Single Randomized Clinical Trial Research Articles

Evaluating Glass Ionomer Cement Longevity in the Primary and Permanent Teeth-An Umbrella Review.

The aim of this umbrella review was to evaluate the longevity of glass ionomer cement (GIC) as a restorative material for primary and permanent teeth. Research in the literature was conducted in three databases (MedLine/PubMed, Web of Science, and Scopus). The inclusion criteria were: (1) to be a systematic review of clinical trials that (2) evaluated the clinical longevity of GICs as a restorative material in primary and/or permanent teeth; the exclusion criteria were: (1) not being a systematic review of clinical trials; (2) not evaluating longevity/clinical performance of GICs as a restorative material; and (3) studies of dental restorative materials in teeth with enamel alterations, root caries, and non-carious cervical lesions. Twenty-four eligible articles were identified, and 13 were included. The follow-up periods ranged from 6 months to 6 years. Different types of GICs were evaluated in the included studies: resin-modified glass ionomer cement (RMGIC), compomers, and low- and high-viscosity glass ionomer cement. Some studies compared amalgam and composite resins to GICs regarding longevity/clinical performance. Analyzing the AMSTAR-2 results, none of the articles had positive criteria in all the evaluated requisites, and none of the articles had an a priori design. The criteria considered for the analysis of the risk of bias of the included studies were evaluated through the ROBIS tool, and the results of this analysis showed that seven studies had a low risk of bias; three studies had positive results in all criteria except for one criterion of unclear risk; and two studies showed a high risk of bias. GRADE tool was used to determine the quality of evidence; for the degree of recommendations, all studies were classified as Class II, meaning there was still conflicting evidence on the clinical performance/longevity of GICs and their recommendations compared to other materials. The level of evidence was classified as Level B, meaning that the data were obtained from less robust meta-analyses and single randomized clinical trials. To the best of our knowledge, this is the first umbrella review approaching GIC in permanent teeth. GICs are a good choice in both dentitions, but primary dentition presents more evidence, especially regarding the atraumatic restorative treatment (ART) technique. Within the limitation of this study, it is still questionable if GIC is a good restorative material in the medium/long term for permanent and primary dentition. Many of the included studies presented a high risk of bias and low quality. The techniques, type of GIC, type of cavity, and operator experience highly influence clinical performance. Thus, clinical decision-making should be based on the dental practitioner's ability, each case analysis, and the patient's wishes. More evidence is needed to determine which is the best material for definitive restorations in permanent and primary dentition.

PP128 A Transparent Methodology To Assess Innovativeness Of Health Technologies At Marketing Authorization Time

IntroductionDefining drug innovation can be challenging and there is no consensus on what a truly “innovative” medicine is. The Italian Medicine Agency (AIFA) has established an approach to assess innovativeness based on therapeutic need, added therapeutic value, and quality of evidence. However, judgment can be subjective and may not be adequate for assessment at the time of marketing authorization, when only preliminary evidence – often from non-comparative or non-randomized trials – are available. We developed a transparent methodology for early assessment of innovativeness at the time of marketing authorization, based on AIFA guidelines.MethodsSince the perspective was the marketing authorization date, only data available at agency’s Medical Review or pivotal trial publications were considered. AIFA criteria were revisited, using oncology medicines approved in the last 10 years as a base case. Impact of preliminary evidence and inadequate study design was considered.ResultsEach assessment should refer to the first approved specific indication and predefined clinically relevant outcomes. When more than one study was presented, best methodological quality, larger sample and/or longer follow-up was selected. Four domains were established: Therapeutical need: existence and clinical benefits of alternative therapies; Clinical benefit added when compared to those alternatives; Suitability of study design considering adequate comparator group, relevant outcome assessed and randomization; Risk of bias. For each domain, clear and specific criteria were defined in consensus by a group of experts in health technology assessment (HTA) and were applied to all cancer drugs evaluated.ConclusionsEfficacy evidence available for marketing authorization are often based on preliminary data, arising from single randomized clinical trials or even non-comparative studies, which difficult early assessments of innovativeness. For this reason, transparent and reproducible methodologies can be useful not only to HTA bodies, but also for other key stakeholders in the pharmaceutical market, such as investors, researchers, doctors, and governments.

