Actus Santé

Fixed dosing of tocilizumab in ICU admitted COVID-19 patients is a superior choice compared to bodyweight based dosing; an observational population pharmacokinetic and pharmacodynamic study

Introduction Tocilizumab improves outcome, including survival, in intensive care unit (ICU) admitted COVID-19 patients. The currently applied dosage of 8 mg/kg is based on use of this drug for other indications, however is has not formally been investigated for COVID-19. In this study pharmacokinetics and dynamics of tocilizumab were investigated in ICU admitted COVID-19 patients. Methods This was an open-label, single-center observational pharmacokinetic and -dynamic evaluation study. Enrolled patients, with polymerase chain reaction confirmed Covid-19 were admitted to the ICU for mechanical ventilation or high flow nasal canula oxygen support. All patients were 18 years of age or older and received tocilizumab within 24 hours after admission to the ICU and received 6 mg dexamethasone daily as concomitant therapy. Results 29 patients were enrolled between 15 December 2020 and 15 March 2021. A total of 139 tocilizumab plasma samples were obtained covering the pharmacokinetic curve of day 0 up to day 20 after tocilizumab initiation. A population pharmacokinetic model with parallel linear and non-linear clearance was developed and validated. Average AUC0-inf 1st DOSE was 938 [+/-190] ug/mL*days. Tocilizumab half-life was estimated to be 4.15 [+/-0.24] days. All patients had tocilizumab exposure above 1 ug/ml for at least 15 days. Conclusion This study provides evidence to support a fixed dose of 600 mg tocilizumab in COVID-19 patients. Furthermore our findings suggest that alternative cost saving regimens with even lower doses are likely to be as effective as the current 8 mg/kg recommendation.
Catégories: Actus Santé

Red Blood Cell-Conditioned Media from Non-Alcoholic Fatty Liver Disease Patients Contain Increased MCP1 and Induce TNF-α Release.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) constitutes a global pandemic. An intricate network among cytokines and lipids possesses a central role in NAFLD pathogenesis. Red blood cells comprise an important source of both cytokines and signaling lipids and have an important role in the molecular crosstalk during immunometabolic deregulation. However, their role in NAFLD has not been investigated in deep. METHODS: Conditioned media from erythrocytes derived from 10 NAFLD patients (4 men, 6 women, aged 57.875+-15,16) and 10 healthy controls (4 men, 6 women, aged 39.3+-15.55) were produced and used for the analysis of 9 cytokines (IFN-{gamma}, TNF-, CCL2, CCL5, IL-8, IL-1{beta}, IL-12p40, IL-17, MIP-1{beta}), 2 signaling lipids (Sphingosine 1-phosphate and Lysophosphatidic Acid), and cholesterol. Their effect on the cytokine profile released by RAW 264.7 macrophages was also studied. RESULTS: Erythrocytes from patients with NAFLD augmented the levels of MCP1 in the growth medium in comparison to the erythrocytes derived from healthy controls (37+-40 pg/ml vs 6.51+-5.63). No statistically significant differences were found between patients and healthy controls with regard to S1P, LPA, cholesterol and 8 other cytokines. TNF-a release by RAW 264.7 cells was increased after incubation with patient-derived erythrocyte conditioned medium compared to medium without RAW 264.7 cells from either healthy of NAFLD subjects. CONCLUSIONS: Erythrocytes could contribute to the liver infiltration by monocytes and to the activation of macrophages, partially due to release of CCL2, in the context of NAFLD.
Catégories: Actus Santé

