Medicaid Crowd-Out of Private Long-Term Care Insurance Demand: Evidence from the Health and Retirement Survey

This paper provides empirical evidence of Medicaid crowd out of demand for private long-term care insurance. Using data on the near- and young-elderly in the Health and Retirement Survey, our central estimate suggests that a $10,000 decrease in the level of assets an individual can keep while qualifying for Medicaid would increase private long-term care insurance coverage by 1.1 percentage points. These estimates imply that if every state in the country moved from their current Medicaid asset eligibility requirements to the most stringent Medicaid eligibility requirements allowed by federal law – a change that would decrease average household assets protected by Medicaid by about$25,000 – demand for private long-term care insurance would rise by 2.7 percentage points. While this represents a 30 percent increase in insurance coverage relative to the baseline ownership rate of 9.1 percent, it also indicates that the vast majority of households would still find it unattractive to purchase private insurance. We discuss reasons why, even with extremely stringent eligibility requirements, Medicaid may still exert a large crowd-out effect on demand for private insurance.

A test of the hypothesis that oxalate secretion produces proximal tubule crystallization in primary hyperoxaluria type I

The sequence of events by which primary hyperoxaluria type 1 (PH1) causes renal failure is unclear. We hypothesize that proximal tubule (PT) is vulnerable because oxalate secretion raises calcium oxalate (CaOx) supersaturation (SS) there, leading to crystal formation and cellular injury. We studied cortical and papillary biopsies from two PH1 patients with preserved renal function, and seven native kidneys removed from four patients at the time of transplant, after short-term (2) or longer term (2) dialysis. In these patients, and another five PH1 patients without renal failure, we calculated oxalate secretion, and estimated PT CaOx SS. Plasma oxalate was elevated in all PH1 patients and inverse to creatinine clearance. Renal secretion of oxalate was present in all PH1 but rare in controls. PT CaOx SS was >1 in all nonpyridoxine-responsive PH1 before transplant and most marked in patients who developed end stage renal disease (ESRD). PT from PH1 with preserved renal function had birefringent crystals, confirming the presence of CaOx SS, but had no evidence of cortical inflammation or scarring by histopathology or hyaluronan staining. PH1 with short ESRD showed CaOx deposition and hyaluronan staining particularly at the corticomedullary junction in distal PT while cortical collecting ducts were spared. Longer ESRD showed widespread cortical CaOx, and in both groups papillary tissue had marked intratubular CaOx deposits and fibrosis. CaOx SS in PT causes CaOx crystal formation, and CaOx deposition in distal PT appears to be associated with ESRD. Minimizing PT CaOx SS may be important for preserving renal function in PH1

Target-D: a stratified individually randomized controlled trial of the diamond clinical prediction tool to triage and target treatment for depressive symptoms in general practice: study protocol for a randomized controlled trial.

BackgroundDepression is a highly prevalent and costly disorder. Effective treatments are available but are not always delivered to the right person at the right time, with both under- and over-treatment a problem. Up to half the patients presenting to general practice report symptoms of depression, but general practitioners have no systematic way of efficiently identifying level of need and allocating treatment accordingly. Therefore, our team developed a new clinical prediction tool (CPT) to assist with this task. The CPT predicts depressive symptom severity in three months' time and based on these scores classifies individuals into three groups (minimal/mild, moderate, severe), then provides a matched treatment recommendation. This study aims to test whether using the CPT reduces depressive symptoms at three months compared with usual care.MethodsThe Target-D study is an individually randomized controlled trial. Participants will be 1320 general practice patients with depressive symptoms who will be approached in the practice waiting room by a research assistant and invited to complete eligibility screening on an iPad. Eligible patients will provide informed consent and complete the CPT on a purpose-built website. A computer-generated allocation sequence stratified by practice and depressive symptom severity group, will randomly assign participants to intervention (treatment recommendation matched to predicted depressive symptom severity group) or comparison (usual care plus Target-D attention control) arms. Follow-up assessments will be completed online at three and 12 months. The primary outcome is depressive symptom severity at three months. Secondary outcomes include anxiety, mental health self-efficacy, quality of life, and cost-effectiveness. Intention-to-treat analyses will test for differences in outcome means between study arms overall and by depressive symptom severity group.DiscussionTo our knowledge, this is the first depressive symptom stratification tool designed for primary care which takes a prognosis-based approach to provide a tailored treatment recommendation. If shown to be effective, this tool could be used to assist general practitioners to implement stepped mental-healthcare models and contribute to a more efficient and effective mental health system.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR 12616000537459 ). Retrospectively registered on 27 April 2016. See Additional file 1 for trial registration data

A Precision Medicine Approach Uncovers a Unique Signature of Neutrophils in Patients With Brushite Kidney Stones

