FDA Approval Summary: Durvalumab and Pembrolizumab, Immune Checkpoint inhibitors for the Treatment of Biliary Tract Cancer.

On September 2, 2022, the Food and Drug Administration (FDA) approved durvalumab in combination with cisplatin and gemcitabine, for the treatment of patients with unresectable or metastatic biliary tract cancers (BTC). On October 31, 2023, the FDA approved pembrolizumab in combination with cisplatin and gemcitabine for the same indication. Approvals were based on two randomized, multiregional, placebo-controlled trials, which randomly allocated patients to receive durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966) in combination with chemotherapy or placebo in combination with chemotherapy. Overall survival (OS) was the primary endpoint in both studies. In both studies, a statistically significant and clinically meaningful improvement in OS was demonstrated. In the TOPAZ-1 trial the median OS of patients receiving durvalumab was 12.8 months (95% confidence interval [CI] 11.1, 14.0) and 11.5 months (95% CI 10.1, 12.5) in patients receiving placebo (HR 0.80 [95% CI 0.66, 0.97]). In the KEYNOTE-966 trial, the median OS of patients receiving pembrolizumab was 12.7 months (95% CI 11.5, 13.6) and 10.9 months (95% CI 9.9, 11.6) in patients receiving placebo (HR 0.83 [95% CI 0.72, 0.95]). The addition of checkpoint inhibitors to standard of care chemotherapy for this indication did not reveal any new adverse event signals and the safety profile was generally consistent with the known clinical experience with durvalumab, pembrolizumab, and the backbone chemotherapy regimen. The approvals of durvalumab and pembrolizumab in combination with standard of care cisplatin and gemcitabine for the treatment of unresectable or metastatic BTC add two new therapeutic option for these patients.

The potential use of mass timber in mid-to high-rise construction and the associated carbon benefits in the United States.

Nonresidential and mid- to high-rise multifamily residential structures in the United States currently use little wood per unit floor area installed, because earlier building codes lacked provisions for structural wood use in those types of buildings. However, revisions to the International Building Code allow for increased wood use in the form of mass timber, as structural and fire safety concerns have been addressed through new science-based design standards and through newly specified construction materials and measures. This study used multiple models to describe alternative futures for new construction, mass timber adoption rates, and the associated carbon benefits in higher than three-story buildings in the United States. The use of mass timber, in place of traditional constructions (i.e., structures dominated by concrete and steel), in projected new higher than three-story buildings was shown to provide combined carbon benefits (i.e., global warming mitigation benefits), including avoided embodied carbon emissions due to the substitution of non-wood alternatives and additional biogenic carbon storage in mass timber materials, of between 9.9 and 16.5 million t CO2e/yr spanning 50 years, 2020 to 2070. These carbon benefits equate to 12% to 20% of the total U.S. harvested wood products carbon storage for 2020. Future research is needed to understand how greater mass timber adoption leads to changes in forest product markets, land use, and total forest sector carbon.

Relative importance of VECTRI model parameters in the malaria disease transmission and prevalence.