Estimated Lifetime Gained With Cancer Screening Tests

Cancer screening tests are promoted to save life by increasing longevity, but it is unknown whether people will live longer with commonly used cancer screening tests. To estimate lifetime gained with cancer screening. A systematic review and meta-analysis was conducted of randomized clinical trials with more than 9 years of follow-up reporting all-cause mortality and estimated lifetime gained for 6 commonly used cancer screening tests, comparing screening with no screening. The analysis included the general population. MEDLINE and the Cochrane library databases were searched, and the last search was performed October 12, 2022. Mammography screening for breast cancer; colonoscopy, sigmoidoscopy, or fecal occult blood testing (FOBT) for colorectal cancer; computed tomography screening for lung cancer in smokers and former smokers; or prostate-specific antigen testing for prostate cancer. Searches and selection criteria followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Data were independently extracted by a single observer, and pooled analysis of clinical trials was used for analyses. Life-years gained by screening was calculated as the difference in observed lifetime in the screening vs the no screening groups and computed absolute lifetime gained in days with 95% CIs for each screening test from meta-analyses or single randomized clinical trials. In total, 2 111 958 individuals enrolled in randomized clinical trials comparing screening with no screening using 6 different tests were eligible. Median follow-up was 10 years for computed tomography, prostate-specific antigen testing, and colonoscopy; 13 years for mammography; and 15 years for sigmoidoscopy and FOBT. The only screening test with a significant lifetime gain was sigmoidoscopy (110 days; 95% CI, 0-274 days). There was no significant difference following mammography (0 days: 95% CI, -190 to 237 days), prostate cancer screening (37 days; 95% CI, -37 to 73 days), colonoscopy (37 days; 95% CI, -146 to 146 days), FOBT screening every year or every other year (0 days; 95% CI, -70.7 to 70.7 days), and lung cancer screening (107 days; 95% CI, -286 days to 430 days). The findings of this meta-analysis suggest that current evidence does not substantiate the claim that common cancer screening tests save lives by extending lifetime, except possibly for colorectal cancer screening with sigmoidoscopy.

Surface decontamination protocols for surgical treatment of peri-implantitis: A systematic review with meta-analysis.

To answer the following PICO question: "In patients requiring surgical treatment of peri-implantitis (P), is any implant surface decontamination protocol (I) superior to others (C) in terms of clinical and radiographic parameters (O)?" Randomized clinical trials (RCTs) comparing two or more decontamination protocols as part of the surgical treatment of peri-implantitis were included. Two authors independently searched for eligible studies, screened titles and abstracts, did full-text analysis, extracted data, and performed the risk-of-bias assessment. Whenever possible, results were summarized through random effects meta-analyses. Twenty-two manuscripts reporting on 16 RCTs were included, testing mechanical, chemical and physical decontamination protocols. All of them resulted in an improvement in clinical parameters; however, the superiority of specific protocols over others is mainly based on single RCTs. The use of titanium brushes and implantoplasty showed favorable results as single decontamination methods. Meta-analyses indicated a lack of added effect of Er:Yag laser on probing pocket depth (PPD) reduction (n=2, WMD=-0.24 mm, 95% confidence interval [CI] [-1.10; 0.63], p=.59); while systemic antimicrobials (amoxicillin or azithromycin) showed an added effect on treatment success ([PPD ≤5 mm, no bleeding or suppuration, no progressive bone loss]; n=2, RR=1.84, 95% CI [1.17;2.91], p=.008), but not in terms of PPD reduction (n=2, WMD=0.93 mm, 95% CI [-0.69; 2.55], p=.26), even if with substantial heterogeneity. No single decontamination method demonstrated clear evidence of superiority compared to the others. Systemic antibiotics, but not Er:Yag laser, may provide short-term clinical benefits in terms of treatment success (CRD42020182303).

Estimating the Complier Average Causal Effect in a Meta-Analysis of Randomized Clinical Trials With Binary Outcomes Accounting for Noncompliance: A Generalized Linear Latent and Mixed Model Approach.

