Major discrepancies between what clinical trial registries record and paediatric randomised controlled trials publish

Background: Whether information from clinical trial registries (CTRs) and published randomised controlled trial (RCTs) differs remains unknown. Knowing more about discrepancies should alert those who rely on RCTs for medical decision-making to possible dissemination or reporting bias. To provide help in critically appraising research relevant for clinical practice we sought possible discrepancies between what CTRs record and paediatric RCTs actually publish. For this purpose, after identifying six reporting domains including funding, design, and outcomes, we collected data from 20 consecutive RCTs published in a widely read peer-reviewed paediatric journal and cross-checked reported features with those in the corresponding CTRs. Methods: We collected data for 20 unselected, consecutive paediatric RCTs published in a widely read peer-reviewed journal from July to November 2013. To assess discrepancies, two reviewers identified and scored six reporting domains: funding and conflict of interests; sample size, inclusion and exclusion criteria or crossover; primary and secondary outcomes, early study completion, and main outcome reporting. After applying the Critical Appraisal Skills Programme (CASP) checklist, five reviewer pairs cross-checked CTRs and matching RCTs, then mapped and coded the reporting domains and scored combined discrepancy as low, medium and high. Results: The 20 RCTs were registered in five different CTRs. Even though the 20 RCTs fulfilled the CASP general criteria for assessing internal validity, 19 clinical trials had medium or high combined discrepancy scores for what the 20 RCTs reported and the matched five CTRs stated. All 20 RCTs selectively reported or failed to report main outcomes, 9 had discrepancies in declaring sponsorship, 8 discrepancies in the sample size, 9 failed to respect inclusion or exclusion criteria, 11 downgraded or modified primary outcome or upgraded secondary outcomes, and 13 completed early without justification. The CTRs for seven trials failed to index automatically the URL address or the RCT reference, and for 12 recorded RCT details, but the authors failed to report the results. Conclusions: Major discrepancies between what CTRs record and paediatric RCTs publish raise concern about what clinical trials conclude. Our findings should make clinicians, who rely on RCT results for medical decision-making, aware of dissemination or reporting bias. Trialists need to bring CTR data and reported protocols into line with published data

Food Policy Processes in the City of Rome: A Perspective on Policy Integration and Governance Innovation

In the food policy arena, the topic of governance and how to create a governance system that would deal with cross-cutting issues, including new ways of perceiving the public sphere, the policymaking, and the involvement of the population, has become an important field of study. The research presented in this article focuses on the case study of Rome, comparing different paths that various groups of actors have taken toward the definition of urban food policy processes: the Agrifood Plan, Food Policy for Rome, and Community Gardens Movement. The aim of the research is to understand the state of the art about different paths toward food strategies and policies that are currently active in the Roman territory while investigating the relationship between policy integration and governance innovation structures. Indeed, this paper dives into the governance structure of the three food policy processes, the actors and sectors involved, and the goals and instruments selected to achieve a more sustainable food system for the city. In this context, their characteristics are analyzed according to an innovative conceptual framework, which, by crossing two recognized theoretical systems, on policy integration and governance innovation frameworks, allows to identify the capacity of policy integration and governance innovation. The analysis shows that every process performs a different form of governance, implemented according to the actor and backgrounds that compose the process itself. The study demonstrates that governance innovation and policy integration are strongly linked and that the conception and application of policy integration changes according to the governance vision that a process has

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Oral microbiota profile is related to cognitive status in centenarians: a clinical and biological study

Objectives: A growing body of evidence supports the potential role of the oral microbiota in influencing cognitive function. Centenarians, at the extreme end of the lifespan, are the ideal cohort to study the long-term effects of inflammaging. Study design: Twenty-three centenarians were examined by a neurologist, neuropsychologist and dentist to assess cognitive status and oral health. They were also profiled for oral microbiota and inflammasome. Results: We found less alpha diversity in the oral microbiota of participants with dementia and an overall depletion of typical oral commensals, including Alloprevotella, Prevotella, Veillonella, Fusobacterium and Leptotrichia. The latter two were also underrepresented in edentulous compared with dentate subjects. Moreover, levels of pro-inflammatory cytokines and chemokines tended to be higher in participants with dementia. Conclusions: Our data support a relationship between oral microbiota, cognitive status and inflammation, which deserves further exploration to counteract cognitive decline while promoting healthy aging

In vivo validation of the adequacy calculator for continuous renal replacement therapies

