Forging Ahead the Repositioning of Multitargeted Drug Ivermectin.

With the advent of ivermectin, tremendous improvement in public health has been observed, especially in the treatment of onchocerciasis and lymphatic filariasis that created chaos mostly in rural, sub-Saharan Africa and Latin American countries. The discovery of ivermectin became a boon to millions of people that had suffered in the pandemic and still hold its pharmacological potential against these. Ivermectin continued to surprise scientists because of its notable role in the treatment of various other tropical diseases (Chagas, leishmaniasis, worm infections, etc.) and is viewed as the safest drug with the least toxic effects. The current review highlights its role in unexplored avenues towards forging ahead of the repositioning of this multitargeted drug in cancer, viral (the evaluation of the efficacy of ivermectin against SARS-Cov-2 is under investigation) and bacterial infection and malaria. This article also provides a glimpse of regulatory considerations of drug repurposing and current formulation strategies. Due to its broad-spectrum activity, multitargeted nature and promising efforts are put towards the repurposing of this drug throughout the field of medicine. This single drug originated from a microbe, changed the face of global health by proving its unmatched success and progressive efforts continue in maintaining its bequestnin the management of global health by decreasing the burden of various diseases worldwide.

Forecasting on Covid-19 infection waves using a rough set filter driven moving average models.

The pandemic outbreak of severe acute respiratory syndrome caused by the Coronavirus 2 disease in 2019, also known as SARS-COV-2 and COVID-19, has claimed over 5.6 million lives till now. The highly infectious nature of the Covid-19 virus has resulted into multiple massive upsurges in counts of new infections termed as 'waves.' These waves consist of numerous rising and falling counts of Covid-19 infection cases with changing dates that confuse analysts and researchers. Due to this confusion, the detection of emergence or drop of Covid waves is currently a subject of intensive research. Hence, we propose an algorithmic framework to forecast the upcoming details of Covid-19 infection waves for a region. The framework consists of a displaced double moving average ( δ DMA) algorithm for forecasting the start, rise, fall, and end of a Covid-19 wave. The forecast is generated by detection of potential dates with specific counts called 'markers.' This detection of markers is guided by decision rules generated through rough set theory. We also propose a novel 'corrected moving average' ( χ SMA) technique to forecast the upcoming count of new infections in a region. We implement our proposed framework on a database of Covid-19 infection specifics fetched from 12 countries, namely: Argentina, Colombia, New Zealand, Australia, Cuba, Jamaica, Belgium, Croatia, Libya, Kenya, Iran, and Myanmar. The database consists of day-wise time series of new and total infection counts from the date of first case till 31st January 2022 in each of the countries mentioned above. The δ DMA algorithm outperforms other baseline techniques in forecasting the rise and fall of Covid-19 waves with a forecast precision of 94.08%. The χ SMA algorithm also surpasses its counterparts in predicting the counts of new Covid-19 infections for the next day with the least mean absolute percentage error (MAPE) of 36.65%. Our proposed framework can be deployed to forecast the upcoming trends and counts of new Covid-19 infection cases under a minimum observation window of 7 days with high accuracy. With no perceptible impact of countermeasures on the pandemic until now, these forecasts will prove supportive to the administration and medical bodies in scaling and allotment of medical infrastructure and healthcare facilities.

COVID-19 outbreak : comprehensive update on epidemiology, transmission, and treatment opportunities

The outbreak of the pandemic, COVID-19, triggered by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) throughout the world took a large number of lives till today and even counting. We have made an effort in this critical hour to compile and contemplate the literature reported till July 13, 2020 about the structure and morphology, epidemiology, transmission, replication cycle, and potential therapeutic strategies to tackle this pandemic. We have also highlighted some unexplored targets and potential gateways for the researchers in the field which may help to unravel some breakthrough therapy against this infection. Additionally, we have focused on the different approaches for vaccine development which could be used by researchers to develop a vaccine strong enough to eradicate this viral infection and to improve the current healthcare of the infected patients.

Hydroxychloroquine: Adverse Drug Reaction Profile of an Old Drug in a New Situation.