In this study, a sensitivity analysis on a VECTRI dynamical model of malaria transmission is investigated to determine the relative importance of model parameters to disease transmission and prevalence. Apart from being most climatic prone, Odisha is a highly endemic state for malaria in India. The lack in sufficient modeling studies severely impacts the malarial process studies which further hinder the possibility of malaria early warning systems and preventive measures to be undertaken beforehand. Therefore, modeling studies and investigating the relationship between malaria transmission process studies and associated climatic factors are the need of the hour. Environmental conditions have pronounced effects on the malaria transmission dynamics and abundance of the poikilothermic vectors, but the exact relationship of sensitivity for these parameters is not well established. Sensitivity analysis is a useful tool for ascertaining model responses to different input variables. Therefore, in order to perform the requisite study, a dynamical model, VECTRI, is utilized. The study period ranges from 2000 to 2013, where several sensitivity tests are performed using different model parameters such as infiltration and evaporation rate loss of ponds, degree-days for parasite development, threshold temperature for parasite development, threshold temperature for egg development in the vector, and maximum and minimum temperature for larvae survival. The experiments suggest that the lower value of minimum temperature for larvae survival (rlarv_tmin), i.e., 16 °C, provides higher vector density and entomological inoculation rate (EIR) values. EIR reaches its maximum, when the threshold temperature for parasite development (rtsporo) is 22 °C and degree-days for parasite development (dsporo) is 8 degree-days. No change is observed in the vector density; even when rtsporo is 30 °C, values of EIR are close to 0. A successive increment of infiltration and evaporation rate loss of ponds (rwaterfrac evap126) values from 130 to 200 mm/day result in approximately 5% consistent decline in vector density and EIR. The study concludes that the most sensitive parameters are dsporo, rlarv_tmin, and rwaterfrac evap126. The VECTRI model is rather insensitive to maximum temperature for larvae survival (rlarv_tmin) for vector density and EIR variables. Further certain modifications and improvements are required in VECTRI to predict out variables like vector density and EIR more accurately in highly endemic region.

Expression pattern of candidate genes and their correlation with various metabolites of abscisic acid biosynthetic pathway under drought stress in rice.

Drought hampers global rice production. Abscisic acid (ABA) plays versatile roles under different environmental stresses. While the link between drought and ABA is known, its effect on ABA biosynthesis genes and metabolites is unclear. This study explored the impact of drought on various metabolites, namely beta-carotene, zeaxanthin, antheraxanthin, violaxanthin, neoxanthin, and candidate genes viz. zeaxanthin epoxidase (ZEP) and 9-cis epoxycarotenoid dioxygenase (NCED) of ABA biosynthesis pathway in rice cultivars (N22 and IR64) at anthesis {65 DAT (Days after transplanting)} with different stress levels. In stressed plants, zeaxanthin significantly increased (92%), while the concentration of beta-carotene, antheraxanthin, violaxanthin and neoxanthin decreased as drought stress progressed. The concentration of metabolites in roots was notably lower than in leaves in both genotypes. The ZEP expression was upregulated in roots (8.24-fold) under drought stress. Among five NCED isoforms, NCED3 showed significant upregulation (7.29-fold) in leaf and root tissue. NCED1 was significantly downregulated as stress progressed and was negatively correlated with ABA accumulation. NCED2, NCED4 and NCED5 showed no significant change in their expression. Drying and rolling of rice leaves was observed after imparting drought stress. The findings revealed that drought stress significantly influenced the expression of candidate genes and the concentration of metabolites of the ABA biosynthesis pathway. There was a significantly higher accumulation of ABA in N22 leaves (47%) and roots (30%) compared to IR64. The N22, a drought-tolerant genotype, exhibited significantly higher concentrations of intermediates and demonstrated increased expression of ZEP and NCED3, potentially contributing to its resilience against drought.

A newer approach in the treatment of seborrheic dermatitis with QR678® and QR678 Neo®-A prospective pilot study.

BACKGROUND: Seborrheic dermatitis is a common chronic inflammatory skin disorder that affects the scalp and is characterized by erythema and oily scales. It could perhaps be difficult to control and could seriously degrade one's quality of life. The study's objective is to assess the effectiveness of intradermal administrations of QR678 Neo® hair growth factor therapy for the treatment of scalp seborrheic dermatitis in both men and women. METHOD: Forty male and female patients with clinically diagnosed seborrheic dermatitis of the scalp in the age 18-45 years, not satisfactorily responding to standard therapy for at least 6 months, were included. 1 mL solution of QR678 Neo® was administered in the scalp skin of all patients at 3-week interval till eight sessions. Patients were advised to continue with antifungal shampoo and topical antifungal solution with steroid combination which they had been on during the treatment. Assessment of disease severity, dermoscopic evaluation, and self-assessment were done at baseline and at the end of the fourth and the eighth sessions. RESULTS: Improvement was observed in adherent scalp flaking score after eighth session (mean = 12) compared to baseline (mean = 60). The dermoscopic evaluation showed a noticeable difference from baseline (mean = 11) in erythema and scaling with the Seborrheic Dermatitis Scalp Severity Index tool at the end of treatment (mean = 2). A high satisfaction score was given for the efficiency in the self-assessment questionnaire. CONCLUSION: Our study proved that treatment with QR678 Neo® led to an improvement in the overall scalp condition by the resolution of flaking and inflammation.

