Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin's lymphoma: a systematic review and network meta-analysis

BACKGROUND Several treatment strategies are available for adults with advanced-stage Hodgkin's lymphoma, but studies assessing two alternative standards of care-increased dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-were not powered to test differences in overall survival. To guide treatment decisions in this population of patients, we did a systematic review and network meta-analysis to identify the best initial treatment strategy. METHODS We searched the Cochrane Library, Medline, and conference proceedings for randomised controlled trials published between January, 1980, and June, 2013, that assessed overall survival in patients with advanced-stage Hodgkin's lymphoma given BEACOPPbaseline, BEACOPPescalated, BEACOPP variants, ABVD, cyclophosphamide (mechlorethamine), vincristine, procarbazine, and prednisone (C[M]OPP), hybrid or alternating chemotherapy regimens with ABVD as the backbone (eg, COPP/ABVD, MOPP/ABVD), or doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (the Stanford V regimen). We assessed studies for eligibility, extracted data, and assessed their quality. We then pooled the data and used a Bayesian random-effects model to combine direct comparisons with indirect evidence. We also reconstructed individual patient survival data from published Kaplan-Meier curves and did standard random-effects Poisson regression. Results are reported relative to ABVD. The primary outcome was overall survival. FINDINGS We screened 2055 records and identified 75 papers covering 14 eligible trials that assessed 11 different regimens in 9993 patients, providing 59 651 patient-years of follow-up. 1189 patients died, and the median follow-up was 5·9 years (IQR 4·9-6·7). Included studies were of high methodological quality, and between-trial heterogeneity was negligible (τ(2)=0·01). Overall survival was highest in patients who received six cycles of BEACOPPescalated (HR 0·38, 95% credibility interval [CrI] 0·20-0·75). Compared with a 5 year survival of 88% for ABVD, the survival benefit for six cycles of BEACOPPescalated is 7% (95% CrI 3-10)-ie, a 5 year survival of 95%. Reconstructed individual survival data showed that, at 5 years, BEACOPPescalated has a 10% (95% CI 3-15) advantage over ABVD in overall survival. INTERPRETATION Six cycles of BEACOPPescalated significantly improves overall survival compared with ABVD and other regimens, and thus we recommend this treatment strategy as standard of care for patients with access to the appropriate supportive care.

Induction of lucid dreams: A systematic review of evidence

In lucid dreams the dreamer is aware of dreaming and often able to influence the ongoing dream content. Lucid dreaming is a learnable skill and a variety of techniques is suggested for lucid dreaming induction. This systematic review evaluated the evidence for the effectiveness of induction techniques. A comprehensive literature search was carried out in biomedical databases and specific resources. Thirty-five studies were included in the analysis (11 sleep laboratory and 24 field studies), of which 26 employed cognitive techniques, 11 external stimulation and one drug application. The methodological quality of the included studies was relatively low. None of the induction techniques were verified to induce lucid dreams reliably and consistently, although some of them look promising. On the basis of the reviewed studies, a taxonomy of lucid dream induction methods is presented. Several methodological issues are discussed and further directions for future studies are proposed.

