Indirect treatment comparison of dabrafenib plus trametinib versus vemurafenib plus cobimetinib in previously untreated metastatic melanoma patients.

BackgroundMetastatic melanoma is an aggressive form of skin cancer with a high mortality rate and the fastest growing global incidence rate of all malignancies. The introduction of BRAF/MEK inhibitor combinations has yielded significant increases in PFS and OS for melanoma. However, at present, no direct comparisons between different BRAF/MEK combinations have been conducted. In light of this, an indirect treatment comparison was performed between two BRAF/MEK inhibitor combination therapies for metastatic melanoma, dabrafenib plus trametinib and vemurafenib plus cobimetinib, in order to understand the relative efficacy and toxicity profiles of these therapies.MethodsA systematic literature search identified two randomized trials as suitable for indirect comparison: the coBRIM trial of vemurafenib plus cobimetinib versus vemurafenib and the COMBI-v trial of dabrafenib plus trametinib versus vemurafenib. The comparison followed the method of Bucher et al. and analyzed both efficacy (overall survival [OS], progression-free survival [PFS], and overall response rate [ORR]) and safety outcomes (adverse events [AEs]).ResultsThe indirect comparison revealed similar efficacy outcomes between both therapies, with no statistically significant difference between therapies for OS (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.68 - 1.30), PFS (HR 1.05, 95% CI 0.79 - 1.40), or ORR (risk ratio [RR] 0.90, 95% CI 0.74 - 1.10). Dabrafenib plus trametinib differed significantly from vemurafenib plus cobimetinib with regard to the incidence of treatment-related AE (RR 0.92, 95% CI 0.87 - 0.97), any AE grade ≥3 (RR 0.71, 95% CI 0.60 - 0.85) or dose interruption/modification (RR 0.77, 95% CI 0.60 - 0.99). Several categories of AEs occurred significantly more frequently with vemurafenib plus cobimetinib, while some occurred significantly more frequently with dabrafenib plus trametinib. For severe AEs (grade 3 or above), four occurred significantly more frequently with vemurafenib plus cobimetinib and no severe AE occurred significantly more frequently with dabrafenib plus trametinib.ConclusionsThis indirect treatment comparison suggested that dabrafenib plus trametinib had comparable efficacy to vemurafenib plus cobimetinib but was associated with reduced adverse events

Mobilizing Marginalized Citizens: Ethnic Parties Without Ethnic Movements.

This dissertation answers three questions: How is the mobilization of marginalized ethnic groups distinct from other groups? How do the social movements of a marginalized group impact its electoral mobilization by political parties? Why do ethnic parties of a marginalized group succeed in some cases, but fail in others? I study the democratic participation and mobilization of Dalits (former untouchables) across four large states in India – Uttar Pradesh, Bihar, Maharashtra, and Tamil Nadu. The study design takes advantage of a natural experiment created by the early movements of Dalits in some states, but not in others. Variation in the electoral performance of Dalit political parties at a moment of opportunity marked by party system fragmentation across all the states enables an exploration of how historical Dalit movements impact the prospects of Dalit parties. Drawing on data from the Indian National Election Study and findings gathered through eighty focus groups and more than four hundred open-ended interviews during fourteen months of fieldwork, I demonstrate that prior social movements demanding social inclusion curtail the electoral success of Dalit-based political parties. Where historically Dalits were able to participate in social movements, political parties seeking their support began to mobilize them directly. Consequently, historical movements opposing the principle of social hierarchy resulted in the early inclusion of Dalits into multiethnic parties. Conversely, the absence of movements prevented multiethnic parties from developing inclusive mobilization strategies; this preserved the opportunity for ethnic parties to mobilize the marginalized on the basis of their exclusion. The divergent paths through inclusive multiethnic politics in some states and exclusive ethnic politics in others point towards different consequences for the quality of governance, in particular for the provision of public services.Ph.D.Political ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/61773/1/aahuja_2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/61773/2/aahuja_1.pd

Evaluation of Lung Volume and Effect of Vital Staining as Motivation to Quit Tobacco among Nicotine Dependents of Kanpur, India

Objective: To quantify and compare respiratory functions and further screen the oral mucosa of tobacco and non-tobacco users. Material and Methods: First control group, non-tobacco users (n=55); Second group, smokers’ group (n=168) who currently smoked cigarettes; Third group smokeless/chewing type, tobacco group (n=81); Fourth group, both smokeless and smoking type tobacco users (n=46). Fagerstrom Test for Nicotine Dependences (FTND) and Fagerström Test for Nicotine Dependence-Smokeless Tobacco (FTND-ST) instruments were used to assess nicotine dependence. Subsequently, spirometry and Toluidine Blue (TB) vital staining were performed. Chi-squared and one-way analysis of variance (ANOVA) were used for statistical analysis. Results: Fagerstrom test resulted in 48.8% of subjects with low dependency, followed by an increase in nicotine dependency from low to moderate (29.2%), moderate (15.6%), and highly dependent (6.4%) groups. All respiratory function tests and oral screening confirmed significant changes amongst tobacco and non-tobacco users. The forced vital capacity of non-smoker group was significantly different from other tobacco users’ group (p<0.05). Conclusion: Early effects of tobacco use can lead to complications with the respiratory system and oral cavity. Such data can be used to delineate the harm of tobacco and should be used to urge individuals to evade the utilization of tobacco

Delivery of Bull Dog Calf from a Hydroallantoic Murrah Buffalo

An 8 years old Murrah buffalo in its 5th party was presented with the history of 9 month of gestation and sudden bilateral abdominal distension since last 25 days. Animal was 7 anorectic with pale mucus membrane and had staggering gait. Per vaginum examination revealed closed cervix with intact cervical seal. By transrectal palpation only the fluid in the uterus could be palpable. Based on history and clinical examination findings, it was diagnosed as hydroallantois. Parturition was induced using cloprostenol and dexamethasone. Beside this an intracervical injection of closprostenol was also given on 6 o’clock and 12 o’clock position (250 µg each) of external os to hasten the cervical dilation. A dead bulldog calf was removed with manual traction after 26 hours of initial treatment. It was concluded that the cloprostenol and dexamethasone are effective for the induction of parturition in animals suffering from hydroallantois provided fluid from the allantoic sac is removed slowly.