Combined magnetic resonance imaging and magnetic resonance spectroscopy imaging in the diagnosis of prostate cancer: a systematic review and meta-analysis

CONTEXT: Magnetic resonance imaging (MRI) combined with magnetic resonance spectroscopy imaging (MRSI) emerged as a promising test in the diagnosis of prostate cancer and showed encouraging results. OBJECTIVE: The aim of this systematic review is to meta-analyse the diagnostic accuracy of combined MRI/MRSI in prostate cancer and to explore risk profiles with highest benefit. EVIDENCE ACQUISITION: The authors searched the MEDLINE and EMBASE databases and the Cochrane Library, and the authors screened reference lists and contacted experts. There were no language restrictions. The last search was performed in August 2008. EVIDENCE SYNTHESIS: We identified 31 test-accuracy studies (1765 patients); 16 studies (17 populations) with a total of 581 patients were suitable for meta-analysis. Nine combined MRI/MRSI studies (10 populations) examining men with pathologically confirmed prostate cancer (297 patients; 1518 specimens) had a pooled sensitivity and specificity on prostate subpart level of 68% (95% CI, 56-78%) and 85% (95% CI, 78-90%), respectively. Compared with patients at high risk for clinically relevant cancer (six studies), sensitivity was lower in low-risk patients (four studies) (58% [46-69%] vs 74% [58-85%]; p>0.05) but higher for specificity (91% [86-94%] vs 78% [70-84%]; p<0.01). Seven studies examining patients with suspected prostate cancer at combined MRI/MRSI (284 patients) had an overall pooled sensitivity and specificity on patients level of 82% (59-94%) and 88% (80-95%). In the low-risk group (five studies) these values were 75% (39-93%) and 91% (77-97%), respectively. CONCLUSIONS: A limited number of small studies suggest that MRI combined with MRSI could be a rule-in test for low-risk patients. This finding needs further confirmation in larger studies and cost-effectiveness needs to be established.

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.

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.

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.

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.

The current prevalence of child sexual abuse worldwide: a systematic review and meta-analysis

OBJECTIVES Systematic reviews on prevalence estimates of child sexual abuse (CSA) worldwide included studies with adult participants referring on a period of abuse of about 50 years. Therefore we aimed to describe the current prevalence of CSA, taking into account geographical region, type of abuse, level of country development and research methods. METHODS We included studies published between 2002 and 2009 that reported CSA in children below 18 years. We performed a random effects meta-analysis and analyzed moderator variables by meta-regression. RESULTS Fifty-five studies from 24 countries were included. According to four predefined types of sexual abuse, prevalence estimates ranged from 8 to 31 % for girls and 3 to 17 % for boys. Nine girls and 3 boys out of 100 are victims of forced intercourse. Heterogeneity between primary studies was high in all analyses. CONCLUSIONS Our results based on most recent data confirm results from previous reviews with adults. Surveys in children offer most recent estimates of CSA. Reducing heterogeneity between studies might be possible by standardized measures to make data more meaningful in international comparisons.

Comparing Haemophilus influenzae type b conjugate vaccine schedules: a systematic review and meta-analysis of vaccine trials

BACKGROUND The optimal schedule and the need for a booster dose are unclear for Haemophilus influenzae type b (Hib) conjugate vaccines. We systematically reviewed relative effects of Hib vaccine schedules. METHODS We searched 21 databases to May 2010 or June 2012 and selected randomized controlled trials or quasi-randomized controlled trials that compared different Hib schedules (3 primary doses with no booster dose [3p+0], 3p+1 and 2p+1) or different intervals in primary schedules and between primary and booster schedules. Outcomes were clinical efficacy, nasopharyngeal carriage and immunological response. Results were combined in random-effects meta-analysis. RESULTS Twenty trials from 15 countries were included; 16 used vaccines conjugated to tetanus toxoid (polyribosylribitol phosphate conjugated to tetanus toxoid). No trials assessed clinical or carriage outcomes. Twenty trials examined immunological outcomes and found few relevant differences. Comparing polyribosylribitol phosphate conjugated to tetanus toxoid 3p+0 with 2p+0, there was no difference in seropositivity at the 1.0 μg/mL threshold by 6 months after the last primary dose (combined risk difference -0.02; 95% confidence interval: -0.10, 0.06). Only small differences were seen between schedules starting at different ages, with different intervals between primary doses, or with different intervals between primary and booster doses. Individuals receiving a booster were more likely to be seropositive than those at the same age who did not. CONCLUSIONS There is no clear evidence from trials that any 2p+1, 3p+0 or 3p+1 schedule of Hib conjugate vaccine is likely to provide better protection against Hib disease than other schedules. Until more data become available, scheduling is likely to be determined by epidemiological and programmatic considerations in individual settings.

