Management of ibrutinib treatment in patients with B-cell malignancies: clinical practice in Portugal and multidisciplinary recommendations.

OBJECTIVES: Ibrutinib, a potent inhibitor of the Bruton tyrosine kinase, has revolutionized the treatment of many B-cell malignancies. Ibrutinib has an established favorable toxicity profile with up to 8 years of experience in clinical trials; however, despite ibrutinib's favorable toxicity profile, dose reductions and treatment discontinuations are becoming more evident in clinical practice, particularly in the setting of specific clinical contexts and patient characteristics. This manuscript is set to provide practical recommendations on the management of patients treated with this agent in daily practice. METHODS: A group of multidisciplinary experts from Portugal met to discuss and highlight practical recommendations, supported on both literature and clinical insights, for the management of the treatment with ibrutinib. RESULTS/DISCUSSION: Handling of both toxicities and drug-drug interactions during ibrutinib treatment poses several challenges to healthcare providers and can benefit from a multidisciplinary approach. The involvement of specialties, such as cardiology, infectiology and pharmacology, can bring an added value to patient care, not only in anticipating/managing safety issues and dose adjustments but also in enhancing adherence to treatment, ultimately improving the risk/benefit balance. CONCLUSION: By involving a multidisciplinary group of experts, this work provides a set of key recommendations to optimize care and outcomes for ibrutinib-treated patients. Despite not being a fully comprehensive review on the topic, it is intended as a framework to hematologists and other healthcare professionals who manage these patients in their daily clinical practice.

Improved Morphine-Loaded Hydrogels for Wound-Related Pain Relief.

The use of morphine applied topically to painful wounds has potential advantages, such as dose reduction, fewer side effects and compound formulations, have been proposed for this purpose. Given the potential high impact of drug product quality on a patient's health, the aim of the present study was to develop two stable sterile hydrogels containing morphine hydrochloride, intended for topical application on painful wounds. Two carboxymethylcellulose sodium-based hydrogels were prepared containing 0.125% w/w (F1-MH semi-solid formulation) and 1.0% w/w (F2-MH fluid formulation) morphine hydrochloride (MH), respectively. Studies included a risk assessment approach for definition of the quality target product profile (QTPP) and assessment of critical quality attributes (CQA) of the hydrogels to support product quality and safety. Safe, odourless, yellowish, translucent and homogeneous gels were obtained, with suitable microbiological and pharmaceutical characteristics. The active substance concentration was adapted according to the characteristics of the dose-metering device. Release profiles were investigated using Franz diffusion cells, and characterised by different kinetic models. Increasing gel viscosity prolonged drug release, with rates of 17.9 ± 2.2 µg·cm-2·h-1 (F1-MH) and 258.0 ± 30.4 µg·cm-2·h-1 (F2-MH), allowing for the reduction of the number of applications and improving patient compliance. The gels proved to be stable for up to 60 days at room temperature. The semi-solid and fluid MH-containing hydrogel formulations are safe, stable and suitable for use in hospital settings, which is rather important for wound-related pain management in cancer palliative care or burn patients.

Betamethasone dipropionate compounding for cutaneous T-cell lymphoma management.

BACKGROUND: Primary cutaneous lymphomas (extranodular non-Hodgkin lymphomas) are rare (incidence 1:100 000). Mycosis fungoides is the most common cutaneous T-cell lymphoma (CTCL) subtype. Treatment options are based on the diagnosis and the stage of the disease. Skin-directed therapies are useful for the initial stages and include topical treatments such as corticosteroids. Betamethasone dipropionate (BD) is a synthetic glucocorticoid with high anti-inflammatory activity, potency and immunosuppressant effects. It is used for topical treatment of CTCL within the following dosage 0.025-0.1% (w/w). In the Portuguese market only one topical cream contains BD at 0.05% (w/w). OBJECTIVES: To develop a new and stable emulsion containing 0.1% of BD. METHODS: To accomplish this aim, development, stability, in vitro release and clinical studies of a new topical water-in-oil emulsion containing BD 0.1% w/w were assessed for the topical treatment of CTCL. RESULTS: The three batches prepared were physically, chemically and microbiologically stable over a period of 90 days. 40% of BD was released over 6 hours and evaluation of skin lesions showed a favourable clinical effect (less itching, less infiltration, fewer patches and a reduced area of plaque). CONCLUSIONS: The clinical results show the effective cutaneous improvement of skin barrier conditions during the study.

In-hospital mortality risk prediction after percutaneous coronary interventions: Validating and updating the Toronto score in Brazil.

OBJECTIVES: We aimed to assess the accuracy of the simple, contemporary and well-designed Toronto PCI mortality risk score in ICP-BR registry, the first Brazilian PCI multicenter registry with follow-up information. BACKGROUND: Estimating percutaneous coronary intervention (PCI) mortality risk by a clinical prediction model is imperative to help physicians, patients and family members make informed clinical decisions and optimize participation in the consent process, reducing anxiety and improving quality of care. At a healthcare system level, risk prediction scores are essential to measure and benchmark performance. METHODS: Between 2009 and 2013, a cohort of 4,806 patients from the ICP-BR registry, treated with PCI in eight tertiary referral medical centers, was included in the analysis. This population was compared to 10,694 patients of the derivation dataset from the Toronto study. To assess predictive performance, an update of the model was performed by three different methods, which were compared by discrimination, calculating the area under the receiver operating characteristic curve (AUC), and by calibration, assessed through Hosmer-Lemeshow (H-L) test and graphical analysis. RESULTS: Death occurred in 2.6% of patients in the ICP-BR registry and in 1.3% in the Toronto cohort. The median age was 64 and 63 years, 23.8 and 32.8% were female, 28.6 and 32.3% were diabetics, respectively. Through recalibration of intercept and slope (AUC = 0.8790; H-L P value = 0.3132), we achieved a well-calibrated and well-discriminative model. CONCLUSIONS: After updating to our dataset, we demonstrated that the Toronto PCI in-hospital mortality risk score performed well in Brazilian hospitals.

