Prostate Cancer Care Before and After Medicare Eligibility.

Prior studies suggest Medicare eligibility confers significant and substantial reductions in mortality and beneficial increases in health service utilization. We compared 13,882 patients diagnosed with prostate cancer at ages 63 to 64 years with 14,774 patients diagnosed at ages 65 to 66 (controls) in 2004 to 2007. Compared with controls, patients diagnosed with prostate cancer before Medicare eligibility had no statistically significant or meaningful differences in cancer stage, time to treatment, or type of treatment

Lung Cancer Care Before and After Medicare Eligibility.

Uninsured and underinsured near-elderly may not have timely investigation, diagnosis, or care of cancer. Prior studies suggest Medicare eligibility confers significant and substantial reductions in mortality and increases in health service utilization. We compared 2245 patients diagnosed with lung cancer at ages 64.5 to 65 years and 2512 patients aged 65 to 65.5 years, with 2492 patients aged 65.5 to 66 years (controls) in 2000 to 2005. Compared with controls, patients diagnosed with lung cancer before Medicare eligibility had no statistically significant differences in cancer stage, time to treatment, type of treatment, and survival. Study power was sufficient to exclude mortality reductions and health service utilization changes of the magnitude found in prior work, suggesting that typically, appropriate lung cancer care may be sought and delivered regardless of insurance status

Could Data Broker Information Threaten Physician Prescribing and Professional Behavior?

Privacy is threatened by the extent of data collected and sold by consumer data brokers. Physicians, as individual consumers, leave a ‘data trail’ in the offline (e.g. through traditional shopping) and online worlds (e.g. through online purchases and use of social media). Such data could easily and legally be used without a physician’s knowledge or consent to influence prescribing practices or other physician professional behavior. We sought to determine the extent to which such consumer data was available on a sample of more than 3,000 physicians, healthcare faculty and healthcare system staff at one university’s health units. Using just work email addresses for these employees we cheaply and quickly obtained external data on nearly two thirds of employees on demographic characteristics (e.g. income, top 10% national wealth, children at home, married), purchases (e.g. baby products, cooking, sports), behavior (e.g. charitable donor, discount shopper) and interests (e.g. automotive, health and wellness). Consumer data brokers have valuable, cost-effective and detailed information on many healthcare professionals, including data that could be used to segment, target, detail and generally market to physicians in ways that seem under‐appreciated. We call for greater attention to this potential aspect of physician-industry relationships

The Veterans Affairs Neuropathy Scale: A Reliable, Remote Polyneuropathy Exam.

Introduction: Polyneuropathy (PN) complaints are common, prompting many referrals for neurologic evaluation. To improve access of PN care in distant community clinics, we developed a telemedicine service (patient-clinician interactions using real-time videoconference technology) for PN. The primary goal of this study was to construct a remote exam for PN that is feasible, reliable, and concordant with in-person assessments for use in our tele-PN clinics. Methods: To construct the VA Neuropathy Scale (VANS), we searched the literature for existing, validated PN assessments. From these assessments, we selected a parsimonious set of exam elements based on literature-reported sensitivity and specificity of PN detection, with modifications as necessary for our teleneurology setting (i.e., a technician examination under the direction of a neurologist). We recruited 28 participants with varying degrees of PN to undergo VANS testing under 5 scenarios. The 5 scenarios differed by mode of VANS grading (in-person vs. telemedicine) and by the in-person examiner type (neurologist vs. technician) in telemedicine scenarios. We analyzed concordance between the VANS and a person's medical chart-derived PN status by modeling the receiver operating characteristic (ROC) curve. We analyzed reliability of the VANS by mixed effects regression and computing the intraclass correlation coefficient (ICC) of scores across the 5 scenarios. Results: The VA Neuropathy Scale (VANS) tests balance, gait, reflexes, foot inspection, vibration, and pinprick. Possible scores range from 0 to 50 (worst). From the ROC curve, a cutoff of >2 points on the VANS sets the sensitivity and specificity of detecting PN at 98 and 91%, respectively. There is a small (1.3 points) but statistically significant difference in VANS scoring between in-person and telemedicine grading scenarios. For telemedicine grading scenarios, there is no difference in VANS scores between neurologist and technician examinations. The ICC is 0.89 across all scenarios. Discussion: The VANS, informed by existing PN instruments, is a promising clinical assessment tool for diagnosing and monitoring the severity of PN in telemedicine settings. This pilot study indicates acceptable concordance and reliability of the VANS with in-person examinations