Landscape Analysis of Generic Availability for Oncologic Drugs.

BACKGROUND: Improving generic drug development in oncology is a key long-term goal in providing safe, effective, and affordable care to patients with a diagnosis of cancer in the United States. There are multiple drug and non-drug related variables that may influence generic drug development. To illustrate pertinent associations relevant to generic drug competition in oncology, our study assessed variables that have potentially led to difference in generic competition as compared to drug products in other therapeutic areas, i.e., cardiovascular disease in this case. METHODS: Using a combination of FDA and publicly available data, we categorized individual drug approvals from 1950 to 2021 with either an oncology or cardiovascular indication. Descriptive statistics highlighted the timeline of approval as stratified by indications. Machine learning methodology was used to assess variables associated with abbreviated new drug application (ANDA) availabilities (i.e., generic drug availabilities). Kaplan-Meier analysis with log-rank test compared the difference in the time to approval of first ANDA among products that were off-patent at the time of analysis. A multivariable Cox proportional hazards model with forward selection was used to identify variables (e.g., regulatory recommendation issued, dosage form) that were associated with ANDA availability among products that were off-patent. RESULTS: 434 separate reference listed drugs (RLDs) with varying strengths were identified, 212 (49%) for oncology and 222 (51%) for cardiovascular indications. Compared with cardiovascular products, a greater proportion of RLDs with an oncology indication were approved after 2000 (61% vs. 34%). Also, a smaller proportion of oncologic products had generics (49% vs. 80%). Machine learning methodology revealed RLD age, patent status, product complexity, sales/prescriptions, and regulatory recommendations as variables that were associated with generic availability. Among products off-patent at the time of analysis, the median time from RLD approval to the first ANDA approval was longer for oncologic products compared to cardiovascular products (15.4 years (95% CI 13.8, 17.9) versus 12.3 years (95% CI 10.7, 13.5), p = 0.008). Cox regression analyses identified the variables of product dosage form and regulatory recommendation of requiring patient enrollment for bioequivalence (BE) establishment as being associated with reduced likelihood of ANDA approval for oncologic drugs. CONCLUSION: Oncology indications were found to have a longer time from RLD approval to first ANDA approval compared with cardiovascular drugs. Our work has identified variables that may influence time to ANDA availability, with the requirement of patient enrollment for BE assessment as one important opportunity for future stakeholder engagement and regulatory considerations.

Patterns and Trends of Facial Fractures at a Tertiary Care Trauma Center in India - A 13 years Retrospective Study.

Study Design: Retrospective study. Objective: The purpose of this study was to retrospectively analyze the prevalence, pattern, diagnosis, and treatment of the facial fractures falling under ambit of facial plastic surgery in a multi-specialty hospital at India from the year 2006-2019. Methods: This retrospective study analyzed 1508 patients, having orbital fractures (from 2006 to 2019) for demographic data, cause of trauma, type of fracture, and the treatment given. The data were compiled in excel and analyzed by using SPSS version 21.0. Results: Out of these 1508 patient (1127 (74.73%)-males and 381 (25.27%)-females), the etiology of injuries was Road traffic accident (RTA) (49.20%), assault (26.52%), and sports injuries (11.47%). The most common fracture pattern was Isolated Orbit and/or Orbital Floor fracture in 451 patients (32.08%), followed by Mid-facial fractures (21.93%). Also, 105 patients (6.96%) experienced ocular/retinal trauma along with other fractures. Conclusions: Orbit, peri-ocular, and mid-face trauma comprised a large position of this study. It requires a great deal of expertise to treat such complex trauma, which is not covered in one specialty alone. Hence, a holistic approach of craniofacial fracture management, rather than limiting these skills to water-tight craniofacial compartments becomes necessary. The study highlights the critical need of multidisciplinary approach for predictable and successful management of such complex cases.

