Osimertinib is an irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that is highly selective for EGFR-activating mutations as well as the EGFR T790M mutation in patients with advanced non-small cell lung cancer (NSCLC) with EGFR oncogene addiction. Despite the documented efficacy of osimertinib in first- and second-line settings, patients inevitably develop resistance, with no further clear-cut therapeutic options to date other than chemotherapy and locally ablative therapy for selected individuals. On account of the high degree of tumour heterogeneity and adaptive cellular signalling pathways in NSCLC, the acquired osimertinib resistance is highly heterogeneous, encompassing EGFR-dependent as well as EGFR-independent mechanisms. Furthermore, data from repeat plasma genotyping analyses have highlighted differences in the frequency and preponderance of resistance mechanisms when osimertinib is administered in a front-line versus second-line setting, underlying the discrepancies in selection pressure and clonal evolution. This review summarises the molecular mechanisms of resistance to osimertinib in patients with advanced EGFR-mutated NSCLC, including MET/HER2 amplification, activation of the RAS–mitogen-activated protein kinase (MAPK) or RAS–phosphatidylinositol 3-kinase (PI3K) pathways, novel fusion events and histological/phenotypic transformation, as well as discussing the current evidence regarding potential new approaches to counteract osimertinib resistance.
A total of 1,670 school going children (urban 1030 and rural 640) in the age range of 12-14 years were screened for hearing loss during a survey conducted by the Department of Otolaryngology of the Postgraduate Institute of Medical Education & Research, Chandigarh. 6.31% of cases in the urban group were found to be having hearing loss as compared to 32.81% of cases in the rural group. Secretory otitis media was found to be the commonest cause of hearing impairment in both the urban and rural group accounting for 5.33% and 33.59% respectively.
ObjectivesHealthcare personnel (HCP) are at an increased risk of acquiring COVID-19 infection especially in resource-restricted healthcare settings, and return to homes unfit for self-isolation, making them apprehensive about COVID-19 duty and transmission risk to their families. We aimed at implementing a novel multidimensional HCP-centric evidence-based, dynamic policy with the objectives to reduce risk of HCP infection, ensure welfare and safety of the HCP and to improve willingness to accept and return to duty.SettingOur tertiary care university hospital, with 12 600 HCP, was divided into high-risk, medium-risk and low-risk zones. In the high-risk and medium-risk zones, we organised training, logistic support, postduty HCP welfare and collected feedback, and sent them home after they tested negative for COVID-19. We supervised use of appropriate personal protective equipment (PPE) and kept communication paperless.ParticipantsWe recruited willing low-risk HCP, aged <50 years, with no comorbidities to work in COVID-19 zones. Social distancing, hand hygiene and universal masking were advocated in the low-risk zone.ResultsBetween 31 March and 20 July 2020, we clinically screened 5553 outpatients, of whom 3012 (54.2%) were COVID-19 suspects managed in the medium-risk zone. Among them, 346 (11.4%) tested COVID-19 positive (57.2% male) and were managed in the high-risk zone with 19 (5.4%) deaths. One (0.08%) of the 1224 HCP in high-risk zone, 6 (0.62%) of 960 HCP in medium-risk zone and 23 (0.18%) of the 12 600 HCP in the low-risk zone tested positive at the end of shift. All the 30 COVID-19-positive HCP have since recovered. This HCP-centric policy resulted in low transmission rates (<1%), ensured satisfaction with training (92%), PPE (90.8%), medical and psychosocial support (79%) and improved acceptance of COVID-19 duty with 54.7% volunteering for re-deployment.ConclusionA multidimensional HCP-centric policy was effective in ensuring safety, satisfaction and welfare of HCP in a resource-poor setting and resulted in a willing workforce to fight the pandemic.
Objectives This study aimed to estimate the prevalence of depression and anxiety, and assess the knowledge, practice, and concerns regarding coronavirus disease 2019 (COVID-19) among the residents of an urban slum in Chandigarh, India. Materials and Methods Participants were screened using Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 scales. Results The mean (standard deviation) age of 200 enrolled participants was 33 (13) years with 83% (n = 166) being females. The prevalence of depression and anxiety was 3.5% (95% confidence interval [CI]: 0.95–6.05) and 2.5% (95% CI: 0.34–4.66), respectively. Of total, 46% (n = 92) knew that COVID-19 can transmit through droplets and 30.5% (n = 61) were concerned that they might get infected with disease. Half of the participants (n = 100) believed that there was unnecessary worry regarding COVID-19 and 78% (n = 156) covered mouth while coughing or sneezing. Conclusion To cope with this critical situation, it is necessary to strengthen the awareness programs targeting the mental health issues of the people.
Introduction: Diabetes mellitus is a chronic and progressive metabolic disorder. According to the World Health Organization (WHO) there is “an apparent epidemic of diabetes, which is strongly related to lifestyle and economic change.” Objective of the study was to assess the quality of life of people living with type 2 diabetes mellitus and factors associated with quality of life. Methods: A hospital-based cross-sectional study was conducted on 215 patients with diabetes mellitus. Quality of life was assessed using a generic instrument SF 36. The data was analyzed using SPSS, version 24.0. An independent t test and analysis of variance (ANOVA) were used to compare the means of each domain of quality of life within groups of various independent variables. Results: The mean age of respondents was 52.5 ± 11.0 years. The majority (87.4%) of the patients were married, Hindu by religion (88.8%), and belonged to upper socio economic class (28.8%). The mean duration since diagnosis of diabetes was 7.82 ± 6.0 years, and 80.4 percent of patients were on oral hypoglycemic agents. Hypertension was found to be the most common (24.6%) comorbidity. Age, education, socioeconomic status, duration of diabetes, type of treatment, complication of diabetes, comorbidities, and body mass index (BMI) were found to be significantly associated with various domains of SF-36. Conclusions: Diabetes has an adverse effect on quality of life of patients with diabetes. The most affected domain in male and female patients was vitality domain followed by general health domain of quality of life.
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