SARS-CoV-2 Catalonia contact tracing program : evaluation of key performance indicators

Background: Guidance on SARS-CoV-2 contact tracing indicators have been recently revised by international public health agencies. The aim of the study is to describe and analyse contact tracing indicators based on Catalonia's (Spain) real data and proposing to update them according to recommendations. Methods: Retrospective cohort analysis including Catalonia's contact tracing dataset from 20 May until 31 December 2020. Descriptive statistics are performed including sociodemographic stratification by age, and differences are assessed over the study period. Results: We analysed 923,072 contacts from 301,522 SARS-CoV-2 cases with identified contacts (67.1% contact tracing coverage). The average number of contacts per case was 4.6 (median 3, range 1-243). A total of 403,377 contacts accepted follow-up through three phone calls over a 14-day quarantine period (84.5% of contacts requiring follow-up). The percentage of new cases declared as contacts 14 days prior to diagnosis evolved from 33.9% in May to 57.9% in November. All indicators significantly improved towards the target over time (p < 0.05 for all four indicators). Conclusions: Catalonia's SARS-CoV-2 contact tracing indicators improved over time despite challenging context. The critical revision of the indicator's framework aims to provide essential information in control policies, new indicators proposed will improve system delay's follow-up. The study provides information on COVID-19 indicators framework experience from country's real data, allowing to improve monitoring tools in 2021-2022. With the SARS-CoV-2 pandemic being so harmful to health systems and globally, is important to analyse and share contact tracing data with the scientific community

Associations between lung function and future cardiovascular morbidity and overall mortality in a predominantly First Nations population : a cohort study.

Background: Spirometric lung function impairment is an independent predictor of respiratory and cardiovascular disease, and mortality across a broad range of socioeconomic backgrounds and environmental settings. No contemporary studies have explored these relationships in a predominantly regional/remote First Nations population, whose health outcomes are worse than for non-First Nations populations, and First Nations people living in urban centres. Methods: This was a retrospective cohort study of 1,734 adults (1,113 First Nations) referred to specialist respiratory outreach clinics in the state of Queensland, Australia from February 2012 to March 2020. Regression modelling was used to test associations between lung function and mortality and cardiovascular disease. Findings: At the time of analysis (August 2020), 189 patients had died: 88 (47%) from respiratory causes and 38 (20%) from cardiovascular causes. When compared to patients with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) Z-scores of >0 to -1, patients with Z-scores 1/FVC% Z-scores <-1 were associated with increased overall mortality (HR=1•6, 95%CI 1•1-2•3), but not cardiovascular disease (OR=1•1, 95%CI 0•8-1•4). These associations were not affected by First Nations status. Interpretation: Reduced lung function even within the clinically normal range is associated with increased mortality, and cardiovascular disease in First Nations Australians. These findings highlight the importance of lung function optimisation and inform the need for future investment to improve outcomes in First Nations populations. Funding: None.</p

Determinants and Follow-up of Lung Function Data from a Predominantly First Nations Cohort of Adults Referred to Specialist Respiratory Outreach Clinics in Regional and Remote Queensland

Purpose: Northern Territory (NT)-based clinical service data suggest substantial lung function impairment amongst First Nations adults as young as 18–40 years. Our objectives were to describe the burden of disease and lung function of adults living in regional-remote Queensland, identify determinants of lung function, and evaluate the impact of a specialist respiratory outreach service on lung function. Methods: Retrospective 8-year cohort study (February 2012–March 2020) of 1113 First Nations Australian adults (and 648 non-First Nations adults) referred to respiratory outreach clinics in regional-remote Queensland. Results: In the combined cohort, the forced expiratory volume in 1 s (FEV1) was clinically abnormal for 54% of First Nations patients (51% of non-First Nations patients), forced vital capacity (FVC) for 46% (36%), FEV1/FVC% for 30% (36%), and gas diffusing capacity (DLCO) for 44% (37%). A respiratory diagnosis was assigned by a respiratory physician in 78% of First Nations (76% non-First Nations) patients. Smoking, household smoke exposure, underweight BMI, and respiratory disease were associated with reduced lung function. In the 40% of patients (709/1765) followed up, FEV1 and FVC significantly improved (mean change: zFEV1 = 0.15 [95% CI 0.10–0.20]; zFVC = 0.25 [0.20, 0.31]), and FEV1/FVC% significantly reduced (mean = − 0.10 [95%CI − 0.07 to − 0.03]), with no significant change in DLCO. Patients with COPD had lower FEV1 improvement, whilst underweight and obese patients had lower FVC improvement. Conclusion: Regional-remote First Nations adult Queenslanders have higher lung function than previously reported, with no lung function decline observed at follow-up visit, including for those with respiratory disease.</p

Nonpeptidic Oxazole-Based Prolyl Oligopeptidase Ligands with Disease-Modifying Effects on alpha-Synuclein Mouse Models of Parkinson's Disease

Prolyl oligopeptidase (PREP) is a widely distributedserine proteasein the human body cleaving proline-containing peptides; however, recentstudies suggest that its effects on pathogenic processes underlyingneurodegeneration are derived from direct protein-protein interactions(PPIs) and not from its regulation of certain neuropeptide levels.We discovered novel nonpeptidic oxazole-based PREP inhibitors, whichdeviate from the known structure-activity relationship forPREP inhibitors. These new compounds are effective modulators of thePPIs of PREP, reducing alpha-synuclein (alpha Syn) dimerizationand enhancing protein phosphatase 2A activity in a concentration-responsemanner, as well as reducing reactive oxygen species production. Fromthe best performing oxazoles, HUP-55 was selected for in vivo studies. Its brain penetration was evaluated, andit was tested in alpha Syn virus vector-based and alpha Syn transgenicmouse models of Parkinson's disease, where it restored motorimpairment and reduced levels of oligomerized alpha Syn in the striatumand substantia nigra.Peer reviewe

Rab46 is a novel mast cell gtpase localised to secretory granules

[[abstract]]Background: In this meta-analysis we evaluated strategies on augmentation of host immunity against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. Method: We searched clinical trials registered at the National Institutes of Health by 30 November 2020, and conducted analyses on inoculated population, involved immunological processes, source of injected components, and trial phases. We then searched PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials for their corresponding reports. A bivariate random-effects meta-analysis was used to derive the pooled estimate of seroconversion and adverse events (AEs). Results: A total of 540,269 participants were enrolled in 225 identified trials. The working mechanisms included heterologous immunity, active immunity, passive immunity, and immunotherapy. A total of 2,565 healthy adults from 10 clinical trials were included for meta-analyses. The odd ratio (OR) was 90.82 for kinetics of serologic responses to anti-SARS-CoV-2 antibody IgG titer (95% CI =36.1 – 228.49; p < 0.00001). The pooled ORs were 2.57 for solicited systemic AEs (95%CI =1.57 – 4.21; p = 0.0002), 5.72 for solicited local AEs (95% CI=2.59 – 12.67; p < 0.0001), and 2.08 for unsolicited systemic events (95% CI=1.42 – 3.05; p = 0.0002), compared to placebo or conservative treatment. Conclusion: Among all immune-augmentative interventions, a paradigm shift to vaccines providing active immunity was observed. The efficacy of these interventions was promising although systemic adverse events were noted