Patients With Prior Myocardial Infarction, Stroke, or Symptomatic Peripheral Arterial Disease in the CHARISMA Trial Deepak L. Bhatt, MD, FACC, Marcus D. Flather, MD, Werner Hacke, MD, Peter B. ...Berger, MD, FACC, Henry R. Black, MD, William E. Boden, MD, FACC, Patrice Cacoub, MD, Eric A. Cohen, MD, Mark A. Creager, MD, FACC, J. Donald Easton, MD, Christian W. Hamm, MD, FACC, Graeme J. Hankey, MD, S. Claiborne Johnston, PhD, MD, Koon-Hou Mak, MD, FACC, Jean-Louis Mas, MD, Gilles Montalescot, MD, PhD, Thomas A. Pearson, MD, FACC, P. Gabriel Steg, MD, FACC, Steven R. Steinhubl, MD, FACC, Michael A. Weber, MD, FACC, Liz Fabry-Ribaudo, MSN, RN, Tingfei Hu, MS, Eric J. Topol, MD, FACC, Keith A. A. Fox, MBChB, for the CHARISMA Investigators Dual antiplatelet therapy with clopidogrel plus aspirin has already been validated in the settings of acute coronary syndromes and coronary stenting. We identified 9,478 patients in the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial who were enrolled with documented prior myocardial infarction (MI), ischemic stroke, or symptomatic peripheral arterial disease. The median duration of follow-up was 27.6 months. The rate of cardiovascular death, MI, or stroke was significantly lower in the clopidogrel plus aspirin arm than in the placebo plus aspirin arm: 7.3% versus 8.8% (hazard ratio 0.83, 95% confidence interval 0.72 to 0.96, p = 0.01); this benefit persisted after multivariate modeling and was not dependent on the time from the ischemic event.
Some commonly used preventive interventions lacked clinical trial data for women, and it was unclear whether results of studies conducted in men could be generalized to women. Since the 2003 ...literature review, numerous clinical trials that have a bearing on CVD prevention in women have been completed (see Appendix). Reviewer Representation Research Grant Other Research Support Speakers' Bureau/ Honoraria Ownership Interest Consultant/ Advisory Board Other Jeffrey L. Anderson American College of Cardiology Foundation Clinical Expert Consensus Document Task Force None None Bristol-Myers Squibb*; Merck* None None None Vera Bittner American College of Cardiology Foundation Prevention Committee National Heart, Lung, and Blood Institutedagger; Pfizerdagger; Atherogenicsdagger; National Institutes of Health/Kosdagger None None None Pfizer*; Reliant*; CV Therapeutics* None Roger S. Blumenthal Johns Hopkins Hospital Pfizer*; Merck*; General Electric* None None None None None Ann Bolger American Heart Association None None None None None None Charles Bridges Society for Thoracic Surgeons None None None None None None Doug Campos-Outcalt American Academy of Family Physicians None None None None None None Vincent F. Carr American College of Cardiology Foundation Board of Governors None None None None None None James I. Cleeman National Heart, Lung and Blood Institute None None None None None None Darla E. Danford National Heart, Lung and Blood Institute None None None None None None Karen A. Donato National Heart, Lung and Blood Institute None None None None None None Mark J. Eisenberg American College of Cardiology Foundation Clinical Expert Consensus Document Task Force None None None None None None Victor Ferraris Society for Thoracic Surgeons Aventis*; THG Med Co*; Bayerdagger; BioMarindagger; Guilforddagger; Medtronicdagger None AstraZeneca*; Bayer*; NATA*; THG Med Co* None None None Valentin Fuster World Heart Federation None None None None Kereos*; Vasogen* GlaxoSmithKline Research & Education Foundation for Cardiovascular Disease* Deborah Grady American College of Physicians Eli Lilly* None None None None None Sharonne Hayes American Heart Association None None None None None None David Herrington American Heart Association None None None None None None Mark Hlaty American College of Cardiology Foundation Board of Trustees None None None None None None Suzanne Hughes American College of Cardiology Foundation Board of Trustees None None Biosite*; Kos*; Pfizer* None Guidant*; Johnson & Johnson*; Merck* Associate editor, Cardiosource Darwin Labarthe Centers for Disease Control and Prevention None None None None None None Robert Lichtenberg American College of Cardiology Foundation Board of Trustees None None None None None None Edward J. Roccella National Heart, Lung and Blood Institute None None None None None None Samuel J. Shubrooks, Jr American College of Cardiology Foundation Clinical Expert Consensus Document Task Force None None None None None None Cynthia Tracy American College of Cardiology Foundation Clinical Expert Consensus Document Task Force None None None None None None Janet S. Wright American College of Cardiology Foundation Board of Trustees None None None None None None Stanley Zinberg American College of Obstetricians and Gynecologists None None None None None None * Reviewer Disclosures This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit.
