Temocillin versus meropenem for the targeted treatment of bacteraemia due to third-generation cephalosporin-resistant Enterobacterales (ASTARTÉ): protocol for a randomised, pragmatic trial.

INTRODUCTION: Alternatives to carbapenems are needed in the treatment of third-generation cephalosporin-resistant Enterobacterales (3GCR-E). Temocillin is a suitable candidate, but comparative randomised studies are lacking. The objective is to investigate if temocillin is non-inferior to carbapenems in the targeted treatment of bacteraemia due to 3GCR-E. METHODS AND ANALYSIS: Multicentre, open-label, randomised, controlled, pragmatic phase 3 trial. Patients with bacteraemia due to 3GCR-E will be randomised to receive intravenously temocillin (2 g three times a day) or carbapenem (meropenem 1 g three times a day or ertapenem 1 g once daily). The primary endpoint will be clinical success 7-10 days after end of treatment with no recurrence or death at day 28. Adverse events will be collected; serum levels of temocillin will be investigated in a subset of patients. For a 10% non-inferiority margin, 334 patients will be included (167 in each study arm). For the primary analysis, the absolute difference with one-sided 95% CI in the proportion of patients reaching the primary endpoint will be compared in the modified intention-to-treat population. ETHICS AND DISSEMINATION: The study started after approval of the Spanish Regulatory Agency and the reference institutional review board. Data will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04478721.

Percepção de dermatologistas sobre a influência da psoríase na qualidade de vida dos pacientes / Percepción de los dermatólogos sobre el impacto de la psoriasis en la calidad de vida de los pacientes / Perception of dermatologists on the influence of psoriasis on quality of life of patients

Resumo: Objetivo: Conhecer como a psoríase interfere na qualidade de vida dos pacientes na percepção de dermatologistas e identificar estratégias para melhoria e reorganização da assistência. Métodos: Pesquisa exploratória e descritiva, realizada em hospital público do interior de São Paulo, no período de dezembro de 2017 a março de 2018, com seis dermatologistas. As entrevistas foram transcritas e analisadas utilizando-se a estratégia metodológica do Discurso do Sujeito Coletivo. Resultados: Psoríase é uma doença que inflige prejuízo à qualidade de vida por estar associada a transtornos psicossociais, estigma, vergonha e perda da autoestima. Reduzir lesões e sintomas, melhorar a aparência, disponibilizar medicamento eficaz e oferecer atendimento humanizado são aspectos fundamentais para melhoria da qualidade de vida destes pacientes. Conclusão: Para os profissionais dermatologistas, a psoríase é uma doença crônica, que interfere na qualidade de vida dos pacientes, em virtude do preconceito sentido, dos transtornos psicossociais e sentimentos negativos que afloram, bem como das dificuldades sociais enfrentadas.

Resumen: Objetivos: conocer cómo la psoriasis afecta la calidad de vida de los pacientes en la percepción de los dermatólogos e identificar estrategias para mejorarla y reorganizar la atención. Métodos: Investigación descriptiva y exploratoria realizada en un hospital público del interior de São Paulo, de diciembre de 2017 a marzo de 2018, con seis dermatólogos. Las entrevistas fueron transcritas y analizadas utilizando la estrategia metodológica del Discurso Colectivo del Sujeto. Resultados: En opinión de los participantes, la psoriasis es una enfermedad que daña la calidad de vida por estar asociada a trastornos psicosociales, estigma, vergüenza y pérdida de la autoestima. Reducir lesiones y síntomas, mejorar la apariencia, disponer de una medicación eficaz vinculada a la atención humanizada son fundamentales para mejorar la calidad de vida de estos pacientes. Conclusión: Se observó que, para los dermatólogos, la psoriasis es una enfermedad crónica que interfiere con la calidad de vida, debido al prejuicio sentido, los trastornos psicosociales y sentimientos negativos que surgen, así como las dificultades sociales que enfrentan los pacientes.

Abstract: Objective: to know how psoriasis affects the quality of life of patients in the perception of dermatologists and identify strategies for improving it and reorganizing care. Methods: Descriptive, exploratory study research conducted in a public hospital in the countryside of São Paulo, from December 2017 to March 2018, with six dermatologists. The interviews were transcribed and analyzed using the methodological strategy of the Collective Subject Discourse. Results: Psoriasis is a disease, which affects the quality of life because it is associated with psychosocial disorders, shame, stigma and loss of self-esteem. Reducing injuries and symptoms, improving appearance, having an effective medication coupled with humanized care are fundamental for improving the quality of life of these patients. Conclusion: It was observed that for dermatologists, psoriasis is a chronic disease that interferes with the quality of life, due to the prejudice felt by patients, the psychosocial disorders and negative feelings that arise, as well as the social difficulties faced, by them.

