Background
Chronic inducible urticaria (CIndU) is characterized by mast cell (MC)‐mediated wheals in response to triggers: cold in cold urticaria (ColdU) and friction in symptomatic dermographism ...(SD). KIT receptor activation by stem cell factor (SCF) is essential for MC function. Barzolvolimab (CDX‐0159) is a humanized antibody that inhibits KIT activation by SCF and was well tolerated in healthy volunteers with dose‐dependent plasma tryptase suppression indicative of systemic mast cell ablation.
Methods
This is an open‐label, trial in patients with antihistamine refractory ColdU or SD, receiving one IV dose of barzolvolimab (3 mg/kg), with a 12‐week follow‐up. Primary endpoint was safety/tolerability; pharmacodynamic (PD)/clinical endpoints included serum tryptase, plasma SCF, skin MC histology, provocation tests, urticaria control test (UCT), and dermatology life quality index (DLQI).
Results
Analysis populations were safety (n = 21) and pharmacodynamics/clinical activity (n = 20). Barzolvolimab was well tolerated; most adverse events were mild and resolved. Treatment resulted in significant depletion of skin MCs, decreased tryptase (<limit of detection), and increased soluble SCF through Week 12. Complete responses (negative provocation test) occurred in 95% (n = 19/20) of patients (n = 10/10 ColdU; n = 9/10 SD), and all (n = 20/20) showed improvement in urticaria control (UCT ≥ 12). The kinetics of clinical activity mirrored that of MC and tryptase reduction. DLQI‐measured impairment significantly decreased to minimal/none in 93% of patients on study.
Conclusion
In CIndU patients, barzolvolimab was well tolerated, demonstrated marked, rapid, durable depletion of skin MCs, circulating tryptase, and reductions in clinical activity with significant improvements in disease control and quality of life (QoL) demonstrating potential therapeutic effects for MC‐mediated disorders.
In this Phase 1b study of CIndU (ColdU and SD) patients, barzolvolimab, a humanized antibody that inhibits KIT activation by SCF, was well tolerated. Barzolvolimab demonstrated marked, rapid, durable depletion of skin MCs, circulating tryptase, reductions in clinical activity, and significant improvements in disease control and QoL. Barzolvolimab has potential as a therapy for MC‐mediated diseases.Abbreviations: CIndU, chronic inducible urticaria; ColdU, cold urticaria; FcR, Fc receptor; Ig, immunoglobulin; KIT, KIT proto‐oncogene, receptor tyrosine kinase; MC, mast cell; MRGPRX2, mas‐related G protein‐coupled receptor‐X2; QoL, quality of life; SCF, stem cell factor; SD, symptomatic dermographism
Aligning treatment with patients' self-determined goals and health priorities is challenging in dementia care. Wearable-based remote health monitoring may facilitate determining the active ...participation of individuals with dementia towards achieving the determined goals. The present study aimed to demonstrate the feasibility of using wearables to assess healthcare goals set by older adults with cognitive impairment. We present four specific cases that assess (1) the feasibility of using wearables to monitor healthcare goals, (2) differences in function after goal-setting visits, and (3) goal achievement. Older veterans (
= 17) with cognitive impairment completed self-report assessments of mobility, then had an audio-recorded encounter with a geriatrician and wore a pendant sensor for 48 h. Follow-up was conducted at 4-6 months. Data obtained by wearables augments self-reported data and assessed function over time. Four patient cases illustrate the utility of combining sensors, self-report, notes from electronic health records, and visit transcripts at baseline and follow-up to assess goal achievement. Using data from multiple sources, we showed that the use of wearable devices could support clinical communication, mainly when patients, clinicians, and caregivers work to align care with the patient's priorities.
Patient priorities care (PPC) is an effective age-friendly health systems (AFHS) approach to aligning care with goals derived from 'what matters'. The purpose of this quality improvement program was ...to evaluate the fidelity and feasibility of the health priorities identification (HPI) process in VA Community Living Centers (CLC).
PPC experts worked with local CLC staff to guide the integration of HPI into the CLC and utilized a Plan-Do-Study-Act (PDSA) model for this quality improvement project. PPC experts reviewed health priorities identification (HPI) encounters and interdisciplinary team (IDT) meetings for fidelity to the HPI process of PPC. Qualitative interviews with local CLC staff determined the appropriateness of the health priorities identification process in the CLC.
Over 8 months, nine facilitators completed twenty HPI encounters. Development of a Patient Health Priorities note template, staff education and PPC facilitator training improved fidelity and documentation of HPI encounters in the electronic health record. Facilitator interviews suggested that PPC is appropriate in this setting, not burdensome to staff and fostered a person-centered approach to AFHS.
The HPI process is an acceptable and feasible approach to ask the 'what matters' component of AFHS in a CLC setting.
Abstract Objective This review answered two questions: (a) what types of specialty medical settings are implementing models for treating depression, and (b) do models for treating depression in ...specialty medical settings effectively treat depression symptoms? Method We searched Medline/Pubmed to identify articles, published between January 1990 and May 2013, reporting on models for treating depression in specialty medical settings. Included studies had to have adult participants with comorbid medical conditions recruited from outpatient, nonstandard primary care settings. Studies also had to report specific, validated depression measures. Results Search methods identified nine studies (six randomized controlled trials, one nonrandomized controlled trial and two uncontrolled trials), all representing integrated care for depression, in three specialty settings (oncology, infectious disease, neurology). Most studies ( N = 7) reported greater reductions in depression among patients receiving integrated care compared to usual care, particularly in oncology clinics. Conclusions Integrated care for depression in specialty medical settings can improve depression outcomes. Additional research is needed to understand the effectiveness of incorporating behavioral and/or psychological treatments into existing methods. When developing or selecting a model for treating depression in specialty medical settings, clinicians and researchers will benefit from choosing specific components and measures most relevant to their target populations.