Noncompliance, a common problem in randomized clinical trials (RCTs), can bias estimation of the effect of treatment receipt using a standard intention-to-treat analysis. The complier average causal effect (CACE) measures the effect of an intervention in the latent subpopulation that would comply with their assigned treatment. Although several methods have been developed to estimate the CACE in analyzing a single RCT, methods for estimating the CACE in a meta-analysis of RCTs with noncompliance await further development. This article reviews the assumptions needed to estimate the CACE in a single RCT and proposes a frequentist alternative for estimating the CACE in a meta-analysis, using a generalized linear latent and mixed model with SAS software (SAS Institute, Inc.). The method accounts for between-study heterogeneity using random effects. We implement the methods and describe an illustrative example of a meta-analysis of 10 RCTs evaluating the effect of receiving epidural analgesia in labor on cesarean delivery, where noncompliance varies dramatically between studies. Simulation studies are used to evaluate the performance of the proposed method.

The Efficacy of O-Mac®, Patent Video Laryngoscope, and Conventional Laryngoscope for Intubation in the Operating Room

BACKGROUND: Management of the airway in patients undergoing surgery is increasingly difficult. The airway management in the operating room in terms of the initial action of anesthesia is very important. Video-laryngoscopy has been shown to provide a better view of the larynx’s structure compared to direct visualization. AIM: We describe our experience using a custom made and inexpensive tool for a video-laryngoscopy. METHODS: This is an experimental research with single randomized clinical trial conducted at the Anesthesiology Department of Sanglah General Hospital Denpasar. There were 270 patients divides into three group with conventional, O-Mac® and Mc-GRATH™ BF laryngoscope, aged 18–65 years old, with Mallampati grade 1–2, randomly selected, and signed informed consent. RESULTS: Intubation time fastest with O-Mac® median 26 (15–36) s, p = 0.000. Laryngoscopy time fastest with O-Mac® median 5.5 (2–13 s), p = 0.000. O-Mac® does not use many tools, p = 0.000. All three did not produce tissue damage with results p = 0.007. Hemodynamic changes p = 0.000. CONCLUSION: The O-Mac® is superior in terms of laryngoscope time and intubation time compared to the Mc-GRATH™ BF blade and has the same level of safety as the patented Mc-GRATH ™ video laryngoscope, and better than conventional laryngoscopes.

Pharmacological and behavioral treatment for trichotillomania: An updated systematic review with meta-analysis.

Trichotillomania (TTM) is a difficult-to-treat psychiatric condition with no first-line medications approved by the Food and Drug Administration. Individuals with TTM often feel that clinicians know little about this disorder. Here, we present an updated meta-analysis of randomized controlled trials (RCTs) examining treatments for TTM. Pubmed, PsychINFO, Embase, and CENTRAL were searched with the terms "Trichotillomania OR Hair Pulling Disorder" to identify randomized controlled clinical trials evaluating treatments for TTM. Twenty-four trials involving 26 comparisons and 857 participants were included in this meta-analysis. Behavioral therapy with habit-reversal training components (BT-HRT) demonstrated a large benefit compared to control conditions (standardized mean difference [SMD] [95% CI] = -1.22 [-1.71, -0.73], p < .0001) for improving TTM symptoms. Clomipramine (SMD [95% CI] = -0.71 [-1.38, -0.05], p = .036), N-acetylcysteine (SMD [95% CI] = -0.75 [-1.36, -0.13], p = .017) and olanzapine (SMD [95% CI] = -0.94 [-1.77, -0.12], p = .025) demonstrated significant benefits compared to placebo in RCTs. BT-HRT has demonstrated the largest treatment effects and has the strongest evidence base for reducing TTM symptoms. In contrast, several pharmacological agents have demonstrated efficacy in single randomized clinical trials that would benefit from replication. Additional trials are needed to identify other effective medications for TTM and determine the relative efficacy of available agents.

Remission in adolescents with bulimia nervosa: Empirical evaluation of current conceptual models.

The few randomized clinical trials (RCTs) investigating adolescent treatment for bulimia nervosa (BN) suggest variability in both rates of, and criteria for remission. The current study examined reactivity in remission rates, relative to various conceptualizations of remission in a single RCT data set. A data set of adolescents with BN who participated in an RCT (N = 110) was used to evaluate remission models based upon behavioral symptoms (e.g., binge eating), psychological symptoms (Eating Disorder Examination [EDE] scores), and combinations of these criteria. At end-of-treatment (EOT), a remission model defined by behavioral symptom abstinence plus meaningful reduction in EDE global scores yielded comparable remission rates to a model defined by behavioral abstinence alone (i.e., 29% remitted). Participants with higher EOT EDE global scores were less likely to be abstinent from behavioral symptoms at 6- and 12-month follow-up (ps < .001). Reduction in psychological symptoms with behavioral abstinence did not inform remission status at EOT, over and above behavioral symptom change alone. However, psychological symptom improvement by EOT may predict positive prognosis in posttreatment assessment. Results underscore the necessity of including psychological symptom improvement, as well as consistency across research and practice, in defining remission in adolescent BN.

