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Objectives: To describe divergence between actionable statements issued by coronavirus disease 2019 (COVID-19) guideline developers cataloged on the “COVID-19 Recommendations and Gateway to Contextualization” platform. Study Design and Setting: We defined divergence as at least two comparable actionable statements with different explicit judgments of strength, direction, or subgroup consideration of the population or intervention. We applied a content analysis to compare guideline development methods for a sample of diverging statements and to evaluate factors associated with divergence. Results: Of the 138 guidelines evaluated, 85 (62%) contained at least one statement that diverged from another guideline. We identified 223 diverging statements in these 85 guidelines. We grouped statements into 66 clusters. Each cluster addressed the same population, intervention, and comparator group or just similar interventions. Clinical practice statements were more likely to diverge in an explicit judgment of strength or direction compared to public health statements. Statements were more likely to diverge in strength than direction. The date of publication, used evidence, interpretation of evidence, and contextualization considerations were associated with divergence. Conclusion: More than half of the assessed guidelines issued at least one diverging statement. This study helps in understanding the types of differences between guidelines issuing comparable statements and factors associated with their divergence. © 2022

Introduction: The COVID-19 pandemic was confirmed to have spread to Slovakia on 6th March 2020. To date of paper submission, it has very favorable course. However, since the beginning healthcare workers have been working under increasing pressure, anxiety and fear. Aim: Authors evaluated the psychosocial impact of COVID-19 pandemic on mental health experts and their clinical practice in Slovakia. Materials and Methods: A total of 157 mental health experts (79% women) submitted their responses via online questionnaire. Results: The most frequent occupation categories were 38.2% outpatient psychiatrists, 26.1% inpatient psychiatrists and 20.4% psychologists. The mental health experts felt maximum of stress during the peak of Slovak COVID-19 crisis, which was identified as the situation just after the declaring the state of emergency by Slovak government. The main sources of stress were statistical data, prognoses and other public presented information. Mental health experts felt mainly personal stress, then general and working stress. They identified also pathological effect of COVID-19 pandemic on the mental status of their patients, especially with anxiety and affective disorders and advantages of use of telemedicine. Conclusion: Psychosocial support in Slovakia was newly organized in COVID-19 pandemic for medical professionals, patients and other inhabitants under high stress within a very short time. This unexpected situation has revealed to Slovakia the need for reform of the mental healthcare system.

BACKGROUND: Vemurafenib, a selective inhibitor of BRAF kinase, is approved for the treatment of adult stage IIIc/IV BRAF V600 mutation-positive melanoma. We conducted a phase I, open-label, dose-escalation study in pediatric patients aged 12–17 years with this tumor type (NCT01519323). PROCEDURE: Patients received vemurafenib orally until disease progression. Dose escalation was conducted using a 3+3 design. Patients were monitored for dose-limiting toxicities (DLTs) during the first 28 days of treatment to determine the maximum tolerated dose (MTD). Safety/tolerability, tumor response, and pharmacokinetics were evaluated. RESULTS: Six patients were enrolled (720 mg twice daily [BID]; n=3]; 960 mg BID [n=3]). The study was terminated prematurely due to low enrollment. No DLTs were observed; thus, the MTD could not be determined. All patients experienced at least one adverse event (AE); the most common were diarrhea, headache, photosensitivity, rash, nausea, and fatigue. Three patients experienced serious AEs, one patient developed secondary cutaneous malignancies, and five patients died following disease progression. Mean steady-state plasma concentrations of vemurafenib following 720 mg and 960 mg BID dosing were similar or higher, respectively, than in adults. There were no objective responses. Median progression-free survival and overall survival were 4.4 months (95% confidence interval [CI]=2.7–5.2) and 8.1 months (95% CI=5.1–12.0), respectively. CONCLUSIONS: A recommended and effective dose of vemurafenib for patients aged 12–17 years with metastatic or unresectable melanoma was not identified. Extremely low enrollment in this trial highlights the importance of considering the inclusion of adolescents with adult cancers in adult trials.