Best Practice for Clinical Somatic Variant Interpretation and Reporting.

Because the clinical impact of cancer genomics is being increasingly recognized, tumor sequencing will likely continue to expand in breadth and scope. Therefore, it is vital for laboratory professionals to adopt the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists guidelines and create a standardized system of classification and nomenclature for somatic variants. Combining robust bioinformatics pipelines with thorough data analysis is necessary to efficiently and reproducibly identify and assess the impact of clinically relevant variants.

Exploring the potential of delivering mental health care services using digital technologies in Bangladesh: A qualitative analysis.

Background: Bangladesh is a lower-middle-income country affected by a severe lack of mental health service availability due to a scarcity of mental health experts, limited mental health literacy, and community stigma. In other low and middle-income countries, the online provision of mental health care services has addressed issues affecting service availability, accessibility, mass awareness of services, and stigma. Objective: The current study sought to understand stakeholders' perceptions of the potential of digital media-based mental health care delivery in strengthening Bangladesh's mental health system. Method: Online in-depth interviews were conducted with seven psychiatrists and eleven people with lived experiences of mental health issues. In addition, two online focus groups were conducted with ten psychologists and nine mental health entrepreneurs. A thematic analysis of the audio transcriptions was used to identify themes. Result: Stakeholders perceived that the benefits of digital media-based mental health services included the potential of increasing the awareness, availability, and accessibility of mental health services. Participants recommended: the rehabilitation of existing pathways; the use of social media to raise awareness; and the implementation of strategies that integrate different digital-based services to strengthen the mental health system and foster positive mental health-seeking behaviors. Conclusion: Growing mental health awareness, combined with the appropriate use of digital media as a platform for distributing information and offering mental services, can help to promote mental health care. To strengthen mental health services in Bangladesh, tailored services, increased network coverage, and training are required on digital mental health.

Turalio risk evaluation and mitigation strategy for treatment of tenosynovial giant cell tumor: framework and experience.

For drugs with enhanced serious safety risks, Risk Evaluation and Mitigation Strategy (REMS) may be required. Pexidartinib is approved for treatment of adult symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Its approval was conditional on its prescription via a mandatory REMS due to serious and potentially fatal liver injury seen in clinical trials. Turalio® REMS aims to mitigate this risk by ensuring provider education on pexidartinib use and required REMS components, prescriber adherence to baseline and periodic monitoring, and enrolling patients in a registry to further assess safe use and acute, chronic and irreversible hepatotoxicity. Through Turalio REMS, benefits of treating patients with pexidartinib may be preserved.

For drugs with serious side effects, specific safety measures may be put in place to manage these serious side effects in the form of Risk Evaluation and Mitigation Strategy (REMS) programs. Pexidartinib (Turalio^®) is approved for treatment of adults who have symptoms of severe tenosynovial giant cell tumor or have limitations in function that do not improve with surgery. Turalio^® has an REMS program because liver injuries that can be serious or fatal were seen in Pexidartinib clinical trials. This program aims to decrease the seriousness of the liver injuries by assuring doctors and pharmacists are educated on how to use the drug, patients are advised of this potential risk and that baseline and periodic monitoring of patients are conducted.

Cultural Adaptation of CBT for Afghan Refugees in Europe: A Retrospective Evaluation.

Background: Culturally adapted CBT (CA CBT) is a well-evaluated, culture-sensitive intervention for refugees that utilizes psychoeducation, problem solving training, meditation, and stretching exercises. However, there is a lack of standard procedures for adapting psychotherapeutic interventions to a specific cultural context. Our working group adapted CA CBT for Afghan refugees at two different stages, which yielded promising results from a pilot trial and an RCT with a waitlist control group. This article aimed to illustrate the ongoing adaptation process of CA CBT for Afghan refugees over the course of several trials and to highlight potential limitations by evaluating how systematic adaptations were performed. Method: The adaptation process of CA CBT was described in detail, including the methods and rationale for changes to the protocol. This process was analyzed according to a new set of proposed reporting criteria. Results: According to the defined target population and based on multiple research strategies, culturally-specific components, such as the rationales for interventions, metaphors, and idioms of distress, were adapted. Relevant surface adaptations were implemented. However, although the steps of our adaptation process corresponded with the reporting criteria, some of the adaptation processes did not follow explicit criteria but resulted from implicit judgments. Conclusion: In the future, compliance with and the documentation of adaptation processes following explicit guidelines are crucial for the transfer of evidence-based approaches for managing the diversity of refugee populations.

Reporting Cultural Adaptation in Psychological Trials - The RECAPT criteria.