Levels of evidence supporting European and American community-acquired pneumonia guidelines.

Optimal clinical decisions should be supported by clinical practice guidelines (CPG) based on evidence generated from randomized clinical trials (RCT). We aimed to evaluate the class and level of evidence (LOE) supporting the international community-acquired pneumonia (CAP) guidelines and their variation over time. The 2019 Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) and the 2011 European Respiratory Society/European Society Clinical Microbiology Infectious Diseases (ERS/ESCMID) CPG and its immediate predecessors (2007 and 2005) were evaluated. The number of recommendations and distribution as LOE A (supported by multiple RCT or a single, large RCT), B (supported by data from a single RCT or observational studies) and C (expert opinion, case studies, or standard of care) was identified. Overall, recommendations for diagnosis, management, and prevention were graded as strong in 51.4%, 62.9%, and 23.5% in spite that they were supported by LOE A in 5.7%, 11.1%, and 52.9%, respectively. In the 2019 ATS/IDSA guidelines (39 recommendations), 7.7% (n= 3) recommendations were classified as LOE A, 30.8% (n= 12) as LOE B, and 61.5% (24%) as LOE C. Across the 2011 ERS/ESCMID guidelines (68 recommendations), 21.2% (n= 14) recommendations were classified as LOE A, 4.6% (n= 3) as LOE B, and 74.2% (n= 49) as LOE C. When comparing with prior versions, the proportion of recommendations that were LOE A did not significantly increase in ERS/ESCMID (21.2% vs 20%) and decreased in ATS/IDSA (7.7% vs 32.0%). In conclusion, large randomized trials or network meta-analysis including comparison of regimens to identify high probability of best cure and mortality is an unmet clinical need on CAP.

Rehabilitation to improve gaze and postural stability in people with multiple sclerosis: study protocol for a prospective randomized clinical trial

BackgroundThe use of vestibular rehabilitation principles in the management of gaze and postural stability impairments in people with multiple sclerosis (PwMS) has shown promise in pilot work completed in our lab and in a recently published randomized clinical trial (RCT). However, further work is needed to fully quantify the gaze and postural impairments present in people with multiple sclerosis and how they respond to rehabilitation.Methods/designThe study is a single blind RCT designed to examine the benefit of a gaze and postural stability (GPS) intervention program compared to a standard of care (SOC) rehabilitation program in dizzy and balance impaired PwMS. Outcomes will be collected across the domains of body structure and function, activity, and participation as classified by the World Health Organization International Classification of Functioning, Disability, and Health (ICF). Our primary outcomes are the Dizziness Handicap Inventory (DHI) and the Functional Gait Assessment (FGA). Secondary outcomes include other measures of gaze and postural stability, fatigue, and functional mobility. Participants who are interested and eligible for enrollment will be consented prior to completing a baseline assessment. Following the baseline assessment each participant will be randomized to either the GPS or SOC intervention group and will complete a 6 week treatment period. During the treatment period, both groups will participate in guided exercise 3x/week. Following the treatment period participants will be asked to return for a post-treatment evaluation and again for a follow-up assessment 1 month later. We anticipate enrolling 50 participants.DiscussionThis study will be an innovative RCT that will utilize gaze and postural stability metrics to assess the efficacy of vestibular rehabilitation in PwMS. It will build on previous work by examining measures across the ICF and improve the current evidence base for treating PwMS.Trial registrationClinicalTrials.gov, May 29th 2018, NCT03521557.

Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder.

