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85 result(s) for "Shinde, Vivek"
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Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine
A recombinant SARS-CoV-2 spike protein nanoparticle vaccine delivered in the deltoid muscle on days 0 and 21 was found to be immunogenic at both 5 μg and 25 μg doses. When given with a saponin-based adjuvant, both doses were equally immunogenic, with little or no reactogenicity, and elicited neutralizing antibody titers higher than those in convalescent serum.
The epidemiology of medically attended respiratory syncytial virus in older adults in the United States: A systematic review
This review was undertaken to assess the historical evidence of the disease incidence and burden of laboratory-confirmed respiratory syncytial virus (RSV) in medically attended older adults. A qualitative systematic literature review was performed; no statistical synthesis of the data was planned, in anticipation of expected heterogeneity across studies in this population. A literature search of PubMed, Embase, and the Cochrane Library was conducted for studies of medically attended RSV in older adults (≥ 50 years) published in the last 15 years. Two independent reviewers screened titles and abstracts based on predefined inclusion and exclusion criteria. From 10 studies reporting incidence proportions, RSV may be the causative agent in up to 12% of medically attended acute respiratory illness in older adults unselected for comorbidities, with variations in clinical setting and by year. In multiple studies, medically attended-RSV incidence among older adults not selected for having underlying health conditions increased with increasing age. Of prospectively followed lung transplant recipients, 16% tested positive for RSV. In hospitalized adults with chronic cardiopulmonary diseases, 8% to 13% were infected with RSV during winter seasons (8%-13%) or metapneumovirus season (8%). Hospitalizations for RSV in older adults typically lasted 3 to 6 days, with substantial proportions requiring intensive care unit admission and mechanical ventilation. Among older adults hospitalized with RSV, the mortality rate was 6% to 8%. Protection of older adults against RSV could reduce respiratory-related burden, especially as age increases and the prevalence of comorbidities (especially cardiopulmonary comorbidities) grows.
Estimates of hospitalization attributable to influenza and RSV in the US during 1997–2009, by age and risk status
Background Estimates of influenza and respiratory syncytial virus (RSV) burden must be periodically updated to inform public health strategies. We estimated seasonal influenza- and RSV-attributable hospitalizations in the US from 1997 to 2009 according to age and risk status (NCT01599390). Methods Multiple linear regression modelling was used to attribute hospitalizations to influenza or RSV using virological surveillance and hospitalization data. Hospitalization data were obtained from the US Nationwide Inpatient Sample and virology data were obtained from FluView (Centers for Disease Control and Prevention). Outcomes included any mention of ICD-coded respiratory disease and cardiorespiratory disease diagnoses. We also explored a broader definition of respiratory disease that included mention of relevant respiratory sign/symptoms and viral infection (“respiratory broad”). Results Applying the respiratory broad outcome, our model attributed ~300,000 and ~200,000 hospitalizations to influenza and RSV, respectively. Influenza A/H3N2 was the predominant cause of influenza-related hospitalizations in most seasons, except in three seasons when influenza B was dominant; likewise, A/H3N2 caused most influenza-related hospitalizations in all age segments, except in children <18 years where the relative contribution of A/H3N2 and B was similar. Most influenza A- and B-related hospitalizations occurred in seniors while approximately one half and one third of all RSV-related events occurred in children 0–4 years and seniors 65+ years, respectively. High-risk status was associated with higher risk of both influenza- and RSV-attributable hospitalizations in adults, but not in children. Conclusions Our study assessed the burden of influenza and RSV, information that is important for both cost effectiveness studies and for prioritization of the development of antivirals and vaccines. For seniors, we found that the burdens of influenza and RSV were both substantial. Among children <18 years, about half of all influenza hospitalizations were due to influenza B, most occurring in children without noted risk conditions. RSV hospitalizations among children were confined to those 0–4 years. Our study also demonstrated the importance of the outcome used to estimate hospitalization burden. Our findings highlight the burden of influenza among children regardless of risk status and underscore the prevalence of RSV infections among both young children and older adults.
The Importance of Frailty in the Assessment of Influenza Vaccine Effectiveness Against Influenza-Related Hospitalization in Elderly People
Background. Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty. Methods. We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011–2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty. Results. Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%–73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%–73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased. Conclusions. Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased.
