Prevalence of QT interval prolongation in patients admitted to cardiac care units and frequency of subsequent administration of QT interval-prolonging drugs: a prospective, observational study in a large urban academic medical center in the US.

PubMed

Tisdale, James E; Wroblewski, Heather A; Overholser, Brian R; Kingery, Joanna R; Trujillo, Tate N; Kovacs, Richard J

2012-06-01

Cardiac arrest due to torsades de pointes (TdP) is a rare but catastrophic event in hospitals. Patients admitted to cardiac units are at higher risk of drug-induced QT interval prolongation and TdP, due to a preponderance of risk factors. Few data exist regarding the prevalence of QT interval prolongation in patients admitted to cardiac units or the frequency of administering QT interval-prolonging drugs to patients presenting with QT interval prolongation. The aim of this study was to determine the prevalence of Bazett's-corrected QT (QT(c)) interval prolongation upon admission to cardiac units and the proportion of patients presenting with QT(c) interval prolongation who are subsequently administered QT interval-prolonging drugs during hospitalization. This was a prospective, observational study conducted over a 1-year period (October 2008-October 2009) in 1159 consecutive patients admitted to two cardiac units in a large urban academic medical centre located in Indianapolis, IN, USA. Patients were enrolled into the study at the time of admission to the hospital and were followed daily during hospitalization. Exclusion criteria were age <18 years, ECG rhythm of complete ventricular pacing, and patient designation as 'outpatient' in a bed and/or duration of stay <24 hours. Data collected included demographic information, past medical history, daily progress notes, medication administration records, laboratory data, ECGs, telemetry monitoring strips and diagnostic reports. All patients underwent continuous cardiac telemetry monitoring and/or had a baseline 12-lead ECG obtained within 4 hours of admission. QT intervals were determined manually from lead II of 12-lead ECGs or from continuous lead II telemetry monitoring strips. QT(c) interval prolongation was defined as ≥470 ms for males and ≥480 ms for females. In both males and females, QT(c) interval >500 ms was considered abnormally high. A medication was classified as QT interval-prolonging if there were published data indicating that the drug causes QT interval prolongation and/or TdP. Study endpoints were (i) prevalence of QT(c) interval prolongation upon admission to the Cardiac Medical Critical Care Unit (CMCCU) or an Advanced Heart Care Unit (AHCU); (ii) proportion of patients admitted to the CMCCU/AHCU with QT(c) interval prolongation who subsequently were administered QT interval-prolonging drugs during hospitalization; (iii) the proportion of these higher-risk patients in whom TdP risk factor monitoring was performed; (iv) proportion of patients with QT(c) interval prolongation who subsequently received QT-prolonging drugs and who experienced further QT(c) interval prolongation. Of 1159 patients enrolled, 259 patients met exclusion criteria, resulting in a final sample size of 900 patients. mean (± SD) age, 65 ± 15 years; female, 47%; Caucasian, 70%. Admitting diagnoses: heart failure (22%), myocardial infarction (16%), atrial fibrillation (9%), sudden cardiac arrest (3%). QT(c) interval prolongation was present in 27.9% of patients on admission; 18.2% had QT(c) interval >500 ms. Of 251 patients admitted with QT(c) interval prolongation, 87 (34.7%) were subsequently administered QT interval-prolonging drugs. Of 166 patients admitted with QT(c) interval >500 ms, 70 (42.2%) were subsequently administered QT interval-prolonging drugs; additional QT(c) interval prolongation ≥60 ms occurred in 57.1% of these patients. QT(c) interval prolongation is common among patients admitted to cardiac units. QT interval-prolonging drugs are commonly prescribed to patients presenting with QT(c) interval prolongation.

Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma: Review of Safety, Response Evaluation Criteria in Solid Tumors 1.1 Imaging Response and Survival.

PubMed

Swinburne, Nathaniel C; Biederman, Derek M; Besa, Cecilia; Tabori, Nora E; Fischman, Aaron M; Patel, Rahul S; Nowakowski, Francis Scott; Gunasekaran, Ganesh; Schwartz, Myron E; Lookstein, Robert A; Kim, Edward

2017-06-01

The optimal palliative treatment for unresectable intrahepatic cholangiocarcinoma (ICC) remains controversial. While selective internal radiation therapy (SIRT) using yttrium-90 microspheres is a well-accepted treatment for hepatocellular carcinoma, data related to its use for locally advanced ICC remain relatively scarce. Twenty-nine patients (mean age 66 ± 11 years; 15 female) with unresectable biopsy-proven ICC treated with SIRT between June 2008 and April 2015 were retrospectively evaluated for post-treatment toxicity, overall survival, and imaging response using response evaluation criteria in solid tumors (RECIST) 1.1 criteria. RECIST 1.1 response was evaluable following 26 treatments [complete response (CR):0, partial response (PR):3; stable disease (SD):16, progression of disease (PD):7]. Objective response rate (CR+PR) was 12%. Disease control rate (CR+PR+SD) was 73%. Median time to progression was 5.6 [95% confidence interval (CI): 0-12.0] months. Median survival following SIRT was 9.1 (95% CI: 1.7-16.4) months. Post-treatment survival was prolonged in patients with absence of extrahepatic disease (p = 0.03) and correlated with RECIST 1.1 response (p = 0.02). Toxicities were limited to grade I severity and occurred following 27% of treatments. These findings support the safe, effective use of SIRT for unresectable ICC. Post-treatment survival is prolonged in patients with absence of extrahepatic disease at baseline. RECIST 1.1 response following SIRT for ICC is predictive of survival.

Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes.

PubMed

Mosley, Jonathan D; Shoemaker, M Benjamin; Wells, Quinn S; Darbar, Dawood; Shaffer, Christian M; Edwards, Todd L; Bastarache, Lisa; McCarty, Catherine A; Thompson, Will; Chute, Christopher G; Jarvik, Gail P; Crosslin, David R; Larson, Eric B; Kullo, Iftikhar J; Pacheco, Jennifer A; Peissig, Peggy L; Brilliant, Murray H; Linneman, James G; Witte, John S; Denny, Josh C; Roden, Dan M

2017-04-01

One potential use for the PR interval is as a biomarker of disease risk. We hypothesized that quantifying the shared genetic architectures of the PR interval and a set of clinical phenotypes would identify genetic mechanisms contributing to PR variability and identify diseases associated with a genetic predictor of PR variability. We used ECG measurements from the ARIC study (Atherosclerosis Risk in Communities; n=6731 subjects) and 63 genetically modulated diseases from the eMERGE network (Electronic Medical Records and Genomics; n=12 978). We measured pairwise genetic correlations (rG) between PR phenotypes (PR interval, PR segment, P-wave duration) and each of the 63 phenotypes. The PR segment was genetically correlated with atrial fibrillation (rG=-0.88; P =0.0009). An analysis of metabolic phenotypes in ARIC also showed that the P wave was genetically correlated with waist circumference (rG=0.47; P =0.02). A genetically predicted PR interval phenotype based on 645 714 single-nucleotide polymorphisms was associated with atrial fibrillation (odds ratio=0.89 per SD change; 95% confidence interval, 0.83-0.95; P =0.0006). The differing pattern of associations among the PR phenotypes is consistent with analyses that show that the genetic correlation between the P wave and PR segment was not significantly different from 0 (rG=-0.03 [0.16]). The genetic architecture of the PR interval comprises modulators of atrial fibrillation risk and obesity. © 2017 American Heart Association, Inc.

Determining factors of electrocardiographic abnormalities in patients with epilepsy: A case-control study.

PubMed

de Sousa, Jorge Murilo Barbosa; Fialho, Guilherme Loureiro; Wolf, Peter; Walz, Roger; Lin, Katia

2017-01-01

Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality in young patients with epilepsy (PWE). Although its mechanisms are still poorly understood, they may include cardiorespiratory dysfunction. Standard 12-lead electrocardiograms (ECGs) were obtained from 62 consecutive patients (aged 18-66y) with a definite diagnosis of epilepsy, without seizures at the day of ECG, and 57 healthy controls matched for sex, age and body mass index (BMI). All ECGs were evaluated by a blinded board-certified cardiologist. Patients with symptomatic focal epilepsy represented 90.3% (N=56), of whom 56.4% (N=35) had temporal lobe epilepsy, with a mean duration of 22.02±14.96years of epilepsy. We observed more prolonged P-wave (p<0.0001) and PR interval (p=0.01) in patients than in controls. Additionally, longer QT intervals (p<0.01), pathologic QT dispersion (p<0.01) and left atrial overload (p<0.01) were more common in PWE. Multiple linear regression analysis evidenced age, gender and polytherapy as factors associated with altered ECG. Therefore, routine ECG should be requested in PWE, especially for males, increasing age and in polytherapy. Findings such as longer PR and QT interval, and pathologic QT dispersion, may reflect cardiac structural changes and/or autonomic nervous system dysfunction and indicate a risk for SUDEP. Copyright © 2016 Elsevier B.V. All rights reserved.

Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit

PubMed Central

Nikolaidou, Theodora; Cai, Xue J.; Stephenson, Robert S.; Yanni, Joseph; Lowe, Tristan; Atkinson, Andrew J.; Jones, Caroline B.; Sardar, Rida; Corno, Antonio F.; Dobrzynski, Halina; Withers, Philip J.; Jarvis, Jonathan C.; Hart, George; Boyett, Mark R.

2015-01-01

Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ. PMID:26509807

Association of low-moderate urine arsenic and QT interval: Cross-sectional and longitudinal evidence from the Strong Heart Study.

PubMed

Moon, Katherine A; Zhang, Yiyi; Guallar, Eliseo; Francesconi, Kevin A; Goessler, Walter; Umans, Jason G; Best, Lyle G; Howard, Barbara V; Devereux, Richard B; Okin, Peter M; Navas-Acien, Ana

2018-05-21

Epidemiologic studies suggest that chronic exposure to arsenic is related to cardiovascular disease (CVD), but the pathophysiological link remains uncertain. We evaluated the association of chronic low-moderate arsenic exposure and arsenic metabolism with baseline difference and annual change in ECG measures (QT interval, JT interval, PR interval, QRS duration, and QT dispersion) using linear mixed models in the Strong Heart Study main cohort (N = 1174, median age 55 years) and family study (N = 1695 diabetes-free, median age 36 years). At baseline, arsenic exposure was measured as the sum of inorganic and methylated species in urine (ΣAs) and arsenic metabolism was measured as the relative percentage of arsenic species. Median ΣAs and Bazett heart rate-corrected QT interval (QTc) were 8.6 μg/g creatinine and 424 ms in the main cohort and 4.3 μg/g and 414 ms in the family study, respectively. In the main cohort, a comparison of the highest to lowest ΣAs quartile (>14.4 vs. <5.2 μg/g creatinine) was associated with a 5.3 (95% CI: 1.2, 9.5) ms higher mean baseline QTc interval but no difference in annual change in QTc interval. In the family study, a comparison of the highest to lowest quartile (>7.1 vs. <2.9 μg/g creatinine) was associated with a 3.2 (95% CI: 0.6, 5.7) ms higher baseline QTc interval and a 0.6 (95% CI: 0.04, 1.2) ms larger annual increase in QTc interval. Associations with JTc interval were similar but stronger in magnitude compared to QTc interval. Arsenic exposure was largely not associated with PR interval, QRS duration or QT dispersion. Similar to arsenic exposure, a pattern of lower %MMA and higher %DMA was associated with longer baseline QTc interval in both cohorts and with a larger annual change in QTc interval in the family study. Chronic low-moderate arsenic exposure and arsenic metabolism were associated with prolonged ventricular repolarization. Copyright © 2018 Elsevier Ltd. All rights reserved.

Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.

PubMed

Lin, Honghuang; van Setten, Jessica; Smith, Albert V; Bihlmeyer, Nathan A; Warren, Helen R; Brody, Jennifer A; Radmanesh, Farid; Hall, Leanne; Grarup, Niels; Müller-Nurasyid, Martina; Boutin, Thibaud; Verweij, Niek; Lin, Henry J; Li-Gao, Ruifang; van den Berg, Marten E; Marten, Jonathan; Weiss, Stefan; Prins, Bram P; Haessler, Jeffrey; Lyytikäinen, Leo-Pekka; Mei, Hao; Harris, Tamara B; Launer, Lenore J; Li, Man; Alonso, Alvaro; Soliman, Elsayed Z; Connell, John M; Huang, Paul L; Weng, Lu-Chen; Jameson, Heather S; Hucker, William; Hanley, Alan; Tucker, Nathan R; Chen, Yii-Der Ida; Bis, Joshua C; Rice, Kenneth M; Sitlani, Colleen M; Kors, Jan A; Xie, Zhijun; Wen, Chengping; Magnani, Jared W; Nelson, Christopher P; Kanters, Jørgen K; Sinner, Moritz F; Strauch, Konstantin; Peters, Annette; Waldenberger, Melanie; Meitinger, Thomas; Bork-Jensen, Jette; Pedersen, Oluf; Linneberg, Allan; Rudan, Igor; de Boer, Rudolf A; van der Meer, Peter; Yao, Jie; Guo, Xiuqing; Taylor, Kent D; Sotoodehnia, Nona; Rotter, Jerome I; Mook-Kanamori, Dennis O; Trompet, Stella; Rivadeneira, Fernando; Uitterlinden, André; Eijgelsheim, Mark; Padmanabhan, Sandosh; Smith, Blair H; Völzke, Henry; Felix, Stephan B; Homuth, Georg; Völker, Uwe; Mangino, Massimo; Spector, Timothy D; Bots, Michiel L; Perez, Marco; Kähönen, Mika; Raitakari, Olli T; Gudnason, Vilmundur; Arking, Dan E; Munroe, Patricia B; Psaty, Bruce M; van Duijn, Cornelia M; Benjamin, Emelia J; Rosand, Jonathan; Samani, Nilesh J; Hansen, Torben; Kääb, Stefan; Polasek, Ozren; van der Harst, Pim; Heckbert, Susan R; Jukema, J Wouter; Stricker, Bruno H; Hayward, Caroline; Dörr, Marcus; Jamshidi, Yalda; Asselbergs, Folkert W; Kooperberg, Charles; Lehtimäki, Terho; Wilson, James G; Ellinor, Patrick T; Lubitz, Steven A; Isaacs, Aaron

2018-05-01

Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability. We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval. We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction ( P <1.2×10 -6 ), including 11 novel loci that have not been reported previously. Many of these loci are involved in heart morphogenesis. In gene-based analysis, we found that multiple rare variants at MYH6 ( P =5.9×10 -11 ) and SCN5A ( P =1.1×10 -7 ) were associated with PR interval. SCN5A locus also was implicated in the common variant analysis, whereas MYH6 was a novel locus. We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health. © 2018 American Heart Association, Inc.

Ventricular Cycle Length Characteristics Estimative of Prolonged RR Interval during Atrial Fibrillation

PubMed Central

CIACCIO, EDWARD J.; BIVIANO, ANGELO B.; GAMBHIR, ALOK; EINSTEIN, ANDREW J.; GARAN, HASAN

2014-01-01

Background When atrial fibrillation (AF) is incessant, imaging during a prolonged ventricular RR interval may improve image quality. It was hypothesized that long RR intervals could be predicted from preceding RR values. Methods From the PhysioNet database, electrocardiogram RR intervals were obtained from 74 persistent AF patients. An RR interval lengthened by at least 250 ms beyond the immediately preceding RR interval (termed T0 and T1, respectively) was considered prolonged. A two-parameter scatterplot was used to predict the occurrence of a prolonged interval T0. The scatterplot parameters were: (1) RR variability (RRv) estimated as the average second derivative from 10 previous pairs of RR differences, T13–T2, and (2) Tm–T1, the difference between Tm, the mean from T13 to T2, and T1. For each patient, scatterplots were constructed using preliminary data from the first hour. The ranges of parameters 1 and 2 were adjusted to maximize the proportion of prolonged RR intervals within range. These constraints were used for prediction of prolonged RR in test data collected during the second hour. Results The mean prolonged event was 1.0 seconds in duration. Actual prolonged events were identified with a mean positive predictive value (PPV) of 80% in the test set. PPV was >80% in 36 of 74 patients. An average of 10.8 prolonged RR intervals per 60 minutes was correctly identified. Conclusions A method was developed to predict prolonged RR intervals using two parameters and prior statistical sampling for each patient. This or similar methodology may help improve cardiac imaging in many longstanding persistent AF patients. PMID:23998759

Prolonged corrected QT interval is predictive of future stroke events even in subjects without ECG-diagnosed left ventricular hypertrophy.

PubMed

Ishikawa, Joji; Ishikawa, Shizukiyo; Kario, Kazuomi

2015-03-01

We attempted to evaluate whether subjects who exhibit prolonged corrected QT (QTc) interval (≥440 ms in men and ≥460 ms in women) on ECG, with and without ECG-diagnosed left ventricular hypertrophy (ECG-LVH; Cornell product, ≥244 mV×ms), are at increased risk of stroke. Among the 10 643 subjects, there were a total of 375 stroke events during the follow-up period (128.7±28.1 months; 114 142 person-years). The subjects with prolonged QTc interval (hazard ratio, 2.13; 95% confidence interval, 1.22-3.73) had an increased risk of stroke even after adjustment for ECG-LVH (hazard ratio, 1.71; 95% confidence interval, 1.22-2.40). When we stratified the subjects into those with neither a prolonged QTc interval nor ECG-LVH, those with a prolonged QTc interval but without ECG-LVH, and those with ECG-LVH, multivariate-adjusted Cox proportional hazards analysis demonstrated that the subjects with prolonged QTc intervals but not ECG-LVH (1.2% of all subjects; incidence, 10.7%; hazard ratio, 2.70, 95% confidence interval, 1.48-4.94) and those with ECG-LVH (incidence, 7.9%; hazard ratio, 1.83; 95% confidence interval, 1.31-2.57) had an increased risk of stroke events, compared with those with neither a prolonged QTc interval nor ECG-LVH. In conclusion, prolonged QTc interval was associated with stroke risk even among patients without ECG-LVH in the general population. © 2014 American Heart Association, Inc.

Prevalence, Risk Factors and In-hospital Outcomes of QTc Interval Prolongation in Liver Cirrhosis.

PubMed

Zhao, Jiancheng; Qi, Xingshun; Hou, Feifei; Ning, Zheng; Zhang, Xintong; Deng, Han; Peng, Ying; Li, Jing; Wang, Xiaoxi; Li, Hongyu; Guo, Xiaozhong

2016-09-01

QTc interval prolongation is an electrocardiographic abnormality in liver cirrhosis. The objective of this study was to evaluate the prevalence, risk factors and in-hospital outcomes of QTc interval prolongation in Chinese patients with liver cirrhosis. This was a retrospective analysis of a total of 1,268 patients with liver cirrhosis who were consecutively admitted to our hospital between January 2011 and June 2014. QTc interval data were collected from the medical records. QTc interval prolongation was defined as QTc interval > 440 milliseconds. The prevalence of QTc interval prolongation was 38.2% (485 of 1268). In the entire cohort, the risk factors for QTc interval prolongation included an older age, a higher proportion of alcohol abuse and ascites, higher bilirubin, blood urea nitrogen, creatinine, prothrombin time, international normalized ratio, Child-Pugh score and model for end-stage liver diseases score, and lower red blood cell (RBC), hemoglobin (Hb), albumin (ALB), alanine aminotransferase and calcium. The in-hospital mortality was not significantly different between patients with and without QTc interval prolongation (2.1% versus 1.3%, P = 0.276). In the subgroup analyses of patients with hepatitis B virus or alcohol alone-related liver cirrhosis, the risk factors included higher bilirubin, creatinine, prothrombin time, international normalized ratio, Child-Pugh score and model for end-stage liver diseases score, and lower RBC, Hb and ALB. In the subgroups analyses of patients with acute upper gastrointestinal bleeding or ascites, the risk factors included lower RBC, Hb and ALB. QTc interval prolongation was frequent in liver cirrhosis. Although QTc interval prolongation was positively associated with alcohol-related liver cirrhosis and more severe liver dysfunction, it did not significantly influence the in-hospital mortality. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

[Effects of 2-(p-dimethylaminostyryl) pyridine methycholide (DSPM-Ci) on ECG, left atrium contractivity and on papillary muscle action potentials].

PubMed

Jiang, X Y; Zhou, C M; Li, D M; Zhang, K J

1996-01-01

The effects of DSPM-Cl on ECG in rats, on the dose-effect curve in guinea pig left atria and on the fast action potential (AP), high-K+ depolarized slow action potential (SAP) in guinea pigs papillary muscle were examined electrophysiologically. DSPM-Cl (2 mg.kg-1) showed significant nagative frequency, negative conductivity effect, and prolonged the PP and PR interval. DSPM-CI (30-50 mumol.L-1) was shown to inhibit left atria contractility and shift the concentration-response curve of Iso and CaCl2 to the right with PD2' values of 4.60 and 4.13, respectively. In addition, DSPM-Cl was found to prolong the duration of action potential 90 (APD90) and effective refractory period (ERP), and decrease the maximal upstroke velocity (Vmax) in K(+)-depolarized guinea pigs papillary muscles. The results suggest that, like verpamil, DSPM-Cl might be a calcium antagonist.

Predictive Analytics for Identification of Patients at Risk for QT Interval Prolongation - A Systematic Review.

PubMed

Tomaselli Muensterman, Elena; Tisdale, James E

2018-06-08

Prolongation of the heart rate-corrected QT (QTc) interval increases the risk for torsades de pointes (TdP), a potentially fatal arrhythmia. The likelihood of TdP is higher in patients with risk factors, which include female sex, older age, heart failure with reduced ejection fraction, hypokalemia, hypomagnesemia, concomitant administration of ≥ 2 QTc interval-prolonging medications, among others. Assessment and quantification of risk factors may facilitate prediction of patients at highest risk for developing QTc interval prolongation and TdP. Investigators have utilized the field of predictive analytics, which generates predictions using techniques including data mining, modeling, machine learning, and others, to develop methods of risk quantification and prediction of QTc interval prolongation. Predictive analytics have also been incorporated into clinical decision support (CDS) tools to alert clinicians regarding patients at increased risk of developing QTc interval prolongation. The objectives of this paper are to assess the effectiveness of predictive analytics for identification of patients at risk of drug-induced QTc interval prolongation, and to discuss the efficacy of incorporation of predictive analytics into CDS tools in clinical practice. A systematic review of English language articles (human subjects only) was performed, yielding 57 articles, with an additional 4 articles identified from other sources; a total of 10 articles were included in this review. Risk scores for QTc interval prolongation have been developed in various patient populations including those in cardiac intensive care units (ICUs) and in broader populations of hospitalized or health system patients. One group developed a risk score that includes information regarding genetic polymorphisms; this score significantly predicted TdP. Development of QTc interval prolongation risk prediction models and incorporation of these models into CDS tools reduces the risk of QTc interval prolongation in cardiac ICUs and identifies health-system patients at increased risk for mortality. The impact of these QTc interval prolongation predictive analytics on overall patient safety outcomes, such as TdP and sudden cardiac death relative to the cost of development and implementation, requires further study. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Alterations of Blood Pressure and ECG following Two-Week Consumption of Berberis integerrima Fruit Extract

PubMed Central

Mahdavi, Naser

2014-01-01

In light of the popularity and also the various nutritional and medicinal properties of Berberis integerrima, this study was conducted to assess the influence of its aqueous extract on hemodynamic and electrocardiogram (ECG) indices of rat. Animals were divided to control (CTL), B50, B100, and B200 groups that orally received tap water, aqueous extracts of B. integerrima fruit 50, 100, and 200 mg/kg/day, respectively, for two weeks and on day 15, data were recorded. Different doses of barberry fruit extract had no significant effect on blood pressure, heart rate, RR interval, P duration, and Q wave amplitude of electrocardiogram. Extract administration was associated with an incremental trend in PR interval that was not statistically significant. Higher doses (100 and 200 mg/kg) of extract significantly increased the QRS interval (P < 0.01 versus CTL and B50 groups) but decreased the QTc interval (P < 0.01 versus CTL group and P < 0.001 versus B50 group), the JT interval, and TpTe interval (P < 0.001 versus CTL and B50 groups). The results suggest that high doses of barberry extract definitely prolong the depolarization phase and shorten the repolarization phase of ventricular muscle and hence induce alteration in heart electrical conductivity. PMID:27351000

Not All Prehospital Time is Equal: Influence of Scene Time on Mortality

PubMed Central

Brown, Joshua B.; Rosengart, Matthew R.; Forsythe, Raquel M.; Reynolds, Benjamin R.; Gestring, Mark L.; Hallinan, William M.; Peitzman, Andrew B.; Billiar, Timothy R.; Sperry, Jason L.

2016-01-01

Background Trauma is time-sensitive and minimizing prehospital (PH) time is appealing. However, most studies have not linked increasing PH time with worse outcomes, as raw PH times are highly variable. It is unclear whether specific PH time patterns affect outcomes. Our objective was to evaluate the association of PH time interval distribution with mortality. Methods Patients transported by EMS in the Pennsylvania trauma registry 2000-2013 with total prehospital time (TPT)≥20min were included. TPT was divided into three PH time intervals: response, scene, and transport time. The number of minutes in each PH time interval was divided by TPT to determine the relative proportion each interval contributed to TPT. A prolonged interval was defined as any one PH interval contributing ≥50% of TPT. Patients were classified by prolonged PH interval or no prolonged PH interval (all intervals<50% of TPT). Patients were matched for TPT and conditional logistic regression determined the association of mortality with PH time pattern, controlling for confounders. PH interventions were explored as potential mediators, and prehospital triage criteria used identify patients with time-sensitive injuries. Results There were 164,471 patients included. Patients with prolonged scene time had increased odds of mortality (OR 1.21; 95%CI 1.02–1.44, p=0.03). Prolonged response, transport, and no prolonged interval were not associated with mortality. When adjusting for mediators including extrication and PH intubation, prolonged scene time was no longer associated with mortality (OR 1.06; 0.90–1.25, p=0.50). Together these factors mediated 61% of the effect between prolonged scene time and mortality. Mortality remained associated with prolonged scene time in patients with hypotension, penetrating injury, and flail chest. Conclusions Prolonged scene time is associated with increased mortality. PH interventions partially mediate this association. Further study should evaluate whether these interventions drive increased mortality because they prolong scene time or by another mechanism, as reducing scene time may be a target for intervention. Level of Evidence IV, prognostic study PMID:26886000

Programming Cardiac Resynchronization Therapy for Electrical Synchrony: Reaching Beyond Left Bundle Branch Block and Left Ventricular Activation Delay.

PubMed

Varma, Niraj; O'Donnell, David; Bassiouny, Mohammed; Ritter, Philippe; Pappone, Carlo; Mangual, Jan; Cantillon, Daniel; Badie, Nima; Thibault, Bernard; Wisnoskey, Brian

2018-02-06

QRS narrowing following cardiac resynchronization therapy with biventricular (BiV) or left ventricular (LV) pacing is likely affected by patient-specific conduction characteristics (PR, qLV, LV-paced propagation interval), making a universal programming strategy likely ineffective. We tested these factors using a novel, device-based algorithm (SyncAV) that automatically adjusts paced atrioventricular delay (default or programmable offset) according to intrinsic atrioventricular conduction. Seventy-five patients undergoing cardiac resynchronization therapy (age 66±11 years; 65% male; 32% with ischemic cardiomyopathy; LV ejection fraction 28±8%; QRS duration 162±16 ms) with intact atrioventricular conduction (PR interval 194±34, range 128-300 ms), left bundle branch block, and optimized LV lead position were studied at implant. QRS duration (QRSd) reduction was compared for the following pacing configurations: nominal simultaneous BiV (Mode I: paced/sensed atrioventricular delay=140/110 ms), BiV+SyncAV with 50 ms offset (Mode II), BiV+SyncAV with offset that minimized QRSd (Mode III), or LV-only pacing+SyncAV with 50 ms offset (Mode IV). The intrinsic QRSd (162±16 ms) was reduced to 142±17 ms (-11.8%) by Mode I, 136±14 ms (-15.6%) by Mode IV, and 132±13 ms (-17.8%) by Mode II. Mode III yielded the shortest overall QRSd (123±12 ms, -23.9% [ P <0.001 versus all modes]) and was the only configuration without QRSd prolongation in any patient. QRS narrowing occurred regardless of QRSd, PR, or LV-paced intervals, or underlying ischemic disease. Post-implant electrical optimization in already well-selected patients with left bundle branch block and optimized LV lead position is facilitated by patient-tailored BiV pacing adjusted to intrinsic atrioventricular timing using an automatic device-based algorithm. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Gene-environment interaction between SCN5A-1103Y and hypokalemia influences QT interval prolongation in African Americans: the Jackson Heart Study.

PubMed

Akylbekova, Ermeg L; Payne, John P; Newton-Cheh, Christopher; May, Warren L; Fox, Ervin R; Wilson, James G; Sarpong, Daniel F; Taylor, Herman A; Maher, Joseph F

2014-01-01

African-American ancestry, hypokalemia, and QT interval prolongation on the electrocardiogram are all risk factors for sudden cardiac death (SCD), but their interactions remain to be characterized. SCN5A-1103Y is a common missense variant, of African ancestry, of the cardiac sodium channel gene. SCN5A-1103Y is known to interact with QT-prolonging factors to promote ventricular arrhythmias in persons at high risk for SCD, but its clinical impact in the general African-American population has not been established. We genotyped SCN5A-S1103Y in 4,476 participants of the Jackson Heart Study, a population-based cohort of African Americans. We investigated the effect of SCN5A-1103Y, including interaction with hypokalemia, on QT interval prolongation, a widely-used indicator of prolonged myocardial repolarization and predisposition to SCD. We then evaluated the two sub-components of the QT interval: QRS duration and JT interval. The carrier frequency for SCN5A-1103Y was 15.4%. SCN5A-1103Y was associated with QT interval prolongation (2.7 milliseconds; P < .001) and potentiated the effect of hypokalemia on QT interval prolongation (14.6 milliseconds; P = .02). SCN5A-1103Y had opposing effects on the two sub-components of the QT interval, with shortening of QRS duration (-1.5 milliseconds; P = .001) and prolongation of the JT interval (3.4 milliseconds; P < .001). Hypokalemia was associated with diuretic use (78%; P < .001). SCN5A-1103Y potentiates the effect of hypokalemia on prolonging myocardial repolarization in the general African-American population. These findings have clinical implications for modification of QT prolonging factors, such as hypokalemia, in the 15% of African Americans who are carriers of SCN5A-1103Y. © 2014.

Acute gastrointestinal illness following a prolonged community-wide water emergency.

PubMed

Gargano, J W; Freeland, A L; Morrison, M A; Stevens, K; Zajac, L; Wolkon, A; Hightower, A; Miller, M D; Brunkard, J M

2015-10-01

The drinking water infrastructure in the United States is ageing; extreme weather events place additional stress on water systems that can lead to interruptions in the delivery of safe drinking water. We investigated the association between household exposures to water service problems and acute gastrointestinal illness (AGI) and acute respiratory illness (ARI) in Alabama communities that experienced a freeze-related community-wide water emergency. Following the water emergency, investigators conducted a household survey. Logistic regression models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for self-reported AGI and ARI by water exposures. AGI was higher in households that lost water service for ⩾7 days (aPR 2·4, 95% CI 1·1-5·2) and experienced low water pressure for ⩾7 days (aPR 3·6, 95% CI 1·4-9·0) compared to households that experienced normal service and pressure; prevalence of AGI increased with increasing duration of water service interruptions. Investments in the ageing drinking water infrastructure are needed to prevent future low-pressure events and to maintain uninterrupted access to the fundamental public health protection provided by safe water supplies. Households and communities need to increase their awareness of and preparedness for water emergencies to mitigate adverse health impacts.

Genome-Wide Association Studies of the PR Interval in African Americans

PubMed Central

Palmer, Cameron; Meng, Yan A.; Soliman, Elsayed Z.; Musani, Solomon K.; Kerr, Kathleen F.; Schnabel, Renate B.; Lubitz, Steven A.; Sotoodehnia, Nona; Redline, Susan; Pfeufer, Arne; Müller, Martina; Evans, Daniel S.; Nalls, Michael A.; Liu, Yongmei; Newman, Anne B.; Zonderman, Alan B.; Evans, Michele K.; Deo, Rajat; Ellinor, Patrick T.; Paltoo, Dina N.

2011-01-01

The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10−8) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta  = 5.1 msec per minor allele, 95% CI  = 4.1–6.1, p = 3×10−23). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8–3.0, p = 3×10−16) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans. PMID:21347284

Bisphenol A exposure and cardiac electrical conduction in excised rat hearts.

PubMed

Posnack, Nikki Gillum; Jaimes, Rafael; Asfour, Huda; Swift, Luther M; Wengrowski, Anastasia M; Sarvazyan, Narine; Kay, Matthew W

2014-04-01

Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys, and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased urinary BPA concentrations and cardiovascular disease, yet the direct effects of BPA on the heart are unknown. The goal of our study was to measure the effect of BPA (0.1-100 μM) on cardiac impulse propagation ex vivo using excised whole hearts from adult female rats. We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential in excised rat hearts exposed to BPA via perfusate media. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1-100 μM BPA), prolonged action potential duration (1-100 μM BPA), and delayed atrioventricular conduction (10-100 μM BPA). These effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals and dropped ventricular beats, and eventually resulted in complete heart block. Our results show that acute BPA exposure slowed electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA's effect on heart electrophysiology and determining whether chronic in vivo exposure can cause or exacerbate conduction abnormalities in patients with preexisting heart conditions and in other high-risk populations.

QT-RR relationships and suitable QT correction formulas for halothane-anesthetized dogs.

PubMed

Tabo, Mitsuyasu; Nakamura, Mikiko; Kimura, Kazuya; Ito, Shigeo

2006-10-01

Several QT correction (QTc) formulas have been used for assessing the QT liability of drugs. However, they are known to under- and over-correct the QT interval and tend to be specific to species and experimental conditions. The purpose of this study was to determine a suitable formula for halothane-anesthetized dogs highly sensitive to drug-induced QT interval prolongation. Twenty dogs were anesthetized with 1.5% halothane and the relationship between the QT and RR intervals were obtained by changing the heart rate under atrial pacing conditions. The QT interval was corrected for the RR interval by applying 4 published formulas (Bazett, Fridericia, Van de Water, and Matsunaga); Fridericia's formula (QTcF = QT/RR(0.33)) showed the least slope and lowest R(2) value for the linear regression of QTc intervals against RR intervals, indicating that it dissociated changes in heart rate most effectively. An optimized formula (QTcX = QT/RR(0.3879)) is defined by analysis of covariance and represents a correction algorithm superior to Fridericia's formula. For both Fridericia's and the optimized formula, QT-prolonging drugs (d,l-sotalol, astemizole) showed QTc interval prolongation. A non-QT-prolonging drug (d,l-propranolol) failed to prolong the QTc interval. In addition, drug-induced changes in QTcF and QTcX intervals were highly correlated with those of the QT interval paced at a cycle length of 500 msec. These findings suggest that Fridericia's and the optimized formula, although the optimized is a little bit better, are suitable for correcting the QT interval in halothane-anesthetized dogs and help to evaluate the potential QT prolongation of drugs with high accuracy.

Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350.

PubMed

Poulsen, Jakob Lykke; Brock, Christina; Grønlund, Debbie; Liao, Donghua; Gregersen, Hans; Krogh, Klaus; Drewes, Asbjørn Mohr

2017-11-01

Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction (OIBD). However, it is unknown whether the inhibition can be reduced by opioid antagonism with prolonged-release (PR) naloxone and how this compares to laxative treatment. To compare the effects of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350 on anal sphincter function and gastrointestinal symptoms. A randomized, double-blind, crossover trial was conducted in 20 healthy men. Participants were treated for 5 days with combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Resting anal pressure, anal canal distensibility, and relaxation of the internal sphincter to rectal distension were evaluated before treatment (baseline) and on day 5. The Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire, stool frequency, and stool consistency were assessed daily. Both PR oxycodone/naloxone and PR oxycodone plus macrogol treatment decreased sphincter relaxation compared to baseline (- 27.5%; P < 0.001 and - 14.7%; P = 0.01). However, sphincter relaxation was increased after PR naloxone/oxycodone treatment compared to macrogol (difference = + 17.6%; P < 0.001). Resting anal pressure and anal canal distensibility did not differ between treatments. PAC-SYM abdominal symptoms score was lower during PR naloxone compared to macrogol (0.2 vs. 3.2; P = 0.002). The number of bowel movements was lower during PR naloxone versus macrogol (4.2 vs. 5.4; P = 0.035). Relaxation of the internal anal sphincter was significantly better after PR oxycodone/naloxone treatment compared to PR oxycodone plus macrogol 3350. These findings highlight that OIBD may require specific therapy against the complex, pan-intestinal effects of opioids.

Short-Duration Spaceflight Does Not Prolong QTc Intervals in Male Astronauts

NASA Technical Reports Server (NTRS)

Mitchell, Brett M.; Meck, Janice V.

2004-01-01

Although ventricular dysrhythmias are not increased during, and QTc intervals are not prolonged after, short-duration (5 to 16 days) spaceflights, QTc intervals have not previously been reported during these shorter flights. Holter monitor recordings, obtained in 11 male astronauts who flew on shuttle missions ranging from 5 to 10 days, showed that QTc intervals did not change significantly 10 days before launch, on 2 separate days of spaceflight, and 2 days after landing. Taken together, these data and our previous report show that QTc interval prolongation occurs sometime between the 9th and 30th days of spaceflight.

Predicting QT prolongation in humans during early drug development using hERG inhibition and an anaesthetized guinea-pig model

PubMed Central

Yao, X; Anderson, D L; Ross, S A; Lang, D G; Desai, B Z; Cooper, D C; Wheelan, P; McIntyre, M S; Bergquist, M L; MacKenzie, K I; Becherer, J D; Hashim, M A

2008-01-01

Background and purpose: Drug-induced prolongation of the QT interval can lead to torsade de pointes, a life-threatening ventricular arrhythmia. Finding appropriate assays from among the plethora of options available to predict reliably this serious adverse effect in humans remains a challenging issue for the discovery and development of drugs. The purpose of the present study was to develop and verify a reliable and relatively simple approach for assessing, during preclinical development, the propensity of drugs to prolong the QT interval in humans. Experimental approach: Sixteen marketed drugs from various pharmacological classes with a known incidence—or lack thereof—of QT prolongation in humans were examined in hERG (human ether a-go-go-related gene) patch-clamp assay and an anaesthetized guinea-pig assay for QT prolongation using specific protocols. Drug concentrations in perfusates from hERG assays and plasma samples from guinea-pigs were determined using liquid chromatography-mass spectrometry. Key results: Various pharmacological agents that inhibit hERG currents prolong the QT interval in anaesthetized guinea-pigs in a manner similar to that seen in humans and at comparable drug exposures. Several compounds not associated with QT prolongation in humans failed to prolong the QT interval in this model. Conclusions and implications: Analysis of hERG inhibitory potency in conjunction with drug exposures and QT interval measurements in anaesthetized guinea-pigs can reliably predict, during preclinical drug development, the risk of human QT prolongation. A strategy is proposed for mitigating the risk of QT prolongation of new chemical entities during early lead optimization. PMID:18587422

Comparative effects of sodium bicarbonate and sodium chloride on reversing cocaine-induced changes in the electrocardiogram.

PubMed

Parker, R B; Perry, G Y; Horan, L G; Flowers, N C

1999-12-01

Cocaine abuse is associated with a number of cardiovascular complications that include arrhythmias and sudden cardiac death. Although the mechanism(s) remain unclear, cocaine-induced block of sodium channels resulting in slowed cardiac conduction is thought to play an important role. Several reports suggest that the effects of cocaine effects on cardiac sodium channels can be reversed by administration of sodium bicarbonate. Whether the beneficial effects of sodium bicarbonate are due to sodium ions or an increase in blood pH is unknown. Therefore the purpose of this study was to compare the effects of sodium loading alone (by using sodium chloride) versus sodium loading with an associated increase in arterial pH (by using sodium bicarbonate) on reversing cocaine-induced effects on the electrocardiogram (ECG) in a canine model. Seventeen anesthetized dogs received three i.v. injections of cocaine, 5 mg/kg, with each dose separated by 15 min. Two minutes after the third cocaine dose, each dog was randomly assigned to receive 2 mEq/kg i.v. sodium bicarbonate (1 mEq/ml) or 2 mEq/kg i.v. sodium chloride (1 mEq/ml). ECG, electrophysiologic, and hemodynamic data were recorded at baseline, after each cocaine injection, and after administration of sodium bicarbonate or sodium chloride. In both groups of animals, the first cocaine injection significantly (p < 0.05) prolonged the PR, QTc, AH, and HV intervals, and QRS duration compared with baseline. All intervals continued to lengthen in a dose-dependent manner after the second and third cocaine doses. Sodium bicarbonate significantly (p < 0.05) reduced cocaine-induced prolongation of PR [(147 +/- 5-130 +/- 5 ms), AH (81 +/- 6 - 72 +/- 6 ms), and HV intervals (55 +/- 2 - 39 +/- 1 ms). and QRS duration (96 +/- 6 - 66 +/- 4 ms), peak effect after third cocaine dose versus after sodium bicarbonate, respectively]. Sodium chloride had no effect on reversing cocaine-induced effects on the ECG. Cocaine produces dose-dependent slowing of cardiac conduction that is effectively reversed by sodium bicarbonate. The lack of efficacy of sodium chloride suggests that the increase in arterial pH associated with sodium bicarbonate is responsible for reversal of the effects of cocaine on the ECG. Therefore sodium bicarbonate may be clinically useful in the treatment of cocaine-induced cardiac arrhythmias, primarily as a result of its effects on arterial pH.

Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

PubMed

Keller, Guillermo A; Alvarez, Paulino A; Ponte, Marcelo L; Belloso, Waldo H; Bagnes, Claudia; Sparanochia, Cecilia; Gonzalez, Claudio D; Villa Etchegoyen, M Cecilia; Diez, Roberto A; Di Girolamo, Guillermo

2016-01-01

The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

Effect of alectinib on cardiac electrophysiology: results from intensive electrocardiogram monitoring from the pivotal phase II NP28761 and NP28673 studies.

PubMed

Morcos, Peter N; Bogman, Katrijn; Hubeaux, Stanislas; Sturm-Pellanda, Carolina; Ruf, Thorsten; Bordogna, Walter; Golding, Sophie; Zeaiter, Ali; Abt, Markus; Balas, Bogdana

2017-03-01

Alectinib, a central nervous system (CNS)-active ALK inhibitor, has demonstrated efficacy and safety in ALK+ non-small-cell lung cancer that has progressed following crizotinib treatment. Other ALK inhibitors have shown concentration-dependent QTc prolongation and treatment-related bradycardia. Therefore, this analysis evaluated alectinib safety in terms of electrophysiologic parameters. Intensive triplicate centrally read electrocardiogram (ECG) and matched pharmacokinetic data were collected across two alectinib single-arm trials. Analysis of QTcF included central tendency analysis [mean changes from baseline with one-sided upper 95% confidence intervals (CIs)], categorical analyses, and relationship between change in QTcF and alectinib plasma concentrations. Alectinib effects on other ECG parameters (heart rate, PR interval and QRS duration) were also evaluated. Alectinib did not cause a clinically relevant change in QTcF. The maximum mean QTcF change from baseline was 5.3 ms observed pre-dose at week 2. The upper one-sided 95% CI was <10 ms at all time points. There was no relevant relationship between change in QTcF and alectinib plasma concentrations. Alectinib treatment resulted in a generally asymptomatic exposure-dependent decrease in mean heart rate of ~11 to 13 beats per minute at week 2. No clinically relevant effects were seen on other ECG parameters. Approximately 5% of patients reported cardiac adverse events of bradycardia or sinus bradycardia; however, these were all grade 1-2. Alectinib does not prolong the QTc interval or cause changes in cardiac function to a clinically relevant extent, with the exception of a decrease in heart rate which was generally asymptomatic.

Electrocardiographic characteristics of atrioventricular block induced by tilt testing.

PubMed

Zyśko, Dorota; Gajek, Jacek; Koźluk, Edward; Mazurek, Walentyna

2009-02-01

The electrocardiographic (ECG) characteristics of atrioventricular (AV) block during reflex syncope may be unique due to the presence of hypervagotonia. The aim of the present study was to define the ECG characteristics of the AV block induced by neurocardiogenic reflex provoked by tilt testing (TT). A series of 31 patients with presumed vasovagal syncope and AV block provoked by TT was studied. The duration of PP and PR interval, AV block grade and type, concomitant arrhythmias, and timing of the AV block occurrence were assessed. The AV block occurred at TT termination in 26 patients, in the recovery in 4 patients, and in both periods in 1 patient. Atrioventricular block was preceded by sinus slowing, and sinus rhythm during AV block was slow and instable. Mobitz I, 2:1 second-degree AV block, and advanced second-degree AV block were recognized in 35.5, 48.4, and 67.8% of patients, respectively. Third-degree AV block was diagnosed in 41.9% of patients. Twenty-one patients had at least two AV block forms. The most prevalent concomitant arrhythmia was junctional escape rhythm (61.3%). (i) The occurrence of the AV block during neurocardiogenic reaction induced by TT is always preceded by sinus rhythm slowing and usually by PR interval prolongation. (ii) The AV block provoked by TT usually occurs at TT termination, but may occur even in the recovery period in a supine position. Sometimes the AV block may be present both at TT termination and during the recovery period.

Prognostic significance of fever-induced Brugada syndrome.

PubMed

Mizusawa, Yuka; Morita, Hiroshi; Adler, Arnon; Havakuk, Ofer; Thollet, Aurélie; Maury, Philippe; Wang, Dao W; Hong, Kui; Gandjbakhch, Estelle; Sacher, Frédéric; Hu, Dan; Amin, Ahmad S; Lahrouchi, Najim; Tan, Hanno L; Antzelevitch, Charles; Probst, Vincent; Viskin, Sami; Wilde, Arthur A M

2016-07-01

In Brugada syndrome (BrS), spontaneous type 1 electrocardiogram (ECG) is an established risk marker for fatal arrhythmias whereas drug-induced type 1 ECG shows a relatively benign prognosis. No study has analyzed the prognosis of fever-induced type 1 ECG (F-type1) in a large BrS cohort. The objectives of this study were to assess the prognosis of F-type1 in asymptomatic BrS and to compare the effects of fever and drugs on ECG parameters. One hundred twelve patients with BrS who developed F-type1 were retrospectively enrolled. Prognosis was evaluated in 88 asymptomatic patients. In a subgroup (n = 52), ECG parameters of multiple ECGs (at baseline, during fever, and after drug challenge) were analyzed. Eighty-eight asymptomatic patients had a mean age of 45.8 ± 18.7 years, and 71.6% (67 of 88) were men. Twenty-one percent (18 of 88) had a family history of sudden cardiac death, and 26.4% (14 of 53) carried a pathogenic SCN5A mutation. Drug challenge was positive in 29 of 36 patients tested (80.6%). The risk of ventricular fibrillation in asymptomatic patients was 0.9%/y (3 of 88; 43.6 ± 37.4 months). ST-segment elevation in lead V2 during fever and after drug challenge was not significantly different (0.41 ± 0.21 ms during fever and 0.40 ± 0.30 ms after drug challenge; P > .05). Fever shortened the PR interval compared to baseline, whereas drug challenge resulted in prolonged PR interval and QRS duration (PR interval: 169 ± 29 ms at baseline, 148 ± 45 ms during fever, and 202 ± 35 ms after drug challenge; QRS duration: 97 ± 18 ms at baseline, 92 ± 28 ms during fever, and 117 ± 21 ms after drug challenge). Patients with BrS who develop F-type1 are at risk of arrhythmic events. F-type1 appears to develop through a more complex mechanism as compared with drug-induced type 1 ECG. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Proarrhythmic potential of halofantrine, terfenadine and clofilium in a modified in vivo model of torsade de pointes

PubMed Central

Batey, Andrew J; Coker, Susan J

2002-01-01

This study was designed to compare the proarrhythmic activity of the antimalarial drug, halofantrine and the antihistamine, terfenadine, with that of clofilium a K+ channel blocking drug that can induce torsade de pointes. Experiments were performed in pentobarbitone-anaesthetized, open-chest rabbits. Each rabbit received intermittent, rising dose i.v. infusions of the α-adrenoceptor agonist phenylephrine. During these infusions rabbits also received increasing i.v. doses of clofilium (20, 60 and 200 nmol kg−1 min−1), terfenadine (75, 250 and 750 nmol kg−1 min−1), halofantrine (6, 20 and 60 μmol kg−1) or vehicle. Clofilium and halofantrine caused dose-dependent increases in the rate-corrected QT interval (QTc), whereas terfenadine prolonged PR and QRS intervals rather than prolonging cardiac repolarization. Progressive bradycardia occurred in all groups. After administration of the highest dose of each drug halofantrine caused a modest decrease in blood pressure, but terfenadine had profound hypotensive effects resulting in death of most rabbits. The total number of ventricular premature beats was highest in the clofilium group. Torsade de pointes occurred in 6 out of 8 clofilium-treated rabbits and 4 out of 6 of those which received halofantrine, but was not seen in any of the seven terfenadine-treated rabbits. These results show that, like clofilium, halofantrine can cause torsade de pointes in a modified anaesthetized rabbit model whereas the primary adverse effect of terfenadine was cardiac contractile failure. PMID:11861329

33 CFR 83.35 - Sound signals in restricted visibility (Rule 35).

Code of Federal Regulations, 2013 CFR

2013-07-01

... more than 2 minutes two prolonged blasts in succession with an interval of about 2 seconds between them... than 2 minutes, three blasts in succession; namely, one prolonged followed by two short blasts. (d..., shall at intervals of not more than 2 minutes sound four blasts in succession; namely, one prolonged...

33 CFR 83.35 - Sound signals in restricted visibility (Rule 35).

Code of Federal Regulations, 2014 CFR

2014-07-01

... more than 2 minutes two prolonged blasts in succession with an interval of about 2 seconds between them... than 2 minutes, three blasts in succession; namely, one prolonged followed by two short blasts. (d..., shall at intervals of not more than 2 minutes sound four blasts in succession; namely, one prolonged...

33 CFR 83.35 - Sound signals in restricted visibility (Rule 35).

Code of Federal Regulations, 2012 CFR

2012-07-01

... more than 2 minutes two prolonged blasts in succession with an interval of about 2 seconds between them... than 2 minutes, three blasts in succession; namely, one prolonged followed by two short blasts. (d..., shall at intervals of not more than 2 minutes sound four blasts in succession; namely, one prolonged...

33 CFR 83.35 - Sound signals in restricted visibility (Rule 35).

Code of Federal Regulations, 2011 CFR

2011-07-01

... more than 2 minutes two prolonged blasts in succession with an interval of about 2 seconds between them... than 2 minutes, three blasts in succession; namely, one prolonged followed by two short blasts. (d..., shall at intervals of not more than 2 minutes sound four blasts in succession; namely, one prolonged...

Prolonged-release fampridine and walking and balance in MS: randomised controlled MOBILE trial

PubMed Central

Hupperts, Raymond; Lycke, Jan; Short, Christine; Gasperini, Claudio; McNeill, Manjit; Medori, Rossella; Tofil-Kaluza, Agata; Hovenden, Maria; Mehta, Lahar R; Elkins, Jacob

2016-01-01

Background: Mobility impairment is a common disability in MS and negatively impacts patients’ lives. Objective: Evaluate the effect of prolonged-release (PR) fampridine (extended-release dalfampridine in the United States) on self-assessed walking disability, dynamic/static balance and safety in patients with MS. Methods: MOBILE was a randomised, double-blind, exploratory, placebo-controlled trial. Patients with progressive/relapsing-remitting MS and Expanded Disability Status Scale score of 4.0–7.0 were treated with PR-fampridine or placebo twice daily for 24 weeks. Efficacy endpoints included change from baseline in the 12-item MS Walking Scale (MSWS-12), Timed Up and Go (TUG) test and Berg Balance Scale (BBS). Results: 132 patients were randomised at 24 sites in six countries. PR-fampridine therapy resulted in greater median improvements from baseline in MSWS-12 score, TUG speed and BBS total score versus placebo over 24 weeks. A higher proportion of patients receiving PR-fampridine versus placebo experienced significant improvements at MSWS-12 improvement thresholds ⩾7 (p = 0.0275), ⩾8 (p = 0.0153) and ⩾9 points (p = 0.0088) and TUG speed thresholds ⩾10% (p = 0.0021) and ⩾15% (p = 0.0262). PR-fampridine was well tolerated. Conclusions: PR-fampridine therapy resulted in early and sustained improvements in broad measures of walking and balance over six months. PMID:25921050

Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

PubMed

Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

2017-11-01

To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (C_max), and plasma concentrations at the end of the dosing interval (C_τ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80.00 - 125.00%. Bioavailability of OOD was not influenced by concomitant food intake. OOD and OTD were generally well tolerated, a difference between the two products could not be observed. The new 10-mg OOD formulation provides sustained oxycodone plasma concentrations over the dosing interval of 24 hours and is suitable for once-daily administration. Bioavailability of OOD could be classified as comparable to the twice-daily administration of the OTD reference formulation. The new formulation widens and optimizes the range of strong opioid drug products in patient-centered therapy of chronic pain with simplified dosing and better compliance.
.

New in vitro model for proarrhythmia safety screening: IKs inhibition potentiates the QTc prolonging effect of IKr inhibitors in isolated guinea pig hearts.

PubMed

Kui, Péter; Orosz, Szabolcs; Takács, Hedvig; Sarusi, Annamária; Csík, Norbert; Rárosi, Ferenc; Csekő, Csongor; Varró, András; Papp, Julius Gy; Forster, Tamás; Farkas, Attila S; Farkas, András

2016-01-01

Preclinical in vivo QT measurement as a proarrhythmia essay is expensive and not reliable enough. The aim of the present study was to develop a sensitive, cost-effective, Langendorff perfused guinea pig heart model for proarrhythmia safety screening. Low concentrations of dofetilide and cisapride (inhibitors of the rapid delayed rectifier potassium current, IKr) were tested alone and co-perfused with HMR-1556 (inhibitor of the slow delayed rectifier potassium current, IKs) in Langendorff perfused guinea pig hearts. The electrocardiographic rate corrected QT (QTc) interval, the Tpeak-Tend interval and the beat-to-beat variability and instability (BVI) of the QT interval were determined in sinus rhythm. Dofetilide and HMR-1556 alone or co-perfused, prolonged the QTc interval by 20±2%, 10±1% and 55±10%, respectively. Similarly, cisapride and HMR-1556 alone or co-perfused, prolonged the QTc interval by 11±3%, 11±4% and 38±6%, respectively. Catecholamine-induced fast heart rate abolished the QTc prolonging effects of the IKr inhibitors, but augmented the QTc prolongation during IKs inhibition. None of the drug perfusions increased significantly the Tpeak-Tend interval and the sinus BVI of the QT interval. IKs inhibition increased the QTc prolonging effect of IKr inhibitors in a super-additive (synergistic) manner, and the QTc interval was superior to other proarrhythmia biomarkers measured in sinus rhythm in isolated guinea pig hearts. The effect of catecholamines on the QTc facilitated differentiation between IKr and IKs inhibitors. Thus, QTc measurement in Langendorff perfused guinea pig hearts with pharmacologically attenuated repolarization reserve and periodic catecholamine perfusion seems to be suitable for preclinical proarrhythmia screening. Copyright © 2016 Elsevier Inc. All rights reserved.

Prolongation anormale d'un bloc fémoral analgésique: cas Clinique

PubMed Central

Koné, Joseph; Bensghir, Mustapha; Boutayeb, El Houcine; Haimeur, Charki

2015-01-01

La prolongation anormale d'un bloc nerveux peut être définie comme un dépassement du délai habituel de récupération sensitive ou motrice. A travers un cas clinique d'une prolongation anormale d'un bloc analgésique et une revue de la littérature, les auteurs discutent les facteurs de risque et les moyens de prévention de cette complication. PMID:26918085

In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig.

PubMed

Hansen, Rie Schultz; Olesen, Søren-Peter; Rønn, Lars Christian B; Grunnet, Morten

2008-07-01

The long QT syndrome is characterized by a prolongation of the QT interval measured on the surface electrocardiogram. Prolonging the QT interval increases the risk of dangerous ventricular fibrillations, eventually leading to sudden cardiac death. Pharmacologically induced QT interval prolongations are most often caused by antagonizing effects on the repolarizing cardiac current called IKr. In humans IKr is mediated by the human ether-a-go-go related gene (hERG) potassium channel. We recently presented NS3623, a compound that selectively activates this channel. The present study was dedicated to examining the in vivo effects of NS3623. Injection of 30 mg/kg NS3623 shortened the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs. Accordingly, 50 mg/kg of NS3623 shortened the QT interval by 30 +/- 6% in conscious guinea pigs. Finally, pharmacologically induced QT prolongation by a hERG channel antagonist (0.15 mg/kg E-4031) could be reverted by injection of NS3623 (50 mg/kg) in conscious guinea pigs. In conclusion, the present in vivo study demonstrates that injection of the hERG channel agonist NS3623 results in shortening of the QTc interval as well as reversal of a pharmacologically induced QT prolongation in both anaesthetized and conscious guinea pigs.

Genetics Home Reference: ankyrin-B syndrome

MedlinePlus

... beats, which is known as a prolonged QT interval (long QT). Some affected individuals have impaired progression ( ... sudden death. When associated with a prolonged QT interval, the condition is sometimes classified as long QT ...

Prolonged-release fampridine treatment improved subject-reported impact of multiple sclerosis: Item-level analysis of the MSIS-29.

PubMed

Gasperini, Claudio; Hupperts, Raymond; Lycke, Jan; Short, Christine; McNeill, Manjit; Zhong, John; Mehta, Lahar R

2016-11-15

Prolonged-release (PR) fampridine is approved to treat walking impairment in persons with multiple sclerosis (MS); however, treatment benefits may extend beyond walking. MOBILE was a phase 2, 24-week, double-blind, placebo-controlled exploratory study to assess the impact of 10mg PR-fampridine twice daily versus placebo on several subject-assessed measures. This analysis evaluated the physical and psychological health outcomes of subjects with progressing or relapsing MS from individual items of the Multiple Sclerosis Impact Scale (MSIS-29). PR-fampridine treatment (n=68) resulted in greater improvements from baseline in the MSIS-29 physical (PHYS) and psychological (PSYCH) impact subscales, with differences of 89% and 148% in mean score reduction from baseline (n=64) at week 24 versus placebo, respectively. MSIS-29 item analysis showed that a higher percentage of PR-fampridine subjects had mean improvements in 16/20 PHYS and 6/9 PSYCH items versus placebo after 24weeks. Post hoc analysis of the 12-item Multiple Sclerosis Walking Scale (MSWS-12) improver population (≥8-point mean improvement) demonstrated differences in mean reductions from baseline of 97% and 111% in PR-fampridine MSIS-29 PHYS and PSYCH subscales versus the overall placebo group over 24weeks. A higher percentage of MSWS-12 improvers treated with PR-fampridine showed mean improvements in 20/20 PHYS and 8/9 PSYCH items versus placebo at 24weeks. In conclusion, PR-fampridine resulted in physical and psychological benefits versus placebo, sustained over 24weeks. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Fine Particulate air Pollution is Associated with Higher Vulnerability to Atrial Fibrillation—The APACR Study

PubMed Central

Liao, Duanping; Shaffer, Michele L.; He, Fan; Rodriguez-Colon, Sol; Wu, Rongling; Whitsel, Eric A.; Bixler, Edward O.; Cascio, Wayne E.

2011-01-01

The acute effects and the time course of fine particulate pollution (PM2.5) on atrial fibrillation/flutter (AF) predictors, including P-wave duration, PR interval duration, and P-wave complexity, were investigated in a community-dwelling sample of 106 nonsmokers. Individual-level 24-h beat-to-beat electrocardiogram (ECG) data were visually examined. After identifying and removing artifacts and arrhythmic beats, the 30-min averages of the AF predictors were calculated. A personal PM2.5 monitor was used to measure individual-level, real-time PM2.5 exposures during the same 24-h period, and corresponding 30-min average PM2.5 concentration were calculated. Under a linear mixed-effects modeling framework, distributed lag models were used to estimate regression coefficients (βs) associating PM2.5 with AF predictors. Most of the adverse effects on AF predictors occurred within 1.5–2 h after PM2.5 exposure. The multivariable adjusted βs per 10-µg/m3 rise in PM2.5 at lag 1 and lag 2 were significantly associated with P-wave complexity. PM2.5 exposure was also significantly associated with prolonged PR duration at lag 3 and lag 4. Higher PM2.5 was found to be associated with increases in P-wave complexity and PR duration. Maximal effects were observed within 2 h. These findings suggest that PM2.5 adversely affects AF predictors; thus, PM2.5 may be indicative of greater susceptibility to AF. PMID:21480044

Pyrilamine-induced prolonged QT interval in adolescent with drug overdose.

PubMed

Paudel, Govinda; Syed, Muhammad; Kalantre, Sarika; Sharma, Jayendra

2011-10-01

The widespread availability of antihistamines in many over-the-counter preparations can lead to significant hazard to the public because of their possible link to potential ventricular arrhythmias secondary to prolongation of QT interval. The effect can be further compounded by the use of other commonly used medications such as macrolides, antifungal agents, antipsychotics, and other antihistamine-containing preparations. The effect of antihistamines on QT interval is not a class effect but is unique to certain medications. Pyrilamine, a first-generation antihistaminic agent, is considered safe as there are no reports regarding its cardiac toxicity available in literature. We report a case of an adolescent with prolonged QT interval after an overdose of pyrilamine.

Brain mapping after prolonged cycling and during recovery in the heat.

PubMed

De Pauw, Kevin; Roelands, Bart; Marusic, Uros; Tellez, Helio Fernandez; Knaepen, Kristel; Meeusen, Romain

2013-11-01

The aim of this study was to determine the effect of prolonged intensive cycling and postexercise recovery in the heat on brain sources of altered brain oscillations. After a max test and familiarization trial, nine trained male subjects (23 ± 3 yr; maximal oxygen uptake = 62.1 ± 5.3 ml·min(-1)·kg(-1)) performed three experimental trials in the heat (30°C; relative humidity 43.7 ± 5.6%). Each trial consisted of two exercise tasks separated by 1 h. The first was a 60-min constant-load trial, followed by a 30-min simulated time trial (TT1). The second comprised a 12-min simulated time trial (TT2). After TT1, active recovery (AR), passive rest (PR), or cold water immersion (CWI) was applied for 15 min. Electroencephalography was measured at baseline and during postexercise recovery. Standardized low-resolution brain electromagnetic tomography was applied to accurately pinpoint and localize altered electrical neuronal activity. After CWI, PR and AR subjects completed TT2 in 761 ± 42, 791 ± 76, and 794 ± 62 s, respectively. A prolonged intensive cycling performance in the heat decreased β activity across the whole brain. Postexercise AR and PR elicited no significant electrocortical differences, whereas CWI induced significantly increased β3 activity in Brodmann areas (BA) 13 (posterior margin of insular cortex) and BA 40 (supramarginal gyrus). Self-paced prolonged exercise in the heat seems to decrease β activity, hence representing decreased arousal. Postexercise CWI increased β3 activity at BA 13 and 40, brain areas involved in somatosensory information processing.

