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Front Public Health ; 9: 729149, 2021.
Article in English | MEDLINE | ID: covidwho-1775856

ABSTRACT

Population aging is a defining demographic reality of our era. It is associated with an increase in the societal burden of delivering care to older adults with chronic conditions or frailty. How to integrate global population aging and technology development to help address the growing demands for care facing many aging societies is both a challenge and an opportunity for innovation. We propose a social technology approach that promotes use of technologies to assist individuals, families, and communities to cope more effectively with the disabilities of older adults who can no longer live independently due to dementia, serious mental illness, and multiple chronic health problems. The main contributions of the social technology approach include: (1) fostering multidisciplinary collaboration among social scientists, engineers, and healthcare experts; (2) including ethical and humanistic standards in creating and evaluating innovations; (3) improving social systems through working with those who deliver, manage, and design older adult care services; (4) promoting social justice through social policy research and innovation, particularly for disadvantaged groups; (5) fostering social integration by creating age-friendly and intergenerational programs; and (6) seeking global benefit by identifying and generalizing best practices. As an emergent, experimental approach, social technology requires systematic evaluation in an iterative process to refine its relevance and uses in different local settings. By linking technological interventions to the social and cultural systems of older people, we aim to help technological advances become an organic part of the complex social world that supports and sustains care delivery to older adults in need.


Subject(s)
Disabled Persons , Frailty , Aged , Delivery of Health Care , Humans , Quality Improvement
4.
Curr Res Transl Med ; 70(2): 103333, 2022 05.
Article in English | MEDLINE | ID: covidwho-1683570

ABSTRACT

BACKGROUND: The human protein transmembrane protease serine type 2 (TMPRSS2) plays a key role in SARS-CoV-2 infection, as it is required to activate the virus' spike protein, facilitating entry into target cells. We hypothesized that naturally-occurring TMPRSS2 human genetic variants affecting the structure and function of the TMPRSS2 protein may modulate the severity of SARS-CoV-2 infection. METHODS: We focused on the only common TMPRSS2 non-synonymous variant predicted to be damaging (rs12329760 C>T, p.V160M), which has a minor allele frequency ranging from 0.14 in Ashkenazi Jewish to 0.38 in East Asians. We analysed the association between the rs12329760 and COVID-19 severity in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units recruited as part of the GenOMICC (Genetics Of Mortality In Critical Care) study. Logistic regression analyses were adjusted for sex, age and deprivation index. For in vitro studies, HEK293 cells were co-transfected with ACE2 and either TMPRSS2 wild type or mutant (TMPRSS2V160M). A SARS-CoV-2 pseudovirus entry assay was used to investigate the ability of TMPRSS2V160M to promote viral entry. RESULTS: We show that the T allele of rs12329760 is associated with a reduced likelihood of developing severe COVID-19 (OR 0.87, 95%CI:0.79-0.97, p = 0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p = 1.3 × 10-3). We demonstrate in vitro that this variant, which causes the amino acid substitution valine to methionine, affects the catalytic activity of TMPRSS2 and is less able to support SARS-CoV-2 spike-mediated entry into cells. CONCLUSION: TMPRSS2 rs12329760 is a common variant associated with a significantly decreased risk of severe COVID-19. Further studies are needed to assess the expression of TMPRSS2 across different age groups. Moreover, our results identify TMPRSS2 as a promising drug target, with a potential role for camostat mesilate, a drug approved for the treatment of chronic pancreatitis and postoperative reflux esophagitis, in the treatment of COVID-19. Clinical trials are needed to confirm this.


Subject(s)
COVID-19 , COVID-19/genetics , Gene Frequency , HEK293 Cells , Humans , SARS-CoV-2 , Serine Endopeptidases/genetics , Virus Internalization
5.
Current research in translational medicine ; 2022.
Article in English | EuropePMC | ID: covidwho-1615101

ABSTRACT

Background : The human protein transmembrane protease serine type 2 (TMPRSS2) plays a key role in SARS-CoV-2 infection, as it is required to activate the virus’ spike protein, facilitating entry into target cells. We hypothesized that naturally-occurring TMPRSS2 human genetic variants affecting the structure and function of the TMPRSS2 protein may modulate the severity of SARS-CoV-2 infection. Methods : We focused on the only common TMPRSS2 non-synonymous variant predicted to be damaging (rs12329760 C>T, p.V160M), which has a minor allele frequency ranging from from 0.14 in Ashkenazi Jewish to 0.38 in East Asians. We analysed the association between the rs12329760 and COVID-19 severity in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units recruited as part of the GenOMICC (Genetics Of Mortality In Critical Care) study. Logistic regression analyses were adjusted for sex, age and deprivation index. For in vitro studies, HEK293 cells were co-transfected with ACE2 and either TMPRSS2 wild type or mutant (TMPRSS2V160M). A SARS-CoV-2 pseudovirus entry assay was used to investigate the ability of TMPRSS2V160M to promote viral entry. Results : We show that the T allele of rs12329760 is associated with a reduced likelihood of developing severe COVID-19 (OR 0.87, 95%CI:0.79-0.97, p=0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p=1.3 × 10−3). We demonstrate in vitro that this variant, which causes the amino acid substitution valine to methionine, affects the catalytic activity of TMPRSS2 and is less able to support SARS-CoV-2 spike-mediated entry into cells. Conclusion : TMPRSS2 rs12329760 is a common variant associated with a significantly decreased risk of severe COVID-19. Further studies are needed to assess the expression of TMPRSS2 across different age groups. Moreover, our results identify TMPRSS2 as a promising drug target, with a potential role for camostat mesilate, a drug approved for the treatment of chronic pancreatitis and postoperative reflux esophagitis, in the treatment of COVID-19. Clinical trials are needed to confirm this.

7.
J Med Internet Res ; 22(9): e21276, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-695325

ABSTRACT

Mobile health (mHealth) and related digital health interventions in the past decade have not always scaled globally as anticipated earlier despite large investments by governments and philanthropic foundations. The implementation of digital health tools has suffered from 2 limitations: (1) the interventions commonly ignore the "law of amplification" that states that technology is most likely to succeed when it seeks to augment and not alter human behavior; and (2) end-user needs and clinical gaps are often poorly understood while designing solutions, contributing to a substantial decrease in usage, referred to as the "law of attrition" in eHealth. The COVID-19 pandemic has addressed the first of the 2 problems-technology solutions, such as telemedicine, that were struggling to find traction are now closely aligned with health-seeking behavior. The second problem (poorly designed solutions) persists, as demonstrated by a plethora of poorly designed epidemic prediction tools and digital contact-tracing apps, which were deployed at scale, around the world, with little validation. The pandemic has accelerated the Indian state's desire to build the nation's digital health ecosystem. We call for the inclusion of regulatory sandboxes, as successfully done in the fintech sector, to provide a real-world testing environment for mHealth solutions before deploying them at scale.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Telemedicine , COVID-19 , Coronavirus Infections/prevention & control , Global Health , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , SARS-CoV-2
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