BACKGROUND: Hydroxychloroquine (HCQ) has been extensively used during the COVID-19 pandemic both as a therapeutic and prophylactic drug. HCQ is generally well tolerated; however, adverse drug reactions (ADRs) in COVID-19 need further exploration. In this study, we have determined the type and pattern of ADRs of HCQ as a prophylactic and therapeutic drug in COVID-19. METHODS: All spontaneous suspected ADR reports due to HCQ in COVID-19 patients submitted to the ADR monitoring of a tertiary care hospital were included. Additionally, a survey was designed for active surveillance of ADRs among healthcare professionals (HCPs) who were on prophylaxis with HCQ. The ADRs were analyzed to determine severity, causality, and preventability using the Hartwig Scale, World Health Organisation-Uppasala Monitoring Centre (WHO-UMC) scale, and modified Schumock and Thornton criterion respectively. RESULTS: Sixty-four ADR reports were received from COVID-19 patients. A total of 78 ADRs were reported by 49 HCPs who were on HCQ prophylaxis. The majority of the patients had ADRs related to skin and soft tissues (37.5%), whereas the HCPs on prophylaxis mostly had gastrointestinal complaints (42.3%). ADRs observed in HCPs on prophylaxis were mild, not requiring any intervention. However, 50% of ADRs in patients were of "moderate" category. CONCLUSION: Undiscerning and unsupervised use of HCQ can expose the general population as well as patients to serious adverse drug effects. Utmost care is necessary before using HCQ prophylactically or for treatment in COVID-19.

Impact of body mass index on critically ill COVID-19 patients admitted in a tertiary care hospital: A retrospective observational study

Background: Increased body mass index (BMI) is a known risk factor for respiratory infection and is being recognized as a predisposing factor in the COVID‐19 pandemic caused by the severe acute respiratory syndrome coronavirus‐2. Aims and Objectives: This study aimed to assess the impact of BMI on critically ill COVID-19 patients. Secondary outcomes include development of respiratory failure, shock, acute cardiac injury, acute kidney injury, acute liver injury, secondary infection and sepsis. Materials and Methods: This retrospective study of 6 months included the laboratory-confirmed COVID-19 patients admitted to an ICU of a tertiary care academic health-care organization. The medical records were reviewed at least 14 days after admission. Results: A total of 484 patients were included, and BMI data were available for 306 patients. About 40.19% had a normal weight, 26.79% were overweight, 17.97% had BMI 30–34.9 Kg/m², and 15.03% had BMI ≥35 Kg/m². Overall, 58 patients (18.95%) died within 14 days of ICU admission, 50.98% were discharged alive or referred from the hospital within 14 days, and 30.06% remained hospitalized at 14 days. After controlling for all covariates, there was a significantly increased risk of mortality in the patients with obesity Class I (RR 2.03, 95% CI 1.07–3.85, P=0.030) and patients with obesity Classes II and III (RR 2.83, 95% CI 1.54–5.22, P<0.001) compared with those with normal BMI. Conclusion: Obesity was associated with an unfavorable outcome among patients with COVID-19. Patients with obesity should be more closely monitored when hospitalized for COVID-19 as there is increasing evidence of relation of severity of COVID-19 and obesity which appears to be a factor in the health risks. [ FROM AUTHOR] Copyright of Asian Journal of Medical Sciences is the property of Manipal Colleges of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Efficacy of two siddha polyherbal decoctions, Nilavembu Kudineer and Kaba Sura Kudineer, along with standard allopathy treatment in the management of mild to moderate symptomatic COVID-19 patients-a double-blind, placebo-controlled, clinical trial.