Homicide-suicides compared to homicides and suicides: systematic review and meta-analysis.

Homicide-suicides, the murder of one or several individuals followed by the suicide of the perpetrator, are rare but have devastating effects on families and communities. We did a systematic review and meta-analysis of studies comparing perpetrators of homicide-suicides with perpetrators of simple homicides and suicides and examined the proportion of firearm use and its correlation with firearm availability. We searched Medline and Embase from inception to July 2012 and identified 27 eligible studies. Perpetrators of homicide-suicides were older and more likely to be male and married to or separated from their victims than perpetrator of simple homicides or suicides. Influence of alcohol and a history of domestic violence or unemployment were less prevalent in homicide-suicides than in homicides. The proportion of firearm use in homicide-suicides varied across countries and was highest in the USA, Switzerland and South Africa, followed by Australia, Canada, The Netherlands and England and Wales, with a strong correlation between the use of firearms and the level of civilian gun ownership in the country. Our results indicate that homicide-suicides represent a distinct entity, with characteristics distinguishing them both from homicides and suicides.

Critical Analysis of Bladder Sparing with Trimodal Therapy in Muscle-invasive Bladder Cancer: A Systematic Review.

CONTEXT Aims of bladder preservation in muscle-invasive bladder cancer (MIBC) are to offer a quality-of-life advantage and avoid potential morbidity or mortality of radical cystectomy (RC) without compromising oncologic outcomes. Because of the lack of a completed randomised controlled trial, oncologic equivalence of bladder preservation modality treatments compared with RC remains unknown. OBJECTIVE This systematic review sought to assess the modern bladder-preservation treatment modalities, focusing on trimodal therapy (TMT) in MIBC. EVIDENCE ACQUISITION A systematic literature search in the PubMed and Cochrane databases was performed from 1980 to July 2013. EVIDENCE SYNTHESIS Optimal bladder-preservation treatment includes a safe transurethral resection of the bladder tumour as complete as possible followed by radiation therapy (RT) with concurrent radiosensitising chemotherapy. A standard radiation schedule includes external-beam RT to the bladder and limited pelvic lymph nodes to an initial dose of 40Gy, with a boost to the whole bladder to 54Gy and a further tumour boost to a total dose of 64-65Gy. Radiosensitising chemotherapy with phase 3 trial evidence in support exists for cisplatin and mitomycin C plus 5-fluorouracil. A cystoscopic assessment with systematic rebiopsy should be performed at TMT completion or early after TMT induction. Thus, nonresponders are identified early to promptly offer salvage RC. The 5-yr cancer-specific survival and overall survival rates range from 50% to 82% and from 36% to 74%, respectively, with salvage cystectomy rates of 25-30%. There are no definitive data to support the benefit of using of neoadjuvant or adjuvant chemotherapy. Critical to good outcomes is proper patient selection. The best cancers eligible for bladder preservation are those with low-volume T2 disease without hydronephrosis or extensive carcinoma in situ. CONCLUSIONS A growing body of accumulated data suggests that bladder preservation with TMT leads to acceptable outcomes and therefore may be considered a reasonable treatment option in well-selected patients. PATIENT SUMMARY Treatment based on a combination of resection, chemotherapy, and radiotherapy as bladder-sparing strategies may be considered as a reasonable treatment option in properly selected patients.

Consistency of thromboelastometry analysis under scrutiny: Results of a systematic evaluation within and between analysers.

