Risk Of Bias In Randomized Controlled Trials Research Articles

Selenium for preventing cancer.

Selenium for preventing cancer.

Evolution of bias and sample size in postoperative pain management trials after hip and knee arthroplasty.

Bias (systematic error) and small trial sample size (random error) may induce imprecise and exaggerated treatment effects in randomised controlled trials (RCTs). To avoid this, SPIRIT- and CONSORT-guidelines, and Cochrane Collaboration bias recommendations were developed. We investigated risk of bias and trial sample size development over time in postoperative pain trials. This study was based on data from two systematic reviews regarding pain management after total hip arthroplasty (THA) or total knee arthroplasty (TKA). RCTs of analgesic interventions with a comparator control group were included. Primary outcomes were risk of bias and trial sample size developments over time. We calculated cumulated bias scores ranging from 0 to 14 based on Cochrane's seven bias domains (0 = low; 1 = unclear, 2 = high). Developments were evaluated with run and control charts. Further, we compared data from trials published between 1990-1999 and 2010-2016. We included 171 trials published between 1989 and 2016. Overall, the summarised risk of bias decreased, mainly due to better randomization and allocation concealment. Visual inspection suggested an on-going improvement that started around 2007. Trial sample size did not change significantly. For trials published between 1990-1999 and 2010-2016 adequate reporting increased from 36% to 75% for random sequence generation, from 9% to 38% for allocation concealment and from 27% to 52% for blinding of participants/personnel. Risk of bias for RCTs regarding postoperative pain management after THA and TKA has decreased from 2007 to 2016, mainly due to better randomization and allocation concealment. Deficiencies remain. Thus, reporting according to validated guidelines is essential. Sample sizes did not change significantly.

Effect of programmed exercise on insulin sensitivity in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effect of programmed exercise for at least 12 weeks, in postmenopausal women on insulin sensitivity-related outcomes (ISROs), including fasting insulin, C-peptide, insulin growth factor (IGF-1) and IGF-binding protein (IGFBP-3), Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), and anthropometric variables. Searches were conducted in PubMed-Medline, Embase, Scopus, Web of Science, and Cochrane Library from inception through May 3, 2016, for studies published in all languages. Extracted data included characteristics of the study design, study participants, intervention, and outcome measures. Types of exercise were classified into "mid-term exercise intervention" (MTEI, 3-4 months exercise duration) and a "long-term exercise intervention" (LTEI, 6-12 months exercise duration). Risk of bias in RCTs was evaluated with the Cochrane tool. We used random-effects models for meta-analyses. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seven RCTS (n = 580) evaluating the effects of programmed exercise on ISROs were included. In three RCTs, MTEI significantly lowered insulin levels (mean difference [MD] -6.50 pmol/L, 95% confidence interval [CI] -11.19, -1.82, P = 0.006) and HOMA-IR values (MD -0.18, 95% CI -0.34, -0.03, P = 0.02) when compared with controls. LTEI had no significant effect on insulin levels (P = 0.19) or HOMA-IR values (P = 0.68) in four and three RCTs, respectively. There were no significant differences between exercise intervention versus controls in circulating IGF-1, glucose, triglycerides with both MTEI and LTEI, and in IGFBP-3 with LTEI. There were significant reductions in body mass index (BMI, kg/m) (MD -1.48, 95% CI -2.48, -0.48, P = 0.004) and in body fat percentage (MD -2.99, 95% CI -4.85, -1.14, P = 0.01) after MTEI; and in waist circumference after both MTEI (MD -1.87, 95% CI -3.02, -0.72, P = 0.001) and LTEI (MD -3.74, 95% CI -6.68, -0.79). Heterogeneity of effects among studies was moderate to low. Exercising for 3 to 4 months significantly lowered insulin levels and HOMA-IR values, BMI waist circumference, and percentage body fat mass; exercising for 6 to 12 months lowered waist circumference in postmenopausal women.

A Systematic Review of Add-on Pharmacologic Therapy in the Treatment of Resistant Hypertension.