Estimates of mortality attributable to influenza and RSV in the United States during 1997–2009 by influenza type or subtype, age, cause of death, and risk status
Background Influenza and respiratory syncytial virus (RSV) cause substantial mortality from respiratory and other causes in the USA, especially among people aged 65 and older. Objectives We estimated the influenza‐attributable mortality and RSV‐attributable mortality in the USA, stratified by age and risk status, using outcome definitions with different sensitivity and specificity. Methods Influenza‐ and RSV‐associated mortality was assessed from October 1997–March 2009 using multiple linear regression modeling on data obtained from designated government repositories. Results The main outcomes and measures included mortality outcome definitions—pneumonia and influenza, respiratory broad, and cardiorespiratory disease. A seasonal average of 10 682 (2287–16 363), 19 100 (4862–29 245), and 28 169 (6797–42 316) deaths was attributed to influenza for pneumonia and influenza, respiratory broad, and cardiorespiratory outcome definitions, respectively. Corresponding values for RSV were 6211 (4584–8169), 11 300 (8546–14 244), and 17 199 (13 384–21 891), respectively. A/H3N2 accounted for seasonal average of 71% influenza‐attributable deaths; influenza B accounted for most (51–95%) deaths during four seasons. Approximately 70% influenza‐attributable deaths occurred in individuals ≥75 years, with increasing mortality for influenza A/H3N2 and B, but not A/H1N1. In children aged 0–4 years, an average of 97 deaths was attributed to influenza (A/H3N2 = 49, B = 33, A/H1N1 = 15) and 165 to respiratory broad outcome definition (RSV). Influenza‐attributable mortality was 2·94‐fold higher in high‐risk individuals. Conclusions Influenza‐attributable mortality was highest in older and high‐risk individuals and mortality in children was higher than reported in passive Centers for Disease Control and Prevention surveillance. Influenza B‐attributable mortality was higher than A in four of 12 seasons. Our estimates represent an updated assessment of influenza‐attributable mortality in the USA.
Wearable Surface Electromyography System to Predict Freeze of Gait in Parkinson’s Disease Patients
Freezing of gait (FOG) is a disabling yet poorly understood paroxysmal gait disorder affecting the vast majority of patients with Parkinson’s disease (PD) as they reach advanced stages of the disorder. Falling is one of the most disabling consequences of a FOG episode; it often results in injury and a future fear of falling, leading to diminished social engagement, a reduction in general fitness, loss of independence, and degradation of overall quality of life. Currently, there is no robust or reliable treatment against FOG in PD. In the absence of reliable and effective treatment for Parkinson’s disease, alleviating the consequences of FOG represents an unmet clinical need, with the first step being reliable FOG prediction. Current methods for FOG prediction and prevention cannot provide real-time readouts and are not sensitive enough to detect changes in walking patterns or balance. To fill this gap, we developed an sEMG system consisting of a soft, wearable garment (pair of shorts and two calf sleeves) embedded with screen-printed electrodes and stretchable traces capable of picking up and recording the electromyography activities from lower limb muscles. Here, we report on the testing of these garments in healthy individuals and in patients with PD FOG. The preliminary testing produced an initial time-to-onset commencement that persisted > 3 s across all patients, resulting in a nearly 3-fold drop in sEMG activity. We believe that these initial studies serve as a solid foundation for further development of smart digital textiles with integrated bio and chemical sensors that will provide AI-enabled, medically oriented data.
Triple-Reassortant Swine Influenza A (H1) in Humans in the United States, 2005–2009
Influenza is known to infect several different hosts, including humans, birds, and pigs. The influenza genome is structured in a way that allows for rapid recombination between strains across host species. In this report, 11 sporadic episodes of human infection from novel swine-associated influenza viruses are documented and the associated clinical illness and virologic characteristics are described. In this report, 11 sporadic episodes of human infection from novel swine-associated influenza viruses are documented and the associated clinical illness and virologic characteristics are described. Pigs have been hypothesized to act as a mixing vessel for the reassortment of avian, swine, and human influenza viruses and might play an important role in the emergence of novel influenza viruses capable of causing a human pandemic. 1 – 3 Recent reports of widespread transmission of swine-origin influenza A (H1N1) viruses in humans in Mexico, the United States, and elsewhere highlight this ever-present threat to global public health. 4 , 5 Between the 1930s and the 1990s, the most commonly circulating swine influenza virus among pigs — classic swine influenza A (H1N1) — underwent little change. However, by the late 1990s, multiple . . .
