ABSTRACT
BACKGROUND: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are usually asymptomatic and seek treatments that improve survival but have a low risk of adverse events. Darolutamide, a structurally distinct androgen receptor inhibitor (ARi), significantly reduced the risk of metastasis and death versus placebo in ARAMIS. We assessed the extended safety and tolerability of darolutamide and the time-course profile of treatment-emergent adverse events (TEAEs) related to ARis and androgen-suppressive treatment. PATIENTS AND METHODS: Patients with nmCRPC were randomized 2:1 to darolutamide (nâ =â 955) or placebo (nâ =â 554). After trial unblinding, patients could receive open-label darolutamide. Tolerability and TEAEs were assessed every 16 weeks. Time interval-specific new and cumulative event rates were determined during the first 24 months of the double-blind period. RESULTS: Darolutamide remained well tolerated during the double-blind and open-label periods, with 98.8% of patients receiving the full planned dose. The incidence of TEAEs of interest in the darolutamide group was low and ≤2% different from that in the placebo group, except for fatigue. When incidences were adjusted for exposure time, there were minimal differences between the darolutamide double-blind and double-blind plus open-label periods. The rate of initial onset and cumulative incidence of grade 3/4 TEAEs and serious TEAEs were similar for darolutamide and placebo groups over 24 months. CONCLUSION: Extended treatment with darolutamide was well tolerated and no new safety signals were observed. Most ARi-associated and androgen-suppressive treatment-related TEAEs occurred at low incidences with darolutamide, were similar to placebo, and showed minimal increase over time with continued treatment. TRIAL NUMBER: ClinicalTrials.gov identifier NCT02200614.
Subject(s)
Prostatic Neoplasms, Castration-Resistant , Pyrazoles , Humans , Male , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Aged , Double-Blind Method , Pyrazoles/therapeutic use , Pyrazoles/adverse effects , Androgen Receptor Antagonists/therapeutic use , Androgen Receptor Antagonists/adverse effects , Androgen Receptor Antagonists/pharmacology , Middle Aged , Aged, 80 and overABSTRACT
OBJECTIVE: Studies have highlighted numerous benefits of ozone therapy in the field of medicine and dentistry, including its antimicrobial efficacy against various pathogenic microorganisms, its ability to modulate the immune system effectively, reduce inflammation, prevent hypoxia, and support tissue regeneration. However, its effects on dental extraction healing remain to be elucidated. .Therefore, this study aimed to evaluate the effects of systemically administered ozone (O3) at different doses in the healing of dental extraction sockets in rats. METHODOLOGY: To this end, 72 Wistar rats were randomly divided into four groups after extraction of the right upper central incisor: Group C - control, no systemic treatment; Group OZ0.3 - animals received a single dose of 0.3 mg/kg O3; Group OZ0.7 - a single dose of 0.7 mg/kg O3; and Group OZ1.0 - a single dose of 1.0 mg/kg O3, intraperitoneally. In total, six animals from each group were euthanized at 7, 14, and 21 days after the commencement of treatment. Bone samples were harvested and further analyzed by descriptive histology, histomorphometry, and immunohistochemistry for osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) protein expression. RESULTS: All applied doses of O3 were shown to increase the percentage of bone tissue (PBT) after 21 days compared to group C. After 14 days, the OZ0.7 and OZ1.0 groups showed significantly higher PBT when compared to group C. The OZ1.0 group presented the most beneficial results regarding PBT among groups, which denotes a dose-dependent response. OCN immunostaining was higher in all groups at 21 days. However, after seven and 14 days, the OZ1.0 group showed a significant increase in OCN immunostaining compared to C group. No differences in TRAP+ osteoclasts were found between groups and time points. CONCLUSION: Therefore, O3 therapy at higher doses might be beneficial for bone repair of the alveolar socket following tooth extraction.
