BRIM-P: A phase I, open-label, multicenter, dose-escalation study of vemurafenib in pediatric patients with surgically incurable, BRAF mutation-positive melanoma.

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.

A multimethods randomized trial found that plain language versions improved adults understanding of health recommendations.

OBJECTIVES: To make informed decisions, the general population should have access to accessible and understandable health recommendations. To compare understanding, accessibility, usability, satisfaction, intention to implement, and preference of adults provided with a digital "Plain Language Recommendation" (PLR) format vs. the original "Standard Language Version" (SLV). STUDY DESIGN AND SETTING: An allocation-concealed, blinded, controlled superiority trial and a qualitative study to understand participant preferences. An international on-line survey. 488 adults with some English proficiency. 67.8% of participants identified as female, 62.3% were from the Americas, 70.1% identified as white, 32.2% had a bachelor's degree as their highest completed education, and 42% said they were very comfortable reading health information. In collaboration with patient partners, advisors, and the Cochrane Consumer Network, we developed a plain language format of guideline recommendations (PLRs) to compare their effectiveness vs. the original standard language versions (SLVs) as published in the source guideline. We selected two recommendations about COVID-19 vaccine, similar in their content, to compare our versions, one from the World Health Organization (WHO) and one from Centers for Disease Control and Prevention (CDC). The primary outcome was understanding, measured as the proportion of correct responses to seven comprehension questions. Secondary outcomes were accessibility, usability, satisfaction, preference, and intended behavior, measured on a 1-7 scale. RESULTS: Participants randomized to the PLR group had a higher proportion of correct responses to the understanding questions for the WHO recommendation (mean difference [MD] of 19.8%, 95% confidence interval [CI] 14.7-24.9%; P < 0.001) but this difference was smaller and not statistically significant for the CDC recommendation (MD of 3.9%, 95% CI -0.7% to 8.3%; P = 0.096). However, regardless of the recommendation, participants found the PLRs more accessible, (MD of 1.2 on the seven-point scale, 95% CI 0.9-1.4%; P < 0.001) and more satisfying (MD of 1.2, 95% CI 0.9-1.4%; P < 0.001). They were also more likely to follow the recommendation if they had not already followed it (MD of 1.2, 95% CI 0.7-1.8%; P < 0.001) and share it with other people they know (MD of 1.9, 95% CI 0.5-1.2%; P < 0.001). There was no significant difference in the preference between the two formats (MD of -0.3, 95% CI -0.5% to 0.03%; P = 0.078). The qualitative interviews supported and contextualized these findings. CONCLUSION: Health information provided in a PLR format improved understanding, accessibility, usability, and satisfaction and thereby has the potential to shape public decision-making behavior.

Neurologic complications and sequellae of infectious diseases in Uganda and Kenya: Analysis of 288 cases from two rural hospitals.

OBJECTIVE: Many infections occurring in area of Sub-Saharan Africa are associated with more or less serious neurologic symptoms or complications. The aim of this study was to assess the incidence of selected infectious diseases in the equatorial part of Uganda and Kenya and to monitor potential neurological complications of these infections. METHODS: The study was performed for May - August 2008. Patients suffering from cerebral malaria, AIDS, meningitis, typhoid, tuberculosis (TB), syphilis, leprosy, and trypanosomiasis patients were enrolled. Besides of standard examination, lumbar puncture (LP) and cerebrospinal fluid (CSF) examination was performed, and the occurrence of neurological disorders and sequellae was recorded and assessed. RESULTS: Altogether 288 patients with neurological manifestation were enrolled. Malaria was the most prevalent disease in this study (102 cases, 35.42%), followed by typhoid (47 cases, 16.2%) and meningitis (38 cases, 13.2%). Leprosy and trypanosomiasis were only rarely detected (2.3% and 1.4%, respectively). CONCLUSION: In malaria and HIV hyper-endemic area of rural Uganda, cerebral malaria is the leading tropical neuroinfection. Also, meningitis is still frequent probably due to insufficient access to vaccination.

A multimethods randomized trial found that plain language versions improved parents' understanding of health recommendations.