While the use of thromboelastometry analysis (ROTEM®) in evaluation of haemostasis is rapidly increasing, important validity parameters of testing remain inadequately examined. We aimed to study systematically the consistency of thromboelastometry parameters within individual tests regarding measurements between different analysers, between different channels of the same analyser, between morning and afternoon measurements (circadian variation), and if measured four weeks apart. Citrated whole blood samples from 40 healthy volunteers were analysed with two analysers in parallel. EXTEM, INTEM, FIBTEM, HEPTEM and APTEM tests were conducted. A Bland-Altman comparison was performed and homogeneity of variances was tested using the pitman test. P-value ranges were used to classify the level of homogeneity (p<0.15 - low homogeneity, p = 0.15 to 0.5 - intermediate homogeneity, p>0.5 high homogeneity). Less than half of all comparisons made showed high homogeneity of variances (p>0.5) and in about a fifth of comparisons data distributions were heterogeneous (p<0.15). There was no clear pattern for homogeneity. On average, comparisons of MCF, ML and LI30 measurements tended to be better, but none of the tests assessed outperformed another. In conclusion, systematic investigation reveals large differences in the results of some thromboelastometry parameters and lack of consistency. Clinicians and scientists should take these inconsistencies into account and focus on parameters with a higher homogeneity such as MCF.

Quantitative Myocardial Contrast Echocardiography during Pharmacological Stress for Diagnosis of Coronary Artery Disease: A Systematic Review and Meta-analysis of Diagnostic Accuracy Studies

AIMS: We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). METHODS AND RESULTS: Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and Abeta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (CI). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and Abeta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and Abeta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and Abeta reserves, respectively. CONCLUSION: Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

Breastfeeding and Childhood Asthma: Systematic Review and Meta-Analysis.

Asthma and wheezing disorders are common chronic health problems in childhood. Breastfeeding provides health benefits, but it is not known whether or how breastfeeding decreases the risk of developing asthma. We performed a systematic review and meta-analysis of studies published between 1983 and 2012 on breastfeeding and asthma in children from the general population. We searched the PubMed and Embase databases for cohort, cross-sectional, and case-control studies. We grouped the outcomes into asthma ever, recent asthma, or recent wheezing illness (recent asthma or recent wheeze). Using random-effects meta-analyses, we estimated pooled odds ratios of the association of breastfeeding with the risk for each of these outcomes. We performed meta-regression and stratified meta-analyses. We included 117 of 1,464 titles identified by our search. The pooled odds ratios were 0.78 (95% confidence interval: 0.74, 0.84) for 75 studies analyzing "asthma ever," 0.76 (95% confidence interval: 0.67, 0.86) for 46 studies analyzing "recent asthma," and 0.81 (95% confidence interval: 0.76, 0.87) for 94 studies analyzing recent wheezing illness. After stratification by age, the strong protective association found at ages 0-2 years diminished over time. We found no evidence for differences by study design or study quality or between studies in Western and non-Western countries. A positive association of breastfeeding with reduced asthma/wheezing is supported by the combined evidence of existing studies.

Fish or n3-PUFA intake and body composition: a systematic review and meta-analysis.

Obesity is a major public health issue and an important contributor to the global burden of chronic disease and disability. Studies indicate that fish and omega-3 polyunsaturated fatty acids (n3-PUFA) supplements may help prevent cardiovascular and metabolic diseases. However, the effect of fish oil on body composition is still uncertain, so we performed a systematic review of randomized controlled trials and the first meta-analysis on the association between fish or fish oil intake and body composition measures. We found evidence that participants taking fish or fish oil lost 0.59 kg more body weight than controls (95% confidence interval [CI]: -0.96 to -0.21). Treatment groups lost 0.24 kg m(-2) (body mass index) more than controls (-0.40 to -0.08), and 0.49 % more body fat than controls (-0.97 to -0.01). Fish or fish oil reduced waist circumference by 0.81 cm (-1.34 to -0.28) compared with control. There was no difference for fat mass and lean body mass. Further research is needed to confirm or refute our findings and to reveal possible mechanisms by which n3-PUFAs might reduce weight.