Background: There is a lack of empirical evidence on the level of cultural adaptation required for psychological interventions developed in Western, Educated, Industrialized, Rich, and Democratic (WEIRD) societies to be effective for the treatment of common mental disorders among culturally and ethnically diverse groups. This lack of evidence is partly due to insufficient documentation of cultural adaptation in psychological trials. Standardised documentation is needed in order to enhance empirical and meta-analytic evidence. Process: A "Task force for cultural adaptation of mental health interventions for refugees" was established to harmonise and document the cultural adaptation process across several randomised controlled trials testing psychological interventions for mental health among refugee populations in Germany. Based on the collected experiences, a sub-group of the task force developed the reporting criteria presented in this paper. Thereafter, an online survey with international experts in cultural adaptation of psychological interventions was conducted, including two rounds of feedback. Results: The consolidation process resulted in eleven reporting criteria to guide and document the process of cultural adaptation of psychological interventions in clinical trials. A template for documenting this process is provided. The eleven criteria are structured along A) Set-up; B) Formative research methods; C) Intervention adaptation; D) Measuring outcomes and implementation. Conclusions: Reporting on cultural adaptation more consistently in future psychological trials will hopefully improve the quality of evidence and contribute to examining the effect of cultural adaptation on treatment efficacy, feasibility, and acceptability.

Fit-for-Purpose Validation and Establishment of Assay Acceptance and Reporting Criteria of Dendritic Cell Activation Assay Contributing to the Assessment of Immunogenicity Risk.

Validation of key analytical and functional performance characteristics of in vitro immunogenicity risk assessment assays increases our confidence in utilizing them for screening biotherapeutics. Herein, we present a fit-for-purpose (FFP) validation of a dendritic cell (DC) activation assay designed to assess the immunogenicity liability of protein biotherapeutics. Characterization of key assay parameters was achieved using monocyte-derived DCs (MoDCs) treated with cell culture medium only (i.e., background control (BC)), keyhole limpet hemocyanin (KLH) as system positive control (SPC), and 2 therapeutic monoclonal antibodies (mAbs) with known clinical immunogenicity profiles (bococizumab and TAM163) as therapeutic controls (TCs). In the absence of established validation guidelines for primary cell-based assays, the present DC activation assay was validated using a novel FFP approach which allows more flexibility in selection of validation parameters and designing of experiments based on the intended use of the assay. The present FFP validation allowed us to understand the impact of experimental variables on assay precision, develop a clear concise readout for DC activation results, establish a reliable response threshold to define a result as a positive DC activation response, and define in-study donor acceptance criteria and cohort size. FFP validation of this DC activation assay indicated that the assay is sufficient to support its context of use, a preclinical immunogenicity risk management tool.

Limited diagnostic impact of duplications <1 Mb of uncertain clinical significance: a 10-year retrospective analysis of reporting practices at the Mayo Clinic.

PURPOSE: Copy-number variants (CNVs) of uncertain clinical significance are routinely reported in a clinical setting only when exceeding predetermined reporting thresholds, typically based on CNV size. Given that very few genes are associated with triplosensitive phenotypes, it is not surprising that many interstitial duplications <1 Mb are found to be inherited and anticipated to be of limited or no clinical significance. METHODS: In an effort to further refine our reporting criteria to maximize diagnostic yield while minimizing the return of uncertain variants, we performed a retrospective analysis of all clinical microarray cases reported in a 10-year window. A total of 1112 reported duplications had parental follow-up, and these were compared by size, RefSeq gene content, and inheritance pattern. De novo origin was used as a rough proxy for pathogenicity. RESULTS: Approximately 6% of duplications 500 kb-1 Mb were de novo observations, compared with approximately 14% for 1-2 Mb duplications (p = 0.0005). On average, de novo duplications had higher gene counts than inherited duplications. CONCLUSION: Our data reveal limited diagnostic utility for duplications of uncertain significance <1 Mb. Considerations for revised reporting criteria are discussed and are applicable to CNVs detected by any genome-wide exploratory methodology, including exome/genome sequencing.

How to manage accidental and unintended exposure in radiology: an ESR white paper.

Since February 2018, the Directive 2013/59/EURATOM (EU-BSS) requires all EU member states to implement a system for recording and analysis of all accidental or unintended medical exposures (Article 63). An ESR questionnaire in May 2018 among ESR member countries including all EU member states (MS) revealed a very heterogeneous and unsatisfactory situation in transposition of the EU-BSS. Some MS just translated this part of the directive, others used effective dose as reporting criteria and others used physical dose parameters from the modalities. This white paper will help national scientific organisations advice their national regulators and authorities on how to provide a simple and practicable implementation of the directive. ESR recommends notification and reporting criteria for significant events based on physical quantities and units and not on effective dose or text-based criteria like "significantly different" (EU-BSS, Article 4 (99)).

