Upadacitinib Reduces Crohn's Disease Symptoms Within the First Week of Induction Therapy.

BACKGROUND & AIMS: Upadacitinib (UPA), an oral Janus kinase inhibitor, is approved to treat moderately to severely active Crohn's disease (CD). Because symptomatic response is an important initial treatment goal for patients, we evaluated the rapidity of symptomatic improvement in patients with CD receiving UPA 45 mg once daily (UPA45) induction therapy. METHODS: This post hoc analysis included pooled data from 2 phase 3, multicenter, double-blind, 12-week induction trials (U-EXCEL and U-EXCEED) and 1 maintenance trial (U-ENDURE). Daily diary data for the first 15 days of UPA45 or placebo (PBO) treatment were used to analyze improvement in very soft/liquid stool frequency (SF) and abdominal pain score (APS). Clinical outcomes were evaluated at every study visit. RESULTS: Overall, 1021 patients (n = 674 UPA45; n = 347 PBO) were analyzed. UPA45 demonstrated greater efficacy vs PBO for SF <3 and APS ≤1, providing rapid relief by day 5 or 6, regardless of prior biologic exposure. Mean changes in SF and APS were greater with UPA45 beginning at week 2 (-2.0 and -0.5, respectively; P < .001) and were maintained through week 12 (-3.0 and -1.0, respectively; P < .001) vs PBO. The first achievement of daily SF/APS clinical remission occurred earlier with UPA45 (median, 13 d) vs PBO (median, 32 d), and patients treated with UPA45 showed improved rates of SF/APS clinical remission (21.1% UPA45 vs 8.9% PBO) and clinical response (58.8% UPA45 vs 37.9% PBO) starting at week 2 (both P ≤ .01). CONCLUSIONS: UPA45 provided rapid relief of clinical symptoms within the first week of treatment in patients with CD. CLINICALTRIALS: gov numbers: NCT03345849, NCT03345836, and NCT03345823.

Content Validity and Psychometric Evaluation of the Crohn's Symptom Severity (CSS) Questionnaire in Patients with Moderately to Severely Active Crohn's Disease.

INTRODUCTION: Individuals living with Crohn's disease (CD) experience burdensome symptoms. As such, it is important to measure CD symptom severity in clinical research. The goal of this study was to evaluate the content validity, psychometric performance, and score interpretability of a new patient-reported instrument, the Crohn's Symptom Severity (CSS) questionnaire, among adolescents and adults with moderately to severely active CD. METHODS: Cognitive debriefing interviews (N = 30; n = 20 adults, n = 10 adolescents) were conducted to evaluate the content validity of the CSS. Additionally, the CSS scores were evaluated for reliability and validity using data from a phase 3 randomized clinical trial of risankizumab (NCT03105128; N = 850). Meaningful within-patient change (MWPC) thresholds were estimated using anchor-based methods. RESULTS: All interview participants (n = 30/30, 100.00%) reported the CSS was easy to complete and most participants (n = 28/29, 96.55%) reported that the CSS was relevant to their experience of CD. Among the clinical trial subjects (N = 850) the following was found for the CSS: mostly acceptable item-total correlations (0.26-0.79); weak to moderate inter-item correlations (r = 0.07-0.57), good internal consistency (Cronbach's α = 0.76-0.87); intraclass correlation coefficients ranged from 0.48 to 0.70, not consistently exceeding the acceptable range for test-retest reliability (0.70); acceptable convergent validity and known-groups results; and demonstrated sensitivity to change. Analyses supported an MWPC estimate of 6-11 points. CONCLUSIONS: This study supports use of the CSS for measuring CD symptoms and sleep impact among adolescents and adults aged 16 and older with moderately to severely active CD in clinical research. TRIAL REGISTRATION: NCT03105128 (registration date 4 April 2017).

Water fluoridation in the ten largest municipalities of the state of Tocantins, Brazil. / Fluoretação da água dos dez maiores municípios do estado do Tocantins, Brasil.

Water fluoridation is a strategy for caries control recommended by the WHO. In Brazil, it is regulated by law but this program has not been successfully implemented in the North region. This research aimed to collect data on the existence of external control (heterocontrol) in the ten largest municipalities in the state of Tocantins, Brazil, and to analyze fluoride concentration in the public water supply of these cities. The study was conducted from May-August/17, and its theoretical-methodological framework was a quantitative, descriptive and cross-sectional analysis. Water collections were carried out monthly, using sampling protocol of water collection of the network. Fluoride concentration in the waters was determined with ion specific electrode by the direct technique. It was verified that water fluoridation monitoring is only been done in Palmas, capital of the state, starting in 2016. Thirty-two percent of waters samples analyzed showed fluoride concentration to obtain the maximum benefit of reduction caries and 27.5% of them presented a high or very high risk of dental fluorosis. It is necessary to implement a program to control the concentration of fluoride in the water of the municipalities of Tocantins, in order to ensure that the population is not deprived of the anticaries' benefits of the adjustment of fluoride concentration of the treated water.

Fluoretação da água é uma estratégia de controle da cárie, recomendada pela OMS. No Brasil ela é regulamentada por lei, mas não tem sido implementada com sucesso na região Norte. Os objetivos desta pesquisa foram levantar dados sobre a existência do heterocontrole nos 10 maiores municípios tocantinenses e analisar a concentração de fluoreto presente na água de abastecimento público destas cidades. A pesquisa foi realizada de maio-agosto/17 e teve como marco teórico-metodológico a análise quantitativa, descritiva e transversal. Coletas de água foram realizadas mensalmente, utilizando protocolo de amostragem de coleta de água da rede. A concentração de fluoreto nas águas foi feita com eletrodo íon específico pela técnica direta. Constatou-se que a vigilância da fluoretação da água está em operação na capital do estado desde 2016. Com relação a concentração de fluoreto na água, foi encontrado que 31,6% das amostras analisadas estavam adequadas para o máximo benefício de redução de cárie e 27,5% delas apresentavam risco alto ou muito alto de fluorose dentária. É necessário implementar um programa de controle da concentração de flúor na água no Tocantins, a fim de garantir que a população não seja privada dos benefícios anticárie da agregação de flúor à agua tratada.

Characterization of the Effect of Hepatic Impairment on Upadacitinib Pharmacokinetics.

Upadacitinib is a selective Janus kinase 1 inhibitor being developed for the treatment of several inflammatory autoimmune diseases, including rheumatoid arthritis. Upadacitinib is a nonsensitive substrate for metabolism by cytochrome P450 3A enzymes. This open-label, single-dose, multicenter study assessed the pharmacokinetics of upadacitinib following oral administration of a single 15-mg dose of the upadacitinib extended-release formulation in subjects with mild (n = 6) and moderate (n = 6) hepatic impairment relative to demographically matched healthy subjects (n = 6). Subjects were assigned to 1 of the 3 groups according to the Child-Pugh classification. Relative to subjects with normal hepatic function, the ratios (90% confidence intervals) of upadacitinib area under the plasma concentration-versus-time profile from time 0 to infinity (AUCinf ) for subjects with mild and moderate hepatic impairment were 1.28 (0.91-1.79) and 1.24 (0.87-1.76), respectively. The central ratios of upadacitinib maximum observed concentration (Cmax ) were 1.04 (0.77-1.39) and 1.43 (1.05-1.95) in subjects with mild and moderate hepatic impairment, respectively, compared with subjects with normal hepatic function. No clinically significant changes in vital signs or hematology measurements were observed, and no new safety events were identified in this study. These results indicate that mild and moderate hepatic impairment has no clinically relevant effect on upadacitinib pharmacokinetics.

Effects of Image Compression on Linear Measurements of Digital Panoramic Radiographs.

This study aimed to evaluate the accuracy of panoramic radiographs obtained by digital system based on charge coupled device (CCD) and a phosphor storage plate (PSP) system with two different file formats, JPEG irreversible type and BMP. Linear measurements of artificial bony defects were made in dry mandibles with a digital caliper. Measures of digital panoramic radiographs were taken in ImageJ(r) software. Each measurement was performed twice by an experienced examiner. The intra-rater agreement was considered very strong (Pearson's correlation coefficient of 0.97). There was no significant difference between the linear measurements of dry mandibles, considered the gold standard, in relation to measurements obtained from digital radiographs (p=0.47). The error of these measures for the CCD was 1.04 mm (9.97%) for JPEG images and 1.03 mm (9.99%) for those with BMP format. For the PSP images, these values were 1.48 mm (14.94%) and 1.43 mm (14.43%), respectively. Although there was no statistical difference between the images with JPEG and BMP format, for both digital systems (p=1.00 for CCD and p=0.98 for PSP system), errors made on radiographs obtained by PSP system were significantly higher than those of CCD (p<0.05). The size of the files saved in JPEG was also significantly lower (p=0.005) compared with the files saved in BMP. It may be concluded that the digital radiographs, both saved in JPEG and BMP formats, are accurate, regardless the used digital system, and JPEG images are more suitable for teleradiology.

Fluoretação da água dos dez maiores municípios do estado do Tocantins, Brasil / Water fluoridation in the ten largest municipalities of the state of Tocantins, Brazil

Resumo Fluoretação da água é uma estratégia de controle da cárie, recomendada pela OMS. No Brasil ela é regulamentada por lei, mas não tem sido implementada com sucesso na região Norte. Os objetivos desta pesquisa foram levantar dados sobre a existência do heterocontrole nos 10 maiores municípios tocantinenses e analisar a concentração de fluoreto presente na água de abastecimento público destas cidades. A pesquisa foi realizada de maio-agosto/17 e teve como marco teórico-metodológico a análise quantitativa, descritiva e transversal. Coletas de água foram realizadas mensalmente, utilizando protocolo de amostragem de coleta de água da rede. A concentração de fluoreto nas águas foi feita com eletrodo íon específico pela técnica direta. Constatou-se que a vigilância da fluoretação da água está em operação na capital do estado desde 2016. Com relação a concentração de fluoreto na água, foi encontrado que 31,6% das amostras analisadas estavam adequadas para o máximo benefício de redução de cárie e 27,5% delas apresentavam risco alto ou muito alto de fluorose dentária. É necessário implementar um programa de controle da concentração de flúor na água no Tocantins, a fim de garantir que a população não seja privada dos benefícios anticárie da agregação de flúor à agua tratada.