The objective of this systematic review was to evaluate the efficacy and safety of add-on pharmacologic therapies in the treatment of resistant hypertension (RH), defined as blood pressure (BP) above target despite three antihypertensive agents. A systematic search was performed in MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and Google Scholar (inception to June 2016) to identify randomized controlled trials (RCTs) that compared any antihypertensive agent with control in patients with RH. Outcomes of interest included differences in BP, cardiovascular events, and serious adverse events. The Cochrane Collaboration's tool for assessing risk of bias in RCTs was used to evaluate the quality of the included trials. Six RCTs were identified, including 749 participants. Four RCTs compared spironolactone with placebo and two used an active comparator. Four of the six studies did not report sufficient information regarding methods. A quantitative meta-analysis was not performed because of clinical heterogeneity among the RCTs. Compared with placebo, spironolactone reduced mean office BP by ~10 to 20mmHg/~3 to 9mmHg and home BP by ~10/4mmHg. Compared with doxazosin or bisoprolol, spironolactone reduced clinic and home systolic BP, but not diastolic BP. Hyperkalemia occurred in ~3% of patients receiving spironolactone. Cardiovascular events were not consistently reported. All trials were limited by low enrollment, short follow-up, and inconsistent reporting of clinically meaningful outcomes and/or serious adverse events. Spironolactone has the best evidence as add-on pharmacologic therapy in patients with RH, but data are limited.

Efficacy and safety of pharmacological treatments for Lyme neuroborreliosis in children: a systematic review.

BackgroundMany aspects of pharmacological treatment of Lyme neuroborreliosis in children, such as choice of drug, dosage, and duration are subject to intense debates, leading to uncertainties in patients’ parents and healthcare providers alike. To assess the available evidence for pharmacological treatment for children with Lyme neuroborreliosis we conducted a systematic review.MethodsThe comprehensive systematic literature search included randomized-controlled trials (RCTs) and non-randomized studies (NRS) on treatment of Lyme neuroborreliosis in children (age <18 years). Our primary outcome was neurological symptoms after treatment. Risk of bias was assessed with the Cochrane risk of bias tools for RCTs and NRS. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsTwo RCTs and four NRS were eligible for inclusion. Risk of bias in RCTs and NRS was generally high. Reporting of studies was generally poor. Regarding the primary outcome neurological symptoms at 1–3 months, no statistically significant difference could be found in cohort studies between doxycycline and beta-lactam antibiotics. In two RCTs comparing penicillin G and ceftriaxone, no patient experienced residual neurological symptoms at the last reported time points. Quality of evidence according to GRADE was judged very low.ConclusionsData is scarce and with limited quality. Several issues could not be addressed due to scarcity of information. No eligible study compared different treatment durations. According to the available evidence, there seems to be no difference between different antibiotic agents for the treatment of Lyme neuroborreliosis in children regarding neurological symptoms. We found no evidence that supports extended antibiotic regimes.Review registrationSystematic review registration: CRD42014008839.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0708-y) contains supplementary material, which is available to authorized users.

A Risk of Bias Assessment of Randomized Controlled Trials (RCTs) on Periodontal Regeneration Published in 2013

ObjectiveThe objective of this assessment is to evaluate the degree of risk of bias in randomized controlled trials published in 2013 and focusing on periodontal regeneration. MethodsThree reviewers searched and selected the trials based on pre-defined inclusion criteria. Predictor variables [number of authors, primary objective of the study, biomaterial employed, follow-up time periods, split mouth study (yes/no), journal, year of publication, country, scale (single/multi-center) and nature of funding] were extracted and risk of bias assessment using Cochrane risk of bias tool were performed independently by the three reviewers. ResultsSeventeen RCTs were included in this assessment. The risk of bias in RCTs published in 2013 with a focus in periodontal regeneration varied significantly with only in less than 30% of the included trials, the overall risk of bias was found to be low, while 41% of trials were designated to have a higher degree of bias. Specifically, when looking at the domains assessed, 70% of the included trials reported an accepted method of sequence generation, blinding (whenever possible), completeness of outcome data or avoided selective outcome reporting. Meanwhile, only 47% of the included trials reported some form of allocation concealment. ConclusionIn this assessment, of the included 17 trials, slightly more than 40% of them had a high risk of bias, underscoring the importance of careful appraisal of trials before implementing the study interventions in clinical practice and the need for more detailed analyses.

