Impact of smoke-free legislation on perinatal and infant mortality:a national quasi-experimental study

Smoke-free legislation is associated with improved early-life outcomes; however its impact on perinatal survival is unclear. We linked individual-level data with death certificates for all registered singletons births in England (1995-2011). We used interrupted time series logistic regression analysis to study changes in key adverse perinatal events following the July 2007 national, comprehensive smoke-free legislation. We studied 52,163 stillbirths and 10,238,950 live-births. Smoke-free legislation was associated with an immediate 7.8% (95%CI 3.5-11.8; p < 0.001) reduction in stillbirth, a 3.9% (95%CI 2.6-5.1; p < 0.001) reduction in low birth weight, and a 7.6% (95%CI 3.4-11.7; p = 0.001) reduction in neonatal mortality. No significant impact on SIDS was observed. Using a counterfactual scenario, we estimated that in the first four years following smoke-free legislation, 991 stillbirths, 5,470 cases of low birth weight, and 430 neonatal deaths were prevented. In conclusion, smoke-free legislation in England was associated with clinically important reductions in severe adverse perinatal outcomes

Effect of intravenous ondansetron on QT interval prolongation in patients with cardiovascular disease and additional risk factors for torsades: a prospective, observational study

Matthew J Hafermann1, Rocsanna Namdar2, Gretchen E Seibold2,3, Robert Lee Page 2nd2,31University of Washington Medical Center, Department of Pharmacy, Seattle, WA; 2University of Colorado Anschutz Medical Campus, School of Pharmacy, Aurora, CO; 3University of Colorado Hospital, Department of Pharmacy, Aurora, CO USABackground: The 5-hydroxytryptamine type 3 antagonists, or setrons (eg, ondansetron), are commonly used for nausea and vomiting in the hospital setting. In 2001, droperidol was given a black box warning because it was found to prolong the QT interval and induce arrhythmias. The setrons share with droperidol the same potential proarrhythmic mechanisms, but limited data exist concerning their effects on the QT interval in individuals at high risk for torsades de pointes.Methods: Forty hospitalized patients admitted for heart failure or acute coronary syndromes with one or more risk factors for torsades de pointes and an order for intravenous ondansetron 4 mg were enrolled in this prospective, observational study. The QT interval corrected for heart rate (QTc) was obtained via a 12-lead electrocardiogram on admission and again 120 minutes after the first dose of ondansetron in order to determine the mean change in QTc following ondansetron exposure.Results: The mean time interval between obtaining the baseline electrocardiogram and the second electrocardiogram following ondansetron administration was 3.5 &amp;plusmn; 2.14 hours. In the total population, the QTc interval was prolonged by 19.3 &amp;plusmn; 18 msec (P &amp;lt; 0.0001) 120 minutes after ondansetron administration. For patients with an acute coronary syndrome and those with heart failure, QTc was prolonged by 18.3 &amp;plusmn; 20 msec (P &amp;lt; 0.0001) and 20.6 &amp;plusmn; 20 msec (P &amp;lt; 0.0012), respectively. Following ondansetron exposure, 31% and 46% in the heart failure and acute coronary syndromes groups, respectively, met gender-related thresholds for a prolonged QTc.Conclusion: Our study found QTc prolongation due to ondansetron administration similar to that found in previous studies. When used in patients with cardiovascular disease (eg, heart failure or acute coronary syndromes) with one or more risk factors for torsades de pointes, ondansetron may significantly increase the QTc interval for up to 120 minutes after administration. From a patient safety perspective, patients who are at high risk for torsades de pointes and receiving ondansetron should be followed via telemetry when admitted to hospital.Keywords: ondansetron, QT prolongation, patient safety, antiemetic

Medication regimen complexity in ambulatory older adults with heart failure

Michael R Cobretti,1 Robert L Page II,2 Sunny A Linnebur,2 Kimberly M Deininger,1 Amrut V Ambardekar,3 JoAnn Lindenfeld,4 Christina L Aquilante1 1Department of Pharmaceutical Sciences, 2Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, 3Division of Cardiology, School of Medicine, University of Colorado, Aurora, CO, 4Advanced Heart Failure and Cardiac Transplant Program, Vanderbilt Heart and Vascular Institute, Nashville, TN, USA Purpose: Heart failure prevalence is increasing in older adults, and polypharmacy is a major problem in this population. We compared medication regimen complexity using the validated patient-level Medication Regimen Complexity Index (pMRCI) tool in &ldquo;young-old&rdquo; (60&ndash;74 years) versus &ldquo;old-old&rdquo; (75&ndash;89 years) patients with heart failure. We also compared pMRCI between patients with ischemic cardiomyopathy (ISCM) versus nonischemic cardiomyopathy (NISCM).Patients and methods: Medication lists were retrospectively abstracted from the electronic medical records of ambulatory patients aged 60&ndash;89 years with heart failure. Medications were categorized into three types &ndash; heart failure prescription medications, other prescription medications, and over-the-counter (OTC) medications &ndash; and scored using the pMRCI tool.Results: The study evaluated 145 patients (n=80 young-old, n=65 old-old, n=85 ISCM, n=60 NISCM, mean age 73&plusmn;7 years, 64% men, 81% Caucasian). Mean total pMRCI scores (32.1&plusmn;14.4, range 3&ndash;84) and total medication counts (13.3&plusmn;4.8, range 2&ndash;30) were high for the entire cohort, of which 72% of patients were taking eleven or more total medications. Total and subtype pMRCI scores and medication counts did not differ significantly between the young-old and old-old groups, with the exception of OTC medication pMRCI score (6.2&plusmn;4 young-old versus 7.8&plusmn;5.8 old-old, P=0.04). With regard to heart failure etiology, total pMRCI scores and medication counts were significantly higher in patients with ISCM versus NISCM (pMRCI score 34.5&plusmn;15.2 versus 28.8&plusmn;12.7, P=0.009; medication count 14.1&plusmn;4.9 versus 12.2&plusmn;4.5, P=0.008), which was largely driven by other prescription medications.Conclusion: Medication regimen complexity is high in older adults with heart failure, and differs based on heart failure etiology. Additional work is needed to address polypharmacy and to determine if medication regimen complexity influences adherence and clinical outcomes in this population. Keywords: medication complexity, heart failure, elderly, geriatric, age