Unreported Antipsychotic Use Increasing in Nursing Homes: The Impact of Quality-Measure Exclusions on the Percentage of Long-Stay Residents Who Got an Antipsychotic Medication Quality-Measure

ObjectiveExcluded from reporting to CMS's Percentage of long-stay residents who got an antipsychotic medication quality-measure are antipsychotics prescribed to nursing home patients with schizophrenia, Tourette's, or Huntington's. Over the 4 years following its 2012 debut, the quality-measure calculated a 27% reduction in inappropriate antipsychotic use but also an 18.3% increase in exclusion claims. This study evaluated the impact of these exclusions on the measure's findings.MethodsClaims data for the years 2011–2016 retrospectively identified the prevalence of schizophrenia, Tourette's, and Huntington's in quarterly cohorts of Virginia long-stay residents prescribed antipsychotics. Annualized diagnoses in 2011 were compared with subsequent years using simple logistic regression.ResultsIn 2016, 29% of the antipsychotics prescribed in Virginia nursing homes were to residents with diagnoses of schizophrenia, Tourette's, and Huntington's, a significant 32% increase from 2011.ConclusionAlmost 30% of the antipsychotics employed in Virginia nursing homes are excluded from CMS's long-stay antipsychotic quality-measure.     

Lymphatic Vessel Memory Stimulated by Recurrent Inflammation

Inflammation stimulates new lymphatic vessel growth (inflammatory lymphangiogenesis). One key question is how recurrent inflammation, a common clinical condition, regulates lymphatic vessel remodeling. We show here that recurrent inflammation accelerated the development a functional lymphatic vessel network. This observation suggests a novel program of lymphangiogenesis and identifies a property of lymphatic vessel memory in response to recurrent inflammation. A brief episode of initial inflammation regressed lymphatic vessels, and a significant increase in CD11b⁺ macrophages were associated with the development of lymphatic vessel memory. These vessels had major differences in the structure and the spatial distribution of specialized lymphatic vessel features. Surprisingly, we found that the lymphatic vessel memory response did not depend on the vascular endothelial growth factor C or A pathway, indicating that different molecular pathways regulate inflammatory lymphangiogenesis and lymphatic vessel memory. These findings uncover a priming mechanism to facilitate a rapid lymphatic vessel memory response: a potential important component of peripheral host defense.The lymphatic vasculature is one component of the inflammatory response that is remarkably understudied. The lymphatic system can be broadly classified into the lymphoid tissue (tonsils, lymph nodes, and spleen) and the conduit system or lymphatic vasculature. The focus of these studies is the lymphatic capillaries which literally are the most peripheral extension of the immune system and reside intimately in the diseased tissue. Aside from the classic functions of the lymphatic vasculature described many years ago (transport of extracellular fluid, cells, antigens, and lipid), surprisingly little is known about the normal physiology of this system and how it regulates inflammation and wound recovery. Multiple lines of evidence have shown that the lymphatic vasculature proliferates in response to inflammatory conditions, suggesting an active, perhaps essential, role during the inflammatory response.^1–6 Inflammatory lymphangiogenesis is thought to be a physiological mechanism that develops to meet the increased demands of fluid, antigen, and cellular transport during an inflammatory response. New lymphatic vessel growth has been associated with beneficial effects in several different preclinical models of acute or chronic inflammatory disease.^3,7–9 It is well recognized that vascular endothelial growth factor (VEGF)-C-VEGF receptor (VEGFR)-3 and VEGF-A-VEGFR-2 pathways are important in inflammatory lymphangiogenesis.¹⁰ The most accepted model of inflammatory lymphangiogenesis is that vessels sprout and elongate from pre-existing lymphatic vessels. In contrast, is some evidence is available that circulating endothelial progenitors or macrophages differentiate into lymphatic endothelial cells to comprise newly synthesized lymphatic vessels.^11,12Clinically, two general outcomes occur after an initial episode of inflammatory disease: wound recovery or recurrent inflammation. We developed a mouse model of wound recovery and recurrent inflammation to simulate these clinical outcomes and to study the lymphatic vasculature during these conditions. We recently demonstrated that lymphatic vessel regression developed during wound recovery in the cornea.¹³ Fragmented lymphatic vessels that persisted over time were visualized in wound recovery conditions.In contrast to wound recovery, recurrent inflammation is a common clinical outcome after an initial episode of inflammation. We studied the effects of recurrent inflammation in corneal tissue recovered from an initial inflammatory response. This approach is different from earlier studies in that it features wound recovery followed by recurrent inflammation rather than an acute or chronic unrelenting pathogen or tumor-based inflammatory stimuli.^3,4,7,14 We induced recurrent inflammation in recovered corneal tissue by placing a subsequent suture in the cornea (re-suturing). Here, we show that one feature of recurrent inflammation was the accelerated localized development of a functional lymphatic vessel network. The rapid kinetics and memory response were reminiscent of an immunological memory response; for this reason we describe this process as lymphatic vessel memory. This response appeared to stimulate the anastomosis of fragmented lymphatic vessels. Unlike inflammatory lymphangiogenesis induced by initial inflammation, we showed that lymphatic vessel memory was independent of the VEGF-C and VEGF-A pathways. Thus, these studies reveal a novel program of lymphatic vessel memory.     

