Reporting of methodologic information on trial registries for quality assessment: a study of trial records retrieved from the WHO search portal

Background: Although randomized clinical trials (RCTs) are considered the gold standard of evidence, their reporting is often suboptimal. Trial registries have the potential to contribute important methodologic information for critical appraisal of study results. Methods and Findings: The objective of the study was to evaluate the reporting of key methodologic study characteristics in trial registries. We identified a random sample (n = 265) of actively recruiting RCTs using the World Health Organization International Clinical Trials Registry Platform (ICTRP) search portal in 2008. We assessed the reporting of relevant domains from the Cochrane Collaboration’s ‘Risk of bias’ tool and other key methodological aspects. Our primary outcomes were the proportion of registry records with adequate reporting of random sequence generation, allocation concealment, blinding, and trial outcomes. Two reviewers independently assessed each record. Weighted overall proportions in the ICTRP search portal for adequate reporting of sequence generation, allocation concealment, blinding (including and excluding open label RCT) and primary outcomes were 5.7% (95% CI 3.0–8.4%), 1.4% (0–2.8%), 41% (35–47%), 8.4% (4.1–13%), and 66% (60–72%), respectively. The proportion of adequately reported RCTs was higher for registries that used specific methodological fields for describing methods of randomization and allocation concealment compared to registries that did not. Concerning other key methodological aspects, weighted overall proportions of RCTs with adequately reported items were as follows: eligibility criteria (81%), secondary outcomes (46%), harm (5%) follow-up duration (62%), description of the interventions (53%) and sample size calculation (1%). Conclusions: Trial registries currently contain limited methodologic information about registered RCTs. In order to permit adequate critical appraisal of trial results reported in journals and registries, trial registries should consider requesting details on key RCT methods to complement journal publications. Full protocols remain the most comprehensive source of methodologic information and should be made publicly available.

Toxicity assessment of refill liquids for electronic cigarettes.

We analyzed 42 models from 14 brands of refill liquids for e-cigarettes for the presence of micro-organisms, diethylene glycol, ethylene glycol, hydrocarbons, ethanol, aldehydes, tobacco-specific nitrosamines, and solvents. All the liquids under scrutiny complied with norms for the absence of yeast, mold, aerobic microbes, Staphylococcus aureus, and Pseudomonas aeruginosa. Diethylene glycol, ethylene glycol and ethanol were detected, but remained within limits authorized for food and pharmaceutical products. Terpenic compounds and aldehydes were found in the products, in particular formaldehyde and acrolein. No sample contained nitrosamines at levels above the limit of detection (1 μg/g). Residual solvents such as 1,3-butadiene, cyclohexane and acetone, to name a few, were found in some products. None of the products under scrutiny were totally exempt of potentially toxic compounds. However, for products other than nicotine, the oral acute toxicity of the e-liquids tested seems to be of minor concern. However, a minority of liquids, especially those with flavorings, showed particularly high ranges of chemicals, causing concerns about their potential toxicity in case of chronic oral exposure.

Improvement of the antibacterial activity of daptomycin-loaded polymeric microparticles by Eudragit RL 100: An assessment by isothermal microcalorimetry.

The aim of the present study was to develop novel daptomycin-loaded acrylic microparticles with improved release profiles and antibacterial activity against two clinically relevant methicillin-susceptible and methicillin-resistant Staphylococcus aureus strains (MSSA and MRSA, respectively). Daptomycin was encapsulated into poly(methyl methacrylate) (PMMA) and PMMA-Eudragit RL 100 (EUD) microparticles by a double emulsion-solvent evaporation method. For comparison purposes similar formulations were prepared with vancomycin. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties, in vitro release and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. The addition of EUD to the formulation caused a shift in the surface charge of the particles from negative zeta potential values (100% PMMA formulations) to strongly positive. It also improved daptomycin encapsulation efficiency and release, whereas vancomycin encapsulation and release were strongly hindered. Plain and antibiotic-loaded particles presented comparable biocompatibility profiles. The antibacterial activity of the particles was assessed by isothermal microcalorimetry against both MSSA and MRSA. Daptomycin-loaded PMMA-EUD particles presented the highest antibacterial activity against both strains. The addition of 30% EUD to the daptomycin-loaded PMMA particles caused a 40- and 20-fold decrease in the minimum inhibitory (MIC) and bactericidal concentration (MBC) values, respectively, when compared to the 100% PMMA formulations. On the other hand, vancomycin-loaded microparticles presented the highest antibacterial activity in PMMA particles. Unlike conventional methods, isothermal microcalorimetry proved to be a real-time, sensitive and accurate method for assessment of antibacterial activity of antibiotic-loaded polymeric microparticles. Finally, the addition of EUD to formulations proved to be a powerful strategy to improve daptomycin encapsulation efficiency and release, and consequently improving the microparticles activity against two relevant S. aureus strains.