Abstract Water fluoridation is a strategy for caries control recommended by the WHO. In Brazil, it is regulated by law but this program has not been successfully implemented in the North region. This research aimed to collect data on the existence of external control (heterocontrol) in the ten largest municipalities in the state of Tocantins, Brazil, and to analyze fluoride concentration in the public water supply of these cities. The study was conducted from May-August/17, and its theoretical-methodological framework was a quantitative, descriptive and cross-sectional analysis. Water collections were carried out monthly, using sampling protocol of water collection of the network. Fluoride concentration in the waters was determined with ion specific electrode by the direct technique. It was verified that water fluoridation monitoring is only been done in Palmas, capital of the state, starting in 2016. Thirty-two percent of waters samples analyzed showed fluoride concentration to obtain the maximum benefit of reduction caries and 27.5% of them presented a high or very high risk of dental fluorosis. It is necessary to implement a program to control the concentration of fluoride in the water of the municipalities of Tocantins, in order to ensure that the population is not deprived of the anticaries' benefits of the adjustment of fluoride concentration of the treated water.

Effects of Image Compression on Linear Measurements of Digital Panoramic Radiographs

Abstract This study aimed to evaluate the accuracy of panoramic radiographs obtained by digital system based on charge coupled device (CCD) and a phosphor storage plate (PSP) system with two different file formats, JPEG irreversible type and BMP. Linear measurements of artificial bony defects were made in dry mandibles with a digital caliper. Measures of digital panoramic radiographs were taken in ImageJ(r) software. Each measurement was performed twice by an experienced examiner. The intra-rater agreement was considered very strong (Pearson's correlation coefficient of 0.97). There was no significant difference between the linear measurements of dry mandibles, considered the gold standard, in relation to measurements obtained from digital radiographs (p=0.47). The error of these measures for the CCD was 1.04 mm (9.97%) for JPEG images and 1.03 mm (9.99%) for those with BMP format. For the PSP images, these values were 1.48 mm (14.94%) and 1.43 mm (14.43%), respectively. Although there was no statistical difference between the images with JPEG and BMP format, for both digital systems (p=1.00 for CCD and p=0.98 for PSP system), errors made on radiographs obtained by PSP system were significantly higher than those of CCD (p<0.05). The size of the files saved in JPEG was also significantly lower (p=0.005) compared with the files saved in BMP. It may be concluded that the digital radiographs, both saved in JPEG and BMP formats, are accurate, regardless the used digital system, and JPEG images are more suitable for teleradiology.

Resumo Este estudo teve como objetivo avaliar a acurácia de radiografias panorâmicas digitais obtidas por sistema digital baseado em dispositivo acoplador de carga (DAC) e por sistema de placa de fósforo (PF) com duas diferentes extensões de arquivo (JPEG e BMP, sendo o primeiro do tipo compactador irreversível). Medidas lineares de defeitos ósseos foram realizadas em mandíbulas secas com paquímetro digital. As medidas correspondentes nas radiografias panorâmicas digitais foram realizadas no software ImageJ(r). As medidas foram realizadas duas vezes por um examinador. A concordância intraexaminador foi considerada muito forte (coeficiente de correlação de Pearson de 0,97). Não houve diferença significante entre as medidas lineares das mandíbulas secas, consideradas padrão-ouro, em relação às medidas obtidas das radiografias digitais (p=0,47). Os erros absolutos e relativos dessas medidas para o DAC foram de 1,04 mm (9,97%) para as imagens JPEG e de 1,03 mm (9,99%) para aquelas com extensão BMP. Para o sistema digital com PF esses valores foram de 1,48 mm (14,94%) e 1,43 mm (14,43%), respectivamente. Apesar de não ter havido diferença estatística entre as imagens com extensão JPEG e BMP, para ambos os sistemas digitais (p=1,00 para DAC e p=0,98 para a PF), os erros das medidas realizadas nas radiografias obtidas pelo sistema de PF foram significativamente maiores que os erros do DAC (p<0,05). O tamanho dos arquivos salvos em JPEG também foram significativamente menores (p=0,005) em comparação com os arquivos salvos em BMP. Pode-se concluir que as radiografias digitais tanto com extensão JPEG quanto BMP são acuradas, independente do sistema digital utilizado e as imagens salvas em JPEG são mais indicadas em telerradiologia.

Atualizaçäo no uso das heparinas de baixo peso molecular 1999

As heparinas de baixo