Premature Discontinuation of Prospective Clinical Studies Approved by a Research Ethics Committee - A Comparison of Randomised and Non-Randomised Studies.

Premature discontinuation of clinical studies affects about 25% of randomised controlled trials (RCTs) which raises concerns about waste of scarce resources for research. The risk of discontinuation of non-randomised prospective studies (NPSs) is yet unclear. To compare the proportion of discontinued studies between NPSs and RCTs that received ethical approval. We systematically surveyed prospective longitudinal clinical studies that were approved by a single REC in Freiburg, Germany between 2000 and 2002. We collected study characteristics, identified subsequent publications, and surveyed investigators to elucidate whether a study was discontinued and, if so, why. Of 917 approved studies, 547 were prospective longitudinal studies (306 RCTs and 241 NPSs). NPSs were on average smaller than RCTs, more frequently single centre and pilot studies, and less frequently funded by industry. NPSs were less frequently discontinued than RCTs: 32/221 (14%) versus 78/288 (27%, p<0.001, missing data excluded). Poor recruitment was the most frequent reason for discontinuation in both NPSs (36%) and RCTs (37%). Compared to RCTs, NPSs were at lower risk for discontinuation. Measures to reliably predict, sustain, and stimulate recruitment could prevent discontinuation of many RCTs but also of some NPSs

Effects of infill patterns on part performances and energy consumption in acrylonitrile butadiene styrene fused filament fabrication via industrial-grade machine

The industrial applications of Additive manufacturing technologies and systems are quickly increasing due to the high flexibility in the part design allowing for mass customisation and reduction of material usage. Besides the absence of manufacturing tools permits a reduction of the time to market. Despite these relevant advantages, building time is generally high and it can typically determine significant energy consumption. Several studies investigate the effect of infill patterns on material mechanical properties to address the design of deposition patterns but these works do not take into consideration relevant aspects related to the manufacturing stage, such as the energy consumption, both the building paths and time. The choice of the infill pattern greatly affects the balance amongst part performances, energy and material consumption. On the other hand, a reduction of the deposited material can effectively reduce the building time and then the process energy. In the present paper, an index that quantifies this balance for a largely used Additive Manufacturing technology is introduced. For this purpose, an experimental investigation is carried out by monitoring the process energy during the manufacturing of specimens characterised by different infill patterns. Then, physical and mechanical properties are measured to compose the proposed index

Protein loop compaction and the origin of the effect of arginine and glutamic acid mixtures on solubility, stability and transient oligomerization of proteins

Addition of a 50 mM mixture of l-arginine and l-glutamic acid (RE) is extensively used to improve protein solubility and stability, although the origin of the effect is not well understood. We present Small Angle X-ray Scattering (SAXS) and Nuclear Magnetic Resonance (NMR) results showing that RE induces protein compaction by collapsing flexible loops on the protein core. This is suggested to be a general mechanism preventing aggregation and improving resistance to proteases and to originate from the polyelectrolyte nature of RE. Molecular polyelectrolyte mixtures are expected to display long range correlation effects according to dressed interaction site theory. We hypothesize that perturbation of the RE solution by dissolved proteins is proportional to the volume occupied by the protein. As a consequence, loop collapse, minimizing the effective protein volume, is favored in the presence of RE

Uma Iniciativa Nacional de Melhoria da Qualidade em Cardiologia: O Programa de Boas Práticas em Cardiologia no Brasil