Port Pocket Infections: Hydrogel Reduces Time to Healing and Clinic Visits Compared with Iodoform Gauze

Pocket infections are an occasional complication of totally implanted central venous catheters. The purpose of this study was to compare the safety, efficacy, and efficiency of the use of hydrogel after port removal vs the conventional method of packed iodoform gauze. In a cohort of 31 patients, the hydrogel group (n = 13) healed significantly faster than the group treated with the conventional method (15.5 vs 26.8 d; P = .009) and required fewer scheduled clinic visits (1.2 vs 10.8; P < .001). There were no differences in complications. This study suggests that hydrogel effectively promotes healing of port pocket infections, with advantages over the established technique.     

Brief Report: Health-Related Quality of Life in Preschoolers with Autism Spectrum Disorder is Related to Diagnostic Age and Autistic Symptom Severity

Journal of Autism and Developmental Disorders - We conducted a cross-sectional study to explore whether clinical characteristics and autism diagnostic-traits severity are associated with...     

Methionine sulfoxide reductase A as a marker for isolating subpopulations of stem and progenitor cells used in regenerative medicine

The essence of cell therapies is to transplant stem and progenitor cells for repairing and/or replacing damaged tissues. Transplanted cells need adapt to the injured site, where they are subjected to high levels of oxidative stress and the failure of those transplanted cells to combat the oxidative stress is considered to be one cause of failure of cell transplants. Moreover, the loss of function in primary tissue cells to combat the oxidative damage is reported to be one potential reason for tissue degeneration. Therefore, the isolation of appropriate subpopulations from autologous and allogeneic stem and progenitor cells, which can resist harsh oxidative stress, would be of great benefit to cell therapies. Currently, isolation techniques based on cell surface markers are widely used in the clinic, but these are far from ideal, while new isolation methods that discriminate cell populations based on cellular activities have been emerging as an alternative choice. The enzyme methionine sulfoxide reductase (Msr) A has been shown to play an important role in protecting cells from oxidative stress and acts as a regulator of the life span of mammals. We hypothesize that the activity of MsrA can be employed as a marker for the isolation of stem and progenitor cell subpopulations for cell therapy applications.     

Three molecular classifications surrogate to four immunohistochemical markers in 374 invasive breast carcinomas with long follow-up: Which is better?

In the early 21st century, a new way to classify breast cancer appeared, based on their gene expression profiles. Various classifications have been proposed in an attempt to subrogate these molecular groups to an immunohistochemical expression of estrogen and progesterone receptors, HER2 and Ki67. We compared the three major molecular classifications (MCs) of 374 infiltrating breast carcinomas with the assumption that one is better than the others to discriminate the prognosis of patients that are classified by it. We found that [1] there was a significant statistical association with tumor grade and presence of associated HG-DCIS, but with differences in kappa indices [2]; MC3 showed a significant relationship with pathological tumor stage (p = 0.012, CI95% of 0.012–0.017); [3] only MC3 showed convincingly that the observed differences in OS were not due to chance in the univariate analysis (p = 0.04); [4] only MC3 is an independent prognostic factor of OS. In conclusion, these three classifications are not interchangeable; MC3, the only one that includes Ki67 expression in their defining criteria, is better in predicting prognosis than the others.     

Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action

Cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and the Programmed Death Receptor 1 (PD-1) are immune checkpoint molecules that are well-established targets of antibody immunotherapies for the management of malignant melanoma. The monoclonal antibodies, Ipilimumab, Pembrolizumab, and Nivolumab, designed to interfere with T cell inhibitory signals to activate immune responses against tumors, were originally approved as monotherapy. Treatment with a combination of immune checkpoint inhibitors may improve outcomes compared to monotherapy in certain patient groups and these clinical benefits may be derived from unique immune mechanisms of action. However, treatment with checkpoint inhibitor combinations also present significant clinical challenges and increased rates of immune-related adverse events. In this review, we discuss the potential mechanisms attributed to single and combined checkpoint inhibitor immunotherapies and clinical experience with their use.