Tapinarof for the treatment of psoriasis.

Although topical drugs are the mainstay of treatment for patients with mild-to-moderate psoriasis, the developments observed in this field in the last two decades have been limited. The most commonly used drugs are still vitamin D analogues and corticosteroids, both with several limitations. The aryl hydrocarbon receptor (AhR) plays a role in the pathogenesis of psoriasis, and tapinarof, a novel, first-in-class, small molecule topical therapeutic AhR-modulating agent has been recently approved by the FDA for the topical treatment of plaque psoriasis in adults. Two large, 12-week, phase III trials, PSOARING 1 and 2, showed that 35.4%-40.2% of patients in the tapinarof 1% cream arm achieved the primary endpoint (Physician's Global Assessment [PGA] score of 0 or 1 and a decrease of ≥2-5 points at week 12) compared with 6.0%-6.3% for vehicle arm, respectively. The most common adverse effects were folliculitis, contact dermatitis, headache and pruritus. In the open label, 40-week, extension trial, PSOARING 3, the efficacy and safety results were similar, with 40.9% of patients achieving a PGA = 0 at least one time during the trial and 58.2% of patients with PGA≥2 achieved PGA = 0/1 at least once during the trial, without tachyphylaxis. There were no new safety signals, with most frequent adverse events being folliculitis, contact dermatitis, and upper respiratory tract infection. Tapinarof 1% cream has shown to be effective and to have a favorable safety profile in the treatment of psoriatic patients, representing an alternative to the current therapeutic options, increasing our armamentarium in the topical treatment of psoriasis.

Bimekizumab for psoriasis.

Psoriasis is a chronic, immune-mediated, inflammatory skin disease, affecting 1% to 3% of the population in Western countries. Due to advances in the understanding of psoriasis pathogenesis, in particular, the role of the interleukin-23 (IL-23)/T-helper 17 (Th17) immune axis, highly effective, targeted biologic therapies have been developed, shifting the psoriasis treatment paradigm. However, some patients do not respond or lose response to these novel therapies. Bimekizumab is a first-in-class humanized monoclonal immunoglobulin G1 (IgG1) antibody that potently and selectively inhibits both IL-17A and IL-17F, functioning as a dual inhibitor. All bimekizumab studies have shown high efficacy in psoriasis patients. Its onset of response was rapid and sustained for periods up to 60 weeks. In active-comparator trials to date, bimekizumab was superior to adalimumab (BE SURE), ustekinumab (BE VIVID) and secukinumab (BE RADIANT). It has demonstrated a consistent safety profile and high tolerability. The most common adverse events were largely restricted to mucosal candidiasis. Dual inhibition of IL-17A and IL-17F with bimekizumab showed to be a highly effective treatment for psoriasis, and the product is already approved for treatment of moderate to severe plaque psoriasis in Europe, Canada and Japan.

[Non-Necrotizing Acute Dermo-Hypodermal Infections: Erysipela and Infectious Cellulitis]. / Dermo-Hipodermites Bacterianas Agudas Não Necrotizantes: Erisipela e Celulite Infeciosa.

Non-necrotizing acute dermo-hypodermal infections are infectious processes that include erysipela and infectious cellulitis, and are mainly caused by group A ß-haemolytic streptococcus. The lower limbs are affected in more than 80% of cases and the risk factors are disruption of cutaneous barrier, lymphoedema and obesity. Diagnosis is clinical and in a typical setting we observe an acute inflammatory plaque with fever, lymphangitis, adenopathy and leucocytosis. Bacteriology is usually not helpful because of low sensitivity or delayed positivity. In case of atypical presentations, erysipela must be distinguished from necrotizing fasciitis and acute vein thrombosis. Flucloxacillin and cefradine remain the first line of treatment. Recurrence is the main complication, so correct treatment of the risk factors is crucial.

