Procesos de validación del informe de resultados estadísticos en ensayos clínicos

Los ensayos clínicos tienen un alto impacto en la práctica clínica y son esenciales para el avance de la ciencia. En base a los resultados obtenidos en ensayos clínicos se toman una serie de decisiones importantes sobre la salud de los futuros pacientes, por lo que es fundamental que el diseño, análisis y presentación de los datos se realice de la forma más exacta posible. Debido a estas razones, la contribución del bioestadístico es esencial en el desarrollo y realización de un ensayo clínico. SCReN, plataforma española de apoyo a los ensayos clínicos multicéntricos, realiza un gran esfuerzo por unificar procesos, construyendo para ello, procedimientos normalizados de trabajo para los diferentes aspectos de los ensayos clínicos. Ante la inexistencia actual de procedimientos de trabajo, en la propia plataforma, destinados a la validación de los informes de resultados estadísticos, el presente estudio tiene como objetivo establecer e implementar un proceso de validación de los informes de resultados estadísticos, que cumpla con los atributos de calidad exigibles dentro de los ensayos clínicos. La validación de resultados estadísticos es un proceso necesario en los ensayos clínicos, aunque la implementación en ensayos clínicos reales requerirá una mejora y adecuación del procedimiento normalizado de trabajo al proceso

Geographical and Temporal Variability of Ultra-Processed Food Consumption in the Spanish Population: Findings from the DRECE Study.

The consumption of ultra-processed foods (UPFs) has increased in recent decades, worldwide. Evidence on the negative impacts of food processing on health outcomes has also been steadily increasing. The aim of this study is to describe changes in consumption patterns of ultra-processed foods in the Spanish population over time and their geographical variability. Data from four representative cohorts of the Spanish population were used (1991–1996–2004–2008). Dietary information was collected using a validated frequency questionnaire and categorized using the NOVA classification. A total increase of 10.8% in UPF consumption between 1991 and 2008 was found in Spain (p-value < 0.001). The products contributing most to UPF consumption were sugar-sweetened beverages, processed meats, dairy products, and sweets. Those who consumed more ultra-processed foods were younger (p-value < 0.001) and female (p-value = 0.01). Significant differences between the different geographical areas of Spain were found. The eastern part of Spain was the area with the lowest UPF consumption, whereas the north-western part was the area with the highest increase in UPF consumption. Given the negative effect that the consumption of ultra-processed foods has on health, it is necessary to implement public health policies to curb this increase in UPF consumption.post-print700 K

Bayesian reasoning with emotional material in patients with schizophrenia.

Delusions are one of the most classical symptoms described in schizophrenia. However, despite delusions are often emotionally charged, they have been investigated using tasks involving non-affective material, such as the Beads task. In this study we compared 30 patients with schizophrenia experiencing delusions with 32 matched controls in their pattern of responses to two versions of the Beads task within a Bayesian framework. The two versions of the Beads task consisted of one emotional and one neutral, both with ratios of beads of 60:40 and 80:20, considered, respectively, as the “difficult” and “easy” variants of the task. Results indicate that patients showed a greater deviation from the normative model, especially in the 60:40 ratio, suggesting that more inaccurate probability estimations are more likely to occur under uncertainty conditions. Additionally, both patients and controls showed a greater deviation in the emotional version of the task, providing evidence of a reasoning bias modulated by the content of the stimuli. Finally, a positive correlation between patients’ deviation and delusional symptomatology was found. Impairments in the 60:40 ratio with emotional content was related to the amount of disruption in life caused by delusions. These results contribute to the understanding of how cognitive mechanisms interact with characteristics of the task (i.e., ambiguity and content) in the context of delusional thinking. These findings might be used to inform improved intervention programs in the domain of inferential reasoning.post-print700 K

Two Dimensions of Nutritional Value: Nutri-Score and NOVA

Front-of-pack labels can improve the ability of consumers to identify which foods are healthier, making them a useful public health tool. Nutri-Score is a front-of-pack labelling system adopted by several European countries. This system ranks foods according to their nutritional quality, but does not consider other dimensions such as the degree of food processing. The aim of this study is to compare the nutritional quality (as assessed by Nutri-Score) and the ultra-processing (as assessed by the NOVA classification) of foods in the Open Food Facts database. A simple correspondence analysis was carried out to study the relationship between the two systems. Ultra-processed foods (NOVA 4) were found in all Nutri-Score categories, ranging from 26.08% in nutritional category A, 51.48% in category B, 59.09% in category C, 67.39% in category D to up to 83.69% in nutritional category E. Given the negative effect that the consumption of ultra-processed foods has on different aspects of health, front-of-pack labelling with Nutri-Score should at least be accompanied by complementary labelling indicating the level of processing, such as the NOVA classification

