New high-performance liquid chromatography-dad method for analytical determination of arbutin and hydroquinone in rat plasma

Natural substances present in herbal preparations should be carefully used because they can give toxic or therapeutic effects despite of their amount or the way of administration. The safety of products of vegetable origin must be assessed before commercialisation by monitoring the active ingredients and their metabolites. This study was therefore designed to identify and quantify arbutin and its metabolite hydroquinone, naturally present in Arctostaphylos uva-ursi (L.) Spreng plant in rat plasma, after an acute and subacute administration of aqueous arbutin solution in Wistar rats. For this purpose a reversed-phase high-performance liquid chromatography coupled with photodiode array detection was developed to assess the pharmacokinetic of arbutin and hydroquinone in plasma of female rats treated with aqueous arbutin solutions. The detection (arbutin: 0.0617 µg/ml and hydroquinone 0.0120 µg/ml) and quantification (arbutin: 0.2060 µg/ml and hydroquinone: 0.0400 µg/ml) limits were determined. At the arbutin concentration level of 10.7 µg/ml repeatability was 13.33% and its recovery 93.4±6.93%, while at the hydroquinone concentration level of 10.6 µg/ml repeatability was 11.66% and its recovery 92.9±7.75%. Furthermore the method was fully validated and the obtained data indicate that the new method provides good performances

Psychometric properties of the WHOQOL-SRPB BREF, Brazilian Portuguese version

Objective: To test the reliability and the discriminant and convergent validity of the abbreviated Brazilian Portuguese World Health Organization’s Quality of Life Instrument – Spirituality, Religion, and Personal Beliefs module (WHOQOL-SRPB BREF). Methods: In a sample of 404 individuals, we applied a general questionnaire, the WHOQOL-BREF, the long-form SRPB, the Brief Religious-Spiritual Coping Scale (RCOPE), and the Beck Depression Inventory (BDI). Priority was given to the 9-item SRPB assessment: its unidimensionality was tested through confirmatory factor analysis and Rasch analysis. Results: Confirmatory factor analysis of the 9-item SRPB assessment indicated an adjusted model with acceptable fit to data. In the Rasch analysis, general fit measures showed adequate performance. The 9-item SRPB assessment showed good internal consistency (alpha = 0.85), and could differentiate (discriminant validity) between religious and atheist/agnostic respondents (mean = 74.7614.1 and 56.8615.5, respectively; t = 6.37; degrees of freedom [df] = 402; p o 0.01) and between nondepressed and depressed respondents (mean = 76.5612.9 and 67.1616.5; t = 5.57; df = 190.5; p o 0.01). Correlations (convergent validity) were significant with the positive-RCOPE subscale (r = 0.58, p o 0.01) and the WHOQOL-BREF domains (Pearson coefficient ranging between 0.24 and 0.49; p o 0.01), but were in the negative direction with the negative-RCOPE subscale (r = -0.10, p o 0.05). Correlation with the long-form SRPB domain (r = 0.934) was almost perfect. Conclusion: The Brazilian Portuguese 9-item SRPB has good psychometric properties and confirmed the findings of the long-form Brazilian Portuguese version and the abbreviated English version

Intra-articular injection of vitamin A: a rabbit model to study osteoarthrosis

An experimental model of osteoarthrosis (OA) induced by injection of vitamin A in knees of rabbits is presented.  This model represents a modification and improvement of a preexisting one (Boni et al., 1977;  Benazzo et al., 1982) based on a higher number of vitamin A injections. In our model, two vitamin A injections  were sufficient to induce OA without exposure of the subchondral bone. The advantages of this model  are: 1) the maintaining of articular cartilage could make the experimental joints suitable to test the reparative  efficiency of candidate intra-articular pharmacological treatments, 2) animal stress and the risk of  infections are strongly reduced in compliance with European legislation on laboratory animal welfare.

p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer

Background: Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer. Patients and methods: Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients. Results: p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2. Conclusions: We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cance

Validação brasileira do Instrumento de Qualidade de Vida/espiritualidade, religião e crenças pessoais

OBJETIVO: Analisar propriedades psicométricas do Instrumento de Qualidade de Vida da Organização Mundial da Saúde - Módulo Espiritualidade, Religiosidade e Crenças Pessoais (WHOQOL-SRPB). MÉTODOS: O WHOQOL-SRPB, a Escala de Coping Religioso/Espiritual Abreviada (CRE-Breve), o WHOQOL-Breve e o BDI foram consecutivamente aplicados em amostra de conveniência de 404 pacientes e funcionários de hospital universitário e funcionários de universidade, em Porto Alegre, RS, entre 2006 e 2009. A amostra foi estratificada por sexo, idade, estado de saúde e religião/crença. O reteste dos dois primeiros instrumentos foi realizado com 54 participantes. Análises fatoriais exploratórias do WHOQOL-SRPB pelo método dos componentes principais foram realizadas sem delimitar o número de fatores, solicitando oito fatores e em conjunto com os itens do WHOQOL-Breve. RESULTADOS: O WHOQOL-SRPB em português brasileiro (Domínio SRPB-Geral) apresentou validade de construto, com validade discriminativa entre crentes de não-crentes (t = 7,40; p = 0,0001); validade relacionada ao critério concorrente, discriminando deprimidos de não-deprimidos (t = 5,03; p = 0,0001); validade convergente com o WHOQOL-Breve (com físico r = 0,18; psicológico r = 0,46; social r = 0,35; ambiental r = 0,29; global r = 0,23; p = 0,0001) e com o Domínio SRPB do WHOQOL-100 (r = 0,78; p = 0,0001); e validade convergente/discriminante com a Escala CRE-Breve (com CREpositivo r = 0,64; p = 0,0001/CREnegativo r = -0,03; p = 0,554). Observou-se excelente fidedignidade teste-reteste (t = 0,74; p = 0,463) e consistência interna (&#945; = 0,96; correlação intrafatorial 0,87 > r > 0,60, p = 0,0001). As análises fatoriais exploratórias realizadas corroboraram a estrutura de oito fatores do estudo multicêntrico do WHOQOL-SRPB. CONCLUSÕES: O WHOQOL-SRPB em português brasileiro apresentou boas qualidades psicométricas e uso válido e fidedigno para uso no Brasil. Sugerem-se novos estudos com populações específicas, como diferentes religiões, grupos culturais e/ou doenças.OBJETIVO: Analizar propiedades psicométricas del Instrumento de Calidad de Vida de la OMS - Módulo Espiritualidad, Religiosidad y Creencias Personales (WHOQOL-SRPB). MÉTODOS: El WHOQOL-SRPB, la Escala de Coping Religioso/Espiritual Abreviada (CRE-Breve), el WHOQOL-Breve y el BDI fueron consecutivamente aplicados en muestra de conveniencia de 404 pacientes y funcionarios de hospital universitario y funcionarios de universidad, en Porto Alegre, Sur de Brasil, entre 2006 y 2009. La muestra fue estratificada por sexo, edad, estado de salud y religión/creencia. La reevaluación de los dos primeros instrumentos fue realizada por 54 participantes. Análisis factoriales exploratorias del WHOQOL-SRPB por el método de los componentes principales fueron realizadas, sin delimitar el número de factores, solicitando ocho factores y en conjunto con los itens del WHOQOL-Breve. RESULTADOS: El WHOQOL-SRPB en portugués-brasileño (Dominio SRPB-General) presentó validez de constructo, con validez discriminativa entre creyentes de no creyentes (t=7,40; p=0,0001); validez relacionada con el criterio concurrente, discriminando deprimidos de no deprimidos (t=5,03; p=0,0001); validez convergente con el WHOQOL-Breve (con físico r=0,18; psicológico r=0,46; social r=0,35; ambiental r=0,29; global r=0,23; p=0,0001) y con el Dominio-SRPB del WHOQOL-100 (r=0,78; p=0,0001); y validez convergente/discriminante con la Escala CRE-Breve (con CRE positivo r=0,64; p=0,0001/CRE negativo r=-0,03; p=0,554). Se observó excelente fidedignidad test-retest (t=0,74; p=0,463) y consistencia interna (&#945;=0,96; correlación intrafactorial 0,87>r>0,60, p=0,0001). Los análisis factoriales exploratorios realizados corroboran la estructura de ocho factores de estudio multicéntrico del WHOQOL-SRPB. CONCLUSIONES: El WHOQOL-SRPB en portugués-brasileño presentó buenas cualidades psicométricas, siendo válido y fidedigno para uso en Brasil. Se sugieren nuevos estudios con poblaciones específicas, como diferentes religiones, grupos culturales y/o enfermedades.OBJECTIVE: To analyze the psychometric properties of the World Health Organization's Quality of Life Instrument - Spirituality, Religion and Personal Beliefs module (WHOQOL-SRPB). METHODS: The WHOQOL-SRPB, the Brief Spiritual/Religious Coping Scale (Brief-SRCOPE Scale), the WHOQOL-BREF and the Beck Depression Inventory (BDI) were consecutively applied in a convenience sample of 404 patients and workers of a university hospital and workers of a university, in the city of Porto Alegre, Southern Brazil, between 2006 and 2009. The sample was stratified by sex, age, health status and religion/belief. The retest of the two first instruments was conducted with 54 participants. Exploratory factorial analyses of the WHOQOL-SRPB with the method of main components were performed, without limiting the number of factors, and requiring eight factors concomitantly with the WHOQOL-BREF items. RESULTS: The Brazilian Portuguese version of the WHOQOL-SRPB (General SRPB-Domain) showed construct validity, with a discriminatory validity between believers and non-believers (t = 7.40; p = 0.0001); concurrent criterion-related validity, distinguishing depressed individuals from non-depressed ones (t = 5.03; p = 0.0001); convergent validity with the WHOQOL-BREF (physical r = 0.18; psychological r = 0.46; social r = 0.35; environmental r = 0.29; global r = 0.23; p = 0.0001) and with the SRPB-Domain of the WHOQOL-100 (r = 0.78; p = 0.0001); and convergent/discriminatory validity with the brief SRCOPE Scale (with positive SRCOPE r = 0.64; p = 0.0001/negative SRCOPE r = -0.03; p = 0.554). Excellent test-retest reliability (t = 0.74; p = 0.463) and internal consistency (&#945; = 0.96; intrafactorial correlation 0.87 > r > 0.60; p = 0.0001) were observed. The exploratory factorial analyses performed corroborated the eight-factor structure of the WHOQOL-SRPB multicenter study. CONCLUSIONS: The Brazilian Portuguese version of the WHOQOL-SRPB showed good psychometric qualities and use valid and reliable in Brazil. It is suggested that new studies be conducted with specific populations, such as different religions, cultural groups and/or diseases

