A signalling cascade of IL-33 to IL-13 regulates metaplasia in the mouse stomach.

OBJECTIVE: Alternatively activated macrophages (M2) are associated with the progression of spasmolytic polypeptide-expressing metaplasia (SPEM) in the stomach. However, the precise mechanism(s) and critical mediators that induce SPEM are unknown. DESIGN: To determine candidate genes important in these processes, macrophages from the stomach corpus of mice with SPEM (DMP-777-treated) or advanced SPEM (L635-treated) were isolated and RNA sequenced. Effects on metaplasia development after acute parietal cell loss induced by L635 were evaluated in interleukin (IL)-33, IL-33 receptor (ST2) and IL-13 knockout (KO) mice. RESULTS: Profiling of metaplasia-associated macrophages in the stomach identified an M2a-polarised macrophage population. Expression of IL-33 was significantly upregulated in macrophages associated with advanced SPEM. L635 induced metaplasia in the stomachs of wild-type mice, but not in the stomachs of IL-33 and ST2 KO mice. While IL-5 and IL-9 were not required for metaplasia induction, IL-13 KO mice did not develop metaplasia in response to L635. Administration of IL-13 to ST2 KO mice re-established the induction of metaplasia following acute parietal cell loss. CONCLUSIONS: Metaplasia induction and macrophage polarisation after parietal cell loss is coordinated through a cytokine signalling network of IL-33 and IL-13, linking a combined response to injury by both intrinsic mucosal mechanisms and infiltrating M2 macrophages.

Nonlinear force propagation during granular impact.

We experimentally study nonlinear force propagation into granular material during impact from an intruder, and we explain our observations in terms of the nonlinear grain-scale force relation. Using high-speed video and photoelastic particles, we determine the speed and spatial structure of the force response just after impact. We show that these quantities depend on a dimensionless parameter, M^{'}=t_{c}v_{0}/d, where v_{0} is the intruder speed at impact, d is the particle diameter, and t_{c} is the collision time for a pair of grains impacting at relative speed v_{0}. The experiments access a large range of M^{'} by using particles of three different materials. When M^{'}≪1, force propagation is chainlike with a speed, v_{f}, satisfying v_{f}∝d/t_{c}. For larger M^{'}, the force response becomes spatially dense and the force propagation speed departs from v_{f}∝d/t_{c}, corresponding to collective stiffening of a strongly compressed packing of grains.

Reflections on implementing a hospital-wide provider-based electronic inpatient mortality review system: lessons learnt.

IMPORTANCE: Death due to preventable medical error is a leading cause of death, with varying estimates of preventable death rates (14%-56% of total deaths based on national extrapolated estimates, 3%-11% based on single-centre estimates). Yet, how best to reduce preventable mortality in hospitals remains unknown. OBJECTIVE: In this article, we detail lessons learnt from implementing a hospital-wide, automated, real-time, electronic mortality reporting system that relies on the opinions of front-line clinicians to identify opportunities for improvement. We also summarise data obtained regarding possible preventability, systems issues identified and addressed, and challenges with implementation. We outline our process of survey, evaluation, escalation and tracking of opportunities identified through the review process. METHODS: We aggregated and analysed 7 years of review data regarding deaths, review responses categorised by ratings of possible preventability and inter-rater reliability of possible preventability. A qualitative analysis of reviews was performed to identify care delivery opportunities and institutional response. RESULTS: Over the course of 7 years, 7856 inpatient deaths occurred, and 91% had at least one review completed. 5.2% were rated by front-line clinicians as potentially being preventable (likely or possibly), and this rate was consistent over time. However, there was only slight inter-rater agreement regarding potential preventability (Cohen's kappa=0.185). Nevertheless, several major systems-level opportunities were identified that facilitated care delivery improvements, such as communication challenges, need for improved end-of-life care and interhospital transfer safety. CONCLUSIONS: Through implementation, we found that a hospital-wide mortality review process that elicits feedback from front-line providers is feasible, and provides valuable insights regarding potential preventable mortality and prioritising actionable opportunities for care delivery improvements.

