The Effect of Fluid Resuscitation Timing in Early Sepsis Resuscitation.

PURPOSE: The dose and timing of early fluid resuscitation in sepsis remains a debated topic. The objective of this study is to evaluate the effect of fluid timing in early sepsis management on mortality and other clinical outcomes. METHODS: Single-center, retrospective cohort study of emergency-department-treated adults (>18 years, n = 1032) presenting with severe sepsis or septic shock. Logistic regression evaluating the impact of 30 mL/kg crystalloids timing and mortality-versus-time plot controlling for mortality in emergency department sepsis score, lactate, antibiotic timing, obesity, sex, systemic inflammatory response syndrome criteria, hypotension, and heart and renal failures. This study is a subanalysis of a previously published investigation. RESULTS: Mortality was 17.1% (n = 176) overall and 20.4% (n = 133 of 653) among those in septic shock. 30 mL/kg was given to 16.9%, 32.2%, 16.2%, 14.5%, and 20.3% of patients within ≤1, 1 ≤ 3, 3 ≤ 6, 6 ≤ 24, and not reached within 24 h, respectively. A 24-h plot of adjusted mortality versus time did not reach significance, but within the first 12 h, the linear function showed a per-hour mortality increase (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.02-1.67) which peaks around 5h, although the quadratic function does not reach significance (P = .09). When compared to patients receiving 30 mL/kg within 1 h, increased mortality was observed when not reached within 24 h (OR 2.69, 95% CI 1.37-5.37) but no difference when receiving this volume between 1 and 3 (OR 1.11, 95% CI 0.62-2.01), 3 and 6 (OR 1.83, 95% CI 0.97-3.52), or 6 and 24 h (OR 1.51, 95% CI 0.75-3.06). Receiving 30 mL/kg between 1 and 3 versus <1 h increased the incidence of delayed hypotension (OR 1.83, 95% CI 1.23-2.72) but did not impact need for intubation, intensive care unit admission, or vasopressors. CONCLUSIONS: We observed weak evidence that supports that earlier is better for survival when reaching fluid goals of 30 mL/kg, but benefits may wane at later time points. These findings should be viewed as hypothesis generating.

International Delphi Expert Consensus on Safe Return to Surgical and Endoscopic Practice: From the Coronavirus Global Surgical Collaborative.

OBJECTIVE: The aim of this work is to formulate recommendations based on global expert consensus to guide the surgical community on the safe resumption of surgical and endoscopic activities. BACKGROUND: The COVID-19 pandemic has caused marked disruptions in the delivery of surgical care worldwide. A thoughtful, structured approach to resuming surgical services is necessary as the impact of COVID-19 becomes better controlled. The Coronavirus Global Surgical Collaborative sought to formulate, through rigorous scientific methodology, consensus-based recommendations in collaboration with a multidisciplinary group of international experts and policymakers. METHODS: Recommendations were developed following a Delphi process. Domain topics were formulated and subsequently subdivided into questions pertinent to different aspects of surgical care in the COVID-19 crisis. Forty-four experts from 15 countries across 4 continents drafted statements based on the specific questions. Anonymous Delphi voting on the statements was performed in 2 rounds, as well as in a telepresence meeting. RESULTS: One hundred statements were formulated across 10 domains. The statements addressed terminology, impact on procedural services, patient/staff safety, managing a backlog of surgeries, methods to restart and sustain surgical services, education, and research. Eighty-three of the statements were approved during the first round of Delphi voting, and 11 during the second round. A final telepresence meeting and discussion yielded acceptance of 5 other statements. CONCLUSIONS: The Delphi process resulted in 99 recommendations. These consensus statements provide expert guidance, based on scientific methodology, for the safe resumption of surgical activities during the COVID-19 pandemic.

Spatial Partitioning of miRNAs Is Related to Sequence Similarity in Overall Transcriptome.

RNAs have been shown to exhibit differential enrichment between nuclear, cytoplasmic, and exosome fractions. A current fundamental question asks why non-coding RNA partition into different spatial compartments. We report on the analysis of cellular compartment models with miRNA data sources for spatial-mechanistic modeling to address the broad area of multi-scalar cellular communication by miRNAs. We show that spatial partitioning of miRNAs is related to sequence similarity to the overall transcriptome. This has broad implications in biological informatics for gene regulation and provides a deeper understanding of nucleotide sequence structure and RNA language meaning for human pathologies resulting from changes in gene expression.