Waldenström macroglobulinemia with secondary pure red cell aplasia in a patient with metastatic castrate resistant prostate cancer receiving an immune checkpoint inhibitor: a case report.

BACKGROUND: Hypoproliferative anemia is a frequently encountered adverse event in cancer patients receiving immune checkpoint inhibitors (ICI). Secondary pure red cell aplasia (PRCA) is a rare but recognized immune related adverse event. With the burgeoning use of ICIs, the association of secondary PRCA with an underlying lymphoproliferative disorder is often overlooked. CASE PRESENTATION: We report a case of a 67-year-old non-Hispanic Caucasian male with metastatic castrate resistant prostate cancer, who developed severe transfusion dependent anemia with reticulocytopenia while receiving treatment with olaparib and pembrolizumab. His bone marrow findings demonstrated erythroid hypoplasia, in addition to a CD5-negative, CD10-negative monotypic B-cell population and a somatic MYD88L265P mutation. With a presence of an IgM-paraprotein, he was diagnosed with Waldenström macroglobulinemia (WM) with secondary PRCA and treated with 6 cycles of bendamustine and rituximab. He achieved a complete response with this regimen and was transfusion independent. CONCLUSION: In this case, underlying WM was uncovered through systematic investigation of anemia caused by ICI therapy. This report highlights the possibility of a lymphoproliferative disorder in patients with concerns for PRCA with prior ICI exposure. If identified, treating the underlying lymphoproliferative disorder is highly efficacious in the management of the secondary PRCA.

COVID-19 vaccination acceptance and adherence among pregnant and lactating high-risk group individuals of Maharashtra State, India.

BACKGROUND: Since the outbreak of the pandemic, the release of the COVID (Corona Virus Disease)-19 vaccine was highly anticipated. Nevertheless, vaccine availability does not symbolize the end of pandemic due to ongoing vaccine hesitancy and anti-vaccination movements. The objective of this study is to evaluate COVID-19 vaccine acceptance among pregnant and lactating individuals in Maharashtra state, India. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted via a hybrid approach using various digital portals such as Whatsapp, telegram, and physical distribution to those who did not have access to smartphone devices. A probability proportional sampling strategy was deployed. A pre-validated structured self-administered questionnaire tool designed by Freeman et al. 2020 (Oxford COVID-19 vaccine hesitancy scale) was used, which consisted of seven close-ended targeted and focused questions. Analysis of several survey items and vaccine acceptance was conducted using the Chi-square test. RESULTS: Analysis revealed that 58% of individuals were willing to take vaccines after government approval and 26% of individuals showed hesitancy toward vaccination. When compared, lactating individuals showed less vaccine hesitancy (22%) than pregnant individuals (27%). The maximum vaccine hesitancy was observed in the third trimester of pregnancy (29.5%). CONCLUSIONS: Trust in vaccines is a crucial factor and is dependent on the ability of the government in promoting vaccines through effective communication; this can be one of the reasons for the high level of acceptance and awareness toward COVID-19 vaccination in this study.

Multidimensional perfectionism trends among various core and allied health care professionals in a major Indian metropolitan city of Western India.