INTRODUCTION: The study was conducted to validate in vivo the Adequacy Calculator, a Microsoft Excel-based program, designed to assess the prescription and delivery of renal replacement therapy in the critical care setting. METHODS: The design was a prospective cohort study, set in two intensive care units of teaching hospitals. The participants were 30 consecutive critically ill patients with acute renal failure treated with 106 continuous renal replacement therapies (CRRT). Urea clearance computation was performed with the Adequacy Calculator (K(CALC)). Simultaneous blood and effluent urea samples were collected to measure the effectively delivered urea clearance (K(DEL)) at the beginning of each treatment and, during 73 treatments, between the 18th and 24th treatment hour. The correlation between 179 computed and 179 measured clearances was assessed. Fractional clearances for urea were calculated as spKt/V (where sp represents single pool, K is clearance, t is time, and V is urea volume of distribution) obtained from software prescription and compared with the delivered spKt/V obtained from empirical data. RESULTS: We found that the value of clearance predicted by the calculator was strongly correlated with the value obtained from computation on blood and dialysate determination (r = 0.97) during the first 24 treatment hours, regardless of the renal replacement modality used. The delivered spKt/V (1.25) was less than prescribed (1.4) from the Adequacy Calculator by 10.7%, owing to therapy downtime. CONCLUSION: The Adequacy Calculator is a simple tool for prescribing CRRT and for predicting the delivered dose. The calculator might be a helpful tool for standardizing therapy and for comparing disparate treatments, making it possible to perform large multi-centre studies on CRRT

Classics in a new perspective: gluten as a special food safety and analytical challenge

In the last couple of decades, the nutritional role and perception of gluten became controversial. In one hand, gluten proteins play a central role in determining the baking quality of wheat and other cereals. On the other hand, hypersensitivity reactions triggered by gluten in susceptible individuals have become subjects of growing interest. Of these gluten-related disorders, with an estimated global prevalence of 1%, the most important one is celiac disease (CD), which is an autoimmune disorder accompanied by villous atrophy. CD can manifest in a wide range of symptoms, its only treatment option is a lifelong gluten-free (GF) diet. To support compliance to this diet, current EU legislation maximizes the gluten-content of products sold with a GF label in 20 mg/kg. It necessitates accurate quantification of gluten in this low concentration range. The method-of-choice for this purpose is the immunoanalytical-based ELISA (enzyme-linked immunosorbent assay). However, validation of different ELISA methods and the comparability of their results and, consequently, the reliability of the data they provide is problematic. The major goal of this paper is to introduce the analytical and protein chemistry issues behind this problem and the efforts to improve the conditions of the methodology. We are also including the special role of oats in the GF diet in an attempt to provide the widest possible overview of the food safety and analytical challenges represented by gluten

Klasszikus témák új megvilágításban: a glutén mint speciális élelmiszerbiztonsági és analitikai kihívás

A glutén, vagy sikér fehérjék táplálkozás-élettani szerepe és megítélése az utóbbi évtizedekben kettőssé vált. A glutén fehérjék egyrészt központi szerepet töltenek be a búza és más gabonák sütőipari minőségének kialakításában. Másrészt azonban egyre inkább előtérbe kerülnek olyan túlérzékenységi reakciók, melyeket szintén a glutén fehérjék váltanak ki az arra érzékeny populációban. A glutén által okozott rendellenességek közül 1% körüli globális előfordulásával az egyik legjelentősebb a lisztérzékenység, vagy más néven cöliákia, mely a vékonybél bolyhainak sorvadásával járó autoimmun betegség. A tünetek széles skáláját okozhatja, jelenleg egyetlen ismert kezelési módja az élethosszig tartó gluténmentes diéta. A diéta betartásának elősegítésére a jelenleg érvényes EU szabályozás 20 mg/kg-ban maximalizálja a gluténmentesként értékesíthető termékek gluténtartalmát. Ez pedig szükségessé teszi a glutén mennyiségének minél pontosabb meghatározását ebben az alacsony koncentráció-tartományban. A meghatározás rutinmódszere az immunanalitikai elven működő ELISA (enzyme-linked immunosorbent assay). A különböző ELISA módszerek validálása és eredményeik összehasonlíthatósága, vagyis az általuk szolgáltatott adatok megbízhatósága azonban problémát jelent. Cikkünk fő célkitűzése az ennek hátterében álló analitikai és fehérjekémiai kérdések, valamint a módszertan feltételrendszerének javítását célzó törekvések bemutatása. Emellett kitérünk a zab gluténmentes diétában betöltött különleges szerepére is, így kísérelve meg minél szélesebb körben rálátást nyújtani a glutén által képviselt élelmiszerbiztonsági és analitikai kihívásokra

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score &gt; 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p &lt; 0.001), RR = 2.19 for ICU admission (p &lt; 0.001), and RR = 2.43 for death (p &lt; 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR&nbsp;=&nbsp;2.05, 95%CI&nbsp;=&nbsp;1.39–3.02, p&nbsp;&lt;&nbsp;0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR&nbsp;=&nbsp;0.42, 95%CI&nbsp;=&nbsp;0.18–0.99, p&nbsp;=&nbsp;0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon