Efficacy and Safety of bimekizumab in elderly patients: real-world multicenter retrospective study - IL PSO (Italian Landscape Psoriasis).

Purpose of the article: The aim of this multicenter observational study is to report data from real world on the use of bimekizumab in patients aged ≥ 65 years with moderate-to-severe plaque psoriasis. Elderly patients are poorly represented in clinical trials on bimekizumab for plaque psoriasis, and real-world studies are important to guide clinical choices.Materials and methods: A retrospective multicenter study was conducted in 33 dermatological outpatient clinics in Italy. Patients aged ≥ 65 years, with moderate-to-severe plaque psoriasis and treated with bimekizumab were enrolled. No exclusion criteria were applied. Bimekizumab was administered following the Italian Guidelines for the management of plaque psoriasis and according to the summary of product characteristics, in adult patients who were candidates for systemic treatments. Overall, 98 subjects were included, and received bimekizumab up to week 36. Clinical and demographic data were collected before the initiation of treatment with bimekizumab. At baseline and each dermatological examination (4, 16, and 36 weeks), clinical outcomes were measured by the following parameters: (1) PASI score; (2) site-specific (scalp, palmoplantar, genital, nail) Psoriasis Global Assessment (PGA). At each visit, the occurrence of any adverse events (AEs) was recorded, including serious AEs and AEs leading to bimekizumab discontinuation.Results: The mean PASI score was 16.6 ± 9.4 at baseline and significantly decreased to 4.3 ± 5.2 after 4 weeks (p < 0.001), and 1.1 ± 1.7 after 16 week (p < 0.001). This level of improvement was maintained after 36 weeks (p < 0.001). PASI ≤2 was recorded in 36 (36.7%) at week 4, 68% and 69.4% at week 16 and 36, respectively. By week 16, 86/98 (87.8%) patients reached PASI75, 71/98 (72.4%) obtained PASI90, and 52/98 (53.1%) PASI100. Binary logistic regression tests showed a significant association of PASI100 by week 4 with lower PASI at baseline. PASI 100 at 16 or 36 weeks was not associated with baseline PASI, obesity, age, gender, previously naïve state, and presence of psoriatic arthritis. Patients naïve to biologics at baseline had similar response to bimekizumab as non-naïve subjects.Conclusions: Bimekizumab is a suitable option for elder patients as it is effective, tolerated and has a convenient schedule.

Potential drug-drug interactions with mitogen-activated protein kinase (MEK) inhibitors used to treat melanoma.

INTRODUCTION: The management of patients with BRAF-mutated advanced melanoma who are undergoing targeted therapy with MEK inhibitors can be complicated by the co-administration of multiple medications, which can give rise to drug-drug interactions of clinical significance. COVERED AREAS: Our review presents a comprehensive analysis of the pharmacokinetic and pharmacodynamic interactions of the three approved for advanced melanoma MEK inhibitor drugs - binimetinib, cobimetinib, and trametinib. MEDLINE (PubMed) was utilized for the literature search, comprising clinical studies, observational studies, and preclinical research. The review discusses the impact of these interactions on efficacy and safety of the treatments and differentiates between interactions supported by pharmacokinetic or pharmacodynamic mechanisms, those encountered in clinical practice, and those observed in preclinical studies. EXPERT OPINION: Physicians should be aware about potential benefits, but also increased toxicity caused by drug interactions between MEK inhibitors and other drugs in the management of patients with metastatic melanoma.

Fosfato e sulfato de cálcio na recuperaçäo de pastagem / Phosphate and calcium sulphate in pasture

Estudou-se o efeito da fertilizaçäo com sulfato de cálcio (gesso agrícola) e com fosfato (termofosfato) em pastagem de capim-braquiária (Brachiaria decumbens Stapf) estabelecida em latossolo vermelho sobre a capacidade de suporte e sobre o rendimento de peso vivo por hectare e por ano da pastagem. As forragens que receberam sulfato de cálcio e fosfato apresentaram níveis mais elevados de proteína bruta, cálcio e fósforo. Verificou-se também maior taxa de lotaçäo e maior rendimento em peso vivo por hectare nas pastagens que receberam fertilizaçäo