Leishmanioses na infância: aspectos epidemiológicos, clínicos e terapêuticos (Estado do Ceará - Brasil) / Leishmaniasis in childhood: epidemiological, clinical and therapeutic aspects (state of Ceará - Brasil)

Säo estudados aspectos epidemiológicos, clínicos e terapêuticos relacionados com a leishmaniose tegumentar americana e leismaniose visceral americana na infância. Destacamos os aspectos referentes ao ciclo de transmissäo da leishmanioses e a provável adaptaçäo dos parasitos ao ambiente peridomiciliar, com relaçäo ao acometimento de crianças menores de cinco anos pela Leishmania brasiliensis, bem como a raridade das formas clínicas que afetam mucosas na leishmaniose tegumentar americana no Estado do ceará - Brasil

Pápulas piezogênicas dolorosas dos pés / Painful piezogenic pedal papules

Os autores apresentam dois casos de pápulas piezogênicas dolorosas dos pés e revisam a literatura abordando aspectos clínicos, etiopatolgênicos e terapêuticos. Casos semelhantes em nosso país até onde sabemos näo foram ainda relatados

Tinea nigra: a propósito de cinco casos / Tinea nigra: report a five cases

Säo apresentados cinco casos de tinea nigra. A pesquisa micológica revelou Phaeoannelomyces werneckii como agente etiológico. Revisa-se a literatura abordando aspectos históricos, epidemiológicos, clínicos e terapêuticos

Cetoconazol no tratamento da pitiríase versicolor em dose única / Treatment of pityriasis versicolor with ketoconazole in single dose

Cinqüenta pacientes com pitiríase versicolor foram tratados com dose única de 400 mg de cetoconazol e avaliados um mês depois. Todos os pacientes responderam ao tratamento; 43 (86%) estavam completamente curados quando examinados com a luz de Wood e exame microscópico com hidróxido de potássio a 20% e sete (14%) apresentaram melhora acentuada do quadro. A droga foi bem tolerada, tendo sido observada como efeito adverso apenas náusea leve em três pacientes. Estes resultados indicam que 400 mg de cetoconazol em dose única säo seguros e efetivos no tratamento da pitiríase versicolor

Piedra branca: revisäo de literatura a respeito de três casos / White piedra: review of the literatura report of three cases

Os autores apresentam três casos de piedra branca comprometendo o couro cabeludo de crianças em idade pré-escolar. O Trichosporon beigelii foi caracterizado por exames micológicos. Revisa-se a literatura abordando aspectos clínicos, micológicos e terapêuticos

Esporotricose cutânea fixa: a propósito de um caso com regressão espontânea / Fixed cutaneous sporotrichosis with spontaneous cure: presentation of a case

É apresentado um caso de esporortricose cutânea fixa da face, em um menino de 10 anos de idade, que evoluiu para cura espontânea. Revisa-se a literatura, demonstrando a raridade do caso

Micoses profundas diagnosticadas no Serviço de Dermatologia do Hospital Universitário Jaffrée e Guinle (HUGG) no período de 1978 a 1989 / Deep mycoses diagnosed in the Serviço de Dermatologia do Hospital Universitário Jaffrée e Guinle (HUGG) in the period of 1979 to 1989

Os autores estudaram os casos de micoses profundas diagnosticados no Serviço d e Dermatologia do HUGG da Universidade do Rio de Janeiro (UNI-RIO) no período de janeiro de 1978 a dezembro de 1989. Foram observados 30 casos no total e, em ordêm de freqüência: esporotricose (17 casos), paracoccidioidomicose (10 casos), cromomicose (dois casos) e doença de Jorge Lôbo (um caso)

Tinha negra palmar bilateral / Bilateral tinea nigra palmaris

Relata-se um caso de tinha negra palmar bilateral, em paciente de nove anos de idade, sendo este o primeiro caso de tinha negra documentado em paciente procedente do Ceará

Piloleiomioma múltiplo / Multiple piloleiomyoma

Os autores relatam um caso de piloleiomioma múltiplo e fazem revisäo da literatura abordando aspectos clínicos, histológicos e terapêuticos. O motivo da apresentaçäo é a raridade do caso

Micoses profundas no Ceará: estudo dos casos diagnosticados no Hospital das Clínicas da Universidade Federal do Ceará (1983-1988) / Deep mycoses in the state of Ceará, Brazil: study of the cases diagnosed in the Hospital das Clínicas da Universidade Federal do Ceará (1983-1988)

Os autores estudaram os casos de micoses profundas diagnosticados no serviço de Dermatologia do Hospital das Clínicas da Universidade Federal do Ceará (HC-UFC) no período de janeiro de 1983 a dezembro de 1988. Foram encontrados quatro casos de paracoccidioidomicose, dois de cromomicose, um de histoplasmose, um de zigomicose e um micetoma

Dermatopitoses: principais agentes etiológicos em Fortaleza / Dermatophytosis: main etiologic agents identified in Fortaleza, Brazil

Foram estudadas 665 culturas positivas para dermatófitos no período de janeiro de 1980 a agosto de 1987, que mostraram ser cinco as espécies impliccadas. Trychophyton tonsurans (43,8%), Trychophyton rubrum (39,2%). Trychophyton mentagrophytes (13,8%). Microsporum canis (2,4%). Epidermophton floccosum (0,8%)