Telehealth Solutions for In-hospital Communication with Patients Under Isolation During COVID-19

The coronavirus disease 2019 (COVID-19) pandemic is a public health crisis that has quickly overwhelmed our healthcare system. It has led to significant shortages in personal protective equipment (PPE), ventilators, and intensive care unit beds across the nation. As the initial entry point for patients with suspected COVID illness, emergency departments (ED) have had to adapt quickly to prioritize the safety of patients and providers while still delivering optimal, timely patient care. COVID-19 has presented many challenges for the ED that also extend to all inpatient services. Some of these key challenges are the fundamental tasks of communicating with patients in respiratory isolation while minimizing PPE usage and enabling all patients who have been affected by hospitals’ visitor restrictions to connect with their families. We discuss the design principles behind implementing a robust in-hospital telehealth system for patient-provider and patient-family communication, provide a review of the strengths and weaknesses of potential videoconferencing options, and deliver concise, step-by-step guides for setting up a secure, low-cost, user-friendly solution that can be rapidly deployed

The alternatively spliced fibronectin CS1 isoform regulates IL-17A levels and mechanical allodynia after peripheral nerve injury.

BackgroundMechanical pain hypersensitivity associated with physical trauma to peripheral nerve depends on T-helper (Th) cells expressing the algesic cytokine, interleukin (IL)-17A. Fibronectin (FN) isoform alternatively spliced within the IIICS region encoding the 25-residue-long connecting segment 1 (CS1) regulates T cell recruitment to the sites of inflammation. Herein, we analyzed the role of CS1-containing FN (FN-CS1) in IL-17A expression and pain after peripheral nerve damage.MethodsMass spectrometry, immunoblotting, and FN-CS1-specific immunofluorescence analyses were employed to examine FN expression after chronic constriction injury (CCI) in rat sciatic nerves. The acute intra-sciatic nerve injection of the synthetic CS1 peptide (a competitive inhibitor of the FN-CS1/α4 integrin binding) was used to elucidate the functional significance of FN-CS1 in mechanical and thermal pain hypersensitivity and IL-17A expression (by quantitative Taqman RT-PCR) after CCI. The CS1 peptide effects were analyzed in cultured primary Schwann cells, the major source of FN-CS1 in CCI nerves.ResultsFollowing CCI, FN expression in sciatic nerve increased with the dominant FN-CS1 deposition in endothelial cells, Schwann cells, and macrophages. Acute CS1 therapy attenuated mechanical allodynia (pain from innocuous stimulation) but not thermal hyperalgesia and reduced the levels of IL-17A expression in the injured nerve. CS1 peptide inhibited the LPS- or starvation-stimulated activation of the stress ERK/MAPK pathway in cultured Schwann cells.ConclusionsAfter physical trauma to the peripheral nerve, FN-CS1 contributes to mechanical pain hypersensitivity by increasing the number of IL-17A-expressing (presumably, Th17) cells. CS1 peptide therapy can be developed for pharmacological control of neuropathic pain

A preexisting rare PIK3CA e545k subpopulation confers clinical resistance to MEK plus CDK4/6 inhibition in NRAS melanoma and is dependent on S6K1 signaling

Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS- mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA E545K mutation as conferring drug resistance. We demonstrate that PIK3CA E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA E545K being nonuniformly distributed. This resistant population rapidly expanded after the initiation of MEKi + CDK4i therapy and persisted in all successive samples even after immune checkpoint therapy and distant metastasis. Functional studies identified activated S6K1 as both a key marker and specific therapeutic vulnerability downstream of PIK3CA E545K -induced resistance. These results demonstrate that difficult-to-detect preexisting resistance mutations may exist more often than previously appreciated and also posit S6K1 as a common downstream therapeutic nexus for the MAPK, CDK4/6, and PI3K pathways. SIGNIFICANCE: We report the first characterization of clinical acquired resistance to MEKi + CDK4i, identifying a rare preexisting PIK3CA E545K subpopulation that expands upon therapy and exhibits drug resistance. We suggest that single-region pretreatment biopsy is insufficient to detect rare, spatially segregated drug-resistant subclones. Inhibition of S6K1 is able to resensitize PIK3CA E545K -expressing NRAS-mutant melanoma cells to MEKi + CDK4i. © 2018 AAC

Hypoglycemia is More Common Among Type 2 Diabetes Patients with Limited Health Literacy: The Diabetes Study of Northern California (DISTANCE)

Little is known about the frequency of significant hypoglycemic events in actual practice. Limited health literacy (HL) is common among patients with type 2 diabetes, may impede diabetes self-management, and thus HL could increase the risk of hypoglycemia. To determine the proportion of ambulatory, pharmacologically-treated patients with type 2 diabetes reporting ≥1 significant hypoglycemic events in the prior 12 months, and evaluate whether HL is associated with hypoglycemia. Cross-sectional analysis in an observational cohort, the Diabetes Study of Northern California (DISTANCE). The subjects comprised 14,357 adults with pharmacologically-treated, type 2 diabetes who are seen at Kaiser Permanente Northern California (KPNC), a non-profit, integrated health care delivery system. Patient-reported frequency of significant hypoglycemia (losing consciousness or requiring outside assistance); patient-reported health literacy. At least one significant hypoglycemic episode in the prior 12 months was reported by 11% of patients, with the highest risk for those on insulin (59%). Patients commonly reported limited health literacy: 53% reported problems learning about health, 40% needed help reading health materials, and 32% were not confident filling out medical forms by themselves. After adjustment, problems learning (OR 1.4, CI 1.1-1.7), needing help reading (OR 1.3, CI 1.1-1.6), and lack of confidence with forms (OR 1.3, CI 1.1-1.6) were independently associated with significant hypoglycemia. Significant hypoglycemia was a frequent complication in this cohort of type 2 diabetes patients using anti-hyperglycemic therapies; those reporting limited HL were especially vulnerable. Efforts to reduce hypoglycemia and promote patient safety may require self-management support that is appropriate for those with limited HL, and consider more vigilant surveillance, conservative glycemic targets or avoidance of the most hypoglycemia-inducing medications