Autism spectrum disorder (ASD) is a frequent developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and nonverbal communication, and stereotyped patterns of interests and activities. It has been previously reported that there is vitamin D deficiency in autistic children; however, there is a lack of randomized controlled trials of vitamin D supplementation in ASD children. This study is a double-blinded, randomized clinical trial (RCT) that was conducted on 109 children with ASD (85 boys and 24 girls; aged 3-10years). The aim of this study was to assess the effects of vitamin D supplementation on the core symptoms of autism in children. ASD patients were randomized to receive vitamin D3 or placebo for 4months. The serum levels of 25-hydroxycholecalciferol (25 (OH)D) were measured at the beginning and at the end of the study. The autism severity and social maturity of the children were assessed by the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and the Autism Treatment Evaluation Checklist (ATEC). UMIN-CTR Study Design: trial number: UMIN000020281. Supplementation of vitamin D was well tolerated by the ASD children. The daily doses used in the therapy group was 300IU vitamin D3/kg/day, not to exceed 5,000IU/day. The autism symptoms of the children improved significantly, following 4-month vitamin D3 supplementation, but not in the placebo group. This study demonstrates the efficacy and tolerability of high doses of vitamin D3 in children with ASD. This study is the first double-blinded RCT proving the efficacy of vitamin D3 in ASD patients. Depending on the parameters measured in the study, oral vitamin D supplementation may safely improve signs and symptoms of ASD and could be recommended for children with ASD. At this stage, this study is a single RCT with a small number of patients, and a great deal of additional wide-scale studies are needed to critically validate the efficacy of vitamin D in ASD.

Abstract 12009: A Prospective Randomized Placebo-Controlled Crossover Trial of Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia

Introduction: Randomized clinical trials (RCTs), the gold standard to evaluate new therapies, have not been performed in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). Up to 30% of CPVT patients have recurrent symptoms or cardiac events despite standard therapy with beta-blockers. In a mouse model flecainide was found to directly target the molecular defect in CPVT and in retrospective clinical studies patients had improved ventricular ectopy during exercise with flecainide added to beta-blockers. Hypothesis: Flecainide + beta-blocker is superior to beta-blocker alone in CPVT. Methods: CPVT patients were enrolled in a single blind placebo-controlled crossover RCT of flecainide added to beta-blocker. Subjects underwent a baseline exercise (Ex) test on maximally-tolerated beta-blocker dose which continued throughout the trial, then were randomized to flecainide or placebo for 3 months, followed by Ex testing. After a 1 week washout, subjects crossed over to placebo or flecainide for 3 months, followed by Ex testing. The primary endpoint of ventricular ectopy during Ex was compared between beta-blocker + flecainide vs. beta-blocker + placebo. Ex tests were scored on an ordinal scale of worst ventricular arrhythmia observed (0 = no ectopy, 1 = isolated PVC’s, 2 = bigeminy, 3 = couplets, 4 = nonsustained VT). Results: A total of 13 subjects (7 males) at 10 centers were randomized. Median age was 16 years and baseline Ex test score was 3 (IQR 1-3.5). Ventricular ectopy during Ex was significantly reduced by flecainide (P&lt;0.01, see Figure); there was no difference between baseline and placebo Ex score (P=0.7). Overall adverse events and serious adverse events did not differ between flecainide and placebo. Conclusions: This placebo-controlled RCT demonstrates that flecainide + beta-blocker is superior to beta-blocker alone in reducing exercise-induced ventricular arrhythmias in CPVT.

Individualizing endpoints in randomized clinical trials to better inform individual patient care: the TARGET proposal.

In practice, critical care practitioners individualize treatments and goals of care for each patient in light of that patient’s acute and chronic pathophysiology, as well as their beliefs and values. Yet critical care researchers routinely measure one endpoint for all patients during randomized clinical trials (RCTs), eschewing any such individualization. More recent methodology work has explored the possibility that enrollment criteria in RCTs can be individualized, as can data analysis plans. Here we propose that the specific endpoints of a RCT can be individualized—that is, different patients within a single RCT might have different secondary endpoints measured. If done rigorously and objectively, based on pre-randomization data, such individualization of endpoints may improve the bedside usefulness of information obtained during a RCT, while perhaps also improving the power and efficiency of any RCT. We discuss the theoretical underpinnings of this proposal in light of related innovations in RCT design such as sliding dichotomies. We discuss what a full elaboration of such individualization would require, and outline a pragmatic initial step towards the use of “individualized secondary endpoints” in a large RCT evaluating optimal enteral nutrition targets in the critically ill.