Childhood cancer in Latin America: from detection to palliative care and survivorship.

BACKGROUND: Treatment options for childhood cancer have improved substantially, although in many low- and middle-income countries survival is lagging behind. Integral childhood cancer care involves the whole spectrum from detection and diagnosis to palliative and survivorship care. METHODS: Based on a literature review and expert opinions, we summarized current practice and recommendations on the following aspects of childhood cancer in Latin America: diagnostic processes and time to diagnosis, stage at diagnosis, treatments and complications, survivorship programs and palliative care and end-of-life services. RESULTS: Latin America is a huge and heterogeneous continent. Identified barriers show similar problems between countries, both logistically (time and distance to centers, treatment interruptions) and financially (cost of care, cost of absence from work). Governmental actions in several countries improved the survival of children with cancer, but difficulties persist in timely diagnosis and providing adequate treatment to all childhood cancer patients in institutions with complete infrastructure. Treatment abandonment is still common, although the situation is improving. Cancer care in the region has mostly focused on acute treatment of the disease and has not adequately considered palliative and end-of-life care and monitoring of survivors. CONCLUSIONS: Decentralizing diagnostic activities and centralizing specialized treatment will remain necessary; measures to facilitate logistics and costs of transportation of the child and caretakers should be implemented. Twinning actions with specialized centers in high income countries for help in diagnosis, treatment and education of professionals and family members have been shown to work. Palliative and end-of-life care as well as childhood cancer survivorship plans are needed.

Quality of life of patients living with psoriasis: a qualitative study.

BACKGROUND: Psoriasis is a multifactorial inflammatory disease prevalent in dermatology. We aimed to understand the perceptions of patients living with psoriasis in relation to their quality of life and to identify aspects to improve it. METHODS: This is qualitative research carried out in a dermatology outpatient clinic of the São Paulo State University (UNESP) medical school, Botucatu, Brazil, with 81 psoriasis patients. The interviews were transcribed and analysed using the Discourse of the Collective Subject method (DCS). RESULTS: Quality of life was linked to well-being, happiness, leisure, good food and financial stability. However, disease symptoms, social and clothing restrictions, impairment of professional activities and the absence of a cure, negatively influenced their perceptions. Suggestions for improvements included an increase of public awareness, stress reduction, disease acceptance and multidisciplinary care. CONCLUSION: The meanings of quality of life revealed by the participants are subjective, multidimensional, linked to moments experienced by them and to the health-disease process. Public health policies promoting reduction in social stigma and stress as well as multidisciplinary approaches towards care can contribute to improvements of QoL in psoriasis.

Strategies discussed at the XIIth international conference on Kangaroo mother care for implementation on a countrywide scale.

AIM: Building strategies for the country-level dissemination of Kangaroo mother care (KMC) to reduce the mortality rate in preterm and low birth weight babies and improve quality of life. KMC is an evidence-based healthcare method for these infants. However, KMC implementation at the global level remains low. METHODS: The international network in Kangaroo mother brought 172 KMC professionals from 33 countries together for a 2-day workshop held in conjunction with the XIIth International KMC Conference in Bogota, Colombia, in November 2018. Participants worked in clusters to formulate strategies for country-level dissemination and scale-up according to seven pre-established objectives. RESULTS: The minimum set of indicators for KMC scale-up proposed by the internationally diverse groups is presented. The strategies for KMC integration and implementation at the country level, as well as the approaches for convincing healthcare providers of the safety of KMC transportation, are also described. Finally, the main aspects concerning KMC follow-up and KMC for term infants are presented. CONCLUSION: In this collaborative meeting, participants from low-, middle- and high-income countries combined their knowledge and experience to identify the best strategies to implement KMC at a countrywide scale.

Could kDNA-PCR in Peripheral Blood Replace the Examination of Bone Marrow for the Diagnosis of Visceral Leishmaniasis?

The aim of this study was to evaluate whether the molecular (kDNA-PCR) and parasitological diagnosis in peripheral blood (PB) could replace the invasive and painful bone marrow collection (BM) in the diagnosis of visceral leishmaniasis (VL). PB from suspected VL patients was evaluated by parasitological and molecular techniques using as the gold standard (GS) a combination of clinical, epidemiological, and immunochromatographic test (PB-rK39) results and parasitological examination of BM. Based on the GS, 38 samples from 32 patients were grouped: Group 1, 20 samples of VL cases, and Group 2, 18 samples of non-VL cases. In order to evaluate the parasitological and molecular techniques in PB, the samples were examined. From Group 1, PB kDNA-PCR was positive in 20 samples and in 19 of 20 in BM kDNA-PCR examination. However, the parasitological examination of buffy coat was insensitive, being able to detect only 4 cases from Group 1. All samples from Group 2 were negative. We concluded that, for the diagnosis of visceral leishmaniasis, the parasitological examination of peripheral blood was not useful; however, molecular diagnosis by kDNA-PCR, performed in peripheral blood, could be useful to replace the parasitological examination of bone marrow.

Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells.

Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells.

Sacroileitis unilateral como manifestación inicial de endocarditis infecciosa / Unilateral sacroileitis as the initial manifestation of infective endocarditis

La sacroileítis unilateral como manifestación inicial de endocarditis bacteriana es una forma inusual de presentación. Frecuentementelos síntomas reumatológicos anteceden en días o incluso en meses a los síntomas clásicos de la endocarditis, simulando enfermedades reumatológicas o infecciosas, generando un retraso en el diagnóstico. Los agentes etiológicos que suelen asociarsea estas formas de presentación son Staphyloccus aureus y Streptococcus viridans. Es importante considerar estas formas de presentación para arribar a un diagnóstico temprano y así intentar disminuir el riesgo de complicaciones y la mortalidad...

Unilateral sacroileitis as the initial manifestation of bacterial endocarditis is an unusual form of presentation. Frequently the rheumatologic symptoms appear days or even months before the classic symptoms of endocarditis, simulating rheumatologic or infectiousdiseases and delaying the diagnosis. The etiologic agents most frequently associated with these presentations are Staphylococcus aureus and Streptococcus viridans. It is important to be aware of these forms of presentation in order to arrive to an early diagnosis, prevent the risk of complications, and reduce mortality...

InGaP 670-nm laser therapy combined with a hydroalcoholic extract of Solidago chilensis Meyen in burn injuries.

Therapies that accelerate the healing of burn injuries, improving the quality of life of the patient and reducing the cost of treatment are important. This study evaluated the effects of InGaP 670-nm laser therapy combined with a hydroalcoholic extract of Solidago chilensis leaves on burn wound healing in rats. Seventy-two rats were divided randomly into four groups: control untreated (C), treated with InGaP 670-nm laser with power density of 0.41 W/cm(2) and energy density of 4.93 J/cm(2) (L), treated with S. chilensis extract (S) and treated with S. chilensis extract and laser (LS). Second-degree burns were produced on the back of the animals with metal plate. Wound samples were collected on days 7, 14 and 21 of treatment for structural analysis, morphometry and Western blotting to quantify the expression of transforming growth factor beta 1 (TGF-ß1) and vascular endothelial growth factor (VEGF). The results showed that InGaP laser irradiation at 670 nm alone and combined with extract of S. chilensis promoted significant tissue repair responses in this experimental model, increasing the number of fibroblasts, collagen fibres and newly formed blood vessels throughout the experimental period and decreasing the number of granulocytes in burn wounds of second degree in all treated groups. Exclusive treatment of burn wounds with the hydroalcoholic extract of S. chilensis provided similar quantitative results to those seen in the untreated group throughout the experimental period. Therefore, it was observed in the L and LS groups different responses in the expression of TGF-ß1 and VEGF. The application of 670-nm laser alone or combined with the extract of S. chilensis promoted favourable responses in tissue repair of second-degree burns in this experimental model.

[Diffuse ganglioneuromatosis: infrequent pathology communication and review of literature]. / Ganglioneuromatosis difusa: comunicación de una patología infrecuente y revisión de la literatura.

Ganglioneuromatosis is an infrequent disease characterized by mienteric plexus and enteric nervous fiber hyperplasia, habitually manifested by constipation, pain and abdominal distension. There are two ways of presentation: mucosa or transmural. Regularly may be associated with another pathologies like multiple endocrine neoplasia type 2 and Von Recklinghausen's disease. The objective of this publication is to present an extremely infrequent pathology and make a bibliographic review of its clinical, diagnostic, prognostic and therapeutical aspects. We present a fifty-six year old male with a six month history ofabdominal pain and pseudo-obstruction syndrome. During the hospitalization he presents infectious complications, with septic shock secondary to nosocomial pneumonia and death. A Necropsy was done and ganglioneuromatosis was diagnosed. Due to the low incidence of this pathology, it is rarely included in the differential diagnosis of pseudo-obstructive syndrome in adults. The post-mortem diagnosis moved us to perform a bibliographic search to amplify our knowledge and compare this particular case with those previously communicated by other authors.