QT interval prolongation associated with sibutramine treatment

PubMed Central

Harrison-Woolrych, Mira; Clark, David W J; Hill, Geraldine R; Rees, Mark I; Skinner, Jonathan R

2006-01-01

Aims To investigate a possible association of sibutramine with QT interval prolongation. Methods Post-marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database. Results The index case displayed a novel mutation in a cardiac potassium channel subunit gene, KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QTc at the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride. Conclusions This case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval. PMID:16542208

A Pilot Study: Cardiac Parameters in Children Receiving New-Generation Antidepressants.

PubMed

Uchida, Mai; Spencer, Andrea E; Kenworthy, Tara; Chan, James; Fitzgerald, Maura; Rosales, Ana Maria; Kagan, Elana; Saunders, Alexandra; Biederman, Joseph

2017-06-01

Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine). To standardize the doses of different antidepressants, we converted doses of individual medicines into "citalopram equivalent doses" (CEDs) based on dosing recommendation for individual antidepressants. Correlation analysis was carried out to compare the continuous and weight-based CED to variables of interest. A QTc grouping was defined as normal, borderline, or abnormal, and CED was compared across QTc groupings using linear regression. An antidepressant dosage group was defined as low or high dose, and a t test compared variables of interest across dosage groups. No significant associations were found between total or weight-corrected CEDs of any antidepressant examined and QTc or any other electrocardiogram or blood pressure parameters. In patients taking citalopram or escitalopram, a significant correlation was found between PR interval and total daily dose, which disappeared when weight-based doses were used or when corrected by age. Although limited by a relatively small sample size, these results suggest that therapeutic doses of non-TCA antidepressants when used in children do not seem to be associated with prolonged QTc interval or other adverse cardiovascular effects.

QT Prolongation, Torsades de Pointes, and Psychotropic Medications: A 5-Year Update.

PubMed

Beach, Scott R; Celano, Christopher M; Sugrue, Alan M; Adams, Caitlin; Ackerman, Michael J; Noseworthy, Peter A; Huffman, Jeff C

Some psychotropic medications have been associated with prolongation of the QT interval and QT prolongation, especially in those with medical illness, and are linked to lethal ventricular arrhythmias, such as Torsades de Pointes (TdP). In 2013, we published a review of QT prolongation, TdP, and psychotropic medications. We provide an update over the past 5 years on the specific concerns most relevant to clinicians who see medically ill patients. In this nonsystematic review, we aimed to carefully and intensively identify new articles by utilizing a structured PubMed search from 2012-present. QT prolongation remains an imperfect, though well-established marker of risk for TdP. Among antidepressant medications, citalopram does appear to prolong the QT interval more than other selective serotonin reuptake inhibitors, though the clinical significance of this prolongation remains unclear. Escitalopram appears to prolong the QT interval to a lesser extent. Haloperidol carries a risk for QT prolongation, but the assertion that intravenous haloperidol is inherently riskier may be confounded by its primary use in medically ill populations. Among atypical antipsychotic agents, ziprasidone-and possibly iloperidone-is associated with the greatest QT prolongation, whereas aripiprazole appears safest from this standpoint. The evidence for clinically meaningful QT prolongation with most classes of psychiatric agents remains minimal. The most important risk-reducing intervention clinicians can make is undertaking a careful analysis of other QT risk factors when prescribing psychiatric medications. Copyright © 2017 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.

BPC 157 counteracts QTc prolongation induced by haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats.

PubMed

Strinic, Dean; Belosic Halle, Zeljka; Luetic, Kresimir; Nedic, Ana; Petrovic, Igor; Sucic, Mario; Zivanovic Posilovic, Gordana; Balenovic, Dijana; Strbe, Sanja; Udovicic, Mario; Drmic, Domagoj; Stupnisek, Mirjana; Lovric Bencic, Martina; Seiwerth, Sven; Sikiric, Predrag

2017-10-01

Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10μg, 10ng/kg ip) immediately after each administrations of haloperidol (0.625, 6.25, 12.5, and 25.0mg/kg ip), fluphenazine (0.5, 5.0mg/kg ip), clozapine (1.0, 10.0mg/kg ip), quetiapine (1.0, 10.0mg/kg ip), sulpiride (1.6, 16.0mg/kg ip), metoclopramide (2.5, 25.0mg/kg ip) or (1.0, 10.0mg/kg ip). Controls simultaneously received saline (5ml/kg ip). To assess the ECG presentation before and after neuroleptic/prokinetic medication, the assessment was at 1, 2, 3, 4, 5, 10, 15, 20 and 30min (first administration) as well as at 30min, 60min and 24h (first administration and subsequent administrations) and the ECG recording started prior to drug administration. Since very early, a prolonged QTc interval has been continually noted with haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats as a central common effect not seen with domperidone. Consistent counteraction appears with the stable gastric pentadecapeptide BPC 157. Thus, BPC 157 rapidly and permanently counteracts the QTc prolongation induced by neuroleptics and prokinetics. Pentadecapeptide BPC 157 is suited for counteracting a prolonged QT interval. Copyright © 2017 Elsevier Inc. All rights reserved.

TEAM-UP for quality: a cluster randomized controlled trial protocol focused on preventing pressure ulcers through repositioning frequency and precipitating factors.

PubMed

Yap, Tracey L; Kennerly, Susan M; Horn, Susan D; Bergstrom, Nancy; Datta, Santanu; Colon-Emeric, Cathleen

2018-02-20

Pressure ulcers/injuries (PrUs), a critical concern for nursing homes (NH), are responsible for chronic wounds, amputations, septic infections, and premature deaths. PrUs occur most commonly in older adults and NH residence is a risk factor for their development, with at least one of every nine U.S. NH residents experiencing a PrU and many NHs having high incidence and prevalence rates, in some instances well over 20%. PrU direct treatment costs are greater than prevention costs, making prevention-focused protocols critical. Current PrU prevention protocols recommend repositioning residents at moderate, high, and severe risk every 2 h. The advent of visco-elastic (VE) high-density foam support-surfaces over the past decade may now make it possible to extend the repositioning interval to every 3 or 4 h without increasing PrU development. The TEAM-UP (Turn Everyone And Move for Ulcer Prevention) study aims to determine: 1) whether repositioning interval can be extended for NH residents without compromising PrU incidence and 2) how changes in medical severity interact with changes in risk level and repositioning schedule to predict PrU development. In this proposed cluster randomized study, 9 NHs will be randomly assigned to one of three repositioning intervals (2, 3, or 4 h) for a 4-week period. Each enrolled site will use a single NH-wide repositioning interval as the standard of care for residents at low, moderate, and high risk of PrU development (N = 951) meeting the following criteria: minimum 3-day stay, without PrUs, no adhesive allergy, and using VE support surfaces (mattresses). An FDA-cleared patient monitoring system that records position/movement of these residents via individual wireless sensors will be used to visually cue staff when residents need repositioning and document compliance with repositioning protocols. This study will advance knowledge about repositioning frequency and clinically assessed PrU risk level in relation to PrU incidence and medical severity. Outcomes of this research will contribute to future guidelines for more precise preventive nursing practices and refinement of PrU prevention guidelines. Clinical Trial Registration: NCT02996331 .

Effects of 4-aminopyridine on cardiac repolarization, PR interval, and heart rate in patients with spinal cord injury.

PubMed

Isoda, Wakana C; Segal, Jack L

2003-02-01

To determine the effects of 4-aminopyridine (4-AP) on heart rate and PR, QT, and QTc intervals in patients with longstanding spinal cord injury (SCI). Randomized, active-treatment-controlled, dose level-blinded study, with allocation concealed. University-affiliated, tertiary care medical center. Sixty otherwise healthy male and female outpatients with traumatic SCI of more than 1 year's duration. Intervention. Oral administration and dose titration to tolerance of an immediate-release formulation of 4-AP. The PR interval, heart rate, QT interval, and QTc interval obtained from standard 12-lead electrocardiograms (ECGs) at baseline (before administration of 4-AP) and after 1 month of treatment were compared. The QTc intervals were derived by using Bazett's formula (equation) incorporated into standard computerized analyses of 12-lead ECG printouts. The paired t test was performed to test for the significance of differences between means and variances. No statistically significant differences were noted in heart rate or between ECG time intervals measured at baseline and after 1 month of treatment with 4-AP among all patients with SCI or between subgroups stratified by injury level (tetraplegia, paraplegia) or sex. During the 1-month period that 4-AP was administered, the heart rate and PR, QT, and QTc intervals all remained unchanged and stayed well within normal range in comparison to literature-derived control values. 4-Aminopyridine does not appear to influence the length of cardiac time intervals or heart rate and, hence, is unlikely to cause potentially life-threatening ventricular dysrrhythmias when administered long-term and taken orally in dosages of up to 30 mg/day. Specifically, cardiac repolarization (QTc interval) is unaffected in patients with SCI who continuously receive 4-AP for up to 1 month.

Direct conversion from tramadol to tapentadol prolonged release for moderate to severe, chronic malignant tumour-related pain.

PubMed

Kress, H G; Koch, E D; Kosturski, H; Steup, A; Karcher, K; Dogan, C; Etropolski, M; Eerdekens, M

2016-10-01

A recent randomized-withdrawal, active- and placebo-controlled, double-blind phase 3 study showed that tapentadol prolonged release (PR) was effective and well tolerated for managing moderate to severe, chronic malignant tumour-related pain in patients who were opioid naive or dissatisfied with current treatment (Pain Physician, 2014, 17, 329-343). This post hoc, subgroup analysis evaluated the efficacy and tolerability of tapentadol PR in patients who previously received and were dissatisfied with tramadol for any reason and who had a pain intensity ≥5 (11-point numerical rating scale) before converting directly to tapentadol PR. In the original study, eligible patients had been randomized (2:1) and titrated to their optimal dose of tapentadol PR (100-250 mg bid) or morphine sulphate-controlled release (40-100 mg bid) over 2 weeks. The present report focuses on results during the titration period for a subgroup of patients randomized to tapentadol PR after having been on tramadol treatment prior to randomization in the study (n = 129). Results for this subgroup are compared with results for all 338 patients who received tapentadol PR during titration (overall tapentadol PR group). Responder rates (responders: completed titration, mean pain intensity <5 [0-10 scale] and ≤20 mg/day rescue medication during last 3 days) were slightly better for the tramadol/tapentadol PR subgroup (69.8% [90/129]) vs. the overall tapentadol PR group (63.9% [214/335]). Tolerability profiles were comparable for both groups. Results of this subgroup analysis indicate that patients with cancer pain could safely switch from prior treatment with the weak centrally acting analgesic tramadol directly to the strong centrally acting analgesic tapentadol PR, for an improved analgesic therapy for severe pain. WHAT DOES THIS STUDY ADD?: Results of this post hoc analysis show that patients who had received prior tramadol therapy could switch directly to tapentadol PR, with the majority (˜70%) experiencing improved efficacy. © 2016 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

Sodium channel blockade with QRS widening after an escitalopram overdose.

PubMed

Schreffler, Susan M; Marraffa, Jeanna M; Stork, Christine M; Mackey, Jennifer

2013-09-01

Escitalopram is rarely associated with prolongation of the QTc interval; however, there are no reported cases of QRS complex widening associated with escitalopram overdose. We report a case of a patient who presented with both QRS complex widening and QTc interval prolongation after an escitalopram overdose. A 16-year-old girl presented to the emergency department after ingestion of escitalopram, tramadol/acetaminophen, and hydrocodone/acetaminophen. Laboratory results were significant for 4-hour acetaminophen 21.1 μg/mL. Serum electrolytes including potassium, magnesium, and calcium were all normal. Initial electrocardiogram (ECG) revealed a widened QRS with an incomplete right bundle branch pattern. After administration of 100-mEq sodium bicarbonate, a repeat ECG revealed narrowing of the QRS complex and a prolonged QTc interval. Magnesium sulfate 2 g intravenous and sodium bicarbonate drip were initiated. A repeat ECG, 1 hour after the second, revealed normalization of the QRS complex and QTc interval. Prolongation of the QTc interval is an expected effect of escitalopram. Both escitalopram and citalopram are metabolized to the cardiotoxic metabolite S-didesmethylcitalopram and didesmethylcitalopram, respectively, which have been implicated in numerous cardiac abnormalities including widening of the QRS complex. Although never previously described with escitalopram, this mechanism provides a reasonable explanation for the QRS complex widening and incomplete right bundle branch block that occurred in our patient. Both QRS complex widening and QTc interval prolongation should be monitored in cases of escitalopram and citalopram overdoses.

Clinical and electrocardiographic presentations of transient trifascicular block in three cats.

PubMed

Oxford, Eva M; Giacomazzi, Flavia B; Moïse, N Sydney; Santilli, Roberto A

2018-06-01

This report describes transient trifascicular block in three cats presented with lethargy and inappetence, and elevated cardiac troponin I concentrations. The electrocardiogram (ECG) of cat 1 showed a sinus rhythm with pronounced first-degree atrioventricular (AV) block, right bundle branch block, and left anterior fascicular block. The ECG of cat 2 showed truncular left bundle branch block alternating with left anterior fascicular block coupled with prolonged PR intervals, second-degree heart block, and paroxysmal third-degree AV block. The ECG of cat 3 showed first-degree AV block with concomitant right bundle branch block. The diagnosis of trifascicular block was made when paroxysmal third-degree AV block was documented. All cats recovered with medical management within weeks. Each cat resumed a sinus rhythm. Elevated cardiac troponin I concentrations suggested myocarditis that improved. Copyright © 2018 Elsevier B.V. All rights reserved.

Manifestations of Lyme carditis.

PubMed

Kostić, Tomislav; Momčilović, Stefan; Perišić, Zoran D; Apostolović, Svetlana R; Cvetković, Jovana; Jovanović, Andriana; Barać, Aleksandra; Šalinger-Martinović, Sonja; Tasić-Otašević, Suzana

2017-04-01

The first data of Lyme carditis, a relatively rare manifestation of Lyme disease, were published in eighties of the last century. Clinical manifestations include syncope, light-headedness, fainting, shortness of breath, palpitations, and/or chest pain. Atrioventricular (AV) electrical block of varying severity presents the most common conduction disorder in Lyme carditis. Although is usually mild, AV block can fluctuates rapidly and progress from a prolonged P-R interval to a His-Purkinje block within minutes to hours and days. Rarely, Lyme disease may be the cause of endocarditis, while some studies and reports, based on serological and/or molecular investigations, have suggested possible influence of Borrelia burgdorferi on degenerative cardiac valvular disease. Myocarditis, pericarditis, pancarditis, dilated cardiomyopathy, and heart failure have also been described as possible manifestations of Lyme carditis. The clinical course of Lyme carditis is generally mild, short term, and in most cases, completely reversible after adequate antibiotic treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and Z-drugs consumption in nine European countries.

PubMed

Clay, Emilie; Falissard, Bruno; Moore, Nicholas; Toumi, Mondher

2013-04-01

Benzodiazepines (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone, altogether Z-drugs) are most commonly prescribed for the treatment of insomnia. However, long-term use of BZD/Z-drugs is associated with major adverse events including, but not limited to, falls and fractures, domestic and traffic accidents, confusion, cognitive impairment, Alzheimer's disease and cancer. The prolonged use of these drugs is thought to be related to severe withdrawal symptoms and potential dependency. The chronic and extensive use of BZD/Z drugs has become a public health issue and has led to multiple campaigns to reduce both prescription and consumption of BZD/Z-drugs. Prolonged-release (PR) melatonin is the first of a new class of melatonin receptor agonist drugs that has demonstrated clinically relevant efficacy on improving quality of sleep and morning alertness, with a good safety profile. This study aimed to analyze and evaluate the impact of anti-BZD/Z-drugs campaigns and the availability of alternative pharmacotherapy (PR-melatonin) on the consumption of BZD and Z-drugs in several European countries. Annual sales data from nine European countries were extracted from the IMS sales database and analyzed to determine whether trends in use of these treatment options were attributed to campaigns and/or availability and affordability of safer alternatives on the market. Campaigns aiming to reduce the use of BZD/Z-drugs failed when they were not associated with the availability and market uptake of PR-melatonin. The reimbursement of PR-melatonin supports better penetration rates and a higher reduction in sales for BZD/Z-drugs.

Creation of a genetic calcium channel blocker by targeted gem gene transfer in the heart.

PubMed

Murata, Mitsushige; Cingolani, Eugenio; McDonald, Amy D; Donahue, J Kevin; Marbán, Eduardo

2004-08-20

Calcium channel blockers are among the most commonly used therapeutic drugs. Nevertheless, the utility of calcium channel blockers for heart disease is limited because of the potent vasodilatory effect that causes hypotension, and other side effects attributable to blockade of noncardiac channels. Therefore, focal calcium channel blockade by gene transfer is highly desirable. With a view to creating a focally applicable genetic calcium channel blocker, we overexpressed the ras-related small G-protein Gem in the heart by somatic gene transfer. Adenovirus-mediated delivery of Gem markedly decreased L-type calcium current density in ventricular myocytes, resulting in the abbreviation of action potential duration. Furthermore, transduction of Gem resulted in a significant shortening of the electrocardiographic QTc interval and reduction of left ventricular systolic function. Focal delivery of Gem to the atrioventricular (AV) node significantly slowed AV nodal conduction (prolongation of PR and AH intervals), which was effective in the reduction of heart rate during atrial fibrillation. Thus, these results indicate that gene transfer of Gem functions as a genetic calcium channel blocker, the local application of which can effectively modulate cardiac electrical and contractile function.

Long-Term Outcome and Predictors of Noninstitutionalized Survival Subsequent to Prolonged Intensive Care Unit Stay After Cardiac Surgical Procedures.

PubMed

Manji, Rizwan A; Arora, Rakesh C; Singal, Rohit K; Hiebert, Brett; Moon, Michael C; Freed, Darren H; Menkis, Alan H

2016-01-01

There are minimal data on long-term functional survival (alive and not institutionalized) in patients undergoing cardiac operations who require a prolonged intensive care unit length of stay (prICULOS). We sought to describe 1- and 5-year functional survival in patients who had a prICULOS (ICULOS ≥ 5 days) and determine predictors of functional survival at 1 year. Data were obtained from linked clinical and administrative databases from January 1, 2000 to December 31, 2011 to conduct this retrospective single-region analysis. Logistic regression was used to develop a model predicting functional survival at 1 year for patients who had a prICULOS after cardiac operations. There were 9,545 admissions to the ICU after cardiac operations; of these patients, 728 (7.6%) experienced a prICULOS. There was an increasing trend in patients who had a prICULOS over this study period. The functional survival at 1 and 5 years from the surgical procedure for the non-prICULOS versus the prICULOS cohort was 1 year (94.9% versus 73.9%) and 5 years (84.9% versus 53.8%) (p < 0.001). Factors associated with lower rates of functional survival at 1 year were age 80 years or older, female sex, peripheral vascular disease, preoperative renal dysfunction, cerebrovascular disease, preoperative infection, need for extracorporeal membrane oxygenation/ventricular assist device (ECMO/VAD) after cardiotomy, number of days on mechanical ventilation, and number of days in the ICU beyond 5 days (area under the receiver operating characteristic [ROC] curve = 0.766). The majority of patients who had a prICULOS experienced successful functional survival up to 5 years after cardiac operations. Identification of risk factors for poor functional survival may be of assistance to clinicians, patients, and families for prognostication and decision making. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Effects of renal sympathetic denervation on heart rate and atrioventricular conduction in patients with resistant hypertension.

PubMed

Ukena, Christian; Mahfoud, Felix; Spies, Aline; Kindermann, Ingrid; Linz, Dominik; Cremers, Bodo; Laufs, Ulrich; Neuberger, Hans-Ruprecht; Böhm, Michael

2013-09-10

Renal sympathetic denervation (RDN) reduces sympathetic activity and blood pressure (BP) in patients with resistant hypertension. The present study aimed to investigate the effects of RDN on HR and other electrocardiographic parameters. 136 patients aged 62.2 ± 0.8 years (58% male, BP 177 ± 2/93 ± 1 mmHg) with resistant hypertension underwent RDN. BP and a 12-lead electrocardiogram (ECG) were recorded before, 3 months (n=127), and 6 months (n=88) after RDN. After 3 months (3M) and 6 months (6M), systolic BP was reduced by 25.5 ± 2.4 mmHg (p<0.0001) and 28.1 ± 3 mmHg (p<0.0001). HR at baseline was 66.1 ± 1 beats per minute (bpm) and was reduced by 2.6 ± 0.8 bpm after 3 months (p=0.001) and 2.1 ± 1.1 bpm after 6 months (p=0.046). Patients with HR at baseline between 60-71 bpm and ≥ 71 bpm had a reduction of 2.9 ± 7.6 bpm (p=0.008) and 9.0 ± 8.6 bpm (p<0.0001), respectively, whereas in patients with baseline HR<60 bpm HR slightly increased after 3 months (2.7 ± 8.4 bpm; p=0.035). Neither baseline HR nor change of HR correlated with the reduction of systolic BP. The PR interval was prolonged by 11.3 ± 2.5 ms (p<0.0001) and 10.3 ± 2.5 ms (p<0.0001) at 3 and 6 months after RDN, respectively. Renal sympathetic denervation reduced heart rate and the PR interval as indicators of cardiac autonomic activity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

QT prolongation and sudden cardiac death risk in hypertrophic cardiomyopathy.

PubMed

Patel, Salma I; Ackerman, Michael J; Shamoun, Fadi E; Geske, Jeffrey B; Ommen, Steve R; Love, William T; Cha, Stephen S; Bos, Johan M; Lester, Steven J

2018-03-07

Risk assessment for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains complex. The goal of this study was to assess electrocardiogram (ECG)-derived risk factors on SCD in a large HCM population Methods: Retrospective review of adults with HCM evaluated at Mayo Clinic, Rochester, MN from 1 December 2002 to 31 December 2012 was performed. Data inclusive of ECG and 24-hour ambulatory Holter monitor were assessed. SCD events were documented by ventricular fibrillation (VF) noted on implantable cardioverter defibrillator (ICD), or appropriate VT or VF-terminating ICD shock. Overall, 1615 patients (mean age 53.7 ± 15.2 years; 943 males, 58.4%) were assessed, with mean follow-up 2.46 years and 110 SCD events. Via logistic regression (n = 820), the odds of SCD increased with increasing number of conventional risk factors. With one risk factor the OR was 4.88 (p < .0001; CI 2.22-10.74), two risk factors the OR was 6.922 (p < .0001; CI 2.94-16.28) and three or more risk factors, the OR was 13.997 (p < .0001; CI 5.649-34.68). Adding QTc > 450 to this logistic regression model had OR 1.722 (p = .04, CI 1.01-2.937) to predict SCD. QTc ≥ 450 was a significant predictor for death (HR 1.88, p = .021, CI 1.10-3.20). There was no correlation between sinus bradycardia, sinus tachycardia, first degree AV block, atrial fibrillation, left bundle branch block, right bundle branch block, premature atrial complexes, premature ventricular complexes, supraventricular tachycardia, PR interval, QRS interval and SCD. Prolonged QTc was a risk factor for SCD and death even when controlling for typical risk factors.

In vitro electrocardiographic and cardiac ion channel effects of (-)-epigallocatechin-3-gallate, the main catechin of green tea.

PubMed

Kang, Jiesheng; Cheng, Hsien; Ji, Junzhi; Incardona, Josephine; Rampe, David

2010-08-01

Epigallocatechin-3-gallate (EGCG) is the major catechin found in green tea. EGCG is also available for consumption in the form of concentrated over-the-counter nutritional supplements. This compound is currently undergoing clinical trials for the treatment of a number of diseases including multiple sclerosis, and a variety of cancers. To date, few data exist regarding the effects of EGCG on the electrophysiology of the heart. Therefore, we examined the effects of EGCG on the electrocardiogram recorded from Langendorff-perfused guinea pig hearts and on cardiac ion channels using patch-clamp electrophysiology. EGCG had no significant effects on the electrocardiogram at concentrations of 3 and 10 microM. At 30 microM, EGCG prolonged PR and QRS intervals, slightly shortened the QT interval, and altered the shape of the ST-T-wave segment. The ST segment merged with the upstroke of the T wave, and we noted a prolongation in the time from the peak of the T wave until the end. Patch-clamp studies identified the KvLQT1/minK K(+) channel as a target for EGCG (IC(50) = 30.1 microM). In addition, EGCG inhibited the cloned human cardiac Na(+) channel Na(v)1.5 in a voltage-dependent fashion. The L-type Ca(2+) channel was inhibited by 20.8% at 30 microM, whereas the human ether-a-go-go-related gene and Kv4.3 cardiac K(+) channels were less sensitive to inhibition by EGCG. ECGC has a number of electrophysiological effects in the heart, and these effects may have clinical significance when multigram doses of this compound are used in human clinical trials or through self-ingestion of large amounts of over-the-counter products enriched in EGCG.

Increased risk of QT prolongation associated with atherosclerotic diseases in arseniasis-endemic area in southwestern coast of Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, C.-H.; Chen, C.-L.; Hsiao, C.K.

2009-09-15

Chronic arsenic exposure has been documented to be associated with various cardiovascular diseases. We aimed to investigate 1) the increased risk of QT prolongation in chronic arsenic exposure, and 2) the relationships of cardiac repolarization (QT interval duration) with ischemic heart disease and carotid atherosclerosis. We studied 280 men and 355 women living in the endemic area of arseniasis in southwestern Taiwan. QT intervals in electrocardiogram and carotid intima-media thickness (IMT) by ultrasonography were measured. Ischemic heart disease was diagnosed by history or abnormal electrocardiogram. Significant associations of the corrected QT interval (QTc) duration with ischemic heart disease and carotidmore » intima-medium thickness and plaque were observed after adjustment for various risk factors in the multiple linear regression analysis (all p values < 0.05). Three indices of chronic arsenic exposure were all significantly associated with the risk of QTc prolongation showing dose-response relationships (p < 0.001). Chronic arsenic exposure was dose-dependently associated with the risk of QTc prolongation. Ischemic heart disease and carotid atherosclerosis were significantly associated with QTc intervals in chronic arsenic exposure. QTc prolongation might be suggested as an early biomarker for ischemic heart disease or carotid atherosclerosis in population with previous exposure to arsenic.« less

The association of long-term glycaemic variability versus sustained chronic hyperglycaemia with heart rate-corrected QT interval in patients with type 2 diabetes.

PubMed

Su, Jian-Bin; Yang, Xiao-Hua; Zhang, Xiu-Lin; Cai, Hong-Li; Huang, Hai-Yan; Zhao, Li-Hua; Xu, Feng; Chen, Tong; Cheng, Xing-Bo; Wang, Xue-Qin; Lu, Yan

2017-01-01

Prolonged heart rate-corrected QT(QTc) interval is related to ventricular arrhythmia and cardiovascular mortality, with considerably high prevalence of type 2 diabetes. Additionally, long-term glycaemic variability could be a significant risk factor for diabetic complications in addition to chronic hyperglycaemia. We compared the associations of long-term glycaemic variability versus sustained chronic hyperglycaemia with the QTc interval among type 2 diabetes patients. In this cross-sectional study, 2904 type 2 diabetes patients were recruited who had undergone at least four fasting plasma glucose (FPG) and 2-hour postprandial plasma glucose (PPG) measurements (at least once for every 3 months, respectively) during the preceding year. Long-term glycaemic variabilities of FPG and 2-hour PPG were assessed by their standard deviations (SD-FPG and SD-PPG, respectively), and chronic fasting and postprandial hyperglycaemia were assessed by their means (M-FPG and M-PPG, respectively). HbA1c was also determined upon enrolment to assess current overall glycaemic control. QTc interval was estimated from resting 12-lead electrocardiograms, and more than 440 ms was considered abnormally prolonged. Patients with prolonged QTc interval (≥440 ms) had greater M-FPG, M-PPG, SD-PPG and HbA1c than those with normal QTc interval but comparable SD-FPG. QTc interval was correlated with M-FPG, M-PPG, SD-PPG and HbA1c (r = 0.133, 0.153, 0.245 and 0.207, respectively, p = 0.000) but not with SD-FPG (r = 0.024, p = 0.189). After adjusting for metabolic risk factors via multiple linear regression analysis, SD-PPG, M-PPG and HbA1c (t = 12.16, 2.69 and 10.16, respectively, p = 0.000) were the major independent contributors to the increased QTc interval. The proportion of prolonged QTc interval increased significantly from 10.9% to 14.2% to 26.6% for the first (T1) to second (T2) to third (T3) tertiles of SD-PPG. After adjusting via multiple logistic regression analysis, the odd ratios of prolonged QTc interval of the T2 and T3 versus the T1 of SD-PPG were 1.15 (95% CI, 0.82-1.60) and 2.62 (1.92-3.57), respectively. Increased long-term variability of PPG is a strong independent risk factor for prolonged QTc interval in type 2 diabetes patients, in addition to long-term postprandial hyperglycaemia and current HbA1c.

Underestimated and unreported prolonged QTc by automated ECG analysis in patients on methadone: can we rely on computer reading?

PubMed

Talebi, Soheila; Azhir, Alaleh; Zuber, Sam; Soman, Sandeep; Visco, Ferdinand; Totouom-Tangho, Holly; Kalantar, Hossein; Worku Hassen, Getaw

2015-04-01

Recognition of prolonged corrected QT (QTc) interval is of particular importance, especially when using medications known to prolong QTc interval. Methadone can prolong the QTc interval and has the potential to induce torsades de pointes. The objective of this study is to investigate the accuracy of computerized ECG analysis in correctly identifying and reporting QTc interval in patients on methadone. We conducted a retrospective review of ECGs in the Muse electronic database of patients on methadone who are above 18 years old between January 2012 and December 2013 at an urban community hospital. ECGs were analyzed by the Marquette 12SL ECG Analysis Program (GE'Healthcare) reviewed by a cardiologist. A total of 826 ECGs of patients on methadone were examined manually for the QTc interval, of which 625 (75.7%) had QTc less than 470 ms, 149 (18%) had QTc between 470-499 ms and 52 (6.3%) had QTc more than 499 ms. QTc between 470-499 ms was underestimated by machine in 19 (12.8%) ECGs and QTc more than 499 ms was underestimated in 10 (19.6%) when compared to manually calculated QTc. QTc prolongation was underreported in 63 ECGs (48.5%) of those whose QTc between 470-499 ms and in 1 ECG (2.4%) of those whose QTc was more than 499 ms. QTc can be underestimated or unreported by the computer analysis. Physicians not only should calculate QTc manually but also examine the actual QTc value displayed on the report before concluding that this parameter is normal, especially in patients who are at risk of QTc prolongation.

A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation derived from the effects of terfenadine, cisapride and E-4031 in the conscious chronic av node--ablated, His bundle-paced dog.

PubMed

Nolan, Emily R; Feng, Meihua Rose; Koup, Jeffrey R; Liu, Jing; Turluck, Daniel; Zhang, Yiqun; Paulissen, Jerome B; Olivier, N Bari; Miller, Teresa; Bailie, Marc B

2006-01-01

Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/pharmacodynamic model of repolarization prolongation was generated from these data. Three male beagle dogs underwent radiofrequency AV nodal ablation, and placement of a His bundle-pacing lead and programmable pacemaker under anesthesia. Each dog was restrained in a sling for a series of increasing dose infusions of each drug while maintained at a constant heart rate of 80 beats/min. RT interval, a surrogate for QT interval in His bundle-paced dogs, was recorded throughout the experiment. E-4031 induced a statistically significant RT prolongation at the highest three doses. Cisapride resulted in a dose-dependent increase in RT interval, which was statistically significant at the two highest doses. Terfenadine induced a dose-dependent RT interval prolongation with a statistically significant change occurring only at the highest dose. The relationship between drug concentration and RT interval change was described by a sigmoid E(max) model with an effect site. Maximum RT change (E(max)), free drug concentration at half of the maximum effect (EC(50)), and free drug concentration associated with a 10 ms RT prolongation (EC(10 ms)) were estimated. A linear correlation between EC(10 ms) and HERG IC(50) values was identified. The conscious dog with His bundle-pacing detects delayed cardiac repolarization related to I(Kr) inhibition, and detects repolarization change induced by drugs with activity at multiple ion channels. A clinically relevant sensitivity and a linear correlation with in vitro HERG data make the conscious His bundle-paced dog a valuable tool for detecting repolarization effect of new chemical entities.

Analyzing Thorough QT Study 1 & 2 in the Telemetric and Holter ECG Warehouse (THEW) using Hannover ECG System HES : A validation study.

PubMed

Khawaja, A; Petrovic, R; Safer, A; Baas, T; Dössel, O; Fischer, R

2010-01-01

Following the ICH E14 clinical evaluation guideline [1], the measurement of QT/QTc interval prolongation has become the standard surrogate biomarker for cardiac drug safety assessment and the faith of a drug development. In Thorough QT (TQT) study, a so-called positive control is employed to assess the ability of this study to detect the endpoint of interest, i.e. the QT prolongation by about five milliseconds. In other words the lower bound of the one-sided 95% confidence interval (CI) must be above 0 [ms]. Fully automated detection of ECG fiducial points and measurement of the corresponding intervals including QT intervals and RR intervals vary between different computerized algorithms. In this work we demonstrate the ability and reliability of Hannover ECG System (HES(®)) to assess drug effects by detecting QT/QTc prolongation effects that meet the threshold of regulatory concern as mentioned by using THEW database studies namely TQT studies one and two.

The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens.

PubMed

Elming, H; Holm, E; Jun, L; Torp-Pedersen, C; Køber, L; Kircshoff, M; Malik, M; Camm, J

1998-09-01

To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality, as well as in cardiac morbidity, in a general population. The QT interval was measured in all leads from a standard 12-lead ECG in a random sample of 1658 women and 1797 men aged 30-60 years. QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads. All cause mortality over 13 years, and cardiovascular mortality as well as cardiac morbidity over 11 years, were the main outcome parameters. Subjects with a prolonged QT interval (430 ms or more) or prolonged QT interval dispersion (80 ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms, or whose QT interval dispersion was less than 30 ms. Cardiovascular death relative risk ratios, adjusted for age, gender, myocardial infarct, angina pectoris, diabetes mellitus, arterial hypertension, smoking habits, serum cholesterol level, and heart rate were 2.9 for the QT interval (95% confidence interval 1.1-7.8) and 4.4 for QT interval dispersion (95% confidence interval 1.0-19-1). Fatal and non-fatal cardiac morbidity relative risk ratios were similar, at 2.7 (95% confidence interval 1.4-5.5) for the QT interval and 2.2 (95% confidence interval 1.1-4.0) for QT interval dispersion. Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.

QTc prolongation after brain surgery.

PubMed

Capparelli, Federico J; Abello, Mauricio; Patricio Maskin, L; Arista, Eugenia; Hlavnicka, Alejandro; Diaz, Maria Fernanda; Varela, Daniel; Wainsztein, Nestor A

2013-03-01

Abnormalities observed in the electrocardiogram (ECG) after acute central nervous system (CNS) events have been reported. Our objective was to assess the incidence of heart rate-corrected QT interval (QTc) prolongation in patients admitted to the intensive care unit (ICU) after brain surgery. Admission standard 12-lead ECGs were analyzed blinded to patient data. The QT interval was measured and Bazzett's formula was used to obtain QTc. Prolonged QTc was defined as ≧450 ms. We included 114 patients in the study. The mean age was 49±17 years. Brain neoplasm was the surgical indication in 90% of the patients. The mean QTc was 470±42 ms. Prolonged QTc was found in 71% patients. The heart rate-corrected QT interval was between 450 ms and 500 ms in 52% and >500 ms in 19% of the patients. The heart rate and concentration of serum glucose were higher in the prolonged QTc group. Only 7·5% of all patients had hypokalemia (≤3 mEq/l). In the prolonged QTc group 9·2% had hypokalemia compared to 3·2% in normal QTc patients (P = 0·406). There were no significant associations between categories of QTc and the serum levels of creatinine, magnesium, calcium, sodium, or pH. Phenytoin and metoclopramide were not frequently used in patients with prolonged QTc. This study supports our hypothesis that prolonged QTc is frequently observed after a brain surgery. Hypokalemia, hypocalcaemia, and drugs such as metoclopramide or phenytoin could not explain the high incidence of prolonged QTc. Brain injury during a surgical procedure may be one of the primary causes of QTc prolongation after neurosurgery.

[Risk management of QT-prolonging drugs by community pharmacists using a mobile electrocardiograph].

PubMed

Shinozaki, Kohki

2010-11-01

Prolongation of the QT interval is associated with a high risk of serious arrhythmia, i.e., torsades de pointes (TdP). However, in many cases, the QT-prolonging drug(s) is prescribed without performing a thorough check-up of the patient's condition, especially an electrocardiogram. In addition to patient interview, we used an electrocardiogram obtained with a mobile electrocardiograph (RMH-ECG) in a community pharmacy in order to improve the risk management for QT-prolonging drugs. A comparison of the results obtained using RMH-ECG (modified I) and 12-lead ECG (I) revealed that both corrected QT (QTc) values were almost identical, and the correlation coefficient was 0.96. In one month, 5 of 948 patients who visited our pharmacy and continuously took QT-prolonging drugs had additional risk factors for TdP (advanced age, female, and drug-drug interaction). We monitored the QT interval of one of these patients. She had received erythromycin for 19 months along with other drugs metabolized by a P450 (CYP3A4); benidipine and prednisolone (for over 2 years), and tacrolimus (for 13 weeks). Three RMH-ECG tests at every 2 weeks revealed that QTcs were normal (0.43-0.45 s); therefore, we dispensed drugs without any change in the prescription. Approximately 1 in 1200 individuals has a prolonged QT interval without any subjective symptoms, and the time window of drug-induced TdP is considered to be from several hours to months after taking these drugs. Therefore, we think that an ECG test should be performed in community pharmacies before dispensing QT-prolonging drugs and that the QT interval should be monitored.

Genetics and fine mapping of a purple leaf gene, BoPr, in ornamental kale (Brassica oleracea L. var. acephala).

PubMed

Liu, Xiao-Ping; Gao, Bao-Zhen; Han, Feng-Qing; Fang, Zhi-Yuan; Yang, Li-Mei; Zhuang, Mu; Lv, Hong-Hao; Liu, Yu-Mei; Li, Zhan-Sheng; Cai, Cheng-Cheng; Yu, Hai-Long; Li, Zhi-Yuan; Zhang, Yang-Yong

2017-03-14

Due to its variegated and colorful leaves, ornamental kale (Brassica oleracea L. var. acephala) has become a popular ornamental plant. In this study, we report the fine mapping and analysis of a candidate purple leaf gene using a backcross population and an F 2 population derived from two parental lines: W1827 (with white leaves) and P1835 (with purple leaves). Genetic analysis indicated that the purple leaf trait is controlled by a single dominant gene, which we named BoPr. Using markers developed based on the reference genome '02-12', the BoPr gene was preliminarily mapped to a 280-kb interval of chromosome C09, with flanking markers M17 and BoID4714 at genetic distances of 4.3 cM and 1.5 cM, respectively. The recombination rate within this interval is almost 12 times higher than the usual level, which could be caused by assembly error for reference genome '02-12' at this interval. Primers were designed based on 'TO1000', another B. oleracea reference genome. Among the newly designed InDel markers, BRID485 and BRID490 were found to be the closest to BoPr, flanking the gene at genetic distances of 0.1 cM and 0.2 cM, respectively; the interval between the two markers is 44.8 kb (reference genome 'TO1000'). Seven annotated genes are located within the 44.8 kb genomic region, of which only Bo9g058630 shows high homology to AT5G42800 (dihydroflavonol reductase), which was identified as a candidate gene for BoPr. Blast analysis revealed that this 44.8 kb interval is located on an unanchored scaffold (Scaffold000035_P2) of '02-12', confirming the existence of assembly error at the interval between M17 and BoID4714 for reference genome '02-12'. This study identified a candidate gene for BoPr and lays a foundation for the cloning and functional analysis of this gene.

QT prolongation in the newborn and maternal alcoholism.

PubMed

Krasemann, Thomas

2004-10-01

I discuss a newborn whose mother is addicted to alcohol. On the third day of life, the newborn was found to have ventricular tachycardia. After spontaneous termination of the abnormal rhythm, the duration of the corrected QT interval was 0.48 s. During the next days, the duration of the interval normalized, and has now remained stable for 5 years. I conclude that the so-called "alcohol withdrawal syndrome of the newborn" might cause postnatal prolongation of the QT interval.

Bisphenol A Exposure and Cardiac Electrical Conduction in Excised Rat Hearts

PubMed Central

Jaimes, Rafael; Asfour, Huda; Swift, Luther M.; Wengrowski, Anastasia M.; Sarvazyan, Narine; Kay, Matthew W.

2014-01-01

Background: Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys, and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased urinary BPA concentrations and cardiovascular disease, yet the direct effects of BPA on the heart are unknown. Objectives: The goal of our study was to measure the effect of BPA (0.1–100 μM) on cardiac impulse propagation ex vivo using excised whole hearts from adult female rats. Methods: We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential in excised rat hearts exposed to BPA via perfusate media. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. Results: Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1–100 μM BPA), prolonged action potential duration (1–100 μM BPA), and delayed atrioventricular conduction (10–100 μM BPA). These effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals and dropped ventricular beats, and eventually resulted in complete heart block. Conclusions: Our results show that acute BPA exposure slowed electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA’s effect on heart electrophysiology and determining whether chronic in vivo exposure can cause or exacerbate conduction abnormalities in patients with preexisting heart conditions and in other high-risk populations. Citation: Posnack NG, Jaimes R III, Asfour H, Swift LM, Wengrowski AM, Sarvazyan N, Kay MW. 2014. Bisphenol A exposure and cardiac electrical conduction in excised rat hearts. Environ Health Perspect 122:384–390; http://dx.doi.org/10.1289/ehp.1206157 PMID:24487307

Associations of electrocardiographic P-wave characteristics with left atrial function, and diffuse left ventricular fibrosis defined by cardiac magnetic resonance: The PRIMERI Study.

PubMed

Tiffany Win, Theingi; Ambale Venkatesh, Bharath; Volpe, Gustavo J; Mewton, Nathan; Rizzi, Patricia; Sharma, Ravi K; Strauss, David G; Lima, Joao A; Tereshchenko, Larisa G

2015-01-01

Abnormal P-terminal force in lead V1 (PTFV1) is associated with an increased risk of heart failure, stroke, atrial fibrillation, and death. Our goal was to explore associations of left ventricular (LV) diffuse fibrosis with left atrial (LA) function and electrocardiographic (ECG) measures of LA electrical activity. Patients without atrial fibrillation (n = 91; mean age 59.5 years; 61.5% men; 65.9% white) with structural heart disease (spatial QRS-T angle ≥105° and/or Selvester QRS score ≥5 on ECG) but LV ejection fraction >35% underwent clinical evaluation, cardiac magnetic resonance, and resting ECG. LA function indices were obtained by multimodality tissue tracking using 2- and 4-chamber long-axis images. T1 mapping and late gadolinium enhancement were used to assess diffuse LV fibrosis and presence of scar. P-prime in V1 amplitude (PPaV1) and duration (PPdV1), averaged P-wave-duration, PR interval, and P-wave axis were automatically measured using 12 SLTM algorithm. PTFV1 was calculated as a product of PPaV1 and PPdV1. In linear regression after adjustment for demographic characteristics, body mass index, maximum LA volume index, presence of scar, and LV mass index, each decile increase in LV interstitial fibrosis was associated with 0.76 mV*ms increase in negative abnormal PTFV1 (95% confidence interval [CI] -1.42 to -0.09; P = .025), 15.3 ms prolongation of PPdV1 (95% CI 6.9 to 23.8; P = .001) and 5.4 ms prolongation of averaged P-duration (95% CI 0.9-10.0; P = .020). LV fibrosis did not affect LA function. PPaV1 and PTFV1 were associated with an increase in LA volumes and decrease in LA emptying fraction and LA reservoir function. LV interstitial fibrosis is associated with abnormal PTFV1, prolonged PPdV1, and P-duration, but does not affect LA function. Copyright © 2015 Heart Rhythm Society. All rights reserved.

Identification of Two Prion Protein Regions That Modify Scrapie Incubation Time

PubMed Central

Supattapone, Surachai; Muramoto, Tamaki; Legname, Giuseppe; Mehlhorn, Ingrid; Cohen, Fred E.; DeArmond, Stephen J.; Prusiner, Stanley B.; Scott, Michael R.

2001-01-01

A series of prion transmission experiments was performed in transgenic (Tg) mice expressing either wild-type, chimeric, or truncated prion protein (PrP) molecules. Following inoculation with Rocky Mountain Laboratory (RML) murine prions, scrapie incubation times for Tg(MoPrP)4053, Tg(MHM2)294/Prnp0/0, and Tg(MoPrP,Δ23–88)9949/Prnp0/0 mice were ∼50, 120, and 160 days, respectively. Similar scrapie incubation times were obtained after inoculation of these lines of Tg mice with either MHM2(MHM2(RML)) or MoPrP(Δ23–88)(RML) prions, excluding the possibility that sequence-dependent transmission barriers could account for the observed differences. Tg(MHM2)294/Prnp0/0 mice displayed prolonged scrapie incubation times with four different strains of murine prions. These data provide evidence that the N terminus of MoPrP and the chimeric region of MHM2 PrP (residues 108 through 111) both influence the inherent efficiency of prion propagation. PMID:11152514

Historical space weather monitoring of prolonged aurora activities in Japan and in China

NASA Astrophysics Data System (ADS)

Kataoka, Ryuho; Isobe, Hiroaki; Hayakawa, Hisashi; Tamazawa, Harufumi; Kawamura, Akito Davis; Miyahara, Hiroko; Iwahashi, Kiyomi; Yamamoto, Kazuaki; Takei, Masako; Terashima, Tsuneyo; Suzuki, Hidehiko; Fujiwara, Yasunori; Nakamura, Takuji

2017-02-01

Great magnetic storms are recorded as aurora sightings in historical documents. The earliest known example of "prolonged" aurora sightings, with aurora persistent for two or more nights within a 7 day interval at low latitudes, in Japan was documented on 21-23 February 1204 in Meigetsuki, when a big sunspot was also recorded in China. We have searched for prolonged events over the 600 year interval since 620 in Japan based on the catalogue of Kanda and over the 700 year interval since 581 in China based on the catalogues of Tamazawa et al. (2017) and Hayakawa et al. (2015). Before the Meigetsuki event, a significant fraction of the 200 possible aurora sightings in Sòng dynasty (960-1279) of China was detected at least twice within a 7 day interval and sometimes recurred with approximately the solar rotation period of 27 days. The majority of prolonged aurora activity events occurred around the maximum phase of solar cycles rather than around the minimum, as estimated from the 14C analysis of tree rings. They were not reported during the Oort Minimum (1010-1050). We hypothesize that the prolonged aurora sightings are associated with great magnetic storms resulting from multiple coronal mass ejections from the same active region. The historical documents therefore provide useful information to support estimation of great magnetic storm frequency, which are often associated with power outages and other societal concerns.

Safety and Efficacy of a Progressively Prolonged Maintenance Interval of Venom Immunotherapy.

PubMed

Kontou-Fili, Kalliopi; Pitsios, Constantinos; Kompoti, Evangelia; Giannakopoulos, Dionysios; Kouridakis, Spyros

2018-01-01

The long-term protection provided by venom immunotherapy (VIT) is related to the dose administered and to its long duration; the latter, however, becomes inconvenient for patients in countries like Greece, with many islanders or inhabitants of distant mountainous areas. Maintenance interval prolongation reduces the number of office visits - saving time and money - and as a consequence contributes to the patients' compliance. The aim of this prospective study was to evaluate the safety and efficacy of VIT on a progressively prolonged maintenance interval (PPMI). 450 venom-allergic patients were reviewed for participation in our study; all of them were initially treated with a modified rush or an ultrarush protocol using freshly reconstituted, pure venoms. Upon reaching the maintenance dose, the VIT interval was scheduled to be gradually prolonged - by 1 week each time - aiming at a maximal interval of 26 weeks. 267/450 patients consented to participate in our VIT PPMI protocol: 98 were treated with vespid(s) venom, 142 with honeybee venom, and 27 with both. The mean duration of patient follow-up was 9.1 ± 4.2 years. The majority of systemic reactions due to VIT injections occurred up to the 8-weeks PPMI; few additional reactions were documented in a small fraction (2.9%) of our patient population beyond 9 weeks and up to 16 weeks; all were caused by honeybee VIT. No reactions were observed during VIT administration at the 26-week interval. Ninety-six patients reported 204 field sting occurrences by the culprit insect. Ten systemic reactions (8 mild and 2 moderate in severity) were registered between the 9- and 18-week PPMI; the honeybee was the culprit insect in all cases. 108 field stings by the offending insect were sustained beyond the 20- and up to the 26-week PPMI; there were no reactions at all. Progressively prolonging the VIT maintenance interval up to 26 weeks appears to be safe and efficacious. © 2018 S. Karger AG, Basel.

Stride-to-stride variability and complexity between novice and experienced runners during a prolonged run at anaerobic threshold speed.

PubMed

Mo, Shiwei; Chow, Daniel H K

2018-05-19

Motor control, related to running performance and running related injuries, is affected by progression of fatigue during a prolonged run. Distance runners are usually recommended to train at or slightly above anaerobic threshold (AT) speed for improving performance. However, running at AT speed may result in accelerated fatigue. It is not clear how one adapts running gait pattern during a prolonged run at AT speed and if there are differences between runners with different training experience. To compare characteristics of stride-to-stride variability and complexity during a prolonged run at AT speed between novice runners (NR) and experienced runners (ER). Both NR (n = 17) and ER (n = 17) performed a treadmill run for 31 min at his/her AT speed. Stride interval dynamics was obtained throughout the run with the middle 30 min equally divided into six time intervals (denoted as T1, T2, T3, T4, T5 and T6). Mean, coefficient of variation (CV) and scaling exponent alpha of stride intervals were calculated for each interval of each group. This study revealed mean stride interval significantly increased with running time in a non-linear trend (p<0.001). The stride interval variability (CV) maintained relatively constant for NR (p = 0.22) and changed nonlinearly for ER (p = 0.023) throughout the run. Alpha was significantly different between groups at T2, T5 and T6, and nonlinearly changed with running time for both groups with slight differences. These findings provided insights into how the motor control system adapts to progression of fatigue and evidences that long-term training enhances motor control. Although both ER and NR could regulate gait complexity to maintain AT speed throughout the prolonged run, ER also regulated stride interval variability to achieve the goal. Copyright © 2018. Published by Elsevier B.V.

Strategies to reduce the risk of drug-induced QT interval prolongation: a pharmaceutical company perspective.

PubMed

Pollard, C E; Valentin, J-P; Hammond, T G

2008-08-01

Drug-induced prolongation of the QT interval is having a significant impact on the ability of the pharmaceutical industry to develop new drugs. The development implications for a compound causing a significant effect in the 'Thorough QT/QTc Study' -- as defined in the clinical regulatory guidance (ICH E14) -- are substantial. In view of this, and the fact that QT interval prolongation is linked to direct inhibition of the hERG channel, in the early stages of drug discovery the focus is on testing for and screening out hERG activity. This has led to understanding of how to produce low potency hERG blockers whilst retaining desirable properties. Despite this, a number of factors mean that when an integrated risk assessment is generated towards the end of the discovery phase (by conducting at least an in vivo QT assessment) a QT interval prolongation risk is still often apparent; inhibition of hERG channel trafficking and partitioning into cardiac tissue are just two confounding factors. However, emerging information suggests that hERG safety margins have high predictive value and that when hERG and in vivo non-clinical data are combined, their predictive value to man, whilst not perfect, is >80%. Although understanding the anomalies is important and is being addressed, of greater importance is developing a better understanding of TdP, with the aim of being able to predict TdP rather than using an imperfect surrogate marker (QT interval prolongation). Without an understanding of how to predict TdP risk, high-benefit drugs for serious indications may never be marketed.

Brachytherapy with Intratumoral Injections of Radiometal-Labeled Polymers That Thermoresponsively Self-Aggregate in Tumor Tissues.

PubMed

Sano, Kohei; Kanada, Yuko; Kanazaki, Kengo; Ding, Ning; Ono, Masahiro; Saji, Hideo

2017-09-01

Brachytherapy is a type of radiotherapy wherein titanium capsules containing therapeutic radioisotopes are implanted within tumor tissues, enabling high-dose radioirradiation to tumor tissues around the seeds. Although marked therapeutic effects have been demonstrated, brachytherapy needs a complicated implantation technique under general anesthesia and the seeds could migrate to other organs. The aim of this study was to establish a novel brachytherapy using biocompatible, injectable thermoresponsive polymers (polyoxazoline [POZ]) labeled with 90 Y, which can self-aggregate above a specific transition temperature (Tt), resulting in long-term intratumoral retention of radioactivity and therapeutic effect. Therefore, we evaluated the tumor retention of radiolabeled POZ derivatives and their therapeutic effects. Methods: Using oxazoline derivatives with ethyl (Et), isopropyl (Isp), and propyl (Pr) side chains, we synthesized EtPOZ, IspPOZ, Isp-PrPOZ (heteropolymer), and PrPOZ and measured their characteristic Tts. The intratumoral retention of 111 In-labeled POZ was evaluated until 7 d after injection in nude mice bearing PC-3 human prostate cancer. The intratumoral localization of 111 In-labeled POZ derivatives was investigated by an autoradiographic study. Furthermore, a therapeutic study using 90 Y-labeled Isp-PrPOZ was performed, and tumor growth and survival rate were evaluated. Results: The Tts of EtPOZ, IspPOZ, Isp-PrPOZ, and PrPOZ (∼20 kDa) were greater than 70°C, 34°C, 25°C, and 19°C, respectively. In the intratumoral injection study, Isp-PrPOZ and PrPOZ (2,000 μM) with Tts lower than tumor temperature (33.5°C under anesthesia) showed a significantly higher retention of radioactivity at 1 d after injection (73.6% and 73.9%, respectively) than EtPOZ (5.6%) and IspPOZ (15.8%). Even at low injected dose (100 μM), Isp-PrPOZ exhibited high retention (68.3% at 1 d). The high level of radioactivity of Isp-PrPOZ was retained in the tumor 7 d after injection (69.5%). The autoradiographic study demonstrated that the radioactivity of 111 In-labeled Isp-PrPOZ and PrPOZ was localized in a small area. In the therapeutic study using 90 Y-labeled Isp-PrPOZ, significant suppression of tumor growth and prolonged survival rate were achieved in an injection dose-dependent manner compared with that observed for the vehicle-injected group and nonradioactive Isp-PrPOZ-injected group. Conclusion: The injectable 90 Y-labeled Isp-PrPOZ was retained for a prolonged period within tumor tissues via self-aggregation and exhibited marked therapeutic effect, suggesting its usefulness for brachytherapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Improved cell metabolism prolongs photoreceptor survival upon retinal-pigmented epithelium loss in the sodium iodate induced model of geographic atrophy

PubMed Central

Zieger, Marina; Punzo, Claudio

2016-01-01

Age-related macular degeneration (AMD) is characterized by malfunction and loss of retinal-pigmented epithelium (RPE) cells. Because the RPE transfers nutrients from the choriocapillaris to photoreceptor (PR), PRs are affected as well. Geographic atrophy (GA) is an advanced form of AMD characterized by severe vision impairment due to RPE loss over large areas. Currently there is no treatment to delay the degeneration of nutrient deprived PRs once RPE cells die. Here we show that cell-autonomous activation of the key regulator of cell metabolism, the kinase mammalian target of rapamycin complex 1 (mTORC1), delays PR death in the sodium iodate induced model of RPE atrophy. Consistent with this finding loss of mTORC1 in cones accelerates cone death as cones fail to balance demand with supply. Interestingly, promoting rod survival does not promote cone survival in this model of RPE atrophy as both, rods and cones suffer from a sick and dying RPE. The findings suggest that activation of metabolic genes downstream of mTORC1 can serve as a strategy to prolong PR survival when RPE cells malfunction or die. PMID:26883199

Methadone, QTc prolongation and torsades de pointes: Current concepts, management and a hidden twist in the tale?

PubMed

Mujtaba, Sobia; Romero, Jorge; Taub, Cynthia C

2013-12-01

Methadone is a drug that has found widespread utility in the management of opioid addiction and pain. Along with its popularity, methadone has also earned an infamous reputation for causing prolongation of the QT interval and an increased risk of torsades de pointes. In this article we will give a brief overview of the long QT syndromes, followed by an in-depth look at the current pathophysiologic mechanisms of methadone induced QT prolongation, a review of the existing literature and the current concepts regarding the prevention and management of methadone induced torsades de pointes. In addition, we explore the idea and implications of a genetic link between methadone induced prolongation of the QT interval and torsades de pointes.

Readthrough of SCN5A Nonsense Mutations p.R1623X and p.S1812X Questions Gene-therapy in Brugada Syndrome.

PubMed

Teng, Siyong; Huang, Jian; Gao, Zhan; Hao, Jie; Yang, Yuejin; Zhang, Shu; Pu, Jielin; Hui, Rutai; Wu, Yongjian; Fan, Zheng

2017-01-01

Nonsense mutation readthrough is used as a gene-specific treatment in some genetic diseases. The response to readthrough treatment is determined by the readthrough efficiency of various nonsense mutations. In this manuscript, we aimed to explore the harmful effects of nonsense mutation suppression. HEK293 cells were transfected with two SCN5A (encode cardiac Na+ channel) nonsense mutations, p.R1623X and p.S1812X. We applied two readthrough-enhancing methods (either aminoglycosides or a siRNA-targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1)) to suppress these SCN5A nonsense mutations. When either of readthrough methods was used, the sodium channel proteins were examined by western blot and immunoblotting and recorded by whole cell patch-clamp to observe the functional characterization of the restored channels. Upon readthrough treatment, the sodium currents were restored to the mutant cDNAs. These mutations reduced full-length sodium channel protein levels, and the sodium currents were reduced to 3% of wild-type. The mutant cDNA sodium currents were increased to 30% of wild-type, and the fulllength proteins also increased. However, the functional characterization of these channels from cDNAs carrying p.R1623X and p.S1812X exhibited abnormal biophysical properties, including a negative shift in steady-state sodium channel inactivation, a positive shift in sodium channel activation and robust late sodium currents. The ramp test showed prolonged QT intervals. These results demonstrated that readthrough-enhancing methods effectively suppressed nonsense mutations in SCN5A and restored the expression of full-length channels. However, the restored channels may increase the risk of arrhythmia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Association of Age, Sex, Body Size and Ethnicity with Electrocardiographic Values in Community-based Older Asian Adults.

PubMed

Tan, Eugene S J; Yap, Jonathan; Xu, Chang Fen; Feng, Liang; Nyunt, Shwe Zin; Santhanakrishnan, Rajalakshmi; Chan, Michelle M Y; Seow, Swee Chong; Ching, Chi Keong; Yeo, Khung Keong; Richards, A Mark; Ng, Tze Pin; Lim, Toon Wei; Lam, Carolyn S P

2016-07-01

Existing electrocardiographic (ECG) reference values were derived in middle-aged Caucasian adults. We aimed to assess the association of age, sex, body size and ethnicity on ECG parameters in a multi-ethnic Asian population. Resting 12-lead ECG and anthropometric measurements were performed in a community-based cohort of 3777 older Asians (age 64.7±9.1 years, 1467 men, 88.8% Chinese, 7.7% Malay, 3.5% Indian, body mass index [BMI] 24.0±3.9kg/m(2)). Men had longer PR interval, wider QRS, shorter QTc interval and taller SV3. In both sexes, older age was associated with longer PR interval, wider QRS, larger R aVL and more leftward QRS axis, while higher BMI was associated with longer PR interval, wider QRS, larger RaVL and more negative QRS axis. There were significant inter-ethnic differences in QRS duration among men, as well as in PR and QTc intervals among women (all adjusted p<0.05). Findings were similar in a healthy subset of 1158 adults (age 61.2±9.1 years, 365 men) without cardiovascular risk factors. These first community-based ECG data in multi-ethnic older Asians highlight the independent effects of age, sex, body size and ethnicity on ECG parameters. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Common Genetic Variant Risk Score Is Associated With Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study.

PubMed

Strauss, David G; Vicente, Jose; Johannesen, Lars; Blinova, Ksenia; Mason, Jay W; Weeke, Peter; Behr, Elijah R; Roden, Dan M; Woosley, Ray; Kosova, Gulum; Rosenberg, Michael A; Newton-Cheh, Christopher

2017-04-04

Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known. We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs. Genetic analysis of 22 subjects was performed in a secondary analysis of a randomized, double-blind, placebo-controlled, crossover trial of 3 QT-prolonging drugs with 15 time-matched QT and plasma drug concentration measurements. Subjects received single doses of dofetilide, quinidine, ranolazine, and placebo. The outcome was the correlation between a genetic QT score comprising 61 common genetic variants and the slope of an individual subject's drug-induced increase in heart rate-corrected QT (QTc) versus drug concentration. The genetic QT score was correlated with drug-induced QTc prolongation. Among white subjects, genetic QT score explained 30% of the variability in response to dofetilide ( r =0.55; 95% confidence interval, 0.09-0.81; P =0.02), 23% in response to quinidine ( r =0.48; 95% confidence interval, -0.03 to 0.79; P =0.06), and 27% in response to ranolazine ( r =0.52; 95% confidence interval, 0.05-0.80; P =0.03). Furthermore, the genetic QT score was a significant predictor of drug-induced torsade de pointes in an independent sample of 216 cases compared with 771 controls ( r 2 =12%, P =1×10 -7 ). We demonstrate that a genetic QT score comprising 61 common genetic variants explains a significant proportion of the variability in drug-induced QT prolongation and is a significant predictor of drug-induced torsade de pointes. These findings highlight an opportunity for recent genetic discoveries to improve individualized risk-benefit assessment for pharmacological therapies. Replication of these findings in larger samples is needed to more precisely estimate variance explained and to establish the individual variants that drive these effects. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01873950. © 2017 American Heart Association, Inc.

Prolonged Tp-e Interval in Down Syndrome Patients with Congenitally Normal Hearts.