Objective To determine the effects of late surfactant on respiratory outcomes determined at 1-year corrected age in the Trial of Late Surfactant (TOLSURF), which randomized newborns of extremely low ...gestational age (≤28 weeks' gestational age) ventilated at 7-14 days to late surfactant and inhaled nitric oxide vs inhaled nitric oxide-alone (control). Study design Caregivers were surveyed in a double-blinded manner at 3, 6, 9, and 12 months' corrected age to collect information on respiratory resource use (infant medication use, home support, and hospitalization). Infants were classified for composite outcomes of pulmonary morbidity (no PM, determined in infants with no reported respiratory resource use) and persistent PM (determined in infants with any resource use in ≥3 surveys). Results Infants (n = 450, late surfactant n = 217, control n = 233) were 25.3 ± 1.2 weeks' gestation and 713 ± 164 g at birth. In the late surfactant group, fewer infants received home respiratory support than in the control group (35.8% vs 52.9%, relative benefit RB 1.28 95% CI 1.07-1.55). There was no benefit of late surfactant for No PM vs PM (RB 1.27; 95% CI 0.89-1.81) or no persistent PM vs persistent PM (RB 1.01; 95% CI 0.87-1.17). After adjustment for imbalances in baseline characteristics, relative benefit of late surfactant treatment increased: RB 1.40 (95% CI 0.89-1.80) for no PM and RB 1.24 (95% CI 1.08-1.42) for no persistent PM. Conclusion Treatment of newborns of extremely low gestational age with late surfactant in combination with inhaled nitric oxide decreased use of home respiratory support and may decrease persistent pulmonary morbidity. Trial registration ClinicalTrials.gov : NCT01022580
Summary Background China has achieved Millennium Development Goal 4 to reduce under-5 mortality rate by two-thirds between 1990 and 2015. In this study, we estimated the national and subnational ...levels and causes of child mortality in China annually from 1996 to 2015 to draw implications for achievement of the SDGs for China and other low-income and middle-income countries. Methods In this systematic analysis, we adjusted empirical data on levels and causes of child mortality collected in the China Maternal and Child Health Surveillance System to generate representative estimates at the national and subnational levels. In adjusting the data, we considered the sampling design and probability, applied smoothing techniques to produce stable trends, fitted livebirth and age-specific death estimates to natvional estimates produced by the UN for international comparison, and partitioned national estimates of infrequent causes produced by independent sources to the subnational level. Findings Between 1996 and 2015, the under-5 mortality rate in China declined from 50·8 per 1000 livebirths to 10·7 per 1000 livebirths, at an average annual rate of reduction of 8·2%. However, 181 600 children still died before their fifth birthday, with 93 400 (51·5%) deaths occurring in neonates. Great inequity exists in child mortality across regions and in urban versus rural areas. The leading causes of under-5 mortality in 2015 were congenital abnormalities (35 700 deaths, 95% uncertainty range UR 28 400–45 200), preterm birth complications (30 900 deaths, 24 200–40 800), and injuries (26 600 deaths, 21 000–33 400). Pneumonia contributed to a higher proportion of deaths in the western region of China than in the eastern and central regions, and injury was a main cause of death in rural areas. Variations in cause-of-death composition by age were also examined. The contribution of preterm birth complications to mortality decreased after the neonatal period; congenital abnormalities remained an important cause of mortality throughout infancy, whereas the contribution of injuries to mortality increased after the first year of life. Interpretation China has achieved a rapid reduction in child mortality in 1996–2015. The decline has been widespread across regions, urban and rural areas, age groups, and cause-of-death categories, but great disparities remain. The western region and rural areas and especially western rural areas should receive most attention in improving child survival through enhanced policy and programmes in the Sustainable Development Goals era. Continued investment is crucial in primary and secondary prevention of deaths due to congenital abnormalities, preterm birth complications, and injuries nationally, and of deaths due to pneumonia in western rural areas. The study also has implications for improving child survival and civil registration and vital statistics in other low-income and middle-income countries. Funding Bill & Melinda Gates Foundation.