Resumo Fundamento Apesar de progresso significativo na melhoria da qualidade do tratamento de doenças cardiovasculares, lacunas persistem em termos de falha na adesão às recomendações de diretrizes. Objetivo Este estudo avalia os efeitos da implementação de um programa de melhoria da qualidade adaptado do Programa Get with the guidelines® da American Heart Association sobre a adesão às diretrizes para síndrome coronária aguda (SCA), fibrilação atrial (FA) e insuficiência cardíaca (IC). Métodos Avaliamos dados demográficos, medidas de qualidade, e desfechos em curto prazo em pacientes com SCA, FA, e IC incluídos no programa Boas Práticas em Cardiologia (BPC) entre 2016 e 2022. Resultados Este estudo incluiu 12167 pacientes em 19 hospitais no Brasil. A idade média foi 62,5 [53,8-71] anos, 61,1% eram do sexo masculino, 68,7% apresentaram hipertensão, 32% diabetes mellitus, e 24,1% dislipidemia. Os escores médios compostos tiveram desempenho sustentável entre o período inicial e o último trimestre do seguimento: 65,8±36,2% a 73± 31,2% para FA (p=0,024); 81,0± 23,6% a 89,9 ± 19,3% para IC (p<0,001), e de 88,0 ± 19,1 a 91,2 ± 14,9 para SCA (p<0,001). Conclusões O programa BPC é um programa de melhoria de qualidade no Brasil, em que dados em tempo real, obtidos usando métricas de diretrizes de cardiologia, foram implementados, resultando em uma melhora global no manejo da FA, IC e SCA

External validation of multidimensional prognostic indices (ADO, BODEx and DOSE) in a primary care international cohort (PROEPOC/COPD cohort)

Background: Due to the heterogeneous and systemic nature of the chronic obstructive pulmonary disease (COPD), the new guidelines are oriented toward individualized attention. Multidimensional scales could facilitate its proper clinical and prognostic assessment, but not all of them were validated in an international primary care cohort, different from the original ones used for model development. Therefore, our main aim is to assess the prognostic capacity of the ADO, BODEx and DOSE indices in primary care for predicting mortality in COPD patients and to validate the models obtained in subgroups of patients, classified by revised Global Initiative for Chronic Obstructive Lung Disease (2011) and updated Spanish Guideline (2014). Besides, we want to confirm that the prognostic capacity of all indices increases if the number of exacerbations is substituted by the interval between them and to assess the impact on health of the patient''s lifestyle, social network and adherence to treatment. Methods: Design: External validation of scales, open and prospective cohort study in primary care. Setting: 36 health centres in 6 European high, medium and low income countries. Subjects: 477 patients diagnosed with COPD, captured in clinical visit by their General Practitioner/Nurse. Predictors: Detailed patient history, exacerbations, lung function test and questionnaires at baseline. Outcomes: Exacerbations, all-cause mortality and specific mortality, within 5 years of recruitment. Analysis: Multivariate logistic regression and Cox regression will be used. Possible non-linear effect of the indices will be studied by using Structured Additive Regression models with penalised splines. Subsequently, we will assess different aspects of the regression models: discrimination, calibration and diagnostic precision. Clinical variables modulated in primary care and the interval between exacerbations will be considered and incorporated into the analysis. Discussion: The Research Agenda for General Practice/Family Medicine highlights that the evidence on predictive values of prognostic indices in primary care is scarce. A prospective cohort like that of PROEPOC/COPD provides good opportunities for research into COPD and make communication easier between family practitioners, nursing staff, pneumologists and other professionals, supporting a multi-disciplinary approach to the treatment of these patients. Trial registration:ISRCTN52402811. Date: 15/01/2015. Prospectively registered

Mortalidade por Insuficiência Cardíaca durante a Pandemia da COVID-19: Insights de uma Coorte de Hospitais Públicos no Brasil

Brazil is one of the most hit countries by the pandemic caused by the novel coronavirus (Coronavirus Disease, COVID-19), with more than half million deaths in June, 2021, the world’s second-highest number of deaths. It has been reported that the COVID-19 outbreak has affected the delivery of care of patients without COVID-19 (non-COVID-19 patients), particularly patients with cardiovascular (CV) diseases, increasing the death toll from the pandemic. Studies have shown a reduction in hospitalizations in tandem with an increase mortality from CV diseases during the outbreak in many countries. However, most of these reports focused on patients with acute coronary syndrome (ACS ) in developed countries, with few data on heart failure (HF) admissions, and the reasons for the worse mortality are not well understood. We evaluated the changes in severity, reasons for decompensation and 30-day mortality of patients admitted for HF in public hospitals included in the Best Practices in Cardiology (BPC) program in Brazil during the COVID-19 outbreak and compared with previous periods

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events