Greater than the sum of the parts: a qualitative content analysis of what constitutes a good treatment in the inpatient setting

Background The evaluation of psychotherapy is guided by established concepts, such as efficacy and effectiveness, and acceptability. Although these concepts serve as valid proxies, little is known about corresponding criteria for those directly involved in this treatment. This study aimed to explore inpatients’ and health professionals’ definitions of a good treatment in the inpatient setting. Methods Fifteen semi-structured interviews were conducted in a private psychiatric clinic in Switzerland and structured by qualitative content analysis. Different subsamples of the inpatient setting (patients N = 5; psychiatrists N = 5; other health professionals N = 5) were interviewed. Results In total, 546 text passages were grouped in 10 superordinate categories and identified as relevant for the concept of a good treatment. Participants stressed patient-specific (i.e., new insights; basic attitudes), treatment-specific (i.e., therapy methods and expertise; treatment success; therapy setting), and relationship-based (i.e., communication and feedback; relationships within the clinical setting; overcoming challenges and hurdles) components that are indispensable for a good therapeutic process. Components that are related to the clinical inpatient setting (i.e., setting and organization of the clinic; code of conduct) were also highlighted. Conclusions Patients’ and health professionals’ definitions of what constitutes a good treatment entails a wide array of aspects. The clinical setting is seen to offer unique components that are emphasized to have a healing effect

Retrospective Analysis of Treatment Pathways in Patients With BRAFV600E-mutant Metastatic Colorectal Carcinoma – MORSECRC

Background/aim: Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAFV600E-mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. Guideline recommendations for this population are mostly based on small cohorts due to lack of clinical data. This retrospective analysis was designed to evaluate (approved) therapeutic approaches and algorithms in BRAFV600E-mutant mCRC prior to approval of the targeted combination encorafenib plus cetuximab in Germany, Austria, and Switzerland. Patients and methods: Anonymized data from BRAFV600E-mutant mCRC patients were analyzed retrospectively regarding 1st-, 2nd- and 3rd-line treatment using descriptive statistics. Results: Forty-two patients were eligible for analysis (mean age 62.1 years, 47.6% female). At initial diagnosis, 20 patients (47.6%) were documented with right-sided tumors. Most patients (81.0%) were tested for BRAF before 1st-line. Four patients (9.5%) showed high microsatellite instability (MSI-H). Based on 94 treatment lines, chemotherapy combined with targeted therapy (TT) was used mostly (61.7%), followed by chemotherapy alone (19.1%). Backbone therapies were most frequently FOLFOXIRI (27.7%), FOLFOX/CAPOX (22.3%), or FOLFIRI (20.2%). Anti-VEGF/VEGFR and anti-EGFR-treatments were used in 45.7% and 23.4% of patients, respectively. Across all treatment lines and types, the predominantly documented reason for discontinuation was lack of efficacy. Conclusion: Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAFV600E-mutated mCRC treatment prior to approval of the targeted combination encorafenib plus cetuximab. Since lack of efficacy was the major reason for treatment discontinuation, newly approved therapies including encorafenib plus cetuximab and - for MSI-H tumors - pembrolizumab represent urgently needed options for future mCRC patients. Keywords: Austria; Chemotherapy; Germany; Switzerland; disease characteristics; targeted therapy; treatment reality

Molecular profiling of soft-tissue sarcomas with FoundationOne® Heme identifies potential targets for sarcoma therapy: a single-centre experience

Background: Molecular diagnosis has become an established tool in the characterisation of adult soft-tissue sarcomas (STS). FoundationOne ® Heme analyses somatic gene alterations in sarcomas via DNA and RNA-hotspot sequencing of tumour-associated genes. Methods: We evaluated FoundationOne ® Heme testing in 81 localised STS including 35 translocation-associated and 46 complex-karyotyped cases from a single institution. Results: Although FoundationOne ® Heme achieved broad patient coverage and identified at least five genetic alterations in each sample, the sensitivity for fusion detection was rather low, at 42.4%. Nevertheless, potential targets for STS treatment were detected using the FoundationOne ® Heme assay: complex-karyotyped sarcomas frequently displayed copy-number alterations of common tumour-suppressor genes, particularly deletions in TP53 , NF1 , ATRX , and CDKN2A . A subset of myxofibrosarcomas (MFS) was amplified for HGF ( n  = 3) and MET ( n  = 1). PIK3CA was mutated in 7/15 cases of myxoid liposarcoma (MLS; 46.7%). Epigenetic regulators (e.g. MLL2 and MLL3 ) were frequently mutated. Conclusions: In summary, FoundationOne ® Heme detected a broad range of genetic alterations and potential therapeutic targets in STS (e.g. HGF/MET in a subset of MFS, or PIK3CA in MLS). The assay’s sensitivity for fusion detection was low in our sample and needs to be re-evaluated in a larger cohort

Retrospective Analysis of Treatment Pathways in Patients With BRAFV600E-mutant Metastatic Colorectal Carcinoma - MORSECRC.

BACKGROUND/AIM Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAFV600E-mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. Guideline recommendations for this population are mostly based on small cohorts due to lack of clinical data. This retrospective analysis was designed to evaluate (approved) therapeutic approaches and algorithms in BRAFV600E-mutant mCRC prior to approval of the targeted combination encorafenib plus cetuximab in Germany, Austria, and Switzerland. PATIENTS AND METHODS Anonymized data from BRAFV600E-mutant mCRC patients were analyzed retrospectively regarding 1st-, 2nd- and 3rd-line treatment using descriptive statistics. RESULTS Forty-two patients were eligible for analysis (mean age 62.1 years, 47.6% female). At initial diagnosis, 20 patients (47.6%) were documented with right-sided tumors. Most patients (81.0%) were tested for BRAF before 1st-line. Four patients (9.5%) showed high microsatellite instability (MSI-H). Based on 94 treatment lines, chemotherapy combined with targeted therapy (TT) was used mostly (61.7%), followed by chemotherapy alone (19.1%). Backbone therapies were most frequently FOLFOXIRI (27.7%), FOLFOX/CAPOX (22.3%), or FOLFIRI (20.2%). Anti-VEGF/VEGFR and anti-EGFR-treatments were used in 45.7% and 23.4% of patients, respectively. Across all treatment lines and types, the predominantly documented reason for discontinuation was lack of efficacy. CONCLUSION Combined chemotherapy+TT (anti-VEGF/VEGFR and anti-EGFR) played a predominant role in BRAFV600E-mutated mCRC treatment prior to approval of the targeted combination encorafenib plus cetuximab. Since lack of efficacy was the major reason for treatment discontinuation, newly approved therapies including encorafenib plus cetuximab and - for MSI-H tumors - pembrolizumab represent urgently needed options for future mCRC patients

Bayesian and frequentist analysis of an Austrian genome-wide association study of colorectal cancer and advanced adenomas

Most genome-wide association studies (GWAS) were analyzed using single marker tests in combination with stringent correction procedures for multiple testing. Thus, a substantial proportion of associated single nucleotide polymorphisms (SNPs) remained undetected and may account for missing heritability in complex traits. Model selection procedures present a powerful alternative to identify associated SNPs in high-dimensional settings. In this GWAS including 1060 colorectal cancer cases, 689 cases of advanced colorectal adenomas and 4367 controls we pursued a dual approach to investigate genome-wide associations with disease risk applying both, single marker analysis and model selection based on the modified Bayesian information criterion, mBIC2, implemented in the software package MOSGWA. For different case-control comparisons, we report models including between 1-14 candidate SNPs. A genome-wide significant association of rs17659990 (P=5.43x10(-9), DOCK3, chromosome 3p21.2) with colorectal cancer risk was observed. Furthermore, 56 SNPs known to influence susceptibility to colorectal cancer and advanced adenoma were tested in a hypothesis-driven approach and several of them were found to be relevant in our Austrian cohort. After correction for multiple testing (alpha=8.9x10(-4)), the most significant associations were observed for SNPs rs10505477 (P=6.08x10(-4)) and rs6983267 (P=7.35x10(-4)) of CASC8, rs3802842 (P=8.98x10(-5), COLCA1,2), and rs12953717 (P=4.64x10(-4), SMAD7). All previously unreported SNPs demand replication in additional samples. Reanalysis of existing GWAS datasets using model selection as tool to detect SNPs associated with a complex trait may present a promising resource to identify further genetic risk variants not only for colorectal cancer