PubMed

Kucuk, Mehmet; Karadeniz, Cem; Ozdemir, Rahmi; Meşe, Timur

2018-03-25

Heterogeneity of ventricular repolarization has been assessed by using the QT dispersion in Down syndrome (DS) patients with congenitally normal hearts. However, novel repolarization indexes, the Tp-e interval and Tp-e/QT ratio, have not previously been evaluated in these patients. The aim of this study was to evaluate the Tp-e interval and Tp-e/QT ratio in DS patients without congenital heart defects. Twelve-lead surface electrocardiograms of 160 DS patients and 110 age- and sex-matched healthy controls were used to evaluate and compare the Tp-e interval, Tp-e dispersion, and Tp-e/QT ratio. Heart rate, Tp-e interval, Tp-e dispersion, Tp-e/QT and Tp-e/QTc ratios were significantly higher in DS group than in the controls. Myocardial repolarization indexes in DS patients with congenitally normal hearts were found to be prolonged compared to those in normal controls. Further evaluation is warranted to reveal a relationship between prolonged repolarization indexes and arrhythmic events in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Identifying QT prolongation from ECG impressions using a general-purpose Natural Language Processor

PubMed Central

Denny, Joshua C.; Miller, Randolph A.; Waitman, Lemuel Russell; Arrieta, Mark; Peterson, Joshua F.

2009-01-01

Objective Typically detected via electrocardiograms (ECGs), QT interval prolongation is a known risk factor for sudden cardiac death. Since medications can promote or exacerbate the condition, detection of QT interval prolongation is important for clinical decision support. We investigated the accuracy of natural language processing (NLP) for identifying QT prolongation from cardiologist-generated, free-text ECG impressions compared to corrected QT (QTc) thresholds reported by ECG machines. Methods After integrating negation detection to a locally-developed natural language processor, the KnowledgeMap concept identifier, we evaluated NLP-based detection of QT prolongation compared to the calculated QTc on a set of 44,318 ECGs obtained from hospitalized patients. We also created a string query using regular expressions to identify QT prolongation. We calculated sensitivity and specificity of the methods using manual physician review of the cardiologist-generated reports as the gold standard. To investigate causes of “false positive” calculated QTc, we manually reviewed randomly selected ECGs with a long calculated QTc but no mention of QT prolongation. Separately, we validated the performance of the negation detection algorithm on 5,000 manually-categorized ECG phrases for any medical concept (not limited to QT prolongation) prior to developing the NLP query for QT prolongation. Results The NLP query for QT prolongation correctly identified 2,364 of 2,373 ECGs with QT prolongation with a sensitivity of 0.996 and a positive predictive value of 1.000. There were no false positives. The regular expression query had a sensitivity of 0.999 and positive predictive value of 0.982. In contrast, the positive predictive value of common QTc thresholds derived from ECG machines was 0.07–0.25 with corresponding sensitivities of 0.994–0.046. The negation detection algorithm had a recall of 0.973 and precision of 0.982 for 10,490 concepts found within ECG impressions. Conclusions NLP and regular expression queries of cardiologists’ ECG interpretations can more effectively identify QT prolongation than the automated QTc intervals reported by ECG machines. Future clinical decision support could employ NLP queries to detect QTc prolongation and other reported ECG abnormalities. PMID:18938105

Slowed atrial and atrioventricular conduction and depressed HRV in a murine model of hypertrophic cardiomyopathy.

PubMed

Lim, Wei-Wen; Baumert, Mathias; Neo, Melissa; Kuklik, Pawel; Ganesan, Anand N; Lau, Dennis H; Tsoutsman, Tatiana; Semsarian, Christopher; Sanders, Prashanthan; Saint, David A

2016-01-01

Hypertrophic cardiomyopathy (HCM) is a common heritable cardiac disorder with diverse clinical outcomes including sudden death, heart failure, and stroke. Depressed heart rate variability (HRV), a measure of cardiac autonomic regulation, has been shown to predict mortality in patients with cardiovascular disease. Cardiac autonomic remodelling in animal models of HCM are not well characterised. This study analysed Gly203Ser cardiac troponin-I transgenic (TG) male mice previously demonstrated to develop hallmarks of HCM by age 21 weeks. 33 mice aged 30 and 50 weeks underwent continuous electrocardiogram (ECG) recording for 30 min under anaesthesia. TG mice demonstrated prolonged P-wave duration (P < 0.001) and PR intervals (P < 0.001) compared to controls. Additionally, TG mice demonstrated depressed standard deviation of RR intervals (SDRR; P < 0.01), coefficient of variation of RR intervals (CVRR; P < 0.001) and standard deviation of heart rate (SDHR; P < 0.001) compared to controls. Additionally, total power was significantly reduced in TG mice (P < 0.05). No significant age-related difference in either strain was observed in ECG or HRV parameters. Mice with HCM developed slowed atrial and atrioventricular conduction and depressed HRV. These changes were conserved with increasing age. This finding may be indicative of atrial and ventricular hypertrophy or dysfunction, and perhaps an indication of worse clinical outcome in heart failure progression in HCM patients. © 2015 Wiley Publishing Asia Pty Ltd.

Association between obesity and ECG variables in children and adolescents: A cross-sectional study.

PubMed

Sun, Guo-Zhe; Li, Yang; Zhou, Xing-Hu; Guo, Xiao-Fan; Zhang, Xin-Gang; Zheng, Li-Qiang; Li, Yuan; Jiao, Yun-DI; Sun, Ying-Xian

2013-12-01

Obesity exhibits a wide variety of electrocardiogram (ECG) abnormalities in adults, which often lead to cardiovascular events. However, there is currently no evidence of an association between obesity and ECG variables in children and adolescents. The present study aimed to explore the associations between obesity and ECG intervals and axes in children and adolescents. A cross-sectional observational study of 5,556 students aged 5-18 years was performed. Anthropometric data, blood pressure and standard 12-lead ECGs were collected for each participant. ECG variables were measured manually based on the temporal alignment of simultaneous 12 leads using a CV200 ECG Work Station. Overweight and obese groups demonstrated significantly longer PR intervals, wider QRS durations and leftward shifts of frontal P-wave, QRS and T-wave axes, while the obese group also demonstrated significantly higher heart rates, compared with normal weight groups within normotensive or hypertensive subjects (P<0.05). Abdominal obesity was also associated with longer PR intervals, wider QRS duration and a leftward shift of frontal ECG axes compared with normal waist circumference (WC) within normotensive or hypertensive subjects (P<0.05). Gender was a possible factor affecting the ECG variables. Furthermore, the ECG variables, including PR interval, QRS duration and frontal P-wave, QRS and T-wave axes, were significantly linearly correlated with body mass index, WC and waist-to-height ratio adjusted for age, gender, ethnicity and blood pressure. However, there was no significant association between obesity and the corrected QT interval (P>0.05). The results of the current study indicate that in children and adolescents, general and abdominal obesity is associated with longer PR intervals, wider QRS duration and a leftward shift of frontal P-wave, QRS and T-wave axes, independent of age, gender, ethnicity and blood pressure.

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

PubMed

Kim, Anhye; Lim, Kyoung Soo; Lee, Howard; Chung, Hyewon; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Jang, In-Jin; Chung, Jae-Yong

2016-07-01

Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.

Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study.

PubMed

Kertai, Miklos D; Ji, Yunqi; Li, Yi-Ju; Mathew, Joseph P; Daubert, James P; Podgoreanu, Mihai V

2016-04-01

We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as > 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes -involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes- was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery.

Methadone, QTc prolongation and torsades de pointes: Current concepts, management and a hidden twist in the tale?

PubMed Central

Mujtaba, Sobia; Romero, Jorge; Taub, Cynthia C.

2013-01-01

Methadone is a drug that has found widespread utility in the management of opioid addiction and pain. Along with its popularity, methadone has also earned an infamous reputation for causing prolongation of the QT interval and an increased risk of torsades de pointes. In this article we will give a brief overview of the long QT syndromes, followed by an in-depth look at the current pathophysiologic mechanisms of methadone induced QT prolongation, a review of the existing literature and the current concepts regarding the prevention and management of methadone induced torsades de pointes. In addition, we explore the idea and implications of a genetic link between methadone induced prolongation of the QT interval and torsades de pointes. PMID:24653586

Is prolongation of corrected QT interval associated with seizures induced by electroconvulsive therapy reduced by atropine sulfate?

PubMed

Suzuki, Yoko; Miyajima, Miho; Ohta, Katsuya; Yoshida, Noriko; Omoya, Rie; Fujiwara, Mayo; Watanabe, Takafumi; Okumura, Masaki; Yamazaki, Hiroaki; Shintaku, Masayuki; Murata, Issei; Ozaki, Shigeru; Sasaki, Takeshi; Nakamura, Mitsuru; Suwa, Hiroshi; Sasano, Tetsuo; Kawara, Tokuhiro; Matsuura, Masato; Matsushima, Eisuke

2017-11-01

Electrocardiogram abnormalities have been reported during electroconvulsive therapy (ECT). A corrected QT interval (QTc) prolongation indicates delayed ventricular repolarization, which can trigger ventricular arrhythmias such as torsade de pointes (TdP). We examined the QTc changes during generalized tonic-clonic seizures induced by ECT, and the effects of atropine sulfate on these QTc changes. We analyzed heart rate, QT interval, and QTc in 32 patients with depression who underwent ECT (25 women, 67.4 ± 8.7 years of age). The QTc from -30 to 0 seconds prestimulation was used as baseline, which was compared with QTc at 20-30 seconds and 140-150 seconds poststimulus onset. QTc was significantly prolonged at 20-30 seconds poststimulus, then significantly decreased at 140-150 seconds poststimulus, compared with baseline. QTc prolongation induced by ECT was significantly decreased by atropine sulfate. These data suggest that the risk of TdP may be enhanced by ECT. Further, the risk of cardiac ventricular arrhythmias, including TdP, may be reduced by administration of atropine sulfate. © 2017 Wiley Periodicals, Inc.

Potential approaches for heterologous prion protein treatment of prion diseases

PubMed Central

Seelig, Davis M.; Goodman, Patricia A.; Skinner, Pamela J.

2016-01-01

ABSTRACT Prion diseases, or transmissible spongiform encephalopathies (TSEs) are progressive, fatal neurodegenerative diseases with no effective treatment. The pathology of these diseases involves the conversion of a protease sensitive form of the cellular prion protein (PrPC) into a protease resistant infectious form (PrPres). The efficiency of this conversion is predicated upon a number of factors, most notably a strong homology between cellular PrPC and PrPres. In our recently published study, we infected mice with the RML-Chandler strain of scrapie and treated them with heterologous hamster prion proteins. This treatment was seen to reduce clinical signs of prion disease, to delay the onset of clinical symptoms and to prolong survival. In this current article we discuss potential mechanisms of action of treatment with heterologous prion proteins. We also discuss potential extensions of these studies using a heterologous rabbit PrP-based treatment strategy or a peptide based strategy, and improvement of treatment delivery including a lentiviral-based system. PMID:26636482

Prolongation of heart rate-corrected QT interval is a predictor of cardiac autonomic dysfunction in patients with systemic lupus erythematosus.

PubMed

Nomura, Atsushi; Kishimoto, Mitsumasa; Takahashi, Osamu; Deshpande, Gautam A; Yamaguchi, Kenichi; Okada, Masato

2014-05-01

Heart rate-corrected QT interval duration (QTc) has been shown to be related to cardiac autonomic dysfunction in patients with diabetes mellitus, although this association has not been previously described in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed the medical records of 91 SLE patients and 144 non-SLE connective tissue disease patients visiting our clinic from November 2010 to April 2011. We compared ambulatory heart rate identified by pulse measured by automated machine in an outpatient waiting area versus resting heart rate identified on prior screening electrocardiogram. Heart rate differences were analyzed in relation to QTc interval and other characteristics. Ambulatory and resting heart rate differences were larger among SLE patients with QTc prolongation (QTc > 430 ms) than those without QTc prolongation (mean difference, 15.9 vs. 9.6, p = 0.001). In multivariate analysis, differences in heart rate were associated with QTc prolongation (OR 1.10, 95 % CI 1.01-1.21; p = 0.038), independent of age, duration of disease, immunosuppressant use, hydroxychloroquine use, diabetes mellitus, cardiac abnormality, anti-Ro/SS-A antibody positivity, or resting heart rate. Cardiac autonomic dysfunction is a common manifestation of SLE and may be related to QTc prolongation.

Effects of anti-malarial drugs on the electrocardiographic QT interval modelled in the isolated perfused guinea pig heart system

PubMed Central

2010-01-01

Background Concern over the potential cardiotoxicity of anti-malarial drugs inducing a prolonged electrocardiographic QT interval has resulted in the almost complete withdrawal from the market of one anti-malarial drug - halofantrine. The effects on the QT interval of four anti-malarial drugs were examined, using the guinea pig heart. Methods The guinea pig heart was isolated, mounted on a Langendorff apparatus, and was then perfused with pyruvate-added Klebs-Henseleit solutions containing graded concentrations of the four agents such as quinidine (0.15 - 1.2 μM), quinine (0.3 - 2.4 μM), halofantrine (0.1 - 2.0 μM) and mefloquine (0.1 - 2.0 μM). The heart rate-corrected QaTc intervals were measured to evaluate drug-induced QT prolongation effects. Results Quinidine, quinine, and halofantrine prolonged the QaTc interval in a dose-dependent manner, whereas no such effect was found with mefloquine. The EC50 values for the QaTc prolongation effects, the concentration that gives a half-maximum effect, were quinidine < quinine ≈ halofantrine. Conclusions In this study, an isolated, perfused guinea pig heart system was constructed to assess the cardiotoxic potential of anti-malarial drugs. This isolated perfused guinea pig heart system could be used to test newly developed anti-malarial drugs for their inherent QT lengthening potential. More information is required on the potential variation in unbound drug concentrations in humans, and their role in cardiotoxicity. PMID:21067575

BCR-crosslinking induces a transcription of protein phosphatase component G5PR that is required for mature B-cell survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huq Ronny, Faisal Mahmudul; Igarashi, Hideya; Core Research for Evolutional Science and Technology

2006-02-03

BCR-crosslinking triggers activation-induced cell death (AICD) selectively in the restricted stage of B-cell differentiation. We examined the transcription of a protein phosphatase subunit G5PR in immature and mature B-cells, because absence of this factor augmented cell sensitivity to AICD, associated with increased activation of JNK and Bim. BCR-crosslinking-induced G5pr transcription in AICD-resistant mature splenic IgM{sup lo}IgD{sup hi} B-cells but not in AICD susceptible immature IgM{sup hi}IgD{sup lo} B-cells. Thus, G5pr induction correlated with the prevention of AICD; High in mature splenic CD23{sup hi} B-cells but low in immature B-cells of neonatal mice, sub-lethally irradiated mice, or xid mice. Lack ofmore » G5pr upregulation was associated with the prolonged activation of JNK. The G5pr cDNA transfection protected an immature B-cell line WEHI-231 from BCR-mediated AICD. The differential expression of G5PR might be responsible for the antigen-dependent selection of B-cells.« less

The effect of the interval from PGF treatment to ovulation on embryo recovery and pregnancy rate in the mare.

PubMed

Cuervo-Arango, J; Mateu-Sánchez, S; Aguilar, J J; Nielsen, J M; Etcharren, V; Vettorazzi, M L; Newcombe, J R

2015-05-01

The objective of this study was to determine the effect of the interval from induced luteolysis to ovulation on fertility of mares from two different farms. At farm 1, 215 mares were inseminated with frozen/thawed semen during 513 estrous cycles over seven consecutive breeding seasons. Estrus was induced with analogues of PGF2α in 179 cycles. At farm 2, 375 embryo flushings were performed in 65 donor mares inseminated with fresh semen; of which, 327 were performed following artificial insemination after PGF-induced luteolysis. In both farms, the intervals from PGF treatment to ovulation (ITO) data were divided into three interval groups: less than 6 days, 6 to 8 days, and greater than 8 days. A mixed regression model was created to determine the effect of different factors on the pregnancy rate (PR) and embryo recovery rate (ERR). Of all factors analyzed, the ITO was the only one that significantly influenced the PR and ERR (P < 0.05). In farm 1, the PR of mares with an ITO of less than 6 days, 6 to 8 days, and greater than 8 days was 26.6%, 39.4%, and 55.9%, respectively (P = 0.01). The PR for mares inseminated after spontaneous luteolysis (without PGF) was 42.5%. In farm 2, the ERR of donor mares for the same ITO groups was 55.0%, 62.6%, and 73.7%, respectively (P = 0.02). The ERR for mares flushed after a previous spontaneous estrus was 75.0%. In conclusion, the ITO had a significant effect on the PR and ERR in the mare. Fertility was reduced as the ITO became shorter. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel Loci Associated with PR Interval in a Genome-Wide Association Study of Ten African American Cohorts

PubMed Central

Butler, Anne M.; Yin, Xiaoyan; Evans, Daniel S.; Nalls, Michael A.; Smith, Erin N.; Tanaka, Toshiko; Li, Guo; Buxbaum, Sarah G.; Whitsel, Eric A.; Alonso, Alvaro; Arking, Dan E.; Benjamin, Emelia J.; Berenson, Gerald S.; Bis, Josh C.; Chen, Wei; Deo, Rajat; Ellinor, Patrick T.; Heckbert, Susan R.; Heiss, Gerardo; Hsueh, Wen-Chi; Keating, Brendan J.; Kerr, Kathleen F.; Li, Yun; Limacher, Marian C.; Liu, Yongmei; Lubitz, Steven A.; Marciante, Kristin D.; Mehra, Reena; Meng, Yan A.; Newman, Anne B.; Newton-Cheh, Christopher; North, Kari E.; Palmer, Cameron D.; Psaty, Bruce M.; Quibrera, P. Miguel; Redline, Susan; Reiner, Alex P.; Rotter, Jerome I.; Schnabel, Renate B.; Schork, Nicholas J.; Singleton, Andrew B.; Smith, J. Gustav; Soliman, Elsayed Z.; Srinivasan, Sathanur R.; Zhang, Zhu-ming; Zonderman, Alan B.; Ferrucci, Luigi; Murray, Sarah S.; Evans, Michele K.; Sotoodehnia, Nona; Magnani, Jared W.; Avery, Christy L.

2013-01-01

Background The PR interval (PR) as measured by the resting, standard 12-lead electrocardiogram (ECG) reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at nine loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and Results We present results from the largest genome-wide association study to date of PR in 13,415 adults of African descent from ten cohorts. We tested for association between PR (ms) and approximately 2.8 million genotyped and imputed single nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (lambda range: 0.9–1.1), although not after genomic control correction was applied to the overall meta-analysis (lambda: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0×10−8), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained two additional independent secondary signals influencing PR (P<5.0×10−8). Conclusions This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European and Asian descent. PMID:23139255

Prevalence and risk factors for prolonged QT interval and QT dispersion in patients with type 2 diabetes.

PubMed

Ninkovic, Vladan M; Ninkovic, Srdjan M; Miloradovic, Vanja; Stanojevic, Dejan; Babic, Marijana; Giga, Vojislav; Dobric, Milan; Trenell, Michael I; Lalic, Nebojsa; Seferovic, Petar M; Jakovljevic, Djordje G

2016-10-01

Prolonged QT interval is associated with cardiac arrhythmias and sudden death. The present study determined the prevalence of prolonged QT interval and QT dispersion and defined their clinical and metabolic predictors in patients with type 2 diabetes. Cross-sectional study included 501 patients with type 2 diabetes. A standard 12-lead electrocardiogram was recorded. QT corrected for heart rate (QTc) >440 ms and QT dispersion (QTd) >80 ms were considered abnormally prolonged. QTc ≥ 500 ms was considered a high-risk QTc prolongation. Demographic, clinical and laboratory data were collected. Independent risk factors for prolonged QTc and QTd were assessed using logistic regression analysis. Prevalence of QTc > 440 ms and QTd > 80 ms were 44.1 and 3.6 %, respectively. Prevalence of high-risk QTc (≥500 ms) was 2 % only. Independent risk factors for QTc prolongation >440 ms were mean blood glucose (β = 2.192, p < 0.001), treatment with sulphonylurea (β = 5.198, p = 0.027), female gender (β = 8.844, p < 0.001), and coronary heart disease (β = 8.636, p = 0.001). Independent risk factors for QTc ≥ 500 ms were coronary heart disease (β = 4.134, p < 0.001) and mean blood glucose level (β = 1.735, p < 0.001). The independent risk factor for prolonged QTd was only coronary heart disease (β = 5.354, p < 0.001). Although the prevalence of prolonged QTc > 440 ms is significant, the prevalence of high-risk QTc (≥500 ms) and QTd > 80 ms is very low in patients with type 2 diabetes. Hyperglycaemia and coronary heart disease are strong predictors of high-risk QTc.

Minimizing right ventricular pacing in pacemaker patients with intact and compromised atrioventricular conduction : Results from the EVITA Trial.

PubMed

Bauer, A; Vermeulen, J; Toivonen, L; Voitk, J; Barr, C; Peytchev, P

2015-12-01

Unnecessary ventricular pacing is associated with increased morbidity and mortality. Over the years different algorithms have been developed to reduce right ventricular pacing. Goal of the present study was to test the efficacy of the ventricular intrinsic preference (VIP) algorithm in patients with atrioventricular intact (AVi) and atrioventricular compromised (AVc) AV-conduction. Evaluation of VIP feature in pacemaker patients (EVITA) was a multicenter, prospective, randomized trial (Trials.gov Identifier: NCT00366158). In total, 389 patients were randomized to AVc group: n = 140/132 VIP OFF/VIP On, AVi group: n = 54/63 VIP OFF/VIP ON). One-month post-implantation AV conduction testing (AVc: PR/AR interval > 210 ms) was performed. Follow-up visits occurred 6 and 12 months after DDD-pacemaker implantation. In AVi and AVc-patients initiation of the VIP feature significantly reduced incidence of ventricular pacing (AVi: 53 ± 38 vs. 9 ± 21%, p = 0.0001; AVc: 79 ± 31 vs. 28 ± 35%, p = 0.0001). DDD-pacemaker implantation per se significantly reduced incidence of AF in VIP ON (AVi 27 vs. 0%, p < 0.0001; AVc 29 vs. 3%, p < 0.0001) and VIP OFF patients (AVi 43 vs. 4%, p < 0.0001; AVc 33 vs. 3, p < 0.0001), without significant differences between VIP ON and OFF groups (p > 0.05). In the AVc group activation of VIP significantly reduced incidence of adverse events (AE). All-cause mortality was not significantly different in VIP ON (n = 5) and VIP OFF (n = 4, p > 0.05) patients. AV search hysteresis (VIP) markedly reduces ventricular pacing both in patients with normal AV conduction and in patients with prolonged PR interval or intermittent AV block.

Effect of mood states on QT interval and QT dispersion in eating disorder patients.

PubMed

Takimoto, Yoshiyuki; Yoshiuchi, Kazuhiro; Akabayashi, Akira

2008-04-01

Prolonged QT interval and QT dispersion have been reported in patients with eating disorders. Although the factors that cause prolongation remain unclear, mood states such as anxiety have been reported to influence QT interval and dispersion, probably via the autonomic nervous system. Therefore the aim of the present paper was to investigate mood effect on prolonged QT interval and QT dispersion. The subjects were 47 female anorexia nervosa (AN) and 48 female bulimia nervosa (BN) patients. In all of the patients, serum electrolyte levels were normal. QT interval and QT dispersion were measured from 12-lead electrocardiographic recordings. Mood states in each patient were measured using a Profile of Mood States (POMS) evaluation, and the patients were divided into high- and low-score groups for each POMS subscale. The differences in QT variables were compared between the two groups for each subscale. In the BN group, QT interval and QT dispersion in the high depression score group were significantly longer than those in the low depression score group, and QT dispersion was significantly greater in the high anxiety score group than in the low anxiety score group. In addition, QT interval and QT dispersion were significantly correlated with depression scores. In the AN group there were no significant differences in QT interval or QT dispersion between the high- and low-score groups for any POMS subscale. BN patients with worse states of depression or anxiety had longer QT intervals and larger QT dispersion. In BN patients, mood disturbance might increase the risk of arrhythmias.

Cardiac conductive disturbance in patients with polycystic ovary syndrome.

PubMed

Huang, Jen-Hung; Tsai, Jen-Chen; Hsu, Ming-I; Chen, Yi-Jen

2010-12-01

Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality of reproductive-aged women and increases the risk of cardiovascular disease. However, the effects of PCOS on electrocardiograms (ECGs) are not fully elucidated. The aim of this study was to evaluate the characteristics of ECGs in patients with PCOS. This study included 24 patients with PCOS and 12 patients without PCOS. The heart rate, PR interval, QRS duration, Sokolow-Lyon voltage (SV1 + RV5/6), Cornell voltage (RaVL + SV3), QT interval and QTc interval were measured in 12-lead ECGs. The QRS duration was wider in patients with PCOS than those without PCOS (91 ± 8 vs. 81 ± 10 ms, p < 0.05). The heart rate, PR interval, Sokolow-Lyon voltage, product of the QRS duration times Cornell voltage combination, QT interval, QTc interval, QT dispersion and QTc dispersion were similar between the two groups. PCOS is associated with a widening QRS duration, which may contribute to its increased cardiovascular risks.

Identifying the translational gap in the evaluation of drug-induced QTc interval prolongation

PubMed Central

Chain, Anne SY; Dubois, Vincent FS; Danhof, Meindert; Sturkenboom, Miriam CJM; Della Pasqua, Oscar

2013-01-01

Aims Given the similarities in QTc response between dogs and humans, dogs are used in pre-clinical cardiovascular safety studies. The objective of our investigation was to characterize the PKPD relationships and identify translational gaps across species following the administration of three compounds known to cause QTc interval prolongation, namely cisapride, d, l-sotalol and moxifloxacin. Methods Pharmacokinetic and pharmacodynamic data from experiments in conscious dogs and clinical trials were included in this analysis. First, pharmacokinetic modelling and deconvolution methods were applied to derive drug concentrations at the time of each QT measurement. A Bayesian PKPD model was then used to describe QT prolongation, allowing discrimination of drug-specific effects from other physiological factors known to alter QT interval duration. A threshold of ≥10 ms was used to explore the probability of prolongation after drug administration. Results A linear relationship was found to best describe the pro-arrhythmic effects of cisapride, d,l-sotalol and moxifloxacin both in dogs and in humans. The drug-specific parameter (slope) in dogs was statistically significantly different from humans. Despite such differences, our results show that the probability of QTc prolongation ≥10 ms in dogs nears 100% for all three compounds at the therapeutic exposure range in humans. Conclusions Our findings indicate that the slope of PKPD relationship in conscious dogs may be used as the basis for the prediction of drug-induced QTc prolongation in humans. Furthermore, the risk of QTc prolongation can be expressed in terms of the probability associated with an increase ≥10 ms, allowing direct inferences about the clinical relevance of the pro-arrhythmic potential of a molecule. PMID:23351036

The independent and combined effects of respiratory events and cortical arousals on the autonomic nervous system across sleep stages.

PubMed

Liang, Jiuxing; Zhang, Xiangmin; He, Xiaomin; Ling, Li; Zeng, Chunyao; Luo, Yuxi

2018-05-10

During sleep, respiratory events readily modulate the autonomic nervous system (ANS). Whether such modulation is caused by the respiratory event itself or the cortical arousal that follows and whether these influences differ across sleep stages are not clear. Thus, we aimed to study the independent and combined effects of respiratory events and cortical arousals on the ANS across sleep stages. We recruited 22 male patients with sleep apnea-hypopnea syndrome (SAHS) and analyzed the differences in the indices of heart rate variability among normal respiration (NR), pathological respiratory events without cortical arousals (PR), cortical arousals without respiratory events (CA), and the coexistence of PR and CA (PR&CA), by sleep stage. Compared with NR, four indices of variation of the beat-to-beat interval demonstrated consistent results in all sleep stages generally: PR&CA showed the biggest difference, followed by PR and followed by CA, which exhibited the least difference. Thus, the respiratory event itself affects ANS modulation, but the cortical arousal that follows generally enhances this effect. For low-frequency power and low-frequency/high-frequency power ratio (LF/HF), PR&CA had the greatest impact. For mean beat-to-beat interval and high-frequency power (HFP), the influence of PR, CA, and PR&CA depended on sleep depth. However, PR&CA had a different influence on HFP in N2 stage vs. REM stage. Sleep stage also has an effect on this neuromodulatory mechanism. These findings may help clarify the relationship between SAHS and cardiovascular disease.

Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease.

PubMed

Louis, John M; Tözsér, József; Roche, Julien; Matúz, Krisztina; Aniana, Annie; Sayer, Jane M

2013-10-29

During treatment, mutations in HIV-1 protease (PR) are selected rapidly that confer resistance by decreasing affinity to clinical protease inhibitors (PIs). As these unique drug resistance mutations can compromise the fitness of the virus to replicate, mutations that restore conformational stability and activity while retaining drug resistance are selected on further evolution. Here we identify several compensating mechanisms by which an extreme drug-resistant mutant bearing 20 mutations (PR20) with >5-fold increased Kd and >4000-fold decreased affinity to the PI darunavir functions. (1) PR20 cleaves, albeit poorly, Gag polyprotein substrates essential for viral maturation. (2) PR20 dimer, which exhibits distinctly enhanced thermal stability, has highly attenuated autoproteolysis, thus likely prolonging its lifetime in vivo. (3) The enhanced stability of PR20 results from stabilization of the monomer fold. Both monomeric PR20(T26A) and dimeric PR20 exhibit Tm values 6-7.5 °C higher than those for their PR counterparts. Two specific mutations in PR20, L33F and L63P at sites of autoproteolysis, increase the Tm of monomeric PR(T26A) by ~8 °C, similar to PR20(T26A). However, without other compensatory mutations as seen in PR20, L33F and L63P substitutions, together, neither restrict autoproteolysis nor significantly reduce binding affinity to darunavir. To determine whether dimer stability contributes to binding affinity for inhibitors, we examined single-chain dimers of PR and PR(D25N) in which the corresponding identical monomer units were covalently linked by GGSSG sequence. Linking of the subunits did not appreciably change the ΔTm on inhibitor binding; thus stabilization by tethering appears to have little direct effect on enhancing inhibitor affinity.

Timothy syndrome-like condition with syndactyly but without prolongation of the QT interval.

PubMed

Kosaki, Rika; Ono, Hiroshi; Terashima, Hiroshi; Kosaki, Kenjiro

2018-05-07

Timothy syndrome is characterized by a unique combination of a prolongation of the corrected QT interval of the electrocardiogram and bilateral cutaneous syndactyly of the fingers and the toes and is caused by heterozygous mutations in CACNA1C, a gene encoding a calcium channel. After the discovery of the CACNA1C gene as the causative gene for Timothy syndrome, patients with CACNA1C mutations with QT prolongation but without syndactyly were described. Here, we report a 5-year-old female patient with cutaneous syndactyly, developmental delay, and pulmonary hypertension. Exome analysis showed a previously undescribed de novo heterozygous mutation in the CACNA1C gene, p.Arg1024Gly. To our knowledge, this patient is the first to exhibit syndactyly and to carry a CACNA1C mutation but to not have QT prolongation, which has long been considered an obligatory feature of Timothy syndrome. © 2018 Wiley Periodicals, Inc.

Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain

PubMed Central

2014-01-01

Introduction Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. Methods We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd’s scale and was conflated into: <25%; 25 to 50%; 50 to 75%; >75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Results Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (<25%) than in denser breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; <0.001). False-negatives and occult tumors had similar phenotypic characteristics to screening-detected cancers, extreme breast density being strongly associated with occult tumors (OR = 6.23 (95% CI:2.65-14.66)). Minimal-sign cancers were biologically close to true interval cancers but showed no association with breast density. Conclusions Our findings revealed that both the distribution of tumor phenotype and breast density play specific and independent roles in each category of interval cancer. Further research is needed to understand the biological basis of the overrepresentation of triple-negative phenotype among predominantly fatty breasts in true interval cancers. PMID:24410848

Translating QT interval prolongation from conscious dogs to humans.

PubMed

Dubois, Vincent F S; Smania, Giovanni; Yu, Huixin; Graf, Ramona; Chain, Anne S Y; Danhof, Meindert; Della Pasqua, Oscar

2017-02-01

In spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between -0.98 ms μM -1 and 6.1 ms μM -1 in dogs and -10 ms μM -1 and 90 ms μM -1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species. For compounds without a mixed ion channel block, a correlation was observed between the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R 2  = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6-fold larger than in dogs. Together with information about the expected therapeutic exposure, the evidence of a correlation between the compound-specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans. © 2016 The British Pharmacological Society.

Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study

PubMed Central

Kertai, Miklos D.; Ji, Yunqi; Li, Yi-Ju; Mathew, Joseph P.; Daubert, James P.; Podgoreanu, Mihai V.

2016-01-01

Background We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. Methods All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as >440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes – involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes–was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. Results After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). Conclusion The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery. PMID:26858093

Dofetilide promotes repolarization abnormalities in perfused Guinea-pig heart.

PubMed

Osadchii, Oleg E

2012-12-01

Dofetilide is class III antiarrhythmic agent which prolongs cardiac action potential duration because of selective inhibition of I (Kr), the rapid component of the delayed rectifier K(+) current. Although clinical studies reported on proarrhythmic risk associated with dofetilide treatment, the contributing electrophysiological mechanisms remain poorly understood. This study was designed to determine if dofetilide-induced proarrhythmia may be attributed to abnormalities in ventricular repolarization and refractoriness. The monophasic action potential duration and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated, perfused guinea-pig heart preparations. Dofetilide was found to produce the reverse rate-dependent prolongation of ventricular repolarization, increased the steepness of action potential duration rate adaptation, and amplified transepicardial variability in electrical restitution kinetics. Dofetilide also prolonged the T peak-to-end interval on ECG, and elicited a greater prolongation of endocardial than epicardial ERP, thereby increasing transmural dispersion of refractoriness. At epicardium, dofetilide prolonged action potential duration to a greater extent than ERP, thus extending the critical interval for ventricular re-excitation. This change was associated with triangulation of epicardial action potential because of greater dofetilide-induced prolonging effect at 90 % than 30 % repolarization. Premature ectopic beats and spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 44 % of dofetilide-treated heart preparations. Proarrhythmic potential of dofetilide in guinea-pig heart is attributed to steepened electrical restitution, increased transepicardial variability in electrical restitution kinetics, amplified transmural dispersion of refractoriness, increased critical interval for ventricular re-excitation, and triangulation of epicardial action potential.

Effects of anthracycline, cyclophosphamide and taxane chemotherapy on QTc measurements in patients with breast cancer.

PubMed

Veronese, Pedro; Hachul, Denise Tessariol; Scanavacca, Mauricio Ibrahim; Hajjar, Ludhmila Abrahão; Wu, Tan Chen; Sacilotto, Luciana; Veronese, Carolina; Darrieux, Francisco Carlos da Costa

2018-01-01

Acute and subacute cardiotoxicity are characterized by prolongation of the corrected QT interval (QTc) and other measures derived from the QTc interval, such as QTc dispersion (QTdc) and transmural dispersion of repolarization (DTpTe). Although anthracyclines prolong the QTc interval, it is unclear whether breast cancer patients who undergo the ACT chemotherapy regimen of anthracycline (doxorubicin: A), cyclophosphamide (C) and taxane (T) may present with QTc, QTdc and DTpTe prolongation. Twenty-three consecutive patients with breast cancer were followed prospectively during ACT chemotherapy and were analyzed according to their QT measurements. QTc, QTdc and DTpTe measurements were determined by a 12-lead electrocardiogram (EKG) prior to chemotherapy (baseline), immediately after the first phase of anthracycline and cyclophosphamide (AC) treatment, and immediately after T treatment. Serum troponin and B-type natriuretic peptide (BNP) levels were also measured. Compared to baseline values, the QTc interval was significantly prolonged after the AC phase (439.7 ± 33.2 ms vs. 472.5 ± 36.3 ms, p = 0.001) and after T treatment (439.7 ± 33.2 ms vs. 467.9 ± 42.6 ms, p < 0.001). Troponin levels were elevated after the AC phase (23.0 pg/mL [min-max: 6.0-85.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) and after T treatment (25.0 pg/mL [min-max: 6.0-80.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) compared to baseline values. In this prospective study of patients with non-metastatic breast cancer who underwent ACT chemotherapy, significant QTc prolongation and an elevation in serum troponin levels were observed.

Prolongement de théories planétaires à variations séculaires sur plusieurs milliers d'années.

NASA Astrophysics Data System (ADS)

Simon, J. L.

Les théories planétaires à variations séculaires construites au Bureau des Longitudes, VSOP82 (Bretagnon, 1982) et TOP82 (Simon, 1983) ne contiennent pas de termes de degré supérieur à 6 dans le développement en puissance du temps des perturbations. Il en résulte que leur précision se dégrade avec le temps pour des intervalles de temps supérieurs à 1000 ans. L'auteur présente ici un travail effectué en collaboration avec P. Bretagnon qui a consisté à construire une solution du mouvement de Jupiter et Saturne gardant une bonne précision sur 6000 ans.

Farsightedness (Hyperopia)

MedlinePlus

... eye discomfort or a headache after a prolonged interval of conducting close tasks, such as reading, writing, ... the American Academy of Ophthalmology recommends the following intervals for regular eye exams: Adults If you're ...

Proportion of the Litter Farrowed, Litter Size, and Progesterone and Estradiol Effects on Piglet Birth Intervals and Stillbirths

USDA-ARS?s Scientific Manuscript database

Stillbirth in swine ranges from 2 to 9%, resulting in a significant loss of piglets. Previous studies clearly indicate a relationship between prolonged birth intervals and stillbirth, but factors influencing birth intervals are not fully known. To characterize birth intervals and stillbirth, farrowi...

Structure and polymorphism of the mouse prion protein gene.

PubMed Central

Westaway, D; Cooper, C; Turner, S; Da Costa, M; Carlson, G A; Prusiner, S B

1994-01-01

Missense mutations in the prion protein (PrP) gene, overexpression of the cellular isoform of PrP (PrPC), and infection with prions containing the scrapie isoform of PrP (PrPSc) all cause neurodegenerative disease. To understand better the physiology and expression of PrPC, we retrieved mouse PrP gene (Prn-p) yeast artificial chromosome (YAC), cosmid, phage, and cDNA clones. Physical mapping positions Prn-p approximately 300 kb from ecotropic virus integration site number 4 (Evi-4), compatible with failure to detect recombination between Prn-p and Evi-4 in genetic crosses. The Prn-pa allele encompasses three exons, with exons 1 and 2 encoding the mRNA 5' untranslated region. Exon 2 has no equivalent in the Syrian hamster and human PrP genes. The Prn-pb gene shares this intron/exon structure but harbors an approximately 6-kb deletion within intron 2. While the Prn-pb open reading frame encodes two amino acid substitutions linked to prolonged scrapie incubation periods, a deletion of intron 2 sequences also characterizes inbred strains such as RIII/S and MOLF/Ei with shorter incubation periods, making a relationship between intron 2 size and scrapie pathogenesis unlikely. The promoter regions of a and b Prn-p alleles include consensus Sp1 and AP-1 sites, as well as other conserved motifs which may represent binding sites for as yet unidentified transcription factors. Images PMID:7912827

Acute coronary syndrome-like presentation with prolonged QT interval: an unusual case of pheochromocytoma.

PubMed

Ozyuncu, Nil; Akturk, Sevinc; Tan Kurklu, Turkan Seda; Erol, Cetin

2016-09-26

Pheochromocytoma is a rare adrenal gland tumour, usually alerting the physician by causing hypertensive tachycardic attacks. Patients with pheochromocytoma can rarely present with clinical signs similar to acute coronary syndrome. QT interval prolongation and ST segment changes due to pheochromocytoma have also been reported in the literature in a few case reports. We report a patient who had been admitted to the emergency department with chest pain, ischaemic ECG changes and marked QT prolongation. Despite a normal coronary angiogram, we observed that the QT interval and ST segment morphologies had changed during the hospitalisation period. Adrenal adenoma was diagnosed incidentally on abdominal CT scan, and the final diagnosis was pheochromocytoma. The tumour was successfully excised and the patient is now symptom free. When there is lack of a typical clinical picture, the diagnosis of pheochromocytoma might be challenging. It is also very crucial, since misdiagnosis can be life-threatening. 2016 BMJ Publishing Group Ltd.

Population pharmacokinetic modelling of tramadol using inverse Gaussian function for the assessment of drug absorption from prolonged and immediate release formulations.

PubMed

Brvar, Nina; Mateović-Rojnik, Tatjana; Grabnar, Iztok

2014-10-01

This study aimed to develop a population pharmacokinetic model for tramadol that combines different input rates with disposition characteristics. Data used for the analysis were pooled from two phase I bioavailability studies with immediate (IR) and prolonged release (PR) formulations in healthy volunteers. Tramadol plasma concentration-time data were described by an inverse Gaussian function to model the complete input process linked to a two-compartment disposition model with first-order elimination. Although polymorphic CYP2D6 appears to be a major enzyme involved in the metabolism of tramadol, application of a mixture model to test the assumption of two and three subpopulations did not reveal any improvement of the model. The final model estimated parameters with reasonable precision and was able to estimate the interindividual variability of all parameters except for the relative bioavailability of PR vs. IR formulation. Validity of the model was further tested using the nonparametric bootstrap approach. Finally, the model was applied to assess absorption kinetics of tramadol and predict steady-state pharmacokinetics following administration of both types of formulations. For both formulations, the final model yielded a stable estimate of the absorption time profiles. Steady-state simulation supports switching of patients from IR to PR formulation. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of atypical antipsychotic drugs on QT interval in patients with mental disorders

PubMed Central

Aronow, Wilbert S.

2018-01-01

Background Drug-induced QT prolongation is associated with higher risk of cardiac arrhythmias and cardiovascular mortality. We investigated the effects of atypical antipsychotic drugs on QT interval in children and adults with mental disorders. Methods We conducted random-effects direct frequentist meta-analyses of aggregate data from randomized controlled trials (RCT) and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our search in PubMed, EMBASE, the Cochrane Library, clinicaltrials.gov, and PharmaPendium up to October 2017 identified studies that examined aripiprazole, quetiapine, risperidone, olanzapine, ziprasidone and brexpiprazole. Results Low quality evidence suggests that aripiprazole (four meta-analyses and twelve RCTs), brexpiprazole (one systematic review and four RCTs) or olanzapine (five meta-analyses and twenty RCTs) do not increase QT interval. Low quality evidence suggests that ziprasidone (five meta-analyses and 11 RCTs) increases QT interval and the rates of QT prolongation while risperidone (four meta-analyses, 70 RCTs) and quetiapine (two meta-analyses and seven RCTs) are associated with QT prolongation and greater odds of torsades de pointes ventricular tachycardia especially in cases of drug overdose. Conclusions The main conclusion of our study is that in people with mental disorders and under treatment with atypical antipsychotic drugs, in order to avoid QT prolongation and reduce the risk of ventricular tachycardia clinicians may recommend aripiprazole, brexpiprazole or olanzapine in licensed doses. Long-term comparative safety needs to be established. PMID:29862236

Mianserin, maprotiline and intracardiac conduction

PubMed Central

Edwards, J. Guy; Goldie, Ann

1983-01-01

1 High speed surface electrocardiograms were recorded in 35 patients during the baseline and after four weeks' treatment in a placebo-controlled trial of mianserin and maprotiline in primary depressive illness. 2 Measurements of the RR, PR and QT intervals, QRS width and T wave height were made blind to patient, drug and treatment interval and compared with plasma drug concentrations. The presence or absence of cardiac arrhythmias was recorded. 3 The only significant findings were an increased heart rate and PR interval and decreased QTc interval in the maprotiline group. Only one patient receiving maprotiline had a cardiac arrhythmia. There was no significant correlation between measurements of ECG parameters and plasma drug levels. 4 The results confirm the lack of cardiac effects of mianserin and show both anticholinergic activity and effects of an intracardiac conduction in the case of maprotiline. The mechanisms of these effects are discussed. PMID:6824556

A guide to treating gait impairment with prolonged-release fampridine (Fampyra®) in patients with multiple sclerosis.

PubMed

Ramió-Torrentà, L; Álvarez-Cermeño, J C; Arroyo, R; Casanova-Estruch, B; Fernández, O; García-Merino, J A; Hernández, M A; Izquierdo, G; Martínez-Yélamos, S; Meca, J; Moral, E; Olascoaga, J; Prieto, J M; Saiz, A

2018-06-01

Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. PR-fampridine dosed at 10mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The impact of new partial AUC parameters for evaluating the bioequivalence of prolonged-release formulations.

PubMed

Boily, Michaël; Dussault, Catherine; Massicotte, Julie; Guibord, Pascal; Lefebvre, Marc

2015-01-23

To demonstrate bioequivalence (BE) between two prolonged-release (PR) drug formulations, single dose studies under fasting and fed state as well as at least one steady-state study are currently required by the European Medicines Agency (EMA). Recently, however, there have been debates regarding the relevance of steady-state studies. New requirements in single-dose investigations have also been suggested by the EMA to address the absence of a parameter that can adequately assess the equivalence of the shape of the curves. In the draft guideline issued in 2013, new partial area under the curve (pAUC) pharmacokinetic (PK) parameters were introduced to that effect. In light of these potential changes, there is a need of supportive clinical evidence to evaluate the impact of pAUCs on the evaluation of BE between PR formulations. In this retrospective analysis, it was investigated whether the newly defined parameters were associated with an increase in discriminatory ability or a change in variability compared to the conventional PK parameters. Among the single dose studies that met the requirements already in place, 20% were found unable to meet the EMA's new requirements in regards to the pAUC PK parameters. When pairing fasting and fed studies for a same formulation, the failure rate increased to 40%. In some cases, due to the high variability of these parameters, an increase of the sample size would be required to prove BE. In other cases however, the pAUC parameters demonstrated a robust ability to detect differences between the shapes of the curves of PR formulations. The present analysis should help to better understand the impact of the upcoming changes in European regulations on PR formulations and in the design of future BE studies. Copyright © 2014 Elsevier B.V. All rights reserved.

The QT Interval and Risk of Incident Atrial Fibrillation

PubMed Central

Mandyam, Mala C.; Soliman, Elsayed Z.; Alonso, Alvaro; Dewland, Thomas A.; Heckbert, Susan R.; Vittinghoff, Eric; Cummings, Steven R.; Ellinor, Patrick T.; Chaitman, Bernard R.; Stocke, Karen; Applegate, William B.; Arking, Dan E.; Butler, Javed; Loehr, Laura R.; Magnani, Jared W.; Murphy, Rachel A.; Satterfield, Suzanne; Newman, Anne B.; Marcus, Gregory M.

2013-01-01

BACKGROUND Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine. OBJECTIVE To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF. METHODS We examined a prolonged QT corrected by the Framingham formula (QTFram) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (Health ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by other formulae. RESULTS Among 14,538 ARIC participants, a prolonged QTFram predicted a roughly two-fold increased risk of AF (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.42–2.96, p<0.001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in CHS and Health ABC and were similar across various QT correction methods. Also in ARIC, each 10-ms increase in QTFram was associated with an increased unadjusted (HR 1.14, 95%CI 1.10–1.17, p<0.001) and adjusted (HR 1.11, 95%CI 1.07–1.14, p<0.001) risk of AF. Findings regarding a short QT were inconsistent across cohorts. CONCLUSIONS A prolonged QT interval is associated with an increased risk of incident AF. PMID:23872693

Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nozaki, Yumiko, E-mail: yumiko-nozaki@ds-pharma.co.jp; Honda, Yayoi, E-mail: yayoi-honda@ds-pharma.co.jp; Tsujimoto, Shinji, E-mail: shinji-tsujimoto@ds-pharma.co.jp

2014-07-01

Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min formore » 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I{sub Kr} blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans.« less

Remodeling of repolarization and arrhythmia susceptibility in a myosin-binding protein C knockout mouse model.

PubMed

Toib, Amir; Zhang, Chen; Borghetti, Giulia; Zhang, Xiaoxiao; Wallner, Markus; Yang, Yijun; Troupes, Constantine D; Kubo, Hajime; Sharp, Thomas E; Feldsott, Eric; Berretta, Remus M; Zalavadia, Neil; Trappanese, Danielle M; Harper, Shavonn; Gross, Polina; Chen, Xiongwen; Mohsin, Sadia; Houser, Steven R

2017-09-01

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac diseases and among the leading causes of sudden cardiac death (SCD) in the young. The cellular mechanisms leading to SCD in HCM are not well known. Prolongation of the action potential (AP) duration (APD) is a common feature predisposing hypertrophied hearts to SCD. Previous studies have explored the roles of inward Na + and Ca 2+ in the development of HCM, but the role of repolarizing K + currents has not been defined. The objective of this study was to characterize the arrhythmogenic phenotype and cellular electrophysiological properties of mice with HCM, induced by myosin-binding protein C (MyBPC) knockout (KO), and to test the hypothesis that remodeling of repolarizing K + currents causes APD prolongation in MyBPC KO myocytes. We demonstrated that MyBPC KO mice developed severe hypertrophy and cardiac dysfunction compared with wild-type (WT) control mice. Telemetric electrocardiographic recordings of awake mice revealed prolongation of the corrected QT interval in the KO compared with WT control mice, with overt ventricular arrhythmias. Whole cell current- and voltage-clamp experiments comparing KO with WT mice demonstrated ventricular myocyte hypertrophy, AP prolongation, and decreased repolarizing K + currents. Quantitative RT-PCR analysis revealed decreased mRNA levels of several key K + channel subunits. In conclusion, decrease in repolarizing K + currents in MyBPC KO ventricular myocytes contributes to AP and corrected QT interval prolongation and could account for the arrhythmia susceptibility. NEW & NOTEWORTHY Ventricular myocytes isolated from the myosin-binding protein C knockout hypertrophic cardiomyopathy mouse model demonstrate decreased repolarizing K + currents and action potential and QT interval prolongation, linking cellular repolarization abnormalities with arrhythmia susceptibility and the risk for sudden cardiac death in hypertrophic cardiomyopathy. Copyright © 2017 the American Physiological Society.

Feasibility, diagnostic validity and limits of postmortem evaluation of a newborn infant following an extremely prolonged freezing interval: a thanatological case study.

PubMed

Krajčovič, Jozef; Janík, Martin; Novomeský, František; Straka, Lubomír; Hejna, Petr

2014-11-01

In forensic assessment, denial and concealment of pregnancy has wide-ranging implications including criminal abortions, extramural deliveries, concealment of birth, newborn infant abandonment or even neonaticide. Clarification of whether a newborn was born alive is the most important factor when evaluating an abandoned neonate or concealment of birth. Other points that need to be addressed are determination of viability and maturity of the newborn infant, and the identity of the mother. A prolonged postmortem interval following illegal disposal of a dead body often leads to advanced decomposition, making postmortem elucidation difficult. We report an exceptionally uncommon autopsy case of a well-preserved female newborn, which was accidentally found after eight years in a home freezer. Despite the prolonged postmortem interval, tissue preservation was sufficient for a meaningful autopsy including a comprehensive histopathological study. The purpose of the present investigations was to expand our understanding of thanatological processes, as well as detectability of particular histological findings on the remains of a newborn after extremely prolonged storage in an artificially frozen environment. In addition, this article discusses forensically important issues regarding concealment of newborn infant under specific conditions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mitral valve prolapse and electrolyte abnormality: a dangerous combination for ventricular arrhythmias

PubMed Central

Rajani, Ali Raza; Murugesan, Vagishwari; Baslaib, Fahad Omar; Rafiq, Muhammad Anwer

2014-01-01

A 27-year-old woman with a history of bileaflet mitral valve prolapse and moderate mitral regurgitation presented to our emergency with untractable polymorphic wide complex tachycardia and unstable haemodynamics. After cardiopulmonary resuscitation, return of spontaneous circulation was achieved 30 min later. Her post-resuscitation ECG showed a prolonged QT interval which progressively normalised over the same day. Her laboratory investigations revealed hypocalcaemia while other electrolytes were within normal limits. A diagnosis of ventricular arrhythmia secondary to structural heart disease further precipitated by hypocalcaemia was made. Further hospital stay did not reveal a recurrence of prolonged QT interval or other arrhythmias except for an episode of non-sustained ventricular tachycardia. However, the patient suffered diffuse hypoxic brain encephalopathy secondary to prolonged cardiopulmonary resuscitation. PMID:24827670

Behavioral Hyperventilation and Central Sleep Apnea in Two Children.

PubMed

Johnston, Thomas P; Tam-Williams, Jade; Schmandt, Margaret; Patel, Anand C; Cleveland, Claudia; Coste, Ferdinand; Kemp, James S

2015-04-01

Behavioral hyperventilation is a rarely recognized cause of central sleep apnea (CSA) among children. We report two pediatric patients who presented with prolonged central sleep apnea secondary to behavioral hyperventilation. One patient also had a prolonged corrected QT (QT(C)) interval resulting from hyperventilation

Cardiovascular drugs inducing QT prolongation: facts and evidence.

PubMed

Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

2010-01-01

Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

Paced QT interval as a risk factor for new-onset left ventricular systolic dysfunction and cardiac death after permanent pacemaker implantation.

PubMed

Cho, Eun Jeong; Park, Seung-Jung; Park, Kyoung Min; On, Young Keun; Kim, June Soo

2016-01-15

Prolongation of corrected QT (QTc) interval reflects an increased risk of fatal arrhythmia and cardiac death in various populations. However, it is not clear whether the paced-QTc (p-QTc) interval is associated with new-onset left ventricular systolic dysfunction (new-LVSD) or cardiac death. In 491 consecutive patients (64 ± 14 years) with preserved LV ejection fraction (64 ± 7%), the p-QTc interval was measured within 2 weeks after PPM implantation. We assessed the rates of new-LVSD and cardiac death based on the degree of p-QTc interval. During the follow-up period (78 ± 51 months), new-LVSD and cardiac death were identified in 53 (10.8%) and 26 (5.3%) patients, respectively. Patients with new-LVSD had more frequent atrioventricular block (P=0.041), a higher percentage of ventricular pacing (P=0.005), a longer p-QRS duration (P<0.001), and more prolonged p-QTc interval (P<0.001) compared to those without new-LVSD. There was a graded increase in the rates of new-LVSD (P<0.001) and cardiac death (P=0.001) from the patients in the lowest to those in the highest tertile of the p-QTc interval. Additionally, the incidence of cardiac death was significantly elevated especially in the patients with new-LVSD and wider p-QTc interval. In Cox regression analyses, the p-QTc interval was independently associated with new-LVSD and cardiac death even after adjusted with various relevant confounding factors. Prolonged p-QTc interval was closely associated with new-LVSD and cardiac death after PPM implantation in patients with preserved LV systolic function. The rate of cardiac death significantly increased especially in patients who showed more p-QTc widening along with new-LVSD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa.

PubMed

Padfield, Gareth J; Escudero, Carolina A; DeSouza, Astrid M; Steinberg, Christian; Gibbs, Karen; Puyat, Joseph H; Lam, Pei Yoong; Sanatani, Shubhayan; Sherwin, Elizabeth; Potts, James E; Sandor, George; Krahn, Andrew D

2016-02-09

Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia. Sixty-one adolescent female patients with anorexia nervosa and 45 age- and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; P<0.001) and lower peak heart rates (159±20 versus 184±9 beats/min; P<0.001). The mean QTc intervals were longer at peak exercise in patients (442±29 versus 422±19 ms; P<0.001). During submaximal exertion at comparable heart rates (114±6 versus 115±11 beats/min; P=0.54), the QTc interval had prolonged significantly more in patients than controls (37±28 versus 24±25 ms; P<0.016). The RR/QT slope, best described by a curvilinear relationship, was more gradual in patients than in controls (13.4; 95% confidence interval, 12.8-13.9 versus 15.8; 95% confidence interval, 15.3-16.4 ms QT change per 10% change in RR interval; P<0.001) and steepest in patients within the highest body mass index tertile versus the lowest (13.9; 95% confidence interval, 12.9-14.9 versus 12.3; 95% confidence interval, 11.3-13.3; P=0.026). Despite the absence of manifest QT prolongation, adolescent anorexic females have impaired repolarization reserve in comparison with healthy controls. Further study may identify impaired QT dynamics as a risk factor for arrhythmias in anorexia nervosa. © 2016 American Heart Association, Inc.

Perceptions and attitudes about preexposure prophylaxis among seronegative partners and the potential of sexual disinhibition.

PubMed

Tripathi, Avnish; Whiteside, Y Omar; Duffus, Wayne A

2013-10-01

Preexposure prophylaxis (PrEP) is a promising strategy to prevent human immunodeficiency virus (HIV) infection, especially among high-risk individuals such as seronegative partners; however, many caveats such as the potential risk of sexual disinhibition and noncompliance need to be considered. We explored the sociodemographic and behavioral factors associated with the adoption of PrEP among HIV seronegative men who have sex with men and heterosexual partners. A prepiloted self-administered survey was conducted among seronegative partners in a Ryan White HIV/AIDS Clinic in South Carolina from 2010 to 2011. Bivariate and multivariable analyses were used to explore the data. The survey was completed by 89 seronegative partners. The median age was 42 years (interquartile range 32-50) and a majority was men (56%), black (70%), and heterosexual (74%). A majority (94%) was willing to use PrEP if available; however, 26% of subjects suggested that they would be more likely to have unprotected sex with an HIV-positive partner while using PrEP, and 27% suggested that it would be difficult to take a daily dose of PrEP and consistently use condoms. The multivariable results suggest that the belief that a condom is no longer needed while taking PrEP was more likely among those who did not use a condom during their last sexual intercourse (adjusted odds ratio 7.45; 95% confidence interval 1.57-35.45) and among those with a higher HIV knowledge score (adjusted odds ratio 0.43; 95% confidence interval 0.23-0.78). Overall, these results suggest high acceptability of PrEP among seronegative partners to lower the risk of HIV transmission; however, there is a substantial risk of sexual disinhibition and noncompliance while using PrEP that may be reduced by ongoing education.

Prolonged QT interval in a man with anorexia nervosa

PubMed Central

Macías-Robles, María Dolores; Perez-Clemente, Ana María; Maciá-Bobes, Carmen; Alvarez-Rueda, María Asunción; Pozo-Nuevo, Sergio

2009-01-01

Anorexia nervosa is an eating disorder characterized by the avoidance of food intake, which usually leads to a weight loss. Cardiac co-morbility is common and we can find sometimes a mass loss from the left ventricle, which can be seen by echocardiography. But the commonest complications are rhythm variations, typically bradycardia with a prolonged QT interval in up to a 40% of the cases, which altogether elevates ventricular tachycardia and sudden death risk. We present the case of a male who was diagnosed with anorexia nervosa and developed asthenia, a long QT interval and also a severe both hypokalaemia and hypomagnesaemia. We intend to discuss the pathogenic paths as well as prophylactic and therapeutic measures to this potentially-lethal pathology. PMID:19646241

Effect of cimetidine and ranitidine on pharmacokinetics and pharmacodynamics of a single dose of dofetilide

PubMed Central

Abel, Samantha; Nichols, Donald J; Brearley, Christopher J; Eve, Malcolm D

2000-01-01

Aims The aim of this open-label, placebo-controlled, randomized, four-period crossover study was to determine the effects of cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of a single dose of dofetilide. Methods Twenty healthy male subjects received 100 or 400 mg twice daily of cimetidine, 150 mg twice daily of ranitidine, or placebo for 4 days. On the second day, a single oral 500 μg dose of dofetilide was administered immediately after the morning doses of cimetidine, ranitidine, or placebo. Treatment periods were separated by 1–2 weeks. Pharmacokinetic parameters were determined from plasma and urinary dofetilide concentrations; prolongation of the QTc interval was determined from three-lead electrocardiograms. Results Ranitidine did not significantly affect the pharmacokinetics or pharmacodynamics of dofetilide; however, a dose-dependent increase in exposure to dofetilide was observed with cimetidine. When dofetilide was administered with 100 and 400 mg of cimetidine, the area under the plasma concentration-time curve of dofetilide increased by 11% and 48% and the maximum plasma dofetilide concentration increased by 11% and 29%, respectively. The respective cimetidine doses reduced renal clearance of dofetilide by 13% and 33% and nonrenal clearance by 5% and 21%. Dofetilide-induced prolongation of the QTc interval was enhanced by cimetidine; the mean maximum change in QTc interval from baseline was increased by 22% and 33% with 100 and 400 mg of cimetidine, respectively. However, the relationship between the prolongation of the QTc interval and plasma dofetilide concentrations was unaffected by cimetidine or ranitidine; a 1 ng ml−1 increase in plasma dofetilide concentration produced a 17–19 ms prolongation of the QTc interval. Dofetilide was well tolerated, with no treatment-related adverse events or laboratory abnormalities. Conclusions These results suggest that cimetidine increased dofetilide exposure by inhibiting renal tubular dofetilide secretion, whereas ranitidine did not. This effect is not an H2-receptor antagonist class effect but is specific to cimetidine. If therapy with an H2-receptor antagonist is required, it is recommended that cimetidine at all doses be avoided; since ranitidine has no effect on dofetilide pharmacokinetics or prolongation of the QTc interval, it can be seen as a suitable alternative. PMID:10606839

Left ventricular epicardial activation increases transmural dispersion of repolarization in healthy, long QT, and dilated cardiomyopathy dogs.

PubMed

Bai, Rong; Lü, Jiagao; Pu, Jun; Liu, Nian; Zhou, Qiang; Ruan, Yanfei; Niu, Huiyan; Zhang, Cuntai; Wang, Lin; Kam, Ruth

2005-10-01

Benefits of cardiac resynchronization therapy (CRT) are well established. However, less is understood concerning its effects on myocardial repolarization and the potential proarrhythmic risk. Healthy dogs (n = 8) were compared to a long QT interval (LQT) model (n = 8, induced by cesium chloride, CsCl) and a dilated cardiomyopathy with congestive heart failure (DCM-CHF, induced by rapid ventricular pacing, n = 5). Monophasic action potential (MAP) recordings were obtained from the subendocardium, midmyocardium, subepicardium, and the transmural dispersion of repolarization (TDR) was calculated. The QT interval and the interval from the peak to the end of the T wave (T(p-e)) were measured. All these characteristics were compared during left ventricular epicardial (LV-Epi), right ventricular endocardial (RV-Endo), and biventricular (Bi-V) pacing. In healthy dogs, TDR prolonged to 37.54 ms for Bi-V pacing and to 47.16 ms for LV-Epi pacing as compared to 26.75 ms for RV-Endo pacing (P < 0.001), which was parallel to an augmentation in T(p-e) interval (Bi-V pacing, 64.29 ms; LV-Epi pacing, 57.89 ms; RV-Endo pacing, 50.29 ms; P < 0.01). During CsCl exposure, Bi-V and LV-Epi pacing prolonged MAPD, TDR, and T(p-e) interval as compared to RV-Endo pacing. The midmyocardial MAPD (276.30 ms vs 257.35 ms, P < 0.0001) and TDR (33.80 ms vs 27.58 ms, P=0.002) were significantly longer in DCM-CHF dogs than those in healthy dogs. LV-Epi and Bi-V pacing further prolonged the MAPD and TDR in this model. LV-Epi and Bi-V pacing result in prolongation of ventricular repolarization time, and increase of TDR accounted for a parallel augmentation of the T(p-e) interval, which provides evidence that T(p-e) interval accurately represents TDR. These effects are magnified in the LQT and DCM-CHF canine models in addition to their intrinsic transmural heterogeneity in the intact heart. This mechanism may contribute to the development of malignant ventricular arrhythmias, such as torsades de pointes (TdP) in congestive heart failure (CHF) patients treated with CRT.