Introduction: We have previously found that papillary histopathology differs greatly between calcium oxalate and brushite stone formers (SF); the latter have much more papillary mineral deposition, tubular cell injury, and tissue fibrosis. Methods: In this study, we applied unbiased orthogonal omics approaches on biopsied renal papillae and extracted stones from patients with brushite or calcium oxalate (CaOx) stones. Our goal was to discover stone type-specific molecular signatures to advance our understanding of the underlying pathogenesis. Results: Brushite SF did not differ from CaOx SF with respect to metabolic risk factors for stones but did exhibit increased tubule plugging in their papillae. Brushite SF had upregulation of inflammatory pathways in papillary tissue and increased neutrophil markers in stone matrix compared with those with CaOx stones. Large-scale 3-dimensional tissue cytometry on renal papillary biopsies showed an increase in the number and density of neutrophils in the papillae of patients with brushite versus CaOx, thereby linking the observed inflammatory signatures to the neutrophils in the tissue. To explain how neutrophil proteins appear in the stone matrix, we measured neutrophil extracellular trap (NET) formation-NETosis-and found it significantly increased in the papillae of patients with brushite stones compared with CaOx stones. Conclusion: We show that increased neutrophil infiltration and NETosis is an unrecognized factor that differentiates brushite and CaOx SF and may explain the markedly increased scarring and inflammation seen in the papillae of patients with brushite stones. Given the increasing prevalence of brushite stones, the role of neutrophil activation in brushite stone formation requires further study

Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders

OBJECTIVE: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. METHODS: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). RESULTS: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. CONCLUSIONS: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings

Sedimentology, stratigraphic context, and implications of Miocene intrashelf bottomset deposits, offshore New Jersey

Drilling of intrashelf Miocene clinothems onshore and offshore New Jersey has provided better understanding of their topset and foreset deposits, but the sedimentology and stratigraphy of their bottomset deposits have not been documented in detail. Three coreholes (Sites M27–M29), collected during Integrated Ocean Drilling Program (IODP) Expedition 313, intersect multiple bottomset deposits, and their analysis helps to refine sequence stratigraphic interpretations and process response models for intrashelf clinothems. At Site M29, the most downdip location, chronostratigraphically well-constrained bottomset deposits follow a repeated stratigraphic motif. Coarse-grained glauconitic quartz sand packages abruptly overlie deeply burrowed surfaces. Typically, these packages coarsen then fine upwards and pass upward into bioturbated siltstones. These coarse sand beds are amalgamated and poorly sorted and contain thin-walled shells, benthic foraminifera, and extrabasinal clasts, consistent with an interpretation of debrites. The sedimentology and mounded seismic character of these packages support interpretation as debrite-dominated lobe complexes. Farther updip, at Site M28, the same chronostratigraphic units are amalgamated, with the absence of bioturbated silts pointing to more erosion in proximal locations. Graded sandstones and dune-scale cross-bedding in the younger sequences in Site M28 indicate deposition from turbidity currents and channelization. The sharp base of each package is interpreted as a sequence boundary, with a period of erosion and sediment bypass evidenced by the burrowed surface, and the coarse-grained debritic and turbiditic deposits representing the lowstand systems tract. The overlying fine-grained deposits are interpreted as the combined transgressive and highstand systems tract deposits and contain the deepwater equivalent of the maximum flooding surface. The variety in thickness and grain-size trends in the coarse-grained bottomset packages point to an autogenic control, through compensational stacking of lobes and lobe complexes. However, the large-scale stratigraphic organization of the bottomset deposits and the coarse-grained immature extrabasinal and reworked glauconitic detritus point to external controls, likely a combination of relative sea-level fall and waxing-and-waning cycles of sediment supply. This study demonstrates that large amounts of sediment gravity-flow deposits can be generated in relatively shallow (~100–200 m deep) and low-gradient (~1°–4°) clinothems that prograded across a deep continental shelf. This physiography likely led to the dominance of debris flow deposits due to the short transport distance limiting transformation to low-concentration turbidity currents

An inherited duplication at the gene p21 protein-activated Kinase 7 (PAK7) is a risk factor for psychosis

FUNDING Funding for this study was provided by the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z), the Wellcome Trust (072894/Z/03/Z, 090532/Z/09/Z and 075491/Z/04/B), NIMH grants (MH 41953 and MH083094) and Science Foundation Ireland (08/IN.1/B1916). We acknowledge use of the Trinity Biobank sample from the Irish Blood Transfusion Service; the Trinity Centre for High Performance Computing; British 1958 Birth Cohort DNA collection funded by the Medical Research Council (G0000934) and the Wellcome Trust (068545/Z/02) and of the UK National Blood Service controls funded by the Wellcome Trust. Chris Spencer is supported by a Wellcome Trust Career Development Fellowship (097364/Z/11/Z). Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust. ACKNOWLEDGEMENTS The authors sincerely thank all patients who contributed to this study and all staff who facilitated their involvement. We thank W. Bodmer and B. Winney for use of the People of the British Isles DNA collection, which was funded by the Wellcome Trust. We thank Akira Sawa and Koko Ishzuki for advice on the PAK7–DISC1 interaction experiment and Jan Korbel for discussions on mechanism of structural variation.Peer reviewedPublisher PD