Patients with Rare Cancers in the Drug Rediscovery Protocol (DRUP) Benefit from Genomics-Guided Treatment

Purpose: Patients with rare cancers (incidence less than 6 cases per 100,000 persons per year) commonly have less treatment opportunities and are understudied at the level of genomic targets. We hypothesized that patients with rare cancer benefit from approved anticancer drugs outside their label similar to common cancers. Experimental Design: In the Drug Rediscovery Protocol (DRUP), patients with therapy-refractory metastatic cancers harboring an actionable molecular profile are matched to FDA/European Medicines Agency–approved targeted therapy or immunotherapy. Patients are enrolled in parallel cohorts based on the histologic tumor type, molecular profile and study drug. Primary endpoint is clinical benefit (complete response, partial response, stable disease ≥ 16 weeks). Results: Of 1,145 submitted cases, 500 patients, including 164 patients with rare cancers, started one of the 25 available drugs and were evaluable for treatment outcome. The overall clinical benefit rate was 33% in both the rare cancer and nonrare cancer subgroup. Inactivating alterations of CDKN2A and activating BRAF aberrations were overrepresented in patients with rare cancer compared with nonrare cancers, resulting in more matches to CDK4/6 inhibitors (14% vs. 4%; P ≤ 0.001) or BRAF inhibitors (9% vs. 1%; P ≤ 0.001). Patients with rare cancer treated with small-molecule inhibitors targeting BRAF experienced higher rates of clinical benefit (75%) than the nonrare cancer subgroup. Conclusions: Comprehensive molecular testing in patients with rare cancers may identify treatment opportunities and clinical benefit similar to patients with common cancers. Our findings highlight the importance of access to broad molecular diagnostics to ensure equal treatment opportunities for all patients with cancer

Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands:the COVID-OLD study

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. OBJECTIVE: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. METHODS: This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. RESULTS: A total of 1,376 patients were included (median age 78 years (interquartile range 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3-3.0)) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8-4.3)). CONCLUSIONS: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms

Measurement of water activity with an electric hygrometer

Specific problems arising from the use of an electric hygrometer for measurement of water activity (aw) are the equilibration period, the calibration of the sensors and the influence of temperature on the values measured in saturated salt solutions and meat products. The instrument proved to be a simple, rapid and reliable means of measuring aw values, provided some precautions are taken

Motivational and Control Mechanisms Underlying Adolescent versus Adult Alcohol Use

Increased motivation towards alcohol use and suboptimal behavioral control are suggested to predispose adolescents to alcohol use disorders (AUDs). Paradoxically however, most adolescent AUDs resolve over time without any formal intervention, suggesting adolescent resilience to AUDs. Importantly, studies directly comparing adolescent and adult alcohol use are largely missing. We therefore aimed to unravel the moderating role of age in the relation between alcohol use and motivational and control-related cognitive processes in 45 adolescent drinkers compared to 45 adults. We found that enhancement drinking motives and impulsivity related positively to alcohol use. Although enhancement drinking motives and impulsivity were higher in adolescents, the strength of the relation between these measures and alcohol use did not differ between age groups. None of the alcohol use-related motivational measures (i.e., craving, attentional bias, and approach bias) and behavioral control measures (i.e., interference control, risky decision making, and working-memory) were associated with alcohol use or differed between age groups. These findings support the role of impulsivity and affective sensitivity in adolescent drinking but question the moderating role of age therein. The current study contributes towards understanding the role of age in the relation between alcohol use and cognition

An improved procedure for integrated behavioral z-scoring illustrated with modified Hole Board behavior of male inbred laboratory mice

Background Guilloux et al. introduced: integrated behavioral z-scoring, a method for behavioral phenotyping of mice. Using this method multiple ethological variables can be combined to show an overall description of a certain behavioral dimension or motivational system. However, a problem may occur when the control group used for the calculation has a standard deviation of zero or when no control group is present to act as a reference group. New method In order to solve these problems, an improved procedure is suggested: taking the pooled data as reference. For this purpose a behavioral study with male mice from three inbred strains was carried out. The integrated behavioral z-scoring methodology was applied, thereby taking five different reference group options. The outcome regarding statistical significance and practical importance was compared. Results Significant effects and effect sizes were influenced by the choice of the reference group. In some cases it was impossible to use a certain population and condition, because one or more behavioral variables in question had a standard deviation of zero. Based on the improved method, male mice from the three inbred strains differed regarding activity and anxiety. Comparison with existing method Taking the method described by Guilloux et al. as basis, the present procedure improved the generalizability to all types of experimental designs in animal behavioral research. Conclusions To solve the aforementioned problems and to avoid getting the diagnosis of data manipulation, the pooled data (combining the data from all experimental groups in a study) as reference option is recommended