Super Dentin and 10-MDP Functional Monomer, does they really prevent Postoperative Patients Complains?A Systematic Review

Objectives: This systematic review was conducted to detect the clinical performance of 10-Methacryloyloxydecyl Dihydrogen Phosphate functional monomer added to self etch adhesives. And their impact on postoperative hypersensitivity. Methods and Analysis: Prisma guidelines for reporting systematic reviews were followed as much as possible in this work. Relevant mesh terms and entry terms were searched in three databases, Medline (PubMed), Cochrane (Wiley) and Science Direct (Elsevier). Search has no date limitations but only English language articles were included. In vitro studies and conference abstracts were excluded as only Randomized Clinical Trials (RCTs ) were included in the search. Findings: According to the set inclusion and exclusion criteria search results were secondarily filtered to result only in one randomized clinical trial, it was filtered among 56 search result. Qualitative assessment of the included study was done after its risk of bias evaluation. While quantitative assessment meta analyses was not possible by using single RCT. Improvement: These findings are strongly suggesting a call for conducting a high quality randomized clinical trials concerning the clinical postoperative hypersensitivity following to resin composite restorations bonded with 10-MDP functional monomer.

Among antithrombotic agents, prasugrel, but not ticagrelor, is associated with reduced 30 day mortality in patients with ST-elevated myocardial infarction

BackgroundST-elevated myocardial infarction (STEMI) holds the highest early mortality among patients with acute coronary syndromes. Despite numerous claims of clinical benefits and superiority over clopidogrel, there are no head-to-head outcome randomized clinical trials (RCTs) directly comparing novel antithrombotic agents in STEMI. Moreover, since most regulatory approvals are based on a single RCT's results, their meta-analyses are rare to compare death rates. We analyzed the 30-day mortality in STEMI patients who underwent percutaneous coronary intervention (PCI) and were treated with antithrombotic agents compared to clopidogrel as a reference. Methods and resultsAltogether, 10 RCT's and 1 retrospective study with a total number of 26,658 STEMI patients were included. Random-effects model with Mantel–Heanszel weighting was used to pool outcomes into a meta-analysis. Therapy with clopidogrel was associated with 2.76% 30-day STEMI mortality which was similar to that of ticagrelor (2.6%; OR=0.9395 [CI=0.76 to 1.17; p=0.58]), and for bivalirudin (2.8%; OR=1.02 [CI=0.82 to 1.27; p=0.86]), but was slightly higher for heparin (3.0%; OR=1.08 [CI=0.86 to 1.35; p=0.52]). There was a trend towards lower mortality after tirofiban (2.1%; OR=0.77 [CI=0.52 to 1.13; p=0.20]), and cangrelor (1.7%; OR=0.59 [CI=0.29 to 1.20; p=0.19]), although the sample size for both agents was woefully small. The only agent which offers a significant 30-day mortality benefit in STEMI was prasugrel with significant lowest 1.75% death rate (OR=0.63 [CI=0.46 to 0.86; p=0.03]). ConclusionsAmong antithrombotic agents, prasugrel, but not ticagrelor, offers significant 30-day mortality benefit over clopidogrel in PCI-treated STEMI patients justifying short-term use in such a high-risk population.

PCV98 - Statin Cost-Effectiveness in Patients with Previous Coronary Heart Disease: A Systematic Review of the Cost-Effectiveness Analysis Derived from Single Randomised Clinical Trials

Large randomized clinical trials (RCT) evidenced the benefits of statins in reducing major cardiovascular events in patients with established coronary heart disease (CHD). These multinational trials are likely to provide internally valid evidence. Cost-effectiveness analysis based on single trials costs and effects are common and represent the potential net benefit of an intervention in a well-controlled environment. The aim of this study is to systematically review the cost-effectiveness studies based on statins single trials in patients with previous CHD. We searched to identify all literature relating to the cost-effectiveness of statins in the secondary prevention in patients with established CHD. Only studies with the effectiveness data extracted from a single RCT and clinical outcomes such as quality assessment, mortality or cardiovascular events rate were included. The cost per QALY was classified according to the WHO, following three categories of cost-effectiveness, Highly cost-effective, Cost-effective and Not cost-effective, adjusted with GDP per capita based on purchasing power parity (constant 2005 international USD). Twenty-one studies were included in the final analysis, covering a period range from 1996 to 2009. 7 large RCTs represented the origin of efficacy data. Most of studies assumed a full compliance, the Markov models were used in 11 out 21 studies. Time horizon ranged from 5 years to time life, with 10 years being the predominant choice. 9 studies performed a cost-utility analysis and showed the average cost per QALY, 8 of them classified as highly cost-effective and 1 cost-effective. Cost per QALY was sensitive for drug price, time horizon and event rates, 6 of this models models worked with composite endpoints. Statins are highly cost-effective in patients with CHD when effect size came from single well designed RCTs. Models heterogeneity and composite endpoints can decrease the robustness of the results.

