Population-Level Identification of Patients With Lynch Syndrome for Clinical Care, Quality Improvement, and Research.

PURPOSE: Identification of those at risk of hereditary cancer syndromes using electronic health record (EHR) data sources is important for clinical care, quality improvement, and research. We describe diagnostic processes, previously seldom reported, for a common hereditary cancer syndrome, Lynch syndrome (LS), using EHR data within a community-based, multicenter, demographically diverse health system. METHODS: Within a retrospective cohort enrolled between 2015 and 2020 at Kaiser Permanente Northern California, we assessed electronic diagnostic domains for LS including (1) family history of LS-associated cancer; (2) personal history of LS-associated cancer; (3) LS screening via mismatch repair deficiency (MMRD) testing of newly diagnosed malignancy; (4) germline genetic test results; and (5) clinician-entered diagnostic codes for LS. We calculated proportions and overlap for each diagnostic domain descriptively. RESULTS: Among 5.8 million individuals, (1) 28,492 (0.49%) had a family history of LS-associated cancer of whom 3,635 (13%) underwent genetic testing; (2) 100,046 (1.7%) had a personal history of a LS-associated cancer; and (3) 8,711 (0.1%) were diagnosed with colorectal cancer of whom 7,533 (86%) underwent MMRD screening and of the positive screens (486), 130 (27%) underwent germline testing. One thousand seven hundred and fifty-seven (0.03%) were diagnosed with endometrial cancer of whom 1,613 (92%) underwent MMRD screening and of the 195 who screened positive, 55 (28%) underwent genetic testing. (4) 30,790 (0.05%) had LS germline genetic testing with 707 (0.01%) testing positive; and (5) 1,273 (0.02%) had a clinician-entered diagnosis of LS. CONCLUSION: It is feasible to electronically characterize the diagnostic processes of LS. No single data source comprehensively identifies all LS carriers. There is underutilization of LS genetic testing for those eligible and underdiagnosis of LS. Our work informs similar efforts in other settings for hereditary cancer syndromes.

A Visual, In-Expensive, and Wireless Capillary Rheometer for Characterizing Wholly-Cellular Bioinks.

Rheological measurements with in situ visualization can elucidate the microstructural origin of complex flow behaviors of an ink. However, existing commercial rheometers suffer from high costs, the need for dedicated facilities for microfabrication, a lack of design flexibility, and cabling that complicates operation in sterile or enclosed environments. To address these limitations, a low-cost ($300) visual, in-expensive and wireless rheometer (VIEWR) using 3D-printed and off-the-shelf components is presented. VIEWR measurements are validated by steady-state and transient flow responses for different complex fluids, and microstructural flow profiles and evolution of yield-planes are revealed via particle image velocimetry. Using the VIEWR, a wholly-cellular bioink system comprised of compacted cell aggregates is characterized, and complex yield-stress and viscoelastic responses are captured via concomitantly visualizing the spatiotemporal evolution of aggregate morphology. A symmetric hyperbolic extensional-flow geometry is further constructed inside a capillary tube using digital light processing. Such geometries allow for measuring the extensional viscosity at varying deformation rates and further visualizing the alignment and stretching of aggregates under external flow. Synchronized but asymmetric evolution of aggregate orientation and strain through the neck is visualized. Using varying geometries, the jamming and viscoelastic deformation of aggregates are shown to contribute to the extensional viscosity of the wholly-cellular bioinks.

New Dimensions of Staffing Patterns in Nursing Homes and Nursing Home Quality: Comparing Staffing Instability to Staffing Turnover.

OBJECTIVE: This study examines how measures of staffing-turnover and instability-are associated with one another and how they independently contribute to quality of care in nursing homes. DESIGN: Cross-sectional analysis of 2021-2022 administrative data. Data included the Payroll Based Journal for daily staffing information, merged with Nursing Home Care Compare (NHCC) data for nursing home characteristics, total staffing turnover, and nursing home quality. SETTING AND PARTICIPANTS: A total of 11,840 nursing homes nationally reporting data on daily staffing and staffing turnover. METHODS: We explored correlations between measures of staffing and estimated facility-level regression models with robust standard errors. The dependent variables were indicators of nursing home quality included in the NHCC 5-star ratings. The independent variables of interest were average total staffing hours per resident-day, total staffing turnover, and total staffing instability. RESULTS: For the 11,840 nursing homes in the study, there was a weak positive correlation between turnover and instability, with some overlap between nursing homes with high instability and high turnover. Regression analysis revealed that staffing instability and turnover contributed independently to nursing home quality, with instability having a stronger association with some measures of quality and turnover with others. Staffing instability was positively and more strongly associated with long-stay residents' decline in activities of daily living levels and receipt of antipsychotic drugs and short-stay residents' functioning at discharge. Turnover was positively and more strongly associated with long-stay residents' prevalence of pressure ulcers and worsening mobility, and short-stay residents' hospitalizations. CONCLUSION AND IMPLICATIONS: Instability and turnover in total nursing home staffing independently contribute to nursing home quality. This suggests that adding measures of staffing instability to the existing measures of average staffing and staff turnover in NHCC may enhance the report card's value for providers engaged in quality improvement and consumers searching for high-quality nursing homes.

Variation And Changes In The Targeting Of Medicaid Disproportionate Share Hospital Payments.

Little is known about how Medicaid disproportionate share hospital payments, which are intended to support hospitals that serve low-income patients, are allocated or whether allocation patterns have changed over time. We employed alternative definitions of targeting, or the degree to which allocations were made in a manner consistent with the statutory goals and intent of the program, to examine disproportionate share hospital payment allocations in forty-nine participating states. The most recent data indicate that 57.2 percent of acute care hospitals received disproportionate share hospital payments, totaling more than $14.5 billion, in 2015. The majority of payments went to hospitals with Medicaid shares above the state-specific median (89.1 percent), hospitals with uncompensated care shares above the state-specific median (60.6 percent), or hospitals deemed as disproportionate share per statutory definitions (64.6 percent). However, among all hospitals receiving these payments, up to 31.6 percent of payments were allocated to hospitals that did not meet a given definition, and 3.2 percent went to hospitals that met none of them. These findings suggest that although the majority of the payments were targeted to hospitals serving low-income patients, opportunities exist to better align allocation with statutory goals and intent or to revise applicable statute.

Association of COVID-19 Vaccination Rates of Staff and COVID-19 Illness and Death Among Residents and Staff in US Nursing Homes.

Importance: It is important to understand the association between staff vaccination rates and adverse COVID-19 outcomes in nursing homes. Objective: To assess the extent to which staff vaccination was associated with preventing COVID-19 cases and deaths among residents and staff in nursing homes. Design, Setting, and Participants: This longitudinal cohort study used data on COVID-19 outcomes in Medicare- and Medicaid-certified nursing homes in the US between May 30, 2021, and January 30, 2022. Participants included the residents of 15 042 US nursing homes that reported COVID-19 data to the Centers for Disease Control and Prevention and passed Centers for Medicare & Medicaid Services data quality checks in the National Healthcare Safety Network. Exposures: Weekly staff vaccination rates. Main Outcomes and Measures: Main outcomes are weekly COVID-19 cases and deaths among residents and weekly COVID-19 cases among staff. The treatment variable is the primary 2-dose staff vaccination rate in each facility each week. Results: In the primary analysis of 15 042 nursing homes before the Omicron variant wave (May 30 to December 5, 2021) using fixed effects of facility and week, increasing weekly staff vaccination rates by 10 percentage points was associated with 0.13 (95% CI, -0.20 to -0.10) fewer weekly COVID-19 cases per 1000 residents, 0.02 (95% CI, -0.03 to -0.01) fewer weekly COVID-19 deaths per 1000 residents, and 0.03 (95% CI, -0.04 to -0.02) fewer weekly COVID-19 staff cases. In the secondary analysis of the Omicron wave (December 5, 2021, to January 30, 2022), increasing staff vaccination rates were not associated with lower rates of adverse COVID-19 outcomes in nursing homes. Conclusions and Relevance: The findings of this cohort study suggest that before the Omicron variant wave, increasing staff vaccination rates was associated with lower incidence of COVID-19 cases and deaths among residents and staff in US nursing homes. However, as newer, more infectious and transmissible variants of the virus emerged, the original 2-dose regimen of the COVID-19 vaccine as recommended in December 2020 was no longer associated with lower rates of adverse COVID-19 outcomes in nursing homes. Policy makers may want to consider longer-term policy options to increase the uptake of booster doses among staff in nursing homes.

Large-Scale Production of Wholly Cellular Bioinks via the Optimization of Human Induced Pluripotent Stem Cell Aggregate Culture in Automated Bioreactors.

