Effects of galcanezumab on acute medication use and health care resource utilization in treatment-resistant migraine: results from randomized, double blind, placebo-controlled clinical trial, conquer

IntroductionAcute headache medication use (AHM) and health care resource utilization (HCRU) in patients with protocol-defined treatment-resistant migraine treated with galcanezumab (GMB).Material and methodsIn the 3-month double-blind (DB) study phase, patients with episodic or chronic migraine and 2-4 migraine preventive category failures due to lack of effectiveness or safety/tolerability, received GMB 120 mg/month (following initial 240 mg loading dose) or placebo (PBO); an optional 3-month open-label (OL) GMB treatment followed. AHM was self-reported daily with eDiary and paper-forms. HCRU was reported at baseline (retrospectively for previous 6 months) and at monthly visits.ResultsOf the 462 patients (GMB n=232, PBO n=230), baseline mean (±SD) days/month of AHM was 12.3 (±6.0); 44.8% had AHM overuse. The percentage of patients reporting migraine-specific HCRU at baseline in the GMB and PBO groups were respectively: 40% and 50% healthcare-professional visits (HCP), 6% and 5% emergency-room (ER) visits, and in each, 2% hospitalizations. LS mean reductions from baseline in the mean number of days/month with AHM in the DB was greater for the GMB group (3.9 to 4.5 days) compared to PBO (0.4 to 1.0 days) in each of the first 3 months; change difference, -3.1 to -3.5, p<0.001 at each month during Months 1-3. During theOL, reductions from baseline ranged -4.7 to -5.3 days; prior PBO group reductions were comparable to that observed in GMB. During the DB, reductions from baseline of migraine-specific HCP (per 100 person- years) were numerically greater with GMB than PBO (-215.5 vs -155.3); during OL, the prior PBO group reductions (-212.9) were similar to GMB (-222.6). For both groups, migraine-specific ER visits were <13 and hospitalizations were <2 per 100 person-years during the DB and OL.ConclusionsGMB-treated patients with treatment-resistant migraine had clinically meaningful reductions in days with AHM and numerically greater reductions in migraine-specific HCP. The abstract was previously presented at EHF (2020)

SGLT2 Inhibitor Therapy Improves Blood Glucose but Does Not Prevent Diabetic Bone Disease in Diabetic DBA/2J Male Mice

Persons with type 1 and type 2 diabetes have increased fracture risk, attributed to deficits in the microarchitecture and strength of diabetic bone, thought to be mediated, in part, by the consequences of chronic hyperglycemia. Therefore, to examine the effects of a glucose-lowering SGLT2 inhibitor on blood glucose (BG) and bone homeostasis in a model of diabetic bone disease, male DBA/2J mice with or without streptozotocin (STZ)-induced hyperglycemia were fed chow containing the SGLT2 inhibitor, canagliflozin (CANA), or chow without drug, for 10 weeks of therapy. Thereafter, serum bone biomarkers were measured, fracture resistance of cortical bone was assessed by μCT analysis and a three-point bending test of the femur, and vertebral bone strength was determined by compression testing. In the femur metaphysis and L6 vertebra, long-term diabetes (DM) induced deficits in trabecular bone microarchitecture. In the femur diaphysis, a decrease in cortical bone area, cortical thickness and minimal moment of inertia occurred in DM (p \u3c 0.0001, for all) while cortical porosity was increased (p \u3c 0.0001). These DM changes were associated with reduced fracture resistance (decreased material strength and toughness; decreased structural strength and rigidity; p \u3c 0.001 for all). Significant increases in PTH (p \u3c 0.0001), RatLAPs (p = 0.0002), and urine calcium concentration (p \u3c 0.0001) were also seen in DM. Canagliflozin treatment improved BG in DM mice by ~35%, but did not improve microarchitectural parameters. Instead, in canagliflozin-treated diabetic mice, a further increase in RatLAPs was evident, possibly suggesting a drug-related intensification of bone resorption. Additionally, detrimental metaphyseal changes were noted in canagliflozin-treated control mice. Hence, diabetic bone disease was not favorably affected by canagliflozin treatment, perhaps due to insufficient glycemic improvement. Instead, in control mice, long-term exposure to SGLT2 inhibition was associated with adverse effects on the trabecular compartment of bone

Effects of Allergen Sensitization on Response to Therapy in Children with Eosinophilic Esophagitis