A model to analyze rideshare data to surveil novel strains of SARS-CoV-2

Background: The emergence of novel, potentially vaccine-resistant strains of SARS-CoV-2 poses a serious risk to public health. The interactions between passengers and drivers facilitated by rideshare platforms such as Uber are, essentially, a series of partially standardized, random experiments of SARS-CoV-2 transmission. Rideshare companies share data with government health agencies, but no statistical method is available to aggregate these data for the systematic study of the transmission dynamics of COVID-19. Methods: We develop a proof-of-concept model for the analysis of data from rideshare interactions merged with COVID-19 diagnosis records. Using simulated data with rideshare volumes, disease prevalence, and diagnosis rates based on a large US city, we use the model to test hypotheses about the emergence of viral strains and their transmission characteristics in the presence of non-pharmaceutical interventions and superspreaders. Findings: Data from 10 simulated trials of SARS-CoV-2 propagation within the Los Angeles rideshare network resulted in an average of 190,387.1 potentially infectious rideshare interactions. Assuming access to data on 25% of the total estimated infections (Partial Reporting), these interactions resulted in an average of 409.0 diagnosed rideshare infections given our transmission model assumptions. For each of the 10 simulated trials, analysis given Partial Reporting could consistently differentiate between a baseline strain and an emergent, more infectious viral strain, enabling hypothesis testing about transmission characteristics. Interpretation: Simulated evaluation of a novel statistical model suggests that rideshare data combined with COVID-19 diagnosis data have the potential to automate continued surveillance of emergent novel strains of SARS-CoV-2 and their transmission characteristics.
Catégories: Actus Santé

SIR-based model with multiple imperfect vaccines.

Since the introduction of vaccination in the current COVID-19 outbreak, many countries have approved and implemented vaccination campaigns to mitigate and ultimately curtail the pandemic. Several types of vaccines have been proposed and many of them have finally been approved and used in different countries. The different types of vaccines have different vaccine parameters, and therefore, this situation induces the necessity of modeling mathematically the scenario of multiple imperfect vaccines. In this paper, we introduce a SIR-based model considering different vaccines, and study the basic properties of the model, including the stability of the Disease-Free Equilibrium (DFE), which is locally asymptotically stable if the reproduction number is less than 1. A sequence of further results aims to enumerate the conditions where the reproduction number can be decreased (or increased). Two important mathematical propositions indicate that in general vaccination might not be enough to contain an outbreak and that the addition of new vaccines could be counterproductive if the leakiness parameter is greater than a threshold {eta}. This model, despite its simplicity, was validated with data of the COVID-19 pandemic in five countries: Israel, Chile, Germany, Lithuania, and Czech Republic, observing that improvements for the vaccine campaigns can be suggested by the developed theory.
Catégories: Actus Santé

Neutralizing response against E484K variant after original SARS-CoV-2 infection

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variants, which are spreading in the United Kingdom (UK) and elsewhere, have been found in infected individuals in Japan. The virus mutates, to facilitate its life in the host, during the process of repeated proliferation in the body of the host, including humans. In other words, it is natural that a human-compatible mutant strain always predominates in infection and proliferation. As a result, the viral mutants acquire strong proliferative potential in the host and are highly pathogenic. The number of people infected with the mutated SARS-CoV-2 variant E484K, which is different from the SARS-CoV-2 variants that are spreading in the UK, South Africa, and Brazil, is increasing in Tokyo. It has been pointed out that the effects of immunity and vaccines may be reduced against the Tokyo-type SARS-CoV-2 variant E484K. We have investigated the neutralization response to various mutations in the spike glycoprotein using the serum of people already infected with the original SARS-CoV-2. The results showed that SARS-CoV-2 variants with Y543F or N501Y mutations in the spike glycoprotein affect the neutralization reaction. However, single E484K mutations within the spiked glycoprotein of the Tokyo-type SARS-CoV-2 variant are unlikely to have a significant effect on the affinity of the host antibody for the virus.
Catégories: Actus Santé

Meta-analysis of rapid direct-to-PCR assays for the qualitative detection of SARS-CoV-2

