Adjustment for imbalances in baseline characteristics in the MAGNITUDE phase 3 study confirms the clinical benefit of niraparib in combination with abiraterone acetate plus prednisone in patients with metastatic prostate cancer.

BACKGROUND: MAGNITUDE (NCT03748641) demonstrated favourable outcomes with niraparib plus abiraterone acetate plus prednisone (+AAP) versus placebo+AAP in patients with BRCA1/2-altered metastatic castration-resistant prostate cancer (mCRPC). Imbalances in prognostic variables were reported between arms, which impacts estimation of both the clinical benefit and cost­effectiveness of niraparib+AAP for healthcare systems. A pre-specified multivariable analysis (MVA) demonstrated improved overall survival (OS) with niraparib+AAP. Here, we used an inverse probability of treatment weighting (IPTW) model to adjust for covariate imbalances and assess time-to-event outcomes. METHODS: IPTW analysis of time-to-event outcomes was conducted using data from patients with BRCA1/2-altered mCRPC (N = 225) in MAGNITUDE. Patients received niraparib+AAP or placebo+AAP. OS, radiographic progression-free survival, time to symptomatic progression, time to initiation of cytotoxic chemotherapy and time to prostate-specific antigen progression were assessed. Weighted Kaplan-Meier curves were generated for each endpoint, and adjusted hazard ratios (HR) were obtained from a weighted Cox model. RESULTS: Improvements in survival outcomes were estimated for niraparib+AAP versus placebo+AAP: unadjusted median OS was 30.4 months versus 28.6 months, respectively (HR: 0.79; 95 % confidence interval [CI]: 0.55, 1.12; p = 0.183). Following IPTW, median OS increased to 34.1 months with niraparib+AAP versus a decrease to 27.4 with placebo (HR: 0.65; 95 % CI: 0.46, 0.93; p = 0.017). Similar improvements were observed for other time-to-event endpoints. CONCLUSIONS: IPTW adjustment provided a more precise estimate of the clinical benefit of niraparib+AAP versus placebo+AAP in patients with BRCA1/2-altered mCRPC. Results were consistent with the pre-specified MVA, and further demonstrated the value of adjusting for baseline imbalances, particularly in smaller studies. TRIAL REGISTRATION: NCT03748641 (MAGNITUDE).

Anatomical factors of the maxillary tuberosity that influence molar distalization.

Objective: To examine the areas of the maxillary tuberosity (MT) (coronal, apical, width, and height) with respect to the presence or absence of the third molar to establish possible anatomical limitations for molar distalization. Methods: A total of 277 tuberosities were evaluated through sagittal computed tomography (CT) images, divided for measurement into coronal (free of bone), apical (area of influence of the maxillary sinus), and tuberosity (bony area) zones, and stratified by the presence or absence of the third molar, sex, and two age subgroups. Mann-Whitney U test was used to compare the groups considering the third molar. Results: The medians of the width and height of the tuberosity decreased significantly in the absence of the third molar (P < 0.001). The apical area also showed differences, with negative values in the absence of the third molar and positive values in the presence of the third molar (P < 0.001). However, no differences were observed for the coronal area (P > 0.05). Conclusions: In the absence of the third molar, the size of the MT, represented by its width and height, was smaller and negative values (decrease) were observed for the maxillary sinus. The sagittal CT provides useful information regarding the amount of bone tissue available for distalization and relationship of the second molar with respect to the maxillary sinus, which allows individualizing each case in relation to the amount and type of movement expected.

Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study.