Subject(s)
Immunohistochemistry , Osteocalcin , Ozone , Random Allocation , Rats, Wistar , Tartrate-Resistant Acid Phosphatase , Tooth Extraction , Tooth Socket , Wound Healing , Animals , Ozone/pharmacology , Tooth Socket/drug effects , Wound Healing/drug effects , Tartrate-Resistant Acid Phosphatase/analysis , Osteocalcin/analysis , Time Factors , Male , Reproducibility of Results , Treatment Outcome , Reference ValuesABSTRACT
PURPOSE: This study evaluated the systemic and local effects of doxycycline (DOX) and low-intensity laser (LIL) treatment as adjuvants to scaling and root planing (SRP) in the treatment of experimental periodontitis in rats. METHODS: The sample consisted of 180 male rats (Rattus norvegicus albinus, Wistar), of which 30 did not receive induction of periodontal disease (negative control [NC] group) and 150 received induction of periodontal disease in the lower first molar. After 7 days, the ligature was removed, and the animals were divided into the following groups: NT (no treatment), SRP (SRP), DOX (SRP and DOX irrigation), LIL (SRP and laser irradiation), and DOX+LIL (SRP, DOX, and LIL). The animals were euthanized at 7, 15, and 30 days; thereafter, biochemical, radiographic, histological, and immunohistochemical analyses were performed. RESULTS: In the intragroup analysis, lower concentrations of α-1-glycoprotein acid (α-1-Ga) and complement 3 (C3) were observed in the DOX+LIL group than in all other groups at all time points, as well as lower levels of complement 4 (C4) at 15 and 30 days (P<0.001). Less bone loss was observed in the DOX, LIL, and DOX+LIL groups than in the NC and SRP groups at all time points (P<0.001). There was a smaller number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the DOX+LIL group than in the other groups at all time points (P<0.001). Positive correlations were observed between the systemic levels of α-1-Ga, C3, and C4 and the number of TRAP-positive cells. CONCLUSIONS: The combination of DOX with LIL as SRP adjuvants was effective both systemically and locally for the treatment of experimental periodontitis in rats.
ABSTRACT
This study evaluated the influence of Doxycycline (DOX) and Low-Intensity Laser (LIL) (InGaAlP diode laser) as scaling and root planing (SRP) adjuvants in the treatment of periodontitis induced in rats. The rats received periodontal disease induction, and after 7 days, the ligature was removed, and the animals were divided into groups/treatments: NT-receive no treatment; SRP-submitted only to SRP; DOX-submitted to SRP and DOX irrigation; LIL-submitted to SRP and LIL irradiation; and DOX + LIL-submitted to SRP treatments, DOX irrigation and LIL irradiation. The animals were sacrificed at 7, 15 and 30 days, and then, the analyses were performed. A lower concentration of Alpha-glycoprotein acid and Complement 3 was observed in the DOX + LIL group compared to all the other groups in all the periods, and for Complement 4 at 15 and 30 days (P < 0.01). A lower bone loss (BL) was observed in the DOX + LIL group compared to all the other groups in all the periods (P < 0.01). It can be concluded that LIL was effective in the reduction of proteins, and its association with DOX was effective in the reduction of proteins and BL, in the treatment of periodontal induction in rats.
Subject(s)
Lasers, Semiconductor , Periodontitis , Animals , Combined Modality Therapy , Doxycycline/pharmacology , Doxycycline/therapeutic use , Lasers, Semiconductor/therapeutic use , Periodontitis/drug therapy , Rats , Rats, Wistar , Root PlaningABSTRACT
Abstract Studies have highlighted numerous benefits of ozone therapy in the field of medicine and dentistry, including its antimicrobial efficacy against various pathogenic microorganisms, its ability to modulate the immune system effectively, reduce inflammation, prevent hypoxia, and support tissue regeneration. However, its effects on dental extraction healing remain to be elucidated. Objective Therefore, this study aimed to evaluate the effects of systemically administered ozone (O3) at different doses in the healing of dental extraction sockets in rats. Methodology To this end, 72 Wistar rats were randomly divided into four groups after extraction of the right upper central incisor: Group C - control, no systemic treatment; Group OZ0.3 - animals received a single dose of 0.3 mg/kg O3; Group OZ0.7 - a single dose of 0.7 mg/kg O3; and Group OZ1.0 - a single dose of 1.0 mg/kg O3, intraperitoneally. In total, six animals from each group were euthanized at 7, 14, and 21 days after the commencement of treatment. Bone samples were harvested and further analyzed by descriptive histology, histomorphometry, and immunohistochemistry for osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) protein expression. Results All applied doses of O3 were shown to increase the percentage of bone tissue (PBT) after 21 days compared to group C. After 14 days, the OZ0.7 and OZ1.0 groups showed significantly higher PBT when compared to group C. The OZ1.0 group presented the most beneficial results regarding PBT among groups, which denotes a dose-dependent response. OCN immunostaining was higher in all groups at 21 days. However, after seven and 14 days, the OZ1.0 group showed a significant increase in OCN immunostaining compared to C group. No differences in TRAP+ osteoclasts were found between groups and time points. Conclusion Therefore, O3 therapy at higher doses might be beneficial for bone repair of the alveolar socket following tooth extraction.