Curing lights for orthodontic bonding: a systematic review and meta-analysis

INTRODUCTION Light cure of resin-based adhesives is the mainstay of orthodontic bonding. In recent years, alternatives to conventional halogen lights offering reduced curing time and the potential for lower attachment failure rates have emerged. The relative merits of curing lights in current use, including halogen-based lamps, light-emitting diodes (LEDs), and plasma arc lights, have not been analyzed systematically. In this study, we reviewed randomized controlled trials and controlled clinical trials to assess the risks of attachment failure and bonding time in orthodontic patients in whom brackets were cured with halogen lights, LEDs, or plasma arc systems. METHODS Multiple electronic database searches were undertaken, including MEDLINE, EMBASE, and the Cochrane Oral Health Group's Trials Register, CENTRAL. Language restrictions were not applied. Unpublished literature was searched on ClinicalTrials.gov, the National Research Register, Pro-Quest Dissertation Abstracts, and Thesis database. Search terms included randomized controlled trial, controlled clinical trial, random allocation, double blind method, single blind method, orthodontics, LED, halogen, bond, and bracket. Authors of primary studies were contacted as required, and reference lists of the included studies were screened. RESULTS Randomized controlled trials and clinical controlled trials directly comparing conventional halogen lights, LEDs, or plasma arc systems involving patients with full arch, fixed, or bonded orthodontic appliances (not banded) with follow-up periods of a minimum of 6 months were included. Using predefined forms, 2 authors undertook independent extraction of articles; disagreements were resolved by discussion. The assessment of the risk of bias of the randomized controlled trials was based on the Cochrane Risk of Bias tool. Ten studies met the inclusion criteria; 2 were excluded because of high risk of bias. In the comparison of bond failure risk with halogen lights and plasma arc lights, 1851 brackets were included in both groups. Little statistical heterogeneity was observed in this analysis (I(2) = 4.8%; P = 0.379). There was no statistical difference in bond failure risk between the groups (OR, 0.92; 95% CI, 0.68-1.23; prediction intervals, 0.54, 1.56). Similarly, no statistical difference in bond failure risk was observed in the meta-analysis comparing halogen lights and LEDs (OR, 0.96; 95% CI, 0.64-1.44; prediction intervals, 0.07, 13.32). The pooled estimates from both comparisons were OR, 0.93; 95% CI, 0.74-1.17; and prediction intervals, 0.69, 1.17. CONCLUSIONS There is no evidence to support the use of 1 light cure type over another based on risk of attachment failure.

Facts and myths regarding the maxillary midline frenum and its treatment: a systematic review of the literature

OBJECTIVE To systematically review the current literature on the maxillary midline frenum and associated conditions and complications, as well as the recommended treatment options. METHOD AND MATERIALS A detailed MEDLINE database search was carried out to provide evidence about the epidemiology, associated pathologies, and treatment options regarding the maxillary frenum. Of the 206 initially identified articles, 48 met the inclusion criteria. RESULTS The maxillary frenum is highly associated with a number of syndromes and developmental abnormalities. A hypertrophic frenum may be involved in the etiology of the midline diastema. There is also a tendency by orthodontists to suggest posttreatment removal of the frenum (frenectomy). Studies on the cause of gingival recession due to the maxillary frenum are inconclusive. An injured frenum in combination with other traumas and doubtful history might point to child abuse. The involvement of hyperplastic frena in the pathogenesis of peri-implant diseases remains uncertain. There seems to be a clinical interest regarding lasers for surgery for treatment of maxillary frena. The superiority of laser treatment in relation to conventional surgical methods has not yet been demonstrated in the literature. CONCLUSION A maxillary frenum is a clinical symptom in numerous syndromic conditions and plays a role in the development of the median midline diastema. Nevertheless, the contribution to gingival recession and peri-implant diseases in the region of the maxillary incisors is rather controversial. Laser techniques are reported as the method of choice for the surgical removal of frena; however, this needs to be substantiated by appropriate prospective controlled studies.

Reporting quality of systematic review abstracts in leading oral implantology journals