Multiple Myeloma Masquerading as Ovarian Carcinosarcoma Metastases: A Case Report and Review of the Approach to Multiple Myeloma Screening and Diagnosis.

Multiple myeloma is the most common plasma cell dyscrasia and causes 2% of all cancer deaths in Western countries. Ovarian carcinosarcomas are very rare gynecological malignancies and account for only 1-2% of all ovarian tumors. In this case, we report a 67-year-old woman with known relapsed ovarian carcinosarcoma who presented with headache and neck pain. She was found to have new lytic lesions in the cranial and thoracic regions. While these lesions were assumed to be metastases, a diligent approach detected an M-spike on serum protein electrophoresis and a monoclonal gammopathy with immunoglobulin G lambda monoclonal immunoglobulin on immunofixation. A bone marrow biopsy confirmed the diagnosis of multiple myeloma. To our knowledge, this is the first ever reported case of concomitant multiple myeloma and ovarian carcinosarcoma. Our case highlights the utmost importance of a systematic approach to lytic lesions and emphasizes the need to consider secondary malignancies in the evaluation of possible metastases. We used the International Myeloma Working Group guidelines for screening and diagnosing multiple myeloma, and we provide a thorough review of this updated approach.

Shed-MEDS: pilot of a patient-centered deprescribing framework reduces medications in hospitalized older adults being transferred to inpatient postacute care.

BACKGROUND: Polypharmacy is common in hospitalized older adults. Deprescribing interventions are not well described in the acute-care setting. The objective of this study was to describe a hospital-based, patient-centered deprescribing protocol (Shed-MEDS) and report pilot results. METHODS: This was a pilot study set in one academic medical center in the United States. Participants consisted of a convenience sample of 40 Medicare-eligible, hospitalized patients with at least five prescribed medications. A deprescribing protocol (Shed-MEDS) was implemented among 20 intervention and 20 usual care control patients during their hospital stay. The primary outcome was the total number of medications deprescribed from hospital enrollment. Deprescribed was defined as medication termination or dose reduction. Enrollment medications reflected all prehospital medications and active in-hospital medications. Baseline characteristics and outcomes were compared between the intervention and usual care groups using simple logistic or linear regression for categorical and continuous measures, respectively. RESULTS: There was no significant difference between groups in mean age, sex or Charlson comorbidity index. The intervention and control groups had a comparable number of medications at enrollment, 25.2 (±6.3) and 23.4 (±3.8), respectively. The number of prehospital medications in each group was 13.3 (±4.6) and 15.3 (±4.6), respectively. The Shed-MEDS protocol compared with usual care significantly increased the mean number of deprescribed medications at hospital discharge and reduced the total medication burden by 11.6 versus 9.1 (p = 0.032) medications. The deprescribing intervention was associated with a difference of 4.6 [95% confidence interval (CI) 2.5-6.7, p < 0.001] in deprescribed medications and a 0.5 point reduction (95% CI -0.01 to 1.1) in the drug burden index. CONCLUSIONS: A hospital-based, patient-centered deprescribing intervention is feasible and may reduce the medication burden in older adults.

Medications associated with geriatric syndromes and their prevalence in older hospitalized adults discharged to skilled nursing facilities.