Minimally Invasive Adductor Release With Obturator Block for Hip Subluxation in Cerebral Palsy: A Report of Two Cases.

Cerebral palsy (CP) is the most common motor disability in childhood and presents with spasticity, increased tone, decreased range of motion, and difficulty with ambulation. Abnormal communication between the cerebrum and the motor fibers leads to functional deficits and long-term adverse sequelae. This case report focuses on hip dysplasia. Two children with CP who were 4.4 and 3.8 years at initial surgery had substantial hip dysplasia with migration percentages (MPs) by X-ray of 60 and 55 and Gross Motor Functional Classification System (GMFCS) levels of 4 and 5. Each patient underwent minimally invasive selective percutaneous myofascial lengthening (SPML) of the hip adductors and ethanol block of the obturator nerves, along with other indicated procedures. Follow-ups were four and six years for the two cases. Indications for surgery included adductor spasticity with contracture, brisk adductor reflexes, scissoring, and hip dysplasia. The goals were to relieve symptoms and to serve as temporizing measures prior to possible later hip reconstruction. Results showed that, in each case, the MP improved substantially. Case 1 was a child who initially took steps with assistance and became independent by age six, with GMFCS scores improving from 4 to 2. The MP improved from 60 to 35 over four years. Case 2 was a child of GMFCS 5 who could not stand or take steps. The MP improved from 55 to 25 over six years. In addition to the initial SPML surgery, he had a second SPML surgery 31 months later at age six. This case is noteworthy in that the child consistently used a hip abduction orthosis and an abducted wheelchair through the entire six-year follow-up period. In conclusion, some young children with a significant hip subluxation can achieve improvement following minimally invasive surgery at medium-term follow-up. Our two children each had special circumstances. One was more highly functioning and became an independent walker. The other had consistent use of a hip abduction orthosis and an abducted wheelchair.

An Open-Source Privacy-Preserving Large-Scale Mobile Framework for Cardiovascular Health Monitoring and Intervention Planning With an Urban African American Population of Young Adults: User-Centered Design Approach.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death worldwide and are increasingly affecting younger populations, particularly African Americans in the southern United States. Access to preventive and therapeutic services, biological factors, and social determinants of health (ie, structural racism, resource limitation, residential segregation, and discriminatory practices) all combine to exacerbate health inequities and their resultant disparities in morbidity and mortality. These factors manifest early in life and have been shown to impact health trajectories into adulthood. Early detection of and intervention in emerging risk offers the best hope for preventing race-based differences in adult diseases. However, young-adult populations are notoriously difficult to recruit and retain, often because of a lack of knowledge of personal risk and a low level of concern for long-term health outcomes. OBJECTIVE: This study aims to develop a system design for the MOYO mobile platform. Further, we seek to addresses the challenge of primordial prevention in a young, at-risk population (ie, Southern-urban African Americans). METHODS: Urban African Americans, aged 18 to 29 years (n=505), participated in a series of co-design sessions to develop MOYO prototypes (ie, HealthTech Events). During the sessions, participants were orientated to the issues of CVD risk health disparities and then tasked with wireframing prototype screens depicting app features that they considered desirable. All 297 prototype screens were subsequently analyzed using NVivo 12 (QSR International), a qualitative analysis software. Using the grounded theory approach, an open-coding method was applied to a subset of data, approximately 20% (5/25), or 5 complete prototypes, to identify the dominant themes among the prototypes. To ensure intercoder reliability, 2 research team members analyzed the same subset of data. RESULTS: Overall, 9 dominant design requirements emerged from the qualitative analysis: customization, incentive motivation, social engagement, awareness, education, or recommendations, behavior tracking, location services, access to health professionals, data user agreements, and health assessment. This led to the development of a cross-platform app through an agile design process to collect standardized health surveys, narratives, geolocated pollution, weather, food desert exposure data, physical activity, social networks, and physiology through point-of-care devices. A Health Insurance Portability and Accountability Act-compliant cloud infrastructure was developed to collect, process, and review data, as well as generate alerts to allow automated signal processing and machine learning on the data to produce critical alerts. Integration with wearables and electronic health records via fast health care interoperability resources was implemented. CONCLUSIONS: The MOYO mobile platform provides a comprehensive health and exposure monitoring system that allows for a broad range of compliance, from passive background monitoring to active self-reporting. These study findings support the notion that African Americans should be meaningfully involved in designing technologies that are developed to improve CVD outcomes in African American communities.