Combining the sustainable culture of billions of human cells and the bioprinting of wholly cellular bioinks offers a pathway toward organ-scale tissue engineering. Traditional 2D culture methods are not inherently scalable due to cost, space, and handling constraints. Here, the suspension culture of human induced pluripotent stem cell-derived aggregates (hAs) is optimized using an automated 250 mL stirred tank bioreactor system. Cell yield, aggregate morphology, and pluripotency marker expression are maintained over three serial passages in two distinct cell lines. Furthermore, it is demonstrated that the same optimized parameters can be scaled to an automated 1 L stirred tank bioreactor system. This 4-day culture results in a 16.6- to 20.4-fold expansion of cells, generating approximately 4 billion cells per vessel, while maintaining >94% expression of pluripotency markers. The pluripotent aggregates can be subsequently differentiated into derivatives of the three germ layers, including cardiac aggregates, and vascular, cortical and intestinal organoids. Finally, the aggregates are compacted into a wholly cellular bioink for rheological characterization and 3D bioprinting. The printed hAs are subsequently differentiated into neuronal and vascular tissue. This work demonstrates an optimized suspension culture-to-3D bioprinting pipeline that enables a sustainable approach to billion cell-scale organ engineering.

LoCHAid: An ultra-low-cost hearing aid for age-related hearing loss.

Hearing aids are the primary tool in non-medical rehabilitation for individuals with hearing loss. While the costs of the electronic components have reduced substantially, the cost of a hearing aid has risen steadily to the point that it has become unaffordable for the majority of the population with Age-Related Hearing Loss (ARHL) especially for those residing in low- and middle-income countries. Here, we present an ultra-low-cost, affordable and accessible hearing aid device ('LoCHAid'), specifically targeted towards treating ARHL in elderly patients. The LoCHAid components cost 98 cents (< $1) when purchased in bulk for 10,000 units and can be personalized for each user through a 3D-printable case. It is designed to be an over-the-counter (OTC) self-serviceable solution for elderly individuals with ARHL. Electroacoustic measurements show that the device meets most of the targets set out by the WHO Preferred Product Profile and Consumer Technology Association for hearing aids. The frequency response of the hearing aid shows selectable gain in the range of 4-8 kHz, and mild to moderate gain between 200-1000 Hz, and shows very limited total distortion (1%). Simulated gain measurements show that the LoCHAid is well fitted to a range of ARHL profiles for males and females between the ages of 60-79 years. Overall, the measurements show that the device offers the potential to benefit individuals with ARHL. Thus, our proposed design has the potential to address the challenge of affordable and accessible hearing technology for hearing impaired elderly individuals especially in low- and middle-income countries.

ElectroPen: An ultra-low-cost, electricity-free, portable electroporator.

Electroporation is a basic yet powerful method for delivering small molecules (RNA, DNA, drugs) across cell membranes by application of an electrical field. It is used for many diverse applications, from genetically engineering cells to drug- and DNA-based vaccine delivery. Despite this broad utility, the high cost of electroporators can keep this approach out of reach for many budget-conscious laboratories. To address this need, we develop a simple, inexpensive, and handheld electroporator inspired by and derived from a common household piezoelectric stove lighter. The proposed "ElectroPen" device can cost as little as 23 cents (US dollars) to manufacture, is portable (weighs 13 g and requires no electricity), can be easily fabricated using 3D printing, and delivers repeatable exponentially decaying pulses of about 2,000 V in 5 ms. We provide a proof-of-concept demonstration by genetically transforming plasmids into Escherichia coli cells, showing transformation efficiency comparable to commercial devices, but at a fraction of the cost. We also demonstrate the potential for rapid dissemination of this approach, with multiple research groups across the globe validating the ease of construction and functionality of our device, supporting the potential for democratization of science through frugal tools. Thus, the simplicity, accessibility, and affordability of our device holds potential for making modern synthetic biology accessible in high school, community, and resource-poor laboratories.

A 3D-printed hand-powered centrifuge for molecular biology.

The centrifuge is an essential tool for many aspects of research and medical diagnostics. However, conventional centrifuges are often inaccessible outside of standard laboratory settings, such as remote field sites, because they require a constant external power source and can be prohibitively costly in resource-limited settings and Science, technology, engineering, and mathematics (STEM)-focused programs. Here we present the 3D-Fuge, a 3D-printed hand-powered centrifuge, as a novel alternative to standard benchtop centrifuges. Based on the design principles of a paper-based centrifuge, this 3D-printed instrument increases the volume capacity to 2 mL and can reach hand-powered centrifugation speeds up to 6,000 rpm. The 3D-Fuge devices presented here are capable of centrifugation of a wide variety of different solutions such as spinning down samples for biomarker applications and performing nucleotide extractions as part of a portable molecular lab setup. We introduce the design and proof-of-principle trials that demonstrate the utility of low-cost 3D-printed centrifuges for use in remote field biology and educational settings.