As dermo-hipodermites bacterianas agudas não necrotizantes são processos infeciosos que incluem a erisipela e a celulite infeciosa, e são geralmente causadas por estreptococos ß­hemolíticos do grupo A. Em mais de 80% dos casos situam-se nos membros inferiores e são fatores predisponentes a existência de solução de continuidade na pele, o linfedema crónico e a obesidade. O seu diagnóstico é essencialmente clínico e o quadro típico baseia-se na presença de placa inflamatória associada a febre, linfangite, adenopatia e leucocitose. Os exames bacteriológicos têm baixa sensibilidade ou positividade tardia. Nos casos atípicos é importante o diagnóstico diferencial com a fasceíte necrotizante e a trombose venosa profunda. A flucloxacilina ou a cefradina são os fármacos de primeira linha. A recidiva constitui a complicação mais frequente, sendo fundamental o correto tratamento dos fatores de risco.

Design and Implementation of Postgraduate Programs in Health in a Resource-Limited Setting in Mozambique (The Lúrio University).

PURPOSE: To describe the strategies used to design and implement three postgraduate programs at Lúrio University (UniLúrio), a resource-limited setting, in northern Mozambique. METHODS: We conducted a longitudinal, descriptive case study from 2011 to 2018 in two phases: 1) needs assessment (2011-2012), 2) implementation strategies (2013-2018), taking into account innovations whenever necessary. RESULTS: Several obstacles and barriers to the establishment of postgraduate programs were identified. These included a lack of a core curricula aimed at postgraduate programs, shortage of human resources for teaching and mentorship, limited teaching and research infrastructures, limited financial resources, and lack of administrative capacity. With the support of the Medical Education Partnership Initiative (MEPI), three Master degree programs were designed and implemented. During the period of 2013-2018, UniLúrio enrolled 202 students, distributed as follows: Master degree in Tropical Medicine and Global Health (55), Master degree in Health Professional Education (99), and Master degree in Nutrition and Food Security (48). Of those, 152 (75.2%) obtained a Postgraduate Diploma as they did not present a master dissertation, 89 (44.0%) obtained their Master degree, 30 (14.8%) dropped out, and 20 (9.9%) are awaiting decision. UniLurio's staff trained a Master's degree or a Postgraduate Diploma in 34 (16.8%) and 15 (7.4%), respectively. Our strategies allowed us to improve research capacity building, and set the basis for long-term sustainability by allowing for the establishment of other postgraduate programs, and offered UniLurio a strong role in its internationalization. CONCLUSION: By sharing multiple resources, long-lasting partnerships were established with multiple institutions, and competency-based training and postgraduate studies management were developed. Research and eLearning were leveraged, retention and faculty development was enhanced, and some inequalities within the country were reduced. These strategies and innovations can be applied to other resource-limited settings, allowing the scaleup of health professional's training and research capacity building.

Diagnosis, Screening and Treatment of Patients with Palmoplantar Pustulosis (PPP): A Review of Current Practices and Recommendations.

Palmoplantar pustulosis (PPP) is a rare, chronic, recurrent inflammatory disease that affects the palms and/or the soles with sterile, erupting pustules, which are debilitating and usually resistant to treatment. It has genetic, histopathologic and clinical features that are not present in psoriasis; thus, it can be classified as a variant of psoriasis or as a separate entity. Smoking and upper respiratory infections have been suggested as main triggers of PPP. PPP is a challenging disease to manage, and the treatment approach involves both topical and systemic therapies, as well as phototherapy and targeted molecules. No gold standard therapy has yet been identified, and none of the treatments are curative. In patients with mild disease, control may be achieved with on-demand occlusion of topical agents. In patients with moderate-to-severe PPP, phototherapy or a classical systemic agent (acitretin being the best treatment option, especially in combination with PUVA) may be effective. Refractory patients or those with contraindications to use these therapies may be good candidates for apremilast or biologic therapy, particularly anti-IL-17A and anti-IL-23 agents. Recent PPP trials are focusing on blockage of IL-36 or IL-1 pathways, which play an important role in innate immunity. Indeed, IL-36 isoforms have been strongly implicated in the pathogenesis of psoriasis. Therefore, blockage of the IL-36 pathway has become a new treatment target in PPP, and three studies are currently evaluating the use of monoclonal antibodies that block the IL-36 receptor in PPP: ANB019 and spesolimab (BI 655130). In this review, we explore the diagnosis, screening and treatment of patients with PPP.

JAK/STAT inhibitors for the treatment of atopic dermatitis.

