Wireless Galvanic Impulse Communication for High-Throughput, Low-Power, Miniaturized Neuromodulation Implants.

Deeply implanted bioelectronic devices that selectively record and stimulate peripheral nerves have the potential to revolutionize healthcare by delivering on-demand, personalized therapy. A key barrier to this goal is the lack of a miniaturized, robust, and energy-efficient wireless link capable of transmitting data from multiple sensing channels. To address this issue, we present a wireless galvanic impulse link that uses two 500µm diameter planar electrodes on the outside of a nerve cuff to transmit data to a wearable receiver on the skin's surface at rates greater than 1Mbps. To achieve an energy-efficient, high data rate link, our protocol encodes information in the timing of narrow biphasic pulses that is reconstructed by the wearable receiver. We use a combination of modeling and in vivo and in vitro experimentation to demonstrate the viability of the link. We demonstrate losses lower than 60dB even with significant, 50mm lateral misalignment, ensuring a sufficient signal-to-noise ratio for robust operation. Using a custom, flexible nerve cuff, we demonstrate data transmission in a 14mm-thick rodent animal model and in a 42mm-thick heterogeneous human tissue phantom.

Increased mortality associated with uncontrolled diabetes mellitus in patients with pulmonary cryptococcosis: a single US cohort study.

BACKGROUND: Diabetes mellitus is an established risk factor for bacterial infections, but its role in cryptococcosis is unclear. The study aimed to determine whether uncontrolled diabetes (HbA1c >7%) was an independent risk factor for mortality in cryptococcosis. METHODS: A retrospective case-control study partially matched by age and gender was performed in patients tested for Cryptococcus infection at the University of Colorado Hospital from 2000 to 2019. A multivariable logistic regression model was used to identify mortality predictors. Cox proportional hazard model was used for survival analysis. RESULTS: We identified 96 cases of cryptococcosis and 125 controls. Among cases, cryptococcal meningitis (49.0%) and pneumonia (36.5%) constituted most infections. Cases with pulmonary cryptococcosis with uncontrolled diabetes had a higher mortality at 10 weeks (50% versus 7%, p = 0.006) and 1 year (66.7% versus 13.8%, p = 0.005) compared to pulmonary cases with controlled or no diabetes. Unadjusted Cox proportional hazard model found an increased rate of death for uncontrolled diabetes at 10 weeks [hazard ratio 8.4, confidence interval (CI): 1.4-50.8, p = 0.02] and 1 year (hazard ratio 7.0, CI: 1.7-28.4, p = 0.007) among pulmonary cryptococcosis cases. Multivariable analysis showed a significantly increased odds of 10 weeks [odds ratio (OR) = 4.3, CI: 1.1-16.5, p = 0.035] and 1 year (OR = 5.0, CI: 1.4-18.3, p = 0.014) mortality for uncontrolled diabetes among pulmonary cryptococcosis cases. After adjustment for gender, age, and case/control, for every 1% increase in HbA1c levels, the odds of pulmonary cryptococcosis mortality at 1 year increased by 11% (OR = 1.6, CI 95%: 1.1-2.3, p = 0.006). CONCLUSION: Uncontrolled diabetes is associated with worse outcomes in pulmonary cryptococcosis, including a 4-fold and 6-fold increased odds of death at 10 weeks and 1 year, respectively. Glucose control interventions should be explored to improve clinical outcomes in patients with pulmonary cryptococcosis.

Risk of Chronic Cardiomyopathy Among Patients With the Acute Phase or Indeterminate Form of Chagas Disease: A Systematic Review and Meta-analysis.

