Qualitative exploration of perspectives of the pharmacists working in public-sector hospitals during COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic, a serious global health threat, has excruciating social and economic implications given its transmissibility, lack of therapy, and severity. In such a situation, pharmacists as frontline healthcare professionals hold a significant position to tackle. This study was designed to explore the perception and preparedness of pharmacists working in public sector hospitals amid such a pandemic in Pakistan. METHODS: A total of 11 pharmacists were interviewed for this qualitative study design through a semi-structured interview guide. The interviews were recorded and transcribed verbatim. RESULTS: The thematic content analysis yielded six major themes; understanding of COVID-19, perceptions towards COVID-19, preventive aspects, management aspects, changes to lifestyle, and psychological aspects. Though efficient preparedness and approach to fighting against such pandemics were reported, pharmacists were found susceptible to infection and psychological stress. They also expressed lockdown as an effective measure to prevent the disease from spreading but still were concerned about its economic and social impact. CONCLUSIONS: Adequate planning and facilities from the national level should be made available for strengthening the hospital pharmacy service that helps improve the overall healthcare system of low- and middle-income countries like Pakistan. The provision of a protective facility, incentives, and occupational health surveillance packages are deemed necessary to boost the self-esteem and morale of hospital pharmacists that safeguard the early and effective management of such disasters.

Molecular epidemiology of SARS-CoV-2 in healthcare workers and identification of viral genomic correlates of transmissibility and vaccine break through infection: A retrospective observational study from a cancer hospital in eastern India.

PURPOSE: Despite COVID vaccination with ChAdOx1 ncov-19 (COVISHIELD®) (ChAdOx1 ncov-19) a large number of healthcare workers (HCWs) were getting infected in wave-2 of the pandemic in a cancer hospital of India. It was important therefore to determine the genotypes responsible for vaccine breakthrough infections. METHODS & OBJECTIVES: Retrospective observational study of HCWs. Whole genome sequencing of SARS CoV-2 using Illumina NovaSeq was done. Mutations from both waves were compared to identify genomic correlates of transmissibility and vaccine breakthrough infections. RESULTS: Vaccine breakthrough infections were seen in 127 HCWs out of 1806 fully vaccinated staff (7.03%). Median number of HCWs infected per day in wave-1 was 0.92 versus 3.25 in wave-2. Majority of wave-1 samples belonged to B.1 and B.1.1 lineage. Variant of concern- Delta variant (90%), and variant of interest- Kappa variant (10%), was seen in only wave-2 samples. Total mutation observed in wave-2 samples (median â€‹= â€‹44) was 1.8 times than wave-1 sample (median â€‹= â€‹24). Spike protein in wave-2 samples had 13 non-synonymous mutation as compared to 8 seen in wave-1 samples. E484Q-vaccine escape mutant was detected in five samples of wave-2; T478K - highly infectious mutation was seen in 31 samples of wave-2. We identified a novelcoding disruptive in-frame deletion (c.467_472delAGTTCA, p. Glu156_Arg158delinsGly) in the Spike protein. This mutation was seen only in wave-2 (78%, n â€‹= â€‹39) samples. CONCLUSION: The circulating virus strains in wave-2 infections demonstrated a greater degree of infectivity. There was a significant change in the genotypes observed in wave-1 and wave-2 infections along with almost twice the number of mutations. We noted that vaccine breakthrough infections (although mostly mild).

Cyclin D3 restricts SARS-CoV-2 envelope incorporation into virions and interferes with viral spread.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a great threat to human health. The interplay between the virus and host plays a crucial role in successful virus replication and transmission. Understanding host-virus interactions are essential for the development of new COVID-19 treatment strategies. Here, we show that SARS-CoV-2 infection triggers redistribution of cyclin D1 and cyclin D3 from the nucleus to the cytoplasm, followed by proteasomal degradation. No changes to other cyclins or cyclin-dependent kinases were observed. Further, cyclin D depletion was independent of SARS-CoV-2-mediated cell cycle arrest in the early S phase or S/G2/M phase. Cyclin D3 knockdown by small-interfering RNA specifically enhanced progeny virus titres in supernatants. Finally, cyclin D3 co-immunoprecipitated with SARS-CoV-2 envelope (E) and membrane (M) proteins. We propose that cyclin D3 impairs the efficient incorporation of envelope protein into virions during assembly and is depleted during SARS-CoV-2 infection to restore efficient assembly and release of newly produced virions.