Introduction: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Lesional skin of AD contains elevated levels of Th2, Th17, Th22 and Th1-citokines. With a growing movement toward use of targeted therapies, parallel to psoriasis, JAK inhibitors are an important focus of therapeutic research for AD.Methods: We review current evidence on the efficacy and safety of oral and topical JAK inhibitors for the treatment of AD.Results: Several JAK inhibitors are in phase II and III clinical trials as oral therapies for moderate-to-severe AD or as topical treatments for mild-to-moderate AD. Results thus far are encouraging, with the majority of the patients achieving the primary outcome of their trial as well as a favorable safety profile.Discussion: JAK inhibitors will most certainly be the first oral targeted option when topical therapy fails. With good oral bioavailability and lack of immunogenicity, they address some of the limitations of biologics. Yet to be defined is whether selective JAK 1 inhibitors or nonselective JAK inhibitors will provide the best equilibrium of efficacy versus side effects. Less clear is the position in the therapeutic ladder for topical JAK inhibitors; although, an unmeet need exists in the topical treatment of AD.

The rise of medical training in Portuguese speaking African countries.

BACKGROUND: Medical training has shown to be strategic for strengthening health systems, especially in those countries identified to have critical shortage of human resources for health. In the past few years, several studies have been conducted to characterize and identify major challenges faced by medical schools worldwide, and particularly in Africa. Nevertheless, none has previously addressed medical training issues in Portuguese Speaking African Countries (PSAC). The aim of this study was to establish baseline knowledge of the PSAC's medical schools in terms of creation and ownership, programmes offered, applicants and registered students, barriers to increased intake of students, teaching workforce and available resources. METHODS: A quantitative, observational, multicentric, cross-sectional study of all medical schools active in 2012 in the PSAC. An adapted version of the questionnaires developed by Chen et al. (2012) was sent to all medical schools electronically. Data were analyzed using descriptive statistics. RESULTS: A total of nine medical schools answered the questionnaire (three from Angola, two from Guinea Bissau and four from Mozambique). Since 2006 an effort has been made to increase the number of medical trainees. Besides the medical degree offered by all schools, some offered other undergraduate and postgraduate training programmes. The number of applicants to medical schools largely outnumbers the available vacancies in all countries but insufficient infrastructures and lack of teaching personnel are important constraints to increase vacancies. The teaching personnel are mainly trained abroad, employed part-time by the medical school and do not have a PhD qualification. CONCLUSION: Governments in the PSAC have significantly invested in training to address medical shortages. However, medical schools are still struggling to give an adequate and effective response. Developing a local postgraduate training capacity for doctors might be an important strategy to help retain medical doctors in the home country and develop local faculty capacity.

Treatment, Services and Follow-up for Victims of Family Violence in Health Clinics in Maputo, Mozambique.

BACKGROUND: Family violence (FV) is a global health problem that not only impacts the victim, but the family unit, local community and society at large. OBJECTIVE: To quantitatively and qualitatively evaluate the treatment and follow up provided to victims of violence amongst immediate and extended family units who presented to three health centers in Mozambique for care following violence. METHODS: We conducted a verbally-administered survey to self-disclosed victims of FV who presented to one of three health units, each at a different level of service, in Mozambique for treatment of their injuries. Data were entered into SPSS (SPSS, version 13.0) and analyzed for frequencies. Qualitative short answer data were transcribed during the interview, coded and analyzed prior to translation by the principal investigator. RESULTS: One thousand two hundred and six assault victims presented for care during the eight-week study period, of which 216 disclosed the relationship of the assailant, including 92 who were victims of FV. Almost all patients (90%) waited less than one hour to be seen, with most patients (67%) waiting less than 30 minutes. Most patients did not require laboratory or radiographic diagnostics at the primary (70%) and secondary (93%) health facilities, while 44% of patients received a radiograph at the tertiary care center. Among all three hospitals, only 10% were transferred to a higher level of care, 14% were not given any form of follow up or referral information, while 13% required a specialist evaluation. No victims were referred for psychological follow-up or support. Qualitative data revealed that some patients did not disclose violence as the etiology, because they believed the physician was unable to address or treat the violence-related issues and/or had limited time to discuss. CONCLUSION: Healthcare services for treating the physical injuries of victims of FV were timely and rarely required advanced levels of medical care, but there were no psychological services or follow-up referrals for violence victims. The healthcare environment at all three surveyed health centers in Mozambique does not encourage disclosure or self-report of FV. Policies and strategies need to be implemented to encourage patient disclosure of FV and provide more health system-initiated victim resources.

