Adverse Events of SARS-CoV-2 Therapy: A Pharmacovigilance Study of the FAERS Database.

BACKGROUND: Over the past 2 years of the several strategies recommended to help fight COVID-19, nirmatrelvir/ritonavir is a novel drug shown in the EPIC-HR phase 2 to 3 clinical trial to lower COVID-19-related death or hospitalization at day 28 when compared with placebo. OBJECTIVE: Our study's aim was to explore the reported adverse events (AEs) associated with nirmatrelvir/ritonavir use for COVID-19. METHOD: We conducted a retrospective analysis using the FDA Adverse Event Reporting System (FAERS) database for AEs, listing nirmatrelvir/ritonavir as the primary drug between January and June 2022. The primary outcome was the incidence of reported AEs associated with nirmatrelvir/ritonavir. The OpenFDA database was queried using Python 3.10 to collect the AEs and Stata 17 was used to analyze the database. Adverse events were analyzed by associated medication, with "Covid-19" excluded. RESULTS: A total of 8098 reports were identified between January and June 2022. Most reported complaints in the AE system were COVID-19 and disease recurrence. The most common symptomatic AEs were dysgeusia, diarrhea, cough, fatigue, and headache. Event rates significantly rose between April and May. Disease recurrence and dysgeusia were the most commonly reported complaints for the top 8 concomitant drugs identified. Cardiac arrest, tremor, akathisia, and death were reported in 1, 3, 67, and 5 cases, respectively. CONCLUSIONS AND RELEVANCE: This is the first retrospective study done on reported AEs associated with nirmatrelvir/ritonavir use for COVID-19. COVID-19 and disease recurrence were the most reported AEs. Further monitoring of the FAERS database is warranted to periodically reassess the safety profile of this medication.

Sex-based differences in left ventricular assist device clinical outcomes.

BACKGROUND: Heart failure (HF) continues to be a significant public health issue, posing a heightened risk of morbidity and mortality for both genders. Despite the widespread use of left ventricular assist device (LVAD), the influence of gender differences on clinical outcomes following implantation remains unclear. OBJECTIVES: We investigated the impact of gender differences on readmission rates and other outcomes following LVAD implantation in patients admitted with advanced HF. METHODS: We conducted a retrospective study of patients who underwent LVAD implantation for advanced HF between 2014 and 2020, using the Nationwide Readmissions Database. Our study cohort was divided into male and female patients. The primary outcome was 30-day readmission (30-dr), while secondary outcomes were inpatient mortality, length of stay (LOS), procedural complication rates, and periadmission rates. Multivariate linear, Cox, and logistic regression analyses were performed. RESULTS: During the study period, 11,492 patients with advanced HF who had LVAD placement were identified. Of these, 22% (n = 2532) were females and 78% (n = 8960) were males. The mean age was 53.9 ± 10.8 years for females and 56.3 ± 10.5 years for males (adjusted Wald test, p < 0.01). Readmissions were higher in females (21% vs. 17%, p = 0.02) when compared to males. Cox regression analysis showed higher readmission events (hazard ratio: 1.24, 95% confidence interval: 1.01-1.52, p = 0.03) in females when compared to males. Inpatient mortality, LOS, and most procedural complication rates were not statistically significantly different between the two groups (p > 0.05, all). CONCLUSION: Women experienced higher readmission rates and were more likely to be readmitted multiple times after LVAD implantation when compared to their male counterparts. However, there were no significant sex-based differences in inpatient mortality, LOS, and nearly all procedural complication rates. These findings suggest that female patients may require closer monitoring and targeted interventions to reduce readmission rates.

Intracardiac leadless versus transvenous permanent pacemaker implantation: Impact on clinical outcomes and healthcare utilization.