BACKGROUND: This exploratory study was done to assess the multidimensional perfectionism trends among various core and allied health care professionals in a major Indian metropolitan city of western India. Unlike other scales, here we considered both individual and intersubjective components of perfectionism by introducing three trait dimensions - self-oriented perfectionism, other-oriented perfectionism, and socially prescribed perfectionism. MATERIALS AND METHODS: A cross-sectional descriptive type of study was conducted with total sample consisting of 500 participants with the main motive of evaluation and comparison of the multidimensional perfectionism among interns of the core and allied health care professionals from fields of medicine, dentistry, ayurveda, and homeopathy residing in the major Indian metropolitan cities of western India. RESULTS: This study showed that under the self-oriented domain, highest mean score is of medical faculty (73.97). In other-oriented domain, dental (62.62) and homeopathy (62.38) professionals have almost similar mean. Lowest being of ayurveda (61.65) compared to the highest score of the medical fraternity (67.62). In the socially prescribed domain, medical professionals (65.53) have the highest mean though it is the lowest mean value of the medical faculty compared to other two domains. Chi-square test is applied to the data for the questions among all the three domains. Correlation has been deduced by applying Pearson's correlation to the collected data from the study. The degree of correlation between self-oriented with self-oriented is 1, self-oriented with other-oriented is 0.763, and that of self-oriented with socially oriented is 0.678. CONCLUSION: Medical professionals scoring maximum in self-oriented perfectionism compared to other two domains reflect their extreme personal standards. Medical professionals are followed by dental professionals in self oriented perfectionism who are demanded of perfection in their routine practice. Ayurveda and homeopathy professionals scored better in other-oriented and socially prescribed perfectionism attributing to their sentiments of fulfilling the expectations and demands of others.

Evolution and Trends of Facial Plastic Surgery and Facial Aesthetic Procedures in India: From Awakening to Revival.

Facial aesthetic surgery is an emerging branch worldwide. India, a torchbearer country in facial plastic surgery, has seen tremendous growth in medical technology, resources, and clientele over the past century. This study aims to study past practices and current trends in facial plastic surgery and aesthetic procedures in India by individually addressing commonly performed nonsurgical procedures (Botox, Kybella [Allergan, Irvine, CA], fillers, threads, micro-focused ultrasound, and nonsurgical hair restoration), and surgical procedures (rhinoplasty, blepharoplasty, hair transplant, and facelift). It also aims to further elaborate on the scope of facial aesthetics and make recommendations on prospects in the field. A structured scoping review and a subsequent evidence-based synthesis were done following an extensive literature search on various databases such as PubMed (National Institutes of Health, Bethesda, MD), LILACS (Latin American and Caribbean Center on Health Sciences Information, São Paulo, Brazil), MEDLINE (National Library of Medicine, Bethesda, MD), EMBASE (Elsevier, Amsterdam, the Netherlands), and Cochrane (Wiley, Hoboken, NJ). The initial search yielded 703 articles, out of which 20 were found to be relevant to the present study and discussed. It was found that there is an upward trend in the growth of facial plastic surgery in India, and a gradual shift in patient attitude toward nonsurgical aesthetic procedures was seen. This article affirms the growth of facial aesthetic surgery in India by highlighting the recent development and trends in the practices of surgeons. It also addresses the shortcomings in the current administration and makes recommendations to fill the existing loopholes in plastic surgery.

Pediatric Dental Fluorosis and Its Correlation with Dental Caries and Oral-Health-Related Quality of Life: A Descriptive Cross-Sectional Study among Preschool Children Living in Belagavi.