Radiofrequency ablation in the treatment of liver metastases from colorectal cancer

Colorectal cancer (CRC) is the most common malignant tumour and the third leading cause of cancer deaths in USA. For advanced CRC, the liver is the first site of metastatic disease; approximately 50 % of patients with CRC will develop liver metastases either synchronously or metachronously within 2 years after primary diagnosis. Hepatic resection (HR) is the only curative option, but only 15-20% of patients with liver metastases from CRC (CRLMs) are suitable for surgical standard treatment. In patients with unresectable CRLMs downsizing chemotherapy can improve resectability (16%). Modern systemic chemotherapy represents the only significant treatment for unresectable CRLMs. However several loco-regional treatments have been developed: hepatic arterial infusion (HAI), cryosurgical ablation (CSA), radiofrequency ablation (RFA), microwave ablation and selective internal radion treatment (SIRT). During the past decade RFA has superseded other ablative therapies, due to its low morbidity, mortality, safety and patient acceptability. The objective of this study was to systematically review the role of radiofrequency ablation (RFA) in the treatment of CRLMs. We performed electronic searches in the following databases:CENTRAL, MEDLINE and EMBASE. Current trials were identified through the Internet using the Clinical-Trials.gov site (to January 2, 2012) and ASCO Proceedings. The reference lists of identified trials were reviewed for additional studies. Randomized clinical trials (RCTs), quasi-randomised or controlled clinical trials (CCTs) comparing RFA to any other therapy for CRLMs were included. Observational study designs including comparative cohort studies comparing RFA to another intervention, single arm cohort studies or case control studies have been included if they have: prospectively collected data, ten or more patients; and have a mean or median follow-up time of 24 months. Patients with CRLMs who have no contraindications for RFA. Patients with unresectable extra-hepatic disease were also included.Trials have been considered regardless of language of origin. A total of 1144 records were identified through the above electronic searching. We included 18 studies: 10 observational studies, 7 Clinical Controlled Trials (CCTs) and an additional 1 Randomized Clinical Trial (RCT) (abstract) identified by hand searching in the 2010 ASCO Annual Meeting. The most appropriate way of summarizing time-to-event data is to use methods of survival analysis and express the intervention effect as a hazard ratio. In the included studies these outcome are mostly reported as dichotomous data so we should have asked authors research data for each participant and perform Individual Patient Data (IPD) meta-analysis. Given the study design and low quality of included studies we decided to give up and not to summarize these data. Seventeen studies were not randomised and this increases the potential for selection bias. In addition, there was imbalance in the baseline characteristics of the participants included in all studies. All studies were classified as having a elevate risk of bias. The assessment of methodological quality of all non-randomized studies included in meta-analysis performed by the STROBE checklist has allowed us to identify several methodological limits in most of the analysed studies. At present, the information from the single RCT included (Ruers 2010) comes from an abstract of 2010 ASCO Annual Meeting where the allocation concealment was not reported; however in original protocol allocation concealment was adequately reported (EORTC 40004 protocol). The heterogeneity regarding interventions, comparisons and outcomes rendered the data not suitable. This systematic review gathers information from several controlled clinical trials and observational studies which are vulnerable to different types of bias. The imbalance between characteristics of patients in the allocated groups appears to be the main concern. Only one randomised clinical trial (published as an abstract), comparing 60 patients receiving RFA plus CT versus 59 patients receiving CT alone, was identified. This study showed that PFS was significantly higher in the group that received RFA. However, it was not able to provide information on overall survival. In conclusion, evidence from the included studies are insufficient to recommend RFA for a radical oncological treatment of CRLMs.