Trending Tubes: A Social Media Analysis of Tympanostomy Tubes in Children.

Objective: To investigate the popular social media platforms Instagram and Facebook for public posts related to tympanostomy tubes in children, to discern attitudes and perceptions surrounding tympanostomy tubes, and to evaluate the content of social media posts related to tympanostomy tubes. Study Design: Qualitative study. Setting: Instagram and Facebook social media platforms. Methods: Instagram and Facebook were searched for public posts from 2018 and 2019 including the search terms "ear tubes,""ear tube surgery,""tympanostomy," and "myringotomy." Posts were excluded if they were unrelated to pediatric tympanostomy tubes or written in a non-English language. Relevant posts underwent subgroup analysis based on 6 domains: media type, perspective, topic, timeframe, popularity, and overall tone. Results: Of 1862 public social media posts, the majority (78.2%) were made by the patient's parents/caregivers and the rest by physicians (6.0%), hospitals (8.2%), and chiropractors (6.1%), with a few posts by the patients themselves (0.4%). The majority (79.3%) of posts portrayed tympanostomy tubes positively. Most negative posts were made by chiropractors (50.8%) and the patient's parents/caregivers (42.9%). The most common themes of posts were reassurance regarding surgery (74.9%), advertisements (12.5%), apprehension (12.4%), and education (10.3%). Conclusion: Most social media posts were made by parents/caregivers in the perioperative period, and there was a low percentage of educational posts. This information could be used by otolaryngologists to optimize their interactions with patients and parents and to potentially increase physician involvement and educational material related to tympanostomy tubes on social media.

HIV-related Neuropathy: Pathophysiology, Treatment and Challenges.

HIV-sensory neuropathy (HIV-SN) is a debilitating complication in HIV patients with or without anti-retroviral treatment (ART). Common symptoms of HIV-SN include pain, decreased sensation, paresthesias, and dysesthesias in a symmetric stocking-glove distribution. While HIV-1 protein such as gp120 is implicated in HIV-SN (e.g. impaired large-diameter fiber), ART itself was recently shown to contribute to HIV-SN in HIV patients and impair thin fiber. Multiple host mechanisms may play roles during the pathogenesis of HIV-SN, including neuron-glia interactions in the spinal dorsal horn (SDH), inflammation, mitochondrial dysfunction and endoplasmic reticulum stress. Concurrent infections, such as tuberculosis, also carry a higher likelihood of HIV-SN as well as environmental or genetic predisposition. Pro-inflammatory cytokines such as IL-1, IL2 receptor-alpha, and tumor necrosis factor (TNF) along with abnormal lactate levels have been identified as potential players within the complex pathophysiology of this condition. In this paper, we review the pathophysiology of HIV neuropathy, focusing on the various treatment options available or under investigation. Although several treatment options are available e.g., the capsaicin patch and spinal cord stimulation, symptomatic control of HIV-SN are often challenging. Alternative approaches such as self-hypnosis, resistance exercise, cannabinoids, and acupuncture have all shown promising results, but need further investigation.

Preventing Cardiovascular Disease Among Urban African Americans With a Mobile Health App (the MOYO App): Protocol for a Usability Study.