AIM: This study aims to assess the prevalence of dental fluorosis and its association with dental caries, oral health behaviors, oral-health-related quality of life and parents' perceptions among preschool children in the 3-5-year-old preschool children living in the Belagavi district of Karnataka, a non-endemic fluorosis region. METHODS: A descriptive cross-sectional questionnaire-based study was conducted among 1200 individuals of the preschool population from 48 government-sponsored child-care development centers in Belagavi, Karnataka, over a three-month period. They were examined following the Dean's fluorosis index (1942) and dmft (decayed, missed, and filled) scores of the participants were also recorded. Parents' perception of oral health was assessed using the self-administered Early Childhood Oral Health Impact Scale (ECOHIS). SPSS software (version 20) was used for statistical analysis. Chi-square test computed categorical data. One-way ANOVA test was used for multiple group comparisons. p < 0.05 was considered statistically significant. RESULTS: Of the 1200 children examined, 10 (0.83%) children exhibited dental fluorosis. Of the 10 children having fluorosis, six had fluorosis present on two or more of their primary teeth, and four had fluorosis on four or more teeth. The mean dmft score was 3.01 ± 1.38 to 3.60 ± 1.72 in 3-5-year-old children, respectively, with statistical significance difference (p < 0.001). The mean score of oral health-related quality of life was 10.74 ± 2.06, which was significantly correlated to the child's age and parents' education level (p < 0.05). CONCLUSION: The study shows a negligible amount of prevalence of dental fluorosis in the non-endemic fluorosis residential district. It also elucidates that children from lower and lower-middle socioeconomic status are more prone to suffer from dental fluorosis as compared to other groups. The mean score of ECOHIS increased proportionally with the caries experience, indicating a significant relationship between the dmft and ECOHIS score. Deciduous dentition fluorosis is often neglected, especially in areas that are not considered endemic for fluorosis and with only optimum fluoride levels in their groundwater, which supports the disease's nature as multi-factorial and shows that a broader perspective is of prime importance to assess, diagnose, and prevent dental fluorosis among the preschoolers, thereby appraising their overall health and hygiene status.

Dynamic routing for efficient waste collection in resource constrained societies.

Waste collection in developing nations faces multi-fold challenges, such as resource constraints and real-time changes in waste values, while finding the optimal routes. This paper attempts to address these challenges by modeling real-time waste values in smart bins and Collection Vehicles (CV). Further, waste value prioritized routes for coordinated CV, during various time intervals are modeled in a multi-agent environment for finding good routes. The CV, as agents, implement the formulated linear program to maximize the collected waste while minimizing the distance to the central depot. The city of Chandigarh, India, was divided into regions and the model was implemented to achieve significantly better performance in terms of waste collected in less distance and total bins covered when compared to the existing scenario. The stakeholders can use the outcomes to effectively plan the resources for better collection practices, which will have a positive impact on the environment.

Effectiveness of HIFU Therapy for Nonsurgical Facial and Body Contouring: A Systematic Review of Prospective and Experimental Studies.

BACKGROUND: Liposuction, the most common body sculpting surgical procedure known today is associated with the risk of numerous complications. A safer and more noninvasive approach involves the use of high-intensity focused ultrasonography (HIFU) lasers, which work by selectively damaging fat tissue through apoptosis or necrosis induction of fat cells. The authors' systematic review was designed to identify the effectiveness of HIFU for nonsurgical facial and body contouring. METHODS: An exhaustive literature search was conducted of the PubMed/MEDLINE, Cochrane Central, Scopus, and EBSCO electronic databases for the period from November of 2005 to July of 2020. The full text of selected articles was reviewed for possible study inclusion, and articles fulfilling the inclusion criteria were recruited. Characteristics of the included studies were noted, and outcomes were assessed. Assessment of quality and risk of bias was performed for all the studies using the RevMan tool and the methodological index for nonrandomized studies. RESULTS: The initial search revealed a total of 4584 citations, of which only 11 were included in the present review: nine used HIFU for recontouring of the abdomen and only two used HIFU over the face and neck. Studies evaluated either the efficacy of HIFU or the safety of its use. The average total energy ranged from 140 to 248 J/cm 2 for the abdominal region and 0.3 to 1.2 J/cm 2 for the face and neck. The focal depth ranged from 1.1 to 1.8 cm. All the studies showed promising results with the use of HIFU. CONCLUSION: HIFU therapy is safe, effective, and minimally invasive, with predictable results when used for body and facial recontouring.