Discriminação de monossílabos em ambiente silencioso e ambiente ruidoso / Intelligibility of monosyllables in quiet and in noise

Em uma avaliação audiométrica convencional (como audiornetria tonal e discriminação auditiva), usualmente utilizamos cabina teoricamente anecoica. No entanto, diversos estudos demonstram que em um ambiente competitivo, a compreensão das palavras diminui para todos os indivíduos. Objetivo: Com o objetivo de efetuar uma avaliação mais próxima da realidade, idealizamos um estudo compreendendo 14 pacientes normais e 10 pacientes com presbiacusia, para se desenvolver uma metodologia de avaliação da discriminação auditiva em ambiente silencioso e ambiente ruidoso; e, paralelamente, observar o comportamento da compreensão das palavras em ambiente competitivo. Material e método: Foi utilizado o ruído branco, por ser facilmente captado pelo próprio audiômetro, assim como adaptamos em uma cabina audiométrica comum alto-falantes, amplificador e um gravador, para reproduzir uma voz feminina que citava a lista de monossílabos foneticamente balanceada de Geraldo de Sá. As avaliações ocorreram em campo livre sem o uso de fones de ouvido. Resultados: Ao final das avaliações, observamos que a metodologia utilizada foi eficiente e confiável, assim como pudemos afirmar que o paciente que apresenta presbiacusia tem um comportamento audiológico em ambiente ruidoso muito aquém do que pacientes jovens com audição normal. Conclusão: Para os presbiacúsicos, a fonte sonora para a compreensão de monossílabos deve sobrepor-se ao ruído ambiental, enquanto que para os jovens a fonte sonora pode ter níveis inferiores de pressão sonora em relação ao ruído ambiental.

In a conventional audiometric evaluation it is usually used a cabin. However, several studies show that in a competitive environment the comprehension of the words decreases for all the individuals. Aim: With the target of evaluating it closer to reality, a study with fourteen normal and ten presbyacusic patients was idealized to develop a methodology of evaluation of the hearing discrimination in both silent and noisy environment, and also to observe the speech recognition in competitive atmosphere. Material and method: It was used the white noise as it is easily picked up in a common audiometric cabin with loudspeakers, amplifier and a recorder to reproduce a female voice that mentioned the Geraldo de Sá's list of phonetically balanced monosyllables. The evaluations took place in a free field without the use of earphones. Results: At the and of the evaluations we observed that the methodology was efficient and trustful and we could also assure that the presbyacusic patients have an audiologic level of discrimination not up to young patients with regular hearing in a competitive environment. Conclusion: The sounding source for the understanding of monosyllables must be higher than the environmental noise to the presbyacusic patients while to the youngs the sounding pressure levels might be lower than the environmental noise.

Baixa discriminação auditiva em ambiente competitivo de pacientes jovens com audiograma normal / Low Intelligibility in Noisy Environment in Young People with Normal Audiometry

Foram estudados seis pacientes com queixa de dificuldade auditiva, entre 14 e 35 anos de idade (média de 27,8), mas que apresentavam avaliação audiométrica convencional normal, inclusive discriminação de 100%. Material e métodos: Utilizamos uma metodologia desenvolvida para avaliação do índice de reconhecimento da fala no silêncio e perante um ruído competitivo (ruído branco) em uma cabina audiométrica, sem fone de ouvido, onde observamos o comportamento da dificuldade crescente em discriminar monossílabos de acordo com o aumento do ruído branco dentro da cabina. Resultados: Comparamos o resultado encontrado com 14 pacientes jovens normais e sem queixas, tendo sido mostrado que os seis pacientes estudados realmente apresentavam uma compreensão das palavras muito aquém da revelada pelos pacientes normais em ambiente competitivo, mesmo apresentando uma discriminação de 100% no silêncio. Conclusão: O presente estudo demonstra que o resultado normal de um audiograma convencional nem sempre traduz a realidade, sendo que devemos lançar mão deste tipo de avaliação para uma definição mais precisa das condições auditivas de um indivíduo.

Six patients between 14 and 35 years old (on avarage of 27,8) with normal audiologic level were studied. They declared that their quality in audition was not good, even though their conventional audiological level was a normal and the intelligibility 100%. Material and methods: We used a methodology developed to evaluate the audiologic level in silence and in the presence of a competitive noise (white noise) in an audiometric cabin without earphone where we could observe the increasing difficulty in discriminating monosyllables according to the rise of white noise into the cabin. Results: It has been showed, comparing the results found in the study with 14 normal patients with any complaint, that the six studied patients in fact, have a comprehension of the words far short of the normal ones in a competitive environment although they showed a 100% of discrimination in silence. Conclusion: The current study proves that a normal result of a conventional audiogram not always shows the reality so that we should use this kind of evaluation to a more accurate definition of an individual's audition condition.