Retinol esterification in Sertoli cells by lecithin-retinol acyltransferase

Esterification of retinol occurs during the metabolism of vitamin A in the testis. An acyl- CoA:retinol acyltransferase (ARAT) activity has been described for microsomes isolated from testis homogenates. That activity was also observed here in microsomal preparations obtained from cultured Sertoli cells from 20-day-old (midpubertal) rats. ARAT catalyzed the synthesis of retinyl laurate when free retinol and lauroyl-CoA were provided as substrates. However, in the absence of exogenous acyl-CoA, retinol was esterified by a different activity in a manner similar to the lecithimretinol acyltransferase (LRAT) activity described recently for liver and intestine. Microsomal preparations obtained from enriched Sertoli cell fractions from the adult rat testis had 75-fold higher levels of LRAT than the preparations from midpubertal animals, but ARAT activity was the same in both these preparations. LRAT utilized an endogenous acyl donor and either unbound retinol or retinol complexed with cellular retinol-binding protein (CRBP) to catalyze the synthesis of retinyl linoleate, retinyl oleate, retinyl palmitate, and retinyl stearate. The addition of exogenous dilaurylphosphatidylcholine (DLPC) resulted in the synthesis of retinyl laurate. The esterification from both exogenous DLPC and endogenous acyl donor was inhibited by 2 mM phenylmethanesulfonyl fluoride (PMSF). ARAT activity was not affected by similar concentrations of PMSF. Furthermore, retinol bound to CRBP, a protein known to be present in Sertoli cells, was not an effective substrate for testicular ARAT. When retinol uptake and metabolism were examined in cultured Sertoli cells from 20-day-old rats, the cells synthesized the same retinyl esters that were produced by microsomal LRAT in vitro. Pretreating the cells with PMSF did not prevent specific retinol accumulation but did inhibit retinol esterification. Consequently, the LRAT-like retinyl esters produced by cultured Sertoli cells and the sensitivity of this esterification to PMSF suggest that LRAT, and not ARAT, is the physiologically important retinyl ester synthase in the Sertoli cell

Characteristics of retinol accumulation from serum retinol-binding protein by cultured Sertoli cells

The uptake of retinol was examined in cultured Sertoli cells when retinol was provided as a complex with the transport protein retinol-binding protein (RBP). Sertoli cells accumulated [3H]retinol in a time- and temperature-dependent manner. At 32 °C, the rate of retinol accumulation was biphasic. Accumulation was linear for approximately 1 h, but then accumulation continued at a linear but decreased rate for 23 h. The change in rate of retinol accumulation occurred when the cells had accumulated approximately 0.53 pmol of retinol/Mg of cellular DNA. This amount of retinol was approximately equal to the cellular content of cellular retinol-binding protein (CRBP). Extraction and HPLC analysis of the cell-associated radioactivity yielded retinol and retinyl esters, indicating that a significant proportion of the accumulated retinol was esterified. Excess unlabeled retinol-RBP competed with [3H]retinol-RBP for [3H]retinol delivery to the cells, indicating that RBP delivery of retinol was a saturable and competable process. However, free [3H]retinol associated with Sertoli cells in a noncompetable manner. The transport constant for specific retinol accumulation from RBP was 3.0 μ , suggesting that any change in the normal circulating retinol-RBP level (approximately 2 μ ) would directly affect the rate of retinol accumulation. Neither iodinated nor reductively methylated RBP was accumulated by or tightly bound to Sertoli cells. In addition, energy inhibitors and lysosomal poisons had no effect on [3H] retinol accumulation, indicating that RBP delivery of retinol to Sertoli cells did not occur by endocytosis of the retinol-RBP complex. Competition studies indicated, however, that protein recognition is important in the retinol uptake process. RBP, CRBP, and CRBP(II) competed with [3H] retinol-RBP for [3H] retinol accumulation, but free retinol, retinol-bovine serum albumin, and retinol-/3-lactoglobulin did not. Transthyretin, bound to [3H] retinol-RBP in the physiological 1:1 ratio, decreased [3H]retinol accumulation by the cells by 25-30% compared to [3H]retinol accumulation from [3H]retinol-RBP. These studies indicated that Sertoli cell uptake of retinol involved recognition of the retinol-RBP complex at the cell surface with subsequent internalization of retinol, but not RBP. The fate of the internalized retinol may first have involved binding by CRBP, but eventually a significant portion of the accumulated retinol was esterified

Bidirectional Representation Learning from Transformers using Multimodal Electronic Health Record Data to Predict Depression