An Assessment of the Risk of Bias in Randomized Controlled Trial Reports Published in Prosthodontic and Implant Dentistry Journals.

The objective of this study was to assess the risk of bias of randomized controlled trials (RCTs) published in prosthodontic and implant dentistry journals. The last 30 issues of 9 journals in the field of prosthodontic and implant dentistry (Clinical Implant Dentistry and Related Research, Clinical Oral Implants Research, Implant Dentistry, International Journal of Oral & Maxillofacial Implants, International Journal of Periodontics and Restorative Dentistry, International Journal of Prosthodontics, Journal of Dentistry, Journal of Oral Rehabilitation, and Journal of Prosthetic Dentistry) were hand-searched for RCTs. Risk of bias was assessed using the Cochrane Collaboration's risk of bias tool and analyzed descriptively. From the 3,667 articles screened, a total of 147 RCTs were identified and included. The number of published RCTs increased with time. The overall distribution of a high risk of bias assessment varied across the domains of the Cochrane risk of bias tool: 8% for random sequence generation, 18% for allocation concealment, 41% for masking, 47% for blinding of outcome assessment, 7% for incomplete outcome data, 12% for selective reporting, and 41% for other biases. The distribution of high risk of bias for RCTs published in the selected prosthodontic and implant dentistry journals varied among journals and ranged from 8% to 47%, which can be considered as substantial.

Management of sleep bruxism in adults: a qualitative systematic literature review.

This paper updates the bruxism management review published by Lobbezoo etal. in 2008 (J Oral Rehabil 2008; 35: 509-23). The review focuses on the most recent literature on management of sleep bruxism (SB) in adults, as diagnosed with polysomnography (PSG) with audio-video (AV) recordings, or with any other approach measuring the sleep-time masticatory muscles' activity, viz., PSG without AV recordings or electromyography (EMG) recorded with portable devices. Fourteen (N=14) papers were included in the review, of which 12 were randomised controlled trials (RCTs) and 2 were uncontrolled before-after studies. Structured reading of the included articles showed a high variability of topics, designs and findings. On average, the risk of bias for RCTs was low-to-unclear, whilst the before-after studies had several methodological limitations. The studies' results suggest that (i) almost every type of oral appliance (OA) (seven papers) is somehow effective to reduce SB activity, with a potentially higher decrease for devices providing large extent of mandibular advancement; (ii) all tested pharmacological approaches [i.e. botulinum toxin (two papers), clonazepam (one paper) and clonidine (one paper)] may reduce SB with respect to placebo; (iii) the potential benefit of biofeedback (BF) and cognitive-behavioural (CB) approaches to SB management is not fully supported (two papers); and (iv) the only investigation providing an electrical stimulus to the masseter muscle supports its effectiveness to reduce SB. It can be concluded that there is not enough evidence to define a standard of reference approach for SB treatment, except for the use of OA. Future studies on the indications for SB treatment are recommended.

Selenium for preventing cancer.