Atrioesophageal fistula formation is a rare but life-threatening complication of atrial fibrillation ablation. Contact force (CF)-sensing catheters improve procedural effectiveness. However, the ...impact of the implementation of CF-sensing technology on the risk of atrioesophageal fistula formation has not been explored.
The purpose of this study was to determine the association between the use of CF-sensing catheters and atrioesophageal fistula development.
We searched the Manufacturer and User Facility Device Experience database for adverse event reports involving Food and Drug Administration-approved ablation catheters.
Among 2689 device reports, we identified 78 atrioesophageal fistula cases, 65 of which involved CF-sensing catheters and 13 non-CF-sensing catheters. The percentage of total reports involving atrioeosphageal fistula was 5.4% for CF-sensing catheters (65 of 1202) and 0.9% for non-CF-sensing catheters (13 of 1487) (P < .0001). Procedural details (CF and power settings) were not consistently reported. Esophageal temperature increases were detected in only 2.5% of cases (2 of 78). The mean time to presentation was 16 ± 9 days. Overall mortality was at least 56%, with patients who underwent surgical repair more likely to survive than those treated with stenting or no intervention.
Atrioesophageal fistula formation accounted for a much higher proportion of reported adverse events with CF-sensing catheters compared with non-CF-sensing catheters. Improved understanding of the relationship between power/force delivery and esophageal damage is needed to minimize the risk of atrioesophageal fistula formation.
Summary Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, ...perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).
Background Monitoring for hypocalcemia after thyroidectomy, using only symptoms and serum calcium levels, can delay the discharge of patients who will remain normocalcemic and can delay the treatment ...of hypocalcemic patients. Study Design We conducted a systematic search for articles describing use of parathyroid hormone (PTH) assay, checked within hours of completing thyroidectomy, to predict postoperative symptomatic hypocalcemia. Studies were excluded if all patients were treated with postoperative calcium, or if early PTH values were used to alter management of the patient. Individual patient data (perioperative PTH and calcium levels, development of hypocalcemia) were obtained for 457 patients from the corresponding authors of 9 studies and pooled to yield the following results. Results PTH, checked at three time periods after removal of the thyroid gland (0 to 20 minutes, 1 to 2 hours, and 6 hours), was substantially lower in patients who became hypocalcemic compared with those who remained normocalcemic. The accuracy of PTH in determining hypocalcemia increased with time and was excellent when checked 1 to 6 hours postoperatively. A single PTH threshold (65% decrease compared with preoperative level), checked 6 hours after completing thyroidectomy, had a sensitivity of 96.4% and specificity of 91.4% in detecting postoperative hypocalcemia. Conclusions PTH assay, when checked 1 to 6 hours after thyroidectomy, has excellent accuracy in determining which patients will become symptomatically hypocalcemic. Routine use of this assay should be considered because it may allow earlier discharge of the normocalcemic patient and earlier identification of patients requiring treatment of postthyroidectomy hypocalcemia.
