A systematic review of ultrasound-guided methods for brachial plexus blockade.

We systematically reviewed 25 randomised controlled trials of ultrasound-guided brachial plexus blockade that recruited 1948 participants: either one approach vs another (axillary, infraclavicular or supraclavicular); or one injection vs multiple injections. There were no differences in the rates of successful blockade with approach, relative risk (95% CI): axillary vs infraclavicular, 1.0 (1.0-1.1), p = 0.97; axillary vs supraclavicular, 1.0 (1.0-1.1), p = 0.68; and infraclavicular vs supraclavicular, 1.0 (1.0-1.1), p = 0.32. There was no difference in the rate of successful blockade with the number of injections, relative risk (95% CI) 1.0 (1.0-1.0), p = 0.69, for one vs multiple injections. The rate of procedural paraesthesia was less with one injection than multiple injections, relative risk (95% CI) 0.6 (0.4-0.9), p = 0.004.

Risk of All-Cause Mortality in Alcohol-Dependent Individuals: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Alcohol dependence (AD) carries a high mortality burden, which may be mitigated by reduced alcohol consumption. We conducted a systematic literature review and meta-analysis investigating the risk of all-cause mortality in alcohol-dependent subjects. METHODS: MEDLINE, MEDLINE In-Process, Embase and PsycINFO were searched from database conception through 26th June 2014. Eligible studies reported all-cause mortality in both alcohol-dependent subjects and a comparator population of interest. Two individuals independently reviewed studies. Of 4540 records identified, 39 observational studies were included in meta-analyses. FINDINGS: We identified a significant increase in mortality for alcohol-dependent subjects compared with the general population (27 studies; relative risk [RR] = 3.45; 95% CI [2.96, 4.02]; p < 0.0001). The mortality increase was also significant compared to subjects qualifying for a diagnosis of alcohol abuse or subjects without alcohol use disorders (AUDs). Alcohol-dependent subjects continuing to drink heavily had significantly greater mortality than alcohol-dependent subjects who reduced alcohol intake, even if abstainers were excluded (p < 0.05). INTERPRETATION: AD was found to significantly increase an individual's risk of all-cause mortality. While abstinence in alcohol-dependent subjects led to greater mortality reduction than non-abstinence, this study suggests that alcohol-dependent subjects can significantly reduce their mortality risk by reducing alcohol consumption.

The use of cost per life year gained as a measurement of cost-effectiveness in Spain: a systematic review of recent publications

The objective of this study was to evaluate the methodological characteristics of cost-effectiveness evaluations carried out in Spain, since 1990, which include LYG as an outcome to measure the incremental cost-effectiveness ratio. METHODS: A systematic review of published studies was conducted describing their characteristics and methodological quality. We analyse the cost per LYG results in relation with a commonly accepted Spanish cost-effectiveness threshold and the possible relation with the cost per quality adjusted life year (QALY) gained when they both were calculated for the same economic evaluation. RESULTS: A total of 62 economic evaluations fulfilled the selection criteria, 24 of them including the cost per QALY gained result as well. The methodological quality of the studies was good (55%) or very good (26%). A total of 124 cost per LYG results were obtained with a mean ratio of 49,529 and a median of 11,490 (standard deviation of 183,080). Since 2003, a commonly accepted Spanish threshold has been referenced by 66% of studies. A significant correlation was found between the cost per LYG and cost per QALY gained results (0.89 Spearman-Rho, 0.91 Pearson). CONCLUSIONS: There is an increasing interest for economic health care evaluations in Spain, and the quality of the studies is also improving. Although a commonly accepted threshold exists, further information is needed for decision-making as well as to identify the relationship between the costs per LYG and per QALY gained.

Systematic evaluation of matrix effects in hydrophilic interaction chromatography versus reversed phase liquid chromatography coupled to mass spectrometry.

Reversed phase liquid chromatography (RPLC) coupled to mass spectrometry (MS) is the gold standard technique in bioanalysis. However, hydrophilic interaction chromatography (HILIC) could represent a viable alternative to RPLC for the analysis of polar and/or ionizable compounds, as it often provides higher MS sensitivity and alternative selectivity. Nevertheless, this technique can be also prone to matrix effects (ME). ME are one of the major issues in quantitative LC-MS bioanalysis. To ensure acceptable method performance (i.e., trueness and precision), a careful evaluation and minimization of ME is required. In the present study, the incidence of ME in HILIC-MS/MS and RPLC-MS/MS was compared for plasma and urine samples using two representative sets of 38 pharmaceutical compounds and 40 doping agents, respectively. The optimal generic chromatographic conditions in terms of selectivity with respect to interfering compounds were established in both chromatographic modes by testing three different stationary phases in each mode with different mobile phase pH. A second step involved the assessment of ME in RPLC and HILIC under the best generic conditions, using the post-extraction addition method. Biological samples were prepared using two different sample pre-treatments, i.e., a non-selective sample clean-up procedure (protein precipitation and simple dilution for plasma and urine samples, respectively) and a selective sample preparation, i.e., solid phase extraction for both matrices. The non-selective pretreatments led to significantly less ME in RPLC vs. HILIC conditions regardless of the matrix. On the contrary, HILIC appeared as a valuable alternative to RPLC for plasma and urine samples treated by a selective sample preparation. Indeed, in the case of selective sample preparation, the compounds influenced by ME were different in HILIC and RPLC, and lower and similar ME occurrence was generally observed in RPLC vs. HILIC for urine and plasma samples, respectively. The complementary of both chromatographic modes was also demonstrated, as ME was observed only scarcely for urine and plasma samples when selecting the most appropriate chromatographic mode.