Progesterone induces progesterone receptor gene (PGR) expression via rapid activation of protein kinase pathways required for cooperative estrogen receptor alpha (ER) and progesterone receptor (PR) genomic action at ER/PR target genes.

PubMed

Diep, Caroline H; Ahrendt, Hannah; Lange, Carol A

2016-10-01

Progesterone Receptors (PRs) are critical effectors of estrogen receptor (ER) signaling required for mammary gland development and reproductive proficiency. In breast and reproductive tract malignancies, PR expression is a clinical prognostic marker of ER action. While estrogens primarily regulate PR expression, other factors likely contribute to a dynamic range of receptor expression across diverse tissues. In this study, we identified estrogen-independent but progestin (R5020)-dependent regulation of ER target genes including PGR in ER+/PR+ cancer cell lines. R5020 (10nM-10μM range) induced dose-dependent PR mRNA and protein expression in the absence of estrogen but required both PR and ERα. Antagonists of either PR (RU486, onapristone) or ERα (ICI 182,780) attenuated R5020 induction of TFF1, CTSD, and PGR. Chromatin immunoprecipitation (ChIP) assays performed on ER+/PR+ cells demonstrated that both ERα and PR were recruited to the same ERE/Sp1 site-containing region of the PGR proximal promoter in response to high dose progestin (10μM). Recruitment of ERα and PR to chromatin and subsequent PR mRNA induction were dependent upon rapid activation of MAPK/ERK and AKT; inhibition of these kinase pathways via U0126 or LY294002 blocked these events. Overall, we have identified a novel mechanism of ERα activation initiated by rapid PR-dependent kinase pathway activation and associated with phosphorylation of ERα Ser118 for estrogen-independent but progestin-dependent ER/PR cross talk. These studies may provide insight into mechanisms of persistent ER-target gene expression during periods of hormone (i.e. estrogen) ablation and suggest caution following prolonged treatment with aromatase or CYP17 inhibitors (i.e. contexts when progesterone levels may be abnormally elevated). Copyright © 2016 Elsevier Inc. All rights reserved.

Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease.

PubMed

Morimoto, Takaaki; Mineharu, Yohei; Ono, Koh; Nakatochi, Masahiro; Ichihara, Sahoko; Kabata, Risako; Takagi, Yasushi; Cao, Yang; Zhao, Lanying; Kobayashi, Hatasu; Harada, Kouji H; Takenaka, Katsunobu; Funaki, Takeshi; Yokota, Mitsuhiro; Matsubara, Tatsuaki; Yamamoto, Ken; Izawa, Hideo; Kimura, Takeshi; Miyamoto, Susumu; Koizumi, Akio

2017-01-01

The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested. We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37-6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16-21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87-16.77; p = 0.076). The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.

Post-marketing surveillance of sertindole.

PubMed

Toumi, Mondher

2002-01-01

The atypical antipsychotic drug, sertindole, like several other drugs, causes QT interval prolongation. Prolongation of the QT interval on the electrocardiogram has been associated with an increased risk of ventricular arrhythmia, including the more serious form, torsades de pointes, and is thus a safety concern for the authorities. In the case of sertindole, however, the available pharmacoepidemiological studies gathering data from about 10 000 patients documented the lack of increased risk associated to sertindole in comparison to other atypical antipsychotics. On the basis of these data, as well as non-clinical and clinical safety data, the CPMP expert group concluded that, although sertindole has the potential to prolong the QT interval, ¤ ¤ QT interval prolongation does not seem to be a reliable proxy for the risk of severe cardiac arrhythmias'', and there are no clinical data suggesting that sertindole is more arrhythmogenic than are other atypical antipsychotics. To further substantiate this conclusion, two post-marketing surveillance studies have been initiated. One is a randomized comparison of sertindole and risperidone under normal conditions of use. Randomization minimizes selection bias and the intention is that allocation to the two treatment arms will yield comparable treatment groups. While the two drugs will be given in an open-label fashion, all safety data will be blinded and reviewed by an independent safety committee. The other study is an observational study that includes all patients prescribed sertindole who, for whatever reason, will not be included in the randomized study. In all, 10 000 patients are expected to take part in the studies, which will run for at least 1 year.

Genetics Home Reference: Jervell and Lange-Nielsen syndrome

MedlinePlus

... KCNQ1 or KCNE1 mutation have a long QT interval with related heart abnormalities, but their hearing is ... disease Jervell-Lange Nielsen syndrome JLNS prolonged QT interval in EKG and sudden death surdo-cardiac syndrome ...

Memory retrieval as a self-propagating process.

PubMed

Bäuml, Karl-Heinz T; Schlichting, Andreas

2014-07-01

Retrieval of a subset of studied items and the presentation of those items as retrieval cues typically impair retrieval of the other items. Previous research on this self-limiting property of memory retrieval has relied heavily on short retention intervals and similar context between encoding and test. Here, we examined retrieval dynamics also after a prolonged retention interval with different spatial and social context between encoding and test, conditions that mimic people's remembering in many situations of daily life. For both unrelated word lists and more integrated prose material, we found retrieval and cuing to impair recall of other studied items after a short retention interval, but to improve recall in the prolonged retention interval condition. The results demonstrate that retrieval dynamics depend critically on situation, indicating that quite often in daily life, retrieval may be a self-propagating, rather than a self-limiting process. Copyright © 2014 Elsevier B.V. All rights reserved.

Electrophysiology and metabolism of caveolin-3 overexpressing mice

PubMed Central

Schilling, Jan M.; Horikawa, Yousuke T.; Zemljic-Harpf, Alice E.; Vincent, Kevin P.; Tyan, Leonid; Yu, Judith K.; McCulloch, Andrew D.; Balijepalli, Ravi C.; Patel, Hemal H.; Roth, David M.

2017-01-01

Caveolin-3 (Cav-3) plays a critical role in organizing signaling molecules and ion channels involved in cardiac conduction and metabolism. Mutations in Cav-3 are implicated in cardiac conduction abnormalities and myopathies. Additionally, cardiac specific overexpression of Cav-3 (Cav-3 OE) is protective against ischemic and hypertensive injury suggesting a potential role for Cav-3 in basal cardiac electrophysiology and metabolism involved in stress adaptation. We hypothesized that overexpression of Cav-3 may alter baseline cardiac conduction and metabolism. We examined: 1) ECG telemetry recordings at baseline and during pharmacological interventions, 2) ion channels involved in cardiac conduction with immunoblotting and computational modeling, and 3) baseline metabolism in Cav-3 OE and transgene negative littermate control mice. Cav-3 OE mice had decreased heart rates, prolonged PR intervals, and shortened QTc intervals with no difference in activity compared to control mice. Dobutamine or propranolol did not cause significant changes between experimental groups in maximal (dobutamine) or minimal (propranolol) heart rate. Cav-3 OE mice had an overall lower chronotropic response to atropine. Expression of Kv1.4 and Kv4.3 channels, Nav1.5 channels and connexin 43 were increased in Cav-3 OE mice. A computational model integrating the immunoblotting results indicated shortened action potential duration in Cav-3 OE mice linking the change in channel expression to the observed electrophysiology phenotype. Metabolic profiling showed no gross differences in VO2, VCO2, respiratory exchange ratio, and heat generation, feeding or drinking. In conclusion, Cav-3 OE mice have changes in ECG intervals, heart rates, and cardiac ion channel expression. These findings give novel mechanistic insights into previously reported Cav-3 dependent cardioprotection. PMID:27023865

Role of mixed ion channel effects in the cardiovascular safety assessment of the novel anti-MRSA fluoroquinolone JNJ-Q2.

PubMed

Eichenbaum, G; Pugsley, M K; Gallacher, D J; Towart, R; McIntyre, G; Shukla, U; Davenport, J M; Lu, H R; Rohrbacher, J; Hillsamer, V

2012-07-01

JNJ-Q2, a novel broad-spectrum fluoroquinolone with anti-methicillin-resistant Staphylococcus aureus activity, was evaluated in a comprehensive set of non-clinical and clinical cardiovascular safety studies. The effect of JNJ-Q2 on different cardiovascular parameters was compared with that of moxifloxacin, sparfloxacin and ofloxacin. Through comparisons with these well-known fluoroquinolones, the importance of effects on compensatory ion channels to the cardiovascular safety of JNJ-Q2 was investigated. JNJ-Q2 and comparator fluoroquinolones were evaluated in the following models/test systems: hERG-transfected HEK293 cells sodium channel-transfected CHO cells, guinea pig right atria, arterially perfused rabbit left ventricular wedge preparations and in vivo studies in anaesthetized guinea pigs, anaesthetized and conscious telemetered dogs, and a thorough QT study in humans. The trend for effects of JNJ-Q2 on Tp-Te, QT, QRS and PR intervals in the non-clinical models and the plateau in QTc with increasing plasma concentration in humans are consistent with offsetting sodium and calcium channel activities that were observed in the non-clinical studies. These mixed ion channel activities result in the less pronounced or comparable increase in QTc interval for JNJ-Q2 compared with moxifloxacin and sparfloxacin despite its greater in vitro inhibition of I(Kr). Based on the non-clinical and clinical cardiovascular safety assessment, JNJ-Q2 has a safe cardiovascular profile for administration in humans with comparable or reduced potential to prolong QT intervals, compared with moxifloxacin. The results demonstrate the importance of compensatory sodium and calcium channel activity in offsetting potassium channel activity for compounds with a fluoroquinolone core. © 2012 Janssen Pharmaceutical Companies of Johnson & Johnson. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Clinical impact of prolonged diagnosis to treatment interval (DTI) among patients with oropharyngeal squamous cell carcinoma.

PubMed

Sharma, Sonam; Bekelman, Justin; Lin, Alexander; Lukens, J Nicholas; Roman, Benjamin R; Mitra, Nandita; Swisher-McClure, Samuel

2016-05-01

We examined practice patterns using the National Cancer Data Base (NCDB) to determine risk factors for prolonged diagnosis to treatment interval (DTI) and survival outcomes in patients receiving chemoradiation for oropharyngeal squamous cell carcinoma (OPSCC). We identified 6606 NCDB patients with Stage III-IV OPSCC receiving chemoradiation from 2003 to 2006. We determined risk factors for prolonged DTI (>30days) using univariate and multivariable logistic regression models. We examined overall survival (OS) using Kaplan Meier and multivariable Cox proportional hazards models. 3586 (54.3%) patients had prolonged DTI. Race, IMRT, insurance status, and high volume facilities were significant risk factors for prolonged DTI. Patients with prolonged DTI had inferior OS compared to DTI⩽30days (Hazard Ratio (HR)=1.12, 95% CI 1.04-1.20, p=0.005). For every week increase in DTI there was a 2.2% (95% CI 1.1-3.3%, p<0.001) increase in risk of death. Patients receiving IMRT, treatment at academic, or high-volume facilities were more likely to experience prolonged DTI (High vs. Low volume: 61.5% vs. 51.8%, adjusted OR 1.38, 95% CI 1.21-1.58; Academic vs. Community: 59.5% vs. 50.6%, adjusted OR 1.26, 95% CI 1.13-1.42; non-IMRT vs. IMRT: 53.4% vs. 56.5%; adjusted OR 1.17, 95% CI 1.04-1.31). Our results suggest that prolonged DTI has a significant impact on survival outcomes. We observed disparities in DTI by socioeconomic factors. However, facility level factors such as academic affiliation, high volume, and IMRT also increased risk of DTI. These findings should be considered in developing efficient pathways to mitigate adverse effects of prolonged DTI. Copyright © 2016 Elsevier Ltd. All rights reserved.

A comparative study of QT prolongation with serotonin reuptake inhibitors.

PubMed

Ojero-Senard, Ana; Benevent, Justine; Bondon-Guitton, Emmanuelle; Durrieu, Geneviève; Chebane, Leila; Araujo, Melanie; Montastruc, Francois; Montastruc, Jean-Louis

2017-10-01

QT interval prolongations were described with citalopram and escitalopram. However, the effects of the other serotonin reuptake inhibitors (SRIs) remained discussed. In order to identify a putative signal with other SRIs, the present study investigates the reports of QT interval prolongation with SRIs in two pharmacovigilance databases (PVDB). Two kinds of investigations were performed: (1) a comparative study in VigiBase®, the WHO PVDB, where notifications of QT prolongation with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were selected. Cases with overdose or pregnancy were excluded. The relationship between the "suspected" SRI and occurrence of QT prolongation was assessed by calculating reporting odds ratio (ROR) in a case/non-case design. (2) A descriptive study of QT prolongation reports with citalopram and escitalopram in the French FPVD. In VigiBase®, 855 notifications were identified (mean age 56.2 years, mainly women 73%). Among them, 172 (20.1%) were associated to escitalopram; 299 (35.0%), to citalopram; 186 (21.8%), to fluoxetine; 94 (11.0%), to sertraline; 66 (7.7%), to paroxetine; and 38 (4.4%) to fluvoxamine. A significant ROR value (higher than 1) was only found for citalopram (3.35 CI95% [2.90-3.87]) or escitalopram (2.50 [2.11-2.95]). In the FPVD, eight reports of QT prolongation were found with citalopram and 27 with escitalopram, mainly in women (77.1%) with a mean age of 73.2 years. In 23 cases (66%), SRIs were associated with other suspected drugs, mainly cardiotropic or psychotropic ones. Hypokalemia was associated in six patients. This study, performed in real conditions of life, shows a clear signal of QT prolongation with only two SRIs, citalopram and escitalopram, indicating that QT prolongation is not a SRI class effect.

Assessment of the QT interval in the electroencephalography (EEG) of children with syncope, epilepsy, and attention-deficit hyperactivity disorder (ADHD).

PubMed

Jha, Om P; Khurana, Divya S; Carvalho, Karen S; Melvin, Joseph J; Legido, Agustin; O'Riordan, Anna C; Valencia, Ignacio

2010-03-01

The interpretation of QT interval is often neglected during electroencephalography (EEG) reading. We compared the incidence of prolonged QT interval, as seen in the electrocardiography (ECG) recording lead of the EEG, in children presenting with seizure, syncope, or attention-deficit hyperactivity disorder (ADHD). Abnormal QT was defined as >460 ms. The incidence of prolonged QT in the seizure, syncope, and ADHD groups was 1/50 (2%), 7/50 (14%), and 2/50 (4%), respectively (P = .036, chi-square). The mean +/- SD of QT were 405 +/- 34, 424 +/- 39, and 414 +/- 36, respectively (P = .035, analysis of variance [ANOVA], syncope group, compared with seizure group). The incidence of prolonged QT as measured in the EEG was unexpectedly high in children presenting with seizure, syncope, or ADHD. These data support the concept that QT evaluation should be emphasized during routine EEG reading, as it may aid in identifying cases of undiagnosed cardiac conduction abnormalities. Prospective studies comparing EEG-ECG tracings with 12-lead ECG are warranted.

The effects of intravenous anesthetics on QT interval during anesthetic induction with sevoflurane.

PubMed

Terao, Yoshiaki; Higashijima, Ushio; Toyoda, Tomomi; Ichinomiya, Taiga; Fukusaki, Makoto; Hara, Tetsuya

2016-12-01

Sevoflurane is known to prolong the QT interval. This study aimed to determine the effect of the interaction between intravenous anesthetics and sevoflurane on the QT interval. The study included 48 patients who underwent lumbar spine surgery. Patients received 3 μg/kg fentanyl and were then randomly allocated to either Group T, in which they received 5 mg/kg thiamylal, or Group P, in which they received 1.5 mg/kg propofol, at 2 min after administration of fentanyl injection for anesthetic induction. Vecuronium (1.5 mg/kg) and sevoflurane (3 % inhaled concentration) were administered immediately after loss of consciousness and tracheal intubation was performed 3 min after vecuronium injection. Heart rate (HR), mean arterial pressure (MAP), bispectral index score (BIS), and the heart rate-corrected QT (QTc) interval on a 12-lead electrocardiogram were recorded immediately before fentanyl administration (T1), 2 min after fentanyl injection (T2), immediately before intubation (T3), and 2 min after intubation (T4). There were no significant differences between the two groups in baseline patient characteristics. BIS and MAP significantly decreased after anesthesia induction in both groups. At T3, MAP in Group T was higher than in Group P, while HR had reduced in both groups. The QTc interval was prolonged after anesthesia induction in Group T, but did not change at any time point in Group P. The QTc interval after anesthesia induction in Group T was longer than in Group P. We concluded that an injection of propofol could counteract QTc interval prolongation associated with sevoflurane anesthesia induction.

Cost-effectiveness of raising HDL cholesterol by adding prolonged-release nicotinic acid to statin therapy in the secondary prevention setting: a French perspective.

PubMed

Roze, S; Ferrières, J; Bruckert, E; Van Ganse, E; Chapman, M J; Liens, D; Renaudin, C

2007-11-01

To evaluate the cost-effectiveness of raising high-density lipoprotein cholesterol (HDL-C) with add-on nicotinic acid in statin-treated patients with coronary heart disease (CHD) and low HDL-C, from the French healthcare system perspective. Computer simulation economic modelling incorporating two decision analytic submodels was used. The first submodel generated a cohort of 2000 patients and simulated lipid changes using baseline characteristics and treatment effects from the ARterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol (ARBITER 2) study. Prolonged-release (PR) nicotinic acid (1 g/day) was added in patients with HDL-C < 40 mg/dl (1.03 mmol/l) on statin alone. The second submodel used standard Markov techniques to evaluate long-term clinical and economic outcomes based on Framingham risk estimates. Direct medical costs were accounted from a third party payer perspective [2004 Euros (euro)] and discounted by 3%. Addition of PR nicotinic acid to statin therapy resulted in substantial health gain and increased life expectancy, at a cost well within the threshold (< 50,000 euros per life year gained) considered good value for money in Western Europe. Raising HDL-C by adding PR nicotinic acid to statin therapy in CHD patients was cost-effective in France at a level considered to represent good value for money by reimbursement authorities in Europe. This strategy was highly cost-effective in CHD patients with type 2 diabetes.

Piperaquine Population Pharmacokinetics and Cardiac Safety in Cambodia

PubMed Central

Lon, Chanthap; Spring, Michele; Sok, Sommethy; Ta-aksorn, Winita; Kodchakorn, Chanikarn; Pann, Sut-Thang; Chann, Soklyda; Ittiverakul, Mali; Sriwichai, Sabaithip; Buathong, Nillawan; Kuntawunginn, Worachet; So, Mary; Youdaline, Theng; Milner, Erin; Wojnarski, Mariusz; Lanteri, Charlotte; Manning, Jessica; Prom, Satharath; Haigney, Mark; Cantilena, Louis; Saunders, David

2017-01-01

ABSTRACT Despite the rising rates of resistance to dihydroartemisinin-piperaquine (DP), DP remains a first-line therapy for uncomplicated malaria in many parts of Cambodia. While DP is generally well tolerated as a 3-day DP (3DP) regimen, compressed 2-day DP (2DP) regimens were associated with treatment-limiting cardiac repolarization effects in a recent clinical trial. To better estimate the risks of piperaquine on QT interval prolongation, we pooled data from three randomized clinical trials conducted between 2010 and 2014 in northern Cambodia. A population pharmacokinetic model was developed to compare exposure-response relationships between the 2DP and 3DP regimens while accounting for differences in regimen and sample collection times between studies. A 2-compartment model with first-order absorption and elimination without covariates best fit the data. The linear slope-intercept model predicted a 0.05-ms QT prolongation per ng/ml of piperaquine (5 ms per 100 ng/ml) in this largely male population. Though the plasma half-life was similar in both regimens, peak and total piperaquine exposures were higher in those treated with the 2DP regimen. Furthermore, the correlation between the plasma piperaquine concentration and the QT interval prolongation was stronger in the population receiving the 2DP regimen. Neither the time since the previous meal nor the baseline serum magnesium or potassium levels had additive effects on QT interval prolongation. As electrocardiographic monitoring is often nonexistent in areas where malaria is endemic, 2DP regimens should be avoided and the 3DP regimen should be carefully considered in settings where viable alternative therapies exist. When DP is employed, the risk of cardiotoxicity can be mitigated by combining a 3-day regimen, enforcing a 3-h fast before and after administration, and avoiding the concomitant use of QT interval-prolonging medications. (This study used data from three clinical trials that are registered at ClinicalTrials.gov under identifiers NCT01280162, NCT01624337, and NCT01849640.) PMID:28193647

Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice

PubMed Central

Eigenbrod, Sabina; Frick, Petra; Bertsch, Uwe; Mitteregger-Kretzschmar, Gerda; Mielke, Janina; Maringer, Marko; Piening, Niklas; Hepp, Alexander; Daude, Nathalie; Windl, Otto; Levin, Johannes; Giese, Armin; Sakthivelu, Vignesh; Tatzelt, Jörg

2017-01-01

Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1–4, H60G, H68G, H76G, H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110; "H95G" allele) and monitored the formation of misfolded PrP in vivo. Novel transgenic mice expressing PrP(TetraH>G) at levels comparable to wild-type (wt) controls were susceptible to mouse-adapted scrapie strain RML but showed significantly prolonged incubation times. In contrast, amino acid replacement at residue 95 accelerated disease progression in corresponding PrP(H95G) mice. Neuropathological lesions in terminally ill transgenic mice were similar to scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition, however, was not synaptic as seen in wt animals, but instead dense globular plaque-like accumulations of PrPSc in TgPrP(TetraH>G) mice and diffuse PrPSc deposition in (TgPrP(H95G) mice), were observed throughout all brain sections. We conclude that OR and site 5 histidine substitutions have divergent phenotypic impacts and that cis interactions between the OR region and the site 5 region modulate pathogenic outcomes by affecting the PrP globular domain. PMID:29220360

HIS bundle electrogram in rheumatic mitral valve disease with special reference to Bachmann's bundle block in P mitrale.

PubMed

Lee, Y S; Lien, W P

1975-08-01

HBEs were recorded from either the right or left ventricle or simultaneously from both in 26 patients with chronic rheumatic mitral stenosis alone or in association with other mild valvular lesions during the diagnostic cardiac catheterization. Eleven of the patients had auricular fibrillation. Of the remaining 15 patients with sinus mechanism and P mitrale in the surface electrocardiogram, 12 were noted to have H potential preceded the termination of P wave and gave P2H interval of negative value- so-called "Bachmann's bundle block". Among these, double atrial activities (A and A' waves) could be identified on the HBE recorded from the left ventricular endocardial surface with catheter electrodes positioned at the subarotic region in 7 patients studied. Interatrial conduction time (P1A' interval) measured in these patients was prolonged in all and ranged from 47 to 82 with an average of 66 msec. Prolongation of intraatrial (or internodal) conduction time was noted in only one patient who also had first degree A-V block and prolonged A-H interval. There was no correlation of either P1P2 or P2H interval to the degree of left atrial enlargement. The P1P2 or P2H interval also had no correlation with hemodynamic parameters. In patients with auricular fibrillation, all impulses unable to conduct to the ventricle were blocked proximal to the His bundle and concealed conduction was not observed distal to it.

Development and evaluation of a centralised computerised registry for ureteric stents: completing the audit cycle.

PubMed

Davis, N F; Murray, G; O'Connor, T; Browne, C; MacCraith, E; Galvin, D; Mulvin, D; Quinlan, D; Lennon, G

2017-11-01

A forgotten ureteric stent may result in severe renal impairment leading to nephrectomy. To compare the effectiveness of a centralised computerised registry for monitoring ureteric stent activity with a previously established theatre stent logbook system. This prospective audit was performed in two 9-monthly intervals. During the first interval, insertion/removal of a ureteric stent was documented in a specific theatre stent logbook. In the second interval, an electronic centralised computerised registry was developed to document insertion/removal of a ureteric stent onto an accessible hospital server. A computerised traffic-light system was also developed to identify patients with an indwelling stent for >3 months. The primary outcome variable was the number of prolonged indwelling ureteric stents in both groups. During the first time interval, 188 ureteric stents were inserted and 182 (96%) were removed or changed. Six (4%) patients underwent insertion of a ureteric stent for a prolonged period of time (>6 months). This subgroup required complex endourological intervention for stent removal due to encrustation. During the second time interval, 157 ureteric stents were inserted and all patients had their stent removed or changed within 6 months. No patients in this group were lost to follow-up. This study demonstrates that a centralised computerised ureteric stent registry is superior to a conventional logbook for monitoring ureteric stent activity. We propose the introduction a centralised nationalised ureteric stent registry for eliminating the potential for prolonged or forgotten ureteric stents.

Knowledge of Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Men Who Have Sex with Men in Denver, Colorado

PubMed Central

Al-Tayyib, Alia A.; Thrun, Mark W.; Haukoos, Jason S.; Walls, N. Eugene

2014-01-01

As part of the National HIV Behavioral Surveillance System among men who have sex with men (MSM) in Denver, Colorado, we assessed knowledge of pre-exposure prophylaxis (PrEP); willingness to use PrEP; and potential changes in risk behaviors among HIV-negative participants reporting sexual activity with a male partner in the preceding 12 months. We examined knowledge of PrEP before (2008) and after (2011) results of the iPrEx trial were available. Of the 425 participants in the 2008 sample, 91 (21 %) were aware of PrEP compared to 131 (28 %) of the 461 participants in the 2011 sample (adjusted prevalence ratio: 1.43, 95 % confidence interval: 1.18, 1.72). Despite the increase in 2011, few MSM in Denver were aware of PrEP. Educating high-risk MSM about the potential utility of PrEP as an adjunct to other effective prevention methods is needed when considering the addition of PrEP to the HIV prevention arsenal. PMID:23824227

Prolonging Microgravity on Parabolic Airplane Flights

NASA Technical Reports Server (NTRS)

Robinson, David W.

2003-01-01

Three techniques have been proposed to prolong the intervals of time available for microgravity experiments aboard airplanes flown along parabolic trajectories. Typically, a pilot strives to keep an airplane on such a trajectory during a nominal time interval as long as 25 seconds, and an experimental apparatus is released to float freely in the airplane cabin to take advantage of the microgravitational environment of the trajectory for as long as possible. It is usually not possible to maintain effective microgravity during the entire nominal time interval because random aerodynamic forces and fluctuations in pilot control inputs cause the airplane to deviate slightly from a perfect parabolic trajectory, such that the freely floating apparatus bumps into the ceiling, floor, or a wall of the airplane before the completion of the parabola.

New technique to prevent prolonged air leak: use of 'Tachosuture' technique.

PubMed

Nishida, Tatsuya; Mikami, Iwao; Fujii, Yoshitaka

2017-02-01

Prolonged air leak (defined as air leak >7 days), caused by pulmonary resection or alveolar-pleural fistula, increases postoperative morbidity, prolongs hospital stay and increases healthcare costs. We describe a new technique ('Tachosuture' technique) to prevent prolonged air leak. The key point of this new technique is that air leak is classified into three types and an absorbable suture is added to a TachoSil ® patch in each type to prevent detachment from the lung parenchyma. Between August 2013 and March 2016, 40 patients underwent thoracoscopic surgery using 'Tachosuture' technique. Postoperative air leak always stopped within 3 days (95% confidence interval for the absence of prolonged air leak: 92.5-100%). It is considered that this simple technique is useful to prevent prolonged air leak.

Functional properties of LRRK2 mutations in Taiwanese Parkinson disease.

PubMed

Chang, Kuo-Hsuan; Chen, Chiung-Mei; Lin, Chih-Hsin; Chang, Wen-Teng; Jiang, Pei-Ru; Hsiao, Ya-Chin; Wu, Yih-Ru; Lee-Chen, Guey-Jen

2017-03-01

Leucine-rich repeat kinase 2 (LRRK2) is a large protein encoding multiple functional domains. Mutations within different LRRK2 domains have been considered to be involved in the development of Parkinson disease by different mechanisms. Our previous study found three LRRK2 mutations-p.R767H, p.S885N, and p.R1441H-in Taiwanese patients with Parkinson disease. We evaluated the functional properties of LRRK2 p.R767H, p.S885N, and p.R1441H mutations by overexpressing them in human embryonic kidney 293 and neuroblastoma SK-N-SH cells. The common p.G2019S mutation in the kinase domain was included for comparison. In 293 cells, overexpressed p.R1441H-but not p.R767H, p.S885N, or p.G2019-increased GTP binding affinity to prolong the active state. Overexpressed p.R1441H and p.G2019S generated inclusions in 293 cells. In SK-N-SH cells, the α-synuclein was coexpressed with wild type as well as mutated p.R767H, p.S885N, p.R1441H, and p.G2019 LRRK2 proteins. Part of the perinuclear inclusions formed by p.R1441H and p.G2019S were colocalized with α-synuclein. Additionally, p.S885N and p.R1441H mutations caused reduced interaction between LRRK2 and ARHGEF7, a putative guanine nucleotide exchange factor for LRRK2, whereas this interaction was well preserved in p.R767H and p.G2019S mutations. Our study suggests that p.R1441H protein facilitates the formation of intracellular inclusions, compromises GTP hydrolysis by increasing its affinity for GTP, and reduces its interaction with ARHGEF7. Copyright © 2016. Published by Elsevier B.V.

Novel orally available salvinorin A analog PR-38 inhibits gastrointestinal motility and reduces abdominal pain in mouse models mimicking irritable bowel syndrome.

PubMed

Sałaga, M; Polepally, P R; Sobczak, M; Grzywacz, D; Kamysz, W; Sibaev, A; Storr, M; Do Rego, J C; Zjawiony, J K; Fichna, J

2014-07-01

The opioid and cannabinoid systems play a crucial role in multiple physiological processes in the central nervous system and in the periphery. Selective opioid as well as cannabinoid (CB) receptor agonists exert a potent inhibitory action on gastrointestinal (GI) motility and pain. In this study, we examined (in vitro and in vivo) whether PR-38 (2-O-cinnamoylsalvinorin B), a novel analog of salvinorin A, can interact with both systems and demonstrate therapeutic effects. We used mouse models of hypermotility, diarrhea, and abdominal pain. We also assessed the influence of PR-38 on the central nervous system by measurement of motoric parameters and exploratory behaviors in mice. Subsequently, we investigated the pharmacokinetics of PR-38 in mouse blood samples after intraperitoneal and oral administration. PR-38 significantly inhibited mouse colonic motility in vitro and in vivo. Administration of PR-38 significantly prolonged the whole GI transit time, and this effect was mediated by µ- and κ-opioid receptors and the CB1 receptor. PR-38 reversed hypermotility and reduced pain in mouse models mimicking functional GI disorders. These data expand our understanding of the interactions between opioid and cannabinoid systems and their functions in the GI tract. We also provide a novel framework for the development of future potential treatments of functional GI disorders. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Cardiac and non-cardiac causes of T-wave inversion in the precordial leads in adult subjects: A Dutch case series and review of the literature

PubMed Central

Said, Salah AM; Bloo, Rene; de Nooijer, Ramon; Slootweg, Andries

2015-01-01

AIM: To describe the electrocardiographic (ECG) phenomena characterized by T-wave inversion in the precordial leads in adults and to highlight its differential diagnosis. METHODS: A retrospective chart review of 8 adult patients who were admitted with ECG T-wave inversion in the anterior chest leads with or without prolongation of corrected QT (QTc) interval. They had different clinical conditions. Each patient underwent appropriate clinical assessment including investigation for myocardial involvement. Single and multimodality non-invasive, semi-invasive and invasive diagnostic approach were used to ascertain the diagnosis. The diagnostic assessment included biochemical investigation, cardiac and abdominal ultrasound, cerebral and chest computed tomography, nuclear medicine and coronary angiography. RESULTS: Eight adult subjects (5 females) with a mean age of 66 years (range 51 to 82) are analyzed. The etiology of T-wave inversion in the precordial leads were diverse. On admission, all patients had normal blood pressure and the ECG showed sinus rhythm. Five patients showed marked prolongation of the QTc interval. The longest QTc interval (639 ms) was found in the patient with pheochromocytoma. Giant T-wave inversion (≥ 10 mm) was found in pheochromocytoma followed by electroconvulsive therapy and finally ischemic heart disease. The deepest T-wave was measured in lead V3 (5 ×). In 3 patients presented with mild T-wave inversion (patients 1, 5 and 4 mm), the QTc interval was not prolonged (432, 409 and 424 msec), respectively. CONCLUSION: T-wave inversion associated with or without QTc prolongation requires meticulous history taking, physical examination and tailored diagnostic modalities to reach rapid and correct diagnosis to establish appropriate therapeutic intervention. PMID:25717356

QTc abnormalities in deliberate self-poisoning with moclobemide.

PubMed

Downes, M A; Whyte, I M; Isbister, G K

2005-07-01

Several medications have been found to prolong the QT interval in overdose. This can predispose to torsade de pointes-type ventricular tachycardia. To analyse the effects of moclobemide deliberate self-poisoning on the length of both QT and corrected QT (QTc) intervals. Electrocardiograms (ECG) of all patients presenting to a regional toxicology service with moclobemide ingestion were reviewed. Cases where a cardiotoxic agent was coingested were excluded. QT and QTc parameters were compared with a comparison group of patients ingesting paracetamol or benzodiazepines. Of 75 patients where ECG were available, the median ingested dose was 4.5 g (interquartile range (IQR): 2.4-7.5; range: 0.6-18 g) and the median age was 34 years (IQR: 26-44). The mean QT interval was 415 ms (standard deviation (SD): 51 ms) with a mean QTc of 459 ms (SD: 44 ms), and were prolonged compared with the comparison group. Twelve female patients had a QTc > 500 ms and in seven of these causality was established based on a pre- or post-ECG with a QTc < 500 ms. Only 10% of the moclobemide cases had a heart rate (HR) > 100 beats per minute, making overcorrection of HR by Bazett's formula an unlikely cause of the findings. No cardiac arrythmias were observed other than one case of first-degree heart block. Moclobemide prolongs the QT and QTc intervals in overdose and a 12-lead ECG should be done on all moclobemide deliberate self-poisonings. Continuous cardiac monitoring for what is otherwise a relatively benign overdose would appear to be an inappropriate use of resources but can be considered in patients with a QTc > 500 ms or with known risks for QT prolongation.

A comparison of an A1 adenosine receptor agonist (CVT-510) with diltiazem for slowing of AV nodal conduction in guinea-pig

PubMed Central

Snowdy, Stephen; Liang, Hui Xiu; Blackburn, Brent; Lum, Robert; Nelson, Marek; Wang, Lisa; Pfister, Jürg; Sharma, Bhavender P; Wolff, Andrew; Belardinelli, Luiz

1999-01-01

The purpose of this study was to compare the pharmacological properties (i.e. the AV nodal depressant, vasodilator, and inotropic effects) of two AV nodal blocking agents belonging to different drug classes; a novel A1 adenosine receptor (A1 receptor) agonist, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside (CVT-510), and the prototypical calcium channel blocker diltiazem.In the atrial-paced isolated heart, CVT-510 was approximately 5 fold more potent to prolong the stimulus-to-His bundle (S–H interval), a measure of slowing AV nodal conduction (EC50=41 nM) than to increase coronary conductance (EC50=200 nM). At concentrations of CVT-510 (40 nM) and diltiazem (1 μM) that caused equal prolongation of S–H interval (∼10 ms), diltiazem, but not CVT-510, significantly reduced left ventricular developed pressure (LVP) and markedly increased coronary conductance. CVT-510 shortened atrial (EC50=73 nM) but not the ventricular monophasic action potentials (MAP).In atrial-paced anaesthetized guinea-pigs, intravenous infusions of CVT-510 and diltiazem caused nearly equal prolongations of P–R interval. However, diltiazem, but not CVT-510, significantly reduced mean arterial blood pressure.Both CVT-510 and diltiazem prolonged S–H interval, i.e., slowed AV nodal conduction. However, the A1 receptor-selective agonist CVT-510 did so without causing the negative inotropic, vasodilator, and hypotensive effects associated with diltiazem. Because CVT-510 did not affect the ventricular action potential, it is unlikely that this agonist will have a proarrythmic action in ventricular myocardium. PMID:10051130

Hyperglycemia and subsequent torsades de pointes with marked QT prolongation during refeeding.

PubMed

Nakashima, Takashi; Kubota, Tomoki; Takasugi, Nobuhiro; Kitagawa, Yuichiro; Yoshida, Takahiro; Ushikoshi, Hiroaki; Kawasaki, Masanori; Nishigaki, Kazuhiko; Ogura, Shinji; Minatoguchi, Shinya

2017-01-01

A fatal cardiac complication can occasionally present in malnourished patients during refeeding; this is known as refeeding syndrome. However, to our knowledge, hyperglycemia preceding torsades de pointes with QT prolongation during refeeding has not been reported. In the present study, we present a case in which hyperglycemia preceded torsades de pointes with QT prolongation during refeeding. The aim of this study was to determine the possible mechanism underlying QT prolongation during refeeding and indicate how to prevent it. A 32-y-old severely malnourished woman (body mass index 14.57 kg/m 2 ) was admitted to the intensive care unit of our institution after resuscitation from cardiopulmonary arrest due to ventricular fibrillation. She was diagnosed with anorexia nervosa. Although no obvious electrolyte abnormalities were observed, her blood glucose level was 11 mg/dL. A 12-lead electrocardiogram at admission showed sinus rhythm with normal QT interval (QTc 0.448). Forty mL of 50% glucose (containing 20 g of glucose) was intravenously injected, followed by a drip infusion of glucose to maintain blood glucose level within normal range. After 9 h, the patient's blood glucose level increased to 569 mg/dL. However, after 38 h, an episode of marked QT prolongation (QTc 0.931) followed by torsades de pointes developed. Hyperglycemia during refeeding can present with QT prolongation; consequently, monitoring blood glucose levels may be useful in avoiding hyperglycemia, which can result in QT prolongation. Furthermore, additional monitoring of QT intervals using a 12-lead electrocardiogram should allow the early detection of QT prolongation when glucose solution is administered to a malnourished patient with (severe) hypoglycemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Magnitude of increase in QTc interval after initiation of dofetilide in patients with persistent atrial fibrillation is associated with increased rates of pharmacological cardioversion and long-term freedom from recurrent atrial fibrillation.

PubMed

Huang, Henry D; Waks, Jonathan W; Steinhaus, Daniel A; Zimetbaum, Peter

2016-07-01

Dofetilide is a class III antiarrhythmic drug approved for the treatment of atrial fibrillation (AF). Dofetilide-induced corrected QT (QTc) interval prolongation is a surrogate for the degree of drug effect, but the relationships between drug-induced QTc interval prolongation, pharmacological cardioversion (PCV), and freedom from recurrent AF are unclear. The purpose of this study was to assess associations between QTc interval change during dofetilide initiation and PCV and long-term AF recurrence. We performed retrospective analyses of a prospective cohort of patients with AF admitted for dofetilide initiation between 2001 and 2014. Clinical characteristics and electrocardiographic variables were assessed. We evaluated outcomes of successful PCV in patients with persistent AF and time to recurrence of AF in patients with paroxysmal and persistent AF. During the study, 243 patients with persistent AF and 176 patients with paroxysmal AF initiated dofetilide. PCV occurred in 93/243 (41.7%) patients with persistent AF. After multivariable adjustment, QTc interval change was associated with PCV (adjusted odds ratio 1.21; P = .003 per 10-ms QTc increase). Inhospital QTc interval change was associated with long-term freedom from AF in patients with persistent AF (adjusted hazard ratio 0.92; P = .011 at 4 years per 10-ms QTc increase), but not in patients with paroxysmal AF. In patients with persistent AF, PCV was also associated with long-term freedom from recurrent AF (adjusted hazard ratio 0.62; P = .009 at 4 years). The magnitude of QTc interval prolongation during dofetilide initiation is an independent predictor of successful PCV and long-term freedom from arrhythmia in patients with persistent AF. QTc interval change had no association with AF recurrence in patients with paroxysmal AF, suggesting that different mechanisms of arrhythmogenesis may be operant in different AF types. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Prolongation of the corrected QT complex--a cause of sudden cardiac death in the mountain environment?

PubMed

Windsor, J S; Rodway, G W; Mukherjee, R; Firth, P G; Shattock, M; Montgomery, H E

2011-03-01

In the mountain environment sudden cardiac death (SCD) has been shown to be responsible for the deaths of up to 52% of downhill skiers and 30% of hikers. The majority of SCD's are precipitated by a ventricular arrhythmia. Although most are likely to result from structural abnormalities associated with conditions such as ischaemic heart disease, a small but significant number may be due to abnormalities in ion channel activity, commonly known as, "channelopathies". Channelopathies have the potential to lengthen the time between ventricular depolarisation and repolarisation that can result in prolongation of the corrected QT interval (QTc) and episodes of polymorphic ventricular tachycardia (PVT) and eventually, ventricular fibrillation. This review examines the factors that prolong the QTc interval in the mountain environment and outlines a practical framework for preventing the life threatening arrhythmias that are associated with this condition.

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

McMillan, Matthew T.; Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Ojerholm, Eric

Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiationmore » therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.« less

Drug-induced QT interval prolongation: does ethnicity of the thorough QT study population matter?

PubMed Central

Shah, Rashmi R

2013-01-01

Inter-ethnic differences in drug responses have been well documented. Drug-induced QT interval prolongation is a major safety concern and therefore, regulatory authorities recommend a clinical thorough QT study (TQT) to investigate new drugs for their QT-prolonging potential. A positive study, determined by breach of a preset regulatory threshold, significantly influences late phase clinical trials by requiring intense ECG monitoring. A few studies that are currently available, although not statistically conclusive at present, question the assumption that ethnicity of the study population may not influence the outcome of a TQT study. Collective consideration of available pharmacogenetic and clinical information suggests that there may be inter-ethnic differences in QT-prolonging effects of drugs and that Caucasians may be more sensitive than other populations. The information also suggest s that (a) these differences may depend on the QT-prolonging potency of the drug and (b) exposure–response (E–R) analysis may be more sensitive than simple changes in QTc interval in unmasking this difference. If the QT response in Caucasians is generally found to be more intense than in non-Caucasians, there may be significant regulatory implications for domestic acceptance of data from a TQT study conducted in foreign populations. However, each drug will warrant an individual consideration when extrapolating the results of a TQT studyfrom one ethnic population to another and the ultimate clinical relevance of any difference. Further adequately designed and powered studies, investigating the pharmacologic properties and E–R relationships of additional drugs with different potencies, are needed in Caucasians, Oriental/Asian and African populations before firm conclusions can be drawn. PMID:22882246

Choline-modulated arsenic trioxide-induced prolongation of cardiac repolarization in Guinea pig.

PubMed

Sun, Hong-Li; Chu, Wen-Feng; Dong, De-Li; Liu, Yan; Bai, Yun-Long; Wang, Xiao-Hui; Zhou, Jin; Yang, Bao-Feng

2006-04-01

Arsenic trioxide (As(2)O(3)) has been found to be effective for relapsed or refractory acute promyelocytic leukaemia, but its clinical use is burdened by QT prolongation, Torsade de pointes tachycardias, and sudden cardiac death. The aim of the present study was to elucidate the ionic mechanisms of As(2)O(3)-induced abnormalities of cardiac electrophysiology and the therapeutic action of choline on As(2)O(3)-caused QT prolongation in guinea pig. Intravenous administration of As(2)O(3) prolonged the QT interval in a dose- and time-dependent manner in guinea pig hearts, and the QT prolongation could be modulated by choline. By using whole-cell patch clamp technique and confocal laser scanning microscopy, we found that As(2)O(3) significantly lengthened action potential duration measured at 50 and 90% of repolarization, enhanced L-type calcium currents (I(Ca-L)), inhibited delayed rectifier potassium currents (I(K)), and increased intracellular calcium concentration ([Ca(2+)](i)) in guinea pig ventricular myocytes. Choline corrected As(2)O(3)-mediated alterations of action potential duration, I(Ca-L) and [Ca(2+)](i), but had no effect on the I(K) inhibition. As(2)O(3) markedly disturbed the normal equilibrium of transmembrane currents (increasing I(Ca-L) and suppressing I(K)) in guinea pig cardiomyocyte, and induced prolongation of action potential duration, further degenerated into QT prolongation. Choline normalized QT interval abnormality and corrected lengthened action potential duration by inhibiting the elevated I(Ca-L) and [Ca(2+)](i) in ventricular myocytes during As(2)O(3) application.

Venetoclax does not prolong the QT interval in patients with hematological malignancies: an exposure-response analysis.

PubMed

Freise, Kevin J; Dunbar, Martin; Jones, Aksana K; Hoffman, David; Enschede, Sari L Heitner; Wong, Shekman; Salem, Ahmed Hamed

2016-10-01

Venetoclax (ABT-199/GDC-0199) is a selective first-in-class B cell lymphoma-2 inhibitor being developed for the treatment of hematological malignancies. The aim of this study was to determine the potential of venetoclax to prolong the corrected QT (QTc) interval and to evaluate the relationship between systemic venetoclax concentration and QTc interval. The study population included 176 male and female patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 105) or non-Hodgkin's lymphoma (n = 71) enrolled in a phase 1 safety, pharmacokinetic, and efficacy study. Electrocardiograms were collected in triplicate at time-matched points (2, 4, 6, and 8 h) prior to the first venetoclax administration and after repeated venetoclax administration to achieve steady state conditions. Venetoclax doses ranged from 100 to 1200 mg daily. Plasma venetoclax samples were collected after steady state electrocardiogram measurements. The mean and upper bound of the 2-sided 90 % confidence interval (CI) QTc change from baseline were <5 and <10 ms, respectively, at all time points and doses (<400, 400, and >400 mg). Three subjects had single QTc values >500 ms and/or ΔQTc > 60 ms. The effect of venetoclax concentration on both ΔQTc and QTc was not statistically significant (P > 0.05). At the mean maximum concentrations achieved with therapeutic (400 mg) and supra-therapeutic (1200 mg) venetoclax doses, the estimated drug effects on QTc were 0.137 (90 % CI [-1.01 to 1.28]) and 0.263 (90 % CI [-1.92 to 2.45]) ms, respectively. Venetoclax does not prolong QTc interval even at supra-therapeutic doses, and there is no relationship between venetoclax concentrations and QTc interval.

QT Interval Prolongation and QRS Voltage Reduction in Patients with Liver Cirrhosis.

PubMed

Cichoż-Lach, Halina; Tomaszewski, Michał; Kowalik, Agnieszka; Lis, Emilia; Tomaszewski, Andrzej; Lach, Tomasz; Boczkowska, Sylwia; Celiński, Krzysztof

2015-01-01

Liver cirrhosis is associated with functional abnormalities of the cardiovascular system with co-existing electrocardiographic (ECG) abnormalities. The aim was to analyze ECG changes in patients with cirrhosis, to evaluate whether alcoholic etiology of cirrhosis and ascites has an impact on ECG changes. The study involved 81 patients with previously untreated alcoholic cirrhosis (64 patients with ascites, classes B and C according to the Child-Pugh classification; and 17 without ascites, categorized as class A); 41 patients with previously untreated cirrhosis due to chronic hepatitis C (HCV--30 patients with ascites, classes B and C; and 11 without ascites, class A); 42 with alcoholic steatohepatitis and 46 with alcoholic steatosis. The control group consisted of 32 healthy volunteers. Twelve-lead ECG recordings were performed and selected parameters were measured. Significantly longer QT and QTc intervals and lower QRS voltage were found in patients with alcoholic and HCV cirrhosis compared to the controls. Significantly lower QRS voltage was found in subjects with ascites than in those without ascites. Removal of ascites significantly increased QRS voltage. In cirrhosis, irrespective of etiology, ECG changes involved prolonged QT and QTc intervals and reduced QRS voltage. Prolonged QT and QTc intervals were not related to the severity of cirrhosis or to the presence of ascites. However, low QRS voltage was associated with the presence of ascites. Removal of ascites reverses low QRS voltage.

Cardiovascular safety of antihistamines

PubMed Central

Olasiński, Jerzy; Grajek, Stefan

2014-01-01

Histamine is a mediator, which increases the permeability of capillaries during the early phase of allergic reaction, causes smooth muscle contraction of bronchi and stimulates mucous glands in the nasal cavity. Antihistamines are the basis of symptomatic treatment in the majority of allergic diseases, especially allergic rhinitis, allergic conjunctivitis, urticaria and anaphylaxis. The cardiotoxic effects of the two withdrawn drugs, terfenadine and astemizole, were manifested by prolonged QT intervals and triggering torsades de pointes (TdP) caused by blockade of the ‘rapid’ IKr potassium channels. These phenomena, however, are not a class effect. This review deals with a new generation of antihistamine drugs in the context of QT interval prolongation risk. PMID:25097491

Hypoglycaemia and QT interval prolongation in type 1 diabetes--bridging the gap between clamp studies and spontaneous episodes.

PubMed

Christensen, T F; Cichosz, S L; Tarnow, L; Randløv, J; Kristensen, L E; Struijk, J J; Eldrup, E; Hejlesen, O K

2014-01-01

We propose a study design with controlled hypoglycaemia induced by subcutaneous injection of insulin and matched control episodes to bridge the gap between clamp studies and studies of spontaneous hypoglycaemia. The observed prolongation of the heart rate corrected QT interval (QTc) during hypoglycaemia varies greatly between studies. We studied ten adults with type 1 diabetes (age 41±15years) without cardiovascular disease or neuropathy. Single-blinded hypoglycaemia was induced by a subcutaneous insulin bolus followed by a control episode on two occasions separated by 4weeks. QT intervals were measured using the semi-automatic tangent approach, and QTc was derived by Bazett's (QTcB) and Fridericia's (QTcF) formulas. QTcB increased from baseline to hypoglycaemia (403±20 vs. 433±39ms, p<0.001). On the euglycaemia day, QTcB also increased (398±20 vs. 410±27ms, p<0.01), but the increase was less than during hypoglycaemia (p<0.001). The same pattern was seen for QTcF. Plasma adrenaline levels increased significantly during hypoglycaemia compared to euglycaemia (p<0.01). Serum potassium levels decreased similarly after insulin injection during both hypoglycaemia and euglycaemia. Hypoglycaemia as experienced after a subcutaneous injection of insulin may cause QTc prolongation in type 1 diabetes. However, the magnitude of prolongation is less than typically reported during glucose clamp studies, possible because of the study design with focus on minimizing unwanted study effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of delivery season on subsequent birth interval in early 20th century in Japan

NASA Astrophysics Data System (ADS)

Nonaka, K.

1989-12-01

Questionnaires of birth dates of family members (13 404 families in total) were analyzed in order to examine the effects of delivery season of a baby on the subsequent birth interval. Deliveries at maternal age of 20 34 years were used. In 1921 1935, the mothers who had been delivered of a baby in August October showed the shortest (30.62 months geometric mean) and those in February April the longest (34.05 months) non-last intervals, with a highly significant difference among the four delivery seasons ( P<0.001, Kruskal-Wallis test, n=5678). Although the intervals were abruptly prolonged just before the last birth, the above difference was also consistent in the last intervals. When seasonal distributions of last and non-last births were compared, last births tended to be concentrated in the summer half of a year ( P<0.05) in 1921 1935. In 1951 1965, overall geometric mean of the interval shortened to 28.44 months, and the length of intervals did not differ appreciably according to the season of preceding delivery. Deliveries in late summer (August October) in 1921 1935, therefore, were associated with increased risk of termination of reproduction, on one hand, but a lowered chance of prolongation of the subsequent interval, on the other hand. Possible environmental factors are discussed to explain this apparently paradoxical phenomenon.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoffmann, Ralf-T., E-mail: rthoffma@med.uni-muenchen.de; Paprottka, Philipp M., E-mail: philipp.paprottka@med.uni-muenchen.de; Schoen, Agnes

Introduction: In unresectable intrahepatic cholangiocarcinoma (ICC), systemic chemotherapy often is viewed as the only option, although efficacy is limited. Radioembolization (RE) using yttrium-90 ({sup 90}Y) microspheres is an accepted therapy for patients with hepatocellular-carcinoma or metastatic liver tumors. However, there are limited data on the value of RE in patients with ICC and few data on factors influencing prognosis. The purpose of our retrospective analysis was to establish which factors influenced time-to-progression (TTP) and overall survival (OS). Methods: Patients with unresectable ICC were treated with {sup 90}Y resin-microspheres and assessed at 3-monthly intervals. Radiologic response was evaluated by using Responsemore » Criteria in Solid Tumors (RECIST). Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on TTP and OS. Results: Thirty-four treatments were administered to 33 patients without major complications. By RECIST, 12 patients had a partial response, 17 had stable disease, and 5 had progressive disease after 3 months. The median OS was 22 months posttreatment and 43.7 months postdiagnosis. Median TTP was 9.8 months. Survival and TTP were significantly prolonged in patients with ECOG 0 (vs. ECOG 1 or 2; median OS: 29.4, 10, and 5.1 months; TTP: 17.5, 6.9, and 2.4 months), tumor burden {<=}25% (OS: 26.7 vs. 6 months; TTP: 17.5 vs. 2.3 months), or tumor response (PR or SD vs. PD; OS: 35.5, 17.7 vs. 5.7 months; TTP: 31.9, 9.8 vs. 2.5 months), respectively (P < 0.001). Conclusions: Radioembolization is an effective and safe option for patients with unresectable ICC. Predictors for prolonged survival are performance status, tumor burden, and RECIST response.« less

A multi-center, randomized, clinical trial comparing adhesive polyurethane foam dressing and adhesive hydrocolloid dressing in patients with grade II pressure ulcers in primary care and nursing homes.

PubMed

Guillén-Solà, Mireia; Soler Mieras, Aina; Tomàs-Vidal, Antònia M

2013-12-21

Pressure ulcers (PrUs) are ischemic wounds in the skin and underlying tissues caused by long-standing pressure force over an external bone or cartilaginous surface. PrUs are an important challenge for the overall health system because can prolong patient hospitalization and reduce quality of life. Moreover, 95% of PrUs are avoidable, suggesting they are caused by poor quality care assistance. PrUs are also costly, increasing national costs. For example, they represent about 5% of overall annual health expenses in Spain. Stages I and II PrUs have a combined prevalence of 65%. According main clinical guidelines, stage II PrUs (PrU-IIs) are usually treated by applying special dressings (polyurethane or hydrocolloid). However, little scientific evidence regarding their efficacy has been identified in scientific literature. Our aim is to assess the comparative efficacy of adhesive polyurethane foam and hydrocolloid dressings in the treatment of PrU-IIs in terms of healed ulcer after 8 weeks of follow-up. This paper describes the development and evaluation protocol of a randomized clinical trial of two parallel treatment arms. A total of 820 patients with at least 1 PrU-II will be recruited from primary health care and home care centers. All patients will receive standardized healing procedures and preventive measures (e.g. positional changes and pressure-relieving support surfaces), following standardized procedures. The main outcome will be the percentage of wounds healed after 8 weeks. Secondary outcomes will include cost-effectiveness, as evaluated by cost per healed ulcer and cost per treated patient and safety evaluated by adverse events. This trial will address the hypothesis that hydrocolloid dressings will heal at least 10% more stage II PrUs and be more cost-effective than polyurethane foam dressings after 8 weeks. This trial has been registered with controlled-trials number ISCRCTN57842461 and EudraCT 2012-003945-14.

Atrioventricular depolarization differences identify coronary artery anomalies in Kawasaki disease.

PubMed

Cortez, Daniel; Sharma, Nandita; Jone, Pei-Ni

2017-03-01

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. Signal average electrocardiogram changes in patients during the acute phase of KD with coronary artery anomalies (CAA) include depolarization changes. We set out to determine if 12-lead-derived atrioventricular depolarization differences can identify CAA in patients with KD. A blinded, retrospective case-control study of patients with KD was performed. Deep Q waves, corrected QT-intervals (QTc), spatial QRS-T angles, T-wave vector magnitudes (RMS-T), and a novel parameter for assessment of atrioventricular depolarization difference (the spatial PR angle) and a two dimensional PR angle were assessed. Comparisons between groups were performed to test for significant differences. One hundred one patients with KD were evaluated, with 68 having CAA (67.3%, mean age 3.6 ± 3.0 years, 82.6% male), and 32 without CAA (31.7%, mean age 2.7 ± 3.2 years, 70.4% male). The spatial PR angle significantly discriminated KD patients with CAA from those without, 59.7° ± 31.1° versus 41.6° ± 11.5° (p < .001). A spatial PR angle cutoff value of 56.9° gave positive/negative predictive values and odds ratios of 93.8%, 43.5%, and 11.5% (95% confidence interval (CI) 2.6-52.2). The two dimensional PR angle either below 7° or above 92° gave positive/negative predictive values and odds ratios of 100.0%, 38.8%, and 21.1% (95% CI 1.2-362.8). No other parameters significantly differentiated the groups. Atrioventricular depolarization differences, measured by the spatial or two dimensional PR angle differentiate KD patients with CAA versus those without. © 2016 Wiley Periodicals, Inc.

Assessment of the effects of ketamine-fentanyl combination versus propofol-remifentanil combination for sedation during endoscopic retrograde cholangiopancreatography

PubMed Central

Heidari, Sayed Morteza; Loghmani, Parisa

2014-01-01

Background: Endoscopic retrograde cholangiopancreatography (ERCP) as a diagnostic and treatment procedure is used in most biliary tract and pancreatic. Either sedation or general anesthesia could be considered for this procedure. Combining a sedative with an opioid agent can provide effective moderate sedation. This study compared the impact of ketamine-fentanyl (KF) versus propofol-remifentanil (PR) on sedation scale in patients undergoing ERCP. Materials and Methods: As a double-blinded randomized clinical trial, 80 patients selected by convenient sampling, allocated randomly into two groups. KF group received ketamine 0.5 mg/kg body weight intravenously over 60 s and then fentanyl 1 mcg/kg body weight intravenously. PR group received propofol l mg/kg body weight intravenously over 60 s and then remifentanil 0.05 mcg/kg body weight/min intravenously. Intravenous (IV) infusion of propofol was maintained by 50 mcg/kg body weight/min throughout ERCP. Ramsay Sedation Score, vital signs, oxygen saturation (SpO2), recovery score (modified Aldrete score) and visual analog scales of pain intensity, and endoscopist's satisfaction were considered as measured outcomes. All analysis were analyzed by SPSS Statistics version 22 and using t-test, Chi-square and repeated measured ANOVA and Mann-Whitney tests for data analysis. Results: Respiratory rate and SpO2 level during the time intervals were lower in PR group (P < 0.001). Sedation score at intervals was not significantly different (P = 0.07). The frequency of apnea in PR group was significantly higher than the KF group (P = 0.003). The percentage of need to supplemental oxygen in PR group was 35.1% that was also significantly higher than 8.8% in the KF group (P = 0.008), but the dosage frequency was significantly higher in KF group (P < 0.001). The KF and PR groups average length of stay in the recovery room were 50.71 standard deviation (SD = 9.99) and 42.57 (SD = 11.99) minutes, respectively, indicating a significant difference (P = 0.003). The mean severity of nausea in KF and PR groups was, respectively, 2.74 confidence interval (CI = 1.68-3.81) and 0.43 (CI = 0.11-0.75), that was significantly higher in KF group (P < 0.001). The average score of surgeon satisfaction in both KF and PR groups were 7.69 (CI = 7.16-8.21) and 8.65 (CI = 8.25-9.05), respectively, which was higher in KF group (P = 0.004), but the average level of patients satisfaction in KF group was 8.86 (CI = 8.53-9.19) and in PR group was 8.95 (CI - 8.54-9.35) that were not significantly different (P = 0.074). Conclusion: There is no statistically significant difference between KF and PR combinations in sedation score, but PR combination provides better pain control, with less nausea and shorter recovery time while causing more respiratory side effects, that is, apnea and need to oxygen. PMID:25535501

Metoprolol and diltiazem ameliorate ziprasidone-induced prolonged corrected QT interval in rats.

PubMed

Erbas, Oytun; Yilmaz, Mustafa

2015-12-01

Ziprasidone, an atypical antipsychotic agent, has been shown to increase the corrected QT (QTc) interval in some patients. The aim of this study was to reveal the effects of metoprolol and diltiazem on ziprasidone drug-induced prolonged QTc interval. A total of 24 rats were equally divided into the following four groups: the first group was used as the control and received 1 mL/kg saline; 3 mg/kg ziprasidone and saline were administered to the second group; 3 mg/kg ziprasidone and 1 mg/kg metoprolol were administered to the third group and 3 mg/kg ziprasidone and 2 mg/kg diltiazem were administered to the fourth group. Two hours following application of the drugs, the QTc was calculated by performing electrocardiography in derivation (D)I. The duration of QTc interval was compared among the four groups. The mean QTc intervals were significantly increased in the third and fourth groups compared with the second group (p < 0.0005 and p < 0.0001, respectively). The study demonstrated the effectiveness of metoprolol and diltiazem in the prevention of ziprasidone-induced elongation in the QTc interval. Both metoprolol and diltiazem may be considered in the prophylactic therapy of high-risk patients who are using ziprasidone. © The Author(s) 2013.

Azithromycin/chloroquine combination does not increase cardiac instability despite an increase in monophasic action potential duration in the anesthetized guinea pig.

PubMed

Fossa, Anthony A; Wisialowski, Todd; Duncan, J Neil; Deng, Shibing; Dunne, Michael

2007-11-01

Prolongation of the electrocardiogram QT interval by some, but not all drugs, has been associated with increased incidence of sudden cardiac death. Current preclinical regulatory assays cannot discriminate the arrhythmia liability of these drugs. Consequently, many new medications that prolong the QT interval are not developed despite their potential therapeutic benefit. Alternans (action potential duration alternations) is a measure of cardiac instability in humans and animals associated with the onset of ventricular fibrillation. Due to potential arrhythmia risk from observed QT prolongation, alternans was assessed in the anesthetized guinea pig after azithromycin or chloroquine alone and after combination treatment at clinically relevant concentrations proposed for the management of malaria. Chloroquine alone, but not azithromycin, caused a profound increase in action potential duration but with only minimal effects on alternans (approximately 10 ms). Azithromycin alone and in combination with chloroquine showed no increase in alternans beyond vehicle baseline responses indicating no additional arrhythmia liability.

Associations of Drug Use, Violence, and Depressive Symptoms with Sexual Risk Behaviors Among Women with Alcohol Misuse.