BACKGROUND AND AIM: Globally, the ongoing pursuit in exploring an effective drug to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has not met with significant success to date. Indian traditional medicines, especially polyherbal formulations like Nilavembu Kudineer (NVK) and Kaba Sura Kudineer (KSK) of the Siddha system of medicine, have been used as public health interventions for controlling viral epidemics like dengue and Chikungunya. These traditional therapies have been found safe, effective, and widely accepted. The current study evaluates the comparative efficacy of NVK and KSK as opposed to the placebo, in the management of mild to moderate COVID-19 disease. METHODS: The study was a double-blind, placebo-controlled comparative clinical trial, with the primary objective of determining the efficacy of KSK and NVK. Patients (n=125) diagnosed with mild to moderate COVID-19 symptoms were enrolled in the study over a period of 4 months (Aug 2020-Dec 2020). Participants were randomized into 3 arms; placebo-decaffeinated tea in Arm I, NVK in Arm II, and KSK in Arm III. Each arm received 60 ml of the respective treatment twice a day, post morning and evening meals, along with standard allopathy treatment for a maximum of 10 days. The main outcome measures of the study were the reduction in SARS-CoV-2 viral load, hospital stay, and time taken by the patients to become asymptomatic from symptomatic. Efficacy assessments included clinical symptoms (fever, cough, and breathlessness) each day and real-time reverse transcription-polymerase chain reaction (RT-PCR), liver function test (LFT), renal function test (RFT), and electrolytes and electrocardiogram (ECG) at baseline (day 0) and days 3, 6, and 10. Post-treatment, participants were followed up for 30 days via phone for adverse effects if any. Effects of drugs on inflammatory markers (IL6) at the end of treatment were also recorded. Adverse events (AE) were monitored throughout the study. RESULTS: The results revealed that when compared to patients in the placebo arm, those in NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and the time taken to become symptomatic from asymptomatic. Out of 125 COVID-19 patients recruited, 120 completed the study; two from the placebo group developed severe symptoms and were shifted to the intensive care unit (ICU) and three patients from Arms II and III withdrew from the study. The mean age of females (n=60) and males (n=60) enrolled was between 40.2 and 44.3 years, respectively. Results were more promising for all the patients in NVK and KSK arms as all enrolled participants (100%) under this group got discharged by day 6 as compared to only 42.5% (n=17) from the placebo group on that day. The hospital stay time for patients in Arm I was significantly longer (mean [SD]=8.4 [2.0] days) as compared to the Arms II and III (mean [SD]=4.7 [1.5] and 4.2 [1.5] days, respectively (Kruskal-Wallis test, P=0.0001). Patients in the three groups took a significantly different number of days to become asymptomatic. While Arm II and III patients took mean of 2.5 and 1.7 days, respectively, Arm I, patients took a mean of 4.2 days (Kruskal-Wallis test, P=0.0001). In all, two adverse events were recorded, one for vomiting and one for diarrhea lasting a day in Arm I and Arm II, respectively. The mean value of interleukin-6 (IL6) was significantly different in comparison to the placebo-decaffeinated tea arm (NVK=2.6 and KSK=2.2, placebo=4.0, P=0.02). The other blood biochemical parameters like C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and D-dimer that were analyzed at the baseline and at the time of discharge from the hospital, were not significantly different in the three arms. CONCLUSION: NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and time taken for patients to become asymptomatic from symptomatic, when compared to the placebo (decaffeinated tea). The primary outcome measures of the KSK arm were significantly better than those in the NVK arm.

Nanomedicine based approaches for combating viral infections.

Millions of people die each year from viral infections across the globe. There is an urgent need to overcome the existing gap and pitfalls of the current antiviral therapy which include increased dose and dosing frequency, bioavailability challenges, non-specificity, incidences of resistance and so on. These stumbling blocks could be effectively managed by the advent of nanomedicine. Current review emphasizes over an enhanced understanding of how different lipid, polymer and elemental based nanoformulations could be potentially and precisely used to bridle the said drawbacks in antiviral therapy. The dawn of nanotechnology meeting vaccine delivery, role of RNAi therapeutics in antiviral treatment regimen, various regulatory concerns towards clinical translation of nanomedicine along with current trends and implications including unexplored research avenues for advancing the current drug delivery have been discussed in detail.

Stressor Combat Strategies and Motivating Factors Among Health Care Service Providers During COVID-19 Pandemic.