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing COVID-19 pandemic present significant challenges to current diagnostic and therapeutic patient care pathways including whether new in vitro diagnostic tests can accurately identify and rule out current SARS-CoV-2 infection. The gold standard diagnostic test to identify a current SARS-CoV-2 infection is a central laboratory-based molecular assay using reverse transcription polymerase chain reaction (RT-PCR) with very high accuracy of detection but which typically requires 1-2 days turn-around for results. Therefore, rapid RTPCR assays and systems have been developed which can be deployed locally (near-patient or point of care (POC), provide faster results and not impact on already stressed central laboratory capacity. Rapid test results can be returned within the same clinical encounter, facilitating timely decisions that optimise the patient care pathway and support more rapid COVID-19 diagnosis, isolation and contract tracing activities. Direct-to-PCR is an evolution of RT-PCR in which the patient sample is added directly to an amplification reaction without being subjected to prior nucleic acid extraction, purification, or quantification to reduce the time and monetary resources required to process samples. Rapid, direct-to-PCR systems further increase the speed of testing by combining rapid PCR instruments with direct-to-PCR assays, to generate results in less than two hours. This appears to be the first meta-analysis assessing the accuracy of rapid direct-to-PCR in the detection of SARS-CoV-2. In total, 10,957 unique records were identified and screened using a search string evaluation, 420 full-text reports and/or supplemental materials were assessed for inclusion. This resulted in 14 studies reporting 20 datasets with 4593 patient samples (1391 positive) included in the analysis. The overall agreement between the rapid direct RT-PCR and gold standard centralised laboratory RT-PCR was 97.1% with 93.60% positive percent agreement and 98.63% negative percent agreement. The Cohens kappa statistical coefficient k = 0.93, indicating an almost perfect agreement and Youden Index = 0.92. These results indicate that direct-to-PCR assays can perform equivalently to the standard centralised laboratory PCR systems for the detection of SARS-CoV-2. Objectives: To assess the efficacy of rapid direct-to-PCR assays and systems for the detection of SARS-CoV-2 in the hospital, care home and medical research population in England from November 2020 to April 2021. Search methods: Electronic searches of the Cochrane COVID-19 Study Register (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) were undertaken on the 30th of April 2020. Please see the PRISMA flow diagram below (figure 2). Selection criteria: Studies of subjects with either suspected SARS-CoV-2 infection, known SARS-CoV-2 infection or known absence of infection, or those who were being screened for infection were included. Commercially available and research use rapid direct-to-PCR assays (without RNA extraction and purification reporting results within two hours) were included in the study. Data collection, extraction and analysis: Studies were screened independently, in duplicate with any disagreements resolved by discussion with a third author. Study characteristics were extracted by one author and checked by a second; extraction of study results and assessments of risk of bias and applicability were undertaken independently in duplicate. Where studies were not publicly available, sites that undertook in-service evaluations of rapid direct-to-PCR system were contacted and asked to supply anonymised datasets. Both reviewers independently performed data extraction and verification and calculated 2x2 contingency tables of the number of true positives, false positives, false negatives and true negatives. They resolved any disagreements by discussion and by review with the third reviewer. Main results: Twenty study cohorts were included (described in 14 study reports, including 4 unpublished reports), reporting results for 4593 samples (1391 with confirmed SARS-CoV-2). Studies were mainly from Europe and North America, and evaluated nine direct-to-PCR assays. Conclusions: This appears to be the first meta-analysis assessing the accuracy of rapid direct-to-PCR in the detection of SARS-CoV-2. In total, 10,957 unique records were identified and screened using a search string evaluation, 420 full-text reports and/or supplemental materials were assessed for inclusion. This resulted in 14 studies reporting 20 datasets with 4593 patient samples (1391 positive) included in the analysis. The overall agreement between the rapid direct RT-PCR and gold standard centralised laboratory RT-PCR was 97.10% with 93.60% positive percent agreement and 98.63% negative percent agreement. The Cohens kappa statistical coefficient k = 0.93, indicating an almost perfect agreement and Youden Index = 0.92. These results show that direct-to-PCR assay perform equivalently to the gold standard centralised laboratory RT-PCR systems for the detection of SARS-CoV-2.
Catégories: Actus Santé

SARS-CoV-2 antibodies rapid tests: a valuable epidemiological tool in challenging settings

