Citations

Abstract Introduction Multiple intravenous doses of ponezumab, an anti‐amyloid antibody, were evaluated in subjects with mild‐to‐moderate Alzheimer's disease (AD). Methods In part A, 77 subjects were randomized to ponezumab 0.1, 0.5, or 1 mg/kg (75 treated) and 26 to placebo (24 treated). In part B, 63 subjects were randomized and treated with ponezumab 3 or 8.5 mg/kg and 32 with placebo. Subjects received 10 infusions over 18 months and were followed for 6 months thereafter. Results Ponezumab was generally safe and well tolerated. Most common adverse events were fall (16.7% ponezumab, 21.4% placebo), headache (13.8%, 21.4%), and cerebral microhemorrhage (13.8%, 19.6%). Plasma ponezumab increased dose‐dependently with limited accumulation. Cerebrospinal fluid penetration was low. Plasma Aβ 1–x and Aβ 1–40 showed robust increases, but cerebrospinal fluid biomarkers showed no dose response. Ponezumab had no effects on cognitive/functional outcomes or brain volume. Conclusions Multiple‐dose ponezumab was generally safe, but not efficacious, in mild‐to‐moderate AD.

INTRODUCTION: Postpartum hemorrhage is the leading cause of maternal mortality worldwide. There are multiple known risk factors, including induction of labor. METHODS: A retrospective cohort study was completed with review of nulliparous women undergoing labor induction at term, from July 2006 to May 2011. Baseline maternal variables and risk factors for postpartum hemorrhage were assessed. All combinations of methods of induction were sequential rather than concurrent. The need for additional uterotonics (beyond routine oxytocin) was used as a surrogate for postpartum hemorrhage. Variables were evaluated for an association with additional uterotonic use based on fitting logistic regression models. RESULTS: A total of 785 women were included in the study. Additional uterotonics were required for 84/785 (11%) of women. Based on univariate analysis, only birth weight and presence of meconium were significantly (p < 0.05) associated with additional uterotonic use, while method of induction approached statistical significance (p=0.06). The mean (SD) birth weight was 3668 (584) vs. 3463 (500) grams in those with and without additional uterotonic use. Multivariate analysis showed an increased risk of additional uterotonics with higher birth weight (adjusted odds ratio (aOR) 1.44 per 500 gram increase in birth weight; 95% CI 1.15, 1.82) and use of Foley plus oxytocin (aOR 4.40; 95% CI 1.36, 14.23). CONCLUSION: In our model, higher birth weight and induction method of Foley followed by oxytocin were associated with increased need for additional uterotonics. This data adds detail to previous studies that have broadly identified induction of labor as a risk factor for postpartum hemorrhage.

BACKGROUNDBreast cancer patients in the MA.27 trial had similar outcomes with steroidal aromatase inhibitor (AI) exemestane and nonsteroidal anastrozole. AIs increase the risk of osteoporosis. This study examined the effects of self‐reported osteoporosis and osteoporosis therapy (OPT) on outcomes.METHODSThe MA.27 phase 3 adjuvant trial enrolled 7576 postmenopausal women. The primary outcome was event‐free survival (EFS), and the secondary outcome was distant disease–free survival (DDFS). Patients were permitted bisphosphonates to prevent or treat osteopenia/osteoporosis. In a multivariate, stratified Cox regression, factors were significant with a 2‐sided Wald test P value ≤ .05.RESULTSOsteoporosis was reported at the baseline by 654 of the 7576 women (8.6%) and in total by 1294 patients. Oral OPT was received at the baseline by 815 of the 7576 women (10.8%) and in total by 2711 patients (36%). With a median follow‐up of 4.1 years, 693 EFS events (9.15%) and 321 DDFS events (4.2%) occurred. Osteoporosis was not associated with EFS or DDFS. Few EFS events occurred before the initiation of OPT, with no substantive evidence of a time‐differing effect on outcomes (nonproportional hazards). OPT (yes vs no) was significantly associated with improved EFS (hazard ratio [HR] for yes vs no, 0.67; 95% confidence interval [CI], 0.57‐0.80; P < .001) and DDFS (HR, 0.57; 95% CI, 0.44‐0.73; P <. 001). Time‐differing (time‐dependent) OPT was not (EFS; P = .45). OPT did not alter the incidence of visceral‐only metastasis (P = .31).CONCLUSIONSOral OPT, administered to postmenopausal breast cancer patients receiving adjuvant AI therapy, was associated with improved EFS and DDFS; the time of OPT initiation (a time‐dependent effect) did not affect the outcome. OPT did not alter the risk of visceral metastasis. Cancer 2017;123:2444–51. © 2017 American Cancer Society.