Cognitive versus emotional modulation within a Stroop paradigm in patients with schizophrenia

Background: Schizophrenia is a complex disorder involving deficits in both cognitive and emotional processes. Specifically, a marked deficit in cognitive control has been found, which seems to increase when dealing with emotional information. Aims: With the aim of exploring the possible common links behind cognitive and emotional deficits, two versions of the emotional Stroop task were administered. Method: In the cognitive-emotional task, participants had to name the ink colour (while ignoring the meaning) of emotional words. In contrast, the emotional-emotional task consisted of emotional words superimposed on emotional faces, and the participants had to indicate the emotional valence of the faces. Fifty-eight participants (29 in-patients diagnosed with schizophrenia and 29 controls) took part in the study. Results: Patients and controls showed similar response times in the cognitive-emotional task; however, patients were significantly slower than controls in the emotional-emotional task. This result supports the idea that patients show a more pronounced impairment in conflict modulation with emotional content. Besides, no significant correlations between the tasks and positive or negative symptoms were found. This would indicate that deficits are relatively independent of the clinical status of patients. However, a significant correlation between the emotional-emotional task and cognitive symptoms was found. Conclusions: These findings suggest a restricted capacity of patients with schizophrenia to deal with the attentional demands arising from emotional stimuli.Spanish Ministerio de Ciencia, Innovación y Universidades (PSI2018-098876-B-100Instituto de Salud Carlos III (PI16/00359)Instituto de Salud Carlos III (PI19/00766)5.165 JCR (2021) Q2, 56/155 Psychiatry1.214 SJR (2021) Q1, 106/556 Psychiatry and Mental HealthNo data IDR 2021UE

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million personyears of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eG FR values 105 mL.min(-1).1.73 m(-2), compared with those with eG FR between 60 and 105 mL.min(-1).1.73 m(-2). Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL.min(-1).1.73 m(-2). Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin Alc, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Frontline immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma patients with poor performance status.

Background Immune checkpoint inhibitor-based combination therapy (ICI-based combination) is a new standard of care for metastatic clear cell renal cell carcinoma (mRCC) in the frontline setting. Patients with poor performance status (PS) (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-based combination therapy in this group of patients is still unknown. Methods We performed a multicentre retrospective study of PS ≥2 mRCC patients who received frontline ICI-based combination, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (AP). Patients' characteristics, clinical outcomes, and toxicity were collected. We analysed overall response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS) and grade ≥3 adverse events (G ≥ 3AEs). The association between the predictive biomarker IPI (immune prognostic index) and ORR/PFS/OS was also evaluated. Results We identified 70 mRCC patients with PS ≥2 treated with ICI-based combination across 14 institutions between October 2017 and December 2021, including 45 and 25 patients were treated with NI and AP, respectively. Median age at diagnosis was 63 years, 51 (73%) were male, only 17 (24%) had prior nephrectomy, 50 (71%) had synchronous metastatic disease at diagnosis, and 16 (23%) had brain metastases. Sixty-one (87%) and 9 (13%) patients had ECOG (Eastern Cooperative Oncology Group) PS 2 and 3, respectively, and 25 (36%) and 45 (64%) patients were intermediate and poor International Metastatic RCC Database Consortium (IMDC) risk, respectively. Among all, 91% were clear cell RCC, 7 patients had sarcomatoid features. At the time of the analysis (median follow-up 11.1 months), 41% patients were dead. Median PFS and mOS in the entire cohort were 5.4 months and 16.0 months, respectively; ORR was 31%. No significant differences in ORR, PFS, OS, or G ≥3AEs were seen between NI and AP. The intermediate and poor IPI groups were significantly associated with reduced ORR and shorter PFS. Conclusion We report the first cohort of PS ≥2 mRCC patients treated with frontline ICI-based combination therapy. The survival outcomes in our cohort were inferior to that reported in pivotal trials. No significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. Prospective real-world studies are needed to confirm these results.pre-print728 K