Background: In children with eosinophilic esophagitis (EoE) foods are the most common disease triggers, but environmental allergens are also suspected culprits. Objective: To determine the effects of environmental allergen sensitization on response to treatment in children with EoE in the southeastern United States. Methods: Patients 2 to 18 years old who were referred to the Arkansas Children’s Hospital Eosinophilic Gastrointestinal Disorders Clinic from January 2012 to January 2016 were enrolled in a prospective, longitudinal cohort study with collection of demographics, clinical symptoms, medical history, allergy sensitization profiles, and response to treatment over time. Comparisons were made between complete responders (peak esophageal eosinophil count \u3c 15 per high-power field [HPF]) and nonresponders (\u3e 25 eosinophils per HPF) after treatment with diet elimination alone, swallowed corticosteroids alone, or diet elimination and swallowed corticosteroids. Sensitization patterns to environmental allergens found in the southeastern United States were analyzed for the effect on treatment response. Results: A total of 223 individuals were enrolled. Of these, 182 had environmental allergy profiling and at least one endoscopy while receiving proton pump inhibitor (PPI) therapy. Twenty-nine individuals had PPI-responsive EoE and were excluded from further analysis, leaving 123 individuals with none-PPI-responsive EoE who were further analyzed; 72 (58.5%) were complete responders and 33 (26.8%) were nonresponders. Seventeen individuals (13.8%) were partial responders (≥ 1 but ≤ 25 eosinophils per HPF) and excluded from further analysis. Nonresponders were more likely to be sensitized to perennial allergens (P = .02). There was no significant difference in response based on seasonal allergen sensitization. Individuals with mold or cockroach sensitization were more likely to fail combination diet and swallowed corticosteroid treatment (P = .02 and P = .002). Conclusion: Perennial allergen and mold sensitization may lead to nonresponse to EoE treatment in some patients. Additional studies are needed to further understand the effect of environmental allergens on EoE

Impact of intensive care unit attending physician training background on outcomes in children undergoing heart operations

Background : The existing training pathways to become a pediatric cardiac intensivist are very variable with physicians coming from varied training backgrounds of pediatric critical care, pediatric cardiology, neonatology, or pediatric anesthesia. Aim : To evaluate the impact of cardiac Intensive Care Unit (ICU) attending physician training background on outcomes in children undergoing heart operations. Setting and Design : Patients in the age group from 1 day to 18 years undergoing heart operation at a Pediatric Health Information System database participating hospital were included (2010–2015). Patients and Methods : Based on the training background of majority of attending physicians in an ICU, the participating ICUs were divided into three groups: critical care medicine (CCM), cardiology, and indeterminate. Statistical Analysis : Multivariable logistic regression models were fitted to evaluate the association of ICU physician training background with study outcomes. Results : A total of 54,935 patients from 42 ICUs were included. Of these, 31,815 patients (58%) were treated in the CCM group (26 ICUs), 19,340 patients (35%) were treated in the cardiology group (12 ICUs), and 3780 patients (7%) were treated in the indeterminate group (4 ICUs). In adjusted models, no specific group based on ICU attending physician training background was associated with lower mortality (CCM vs. cardiology, odds ratio: 0.75, 95% confidence interval: 0.48–1.18), or lower incidence of cardiac arrest, or prolonged hospital length of stay, or prolonged mechanical ventilation. Conclusions : This large observational study did not demonstrate any impact of ICU attending training background on outcomes in children undergoing heart operations

Relationships among active listening, self-awareness, empathy, and patient-centered care in associate and baccalaureate degree nursing students

Objective: The purpose of this research was to examine the relationships among active listening, self-awareness, empathy, and patient-centered care in nursing students. Background: Empathy and patient-centered care have been associated with better patient outcomes. Active listening and self-awareness are suggested to be associated with empathy, and, in turn, patient-centered care. However, the relationships among active listening, self-awareness, empathy, and patient-centered care have not been investigated. Method: Data on active listening, self-awareness, empathy, and patient-centered care were collected from 53 nursing students, and were analyzed using multiple regression. Results: Active listening (p < .001) and self-awareness (p < .001) were significantly associated with empathy. Empathy was significantly associated with patient-centered care (p = .003). Empathy was a partial mediator of the relationship between active listening and PCC and a full mediator of the relationship between self-awareness and patient-centered care. Conclusion: Improvement in active listening and self-awareness may lead to improvement in empathy, and, in turn, improvement in patient-centered care

Efficacy of galcanezumab in patients with episodic cluster headaches and a history of preventive treatment failure

Objective: The efficacy of galcanezumab was evaluated in patients with episodic cluster headache and history of preventive treatment failure. Methods: In the randomized, 8-week, double-blind study (CGAL), patients with episodic cluster headache received once-monthly subcutaneous injections of galcanezumab 300 mg or placebo. Patients who completed CGAL and enrolled in an open-label study were queried for preventive treatment history. In a subset of patients with a known history of failure of verapamil or any other prior preventive treatment, a post hoc analysis of least square mean change from baseline in weekly cluster headache attack frequency across Weeks 1 to 3 was assessed. Results: Fifteen patients provided data for known history of prior preventive treatment failure (6 placebo, 9 galcanezumab), of whom 11 failed verapamil. The mean reduction in the weekly frequency of cluster headache attacks was greater with galcanezumab compared to placebo among patients with prior preventive treatment failure (8.2 versus 2.4); mean difference 5.8 (95% confidence interval [CI] 2.0, 13.6) and among patients with verapamil failure (10.1 versus 1.6); mean difference 8.5 (95% CI 0.4, 16.7). Conclusion: In this exploratory analysis of patients with a known history of prior preventive treatment failures, treatment with galcanezumab resulted in greater mean reductions in weekly cluster headache attacks compared with placebo. ClinicalTrials.gov: NCT02397473 (I5Q-MC-CGAL) NCT02797951 (I5Q-MC-CGAR