Hidden population size estimation and diagnostics using two respondent-driven samples with applications in Armenia.

Estimating the size of hidden populations is essential to understand the magnitude of social and healthcare needs, risk behaviors, and disease burden. However, due to the hidden nature of these populations, they are difficult to survey, and there are no gold standard size estimation methods. Many different methods and variations exist, and diagnostic tools are needed to help researchers assess method-specific assumptions as well as compare between methods. Further, because many necessary mathematical assumptions are unrealistic for real survey implementation, assessment of how robust methods are to deviations from the stated assumptions is essential. We describe diagnostics and assess the performance of a new population size estimation method, capture-recapture with successive sampling population size estimation (CR-SS-PSE), which we apply to data from 3 years of studies from three cities and three hidden populations in Armenia. CR-SS-PSE relies on data from two sequential respondent-driven sampling surveys and extends the successive sampling population size estimation (SS-PSE) framework by using the number of individuals in the overlap between the two surveys and a model for the successive sampling process to estimate population size. We demonstrate that CR-SS-PSE is more robust to violations of successive sampling assumptions than SS-PSE. Further, we compare the CR-SS-PSE estimates to population size estimations using other common methods, including unique object and service multipliers, wisdom of the crowd, and two-source capture-recapture to illustrate volatility across estimation methods.

Population Size Estimation Using Multiple Respondent-Driven Sampling Surveys.

Respondent-driven sampling (RDS) is commonly used to study hard-to-reach populations since traditional methods are unable to efficiently survey members due to the typically highly stigmatized nature of the population. The number of people in these populations is of primary global health and demographic interest and is usually hard to estimate. However, due to the nature of RDS, current methods of population size estimation are insufficient. We introduce a new method of estimating population size that uses concepts from capture-recapture methods while modeling RDS as a successive sampling process. We assess its statistical validity using information from the CDC's National HIV Behavioral Surveillance system in 2009 and 2012.

Bacterial coinfections with coronavirus disease 2019 (COVID-19).

Background: The pandemic caused by severe acute respiratory coronavirus virus 2 (SARS-CoV-2) has dramatically increased cheshospitalizations, and it is often difficult to determine whether there is a bacterial or fungal coinfection at time of presentation. In this study, we sought to determine the rates of coinfection and utilization of antibiotics in SARS-CoV-2 disease. Methods: Retrospective chart review of patients hospitalized with COVID-19 pneumonia from April 13, 2020, to July 14, 2020. Results: In total, 277 patients were hospitalized for COVID-19 pneumonia during this period. Patients that received antibiotics within 48 hours of presentation were more likely to be febrile (59.3% vs 41.2%; P = .01) and to have leukocytosis (23.9% vs 5.9%; P < .01) and were less likely to have a procalcitonin level <0.25 ng/mL (58.8% vs 74.5%; P = .04). In total, 45 patients had positive blood cultures collected during hospitalization, 16 of which were clinically significant. Of the clinically significant blood cultures, 5 were collected <48 hours of admission. Moreover, 18 sputum cultures were clinically significant, 2 of which were collected within 48 hours of admission. Conclusion: Bacterial and fungal coinfections in COVID-19 appear to be rare on presentation; thus, this factor may be a good target for enhanced antibiotic stewardship.

The effects of inflammatory bowel disease on caregivers: significant burden and loss of productivity.

BACKGROUND: Caregiver burden is the emotional, physical, practical, and/or financial burden associated with taking care of a patient with a chronic condition. Limited literature on caregiver burden in Inflammatory Bowel Diseases (IBD) has accounted for some predictors, but its effect on work productivity (absenteeism and presenteeism) is unknown. METHODS: In a prospective study, patients and their respective caregivers were surveyed from November 2015 until July 2017. Data on demographics, work productivity, quality of life, disease activity, caregiver burden and productivity were collected. The burden on caregivers was assessed and associations between caregiver productivity and caregiver burden were analyzed. Additionally, predictors for caregiver burden were identified. RESULTS: One hundred two IBD patients and their respective caregiver were included. In total, 39% of IBD caregivers experienced burden. Caregivers with burden experienced significantly more absenteeism and presenteeism (65 and 85% respectively). Furthermore, 51% of caregivers felt that they should be doing more for their care recipient and felt they could do a better job at caregiving. Predictors of burden included race/ethnicity, history of fistulas, diagnosis of ulcerative colitis, higher caregiver education, and hours spent caregiving. CONCLUSION: Caregivers with burden had significantly more productivity decrease compared to those without burden. Additionally, the majority of caregivers feel they should be providing more and better care for their recipients. The development of strategies to address caregiver's distress and perceived burden when caring for IBD patients is warranted.