This review is an update of the first Cochrane publication on selenium for preventing cancer (Dennert 2011).Selenium is a metalloid with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. Two research questions were addressed in this review: What is the evidence for:1. an aetiological relation between selenium exposure and cancer risk in humans? and2. the efficacy of selenium supplementation for cancer prevention in humans? We conducted electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals indexed in CancerLit, no further searches were conducted in this database after 2004. We included prospective observational studies (cohort studies including sub-cohort controlled studies and nested case-control studies) and randomised controlled trials (RCTs) with healthy adult participants (18 years of age and older). For observational studies, we conducted random effects meta-analyses when five or more studies were retrieved for a specific outcome. For RCTs, we performed random effects meta-analyses when two or more studies were available. The risk of bias in observational studies was assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies; the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias in RCTs. We included 55 prospective observational studies (including more than 1,100,000 participants) and eight RCTs (with a total of 44,743 participants). For the observational studies, we found lower cancer incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to 0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6) associated with higher selenium exposure. Gender-specific subgroup analysis provided no clear evidence of different effects in men and women (P value 0.47), although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6) than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced decreases in risk of site-specific cancers were seen for stomach, bladder and prostate cancers. However, these findings have limitations due to study design, quality and heterogeneity that complicate interpretation of the summary statistics. Some studies suggested that genetic factors may modify the relation between selenium and cancer risk-a hypothesis that deserves further investigation.In RCTs, we found no clear evidence that selenium supplementation reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two studies, N = 18,698), and this finding was confirmed when the analysis was restricted to studies with low risk of bias. The effect on prostate cancer was imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the analysis was limited to trials with low risk of bias, the interventions showed no effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non-melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies, N = 1900). Results of two trials-the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)-also raised concerns about possible increased risk of type 2 diabetes, alopecia and dermatitis due to selenium supplements. An early hypothesis generated by NPCT that individuals with the lowest blood selenium levels at baseline could reduce their risk of cancer, particularly of prostate cancer, by increasing selenium intake has not been confirmed by subsequent trials. As the RCT participants were overwhelmingly male (94%), gender differences could not be systematically assessed. Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution. These studies have many limitations, including issues with assessment of exposure to selenium and to its various chemical forms, heterogeneity, confounding and other biases. Conflicting results including inverse, null and direct associations have been reported for some cancer types.RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results, although the most recent studies, characterised by a low risk of bias, found no beneficial effect on cancer risk, more specifically on risk of prostate cancer, as well as little evidence of any influence of baseline selenium status. Rather, some trials suggest harmful effects of selenium exposure. To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans.

The External Validity of Randomized Controlled Trials of Hypertension within China: from the Perspective of Sample Representation

ObjectiveTo explore external validity of randomized controlled trials (RCTs) of hypertension within China from the view of sample representation. MethodsComprehensive literature searches were performed in Medline, Embase, Cochrane Central Register of Controlled Trials (CCTR) et al and advanced search strategies were used to locate hypertension RCTs as well as observational studies conducted in China during 1996 to 2009 synchronously. The risk of bias in RCTs and observational studies was assessed by two modified scales respectively, and then both types of studies with 3 or more grading scores were included for the purpose of evaluating of external validity. Following that the study characteristics relative to sample representation were extracted from RCTs and observational studies synchronously, and the later were taken as external references for validating sample representation of RCTs. Results226 hypertension RCTs and 21 observational studies were included for final analysis. Comparing samples with observational studies, the mean age of samples within RCTs was 54.46 years, significantly lower than that of observational studies (66.35 years) (P=0.002). The average disease course in patients of RCTs was 3.89 years and grade III hypertensive patients accounted for 17%; both were lower than that of the observational studies (12.96 years, P<0.001; 34%, P=0.026 respectively). In addition, the proportions of patients with complications due to heart failure, stroke, diabetes, or coronary heart disease in RCTs were 8%, 5%, 12% and 11% correspondingly, all of which were significantly less than that of observational studies (11%, 18%, 17% and 29%). ConclusionSample characteristics within hypertension RCTs were significantly different from those in observational studies. The samples in most RCTs were under-represented. It’s feasible to take samples of observational studies as a mirror of the actual composition of hypertension patients in the real world, if the reporting of observational studies is abundant and available.

Mo2055 Rifaximin for Treatment of Small Intestine Bacterial Overgrowth (SIBO): A Systematic Review and Meta-Analysis

