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

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

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

Women’s experiences of wearing therapeutic footwear in three European countries

Background: Therapeutic footwear is recommended for those people with severe foot problems associated with rheumatoid arthritis (RA). However, it is known that many do not wear them. Although previous European studies have recommended service and footwear design improvements, it is not known if services have improved or if this footwear meets the personal needs of people with RA. As an earlier study found that this footwear has more impact on women than males, this study explores women’s experiences of the process of being provided with it and wearing it. No previous work has compared women’s experiences of this footwear in different countries, therefore this study aimed to explore the potential differences between the UK, the Netherlands and Spain. Method: Women with RA and experience of wearing therapeutic footwear were purposively recruited. Ten women with RA were interviewed in each of the three countries. An interpretive phenomenological approach (IPA) was adopted during data collection and analysis. Conversational style interviews were used to collect the data. Results: Six themes were identified: feet being visibly different because of RA; the referring practitioners’ approach to the patient; the dispensing practitioners’ approach to the patient; the footwear being visible as different to others; footwear influencing social participation; and the women’s wishes for improved footwear services. Despite their nationality, these women revealed that therapeutic footwear invokes emotions of sadness, shame and anger and that it is often the final and symbolic marker of the effects of RA on self perception and their changed lives. This results in severe restriction of important activities, particularly those involving social participation. However, where a patient focussed approach was used, particularly by the practitioners in Spain and the Netherlands, the acceptance of this footwear was much more evident and there was less wastage as a result of the footwear being prescribed and then not worn. In the UK, the women were more likely to passively accept the footwear with the only choice being to reject it once it had been provided. All the women were vocal about what would improve their experiences and this centred on the consultation with both the referring practitioner and the practitioner that provides the footwear. Conclusion: This unique study, carried out in three countries has revealed emotive and personal accounts of what it is like to have an item of clothing replaced with an ‘intervention’. The participant’s experience of their consultations with practitioners has revealed the tension between the practitioners’ requirements and the women’s ‘social’ needs. Practitioners need greater understanding of the social and emotional consequences of using therapeutic footwear as an intervention

Pharmacological evaluation of novel bioisosteres of an adamantanyl benzamide P2X7 receptor antagonist

Adamantanyl benzamide 1 was identified as a potent P2X7R antagonist but failed to progress further due to poor metabolic stability. We describe the synthesis and SAR of a series of bioisosteres of benzamide 1 to explore improvements in the pharmacological properties of this lead. Initial efforts investigated a series of heteroaromatic bioisosteres, which demonstrated improved physicochemical properties but reduced P2X7R antagonism. Installation of bioisosteric fluorine on the adamantane bridgeheads was well tolerated and led to a series of bioisosteres with improved physicochemical properties and metabolic stability. Trifluorinated benzamide 34 demonstrated optimal physicochemical parameters, superior metabolic stability (ten times longer than lead benzamide 1), and an improved physicokinetic profile and proved effective in the presence of several known P2X7R polymorphisms