81 research outputs found

    Disrupted endothelial cell heterogeneity and network organization impair vascular function in prediabetic obesity

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    Background: Obesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, and stroke. Impaired endothelial function occurs in the earliest stages of obesity and underlies vascular alterations that give rise to cardiovascular disease. However, the mechanisms that link weight gain to endothelial dysfunction are ill-defined. Increasing evidence suggests that endothelial cells are not a population of uniform cells but are highly heterogeneous and are organized as a communicating multicellular network that controls vascular function. Purpose: To investigate the hypothesis that disrupted endothelial heterogeneity and network-level organization contribute to impaired vascular reactivity in obesity. Methods and Results: To study obesity-related vascular function without complications associated with diabetes, a state of prediabetic obesity was induced in rats. Small artery diameter recordings confirmed nitric-oxide mediated vasodilator responses were dependent on increases in endothelial calcium levels and were impaired in obese animals. Single-photon imaging revealed a linear relationship between blood vessel relaxation and population-wide calcium responses. Obesity did not alter the slope of this relationship, but impaired calcium responses in the endothelial cell network. The network comprised structural and functional components. The structural architecture, a hexagonal lattice network of connected cells, was unchanged in obesity. The functional network contained sub-populations of clustered specialized agonist-sensing cells from which signals were communicated through the network. In obesity there were fewer but larger clusters of sensory cells and communication path lengths between clusters increased. Communication between neighboring cells was unaltered in obesity. Altered network organization resulted in impaired, population-level calcium signaling and deficient endothelial control of vascular tone. Conclusions: The distribution of cells in the endothelial network is critical in determining overall vascular response. Altered cell heterogeneity and arrangement in obesity decreases endothelial function and provides a novel framework for understanding compromised endothelial function in cardiovascular disease

    Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection

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    Abstract in English, Arabic, Chinese, French, Russian, SpanishThe formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.info:eu-repo/semantics/publishedVersio

    Influenza surveillance capacity improvements in Africa during 2011-2017.

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    BACKGROUND: Influenza surveillance helps time prevention and control interventions especially where complex seasonal patterns exist. We assessed influenza surveillance sustainability in Africa where influenza activity varies and external funds for surveillance have decreased. METHODS: We surveyed African Network for Influenza Surveillance and Epidemiology (ANISE) countries about 2011-2017 surveillance system characteristics. Data were summarized with descriptive statistics and analyzed with univariate and multivariable analyses to quantify sustained or expanded influenza surveillance capacity in Africa. RESULTS: Eighteen (75%) of 24 ANISE members participated in the survey; their cumulative population of 710 751 471 represent 56% of Africa's total population. All 18 countries scored a mean 95% on WHO laboratory quality assurance panels. The number of samples collected from severe acute respiratory infection case-patients remained consistent between 2011 and 2017 (13 823 vs 13 674 respectively) but decreased by 12% for influenza-like illness case-patients (16 210 vs 14 477). Nine (50%) gained capacity to lineage-type influenza B. The number of countries reporting each week to WHO FluNet increased from 15 (83%) in 2011 to 17 (94%) in 2017. CONCLUSIONS: Despite declines in external surveillance funding, ANISE countries gained additional laboratory testing capacity and continued influenza testing and reporting to WHO. These gains represent important achievements toward sustainable surveillance and epidemic/pandemic preparedness

    The Cost-Effectiveness of Early Access to HIV Services and Starting cART in the UK 1996–2008

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    To calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PI(boosted), comparing PLHIV with CD4≤200 cells/mm3 and CD4>200 cells/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and below CD4 200 cells/mm3.Use, costs and cost-effectiveness were calculated for PLHIV in routine pre-cART and starting first-line cART, comparing CD4≤200 cells/mm3 with CD4>200 cells/mm3 (2008 UK prices).cART naïve patients CD4≤200 cells/mm3 had an annual cost of £6,407 (95%CI £6,382 to £6,425) PPY compared with £2,758 (95%CI £2,752 to £2,761) PPY for those with CD4>200 cells/mm3; cost per life year gained of pre-cART treatment and care for those with CD4>200 cells/mm3 was £1,776 (cost-saving to £2,752). Annual cost for starting 2NRTIs+NNRTI or 2NRTIs+PI(boosted) with CD4≤200 cells/mm3 was £12,812 (95%CI £12,685-£12,937) compared with £10,478 (95%CI £10,376-£10,581) for PLHIV with CD4>200 cells/mm3. Cost per additional life-year gained on first-line therapy for those with CD4>200 cells/mm3 was £4639 (£3,967 to £2,960).PLHIV starting to use HIV services before CD4≤200 cells/mm3 is cost-effective and enables them to be monitored so they start cART with a CD4>200 cells/mm3, which results in better outcomes and is cost-effective. However, 25% of PLHIV accessing services continue to present with CD4≤200 cells/mm3. This highlights the need to investigate the cost-effectiveness of testing and early treatment programs for key populations in the UK

    Rising Population Cost for Treating People Living with HIV in the UK, 1997-2013

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    Background The number of people living with HIV (PLHIV) is increasing in the UK. This study estimated the annual population cost of providing HIV services in the UK, 1997–2006 and projected them 2007–2013. Methods Annual cost of HIV treatment for PLHIV by stage of HIV infection and type of ART was calculated (UK pounds, 2006 prices). Population costs were derived by multiplying the number of PLHIV by their annual cost for 1997–2006 and projected 2007–2013. Results Average annual treatment costs across all stages of HIV infection ranged from £17,034 in 1997 to £18,087 in 2006 for PLHIV on mono-therapy and from £27,649 in 1997 to £32,322 in 2006 for those on quadruple-or-more ART. The number of PLHIV using NHS services rose from 16,075 to 52,083 in 2006 and was projected to increase to 78,370 by 2013. Annual population cost rose from £104 million in 1997 to £483 million in 2006, with a projected annual cost between £721 and £758 million by 2013. When including community care costs, costs increased from £164 million in 1997, to £683 million in 2006 and between £1,019 and £1,065 million in 2013. Conclusions Increased number of PLHIV using NHS services resulted in rising UK population costs. Population costs are expected to continue to increase, partly due to PLHIV's longer survival on ART and the relative lack of success of HIV preventing programs. Where possible, the cost of HIV treatment and care needs to be reduced without reducing the quality of services, and prevention programs need to become more effective. While high income countries are struggling to meet these increasing costs, middle- and lower-income countries with larger epidemics are likely to find it even more difficult to meet these increasing demands, given that they have fewer resources

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Leveraging International Influenza Surveillance Systems and Programs during the COVID-19 Pandemic.

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    A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential
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