varied between 0.15 and 0.33.There were no appreciable changes in the results when we included the extremes of the range of effect sizes from the STAR experiment. The reading outcome lost statistical significance when the effect size from the primary study reporting a result with an unclear direction was included with a negative sign and when the results from the studies using class size as a continuous variable were included with a one student reduction in class size instead of a standard deviation reduction in class size.Otherwise, there were no appreciable changes in the results. There is some evidence to suggest that there is an effect of reducing class size on reading achievement, although the effect is very small. We found a statistically significant positive effect of reducing the class size on reading. The effect on mathematics achievement was not statistically significant, thus it is uncertain if there may be a negative effect.The overall reading effect corresponds to a 53 per cent chance that a randomly selected score of a student from the treated population of small classes is greater than the score of a randomly selected student from the comparison population of larger classes. The overall effect on mathematics achievement corresponds to a 49 per cent chance that a randomly selected score of a student from the treated population of small classes is greater than the score of a randomly selected student from the comparison population of larger classes.Class size reduction is costly and the available evidence points to no or only very small effect sizes of small classes in comparison to larger classes. Taking the individual variation in effects into consideration, we cannot rule out the possibility that small classes may be counterproductive for some students. It is therefore crucial to know more about the relationship between class size and achievement and how it influences what teachers and students do in the classroom in order to determine where money is best allocated.
PubMed: 37131395
DOI: 10.4073/csr.2018.10 -
PloS One 2018Perception of verticality is required for normal daily function, yet the typical human detection error range has not been well characterized. Vertical misperception has... (Meta-Analysis)
Meta-Analysis
Perception of verticality is required for normal daily function, yet the typical human detection error range has not been well characterized. Vertical misperception has been correlated with poor postural control and functionality in patients after stroke and after vestibular disorders. Until now, all the published studies that assessed Subjective Postural Vertical (SPV) in the seated position used small groups to establish a reference value. However, this sample size does not represent the healthy population for comparison with conditions resulting in pathological vertical. Therefore, the primary objective was to conduct a systematic review with meta-analyses of Subjective Postural Vertical (SPV) data in seated position in healthy adults to establish the reference value with a representative sample. The secondary objective was to investigate the methodological characteristics of different assessment protocols of SPV described in the literature. A systematic literature search was conducted using Medline, EMBASE, and Cochrane libraries. Mean and standard deviation of SPV in frontal and sagittal planes were considered as effect size measures. Sixteen of 129 identified studies met eligibility criteria for our systematic review (n = 337 subjects in the frontal plane; n = 187 subjects in sagittal plane). The meta-analyses measure was estimated using the pooled mean as the estimator and its respective error. Mean reference values were 0.12°±1.49° for the frontal plane and 0.02°±1.82° for the sagittal plane. There was a small variability of the results and this systematic review resulted in representative values for SPV. The critical analysis of the studies and observed homogeneity in the sample suggests that the methodological differences used in the studies did not influence SPV assessment of directional bias in healthy subjects. These data can serve as a reference for clinical studies in disorders of verticality.
Topics: Databases as Topic; Humans; Posture; Reference Values; Statistics as Topic
PubMed: 30265701
DOI: 10.1371/journal.pone.0204122 -
The Cochrane Database of Systematic... Sep 2018Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat scrub typhus include tetracyclines, chloramphenicol, macrolides, and rifampicin.
OBJECTIVES
To assess and compare the effects of different antibiotic regimens for treatment of scrub typhus.
SEARCH METHODS
We searched the following databases up to 8 January 2018: the Cochrane Infectious Diseases Group specialized trials register; CENTRAL, in the Cochrane Library (2018, Issue 1); MEDLINE; Embase; LILACS; and the metaRegister of Controlled Trials (mRCT). We checked references and contacted study authors for additional data. We applied no language or date restrictions.
SELECTION CRITERIA
Randomized controlled trials (RCTs) or quasi-RCTs comparing antibiotic regimens in people with the diagnosis of scrub typhus based on clinical symptoms and compatible laboratory tests (excluding the Weil-Felix test).
DATA COLLECTION AND ANALYSIS
For this update, two review authors re-extracted all data and assessed the certainty of evidence. We meta-analysed data to calculate risk ratios (RRs) for dichotomous outcomes when appropriate, and elsewhere tabulated data to facilitate narrative analysis.
MAIN RESULTS
We included six RCTs and one quasi-RCT with 548 participants; they took place in the Asia-Pacific region: Korea (three trials), Malaysia (one trial), and Thailand (three trials). Only one trial included children younger than 15 years (N = 57). We judged five trials to be at high risk of performance and detection bias owing to inadequate blinding. Trials were heterogenous in terms of dosing of interventions and outcome measures. Across trials, treatment failure rates were low.Two trials compared doxycycline to tetracycline. For treatment failure, the difference between doxycycline and tetracycline is uncertain (very low-certainty evidence). Doxycycline compared to tetracycline may make little or no difference in resolution of fever within 48 hours (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.90 to 1.44, 55 participants; one trial; low-certainty evidence) and in time to defervescence (116 participants; one trial; low-certainty evidence). We were unable to extract data for other outcomes.Three trials compared doxycycline versus macrolides. For most outcomes, including treatment failure, resolution of fever within 48 hours, time to defervescence, and serious adverse events, we are uncertain whether study results show a difference between doxycycline and macrolides (very low-certainty evidence). Macrolides compared to doxycycline may make little or no difference in the proportion of patients with resolution of fever within five days (RR 1.05, 95% CI 0.99 to 1.10; 185 participants; two trials; low-certainty evidence). Another trial compared azithromycin versus doxycycline or chloramphenicol in children, but we were not able to disaggregate date for the doxycycline/chloramphenicol group.One trial compared doxycycline versus rifampicin. For all outcomes, we are uncertain whether study results show a difference between doxycycline and rifampicin (very low-certainty evidence). Of note, this trial deviated from the protocol after three out of eight patients who had received doxycycline and rifampicin combination therapy experienced treatment failure.Across trials, mild gastrointestinal side effects appeared to be more common with doxycycline than with comparator drugs.
AUTHORS' CONCLUSIONS
Tetracycline, doxycycline, azithromycin, and rifampicin are effective treatment options for scrub typhus and have resulted in few treatment failures. Chloramphenicol also remains a treatment option, but we could not include this among direct comparisons in this review.Most available evidence is of low or very low certainty. For specific outcomes, some low-certainty evidence suggests there may be little or no difference between tetracycline, doxycycline, and azithromycin as treatment options. Given very low-certainty evidence for rifampicin and the risk of inducing resistance in undiagnosed tuberculosis, clinicians should not regard this as a first-line treatment option. Clinicians could consider rifampicin as a second-line treatment option after exclusion of active tuberculosis.Further research should consist of additional adequately powered trials of doxycycline versus azithromycin or other macrolides, trials of other candidate antibiotics including rifampicin, and trials of treatments for severe scrub typhus. Researchers should standardize diagnostic techniques and reporting of clinical outcomes to allow robust comparisons.
Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Chloramphenicol; Doxycycline; Humans; Macrolides; Randomized Controlled Trials as Topic; Rifampin; Scrub Typhus; Tetracycline
PubMed: 30246875
DOI: 10.1002/14651858.CD002150.pub2