Background: The prevalence of pathogenic germline mutations in DNA damage repair (gDDR) genes in the Italian population is unknown. Objective: In this prospective multicenter cohort study, we evaluated the prevalence of gDDR alterations in the Italian population affected by metastatic prostate cancer (mPCa) and analyzed the impact on response to therapy, survival, and time to castration resistance. Design setting and participants: In an observational prospective trial, 300 consecutive Italian mPCa patients, enrolled in the Meet-Uro-10 trial from three academic Italian centers, were recruited between 2017 and 2019 and were screened for gDDR mutations in 107 genes. Outcome measurements and statistical analysis: The primary endpoint was to assess the prevalence of gDDR mutations in the Italian population of patients with mPCa. The secondary endpoints included the association of gDDR subgroups with metastatic onset, Gleason score, and time to castration resistance. Results and limitations: We identified 297 valuable patients. Forty-six patients had a pathogenic/likely pathogenic variant (15.5%, 95% confidence interval: 11.4-19.6): the more frequent was gBRCA2 found in nine cases (3%), followed by gATM in five cases (1.7%). In patients without mutations, longer median overall survival was observed with the sequence docetaxel-androgen receptor signaling inhibitor (ARSI) than with the sequence ARSI-docetaxel (87.9 vs 42 mo, p = 0.0001). In a univariate analysis, the median time to castration resistance in gDDR mutated patients was 19.8 mo, versus 23.7 mo in no mutated patients (p = 0.024). There were no associations of gDDR subgroups with metastatic onset and Gleason score ≥8. In our cohort, variants of unknown significance in gDDR genes were found in 80 patients and might have a prognostic relevance. Conclusions: The study reported the prevalence of gDDR in the Italian population. The presence of gBRCA2 mutations correlates with a shorter time to the onset of castration resistance disease. Patient summary: The prevalence of gBRCA2 in the Italian population is 3%, which is similar to that in the Spanish population, identifying similarities between people of the Western Mediterranean area.

Consideraciones especiales de bioseguridad en ortodoncia durante pandemia (SARS COV-2) / Special biosecurity considerations in orthodontics during pandemic (SARS COV-2) / Considerações especiais de biossegurança em ortodontia durante pandemia (SARS-COV-2)

Resumen El control periódico en un tratamiento de Ortodoncia permite establecer una buena secuencia de tratamiento sin riesgos para el paciente. Un tratamiento sin la vigilancia adecuada puede llegar a generar daños irreversibles. Sin embargo, por la pandemia de COVID-19 que enfrenta el mundo actualmente y los riesgos en el área de la salud, se han suspendido temporalmente los servicios no vitales y potencialmente expuestos a contagios como lo son los servicios odontológicos de consulta programada. Teniendo en cuenta esta situación, y que este virus puede llegar a ser endémico en la población humana, se hace necesario establecer protocolos de bioseguridad que permitan reactivar las prácticas odontológicas, y a su vez genear garantías para operadores, personal de apoyo, pacientes y el entorno de los mismos. En este contexto, es de gran importancia desarrollar un protocolo con profesionales expertos en tratamientos ortodóncicos y en el manejo de la pandemia, para delinear procesos de calidad que garanticen un ambiente seguro y minimicen los riesgos de contagio.

Abstract Periodic control in an Orthodontic treatment allows establishing a good treatment sequence without risks for the patient. Treatment without proper monitoring can lead to irreversible damage. However, due to the COVID-19 pandemic facing the world today and the risks in the health area, non-vital and potentially contagious services such as scheduled consultation dental services have been temporarily closed. Taking into account this situation, and that this virus will end up being endemic, it is necessary to establish biosafety protocols that allow reactivating dental practices, and in turn generate guarantees for operators, support staff, patients and the environment of the themselves. In this context, it is of great importance to develop a protocol carried out with expert professionals in orthodontic treatments and in the pandemic, to outline the quality protocol that guarantees a safe environment and minimizes the risks of infection.

Resumo O controle periódico em um tratamento ortodôntico permite estabelecer uma boa sequência de tratamento sem riscos para o paciente. O tratamento sem monitoramento adequado pode levar a danos irreversíveis. No entanto, devido à pandemia do COVID-19 que o mundo enfrenta atualmente e aos riscos na área da saúde, serviços não vitais e potencialmente contagiosos foram temporariamente suspensos, como serviços odontológicos agendados para consultas. Considerando essa situação e que esse vírus pode se tornar endêmico na população humana, é necessário estabelecer protocolos de biossegurança que permitam reativar as práticas odontológicas e, por sua vez, gerar garantias aos operadores, pessoal de apoio, pacientes e meio ambiente. Dos mesmos. Nesse contexto, é de grande importância o desenvolvimento de um protocolo com profissionais especialistas em tratamentos ortodônticos e no manejo da pandemia, para delinear processos de qualidade que garantam um ambiente seguro e minimizem os riscos de infecção.