Context Since its inception in December 2019 in Wuhan, China, the severe acute respiratory syndrome coronavirus-2, the etiological agent for coronavirus disease 2019 (COVID-19), is spreading rapidly both locally and internationally, and became certified as a pandemic by the World Health Organization (WHO) in March 2020. Working in an environment of high risk, coupled with adherence to quarantine and stressors related to the job, has been found to exacerbate the psychological health of frontline healthcare workers. Aims To assess the perceived stressors, combat strategies, and motivating factors among health care service providers during the COVID-19 pandemic. Setting and design A cross-sectional study was conducted among healthcare workers at a tertiary care hospital in the north-central region of India from May to September 2020. Methods and materials A convenience sample of 150 health care workers was taken. A self-reported pretested structured "COVID 19 staff questionnaire" was used as a study tool. The health care workers (HCWs) included nurses, physicians, laboratory technicians, and radiology technicians who worked in high-risk areas (isolation ward, COVID intensive care unit, emergency department, and outpatient cough outdoor walk-in clinics) during the outbreak constituted our study population.  Statistical analysis used The varying levels of stress or effectiveness of measures were reported as mean and standard deviation, as appropriate. Descriptive statistics were used for data presentation. A Mann-Whitney U test was used to analyse differences between two groups of non-normally distributed data. A p-value of less than 0.05 was considered statistically significant. Results As compared to doctors, paramedical staffs were more stressed with frequent protocol changes (88%), emotional exhaustion (68%), and conflicts with duties (62.7%). The factors like seeing colleague getting better (78.7%) and hoping for financial compensation (49.3%) were reported as stress busters; family compensation in case of death at the workplace and disability benefits in case of disease-related disability development were more effective motivational factors for paramedical staff in case of future outbreaks (p-value <0.05). Conclusions It is needful that secondarily traumatized team members should be always observed, educated, and properly handled. Certain personal coping strategies adopted by health workers should be well addressed and motivated if scientifically sustainable. We have to include psychiatric preparedness and stress monitoring also for health care teams along with emphasizing hygiene, temperature monitoring, and fever management, in planning to fight the pandemic.

Healthcare professionals' knowledge, attitudes, and practices on coronavirus disease in Western Uttar Pradesh.

BACKGROUND AND OBJECTIVES: The ongoing coronavirus disease pandemic caused by a novel genetically-mutated strain of coronavirus has posed a tremendous challenge to healthcare professionals, worldwide. This study aimed to explore the healthcare professionals' knowledge, attitudes, and practices (KAP) related to coronavirus disease in Western Uttar Pradesh and provide data to improve awareness about this disease and remove the knowledge gap, if any, by disseminating the updated information to the corona warriors. MATERIALS AND METHODS: A cross-sectional survey was conducted in the form of a structured 28-item online questionnaire using SurveyMonkey software. The qualitative data were coded numerically, and the KAP score was calculated. Pearson Chi-square test was used to study the association, among variables. RESULTS: Of 509 respondents, 296 (58.19%) were males and 213 (41.81%) were females. The median age bracket of the sample was 20-40 years. By profession, 255 (50.10%) were doctors, 167 (32.74%) were medical students, 80 (15.78%) were other healthcare workers, and a minority 7 (1.38%) were the nursing staff. Educational status covered a range from secondary (2.01%) to senior secondary (17.51%) to bachelors and equivalent (29.18%) to masters and equivalent (51.31%). The average KAP scores were 54%, and the score was highest among doctors as compared to other healthcare professionals (P < 0.001). CONCLUSIONS: In light of these study findings, we conclude that healthcare professionals are aware of coronavirus disease. However, the overall KAP score regarding its clinical course, preventive strategies, and judicious use of personal protective equipment was less than expected. There is a need to address all misconceptions and empower the corona warriors with the right information through effective mass media communication and reinforcement through seminars and workshops in the medical institutes and hospitals. The healthcare professionals are a cornerstone to prevent the nosocomial and community spread of this pandemic.