2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Executive Summary

2011;58;2703-2738; originally published online Nov 8, 2011; J. Am. Coll. Cardiol. W. Yancy Rakowski, Christine E. Seidman, Jeffrey A. Towbin, James E. Udelson, and Clyde Fifer, Mark S. Link, Srihari S. Naidu, Rick A. Nishimura, Steve R. Ommen, Harry Bernard J. Gersh, Barry J. Maron, Robert O. Bonow, Joseph A. Dearani, Michael A. Thoracic Surgeons Society for Cardiovascular Angiography and Interventions, and Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, of Thoracic Surgery, American Society of Echocardiography, American Society Developed in Collaboration With the American Association for Guidelines Cardiology Foundation/American Heart Association Task Force on Practice Cardiomyopathy: Executive Summary: A Report of the American College of 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic This information is current as of May 14, 2012 http://content.onlinejacc.org/cgi/content/full/58/25/2703 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Efficacy of Intra-Arterial Fibrinolysis for Acute Ischemic Stroke

Although intra-arterial (IA) fibrinolysis for acute ischemic stroke has been clinically available for many years, it is not a therapy approved by the US Food and Drug Administration. Single, randomized, clinical trials (RCTs) have suggested beneficial effects, but no single RCT has demonstrated that IA fibrinolysis yields increases in both good (modified Rankin Scale score 0 to 2) and excellent (modified Rankin Scale score 0 to 1) outcomes when compared with the control group. Relatively few participants and inadequate statistical power in single RCTs may have contributed to this difficulty. Method- We performed a systematic literature search to identified RCTs of IA fibrinolysis in acute ischemic stroke. Multiple outcomes were analyzed, with emphasis on good and excellent outcomes at 90 days or at trial end point. The systematic search identified 5 RCTs with 395 participants comparing IA fibrinolysis and control. IA fibrinolysis was associated with increased good (odds ratio=2.05; 95% CI, 1.33 to 3.14; P=0.001) and excellent (odds ratio=2.14; 95% CI, 1.31 to 3.51; P=0.003) outcomes. For additional end points, IA fibrinolysis was associated with increased frequencies of minimal neurologic deficit (National Institutes of Health Stroke Scale score 0 to 1), minimal impairment of activities of daily living (Barthel Index 90 to 100 or 95 to 100), and recanalization. IA fibrinolysis was associated with increased radiological and symptomatic intracerebral hemorrhage. However, there was no difference in mortality between groups. Formal meta-analysis suggests that IA fibrinolysis substantially increases recanalization rates and good and excellent clinical outcomes in acute ischemic stroke. Increased hemorrhage frequencies are not associated with any increase in mortality.

Canadian Thoracic Society guidelines: diagnosis and treatment of sleep disordered breathing in adults.

The Canadian Thoracic Society (CTS) guidelines for the diagnosis and treatment of sleep disordered breathing in adults were developed over the past year. A one-day meeting was held in Montreal, Quebec, on October 28, 2005, just before the annual CTS meeting. The meeting was facilitated by Dr R Davies (Oxford, United Kingdom), and speakers included D Morrison (Halifax, Nova Scotia), J Kimoff (Montreal), J Fleetham (Vancouver, British Columbia), C George (London, Ontario), M Kryger (Winnipeg, Manitoba), P Hanly (Calgary, Alberta), F Hill (Saskatoon, Saskatchewan), D Bradley (Toronto, Ontario), N Ayas (Vancouver), M Fitzpatrick (Kingston, Ontario), F Series (Quebec City, Quebec), K Ferguson (London) and W Tsai (Calgary). This meeting was attended by 28 Canadian physicians with an interest in sleep disordered breathing. A draft of an Executive Summary was developed, and then reviewed and finalized by the CTS Sleep Disordered Breathing Committee at a one-day meeting in Toronto on February 17, 2006. The Committee members then individually ranked the level of evidence as: grade A – high-quality meta-analysis or single randomized clinical trial (RCT) that had a low risk of bias; grade B – high-quality systematic review of cohort studies or single cohort study with a low risk of bias or extrapolated evidence from high-quality RCTs or RCTs with a risk of bias; grade C – case-control studies or cohort studies with a risk of bias; or grade D – case series, case reports or expert opinion. The Committee members also ranked their agreement with each statement (strongly agree, agree, neutral, disagree or strongly disagree). No statement was included unless at least 90% of the Committee either strongly agreed or agreed with it.