Antecedentes favoráveis ao desenvolvimento de habilidades criativas em reconhecidos profissionais da música / Antecedents that contribute to the development of creativity in musicians

Investiga os antecedentes que contribuíram para o desenvolvimento de habilidades criativas de conceituados profisionais de música. A amostra é composta de 14 Ss, reconhecidos profissionais de vários gêneros de música, residentes em Brasília. Realiza entrevistas semi-estruturadas envolvendo questöes relativas a antecedentes sociais, familiares, escolares, profissionais e de saúde. Os relatos sugerem que a família desempenha papel preponderante na estimulaçäo e desenvolvimento das habilidades musicais dos Ss, ao passo que as influências escolares säo pouco relevantes. Observa, também, as diversas barreiras que afetam o início da carreira musical e os problemas sérios de saúde que interferem no desenvolvimento das habilidades musicais, ainda que vivenciados apenas por alguns dos Ss

Antecedentes favoraveis ao desenvolvimento de habilidades criativas em reconhecidos profissionais da musica

Dentre as questoes de interesse da Psicologia da Criatividade que vem sendo objeto de investigacao nas duas ultimas decadas, destaca-se o exame dos processos pelos quais os individuos que alcancam um grau de excelencia em sua areas, desenvolveram suas habilidades criativas. A hipotese e a de que tais informacoes poderao oferecer subsidios para a implementacao de condicoes estimuladoras do pleno potencial criativo dos individuos. Foi objetivo desta pesquisa investigar os antecedentes que contribuiram para o desenvolvimento de habilidades criativas de conceituados profissionais de musica. A amostra foi composta por 14 (quatorze) sujeitos, reconhecidos profissionais de varios generos de musica, residentes em Brasilia. Foram realizadas entrevistas semi-estruturadas envolvendo questoes relativas a antecedentes sociais, familiares, escolares, profissionais e de saude. Os relatos sugerem que a familia desempenhou papel preponderante na estimulacao e desenvolvimento das habilidades musicais destes sujeitos, ao passo que as influencias escolares foram pouco relevantes. Tambem foi salientado que o inicio da vida profissional diversas foram as barreiras que afetaram a carreira musical. Problemas serios de saude, embora ocorridos com apenas alguns dos sujeitos, interferiram no desenvolvimento de tais habilidades.

Recasamento e recomposiçäo familiar: questöes metodológicas, de linguagem e das teorias / Remarriage and family reconstitution: questions regarding methodology, linguage and theorien

Neste trabalho apresentamos uma reflexäo acerca das mudanças na concepçäo legal de casamento e filiaçäo, decorrentes da nova Constituiçäo Brasileira. Em seguida avaliamos os estudos sobre recasamento e a recomposiçäo familiar, realizados nos últimos 10 anos. Abordamos as principais questöes metodológicas decorrentes deste novo objeto de estudo e a problemática em relaçäo à nomenclatura utilizada pelos pesquisadores. Analisamos também a linguagem usada entre as pessoas pertencentes a essas novas redes de relaçöes. Refletimos ainda sobre a contribuiçäo das principais abordagens teóricas acerca do recasamento e da recomposiçäo familiar

Recasamento e Recomposicao familiar: questoes metodologicas, de linguagem e das teorias

Neste trabalho apresentamos uma reflexao acerca das mudancas na concepcao legal de casamento e filiacao, decorrentes da nova Constituicao Brasileira. Em seguida avaliamos os estudos sobre recasamento e a recomposicao familiar, realizados nos ultimos 10 anos. Abordamos as principais questoes metodologicas decorrentes deste novo objeto de estudo e a problematica em relacao a nomenclatura utilizada pelos pesquisadores. Analisamos tambem a linguagem usada entre as pessoas pertencentes a essas novas redes de relacoes. Refletimos ainda sobre a contribuicao das principais abordagens teoricas acerca do recasamento e da recomposicao familiar.