OBJECTIVES Abstracts of systematic reviews are of critical importance, as consumers of research often do not access the full text. This study aimed to assess the reporting quality of systematic review (SR) abstracts in leading oral implantology journals. METHODS Six specialty journals were screened for SRs between 2008 and 2012. A 16-item checklist, based on the PRISMA statement, was used to examine the completeness of abstract reporting. RESULTS Ninety-three SR abstracts were included in this study. The majority were published in Clinical Oral Implants Research (43%). The mean overall reporting quality score was 72.5% (95% CI: 70.8-74.2). Most abstracts were structured (97.9%), adequately reporting objectives (97.9%) and conclusions (93.6%). Conversely, inadequate reporting of methods of the study, background (79.6%), appraisal (65.6%), and data synthesis (65.6%) were observed. Registration of reviews was not reported in any of the included abstracts. Multivariate analysis revealed no difference in reporting quality with respect to continent, number of authors, or meta-analysis conduct. CONCLUSIONS The results of this study suggest that the reporting quality of systematic review abstracts in implantology journals requires further improvement. CLINICAL SIGNIFICANCE Better reporting of SR abstracts is particularly important in ensuring the reliability of research findings, ultimately promoting the practice of evidence-based dentistry. Optimal reporting of SR abstracts should be encouraged, preferably by endorsing the PRISMA for abstracts guidelines.

In vivo bisphenol-a release from dental pit and fissure sealants: a systematic review

OBJECTIVE To search the literature and assess the short- and long-term release of bisphenol-A (BPA) in human tissues after treatment with dental sealants. DATA Two review authors performed data extraction independently and in duplicate using data collection forms. Disagreements were resolved by discussion with an arbiter. SOURCES Electronic database searches of published and unpublished literature were performed. The following electronic databases with no language and publication date restrictions were searched: MEDLINE (via Ovid and Pubmed), EMBASE (via ovid), Cochrane Trials Register and CENTRAL. The reference lists of all eligible studies were hand-searched. STUDY SELECTION In the absence of RCTs, six interventional and two observational studies, examining in vivo BPA release in human salivary, blood and urinary samples, were included. Due to the heterogeneity in methodology and reporting, the main synthesis of the results was qualitative. The quantitative synthesis based on the weighted Z-test could only include two studies. BPA levels identified in saliva ranged from traces below the method's detection limit to 30 μg/ml. In urine, BPA quantities spanned from 0.17 mg/g to 45.4 mg/g. BPA was not traced in any blood sample at any point of time in the relevant studies. The quantitative analysis showed evidence of BPA release one hour after sealant placement compared to the amount traced before restoration (Stouffer's z trend: <0.001). CONCLUSIONS The available evidence on this topic derived from studies that represent a moderate level of evidence. Nevertheless, the available evidence supports that BPA is released in saliva after sealant placement. CLINICAL SIGNIFICANCE From the qualititative and quantitative synthesis of studies, it is reasonable to conclude that BPA is released after placement of some dental pit and fissure sealants in the oral cavity. The biggest quantities are detected in saliva immediately after or one hour after their placement.

Bisphenol-A and residual monomer leaching from orthodontic adhesive resins and polycarbonate brackets: a systematic review

INTRODUCTION The objective of this systematic review was to assess the short- and long-term release of components of orthodontic adhesives and polycarbonate brackets in the oral environment. METHODS Electronic database searches of published and unpublished literature were performed. The following electronic databases with no language and publication date restrictions were searched: MEDLINE (via Ovid and PubMed), EMBASE (via Ovid), Cochrane Oral Health Group's Trials Register, and CENTRAL. Unpublished literature was searched on ClinicalTrials.gov, the National Research Register, and Pro-Quest Dissertation Abstracts and Thesis database. The reference lists of all eligible studies were checked for additional studies. Two review authors performed data extraction independently and in duplicate using data collection forms. Disagreements were resolved by discussion or the involvement of an arbiter. RESULTS No randomized controlled trial was identified. In the absence of randomized controlled trials, observational studies were included. Eleven studies met the inclusion criteria. All were observational studies conducted in vivo or in vitro. The bisphenol-A release from orthodontic bonding resins was found to be between 0.85 and 20.88 ng per milliliter in vivo, and from traces to 65.67 ppm in vitro. Polycarbonate brackets released amounts of 22.24 μg per gram in ethanol solution and 697 μg per gram after 40 months in water. Bis-GMA and TEGDMA leaching in vitro reached levels of 64 and 174 mg per 10 μL, respectively. Because of the heterogeneity in methodologies and reporting, only qualitative synthesis was performed. CONCLUSIONS The available evidence on this topic derived from observational in-vivo and in-vitro studies that represent a moderate level of evidence. The variety of setups and the different units allied to the diversity of reporting among studies did not allow calculation of pooled estimates.