Abstract Aims High-intensity interval training (HIIT) improves peak oxygen uptake and left ventricular diastology in patients with heart failure with preserved ejection fraction (HFpEF). However, its effects on myocardial strain in HFpEF remain unknown. We explored the effects of HIIT and moderate-intensity aerobic continuous training (MI-ACT) on left and right ventricular strain parameters in patients with HFpEF. Furthermore, we explored their relationship with peak oxygen uptake (VO2peak). Methods and results Fifteen patients with HFpEF (age = 70 ± 8.3 years) were randomized to either: (i) HIIT (4 × 4 min, 85–90% peak heart rate, interspersed with 3 min of active recovery; n = 9) or (ii) MI-ACT (30 min at 70% peak heart rate; n = 6). Patients were trained 3 days/week for 4 weeks and underwent VO2peak testing and 2D echocardiography at baseline and after completion of the 12 sessions of supervised exercise training. Left ventricular (LV) and right ventricular (RV) average global peak systolic longitudinal strain (GLS) and peak systolic longitudinal strain rate (GSR) were quantified. Paired t-tests were used to examine within-group differences and unpaired t-tests used for between-group differences (α = 0.05). Right ventricular average global peak systolic longitudinal strain improved significantly in the HIIT group after training (pre = −18.4 ± 3.2%, post = −21.4 ± 1.7%; P = 0.02) while RV-GSR, LV-GLS, and LV-GSR did not (P &gt; 0.2). No significant improvements were observed following MI-ACT. No significant between-group differences were observed for any strain measure. ΔLV-GLS and ΔRV-GLS were modestly correlated with ΔVO2peak (r = −0.48 and r = −0.45; P = 0.1, respectively). Conclusions In patients with HFpEF, 4 weeks of HIIT significantly improved RV-GLS.

Objectives/HypothesisChildren with bilateral true vocal fold immobility (BTVFI) may present with significant airway distress necessitating tracheostomy. The objective of this study was to review our preliminary experience with the anterior–posterior cricoid split (APCS), an endoscopic intervention used as an alternative to tracheostomy in children with BTVFI.Study DesignMulticenter review.MethodsA review of patients undergoing endoscopic APCS for BTVFI at four institutions was performed. Patients were evaluated for the ability to ventilate without the requirement for tracheostomy or reintubation. Additional data extracted included the duration of intubation following APCS, the requirement for additional procedures, and demographics. Surgical success was defined as the ability to avoid tracheostomy and to cap or decannulate without respiratory symptoms if a tracheostomy was present prior to APCS.ResultsNineteen APCS procedures were performed between October 2010 and June 2016. There were 12 male patients, the mean age at APCS was 4.7 months. BTVFI was primarily idiopathic (58%) and associated with other comorbidities (74%). All patients were candidates for tracheostomy prior to APCS. Fourteen patients (74%) were considered surgical successes. Of the unsuccessful patients, three (66%) required tracheostomy following APCS, and one was treated with a posterior cartilage graft. There was one nonsurgical mortality greater than 2 months after APCS and thought to be unrelated to the airway.ConclusionsEndoscopic APCS appears to be a safe and effective intervention for pediatric BTVFI. Under the correct circumstances, this can be performed as a single procedure, obviating tracheostomy. Further study is warranted.Level of Evidence4. Laryngoscope, 128:257–263, 2018