Methodology used in studies reporting chronic kidney disease prevalence : a systematic literature review.

BACKGROUND: Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. METHODS: For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. RESULTS: We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. CONCLUSIONS: The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study results.

Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects. METHODS: We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia). RESULTS: Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67-0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74-0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70-0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66-0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76-0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74-0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71-0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77-0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74-0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased. CONCLUSION: Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.

O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

Background: The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. Methods A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Results Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Conclusions Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably.

Analysis of translational errors in frame-based and frameless cranial radiosurgery using an anthropomorphic phantom

Abstract Objective: To evaluate three-dimensional translational setup errors and residual errors in image-guided radiosurgery, comparing frameless and frame-based techniques, using an anthropomorphic phantom. Materials and Methods: We initially used specific phantoms for the calibration and quality control of the image-guided system. For the hidden target test, we used an Alderson Radiation Therapy (ART)-210 anthropomorphic head phantom, into which we inserted four 5mm metal balls to simulate target treatment volumes. Computed tomography images were the taken with the head phantom properly positioned for frameless and frame-based radiosurgery. Results: For the frameless technique, the mean error magnitude was 0.22 ± 0.04 mm for setup errors and 0.14 ± 0.02 mm for residual errors, the combined uncertainty being 0.28 mm and 0.16 mm, respectively. For the frame-based technique, the mean error magnitude was 0.73 ± 0.14 mm for setup errors and 0.31 ± 0.04 mm for residual errors, the combined uncertainty being 1.15 mm and 0.63 mm, respectively. Conclusion: The mean values, standard deviations, and combined uncertainties showed no evidence of a significant differences between the two techniques when the head phantom ART-210 was used.

Host Genetics of Response to Hepatitis B Vaccine: A Systematic Review

Background. Hepatitis B virus (HBV) is an important cause of chronic viral disease worldwide and can be life threatening. While a safe and effective vaccine is widely available, 5 to 10% of healthy vaccinees fail to achieve a protective anti-hepatitis B surface antigen antibody (anti-HBs) titer (>10mIU/ml). A limited number of studies investigated host genetics of the response to HBV vaccine. To our knowledge, no comprehensive overview of genetic polymorphisms both within and outside the HLA system has been done so far. Aim. The aim of this study was to perform a systematic review of the literature of human genetics influencing immune response after hepatitis B vaccination. Methods. Literature searches using keywords were conducted in the electronic databases Medline, Embase and ISI Web of Science the cut-off date being March 2014. After selection of papers according to stringent inclusion criteria, relevant information was systematically collected from the remaining articles, including demographic data, number of patients, schedule and type of vaccine, phenotypes, genes and single nucleotide polymorphisms (SNPs) genotyping results and their association with immune response to hepatitis B vaccine. Results. The literature search produced a total of 1968 articles from which 46 studies were kept for further analyses. From these studies, data was extracted for 19 alleles from the human leukocyte antigen (HLA) region that were reported as significant at least twice. Among those alleles, 9 were firmly associated with vaccine response outcome (DQ2 [DQB1*02 and DQB1*0201], DR3 [DRB1*03 and DRB1*0301], DR7 [DRB1*07 and DRB1*0701], C4AQ0, DPB1*0401, DQ3, DQB1*06, DRB1*01 and DRB1*13 [DRB1*1301]). In addition, data was extracted for 55 different genes from which 13 extra-HLA genes had polymorphisms that were studied by different group of investigators or by the same group with a replication study. Among the 13 genes allowing comparison, 4 genes (IL-1B, IL-2, IL-4R and IL- 6) revealed no significant data, 6 genes (IL-4, IL-10, IL-12B, IL-13, TNFA, IFNG and TLR2) were explored with inconsistent results and 2 genes (CD3Z and ITGAL) yielded promising results as their association with vaccine response was confirmed by a replication approach. Furthermore, this review produced a list of 46 SNPs from 26 genes that were associated with immune response to vaccine only once, providing novel candidates to be tested in datasets from existing genome-wide association studies (GWAS). Conclusion. To the best of our knowledge, this is the first systematic review of immunogenetic studies of response to hepatitis B vaccine. While this work reassesses the role of several HLA alleles on vaccine response outcome, the associations with polymorphisms in genes outside the HLA region were rather inconsistent. Moreover, this work produced a list of 46 significant SNPs that were reported by a single group of investigators, opening up some interesting possibilities for further research.