Healthcare utilization in men with poorer sexual and urinary function recovery following robot-assisted radical prostatectomy.

PURPOSE: Robotic radical prostatectomy focuses on oncologic cure, urinary continence and sexual function recovery. However, little is known about the effect of declines in urinary continence and sexual function on healthcare utilization. We aim to identify these factors. MATERIALS AND METHODS: From March 2011 to September 2013, all men undergoing robotic prostatectomy within our healthcare system were enrolled. Men completed the expanded prostate cancer index composite-26 survey at the time of diagnosis and 90 days post-operatively. Patients were stratified according to change in scores in the sexual function and urinary incontinence domains. Patient, treatment and post-op utilization patterns were examined for association with the extent of decline in sexual function and urinary continence. Multivariate linear regression was used to identify factors independently associated with decline in continence and sexual function. RESULTS: A total of 411 men who completed the baseline survey and at 90 days postoperatively were included. On multivariate linear regression, younger age (p < 0.01), higher preoperative sexual function (< 0.01), single marital status (p = 0.04) and more post-surgery email contacts (p = 0.04) were associated with higher declines in sexual function. For continence, no family history of prostate cancer (p = 0.01), higher baseline continence (p < 0.01) and more post-surgery physical therapy visits (p < 0.01) were associated with higher declines. CONCLUSIONS: Patients with the poorest quality of life outcomes at 90 days post-operatively were more likely to seek care via email and physical therapy encounters related to sexual function and urinary incontinence, respectively. This suggests that maximizing post-treatment quality of life can potentially reduce healthcare utilization.

Long-term stability of intracortical recordings using perforated and arrayed Parylene sheath electrodes.

OBJECTIVE: Acquisition of reliable and robust neural recordings with intracortical neural probes is a persistent challenge in the field of neuroprosthetics. We developed a multielectrode array technology to address chronic intracortical recording reliability and present in vivo recording results. APPROACH: The 2 × 2 Parylene sheath electrode array (PSEA) was microfabricated and constructed from only Parylene C and platinum. The probe includes a novel three-dimensional sheath structure, perforations, and bioactive coatings that improve tissue integration and manage immune response. Coatings were applied using a sequential dip-coating method that provided coverage over the entire probe surface and interior of the sheath structure. A sharp probe tip taper facilitated insertion with minimal trauma. Fabricated probes were subject to examination by optical and electron microscopy and electrochemical testing prior to implantation. MAIN RESULTS: 1 × 2 arrays were successfully fabricated on wafer and then packaged together to produce 2 × 2 arrays. Then, probes having electrode sites with adequate electrochemical properties were selected. A subset of arrays was treated with bioactive coatings to encourage neuronal growth and suppress inflammation and another subset of arrays was implanted in conjunction with a virally mediated expression of Caveolin-1. Arrays were attached to a custom-made insertion shuttle to facilitate precise insertion into the rat motor cortex. Stable electrophysiological recordings were obtained during the period of implantation up to 12 months. Immunohistochemical evaluation of cortical tissue around individual probes indicated a strong correlation between the electrophysiological performance of the probes and histologically observable proximity of neurons and dendritic sprouting. SIGNIFICANCE: The PSEA demonstrates the scalability of sheath electrode technology and provides higher electrode count and density to access a greater volume for recording. This study provided support for the importance of creating a supportive biological environment around the probes to promote the long-term electrophysiological performance of flexible probes in the cerebral cortex. In particular, we demonstrated beneficial effects of the Matrigel coating and the long-term expression of Caveolin-1. Furthermore, we provided support to an idea of using an artificial acellular tissue compartment as a way to counteract the walling-off effect of the astrocytic scar formation around the probes as a means of establishing a more intimate and stable neural interface.

Parylene MEMS patency sensor for assessment of hydrocephalus shunt obstruction.