[Reporting and information system for significant events related to radiation exposures in medicine: Structure, responsibilities and reporting criteria]. / Melde- und Informationssystem für bedeutsame Vorkommnisse bei Strahlenanwendungen in der Medizin: Struktur, Zuständigkeiten und Meldekriterien.

The increasing frequency and complexity of medical radiation exposures to humans inevitably result in higher risks of harmful unintended or accidental radiation exposures. To ensure a high level of protection and its continuous improvement, the Directive 2013/59/Euratom thus requires to systematically record and analyze both events and near-miss events as well as, in the case of their significance, to disseminate information regarding lessons learned from these events promptly and nationwide to improve radiation protection in medicine. These requirements have been transposed into German legislation by the new radiation protection law and radiation protection ordinance that entered into force simultaneously on December 31th, 2018. The reporting and information system as provided by these regulations as well as the tasks, duties and powers of the parties involved are presented in the first part of this review article. In the second part, the established application-specified criteria for the significance - and thus the notification requirement - of (near-miss) events are itemized and explicated.

MET amplification assessed using optimized FISH reporting criteria predicts early distant metastasis in patients with non-small cell lung cancer.

To investigate the prognostic impact of MET copy number (MET-CN) in patients with non-small cell lung cancer (NSCLC), we retrospectively reviewed clinical and pathologic data of NSCLC patients whose tumors were assessed for MET-CN using fluorescence in situ hybridization (FISH). We correlated MET-CN status with patient overall survival (OS) and optimized MET-FISH reporting criteria. The study group included 384 patients with NSCLC of which 88% were adenocarcinoma and 55.7% of patients had distant metastases. There were 170 patients with stages I-III and 214 patients with stage IV disease. Based on the MET-CN and MET/CEP7 ratio the patients were classified into 3 categories: MET-amplification (METamp): MET/CEP7 ≥ 2 or MET-CN ≥ 5; MET-CN-gain (METcng): MET-CN ≥ 4 to < 5; and MET-negative (METneg): MET-CN < 4. METamp was associated with high fatality (P=.036) and stage IV tumors (P=.038). In patients with stages I-III NSCLC, patients in the METamp category had the shortest OS (P=.015) and more often developed distant metastases within 1 year (P=.004). In patients with stage IV tumors, METamp did not further impact the OS. Patients in the METcng category had the longest OS (P=.053). Multivariate analysis confirmed METamp to be an independent high-risk factor (HR 3.26; P=.026) and predicted earlier progression to distant metastasis (HR 4.86; P=.001). In conclusion, we suggest that the MET-FISH criteria presented optimizes risk stratification by defining 3 categories of NSCLC patients. METamp is an independent risk factor predicting early distant metastasis and patients with METcng could represent a lower-risk group.

[Reporting criteria for clinical experts consensus of Chinese medicine].

Due to its own characteristics and research status, traditional Chinese medicine research often faces the reality of "insufficient evidence" or "very low quality" when making clinical practice guidelines. Therefore, in many cases, clinical decision-making of traditional Chinese medicine should rely mainly on expert consensus to achieve. A clear and detailed list of expert consensus report specifications will provide a good reporting tool for Chinese clinical expert consensus makers, which is very important for promoting the quality of consensus production and the promotion and application of consensus results. The author consulted the internationally published authoritative expert consensus, summarized the main points of the reports, combined with the formulation process of the clinical experts consensus of Chinese medicine, and the demonstration of clinical experts and methodologists, and then formulated the list of items for clinical expert consensus reports adapt to the field of Chinese medicine. This article introduces the entire list of items and elaborates on the key parts. It is expected to provide reference for the standardization of future clinical expert consensus reports.

Reporting criteria for clinical experts consensus of Chinese medicine / 中国中药杂志

Due to its own characteristics and research status, traditional Chinese medicine research often faces the reality of "insufficient evidence" or "very low quality" when making clinical practice guidelines. Therefore, in many cases, clinical decision-making of traditional Chinese medicine should rely mainly on expert consensus to achieve. A clear and detailed list of expert consensus report specifications will provide a good reporting tool for Chinese clinical expert consensus makers, which is very important for promoting the quality of consensus production and the promotion and application of consensus results. The author consulted the internationally published authoritative expert consensus, summarized the main points of the reports, combined with the formulation process of the clinical experts consensus of Chinese medicine, and the demonstration of clinical experts and methodologists, and then formulated the list of items for clinical expert consensus reports adapt to the field of Chinese medicine. This article introduces the entire list of items and elaborates on the key parts. It is expected to provide reference for the standardization of future clinical expert consensus reports.