BACKGROUND: More than half of the hospitalized older adults discharged to skilled nursing facilities (SNFs) have more than 3 geriatric syndromes. Pharmacotherapy may be contributing to geriatric syndromes in this population. OBJECTIVES: Develop a list of medications associated with geriatric syndromes and describe their prevalence in patients discharged from acute care to SNFs. DESIGN: Literature review and multidisciplinary expert panel discussion, followed by cross-sectional analysis. SETTING: Academic medical center in the United States PARTICIPANTS: One hundred fifty-four hospitalized Medicare beneficiaries discharged to SNFs. MEASUREMENTS: Development of a list of medications that are associated with 6 geriatric syndromes. Prevalence of the medications associated with geriatric syndromes was examined in the hospital discharge sample. RESULTS: A list of 513 medications was developed as potentially contributing to 6 geriatric syndromes: cognitive impairment, delirium, falls, reduced appetite or weight loss, urinary incontinence, and depression. Medications included 18 categories. Antiepileptics were associated with all syndromes, whereas antipsychotics, antidepressants, antiparkinsonism, and opioid agonists were associated with 5 geriatric syndromes. In the prevalence sample, patients were discharged to SNFs with an overall average of 14.0 (±4.7) medications, including an average of 5.9 (±2.2) medications that could contribute to geriatric syndromes, with falls having the most associated medications at discharge at 5.5 (±2.2). CONCLUSIONS: Many commonly prescribed medications are associated with geriatric syndromes. Over 40% of all medications ordered upon discharge to SNFs were associated with geriatric syndromes and could be contributing to the high prevalence of geriatric syndromes experienced by this population. Journal of Hospital Medicine 2016;11:694-700. © 2016 Society of Hospital Medicine.

Collisional model for granular impact dynamics.

When an intruder strikes a granular material from above, the grains exert a stopping force which decelerates and stops the intruder. Many previous studies have used a macroscopic force law, including a drag force which is quadratic in velocity, to characterize the decelerating force on the intruder. However, the microscopic origins of the force-law terms are still a subject of debate. Here, drawing from previous experiments with photoelastic particles, we present a model which describes the velocity-squared force in terms of repeated collisions with clusters of grains. From our high speed photoelastic data, we infer that "clusters" correspond to segments of the strong force network that are excited by the advancing intruder. The model predicts a scaling relation for the velocity-squared drag force that accounts for the intruder shape. Additionally, we show that the collisional model predicts an instability to rotations, which depends on the intruder shape. To test this model, we perform a comprehensive experimental study of the dynamics of two-dimensional granular impacts on beds of photoelastic disks, with different profiles for the leading edge of the intruder. We particularly focus on a simple and useful case for testing shape effects by using triangular-nosed intruders. We show that the collisional model effectively captures the dynamics of intruder deceleration and rotation; i.e., these two dynamical effects can be described as two different manifestations of the same grain-scale physical processes.

Health literacy of living kidney donors and kidney transplant recipients.

BACKGROUND: Health literacy (HL) may be a mediator for known socioeconomic and racial disparities in living kidney donation. METHODS: We evaluated the associations of patient and demographic characteristics with HL in living kidney donors (LD), living donor kidney transplant recipients (LDR), and deceased donor recipients (DDR) in a single-center retrospective review of patients undergoing kidney donation or transplantation from September 2010 to July 2012. HL and demographic data were collected. HL was assessed via the Short Literacy Survey (SLS) comprising three self-reported screening questions scored using the five-point Likert scale (low, moderate, high). Chi-square and logistic regression were used to test factors associated with lower HL. RESULTS: The sample included 360 adults (105 LD, 103 LDR, and 152 DDR; 46±14 years; 70% white; 56% male; 14±3 years of education). HL scores were skewed (49% high, 41% moderate, and 10% low). The distribution of HL categories differed significantly among groups (P=0.019). After controlling for age, race, sex, education, and a race-education interaction term, DDR was more likely to have moderate or low HL than LDR (OR, 1.911; 95% CI, 1.096-3.332; P=0.022). CONCLUSION: Overall, living donors had high HL. The distribution of low, moderate, and high HL differed significantly between LD, DDR, and LDR. DDR had a higher likelihood of having low HL than LDR. Screening kidney transplant candidates and donors for lower HL may identify barriers to living donation. Future interventions addressing HL may be important to increase living donation and reduce disparities.