“We see each other from a distance”: Neighbourhood social relationships during the COVID-19 pandemic matter for older adults’ social connectedness

IntroductionWe extend previous research to illustrate how individual, interpersonal and neighbourhood factors in a high-density urban setting in Vancouver, Canada, shape social connectedness experiences of community-dwelling older adults during the first wave of the COVID-19 pandemic.MethodsWe conducted 31 semi-structured interviews and collected objective measures of loneliness and social connectedness (surveys).ResultsThree dimensions of the neighbourhood environment influenced social connectedness: (i) interactions with neighbours, (ii) involvement with neighbourhood-based organizations, and (ii) outdoor pedestrian spaces. Seventy-one percent of participants felt a strong sense of belonging to their local community, while 39% were classified as high or extremely lonely.SummaryMany participants leveraged pre-existing social ties to maintain connections during the pandemic. However, volunteer outreach was vital for more isolated older adults. Although many participants felt lonely and isolated at times, the relative ease and accessibility with which they could connect with others in their neighbourhood environment, may have helped mitigate persistent loneliness.ConclusionStrategies that foster social connectedness over the longer term, need to prioritize the needs of older adults who face multiple barriers to equitable social participation.     

Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most prevalent malignancies that seriously threaten people’s health worldwide.DEAD-box helicase 51(DDX51)is a member of the DEAD-box(DDX)RNA helicase family,and drives or inhibits tumor progression in multiple cancer types.AIM To determine whether DDX51 affects the biological behavior of ESCC.METHODS The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry(IHC)analyses and quantitative PCR(qPCR).We knocked down DDX51 in ESCC cell lines by using a small interfering RNA(siRNA)transfection.The proliferation,apoptosis,and mobility of DDX51 siRNAtransfected cells were detected.The effect of DDX51 on the phosphoinositide 3-kinase(PI3K)/AKT pathway was investigated by western blot analysis.A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.RESULTS DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC.Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis.Moreover,DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates.Investigations into the underlying mechanisms suggested that DDX51 knock down induced inactivation of the PI3K/AKT pathway,including decreased phosphorylation levels of phosphate and tensin homolog,PI3K,AKT,and mammalian target of rapamycin.Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development.Finally,we injected DDX51 siRNA-transfected TE-1 cells into an animal model,which resulted in slower tumor growth.CONCLUSION Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway;thus,DDX51 might be a therapeutic target for ESCC.     

Therapeutic plasma exchange in pediatric patients with acute demyelinating syndromes of the central nervous system: A single-center experience

BackgroundTherapeutic plasma exchange (TPE) is an extracorporeal treatment that can be used in adult and pediatric patients with acute demyelinating syndromes of the central nervous system. In this study, the efficacy and safety of TPE was evaluated in 10 pediatric patients who underwent TPE that were unresponsive to corticosteroid treatment.MethodsRecords of 10 pediatric patients who underwent TPE in our pediatric intensive care unit (PICU) between May 2017 and June 2020 were used. Expanded Disability Status Scale (EDSS), Gait Scale (GS), and Visual Outcome Scale (VOS) were applied to the patients before and after TPE.ResultsOf the 10 patients who underwent TPE, five were diagnosed with multiple sclerosis (MS), three with transverse myelitis (TM), and two with acute disseminated encephalomyelitis (ADEM). The median age of the patients was 13.3 years (IQR 8-15), and the median day from symptom onset to onset of TPE was 12.5 days (IQR 7-28). A total of 104 TPE sessions were performed successfully. While no complications were encountered in three patients during the sessions, the most common complication was hypofibrinogenemia. The decrease in EDSS and GS scores was found to be consistent with the clinical response of the patients. There was no statistically significant decrease in the VOS.ConclusionsWith this study, we can say that TPE is a feasible, effective, and safe treatment modality in children with acute demyelinating syndromes of the central nervous system.     