Background: During the last year, mass screening campaigns have been carried out to identify immunological response to SARS-CoV-2 and establish a possible seroprevalence. The obtained results gained new importance with the beginning of SARS-CoV-2 vaccination campaign, as the lack of doses has persuaded several countries to introduce different policies for individuals who had a history of COVID 19. LFAs may represent an affordable tool to support population screening in LMICs, where diagnostic tests are lacking, and epidemiology is still widely unknown. However, LFAs have demonstrated a wide range of performance and the question of which one could be more valuable in these settings still remains. Methods: We evaluated the performance of 11 LFAs in detecting SARS-CoV-2 infection, analysing samples collected from 350 subjects. In addition, samples from 57 health care workers collected at 21-24 days after the first dose of Pfizer-BioNTech vaccine were also evaluated. Findings: LFAs demonstrated a wide range of specificity (92.31% to 100%) and sensitivity (50 to 100%). The analysis of serum samples post vaccination was used to describe the most suitable tests to detect IgG response against S protein RBD. History of TB therapy was identified as a potential factor affecting the specificity of LFAs. Conclusions: This analysis identified which LFAs represent a valuable tool not only for the detection of prior SARS-CoV-2 infection, but also to detect IgG elicited in response to vaccination. These results demonstrated that different LFAs may have different applications and the possible risks of their use in high TB burden settings.
Catégories: Actus Santé

No excess mortality detected in rural Bangladesh in 2020 from repeated surveys of a population of 81,000

Background Excess mortality has demonstrated under-counting of COVID-19 deaths in many countries but cannot be measured in low-income countries where civil registration is incomplete. Methods Enumerators conducted an in-person census of all 16,054 households in a sample of 135 villages within a 350 km2 region of Bangladesh followed by a census conducted again in May and November 2020 over the phone. The date and cause of any changes in household composition, as well as changes in income and food availability, were recorded. For analysis, we stratify the mortality data by month, age, gender, and household education. Mortality rates were modeled by Bayesian multilevel regression and the strata aggregated to the population by poststratification. Results A total of 276 deaths were reported between February and the end of October 2020 for the subset of the population that could be contacted twice over the phone, slightly below the 289 deaths reported for the same population over the same period in 2019. After adjustment for survey non-response and poststratification, 2020 mortality changed by -8% (95% CI, -21% to 7%) relative to an annualized mortality of 6.1 per thousand in 2019. However, salaried breadwinners reported a 40% decline in income and businesses a 60% decline in profits in May 2020. Discussion All-cause mortality in the surveyed portion of rural Bangladesh was if anything lower in 2020 compared to 2019. Our findings suggest various restrictions imposed by the government limited the scale of the pandemic, although they need to be accompanied by expanded welfare programs.
Catégories: Actus Santé

MASK MANDATES REDUCE COVID-19 MORTALITY: Analysis of 37 States and the District of Columbia, with a further analysis of the impact of demographic and medical factors on efficacy.

As the number of COVID-19 deaths in the US increased, various policies were enacted to slow the spread of the pandemic. While the situation has improved in recent months, determining how best to combat the current pandemic is still essential. Failure to do so invites both further resurgences of the current pandemic, and more pandemics in the years to come. As a result of the widespread failure to contain the spread of COVID-19, enough deaths have occurred that the impact of policy on mortality may be statistically evaluated. This paper uses Optimal Discriminant Analysis (ODA) to evaluate the hypothesized ability of limited mask mandates (MM) to reduce the daily number of COVID-19 deaths in the states analyzed. The mandates were found to reduce mortality in half the states analyzed and did not result in increased mortality in any states. A full range of cofactors were analyzed to determine which, if any, influenced the efficacy of the mandates in the states in which mandates had an effect. Institutional Health Subindex of the Social Capital Index, state health score, population density, portion of the population with nongroup health insurance, state GDP, and the rate of pregnancy related diabetes were all correlated with increased mandate efficacy. In contrast, incarceration rate, overcrowded housing, severely overcrowded housing, portion of the population with military provided insurance, portion of the population uninsured, the portion of the population unable to see a doctor due to cost, and the portion of the population who were American Indian/Native Alaskan were all correlated with reduced mandate efficacy.
Catégories: Actus Santé