Novavax NVX-COV2373 triggers neutralization of Omicron sub-lineages
The SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern (VOC) and its sub-lineages (including BA.2, BA.4, BA.5, BA.2.12.1) contain spike mutations that confer high level resistance to neutralizing antibodies induced by vaccination with ancestral spike or infection with previously circulating variants. The NVX-CoV2373 vaccine, a protein nanoparticle vaccine containing the ancestral spike sequence, has value in countries with constrained cold-chain requirements. Here we report neutralizing titers following two or three doses of NVX-CoV2373. We show that after two doses, Omicron sub-lineages BA.1 and BA.4/BA.5 were resistant to neutralization by 72% (21/29) and 59% (17/29) of samples respectively. However, after a third dose of NVX-CoV2373, we observed high titers against Omicron BA.1 (GMT: 1,197) and BA.4/BA.5 (GMT: 582), with responses similar in magnitude to those triggered by three doses of an mRNA vaccine. These data are of particular relevance as BA.4/BA.5 is dominating in multiple locations, and highlight the potential utility of the NVX-CoV2373 vaccine as a booster in resource-limited environments.
Severe Human Influenza Infections in Thailand: Oseltamivir Treatment and Risk Factors for Fatal Outcome
Influenza is often not recognized as an important cause of severe or fatal disease in tropical and subtropical countries in Southeast Asia. The extent to which Oseltamivir treatment may protect against a fatal outcome in severe influenza infections is not known. Thailand's National Avian Influenza Surveillance (NAIS) system affords a unique opportunity to describe the epidemiology of laboratory-confirmed severe and fatal human influenza infections. During January 2004 through December 2006, 11,641 notifications to the NAIS were investigated in 73 of 76 Thai provinces. Clinical and demographic data and respiratory swab specimens were collected and tested by PCR for influenza. Using the NAIS database, we identified all patients with laboratory confirmed human influenza (A/H3N2, A/H1N1 and Type B) infection. A retrospective medical record review was conducted on all fatal cases with laboratory confirmed influenza and from a sample of hospitalized cases in 28 provinces. The association of underlying risk factors, Oseltamivir treatment and risk of a fatal outcome were examined. Human influenza infections were identified in 2,075 (18%) cases. Twenty-two (1%) deaths occurred including seven deaths in children less than ten years of age. Thirty-five percent of hospitalized human influenza infections had chest X-ray confirmed pneumonia. Current or former smoking; advanced age, hypertension and underlying cardiovascular, pulmonary or endocrine disease were associated with a fatal outcome from human influenza infection. Treatment with Oseltamivir was statistically associated with survival with a crude OR of .11 (95% CI: 0.04-0.30) and .13 (95% CI: 0.04-0.40) after controlling for age. Severe and fatal human influenza infections were commonly identified in the NAIS designed to identify avian A/H5N1 cases. Treatment with Oseltamivir is associated with survival in hospitalized human influenza pneumonia patients.
Twin Peaks: A/H1N1 Pandemic Influenza Virus Infection and Vaccination in Norway, 2009–2010
Vaccination campaigns against A/H1N1 2009 pandemic influenza virus (A/H1N1p) began in autumn 2009 in Europe, after the declaration of the pandemic at a global level. This study aimed to estimate the proportion of individuals vaccinated against A/H1N1p in Norway who were already infected (asymptomatically or symptomatically) by A/H1N1p before vaccination, using a mathematical model. A dynamic, mechanistic, mathematical model of A/H1N1p transmission was developed for the Norwegian population. The model parameters were estimated by calibrating the model-projected number of symptomatic A/H1N1p cases to the number of laboratory-confirmed A/H1N1p cases reported to the surveillance system, accounting for potential under-reporting. It was assumed in the base case that the likelihood of vaccination was independent of infection/disease state. A sensitivity analysis explored the effects of four scenarios in which current or previous symptomatic A/H1N1p infection would influence the likelihood of being vaccinated. The number of model-projected symptomatic A/H1N1p cases by week during the epidemic, accounting for under-reporting and timing, closely matched that of the laboratory-confirmed A/H1N1p cases reported to the surveillance system. The model-projected incidence of symptomatic A/H1N1p infection was 27% overall, 55% in people <10 years old and 41% in people 10-20 years old. The model-projected percentage of individuals vaccinated against A/H1N1p who were already infected with A/H1N1p before being vaccinated was 56% overall, 62% in people <10 years old and 66% in people 10-20 years old. The results were sensitive to assumptions about the independence of vaccination and infection; however, even when current or previous symptomatic A/H1N1p infection was assumed to reduce the likelihood of vaccination, the estimated percentage of individuals who were infected before vaccination remained at least 32% in all age groups. This analysis suggests that over half the people vaccinated against A/H1N1p in Norway during the 2009 pandemic may already have been infected by A/H1N1p before being vaccinated.