Sleep Disorders in Patients with Parkinson's Disease during COVID-19 Pandemic: A Case-Control Study.

Objective: To assess the impact of coronavirus disease 2019 (COVID-19) pandemic on sleep disorders among Parkinson's disease (PD) patients using validated questionnaires. Materials and Methods: This prospective study involved 50 PD patients and 50 age, gender, and body mass index-matched controls. All participants underwent assessment of cognition using Montreal Cognitive Assessment scale, sleep quality using Parkinson's disease sleep scale-2 (PDSS-2; for PD patients) and Pittsburgh Sleep Quality Index (PSQI; for PD patients and healthy controls), excessive daytime sleepiness (EDS) using Epworth sleepiness scale (ESS), insomnia symptoms and severity using insomnia severity index (ISI), restless legs syndrome (RLS) using International RLS Study Group criteria, rapid eye movement sleep behavior disorder (RBD) using RBD Single-Question Screen (RBD1Q), and depression using Patient Health Questionnaire-9 scale. Results: Eighty-eight percent of PD patients reported one or more sleep disorders, compared to 28% controls. While 72% of PD patients reported poor sleep quality (PDSS-2 ≥15, PSQI >5), 60% had insomnia, 58% reported RBD, 50% had EDS, and 36% reported RLS. Depressive symptoms were reported by 70% patients. PD patients with and without poor sleep quality were comparable with regards to demographic and clinical variables, except for depressive symptoms (P < 0.001). Depressive symptoms showed a significant association with EDS (P = 0.008), RBD (P < 0.001), and insomnia (P = 0.001). Conclusion: Prevalence of sleep disorders increased in PD patients during the COVID-19 pandemic. Prevalence of EDS, RBD, and RLS in PD patients was higher compared to that reported in studies during the pre-COVID-19 times. Presence of depressive symptoms was a significant correlate of presence of sleep disorders in PD patients.

The Origin and Clinical Relevance of Yoga Nidra.

Yoga nidra, also known as 'yogic sleep', is a simplified form of an ancient tantric relaxation technique. The most general description of the practice is that it combines guided mental imagery with a specific yoga posture called Shavasana (or "corpse pose"). The goal of yoga nidra is to promote a profound state of relaxation, which differs from sleep inasmuch as there is still an awareness of one's surroundings. While several components of the practice have been known since ancient times, it was not until the 1960s that an updated and systematized system of practice was introduced to the public through the writings of Swami Satyananda Saraswati. Unlike other schools of yoga, which emphasize concentration or contemplation, yoga nidra's goal is complete relaxation. As such, its advocates claim that it is suitable for all individuals, from beginners to advanced practitioners of yoga. The calm inner stillness induced by yoga nidra is claimed by practitioners to be an effective stress management tool as well as a means for attaining greater receptivity to personal resolutions. These resolutions can range from the goal of achieving self-transformation, enhancing creativity, or improving one's learning ability. Additionally, yoga nidra is claimed to promote beneficial changes in physiological and mental health. The following narrative review summarizes the basic steps used to achieve the final state of yoga nidra relaxation as well as some recent experimental findings regarding its physiological and psychological effects. Standard research databases were searched for relevant articles. Clinical studies have shown that yoga nidra meditation is associated with positive physiological changes, including improvements in several hematological variables, red blood cell counts, blood glucose levels, and hormonal status. Two neuroimaging studies have shown that yoga nidra produces changes in endogenous dopamine release and cerebral blood flow, a further confirmation that its effects on the CNS are objectively measurable. The practice has also been shown to reduce psychometrically measured indices of mild depression and anxiety, although these benefits were not shown in an experimental study to extend to severe depression or severe anxiety.

SARS-CoV-2 infection is associated with increased odds of insomnia, RLS and dream enactment behavior.

