A Phase II Study of Metformin with Pemetrexed/Carboplatin in Patients with Metastatic Non-Squamous Non-Small Cell Lung Cancer

Introduction: There is a subset of NSCLC patients ineligible for benefit from TKIs/Immunotherapy (e.g. STK11 mutation conferring resistance to Immunotherapy). Besides, many patients cannot afford these therapies. Metformin has anticancer properties acting both on glycolytic metabolism and tumor microenvironment. In vitro studies suggest synergism between metformin and pemetrexed. STK11 deficient cell lines are more sensitive to metformin. Clinical studies combining metformin with chemotherapy are limited by small sample size. We conducted an exploratory phase-2 clinical trial of metformin with pemetrexed/carboplatin in advanced non-squamous NSCLC. Methods: This was a single center, open label, single arm phase 2 clinical trial with a Simon’s two stage design. The null hypothesis was that the combination would not improve the 6-month PFS rate by 15%, from 50%. Treatment-naive, non-diabetic patients aged 18-75 years with NSCLC (adenocarcinoma/not-otherwise-specified) with stage IV disease having ECOG PS 0-2 with unmutated EGFR/ALK and without brain metastasis or with asymptomatic brain metastases were treated with pemetrexed-carboplatin chemotherapy and metformin for six months. The primary outcome was 6-month progression free survival (PFS) rate. Secondary outcomes were safety, overall survival (OS), overall response rate (ORR), proportion of STK 11 mutation and effect of STK 11 mutation on 6-month PFS rate. PFS and OS were estimated using the Kaplan-Meier method. Targeted sequencing was attempted for available tissue specimens. Results: The first interim analysis was performed after enrollment of 26 patients for the first stage (before the target accrual of first stage was reached) due to slow accrual, in view of COVID pandemic. The study was terminated after first stage for futility. The median age of patients in the study was 52 years (range, 30 to 68) and 18 patients (69.0%) were males. Half of the patients had ECOG-PS 2. Brain metastases were present in eight (31%) patients and among these four (50%) were symptomatic at presentation. The median follow-up time was 25 months. The median PFS was four months. 6-month PFS rate was 28% (95% CI - 0.12 to 0.46). Of the 25 evaluable patients, five (20%) had a partial response, and eight (32%) had stable disease;13 (52%) of the patients had disease control. The median OS was 16 months. During combined therapy, 14 (54%) and 3 (11%) patients had any grade and grade 3 anemia respectively. One patient had grade 3 neutropenia. Among non-hematological toxicities, gastrointestinal toxicities (nausea, vomiting and diarrhea) were the most common. No grade 4 toxicities were reported. There were no treatment discontinuations, however treatment delay due to grade three toxicities was present in two patients. Dose modification for Metformin was required in four patients. Targeted Sequencing was possible in nine cases. Two of these patients had STK11 mutation and an associated bad outcome (PFS < 2 months). Conclusions: We could not demonstrate the benefit of combination of Metformin with pemetrexed-carboplatin in terms of improvement in 6-month PFS rate. The addition of metformin to pemetrexed-carboplatin has an acceptable safety profile. Future trials should test metformin in specific subsets (STK11 mutated) and in combination with immunotherapy and TKIs. Keywords: Metformin, NSCLC, STK11

A Study on How Indian Brands Connected with Customers During Coronavirus Lockdown in India

Every year, new companies and brands come into existence in India;and in this race standing a chance to be the best is endless. Hence to position itself to be the best, companies always aim at increasing their brand reach through various platforms. The most proven way to improvise the brand reach had always been through advertising. It had been evident that the most companies' highly preferred mediums to advertise their products are television and the internet. In the past more than a decade the research reports have shown that the maximum number of viewership medium had been television and digital media. Keeping the desired results in consideration, most brands choose to spend millions on advertisements over these mediums. Even when the whole country came to a standstill due to the COVID pandemic, brands continued to advertise and promote their products. Some brands even changed their approach after considering COVID-19 and the lockdown, while others continued with their old advertisement sources and mediums. This study has analysed how brands in India have promoted their products on television and the social media platform such as Instagram, facebook, and so on. The brands that have been selected in this study are Indian and international brands that have majority of their buyers in India. © The Electrochemical Society