Coping religioso/espiritual em pessoas com doença renal crônica em tratamento hemodialítico

O estudo tem como objetivo investigar o uso do coping religioso/espiritual em pacientes com doença renal crônica em hemodiálise. A investigação ocorreu em uma clínica de hemodiálise, por meio de entrevista utilizando um questionário sociodemográfico e a escala de coping religioso/espiritual. Para análise dos dados, foram empregados a estatística descritiva e o teste coeficiente de correlação de Sperman, a análise de variância e o modelo de regressão linear múltipla. Foram entrevistados 123 indivíduos, dos quais 79,6% apresentaram escore alto para o coping religioso/espiritual e nenhum deles apresentou os escores baixos e irrisórios. As variáveis que influenciaram no comportamento do coping religioso/espiritual foram: sexo, faixa etária, tempo de tratamento, renda familiar e prática religiosa. Conclui-se que os pacientes em estudo utilizam de modo positivo o coping religioso/espiritual como estratégia de enfrentamento da doença, destacando-se as mulheres, com renda familiar maior e que frequentam semanalmente a igreja

Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program

Objective: This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy. Methods: This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (&gt;= 50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses. Results: A total of 236 subjects with a median age of 38 (Q(1)-Q(3) = 27-49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q(1)-Q(3) = 2.50-4.47) at baseline to 2.50 (Q(1)-Q(3) = 1.67-3.50) at 12 months (p &lt; .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and gamma-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel. Significance: Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam

The weekend effect on the provision of Emergency Surgery before and during the COVID-19 pandemic: case–control analysis of a retrospective multicentre database

Introduction: The concept of “weekend effect”, that is, substandard healthcare during weekends, has never been fully demonstrated, and the different outcomes of emergency surgical patients admitted during weekends may be due to different conditions at admission and/or different therapeutic approaches. Aim of this international audit was to identify any change of pattern of emergency surgical admissions and treatments during weekends. Furthermore, we aimed at investigating the impact of the COVID-19 pandemic on the alleged “weekend effect”. Methods: The database of the CovidICE-International Study was interrogated, and 6263 patients were selected for analysis. Non-trauma, 18+ yo patients admitted to 45 emergency surgery units in Europe in the months of March–April 2019 and March–April 2020 were included. Demographic and clinical data were anonymised by the referring centre and centrally collected and analysed with a statistical package. This study was endorsed by the Association of Italian Hospital Surgeons (ACOI) and the World Society of Emergency Surgery (WSES). Results: Three-quarters of patients have been admitted during workdays and only 25.7% during weekends. There was no difference in the distribution of gender, age, ASA class and diagnosis during weekends with respect to workdays. The first wave of the COVID pandemic caused a one-third reduction of emergency surgical admission both during workdays and weekends but did not change the relation between workdays and weekends. The treatment was more often surgical for patients admitted during weekends, with no difference between 2019 and 2020, and procedures were more often performed by open surgery. However, patients admitted during weekends had a threefold increased risk of laparoscopy-to-laparotomy conversion (1% vs. 3.4%). Hospital stay was longer in patients admitted during weekends, but those patients had a lower risk of readmission. There was no difference of the rate of rescue surgery between weekends and workdays. Subgroup analysis revealed that interventional procedures for hot gallbladder were less frequently performed on patients admitted during weekends. Conclusions: Our analysis revealed that demographic and clinical profiles of patients admitted during weekends do not differ significantly from workdays, but the therapeutic strategy may be different probably due to lack of availability of services and skillsets during weekends. The first wave of the COVID-19 pandemic did not impact on this difference