Neuroconducción en las disfunciones sexuales masculinas / Neural conduction in male sexual disfunction

Se describen los métodos clásicos electrofisiológicos para evaluar la disfunción sexual masculina (reflejo bulbocarvenoso (RBC) y potencial evocado somatosensitivo (PESS) practicados en el nervio pudendo y las técnicas recientes de exploración del nervio eringente desarrollada por los autores, en sujetos normales y en pacientes con impotencia y antecedentes de diabetes, prostatectomía, eyaculación precoz, ingesta alcohólica y tratamiento de HTA (hipertensión arterial) y depresión. En todos ellos se efectuó un estudio comparativo tanto de las respuestas de ambos nervios, como de la sensibilidad de ambos exámenes; los resultados fueron evaluados estadísticamente (Test de Mc Nemar), demostrando que el PESS practicado en el nervio eringente es el único examen estadísticamente significativo para evaluar la impotencia de origen neuropático. Por otra parte, debido a la constitución anatómica simpática (D12 a L4) del nervio eringente y su control preponderante neurovascular de la irrigación de los cuerpos cavernosos, la evaluación electrofisiológica precoz de este nervio tiene una relación muy estrecha con el comportamiento simpático de los cuerpos cavernosos en la función eréctil (neuropatía autonómica)

Extra-high-frequency noise remotely masks and alters temporal integration at lower frequencies.

A quasi-free-field technique was used to assess the effects of extra-high-frequency-band masking on detection threshold of middle and high (1-7 kHz) frequencies. At an SPL of 60 dB, the 10- to 20-kHz masker produced a slight amount of masking. Increasing the masking level by another 5 dB produced a disproportionate increase of the detection thresholds. This increase was greatest in response to 4- and 5-kHz stimuli, and was detected with both constant and pulsed tones. Decreasing the bandwidth of the masker reduced the magnitude of the effect, but not the frequency-specific pattern of the remote masking. Extra-high-frequency masking also increased the amount of temporal integration at middle and high frequencies. The data are discussed in reference to peripheral and central neural changes associated with sensorineural hearing loss.

Extra-high-frequency auditory thresholds: fine structure, reliability, temporal integration and relation to ear canal resonance.

Three trained subjects were repeatedly tested for detection of auditory thresholds at 27 frequencies, from 2 to 18 kHz. A double-blind procedure was used with the method of adjustment, and the quasi-free-field delivery system of Osterhammel et al. [Scand. Audiol. 6:91-95, 1977] was used to monaurally stimulate the ear. A very reliable series of high- and low-threshold changes, termed the fine structure of the extra-high-frequency audiogram, was observed from 8 to 16 kHz. All 6 ears had a major low-threshold region at or near 13.5 kHz, and up to 3 other replicable sensitive frequencies along this one octave range. Thresholds were invariant over 3 conditions of stimulus presentation (constant tone; 500 ms duration, 25 ms rise and decay, 1 s interstimulus interval; and 100 ms duration, 1.5 ms rise and decay, 200 ms interstimulus interval). As the duration of the tone was decreased from 100 to 5 ms, temporal integration (an average of approximately 2.5 dB threshold increase as the duration was halved) was noted. Although temporal integration was slightly less at higher frequencies, the shape of the audiograms remained essentially unchanged as the stimulus duration was decreased to 5 ms. There was no consistent relationship between the maximally sensitive high frequencies and the amount of temporal integration. But there was a general association between the maximally sensitive high frequencies and the resonant frequency characteristics of that particular ear.

Experiencias clínicas con musicoterapia en pacientes inválidos / Clinical experiences with music therapy in invalid patients

El objetivo del presente trabajo fue llevar a cabo una experiencia previa de musicoterapia con pacientes inválidos ambulatorios, del Servicio de Medicina Física y Rehabilitación, Sección Terapia Ocupacional, Hospital José Joaquín Aguirre, de la Universidad de Chile, con el propósito de obtener experiencia para elaborar un programa de este tipo de actividades para pacientes afectados por diversas invalideces. Este trabajo se realizó en conjunto con la unidad de Patología de Lenguaje del Servicio de Neurología de este Hospital, y se contó, además, con la valiosa colaboración ad-honorem del profesor de baile, señor Sergio Valero. (AU)