A double blinded placebo controlled comparative clinical trial to evaluate the effectiveness of Siddha medicines, Kaba Sura Kudineer (KSK) & Nilavembu Kudineer (NVK) along with standard Allopathy treatment in the management of symptomatic COVID 19 patients - a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: The primary objectives of the study are to determine the effectiveness of the Kaba Sura Kudineer (KSK) & Nilavembu Kudineer (NVK) along with standard Allopathy Treatment to compared with Placebo (Decaffeinated Tea) with standard Allopathy Treatment in the management of Symptomatic COVID 19 patients and also in reduction of Hospital Stay Time & Changes in Immunological (IL6) and Bio Chemical Markers (Ferritin, CRP, D-Dimer and LDH). The secondary objectives are to evaluate the safety of the trial medicines and their effects in the reduce the risks of the disease. In addition, to document the profile of Symptomatic COVID 19 patients as per Siddha Principles. TRIAL DESIGN: A Double Blinded, Three arm, Single Centre, Placebo Controlled, Exploratory and comparative Randomized Controlled Trial PARTICIPANTS: Patients who were admitted to the COVID Care Centre at Govt. Institute of Medical Sciences. Noida in India will be recruited. These will be patients with Mild and Moderate symptoms with laboratory confirmed COVID 19 (RT - PCR Tested Positive) aged 18-65, willing and consenting to participate. INTERVENTION AND COMPARATOR: Arm I: Decaffeinated Tea (Placebo - similar in taste and appearance to the other Two Decoctions), 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. Arm II: Nilavembu Kudineer (The Siddha Medicines which is used as a standard Anti-Viral drug for the past Pandemics by Siddha Physicians) 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. Arm III: Kaba Sura Kudineer (The Siddha Medicine which is proposed to be used as a Treatment for COVID 19 based on Siddha Literature) 60 Ml Morning and Night after Food, along with standard Allopathy Treatment for 10 days. The investigational drugs are registered products under the Govt.of India and bought from GMP Certified Manufacturing Units. MAIN OUTCOMES: Primary outcomes: 1. Reduction in Viral load of SARS-CoV-2 at the end of treatment (10 days). 2. Time taken to convert Patient from symptomatic to Asymptomatic based on Reduction in clinical symptoms (10 days). 3. Effect of drugs inflammatory markers (IL6,) at the end of treatment (10 days). 4. Reduction in hospital stay time (20 days follow up). (Based on RT PCR CT Value 3rd, 6th if needed 10th day). (Based on IL 6 Value needed 10th day or IL6 value on turning negative. (entry level/exit level). Secondary outcomes (10 days): 1. Reduction in use of Intensive Supportive Care. 2. Reduction in incidence of complications (Acute Respiratory Distress Syndrome, other systemic complications). 3. MuLBSTA score for viral pneumonia (multinodular infiltration, hypo-lymphocytosis, bacterial co infection, Total Leucocyte Count (TLC ≤ 0.8 x 109/L), smoking history, hyper-tension and age) score. 4. Laboratory markers (Haematological & Biochemical Markers). 5. Adverse events/effects Siddha-based measurements. 6. Siddha Udaliyal assessment by using Yakkai Ilakkanam (YI) Tool to diagnose body condition for covid-19 patients. RANDOMISATION: The assignment of the participants into 3 Groups will be allocated in 1:1:1 Ratio through randomization Blocks in Microsoft Excel by a Statistician who is not involved in the study. The allocation scheme will be made by another statistician by using a closed envelope after the assessment of eligibility and Informed consent procedures. The groups will be balanced for age and sex with 3:1 Ratio in each group for mild: severe COVID-19 symptoms. BLINDING: The Study is Double Blinded. Participants and Investigators were blinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Sample size could not be calculated, Since there are no prior trials on KSK and NVK as a comparative trial. In addition, there are no prior trials on KSK and NVK in this region. A total Number of 120 Patients, 40 each in 3 groups will be recruited in 1:1:1 Ratio. TRIAL STATUS: Protocol Number : SCRUND GIMS Noida Study 1,Version: 2.0 Protocol Date : 20.08.2020 The recruitment period is completed for the trial. The Trial started its recruitment on 22.8.2020. We anticipate study including data analysis will finish in January 2021. This is to state that it was a late submission from authors for publication of the protocol to the BMC, after enrolment in the study was over. TRIAL REGISTRATION: The trial protocol was registered with CTRI (Clinical Trial Registry of India) and number is CTRI/2020/08/027286 on 21.08.2020 FULL PROTOCOL: The full Protocol is attached as an additional file, Accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated. This letter serves as a summary of the key elements of the full protocol. The Study protocol has been reported in accordance with the SPIRIT guidelines.

Integration of cardiovascular risk assessment with COVID-19 using artificial intelligence.

Artificial Intelligence (AI), in general, refers to the machines (or computers) that mimic "cognitive" functions that we associate with our mind, such as "learning" and "solving problem". New biomarkers derived from medical imaging are being discovered and are then fused with non-imaging biomarkers (such as office, laboratory, physiological, genetic, epidemiological, and clinical-based biomarkers) in a big data framework, to develop AI systems. These systems can support risk prediction and monitoring. This perspective narrative shows the powerful methods of AI for tracking cardiovascular risks. We conclude that AI could potentially become an integral part of the COVID-19 disease management system. Countries, large and small, should join hands with the WHO in building biobanks for scientists around the world to build AI-based platforms for tracking the cardiovascular risk assessment during COVID-19 times and long-term follow-up of the survivors.