Background: Small intestinal bacterial overgrowth (SIBO) is a condition caused by an increased number and/or abnormal type of bacteria (i.e. oropharyngeal or colonic type bacteria) in the small bowel. Eradication of SIBO relies on antibiotic therapy that must cover both aerobic and anaerobic enteric bacteria. Rifaximin is a poorly absorbable antibiotic, with a broad spectrum of antibacterial activity, covering Gram-positive and Gram-negative microorganisms, both aerobes and anaerobes. Aim: To perform a systematic review and metaanalysis of clinical trials using rifaximin to eradicate SIBO. Methods: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials as well as abstract from the Digestive Disease Week, the American College of GastroenterologyMeeting, the United European Gastroenterological Week as well as Asian Pacific Digestive Week were searched up to November 2012. Case series, open label studies, cross-over and randomized controlled trials (RCTs) in adult patients with proven SIBO, treated with rifaximin, were eligible. Hydrogen (glucose or lactulose) breath test was used to diagnose the bacterial overgrowth and repeated after therapy to assess eradication. Risk of bias for RCTs was assessed as described in the Cochrane handbook. The proportion of individuals eradicated was combined from all studies to give a pooled eradication rate using a random effects model in order to provide a more conservative estimate. Results: Twenty-eight studies were identified containing 921 subjects, meeting the pre-specified entry criteria and treated for SIBO. Only 4 studies were RCTs: 2 compared rifaximin to systemic antibiotics (namely tetracycline or metronidazole), and 2 compared different doses of rifaximin. All RCTs were at unclear or high risk of bias. To diagnose and follow-up the patients 16 studies used the hydrogen-glucose breath test and 12 the hydrogenlactulose breath test. Doses of rifaximin used ranged from 600 to 1650 mg daily. Pooled eradication rate was 67.0% (95% CI: 59.1 to 69.8) with evidence of heterogeneity [Q-value: 123,714, df(Q) = 27; p ,0.0001; I2 = 78.17]. Eradication rate was dose-dependent (r= 0.999, p =0.019). In the 2 RTCs comparing rifaximin to other antibiotics, the pooled

Influence of reported study design characteristics on intervention effect estimates from randomised controlled trials: combined analysis of meta-epidemiological studies.

The design of randomised controlled trials (RCTs) should incorporate characteristics (such as concealment of randomised allocation and blinding of participants and personnel) that avoid biases resulting from lack of comparability of the intervention and control groups. Empirical evidence suggests that the absence of such characteristics leads to biased intervention effect estimates, but the findings of different studies are not consistent. To examine the influence of unclear or inadequate random sequence generation and allocation concealment, and unclear or absent double blinding, on intervention effect estimates and between-trial heterogeneity, and whether or not these influences vary with type of clinical area, intervention, comparison and outcome measure. Data were combined from seven contributing meta-epidemiological studies (collections of meta-analyses in which trial characteristics are assessed and results recorded). The resulting database was used to identify and remove overlapping meta-analyses. Outcomes were coded such that odds ratios < 1 correspond to beneficial intervention effects. Outcome measures were classified as mortality, other objective or subjective. We examined agreement between assessments of trial characteristics in trials assessed in more than one contributing study. We used hierarchical Bayesian bias models to estimate the effect of trial characteristics on average bias [quantified as ratios of odds ratios (RORs) with 95% credible intervals (CrIs) comparing trials with and without a characteristic] and in increasing between-trial heterogeneity. The analysis data set contained 1973 trials included in 234 meta-analyses. Median kappa statistics for agreement between assessments of trial characteristics were: sequence generation 0.60, allocation concealment 0.58 and blinding 0.87. Intervention effect estimates were exaggerated by an average 11% in trials with inadequate or unclear (compared with adequate) sequence generation (ROR 0.89, 95% CrI 0.82 to 0.96); between-trial heterogeneity was higher among such trials. Bias associated with inadequate or unclear sequence generation was greatest for subjective outcomes (ROR 0.83, 95% CrI 0.74 to 0.94) and the increase in heterogeneity was greatest for such outcomes [standard deviation (SD) 0.20, 95% CrI 0.03 to 0.32]. The effect of inadequate or unclear (compared with adequate) allocation concealment was greatest among meta-analyses with a subjectively assessed outcome intervention effect (ROR 0.85, 95% CrI 0.75 to 0.95), and the increase in between-trial heterogeneity was also greatest for such outcomes (SD 0.20, 95% CrI 0.02 to 0.33). Lack of, or unclear, double blinding (compared with double blinding) was associated with an average 13% exaggeration of intervention effects (ROR 0.87, 95% CrI 0.79 to 0.96), and between-trial heterogeneity was increased for such studies (SD 0.14, 95% CrI 0.02 to 0.30). Average bias (ROR 0.78, 95% CrI 0.65 to 0.92) and between-trial heterogeneity (SD 0.37, 95% CrI 0.19 to 0.53) were greatest for meta-analyses assessing subjective outcomes. Among meta-analyses with subjectively assessed outcomes, the effect of lack of blinding appeared greater than the effect of inadequate or unclear sequence generation or allocation concealment. Bias associated with specific reported study design characteristics leads to exaggeration of beneficial intervention effect estimates and increases in between-trial heterogeneity. For each of the three characteristics assessed, these effects were greatest for subjectively assessed outcomes. Assessments of the risk of bias in RCTs should account for these findings. Further research is needed to understand the effects of attrition bias, as well as the relative importance of blinding of patients, care-givers and outcome assessors, and thus separate the effects of performance and detection bias. National Institute for Health Research Health Technology Assessment programme.