Neurosurgical ventricular shunts inserted to treat hydrocephalus experience a cumulative failure rate of 80 % over 12 years; obstruction is responsible for most failures with a majority occurring at the proximal catheter. Current diagnosis of shunt malfunction is imprecise and involves neuroimaging studies and shunt tapping, an invasive measurement of intracranial pressure and shunt patency. These patients often present emergently and a delay in care has dire consequences. A microelectromechanical systems (MEMS) patency sensor was developed to enable direct and quantitative tracking of shunt patency in order to detect proximal shunt occlusion prior to the development of clinical symptoms thereby avoiding delays in treatment. The sensor was fabricated on a flexible polymer substrate to eventually allow integration into a shunt. In this study, the sensor was packaged for use with external ventricular drainage systems for clinical validation. Insights into the transduction mechanism of the sensor were obtained. The impact of electrode size, clinically relevant temperatures and flows, and hydrogen peroxide (H2O2) plasma sterilization on sensor function were evaluated. Sensor performance in the presence of static and dynamic obstruction was demonstrated using 3 different models of obstruction. Electrode size was found to have a minimal effect on sensor performance and increased temperature and flow resulted in a slight decrease in the baseline impedance due to an increase in ionic mobility. However, sensor response did not vary within clinically relevant temperature and flow ranges. H2O2 plasma sterilization also had no effect on sensor performance. This low power and simple format sensor was developed with the intention of future integration into shunts for wireless monitoring of shunt state and more importantly, a more accurate and timely diagnosis of shunt failure.

Matrigel coatings for Parylene sheath neural probes.

The biologically derived hydrogel Matrigel (MG) was used to coat a Parylene-based sheath intracortical electrode to act as a mechanical and biological buffer as well as a matrix for delivering bioactive molecules to modulate the cellular response and improve recording quality. MG was loaded with dexamethasone to reduce the immune response together with nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) to maintain neuronal density and encourage neuronal ingrowth toward electrodes within the sheath. Coating the Parylene sheath electrode with the loaded MG significantly improved the signal-to-noise ratio for neural events recorded from the motor cortex in rat for more than 3 months. Electron microscopy showed even coverage of both the Parylene substrate and the platinum recording electrodes. Electrochemical impedance spectroscopy (EIS) of coated electrodes in 1× phosphate-buffered saline demonstrated low impedance required for recording neural signals. This result was confirmed by in vivo EIS data, showing significantly decreased impedance during the first week of recording. Dexamethasone, NGF, and BDNF loaded into MG were released within 1 day in 1× phosphate-buffered saline. Although previous studies showed that MG loaded with either the immunosuppressant or the neurotrophic factor cocktail provided modest improvement in recording quality in a 1-month in vivo study, the combination of these bioactive molecules did not improve the signal quality over coating probes with only MG in a 3-month in vivo study. The MG coating may further improve recording quality by optimizing the in vivo release profile for the bioactive molecules.

The effect of urologist experience on choosing active surveillance for prostate cancer.

PURPOSE: To evaluate the impact of the urologist's experience in selecting active surveillance (AS) versus immediate treatment (IT) for low-risk prostate cancer. METHODS: Men with low-risk prostate cancer were enrolled from March 2011 to August 2013 at 13 medical centers in Kaiser Permanente Southern California. The AS cohort was defined as men who had cT1-T2a stage prostate cancer, prostate-specific antigen <10 ng/ml, a biopsy revealing Gleason grade ≤6, fewer than three biopsy cores positive, ≤50 % cancer in any core, and not undergone immediate therapy (surgery, radiation, other) within 6 months following diagnosis. The urologist's experience (age, number of years in practice, number of robotic surgeries performed, and fellowship experience in oncology and/or robotics) was then compared between AS and IT cohorts. RESULTS: A total of 4754 men were diagnosed with prostate cancer, and 713 men satisfied with inclusion criteria; 433 (60.7 %) and 280 (39.3 %) chose AS and IT, respectively. A total of 87 urologists were included. Univariate and multivariate adjusted analyses revealed no differences in urologist's age or years in practice. Patients who saw urologists who had performed ≥50 robotic surgeries were less likely to choose AS (OR 0.40, 95 % CI 0.25-0.66). Patients who saw urologists with a fellowship in oncology and/or robotics were more than twice as likely to choose AS (OR 2.27, 95 % CI 1.38-3.75). CONCLUSION: These data suggest that the decision to pursue AS may be influenced by the urologist's experience.

Chronically implanted pressure sensors: challenges and state of the field.