fNIRS-derived Neurocognitive Ratio as a Biomarker for Neuropsychiatric Diseases

Clinical use of fNIRS derived features has always suffered low sensitivity and specificity due to signal contamination from background systemic physiological fluctuations. The aim in this study is to investigate the classification accuracy of a an fNIRS derived biomarker based on global efficiency. To this end, fNIRS data were collected during a computerized Stroop Task from healthy controls, and patients with migraine, obsessive compulsive disorder, and schizophrenia. Functional connectivity (FC) maps were computed from [HbO] time series data for Neutral, Congruent and Incongruent stimuli using the partial correlation approach. Reconstruction of FC matrices with optimal choice of principal components yielded two independent networks: Cognitive Mode Network (CM) and Default Mode Network(DM). Global Efficiency (GE) values computed for each FC matrix after applying principal component analysis yielded strong statistical significance leading to a higher specificity and accuracy. A new index, Neurocognitive Ratio (NCR), was computed by multiplying the Cognitive Quotients (CQ) and ratio of GE of CM to GE of DM. When mean values of NCR (NCR) over all stimuli were computed, they showed high sensitivity (100%), specificity (95.5%), and accuracy (96.3%) for all subjects groups. NCR can reliable be used as a biomarker to improve the classification of healthy to neuropsychiatric patients.
Catégories: Actus Santé

Genome-wide transethnic meta-analysis identifies novel susceptibility loci for childhood acute lymphoblastic leukemia

The incidence patterns of childhood acute lymphoblastic leukemia (ALL) differ across ethnic groups but have been studied mostly in populations of predominantly European ancestries. Risk variants identified from previous genome-wide association studies (GWAS) do not fully explain heritable risk. In an effort to address these limitations, we performed a meta-analysis of ALL in 76,317 participants across four ethnic groups, including 17,814 non-European individuals and 3,482 total cases. We generally replicated previously identified loci associated with ALL (15 out of 16 loci replicated after Bonferroni corrections). We further identified five novel associations at genome-wide significance, including three novel loci and two secondary associations at previously known loci (17q12 and near CEBPE). The three putatively novel loci (rs9376090 near MYB/HBS1L on chr6q23.3, rs10998283 near TET1 on chr10q21.3, and rs9415680 near JMJD1C/NRBF2 on chr10q21.3) were previously shown to be associated with multiple blood cell traits and other hematopoietic cancers. When trans-ethnic information is used, polygenic risk scores constructed from GWAS loci in our trans-ethnic meta-analysis showed similar efficacy in independent Latino (LAT) and non-Latino white (NLW) ALL cohorts (AUC ~ 0.67-0.68) and could partly explain the increased risk of ALL in LAT compared to NLW. Cross-population analysis also showed high but significantly less than 100% genetic correlation between LAT and NLW, suggesting potential differences in the underlying genetic architecture between ethnic groups. In summary, our findings enhance the understanding of genetic contribution to ALL risk across diverse populations and highlight the importance to include multiple ethnic groups in GWAS.
Catégories: Actus Santé

INFLUENCE OF NOVEL CORONAVIRUS DISEASE (COVID-19) ON PARKINSONS DISEASE: SYSTEMATIC REVIEW

Background: The novel Coronavirus (COVID 19) infection has affected the population with various medical issues including the underlying neurological comorbidities such as Parkinson disease. COVID 19 is found to bind with the host angiotensin-converting enzyme 2 (ACE2) receptors for viral entry. ACE2 receptors are normally expressed in various body surfaces as well as in the neurons and glial cells where they act as an entry port to SARS-CoV-2 infection to invade the central nervous system (CNS). ACE2 are also highly expressed in dopamine neurons which might worsen the outcome in terms of motor symptoms in PD with the treatment course. It may lead to an indirect response via immune-mediated cytokine storms and propagate through CNS leading to damage. Parkinsons disease has also been noticed due to certain post viral infections apart from COVID-19 such as, HSV, Influenza virus A, Measles virus, Cytomegalovirus and Mumps (Olsen et al, 2018). We aim to provide a thorough review on neurological outcomes and impact of COVID-19 in Parkinson disease. Methods: A systematic review was conducted to analyze the impact of COVID 19 in patients with Parkinson disease (> 21 yo). Systematic literature search was done using PubMed, Science Direct, Google Scholar and Cochrane databases. PRISMA guidelines were followed summarized in Fig. 3 for study acquisition. Results: Of the Parkinsons patients that were tested positive for SARS-CoV 2, worsening of motor symptoms were reported along with other COVID 19 symptoms (Fig. 4 and 5). These symptoms include bradykinesia, tremors, gait disturbances, delirium and dementia and severe spasms of arms and legs. Encephalopathy was also one of the main symptoms presented in two of the studies. Increased mortality rates were identified for those who were hospitalized due to COVID-19 and PD when compared to other patients. Conclusion: Parkinsons disease may experience substantial worsening of motor and non motor symptoms during COVID 19. Due to the novelty of the virus, studies were reported from recent years and further extensive studies are needed to explore more about the disease severity and neurological outcomes when compared to other non-PD patients. Authors identify this as a limitation for this paper. Additional studies are needed to understand the role of ACE2 in increasing vulnerability to viruses and role of ACE inhibitors as treatment modality.
Catégories: Actus Santé