Advancements in machine learning algorithms have had a beneficial impact on representation learning, classification, and prediction models built using electronic health record (EHR) data. Effort has been put both on increasing models' overall performance as well as improving their interpretability, particularly regarding the decision-making process. In this study, we present a temporal deep learning model to perform bidirectional representation learning on EHR sequences with a transformer architecture to predict future diagnosis of depression. This model is able to aggregate five heterogenous and high-dimensional data sources from the EHR and process them in a temporal manner for chronic disease prediction at various prediction windows. We applied the current trend of pretraining and fine-tuning on EHR data to outperform the current state-of-the-art in chronic disease prediction, and to demonstrate the underlying relation between EHR codes in the sequence. The model generated the highest increases of precision-recall area under the curve (PRAUC) from 0.70 to 0.76 in depression prediction compared to the best baseline model. Furthermore, the self-attention weights in each sequence quantitatively demonstrated the inner relationship between various codes, which improved the model's interpretability. These results demonstrate the model's ability to utilize heterogeneous EHR data to predict depression while achieving high accuracy and interpretability, which may facilitate constructing clinical decision support systems in the future for chronic disease screening and early detection.Comment: in IEEE Journal of Biomedical and Health Informatics (2021

Teleneurology clinics for polyneuropathy: a pilot study.

INTRODUCTION:Polyneuropathy (PN) is a common condition with significant morbidity. We developed tele-polyneuropathy (tele-PN) clinics to improve access to neurology and increase guideline-concordant PN care. This article describes the mixed-methods evaluation of pilot tele-PN clinics at three community sites within the Greater Los Angeles VA Healthcare System. METHODS:For the first 25 patients (48 scheduled visits), we recorded the duration of the tele-PN visit and exam; the performance on three guideline-concordant care indicators (PN screening labs, opiate reduction, physical therapy for falls); and patient-satisfaction scores. We elicited comments about the tele-PN clinic from patients and the clinical team. We combined descriptive statistics with qualitative themes to determine the feasibility and acceptability of the tele-PN clinics. RESULTS:The average tele-PN encounter and exam times were 28.5 and 9.1 min, respectively. PN screening lab completion increased from 80 to 100%. Opiate freedom improved from 68 to 88%. Physical therapy for patients with recent falls increased from 58 to 100%. The tele-PN clinic was preferred for follow-up over in-person clinics in 86% of cases. Convenience was paramount to the clinic's success, saving an average of 231 min per patient in round-trip travel. The medical team's caring and collaborative spirit received high praise. While the clinic's efficiency was equal or superior to in-person care, the limited treatment options for PN and the small clinical exam space are areas for improvement. CONCLUSION:In this pilot, we were able to efficiently see and examine patients remotely, promote guideline-concordant PN care, and provide a high-satisfaction encounter

The Guinea Pig as a Model for Sporadic Alzheimer\u27s Disease (AD): The Impact of Cholesterol Intake on Expression of AD-Related Genes

We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer’s disease (AD), both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high cholesterol intake. Unlike rats and mice, guinea pigs possess an Ab peptide sequence identical to human Ab. Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high cholesterol diet leads to up-regulation of BACE1 (b-secretase) transcription and down-regulation of ADAM10 (a-secretase) transcription which should increase release of Ab from APP. Significantly, guinea pigs possess isoforms of AD-related genes found in humans but not present in mice or rats. For example, we discovered that the truncated PS2V isoform of human PSEN2, that is found at raised levels in AD brains and that increases c-secretase activity and Ab synthesis, is not uniquely human or aberrant as previously believed. We show that PS2V formation is up-regulated by hypoxia and a high-cholesterol diet while, consistent with observations in humans, Ab concentrations are raised in some brain regions but not others. Also like humans, but unlike mice, the guinea pig gene encoding tau, MAPT, encodes isoforms with both three and four microtubule binding domains, and cholesterol alters the ratio of these isoforms. We conclude that AD-related genes are highly conserved and more similar to human than the rat or mouse. Guinea pigs represent a superior rodent model for analysis of the impact of dietary factors such as cholesterol on the regulation of AD-related genes

Universal Gelation of Metal Oxide Nanocrystals via Depletion Attractions

Nanocrystal gelation provides a powerful framework to translate nanoscale properties into bulk materials and to engineer emergent properties through the assembled microstructure. However, many established gelation strategies rely on chemical reactions and specific interactions, e.g., stabilizing ligands or ions on the surface of the nanocrystals, and are therefore not easily transferrable. Here, we report a general gelation strategy via non-specific and purely entropic depletion attractions applied to three types of metal oxide nanocrystals. The gelation thresholds of two compositionally distinct spherical nanocrystals agree quantitatively, demonstrating the adaptability of the approach for different chemistries. Consistent with theoretical phase behavior predictions, nanocrystal cubes form gels at a lower polymer concentration than nanocrystal spheres, allowing shape to serve as a handle to control gelation. These results suggest that the fundamental underpinnings of depletion-driven assembly, traditionally associated with larger colloidal particles, are also applicable at the nanoscale