Several conditions and diseases are linked to the elevation or depression of internal pressures from a healthy, normal range, motivating the need for chronic implantable pressure sensors. A simple implantable pressure transduction system consists of a pressure-sensing element with a method to transmit the data to an external unit. The biological environment presents a host of engineering issues that must be considered for long term monitoring. Therefore, the design of such systems must carefully consider interactions between the implanted system and the body, including biocompatibility, surgical placement, and patient comfort. Here we review research developments on implantable sensors for chronic pressure monitoring within the body, focusing on general design requirements for implantable pressure sensors as well as specifications for different medical applications. We also discuss recent efforts to address biocompatibility, efficient telemetry, and drift management, and explore emerging trends.

A natural language processing program effectively extracts key pathologic findings from radical prostatectomy reports.

INTRODUCTION AND OBJECTIVE: Natural language processing (NLP) software programs have been widely developed to transform complex free text into simplified organized data. Potential applications in the field of medicine include automated report summaries, physician alerts, patient repositories, electronic medical record (EMR) billing, and quality metric reports. Despite these prospects and the recent widespread adoption of EMR, NLP has been relatively underutilized. The objective of this study was to evaluate the performance of an internally developed NLP program in extracting select pathologic findings from radical prostatectomy specimen reports in the EMR. METHODS: An NLP program was generated by a software engineer to extract key variables from prostatectomy reports in the EMR within our healthcare system, which included the TNM stage, Gleason grade, presence of a tertiary Gleason pattern, histologic subtype, size of dominant tumor nodule, seminal vesicle invasion (SVI), perineural invasion (PNI), angiolymphatic invasion (ALI), extracapsular extension (ECE), and surgical margin status (SMS). The program was validated by comparing NLP results to a gold standard compiled by two blinded manual reviewers for 100 random pathology reports. RESULTS: NLP demonstrated 100% accuracy for identifying the Gleason grade, presence of a tertiary Gleason pattern, SVI, ALI, and ECE. It also demonstrated near-perfect accuracy for extracting histologic subtype (99.0%), PNI (98.9%), TNM stage (98.0%), SMS (97.0%), and dominant tumor size (95.7%). The overall accuracy of NLP was 98.7%. NLP generated a result in <1 second, whereas the manual reviewers averaged 3.2 minutes per report. CONCLUSIONS: This novel program demonstrated high accuracy and efficiency identifying key pathologic details from the prostatectomy report within an EMR system. NLP has the potential to assist urologists by summarizing and highlighting relevant information from verbose pathology reports. It may also facilitate future urologic research through the rapid and automated creation of large databases.

Comparison of bumetanide- and metolazone-based diuretic regimens to furosemide in acute heart failure.

INTRODUCTION: Limited data exist comparing the efficacy and safety of bumetanide- or metolazone-based diuretic regimens to furosemide in acute heart failure (HF). Our purpose was to evaluate the comparative effect on urine output (UO) and renal function between these regimens. METHODS: A retrospective study of hospitalized HF patients treated with continuous infusion furosemide (CIF), combination furosemide plus metolazone (F + M), or continuous infusion bumetanide (CIB). Primary end points were between regimen comparisons for change in mean hourly UO versus baseline and incidence of worsening renal function. RESULTS: Data on 242 patients with acute HF (age 58 ± 12 years, 63% male, left ventricular ejection fraction 38% ± 17%) were analyzed (160 CIF, 42 F + M, 40 CIB). The mean duration of diuretic regimens was 41 ± 32 hours. Compared to baseline, all regimens increased mean hourly UO (P < .0001 for all), with greater increases with F + M (109 ± 171 mL) and CIB (90 ± 90 mL) compared to CIF (48 ± 103 mL; P = .009). Incidence of worsening renal function was not different between regimens; however, blood urea nitrogen (BUN) tended to increase more with F + M (4.4 ± 9.8 mg/dL) and CIB (4.3 ± 9.7 mg/dL) than CIF (1.8 ± 10.8 mg/dL), P = .09. The incidence of hyponatremia was higher with F + M and CIB. Differences in UO, BUN, and hyponatremia were retained in the subgroup analysis limited to patients with baseline serum creatinine <1.5 mg/dL, where renal function between the groups was not different. CONCLUSION: Compared to CIF, F + M or CIB was associated with greater increases in UO. No difference in the incidence of worsening renal function was found; however, electrolyte abnormalities may be more prevalent when furosemide is combined with metolazone or when bumetanide is used. These therapeutic differences warrant prospective study.

Novel flexible Parylene neural probe with 3D sheath structure for enhancing tissue integration.