Background: Literature suggests that the COVID-19 pandemic has resulted in poor sleep quality, especially among the infected population. However, literature regarding the effect of COVID-19 pandemic and SARS-CoV-2 infection on occurrence of insomnia, restless legs syndrome and dream enactment behavior is either scarce or unavailable. Methods: This study was planned to assess the effect of SARS-CoV-2 infection on the occurrence of insomnia, restless legs syndrome (RLS) and dream enactment behavior (DEB). For this cross-sectional study, a questionnaire comprising of items related to demographic details, past medical history, and information related to SARS-CoV-2 infection was distributed through social media. Insomnia was diagnosed using clinical criteria. RLS, DEB, sleep quality, depression and anxiety were assessed using a validated questionnaire. Information regarding the use of hypnotic medications was also gathered. Results: Of the 1596 respondents, 37.2% reported disturbed sleep while insomnia was reported by 22.6% respondents. 27.3% of respondents reported RLS and 17.4% suffered DEB. The odds of insomnia were greater among males (OR = 1.27; 95% CI: 1.03-1.58; P < 0.02) and among those who had SARS-CoV-2 infection (OR = 1.76; 95% CI = 1.42-2.19; P < 0.001). Similarly, SARS-CoV-2 infection was also associated with increased odds of RLS (OR = 2.48; 95% CI = 1.98-3.11; P < 0.001) and DEB (OR = 1.58; 95%CI = 1.21-2.06; P < 0.001). Insomnia, RLS and DEB were more frequent among respondents who required oxygen therapy, those who experienced loss of taste and/or smell, depression and anxiety. Prevalence of insomnia, DEB and RLS was higher than said prevalence among respondents with no history of SARS-CoV-2 infection, but lower than that of those with positive history of SARS-CoV-2 infection. 5.3% of respondents reported taking hypnotic medications before infection, 7% during infection and 5.3% after infection. Conclusion: SARS-CoV-2-infection-related factors in association with environmental factors have increased the prevalence of insomnia, DEB and RLS among subjects having infection. SARS-CoV-2-associated immunological changes, hypoxia and neurotropism may play a role in occurrence of insomnia, DEB and RLS.

Neuropsychiatric Consequences of COVID-19 Pandemic: A Synthetic Review from a Global Perspective.

Some research suggests that distress, secondary to isolation and fear following COVID-19 infection, can negatively affect the long-term more than the COVID-19 infection itself. This narrative review aims to provide a global view on the neuropsychiatric consequences of COVID-19 that can be ascribed to several factors, ranging from the direct effect of infection, to the body's responses against the infection, or to the psychological sequelae of social isolation, unemployment, and fear for one's health and livelihood. Current findings show that the more severe the respiratory infection, the more likely are central nervous system (CNS) complications regarding the infection itself. The immune reactions to the infection may result in symptoms similar to chronic fatigue as well as neurocognitive deficits, which last long after the infection is gone. An increase in symptoms of depression, anxiety, and trauma-related stress may also follow upon economic fears and isolation from friends and family. The consequences of the pandemic are not limited to adults; children learning remotely and away from classmates and routine activities may develop adjustment disorders, acute stress disorder, and a variety of manifestations of grief. A summary of case reports suggests that COVID-19-related stress, economic recession, and political unrest increase the risk of suicidal behaviors and acts of violence. However, it is unknown whether manifestations of mental disorders result from social causes or whether CNS complications may be responsible.

Management of Chronic Insomnia Using Cognitive Behavior Therapy for Insomnia (CBT-I) During COVID-19 Pandemic: Does One Shoe Fit All?

Purpose: Insomnia is a highly prevalent disorder that is seen across all age groups causing significant morbidity to the patients. Its prevalence has further risen during COVID-19 pandemic. It is widely acknowledged that untreated insomnia can lead to significant health risks and socio-occupational dysfunction. Methods: A narrative review was conducted following focused search of databases. Results: Available guidelines mention two different approaches for the management of insomnia-pharmacological and non-pharmacological. Non-pharmacological therapies like multicomponent cognitive behavior therapy for insomnia (CBT-I) have been advocated for the management of acute as well as chronic insomnia in the literature as it has been found efficacious and useful. Multiple variants of CBT-I, e.g., digitally delivered CBT-I, brief CBT-I have been tested during pandemic owing to closure of clinics. However, there are certain issues to be considered while choosing CBT-I as therapy. For example, like other forms of psychotherapies, is there a need for assessing the candidature of patient before administering CBT-I; is CBT-I free of adverse effects as commonly thought; is CBT-I more efficacious than hypnotics; and at last, how to manage cases that are not candidate for CBT-I. Conclusion: This narrative review addresses the scientific robustness of evidence for issues related to adherence, efficacy and adverse effects of non-pharmacological therapies. Available literature suggests that data related to adherence and efficacy of CBT-I suffer from methodological shortcomings and careful selection of patient is important for the successful therapy. At the same time, attempts have been made to shed light to the areas where CBT-I can be helpful in the management of insomnia.