BACKGROUND: Transvenous permanent pacemakers are used frequently to treat cardiac rhythm disorders. Recently, intracardiac leadless pacemakers offer potential treatment using an alternative insertion procedure due to their novel design. Literature comparing outcomes between the two devices is scarce. We aim to assess the impact of intracardiac leadless pacemakers on readmissions and hospitalization trends. METHODS: We analyzed the National Readmissions Database from 2016 to 2019, seeking patients admitted for sick sinus syndrome, second-degree-, or third-degree atrioventricular block who received either a transvenous permanent pacemaker or an intracardiac leadless pacemaker. Patients were stratified by device type and assessed for 30-day readmissions, inpatient mortality, and healthcare utilization. Descriptive statistics, Cox proportional hazards, and multivariate regressions were used to compare the groups. RESULTS: Between 2016 and 2019, 21,782 patients met the inclusion criteria. The mean age was 81.07 years, and 45.52 % were female. No statistical difference was noted for 30-day readmissions (HR 1.14, 95 % CI 0.92-1.41, p = 0.225) and inpatient mortality (HR 1.36, 95 % CI 0.71-2.62, p = 0.352) between the transvenous and intracardiac groups. Multivariate linear regression revealed that length of stay was 0.54 (95 % CI 0.26-0.83, p < 0.001) days longer for the intracardiac group. CONCLUSION: Hospitalization outcomes associated with intracardiac leadless pacemakers are comparable to traditional transvenous permanent pacemakers. Patients may benefit from using this new device without incurring additional resource utilization. Further studies are needed to compare long-term outcomes between transvenous and intracardiac pacemakers.

Ominous Sign of Pneumatosis Intestinalis With Portal Venous Gas.

The presence of gas and free air in the extraluminal space of the intestines is known as pneumatosis intestinalis (PI). There are many different causes of this finding, including gastrointestinal, pulmonary, autoimmune, and many more. It is often difficult to differentiate the etiology and clinical importance of the radiographic evidence on pneumatosis intestinalis due to the unclear pathophysiology causing the disease. To complicate things further, the ominous sign of portal venous gas poses the question of whether surgical intervention is needed. We report two cases both with clinical and radiographic evidence of secondary pneumatosis intestinalis with an associated sinister finding of portal venous gas. The cases differ by urgent surgical intervention versus observation before surgery. In this case series, we emphasize the importance of recognizing the radiographic finding and stress the need for further research to standardize a plan of care, including indications for surgery. We encourage more cases like this to be reported to aid in diagnosing and treating this condition early on with the aim of improving the mortality associated with it.

Advances in Endoscopic Ultrasound (EUS)-Guided Liver Biopsy.

Recent years have seen the emergence of endoscopic-ultrasound-guided liver biopsy (EUS-LB) as an effective alternative to traditional (percutaneous or transjugular) liver biopsy techniques. Comparative studies have demonstrated that both endoscopic and non-endoscopic approaches are similar in terms of diagnostic adequacy, accuracy, and adverse events; however, EUS-LB offers the advantage of reduced recovery time. Additionally, EUS-LB enables the sampling of both lobes of the liver as well as the advantage of portal pressure measurements. However, EUS-LB may be argued to have a high cost, although this procedure can be cost-effective if bundled with other endoscopic procedures. Approaches utilizing EUS-guided liver therapy, such as the administration of chemotherapeutic agents and EUS elastography, are in development, and their optimal integration into clinical care is likely to emerge in the coming years. In the present review, we evaluate the available literature on EUS-LB indications, contraindications, variations in needle biopsy techniques, comparative outcomes, advantages and disadvantages, and future trends and perspectives.

A Rare and Unusual Cause of Ischemic Stroke to Be Aware of.

Congenital absence of an internal carotid artery (ICA) is an extremely rare vascular anomaly. This case report presents an instance of right ICA agenesis to highlight the importance of early identification of this anomaly and its impact on disease presentation and complications. With transient ischemic attack (TIA), cerebrovascular accident (CVA), and cerebral aneurysms being among the chief presenting scenarios or course of the anomaly, it is important to have a high level of suspicion for these in patients with known ICA agenesis. Understanding the underlying development of this vasculature and its impact on cerebral circulation aids in identifying possible findings on imaging. This case report aims to delineate the pathophysiology of ICA agenesis, recognition of the vasculature that contributes to the anomaly, different presentations of the disease, complications, and obstacles in management.

Methotrexate Failure in the Treatment of Adult-Onset Still's Disease: A Case Report.