The effectiveness of laceback ligatures during initial orthodontic alignment: a systematic review and meta-analysis

Lacebacks may be used to limit unwanted incisor proclination during initial orthodontic alignment; however, their use has not met with universal approval. This systematic review aims to appraise the evidence in relation to the effectiveness of lacebacks in controlling incisor position during initial alignment. Electronic database searches of published literature (MEDLINE via Ovid, Cochrane Central Register of Controlled Trials, LILACS, and IBECS) and unpublished literature were performed. Search terms used included randomized controlled trial, controlled clinical trial, random allocation, double blind method, orthodontics, and laceback. Data were extracted using custom forms. Risk of bias assessment was made using the Cochrane Collaboration risk of bias tool. The quality of the evidence was also assessed using GRADE. Mean differences in incisor inclination and antero-posterior changes in incisor and molar position during alignment were calculated. Two studies involving 97 participants were found to be at low risk of bias and were included in the quantitative synthesis. The random effects meta-analysis demonstrated that the use of lacebacks was associated with 0.5 mm greater posterior movement of the incisors during alignment; this finding was of limited clinical importance and statistically non-significant [95 per cent confidence interval (CI): -1.25, 0.25, P = 0.19]. Little difference (0.46 mm) was also found between laceback and non-laceback groups with regards to mesial molar movement (95 per cent CI: -0.33, 1.24, P = 0.26). According to the GRADE assessment, the overall quality of evidence relating to the use of lacebacks was high. There is no evidence to support the use of lacebacks for the control of the sagittal position of the incisors during initial orthodontic alignment.

Subjective and objective perception of orthodontic treatment need: a systematic review

The aim of this work was to investigate the published evidence on the comparison of self-perception and diagnosis of orthodontic treatment need. A search of Cochrane Library, MEDLINE, Scopus databases, and archives of two orthodontic journals was carried out from January 1966 to August 2011 by the two authors using Medical Subject Heading terms. Studies that investigated solely either self-perception of orthodontic need by laypersons or assessment of orthodontic need by professionals were excluded from the data analysis. The methodological soundness of each study and the aggregate level of evidence were evaluated according to predetermined criteria. Moderate level of evidence, the relatively highest grade, was assigned to 9.1 per cent of the 22 studies, finally included in the data analysis. The overall evidence level provided by the evaluated publications was rated as limited. However, the existing body of evidence indicated a highly variable association between self-perception of orthodontic treatment need and orthodontist's assessment. Future controlled studies with well-defined samples and common assessment methodology will clarify further the relationship between perception of treatment need by laypersons and orthodontists and enhance international comparison and development of health care strategies.

Valuing the Health States Associated with Chlamydia trachomatis Infections and Their Sequelae: A Systematic Review of Economic Evaluations and Primary Studies

OBJECTIVES Economic evaluations of interventions to prevent and control sexually transmitted infections such as Chlamydia trachomatis are increasingly required to present their outcomes in terms of quality-adjusted life-years using preference-based measurements of relevant health states. The objectives of this study were to critically evaluate how published cost-effectiveness studies have conceptualized and valued health states associated with chlamydia and to examine the primary evidence available to inform health state utility values (HSUVs). METHODS A systematic review was conducted, with searches of six electronic databases up to December 2012. Data on study characteristics, methods, and main results were extracted by using a standard template. RESULTS Nineteen economic evaluations of relevant interventions were included. Individual studies considered different health states and assigned different values and durations. Eleven studies cited the same source for HSUVs. Only five primary studies valued relevant health states. The methods and viewpoints adopted varied, and different values for health states were generated. CONCLUSIONS Limitations in the information available about HSUVs associated with chlamydia and its complications have implications for the robustness of economic evaluations in this area. None of the primary studies could be used without reservation to inform cost-effectiveness analyses in the United Kingdom. Future debate should consider appropriate methods for valuing health states for infectious diseases, because recommended approaches may not be suitable. Unless we adequately tackle the challenges associated with measuring and valuing health-related quality of life for patients with chlamydia and other infectious diseases, evaluating the cost-effectiveness of interventions in this area will remain problematic.