OBJECTIVES: To assess the effectiveness of plain language compared with standard language versions of COVID-19 recommendations specific to child health. STUDY DESIGN AND SETTING: Pragmatic, allocation-concealed, blinded, superiority randomized controlled trial with nested qualitative component. Trial was conducted online, internationally. Parents or legal guardians (≥18 years) of a child (<18 years) were eligible. Participants were randomized to receive a plain language recommendation (PLR) or standard (SLV) verison of a COVID-19 recommendation specific to child health. Primary outcome was understanding. Secondary outcomes included: preference, accessibility, usability, satisfaction, and intended behavior. Interviews explored perceptions and preferences for each format. RESULTS: Between July and August 2022, 295 parents were randomized; 241 (81.7%) completed the study (intervention n = 121, control n = 120). Mean understanding scores were significantly different between groups (PLR 3.96 [standard deviation (SD) 2.02], SLV 3.33 [SD 1.88], P = 0.014). Overall participants preferred the PLR version: mean rating 5.05/7.00 (95% CI 4.81, 5.29). Interviews (n = 12 parents) highlighted their preference for the PLR and provided insight on elements to enhance future knowledge mobilization of health recommendations. CONCLUSION: Compared to SLVs, parents preferred PLRs and better understood the recommendation. Guideline developers should strive to use plain language to increase understanding, uptake, and implementation of evidence by the public.

Integration of migrant and refugee data in health information systems in Europe: advancing evidence, policy and practice.

Coverage of migrant and refugee data is incomplete and of insufficient quality in European health information systems. This is not because we lack the knowledge or technology. Rather, it is due to various political factors at local, national and European levels, which hinder the implementation of existing knowledge and guidelines. This reflects the low political priority given to the topic, and also complex governance challenges associated with migration and displacement. We review recent evidence, guidelines, and policies to propose four approaches that will advance science, policy, and practice. First, we call for strategies that ensure that data is collected, analyzed and disseminated systematically. Second, we propose methods to safeguard privacy while combining data from multiple sources. Third, we set out how to enable survey methods that take account of the groups' diversity. Fourth, we emphasize the need to engage migrants and refugees in decisions about their own health data. Based on these approaches, we propose a change management approach that narrows the gap between knowledge and action to create healthcare policies and practices that are truly inclusive of migrants and refugees. We thereby offer an agenda that will better serve public health needs, including those of migrants and refugees and advance equity in European health systems. Funding: No specific funding received.

Knowledge mobilization activities to support decision-making by youth, parents, and adults using a systematic and living map of evidence and recommendations on COVID-19: protocol for three randomized controlled trials and qualitative user-experience studies.

INTRODUCTION: The COVID-19 pandemic underlined that guidelines and recommendations must be made more accessible and more understandable to the general public to improve health outcomes. The objective of this study is to evaluate, quantify, and compare the public's understanding, usability, satisfaction, intention to implement, and preference for different ways of presenting COVID-19 health recommendations derived from the COVID-19 Living Map of Recommendations and Gateway to Contextualization (RecMap). METHODS AND ANALYSIS: This is a protocol for a multi-method study. Through an online survey, we will conduct pragmatic allocation-concealed, blinded superiority randomized controlled trials (RCTs) in three populations to test alternative formats of presenting health recommendations: adults, parents, and youth, with at least 240 participants in each population. Prior to initiating the RCT, our interventions will have been refined with relevant stakeholder input. The intervention arm will receive a plain language recommendation (PLR) format while the control arm will receive the corresponding original recommendation format as originally published by the guideline organizations (standard language version). Our primary outcome is understanding, and our secondary outcomes are accessibility and usability, satisfaction, intended behavior, and preference for the recommendation formats. Each population's results will be analyzed separately. However, we are planning a meta-analysis of the results across populations. At the end of each survey, participants will be invited to participate in an optional one-on-one, virtual semi-structured interview to explore their user experience. All interviews will be transcribed and analyzed using the principles of thematic analysis and a hybrid inductive and deductive approach. ETHICS AND DISSEMINATION: Through Clinical Trials Ontario, the Hamilton Integrated Research Ethics Board has reviewed and approved this protocol (Project ID: 3856). The University of Alberta has approved the parent portion of the trial (Project ID:00114894). Findings from this study will be disseminated through open-access publications in peer-reviewed journals and using social media. TRIAL REGISTRATION: Clinicaltrials.gov NCT05358990 . Registered on May 3, 2022.

An evaluation of the COVID-19 recommendation map identified diverging clinical and public health guidance.

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.

What mental health experts in Slovakia are learning from COVID-19 pandemic?

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.