Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer.

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.

Prevalence of Depression and Anxiety during the COVID-19 Pandemic among the Residents of an Urban Slum in North India.

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.

Quality of life of type 2 diabetes mellitus patients attending a tertiary care hospital of Northern India: A cross sectional study.

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.

Higher coronavirus disease-19 mortality linked to comorbidities: A comparison between low-middle income and high-income countries.

BACKGROUND: Global burden of disease (GBD) provides the estimates of mortality and morbidity, while case fatality rate (CFR) helps in understanding the severity of the disease. People infected with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) with underlying medical conditions have shown higher levels of unfavorable outcomes including mortality. We assessed the association of SARS-CoV-2 CFR with disability-adjusted life years (DALY) of various comorbidities in the low-middle income countries (LMIC) and high-income countries (HIC) to study the relationship of coronavirus disease-19 (COVID-19) mortality with GBDs and to understand the linkage between COVID-19 mortality and comorbidities. MATERIALS AND METHODS: This was an ecological study with secondary data analysis comparing the DALY of various morbidities from GBD with CFR of COVID-19. Gross domestic product was the basis of stratifying 177 countries into low-middle income (LMIC) and high-income groups (HIC). The mortality was analyzed using Pearson correlation and linear regression. RESULTS: The median global CFR of SARS-CoV-2 was 2.15. The median CFR among LMIC (n = 60) and HIC (n = 117) was 2.01 (0.00-28.20) and 2.29 (0.00-17.26), respectively. The regression analysis found that, in both LMIC and HIC, maternal disorders were associated with higher SARS-CoV-2 CFR, while tuberculosis, mental health disorders, and were associated with lower CFR. Further, in LMIC, musculoskeletal disorders and nutritional deficiencies were associated with higher CFR, while respiratory disorders were associated with lower CFR. CONCLUSIONS: SARS-CoV-2 infection appears to be a systemic disease. Individuals with comorbidities, such as maternal disorders, neurological diseases, musculoskeletal disorders, and nutritional deficiencies, have poorer outcomes with COVID-19, leading to higher mortality.

Assessment of Potential Risk Factors for 2019-Novel Coronavirus (2019-nCov) Infection among Health Care Workers in a Tertiary Care Hospital, North India.

INTRODUCTION: Health care workers (HCWs) are at the forefront to fight against COVID-19 pandemic. They are at more risk of contracting the infection. This study was planned to assess potential risk factors of 2019-novel coronavirus infection among HCWs working in a health facility and to evaluate the effectiveness of infection prevention and control measures among them. METHODS: A study was conducted in a tertiary care hospital among HCWs who were directly or indirectly involved in the management of a confirmed or suspected case of COVID-19. The socio-demographic characteristics, history of exposure, IPC measures followed and clinical symptoms were compared between health care workers in COVID and non-COVID areas. RESULTS: Majority (45%) of HCWs were nurses, followed by hospital/sanitary/technical attendants (30%) and doctors (24%). Out of a total of 256 HCWs, 2% tested positive. Around 80% of HCWs had ever attended any IPC training. A statistically significant association was found between posting area of HCWs and their exposure to COVID patients (duration of exposure, PPE has worn by HCWs, direct contact of HCWs with the patient's material) and COVID positivity (P value <.001). CONCLUSION: If health care workers were trained and take adequate precautions then the risk of getting an infection is minimized.

Multidimensional dynamic healthcare personnel (HCP)-centric model from a low-income and middle-income country to support and protect COVID-19 warriors: a large prospective cohort study.

OBJECTIVES: Healthcare 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. SETTING: Our 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. PARTICIPANTS: We 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. RESULTS: Between 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. CONCLUSION: A 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.

Estimation of cardiovascular risk in a rural population of Lucknow district using WHO/ISH risk prediction charts.

CONTEXT: Cardiovascular diseases (CVDs) are the number one cause of death globally, with low- and middle-income countries being affected disproportionately. By 2020, it is projected that there will be 25 million deaths from CVD worldwide, 19 million of which would be from middle- and low-income countries. AIMS: The aim of this study was to estimate the 10-year risk of cardiovascular events among adults aged ≥40 years in a rural population of Lucknow district using the World Health Organization (WHO)/International Society of Hypertension (ISH) risk prediction charts for SEAR-D region. SETTINGS AND DESIGN: This was a community based cross-sectional study, conducted from September 2017 to August 2018, in the rural areas of Lucknow district. METHODS AND MATERIAL: This study was conducted on 397 subjects aged ≥40 years. The two sets of the WHO/ISH risk prediction charts, with and without cholesterol, for WHO SEAR-D region were used in the study. STATISTICAL ANALYSIS USED: SPSS, version 23 was used for data analysis. RESULTS: Using the risk assessment tools, with and without cholesterol, 78.5 and 76.8%, respectively, of the study population were in the 10-year cardiovascular risk category of <10% risk, while 11.2 and 10.4%, respectively, were in the category of ≥20% risk. Risk categories were found to be concordant in 86.3% of the population. CONCLUSIONS: The WHO/ISH risk prediction charts can be used at low-cost resource setting as a tool to predict CVD risk among asymptomatic individuals, thus, helping in early detection and prevention of CVDs in resource-scarce settings.