PubMed

Lee, Kristen; Hutton, Heidi E; Lesko, Catherine R; Monroe, Anne K; Alvanzo, Anika; McCaul, Mary E; Chander, Geetanjali

2018-05-18

Alcohol misuse is associated with increased human immunodeficiency virus sexual risk behaviors by women. Drug use, intimate partner violence (IPV), and depressive symptoms frequently co-occur, are well-recognized alcohol misuse comorbidities, and may interact to increase risk behaviors. Using a syndemic framework we examined associations between drug use, IPV, and depressive symptoms and sexual risk behaviors by 400 women with alcohol misuse attending an urban sexually transmitted infections clinic. Participants completed computer-assisted interviews querying drug use, IPV, and depressive symptoms and sexual risk behavior outcomes-unprotected sex under the influence of alcohol, sex for drugs/money, and number of lifetime sexual partners. We used multivariable analysis to estimate prevalence ratios (PR) for independent and joint associations between drug use, IPV, and depressive symptoms and our outcomes. To investigate synergy between risk factors we calculated the relative excess prevalence owing to interaction for all variable combinations. In multivariable analysis, drug use, IPV, and depressive symptoms alone and in combination were associated with higher prevalence/count of risk behaviors compared with women with alcohol misuse alone. The greatest prevalence/count occurred when all three were present (unprotected sex under the influence of alcohol [PR, 2.6; 95% confidence interval, 1.3-4.9]), sex for money or drugs [PR, 2.6; 95% confidence interval, 1.7-4.2], and number of lifetime partners [PR, 3.2; 95% confidence interval, 1.9-5.2]). Drug use, IPV, and depressive symptoms did not interact synergistically to increase sexual risk behavior prevalence. A higher prevalence of sexual risk behaviors by women with alcohol misuse combined with drug use, IPV, and depressive symptoms supports the need for alcohol interventions addressing these additional comorbidities. Copyright © 2018 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Electrocardiographic findings in chronic hemodialysis patients.

PubMed

Bignotto, Luís Henrique; Kallás, Marina Esteves; Djouki, Rafael Jorge Teixeira; Sassaki, Marcela Mayume; Voss, Guilherme Ota; Soto, Cristina Lopez; Frattini, Fernando; Medeiros, Flávia Silva Reis

2012-01-01

Cardiovascular disease is the leading cause of mortality among patients on dialysis. When considering all causes of death, about 30% are classified as cardiac arrest, death of unknown cause or cardiac arrhythmia. The increasing time of ventricular depolarization and repolarization, measured non-invasively by measuring the QT interval on the electrocardiogram at rest, has emerged as a predictor of complex ventricular arrhythmias, a major cause of sudden cardiac death. To determine the electrocardiographic alterations present in hemodialysis (HD) patients, measuring the QT interval and its relationship with clinical and laboratory variables. Patients above 18 years on dialysis were approached to participate in the study and, after consent, were submitted to the examination of 12-lead electrocardiogram. Clinical data were reviewed to assess the presence of comorbidities, as well as anthropometric and blood pressure measures. Blood samples were collected to determinate hemoglobin and serum levels of calcium, phosphorus and potassium. One hundred and seventy nine patients were included in the study. The majority of the patients were male (64.8%) and white (54.7%); the average age was 58.5 ± 14.7 years old. About 50% of all patients had, at least, one electrical conduction disturb. About 50% of all patients had QTc prolongation and experienced a significant increase in the frequency of Left Ventricular Hypertrophy (LVH), changes of the cardiac rhythm and bundle branch blocks, and a lower body mass index (BMI), when compared with normal QTc interval patients. Patients with chronic kidney disease (CKD) on hemodialysis had high frequency of abnormal electrocardiographic findings, including a high prevalence of patients with prolonged QTc interval. This study also found a significant association between prolonged QTc interval and the presence of Diabetes and lower values of BMI.

Role of working memory and lexical knowledge in perceptual restoration of interrupted speech.

PubMed

Nagaraj, Naveen K; Magimairaj, Beula M

2017-12-01

The role of working memory (WM) capacity and lexical knowledge in perceptual restoration (PR) of missing speech was investigated using the interrupted speech perception paradigm. Speech identification ability, which indexed PR, was measured using low-context sentences periodically interrupted at 1.5 Hz. PR was measured for silent gated, low-frequency speech noise filled, and low-frequency fine-structure and envelope filled interrupted conditions. WM capacity was measured using verbal and visuospatial span tasks. Lexical knowledge was assessed using both receptive vocabulary and meaning from context tests. Results showed that PR was better for speech noise filled condition than other conditions tested. Both receptive vocabulary and verbal WM capacity explained unique variance in PR for the speech noise filled condition, but were unrelated to performance in the silent gated condition. It was only receptive vocabulary that uniquely predicted PR for fine-structure and envelope filled conditions. These findings suggest that the contribution of lexical knowledge and verbal WM during PR depends crucially on the information content that replaced the silent intervals. When perceptual continuity was partially restored by filler speech noise, both lexical knowledge and verbal WM capacity facilitated PR. Importantly, for fine-structure and envelope filled interrupted conditions, lexical knowledge was crucial for PR.

Intimate Partner Violence and Adherence to HIV Pre-exposure Prophylaxis (PrEP) in African Women in HIV Serodiscordant Relationships: A Prospective Cohort Study

PubMed Central

Haberer, Jessica; Celum, Connie; Mugo, Nelly; Ware, Norma C.; Cohen, Craig R.; Tappero, Jordan W.; Kiarie, James; Ronald, Allan; Mujugira, Andrew; Tumwesigye, Elioda; Were, Edwin; Irungu, Elizabeth; Baeten, Jared M.

2016-01-01

Background: Intimate partner violence (IPV) is associated with higher HIV incidence, reduced condom use, and poor adherence to antiretroviral therapy and other medications. IPV may also affect adherence to pre-exposure prophylaxis (PrEP). Methods: We analyzed data from 1785 HIV-uninfected women enrolled in a clinical trial of PrEP among African HIV serodiscordant couples. Experience of verbal, physical, or economic IPV was assessed at monthly visits by face-to-face interviews. Low PrEP adherence was defined as clinic-based pill count coverage <80% or plasma tenofovir levels <40 ng/mL. The association between IPV and low adherence was analyzed using generalized estimating equations, adjusting for potential confounders. In-depth interview transcripts were examined to explain how IPV could impact adherence. Results: Sixteen percent of women reported IPV during a median of 34.8 months of follow-up (interquartile range 27.0–35.0). Overall, 7% of visits had pill count coverage <80%, and 32% had plasma tenofovir <40 ng/mL. Women reporting IPV in the past 3 months had increased risk of low adherence by pill count (adjusted risk ratio 1.49, 95% confidence interval: 1.17 to 1.89) and by plasma tenofovir (adjusted risk ratio 1.51, 95% confidence interval: 1.06 to 2.15). Verbal, economic, and physical IPV were all associated with low adherence. However, the impact of IPV diminished and was not statistically significant 3 months after the reported exposure. In qualitative interviews, women identified several ways in which IPV affected adherence, including stress and forgetting, leaving home without pills, and partners throwing pills away. Conclusions: Women who reported recent IPV in the Partners PrEP Study were at increased risk of low PrEP adherence. Strategies to mitigate PrEP nonadherence in the context of IPV should be evaluated. PMID:27243900

[Factors related to the QT prolongation in chronic renal failure].

PubMed

Kurosu, M; Ando, Y; Akimoto, T; Ono, S; Kusano, E; Asano, Y

1999-04-01

QT prolongation, a risk factor for arrhythmia and cardiac death, is observed in uremic patients. Though hypocalcemia, autonomic nerve dysfunction and cardiac hypertrophy are assumed to cause the uremic QT prolongation, the exact mechanism remains unspecified. We therefore examined factors related to the QT interval in chronic renal failure (CRF). Corrected QT interval (QTc) was significantly prolonged in CRF just before the induction of dialysis therapy (group A) compared with nephrotic syndrome with the intact or mildly impaired renal function (group B). QTc was also prolonged in acute renal failure (group C). Cardio-thoracic ratio, serum albumin and Ca correlated with QTc in group A, but not in B or C. A single HD session in group A failed to shorten QTc, despite a significant increase in serum Ca++. Autonomic dysfunction did not appear to be a major determinant of QT prolongation, since QTc was not different between diabetics and non-diabetics in group A and in chronic HD patients (group D). In group D, QTc did not correlate with SV1 + RV5 on ECG or left ventricular wall thickness (LVWT) on echocardiography. In another group of chronic HD patients (group E), there was no significant correlation between QTc and the parameters of left ventricular mass, plasma brain natriuretic peptide (BNP). However, in the patients subjected to repeated echocardiography in group D, QTc and LVWT changed in parallel. In a retrospective analysis of QTc in group D, QTc was maximally prolonged at the time of starting HD therapy, and gradually improved in the following 1-5 years in both diabetics and non-diabetics. In contrast, chronic CAPD patients (group F) revealed no improvement of QTc. Thus, uremic QT prolongation cannot be explained simply by any of the previously assumed factors, but appears to be affected by multiple factors, which are partially correctable by chronic HD therapy.

[Conversion to tapentadol PR improves analgesia and quality of life in patients with severe and chronic pain despite using tramadol > 300 mg/d].

PubMed

Richter, Uwe; Waldmann-Rex, Susanne; Lehmann, Ute

2015-06-01

This subgroup analysis of a non-interventional study involving general practitioners and internists investigated the administration of tapentadol PR (prolonged release) in patients with widely-utilized tramadol pretreatment in routine clinical practice in Germany. Data of all patients in the study cohort who had tramadol as the only opioid in their previous therapy were included in the analysis (n = 685); among them especially the 99 patients with tramadol dosages exceeding 300 mg/d were focused. Data collection during the 3-month observation period included previous and concomitant analgesic treatment, tapentadol PR dosage, pain intensity, sleep and quality of life parameters, and tolerability of tapentadol PR. Back pain was the most common cause of pain (n = 86/99), other pain diagnoses were (partly additionally) recorded in 68 cases. A mixed type of pain dominated. The previous tramadol therapy was usually combined with non-opioids (n = 74), co-analgesics (n = 44) and analgesic rescue medication (n = 35). Tapentadol PR therapy reduced the mean initial pain intensity of 7.3 ± 1.5 to 3.1 ± 1.8 points (NRS-11, 11-point pain scale, n = 96) at the end of observation, using an average dosage of 218.7 mg/d. Tapentadol PR was finally applied as the sole analgesic in 32/95 patients. 69/96 patients achieved a clinically meaningful pain relief of at least 50 %, while 63 patients gained a pain reduction of ≥ 4 NRS-points. 89/95 patients reached or exceeded their additional individual treatment goal. This was accompanied by a significant decrease in pain-related impairments of daily activities and an improvement in quality of life with an overall good tolerability of tapentadol PR. Treatment with tapentadol PR was assessed positively by physicians and patients. Data analysis shows a clinically relevant benefit in patients unsuccessfully pretreated with tramadol by consecutive conversion to the potent analgesic tapentadol PR.

Cardiac safety of lacosamide: the non-clinical perspective.

PubMed

Delaunois, A; Colomar, A; Depelchin, B O; Cornet, M

2015-11-01

Lacosamide is indicated for the adjunctive treatment of partial-onset seizures in adult patients. Unlike other sodium channel-blocking antiepileptic drugs, lacosamide selectively enhances sodium channel slow inactivation. Potential effects of lacosamide on cardiac sodium channels and their cardiovascular consequences were comprehensively assessed. This manuscript presents the non-clinical cardiac safety profile of lacosamide. Lacosamide was tested in vitro on sodium and L-type calcium currents from isolated human atrial myocytes and on hERG-mediated potassium currents from stably transfected HEK293 cells. Cardiac action potentials were recorded in guinea pig ventricular myocytes. In vivo, hemodynamic and ECG parameters were evaluated in anesthetized dogs and monkeys receiving acute cumulative intravenous doses of lacosamide. Following intravenous dosing with lacosamide, dose-dependent PR and QRS prolongation and ECG abnormalities (loss of P waves, atrioventricular and intraventricular blocks, junctional premature contractions) were observed in anesthetized dogs and monkeys. In vitro, lacosamide reduced human cardiac sodium currents in a concentration-, voltage- and state-dependent manner. Lacosamide reductions in Vmax in guinea pig myocytes were similar to lamotrigine and carbamazepine. Lacosamide showed no relevant inhibitory effects on hERG and L-type calcium channels and did not prolong QTc in vivo. ECG findings in anesthetized animals correlate well with in vitro sodium channel-related effects and are also consistent with those (PR prolongation, first-degree atrioventricular block) reported in healthy volunteers and patients with epilepsy. Both in vivo and in vitro effects were detected from exposure levels 1.5- to 2-fold above those achieved with the maximum-recommended human lacosamide dose (400 mg/day). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of Intrauterine Devices in Mares: A Histomorphological and Immunohistochemical Evaluation of the Endometrium.

PubMed

Klein, V; Müller, K; Schoon, H A; Reilas, T; Rivera del Alamo, M M; Katila, T

2016-02-01

Oestrous suppression by intrauterine devices (IUDs) is caused by prolongation of luteal function, but the biological mechanism is unknown. The aim of the study was to investigate mechanisms which could explain the action of IUDs. Thirty mares were age-matched and either inseminated (AI, n = 15) or fitted with an IUD (IUD, n = 15) and subsequently divided into four groups: AI-P, pregnant (n = 8); AI-N, non-pregnant (n = 7); IUD-P, prolonged luteal phase (n = 7); and IUD-N, normal luteal phase (n = 8). The median ages were 5.5 and 7 years in AI-P and IUD-P groups and 14 and 11 years in AI-N and IUD-N groups, respectively. On Day 15 after ovulation, an endometrial biopsy was obtained to study histomorphological and immunohistochemical expression patterns of uterine proteins (uteroferrin, UF; uterocalin, UC; uteroglobin, UG), oestrogen and progesterone receptors (ER, PR), proliferation marker Ki-67 and content of inflammatory cells. Expression of UF was higher in IUD mares; the difference between pregnant and IUD-P mares was significant. Mares exhibiting a prolonged luteal phase (AI-P, IUD-P) showed only mild angiosclerosis and lower expression of both ER and PR than mares with a normal luteal phase (AI-N, IUD-N). No significant differences were detected in the numbers of inflammatory cells, with the exception of macrophages, which were more numerous in AI-P than AI-N mares. Although inflammatory cells were not detected in IUD mares, increased UF levels may indicate chronic inflammation. Young age and normality of the endometrial blood vessels may improve the efficacy of IUDs. © 2015 Blackwell Verlag GmbH.

A case report of QT prolongation with glycopyrronium bromide in a patient with chronic tamoxifen use.

PubMed

Chiu, Michael H; Al-Majed, Nawaf S; Stubbins, Ryan; Pollmann, Dylan; Sandhu, Roopinder K

2016-06-14

Glycopyrronium bromide has recently been approved as a once daily maintenance inhalation therapy for moderate to severe chronic obstructive pulmonary disease (COPD). Efficacy and safety trial data have found rare cases of significant QT prolongation. To our knowledge, we describe the first case report of QT prolongation >600 ms with initiation of glycopyrronium bromide in a real world setting. A 78-year-old female with moderate COPD recently started on glycopyrronium bromide, presented to Emergency Department (ED) with syncope. Her past medical history was significant for a left total mastectomy and she had been on Tamoxifen for 9 months. One day prior to her presentation, she had visited a naturopathic clinic for a vitamin infusion resulting in emesis. The following day she continued to feel dizzy and had a witnessed syncopal episode without any reported cardiac or neurological symptoms preceding the event or after regaining consciousness. In the emergency department, she reported dizziness and was found to be hypotensive. Her symptoms completely resolved with intravenous fluids. Lab work was normal however her electrocardiogram (ECG) demonstrated a QTc interval of 603 and 631 ms (Friderica and Bazett's respectively) with a normal QT interval on her baseline ECG prior to initiating Tamoxifen. She was admitted to the Cardiology service for further work-up of QT prolongation. Her syncope was felt to be due to orthostatic hypotension and the QT prolongation secondary to medications, which were both discontinued during her admission. After 2 days, her QT interval normalized consistent with the half-life of Glycopyrronium bromide (13-57 h) compared to Tamoxifen (8-14 days). Glycopyrronium bromide is guideline recommended as first line therapy for prevention of exacerbation in moderate to severe COPD however safety data had been limited to select populations. This case report highlights the need for future studies to identify high-risk populations at potential risk of life-threatening arrhythmias who may benefit from periodic ECG surveillance.

Upregulation of microRNA-1 and microRNA-133 contributes to arsenic-induced cardiac electrical remodeling.

PubMed

Shan, Hongli; Zhang, Yong; Cai, Benzhi; Chen, Xi; Fan, Yuhua; Yang, Lili; Chen, Xichuang; Liang, Haihai; Zhang, Ying; Song, Xiaohui; Xu, Chaoqian; Lu, Yanjie; Yang, Baofeng; Du, Zhimin

2013-09-10

A large body of evidence showed that arsenic trioxide (As2O3), a front-line drug for the treatment of acute promyelocytic leukemia, induced abnormal cardiac QT prolongation, which hampers its clinical use. The molecular mechanisms for this cardiotoxicity remained unclear. This study aimed to elucidate whether microRNAs (miRs) participate in As2O3-induced QT prolongation. A guinea pig model of As2O3-induced QT prolongation was established by intravenous injection with As2O3. Real-time PCR and Western blot were employed to determine the expression alterations of miRs and mRNAs, and their corresponding proteins. The QT interval and QRS complex were significantly prolonged in a dose-dependent fashion after 7-day administration of As2O3. As2O3 induced a significant upregulation of the muscle-specific miR-1 and miR-133, as well as their transactivator serum response factor. As2O3 depressed the protein levels of ether-a-go-go related gene (ERG) and Kir2.1, the K(+) channel subunits responsible for delayed rectifier K(+) current IKr and inward rectifier K(+) current IK1, respectively. In vivo transfer of miR-133 by direct intramuscular injection prolonged QTc interval and increased mortality rate, along with depression of ERG protein and IKr in guinea pig hearts. Similarly, forced expression of miR-1 widened QTc interval and QRS complex and increased mortality rate, accompanied by downregulation of Kir2.1 protein and IK1. Application of antisense inhibitors to knockdown miR-1 and miR-133 abolished the cardiac electrical disorders caused by As2O3. Deregulation of miR-133 and miR-1 underlies As2O3-induced cardiac electrical disorders and these miRs may serve as potential therapeutic targets for the handling of As2O3 cardiotoxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Adolescent Health Providers' Willingness to Prescribe Pre-Exposure Prophylaxis (PrEP) to Youth at Risk of HIV Infection in the United States.

PubMed

Hart-Cooper, Geoffrey D; Allen, Isabel; Irwin, Charles E; Scott, Hyman

2018-05-26

HIV disproportionately affects young men who have sex with men. Pre-exposure prophylaxis (PrEP) can prevent HIV acquisition; however, youth access to PrEP is limited by provider willingness to prescribe PrEP. We conducted an online survey of clinicians working with adolescents (aged 13-17 years) and young adults (aged 18-26 years) in the United States through the Society of Adolescent Health and Medicine. We used multivariate logistic regression to assess provider beliefs associated with willingness to provide PrEP. Nearly all (93.2%) providers had heard of PrEP, and 57 (35.2%) had prescribed PrEP. While almost all providers (95%) agreed that PrEP prevents HIV, fewer were willing to prescribe to young adults (77.8%) or adolescents (64.8%). Willingness to prescribe PrEP was strongly associated with the belief that providers had enough knowledge to safely provide PrEP to adolescents (OR 2.11, confidence interval [CI]: 1.18-3.76, p = .01) and young adults (odds ratio 5.19, CI: 2.15-12.50, p ≤ .001), and that adolescents would be adherent (odds ratio 3, CI: 1.30-6.90, p = .01). Response rate was 17%. Almost all providers had heard of PrEP and most providers were willing to prescribe PrEP. Provider education and tools to promote provider self-efficacy and adolescent adherence might improve provider willingness to provide PrEP. Copyright © 2018 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Reversible chronic acquired complete atrioventricular block.

PubMed

Rakovec, P; Milcinski, G; Voga, G; Korsic, L

1982-01-01

The return of atrioventricular conduction is reported in a case after nearly four years of complete acquired heart block. After recovery from atrioventricular block, right bundle branch block persisted, but P-R interval and H-V interval were normal. Three months later a relapse of second degree infranodal atrioventricular block was noted. A short review of similar cases from the literature is given.

Brief Report: PrEP Uptake, Adherence, and Discontinuation Among California YMSM Using Geosocial Networking Applications.

PubMed

Holloway, Ian W; Dougherty, Ryan; Gildner, Jennifer; Beougher, Sean C; Pulsipher, Craig; Montoya, Jorge A; Plant, Aaron; Leibowitz, Arleen

2017-01-01

We investigated pre-exposure prophylaxis (PrEP) uptake, adherence, and discontinuation among young app-using men who have sex with men in California (N = 761). Approximately, 9.7% of participants had ever used PrEP; 87% of those deemed good candidates for screening (indicated by a Centers for Disease Control and Prevention risk index score ≥10) were not current or past users. PrEP use was associated with higher income [adjusted odds ratio (aOR): 4.13; confidence interval (CI): 1.87 to 9.12], receptive condomless anal sex (aOR: 3.41; CI: 1.71 to 6.78), HIV-positive sex partners (aOR: 2.87; CI: 1.53 to 5.38), popper use (aOR: 3.47; CI: 1.96 to 6.13), and recent sexually transmitted infection diagnosis (aOR: 2.90; CI: 1.64 to 5.13). Some users (41.5%) wanted help remembering to take PrEP. The top reason for discontinuation was concern about long-term side effects (33.0%). Young men who have sex with men app users are prime candidates for PrEP, despite low uptake. Apps may be useful tools for PrEP information dissemination, adherence monitoring, and support.

Primary Realignment for Pelvic Fracture Urethral Injury Is Associated With Prolonged Time to Urethroplasty and Increased Stenosis Complexity.

PubMed

Horiguchi, Akio; Shinchi, Masayuki; Masunaga, Ayako; Okubo, Kazuki; Kawamura, Kazuki; Ojima, Kenichiro; Ito, Keiichi; Asano, Tomohiko; Azuma, Ryuichi

2017-10-01

To compare the clinical courses of patients with pelvic fracture urethral injury (PFUI) according to initial management strategy. We reviewed the clinical courses of 63 patients with PFUI who were initially treated elsewhere and underwent delayed anastomotic urethroplasty by a single surgeon between 2008 and 2015. Patients were grouped according to their initial treatment: by suprapubic tube placement alone (49 patients, SPT group) or primary realignment (14 patients, PR group). Time to urethroplasty was defined as the period between injury and delayed urethroplasty. Clinical data regarding the status of urethral stenosis, urethroplasty procedure, and treatment outcome were analyzed. The mean time to urethroplasty in the PR group was about 3 times than that in the SPT group (133 months vs 47 months, P = .035). Fifty percent of the PR group (7 of 14) had a history of repeated urethrotomy or dilation before referral, a percentage significantly higher than that of the SPT group (20.4%, 10 of 49, P = .027). The percentage of patients having a false passage and iatrogenic scar was significantly higher in the PR group (42.9% vs 16.3%, P = .035), but there was no significant between-group difference in urethral stenosis length, operative time, operative blood loss, or the percentage of patients requiring inferior pubectomy or urethral rerouting. PR does not facilitate delayed urethroplasty, and patients who undergo PR are at high risk of having a more complicated stenosis and longer time to urethroplasty, presumably because of repeated transurethral procedures. Copyright © 2017 Elsevier Inc. All rights reserved.

The prefrontal cortical endocannabinoid system modulates fear-pain interactions in a subregion-specific manner.

PubMed

Rea, Kieran; McGowan, Fiona; Corcoran, Louise; Roche, Michelle; Finn, David P

2018-05-30

The emotional processing and coordination of top-down responses to noxious and conditioned aversive stimuli involves the medial prefrontal cortex (mPFC). Evidence suggests that subregions of the mPFC, (infralimbic (IL), prelimbic (PrL), anterior cingulate (ACC) cortices), differentially alter the expression of contextually-induced fear and nociceptive behaviour. We investigated the role of the endocannabinoid system in the IL, PrL and ACC in formalin-evoked nociceptive behaviour, fear-conditioned analgesia (FCA) and conditioned fear in the presence of nociceptive tone. FCA was modelled in male Lister-hooded rats by assessing formalin-evoked nociceptive behaviour in an arena previously paired with footshock. The effects of intra-mPFC administration of AM251 (CB 1 receptor antagonist/inverse agonist), URB597 (fatty acid amide hydrolase inhibitor) or URB597 + AM251 on FCA and freezing behaviour were assessed. AM251 attenuated FCA when injected into the IL or PrL and reduced contextually induced freezing behaviour when injected intra-IL, but not intra-PrL or intra-ACC. Intra-ACC administration of AM251 alone or in combination with URB597 had no effect on FCA or freezing. URB597 attenuated FCA and freezing behaviour when injected intra-IL, prolonged the expression of FCA when injected intra-PrL and had no effect on these behaviours when injected intra-ACC. These results suggest important and differential roles for FAAH substrates or CB 1 receptors in the PrL, IL and ACC in the expression of FCA and conditioned fear in the presence of nociceptive tone. This article is protected by copyright. All rights reserved.

Soil zinc content, groundwater usage, and prostate cancer incidence in South Carolina.

PubMed

Wagner, Sara E; Burch, James B; Hussey, Jim; Temples, Tom; Bolick-Aldrich, Susan; Mosley-Broughton, Catishia; Liu, Yuan; Hebert, James R

2009-04-01

Prostate cancer (PrCA) incidence in South Carolina (SC) exceeds the national average, particularly among African Americans (AAs). Though data are limited, low environmental zinc exposures and down-regulation of prostatic zinc transporter proteins among AAs may explain, in part, the racial PrCA disparity. Age-adjusted PrCA rates were calculated by census tract. Demographic data were obtained from the 1990 census. Hazardous waste site locations and soil zinc concentrations were obtained from existing federal and state databases. A geographic information system and Poisson regression were used to test the hypothesis that census tracts with reduced soil zinc concentrations, elevated groundwater use, or more agricultural or hazardous waste sites had elevated PrCA risks. Census tracts with high groundwater use and low zinc concentrations had higher PrCA rate ratios (RR: 1.270; 95% confidence interval: 1.079, 1.505). This effect was not more apparent in areas populated primarily by AAs. Increased PrCA rates were associated with reduced soil zinc concentrations and elevated groundwater use, although this observation is not likely to contribute to SC's racial PrCA disparity. Statewide mapping and statistical modeling of relationships between environmental factors, demographics, and cancer incidence can be used to screen hypotheses focusing on novel PrCA risk factors.

Why are we prolonging QT interval monitoring?

PubMed

Barrett, Trina

2015-01-01

At present, monitoring of the QT interval (QTI) is not a standard practice in the medical intensive care unit setting, where many drugs that prolong the QTI are administered. This literature review looked at the current research for evidence-based standards to support QTI monitoring of patients with risk factors for QTI prolongation, which can result in life-threatening arrhythmias such as torsade de pointes. The objective of this article is to establish the existence of evidence-based standards for monitoring of the QTI and to raise awareness in the nursing profession of the need for such monitoring among patients who are at high risk for prolonged QTI. To determine whether published standards for QTI monitoring exist, a search was conducted of the bibliographic databases CINAHL, EBSCOhost, Medline, PubMed, Google Scholar, and the Cochrane Library for the years 2013 and 2014. Also, a survey was conducted to determine whether practice standards for QTI monitoring are being implemented at 4 major hospitals in the Memphis area, including a level 1 trauma center. The database search established the existence of published guidelines that support the need for QTI monitoring. Results of the hospital survey indicated that direct care nurses were not aware of the need to identify high-risk patients, drugs with the potential to prolong QTI that were being administered to their patients, or evidence-based standards for QTI monitoring. Review of the research literature underscored the need for QTI monitoring among high-risk patients, that is, those with genetic conditions that predispose them to QTI prolongation, those with existing cardiac conditions being treated with antiarrhythmic medications, or those who are prescribed any new medication classified as high risk on the basis of clinical research. This need is especially crucial in intensive care unit settings, where many antiarrhythmic medications are administered.

Prolonged QRS Widening After Aripiprazole Overdose.

PubMed

Mazer-Amirshahi, Maryann; Porter, Robert; Dewey, Kayla

2018-05-05

Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation. This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening. A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer. This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.

A common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans.

PubMed

Ilkhanoff, Leonard; Arking, Dan E; Lemaitre, Rozenn N; Alonso, Alvaro; Chen, Lin Y; Durda, Peter; Hesselson, Stephanie E; Kerr, Kathleen F; Magnani, Jared W; Marcus, Gregory M; Schnabel, Renate B; Smith, J Gustav; Soliman, Elsayed Z; Reiner, Alexander P; Sotoodehnia, Nona

2014-11-01

We examined the association of rs7626962 (S1103Y) or rs7629265, a variant in high linkage disequilibrium with S1103Y (r(2) = 0.87 - 1), with sudden cardiac death (SCD) and atrial fibrillation (AF) among African Americans. The SCN5A missense variant S1103Y has been associated with SCD among African Americans in small case-control studies, but larger population-based studies are needed to validate these findings. The association of this variant with AF has not been fully explored. Using genotyping data on over 7,000 African Americans from 5 cohorts (Atherosclerosis Risk in Communities [ARIC], Cleveland Family Study [CFS], Jackson Heart Study [JHS], Multi-Ethnic Study of Atherosclerosis [MESA], Cardiovascular Health Study [CHS]), we examined the association of rs7629265 with electrocardiographic PR, QRS, and QT intervals, and with incident AF and SCD. We examined association of S1103Y (rs7626962) with SCD using a population-based case-control study of SCD Cardiac Arrest Blood Study (CABS). Meta-analyses across 5 cohorts demonstrated that rs7629265 was significantly associated with PR duration (β = -4.1 milliseconds; P = 2.2×10(-6) ), but not significantly associated with QRS or QT intervals. In meta-analyses of prospectively followed ARIC and CHS participants (n = 3,656), rs7629265 was associated with increased AF risk (n = 299 AF cases; HR = 1.74, P = 1.9 × 10(-4) ). By contrast, rs7629265 was not significantly associated with SCD risk in ARIC (n = 83 SCD cases; P = 0.30) or CHS (n = 54 SCD cases; P = 0.47). Similarly, S1103Y was not significantly associated with SCD risk in CABS (n = 225 SCD cases; P = 0.29). The common SCN5A variant, rs7629265, is associated with increased AF risk and shorter PR interval among African Americans. In contrast to prior reports, we found no evidence of association of rs7629265 or rs7626962 (S1103Y) with SCD risk in the general population. © 2014 Wiley Periodicals, Inc.

Prolonged dry periods between rainfall events shorten the growth period of the resurrection plant Reaumuria soongorica.

PubMed

Zhang, Zhengzhong; Shan, Lishan; Li, Yi

2018-01-01

The resurrection plant Reaumuria soongorica is widespread across Asia, southern Europe, and North Africa and is considered to be a constructive keystone species in desert ecosystems, but the impacts of climate change on this species in desert ecosystems are unclear. Here, the morphological responses of R. soongorica to changes in rainfall quantity (30% reduction and 30% increase in rainfall quantity) and interval (50% longer drought interval between rainfall events) were tested. Stage-specific changes in growth were monitored by sampling at the beginning, middle, and end of the growing season. Reduced rainfall decreased the aboveground and total biomass, while additional precipitation generally advanced R. soongorica growth and biomass accumulation. An increased interval between rainfall events resulted in an increase in root biomass in the middle of the growing season, followed by a decrease toward the end. The response to the combination of increased rainfall quantity and interval was similar to the response to increased interval alone, suggesting that the effects of changes in rainfall patterns exert a greater influence than increased rainfall quantity. Thus, despite the short duration of this experiment, consequences of changes in rainfall regime on seedling growth were observed. In particular, a prolonged rainfall interval shortened the growth period, suggesting that climate change-induced rainfall variability may have significant effects on the structure and functioning of desert ecosystems.

Reporting pre-exposure prophylaxis use in Craigslist personal advertisements among men seeking sex with men in the United States.

PubMed

Hill, Brandon J; Bak, Trevor; VandeVusse, Alicia; Rosentel, Kris

2017-08-01

This study describes the self-reported use of pre-exposure prophylaxis (PrEP) in the personal advertisements of men seeking sex with men in the United States on the online classified advertisement site, Craigslist. Overall self-reported PrEP use was low (0.20%; 95% confidence interval (CI)=0.18-0.22). However, PrEP use in personal ads was described in conjunction with seeking sexual risk behaviours including 'bareback' sex (22.7%; 95% CI=17.7-27.7%) and sex with substance use (26.8%; 95% CI=21.5-32.1%). Only 4.0% of personal ads sought safe sex (3.3%; 95% CI=1.2-5.4%) or required condoms (0.7%; 95% CI=-0.3-1.7%). Our findings underscore the need for increased public PrEP awareness, particularly among men seeking sex with men, as well as the importance of healthcare providers emphasising sexually transmissible infection prevention behaviours (i.e. condom use) used in conjunction with PrEP.

Effects of cold water immersion and active recovery on post-exercise heart rate variability.

PubMed

Bastos, F N; Vanderlei, L C M; Nakamura, F Y; Bertollo, M; Godoy, M F; Hoshi, R A; Junior, J N; Pastre, C M

2012-11-01

The aim of the present study was to investigate the potential benefits of cold water immersion (CWI) and active recovery (AR) on blood lactate concentration ([Lac]) and heart rate variability (HRV) indices following high-intensity exercise. 20 male subjects were recruited. On the first visit, an incremental test was performed to determine maximal oxygen consumption and the associated speed (MAS). The remaining 3 visits for the performance of constant velocity exhaustive tests at MAS and different recovery methods (6 min) were separated by 7-day intervals [randomized: CWI, AR or passive recovery (PR)]. The CWI and AR lowered [Lac] (p<0.05) at 11, 13 and 15 min after exercise cessation in comparison to PR. There was a 'time' and 'recovery mode' interaction for 2 HRV indices: standard deviation of normal R-R intervals (SDNN) (partial eta squared=0.114) and natural log of low-frequency power density (lnLF) (partial eta squared=0.090). CWI presented significantly higher SDNN compared to PR at 15 min of recovery (p<0.05). In addition, greater SDNN values were found in CWI vs. AR during the application of recovery interventions, and at 30 and 75 min post-exercise (p<0.05 for all differences). The lnLF during the recovery interventions and at 75 min post-exercise was greater using CWI compared with AR (p<0.05). For square root of the mean of the sum of the squares of differences between adjacent R-R intervals (RMSSD) and natural log of high-frequency power density (lnHF), a moderate effect size was found between CWI and PR during the recovery interventions and at 15 min post-exercise. Our findings show that AR and CWI offer benefits regarding the removal of [Lac] following high-intensity exercise. While limited, CWI results in some improvement in post-exercise cardiac autonomic regulation compared to AR and PR. Further, AR is not recommended if the aim is to accelerate the parasympathetic reactivation. © Georg Thieme Verlag KG Stuttgart · New York.

The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction

PubMed Central

Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila

2015-01-01

Objective: To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. Background: QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. Material and methods: We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X2 test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. Results: QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max. interval was found in 33% of patients, indiabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function, (Chi-square: 16.77, P<0.0001). A prolonged QTc dispersion, was found in 40.6% of patients, in diabetic group with subclinical left ventricular diastolic dysfunction vs. 20% of patients in diabetic group with normal left ventricular diastolic function Chi-square: 14.11, P<0.0002). A prolonged dispersion of Tpeak-Tend interval was found in 24% of patients in diabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function (Chi-square: 12.00, P<0.005). Females in diabetic group with subclinical left ventricular diastolic dysfunction in comparison with males in diabetic group with subclinical left ventricular diastolic dysfunction, have a significantly prolonged: mean QTc max. interval (23.3% vs. 10%, Chisquare: 12.0, P<0.005), mean QTc dispersion (27.3% vs. 13.3%, Chi-square: 10.24, P<0.001), mean Tpeak-Tend interval (10% vs. 3.3%, Chi-square: 5.77, P<0.01), mean Tpek-Tend dispersion (16.6% vs. 6.6%, Chi-square: 8.39, P<0.003). Conclusion: The present study has shown that influences of type 2 diabetes and gender in diabetics with sub-clinical left-ventricular diastolic dysfunction are reflected in a set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization than in diabetic patients with normal diastolic function. In addition, it demonstrates that there exist differences between diabetic females with sub-clinic LV dysfunction and those with diabetes and normal LV function in the prevalence of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization. PMID:26550530

The influence of type 2 diabetes and gender on ventricular repolarization dispersion in patients with sub-clinic left ventricular diastolic dysfunction.

PubMed

Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila

2015-01-01

To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X(2) test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max. interval was found in 33% of patients, indiabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function, (Chi-square: 16.77, P<0.0001). A prolonged QTc dispersion, was found in 40.6% of patients, in diabetic group with subclinical left ventricular diastolic dysfunction vs. 20% of patients in diabetic group with normal left ventricular diastolic function Chi-square: 14.11, P<0.0002). A prolonged dispersion of Tpeak-Tend interval was found in 24% of patients in diabetic group with subclinical left ventricular diastolic dysfunction vs. 13.3% of patients in diabetic group with normal left ventricular diastolic function (Chi-square: 12.00, P<0.005). Females in diabetic group with subclinical left ventricular diastolic dysfunction in comparison with males in diabetic group with subclinical left ventricular diastolic dysfunction, have a significantly prolonged: mean QTc max. interval (23.3% vs. 10%, Chisquare: 12.0, P<0.005), mean QTc dispersion (27.3% vs. 13.3%, Chi-square: 10.24, P<0.001), mean Tpeak-Tend interval (10% vs. 3.3%, Chi-square: 5.77, P<0.01), mean Tpek-Tend dispersion (16.6% vs. 6.6%, Chi-square: 8.39, P<0.003). The present study has shown that influences of type 2 diabetes and gender in diabetics with sub-clinical left-ventricular diastolic dysfunction are reflected in a set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization than in diabetic patients with normal diastolic function. In addition, it demonstrates that there exist differences between diabetic females with sub-clinic LV dysfunction and those with diabetes and normal LV function in the prevalence of increased set of electrophysiological parameters that indicate a prolonged and more heterogeneous repolarization.

Quinacrine promotes replication and conformational mutation of chronic wasting disease prions.

PubMed

Bian, Jifeng; Kang, Hae-Eun; Telling, Glenn C

2014-04-22

Quinacrine's ability to reduce levels of pathogenic prion protein (PrP(Sc)) in mouse cells infected with experimentally adapted prions led to several unsuccessful clinical studies in patients with prion diseases, a 10-y investment to understand its mechanism of action, and the production of related compounds with expectations of greater efficacy. We show here, in stark contrast to this reported inhibitory effect, that quinacrine enhances deer and elk PrP(Sc) accumulation and promotes propagation of prions causing chronic wasting disease (CWD), a fatal, transmissible, neurodegenerative disorder of cervids of uncertain zoonotic potential. Surprisingly, despite increased prion titers in quinacrine-treated cells, transmission of the resulting prions produced prolonged incubation times and altered PrP(Sc) deposition patterns in the brains of diseased transgenic mice. This unexpected outcome is consistent with quinacrine affecting the intrinsic properties of the CWD prion. Accordingly, quinacrine-treated CWD prions were comprised of an altered PrP(Sc) conformation. Our findings provide convincing evidence for drug-induced conformational mutation of prions without the prerequisite of generating drug-resistant variants of the original strain. More specifically, they show that a drug capable of restraining prions in one species/strain setting, and consequently used to treat human prion diseases, improves replicative ability in another and therefore force reconsideration of current strategies to screen antiprion compounds.

Quinacrine promotes replication and conformational mutation of chronic wasting disease prions

PubMed Central

Bian, Jifeng; Kang, Hae-Eun; Telling, Glenn C.

2014-01-01

Quinacrine’s ability to reduce levels of pathogenic prion protein (PrPSc) in mouse cells infected with experimentally adapted prions led to several unsuccessful clinical studies in patients with prion diseases, a 10-y investment to understand its mechanism of action, and the production of related compounds with expectations of greater efficacy. We show here, in stark contrast to this reported inhibitory effect, that quinacrine enhances deer and elk PrPSc accumulation and promotes propagation of prions causing chronic wasting disease (CWD), a fatal, transmissible, neurodegenerative disorder of cervids of uncertain zoonotic potential. Surprisingly, despite increased prion titers in quinacrine-treated cells, transmission of the resulting prions produced prolonged incubation times and altered PrPSc deposition patterns in the brains of diseased transgenic mice. This unexpected outcome is consistent with quinacrine affecting the intrinsic properties of the CWD prion. Accordingly, quinacrine-treated CWD prions were comprised of an altered PrPSc conformation. Our findings provide convincing evidence for drug-induced conformational mutation of prions without the prerequisite of generating drug-resistant variants of the original strain. More specifically, they show that a drug capable of restraining prions in one species/strain setting, and consequently used to treat human prion diseases, improves replicative ability in another and therefore force reconsideration of current strategies to screen antiprion compounds. PMID:24711410

Effects of three postexercice recovery treatments on femoral artery blood flow kinetics.

PubMed

Ménétrier, A; Mourot, L; Degano, B; Bouhaddi, M; Walther, G; Regnard, J; Tordi, N

2015-04-01

This study aimed to compare the kinetics of muscle leg blood flow during three recovery treatments following a prolonged exercise: contrast water therapy (CWT), compression stockings (CS) or passive recovery (PR). Fifteen men came to the laboratory three times to perform a 45-min exercise followed 5 min after by a standardized 12-min recovery treatment in upright position, alternating between two vats every 2 min: CWT (cold: ~12 °C to warm: 36 °C), CS (~20 mmHg) or PR. The order of treatments was randomized. Blood flow was measured using Doppler ultrasound during the recovery treatments (i.e., min 3, 5, 7 and 9) in the superficial femoral artery distally to the common bifurcation (~3 cm) (above the water and stocking). Blood flow was significantly higher during CWT (P<0.01; +22.91%) and CS (P<0.05; +15.26%) than during PR. Although no statistical difference between CWT and CS was observed, effect sizes were larger during CWT (large) than during CS (moderate). No changes in blood flow occurred in the femoral artery between hot and cold transitions of CWT. During immediate recovery of a high intensity exercise, CWT and CS trigger higher femoral artery blood flow than PR. Moreover, effect sizes were greater during CWT than during CS.

A multi-center, randomized, clinical trial comparing adhesive polyurethane foam dressing and adhesive hydrocolloid dressing in patients with grade II pressure ulcers in primary care and nursing homes

PubMed Central

2013-01-01

Background Pressure ulcers (PrUs) are ischemic wounds in the skin and underlying tissues caused by long-standing pressure force over an external bone or cartilaginous surface. PrUs are an important challenge for the overall health system because can prolong patient hospitalization and reduce quality of life. Moreover, 95% of PrUs are avoidable, suggesting they are caused by poor quality care assistance. PrUs are also costly, increasing national costs. For example, they represent about 5% of overall annual health expenses in Spain. Stages I and II PrUs have a combined prevalence of 65%. According main clinical guidelines, stage II PrUs (PrU-IIs) are usually treated by applying special dressings (polyurethane or hydrocolloid). However, little scientific evidence regarding their efficacy has been identified in scientific literature. Our aim is to assess the comparative efficacy of adhesive polyurethane foam and hydrocolloid dressings in the treatment of PrU-IIs in terms of healed ulcer after 8 weeks of follow-up. Methods/design This paper describes the development and evaluation protocol of a randomized clinical trial of two parallel treatment arms. A total of 820 patients with at least 1 PrU-II will be recruited from primary health care and home care centers. All patients will receive standardized healing procedures and preventive measures (e.g. positional changes and pressure-relieving support surfaces), following standardized procedures. The main outcome will be the percentage of wounds healed after 8 weeks. Secondary outcomes will include cost-effectiveness, as evaluated by cost per healed ulcer and cost per treated patient and safety evaluated by adverse events. Discussion This trial will address the hypothesis that hydrocolloid dressings will heal at least 10% more stage II PrUs and be more cost-effective than polyurethane foam dressings after 8 weeks. Trial registration This trial has been registered with controlled-trials number ISCRCTN57842461 and EudraCT 2012-003945-14. PMID:24359122

ENU mutagenesis identifies mice with cardiac fibrosis and hepatic steatosis caused by a mutation in the mitochondrial trifunctional protein beta-subunit.

PubMed

Kao, Hsiao-Jung; Cheng, Ching-Feng; Chen, Yen-Hui; Hung, Shuen-Iu; Huang, Cheng-Chih; Millington, David; Kikuchi, Tateki; Wu, Jer-Yuarn; Chen, Yuan-Tsong

2006-12-15

Using the metabolomics-guided screening coupled to N-ethyl-N-nitrosourea-mediated mutagenesis, we identified mice that exhibited elevated levels of long-chain acylcarnitines. Whole genome homozygosity mapping with 262 SNP markers mapped the disease gene to chromosome 5 where candidate genes Hadha and Hadhb, encoding the mitochondria trifunctional protein (MTP) alpha- and beta-subunits, respectively, are located. Direct sequencing revealed a normal alpha-subunit, but detected a nucleotide T-to-A transversion in exon 14 (c.1210T>A) of beta-subunit (Hadhb) which resulted in a missense mutation of methionine to lysine (M404K). Western blot analysis showed a significant reduction of both the alpha- and beta-subunits, consistent with reduced enzyme activity in both the long-chain 3-hydroxyacyl-CoA dehydrogenase and the long-chain 3-ketoacyl-CoA thiolase activities. These mice had a decreased weight gain and cardiac arrhythmias which manifested from a prolonged PR interval to a complete atrio-ventricular dissociation, and died suddenly between 9 and 16 months of age. Histopathological studies showed multifocal cardiac fibrosis and hepatic steatosis. This mouse model will be useful to further investigate the mechanisms underlying arrhythmogenesis relating to lipotoxic cardiomyopathy and to investigate pathophysiology and treatment strategies for human MTP deficiency.

Large Outbreaks of Ciguatera after Consumption of Brown Marbled Grouper

PubMed Central

Chan, Thomas Y. K.

2014-01-01

Brown marbled grouper (Epinephelus fuscoguttatus) is an apex predator from coral reefs of the Indo-Pacific region. All five published case series of ciguatera after consumption of brown marbled grouper were reviewed to characterize the types, severity and chronicity of ciguatera symptoms associated with its consumption. Three of these case series were from large outbreaks affecting over 100–200 subjects who had eaten this reef fish served at banquets. Affected subjects generally developed a combination of gastrointestinal, neurological and, less commonly, cardiovascular symptoms. Gastrointestinal symptoms occurred early and generally subsided in 1–2 days. Some neurological symptoms (e.g., paresthesia of four limbs) could last for weeks or months. Sinus bradycardia and hypotension occurred early, but could be severe and prolonged, necessitating the timely use of intravenous fluids, atropine and dopamine. Other cardiovascular and neurological features included atrial ectopics, ventricular ectopics, dyspnea, chest tightness, PR interval >0.2 s, ST segment changes, polymyositis and coma. Concomitant alcohol consumption was associated with a much higher risk of developing bradycardia, hypotension and altered skin sensation. The public should realize that consumption of the high-risk fish (especially the ciguatoxin-rich parts and together with alcohol use) and repeated ciguatoxin exposures will result in more severe and chronic illness. PMID:25019942

Large outbreaks of ciguatera after consumption of brown marbled grouper.

PubMed

Chan, Thomas Y K

2014-07-11

Brown marbled grouper (Epinephelus fuscoguttatus) is an apex predator from coral reefs of the Indo-Pacific region. All five published case series of ciguatera after consumption of brown marbled grouper were reviewed to characterize the types, severity and chronicity of ciguatera symptoms associated with its consumption. Three of these case series were from large outbreaks affecting over 100-200 subjects who had eaten this reef fish served at banquets. Affected subjects generally developed a combination of gastrointestinal, neurological and, less commonly, cardiovascular symptoms. Gastrointestinal symptoms occurred early and generally subsided in 1-2 days. Some neurological symptoms (e.g., paresthesia of four limbs) could last for weeks or months. Sinus bradycardia and hypotension occurred early, but could be severe and prolonged, necessitating the timely use of intravenous fluids, atropine and dopamine. Other cardiovascular and neurological features included atrial ectopics, ventricular ectopics, dyspnea, chest tightness, PR interval >0.2 s, ST segment changes, polymyositis and coma. Concomitant alcohol consumption was associated with a much higher risk of developing bradycardia, hypotension and altered skin sensation. The public should realize that consumption of the high-risk fish (especially the ciguatoxin-rich parts and together with alcohol use) and repeated ciguatoxin exposures will result in more severe and chronic illness.

Safety of intravenous lacosamide in critically ill children.

PubMed

Welsh, Sarah S; Lin, Nan; Topjian, Alexis A; Abend, Nicholas S

2017-11-01

Acute seizures are common in critically ill children. These patients would benefit from intravenous anti-seizure medications with few adverse effects. We reviewed the usage and effects of intravenous lacosamide in critically ill children with seizures or status epilepticus. This retrospective series included consecutive patients who received at least one dose of intravenous lacosamide from April 2011 to February 2016 in the pediatric intensive care unit of a quaternary care children's hospital, including patients with new lacosamide initiation and continuation of outpatient oral lacosamide. Dosing and prescribing practices were reviewed. Adverse effects were defined by predefined criteria, and most were evaluated during the full admission. We identified 51 intensive care unit admissions (47 unique patients) with intravenous lacosamide administration. Lacosamide was utilized as a third or fourth-line anti-seizure medication for acute seizures or status epilepticus in the lacosamide-naïve cohort. One patient experienced bradycardia and one patient experienced a rash that were considered potentially related to lacosamide. No other adverse effects were identified, including no evidence of PR interval prolongation. Lacosamide was well tolerated in critically ill children. Further study is warranted to evaluate the effectiveness of earlier lacosamide use for pediatric status epilepticus and acute seizures. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Drug-physiology interaction and its influence on the QT prolongation-mechanistic modeling study.

PubMed

Wiśniowska, Barbara; Polak, Sebastian

2018-06-01

The current study is an example of drug-disease interaction modeling where a drug induces a condition which can affect the pharmacodynamics of other concomitantly taken drugs. The electrophysiological effects of hypokaliemia and heart rate changes induced by the antiasthmatic drugs were simulated with the use of the cardiac safety simulator. Biophysically detailed model of the human cardiac physiology-ten Tusscher ventricular cardiomyocyte cell model-was employed to generate pseudo-ECG signals and QTc intervals for 44 patients from four clinical studies. Simulated and observed mean QTc values with standard deviation (SD) for each reported study point were compared and differences were analyzed with Student's t test (α = 0.05). The simulated results reflected the QTc interval changes measured in patients, as well as their clinically observed interindividual variability. The QTc interval changes were highly correlated with the change in plasma potassium both in clinical studies and in the simulations (Pearson's correlation coefficient > 0.55). The results suggest that the modeling and simulation approach could provide valuable quantitative insight into the cardiological effect of the potassium and heart rate changes caused by electrophysiologically inactive, non-cardiological drugs. This allows to simulate and predict the joint effect of several risk factors for QT prolongation, e.g., drug-dependent QT prolongation due to the ion channels inhibition and the current patient physiological conditions.

Increased mean time from end of surgery to operating room exit in a historical cohort of cases with prolonged time to extubation.

PubMed

Dexter, Franklin; Epstein, Richard H

2013-12-01

Prolonged time to extubation has been defined as the occurrence of a ≥ 15-minute interval from the end of surgery to removal of the tracheal tube. We quantified the increases in the mean times from end of surgery to exit from the OR associated with prolonged extubations and tested whether the increases were economically important (≥ 5 minutes). Anesthesia information management system data from 1 tertiary hospital were collected from November 2005 through December 2012 (i.e., sample sizes were N = 22 sequential quarters). Cases were excluded in which the patient's trachea was not intubated or extubated while physically in the operating room (OR). For each combination of stratification variable (below) and quarter, the mean time from end of surgery to OR exit was calculated for the extubations that were not prolonged and for those that were prolonged. Results are reported as mean ± SEM, with "at least" denoting the lower 95% confidence interval. The mean times from end of surgery to OR exit were at least 12.6 minutes longer for prolonged extubations when calculated with stratification by duration of surgery and prone or other positioning (13.0 ± 0.1 minutes), P < 0.0001 compared to 5 minutes (i.e., times were substantively long economically). The mean times were at least 11.7 minutes longer when calculated stratified by anesthesia procedure code (12.4 ± 0.4, P < 0.0001) and at least 11.3 minutes longer when calculated stratified by surgeon (12.4 ± 0.6, P < 0.0001). We recommend that anesthesia providers document the times of extubations and monitor the incidence of prolonged extubations as an economic measure. This would be especially important for providers at facilities with many ORs that have at least 8 hours of cases and turnovers.

Solifenacin

MedlinePlus

... prolonged QT interval (a problem with the way electricity is conducted in the heart that may cause ... may cause blurred vision. Do not drive a car or operate machinery until you know how this ...

Morphological Simulation of Phase Separation Coupled Oscillation Shear and Varying Temperature Fields

NASA Astrophysics Data System (ADS)

Wang, Heping; Li, Xiaoguang; Lin, Kejun; Geng, Xingguo

2018-05-01

This paper explores the effect of the shear frequency and Prandtl number ( Pr) on the procedure and pattern formation of phase separation in symmetric and asymmetric systems. For the symmetric system, the periodic shear significantly prolongs the spinodal decomposition stage and enlarges the separated domain in domain growth stage. By adjusting the Pr and shear frequency, the number and orientation of separated steady layer structures can be controlled during domain stretch stage. The numerical results indicate that the increase in Pr and decrease in the shear frequency can significantly increase in the layer number of the lamellar structure, which relates to the decrease in domain size. Furthermore, the lamellar orientation parallel to the shear direction is altered into that perpendicular to the shear direction by further increasing the shear frequency, and also similar results for larger systems. For asymmetric system, the quantitative analysis shows that the decrease in the shear frequency enlarges the size of separated minority phases. These numerical results provide guidance for setting the optimum condition for the phase separation under periodic shear and slow cooling.

Poly-L-arginine synergizes with oligodeoxynucleotides containing CpG-motifs (CpG-ODN) for enhanced and prolonged immune responses and prevents the CpG-ODN-induced systemic release of pro-inflammatory cytokines.

PubMed

Lingnau, Karen; Egyed, Alena; Schellack, Carola; Mattner, Frank; Buschle, Michael; Schmidt, Walter

2002-10-04

This study describes an entirely synthetic vaccine composed of antigenic peptides (T cell epitopes), oligodeoxynucleotides containing CpG-motifs (CpG-ODN) and poly-L-arginine (pR). CpG-ODN are known to be potent inducers of predominantly type 1-like immune responses, while polycationic amino acids, like pR, facilitate the uptake of antigens into antigen presenting cells (APCs). We demonstrate that the application of peptides and pR/CpG-ODN results in strongly enhanced peptide-specific immune responses as compared to the application of peptides with either of the immunomodulators alone. High numbers of antigen-specific T cells can be observed even after only one injection of the vaccine for a remarkably long period of time (at least 372 days). Furthermore, the potentially harmful systemic release of pro-inflammatory cytokines induced upon injection of CpG-ODN is inhibited. Thus, the combined application of CpG-ODN and pR may represent a novel vaccine strategy in humans.

Mutation of the Na+/K+-ATPase Atp1a1a.1 causes QT interval prolongation and bradycardia in zebrafish.

PubMed

Pott, Alexander; Bock, Sarah; Berger, Ina M; Frese, Karen; Dahme, Tillman; Keßler, Mirjam; Rinné, Susanne; Decher, Niels; Just, Steffen; Rottbauer, Wolfgang

2018-05-08

The genetic underpinnings that orchestrate the vertebrate heart rate are not fully understood yet, but of high clinical importance, since diseases of cardiac impulse formation and propagation are common and severe human arrhythmias. To identify novel regulators of the vertebrate heart rate, we deciphered the pathogenesis of the bradycardia in the homozygous zebrafish mutant hiphop (hip) and identified a missense-mutation (N851K) in Na + /K + -ATPase α1-subunit (atp1a1a.1). N851K affects zebrafish Na + /K + -ATPase ion transport capacity, as revealed by in vitro pump current measurements. Inhibition of the Na + /K + -ATPase in vivo indicates that hip rather acts as a hypomorph than being a null allele. Consequently, reduced Na + /K + -ATPase function leads to prolonged QT interval and refractoriness in the hip mutant heart, as shown by electrocardiogram and in vivo electrical stimulation experiments. We here demonstrate for the first time that Na + /K + -ATPase plays an essential role in heart rate regulation by prolonging myocardial repolarization. Copyright © 2018. Published by Elsevier Ltd.

Effects of ice massage of the head and spine on heart rate variability in healthy volunteers.

PubMed

Mooventhan, A; Nivethitha, L

2016-07-01

Ice massage (IM) is one of the treatment procedures used in hydrotherapy. Though its various physiological/therapeutic effects have been reported, effects of IM of the head and spine on heart rate variability (HRV) have not been studied. Thus, this study evaluated the effects of IM of the head and spine on HRV in healthy volunteers. Thirty subjects were randomly divided into 3 sessions: (1) IM, (2) tap water massage (TWM) and (3) prone rest (PR). Heart rate (HR) and HRV were assessed before and after each intervention session. A significant increase in the mean of the intervals between adjacent QRS complexes or the instantaneous HR (RRI), square root of mean of sum of squares of differences between adjacent normal to normal (NN) intervals (RMSSD), number of interval differences of successive NN intervals greater than 50 milliseconds (NN50), proportion derived by dividing NN50 by total number of NN intervals along with significant reduction in HR after IM session; significant increase in RRI along with significant reduction in HR after TWM, and a significant increase only in RMSSD after PR were observed. However, there was no significant difference between the sessions. Results of this study suggest that 20 min of IM of the head and spine is effective in reducing HR and improving HRV through vagal dominance in healthy volunteers.

Electrocardiographic and blood pressure effects of energy drinks and Panax ginseng in healthy volunteers: A randomized clinical trial.

PubMed

Shah, Sachin A; Occiano, Andrew; Nguyen, Tinh An; Chan, Amanda; Sky, Joseph C; Bhattacharyya, Mouchumi; O'Dell, Kate M; Shek, Allen; Nguyen, Nancy N

2016-09-01

Energy drink usage has been linked to emergency room visits and deaths. The objective of the study is to assess the electrocardiographic and blood pressure effects of energy drinks, Panax ginseng and placebo in healthy individuals. This was a randomized, double blinded, placebo controlled, crossover study. Young healthy volunteers with no comorbid conditions consumed 32oz of an energy drink, control drink with 800mg of Panax ginseng or matching placebo-control drink over 45min. Primary endpoints were QTc interval and systolic blood pressure. Secondary endpoints included QT interval, PR interval, QRS duration, heart rate, and diastolic blood pressure. All endpoints were assessed at baseline, 1, 2, 3.5, and 5.5h. A significant increase in QTc interval 2h post energy drink consumption was evident when compared to placebo (3.37±10.7ms and -3.19±11.8ms respectively; p=0.030). Similarly, systolic blood pressure 2h post energy drink consumption increased when compared to placebo (2.00±6.37mmHg and -2.67±5.83mmHg respectively; p=0.014). The PR interval significantly reduced over a 2h period post energy drink use in a clinically non-meaningful manner. Heart rate at 2h was not significantly higher in the energy drink group when compared to others. The QT interval, QRS interval and diastolic blood pressure were not impacted at any time point. Certain energy drinks consumed at a high volume significantly increase the QTc interval and systolic blood pressure by over 6ms and 4mmHg respectively. Panax ginseng does not have a significant impact on ECG or blood pressure parameters. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Preparing for PrEP: Perceptions and Readiness of Canadian Physicians for the Implementation of HIV Pre-Exposure Prophylaxis

PubMed Central

Sharma, Malika; Wilton, James; Senn, Heather; Fowler, Shawn; Tan, Darrell H. S.

2014-01-01

Recent evidence has demonstrated the efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention, but concerns persist around its use. Little is known about Canadian physicians' knowledge of and willingness to prescribe PrEP. We disseminated an online survey to Canadian family, infectious disease, internal medicine, and public health physicians between September 2012–June 2013 to determine willingness to prescribe PrEP. Criteria for analysis were met by 86 surveys. 45.9% of participants felt “very familiar” with PrEP, 49.4% felt that PrEP should be approved by Health Canada, and 45.4% of respondents were willing to prescribe PrEP. Self-identifying as an HIV expert (odds ratio, OR = 4.1, 95% confidence interval, CI = 1.6–10.2), familiarity with PrEP (OR = 5.0, 95%CI = 1.3–19.0) and having been asked by patients about PrEP (OR = 4.0, 95%CI = 1.5–10.5) were positively associated with willingness to prescribe PrEP on univariable analysis. The latter two were the strongest predictors on multivariate analysis. Participants cited cost and efficacy as major concerns. 75.3% did not feel that information had been adequately disseminated among physicians. In summary, Canadian physicians demonstrate varying levels of support for PrEP and express concerns about its implementation. Further research on real-world effectiveness, continuing medical education, and clinical support is needed to prepare physicians for this prevention strategy. PMID:25133648

Pulmonary effects of exposure to fine fibreglass: irregular opacities and small airways obstruction.

PubMed Central

Kilburn, K H; Powers, D; Warshaw, R H

1992-01-01

OBJECTIVE--Man made mineral fibres imitate asbestos and produce tumours of the pleura in animals. To answer the question, Does prolonged exposure to fibreglass adversely affect pulmonary function or produce radiographic abnormalities in human subjects? we studied workers in a midwestern appliance plant where refrigerator doors and previously entire cabinets were insulated with fibreglass sheeting and loose rotary spun fibreglass. METHODS--Spirometry and lung volumes were measured, respiratory and occupational questionnaires were administered, and chest x-ray films were read for pneumoconiosis using International Labour Office (ILO) 1980 criteria in 284 workers with exposure of 20 years or more. RESULTS--Expiratory flows were reduced including FEV1 (mean 90.3% of predicted (pr), FEF25-75 (85.5% pr), and FEF75-85 (76.2% pr). Forced vital capacity was significantly reduced (92.8% pr) and total lung capacity was significantly increased (109.2% pr). In white male smokers, a group large enough for comparisons, parameters of pulmonary function were reduced further in the presence of irregular opacities. Forty three workers (15.1%) had evidence of pneumoconiosis on chest radiographs: 26 of these (9.1%), had no known exposure to asbestos and 17 (6.0%) had some exposure. The best judgement was that in 36 (13.0%), pulmonary opacities or pleural abnormalities were due to fibreglass. CONCLUSION--Commercial rotary spun fibreglass used for insulating appliances appears to produce human disease that is similar to asbestosis. PMID:1419860

[Evaluation of estimation of prevalence ratio using bayesian log-binomial regression model].