BACKGROUND: Cardiovascular disease (CVD) disparities are a particularly devastating manifestation of health inequity. Despite advancements in prevention and treatment, CVD is still the leading cause of death in the United States. Additionally, research indicates that African American (AA) and other ethnic-minority populations are affected by CVD at earlier ages than white Americans. Given that AAs are the fastest-growing population of smartphone owners and users, mobile health (mHealth) technologies offer the unparalleled potential to prevent or improve self-management of chronic disease among this population. OBJECTIVE: To address the unmet need for culturally tailored primordial prevention CVD-focused mHealth interventions, the MOYO app was cocreated with the involvement of young people from this priority community. The overall project aims to develop and evaluate the effectiveness of a novel smartphone app designed to reduce CVD risk factors among urban-AAs, 18-29 years of age. METHODS: The theoretical underpinning will combine the principles of community-based participatory research and the agile software development framework. The primary outcome goals of the study will be to determine the usability, acceptability, and functionality of the MOYO app, and to build a cloud-based data collection infrastructure suitable for digital epidemiology in a disparity population. Changes in health-related parameters over a 24-week period as determined by both passive (eg, physical activity levels, sleep duration, social networking) and active (eg, use of mood measures, surveys, uploading pictures of meals and blood pressure readings) measures will be the secondary outcome. Participants will be recruited from a majority AA "large city" school district, 2 historically black colleges or universities, and 1 urban undergraduate college. Following baseline screening for inclusion (administered in person), participants will receive the beta version of the MOYO app. Participants will be monitored during a 24-week pilot period. Analyses of varying data including social network dynamics, standard metrics of activity, percentage of time away from a given radius of home, circadian rhythm metrics, and proxies for sleep will be performed. Together with external variables (eg, weather, pollution, and socioeconomic indicators such as food access), these metrics will be used to train machine-learning frameworks to regress them on the self-reported quality of life indicators. RESULTS: This 5-year study (2015-2020) is currently in the implementation phase. We believe that MOYO can build upon findings of classical epidemiology and longitudinal studies like the Jackson Heart Study by adding greater granularity to our knowledge of the exposures and behaviors that affect health and disease, and creating a channel for outreach capable of launching interventions, clinical trials, and enhancements of health literacy. CONCLUSIONS: The results of this pilot will provide valuable information about community cocreation of mHealth programs, efficacious design features, and essential infrastructure for digital epidemiology among young AA adults. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16699.

Safety of 6-Hz primed low-frequency rTMS in stroke.

BACKGROUND: Suppression of activity in the contralesional motor cortex may promote recovery of function after stroke. Furthermore, the known depressant effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) can be increased and prolonged by preceding it with 6-Hz priming stimulation. OBJECTIVE: The authors explored the safety of 6-Hz primed low-frequency rTMS in 10 patients with ischemic stroke. METHODS: Priming consisted of 10 minutes of 6-Hz rTMS applied to the contralesional hemisphere at 90% of resting motor threshold delivered in 2 trains/min with 5 s/train and 25-second intervals between trains. Low-frequency rTMS consisted of an additional 10 minutes of 1-Hz rTMS at 90% of resting motor threshold without interruption. Possible adverse effects were assessed with the National Institutes of Health Stroke Scale (NIHSS), the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Hopkins Verbal Learning Test-Revised (HVLT-R), the Beck Depression Inventory-Second Edition (BDI-II), a finger movement tracking test, and individual self-assessments. Pretest, treatment, and posttest occurred on the first day with follow-up tests on the next 5 weekdays. RESULTS: There were no seizures and no impairment of NIHSS, WAIS-III, or BDI-II scores. Transient impairment occurred on the HVLT-R. Transient tiredness was common. Occasional reports of headache, neck pain, increased sleep, reduced sleep, nausea, and anxiety occurred. CONCLUSION: Because there were no major adverse effects, the authors concluded that the treatment was safe for the individuals in this study and that further investigation is now warranted to examine efficacy and safety of serial treatments of 6-Hz primed low-frequency rTMS.

Machine Learning Data Imputation and Classification in a Multicohort Hypertension Clinical Study.

Health-care initiatives are pushing the development and utilization of clinical data for medical discovery and translational research studies. Machine learning tools implemented for Big Data have been applied to detect patterns in complex diseases. This study focuses on hypertension and examines phenotype data across a major clinical study called Minority Health Genomics and Translational Research Repository Database composed of self-reported African American (AA) participants combined with related cohorts. Prior genome-wide association studies for hypertension in AAs presumed that an increase of disease burden in susceptible populations is due to rare variants. But genomic analysis of hypertension, even those designed to focus on rare variants, has yielded marginal genome-wide results over many studies. Machine learning and other nonparametric statistical methods have recently been shown to uncover relationships in complex phenotypes, genotypes, and clinical data. We trained neural networks with phenotype data for missing-data imputation to increase the usable size of a clinical data set. Validity was established by showing performance effects using the expanded data set for the association of phenotype variables with case/control status of patients. Data mining classification tools were used to generate association rules.