Importance: Chagas cardiomyopathy is associated with substantial morbidity and mortality. Precise estimates of the risk of developing cardiomyopathy among patients with the acute or indeterminate chronic forms of Chagas disease are lacking. Objective: To estimate the risk of developing chronic cardiomyopathy in patients with acute and indeterminate chronic forms of Chagas disease. Data Sources: A systematic search in the Cochrane Library, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), Medline, and Web of Science Core Collection databases was conducted from October 8 to October 24, 2018. Studies published between January 1, 1946, and October 24, 2018, that were written in the English, Spanish, and Portuguese languages were included. Search terms included Chagas disease; development of cardiomyopathy; latency duration; and determinants of the Chagas latency period. Study Selection: Longitudinal observational studies of participants diagnosed with the acute phase of Chagas infection or the indeterminate chronic form of Chagas disease who were followed up until the development of cardiomyopathy were included. Studies were excluded if they did not provide sufficient outcome data. Of 10 761 records initially screened, 32 studies met the criteria for analysis. Data Extraction and Synthesis: Critical appraisals of studies were performed using checklists from the Joanna Briggs Institute Reviewer's Manual, and data were collected from published studies. A random-effects meta-analysis was used to obtain pooled estimated annual rates. Data were analyzed from September 11 to December 4, 2019. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for the registration of the protocol, data collection and integrity, assessment of bias, and sensitivity analyses. Main Outcomes and Measures: Main outcomes were defined as the composite of the development of any new arrhythmias or changes in electrocardiogram results, dilated cardiomyopathy and segmental wall motion abnormalities in echocardiogram results, and mortality associated with Chagas disease. Results: A total of 5005 records were screened for eligibility. Of those, 298 full-text articles were reviewed, and 178 of those articles were considered for inclusion in the quantitative synthesis. After exclusions, 32 studies that included longitudinal observational outcomes were selected for the analysis; 23 of those studies comprised patients with the indeterminate chronic form of Chagas disease, and 9 of those studies comprised patients in the acute phase of Chagas infection. The analysis indicated that the pooled estimated annual rate of cardiomyopathy development was 1.9% (95% CI, 1.3%-3.0%; I2 = 98.0%; τ2 [ln scale] = 0.9992) in patients with indeterminate chronic Chagas disease and 4.6% (95% CI, 2.7%-7.9%; I2 = 86.6%; τ2 [ln scale] = 0.4946) in patients with acute Chagas infection. Conclusions and Relevance: Patients with the indeterminate chronic form of Chagas disease had a significant annual risk of developing cardiomyopathy. The annual risk was more than double among patients in the acute phase of Chagas infection.

Ensuring the Safety of Yellow Fever Vaccination in Travelers-The Experience at a Large U.S. Academic Medical Center in Colorado.

Background: Yellow fever (YF) virus has the potential to cause fatal outcomes among at-risk individuals visiting endemic areas. Vaccinating travelers who are at risk is necessary to prevent virus-related life-threatening complications. We lack data on the clinical features of persons seeking YF vaccination. We aim to describe the characteristics of a cohort of persons receiving the YF vaccine before travel. Methods: A retrospective analysis of 964 travelers receiving the YF vaccine (Stamaril®) from Oct 2016 to Jul 2019 was performed at the University of Colorado Hospital, U.S. Percentages, means, and standard deviations were calculated. A multivariate logistic regression model was built to evaluate the association between receiving YF vaccination less than 10 days before departure and visiting friends and relatives (VFR). Results: The average age of the subjects was 39 ± 18 years with a range of nine months to 83 years. Persons who were 60 years of age and older represented 17%. Women consisted of 52%, and most of the travelers were Caucasians (64%). Travelers reported traveling to Africa (57%) or South America (40%). The primary destinations for travelers overall were Kenya (19%), Uganda (11%), and Tanzania (11%) in Africa; and Peru (14%) and Brazil (13%) in South America. The most common reasons for travel included leisure (44%), VFR (18%), and mission trips (10%). Comorbidities included a history of hematologic disorders (4%), HIV infection (2%), and diabetes mellitus (3%). The average duration between vaccine administration and travel was 43 days. Those VFR were two times more likely to receive the YF vaccination <10 days before departure. Conclusions: Identifying the type of travel, itinerary, and underlying medical conditions allows providers to administer the YF vaccine to travelers safely. There is a need to identify strategies to improve the timing of YF vaccination among VFR travelers.