526: Transabdominal amnioinfusion in preterm premature rupture of membranes: a systematic review and a metaanalysis

premature rupture of membranes: a systematic review and a metaanalysis Shay Porat, Hagai Amsalem, Prakesh S. Shah, Kellie E. Murphy Mount Sinai Hospital, Obstetrics and Gynecology, Toronto, ON, Canada, Hadassah University Hospital, Mount Scopus, Obstetrics and Gynecology, Jerusalem, Israel, Mount Sinai Hospital, Department of Paediatrics, Toronto, ON, Canada OBJECTIVE: Transabdominal amnioinfusion (TA) was investigated in several studies as an intervention for improving neonatal outcomes following second trimester preterm premature rupture of membranes (PPROM). The objective of this study was to systematically review the efficacy and safety of TA in early PPROM. STUDY DESIGN: A comprehensive literature search was performed with no language barrier, using the EMBASE and MEDLINE from 19502011. Observational and randomized controlled trials (RCT) were identified. Only studies with proven PPROM and oligohydramnios were included. Two reviewers independently assessed titles, abstracted data and full text. Quality of the studies was assessed using the Newcastle-Ottawa scale and the Cochrane’s tool for assessing risk of bias for RCTs. Primary outcomes were gestational age at delivery, latency period length, birthweight, perinatal mortality, pulmonary hypoplasia and chorioamnionitis. Secondary outcomes were: early onset neonatal sepsis, neonatal mortality, bronchopulmonary dysplasia, genitourinary infections, cesarean section and post-partum sepsis. Statistical analysis was performed using Review Manager 5 software (RevMan 5.0). RESULTS: Seven studies including two RCTs, one quasi-randomized and four observational studies were eligible. The two RCTs and the quasi-randomized studies were meta-analyzed together and observational studies were meta-analyzed separately. Favorable results for the treatment group were concordant in both meta-analyses with regards to latency period length, perinatal mortality, pulmonary hypoplasia and neonatal mortality (table 1). These results even intensify in face of significantly lower gestational age at rupture of membranes in the observational studies. CONCLUSION: Serial TA for early PPROM may improve early PPROMassociated morbidity and mortality. The possible benefits of this treatment modality warrant additional adequately powered randomized control trials. 527 Maternal IL6 levels: a failed biomarker for preterm birth Sindhu K. Srinivas, Jamie A. Bastek, Markley Foreman, Meghan McShea, Laura Anglim, Anita Weber, Michal A. Elovitz University of Pennsylvania Perelman School of Medicine, Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Philadelphia, PA, University of Pennsylvania Perelman School of Medicine, CCEB, Philadelphia, PA OBJECTIVE: Interleukin 6 (IL6) levels have been investigated as a predictor of preterm birth (PTB) and adverse neonatal outcomes including cerebral palsy. Our objective was to evaluate the association between maternal serum IL6 levels and PTB, interval to delivery, chorioamnionitis, and adverse neonatal outcomes in women with symptoms of preterm labor (PTL). STUDY DESIGN: We performed a cohort study of women with singleton pregnancies who presented at 22-33 6/7 wks with signs/symptoms of PTL from April 2009 to June 2011. Maternal medical, obstetric history, and delivery information were obtained through chart abstraction. Blood was drawn at the time of presentation with PTL. IL6 (pg/ ml) was measured in maternal serum using a high sensitivity ELISA (RD OR 1.00 (0.98-1.04), p 0.7). The mean gestational age at delivery and interval from presentation to delivery did not differ among quartiles of IL6 levels (table). There was no association between IL6 and chorioamnionitis (p 0.83) or adverse neonatal outcome (P 0.2). CONCLUSION: Maternal IL6 levels have been posited as a potential reliable biomarker for PTB. This adequately powered study demonstrates that maternal IL6 levels are not associated with PTB. Additionally, maternal IL6 is not associated with interval to delivery, chorioamnionitis or adverse neonatal outcomes. Maternal IL6 cannot be used clinically to predict PTB or chorioamnionitis in women with PTL symptoms. Further research is needed to evaluate other maternal biomarkers as accurate predictors of PTB and adverse neonatal outcomes. MOD#21FY08-539 (Elovitz) Poster Session III Doppler Assessment, Fetus, Prematurity www.AJOG.org