Seis islas temporales en Still — The Economy of Waiting

This article focuses on the analysis of the performative installation Still — The Economy of Waiting, work by German artist Julian Hetzel. This project addresses specific issues related to the mechanisms in labour productivity and work ethics. Taking as a starting point post-Fordist production models, Hetzel observes the current transformation of the idea of "work" into the notion of "occupation". While "labour and work" concepts have been oriented towards a productive model that pursues specific results and objectives, the concept "occupation" focuses on activity as a process, that is, its purpose is none other than to remain busy, thereby raising a temporary counter-model with which to generate a gap in the flow of capitalist circulation.El artículo se centra en el análisis de la instalación performática Still — The Economy of Waiting, obra del artista alemán Julian Hetzel. En dicho proyecto se abordan ciertas problemáticas asociadas a los mecanismos en la producción laboral y las éticas del trabajo. Tomando como punto de partida modelos de producción posfordistas, Hetzel observa la actual transformación de la idea de "trabajo" en la idea de "ocupación". Mientras que la idea de "labor y trabajo" han estado orientadas hacia un modelo productivo que persigue resultados y objetivos específicos, la idea de "ocupación" se centra en la actividad como proceso, es decir, su finalidad no es otra que la de permanecer ocupado, planteando con ello un contra-modelo temporal con el que generar una brecha en el flujo de la circulación capitalista

Instrumental variable approaches to identifying the causal effect of educational attainment on dementia risk

PURPOSE: Education is an established correlate of cognitive status in older adulthood, but whether expanding educational opportunities would improve cognitive functioning remains unclear given limitations of prior studies for causal inference. Therefore, we conducted instrumental variable (IV) analyses of the association between education and dementia risk, using for the first time in this area, genetic variants as instruments as well as state-level school policies. METHODS: IV analyses in the Health and Retirement Study cohort (1998-2010) used two sets of instruments: (1) a genetic risk score constructed from three single-nucleotide polymorphisms (SNPs; n = 7981); and (2) compulsory schooling laws (CSLs) and state school characteristics (term length, student teacher ratios, and expenditures; n = 10,955). RESULTS: Using the genetic risk score as an IV, there was a 1.1% reduction in dementia risk per year of schooling (95% confidence interval, -2.4 to 0.02). Leveraging compulsory schooling laws and state school characteristics as IVs, there was a substantially larger protective effect (-9.5%; 95% confidence interval, -14.8 to -4.2). Analyses evaluating the plausibility of the IV assumptions indicated estimates derived from analyses relying on CSLs provide the best estimates of the causal effect of education. CONCLUSIONS: IV analyses suggest education is protective against risk of dementia in older adulthood

Measuring Coverage in MNCH:A Validation Study Linking Population Survey Derived Coverage to Maternal, Newborn, and Child Health Care Records in Rural China

Accurate data on coverage of key maternal, newborn, and child health (MNCH) interventions are crucial for monitoring progress toward the Millennium Development Goals 4 and 5. Coverage estimates are primarily obtained from routine population surveys through self-reporting, the validity of which is not well understood. We aimed to examine the validity of the coverage of selected MNCH interventions in Gongcheng County, China.We conducted a validation study by comparing women's self-reported coverage of MNCH interventions relating to antenatal and postnatal care, mode of delivery, and child vaccinations in a community survey with their paper- and electronic-based health care records, treating the health care records as the reference standard. Of 936 women recruited, 914 (97.6%) completed the survey. Results show that self-reported coverage of these interventions had moderate to high sensitivity (0.57 [95% confidence interval (CI): 0.50-0.63] to 0.99 [95% CI: 0.98-1.00]) and low to high specificity (0 to 0.83 [95% CI: 0.80-0.86]). Despite varying overall validity, with the area under the receiver operating characteristic curve (AUC) ranging between 0.49 [95% CI: 0.39-0.57] and 0.90 [95% CI: 0.88-0.92], bias in the coverage estimates at the population level was small to moderate, with the test to actual positive (TAP) ratio ranging between 0.8 and 1.5 for 24 of the 28 indicators examined. Our ability to accurately estimate validity was affected by several caveats associated with the reference standard. Caution should be exercised when generalizing the results to other settings.The overall validity of self-reported coverage was moderate across selected MNCH indicators. However, at the population level, self-reported coverage appears to have small to moderate degree of bias. Accuracy of the coverage was particularly high for indicators with high recorded coverage or low recorded coverage but high specificity. The study provides insights into the accuracy of self-reports based on a population survey in low- and middle-income countries. Similar studies applying an improved reference standard are warranted in the future