Antibody Response to COVID-19 vaccination in Patients Receiving Dialysis

Background: Patients receiving dialysis may mount impaired responses to COVID19 vaccination. Methods: We report antibody response to vaccination from 1140 patients without, and 493 patients with pre-vaccination SARS-CoV-2 RBD antibody. We used commercially available assays (Siemens) to test remainder plasma monthly in association with vaccination date and type, and assess prevalence of absent total receptor binding antibody, and absent or attenuated (index value < 10) semiquantitative receptor binding domain IgG index values. We used Poisson regression to evaluate risk factors for absent or attenuated response to vaccination. Results: Among patients who were seronegative versus seropositive before vaccination, 62% and 56% were [≥]65 years old, 20% and 24% were Hispanic, and 22% and 23% were Black. Median IgG index values rose steadily over time, and were higher among the seropositive than in the seronegative patients after completing vaccination (150 [25th, 75th percentile 23.2, 150.0] versus 41.6 [11.3, 150.0]). Among 610 patients who completed vaccination (assessed [≥]14 days later, median 29 days later), the prevalence of absent total RBD response, and absent and attenuated semiquantitative IgG response was 4.4% (95% CI 3.1, 6.4%), 3.4% (2.4, 5.2%), and 14.3% (11.7, 17.3%) respectively. Risk factors for absent or attenuated response included longer vintage of end-stage kidney disease, and lower pre-vaccination serum albumin. Conclusions: More than one in five patients receiving dialysis had evidence of an attenuated immune response to COVID19 vaccination.
Catégories: Actus Santé

Technology-delivered undergraduate medical education involving patients and carers: A rapid systematic review

Background: Involving patients and carers in medical education centralises their voice in healthcare and supports students to develop key professional and person-centred skills. Medical schools are increasingly using technology to deliver educational activities. No review currently exists to establish the variety of technologies and their uses in undergraduate medical education when patients and/or carers are involved. Methods: Ovid MEDLINE, Ovid EMBASE and medRxiv were searched in October 2020 and reference lists of key articles were hand searched. Eligible studies reported technology-assisted education, in any setting, involving authentic patients and/or carers. Studies in foreign languages, or describing actors or non-authentic patients were excluded. Study quality was assessed using the Mixed Methods Appraisal Tool (MMAT). Levels of patient involvement were assessed using Towle et al (2010) taxonomy. Results: Twenty studies were included. The majority involved patients and/or carers via pre-recorded videos or online scenarios, with no student-interaction. Four studies evaluated remote consultations using telehealth technology, involving real-time interactions with authentic patients. Technology-supported teaching sessions involving patients and/or carers were found to be acceptable to students, educationally valuable (to students and educators), and enhanced student engagement, patient-centred attitudes, knowledge of specific patient groups, and communication and clinical skills. Two studies describing real-time remote interactions with authentic patients indicated potential barriers for students (reduced ability to build relationship with patients and examine them), educators (reduced ability to build rapport with students) and patients (issues with using or accessing telehealth). Conclusions: No studies directly measured the perspective of patients or carers involved in technology-delivered medical education. Future research should establish barriers and facilitators to patients and carers taking up a role in medical students education when technology is used, and evaluate PPI activities at Levels 3 and above as described by Towle et al taxonomy.
Catégories: Actus Santé

Is a fair comparison between doping tested and doping untested powerlifters possible?