Retention in care of HIV-infected children from HIV test to start of antiretroviral therapy: systematic review

BACKGROUND In adults it is well documented that there are substantial losses to the programme between HIV testing and start of antiretroviral therapy (ART). The magnitude and reasons for loss to follow-up and death between HIV diagnosis and start of ART in children are not well defined. METHODS We searched the PubMed and EMBASE databases for studies on children followed between HIV diagnosis and start of ART in low-income settings. We examined the proportion of children with a CD4 cell count/percentage after after being diagnosed with HIV infection, the number of treatment-eligible children starting ART and predictors of loss to programme. Data were extracted in duplicate. RESULTS Eight studies from sub-Saharan Africa and two studies from Asia with a total of 10,741 children were included. Median age ranged from 2.2 to 6.5 years. Between 78.0 and 97.0% of HIV-infected children subsequently had a CD4 cell count/percentage measured, 63.2 to 90.7% of children with an eligibility assessment met the eligibility criteria for the particular setting and time and 39.5 to 99.4% of the eligible children started ART. Three studies reported an association between low CD4 count/percentage and ART initiation while no association was reported for gender. Only two studies reported on pre-ART mortality and found rates of 13 and 6 per 100 person-years. CONCLUSION Most children who presented for HIV care met eligibility criteria for ART. There is an urgent need for strategies to improve the access to and retention to care of HIV-infected children in resource-limited settings.

Serologic vaccination response after solid organ transplantation: a systematic review

BACKGROUND Infectious diseases after solid organ transplantation (SOT) are one of the major complications in transplantation medicine. Vaccination-based prevention is desirable, but data on the response to active vaccination after SOT are conflicting. METHODS In this systematic review, we identify the serologic response rate of SOT recipients to post-transplantation vaccination against tetanus, diphtheria, polio, hepatitis A and B, influenza, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitides, tick-borne encephalitis, rabies, varicella, mumps, measles, and rubella. RESULTS Of the 2478 papers initially identified, 72 were included in the final review. The most important findings are that (1) most clinical trials conducted and published over more than 30 years have all been small and highly heterogeneous regarding trial design, patient cohorts selected, patient inclusion criteria, dosing and vaccination schemes, follow up periods and outcomes assessed, (2) the individual vaccines investigated have been studied predominately only in one group of SOT recipients, i.e. tetanus, diphtheria and polio in RTX recipients, hepatitis A exclusively in adult LTX recipients and mumps, measles and rubella in paediatric LTX recipients, (3) SOT recipients mount an immune response which is for most vaccines lower than in healthy controls. The degree to which this response is impaired varies with the type of vaccine, age and organ transplanted and (4) for some vaccines antibodies decline rapidly. CONCLUSION Vaccine-based prevention of infectious diseases is far from satisfactory in SOT recipients. Despite the large number of vaccination studies preformed over the past decades, knowledge on vaccination response is still limited. Even though the protection, which can be achieved in SOT recipients through vaccination, appears encouraging on the basis of available data, current vaccination guidelines and recommendations for post-SOT recipients remain poorly supported by evidence. There is an urgent need to conduct appropriately powered vaccination trials in well-defined SOT recipient cohorts.