Determinants of the influence and experiences of cosmetic and aesthetics profiling on interpersonal relationships among Indian patients.

BACKGROUND: The notion of facial beauty is a fast-expanding field in many different disciplines. The determinants and the nature of inter-personal relationships remain a controversial issue. Here, we tackle such questions proposing a novel experimental approach by analyzing first-hand experiences and quality of life among Indian patients, who underwent cosmetic procedures and the subsequent impact of these aesthetic treatments on interpersonal relationships. METHODS: The data collection tool consisted of questions pertaining to the relations between the human face and facial image, relations between the race and facial image and interpersonal relationships and facial image. The tool consisted of 27 questions that were descriptive and closed ended without alternate choices. RESULTS: The study gauged the perception of an ideal facial image among both genders also highlighting the multifaceted nature of a persons' beauty and how its perception is affected by peers, society, and race. CONCLUSION: Though there was a gender-based difference found in the opinions on facial image, majority of the people experienced an ameliorated experience in their relationships with family and peers.

FDA Approval Summary: Ripretinib for Advanced Gastrointestinal Stromal Tumor.

On May 15, 2020, the FDA approved ripretinib for adult patients with advanced gastrointestinal stromal tumor who have received prior treatment with three or more kinase inhibitors, including imatinib. The approval was based on results from INVICTUS (NCT03353753), an international, multi-center, double-blind, placebo-controlled trial. Patients were randomly allocated (2:1) to receive either ripretinib 150 mg once daily (n = 85) or matching placebo (n = 44). The trial demonstrated a statistically significant improvement in progression-free survival (PFS) as assessed by modified RECIST v1.1 by blinded independent central review for patients randomized to ripretinib, with a median PFS of 6.3 months [95% confidence interval (CI): 4.6-6.9] compared with 1.0 month (95% CI: 0.9-1.7) for placebo [HR: 0.15 (95% CI: 0.09-0.25); P < 0.0001, stratified log-rank test]. There was no statistically significant difference in objective response rate in the ripretinib arm, 9% (95% CI: 4.2-18) compared with placebo 0% [(95% CI: 0-8); P = 0.0504, Fisher exact test]. The median overall survival (OS) in the ripretinib arm was 15.1 months (95% CI: 12.3-15.1) compared with 6.6 months (95% CI: 4.1-11.6) in the placebo arm. A formal statistical comparison of OS was not made due to the prespecified hierarchical analysis plan. The most common (≥20%) adverse events with ripretinib, in order of decreasing frequency, were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia, and vomiting. Other important risks of ripretinib include new primary cutaneous malignancies, hypertension, and cardiac dysfunction.

Toxicity assessment of metribuzin and its amelioration through plant growth regulators in Vigna radiata (L.) R. Wilczek.

The present experiment was conducted to evaluate the metribuzin-induced stress response in Vigna radiata and to explore the ameliorative role of exogenous application of plant growth regulators (PGRs) against metribuzin toxicity by assessing important biochemical and yield parameters. Prior to the field experiment, dose standardization experiments were performed, and EC50 was calculated for metribuzin. On day 21, field grown V. radiata plants were treated with graded concentrations of metribuzin (0-1000 mg [Formula: see text]). Plants treated with 600 mg [Formula: see text] (EC50) and 1000 mg [Formula: see text] (highest dose) of metribuzin were co-treated individually and simultaneously with gibberellic acid-3 (GA), indole-3 acetic acid (IAA), and salicylic acid (SA). After 7 days of treatment, leaf tissues were analyzed for biochemical parameters, whereas those related to yield were recorded during harvest. The result of this study indicated that metribuzin treatment to V. radiata resulted in increase in lipid peroxidation and reduce chlorophyll and carotenoid contents as well as yield parameters. However, metribuzin-treated plants induced proline accumulation and activity of antioxidant enzymes. Exogenous application of GA, IAA, and SA significantly reduced lipid peroxidation and increased contents of photosynthetic pigments, proline, and antioxidant enzymes thereby increasing yield parameters. It was observed that during metribuzin stress, SA exhibited a better ameliorative response out of the three exogenously applied PGRs, while the combined use of all PGRs exhibited much improved ameliorative response on biochemical and yield parameters of plants.