Purpose: Powerlifting is clearly divided into doping tested amateur competitions and doping untested pro competitions with pro competition money prizes ranging from a few thousand USD to over 120 000 USD in a single competition. However, the results of both pro and amateur powerlifting competitions are then collected and put into the same result database (although there is the possibility to filter the results using doping control status). The powerlifting results are compared by scores to have a fair comparison between different weight class athletes. This study plays with the thought of comparing doping tested and doping untested athletes, and creates a coefficient for the comparison. Methods: The powerlifting results (noted in kg) of the 10 top ranked athletes per weight class and separately for men and women, and for doping tested and doping untested categories were collected from the openpowerlifting.org database. A weight adjusted model was fit to these results separately for men and women with the doping control status used a binary factor. Results: Doping control status was a significant factor when modelling the powerlifting results, p<0.001 for both men and women. Men's doping untested results were 1.0725 times as large as the doping tested results. Women's doping untested results were 1.1208 times as large as the doping tested results. These separate and precise factors could be used as coefficients for scoring doping tested and doping untested athletes' powerlifting results. Moreover, the coefficients approximate the effect of doping on an elite level athlete's results.
Catégories: Actus Santé

Indexing Cerebrovascular Health Using Near-infrared Spectroscopy

Near-infrared spectroscopy (NiRS) is a relatively new technology of brain imaging with its potential in the assessment of cerebrovascular health only recently discovered. Encouraging early results suggest that NiRS can be used as an inexpensive and portable cerebrovascular health tracking device using a recently proposed pulse relaxation function (PReFx). In this paper, we propose a new NiRS timing index, TI-NiRS, of cerebrovascular health. TI-NiRS is a novel use of the NiRS technology. TI-NiRS is motivated by the previously proved relationship of the timing of the reflected wave with vascular resistance and compliance in the context of pressure waveforms. We correlated both TI-NiRS and PReFx against age, a non-exercise cardiorespiratory fitness (CRF) index, and two existing indices of cerebrovascular health, namely Transcranial Doppler (TCD) augmentation index, AI-TCD, and magnetic resonance imaging (MRI) blood flow pulsatility index, PI-MRI. The TI-NiRS correlations with Age, CRF, PI-MRI and AI-TCD all are significant, i.e., r = 0.53 (p = 0.002), r = 0.44 (p = 0.011), r = 0.45 (p = 0.012) and r = 0.46 (p = 0.010), respectively. PReFx, however, did not have significant correlations with any of the vascular health factors. The proposed timing index is a reliable indicator of cerebrovascular aging factors in the NiRS waveform.
Catégories: Actus Santé

Homebrew reagents for low cost RT-LAMP

RT-LAMP (reverse transcription - Loop-mediated isothermal amplification) has gained popularity for the detection of SARS-CoV-2. The high specificity, sensitivity, simple protocols and potential to deliver results without the use of expensive equipment has made it an attractive alternative to RT-PCR. However, the high cost per reaction, the centralized manufacturing of required reagents and their distribution under cold chain shipping limits RT-LAMP applicability in low-income settings. The preparation of assays using homebrew enzymes and buffers has emerged worldwide as a response to these limitations and potential shortages. Here, we describe the production of Moloney murine leukemia virus (M-MLV) Reverse Transcriptase and BstLF DNA polymerase for the local implementation of RT-LAMP reactions at low cost. These reagents compared favorably to commercial kits and optimum concentrations were defined in order to reduce time to threshold, increase ON/OFF range and minimize enzyme quantities per reaction. As a validation, we tested the performance of these reagents in the detection of SARS-CoV-2 from RNA extracted from clinical nasopharyngeal samples, obtaining high agreement between RT-LAMP and RT-PCR clinical results. The in-house preparation of these reactions results in an order of magnitude reduction in costs, and thus we provide protocols and DNA to enable the replication of these tests at other locations. These results contribute to the global effort of developing open and low cost diagnostics that enable technological autonomy and distributed capacities in viral surveillance.
Catégories: Actus Santé