Analysis on Prediction of COVID-19 with Machine Learning Algorithms

During the pandemic, the most significant reason for the deep concern for COVID-19 is that it spreads from individual to individual through contact or by staying close with the diseased individual. COVID-19 has been understood as an overall pandemic, and a couple of assessments is being performed using various numerical models. Machine Learning (ML) is commonly used in every field. Forecasting systems based on ML have shown their importance in interpreting perioperative effects to accelerate decision-making in the potential course of action. ML models have been used for long to define and prioritize adverse threat variables in several technology domains. To manage forecasting challenges, many prediction approaches have been used extensively. The paper shows the ability of ML models to estimate the amount of forthcoming COVID-19 victims that is now considered a serious threat to civilization. COVID-19 describes the comparative study on ML algorithms for predicting COVID-19, depicts the data to be predicted, and analyses the attributes of COVID-19 cases in different places. It gives an underlying benchmark to exhibit the capability of ML models for future examination.

Disrupted Sleep During a Pandemic.

The COVID-19 pandemic affected sleep in several people. Though most of the studies argued that age, gender, employment, finances, responsibilities, and exposure to sunlight governed sleep-wake schedule and sleep disturbances, there is also scientific evidence to suggest that these issues could have aroused because of the infiltration of the central nervous system (CNS) by SARS-CoV-2. Sleep disturbances must be addressed during the pandemic as sleep disturbances and systemic inflammation run in a vicious cycle; quality of sleep and timing of vaccination can influence the immune response to vaccination and subjects having obstructive sleep apnea (OSA) are at higher risk for having SARS-CoV-2 infection-related complications.

Epidemiologic characteristics and pre-hospital care of traumatic injuries during the COVID-19 pandemic in an emerging and developing country: A single tertiary centre experience.

BACKGROUND: Pre-hospital care has been shown to reduce the mortality in trauma patients. The present study is an attempt to identify the status of pre-hospital orthopaedic trauma care in developing countries during COVID-19 pandemic. METHODS: This was a prospective observational study carried out in a tertiary care setup from March 25th, 2020 to January 31st, 2021. All the data pertaining to the traumatic injuries including demographic details and epidemiologic characteristics were recorded in an electronic database. RESULTS: A total of 1044 patients were included in the study for evaluation. The mean age was 35.24 ± 19.84 years. There were 873 males and 171 females. A total of 748 presented from nearby states, with 401 being the referrals and 347 cases coming directly to hospital. A total of 141 open fractures presented directly and 269 were referred from nearby states. Out of 269 cases of open fractures, only 67 and 139 were given intravenous antibiotics and had wound dressing done respectively at the periphery site. A total of 125, 112, 92 and 84 patients were received without traction/splintage, intravenous fluids, dose of analgesics and recording of vitals respectively. Delay from injury to presentation in emergency/administration of antibiotic (Hours) was 7.06. Road side accidents were main cause comprising of 52.58% cases. Gustilo Anderson classification grade-2 comprised of majority of the open fractures (51.63%). Lower limb fractures comprised of majority of the injuries (70.59%). Majority were adults and conservative management was the most common mode of treatment. A total of 197 and 265 patients had associated head injuries and blunt trauma chest/blunt trauma abdomen respectively. CONCLUSION: Emphasizing on pre-hospital care measures, with special focus on co-ordination between primary, secondary and tertiary health care facilities is the need of the hour and can prevent additional morbidities, avoiding overburden of the already compromised healthcare centres.

Small and medium-sized enterprises' contribution in digital technology.