Adult-onset Still's disease (AOSD) is a rheumatological condition associated with significant morbidity and mortality. Typically a diagnosis of exclusion, the therapeutic management has relied mainly on symptom control and immune suppression. Methotrexate (MTX), a disease-modifying anti-rheumatoid drug (DMARDs), has become a drug of choice in treating several autoimmune conditions, including AOSD. Unfortunately, despite being largely effective, this medication can result in treatment failure, exacerbation, and a flare of symptoms. We present the case of a 31-year-old male who presented to us with weakness and palpitations, who was ultimately found to have a flare of his Still's disease, despite being on MTX therapy. Our hope is to encourage a suspicion for treatment failure in patients with similar symptoms, in order to encourage a faster initiation of alternative therapies to alleviate their discomfort.

Ayurvedic Herbal Therapies: A Review of Treatment and Management of Dementia.

Dementia has been characterized by atypical neurological syndromes and several cognitive deficits, such as extended memory loss, strange behavior, unusual thinking, impaired judgment, impotence, and difficulty with daily living activities. Dementia is not a disease, but it is caused by several neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Lewy's bodies. Several drugs and remedies are indicated for alleviating unusual cognitive decline, but no effective pharmacological treatment regimens are available without side effects. Herbal drugs or traditional medicines like Ayurveda have been known for facilitating and corroborating the balance between mind, brain, body, and environment. Ayurvedic therapy comprises 600 herbal formulas, 250 single plant remedies, and natural and holistic health-giving treatments that relieve dementia in patients and increase vitality. Ayurvedic Rasayana herbs [rejuvenating elements] strengthen the brain cells, enhance memory, and decrease stress. The current medicine scenario in the treatment of dementia has prompted the shift in exploring the efficacy of ayurvedic medicine, its safety, and its efficiency. This review presents the literature on several herbal treatments for improving dementia symptomatology and patients' quality of life.

Yoga as a Preventive Intervention for Cardiovascular Diseases and Associated Comorbidities: Open-Label Single Arm Study.

Aim: Common Yoga Protocol (CYP) is a standardized yoga protocol authored by experts from all over the world under the aegis of the Ministry of AYUSH, Ayurveda, Yoga and Naturopathy, Unani, Siddha, Sowa Rigpa and Homeopathy (AYUSH). The potential of CYP can be determined as a cost-effective lifestyle modification to prevent the risk of developing cardiovascular diseases (CVD). Methods: In this prospective trial, we compared the effect of CYP at baseline and after 1 month. A total of 374 yoga-naïve participants performed CYP under the supervision of experienced trainers. Physiological [body mass index (BMI), blood pressure, percent oxygen saturation], biochemical (fasting blood glucose and lipid profile), and neurocognitive parameters were measured before and after the intervention. Results: At day 30 of yoga practice, serum levels of low-density lipoprotein (LDL), total cholesterol (TC), and high-density lipoprotein (HDL) were found significantly improved as compared to the baseline levels observed at the time of enrollment. Similarly, the lipid profile was also obtained from experienced trainers and found to be significantly different from those of yoga-naïve volunteers. When the intervention was compared between the healthy yoga-naïve participants with yoga-naïve participants suffering from medical issues, it was found that cholesterol profile improved significantly in the healthy-naive group as compared to the diseased group (hypertension, diabetes, underwent surgery, and CVD). Conclusion: These results highlight the need for further research to better understand the effects of yoga on the primary prevention of CVD.

Neuromyelitis Optica Spectrum Disorder: A Rare Cause of Spinal Cord and Optic Nerve Involvement.

Neuromyelitis optica spectrum disorder (NMOSD) is defined as a rare central nervous system, demyelinating, autoimmune disorder with autoantibodies against aquaporin-4. Commonly affecting females, NMOSD is known to also be a relapsing disease and can increase in severity during each episode. Diagnostic criteria include ruling out multiple sclerosis, spinal magnetic resonance imaging, and autoantibody detection. While management focuses on relapse treatment and prevention, high-dose steroids and plasma exchange have proven to be useful options. We present a case of a young female presenting with NMOSD relapse appropriately managed with plasma exchange.

Role of Mind-Body Intervention on Lipid Profile: A Cross-sectional Study.