Clinical outcomes and cost-effectiveness of COVID-19 vaccination in South Africa

Low- and middle-income countries are implementing COVID-19 vaccination strategies in light of varying and uncertain vaccine efficacies and costs, supply shortages, and resource constraints. We used a microsimulation model to evaluate clinical outcomes and cost-effectiveness of a COVID-19 vaccination program in South Africa. We varied vaccination coverage, pace, acceptance, effectiveness, and cost as well as epidemic dynamics. Providing vaccine to at least 40% of the population and prioritizing accelerated vaccine rollout prevented >9 million infections and >73,000 deaths and reduced costs due to fewer hospitalizations. Further, the vaccination program was cost-saving even at the lowest examined levels of acceptance (50%), effectiveness against infection (20%), effectiveness against symptomatic disease (30%), and effectiveness against severe/critical disease requiring hospitalization (40%), and with vaccination costs of up to USD25/person. In summary, a COVID-19 vaccination program would reduce both deaths and health care costs in South Africa across a wide range of assumptions. Vaccination program implementation factors, including prompt procurement, distribution, and rollout, are likely more influential than characteristics of the vaccine itself in maximizing public health benefits and economic efficiency.
Catégories: Actus Santé

Comprehensive and Temporal Surveillance of SARS-CoV-2 in Urban Water Bodies: Early Signal of Second Wave Onset

The possible faecal-oral transmission of SARS-CoV-2 through domestic discharges has emerged as a serious public health concern. Based on persistence of the virus in environment, the wastewater-based epidemiology (WBE) enabled the surveillance of infection in a community. The water bodies connected to the anthropogenic activities have strong possibility of presence of the SARS-CoV-2 genetic material. In this work, we monitored urban, peri-urban and rural lakes in and around Hyderabad as a long-term surveillance study for presence of enteric virus SARS-CoV-2 gene fragments. The study time of seven months coincided with the first and second wave of COVID-19 infection. The study depicted differential viral RNA copies in the urban lake with high viral load observed during the peaks of wave I and wave II. Distinct variability in viral genes detection was observed amongst all five lakes which were in concordance with the human activity of the catchment area. The SARS-CoV-2 genes were not detected in peri-urban and rural lakes, whereas the urban lakes having direct functional attributes from domestic activity, in the community showed presence of viral load. The outcome of the study clearly shows that the urban water streams linked with domestic discharge will function as a proxy for wastewater epidemiological studies. The surge in viral gene load from February 2021 sample suggests the on shoot of the second wave of infection, which correlated well with the prevailing pandemic situation. Implementation of regular WBE based monitoring system for the water bodies/wastewater in the urban and semi-urban areas will help to understand the outbreak and spread of virus in the community.
Catégories: Actus Santé

Impact of vaccination on the COVID-19 pandemic: Evidence from U.S. states

Governments worldwide are implementing mass vaccination programs in an effort to end the novel coronavirus (COVID-19) pandemic. Although the approved vaccines exhibited high efficacies in randomized controlled trials, their population effectiveness in the real world remains less clear, thus casting uncertainty over the prospects for herd immunity. In this study, we evaluated the effectiveness of the COVID-19 vaccination program and predicted the path to herd immunity in the U.S. Using data from 12 October 2020 to 7 March 2021, we estimated that vaccination reduced the total number of new cases by 4.4 million (from 33.0 to 28.6 million), prevented approximately 0.12 million hospitalizations (from 0.89 to 0.78 million), and decreased the population infection rate by 1.34 percentage points (from 10.10% to 8.76%). We then built a Susceptible-Infected-Recovered (SIR) model with vaccination to predict herd immunity. Our model predicts that if the average vaccination pace between January and early March 2021 (2.08 doses per 100 people per week) is maintained, the U.S. can achieve herd immunity by the last week of July 2021, with a cumulative vaccination coverage of 60.2%. Herd immunity could be achieved earlier with a faster vaccination pace, lower vaccine hesitancy, or higher vaccine effectiveness. These findings improve our understanding of the impact of COVID-19 vaccines and can inform future public health policies regarding vaccination, especially in countries with ongoing vaccination programs.
Catégories: Actus Santé

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