A Parylene C neural probe with a three dimensional sheath structure was designed, fabricated, and characterized. Multiple platinum (Pt) electrodes for recording neural signals were fabricated on both inner and outer surfaces of the sheath structure. Thermoforming of Parylene was used to create the three dimensional sheath structures from flat surface micromachined microchannels using solid microwires as molds. Benchtop electrochemical characterization was performed on the thin film Pt electrodes using cyclic voltammetry and electrochemical impedance spectroscopy and showed that electrodes possessed low impedances suitable for neuronal recordings. A procedure for implantation of the neural probe was developed and successfully demonstrated in vitro into an agarose brain tissue model. The electrode-lined sheath will be decorated with eluting neurotrophic factors to promote in vivo neural tissue ingrowth post-implantation. These features will enhance tissue integration and improve recording quality towards realizing reliable chronic neural interfaces.

Asymptotic model of electrical stimulation of nerve fibers.

We present a novel theory and computational algorithm for modeling electrical stimulation of nerve fibers in three dimensions. Our approach uses singular perturbation to separate the full 3D boundary value problem into a set of 2D "transverse" problems coupled with a 1D "longitudinal" problem. The resulting asymptotic model contains not one but two activating functions (AF): the longitudinal AF that drives the slow development of the mean transmembrane potential and the transverse AF that drives the rapid polarization of the fiber in the transverse direction. The asymptotic model is implemented for a prototype 3D cylindrical fiber with a passive membrane in an isotropic extracellular region. The validity of this approach is tested by comparing the numerical solution of the asymptotic model to the analytical solutions. The results show that the asymptotic model predicts steady-state transmembrane potential directly under the electrodes with the root mean square error of 0.539 mV, i.e., 1.04% of the maximum transmembrane potential. Thus, this work has created a computationally efficient algorithm that facilitates studies of the complete spatiotemporal dynamics of nerve fibers in three dimensions.

Pre-implantation electrochemical characterization of a Parylene C sheath microelectrode array probe.

We present the preliminary electrochemical characterization of 3D Parylene C sheath microelectrode array probes towards realizing reliable chronic neuroprosthetic recordings. Electrochemical techniques were used to verify electrode integrity after our novel post-fabrication thermoforming process was applied to flat surface micromachined structures to achieve a hollow sheath probe shape. Characterization of subsequent neurotrophic coatings was performed and accelerated life testing was used to simulate six months in vivo. Prior to probe implantation, crosstalk was measured and electrode surface properties were evaluated through the use of electrochemical impedance spectroscopy.

The nuclear I kappaB protein I kappaB zeta specifically binds NF-kappaB p50 homodimers and forms a ternary complex on kappaB DNA.

Although they share sequence homology to classical cytoplasmic I kappaB inhibitors of transcription factor NF-kappaB, the proteins I kappaB zeta, Bcl-3, and I kappa BNS function in the nucleus as factors that influence NF-kappaB-dependent gene expression profiles. Through the use of purified recombinant proteins and by comparison with the classical I kappaB protein I kappaB alpha, we have discovered mechanistic details of the interaction between I kappaB zeta and functional NF-kappaB dimers. Whereas I kappaB alpha and other classical I kappaB proteins bind tightly to NF-kappaB dimers that possess the p65 subunit, I kappaB zeta binds preferentially to NF-kappaB p50 homodimers. This altered specificity is particularly interesting in light of the fact that both NF-kappaB subunits exhibit high sequence and structural homology, while the I kappaB alpha and I kappaB zeta proteins are also conserved in primary amino acid sequence. We further show that I kappaB zeta is capable of forming a stable ternary complex with the NF-kappaB p50 homodimer and kappaB DNA. Again, this is a stark contrast from I kappaB alpha, which inhibits NF-kappaB p65 homodimer binding to NF-kappaB target DNA sequences. Removal of the DNA sequences flanking the NF-kappaB binding site does not directly affect the interaction of p50 and I kappaB zeta. Rather, we have discovered that the carboxy-terminal glycine-rich region of the NF-kappaB p50 homodimer is involved in mediating high-affinity binding of I kappaB zeta and NF-kappaB p50. We conclude that the NF-kappaB p50 homodimer functions as a legitimate activator of gene expression through formation of a ternary complex between itself, I kappaB zeta, and DNA. The requirement for formation of this complex could explain why the nuclear I kappaB protein I kappaB zeta is absolutely required for expression of the pluripotent pro-inflammatory cytokine interleukin-6 in peritoneal macrophages.