Cost-effectiveness of the Flapless Insertion of Zygomatic Implants Using Dynamic Navigation - A Retrospective Study.

Introduction: Zygomatic implants are an effective solution for rehabilitation of edentulous atrophic maxillae. However, the conventional technique of zygomatic implant placement is invasive, requires a longer healing period and is economically cumbersome. Therefore, the flapless technique of insertion of zygomatic implants using dynamic navigation system has been introduced. This study aims to compare the cost-effectiveness of flapless insertion of zygomatic implants using dynamic navigation to the conventional flap technique. Materials and Methods: The study participants were divided into two groups: Group A (n = 20) included patients treated by flapless insertion of zygomatic implants using dynamic navigation and Group B (n = 20) included patients treated with zygomatic implants using the flap technique. An analysis of the effectiveness of the implants was done using the concept of quality-adjusted prosthesis years, and an analysis of the costs was done by evaluating the treatment costs at each step. The data were collected, and analysis was done using IBM SPSS software. The Kruskal-Wallis rank-sum test was employed to analyse variations in costs and effects between the two groups. Results: The study showed that the distribution of costs varies across both the categories of the procedure. Group B shows lesser cost-effectiveness as compared to Group A. Conclusion: The technique of flapless insertion of zygomatic implants is cost-effective. However, further studies considering factors such as time and cost of productivity evaluating the cost-effectiveness should be conducted.

Interest of Oral and Maxillofacial Surgeons Towards Specialised Training in Facial Aesthetic and Plastic Surgery in India - An Evaluative Study.

Introduction: The Dental Council of India has included facial plastic surgery in the scope of practice of Oral and Maxillofacial Surgeons (OMFSs) in India. However, the knowledge and interests of these specialists towards facial plastic surgery are unexplored. Materials and Methods: A descriptive cross-sectional study consisting of a structured questionnaire tool with six domains and 46 questions was circulated amongst registered OMFSs in India. The study consisted of 950 participants. The data obtained from this questionnaire were coded and entered into Statistical Package for Social Sciences (SPSS) and a descriptive analysis was conducted. Results: The study yielded that only 33% of the participants were completely aware of facial fillers and 30.5% were aware of Botox procedure. However, there was complete awareness of blepharoplasty in 42%, cheiloplasty/palatoplasty in 65.8%, laser facial resurfacing in 23.7% and facial rejuvenation in 23.5% of the participants. Discussion: It was found that a high number of OMFSs felt that their exposure to plastic surgery during their post-graduation years was not sufficient.

Multidimensional Indicators as Enablers on Perception of Facial Beauty and Appearance among Indian Population: A Descriptive Cross-Sectional Study.

Background: Facial appearance has been a flagbearer of "beauty" since time immemorial. Perception of beauty is highly influenced by cultural, interpersonal, and intra-personal variations. Objectives: This study aimed to assess the perception of facial beauty and appearance through multidimensional influencing indicators among the Indian population, and to determine whether the physically attractive person possesses more personal and socially desirable traits than the comparatively less attractive individual. Materials and Methods: A study population of 474 with equal male and female population of Indian origin was selected. Their perception was assessed based on the prevalidated, self-administered questionnaire using a tool with five major multidimensional indicators. Six images were selected, three each of male and female subjects, and labeled as A, B, and C, in descending order of attractiveness. The multidimensional influencing indicator tool was self-administered to the participants and the responses were recorded individually. Results: Photograph A scored the highest out of the three grading scales in both males and females. Conclusion: The most attractive photograph, in both males and females, was deemed to be associated with higher scores of attractiveness and success.