The prevalence of child sexual abuse in community and student samples: A meta-analysis

Background: Studies conducted internationally confirm that child sexual abuse is a much more widespread problem than previously thought, with even the lowest prevalence rates including a large number of victims that need to be taken into account. Objective: To carry out a meta-analysis of the prevalence of child sexual abuse in order to establish an overall international figure. Methods: Studies were retrieved from various electronic databases. The measure of interest was the prevalence of abuse reported in each article, these values being combined via a random effects model. A detailed analysis was conducted of the effects of various moderator variables. Results: Sixty-five articles covering 22 countries were included. The analysis showed that 7.9% of men (7.4% without outliers) and 19.7% of women (19.2% without outliers) had suffered some form of sexual abuse prior to the age of eighteen. Conclusions: The results of the present meta-analysis indicate that child sexual abuse is a serious problem in the countries analysed.

Humeral development from neonatal period to skeletal maturity—application in age and sex assessment

The goal of the present study is to examine cross-sectional information on the growth of the humerus based on the analysis of four measurements, namely, diaphyseal length, transversal diameter of the proximal (metaphyseal) end of the shaft, epicondylar breadth and vertical diameter of the head. This analysis was performed in 181 individuals (90 ♂ and 91 ♀) ranging from birth to 25 years of age and belonging to three documented Western European skeletal collections (Coimbra, Lisbon and St. Bride). After testing the homogeneity of the sample, the existence of sexual differences (Student"s t- and Mann-Whitney U-test) and the growth of the variables (polynomial regression) were evaluated. The results showed the presence of sexual differences in epicondylar breadth above 20 years of age and vertical diameter of the head from 15 years of age, thus indicating that these two variables may be of use in determining sex from that age onward. The growth pattern of the variables showed a continuous increase and followed first- and second-degree polynomials. However, growth of the transversal diameter of the proximal end of the shaft followed a fourth-degree polynomial. Strong correlation coefficients were identified between humeral size and age for each of the four metric variables. These results indicate that any of the humeral measurements studied herein is likely to serve as a useful means of estimating sub-adult age in forensic samples.

Assessment of subjective and hemodynamic tolerance of different high- and low-flux dialysis membranes in patients undergoing chronic intermittent hemodialysis: a randomized controlled trial.

Clinical experience and experimental data suggest that intradialytic hemodynamic profiles could be influenced by the characteristics of the dialysis membranes. Even within the worldwide used polysulfone family, intolerance to specific membranes was occasionally evoked. The aim of this study was to compare hemodynamically some of the commonly used polysulfone dialyzers in Switzerland. We performed an open-label, randomized, cross-over trial, including 25 hemodialysis patients. Four polysulfone dialyzers, A (Revaclear high-flux, Gambro, Stockholm, Sweden), B (Helixone high-flux, Fresenius), C (Xevonta high-flux, BBraun, Melsungen, Germany), and D (Helixone low-flux, Fresenius, Bad Homburg vor der Höhe, Germany), were compared. The hemodynamic profile was assessed and patients were asked to provide tolerance feedback. The mean score (±SD) subjectively assigned to dialysis quality on a 1-10 scale was A 8.4 ± 1.3, B 8.6 ± 1.3, C 8.5 ± 1.6, D 8.5 ± 1.5. Kt/V was A 1.58 ± 0.30, B 1.67 ± 0.33, C 1.62 ± 0.32, D 1.45 ± 0.31. The low- compared with the high-flux membranes, correlated to higher systolic (128.1 ± 13.1 vs. 125.6 ± 12.1 mmHg, P < 0.01) and diastolic (76.8 ± 8.7 vs. 75.3 ± 9.0 mmHg; P < 0.05) pressures, higher peripheral resistance (1.44 ± 0.19 vs. 1.40 ± 0.18 s × mmHg/mL; P < 0.05) and lower cardiac output (3.76 ± 0.62 vs. 3.82 ± 0.59 L/min; P < 0.05). Hypotension events (decrease in systolic blood pressure by >20 mmHg) were 70 with A, 87 with B, 73 with C, and 75 with D (P < 0.01 B vs. A, 0.05 B vs. C and 0.07 B vs. D). The low-flux membrane correlated to higher blood pressure levels compared with the high-flux ones. The Helixone high-flux membrane ensured the best efficiency. Unfortunately, the very same dialyzer correlated to a higher incidence of hypotensive episodes.