Current Status of Long Non-Coding RNAs in Human Cancer with Specific Focus on Colorectal Cancer

The latest investigations of long non-coding RNAs (lncRNAs) have revealed their important role in human cancers. LncRNAs are larger than 200 nucleotides in length and fulfill their cellular purpose without being translated into proteins. Though the molecular functions of some lncRNAs have been elucidated, there is still a high number of lncRNAs with unknown or controversial functions. In this review, we provide an overview of different lncRNAs and their role in human cancers. In particular, we emphasize their importance in tumorigenesis of colorectal cancer, the third most common cancer worldwide

Neutron transmission measurements on hydrogen filled microspheres

Hollow microspheres are promising candidates for future hydrogen storage technologies. Although the physical process for hydrogen diffusion through glass is well understood, measurements of static quantities (e.q. hydrogen pressure inside the spheres) as well as dynamic properties (e.g. diffusion rate of hydrogen through glass) are still difficult to handle due to the small size of the spheres (d ! 15 lm). For diffusion rate measurements, the long-term stability of the experiment is also mandatory due to the relatively slow diffusion rate. In this work, we present an accurate and long-term stable measurement technique for static and dynamic properties, using neutron radiography. Furthermore, possible applications for hydrogen filled microspheres within the scope of radiation issues are discussed

Greater than the sum of the parts: a qualitative content analysis of what constitutes a good treatment in the inpatient setting

Background: The evaluation of psychotherapy is guided by established concepts, such as efficacy and effectiveness, and acceptability. Although these concepts serve as valid proxies, little is known about corresponding criteria for those directly involved in this treatment. This study aimed to explore inpatients’ and health professionals’ definitions of a good treatment in the inpatient setting. Methods: Fifteen semi-structured interviews were conducted in a private psychiatric clinic in Switzerland and structured by qualitative content analysis. Different subsamples of the inpatient setting (patients N = 5; psychiatrists N = 5; other health professionals N = 5) were interviewed. Results: In total, 546 text passages were grouped in 10 superordinate categories and identified as relevant for the concept of a good treatment. Participants stressed patient-specific (i.e., new insights; basic attitudes), treatment-specific (i.e., therapy methods and expertise; treatment success; therapy setting), and relationship-based (i.e., communication and feedback; relationships within the clinical setting; overcoming challenges and hurdles) components that are indispensable for a good therapeutic process. Components that are related to the clinical inpatient setting (i.e., setting and organization of the clinic; code of conduct) were also highlighted. Conclusions: Patients’ and health professionals’ definitions of what constitutes a good treatment entails a wide array of aspects. The clinical setting is seen to offer unique components that are emphasized to have a healing effect

Associations of Lipophilic Micronutrients with Physical and Cognitive Fitness in Persons with Mild Cognitive Impairment

Age-associated cognitive impairment in general and dementia in particular are a global concern. Preventive lifestyle strategies are highly used but there is a lack of information on the reciprocal relationships between nutrition biomarkers and measures of both cognitive and physical performance. To fill this gap of knowledge, the relationship between plasma levels of the robust nutrition- and antioxidant defense-related biomarkers carotenoid and tocopherols and both indicators of cognitive and physical performance was investigated in a group of persons with mild cognitive impairment participating in the NeuroExercise Study at the German Sport University in Cologne, Germany. In 56 participants with full dataset, significant correlations independently of fruit and vegetable intake were found between plasma levels of -cryptoxanthin and Timed Up&Go test (p < 0.05), -tocopherol and number of daily steps (p < 0.01), as well as between four out of six measured carotenoidslutein; zeaxanthin; -cryptoxanthin and -caroteneand the computerized CogState International Shopping List subtest (p < 0.01). In light of the increasing attention towards the nutritional cognitive neuroscience of carotenoids, computerized measures of cognitive performance might be further implemented in future studies investigating the effects of lifestyle interventions against cognitive and physical impairment