Researchers have mentioned the importance of digitization in improving efficiency and productivity in Small and Medium Enterprises (SME). Fortunately, there is no proof that Digitization can be used to deal with the outcome of severe incidents like COVID-19. The research paper suggested that the increased rate of SMEs has increased significantly. This was entirely due to the advent of Digital Technology (DT). In this way, both product and the process become more automated in digitalization, resulting in increased quality and demand. Considering the high scope for higher development, India's SME sector still has much space for new digital technologies to be integrated. This paper addresses the main scenario of SMEs in India and their benefit in GDP. Also, the research includes a brief analysis of CRM applications and digital payment options in SMEs.

Awake Proning for Nonintubated Adult Hypoxic Patients with COVID-19: A Systematic Review of the Published Evidence.

Objective: Awake proning is an intervention that is being advocated for COVID-19 patients and has been suggested to improve the oxygenation, thereby decreasing oxygen requirements. We performed this systematic review with the aim of appraising the latest published evidence on the clinical effectiveness of awake proning in COVID-19 patients. Data sources: PubMed, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Google Scholar, and one trial registry were searched until September 23, 2020, for studies on the use of awake proning for nonintubated COVID-19 patients. Study selection: Published or in-press peer-reviewed randomized control trials, case-control trials, and prospective or retrospective cohort studies in English language only were sought, assessing the effectiveness of awake proning for nonintubated patients diagnosed with COVID-19. Data results: We included 21 published studies (19 single arm and 2 with comparison group). Twenty-three registered clinical trials were identified. No randomized clinical trial has been published so far. Conclusions: Awake proning is probably safe and effective in enhancing oxygenation in nonintubated COVID-19 patients; however, there is insufficient evidence. Further high-quality clinical trials are urgently needed to assess the effectiveness of awake proning on a variety of patient-centered outcomes. How to cite this article: Parashar S, Karthik AR, Gupta R, Malviya D. Awake Proning for Nonintubated Adult Hypoxic Patients with COVID-19: A Systematic Review of the Published Evidence. Indian J Crit Care Med 2021;25(8):906-916.

Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals.

The COVID-19 pandemic has revealed a range of disease phenotypes in infected patients with asymptomatic, mild, or severe clinical outcomes, but the mechanisms that determine such variable outcomes remain unresolved. In this study, we identified immunodominant CD8 T-cell epitopes in the spike antigen using a novel TCR-binding algorithm. The predicted epitopes induced robust T-cell activation in unexposed donors demonstrating pre-existing CD4 and CD8 T-cell immunity to SARS-CoV-2 antigen. The T-cell reactivity to the predicted epitopes was higher than the Spike-S1 and S2 peptide pools in the unexposed donors. A key finding of our study is that pre-existing T-cell immunity to SARS-CoV-2 is contributed by TCRs that recognize common viral antigens such as Influenza and CMV, even though the viral epitopes lack sequence identity to the SARS-CoV-2 epitopes. This finding is in contrast to multiple published studies in which pre-existing T-cell immunity is suggested to arise from shared epitopes between SARS-CoV-2 and other common cold-causing coronaviruses. However, our findings suggest that SARS-CoV-2 reactive T-cells are likely to be present in many individuals because of prior exposure to flu and CMV viruses.

Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2.

COVID-19 is a respiratory illness caused by a novel coronavirus called SARS-CoV-2. The viral spike (S) protein engages the human angiotensin-converting enzyme 2 (ACE2) receptor to invade host cells with ~10-15-fold higher affinity compared to SARS-CoV S-protein, making it highly infectious. Here, we assessed if ACE2 polymorphisms can alter host susceptibility to SARS-CoV-2 by affecting this interaction. We analyzed over 290,000 samples representing >400 population groups from public genomic datasets and identified multiple ACE2 protein-altering variants. Using reported structural data, we identified natural ACE2 variants that could potentially affect virus-host interaction and thereby alter host susceptibility. These include variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R that were predicted to increase susceptibility, while variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y were predicted to be protective variants that show decreased binding to S-protein. Using biochemical assays, we confirmed that K31R and E37K had decreased affinity, and K26R and T92I variants showed increased affinity for S-protein when compared to wildtype ACE2. Consistent with this, soluble ACE2 K26R and T92I were more effective in blocking entry of S-protein pseudotyped virus suggesting that ACE2 variants can modulate susceptibility to SARS-CoV-2.