To evaluate the Prevalence of anxiety and depression during COVID-19 pandemic

Aim: To evaluate the Prevalence of anxiety and depression during COVID-19 pandemic. Methods: This study was conducted during the Coronavirus outbreak. Following development by the research team, the online survey was tested during these study periods. 100 participants were included in this study. Results: 40% of participants reported feeling tight or wounded up from time to time (sometimes), whereas 23% reported feeling this way all of the time. Many (35%) were worried as if something terrible was going to happen, but 'not too severely,' while 33 percent felt frightened 'a bit' as if something terrible was about to happen, but it did not bother them. Many people (38 percent) had anxious thoughts from time to time, while others (24 percent) had them all the time. Only 41% said they sat at ease and felt calm "generally," while others said they didn't sit at ease and felt relaxed "very frequently" (33 percent). More than half of the students (55%) reported not being afraid or having a 'butterfly' feeling in their stomach, whereas many others (24%) had that scared emotion 'sometimes.' Only 15% of the participants reported being restless and on the move. In terms of experiencing a sudden sense of panic attacks, just a small percentage (9%) reported having had this 'often' or 'very frequently' (20 percent). When asked if they still enjoyed the things they used to appreciate, just 36% said they didn't enjoy them as much anymore. Only half of the students (50%) said they could laugh and see the funny side of things "as much as they always could." A fresh look at the participants' emotions indicated that just 47 percent of them felt joyful'sometimes,' while others felt cheery 'not often/not at all' (24 percent, 14 percent respectively). Conclusion: During the COVID-19 pandemic, participants' anxiety and depression levels were found to be high. Furthermore, more than half of the pupils did not embrace the learning method throughout the epidemic. Implementing psychological therapies for healthcare students during pandemics is strongly advised in order to improve students' mental health as well as their learning process.

Worry, Perceived Discrimination, Lifestyle Changes, and Protective Factors During COVID-19: A Study With Recovering Patients in Delhi, India

COVID-19 has affected people all over the world. For those who were infected by the virus, the repercussions go beyond immediate medical conditions to include social stigma, fear, uncertainty, and lifestyle changes. This study presents data collected as part of a mental health intervention (COVID Response) with individuals who had been diagnosed with coronavirus and had completed the minimum 14 days isolation period, in the city of Delhi, India. Through a survey conducted telephonically, participants self reported on six major mental health indicators: levels of worry, mood, lifestyle changes made through the phase of diagnosis and recovery, perceived discrimination faced due to the diagnosis, and the willingness to donate blood plasma. Descriptive findings show lower levels of worry than at the time of testing and diagnosis, positive mood states, and availability of social support. One Way Anova results further indicate that worry differed significantly across groups with differences in lifestyle changes, reported mood, availability of medical care, and the willingness to donate plasma. These findings contribute toward an informed understanding about recovery from coronavirus and sustainable coping with the pandemic, which can aid related health initiatives and evolving policy.

An intelligent fine-tuned forecasting technique for covid-19 prediction using neuralprophet model

COVID-19, being the virus of fear and anxiety, is one of the most recent and emergent of various respiratory disorders. It is similar to the MERS-COV and SARS-COV, the viruses that affected a large population of different countries in the year 2012 and 2002, respectively. Various standard models have been used for COVID-19 epidemic prediction but they suffered from low accuracy due to lesser data availability and a high level of uncertainty. The proposed approach used a machine learning-based time-series Facebook NeuralProphet model for prediction of the number of death as well as confirmed cases and compared it with Poisson Distribution, and Random Forest Model. The analysis upon dataset has been performed considering the time duration from January 1st 2020 to16th July 2021. The model has been developed to obtain the forecast values till September 2021. This study aimed to determine the pandemic prediction of COVID-19 in the second wave of coronavirus in India using the latest Time-Series model to observe and predict the coronavirus pandemic situation across the country. In India, the cases are rapidly increasing day-by-day since mid of Feb 2021. The prediction of death rate using the proposed model has a good ability to forecast the COVID-19 dataset essentially in the second wave. To empower the prediction for future validation, the proposed model works effectively. © 2022 Tech Science Press. All rights reserved.

Strengthening of molecular diagnosis of SARS-CoV-2/COVID-19 with a special focus on India. (Special Issue: Coronaviruses and COVID-19- Past, Present, and Future.)

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2), a novel coronavirus initially reported in Wuhan, China, is the causative agent of coronavirus disease (COVID-19) pandemic. Symptoms of the disease comprise of fever, tiredness, dry cough, aches and pains, nasal congestion, runny nose, sore throat, diarrhoea and pneumonia at the late stage. SARS-CoV-2 has severely crippled the healthcare system and has caused huge economic losses. Following the outbreak, the SARS-CoV-2 was recognized timely and its genome was sequenced, leading to the development of real-time polymerase chain reaction assays for its detection in clinical samples collected from suspected cases. The management of the pandemic is limited by a number of misconceptions and insufficient information about laboratory testing for SARS-CoV-2 to confirm the disease. This includes a lack of awareness about procedures for the collection, transport, testing, and handling of biological samples for COVID diagnosis. This article provides an overview of the current laboratory diagnostic methods with a purpose to provide information and guidance to laboratories, stakeholders, broader community and especially public health professionals involved in laboratory testing for SARS-CoV-2.