ABSTRACT
Introduçäo: em todo o mundo, especialistas em Educaçäo Médica têm se reunido na busca da melhoria do ensino. Na área de Otorrinolaringologia (ORL), principalmente no Brasil, poucos estudos têm sido feitos com relaçäo ao ensino e à mudança curricular. Objetivo: Para tal, objetivamos avaliar as necessidades para um currículo de ORL na graduaçäo em Medicina, na visäo de otorrinolaringologistas e de médicos generalistas. Forma de estudo: prospectivo. Material e método: Questionários foram aplicados a dois grupos: Grupo 1 - otorrinolaringologistas; Grupo 2 - médicos generalistas. O questionário continha uma lista de 88 áreas de conhecimento e 65 de habilidades em ORL. Os entrevistados avaliaram cada área de acordo com uma escala de relevância para o currículo de graduaçäo, sendo 4 indispensável, 3 importante, 2 útil para poucos médicos generalistas, 1 interessante, mas desnecessária sua inclusäo, e 0 dispensável. Baseado neste sistema de pontuaçäo, para cada área foi calculada a média. Areas do conhecimento como amigdalite, otites, rinite alérgica, epistaxe, sinusites e faringites receberam as maiores pontuaçöes. Resultado: Os otorrinolaringologistas priorizaram as complicaçöes das otites e sinusites. Na área das habilidades, os tópicos com maiores pontuaçöes foram: tomar história do paciente; otoscopia; exame físico otorrinolaringológico; exames dos pares cranianos; tamponamento nasal anterior. Os médicos generalistas priorizaram remoçäo de corpo estranho de ouvido e nariz, retirada de cerume e colheita de material de orofaringe para cultura. Conclusäo: Este estudo demonstrou dados que podem subsidiar educadores da área médica quando da reformulaçäo do currículo de ORL para o curso de graduaçäo em medicina
ABSTRACT
Resumo: As mudanças no ensino superior, no espírito da Lei de Diretrizes e Bases, realçam a necessidade de maior flexibilização curricular a de um melhor conhecimento da realidade educacional de cada curso. Este estudo objetivou uma diagnose melhor da situação atual do Curso de Medicina da UFU, através de uma abordagem quali-quantitativa para avaliação das disciplinas curriculares. Foram usados análise documental, abordagem quantitativa com aplicação de questionário final de avaliação de disciplinas e abordagem qualitativa com observação participante de cada disciplina, realizada por dois observadores independentes. As respostas foram agrupadas em cinco áreas temáticas: processo ensino-aprendizagem, cenário de aprendizagem, relacionamento professor-aluno, ética no curso e avaliação do aluno. Há uma razoável satisfação dos alunos em relação ao modo como vêm sendo ministradas as disciplinas. Entretanto, as observações qualitativas e os registros quantitativos indicam que há um significativo espaço para a introdução de melhorias. A abordagem quali-quantitativa de avaliação permite a coleta de informações ricas e detalhadas, tendo como resultante uma visão mais integral da realidade.
Abstract: Recent changes in Brazilian higher education reinforce the need for flexible curricula and improved understanding of the educational reality in schools. This study aimed to diagnose the current situation of a Brazilian medical school using a qualitative/quantitative approach to evaluate core disciplines. We used documental analyzes, a quantitative approach with a questionnaire to evaluate courses, and a qualitative approach with participant observation of each couse evaluated by two independent observers. Answers were grouped into five categories: the teaching-learning process, the context of learning, the teacher-student relationship, ethics in the course, and students evaluation. There is a fair amount of satisfaction among students concerning the way courses have been taught, but qualitative observations and quantitative records suggest room for considerable improvement. A qualitative/quantitative approach can provide a detailed and integral view of reality.