Absorbable collagen membranes for periodontal regeneration: a systematic review

Guided tissue regeneration (GTR) with bioabsorbable collagen membranes (CM) is commonly used for the treatment of periodontal defects. The objective of this systematic review of randomized clinical trials was to assess the clinical efficacy of GTR procedures with CM, with or without bone substitutes, in periodontal infrabony defects compared with that of open flap debridement (OFD) alone. Primary outcomes were tooth loss and gain in clinical attachment level (CAL). Screening of records, data extraction, and risk-of-bias assessments were performed by two reviewers. Weighted mean differences were estimated by random effects meta-analysis. We included 21 reports on 17 trials. Risk of bias was generally high. No data were available for the primary outcome tooth loss. The summary treatment effect for change in CAL for GTR with CM compared with OFD was 1.58 mm (95% CI, 1.27 to 1.88). Despite large between-trial heterogeneity (I2 = 75%, p < .001), all trials favored GTR over OFD. No differences in treatment effects were detected between trials of GTR with CM alone and trials of GTR with CM in combination with bone substitutes (p for interaction, .31). GTR with CM, with or without substitutes, may result in improved clinical outcomes compared with those achieved with OFD alone. Our findings support GTR with CM for the treatment of infrabony periodontal defects.

The potential association between gingival crevicular fluid inflammatory mediators and adverse pregnancy outcomes: a systematic review

OBJECTIVES The association between periodontal disease and adverse pregnancy outcomes (APO), primarily preterm birth (PTB), is still controversially discussed in the literature. Therefore, the aim of the present systematic review was to analyze the existing literature on the potential association between inflammatory mediators detected in gingival crevicular fluid (GCF) and APO. MATERIALS AND METHODS MEDLINE (PubMed) and EMBASE databases were searched for entries up to April 2012 and studies were selected by two independent reviewers. RESULTS The majority of the eight studies included confirmed a positive association between GCF mediators, such as interleukin-1β, prostaglandin E2, and tumor necrosis factor-alpha, and APO. Due to the heterogeneity and variability of the available studies, no meta-analysis could be performed. CONCLUSIONS A positive association between GCF inflammatory mediator levels and APO/PTB might be present but the results need to be considered with great caution because of the heterogeneity and variability among the studies. Further studies with an adequate number of patients allowing for an appropriate analysis are warranted to definitely confirm this association. CLINICAL RELEVANCE The present findings suggest that an association between GCF inflammatory mediator levels and APO might exist.

Efficacy of psychological interventions for sexual dysfunction: a systematic review and meta-analysis

Sexual dysfunction is highly prevalent in the general population and associated with psychological distress and impaired sexual satisfaction. Psychological interventions are promising treatment options, as sexual dysfunction is frequently caused by and deteriorates because of psychological factors. However, research into the efficacy of psychological interventions is rather scarce and an up-to-date review of outcome studies is currently lacking. Therefore, we conducted a systematic review and meta-analysis of all available studies from 1980 to 2009 to examine the efficacy of psychological interventions for patients with sexual dysfunction. A total of 20 randomized controlled studies comparing a psychological intervention with a wait-list were included in the meta-analysis. The overall post-treatment effect size for symptom severity was d = 0.58 (95% CI: 0.40 to 0.77) and for sexual satisfaction d = 0.47 (95% CI: 0.27 to 0.70). Psychological interventions were shown to especially improve symptom severity for women with Hypoactive Sexual Desire Disorder and orgasmic disorder. Our systematic review of 14 studies comparing at least two active interventions head-to-head revealed that very few comparative studies are available with large variability in effect sizes across studies (d between -0.69 and 2.29 for symptom severity and -0.56 and 14.02 for sexual satisfaction). In conclusion, psychological interventions are effective treatment options for sexual dysfunction. However, evidence varies considerably across single disorders. Good evidence exists to date for female hypoactive sexual desire disorder and female orgasmic disorder. Further research is needed on psychological interventions for other sexual dysfunctions, their long-term and comparative effects.