PubMed

Gao, W L; Lin, H; Liu, X N; Ren, X W; Li, J S; Shen, X P; Zhu, S L

2017-03-10

To evaluate the estimation of prevalence ratio ( PR ) by using bayesian log-binomial regression model and its application, we estimated the PR of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea in their infants by using bayesian log-binomial regression model in Openbugs software. The results showed that caregivers' recognition of infant' s risk signs of diarrhea was associated significantly with a 13% increase of medical care-seeking. Meanwhile, we compared the differences in PR 's point estimation and its interval estimation of medical care-seeking prevalence to caregivers' recognition of risk signs of diarrhea and convergence of three models (model 1: not adjusting for the covariates; model 2: adjusting for duration of caregivers' education, model 3: adjusting for distance between village and township and child month-age based on model 2) between bayesian log-binomial regression model and conventional log-binomial regression model. The results showed that all three bayesian log-binomial regression models were convergence and the estimated PRs were 1.130(95 %CI : 1.005-1.265), 1.128(95 %CI : 1.001-1.264) and 1.132(95 %CI : 1.004-1.267), respectively. Conventional log-binomial regression model 1 and model 2 were convergence and their PRs were 1.130(95 % CI : 1.055-1.206) and 1.126(95 % CI : 1.051-1.203), respectively, but the model 3 was misconvergence, so COPY method was used to estimate PR , which was 1.125 (95 %CI : 1.051-1.200). In addition, the point estimation and interval estimation of PRs from three bayesian log-binomial regression models differed slightly from those of PRs from conventional log-binomial regression model, but they had a good consistency in estimating PR . Therefore, bayesian log-binomial regression model can effectively estimate PR with less misconvergence and have more advantages in application compared with conventional log-binomial regression model.

Association of Ring Finger Protein 213 Gene P.R4810k Polymorphism with Intracranial Major Artery Stenosis/Occlusion.

PubMed

Zhang, Qian; Yu, Lebao; Ge, Peicong; Ma, Yonggang; Zhang, Dong; Zhang, Yan; Wang, Rong; Wang, Shuo; Zhao, Yuanli; Cao, Yong; Liu, Xingju; Deng, Xiaofeng; Zhao, Jizong

2018-06-01

Intracranial major artery stenosis/occlusion (ICASO) is a common cause of ischemic stroke worldwide. A number of studies have assessed the association of the p.R4810K polymorphism in the ring finger protein 213 (RNF213) gene with ICASO, but the results have not been entirely consistent. We conducted a case-control study to estimate the association between the p.R4810K polymorphism and the risk of ICASO in a Chinese population. A total of 124 patients and 230 controls were enrolled. Moreover, a meta-analysis was performed to evaluate this association in the East Asian populations. In our case-control study, the frequencies of the G/A genotype of p.R4810K were significantly higher in the ICASO patients than in the control group (4.03% versus .43%, P = .021, respectively). Moreover, in the meta-analysis, we assessed 7 case-control studies that included 1239 patients and 1377 controls. The pooled odds ratios (ORs) indicated significant association between the p.R4810K polymorphism and the ICASO risk in the dominant model (OR = 9.37, 95% confidence interval: 4.61-19.02, P = .000), the heterozygote comparison (OR = 8.97, 95% CI: 4.41-18.25, P = .000), and the allele comparison (OR = 9.50, 95% confidence interval: 4.71-19.19, P = .000) in the East Asian populations. Subgroup analysis based on ethnicity revealed that the risks in the Japanese and the Korean populations were higher than that in the Chinese population. The p.R4810K polymorphism was associated with an increased risk of ICASO in the East Asian populations. Further studies on the function of the RNF213 protein and the clinical features of this subtype of ICASO are needed. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

LED therapy or cryotherapy between exercise intervals in Wistar rats: anti-inflammatory and ergogenic effects.

PubMed

da Costa Santos, Vanessa Batista; de Paula Ramos, Solange; Milanez, Vinícius Flávio; Corrêa, Julio Cesar Molina; de Andrade Alves, Rubens Igor; Dias, Ivan Frederico Lupiano; Nakamura, Fábio Yuzo

2014-03-01

The aim of this study was to test, between two bouts of exercise, the effects of light-emitting diode (LED) therapy and cryotherapy regarding muscle damage, inflammation, and performance. Male Wistar rats were allocated in four groups: control, passive recovery (PR), cryotherapy (Cryo), and LED therapy. The animals were submitted to 45 min of swimming exercise followed by 25 min of recovery and then a second bout of either 45 min of exercise (muscle damage analysis) or time to exhaustion (performance). During the rest intervals, the rats were kept in passive rest (PR), submitted to cold water immersion (10 min, 10 °C) or LED therapy (940 nm, 4 J/cm(2)) of the gastrocnemius muscle. Blood samples were collected to analyze creatine kinase activity (CK), C-reactive protein (CRP), and leukocyte counts. The soleus muscles were evaluated histologically. Time to exhaustion was recorded during the second bout of exercise. After a second bout of 45 min, the results demonstrated leukocytosis in the PR and Cryo groups. Neutrophil counts were increased in all test groups. CK levels were increased in the Cryo group. CRP was increased in PR animals. The PR group presented a high frequency of necrosis, but the LED group had fewer necrotic areas. Edema formation was prevented, and fewer areas of inflammatory cells were observed in the LED group. The time to exhaustion was greater in both the LED and Cryo groups, without differences in CK levels. CRP was decreased in LED animals. We conclude that LED therapy and cryotherapy can improve performance, although LED therapy is more efficient in preventing muscle damage and local and systemic inflammation.

No effect of season on the electrocardiogram of long-eared bats (Nyctophilus gouldi) during torpor.

PubMed

Currie, Shannon E

2018-04-05

Heterothermic animals regularly undergo profound alterations of cardiac function associated with torpor. These animals have specialised tissues capable of withstanding fluctuations in body temperature > 30 °C without adverse effects. In particular, the hearts of heterotherms are able to resist fibrillation and discontinuity of the cardiac conduction system common in homeotherms during hypothermia. To investigate the patterns of cardiac conduction in small insectivorous bats which enter torpor year round, I simultaneously measured ECG and subcutaneous temperature (T sub ) of 21 Nyctophilus gouldi (11 g) during torpor at a range of ambient temperatures (T a 1-28 °C). During torpor cardiac conduction slowed in a temperature dependent manner, primarily via prolongation along the atrioventricular pathway (PR interval). A close coupling of depolarisation and repolarisation was retained in torpid bats, with no isoelectric ST segment visible until animals reached T sub <6 °C. There was little change in ventricular repolarisation (JT interval) with decreasing T sub , or between rest and torpor at mild T a . Bats retained a more rapid rate of ventricular conduction and repolarisation during torpor relative to other hibernators. Throughout all recordings across seasons (> 2500 h), there was no difference in ECG morphology or heart rate during torpor, and no manifestations of significant conduction blocks or ventricular tachyarrhythmias were observed. My results demonstrate the capacity of bat hearts to withstand extreme fluctuations in rate and temperature throughout the year without detrimental arrhythmogenesis. I suggest that this conduction reserve may be related to flight and the daily extremes in metabolism experienced by these animals, and warrants further investigation of cardiac electrophysiology in other flying hibernators.

The effect of oral preexposure prophylaxis on the progression of HIV-1 seroconversion

PubMed Central

Donnell, Deborah; Ramos, Eric; Celum, Connie; Baeten, Jared; Dragavon, Joan; Tappero, Jordan; Lingappa, Jairam R.; Ronald, Allan; Fife, Kenneth; Coombs, Robert W.

2017-01-01

Objective: To investigate whether oral preexposure prophylaxis (PrEP) alters timing and patterns of seroconversion when PrEP use continues after HIV-1 infection. Design: Retrospective testing of the timing of Fiebig stage HIV-1 seroconversion in the Partners PrEP Study, a randomized placebo-controlled clinical trial of PrEP conducted in Kenya and Uganda. Methods: Specimens from 138 seroconverters were collected every 3 months and when HIV-1 infection was suspected based on monthly rapid HIV-1 tests. Progression of seroconversion was compared between randomized groups (PrEP versus placebo) and per-protocol groups (placebo versus PrEP participants with detectable tenofovir during the seroconversion period) using laboratory assessment of Fiebig stage. Delay in site-detection of seroconversion and association with PrEP drug-regimen resistant virus were assessed using logistic regression. Analysis of time to each Fiebig stage used maximum likelihood estimation with a parametric model to accommodate the varying lengths of HIV-infection intervals. Results: There was a significant increase in delayed site detection of infection associated with PrEP (odds ratio = 3.49, P = 0.044). Delay in detection was not associated with increased risk of resistance in the PrEP arm (odds ratio = 0.93, P = 0.95). Estimated time to each Fiebig stage was elongated in seroconverters with evidence of ongoing PrEP use, significantly for only Stage 5 (28 versus 17 days, P = 0.05). Adjusted for Fiebig stage, viral RNA was ∼2/3 log lower in those assigned to PrEP compared with placebo; no differences were found in Architect signal to cut-off at any stage. Conclusion: Ongoing PrEP use in seroconverters may delay detection of infection and elongate seroconversion, although the delay does not increase risk of resistance. PMID:28692542

Bile Acids Reduce Prion Conversion, Reduce Neuronal Loss, and Prolong Male Survival in Models of Prion Disease

PubMed Central

Cortez, Leonardo M.; Campeau, Jody; Norman, Grant; Kalayil, Marian; Van der Merwe, Jacques; McKenzie, Debbie

2015-01-01

ABSTRACT Prion diseases are fatal neurodegenerative disorders associated with the conversion of cellular prion protein (PrPC) into its aberrant infectious form (PrPSc). There is no treatment available for these diseases. The bile acids tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) have been recently shown to be neuroprotective in other protein misfolding disease models, including Parkinson's, Huntington's and Alzheimer's diseases, and also in humans with amyotrophic lateral sclerosis. Here, we studied the therapeutic efficacy of these compounds in prion disease. We demonstrated that TUDCA and UDCA substantially reduced PrP conversion in cell-free aggregation assays, as well as in chronically and acutely infected cell cultures. This effect was mediated through reduction of PrPSc seeding ability, rather than an effect on PrPC. We also demonstrated the ability of TUDCA and UDCA to reduce neuronal loss in prion-infected cerebellar slice cultures. UDCA treatment reduced astrocytosis and prolonged survival in RML prion-infected mice. Interestingly, these effects were limited to the males, implying a gender-specific difference in drug metabolism. Beyond effects on PrPSc, we found that levels of phosphorylated eIF2α were increased at early time points, with correlated reductions in postsynaptic density protein 95. As demonstrated for other neurodegenerative diseases, we now show that TUDCA and UDCA may have a therapeutic role in prion diseases, with effects on both prion conversion and neuroprotection. Our findings, together with the fact that these natural compounds are orally bioavailable, permeable to the blood-brain barrier, and U.S. Food and Drug Administration-approved for use in humans, make these compounds promising alternatives for the treatment of prion diseases. IMPORTANCE Prion diseases are fatal neurodegenerative diseases that are transmissible to humans and other mammals. There are no disease-modifying therapies available, despite decades of research. Treatment targets have included inhibition of protein accumulation, clearance of toxic aggregates, and prevention of downstream neurodegeneration. No one target may be sufficient; rather, compounds which have a multimodal mechanism, acting on different targets, would be ideal. TUDCA and UDCA are bile acids that may fulfill this dual role. Previous studies have demonstrated their neuroprotective effects in several neurodegenerative disease models, and we now demonstrate that this effect occurs in prion disease, with an added mechanistic target of upstream prion seeding. Importantly, these are natural compounds which are orally bioavailable, permeable to the blood-brain barrier, and U.S. Food and Drug Administration-approved for use in humans with primary biliary cirrhosis. They have recently been proven efficacious in human amyotrophic lateral sclerosis. Therefore, these compounds are promising options for the treatment of prion diseases. PMID:25972546

Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk

DOE PAGES

Johannesen, Lars; Vicente, Jose; Hosseini, Meisam; ...

2016-12-30

Prolongation of the heart rate corrected QT (QTc) interval is a sensitive marker of torsade de pointes risk; however it is not specific as QTc prolonging drugs that block inward currents are often not associated with torsade. Recent work demonstrated that separate analysis of the heart rate corrected J-T peakc (J-T peakc) and T peak-T end intervals can identify QTc prolonging drugs with inward current block and is being proposed as a part of a new cardiac safety paradigm for new drugs (the “CiPA” initiative). In this work, we describe an automated measurement methodology for assessment of the J-T peakcmore » and T peak-T end intervals using the vector magnitude lead. The automated measurement methodology was developed using data from one clinical trial and was evaluated using independent data from a second clinical trial. Comparison between the automated and the prior semi-automated measurements shows that the automated algorithm reproduces the semi-automated measurements with a mean difference of single-deltas <1 ms and no difference in intra-time point variability (p for all > 0.39). In addition, the time-profile of the baseline and placebo-adjusted changes are within 1 ms for 63% of the time-points (86% within 2 ms). Importantly, the automated results lead to the same conclusions about the electrophysiological mechanisms of the studied drugs. We have developed an automated algorithm for assessment of J-T peakc and T peak-T end intervals that can be applied in clinical drug trials. Under the CiPA initiative this ECG assessment would determine if there are unexpected ion channel effects in humans compared to preclinical studies. In conclusion, the algorithm is being released as open-source software.« less

Automated Algorithm for J-Tpeak and Tpeak-Tend Assessment of Drug-Induced Proarrhythmia Risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johannesen, Lars; Vicente, Jose; Hosseini, Meisam

Prolongation of the heart rate corrected QT (QTc) interval is a sensitive marker of torsade de pointes risk; however it is not specific as QTc prolonging drugs that block inward currents are often not associated with torsade. Recent work demonstrated that separate analysis of the heart rate corrected J-T peakc (J-T peakc) and T peak-T end intervals can identify QTc prolonging drugs with inward current block and is being proposed as a part of a new cardiac safety paradigm for new drugs (the “CiPA” initiative). In this work, we describe an automated measurement methodology for assessment of the J-T peakcmore » and T peak-T end intervals using the vector magnitude lead. The automated measurement methodology was developed using data from one clinical trial and was evaluated using independent data from a second clinical trial. Comparison between the automated and the prior semi-automated measurements shows that the automated algorithm reproduces the semi-automated measurements with a mean difference of single-deltas <1 ms and no difference in intra-time point variability (p for all > 0.39). In addition, the time-profile of the baseline and placebo-adjusted changes are within 1 ms for 63% of the time-points (86% within 2 ms). Importantly, the automated results lead to the same conclusions about the electrophysiological mechanisms of the studied drugs. We have developed an automated algorithm for assessment of J-T peakc and T peak-T end intervals that can be applied in clinical drug trials. Under the CiPA initiative this ECG assessment would determine if there are unexpected ion channel effects in humans compared to preclinical studies. In conclusion, the algorithm is being released as open-source software.« less

The Presence or Absence of QTc Prolongation in Buprenorphine-Naloxone Among Youth with Opioid Dependence

PubMed Central

Poole, Sabrina A.; Pecoraro, Anna; Subramaniam, Geetha; Woody, George; Vetter, Victoria L

2015-01-01

Objective To evaluate buprenorphine-naloxone effects on the QTc in youth with opioid dependence. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared to methadone it has a lower risk of QTc prolongation in adults but is less well studied in youth. It may also reduce the risk for torsades de pointes (TdP) an uncommon variant of polymorphic ventricular tachycardia, that can result in syncope, ventricular fibrillation, and sudden death. Methods Secondary analysis of ECG data from 95 subjects who participated in a multi-site trial for youth with opioid dependence. Subjects were randomized to a 2-week (DETOX), or a 12-week course of buprenorphine-naloxone (BUP). 12-lead ECGs were done at baseline, weeks 4 and 12, and QTc intervals were hand measured and calculated using Bazett's formula. Increases > 60 milliseconds (ms) were considered clinically significant, and readings > 450 ms (males) and 470 ms (females) indicated a prolonged QTc. Results Mean QTc intervals were higher for BUP than DETOX participants at baseline, week 4, and week 12 (p = 0.045), and females had longer mean QTc intervals than males (p < 0.0005). Variations in QTc intervals were observed in some, however none were above 500 ms, the level at which risk for TdP becomes more significant. Conclusion In this randomized trial, the mean QTc at baseline, before randomization, was higher in BUP than DETOX patients. Minimal changes in the QTc were seen at 4 and 12-weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP. PMID:26690291

Presence or Absence of QTc Prolongation in Buprenorphine-Naloxone Among Youth With Opioid Dependence.

PubMed

Poole, Sabrina A; Pecoraro, Anna; Subramaniam, Geetha; Woody, George; Vetter, Victoria L

2016-01-01

The aim of the study was to evaluate buprenorphine-naloxone effects on the QTc in youth with opioid dependence. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared with methadone, it has a lower risk of QTc prolongation in adults, but is less studied in the youth. It may also reduce the risk of torsades de pointes (TdP)--an uncommon variant of polymorphic ventricular tachycardia--that can result in syncope, ventricular fibrillation, and sudden death. Secondary analysis of the electrocardiogram data from 95 individuals who participated in a multisite trial for youth with opioid dependence. The participants were randomized to a 2-week (DETOX) or a 12-week course of buprenorphine-naloxone (BUP). At baseline, 12-lead electrocardiograms were done at weeks 4 and 12, and QTc intervals were hand-measured and calculated using Bazett formula. Increases above 60 milliseconds were considered clinically significant, and readings above 450 milliseconds (in men) and 470 milliseconds (in women) indicated a prolonged QTc. Mean QTc intervals were higher for BUP than for DETOX participants at baseline, week 4, and week 12 (P = 0.045), and women had longer mean QTc intervals than men (P < 0.0005). Variations in the QTc intervals were observed in some; however, none were above 500 milliseconds--the level at which risk for TdP becomes more significant. In this randomized trial, the mean QTc at baseline, before randomization, was higher in BUP than in DETOX patients. Minimal changes in the QTc were seen at 4 and 12 weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP.

Predictive value of preoperative electrocardiography for perioperative cardiovascular outcomes in patients undergoing noncardiac, nonvascular surgery.

PubMed

Biteker, Murat; Duman, Dursun; Tekkeşin, Ahmet Ilker

2012-08-01

The utility of routine preoperative electrocardiography (ECG) for assessing perioperative cardiovascular risk in patients undergoing noncardiac, nonvascular surgery (NCNVS) is unclear. There would be an association between preoperative ECG and perioperative cardiovascular outcomes in patients undergoing NCNVS. A total of 660 patients undergoing NCNVS were prospectively evaluated. Patients age >18 years who underwent an elective, nonday case, open surgical procedure were enrolled. Troponin I concentrations and 12-lead ECG were evaluated the day before surgery, immediately after surgery, and on the first 5 postoperative days. Preoperative ECG showing atrial fibrillation, left or right bundle branch block, left ventricular hypertrophy, frequent premature ventricular complexes, pacemaker rhythm, Q-wave, ST-segment changes, or sinus tachycardia or bradycardia were classified as abnormal. The patients were followed up during hospitalization and were evaluated for the presence of perioperative cardiovascular events (PCE). Eighty patients (12.1%) experienced PCE. Patients with abnormal ECG findings had a greater incidence of PCE than those with normal ECG results (16% vs 6.4%; P < 0.001). Mean QTc interval was significantly longer in the patients who had PCE (436.6 ± 31.4 vs 413.3 ± 16.7 ms; P < 0.001). Univariate analysis showed a significant association between preoperative atrial fibrillation, pacemaker rhythm, ST-segment changes, QTc prolongation, and in-hospital PCE. However, only QTc prolongation (odds ratio: 1.15, 95% confidence interval: 1.06-1.2, P < 0.001) was an independent predictor of PCE according to the multivariate analysis. Every 10-ms increase in QTc interval was related to a 13% increase for PCE. Prolongation of the QTc interval on the preoperative ECG was related with PCE in patients undergoing NCNVS. © 2011 Wiley Periodicals, Inc.

Different 2-Aminothiazole Therapeutics Produce Distinct Patterns of Scrapie Prion Neuropathology in Mouse Brains.

PubMed

Giles, Kurt; Berry, David B; Condello, Carlo; Hawley, Ronald C; Gallardo-Godoy, Alejandra; Bryant, Clifford; Oehler, Abby; Elepano, Manuel; Bhardwaj, Sumita; Patel, Smita; Silber, B Michael; Guan, Shenheng; DeArmond, Stephen J; Renslo, Adam R; Prusiner, Stanley B

2015-10-01

Because no drug exists that halts or even slows any neurodegenerative disease, developing effective therapeutics for any prion disorder is urgent. We recently reported two compounds (IND24 and IND81) with the 2-aminothiazole (2-AMT) chemical scaffold that almost doubled the incubation times in scrapie prion-infected, wild-type (wt) FVB mice when given in a liquid diet. Remarkably, oral prophylactic treatment with IND24 beginning 14 days prior to intracerebral prion inoculation extended survival from ∼120 days to over 450 days. In addition to IND24, we evaluated the pharmacokinetics and efficacy of five additional 2-AMTs; one was not followed further because its brain penetration was poor. Of the remaining four new 2-AMTs, IND114338 doubled and IND125 tripled the incubation times of RML-inoculated wt and Tg4053 mice overexpressing wt mouse prion protein (PrP), respectively. Neuropathological examination of the brains from untreated controls showed a widespread deposition of self-propagating, β-sheet-rich "scrapie" isoform (PrP(Sc)) prions accompanied by a profound astrocytic gliosis. In contrast, mice treated with 2-AMTs had lower levels of PrP(Sc) and associated astrocytic gliosis, with each compound resulting in a distinct pattern of deposition. Notably, IND125 prevented both PrP(Sc) accumulation and astrocytic gliosis in the cerebrum. Progressive central nervous system dysfunction in the IND125-treated mice was presumably due to the PrP(Sc) that accumulated in their brainstems. Disappointingly, none of the four new 2-AMTs prolonged the lives of mice expressing a chimeric human/mouse PrP transgene inoculated with Creutzfeldt-Jakob disease prions. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Mulligan, Kathleen; Glidden, David V.; Anderson, Peter L.; Liu, Albert; McMahan, Vanessa; Gonzales, Pedro; Ramirez-Cardich, Maria Esther; Namwongprom, Sirianong; Chodacki, Piotr; de Mendonca, Laura Maria Carvalo; Wang, Furong; Lama, Javier R.; Chariyalertsak, Suwat; Guanira, Juan Vicente; Buchbinder, Susan; Bekker, Linda-Gail; Schechter, Mauro; Veloso, Valdilea G.; Grant, Robert M.; Vargas, Lorena; Sanchez, Jorge; Mai, Chiang; Saokhieo, Pongpun; Murphy, Kerry; Gilmore, Hailey; Holland, Sally; Faber, Elizabeth; Duda, John; Bewerunge, Linda; Batist, Elizabeth; Hoskin, Christine; Brown, Ben; de Janeiro, Rio; Beppu-Yoshida, Carina; da Costa, Marcellus Dias; Assis de Jesus, Sergio Carlos; Grangeiro da Silva, Jose Roberto; Millan, Roberta; de Siqueira Hoagland, Brenda Regina; Martinez Fernandes, Nilo; da Silva Freitas, Lucilene; Grinsztejn, Beatriz; Pilotto, Jose; Bushman, Lane; Zheng, Jia-Hua; Anthony Guida, Louis; Kline, Brandon; Goicochea, Pedro; Manzo, Jonathan; Hance, Robert; McConnell, Jeff; Defechereux, Patricia; Levy, Vivian; Robles, Malu; Postle, Brian; Burns, David; Rooney, James

2015-01-01

Background. Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, −0.91% [95% confidence interval {CI}, −1.44% to −.38%]; P = .001) and hip (−0.61% [95% CI, −.96% to −.27%], P = .001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged −1.42% ± 29% and −0.85% ± 19% in the spine and hip, respectively (P < .001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P = .62) or incidence of low BMD. Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter. Clinical Trials Registration. NCT00458393. PMID:25908682

Sexual risk trajectories among MSM in the United States: implications for pre-exposure prophylaxis delivery

PubMed Central

Pines, Heather A.; Gorbach, Pamina M.; Weiss, Robert E.; Shoptaw, Steve; Landovitz, Raphael J.; Javanbakht, Marjan; Ostrow, David G.; Stall, Ron D.; Plankey, Michael

2014-01-01

Background Despite evidence supporting pre-exposure prophylaxis (PrEP) efficacy, there are concerns regarding the feasibility of widespread PrEP implementation among men who have sex with men (MSM). To inform the development of targeted PrEP delivery guidelines, we characterized sexual risk trajectories among HIV-negative MSM. Methods At semiannual visits from 2003–2011, HIV-negative MSM (N=419) participating in the Multicenter AIDS Cohort Study provided data on sexual risk behaviors since their last visit. Based on reported behaviors, participants were assigned a sexual risk behavior (SRB) score at each visit as follows: (0) no insertive or receptive anal intercourse (IAI/RAI), (1) no unprotected IAI/RAI (UIAI/URAI), (2) only UIAI, (3) URAI with 1 HIV-negative partner, (4) condom-serosorting, (5) condom-seropositioning, and (6) no seroadaptive behaviors. Group-based trajectory modeling was used to examine SRB scores (<4 vs. ≥4) and identify groups with distinct sexual risk trajectories. Results Three sexual risk trajectory groups were identified: low risk (N=264; 63.0%), moderate risk (N=96; 22.9%; mean duration of consecutive high risk intervals~1 year), and high risk (N=59; 14.1%; mean duration of consecutive high risk intervals~2 years). Compared to low risk group membership, high risk group membership was associated with younger age (in years) (adjusted odds ratio [AOR]=0.92, 95% confidence interval [CI]: 0.88–0.96), being White (AOR=3.67, 95% CI: 1.48–9.11), earning an income ≥$20,000 (AOR=4.98, 95% CI: 2.13–11.64), distress/depression symptoms (CESD≥16) (AOR=2.36, 95% CI: 1.14–4.92), and substance use (AOR=2.00, 95% CI: 1.01–3.97). Conclusion Screening for the socio-demographic and behavioral factors described above may facilitate targeted PrEP delivery during high risk periods among MSM. PMID:24378726

Co-Prescription of QT-Interval Prolonging Drugs: An Analysis in a Large Cohort of Geriatric Patients.

PubMed

Schächtele, Simone; Tümena, Thomas; Gaßmann, Karl-Günter; Fromm, Martin F; Maas, Renke

2016-01-01

Drug-induced QT-interval prolongation is associated with occurrence of potentially fatal Torsades de Pointes arrhythmias (TdP). So far, data regarding the overall burden of QT-interval prolonging drugs (QT-drugs) in geriatric patients are limited. This study was performed to assess the individual burden of QT-interval prolonging drugs (QT-drugs) in geriatric polymedicated patients and to identify the most frequent and risky combinations of QT-drugs. In the discharge medication of geriatric patients between July 2009 and June 2013 from the Geriatrics in Bavaria-Database (GiB-DAT) (co)-prescriptions of QT-drugs were investigated. QT-drugs were classified according to a publicly available reference site (CredibleMeds®) as ALL-QT-drugs (associated with any QT-risk) or High-risk-QT-drugs (corresponding to QT-drugs with known risk of Torsades de Pointes according to CredibleMeds®) and in addition as SmPC-high-risk-QT-drugs (according to the German prescribing information (SmPC) contraindicated co-prescription with other QT-drugs). Of a cohort of 130,434 geriatric patients (mean age 81 years, 67% women), prescribed a median of 8 drugs, 76,594 patients (58.7%) received at least one ALL-QT-drug. Co-prescriptions of two or more ALL-QT-drugs were observed in 28,768 (22.1%) patients. Particularly risky co-prescriptions of High-risk-QT-drugs or SmPC-high-risk-QT-drugs with at least on further QT-drug occurred in 55.9% (N = 12,633) and 54.2% (N = 12,429) of these patients, respectively. Consideration of SmPCs (SmPC-high-risk-QT-drugs) allowed the identification of an additional 15% (N = 3,999) patients taking a risky combination that was not covered by the commonly used CredibleMeds® classification. Only 20 drug-drug combinations accounted for more than 90% of these potentially most dangerous co-prescriptions. In a geriatric study population co-prescriptions of two and more QT-drugs were common. A considerable proportion of QT-drugs with higher risk only could be detected by using more than one classification-system. Local adaption of international classifications can improve identification of patients at risk.

Abnormal myocardial repolarisation in response to hypoxaemia and fenoterol.

PubMed Central

Kiely, D. G.; Cargill, R. I.; Grove, A.; Struthers, A. D.; Lipworth, B. J.

1995-01-01

BACKGROUND--Prolongation of the QTc interval has been associated with cardiac dysrhythmias and sudden death. QTc dispersion (interlead variability in QTc interval) has recently been proposed as being a more sensitive marker of repolarisation abnormalities and shown to be a more specific index of arrhythmia risk. Although hypoxaemia and fenoterol have previously been shown to prolong the QTc interval, this does not reflect regional myocardial repolarisation abnormalities. METHODS--Electrophysiological effects were measured at baseline and after 30 minutes steady state hypoxaemia at an arterial oxygen saturation (SaO2) of 75-80% (study 1) and at baseline then 30 minutes after inhaled fenoterol 2.4 mg (study 2). From the ECG, lead II corrected QT interval (QTc) and overall corrected QT dispersion were measured using a computer linked digitising tablet according to standard criteria. RESULTS--QTc dispersion was increased during hypoxia compared with baseline values (mean (SE) 69 (6) ms v 50 (5) ms) and after fenoterol compared with baseline (79 (13) v 46 (4) ms), respectively. There was also an increase in QTc interval and heart rate after fenoterol (493 (23) v 420 (6) ms and 98 (3) v 71 (6) bpm, respectively). The heart rate was increased during hypoxaemia compared with baseline (78 (3) v 64 (2) bpm), but no change occurred in the QTc interval. CONCLUSIONS--Both hypoxaemia and fenoterol cause myocardial repolarisation abnormalities in man in terms of increased QTc dispersion, but only fenoterol increased the QTc interval. This may be relevant in the aetiology of arrhythmias in patients with acute severe asthma where beta agonist therapy and hypoxaemia coexist. PMID:7491554

The analysis of QT interval and repolarization morphology of the heart in chronic exposure to lead.

PubMed

Kiełtucki, J; Dobrakowski, M; Pawlas, N; Średniawa, B; Boroń, M; Kasperczyk, S

2017-10-01

There are no common recommendations regarding electrocardiographic monitoring in occupationally exposed workers. Therefore, the present study was designed to investigate whether exposure to lead results in an increase of selected electrocardiography (ECG) pathologies, such as QT interval prolongation and repolarization disorders, in occupationally exposed workers. The study group included 180 workers occupationally exposed to lead compounds. The exposed group was divided according to the median of the mean blood lead level (PbB mean ) calculated based on a series of measurements performed during 5-year observation period (35 µg/dl) into two subgroups: low exposure (LE, PbB mean = 20.0-35.0 µg/dl) and high exposure (HE, PbB mean = 35.1-46.4 µg/dl). The control group consisted of 69 healthy workers without occupational exposure to lead. ECG evaluation included the analysis of heart rate (HR), QT interval and repolarization abnormalities. Mean QT interval was significantly greater in the exposed population than in the control group by 2%. In the HE group, mean QT interval was significantly greater than in the control group by 4% and significantly different from those noted in the LE group. Positive correlations between QT interval and lead exposure indices were also reported. Besides, there was a negative correlation between HR and blood lead level. Increased concentration of lead in the blood above 35 μg/dl is associated with the QT interval prolongation, which may trigger arrhythmias when combined with other abnormalities, such as long QT syndrome. Therefore, electrocardiographic evaluation should be a part of a routine monitoring of occupationally exposed populations.

Motexafin Gadolinium Combined With Prompt Whole Brain Radiotherapy Prolongs Time to Neurologic Progression in Non-Small-Cell Lung Cancer Patients With Brain Metastases: Results of a Phase III Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehta, Minesh P.; Shapiro, William R.; Phan, See C.

2009-03-15

Purpose: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. Methods and Materials: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. Results: Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% ofmore » the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed. Conclusion: In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable.« less

Pre-exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Kidney Tubular Dysfunction in HIV-Uninfected Individuals.

PubMed

Jotwani, Vasantha; Scherzer, Rebecca; Glidden, David V; Mehrotra, Megha; Defechereux, Patricia; Liu, Albert; Gandhi, Monica; Bennett, Michael; Coca, Steven G; Parikh, Chirag R; Grant, Robert M; Shlipak, Michael G

2018-06-01

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: α1-microglobulin (α1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria. The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC. A cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE. In iPrEx, there were no significant differences in urine α1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine α1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable α1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: -7% to 20%). PrEP with TDF/FTC was associated with a statistically significant rise in urine α1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.

Vectorcardiographic changes during extended space flight

NASA Technical Reports Server (NTRS)

Smith, R. F.; Stanton, K.; Stoop, D.; Brown, D.; Janusz, W.; King, P.

1974-01-01

To assess the effects of space flight on cardiac electrical properties, vectorcardiograms were taken on the 9 Skylab astronauts during the flights of 28, 59, and 84 days. The Frank lead system was used and observations were made at rest; during 25%, 50% and 75% of maximum exercise; during a short pulse of exercise (150 watts, 2 minutes); and after exercise. Data from 131 in-flight tests were analyzed by computer and compared to preflight and postflight values. Statistically significant increase in QRS vector magnitude (six of nine crewmen); T vector magnitude (five of nine crewmen); and resting PR interval duration (six of nine crewmen) occurred. During exercise the PR interval did not differ from preflight. Exercise heart rates inflight were the same as preflight, but increased in the immediate postflight period. With the exception of the arrhythmias, no deleterious vectorcardiographic changes were observed during the Skylab missions.

[Evaluation of the principles of distribution of electrocardiographic R-R intervals for elaboration of methods of automated diagnosis of cardiac rhythm disorders].

PubMed

Tsukerman, B M; Finkel'shteĭn, I E

1987-07-01

A statistical analysis of prolonged ECG records has been carried out in patients with various heart rhythm and conductivity disorders. The distribution of absolute R-R duration values and relationships between adjacent intervals have been examined. A two-step algorithm has been constructed that excludes anomalous and "suspicious" intervals from a sample of consecutively recorded R-R intervals, until only the intervals between contractions of veritably sinus origin remain in the sample. The algorithm has been developed into a programme for microcomputer Electronica NC-80. It operates reliably even in cases of complex combined rhythm and conductivity disorders.

Electrocardiographic Characterization of Cardiac Hypertrophy in Mice that Overexpress the ErbB2 Receptor Tyrosine Kinase

PubMed Central

Sysa-Shah, Polina; Sørensen, Lars L; Abraham, M Roselle; Gabrielson, Kathleen L

2015-01-01

Electrocardiography is an important method for evaluation and risk stratification of patients with cardiac hypertrophy. We hypothesized that the recently developed transgenic mouse model of cardiac hypertrophy (ErbB2tg) will display distinct ECG features, enabling WT (wild type) mice to be distinguished from transgenic mice without using conventional PCR genotyping. We evaluated more than 2000 mice and developed specific criteria for genotype determination by using cageside ECG, during which unanesthetized mice were manually restrained for less than 1 min. Compared with those from WT counterparts, the ECG recordings of ErbB2tg mice were characterized by higher P- and R-wave amplitudes, broader QRS complexes, inverted T waves, and ST interval depression. Pearson's correlation matrix analysis of combined WT and ErbB2tg data revealed significant correlation between heart weight and the ECG parameters of QT interval (corrected for heart rate), QRS interval, ST height, R amplitude, P amplitude, and PR interval. In addition, the left ventricular posterior wall thickness as determined by echocardiography correlated with ECG-determined ST height, R amplitude, QRS interval; echocardiographic left ventricular mass correlated with ECG-determined ST height and PR interval. In summary, we have determined phenotypic ECG criteria to differentiate ErbB2tg from WT genotypes in 98.8% of mice. This inexpensive and time-efficient ECG-based phenotypic method might be applied to differentiate between genotypes in other rodent models of cardiac hypertrophy. Furthermore, with appropriate modifications, this method might be translated for use in other species. PMID:26310459

[Effect of short term graded physical exercise on the level of glycemia in children and adolescents with type 1 diabetes mellitus: data of long term ECG monitoring and registration of motor activity].

PubMed

Laptev, D N; Kruzhkova, M N; Riabykina, G V; Poliakov, S D; Korneeva, I T

2012-01-01

Study aim was to elucidate effect of graded physical exercise on glycemia level and interval QT duration in children and adolescents with type 1 diabetes mellitus. We carried out 25-hours parallel monitoring of glycemia, ECG and physical activity in 15 children and adolescents aged 9-17 years. During monitoring these patients performed an exercise test (PWC170). We found that there were two periods of significant and prolonged lowering of glycemia: in 120-420 min and 19-21 hours after exercise. Lowering of glycemia after physical exercise was associated with prolongation of QT interval. Registration of motor activity allowed to exclude changes of glycemia due to physical activity unrelated to graded exercise.

Electromagnetic energy radiated from mobile phone alters electrocardiographic records of patients with ischemic heart disease.

PubMed

Alhusseiny, Ah; Al-Nimer, Ms; Majeed, Ad

2012-07-01

Electromagnetic energy radiated from mobile phones did not show significant effect on the blood pressure, heart rate, and electrocardiographic (ECG) parameters in animals and humans. This study aimed to investigate the effect of radiofrequency of mobile phone on the electrocardiographic parameters in patients with history of ischemic heart disease, taking into consideration the gender factor. A total number of 356 participants (129 males and 227 females) were admitted in this study. They were grouped into: subjects without cardiac diseases (Group I), patients with ischemic heart disease (Group II), and patients with history of cardiac diseases not related to myocardial ischemia (Group III). Electrocardiogram was obtained from each patient when the mobile phone was placed at the belt level and over precordium in turn-off mode (baseline) and turn-on mode for 40 sec ringing. The records of ECG were electronically analyzed. Prolongation of QTc interval was significantly observed in male gender of Groups I and III (P < 0.001). Male patients of Group II showed significant QTc interval prolongation (P = 0.01) and changes in the voltage criteria (P = 0.001). These changes were not observed in female patients with ischemic heart disease. The position of mobile at the belt level or over the precordium showed effects on the heart. The radiofrequency of cell phone prolongs the QT interval in human beings and it interferes with voltage criteria of ECG records in male patients with myocardial ischemia.

Single therapeutic and supratherapeutic doses of corifollitropin alfa, a sustained follicle stimulant, do not prolong the QTcF-interval in healthy postmenopausal volunteers.

PubMed

de Kam, Pieter-Jan; van Kuijk, Jacqueline H M; Zandvliet, Anthe S; Thomsen, Torben

2015-09-01

Corifollitropin alfa (Elonva®) is the first hybrid follicle-stimulating hormone molecule with demonstrated sustained follicle-stimulating activity after a single subcutaneous injection. This trial evaluated if corifollitropin alfa is associated with QT/QTc prolongation and/ or proarrhythmic potential as compared to placebo in healthy post-menopausal women. Participants were healthy, postmenopausal women. Study treatments were corifollitropin alfa 150 μg, corifollitropin alfa 240 μg, and moxifloxacin 400 mg with placebo. This randomized, double blind, double-dummy, 4-period crossover trial compared single doses of corifollitropin alfa 150 μg (therapeutic dose), corifollitropin alfa 240 μg (supratherapeutic dose), and moxifloxacin 400 mg (positive control) with placebo. Corifollitropin alfa was administered on day 1 and moxifloxacin on day 2. The largest time-matched mean QTcF difference versus placebo for the therapeutic dose of corifollitropin alfa was 1.4 ms (upper limit of 1-sided 95% confidence interval (UL 95% CI) = 3.4 ms), and for the supratherapeutic dose was 1.2 ms (UL 95% CI = 3.6 ms). For both the therapeutic and the supratherapeutic dose of corifollitropin alfa and at all time points, the UL 95% CI for the time matched QTcF differences compared with placebo was below 10 ms, the threshold of relevance defined by the ICH E14 guideline. Single therapeutic and supratherapeutic doses of corifollitropin alfa are not associated with clinically relevant QT/QTc-interval prolongation in healthy post-menopausal women.

Behavioral Hyperventilation and Central Sleep Apnea in Two Children

PubMed Central

Johnston, Thomas P.; Tam-Williams, Jade; Schmandt, Margaret; Patel, Anand C.; Cleveland, Claudia; Coste, Ferdinand; Kemp, James S.

2015-01-01

Behavioral hyperventilation is a rarely recognized cause of central sleep apnea (CSA) among children. We report two pediatric patients who presented with prolonged central sleep apnea secondary to behavioral hyperventilation. One patient also had a prolonged corrected QT (QTC) interval resulting from hyperventilation. Citation: Johnston TP, Tam-Williams J, Schmandt M, Patel AC, Cleveland C, Coste F, Kemp JS. Behavioral hyperventilation and central sleep apnea in two children. J Clin Sleep Med 2015;11(4):487–489. PMID:26106657

Falls among the elderly: risk factors in a population-based study.

PubMed

Rodrigues, Iara Guimarães; Fraga, Gustavo Pereira; Barros, Marilisa Berti de Azevedo

2014-01-01

The aim of the present study was to identify factors associated with the occurrence of falls among elderly adults in a population-based study (ISACamp 2008). A population-based cross-sectional study was carried out with two-stage cluster sampling. The sample was composed of 1,520 elderly adults living in the urban area of the city of Campinas, São Paulo, Brazil. The occurrence of falls was analyzed based on reports of the main accident occurred in the previous 12 months. Data on socioeconomic/demographic factors and adverse health conditions were tested for possible associations with the outcome. Prevalence ratios (PR) were estimated and adjusted for gender and age using the Poisson multiple regression analysis. Falls were more frequent, after adjustment for gender and age, among female elderly participants (PR = 2.39; 95% confidence interval (95% CI) 1.47 - 3.87), elderly adults (80 years old and older) (PR = 2.50; 95% CI 1.61 - 3.88), widowed (PR = 1.74; 95% CI 1.04 - 2.89) and among elderly adults who had rheumatism/arthritis/arthrosis (PR = 1.58; 95% CI 1.00 - 2.48), osteoporosis (PR = 1.71; 95% CI 1.18 - 2.49), asthma/bronchitis/emphysema (PR = 1,73; 95% CI 1.09 - 2.74), headache (PR = 1.59; 95% CI 1.07 - 2.38), mental common disorder (PR = 1.72; 95% CI 1.12 - 2.64), dizziness (PR = 2.82; 95% CI 1.98 - 4.02), insomnia (PR = 1.75; 95% CI 1.16 - 2.65), use of multiple medications (five or more) (PR = 2.50; 95% CI 1.12 - 5.56) and use of cane/walker (PR = 2.16; 95% CI 1.19 - 3,93). The present study shows segments of the elderly population who are more prone to falls through the identification of factors associated with this outcome. The findings can contribute to the planning of public health policies and programs addressed to the prevention of falls.

United States family planning providers' knowledge of and attitudes towards preexposure prophylaxis for HIV prevention: a national survey.

PubMed

Seidman, Dominika; Carlson, Kimberly; Weber, Shannon; Witt, Jacki; Kelly, Patricia J

2016-05-01

The Centers for Disease Control and Prevention defines HIV prevention as a core family planning service. The HIV community identified family planning visits as key encounters for women to access preexposure prophylaxis (PrEP) for HIV prevention. No studies explore US family planning providers' knowledge of and attitudes towards PrEP. We conducted a national survey of clinicians to understand barriers and facilitators to PrEP implementation in family planning. Family planning providers recruited via website postings, national meetings, and email completed an anonymous survey in 2015. Descriptive statistics were performed. Among 604 respondents, 495 were eligible for analysis and 342 were potential PrEP prescribers (physicians, nurse practitioners, midwives or physicians assistants). Among potential prescribers, 38% correctly defined PrEP [95% confidence interval (CI): 32.5-42.8], 37% correctly stated the efficacy of PrEP (95% CI: 32.0-42.4), and 36% chose the correct HIV test after a recent exposure (95% CI: 30.6-40.8). Characteristics of those who answered knowledge questions correctly included age less than 35 years, practicing in the Northeast or West, routinely offering HIV testing, providing rectal sexually transmitted infection screening or having seen any PrEP guidelines. Even among providers in the Northeast and West, the proportion of respondents answering questions correctly was less than 50%. Thirty-six percent of respondents had seen any PrEP guidelines. Providers identified lack of training as the main barrier to PrEP implementation; 87% wanted PrEP education. To offer comprehensive HIV prevention services, family planning providers urgently need training on PrEP and HIV testing. US family planning providers have limited knowledge about HIV PrEP and HIV testing, and report lack of provider training as the main barrier to PrEP provision. Provider education is needed to ensure that family planning clients access comprehensive HIV prevention methods. Copyright © 2016 Elsevier Inc. All rights reserved.

Familial Prion Disease with Alzheimer Disease-Like Tau Pathology and Clinical Phenotype

PubMed Central

Jayadev, Suman; Nochlin, David; Poorkaj, Parvoneh; Steinbart, Ellen J.; Mastrianni, James A.; Montine, Thomas J.; Ghetti, Bernardino; Schellenberg, Gerard D.; Bird, Thomas D.; Leverenz, James B.

2011-01-01

Objective To describe the Alzheimer disease (AD)-like clinical and pathological features, including marked neurofibrillary tangle (NFT) pathology, of a familial prion disease due to a rare nonsense mutation of the prion gene (PRNP). Methods Longitudinal clinical assessments were available for the proband and her mother. After death, both underwent neuropathological evaluation. PRNP was sequenced after failure to find immunopositive Aβ deposits in the proband and the documentation of prion protein (PrP) immunopositive pathology. Results The proband presented at age 42 years with a 3-year history of progressive short-term memory impairment and depression. Neuropsychological testing found impaired memory performance, with relatively preserved attention and construction. She was diagnosed with AD and died at age 47 years. Neuropathologic evaluation revealed extensive limbic and neocortical NFT formation and neuritic plaques consistent with a Braak stage of VI. The NFTs were immunopositive, with multiple tau antibodies, and electron microscopy revealed paired helical filaments. However, the neuritic plaques were immunonegative for Aβ, whereas immunostaining for PrP was positive. The mother of the proband had a similar presentation, including depression, and had been diagnosed clinically and pathologically as AD. Reevaluation of her brain tissue confirmed similar tau and PrP immunostaining findings. Genetic analysis revealed that both the proband and her mother had a rare PRNP mutation (Q160X) that resulted in the production of truncated PrP. Interpretation We suggest that PRNP mutations that result in a truncation of PrP lead to a prolonged clinical course consistent with a clinical diagnosis of AD and severe AD-like NFTs. PMID:21416485

Induction of PrPSc-specific systemic and mucosal immune responses in white-tailed deer with an oral vaccine for chronic wasting disease

PubMed Central

Scruten, Erin; Woodbury, Murray; Potter, Andrew; Griebel, Philip; Tikoo, Suresh K.; Napper, Scott

2017-01-01

ABSTRACT The ongoing epidemic of chronic wasting disease (CWD) within cervid populations indicates the need for novel approaches for disease management. A vaccine that either reduces susceptibility to infection or reduces shedding of prions by infected animals, or a combination of both, could be of benefit for disease control. The development of such a vaccine is challenged by the unique nature of prion diseases and the requirement for formulation and delivery in an oral format for application in wildlife settings. To address the unique nature of prions, our group targets epitopes, termed disease specific epitopes (DSEs), whose exposure for antibody binding depends on disease-associated misfolding of PrPC into PrPSc. Here, a DSE corresponding to the rigid loop (RL) region, which was immunogenic following parenteral vaccination, was translated into an oral vaccine. This vaccine consists of a replication-incompetent human adenovirus expressing a truncated rabies glycoprotein G recombinant fusion with the RL epitope (hAd5:tgG-RL). Oral immunization of white-tailed deer with hAd5:tgG-RL induced PrPSc-specific systemic and mucosal antibody responses with an encouraging safety profile in terms of no adverse health effects nor prolonged vector shedding. By building upon proven strategies of formulation for wildlife vaccines, these efforts generate a particular PrPSc-specific oral vaccine for CWD as well as providing a versatile platform, in terms of carrier protein and biological vector, for generation of other oral, peptide-based CWD vaccines. PMID:28968152

Common Coding Variants in SCN10A Are Associated With the Nav1.8 Late Current and Cardiac Conduction.

PubMed

Macri, Vincenzo; Brody, Jennifer A; Arking, Dan E; Hucker, William J; Yin, Xiaoyan; Lin, Honghuang; Mills, Robert W; Sinner, Moritz F; Lubitz, Steven A; Liu, Ching-Ti; Morrison, Alanna C; Alonso, Alvaro; Li, Ning; Fedorov, Vadim V; Janssen, Paul M; Bis, Joshua C; Heckbert, Susan R; Dolmatova, Elena V; Lumley, Thomas; Sitlani, Colleen M; Cupples, L Adrienne; Pulit, Sara L; Newton-Cheh, Christopher; Barnard, John; Smith, Jonathan D; Van Wagoner, David R; Chung, Mina K; Vlahakes, Gus J; O'Donnell, Christopher J; Rotter, Jerome I; Margulies, Kenneth B; Morley, Michael P; Cappola, Thomas P; Benjamin, Emelia J; Muzny, Donna; Gibbs, Richard A; Jackson, Rebecca D; Magnani, Jared W; Herndon, Caroline N; Rich, Stephen S; Psaty, Bruce M; Milan, David J; Boerwinkle, Eric; Mohler, Peter J; Sotoodehnia, Nona; Ellinor, Patrick T

2018-05-01

Genetic variants at the SCN5A / SCN10A locus are strongly associated with electrocardiographic PR and QRS intervals. While SCN5A is the canonical cardiac sodium channel gene, the role of SCN10A in cardiac conduction is less well characterized. We sequenced the SCN10A locus in 3699 European-ancestry individuals to identify variants associated with cardiac conduction, and replicated our findings in 21,000 individuals of European ancestry. We examined association with expression in human atrial tissue. We explored the biophysical effect of variation on channel function using cellular electrophysiology. We identified 2 intronic single nucleotide polymorphisms in high linkage disequilibrium ( r   2 =0.86) with each other to be the strongest signals for PR (rs10428132, β=-4.74, P =1.52×10 -14 ) and QRS intervals (rs6599251, QRS β=-0.73; P =1.2×10 -4 ), respectively. Although these variants were not associated with SCN5A or SCN10A expression in human atrial tissue (n=490), they were in high linkage disequilibrium ( r   2 ≥0.72) with a common SCN10A missense variant, rs6795970 (V1073A). In total, we identified 7 missense variants, 4 of which (I962V, P1045T, V1073A, and L1092P) were associated with cardiac conduction. These 4 missense variants cluster in the cytoplasmic linker of the second and third domains of the SCN10A protein and together form 6 common haplotypes. Using cellular electrophysiology, we found that haplotypes associated with shorter PR intervals had a significantly larger percentage of late current compared with wild-type (I962V+V1073A+L1092P, 20.2±3.3%, P =0.03, and I962V+V1073A, 22.4±0.8%, P =0.0004 versus wild-type 11.7±1.6%), and the haplotype associated with the longest PR interval had a significantly smaller late current percentage (P1045T, 6.4±1.2%, P =0.03). Our findings suggest an association between genetic variation in SCN10A , the late sodium current, and alterations in cardiac conduction. © 2018 American Heart Association, Inc.

Baseline Preferences for Daily, Event-Driven, or Periodic HIV Pre-Exposure Prophylaxis among Gay and Bisexual Men in the PRELUDE Demonstration Project.

PubMed

Vaccher, Stefanie J; Gianacas, Christopher; Templeton, David J; Poynten, Isobel M; Haire, Bridget G; Ooi, Catriona; Foster, Rosalind; McNulty, Anna; Grulich, Andrew E; Zablotska, Iryna B

2017-01-01

The effectiveness of daily pre-exposure prophylaxis (PrEP) is well established. However, there has been increasing interest in non-daily dosing schedules among gay and bisexual men (GBM). This paper explores preferences for PrEP dosing schedules among GBM at baseline in the PRELUDE demonstration project. Individuals at high-risk of HIV were enrolled in a free PrEP demonstration project in New South Wales, Australia, between November 2014 and April 2016. At baseline, they completed an online survey containing detailed behavioural, demographic, and attitudinal questions, including their ideal way to take PrEP: daily (one pill taken every day), event-driven (pills taken only around specific risk events), or periodic (daily dosing during periods of increased risk). Overall, 315 GBM (98% of study sample) provided a preferred PrEP dosing schedule at baseline. One-third of GBM expressed a preference for non-daily PrEP dosing: 20% for event-driven PrEP, and 14% for periodic PrEP. Individuals with a trade/vocational qualification were more likely to prefer periodic to daily PrEP [adjusted odds ratio (aOR) = 4.58, 95% confidence intervals (95% CI): (1.68, 12.49)], compared to individuals whose highest level of education was high school. Having an HIV-positive main regular partner was associated with strong preference for daily, compared to event-driven PrEP [aOR = 0.20, 95% CI: (0.04, 0.87)]. Participants who rated themselves better at taking medications were more likely to prefer daily over periodic PrEP [aOR = 0.39, 95% CI: (0.20, 0.76)]. Individuals' preferences for PrEP schedules are associated with demographic and behavioural factors that may impact on their ability to access health services and information about PrEP and patterns of HIV risk. At the time of data collection, there were limited data available about the efficacy of non-daily PrEP schedules, and clinicians only recommended daily PrEP to study participants. Further research investigating how behaviours and PrEP preferences change correspondingly over time is needed. ClinicalTrials.gov NCT02206555. Registered 28 July 2014.

Mouse-hamster chimeric prion protein (PrP) devoid of N-terminal residues 23-88 restores susceptibility to 22L prions, but not to RML prions in PrP-knockout mice.

PubMed

Uchiyama, Keiji; Miyata, Hironori; Yano, Masashi; Yamaguchi, Yoshitaka; Imamura, Morikazu; Muramatsu, Naomi; Das, Nandita Rani; Chida, Junji; Hara, Hideyuki; Sakaguchi, Suehiro

2014-01-01

Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp 0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp 0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp 0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice, compared with RML- and 22L-inoculated Prnp 0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc.

Mouse-Hamster Chimeric Prion Protein (PrP) Devoid of N-Terminal Residues 23-88 Restores Susceptibility to 22L Prions, but Not to RML Prions in PrP-Knockout Mice

PubMed Central

Yano, Masashi; Yamaguchi, Yoshitaka; Imamura, Morikazu; Muramatsu, Naomi; Das, Nandita Rani; Chida, Junji; Hara, Hideyuki; Sakaguchi, Suehiro

2014-01-01

Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice, compared with RML- and 22L-inoculated Prnp0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc. PMID:25330286

Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes.

PubMed

Song, Yejia; Belardinelli, Luiz

2017-12-14

Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na + current (I NaL ); 3) inhibition of I NaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H 2 O 2 ). Experiments were performed on ventricular myocytes isolated from one-month (young) and one-year (old) guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the I NaL inhibitors GS967 and tetrodotoxin. The magnitude of I NaL was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and AIP and the Na V 1.5-channel blocker MTSEA blocked the I NaL . There were no significant differences between myocytes from young and old GPs in L-type Ca 2+ current and the rapidly- and slowly-activating delayed rectifier K + currents, although the inward rectifier K + current was slightly decreased in myocytes from old GPs. H 2 O 2 induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H 2 O 2 was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in Na V 1.5-channel I NaL is responsible for the prolongation of APD, and 3) Inhibition of I NaL may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs.

Degree Of Diminution In Vagal-Cardiac Activity Predicts Sudden Death In Familial Dysautonomia When Resting Tachycardia Is Absent

NASA Technical Reports Server (NTRS)

Schlegel, T. T.; Marthol, H.; Bucchner, S.; Tutaj, M.; Berlin, D.; Axelrod, F. B.; Hilz, M. J.

2004-01-01

Patients with familial dysautonomia (FD) have an increased risk of sudden death, but sensitive and specific predictors of sudden death in FD are lacking. Methods. We recorded 10-min resting high-fidelity 12-lead ECGs in 14 FD patients and in 14 age/gender-matched healthy subjects and studied 25+ different heart rate variability (HRV) indices for their ability to predict sudden death in the FD patients. Indices studied included those from 4 "nonlinear" HRV techniques (detrended fluctuation analysis, approximate entropy, correlation dimension, and PoincarC analyses). The predictive value of PR, QRS, QTc and JTc intervals, QT dispersion (QTd), beat-to-beat QT and PR interval variability indices (QTVI and PRVI) and 12- lead high frequency QRS ECG (150-250 Hz) were also studied. FD patients and controls (C) differed (Pless than 0.0l) with respect to 20+ of the HRV indices (FD less than C) and with respect to QTVI and PRVI (FDBC) and HF QRS- related root mean squared voltages (FDBC) and reduced amplitude zone counts (FD less than C). They differed less with respect to PR intervals (FD less than C) and JTc intervals (FD greater than C) (P less than 0.05 for both) and did not differ at all with respect to QRS and QTc intervals and to QTd. Within 12 months after study, 2 of the 14 patients succumbed to sudden cardiac arrest. The best predictor of sudden death was the degree of diminution in HRV vagal-cardiac (parasympathetic) parameters such as RMSSD, the SDl of Poincare plots, and HF spectral power. Excluding the two FD patients who had resting tachycardia (HR greater than 100, which confounds traditional HRV analyses), the following criteria were independently 100% sensitive and 100% specific for predicting sudden death in the remaining 12 FD patients during spontaneous breathing: RMSSD less than 13 ms and/or PoincarC SD1 less than 9 ms. In FD patients without supine tachycardia, the degree of diminution in parasympathetic HRV parameters (by high-fidelity ECG) predicts incipient death.

Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.

PubMed

Schumacher, Fredrick R; Al Olama, Ali Amin; Berndt, Sonja I; Benlloch, Sara; Ahmed, Mahbubl; Saunders, Edward J; Dadaev, Tokhir; Leongamornlert, Daniel; Anokian, Ezequiel; Cieza-Borrella, Clara; Goh, Chee; Brook, Mark N; Sheng, Xin; Fachal, Laura; Dennis, Joe; Tyrer, Jonathan; Muir, Kenneth; Lophatananon, Artitaya; Stevens, Victoria L; Gapstur, Susan M; Carter, Brian D; Tangen, Catherine M; Goodman, Phyllis J; Thompson, Ian M; Batra, Jyotsna; Chambers, Suzanne; Moya, Leire; Clements, Judith; Horvath, Lisa; Tilley, Wayne; Risbridger, Gail P; Gronberg, Henrik; Aly, Markus; Nordström, Tobias; Pharoah, Paul; Pashayan, Nora; Schleutker, Johanna; Tammela, Teuvo L J; Sipeky, Csilla; Auvinen, Anssi; Albanes, Demetrius; Weinstein, Stephanie; Wolk, Alicja; Håkansson, Niclas; West, Catharine M L; Dunning, Alison M; Burnet, Neil; Mucci, Lorelei A; Giovannucci, Edward; Andriole, Gerald L; Cussenot, Olivier; Cancel-Tassin, Géraldine; Koutros, Stella; Beane Freeman, Laura E; Sorensen, Karina Dalsgaard; Orntoft, Torben Falck; Borre, Michael; Maehle, Lovise; Grindedal, Eli Marie; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Martin, Richard M; Travis, Ruth C; Key, Tim J; Hamilton, Robert J; Fleshner, Neil E; Finelli, Antonio; Ingles, Sue Ann; Stern, Mariana C; Rosenstein, Barry S; Kerns, Sarah L; Ostrer, Harry; Lu, Yong-Jie; Zhang, Hong-Wei; Feng, Ninghan; Mao, Xueying; Guo, Xin; Wang, Guomin; Sun, Zan; Giles, Graham G; Southey, Melissa C; MacInnis, Robert J; FitzGerald, Liesel M; Kibel, Adam S; Drake, Bettina F; Vega, Ana; Gómez-Caamaño, Antonio; Szulkin, Robert; Eklund, Martin; Kogevinas, Manolis; Llorca, Javier; Castaño-Vinyals, Gemma; Penney, Kathryn L; Stampfer, Meir; Park, Jong Y; Sellers, Thomas A; Lin, Hui-Yi; Stanford, Janet L; Cybulski, Cezary; Wokolorczyk, Dominika; Lubinski, Jan; Ostrander, Elaine A; Geybels, Milan S; Nordestgaard, Børge G; Nielsen, Sune F; Weischer, Maren; Bisbjerg, Rasmus; Røder, Martin Andreas; Iversen, Peter; Brenner, Hermann; Cuk, Katarina; Holleczek, Bernd; Maier, Christiane; Luedeke, Manuel; Schnoeller, Thomas; Kim, Jeri; Logothetis, Christopher J; John, Esther M; Teixeira, Manuel R; Paulo, Paula; Cardoso, Marta; Neuhausen, Susan L; Steele, Linda; Ding, Yuan Chun; De Ruyck, Kim; De Meerleer, Gert; Ost, Piet; Razack, Azad; Lim, Jasmine; Teo, Soo-Hwang; Lin, Daniel W; Newcomb, Lisa F; Lessel, Davor; Gamulin, Marija; Kulis, Tomislav; Kaneva, Radka; Usmani, Nawaid; Singhal, Sandeep; Slavov, Chavdar; Mitev, Vanio; Parliament, Matthew; Claessens, Frank; Joniau, Steven; Van den Broeck, Thomas; Larkin, Samantha; Townsend, Paul A; Aukim-Hastie, Claire; Dominguez, Manuela Gago; Castelao, Jose Esteban; Martinez, Maria Elena; Roobol, Monique J; Jenster, Guido; van Schaik, Ron H N; Menegaux, Florence; Truong, Thérèse; Koudou, Yves Akoli; Xu, Jianfeng; Khaw, Kay-Tee; Cannon-Albright, Lisa; Pandha, Hardev; Michael, Agnieszka; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Lindstrom, Sara; Turman, Constance; Ma, Jing; Hunter, David J; Riboli, Elio; Siddiq, Afshan; Canzian, Federico; Kolonel, Laurence N; Le Marchand, Loic; Hoover, Robert N; Machiela, Mitchell J; Cui, Zuxi; Kraft, Peter; Amos, Christopher I; Conti, David V; Easton, Douglas F; Wiklund, Fredrik; Chanock, Stephen J; Henderson, Brian E; Kote-Jarai, Zsofia; Haiman, Christopher A; Eeles, Rosalind A

2018-06-11

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10 -8 ) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10 -9 ; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10 -9 ; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa 1 .