Summary Background Amyloid-related imaging abnormalities (ARIA) have been reported in patients with Alzheimer's disease treated with bapineuzumab, a humanised monoclonal antibody against amyloid β. ...ARIA include MRI signal abnormalities suggestive of vasogenic oedema and sulcal effusions (ARIA-E) and microhaemorrhages and haemosiderin deposits (ARIA-H). Our aim was to investigate the incidence of ARIA during treatment with bapineuzumab, and evaluate associated risk factors. Methods Two neuroradiologists independently reviewed 2572 fluid-attenuated inversion recovery (FLAIR) MRI scans from 262 participants in two phase 2 studies of bapineuzumab and an open-label extension study. Readers were masked to the patient's treatment, APOE ε4 genotype, medical history, and demographics. Patients were included in risk analyses if they had no evidence of ARIA-E in their pre-treatment MRI, had received bapineuzumab, and had at least one MRI scan after treatment. We used Kaplan-Meier survival analysis to examine the distribution of incident ARIA-E from the start of bapineuzumab treatment and proportional hazards regression models to assess risk factors associated with ARIA. Findings 210 patients were included in the risk analyses. 36 patients (17%) developed ARIA-E during treatment with bapineuzumab; 15 of these ARIA-E cases (42%) had not been detected previously. 28 of these patients (78%) did not report associated symptoms. Adverse events, reported in eight symptomatic patients, included headache, confusion, and neuropsychiatric and gastrointestinal symptoms. Incident ARIA-H occurred in 17 of the patients with ARIA-E (47%), compared with seven of 177 (4%) patients without ARIA-E. 13 of the 15 patients in whom ARIA were detected in our study received additional treatment infusions while ARIA-E were present, without any associated symptoms. Occurrence of ARIA-E increased with bapineuzumab dose (hazard ratio HR 2·24 per 1 mg/kg increase in dose, 95% CI 1·40–3·62; p=0·0008) and presence of APOE ε4 alleles (HR 2·55 per allele, 95% CI 1·57–4·12; p=0·0001). Interpretation ARIA consist of a spectrum of imaging findings with variable clinical correlates, and some patients with ARIA-E remain asymptomatic even if treatment is continued. The increased risk of ARIA among APOE ε4 carriers, its association with high bapineuzumab dose, and its timecourse in relation to dosing suggest an association between ARIA and alterations in vascular amyloid burden. Funding Elan Corporation, Janssen Alzheimer Immunotherapy, Wyeth Pharmaceuticals, and Pfizer.
Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). Few studies have compared clinical outcomes after catheter ablation between patients with and those without DM.
The ...purpose of this study was to compare AF ablation outcomes in patients with and those without DM.
We performed a retrospective analysis of 351 consecutive patients who underwent first-time AF ablation. Clinical outcomes included freedom from recurrent atrial arrhythmia, symptom burden (Mayo AF Symptom Inventory score), cardiovascular and all-cause hospitalizations, and periprocedural complications.
Patients with DM (n = 65) were older, had a higher body mass index, more persistent AF, more hypertension, and larger left atrial diameter (P <.05 for all). Median (Q1, Q3) total radiofrequency duration 64.0 (43.6, 81.4) minutes vs 54.3 (39.2, 76.4) minutes; P = .132 and periprocedural complications (P = .868) did not differ between patients with and those without DM. After a median follow-up of 29.5 months, arrhythmia recurrence was significantly higher in the DM group compared to the no-DM group after adjustment for baseline differences (adjusted hazard ratio HR 2.24; 95% confidence CI 1.42–3.55; P = .001). There was a nonsignificant trend toward higher AF recurrence with worse glycemic levels (HR 1.29; 95% CI 0.99–1.69; P = .064).
Although safety outcomes associated with AF ablation were similar between patients with and those without DM, arrhythmia-free survival was significantly lower among patients with DM. Poor glycemic control seems to an important risk factor for AF recurrence.
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