BACKGROUND: Yoga is a combination of physical-breathing and meditative techniques that assist in the unification of the mind-body, which improves the quality of life. It was shown that long-term Yoga practitioners had superior control over respiratory rate, reduced stress and anxiety, and a better-controlled lipid profile. PURPOSE: We aimed to investigate the lipid profile of long-term yoga practitioners who were practicing yoga for more than 1 year in comparison with the nonyoga group. METHODS: A nationwide survey was conducted in which the long-term yoga practitioners (n = 76) and nonyoga practitioners (n = 80) were recruited for assessment for the lipid parameters. RESULTS: The mean (standard deviation) values of both groups were within normal range with serum cholesterol at 189.715 ± 20.4 and 180.88 ± 29.7 and triglycerides at 216.72 ± 92.5 and 207.665 ± 88.3, low-density lipoprotein at 126.65 ± 18.5 and 120.775 ± 26.5, and high-density lipoprotein at 47.17 ± 6.6 and 44.99 ± 7.0, respectively, in yoga and no-yoga groups. CONCLUSION: The lipid profile values were similar in yoga and nonyoga practitioners in the 2017 survey.

Prevalence of prediabetes, and diabetes in Chandigarh and Panchkula region based on glycated haemoglobin and Indian diabetes risk score.

There is a rapid increase in the prevalence of diabetes in India. We wanted to review the status of prediabetes and diabetes in the combined population of Chandigarh and Panchkula region based on both Indian Diabetes Risk Score (IDRS) and Glycated Haemoglobin (HbA1c). A total of 1215 subjects were recruited during the screening process, out of which 444 i subjects have been analysed for the current study on the basis of high risk for IDRS (≥60) and their known diabetes status. This study included 431 subjects having high risk for IDRS (≥60) and 13 known subjects with diabetes (IDRS < 60) which were further analysed for biochemical and anthropometric parameters. The prevalence of diabetes was found to be 12.67% and prediabetes 11.69% in the combined population of Chandigarh and Panchkula. There was an increased level of fasting blood glucose (183.12 ± 68.61), postprandial blood glucose (262.57 ± 96.92), triglyceride (193.84 ± 119.88), very low-density lipoprotein (VLDL) (34.87 ± 15.42) and High Density Lipoprotein(HDL) (4.61 ± 1.39) in the said diabetes population. Mean HDL was found to be decreased in subjects having diabetes. Glucose-induced lipid intolerance study revealed significant alteration in triglyceride, HDL and VLDL. The study has revealed that high prevalence of diabetes in the sampled population when compared with the national average of 8.8%.

Effects of one month of Common Yoga Protocol practice appear to be mediated by the angiogenic and neurogenic pathway: A pilot study.

OBJECTIVE: To examine the molecular effects of mindful activities such as yoga and meditation DESIGN: This was an open label single arm exploratory yoga intervention study. STUDY PARTICIPANTS: 64 healthy individuals within the age of 18-60 years were recruited for this one month yoga intervention study. INTERVENTION: Common Yoga Protocol (CYP) is a standardized yoga protocol released by Ministry of AYUSH, India for International Yoga Day. It includes all aspects of yoga i.e. asanas, pranayama and meditation. It is designed for adoption by all age groups for the health of community. OUTCOME MEASURES: The participants were assessed for biochemical parameters including Fasting Sugar and Lipid profile. The molecular markers of neurogenesis (i.e. Brain derived Neurotropic Factor, BDNF) and Angiogenesis (i.e. Vascular Endothelial Growth Factor, VEGF and Angiogenin) along with Amyloid ß (marker related to neuro-degenerative diseases) were assessed. All the assessments were made at baseline and after one month of the intervention. RESULTS: After one month of CYP practice High Density Lipoprotein (HDL) levels increased significantly (p<0.001), although other biochemical parameters i.e. fasting sugar and other lipid assessments were found to be unaltered. Angiogenesis marker, angiogenin was increased significantly (p<0.002), other angiogenesis marker VEGF did not show any change along with BDNF, marker of neurogenesis. Amyloid ß levels were also unaltered. Even though individual levels of VEGF and Amyloid ß did not show any change, proportion of VEGF to Amyloid ß showed a significant increase (p<0.001) after one month of CYP intervention indicating that the change in VEGF levels was significantly higher than the change in Amyloid ß levels. CONCLUSION: CYP practice may influence cell survival pathways mediated by angiogenic and neurogenic cross talk. Hence, CYP can be considered as a preventive measure for diseases associated with impaired angiogenic and neurogenic mechanism. This is the first study to examine the effects of CYP at the molecular level.