Assessing the risk of bias in randomized controlled trials in the field of dentistry indexed in the Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) database.

Well-conducted randomized controlled trials (RCTs) represent the highest level of evidence when the research question relates to the effect of therapeutic or preventive interventions. However, the degree of control over bias between RCTs presents great variability between studies. For this reason, with the increasing interest in and production of systematic reviews and meta-analyses, it has been necessary to develop methodology supported by empirical evidence, so as to encourage and enhance the production of valid RCTs with low risk of bias. The aim here was to conduct a methodological analysis within the field of dentistry, regarding the risk of bias in open-access RCTs available in the Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) database. This was a methodology study conducted at Universidade Federal de São Paulo (Unifesp) that assessed the risk of bias in RCTs, using the following dimensions: allocation sequence generation, allocation concealment, blinding, and data on incomplete outcomes. Out of the 4,503 articles classified, only 10 studies (0.22%) were considered to be true RCTs and, of these, only a single study was classified as presenting low risk of bias. The items that the authors of these RCTs most frequently controlled for were blinding and data on incomplete outcomes. The effective presence of bias seriously weakened the reliability of the results from the dental studies evaluated, such that they would be of little use for clinicians and administrators as support for decision-making processes.

A pilot study of occlusal sound in adults with functional occlusion : Ou Meigi et al. (1987) West China J. Stomatol.5,(2), 103–107

The systematic review and meta-analysis aimed to answer the PICO question: “Do patients that received external connection implants show similar marginal bone loss, implant survival and complication rates as internal connection implants?”.Meta-analyses of marginal bone loss, survival rates of implants and complications rates were performed for the included studies. Study eligibility criteria included (1) randomized controlled trials (RCTs) and/or prospective, (2) studies with at least 10 patients, (3) direct comparison between connection types and (4) publications in English language. The Cochrane risk of bias tool was used to assess the quality and risk of bias in RCTs, while Newcastle-Ottawa scale was used for non-RCTs.A comprehensive search strategy was designed to identify published studies on PubMed/MEDLINE, Scopus, and The Cochrane Library databases up to October 2017.The search identified 661 references. Eleven studies (seven RCTs and four prospective studies) were included, with a total of 530 patients (mean age, 53.93 years), who had received a total of 1089 implants (461 external-connection and 628 internal-connection implants). The internal-connection implants exhibited lower marginal bone loss than external-connection implants (P < 0.00001; Mean Difference (MD): 0.44 mm; 95% Confidence interval (CI): 0.26–0.63 mm). No significant difference was observed in implant survival (P = 0.65; Risk Ratio (RR): 0.83; 95% CI: 0.38–1.84), and complication rates (P = 0.43; RR: 1.15; 95% CI: 0.81–1.65).Internal connections had lower marginal bone loss when compared to external connections. However, the implant-abutment connection had no influence on the implant’s survival and complication rates. Based on the GRADE approach the evidence was classified as very low to moderate due to the study design, inconsistency, and publication bias. Thus, future research is highly encouraged.Internal connection implants should be preferred over external connection implants, especially when different risk factors that may contribute to increased marginal bone loss are present.