External assessment of the Early Mortality Risk Score in patients with adenocarcinoma undergoing pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomies (PD) still have a substantial mortality rate. Recently, different scores have been published to predict the mortality risk pre-operatively after PD. This retrospective study was designed to perform an external assessment of an Early Mortality Risk Score (EMRS). METHODS: From 2000 to 2012, all PD cases performed at our institution were documented. Only patients treated for pancreatic head adenocarcinomas were included. Survival time and EMRS (based on age, tumour size, tumour differentiation and comorbidities) were calculated for every patient. Relative risks (RR) of early death 9 and 12 months after PD were then calculated. RESULTS: Of 270 PD for various aetiologies, 120 PD for adenocarcinomas were included. The median follow-up was 37 months, and the overall median survival was 19 months. EMRS of 4 showed a mortality RR of 5.1 at 9 months (P = 0.048) and of 4.5 at 12 months (P = 0.020). CONCLUSIONS: EMRS of 4 is a predictor of tumour-related mortality at 9 and 12 months after PD for adenocarcinoma. The EMRS was externally assessed in our patient cohort and can be implemented in clinical practice. Clinical implications of this score still need to be studied.

An Evaluation of the Paper Profile - a comparative assessment of the applicability of an emerging environmental communication tool in pulp and paper industry

Diplomityön tavoitteena oli arvioida uutta sellu-, paperi- ja kartonkiteollisuuden Paper Profile -ympäristötuoteselostetta. Paper Profilen tarkoituksena on tarjota paperiteollisuuden asiakkaille ja muille kiinnostuneilla sidosryhmille yhtenäistä ympäristöinformaatiota koskien paperituotteiden koostumusta ja tuotteiden tärkeimpiä ympäristöparametrejä. Työn tärkein tavoite oli arvioida kriittisesti Paper Profilea ja verrata konseptia ISO:n, Kansainvälisen stardardisoimisliiton tuoteselosteeseen sekä löytää konseptien yhtäläisyydet ja erot. Tärkein tehtävä oli tunnistaa ne avaintekijät, joiden avulla Paper Profile -tuoteselostetta voitaisiin pitää yhtenevänä ISO/TR 14025 teknisen raportin kanssa. Lisäksi Paper Profile -tuoteselosteen mahdolliset kehittämistarpeet arvioitiin ISO-tuoteselosteen näkökulmasta. Työn toinen tavoite oli kerätä ja analysoida uuteen tuoteselosteeseen liittyvä asiakaspalaute ja verrata sitä Stora Enson tehtaiden ympäristöpäälliköiden antamiin Paper Profilea koskeviin kommentteihin. Työn tuloksena huomattiin, että Paper Profile -konsepti sellaisenaan ei ole kovin informatiivinen vaan tuoteseloste jättää monia ympäristökysymyksiä avoimeksi. Siitä huolimatta Paper Profile tarjoaa riittävän taustan eri paperituotteiden ympäristökuormitusten keskinäiselle vertailuille. Konseptin viestinnällinen näkökulma paranisi huomattavasti, jos tuoteselosteeseen lisättäisiin kolmannen osapuolen verifiointi. Lisäksi referenssiarvot kertoisivat asiakkaille paremmin esitettyjen parametrien taustoista. Stora Enson tehtaiden ympäristöpäälliköiden, samoin kuin asiakkaidenkin mielestä Paper Profile on yleisesti ottaen potentiaalinen ympäristöviestinnän työkalu, mutta silti konseptiin ehdotettiin joitakin pieniä muutoksia. Avoinna olevat metsäsertifiointikysymykset ja niiden puutteellinen tiedottaminen tuoteselosteessa puhututtivat sekä tehtaiden henkilöstöä että yritysasiakkaita.