Impact of the PROCESS guideline on the reporting of surgical case series: A before and after study.

INTRODUCTION: The PROCESS guideline was developed in 2016 through expert Delphi consensus. It aimed to improve the quality of reporting of surgical case series. This study assessed the impact of the introduction of the PROCESS guideline on reporting for surgical case series submitted to three journals. METHODS: 20 case series published in the International Journal of Surgery Case Reports (IJSCR), the International Journal of Surgery (IJS) or the Annals of Medicine and Surgery (AMS) in September to December 2016, prior to the introduction of the PROCESS guideline (the pre-PROCESS period), were randomly identified and scored against the PROCESS criteria. Two authors independently scored each article a total score out of 29, the 'PROCESS score' (expressed as a percentage). Scores for the two researchers were compared and consensus was reached to achieve a final score set. The process was repeated for the January 2017 to April 2017 issues of the three journals, post PROCESS implementation (the post-PROCESS period). RESULTS: The mean PROCESS score was 80% (range 66-90%) for the pre-PROCESS period and 84% (range 72-95%) for the post-PROCESS period, a 4% relative increase [STATS]. The Cohen's Kappa score between researchers was 0.907 implying very substantial agreement. CONCLUSION: Implementation of the PROCESS guideline resulted in a 5% improvement in the reporting quality of surgical case series published in three journals. Further research is needed to identify and successfully navigate existing barriers to greater compliance. Authors, reviewers and editors should adhere to the guidelines to boost reporting quality. Journals should develop their policies and guide for authors to incorporate the guideline and mandate compliance.

Establishing guidelines for executing and reporting Internet intervention research.

The field of Internet interventions is growing rapidly. New programs are continually being developed to facilitate health and mental health promotion, disease and emotional distress prevention, risk factor management, treatment, and relapse prevention. However, a clear definition of Internet interventions, guidelines for research, and evidence of effectiveness have been slower to follow. This article focuses on the quality standardization of research on Internet-delivered psychological and behavioural interventions. Although the science underpinning Internet interventions is just starting to be established, across research studies there are often conceptual and methodological difficulties. The authors argue that this situation is due to the lack of universally accepted operational guidelines and evaluation methods. Following a critical appraisal of existing codes of conduct and guidelines for Internet-assisted psychological and health interventions, the authors developed a framework of guidelines for Internet intervention research utilizing aspects of facet theory (Guttman & Greenbaum, 1998). The framework of facets, elements, and guidelines of best practice in reporting Internet intervention research was then sent to several leading researchers in the field for their comment and input, so that a consensus framework could be agreed on. The authors outline 12 key facets to be considered when evaluating and reporting Internet intervention studies. Each facet consists of a range of recommended elements, designed as the minimum features for reporting Internet intervention studies. The authors propose that this framework be utilized when designing and reporting Internet intervention research, so results across studies can be replicated, extended, compared, and contrasted with greater ease and clarity.

Feasibility Study of Constructing an Occupational Disease Surveillance System in Inchon / 대한산업의학회지

The occurrence of occupational illnesses and injuries has been seriously underestimated in Korea. This underdiagnosis and underreporting of occupational illnesses and injuries subsequently contribute to difficulties in performing effective control of occupational hazards and implementing intervention programs to protect workers. An Inchon model for an occupational disease surveillance system was constructed using multiple data sources. Available data were obtained from medical providers' reports, hospital medical records, medical examination data of employees, and environmental measurement data. This Jnchon model was constructed with the following procedure: 1. assembled multidisciplinary staff 2. geographic targeting was to Inchon 3. established community liaison 4. collected related data to establish the magnitude of problem 5. selected, recruited, and trained case reporters 6. developed mechanisms and guidelines for reporting 7. received, screened, and prioritized case reports 8. analyzed data from case reports and field investigations 9. made and disseminated recommendations 10. evaluated the feasibility of the system. An information system based on the Internet for the occupational disease surveillance was also constructed to support the case reporting of occupational diseases. 133 cases of occupational diseases were collected in Inchon from 1 January to 31 December 1998. These cases included cumulative traumatic disorder, occupational asthma, occupational contact dermatitis, allergic pneumonitis, occupational cancer, noise-induced hearing loss, and pneumoconiosis. These data were different from the previously reported data The occurrence pattern of occupational diseases obtained from this surveillance system will be useful for preventing occupational hazards and for enforcing occupational disease prevention programs. Our experiences in establishing this surveillance system may be also used in other regional settings.