Performance of 18F-FET versus 18F-FDG-PET for the diagnosis and grading of brain tumors: systematic review and meta-analysis.

BACKGROUND: For the past decade (18)F-fluoro-ethyl-l-tyrosine (FET) and (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) have been used for the assessment of patients with brain tumor. However, direct comparison studies reported only limited numbers of patients. Our purpose was to compare the diagnostic performance of FET and FDG-PET. METHODS: We examined studies published between January 1995 and January 2015 in the PubMed database. To be included the study should: (i) use FET and FDG-PET for the assessment of patients with isolated brain lesion and (ii) use histology as the gold standard. Analysis was performed on a per patient basis. Study quality was assessed with STARD and QUADAS criteria. RESULTS: Five studies (119 patients) were included. For the diagnosis of brain tumor, FET-PET demonstrated a pooled sensitivity of 0.94 (95% CI: 0.79-0.98) and pooled specificity of 0.88 (95% CI: 0.37-0.99), with an area under the curve of 0.96 (95% CI: 0.94-0.97), a positive likelihood ratio (LR+) of 8.1 (95% CI: 0.8-80.6), and a negative likelihood ratio (LR-) of 0.07 (95% CI: 0.02-0.30), while FDG-PET demonstrated a sensitivity of 0.38 (95% CI: 0.27-0.50) and specificity of 0.86 (95% CI: 0.31-0.99), with an area under the curve of 0.40 (95% CI: 0.36-0.44), an LR+ of 2.7 (95% CI: 0.3-27.8), and an LR- of 0.72 (95% CI: 0.47-1.11). Target-to-background ratios of either FDG or FET, however, allow distinction between low- and high-grade gliomas (P > .11). CONCLUSIONS: For brain tumor diagnosis, FET-PET performed much better than FDG and should be preferred when assessing a new isolated brain tumor. For glioma grading, however, both tracers showed similar performances.

DFM/DFMA(A) – analysis and aspects of applying systematic engineering for a microwave testfixture design

In this paper, manufacturability analysis and collection of design aspects is made for a microwave test-fixture. Aspects of applying systematic design for a microwave test-fixture design and manufacturing are also analysed. Special questionnaires for the component and machining are made in order to enable necessary information to ensure DFM(A) – aspects of the component. The aspects of easy manufacturing for machining the microwave test-fixture are collected. Material selection is discussed and manufacturing stages of prototype manufacturing are presented.

Padronização interna em espectrometria de absorção atômica

This paper describes a review on internal standardization in atomic absorption spectrometry with emphasis to the systematic and random errors in atomic absorption spectrometry and applications of internal standardization in flame atomic absorption spectrometry and electrothermal atomic absorption spectrometry. The rules for selecting an element as internal standard, limitations of the method, and some comments about the application of internal standardization in atomic absorption spectrometry and the future of this compensation strategy are critically discussed.

Case-Crossover Analysis of Air Pollution Health Effects: A Systematic Review of Methodology and Application

Case-crossover is one of the most used designs for analyzing the health-related effects of air pollution. Nevertheless, no one has reviewed its application and methodology in this context. Objective: We conducted a systematic review of case-crossover (CCO) designs used to study the relationship between air pollution and morbidity and mortality, from the standpoint of methodology and application.Data sources and extraction: A search was made of the MEDLINE and EMBASE databases.Reports were classified as methodologic or applied. From the latter, the following information was extracted: author, study location, year, type of population (general or patients), dependent variable(s), independent variable(s), type of CCO design, and whether effect modification was analyzed for variables at the individual level. Data synthesis: The review covered 105 reports that fulfilled the inclusion criteria. Of these, 24 addressed methodological aspects, and the remainder involved the design’s application. In the methodological reports, the designs that yielded the best results in simulation were symmetric bidirectional CCO and time-stratified CCO. Furthermore, we observed an increase across time in the use of certain CCO designs, mainly symmetric bidirectional and time-stratified CCO. The dependent variables most frequently analyzed were those relating to hospital morbidity; the pollutants most often studied were those linked to particulate matter. Among the CCO-application reports, 13.6% studied effect modification for variables at the individual level.Conclusions: The use of CCO designs has undergone considerable growth; the most widely used designs were those that yielded better results in simulation studies: symmetric bidirectional and time-stratified CCO. However, the advantages of CCO as a method of analysis of variables at the individual level are put to little use

Peutz-Jeghers syndrome: a systematic review and recommendations for management

Peutz¿Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype¿phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.