Background
Chronic inducible urticaria (CIndU) constitutes a group of nine different CIndUs in which pruritic wheals and/or angioedema occur after exposure to specific and definite triggers. ...Histamine released from activated and degranulating skin mast cells is held to play a key role in the pathogenesis of CIndU, but evidence to support this has, as of yet, not been reviewed systematically or in detail. We aim to characterize the role and relevance of histamine in CIndU.
Methods
We systematically searched 3 electronic databases (PubMed, Scopus, and Embase) for studies that reported increased serum or skin histamine concentration (direct evidence) or
in vitro
or
ex vivo
histamine release (indirect evidence) following trigger exposure.
Results
An initial total of 3,882 articles was narrowed down to 107 relevant studies of which 52 were in cold urticaria, 19 in cholinergic urticaria, 14 in heat urticaria, 10 in contact urticaria, 7 each in solar urticaria and vibratory angioedema, 4 each in symptomatic dermographism and aquagenic urticaria, and 3 in delayed pressure urticaria. The results of our review support that histamine has a key pathogenic role in the pathogenesis of all CIndUs, but it is not the sole mediator as evidenced by the often poor relationship between the level of histamine and severity of symptoms and the variable clinical efficacy of H
1
-antihistamines.
Conclusions
Histamine released from skin mast cells is a key driver of the development of signs and symptoms and a promising therapeutic target in CIndU.
Objectives
To evaluate the effectiveness of a collaborative goal‐setting intervention (Empowering Patients in Chronic Care EPIC) to improve glycaemic control and diabetesrelated distress, and ...implementation into routine care across multiple primary care clinics.
Design
Randomized controlled trial comparing the effectiveness of the EPIC intervention with enhanced usual care (EUC) at five clinic sites located in the greater Chicago and Houston areas. We will measure differences in haemoglobin A1c (HbA1c) and diabetes distress scale scores among study arms at post‐intervention and maintenance (6 months post‐intervention). We will evaluate implementation of the intervention across sites using the RE‐AIM framework. We will evaluate reach by comparing the per cent and characteristics of enrolled study participants among all potentially eligible participants in the given clinic population. Adoption is reflected by the characteristics of the involved providers and the number of intervention sessions conducted. Implementation of EPIC will be evaluated by number of sessions delivered, participants' evaluation of group sessions, and evaluation of quality of goal‐setting.
Patients
We randomized 280 participants with equal allocation to EPIC and enhanced usual care (EUC).
Results
At baseline, the groups were similar with the exception that EUC participants were more likely to have prior diabetes education. At baseline, participants were predominately older men who have poorly controlled diabetes (mean HbA1c = 76 mmol/mol 9.1%) and moderate levels of diabetes distress (mean DDS = 2.43).
Conclusions
This hybrid effectiveness‐implementation protocol is designed to accelerate the translation of a patient‐centred diabetes care intervention from research to clinical practice.
The Empowering Patients in Chronic Care (EPIC) intervention is an efficacious patient‐centred, goal‐oriented programme that combines group and individual approaches to help individuals with treated but uncontrolled diabetes reach their diabetic goals. The current trial is intended to examine EPIC as it transitions from laboratory setting into routine primary care.
RNA sequencing (RNA-seq) offers a snapshot of cellular RNA populations, but not temporal information about the sequenced RNA. Here we report TimeLapse-seq, which uses oxidative-nucleophilic-aromatic ...substitution to convert 4-thiouridine into cytidine analogs, yielding apparent U-to-C mutations that mark new transcripts upon sequencing. TimeLapse-seq is a single-molecule approach that is adaptable to many applications and reveals RNA dynamics and induced differential expression concealed in traditional RNA-seq.
Pebbly mudstones are a conspicuous element of sedimentary sequences deposited in different tectonic settings and sedimentary environments. Whereas for many diamictites a glacial origin seems ...plausible, the problem to distinguish glacial from non-glacial diamictites is often difficult for Precambrian examples where palaeoclimatic constraints are generally lacking. This article documents an Eocene pebbly mudstone of the Southhelvetic nappes of eastern Central Switzerland (
Blockmergel
) for which a glacial origin can be firmly rejected and which may thus serve as an example for non-glacial marine diamictites and their sedimentary and palaeotectonic environment. The Blockmergel are interpreted as the product of gravitational deposition of single blocks across steep palaeo-slopes (subaqueous rockfall) into a basin otherwise dominated by suspension settling sedimentation. The Blockmergel occur within the basal part of the early fill of the North Alpine Foreland Basin, which constitutes a deepening upward sequence above basal shallow marine limestones. The Blockmergel demonstrate substantial Middle to Late Eocene sub-aerial erosion and fluvial transport (producing the rounded pebbles) and local extensional fault movements in the proximal part of the incipient North Alpine Foreland Basin. They are capped sharply by forced-regressive shoreface sandstones and the whole sequence thus demonstrates locally very shallow to subaerial conditions within an otherwise rather deep hemipelagic marine basin. This, and the extensional fault movements, are linked to a long-standing feature of Helvetic palaeogeography—the Southhelvetic swell zone. That this swell still operated during the Priabonian i.e. shortly before finally being overthrust by the orogenic wedge of the evolving Alpine orogen is a new element in Alpine palaeotectonics and seems to highlight the importance of the reactivation of inherited palaeotectonic faults. Finally, the example of the Blockmergel is suggested as a useful analogue to help distinguishing glacial-sourced from slope-derived diamictites in the Neoproterozoic sedimentary record and may thus help resolving the “diamictite dichotomy”.
PDF