High-Order Positivity-Preserving Well-Balanced Discontinuous Galerkin Methods for Euler Equations with Gravitation on Unstructured Meshes

In this paper, we propose a high-order accurate discontinuous Galerkin (DG) method for the compressible Euler equations under gravitational fields on unstructured meshes. The scheme preserves a general hydrostatic equilibrium state and provably guarantees the positivity of density and pressure at the same time. Comparing with the work on the well-balanced scheme for Euler equations with gravitation on rectangular meshes, the extension to triangular meshes is conceptually plausible but highly nontrivial. We first introduce a special way to recover the equilibrium state and then design a group of novel variables at the interface of two adjacent cells, which plays an important role in the well-balanced and positivity-preserving properties. One main challenge is that the well-balanced schemes may not have the weak positivity property. In order to achieve the well-balanced and positivity-preserving properties simultaneously while maintaining high-order accuracy, we carefully design DG spatial discretization with well-balanced numerical fluxes and suitable source term approximation. For the ideal gas, we prove that the resulting well-balanced scheme, coupled with strong stability preserving time discretizations, satisfies a weak positivity property. A simple existing limiter can be applied to enforce the positivity-preserving property, without losing high-order accuracy and conservation. Extensive one- and two-dimensional numerical examples demonstrate the desired properties of the proposed scheme, as well as its high resolution and robustness.     

Considerations for systematic reviews of quantitative surveys: Learnings from a systematic review of the Patients’ Attitudes Towards Deprescribing questionnaire

This commentary looks at the process of conducting a systematic review of surveys and validated questionnaires. Surveys and other questionnaire style tools are often used in the field of social and administrative pharmacy, to capture beliefs, attitudes and experiences of patients and healthcare professionals (including pharmacists). Currently, there is little guidance available on how to conduct a systematic review of these types of studies. Considerations related to the process of a systematic review are highlighted, including identification of articles, data extraction, assessing quality of articles and synthesis and analysis of data.     

The price of cost-effectiveness thresholds under therapeutic competition in pharmaceutical markets

Health systems around world are increasingly adopting cost-effectiveness (CE) analysis to inform decisions about access and reimbursement. We study how CE thresholds imposed by a health plan for granting reimbursement affect drug producers’ pricing incentives and patients’ access to new drugs. Analysing a sequential pricing game between an incumbent drug producer and a potential entrant with a new drug, we show that CE thresholds may have adverse effects for payers and patients. A stricter CE threshold may induce the incumbent to switch pricing strategy from entry accommodation to entry deterrence, limiting patients’ access to the new drug. Otherwise, irrespective of whether entry is deterred or accommodated, a stricter CE threshold is never pro-competitive and may in fact facilitate a collusive outcome with higher prices of both drugs. Compared to a laissez-faire policy, the use of CE thresholds when an incumbent monopolist is challenged by therapeutic substitutes can only increase the surplus of a health plan if it leads to entry deterrence. In this case the price reduction by the incumbent necessary to deter entry outweighs the health loss to patients who do not get access to the new drug.     

Mobile daily diaries to characterize stressors and acute health symptoms in an environmental justice neighborhood

Low-income communities and communities of color face multiple, cumulative environmental and social burdens. Methods development in environmental justice research has largely focused on spatial and quantitative approaches. Less attention has been paid to developing methodologies that help collect information on everyday stressors and quality of life experiences for residents in overburdened communities. Mixed methods approaches can be one way to structure study designs that help consider how residents experience environmental and socioeconomic impacts in a localized community context. In neighborhoods burdened by cumulative stressors, traditional cross-sectional epidemiological research designs can also be challenging, as well as limited or narrow in their application. However, repeat sampling of measures within a vulnerable population can approach a quasi-experimental design and help consider variations within residents in a single neighborhood as well as better parse relationships between exposures and outcomes. Through a community-academic partnership with university partners, local community partners, and a local promotores de salud (community health workers) network, we pilot tested a novel mobile daily diary approach in both English and Spanish in an urban, predominantly immigrant community in South Los Angeles as a potential method to collect information on daily stress, environmental quality, and health status/symptoms. We collected resident responses via a once per day 7-day SMS/text messaging survey. We sought to gather granular data on daily resident experiences of air pollution and environmental hazards. Residents reported acute health symptoms and stressors, with repeat measures demonstrating how residents might rank, categorize, or cope with stressors. We find that residents in environmental justice communities record variation in their daily diary responses and document changes in environmental quality, stressors, and odors. Refining this type of method could enable a more rigorous examination of co-occurrences of environmental quality and acute health symptoms. This approach supports the inclusion of residents in the research process and helps more systematically integrate open-ended environmental health relevant data in environmental justice efforts. Used with measured data such as air monitoring or health measures, mixed methods generated data can help support efforts that aim to alleviate sources of daily stress, alongside efforts to reduce overall pollution burdens. Mobile daily diaries can be one way to capture variable responses to environmental quality, acute health symptoms, and stressors.