Digital health paradox: international policy perspectives to address increased health inequalities for people living with disabilities

The COVID-19 pandemic accelerated the uptake of digital health worldwide and highlighted many benefits of these innovations. However, it also stressed the magnitude of inequalities regarding accessing digital health. Using a scoping review, this article explores the potential benefits of digital technologies for the global population, with particular reference to people living with disabilities, using the autism community as a case study. We ultimately explore policies in Sweden, Australia, Canada, Estonia, the United Kingdom, and the United States to learn how policies can lay an inclusive foundation for digital health systems. We conclude that digital health ecosystems should be designed with health equity at the forefront to avoid deepening existing health inequalities. We call for a more sophisticated understanding of digital health literacy to better assess the readiness to adopt digital health innovations. Finally, people living with disabilities should be positioned at the center of digital health policy and innovations to ensure they are not left behind

IgG Conformer's Binding to Amyloidogenic Aggregates

Amyloid-reactive IgGs isolated from pooled blood of normal individuals (pAbs) have demonstrated clinical utility for amyloid diseases by in vivo targeting and clearing amyloidogenic proteins and peptides. We now report the following three novel findings on pAb conformer's binding to amyloidogenic aggregates: 1) pAb aggregates have greater activity than monomers (HMW species > dimers > monomers), 2) pAbs interactions with amyloidogenic aggregates at least partially involves unconventional (non-CDR) interactions of F(ab) regions, and 3) pAb's activity can be easily modulated by trace aggregates generated during sample processing. Specifically, we show that HMW aggregates and dimeric pAbs present in commercial preparations of pAbs, intravenous immunoglobulin (IVIg), had up to ~200- and ~7-fold stronger binding to aggregates of Aβ and transthyretin (TTR) than the monomeric antibody. Notably, HMW aggregates were primarily responsible for the enhanced anti-amyloid activities of Aβ- and Cibacron blue-isolated IVIg IgGs. Human pAb conformer's binding to amyloidogenic aggregates was retained in normal human sera, and mimicked by murine pAbs isolated from normal pooled plasmas. An unconventional (non-CDR) component to pAb's activity was indicated from control human mAbs, generated against non-amyloid targets, binding to aggregated Aβ and TTR. Similar to pAbs, HMW and dimeric mAb conformers bound stronger than their monomeric forms to amyloidogenic aggregates. However, mAbs had lower maximum binding signals, indicating that pAbs were required to saturate a diverse collection of binding sites. Taken together, our findings strongly support further investigations on the physiological function and clinical utility of the inherent anti-amyloid activities of monomeric but not aggregated IgGs

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Aβ Dimers Rapidly Form Stable Synaptotoxic Protofibrils

Nonfibrillar, water-soluble low-molecular weight assemblies of the amyloid beta-protein (A beta) are believed to play an important role in Alzheimer's disease (AD). Aqueous extracts of human brain contain A beta assemblies that migrate on SDS-polyacrylamide gels and elute from size exclusion as dimers (similar to 8 kDa) and can block long-term potentiation and impair memory consolidation in the rat. Such species are detected specifically and sensitively in extracts of Alzheimer brain suggesting that SDS-stable dimers may be the basic building blocks of AD-associated synaptotoxic assemblies. Consequently, understanding the structure and properties of A beta dimers is of great interest. In the absence of sufficient brain-derived dimer to facilitate biophysical analysis, we generated synthetic dimers designed to mimic the natural species. For this, A beta(1-40) containing cysteine in place of serine 26 was used to produce disulphide cross-linked dimer, (A beta S26C)(2). Such dimers had no detectable secondary structure, produced an analytical ultracentrifugation profile consistent for an similar to 8.6 kDa protein, and had no effect on hippocampal long-term potentiation (LTP). However, (A beta S26C)(2) aggregated more rapidly than either A beta S26C or wild-type monomers and formed parastable beta-sheet rich, thioflavin T-positive, protofibril-like assemblies. Whereas wildtype A beta aggregated to form typical amyloid fibrils, the protofibril-like structures formed by (A beta S26C)(2) persisted for prolonged periods and potently inhibited LIP in mouse hippocampus. These data support the idea that A beta dimers may stabilize the formation of fibril intermediates by a process distinct from that available to A beta monomer and that higher molecular weight prefibrillar assemblies are the proximate mediators of A beta toxicity.Health Research BoardScience Foundation IrelandNational Institutes of Healt

Digital Health Paradox: International Policy Perspectives to Address Increased Health Inequalities for People Living With Disabilities (Preprint)

UNSTRUCTURED The COVID-19 pandemic accelerated the uptake of digital health worldwide and highlighted many benefits of these innovations. However, it also stressed the magnitude of inequalities regarding accessing digital health. Using a scoping review, this article explores the potential benefits of digital technologies for the global population, with particular reference to people living with disabilities, using the autism community as a case study. We ultimately explore policies in Sweden, Australia, Canada, Estonia, the United Kingdom, and the United States to learn how policies can lay an inclusive foundation for digital health systems. We conclude that digital health ecosystems should be designed with health equity at the forefront to avoid deepening existing health inequalities. We call for a more sophisticated understanding of digital health literacy to better assess the readiness to adopt digital health innovations. Finally, people living with disabilities should be positioned at the center of digital health policy and innovations to ensure they are not left behind. </sec