Outcomes with COVID-19 in patients with hematopoietic stem cell transplant and cellular therapy: A systemic review and meta-analysis

Background: Coronavirus Disease 2019 (COVID19) was declared a pandemic on March 11, 2020. COVID-19 has caused over 100 million infections and over 2 million deaths globally. Patients who have received a hematogenic stem cell transplant or cellular therapy (HCT) have a high risk of mortality and morbidity with COVID-19 due to severe immune dysregulation. We conducted a systematic review and metaanalysis aimed to evaluate the outcomes of COVID-19 in HCT patients. Methods: A literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA) guidelines was performed on 3 databases (PubMed, Cochrane, and Clinical trials.gov) from the date of inception to Jan 2021. MeSH terms included 'hematological malignancies', 'hematopoietic stem cell transplantation', 'SARS-CoV-2', and 'COVID 19'. We screened 99 articles and 6 studies (4 retrospective studies, 2 prospective) were included after excluding review, duplicate, and non-relevant articles. Quality evaluation was done using the NIH quality assessment tool. The Inter-study heterogeneity among the studies was assessed using the Q statistic proposed by Cochrane and the I2 index introduced by Higgins and Thompson. Pooled analysis was done using the 'metaXL', and the random effects model was used to estimate the pooled prevalence with 95% CI. Results: Of 1619 patients in 6studies, 646 HCT patients were analyzed (Table ). The median age of patients was 63 years and 59% were males. Median days since HCT for autologous (auto) HCT and allogeneic (allo) HCT patients were 690 and 450 days respectively. The average follow-up duration after COVID-19 was 24 days. COVID-19 mortality in HCT patients was 20% (95%CI 0.17 to 0.23, I2=0). Roedl et al (n=6) reported a mortality of 83% and was excluded from the pooled analysis. The mortality rate was 19% (95% CI 0.15 to 0.24, I2=0%) in auto HCT patients and 21% (95% CI 0.17 to 0.25, I2=0%) in allo HCT patients. Conclusions: The HCT patients are at significant risk of increased mortality and morbidity due to COVID-19. There is a need to prioritize HCT patients for COVID-19 vaccination, close surveillance, and aggressive management. (Table Presented).

Antiviral and immuno-boosting potential of ashwagandha (Withania somnifera l.)

Now-a-days, the novel coronavirus pandemic has projected millions of deaths around the globe. An effective popular medicinal plant identified during this pandemic is Withania somnifera (L.) Dunal, locally called Ashwagandha or Indian Ginseng. The antiviral activity of this plant is well established in the fight against serious virus infections. This review mainly focuses on the antiviral and immuno-booster efficacy of the plant for combating various virus diseases. The bioactive principles of the plant, withanaloids, has been effectively used for human health. W. somnifera has distinct effects on the viral RBD (receptor-binding domain) and host ACE2 (angiotensin-converting enzyme 2) receptor complex. This may be useful in curing COVID-19 and other virus infection because of its tremendous immuno boosting properties. © 2021, Indian journals. All rights reserved.

Improving colorectal cancer screening compliance with resident education

INTRODUCTION: The incidence of CRC continues to increase at a rate of 2.1% per year in both men and women. Screening for CRC improves prognosis by identifying early-stages for treatment, resulting in lower mortality. Compliance rates for CRC screening have been low, and in optimized clinical settings, range from 50% to 70%. Fecal Immunochemical Test (FIT) has advantages over colonoscopy as it does not require bowel preparation and anesthesia, and is an easier test to complete. We hypothesize that CRC screening rates at our academic community hospital-affiliated clinic will improve by increasing resident education about FIT. METHODS: We reviewed the charts of patients aged 50-75 seen by resident physicians at our clinic from June 1, 2019 to December 31, 2019. Patients who did not have a follow-up or comprehensive visit within the mentioned timeframe, had an active diagnosis of CRC or history of colorectal surgery, or with risk factors placing them at high lifetime risk for CRC were excluded. Variables included patient age, gender, ethnicity, colonoscopy referral, FIT order, and reasons why CRC screening was not offered. Resident physicians were given an educational presentation and an informational e-mail addressing self-reported barriers to ordering FIT for patients. We then conducted a post-intervention chart review of patients aged 50-75 evaluated by residents from January 1, 2020 to March 31, 2020 and assessed the association of each variable with multivariate logistic regression. RESULTS: There was no significant difference in age, gender, ethnicity and overall CRC screening rates between the pre- and post-intervention groups (Figure 1.). There was a significant increase in FIT testing over colonoscopy (P=0.012, OR=2.10, 95% CI: 1.104-3.999) and in CRC screening rates in unscreened patients post-intervention (P=0.037, OR=1.55, 95% CI: 0.960-2.501) (Figure 2.). There was a significant reduction in amount of resident physicians forgetting to screen patients (P=0.003, OR=4.44, 95% CI: 1.664-11.82) (Figure 3.). CONCLUSION: Education improved the utilization of FIT testing over colonoscopy as well as the overall CRC screening rates in previously unscreened patients at our outpatient clinic. Recent EHR data showed a decrease of approximately 86% in CRC screenings across the U.S. - presumably due to access disruptions due to COVID-19. However, our clinic after resident education shifted towards theutilization of FIT, and ultimately increasing our CRC screening rates for previously unscreened patients. (Figure Presented) .