Prevalence of Diabetes and Its Determinants in the Young Adults Indian Population-Call for Yoga Intervention.

Background: The young Indian population, which constitutes 65% of the country, is fast adapting to a new lifestyle, which was not known earlier. They are at a high risk of the increasing burden of diabetes and associated complications. The new evolving lifestyle is not only affecting people's health but also mounting the monetary burden on a developing country such as India. Aim: We aimed to collect information regarding the prevalence of risk of diabetes in young adults (<35 years) in the 29 most populous states and union territories (7 zones) of India, using a validated questionnaire. Methods: A user-friendly questionnaire-based survey using a mobile application was conducted on all adults in the 29 most populous states/union territories of India, after obtaining ethical clearance for the study. Here, we report the estimation of the prevalence of the risk of diabetes and self-reported diabetes on 58,821 young individuals below the age of 35 years. Risk for diabetes was assessed using a standardized instrument, the Indian diabetes risk score (IDRS), that has 4 factors (age, family history of diabetes, waist circumference, and physical activity). Spearman's correlation coefficient was used to check the correlations. Results: The prevalence of high (IDRS score > 60), moderate (IDRS score 30-50), and low (IDRS < 30) diabetes risk in young adults (<35 years) was 10.2%, 33.1%, and 56.7%, respectively. Those with high-risk scores were highest (14.4%) in the Jammu zone and lowest (4.1%) in the central zone. The prevalence of self-reported diabetes was 1.8% with a small difference between men (1.7%) and women (1.9%), and the highest (8.4%) in those with a parental history of diabetes. The south zone had the highest (2.5%), and the north west zone had the lowest (4.4%) prevalence. Conclusions: Indian youth are at high risk for diabetes, which calls for an urgent action plan through intensive efforts to promote lifestyle behavior modifications during the pandemics of both communicable and noncommunicable diseases.

Identifying putative cerebrospinal fluid biomarkers of amyotrophic lateral sclerosis in a north Indian population.

INTRODUCTION: Evidence-based information about cerebrospinal fluid (CSF) levels of biomarkers in patients with amyotrophic lateral sclerosis (ALS) is limited. METHODS: Vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2), optineurin (OPTN), monocyte chemoattractant protein-1 (MCP-1), angiogenin (ANG), and TAR DNA-binding protein (TDP-43) were quantified by enzyme-linked immunoassay in the CSF of 54 patients with sporadic ALS and 32 controls in a case-control study design. RESULTS: CSF levels of VEGF (P = .014) and ANG (P = .009) were decreased, whereas VEGFR2 was higher (P = .002) in patients with ALS than in controls. TDP-43 positively correlated with MCP-1 (P = .003), VEGF (P < .001), and VEGFR2 (P < .001) in patients with ALS. DISCUSSION: Our findings suggest possible utility of VEGF, VEGFR2, and ANG as biomarkers for use in ALS treatment trials.

Primer for Mainstreaming Mind-Body Techniques for Extreme Climates-Insights and Future Directions.

Background: The deprivation of oxygen reaching the tissues (also termed as hypoxia) affects the normal functioning of the body. This results in development of many diseases like ischemia, glaucoma, MCI (Mild Cognitive Impairment), pulmonary and cerebral edema, stress and depression. There are no effective drugs that can treat such diseases. Despite such failure, alternative interventions such as mind-body techniques (MBTs) have not been adequately investigated. Methods: The first part of this review has been focused on philosophical aspects of various MBTs besides evolving an ayurgenomic perspective. The potential of MBTs as a preventive non-pharmacological intervention in the treatment of various general and hypoxic pathologies has been further described in this section. In the second part, molecular, physiological, and neuroprotective roles of MBTs in normal and hypoxic/ischemic conditions has been discussed. Results: In this respect, the importance of and in vivo studies has also been discussed. Conclusions: Although several studies have investigated the role of protective strategies in coping with the hypoxic environment, the efficacy of MBTs at the molecular level has been ignored.