Social justice in education : how the function of selection in educational institutions predicts support for (non)egalitarian assessment practices

Educational institutions are considered a keystone for the establishment of a meritocratic society. They supposedly serve two functions: an educational function that promotes learning for all, and a selection function that sorts individuals into different programs, and ultimately social positions, based on individual merit. We study how the function of selection relates to support for assessment practices known to harm vs. benefit lower status students, through the perceived justice principles underlying these practices. We study two assessment practices: normative assessment-focused on ranking and social comparison, known to hinder the success of lower status students-and formative assessment-focused on learning and improvement, known to benefit lower status students. Normative assessment is usually perceived as relying on an equity principle, with rewards being allocated based on merit and should thus appear as positively associated with the function of selection. Formative assessment is usually perceived as relying on corrective justice that aims to ensure equality of outcomes by considering students' needs, which makes it less suitable for the function of selection. A questionnaire measuring these constructs was administered to university students. Results showed that believing that education is intended to select the best students positively predicts support for normative assessment, through increased perception of its reliance on equity, and negatively predicts support for formative assessment, through reduced perception of its ability to establish corrective justice. This study suggests that the belief in the function of selection as inherent to educational institutions can contribute to the reproduction of social inequalities by preventing change from assessment practices known to disadvantage lowerstatus student, namely normative assessment, to more favorable practices, namely formative assessment, and by promoting matching beliefs in justice principles.

Participation rates for organized colorectal cancer screening programmes: an international comparison.

OBJECTIVE: Participation, an indicator of screening programme acceptance and effectiveness, varies widely in clinical trials and population-based colorectal cancer (CRC) screening programmes. We aimed to assess whether CRC screening participation rates can be compared across organized guaiac fecal occult blood test (G-FOBT)/fecal immunochemical test (FIT)-based programmes, and what factors influence these rates. METHODS: Programme representatives from countries participating in the International Cancer Screening Network were surveyed to describe their G-FOBT/FIT-based CRC screening programmes, how screening participation is defined and measured, and to provide participation data for their most recent completed screening round. RESULTS: Information was obtained from 15 programmes in 12 countries. Programmes varied in size, reach, maturity, target age groups, exclusions, type of test kit, method of providing test kits and use, and frequency of reminders. Coverage by invitation ranged from 30-100%, coverage by the screening programme from 7-67.7%, overall uptake/participation rate from 7-67.7%, and first invitation participation from 7-64.3%. Participation rates generally increased with age and were higher among women than men and for subsequent compared with first invitation participation. CONCLUSION: Comparisons among CRC screening programmes should be made cautiously, given differences in organization, target populations, and interpretation of indicators. More meaningful comparisons are possible if rates are calculated across a uniform age range, by gender, and separately for people invited for the first time vs. previously.

Assessment of the levels of degradation in fat co- and by-products for feed uses and their relationships with some lipid composition parameters

This paper discusses the levels of degradation of some co- and byproducts of the food chain intended for feed uses. As the first part of a research project, 'Feeding Fats Safety', financed by the sixth Framework Programme-EC, a total of 123 samples were collected from 10 European countries, corresponding to fat co- and byproducts such as animal fats, fish oils, acid oils from refining, recycled cooking oils, and other. Several composition and degradation parameters (moisture, acid value, diacylglycerols and monoacylglycerols, peroxides, secondary oxidation products, polymers of triacylglycerols, fatty acid composition, tocopherols, and tocotrienols) were evaluated. These findings led to the conclusion that some fat by- and coproducts, such as fish oils, lecithins, and acid oils, show poor, nonstandardized quality and that production processes need to be greatly improved. Conclusions are also put forward about the applicability and utility of each analytical parameter for characterization and quality control.