Phasic heart rate responses and cardiac cycle time in auditory choice reaction time.

PubMed

van der Molen, M W; Somsen, R J; Orlebeke, J F

1983-01-01

This study investigated the cardiovascular-behavioral interaction under short and long stimulus interval conditions. In addition, the cardiovascular-behavioral interaction was studied as affected by cardiac cycle duration. Fourteen subjects performed a choice reaction time (RT) task employing a mixed speed-accuracy tradeoff design in which reactions were paced to coincide with a signal that occurs randomly at either 200 or 500 msec after the reaction stimulus. The preparatory interval between a warning stimulus and a lead-reaction stimulus complex was also varied (2 vs. 4.5 sec). Anticipatory deceleration occurred within the 4.5 sec interval but not in the 2 sec interval. The depth of anticipatory deceleration did not discriminate between fast and slow reactions; but an earlier shift from deceleration to acceleration was associated with fast reactions. The effect of stimulus timing relative to the R-wave of the electrocardiogram was also analysed. Meaningful stimuli tended to produce cardiac slowing as previously described in the literature. Early occurring stimuli prolong the cycle of their occurrence more than late occurring stimuli. The later prolong the subsequent cycle. Cardiac cycle time effects were absent for unattended stimuli. The results of anticipatory deceleration suggested that the depth of deceleration was regulated by time-uncertainty and speed-accuracy criterion.

[Factors associated with slow walking speed in older adults of a district in Lima, Peru].

PubMed

Rodríguez, Gabriela; Burga-Cisneros, Daniella; Cipriano, Gabriela; Ortiz, Pedro J; Tello, Tania; Casas, Paola; Aliaga, Elizabeth; Varela, Luis F

2017-01-01

To determine the factors associated with slow walking speed in older adults living in a district of Lima, Peru. Analysis of secondary data. Adults older than 60 years were included in the study, while adults with physical conditions who did not allow the evaluation of the walking speed were excluded. The dependent variable was slow walking speed (less than 1 m/s), and the independent variables were sociodemographic, clinical, and geriatric data. Raw and adjusted prevalence ratios (PR) were calculated with 95% confidence intervals (95% CI). The study sample included 416 older adults aged 60 to 99 years, and 41% of the participants met the slow walking speed criterion. The factors associated with slow walking speed in this sample were female gender (PR, 1.45; 95% CI, 1.13-1.88), age > 70 years (PR, 1.73; 95% CI, 1.30- 2.30), lower level of education (PR, 2.07, 95% CI, 1.20-3.55), social-familial problems (PR, 1.66; 95% CI, 1.08-2.54), diabetes mellitus (PR, 1.35; 95% CI, 1.01-1.80), and depression (PR, 1.41; 95% CI, 1.02-1.95). The modifiable factors associated with slow walking speed in older adults included clinical and social-familial problems, and these factors are susceptible to interventions from the early stages of life.

Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status--a meta-analysis.

PubMed

Suzuki, Reiko; Orsini, Nicola; Saji, Shigehira; Key, Timothy J; Wolk, Alicja

2009-02-01

Epidemiological evidence indicates that the association between body weight and breast cancer risk may differ across menopausal status as well as the estrogen receptor (ER) and progesterone receptor (PR) tumor status. To date, no meta-analysis has been conducted to assess the association between body weight and ER/PR defined breast cancer risk, taking into account menopausal status and study design. We searched MEDLINE for relevant studies published from January 1, 1970 through December 31, 2007. Summarized risk estimates with 95% confidence intervals (CIs) were calculated using a random-effects model. The summarized results of 9 cohorts and 22 case-control studies comparing the highest versus the reference categories of relative body weight showed that the risk for ER+PR+ tumors was 20% lower (95% CI=-30% to -8%) among premenopausal (2,643 cases) and 82% higher (95% CI=55-114%) among postmenopausal (5,469 cases) women. The dose-response meta-analysis of ER+PR+ tumors showed that each 5-unit increase in body mass index (BMI, kg/m2) was associated with a 33% increased risk among postmenopausal women (95% CI=20-48%) and 10% decreased risk among premenopausal women (95% CI=-18% to -1%). No associations were observed for ER-PR- or ER+PR- tumors. For discordant tumors ER+PR- (pre) and ER-PR+ (pre/post) the number of cases were too small (<200) to interpret results. The relation between body weight and breast cancer risk is critically dependent on the tumor's ER/PR status and the woman's menopausal status. Body weight control is the effective strategy for preventing ER+PR+ tumors after menopause. Copyright (c) 2008 Wiley-Liss, Inc.

[The effect of esmolol on corrected-QT interval, corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients taking an angiotensin-converting enzyme inhibitor].

PubMed

Ceker, Zahit; Takmaz, Suna Akın; Baltaci, Bülent; Başar, Hülya

2015-01-01

The importance of minimizing the exaggerated sympatho-adrenergic responses and QT interval and QT interval dispersion changes that may develop due to laryngoscopy and tracheal intubation during anesthesia induction in the hypertensive patients is clear. Esmolol decreases the hemodynamic response to laryngoscopy and intubation. However, the effect of esmolol in decreasing the prolonged QT interval and QT interval dispersion as induced by laryngoscopy and intubation is controversial. We investigated the effect of esmolol on the hemodynamic, and corrected-QT interval and corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients using angiotensin converting enzyme inhibitors. 60 ASA I-II patients, with essential hypertension using angiotensin converting enzyme inhibitors were included in the study. The esmolol group received esmolol at a bolus dose of 500mcg/kg followed by a 100mcg/kg/min infusion which continued until the 4th min after intubation. The control group received 0.9% saline similar to the esmolol group. The mean blood pressure, heart rate values and the electrocardiogram records were obtained as baseline values before the anesthesia, 5min after esmolol and saline administration, 3min after the induction and 30s, 2min and 4min after intubation. The corrected-QT interval was shorter in the esmolol group (p=0.012), the corrected-QT interval dispersion interval was longer in the control group (p=0.034) and the mean heart rate was higher in the control group (p=0.022) 30s after intubation. The risk of arrhythmia frequency was higher in the control group in the 4-min period following intubation (p=0.038). Endotracheal intubation was found to prolong corrected-QT interval and corrected-QT interval dispersion, and increase the heart rate during anesthesia induction with propofol in hypertensive patients using angiotensin converting enzyme inhibitors. These effects were prevented with esmolol (500mcg/kg bolus, followed by 100mcg/kg/min infusion). During induction, the blood pressure tends to decrease with esmolol where care is needed. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Long QT interval in Turner syndrome--a high prevalence of LQTS gene mutations.

PubMed

Trolle, Christian; Mortensen, Kristian H; Pedersen, Lisbeth N; Berglund, Agnethe; Jensen, Henrik K; Andersen, Niels H; Gravholt, Claus H

2013-01-01

QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc) over time and relate the findings to the Turner syndrome phenotype. Adult women with Turner syndrome (n = 88) were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%), and adjusted for influence of heart rate by Bazett's (bQTc) and Hodges's formula (hQTc). The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms). Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done. The mean hQTc in women with Turner syndrome (414.0 ± 25.5 ms) compared to controls (390.4 ± 17.8 ms) was prolonged (p<0.001) and did not change over time (416.9 ± 22.6 vs. 415.6 ± 25.5 ms; p =0.4). 45,X karyotype was associated with increased hQTc prolongation compared to other Turner syndrome karyotypes (418.2 ± 24.8 vs. 407.6 ± 25.5 ms; p = 0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2). There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women. NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.

Combined influence of adjuvant therapy and interval after surgery on peripheral CD4+ T lymphocytes in patients with esophageal squamous cell carcinoma

PubMed Central

LING, YANG; FAN, LIEYING; DONG, CHUNLEI; ZHU, JING; LIU, YONGPING; NI, YAN; ZHU, CHANGTAI; ZHANG, CHANGSONG

2010-01-01

The aim of this study was to investigate possible differences in cellular immunity between chemo- and/or radiotherapy groups during a long interval after surgery in esophageal squamous cell carcinoma (ESCC) patients. Cellular immunity was assessed as peripheral lymphocyte subsets in response to chemotherapy (CT), radiotherapy (RT) and CT+RT by flow cytometric analysis. There were 139 blood samples obtained at different time points relative to surgery from 73 patients with ESCC. The changes in the absolute and relative proportions of lymphocyte phenotypes were significant among the adjuvant therapy groups. There were significant differences in the absolute counts of CD4+ and CD8+ T cells among the interval groups, and a lower CD4/CD8 ratio was found in patients following a prolonged interval. RT alone had a profound effect on the absolute counts of CD3+, CD4+ and CD8+ T cells compared with the other groups. CD4+ T cells exhibited a decreasing trend during a long interval, leading to a prolonged T-cell imbalance after surgery. Univariate analysis revealed that the interaction of the type of adjuvant therapy and the interval after surgery was correlated only with the percentage of CD4+ T cells. The percentage of CD4+ T cells can be used as an indicator of the cellular immunity after surgery in ESCC patients. However, natural killer cells consistently remained suppressed in ESCC patients following adjuvant therapy after surgery. These findings confirm an interaction between adjuvant therapy and the interval after surgery on peripheral CD4+ T cells, and implies that adjuvant therapy may have selective influence on the cellular immunity of ESCC patients after surgery. PMID:23136603

Perceived discrimination and smoking among rural-to-urban migrant women in China.

PubMed

Shin, Sanghyuk S; Wan, Xia; Wang, Qian; Raymond, H Fisher; Liu, Huilin; Ding, Ding; Yang, Gonghuan; Novotny, Thomas E

2013-02-01

Smoking may be a coping mechanism for psychosocial stress caused by discrimination. We conducted a cross-sectional survey of rural-to-urban migrant women working as restaurant/hotel workers (RHWs) and those working as sex workers (FSWs) in 10 Chinese cities to investigate whether perceived discrimination is associated with smoking. We interviewed RHWs at medical examination clinics and FSWs at entertainment venues. Modified Poisson regression was used to estimate prevalence ratios. Of the 1,696 RHWs and 532 FSWs enrolled, 155 (9.1%) and 63 (11.8%) reported perceived discrimination, respectively. Perceived discrimination was independently associated with ever tried smoking (prevalence ratio [PR], 1.71; 95% confidence interval [CI], 1.31-2.23) and current smoking (PR, 2.52; 95% CI, 1.32-4.79) among RHWs and ever tried smoking (PR, 1.36; 95% CI, 1.16-1.61) and current smoking (PR, 1.63; 95% CI, 1.28-2.06) among FSWs. Perceived discrimination is associated with higher prevalence of smoking among rural-to-urban migrant women in China.

Molecular Epidemiology of HIV-1 Subtype B Reveals Heterogeneous Transmission Risk: Implications for Intervention and Control

PubMed Central

Le Vu, Stephane; Ratmann, Oliver; Tostevin, Anna; Dunn, David; Orkin, Chloe; O’Shea, Siobhan; Delpech, Valerie; Brown, Alison; Gill, Noel; Fraser, Christophe

2018-01-01

Abstract Background The impact of HIV pre-exposure prophylaxis (PrEP) depends on infections averted by protecting vulnerable individuals as well as infections averted by preventing transmission by those who would have been infected if not receiving PrEP. Analysis of HIV phylogenies reveals risk factors for transmission, which we examine as potential criteria for allocating PrEP. Methods We analyzed 6912 HIV-1 partial pol sequences from men who have sex with men (MSM) in the United Kingdom combined with global reference sequences and patient-level metadata. Population genetic models were developed that adjust for stage of infection, global migration of HIV lineages, and changing incidence of infection through time. Models were extended to simulate the effects of providing susceptible MSM with PrEP. Results We found that young age <25 years confers higher risk of HIV transmission (relative risk = 2.52 [95% confidence interval, 2.32–2.73]) and that young MSM are more likely to transmit to one another than expected by chance. Simulated interventions indicate that 4-fold more infections can be averted over 5 years by focusing PrEP on young MSM. Conclusions Concentrating PrEP doses on young individuals can avert more infections than random allocation. PMID:29506269

Mapping PrBn and Other Quantitative Trait Loci Responsible for the Control of Homeologous Chromosome Pairing in Oilseed Rape (Brassica napus L.) Haploids

PubMed Central

Liu, Zhiqian; Adamczyk, Katarzyna; Manzanares-Dauleux, Maria; Eber, Frédérique; Lucas, Marie-Odile; Delourme, Régine; Chèvre, Anne Marie; Jenczewski, Eric

2006-01-01

In allopolyploid species, fair meiosis could be challenged by homeologous chromosome pairing and is usually achieved by the action of homeologous pairing suppressor genes. Oilseed rape (Brassica napus) haploids (AC, n = 19) represent an attractive model for studying the mechanisms used by allopolyploids to ensure the diploid-like meiotic pairing pattern. In oilseed rape haploids, homeologous chromosome pairing at metaphase I was found to be genetically based and controlled by a major gene, PrBn, segregating in a background of polygenic variation. In this study, we have mapped PrBn within a 10-cM interval on the C genome linkage group DY15 and shown that PrBn displays incomplete penetrance or variable expressivity. We have identified three to six minor QTL/BTL that have slight additive effects on the amount of pairing at metaphase I but do not interact with PrBn. We have also detected a number of other loci that interact epistatically, notably with PrBn. Our results support the idea that, as in other polyploid species, metaphase I homeologous pairing in oilseed rape haploids is controlled by an integrated system of several genes, which function in a complex manner. PMID:16951054

Associations of Workplace Aggression With Work-Related Well-Being Among Nurses in the Philippines

PubMed Central

Gee, Gilbert C.; de Castro, A. B.

2011-01-01

Objectives. We examined whether workplace aggression was associated with self-rated health and work-related injury and illness among nurses in the Philippines. Methods. Our data came from a cross-sectional survey of nurses (n = 687) in the Philippines. We assessed the associations of self-reported physical assault and verbal abuse with self-rated health, work-related injury and illness, and missed workdays with Poisson regression. Control variables included demographic and work characteristics (e.g., hours worked, work setting, shift). Results. Verbal abuse was associated with poor general health (prevalence ratio [PR] = 1.94; 95% confidence interval [CI] = 1.09, 3.45). Both physical assault and verbal abuse were associated with work-related injury (PR = 1.48; 95% CI = 1.00, 2.20; PR = 1.72; 95% CI = 1.34, 2.23, respectively) and work-related illness (PR = 1.46; 95% CI = 0.99, 2.15; PR = 1.68; 95% CI = 1.32, 2.14, respectively) after demographic and work characteristics were accounted for in the model. In addition, physical assault was associated with missed workdays (PR = 1.56; 95% CI = 1.02, 2.33). Conclusions. Workplace aggression was associated with increased risks of poor general health and adverse work-related health outcomes among nurses in the Philippines. PMID:21088262

Insufficient free-time physical activity and occupational factors in Brazilian public school teachers

PubMed Central

Dias, Douglas Fernando; Loch, Mathias Roberto; González, Alberto Durán; de Andrade, Selma Maffei; Mesas, Arthur Eumann

2017-01-01

ABSTRACT OBJECTIVE To evaluate if perceived occupational factors are associated with insufficient free-time physical activity in Brazilian public school teachers. METHODS The relationship between insufficient physical activity (< 150 minutes/week) and variables related to work was analyzed in 978 elementary and high school teachers calculating the prevalence ratio (PR) and 95% confidence interval (95%CI) in Poisson regression models, adjusted for sociodemographic and health variables. RESULTS The prevalence of insufficient physical activity was 71.9%, and this condition was associated independently with the perception of bad or regular balance between personal and professional life (PR = 1.09; 95%CI 1.01–1.18), perception that standing time affects the work (PR = 1.16; 95%CI 1.01–1.34), low or very low perception of current ability for the physical requirements of work (PR = 1.21; 95%CI 1.08–1.35), and temporary employment contract (PR = 1.13; 95%CI 1.03–1.25). The teaching of physical education was associated with lower prevalence of insufficient physical activity (PR = 0.78; 95%CI 0.64–0.95). CONCLUSIONS The perception of adverse working conditions is associated with increased prevalence of insufficient physical activity in teachers and should be considered for the promotion of physical activity in this population. PMID:28746571

Internet-purchased ibogaine toxicity confirmed with serum, urine, and product content levels.

PubMed

O'Connell, Charles W; Gerona, Roy R; Friesen, Matthew W; Ly, Binh T

2015-07-01

Ibogaine, a psychotropic indole alkaloid, is gaining popularity among medical subcultures for its purported anti addictive properties. Its use has been associated with altered mental status, ataxia, gastrointestinal distress, ventricular arrhythmias, and sudden and unexplained deaths.Its pharmacokinetics in toxic states is not well understood. Case report:A 33-year-old man overdosed on ibogaine in an attempt to quit his use of heroin. He developed altered state of consciousness, tremor, ataxia,nausea, vomiting, and transient QT interval prolongation, which all remitted as he cleared the substance. Ibogaine was confirmed in his urine and serum with a peak serum concentration of 377 ng/mL. Nonlinear elimination kinetics and a formula match to its active metabolite noriobgaine were observed as well. This case presents the unique description of serial serum concentrations as well as urine and product-confirmed ibogaine toxicity with transient toxin-related QT interval prolongation.

ECG Changes in Young Healthy Smokers: A Simple and Cost-Effective Method to Assess Cardiovascular Risk According to Pack-Years of Smoking.

PubMed

Sharma, Nirmal Kumar; Jaiswal, Kapil Kumar; Meena, S R; Chandel, Rahul; Chittora, Saurabh; Goga, Prem Singh; Harish, H B; Sagar, Rajesh

2017-06-01

To document the prevalence of ECG abnormalities in young healthy smokers and compare ECG changes in smokers, young healthy non-smokers and amongst smokers with different pack years. This was a prospective case-control study consisting of 200 young healthy male and female individuals, 150 smokers and 50 non-smokers between ages 25-40 years, further categorized and compared according to age, sex and pack years of smoking. The ECG recordings were analyzed for different ECG parameters like heart rate, P-wave duration, P-wave amplitude, PR interval, QRS duration, RR-interval, ST-segment duration, QT interval and QTc interval. The results were compared using statistical tools. In present study abnormalities in ECG parameters were significantly more prevalent in smokers as compared to non-smokers (56.66 % Vs 6.00 %) (p <.0001). Heart rate and QTc-interval increased with increase in the number of pack-years. This increase was reflected more in female with a similar number of pack years. P-wave amplitude tended to increase with increase in the number of pack years more so in males. P-wave duration, PR-interval, QRS-duration and RR-interval tended to decrease with increase in the number of pack years more so in females with similar number of pack years. QT-interval and ST-segment duration tended to decrease with increase in the number of pack years more so in males. ECG abnormalities in this study indicate cardiovascular risk in term of cardiac arrhythmia, pulmonary arterial hypertension, heart blocks etc in such subjects. As this procedure is non-invasive and cost effective it is potentially an effective and yet a simple method for cardiovascular risk evaluation in smokers. Furthermore, such ECG abnormalities may guide the clinician for risk evaluation in smokers and may be used to convince the smokers to quit smoking.

Opioid analgesia in mechanically ventilated children: results from the multicenter Measuring Opioid Tolerance Induced by Fentanyl study.

PubMed

Anand, Kanwaljeet J S; Clark, Amy E; Willson, Douglas F; Berger, John; Meert, Kathleen L; Zimmerman, Jerry J; Harrison, Rick; Carcillo, Joseph A; Newth, Christopher J L; Bisping, Stephanie; Holubkov, Richard; Dean, J Michael; Nicholson, Carol E

2013-01-01

To examine the clinical factors associated with increased opioid dose among mechanically ventilated children in the pediatric intensive care unit. Prospective, observational study with 100% accrual of eligible patients. Seven pediatric intensive care units from tertiary-care children's hospitals in the Collaborative Pediatric Critical Care Research Network. Four hundred nineteen children treated with morphine or fentanyl infusions. None. Data on opioid use, concomitant therapy, demographic and explanatory variables were collected. Significant variability occurred in clinical practices, with up to 100-fold differences in baseline opioid doses, average daily or total doses, or peak infusion rates. Opioid exposure for 7 or 14 days required doubling of the daily opioid dose in 16% patients (95% confidence interval 12%-19%) and 20% patients (95% confidence interval 16%-24%), respectively. Among patients receiving opioids for longer than 3 days (n = 225), this occurred in 28% (95% confidence interval 22%-33%) and 35% (95% confidence interval 29%-41%) by 7 or 14 days, respectively. Doubling of the opioid dose was more likely to occur following opioid infusions for 7 days or longer (odds ratio 7.9, 95% confidence interval 4.3-14.3; p < 0.001) or co-therapy with midazolam (odds ratio 5.6, 95% confidence interval 2.4-12.9; p < 0.001), and it was less likely to occur if morphine was used as the primary opioid (vs. fentanyl) (odds ratio 0.48, 95% confidence interval 0.25-0.92; p = 0.03), for patients receiving higher initial doses (odds ratio 0.96, 95% confidence interval 0.95-0.98; p < 0.001), or if patients had prior pediatric intensive care unit admissions (odds ratio 0.37, 95% confidence interval 0.15-0.89; p = 0.03). Mechanically ventilated children require increasing opioid doses, often associated with prolonged opioid exposure or the need for additional sedation. Efforts to reduce prolonged opioid exposure and clinical practice variation may prevent the complications of opioid therapy.

[Why does the prevalence of cytopathological results of cervical cancer screening can vary significantly between two regions of Brazil?].

PubMed

Discacciati, Michelle Garcia; Barboza, Bárbara Maria Santos; Zeferino, Luiz Carlos

2014-05-01

To analyze the prevalence of cervical cytopathological results for the screening of cervical cancer with regard to women's age and time since the last examination in Maceió and Rio de Janeiro, Brazil, among those assisted by the Brazilian Unified Health System. Cervical cytopathological results available in the Information System of Cervical Cancer Screening for the year 2011 were analyzed, corresponding to 206,550 for Rio de Janeiro and 45,243 for Maceió. In Rio de Janeiro, examination at one and two year intervals predominated, while in Maceió examination at one and three year intervals had a higher predominance. Women who underwent cervical smear screening in Maceió were older than those in Rio de Janeiro. The prevalence of invasive squamous cell carcinoma was similar for the two cities, but all the other results presented a higher prevalence in Rio de Janeiro: ASCUS (PR=5.32; 95%CI 4.66-6.07); ASCH (PR=4.27; 95%CI 3.15-5.78); atypical glandular cells (PR=10.02; 95%CI 5.66-17.76); low-grade squamous intraepithelial lesions (PR=6.10; 95%CI 5.27-7.07); high-grade squamous intraepithelial lesions (PR=8.90; 95%CI 6.50-12.18) and adenocarcinoma (PR=3.00; 95%CI 1.21-7.44). The rate of unsatisfactory cervical samples was two times higher in Maceió and that of rejected samples for analysis was five times higher in Maceió when compared to Rio de Janeiro. The prevalence rates of altered cervical cytopathological results was significantly higher in Rio de Janeiro than in Maceió. There is no objective information that may justify this difference. One hypothesis is that there may be a difference in the diagnostic performance of the cervical cancer screening, which could be related to the quality of the Pap smear. Thus, these findings suggest that it would be necessary to perform this evaluation at national level, with emphasis on the performance of cervical cancer screening in order to improve the effectiveness of cervical cancer control.

Decreased dromotropic response to verapamil despite pronounced increased drug concentration in rheumatoid arthritis.

PubMed

Mayo, P R; Skeith, K; Russell, A S; Jamali, F

2000-12-01

Inflammation reduces hepatic clearance of many drugs with unknown therapeutic consequences. This study was carried out to examine the effect of rheumatoid arthritis (RA) on the pharmacokinetics and pharmacodynamics of verapamil. Eight RA patients were age- and sex-matched with eight healthy volunteers. The disease severity was assessed, and ECG, blood pressure and verapamil enantiomers concentrations were measured for 12 h post 80 mg oral verapamil. Serum interleukin-6 (IL-6) and nitrite (NO2-) were measured in predose samples. IL-6 and NO2- concentrations were significantly increased in parallel with disease severity. Oral clearance of both S- and R-verapamil was significantly decreased by RA. While the unbound fraction of S- and R-verapamil decreased by 5 and 7-fold, respectively, the unbound AUC remained unchanged for the more potent enantiomer, S-verapamil. AUC of norverapamil enantiomers was increased 2-3-fold. Despite elevated serum drug concentrations in RA, the potential to prolong the PR-interval was significantly reduced by one fold and the effect on the heart rate and blood pressure did not increase. RA results in increased verapamil concentrations due likely to changes in protein binding, decreased clearance and/or altered hepatic blood flow. A significant decrease in dromotropic effect, despite increased serum drug concentrations, may be attributed to receptor down regulation caused by pro-inflammatory cytokines and/or NO.

Prolonged length of stay in hospitalized internal medicine patients.

PubMed

Barba, Raquel; Marco, Javier; Canora, Jesús; Plaza, Susana; Juncos, Sara Nistal; Hinojosa, Juan; Bailon, Manuel Mendez; Zapatero, Antonio

2015-12-01

Targeting patients with prolonged hospitalizations may represent an effective strategy for reducing average hospital length of stay (LOS). We sought to characterize predictors of prolonged hospitalization among internal medicine patients in an effort to guide future improvement efforts. We conducted a retrospective cohort study using administrative data of internal medicine patients from all hospitals of the Spanish Public Health Service between January 1st, 2005 and December 31st, 2013. Multivariable logistic regression was performed to assess the association between sociodemographic and clinical variables and prolonged LOS, defined as >30days. Of 5,275,139 discharges, 166,470 (3.2%) had a prolonged LOS. Prolonged hospitalizations accounted for 17.4% of total inpatient days and contributed 0.5days to an average LOS of 9.8days during the study period. Prolonged hospitalizations were associated with younger age (odds ratio [OR]: 0.97 per 10-year increase in age, 95% confidence interval [CI]: 0.96-0.98) and male gender (OR 0.88 IC95% 0.87-0.89). Compared to patients without prolonged LOS, prolonged LOS patients were more likely to require a palliative care consult (OR: 2.48, 95% CI: 2.39-2.58), surgery (OR: 6.9 95% CI: 6.8-7.0); and be discharged to a post-acute-care facility (OR: 2.91, 95% CI: 2.86-2.95). Prolonged hospitalizations in a small proportion of patients were an important contributor to overall LOS and particularly affected complex hospital stays who were not discharged home. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Prolonged pain and disability are common after rib fractures.

PubMed

Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John

2013-05-01

The contribution of rib fractures to prolonged pain and disability may be underappreciated and undertreated. Clinicians are traditionally taught that the pain and disability of rib fractures resolves in 6 to 8 weeks. This study was a prospective observation of 203 patients with rib fractures at a level 1 trauma center. Chest wall pain was evaluated by the McGill Pain Questionnaire (MPQ) pain rating index (PRI) and present pain intensity (PPI). Prolonged pain was defined as a PRI of 8 or more at 2 months after injury. Prolonged disability was defined as a decrease in 1 or more levels of work or functional status at 2 months after injury. Predictors of prolonged pain and disability were determined by multivariate analysis. One hundred forty-five male patients and 58 female patients with a mean injury severity score (ISS) of 20 (range, 1 to 59) had a mean of 5.4 rib fractures (range, 1 to 29). Forty-four (22%) patients had bilateral fractures, 15 (7%) had flail chest, and 92 (45%) had associated injury. One hundred eighty-seven patients were followed 2 months or more. One hundred ten (59%) patients had prolonged chest wall pain and 142 (76%) had prolonged disability. Among 111 patients with isolated rib fractures, 67 (64%) had prolonged chest wall pain and 69 (66%) had prolonged disability. MPQ PPI was predictive of prolonged pain (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4 to 2.5), and prolonged disability (OR, 2.2; 95% CI, 1.5 to 3.4). The presence of significant associated injuries was predictive of prolonged disability (OR, 5.9; 95% CI, 1.4 to 29). Prolonged chest wall pain is common, and the contribution of rib fractures to disability is greater than traditionally expected. Further investigation into more effective therapies that prevent prolonged pain and disability after rib fractures is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer: HAL.

PubMed

O'Connell, Oisin J; Almeida, Francisco A; Simoff, Michael J; Yarmus, Lonny; Lazarus, Ray; Young, Benjamin; Chen, Yu; Semaan, Roy; Saettele, Timothy M; Cicenia, Joseph; Bedi, Harmeet; Kliment, Corrine; Li, Liang; Sethi, Sonali; Diaz-Mendoza, Javier; Feller-Kopman, David; Song, Juhee; Gildea, Thomas; Lee, Hans; Grosu, Horiana B; Machuzak, Michael; Rodriguez-Vial, Macarena; Eapen, George A; Jimenez, Carlos A; Casal, Roberto F; Ost, David E

2017-06-15

Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with non-small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies. To develop a clinical prediction model for estimating the prN2/3. We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1-3, N0-3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals. The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography-computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82-0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85-0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132). Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC.

Turning for Ulcer Reduction (TURN) Study: An Economic Analysis.

PubMed

Paulden, Mike; Bergstrom, Nancy; Horn, Susan D; Rapp, Mary; Stern, Anita; Barrett, Ryan; Watkiss, Michael; Krahn, Murray

2014-01-01

The Turning for Ulcer Reduction (TURN) study was a multisite, randomized controlled trial that aimed to determine the optimal frequency of turning nursing facility residents with mobility limitations who are at moderate and high risk for pressure ulcer (PrU) development. Here we present data from the economic analysis. This economic analysis aims to estimate the economic consequences for Ontario of switching from a repositioning schedule of 2-hour intervals to a schedule of 3-hour or 4-hour intervals. Costs considered in the analysis included those associated with nursing staff time spent repositioning residents and with incontinent care supplies, which included briefs, barrier cream, and washcloths. The total economic benefit of switching to 3-hour or 4-hour repositioning is estimated to be $11.05 or $16.74 per day, respectively, for every resident at moderate or high risk of developing PrUs. For a typical facility with 123 residents, 41 (33%) of whom are at moderate or high risk of developing PrUs, the total economic benefit is estimated to be $453 daily for 3-hour or $686 daily for 4-hour repositioning. For Ontario as a whole, assuming that there are 77,933 residents at 634 LTC facilities, 25,927 (33%) of whom are at moderate or high risk of developing PrUs, the total economic benefits of switching to 3-hour or 4-hour repositioning are estimated to be $286,420 or $433,913 daily, respectively, equivalent to $104.5 million or $158.4 million per year. We did not consider the savings the Ontario Ministry of Health and Long-Term Care might incur should less frequent repositioning reduce the incidence of work-related injury among nursing staff, so our findings are potentially conservative. A switch to 3-hour or 4-hour repositioning appears likely to yield substantial economic benefits to Ontario without placing residents at greater risk of developing PrUs.

Turning for Ulcer Reduction (TURN) Study: An Economic Analysis

PubMed Central

Paulden, Mike; Bergstrom, Nancy; Horn, Susan D.; Rapp, Mary; Stern, Anita; Barrett, Ryan; Watkiss, Michael; Krahn, Murray

2014-01-01

Background The Turning for Ulcer Reduction (TURN) study was a multisite, randomized controlled trial that aimed to determine the optimal frequency of turning nursing facility residents with mobility limitations who are at moderate and high risk for pressure ulcer (PrU) development. Here we present data from the economic analysis. Objectives This economic analysis aims to estimate the economic consequences for Ontario of switching from a repositioning schedule of 2-hour intervals to a schedule of 3-hour or 4-hour intervals. Data Sources Costs considered in the analysis included those associated with nursing staff time spent repositioning residents and with incontinent care supplies, which included briefs, barrier cream, and washcloths. Results The total economic benefit of switching to 3-hour or 4-hour repositioning is estimated to be $11.05 or $16.74 per day, respectively, for every resident at moderate or high risk of developing PrUs. For a typical facility with 123 residents, 41 (33%) of whom are at moderate or high risk of developing PrUs, the total economic benefit is estimated to be $453 daily for 3-hour or $686 daily for 4-hour repositioning. For Ontario as a whole, assuming that there are 77,933 residents at 634 LTC facilities, 25,927 (33%) of whom are at moderate or high risk of developing PrUs, the total economic benefits of switching to 3-hour or 4-hour repositioning are estimated to be $286,420 or $433,913 daily, respectively, equivalent to $104.5 million or $158.4 million per year. Limitations We did not consider the savings the Ontario Ministry of Health and Long-Term Care might incur should less frequent repositioning reduce the incidence of work-related injury among nursing staff, so our findings are potentially conservative. Conclusions A switch to 3-hour or 4-hour repositioning appears likely to yield substantial economic benefits to Ontario without placing residents at greater risk of developing PrUs. PMID:26330894

[Association of cardiovascular autonomic neuropathy and prolonged QT interval with cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus].

PubMed

Ticse Aguirre, Ray; Villena, Jaime E

2011-03-01

In order to evaluate the relationship between cardiovascular autonomic neuropathy and corrected QT interval (QTc) with cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus, we followed up for 5 years 67 patients attending the outpatient Endocrinology Service. 82% completed follow-up and cardiovascular events occurred in 16 patients. We found that long QTc interval was the only variable significantly associated with cardiovascular morbidity and mortality in the multiple logistic regression analysis (RR: 13.56, 95% CI: 2.01-91.36) (p = 0.0074).

Association of functional genetic variants of A-kinase anchoring protein 10 with QT interval length in full-term Polish newborns.

PubMed

Łoniewska, Beata; Kaczmarczyk, Mariusz; Clark, Jeremy Simon; Gorący, Iwona; Horodnicka-Józwa, Anita; Ciechanowicz, Andrzej

2015-03-16

A-Kinase Anchoring Proteins (AKAPs) coordinate the specificity of protein kinase A signaling by localizing the kinase to subcellular sites. The 1936G (V646) AKAP10 allele has been associated in adults with low cholinergic/vagus nerve sensitivity, shortened PR intervals in ECG recording and in newborns with increased blood pressure and higher cholesterol cord blood concentration. The aim of the study was to answer the question of whether 1936A > G AKAP10 polymorphism is associated with the newborn electrocardiographic variables. Electrocardiograms were recorded from 114 consecutive healthy Polish newborns (55 females, 59 males), born after 37 gestational weeks to healthy women with uncomplicated pregnancies. All recordings were made between 3(rd) and 7(th) day of life to avoid QT variability. The heart rate per minute and duration of PR, QRS, RR and QT intervals were usually measured. The ECGs were evaluated independently by three observers. At birth, cord blood of neonates was obtained for isolation of genomic DNA. The distribution of anthropometric and electrocardiographic variables in our cohort approached normality (skewness < 2 for all variables). No significant differences in anthropometric variables and electrocardiographic traits with respect to AKAP10 genotype were found. Multiple regression analysis with adjustment for gender, gestational age and birth mass revealed that QTc interval in GG AKAP10 homozygotes was significantly longer, but in range, when compared with A alleles carriers (AA + AG, recessive mode of inheritance). No rhythm disturbances were observed. Results demonstrate possible association between AKAP10 1936A > G variant and QTc interval in Polish newborns.

Co-Prescription of QT-Interval Prolonging Drugs: An Analysis in a Large Cohort of Geriatric Patients

PubMed Central

Schächtele, Simone; Tümena, Thomas; Gaßmann, Karl-Günter; Fromm, Martin F.; Maas, Renke

2016-01-01

Background Drug-induced QT-interval prolongation is associated with occurrence of potentially fatal Torsades de Pointes arrhythmias (TdP). So far, data regarding the overall burden of QT-interval prolonging drugs (QT-drugs) in geriatric patients are limited. Objective This study was performed to assess the individual burden of QT-interval prolonging drugs (QT-drugs) in geriatric polymedicated patients and to identify the most frequent and risky combinations of QT-drugs. Methods In the discharge medication of geriatric patients between July 2009 and June 2013 from the Geriatrics in Bavaria–Database (GiB-DAT) (co)-prescriptions of QT-drugs were investigated. QT-drugs were classified according to a publicly available reference site (CredibleMeds®) as ALL-QT-drugs (associated with any QT-risk) or High-risk-QT-drugs (corresponding to QT-drugs with known risk of Torsades de Pointes according to CredibleMeds®) and in addition as SmPC-high-risk-QT-drugs (according to the German prescribing information (SmPC) contraindicated co-prescription with other QT-drugs). Results Of a cohort of 130,434 geriatric patients (mean age 81 years, 67% women), prescribed a median of 8 drugs, 76,594 patients (58.7%) received at least one ALL-QT-drug. Co-prescriptions of two or more ALL-QT-drugs were observed in 28,768 (22.1%) patients. Particularly risky co-prescriptions of High-risk-QT-drugs or SmPC-high-risk-QT-drugs with at least on further QT-drug occurred in 55.9% (N = 12,633) and 54.2% (N = 12,429) of these patients, respectively. Consideration of SmPCs (SmPC-high-risk-QT-drugs) allowed the identification of an additional 15% (N = 3,999) patients taking a risky combination that was not covered by the commonly used CredibleMeds® classification. Only 20 drug-drug combinations accounted for more than 90% of these potentially most dangerous co-prescriptions. Conclusion In a geriatric study population co-prescriptions of two and more QT-drugs were common. A considerable proportion of QT-drugs with higher risk only could be detected by using more than one classification-system. Local adaption of international classifications can improve identification of patients at risk. PMID:27192430

Incremenal Value of Cardiac Magnetic Resonance for Assessing Pulmonic Valve Regurgitation.

PubMed

Zdradzinski, Michael; Elkin, Rachel; Flamm, Scott; Krasuski, Richard

2015-07-01

Cardiac magnetic resonance (CMR) is the 'gold standard' for quantifying pulmonic regurgitation (PR) in adults with congenital heart disease, but remains costly and is less readily available than echocardiography. Qualitative echocardiographic assessment of PR is challenging, and guiding criteria are limited. It is unknown if echocardiography is sufficient to screen for significant PR. The study aim was to determine whether cardiac MRI provides additional benefit in the assessment of PR in adults with congenital heart disease. Patients with repaired tetralogy of Fallot or congenital pulmonic stenosis after valvotomy undergoing transthoracic echocardiography and CMR with no interval intervention were identified from a prospective registry. Patients with greater than mild pulmonic stenosis, residual ventricular septal defect or poor echocardiographic windows were excluded. Whole-cohort and subgroup (tetralogy of Fallot versus pulmonic stenosis) analyses for inter-modality agreement were performed. A total of 48 patients (24 men, 24 women; mean age 43 +/- 12 years) was included in the analysis. The unweighted kappa value for the two modalities was 0.30, suggesting 'fair' agreement, though only 52% had matching PR assessments. The indexed right ventricular end-systolic volume (RVESVi) correlated closely with cardiac MRI-monitored PR (p = 0.011 by analysis of variance), but not with that monitored with echocardiography (p = 0.081). Subgroup analysis demonstrated less inter-modality agreement in the tetralogy of Fallot population (kappa 0.25) than in the pulmonic stenosis population (kappa 0.35). CMR measurement of PR correlates closely with the RVESVi, and appears superior to echocardiography when assessing patients at risk for PR. The study results suggest a vital role for CMR whenever significant PR is suspected in the adult congenital heart disease population.

Height, age at menarche and risk of hormone receptor-positive and -negative breast cancer: a cohort study.

PubMed

Ritte, Rebecca; Lukanova, Annekatrin; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Mesrine, Sylvie; Fagherazzi, Guy; Dossus, Laure; Teucher, Birgit; Steindorf, Karen; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Quirós, José Ramón; Buckland, Genevieve; Molina-Montes, Esther; Chirlaque, María-Dolores; Ardanaz, Eva; Amiano, Pilar; Bueno-de-Mesquita, Bas; van Duijnhoven, Franzel; van Gils, Carla H; Peeters, Petra Hm; Wareham, Nick; Khaw, Kay-Tee; Key, Timothy J; Travis, Ruth C; Krum-Hansen, Sanda; Gram, Inger Torhild; Lund, Eiliv; Sund, Malin; Andersson, Anne; Romieu, Isabelle; Rinaldi, Sabina; McCormack, Valerie; Riboli, Elio; Kaaks, Rudolf

2013-06-01

Associations of breast cancer overall with indicators of exposures during puberty are reasonably well characterized; however, uncertainty remains regarding the associations of height, leg length, sitting height and menarcheal age with hormone receptor-defined malignancies. Within the European Prospective Investigation into Cancer and Nutrition cohort, Cox proportional hazards models were used to describe the relationships of adult height, leg length and sitting height and age at menarche with risk of estrogen and progesterone receptor negative (ER-PR-) (n = 990) and ER+PR+ (n = 3,524) breast tumors. Height as a single risk factor was compared to a model combining leg length and sitting height. The possible interactions of height, leg length and sitting height with menarche were also analyzed. Risk of both ER-PR- and ER+PR+ malignancies was positively associated with standing height, leg length and sitting height and inversely associated with increasing age at menarche. For ER+PR+ disease, sitting height (hazard ratios: 1.14[95% confidence interval: 1.08-1.20]) had a stronger risk association than leg length (1.05[1.00-1.11]). In comparison, for ER-PR- disease, no distinct differences were observed between leg length and sitting height. Women who were tall and had an early menarche (≤13 years) showed an almost twofold increase in risk of ER+PR+ tumors but no such increase in risk was observed for ER-PR- disease. Indicators of exposures during rapid growth periods were associated with risks of both HR-defined breast cancers. Exposures during childhood promoting faster development may establish risk associations for both HR-positive and -negative malignancies. The stronger associations of the components of height with ER+PR+ tumors among older women suggest possible hormonal links that could be specific for postmenopausal women. Copyright © 2012 UICC.

The algorithmic performance of J-Tpeak for drug safety clinical trial.

PubMed

Chien, Simon C; Gregg, Richard E

The interval from J-point to T-wave peak (JTp) in ECG is a new biomarker able to identify drugs that prolong the QT interval but have different ion channel effects. If JTp is not prolonged, the prolonged QT may be associated with multi ion channel block that may have low torsade de pointes risk. From the automatic ECG measurement perspective, accurate and repeatable measurement of JTp involves different challenges than QT. We evaluated algorithm performance and JTp challenges using the Philips DXL diagnostic 12/16/18-lead algorithm. Measurement of JTp represents a different use model. Standard use of corrected QT interval is clinical risk assessment on patients with cardiac disease or suspicion of heart disease. Drug safety trials involve a very different population - young healthy subjects - who commonly have J-waves, notches and slurs. Drug effects include difficult and unusual morphology such as flat T-waves, gentle notches, and multiple T-wave peaks. The JTp initiative study provided ECGs collected from 22 young subjects (11 males and females) in randomized testing of dofetilide, quinidine, ranolazine, verapamil and placebo. We compare the JTp intervals between DXL algorithm and the FDA published measurements. The lead wise, vector-magnitude (VM), root-mean-square (RMS) and principal-component-analysis (PCA) representative beats were used to measure JTp and QT intervals. We also implemented four different methods for T peak detection for comparison. We found that JTp measurements were closer to the reference for combined leads RMS and PCA than individual leads. Differences in J-point location led to part of the JTp measurement difference because of the high prevalence of J-waves, notches and slurs. Larger differences were noted for drug effect causing multiple distinct T-wave peaks (Tp). The automated algorithm chooses the later peak while the reference was the earlier peak. Choosing among different algorithmic strategies in T peak measurement results in the tradeoff between stability and the accurate detection of calcium or sodium channel block. Measurement of JTp has different challenges than QT measurement. JTp measurement accuracy improved with combined leads RMS and PCA over lead II or V5. Copyright © 2017 Elsevier Inc. All rights reserved.

Incidence of oral cavity and pharyngeal cancers by anatomical sites in population-based registries in Puerto Rico and the United States of America.

PubMed

Suárez, Erick; González, Lorena; Díaz-Toro, Elba C; Calo, William A; Bermúdez, Francisco; Ortiz, Ana P

2013-12-01

Puerto Rico's (PR) epidemiological data on each oral cavity and pharynx cancer (OCPC) site is yet largely unexplored. Our aim was to compare OCPC incidence in PR, by anatomical site, with that of non-Hispanic whites (NHW), non-Hispanic blacks (NHB), and Hispanic (USH) individuals in the USA. Data from the Surveillance Epidemiology and End Results program and the PR Central Cancer Registry were collected and analyzed. Age-standardized rates, percent changes, and standardized rate ratios were estimated with 95% confidence intervals. Although declining incidence rates were observed for most anatomical sites in most racial/ethnic groups and in both sexes, the incidence of oropharynx cancers slightly increased for cancers in the oropharynx among PR women, both in the base of tongue and soft palate/other oropharynx (p>0.05). The incidence of soft palate/other oropharynx cancers in PR men was about 2.8 times higher than in USH men (p<0.05) and about 1.4 times higher than in NHW men but 21% lower than in NHB men (p>0.05). Significant interactions terms formed with racial/ethnic group and age were shown in various sites. The largest differences between sexes were consistently noted in PR. Further research in PR should assess the effect of the HPV infection, as well as of other risk factors, in OCPC incidence by anatomical site in younger populations. These data could explain more precisely the reasons for the differences observed in this study, particularly among sexes in PR.

High Willingness to Use HIV Pre-Exposure Prophylaxis Among Transgender Women in Argentina.

PubMed

Zalazar, Virginia; Arístegui, Inés; Kerr, Thomas; Marshall, Brandon D L; Romero, Marcela; Sued, Omar; Socías, M Eugenia

2016-01-01

Purpose: In Argentina, transgender women face a disproportionately high prevalence of HIV infection (34%). Although not currently approved in Argentina, pre-exposure prophylaxis (PrEP) may offer a potential effective HIV prevention tool for this population. In this study, we assessed the willingness to use PrEP among transgender women in Argentina. Methods: Data were drawn from a nationwide cross-sectional survey conducted among transgender women in 2013. Using multivariable logistic regression, we assessed the prevalence of and factors associated with willingness to use PrEP among transgender women with negative or unknown HIV status. Results: This study included 337 transgender women (278 HIV negative and 59 with unknown HIV status), most of whom had a history of sex work involvement (81.8%). Overall, 301 (89.3%) expressed willingness to use PrEP. In a multivariable analysis, having casual sexual partners was positively associated with willingness to use PrEP (adjusted odds ratio [AOR]=4.26, 95% confidence interval [CI] 1.73-10.51), while discrimination by healthcare workers was negatively associated (AOR=0.33, 95% CI 0.12-0.88). Conclusion: We found high levels of willingness to use PrEP among transgender women in Argentina, suggesting that there is high perception of HIV risk in this population. However, discrimination by healthcare workers was a strong negative correlate of willingness to use PrEP, suggesting that multilevel interventions that address gender-based stigma in healthcare settings will be critical for the success of PrEP as an HIV prevention strategy in this population.

High Willingness to Use HIV Pre-Exposure Prophylaxis Among Transgender Women in Argentina

PubMed Central

Zalazar, Virginia; Arístegui, Inés; Kerr, Thomas; Marshall, Brandon D.L.; Romero, Marcela; Sued, Omar; Socías, M. Eugenia

2016-01-01

Abstract Purpose: In Argentina, transgender women face a disproportionately high prevalence of HIV infection (34%). Although not currently approved in Argentina, pre-exposure prophylaxis (PrEP) may offer a potential effective HIV prevention tool for this population. In this study, we assessed the willingness to use PrEP among transgender women in Argentina. Methods: Data were drawn from a nationwide cross-sectional survey conducted among transgender women in 2013. Using multivariable logistic regression, we assessed the prevalence of and factors associated with willingness to use PrEP among transgender women with negative or unknown HIV status. Results: This study included 337 transgender women (278 HIV negative and 59 with unknown HIV status), most of whom had a history of sex work involvement (81.8%). Overall, 301 (89.3%) expressed willingness to use PrEP. In a multivariable analysis, having casual sexual partners was positively associated with willingness to use PrEP (adjusted odds ratio [AOR]=4.26, 95% confidence interval [CI] 1.73–10.51), while discrimination by healthcare workers was negatively associated (AOR=0.33, 95% CI 0.12–0.88). Conclusion: We found high levels of willingness to use PrEP among transgender women in Argentina, suggesting that there is high perception of HIV risk in this population. However, discrimination by healthcare workers was a strong negative correlate of willingness to use PrEP, suggesting that multilevel interventions that address gender-based stigma in healthcare settings will be critical for the success of PrEP as an HIV prevention strategy in this population. PMID:28861540

Disrespect and abuse during childbirth in fourteen hospitals in nine cities of Peru.

PubMed

Montesinos-Segura, Reneé; Urrunaga-Pastor, Diego; Mendoza-Chuctaya, Giuston; Taype-Rondan, Alvaro; Helguero-Santin, Luis M; Martinez-Ninanqui, Franklin W; Centeno, Dercy L; Jiménez-Meza, Yanina; Taminche-Canayo, Ruth C; Paucar-Tito, Liz; Villamonte-Calanche, Wilfredo

2018-02-01

To assess the prevalence of disrespect and abuse during childbirth and its associated factors in Peru. In an observational cross-sectional study, women were surveyed within 48 hours of live delivery at 14 hospitals located in nine Peruvian cities between April and July 2016. The survey was based on seven categories of disrespect and abuse proposed by Bowser and Hill. To evaluate factors associated with each category, prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated using adjusted Poisson models with robust variances. Among 1528 participants, 1488 (97.4%) had experienced at least one category of disrespect and abuse. Frequency of abandonment of care was increased with cesarean delivery (PR 1.27, 95% CI 1.03-1.57) but decreased in the jungle region (PR 0.27, 0.14-0.53). Discrimination was associated with the jungle region (PR 5.67, 2.32-13.88). Physical abuse was less frequent with cesarean than vaginal delivery (PR 0.23, 0.11-0.49). The prevalences of abandonment of care (PR 0.42, 0.29-0.60), non-consented care (PR 0.70, 0.57-0.85), discrimination (PR 0.40, 0.19-0.85), and non-confidential care (PR 0.71, 0.55-0.93) were decreased among women who had been referred. Nearly all participants reported having experienced at least one category of disrespect and abuse during childbirth care, which was associated with type of delivery, being referred, and geographic region. © 2017 International Federation of Gynecology and Obstetrics.

A Health Profile of Arab Americans in Michigan: A Novel Approach to Using a Hospital Administrative Database.

PubMed

Dallo, Florence J; Ruterbusch, Julie J; Kirma, Joseph David; Schwartz, Kendra; Fakhouri, Monty

2016-12-01

The objectives of this study were to estimate and compare the prevalence of heart disease, cancer, chronic lower respiratory disease, stroke, Alzheimer's, diabetes, nephrosis, flu/pneumonia, hypertension, and atherosclerosis between Arab Americans and whites attending a large, metropolitan hospital system. The sample included 68,047 patients, 18 years of age or older, who visited the hospital during 2012. Demographic and disease variables were electronically abstracted. Demographic characteristics were compared between Arab Americans and whites using Chi square tests. Sex specific, age-adjusted prevalence ratios (PR) and 95 % confidence intervals were estimated for these two groups using a log-binomial regression model. Compared to white men, Arab American men had a higher prevalence of diabetes (PR 1.40, 95 % CI 1.29-1.52) and hypertension (PR 1.07, 95 % CI 1.04-1.10), and a lower prevalence of chronic lower respiratory disease (PR 0.74, 95 % CI 0.66-0.83). Compared to white women, Arab American women had a higher prevalence of chronic lower respiratory disease (PR 1.12, 95 % CI 1.01-1.25), diabetes (PR 1.49, 95 % CI 1.38-1.60), influenza/pneumonia (PR 1.26, 95 % CI 1.05-1.51) and hypertension (PR 1.04, 95 % CI 1.01-1.08). This study supports previous findings that health disparities exist for Arab Americans, who are classified as "white" in health statistics. Standard inclusion of Arab American as a separate ethnicity category will aid researchers in assessing the health care needs of this growing minority community.

Prolonged survival after diagnosis of brain metastasis from breast cancer: contributing factors and treatment implications.

PubMed

Honda, Yayoi; Aruga, Tomoyuki; Yamashita, Toshinari; Miyamoto, Hiromi; Horiguchi, Kazumi; Kitagawa, Dai; Idera, Nami; Goto, Risa; Kuroi, Katsumasa

2015-08-01

The prognosis of breast cancer-derived brain metastasis is poor, but new drugs and recent therapeutic strategies have helped extend survival in patients. Prediction of therapeutic responses and outcomes is not yet possible, however. In a retrospective study, we examined prognostic factors in patients with breast cancer-derived brain metastasis, and we tested the prognostic utility of a breast cancer-specific Graded Prognostic Assessment in these patients. Sixty-three patients diagnosed with brain metastasis from breast cancer treated surgically and adjuvantly were included. We examined clinical variables per primary tumor subtype: ER+/HER2- (luminal), HER2+ (human epidermal growth factor receptor type 2-enriched) or ER-/PR-/HER2- (triple negative). We also categorized patients' breast cancer-specific Graded Prognostic Assessment scores and analyzed post-brain metastasis survival time in relation to these categories. The breast cancers comprised the following subtypes: luminal, n = 18; human epidermal growth factor receptor type 2-enriched, n = 27 and triple-negative, n = 18; median survival per subtype was 11, 37 and 3 months, respectively. Survival of human epidermal growth factor receptor type 2-enriched patients was longer, though not significantly (P = 0.188), than that of luminal patients. Survival of triple-negative patients was significantly short (vs. human epidermal growth factor receptor type 2-enriched patients, P < 0.001). Karnofsky performance status, HER2 status and the disease-free interval (from initial treatment to first recurrence) were shown to be significant prognostic factors (Karnofsky performance status < 70: relative risk 2.08, P = 0.028; HER2+: relative risk 2.911, P = 0.004; disease-free interval < 24 months: relative risk 1.933, P = 0.011). Breast cancer-specific Graded Prognostic Assessment scores reflected disease-free intervals and survival times. Our data indicate that breast cancer-specific Graded Prognostic Assessment-based prediction will be helpful in determining appropriate therapeutic strategies for patients with brain metastasis from breast cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The developmental effects of extremely low frequency electric fields on visual and somatosensory evoked potentials in adult rats.

PubMed

Gok, Deniz Kantar; Akpinar, Deniz; Hidisoglu, Enis; Ozen, Sukru; Agar, Aysel; Yargicoglu, Piraye

2016-01-01

The purpose of our study was to investigate the developmental effects of extremely low frequency electric fields (ELF-EFs) on visual evoked potentials (VEPs) and somatosensory-evoked potentials (SEPs) and to examine the relationship between lipid peroxidation and changes of these potentials. In this context, thiobarbituric acid reactive substances (TBARS) levels were determined as an indicator of lipid peroxidation. Wistar albino female rats were divided into four groups; Control (C), gestational (prenatal) exposure (Pr), gestational+ postnatal exposure (PP) and postnatal exposure (Po) groups. Pregnant rats of Pr and PP groups were exposed to 50 Hz electric field (EF) (12 kV/m; 1 h/day), while those of C and Po groups were placed in an inactive system during pregnancy. Following parturition, rats of PP and Po groups were exposed to ELF-EFs whereas rats of C and Pr groups were kept under the same experimental conditions without being exposed to any EF during 68 days. On postnatal day 90, rats were prepared for VEP and SEP recordings. The latencies of VEP components in all experimental groups were significantly prolonged versus C group. For SEPs, all components of PP group, P2, N2 components of Pr group and P1, P2, N2 components of Po group were delayed versus C group. As brain TBARS levels were significantly increased in Pr and Po groups, retina TBARS levels were significantly elevated in all experimental groups versus C group. In conclusion, alterations seen in evoked potentials, at least partly, could be explained by lipid peroxidation in the retina and brain.

Effects of milrinone and epinephrine or dopamine on biventricular function and hemodynamics in right heart failure after pulmonary regurgitation.

PubMed

Hyldebrandt, Janus Adler; Agger, Peter; Sivén, Eleonora; Wemmelund, Kristian Borup; Heiberg, Johan; Frederiksen, Christian Alcaraz; Ravn, Hanne Berg

2015-09-01

Right ventricular failure (RVF) secondary to pulmonary regurgitation (PR) impairs right ventricular (RV) function and interrupts the interventricular relationship. There are few recommendations for the medical management of severe RVF after prolonged PR. PR was induced in 16 Danish landrace pigs by plication of the pulmonary valve leaflets. Twenty-three pigs served as controls. At reexamination the effect of milrinone, epinephrine, and dopamine was evaluated using biventricular conductance and pulmonary catheters. Seventy-nine days after PR was induced, RV end-diastolic volume index (EDVI) had increased by 33% (P = 0.006) and there was a severe decrease in the load-independent measurement of contractility (PRSW) (-58%; P = 0.003). Lower cardiac index (CI) (-28%; P < 0.0001), mean arterial pressure (-15%; P = 0.01) and mixed venous oxygen saturation (SvO2) (36%; P < 0.0001) were observed compared with the control group. The interventricular septum deviated toward the left ventricle (LV). Milrinone improved RV-PRSW and CI and maintained systemic pressure while reducing central venous pressure (CVP). Epinephrine and dopamine further improved biventricular PRSW and CI equally in a dose-dependent manner. Systemic and pulmonary pressures were higher in the dopamine-treated animals compared with epinephrine-treated animals. None of the treatments improved stroke volume index (SVI) despite increases in contractility. Strong correlation was detected between SVI and LV-EDVI, but not SVI and biventricular contractility. In RVF due to PR, milrinone significantly improved CI, SvO2, and CVP and increased contractility in the RV. Epinephrine and dopamine had equal inotropic effect, but a greater vasopressor effect was observed for dopamine. SV was unchanged due to inability of both treatments to increase LV-EDVI. Copyright © 2015 the American Physiological Society.

Specificity and Immunosuppressive Potency of a Rabbit Antimouse T Cell- Specific Antiserum

DTIC Science & Technology

1974-12-10

some controversy as to SurgerN. Scho’ol of Medicine, (’hiha UrniversitY. Ja the ability of murine anti-H serum to prolong pan. skin graft survival...bit s were survival, others have shown the inability of exsanguinated and the serum was collected. anti -/ sermio to pr,h skin graft survival and The...absorbed ATG-I, or anti-! C3H sera I day before Maryland) for 1 hr at 4 C and used as target and on days 1. 3, and 5 after skin grafting . The cells. The

Influence of gender and types of sports training on QT variables in young elite athletes.

PubMed

Omiya, Kazuto; Sekizuka, Hiromitsu; Kida, Keisuke; Suzuki, Kengo; Akashi, Yoshihiro J; Ohba, Haruo; Musha, Haruki

2014-01-01

Influence of gender and sports training on QT variables such as QT interval and dispersion (QT dispersion: QTD) in young elite athletes were evaluated. Subjects included 104 male and 97 female Japanese elite athletes (mean age 21.6 years). Sports included basketball, fencing, gymnastics, judo, swimming, tennis, track and field and volleyball. Age-matched healthy non-athletes (32 men and 20 women) were enrolled as controls. QT measurements were manually obtained from a 12-lead resting electrocardiogram and QTD was calculated as the difference between the longest and shortest QT intervals. A corrected QT interval (QTc) was obtained using Bazett's formula. Subjects were divided into two groups; an endurance training group and a static training group on the basis of their training types. Maximum and minimum QTc were significantly longer in female athletes than in male athletes (max: 414.2 vs. 404.5 ms, min: 375.1 vs. 359.2 ms, p<0.0001 respectively), whereas QTc dispersion (QTcD) was shorter in female athletes than in male athletes (39.2 vs. 45.3 ms, p<0.0001). QTcD was significantly shorter in female athletes than in the female control group (39.2 vs. 45.2 ms, p<0.05). However, no statistically significant difference was observed between male athletes and the male control group. Male gymnasts exhibited significantly longer QTcD than the control group (p<0.01), but female gymnasts had significantly shorter QTcD than the control group (p<0.05). Maximum QTc intervals were prolonged in the male static training group compared with non-athletes, and QTcDs in the static training group were prolonged compared with the endurance training group. However, no significant difference was observed in the female group. In conclusion, both gender and different characteristics of sports training may affect QT variables even in young elite athletes. Vigorous static exercise training may independently prolong QT variables.

Feasibility and acceptability of HIV self-testing among pre-exposure prophylaxis users in Kenya.

PubMed

Ngure, Kenneth; Heffron, Renee; Mugo, Nelly; Thomson, Kerry A; Irungu, Elizabeth; Njuguna, Njambi; Mwaniki, Lawrence; Celum, Connie; Baeten, Jared M

2017-02-10

HIV testing is key to the delivery of pre-exposure prophylaxis (PrEP): testing HIV-uninfected at-risk persons is the first step for PrEP initiation and ongoing HIV testing is an essential part of PrEP delivery. Thus, novel and cost-effective HIV-testing approaches to streamline delivery of PrEP are urgently needed. Within a demonstration project of PrEP for HIV prevention among high-risk HIV serodiscordant couples in Kenya (the Partners Demonstration Project), we conducted a pilot evaluation of HIV self-testing. Clinic visits were scheduled quarterly and included in-clinic HIV testing using fingerstick rapid HIV tests and refills of PrEP prescriptions. HIV oral fluid self-test kits were provided for participants to use in the two-month interval between scheduled quarterly clinic visits. Acceptability of HIV self-testing was assessed using both quantitative and qualitative methods. We found that 222 of 226 (98%) HIV-uninfected persons who were offered accepted self-testing. Nearly all (96.8%) reported that using the self-testing kit was easy. More than half (54.5%) reportedly did not share the HIV results from self-testing with anyone and almost all (98.7%) the participants did not share the HIV self-testing kits with anyone. Many participants reported that HIV self-testing was empowering and reduced anxiety associated with waiting between clinic HIV tests. HIV self-testing was highly acceptable and may therefore be a feasible strategy to efficiently permit routine HIV testing between PrEP refills.

A modeling and simulation approach to characterize methadone QT prolongation using pooled data from five clinical trials in MMT patients.

PubMed

Florian, J; Garnett, C E; Nallani, S C; Rappaport, B A; Throckmorton, D C

2012-04-01

Pharmacokinetic (PK)-pharmacodynamic modeling and simulation were used to establish a link between methadone dose, concentrations, and Fridericia rate-corrected QT (QTcF) interval prolongation, and to identify a dose that was associated with increased risk of developing torsade de pointes. A linear relationship between concentration and QTcF described the data from five clinical trials in patients on methadone maintenance treatment (MMT). A previously published population PK model adequately described the concentration-time data, and this model was used for simulation. QTcF was increased by a mean (90% confidence interval (CI)) of 17 (12, 22) ms per 1,000 ng/ml of methadone. Based on this model, doses >120 mg/day would increase the QTcF interval by >20 ms. The model predicts that 1-3% of patients would have ΔQTcF >60 ms, and 0.3-2.0% of patients would have QTcF >500 ms at doses of 160-200 mg/day. Our predictions are consistent with available observational data and support the need for electrocardiogram (ECG) monitoring and arrhythmia risk factor assessment in patients receiving methadone doses >120 mg/day.

Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

PubMed Central

Reinier, Kyndaron; Teodorescu, Carmen; Uy-Evanado, Audrey; Carter-Monroe, Naima; Kaikkonen, Kari S.; Kortelainen, Marja-Leena; Boucher, Gabrielle; Lagacé, Caroline; Moes, Anna; Zhao, XiaoQing; Kolodgie, Frank; Rivadeneira, Fernando; Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, André G.; Marsman, Roos F.; Pazoki, Raha; Bardai, Abdennasser; Koster, Rudolph W.; Dehghan, Abbas; Hwang, Shih-Jen; Bhatnagar, Pallav; Post, Wendy; Hilton, Gina; Prineas, Ronald J.; Li, Man; Köttgen, Anna; Ehret, Georg; Boerwinkle, Eric; Coresh, Josef; Kao, W. H. Linda; Psaty, Bruce M.; Tomaselli, Gordon F.; Sotoodehnia, Nona; Siscovick, David S.; Burke, Greg L.; Marbán, Eduardo; Spooner, Peter M.; Cupples, L. Adrienne; Jui, Jonathan; Gunson, Karen; Kesäniemi, Y. Antero; Wilde, Arthur A. M.; Tardif, Jean-Claude; O'Donnell, Christopher J.; Bezzina, Connie R.; Virmani, Renu; Stricker, Bruno H. C. h.; Tan, Hanno L.; Albert, Christine M.; Chakravarti, Aravinda; Rioux, John D.; Huikuri, Heikki V.; Chugh, Sumeet S.

2011-01-01

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006). PMID:21738491

Assessment of Safety Margin of an Antipsychotic Drug Haloperidol for Torsade de Pointes Using the Chronic Atrioventricular Block Dogs.

PubMed

Izumi-Nakaseko, Hiroko; Nakamura, Yuji; Cao, Xin; Wada, Takeshi; Ando, Kentaro; Sugiyama, Atsushi

2017-07-01

Since an antipsychotic drug haloperidol has been clinically reported to induce QT interval prolongation and torsade de pointes, in this study its risk stratification for the onset of torsade de pointes was performed by using the chronic atrioventricular block canine model with a Holter electrocardiogram. Haloperidol in a dose of 3 mg kg -1 p.o. prolonged the QT interval, but it did not induce torsade de pointes during the observation period of 21 h (n = 4), indicating that the dose would be safe. Meanwhile, haloperidol in a dose of 30 mg kg -1 p.o. significantly increased the short-term variability in beat-to-beat analysis of QT interval (n = 4), and it induced torsade de pointes in 4 animals out of 4, showing that the dose could be torsadogenic. Since 3 mg kg -1 p.o. of haloperidol in this study can be estimated to provide about 8 times higher plasma concentrations than its therapeutic level, haloperidol may be used safely for most of the patients, as long as its plasma drug concentration is kept within the therapeutic range.

Hepatitis A outbreak on a floating restaurant in Florida, 1986.

PubMed

Lowry, P W; Levine, R; Stroup, D F; Gunn, R A; Wilder, M H; Konigsberg, C

1989-01-01

In April and May 1986, the largest reported foodborne outbreak of hepatitis A in Florida state history occurred among patrons and employees of a floating restaurant. A total of 103 cases (97 patrons and six employees) were identified. The exposure period lasted 31 days (March 20-April 19), making this the most prolonged hepatitis A outbreak to occur in a restaurant that to date has been reported to the Centers for Disease Control. The exposure period was divided into time intervals (peak, early, late, and total) for calculation of food-specific attack rates. The authors showed that green salad was an important vehicle of transmission for each phase of the exposure period, with the highest adjusted odds ratio for the three-day peak exposure interval (March 28-30), 6.8 (p = 0.001). Non-salad pantry items and mixed bar drinks were also identified as vehicles of transmission; both were more important during the early interval of the exposure period than during the late interval. Two of six infected employees worked in the pantry and may have sequentially infected patrons. Though rare, this outbreak suggests that hepatitis A infection among employees may allow for transmission to patrons for prolonged periods of time. Prevention of such outbreaks requires prompt reporting of ill patrons with rapid identification of infected employees and correction of food handling practices.

Impact of Hypokalemia on Electromechanical Window, Excitation Wavelength and Repolarization Gradients in Guinea-Pig and Rabbit Hearts

PubMed Central

Osadchii, Oleg E.

2014-01-01

Normal hearts exhibit a positive time difference between the end of ventricular contraction and the end of QT interval, which is referred to as the electromechanical (EM) window. Drug-induced prolongation of repolarization may lead to the negative EM window, which was proposed to be a novel proarrhythmic marker. This study examined whether abnormal changes in the EM window may account for arrhythmogenic effects produced by hypokalemia. Left ventricular pressure, electrocardiogram, and epicardial monophasic action potentials were recorded in perfused hearts from guinea-pig and rabbit. Hypokalemia (2.5 mM K+) was found to prolong repolarization, reduce the EM window, and promote tachyarrhythmia. Nevertheless, during both regular pacing and extrasystolic excitation, the increased QT interval invariably remained shorter than the duration of mechanical systole, thus yielding positive EM window values. Hypokalemia-induced arrhythmogenicity was associated with slowed ventricular conduction, and shortened effective refractory periods, which translated to a reduced excitation wavelength index. Hypokalemia also evoked non-uniform prolongation of action potential duration in distinct epicardial regions, which resulted in increased spatial variability in the repolarization time. These findings suggest that arrhythmogenic effects of hypokalemia are not accounted for by the negative EM window, and are rather attributed to abnormal changes in ventricular conduction times, refractoriness, excitation wavelength, and spatial repolarization gradients. PMID:25141124

Abnormalities of the QT interval in primary disorders of autonomic failure.

PubMed

Choy, A M; Lang, C C; Roden, D M; Robertson, D; Wood, A J; Robertson, R M; Biaggioni, I

1998-10-01

Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P < .05 and P < .01, respectively). A similar but not significant trend was observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P < .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not have significantly different RR, QT, QTc intervals, or QTc dispersion when compared with controls. Patients with primary autonomic failure who have combined parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not solely caused by lesions of the sympathetic nervous system, and that the parasympathetic nervous system is likely to have a modulatory role in ventricular repolarization.

Analysis of Relationship between Levofloxacin and Corrected QT Prolongation Using a Clinical Data Warehouse

PubMed Central

Park, Man Young; Kim, Eun Yeob; Lee, Young Ho; Kim, Woojae; Kim, Ku Sang; Sheen, Seung Soo; Lim, Hong Seok

2011-01-01

Objective The aim of this study was to examine whether or not levofloxacin has any relationship with QT prolongation in a real clinical setting by analyzing a clinical data warehouse of data collected from different hospital information systems. Methods Electronic prescription data and medical charts from 3 different hospitals spanning the past 9 years were reviewed, and a clinical data warehouse was constructed. Patients who were both administrated levofloxacin and given electrocardiograms (ECG) were selected. The correlations between various patient characteristics, concomitant drugs, corrected QT (QTc) prolongation, and the interval difference in QTc before and after levofloxacin administration were analyzed. Results A total of 2,176 patients from 3 different hospitals were included in the study. QTc prolongation was found in 364 patients (16.7%). The study revealed that age (OR 1.026, p < 0.001), gender (OR 0.676, p = 0.007), body temperature (OR 1.267, p = 0.024), and cigarette smoking (OR 1.641, p = 0.022) were related with QTc prolongation. After adjusting for related factors, 12 drugs concomitant with levofloxacin were associated with QTc prolongation. For patients who took ECGs before and after administration of levofloxacin during their hospitalization (n = 112), there was no significant difference in QTc prolongation. Conclusions The age, gender, body temperature, cigarette smoking and various concomitant drugs might be related with QTc prolongation. However, there was no definite causal relationship or interaction between levofloxacin and QTc prolongation. Alternative surveillance methods utilizing the massive accumulation of electronic medical data seem to be essential to adverse drug reaction surveillance in future. PMID:21818458

Intravenous or local injections of flavoxate in the rostral pontine reticular formation inhibit urinary frequency induced by activation of medial frontal lobe neurons in rats.

PubMed

Sugaya, Kimio; Nishijima, Saori; Kadekawa, Katsumi; Ashitomi, Katsuhiro; Ueda, Tomoyuki; Yamamoto, Hideyuki

2014-10-01

The rostral pontine reticular formation has a strong inhibitory effect on micturition by facilitating lumbosacral glycinergic neurons. We assessed the influence of the rostral pontine reticular formation on the micturition reflex after noradrenaline injection in the medial frontal lobe. We also examined the relation between the medial frontal lobe and the rostral pontine reticular formation. Continuous cystometry was performed in 28 female rats. After the interval between bladder contractions was shortened by noradrenaline injection in the medial frontal lobe we injected glutamate or flavoxate hydrochloride in the rostral pontine reticular formation or intravenously injected flavoxate or propiverine. The change in bladder activity was examined. Noradrenaline injection in the medial frontal lobe shortened the interval between bladder contractions. In contrast to the bladder contraction interval before and after noradrenaline injection in the medial frontal lobe, the interval was prolonged after noradrenaline injection when glutamate or flavoxate was injected in the rostral pontine reticular formation, or flavoxate was injected intravenously. Noradrenaline injection in the medial frontal lobe plus intravenous propiverine injection also prolonged the interval compared to that after noradrenaline injection alone. However, the interval after noradrenaline injection in the medial frontal lobe plus intravenous injection of propiverine was shorter than that before noradrenaline injection only. Medial frontal lobe neurons excited by noradrenaline may facilitate the micturition reflex via activation of inhibitory interneurons, which inhibit descending rostral pontine reticular formation neurons that innervate the lumbosacral glycinergic inhibitory neurons. Therefore, the mechanism of micturition reflex facilitation by the activation of medial frontal lobe neurons involves the rostral pontine reticular formation. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Biocompatibility of “On-Command” Dissolvable Tympanostomy Tube in the Rat Model

PubMed Central

Mai, Johnny P.; Dumont, Matthieu; Rossi, Christopher; Cleary, Kevin; Wiedermann, Joshua; Reilly, Brian K.

2016-01-01

Objectives/Hypothesis A prototype tympanostomy tube, composed of (polybutyl/methyl methacrylate-co-dimethyl amino ethyl methacrylate (PBM)), was tested to (1) evaluate the effect of PBM tubes on rat dermis as a corollary for biocompatibility and (2) to observe the efficacy of dissolution with isopropyl alcohol (iPrOH) and ethanol (EtOH). Subjects and Methods A two-part study was conducted to assess biocompatible substance with inducible dissolvability as a critical characteristic for a newly engineered tympanostomy tube. First, tympanostomy tubes were inserted subcutaneously in 10 rats, which served as an animal model for biosafety and compared to traditional tubes with respect to histologic reaction. Tissue surrounding the PBM prototype tubes was submitted for histopathology and demonstrated no tissue reactivity or signs of major inflammation. In the second part, we evaluated the dissolvability of the tube with either isopropyl alcohol, ethanol, ofloxacin, ciprodex, water, and soapy water. PBM tubes were exposed to decreasing concentrations of iPrOH and EtOH with interval qualitative assessment of dissolution. Results (1) Histologic examination did not reveal pathology with PBM tubes; (2) Concentrations of at least 50% iPrOH and EtOH dissolve PBM tubes within 48 hours while concentrations of at least 75% iPrOH and EtOH were required for dissolution when exposure was limited to four 20-minute intervals. Conclusion PBM is biocompatible in the rat model. Additionally, PBM demonstrates rapid dissolution upon alcohol-based stimuli, validating the proof-of-concept of dissolvable “on-command” or biocommandible ear tubes. Further testing of PBM is needed with a less ototoxic dissolver and in a better simulated middle ear environment, before testing can be performed in humans. PMID:27796039

[Depression in former slave communities in Brazil: screening and associated factors].

PubMed

Barroso, Sabrina Martins; Melo, Ana Paula Souto; Guimarães, Mark Drew Crosland

2014-04-01

To assess the prevalence and the factors associated with positive screening for major depressive episode (MDE) in former slave communities in the state of Bahia, Brazil. In this population-based, cross-sectional study, 764 participants were randomly selected from five former slave communities in Vitória da Conquista, Bahia, Brazil. Depression was defined as a cutoff score of 10 or more points and the presence of five or more symptoms according to the Patient Health Questionnaire (PHQ-9). Poisson regression was used to assess prevalence ratios (PR), with a 95% confidence interval (95%CI). Screening for MDE was positive in 12% of participants (95%CI: 10 - 14%), but only 2.3% reported a previous diagnosis. Depression was associated with self-reported poor or very poor health status (PR = 1.14; 95%CI: 1.04 - 1.26), chronic disease (PR = 1.08; 95%CI: 1.04 - 1.13), no physical activity (PR = 1.06; 95%CI: 1.01 - 1.11), and reasonable (PR = 1.07; 95%CI: 1.01 - 1.13) or poor access to health services (PR = 1.07; 95%CI: 1.02 - 1.12). The prevalence of MDE in this population was similar to that of the general Brazilian population. The association between MDE and poor access to health services indicates a missed opportunity for early diagnosis. Public measures against social and health inequalities are necessary to ensure equity in these communities.

Risk and Protective Factors for Difficulty Controlling Violent Behavior in National Guard and Reserve Service Members.

PubMed

Worthen, Miranda; Rathod, Sujit D; Cohen, Gregory; Sampson, Laura; Ursano, Robert; Gifford, Robert; Fullerton, Carol; Galea, Sandro; Ahern, Jennifer

2017-11-01

Violent behavior is an important problem for military service members and veterans. A representative cohort of U.S. Reserve and National Guard personnel ( N = 1,293) were interviewed to assess self-reported problems controlling violent behavior, deployment traumas, posttraumatic stress disorder (PTSD), alcohol abuse, and social support. Poisson regression models were used to estimate the associations of violent behavior with risk and protective factors. Problems controlling violent behavior were uncommon among male (3.3%) and female (1.7%) service members. Adjusted prevalence ratios (aPR) showed associations between violent behavior and deployment traumas (aPR = 1.67, 95% confidence interval [CI] = [1.34, 2.08]), PTSD (aPR = 9.95, 95% CI = [5.09, 19.48]), and PTSD symptom severity (aPR for each additional PTSD symptom = 1.07, 95% CI = [1.06, 1.09]). Social support was associated with lower prevalence of violent behavior (aPR = 0.62, 95% CI = [0.52, 0.76]). The association between violent behavior and alcohol abuse was not statistically significant (aPR = 1.94, 95% CI = [0.92, 4.09]). Results were consistent when the population was restricted to personnel who had deployed to a war zone. Problems controlling violent behavior were less common in this cohort than has been documented in other studies. Associations of violent behavior with risk and protective factors are consistent with prior research.

Racial/ethnic disparities in self-reported short sleep duration among US-born and foreign-born adults.

PubMed

Cunningham, Timothy J; Wheaton, Anne G; Ford, Earl S; Croft, Janet B

2016-12-01

Racial/ethnic health disparities are infrequently considered by nativity status in the United States, although the immigrant population has practically doubled since 1990. We investigated the modifying role of nativity status (US- vs. foreign-born) on racial/ethnic disparities in short sleep duration (<7 h), which has serious health consequences. Cross-sectional data from 23,505 US-born and 4,326 foreign-born adults aged ≥ 18 years from the 2012 National Health Interview Survey and multivariable log-linear regression were used to estimate prevalence ratios (PR) for reporting short sleep duration and their corresponding 95% confidence intervals (CI). After controlling for sociodemographic covariates, short sleep was more prevalent among blacks (PR 1.29, 95% CI: 1.21-1.37), Hispanics (PR 1.18, 95% CI: 1.08, 1.29), and Asians (PR 1.37, 95% CI: 1.16-1.61) than whites among US-born adults. Short sleep was more prevalent among blacks (PR 1.71, 95% CI: 1.38, 2.13) and Asians (PR 1.23, 95% CI: 1.02, 1.47) than whites among the foreign-born. Among both US- and foreign-born adults, blacks and Asians had a higher likelihood of short sleep compared to whites. US-born Hispanics, but not foreign-born Hispanics, had a higher likelihood than their white counterparts. Future research should aim to uncover mechanisms underlying these disparities.

Facilitators and Barriers to Pre-Exposure Prophylaxis Willingness Among Young Men Who Have Sex with Men Who Use Geosocial Networking Applications in California.

PubMed

Holloway, Ian W; Tan, Diane; Gildner, Jennifer L; Beougher, Sean C; Pulsipher, Craig; Montoya, Jorge A; Plant, Aaron; Leibowitz, Arleen

2017-12-01

While correlates of pre-exposure prophylaxis (PrEP) uptake have been explored among older men who have sex with men (MSM), less is known about the facilitators and barriers that encourage uptake among younger MSM (YMSM). This study explores the association between willingness to take PrEP and demographic characteristics, sexual risk, and substance use, and attitudinal factors among YMSM in California who use geosocial networking applications (GSN apps). Based on survey data from YMSM recruited through GSN apps (n = 687), PrEP willingness was positively associated with Hispanic ethnicity [adjusted odds ratio (aOR): 1.73; confidence interval (CI): 1.01-2.98; p = 0.046], concerns about drug effects (aOR: 0.46; CI: 0.33-0.65; p < 0.001), medical mistrust (aOR: 0.71; CI: 0.53-0.96; p < 0.001), and concerns about adherence (aOR: 0.65; CI: 0.49-0.89; p = 0.005). PrEP willingness was positively associated with medium (aOR: 1.87; CI: 1.14-3.07; p = 0.014) and high concern (aOR: 1.84; CI: 1.13-3.01; p < 0.001) about contracting HIV and perceived benefits of taking PrEP (aOR: 2.59; CI: 1.78-3.78; p < 0.001). In addition to emphasizing the benefits of using PrEP, campaigns that address concerns regarding adherence and side effects may increase interest in and demand for PrEP among YMSM. More opportunities are needed to educate YMSM about PrEP, including addressing their concerns about this new prevention strategy. Providers should speak openly and honestly to YMSM considering PrEP about what to do if side effects occur and how to handle missed doses. Outreach using GSN apps for PrEP education and screening may be an effective way to reach YMSM.

Cardiovascular risk factors among Russian, Somali and Kurdish migrants in comparison with the general Finnish population.

PubMed

Skogberg, Natalia; Laatikainen, Tiina; Koskinen, Seppo; Vartiainen, Erkki; Jula, Antti; Leiviskä, Jaana; Härkänen, Tommi; Koponen, Päivikki

2016-08-01

There is limited information on cardiovascular risk among migrants. We compared cardiovascular risk factors among three major migrant groups in Finland with the general population. Cross-sectional data from 30- to 64-year-old health examination participants (n = 921) of the Migrant Health and Wellbeing Study (2010-12) were used. Data for comparison with the general Finnish population were obtained from the Health 2011 Study (n = 892). Russian men had a similar risk profile to that of the reference group. Kurdish men had lower prevalence of hypertension [prevalence ratio (PR) 0.55, 95% confidence interval (CI) 0.39-0.79] but higher prevalence of dyslipidaemia (PR: 1.12, 95% CI: 1.02-1.24) and hyperglycaemia (PR: 2.61, 95% CI: 1.88-3.64) compared with the reference group. Somali men had lower prevalence of smoking (PR: 0.18, 95% CI: 0.08-0.44), hypertension (PR: 0.55, 95% CI: 0.32-0.97)) and obesity (PR: 0.35, 95% CI: 0.17-0.71) but higher prevalence of hyperglycaemia (PR: 2.59, 95% CI: 1.73-3.86) compared with the reference group. Similar patterns were observed for women, except for higher prevalence of hyperglycaemia among Russian women (PR: 1.95, 95% CI: 1.26-3.01) and obesity among Kurdish and Somali women (PR: 1.41, 95% CI: 1.15-1.72 and PR: 1.68, 95% CI: 1.40-2.03, respectively) compared with the reference group. All migrant women had significantly lower prevalence of smoking than the reference group. There were significant variations in cardiovascular risk profiles of Kurdish and Somali migrants compared with the general population. Differences in cardiovascular risk factors by migrant group need to be taken into account in planning and implementing health promotion strategies. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Predictors of interest in taking pre-exposure prophylaxis among men who have sex with men who used a rapid HIV-testing site in Montreal (Actuel sur Rue).

PubMed

Lebouché, B; Engler, K; Machouf, N; Lessard, D; Thomas, R

2016-02-01

The effective use of pre-exposure prophylaxis (PrEP) as an HIV prevention strategy depends on its uptake by individuals at high risk of infection. Few Canadian data are available on interest in PrEP among men who have sex with men (MSM). This study aimed to identify predictors of interest in PrEP among MSM clients of a rapid HIV-testing site in Montreal's gay village (Actuel sur Rue). Data were collected using a self-administered and a community agent-administered questionnaire. Among men reporting at least one male sexual partner and visiting the site between July 2012 and November 2013, we aimed to identify sociodemographic, sexual and temporal predictors of interest in taking effective PrEP with logistic regression analyses (univariate and multivariable). Over half (55%; n = 653) of the sample of 1179 MSM were interested in PrEP. Among the 14 variables considered in the univariate analyses, only (younger) age, (greater) number of sexual partners (in the past 3 months), being part of a serodiscordant couple (in the past 12 months), ever combining sex with drugs and temporal events were associated with interest in PrEP at P < 0.20 and were included in the multivariable analyses. In the multivariable model, only being part of a serodiscordant couple [adjusted odds ratio (aOR) 2.56; 95% confidence interval (CI) 1.44-4.58], having > 10 partners (aOR 1.73; 95% CI 1.17-2.55) and responding after the publication of Quebec's interim PrEP guidelines (aOR 1.82; 95% CI 1.22-2.71) proved significant. In this assessment of predictors of PrEP interest among Canadian MSM, partnering issues and the arrival of PrEP guidelines in Quebec (10 July 2013) were most closely linked to PrEP interest. © 2015 British HIV Association.

Weather-Corrected Performance Ratio

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dierauf, T.; Growitz, A.; Kurtz, S.

Photovoltaic (PV) system performance depends on both the quality of the system and the weather. One simple way to communicate the system performance is to use the performance ratio (PR): the ratio of the electricity generated to the electricity that would have been generated if the plant consistently converted sunlight to electricity at the level expected from the DC nameplate rating. The annual system yield for flat-plate PV systems is estimated by the product of the annual insolation in the plane of the array, the nameplate rating of the system, and the PR, which provides an attractive way to estimatemore » expected annual system yield. Unfortunately, the PR is, again, a function of both the PV system efficiency and the weather. If the PR is measured during the winter or during the summer, substantially different values may be obtained, making this metric insufficient to use as the basis for a performance guarantee when precise confidence intervals are required. This technical report defines a way to modify the PR calculation to neutralize biases that may be introduced by variations in the weather, while still reporting a PR that reflects the annual PR at that site given the project design and the project weather file. This resulting weather-corrected PR gives more consistent results throughout the year, enabling its use as a metric for performance guarantees while still retaining the familiarity this metric brings to the industry and the value of its use in predicting actual annual system yield. A testing protocol is also presented to illustrate the use of this new metric with the intent of providing a reference starting point for contractual content.« less

Willingness to Accept HIV Pre-Exposure Prophylaxis among Chinese Men Who Have Sex with Men

PubMed Central

Li, Shuming; Li, Dongliang; Zhang, Lifen; Fan, Wensheng; Yang, Xueying; Yu, Mingrun; Xiao, Dong; Yan, Li; Zhang, Zheng; Shi, Wei; Luo, Fengji; Ruan, Yuhua; Jin, Qi

2012-01-01

Objective We investigated the awareness and acceptability of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and potential predicting factors. Methods This study was conducted among MSM in Beijing, China. Study participants, randomly selected from an MSM cohort, completed a structured questionnaire, and provided their blood samples to test for HIV infection and syphilis. Univariate logistic regression analyses were performed to evaluate the factors associated with willingness to accept (WTA) PrEP. Factors independently associated with willingness to accept were identified by entering variables into stepwise logistic regression analysis. Results A total of 152 MSM completed the survey; 11.2% had ever heard of PrEP and 67.8% were willing to accept it. Univariate analysis showed that age, years of education, consistent condom use in the past 6 months, heterosexual behavior in the past 6 months, having ever heard of PrEP and the side effects of antiretroviral drugs, and worry about antiretroviral drugs cost were significantly associated with willingness to accept PrEP. In the multivariate logistic regression model, only consistent condom use in the past 6 months (odds ratio [OR]: 0.31; 95% confidence interval [CI]: 0.13–0.70) and having ever heard of the side effects of antiretroviral drugs (OR: 0.30; 95% CI: 0.14–0.67) were independently associated with willingness to accept PrEP. Conclusions The awareness of PrEP in the MSM population was low. Sexual behavioral characteristics and knowledge about ART drugs may have effects on willingness to accept PrEP. Comprehensive prevention strategies should be recommended in the MSM community. PMID:22479320

[Risk factors for cardiovascular disease in prison institution staff: a cross-sectional study].

PubMed

Audi, Celene Aparecida Ferrari; Santiago, Silvia Maria; Andrade, Maria da Graça Garcia; Francisco, Priscila Maria Stolses Bergamo

2016-01-01

to analyze risk factors for cardiovascular disease in prison institution staff. this was a cross-sectional study with a sample of 127 staff of both sexes; prevalence ratios (PR) were estimated adjusted for age and education, as were the respective 95% confidence intervals (95%CI). higher proportions of waist circumference ratios were found above the recommended values (58.1%) and the accumulation of two risk factors for females (33.8%); among males there was higher prevalence of abnormal glucose levels (PR=10.73 - 95%CI 1.31;87.92) and blood pressure (PR=2.63 - 95%CI 1.31;6.50). the risk factors for cardiovascular disease found among staff in this study were waist circumference, glucose levels and blood pressure above the recommended values; these health risks can to be addressed through health promotion and disease prevention measures, as well as effective attention to those who are already sick.

The effect of additional carbohydrate supplements for 7 days after prolonged interval exercise on exercise performance and energy metabolism during submaximal exercise in team-sports athletes

PubMed Central

Park, Hun-Young; Kim, Jisu; Park, Miyoung; Chung, Nana; Lim, Kiwon

2018-01-01

[Purpose] The purpose of our study was to determine the effectiveness of carbohydrate loading by additional carbohydrate supplements for 7 days after prolonged interval exercise on exercise performance and energy metabolism during submaximal exercise in team-sports athletes. [Methods] Twenty male team-sports athletes (14 soccer and 6 rugby players) volunteered to participate in the study and were equally divided into the experimental group (EXP, n=10) performing additional carbohydrate supplementation for 7 days after prolonged interval exercise until blood glucose level reaches 50 mg/dL or less and the control group (CON, n=10). Then, maximal oxygen consumption (VO2max) and minute ventilation (VE), oxygen consumption (VO2), carbon dioxide excretion (VCO2), respiratory exchange ratio (RER), blood glucose level, and blood lactate level were measured in all team-sports players during submaximal exercise corresponding to 70% VO2max before and after intervention. [Results] There was no significant interaction in all parameters, but team-sports players in the EXP presented more improved VO2max (CON vs EXP = vs 5.3% vs 6.3%), VE (CON vs EXP = vs 3.8% vs 6.6%), VO2 (CON vs EXP = vs 8.5% vs 9.9%), VCO2 (CON vs EXP = vs 2.8% vs 4.0%), blood glucose level (CON vs EXP = vs -12.9% vs -7.6%), and blood lactate level (CON vs EXP = -18.2% vs -25%) compared to those in the CON. [Conclusion] These findings showed that additional carbohydrate supplementation conducted in our study is not effective in exercise performance and energy metabolism during submaximal exercise. PMID:29673243

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

PubMed

Stracina, Tibor; Slaninova, Iva; Polanska, Hana; Axmanova, Martina; Olejnickova, Veronika; Konecny, Petr; Masarik, Michal; Krizanova, Olga; Novakova, Marie

2015-07-01

Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

The effect of additional carbohydrate supplements for 7 days after prolonged interval exercise on exercise performance and energy metabolism during submaximal exercise in team-sports athletes.

PubMed

Park, Hun-Young; Kim, Jisu; Park, Miyoung; Chung, Nana; Lim, Kiwon

2018-03-30

The purpose of our study was to determine the effectiveness of carbohydrate loading by additional carbohydrate supplements for 7 days after prolonged interval exercise on exercise performance and energy metabolism during submaximal exercise in team-sports athletes. Twenty male team-sports athletes (14 soccer and 6 rugby players) volunteered to participate in the study and were equally divided into the experimental group (EXP, n=10) performing additional carbohydrate supplementation for 7 days after prolonged interval exercise until blood glucose level reaches 50 mg/dL or less and the control group (CON, n=10). Then, maximal oxygen consumption (VO2max) and minute ventilation (VE), oxygen consumption (VO2), carbon dioxide excretion (VCO2), respiratory exchange ratio (RER), blood glucose level, and blood lactate level were measured in all team-sports players during submaximal exercise corresponding to 70% VO2max before and after intervention. There was no significant interaction in all parameters, but team-sports players in the EXP presented more improved VO2max (CON vs EXP = vs 5.3% vs 6.3%), VE (CON vs EXP = vs 3.8% vs 6.6%), VO2 (CON vs EXP = vs 8.5% vs 9.9%), VCO2 (CON vs EXP = vs 2.8% vs 4.0%), blood glucose level (CON vs EXP = vs -12.9% vs -7.6%), and blood lactate level (CON vs EXP = -18.2% vs -25%) compared to those in the CON. These findings showed that additional carbohydrate supplementation conducted in our study is not effective in exercise performance and energy metabolism during submaximal exercise. ©2018 The Korean Society for Exercise Nutrition.

Population Pharmacokinetic-Pharmacodynamic Analysis to Compare the Effect of Moxifloxacin on QT Interval Prolongation Between Healthy Korean and Japanese Subjects.

PubMed

Choi, Hyang-Ki; Jung, Jin Ah; Fujita, Tomoe; Amano, Hideki; Ghim, Jong-Lyul; Lee, Dong-Hwan; Tabata, Kenichi; Song, Il-Dae; Maeda, Mika; Kumagai, Yuji; Mendzelevski, Boaz; Shin, Jae-Gook

2016-12-01

The goal of this study was to evaluate the moxifloxacin-induced QT interval prolongation in healthy male and female Korean and Japanese volunteers to investigate interethnic differences. This multicenter, randomized, double-blind, placebo-controlled, 2-way crossover study was conducted in healthy male and female Korean and Japanese volunteers. In each period, a single dose of moxifloxacin or placebo 400 mg was administered orally under fasting conditions. Triplicate 12-lead ECGs were recorded at defined time points before, up to 24 hours after dosing, and at corresponding time points during baseline. Serial blood sampling was conducted for pharmacokinetic analysis of moxifloxacin. The pharmacokinetic-pharmacodynamic data between the 2 ethnic groups were compared by using a typical analysis based on the intersection-union test and a nonlinear mixed effects method. A total of 39 healthy subjects (Korean, male: 10, female: 10; Japanese, male: 10, female: 9) were included in the analysis. The concentration-effect analysis revealed that there was no change in slope (and confirmed that the difference was caused by a change in the pharmacokinetic model of moxifloxacin). A 2-compartment model with first-order absorption provided the best description of moxifloxacin's pharmacokinetic parameters. Weight and sex were selected as significant covariates for central volume of distribution and intercompartmental clearance, respectively. An E max model (E[C]=[E max ⋅C]/[EC 50 +C]) described the QT interval data of this study well. However, ethnicity was not found to be a significant factor in a pharmacokinetic-pharmacodynamic link model. The drug-induced QTc prolongations evaluated using moxifloxacin as the probe did not seem to be significantly different between these Korean and Japanese subjects. ClinicalTrials.gov identifier: NCT01876316. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Willingness to use pre-exposure prophylaxis for HIV prevention among female sex workers: a cross-sectional study in China

PubMed Central

Peng, Bin; Yang, Xiaowei; Zhang, Yan; Dai, Jianghong; Liang, Hao; Zou, Yunfeng; Luo, Jinkun; Peng, Hongbin; Zhong, Xiaoni; Huang, Ailong

2012-01-01

Background Pre-exposure prophylaxis (PrEP) is a strategy developed to prevent individuals who are human immunodeficiency virus (HIV)-negative from developing HIV infection. In China, while conducting a clinical trial to investigate the effectiveness and safety of PrEP, we performed this survey to assess the willingness of female sex workers to use PrEP, and identify predictors of this willingness. Methods From July 2009 to April 2010, a cross-sectional study was carried out in four provinces of China. We recruited 1611 female sex workers who completed a self-administered survey to assess their awareness of and intention to use PrEP. The survey also canvassed demographic, behavioral, and psychosocial variables. Bivariate and multivariable logistic regression models were fitted to identify predictors of intent to use PrEP. Results In total, 69% of the women (95% confidence interval [CI] 66.7–71.3) reported intent to use PrEP, and 12% (95% CI 10.5–13.7) had used drugs in the past to prevent a sexually transmitted infection. Further, 16.5% (95% CI 14.7–18.4) had previously heard of PrEP, and 1.4% (95% CI 0.9–2.1) had used PrEP previously to prevent HIV infection. Multivariate analysis indicated the following significant predictors of intent to use PrEP: Han ethnicity (adjusted odds ratio [AOR] 1.446; P = 0.011), urban residence (AOR 1.302; P = 0.027), knowledge about transmission of HIV/acquired immune deficiency virus syndrome (AIDS, AOR 1.817; P = 0.0007), a history of sexually transmitted infection (AOR 1.830; P < 0.0001), a history of using medication to prevent a sexually transmitted disease (AOR 2.547; P < 0.0001), and willingness to access knowledge about HIV/AIDS (AOR 2.153; P < 0.0001). Conclusion The majority of female sex workers reported intent to use PrEP if it is safe and effective. Given that most of the participants had never heard of PrEP before, we strongly recommend that educational materials be developed with detailed introduction of PrEP. The risks and benefits of PrEP use should be fully explained to potential users when promoting PrEP in the future. PMID:23055781

Low agreement between the fitnessgram criterion references for adolescents

PubMed Central

Coledam, Diogo Henrique Constantino; Batista, João Pedro; Glaner, Maria Fátima

2015-01-01

OBJECTIVE: To analyze the association and agreement of fitnessgram reference criteria (RC) for cardiorespiratory fitness, body mass index (BMI) and strength in youth. METHODS: The study included 781 youth, 386 females, aged 10 to 18 years of Londrina-PR. It were performed cardiorespiratory fitness and muscular strength tests and was calculated body mass index. The association between the tests was analyzed using Poisson regression to obtain prevalence ratio (PR) and confidence intervals of 95%, while agreement of the reference criteria was tested by Kappa index. RESULTS: Significant associations were found between cardiorespiratory fitness and BMI (PR=1,49, 1,27-1,75), muscle strength and BMI (PR=1,55, 1,17-2,08), cardiorespiratory fitness and muscle strength (PR=1,81, 1,47-2,24). The agreement between reference criteria ranged from weak to fair, 48.8% (k=0.05, p=0.10) for cardiorespiratory fitness and BMI, 52.9% (k=0.09, p=0.001) for muscle strength and BMI and 38.4% (k=0.22, p<0.001) for cardiorespiratory fitness and muscle strength. CONCLUSIONS: Although RC for cardiorespiratory fitness, muscle strength and BMI are associated, the agreement between them ranged from weak to fair. To evaluate health related physical fitness it is suggest the execution of all tests, since each test has specific characteristics. PMID:25649383

Physical activity and depression symptom profiles in young men and women with major depression.

PubMed

McKercher, Charlotte; Patton, George C; Schmidt, Michael D; Venn, Alison J; Dwyer, Terence; Sanderson, Kristy

2013-05-01

This study explored whether young adults with major depression who are physically active differ in their depression symptom profile from those physically inactive. Analyses included data from 950 (47.6%) men and 1045 women (mean [standard deviation] age = 31.5 [2.6] years) participating in a national study. Participants reported leisure physical activity (International Physical Activity Questionnaire) and ambulatory activity (pedometer steps per day). Diagnosis and symptoms of major depression were assessed using the Composite International Diagnostic Interview. Prevalence of major depression was 5.5% (n = 52) for men and 11.6% (n = 121) for women. Interactions between physical activity and sex were observed for depressed mood, appetite changes, vacillating thoughts, and suicidality (all, p < .050). Among those with major depression, physically active men were significantly less likely to endorse the presence of insomnia (prevalence ratio [PR] = 0.78, 95% confidence interval [CI] = 0.63-0.96), fatigue (PR = 0.82, 95% CI = 0.69-0.99), and suicidality (PR = 0.69, 95% CI = 0.49-0.96) compared with inactive men. Physically active women were significantly less likely to endorse hypersomnia (PR = 0.50, 95% CI = 0.27-0.95), excessive/irrational guilt (PR = 0.76, 95% CI = 0.59-0.97), vacillating thoughts (PR = 0.74, 95% CI = 0.58-0.95), and suicidality (PR = 0.43, 95% CI = 0.20-0.89) compared with inactive women. Associations were adjusted for age, physical health, educational attainment, depression severity, and other depressive symptoms. Among adults with major depression, those physically active seem to differ in their depression symptom profile from those physically inactive.

Moxifloxacin-induced QTc interval prolongations in healthy male Japanese and Caucasian volunteers: a direct comparison in a thorough QT study

PubMed Central

Morganroth, Joel; Wang, Yaning; Thorn, Michael; Kumagai, Yuji; Harris, Stuart; Stockbridge, Norman; Kleiman, Robert; Shah, Rashmi

2015-01-01

Aim We investigated whether moxifloxacin-induced QTc prolongations in Japanese and Caucasian healthy male volunteers were significantly different. Methods A two period, randomized, crossover, ICH-E14-compliant thorough QT (TQT) study compared placebo-corrected changes in QTc interval from baseline (ΔΔQTcF) and concentration–effect relationships following administration of placebo and 400 mg moxifloxacin to 40 healthy male volunteers from each ethnic population. The point estimates of ΔΔQTcF for each population, and the difference between the two, were calculated at a geometric mean Cmax of moxifloxacin using a linear mixed effects model. The concentration–effect slopes of the two populations were also compared. Equivalence was concluded if the two-sided 90% confidence interval of the difference in ΔΔQTcF was contained within −5 ms to +5 ms limits and the ratio of the slopes was between 0.5 and 2. Results There were no statistically significant differences between the two populations studied, Japanese vs. Caucasians, respectively, for moxifloxacin Cmax (3.27 ± 0.6 vs. 2.98 ± 0.7 µg ml–1), ΔΔQTcF (9.63 ± 1.15 vs. 11.46 ± 1.19 ms at Cmax of 3.07 µg ml–1) and concentration–response slopes (2.58 ± 0.62 vs. 2.34 ± 0.64 ms per µg ml–1). The difference in the two ΔΔQTcF of −1.8 (90% CI −4.6, 0.9) and the ratio of the two slopes (1.1; 90% CI 0.63, 1.82) were within pre-specified equivalence limits. Conclusions Moxifloxacin-induced QTc prolongations did not differ significantly between the Japanese and Caucasian subjects. However, before our findings are more widely generalized, further studies in other populations and with other QT-prolonging drugs are needed to clarify whether inter-ethnic differences in QT sensitivity exist and whether ethnicity of the study population may affect the outcome of a TQT study. PMID:26011050

Comparison of corrected QT interval as measured on electroencephalography versus 12-lead electrocardiography in children with a history of syncope.

PubMed

Massey, Shavonne L; Wise, Marshall S; Madan, Nandini; Carvalho, Karen; Khurana, Divya; Legido, Agustin; Valencia, Ignacio

2011-11-01

Long QT syndrome can present with neurological manifestations, including syncope and seizure-like activity. These patients often receive an initial neurologic evaluation, including electroencephalography (EEG). Our previous retrospective study suggested an increased prevalence of prolonged corrected QT interval (QTc) measured during the EEG of patients with syncope. The aim of the current study is to assess the accuracy of the EEG QTc reading compared with the nonsimultaneous 12-lead electrocardiography (ECG) in children with syncope. Abnormal QTc was defined as ≥450 ms in boys, ≥460 ms in girls. Forty-two children were included. There was no significant correlation between QTc readings in the EEG and ECG. EEG failed to identify 2 children with prolonged QTc in the ECG and overestimated the QTc in 3 children with normal QTc in the ECG. This study suggests that interpretation of the QTc segment during an EEG is limited. Further studies with simultaneous EEG and 12-lead ECG are warranted.

Inside the black box: current policies and concerns with the United States Food and Drug Administration's highest drug safety warning system.

PubMed

Halloran, Kylene; Barash, Paul G

2010-06-01

To evaluate the United States Food and Drug Administration use of the black-box warning system to promote drug safety and to examine the droperidol black-box warning as a case study. Scientific studies report that there is no basis to issue a black-box warning for perioperative administration of droperidol for postoperative nausea and vomiting on the basis of the potential of adverse cardiac events (prolongation of the QT interval and/or development of torsades de pointes). Rather than relying on well conducted clinical investigations, the Food and Drug Administration subjectively issued a black-box warning to droperidol, which effectively removed droperidol from clinical practice for the indication of postoperative nausea and vomiting. Newer data suggest that the incidence of prolongation of the QT interval and the occurrence of torsades de pointes is similar to more expensive alternative medications used to treat postoperative nausea and vomiting.

Grading of Emphysema Is Indispensable for Predicting Prolonged Air Leak After Lung Lobectomy.

PubMed

Murakami, Junichi; Ueda, Kazuhiro; Tanaka, Toshiki; Kobayashi, Taiga; Hamano, Kimikazu

2018-04-01

The aim of this study was to assess the utility of quantitative computed tomography-based grading of emphysema for predicting prolonged air leak after thoracoscopic lobectomy. A consecutive series of 284 patients undergoing thoracoscopic lobectomy for lung cancer was retrospectively reviewed. Prolonged air leak was defined as air leaks lasting 7 days or longer. The grade of emphysema (emphysema index) was defined by the proportion of the emphysematous lung volume (less than -910 HU) to the total lung volume (-600 to -1,024 HU) by a computer-assisted histogram analysis of whole-lung computed tomography scans. The mean length of chest tube drainage was 1.5 days. Fifteen patients (5.3%) presented with prolonged air leak. According to a receiver-operating characteristics curve analysis, the emphysema index was the best predictor of prolonged air leak, with an area under the curve of 0.85 (95% confidence interval: 0.73 to 0.98). An emphysema index of 35% or greater was the best cutoff value for predicting prolonged air leak, with a negative predictive value of 0.99. The emphysema index was the only significant predictor for the length of postoperative chest tube drainage among conventional variables, including the pulmonary function and resected lobe, in both univariate and multivariate analyses. Prolonged air leak resulted in an increased duration of hospitalization (p < 0.001) and was frequently accompanied by pneumonia or empyema (p < 0.001). The grade of emphysema on computed tomography scan is the best predictor of prolonged air leak that adversely influences early postoperative outcomes. We must take new measures against prolonged air leak in quantitative computed tomography-based high-risk patients. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Ventricular conduction and long-term heart failure outcomes and mortality in African Americans: insights from the Jackson Heart Study.

PubMed

Mentz, Robert J; Greiner, Melissa A; DeVore, Adam D; Dunlay, Shannon M; Choudhary, Gaurav; Ahmad, Tariq; Khazanie, Prateeti; Randolph, Tiffany C; Griswold, Michael E; Eapen, Zubin J; O'Brien, Emily C; Thomas, Kevin L; Curtis, Lesley H; Hernandez, Adrian F

2015-03-01

QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0-14.4) versus 7.1% (95% CI, 6.3-8.0) and 8.2% (95% CI, 6.9-9.7) versus 4.4% (95% CI, 3.7-5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03-1.56; P=0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01-1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities. © 2015 American Heart Association, Inc.

Sedentary bout durations and metabolic syndrome among working adults: a prospective cohort study.

PubMed

Honda, Takanori; Chen, Sanmei; Yonemoto, Koji; Kishimoto, Hiro; Chen, Tao; Narazaki, Kenji; Haeuchi, Yuka; Kumagai, Shuzo

2016-08-26

This study aimed to examine the associations between time spent in prolonged and non-prolonged sedentary bouts and the development of metabolic syndrome. We used data from a prospective study of Japanese workers. Baseline examination was conducted between 2010 and 2011. A total of 430 office workers (58 women) aged 40-64 years without metabolic syndrome were followed up by annual health checkups until 2014. Metabolic syndrome was defined as having ≥ 3 out of 5 diagnostic criteria from the Joint Interim Statement 2009 definition. Sedentary time was assessed using a tri-axial accelerometer. Time spent in total, prolonged (accumulated ≥ 30 min) and non-prolonged sedentary bouts (accumulated < 30 min) was calculated. Cox proportional hazards models were used to estimate the risk of developing metabolic syndrome. During a median follow-up of 3 years, 83 participants developed metabolic syndrome. After adjustment for age, sex, education, smoking, and family income, positive associations were observed between time spent in prolonged sedentary bouts and the development of metabolic syndrome. After additional adjustment for moderate-to-vigorous physical activity, those in the three highest quartiles of time spent in prolonged sedentary bouts showed higher risk of metabolic syndrome compared to the lowest quartile group, with adjusted hazard ratios (95 % confidence intervals) of 2.72 (1.30 - 5.73), 2.42 (1.11 - 5.50), and 2.85 (1.31 - 6.18), respectively. No associations were seen for time spent in total and non-prolonged sedentary bouts. Sedentary behavior accumulated in a prolonged manner was associated with an increased risk of metabolic syndrome. In devising public health recommendations for the prevention of metabolic disease, the avoidance of prolonged uninterrupted periods of sedentary behavior should be considered.

Early Minocycline and Late FK506 Treatment Improves Survival and Alleviates Neuroinflammation, Neurodegeneration, and Behavioral Deficits in Prion-Infected Hamsters.

PubMed

Shah, Syed Zahid Ali; Zhao, Deming; Taglialatela, Giulio; Khan, Sher Hayat; Hussain, Tariq; Dong, Haodi; Lai, Mengyu; Zhou, Xiangmei; Yang, Lifeng

2017-04-01

Prion infections of the central nervous system (CNS) are characterized by initial reactive gliosis followed by overt neuronal death. Gliosis is likely to be caused initially by the deposition of misfolded, proteinase K-resistant, isoforms (termed PrP Sc ) of the normal cellular prion protein (PrP c ) in the brain. Proinflammatory cytokines and chemokines released by PrP Sc -activated glia and stressed neurons may also contribute directly or indirectly to the disease development by enhancing gliosis and inducing neurotoxicity. Recent studies have illustrated that early neuroinflammation activates nuclear factor of activated T cells (NFAT) in the calcineurin signaling cascade, resulting in nuclear translocation of nuclear factor kappa B (NF-κB) to promote apoptosis. Hence, useful therapeutic approaches to slow down the course of prion disease development should control early inflammatory responses to suppress NFAT signaling. Here we used a hamster model of prion diseases to test, for the first time, the neuroprotective and NFAT-suppressive effect of a second-generation semisynthetic tetracycline derivative, minocycline, versus a calcineurin inhibitor, FK506, with known NFAT suppressive activity. Our results indicate that prolonged treatment with minocycline, starting from the presymptomatic stage of prion disease was more effective than FK506 given either during the presymptomatic or symptomatic stage of prion disease. Specifically, minocycline treatment reduced the expression of the astrocyte activation marker glial fibrillary acidic protein and of the microglial activation marker ionized calcium-binding adapter molecule-1, subsequently reducing the level of proinflammatory cytokines interleukin 1β and tumor necrosis factor-α. We further found that minocycline and FK506 treatment inhibited mitogen-activated protein kinase p38 phosphorylation and NF-κB nuclear translocation in a caspase-dependent manner, and enhanced phosphorylated cyclic adenosine monophosphate response element-binding protein and phosphorylated Bcl2-associated death promoter levels to reduce cognitive impairment and apoptosis. Taken together, our results indicate that minocycline is a better choice for prolonged use in prion diseases and encourage its further clinical development as a possible treatment for this disease.

Pregnancy outcomes in patients with acute kidney injury during pregnancy: a systematic review and meta-analysis.

PubMed

Liu, Youxia; Ma, Xinxin; Zheng, Jie; Liu, Xiangchun; Yan, Tiekun

2017-07-18

Presently, the matter of pregnancy outcomes of patients with pregnancy related AKI (PR-AKI) were disputed. Thus, we conducted a meta-analysis to evaluate the impact of PR-AKI on pregnancy outcomes. We systematically searched MEDLINE, Embase, VIP, CNKI and Wanfang Databases for cohort or case-control studies in women with PR-AKI and those without AKI as a control group to assess the influence of PR-AKI on pregnancy outcomes and kidney outcome. Reduction of odd ratio (OR) was calculated by a random-effects model. One thousand one hundred fifty two articles were systematically reviewed, of those 11 studies were included, providing data of 845 pregnancies in 834 women with PR-AKI and 5387 pregnancies in 5334 women without AKI. In terms of maternal outcomes, women with PR-AKI had a greater likelihood of cesarean delivery (OR, 1.49; 95% confidence interval [CI], 1.37 to 1.61), hemorrhage (1.26; 1.02 to 1.56), HELLP syndrome (1.86; 1.41 to 2.46), placental abruption (3.13; 1.96 to 5.02), DIC (3.41; 2.00 to 5.84), maternal death (4.50; 2.73 to 7.43), but had a lower risk of eclampsia (0.53; 0.34 to 0.83). Women with PR-AKI also had a longer stay in ICU (weighted mean difference, 2.13 day [95% CI 1.43 to 2.83 day]) compared with those without PR-AKI. As for fetal outcomes, higher incidence of stillbirth/perinatal death (3.39, 2.76 to 4.18), lower mean gestational age at delivery (-0.70 week [95% CI -1.21 to -0.19 week]) and lower birth weight (-740 g [95% CI -1180 to 310 g]) were observed in women with PR-AKI. The occurrence of kidney outcome, defined as ESRD requiring dialysis, in women with PR-AKI was 2.4% (95% CI 1.3% to 4.2%). PR-AKI remains a grave complication and has been associated with increased maternal and fetal mortality.

High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.

PubMed

Minicozzi, Pamela; Berrino, Franco; Sebastiani, Federica; Falcini, Fabio; Vattiato, Rosa; Cioccoloni, Francesca; Calagreti, Gioia; Fusco, Mario; Vitale, Maria Francesca; Tumino, Rosario; Sigona, Aurora; Budroni, Mario; Cesaraccio, Rosaria; Candela, Giuseppa; Scuderi, Tiziana; Zarcone, Maurizio; Campisi, Ildegarda; Sant, Milena

2013-12-01

We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008. For 1607 Italian women (≥15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (≤84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (≤23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER-PR- cases were also run. Patients often had T1-3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95% confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1-94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Les médicaments à libération prolongée pour les enfants et les adolescents ayant un trouble de déficit de l’attention avec hyperactivité

PubMed Central

Feldman, M; Bélanger, S

2009-01-01

Le trouble de déficit de l’attention avec hyperactivité (TDAH) touche un enfant canadien sur 20 et s’associe à un dossier scolaire et à un registre d’emploi défavorables, à des taux élevés de blessures et de consommation de drogues ou d’alcool, à des relations interpersonnelles médiocres, à de mauvaises issues en santé mentale et à une qualité de vie insatisfaisante. Des essais contrôlés démontrent que les médica-ments sont efficaces pour traiter les symptômes de TDAH tandis que des études d’observation indiquent qu’ils s’associent à de meilleures issues sociales et de santé. De nombreuses familles, ainsi que leur médecin traitant, préfèrent les médicaments à libération prolongée (LP) contre le TDAH aux médicaments à libération immédiate (LI) et à action brève. Toutefois, les préparations à LP sont souvent inabor-dables pour les familles, dont un nombre disproportionné fait partie de la strate à faible statut socioéconomique. Le présent document de principes vise à proposer une évaluation critique des données probantes sur l’efficacité relative des médicaments à LP par rapport aux médicaments à LI ainsi que des recommandations au sujet de leur utilisation convenable dans le traitement du TDAH. Lorsque les médicaments sont indiqués, il faut envisager d’utiliser des préparations à LP comme traitement de première intention contre le TDAH parce qu’elles sont plus efficaces et moins susceptibles d’être détournées. Les futures recherches et les analyses coûts-avantages doivent tenir compte à la fois de l’efficacité de médicaments dans des études contrôlées et de leur efficacité clinique en situation réelle ainsi que du potentiel de détournement et de mésusage de ces médicaments. L’industrie, les sociétés d’assurance et le gouvernement doivent collaborer pour rendre ces médicaments accessibles à tous les enfants et adolescents ayant un TDAH.

Malaria surveillance-response strategies in different transmission zones of the People's Republic of China: preparing for climate change.

PubMed

Yang, Guo-Jing; Tanner, Marcel; Utzinger, Jürg; Malone, John B; Bergquist, Robert; Chan, Emily Y Y; Gao, Qi; Zhou, Xiao-Nong

2012-12-21

A sound understanding of malaria transmission patterns in the People's Republic of China (P.R. China) is crucial for designing effective surveillance-response strategies that can guide the national malaria elimination programme (NMEP). Using an established biology-driven model, it is expected that one may design and refine appropriate surveillance-response strategies for different transmission zones, which, in turn, assist the NMEP in the ongoing implementation period (2010-2020) and, potentially, in the post-elimination stage (2020-2050). Environmental data obtained from 676 locations across P.R. China, such as monthly temperature and yearly relative humidity (YRH), for the period 1961-2000 were prepared. Smoothed surface maps of the number of months suitable for parasite survival derived from monthly mean temperature and YRH were generated. For each decade, the final malaria prediction map was overlaid by two masked maps, one showing the number of months suitable for parasite survival and the other the length of YRH map in excess of 60%. Considering multiple environmental factors simultaneously, the environmental variables suitable for malaria transmission were found to have shifted northwards, which was especially pronounced in northern P.R. China. The unstable suitable regions (transmission periods between five and six months) showed increased transmission intensity due to prolonged suitable periods, especially in the central part of the country. Adequate and effective surveillance-response strategies for NMEP should be designed to achieve the goal of malaria elimination in P.R. China by 2020, especially in the zones predicted to be the most vulnerable for climate change.

Do Studies Evaluating QT/QTc Interval Prolongation with Dietary Supplements Meet FDA Standards: A Systematic Review.

PubMed

Nguyen, Tinh An; Kurian, Amy; Leong, Jessica; Patel, Umang M; Shah, Sachin A

2017-07-04

Dietary supplement use is continuously increasing, but the safety evaluation of these products remains partial. While dietary supplements have no mandate for assessing cardiovascular safety, all new drug entities (NDE) are required to undergo a thorough QT/corrected QT (QTc) assessment to determine their propensity to impact cardiac repolarization. Independent investigators and manufacturers of dietary supplements voluntarily initiate safety studies; however, the quality of these studies is controversial. We sought to compare studies evaluating the QT/QTc effects of dietary supplements based on the International Conference of Harmonization (ICH)-E14 recommendations for NDE. Twenty-six published dietary supplement studies assessed QT/QTc interval prolongation. Sample sizes ranged from nine subjects to 206 among the 15 crossover studies, six parallel design studies, and five observational studies. A plan to account for electrocardiogram (ECG) morphological abnormalities was included in 10 studies, and two studies reported cardiovascular adverse events. Eight studies found a significant change in QT/QTc intervals. The majority of studies included in this review contained many of the critical elements recommended by the ICH E14, which includes the U.S. Food and Drug Administration guidance document for QT/QTc interval assessment. Compared with the thorough QT (TQT) standards, studies are typically well performed but can be bolstered by some study design changes. More than 30% of the included studies showed some degree of ECG changes, suggesting the need for continued cardiovascular safety assessment of dietary supplements.

Sex Differences in the Effect of Atomoxetine on the QT Interval in Adult Patients With Attention-Deficit Hyperactivity Disorder.

PubMed

Suzuki, Yutaro; Tajiri, Misuzu; Sugimoto, Atsunori; Orime, Naoki; Hayashi, Taketsugu; Egawa, Jun; Sugai, Takuro; Inoue, Yoshimasa; Someya, Toshiyuki

2017-02-01

The effects of atomoxetine on QT in adults remain unclear. In this study, we examined whether the use of atomoxetine to treat attention-deficit hyperactivity disorder in adults is associated with QT prolongation. Forty-one subjects with attention-deficit hyperactivity disorder were enrolled in this study. Participants were administered 40, 80, or 120 mg atomoxetine daily and were maintained on their respective dose for at least 2 weeks. We conducted electrocardiographic measurements and blood tests, measuring plasma atomoxetine concentrations after treatment. Electrocardiograms of 24 of the patients were also obtained before atomoxetine treatment. The QT interval was corrected using Bazett (QTcB) and Fridericia (QTcF) correction formulas. In these 24 patients, only the female patients had prolonged QTcB (P = 0.039) after atomoxetine treatment. There was no correlation between plasma atomoxetine concentrations and the corrected QT interval (QTc), or between atomoxetine dosage and the QTc. However, in female patients, there was a significant positive correlation between atomoxetine dosage and the QTcB (r = 0.631, P = 0.012), and there was a marginally significant positive correlation between atomoxetine dosage and the QTcF (r = 0.504, P = 0.055). In male patients, there was no correlation between atomoxetine dosage and the QTcB or QTcF intervals. There was no correlation between plasma atomoxetine concentrations and the QTc in either female or male patients. Clinicians should exhibit caution when prescribing atomoxetine, particularly for female patients.

The Application of Root Mean Square Electrocardiography (RMS ECG) for the Detection of Acquired and Congenital Long QT Syndrome

PubMed Central

Lux, Robert L.; Sower, Christopher Todd; Allen, Nancy; Etheridge, Susan P.; Tristani-Firouzi, Martin; Saarel, Elizabeth V.

2014-01-01

Background Precise measurement of the QT interval is often hampered by difficulty determining the end of the low amplitude T wave. Root mean square electrocardiography (RMS ECG) provides a novel alternative measure of ventricular repolarization. Experimental data have shown that the interval between the RMS ECG QRS and T wave peaks (RTPK) closely reflects the mean ventricular action potential duration while the RMS T wave width (TW) tracks the dispersion of repolarization timing. Here, we tested the precision of RMS ECG to assess ventricular repolarization in humans in the setting of drug-induced and congenital Long QT Syndrome (LQTS). Methods RMS ECG signals were derived from high-resolution 24 hour Holter monitor recordings from 68 subjects after receiving placebo and moxifloxacin and from standard 12 lead ECGs obtained in 97 subjects with LQTS and 97 age- and sex-matched controls. RTPK, QTRMS and RMS TW intervals were automatically measured using custom software and compared to traditional QT measures using lead II. Results All measures of repolarization were prolonged during moxifloxacin administration and in LQTS subjects, but the variance of RMS intervals was significantly smaller than traditional lead II measurements. TW was prolonged during moxifloxacin and in subjects with LQT-2, but not LQT-1 or LQT-3. Conclusion These data validate the application of RMS ECG for the detection of drug-induced and congenital LQTS. RMS ECG measurements are more precise than the current standard of care lead II measurements. PMID:24454918

The application of root mean square electrocardiography (RMS ECG) for the detection of acquired and congenital long QT syndrome.

PubMed

Lux, Robert L; Sower, Christopher Todd; Allen, Nancy; Etheridge, Susan P; Tristani-Firouzi, Martin; Saarel, Elizabeth V

2014-01-01

Precise measurement of the QT interval is often hampered by difficulty determining the end of the low amplitude T wave. Root mean square electrocardiography (RMS ECG) provides a novel alternative measure of ventricular repolarization. Experimental data have shown that the interval between the RMS ECG QRS and T wave peaks (RTPK) closely reflects the mean ventricular action potential duration while the RMS T wave width (TW) tracks the dispersion of repolarization timing. Here, we tested the precision of RMS ECG to assess ventricular repolarization in humans in the setting of drug-induced and congenital Long QT Syndrome (LQTS). RMS ECG signals were derived from high-resolution 24 hour Holter monitor recordings from 68 subjects after receiving placebo and moxifloxacin and from standard 12 lead ECGs obtained in 97 subjects with LQTS and 97 age- and sex-matched controls. RTPK, QTRMS and RMS TW intervals were automatically measured using custom software and compared to traditional QT measures using lead II. All measures of repolarization were prolonged during moxifloxacin administration and in LQTS subjects, but the variance of RMS intervals was significantly smaller than traditional lead II measurements. TW was prolonged during moxifloxacin and in subjects with LQT-2, but not LQT-1 or LQT-3. These data validate the application of RMS ECG for the detection of drug-induced and congenital LQTS. RMS ECG measurements are more precise than the current standard of care lead II measurements.

QT prolongation and proarrhythmia by moxifloxacin: concordance of preclinical models in relation to clinical outcome

PubMed Central

Chen, Xian; Cass, Jessica D; Bradley, Jenifer A; Dahm, Corinn M; Sun, Zhuoqian; Kadyszewski, Edmund; Engwall, Michael J; Zhou, Jun

2005-01-01

Moxifloxacin, a fluoroquinolone antibiotic associated with QT prolongation, has been recommended as a positive control by regulatory authorities to evaluate the sensitivity of both clinical and preclinical studies to detect small but significant increases in QT interval measurements. In this study, we investigated effects of moxifloxacin on the hERG current in HEK-293 cells, electrocardiograms in conscious telemetered dogs, and repolarization parameters and arrhythmogenic potentials in the arterially perfused rabbit ventricular wedge model. Moxifloxacin inhibited the hERG current with an IC50 of 35.7 μM. In conscious telemetered dogs, moxifloxacin significantly prolonged QTc at 30 and 90 mg kg−1, with mean serum Cmax of 8.52 and 22.3 μg ml−1, respectively. In the wedge preparation, moxifloxacin produced a concentration-dependent prolongation of the action potential duration, QT interval, and the time between peak and end of the T wave, an indicator for transmural dispersion of repolarization. Phase 2 early after-depolarizations were observed in one of five experiments at 30 μM and five of five experiments at 100 μM. The arrhythmogenic potential was also concentration-dependent, and 100 μM (∼18-fold above the typical unbound Cmax exposure in clinical usage) appeared to have a high risk of inducing torsade de pointes (TdP). Our data indicated a good correlation among the concentration–response relationships in the three preclinical models and with the available clinical data. The lack of TdP report by moxifloxacin in patients without other risk factors might be attributable to its well-behaved pharmacokinetic profile and other dose-limiting effects. PMID:16158069

Left Ventricular Isovolumetric Relaxation Time Is Prolonged in Fetal Long-QT Syndrome.

PubMed

Clur, Sally-Ann B; Vink, Arja S; Etheridge, Susan P; Robles de Medina, Pascale G; Rydberg, Annika; Ackerman, Michael J; Wilde, Arthur A; Blom, Nico A; Benson, D Woodrow; Herberg, Ulrike; Donofrio, Mary T; Cuneo, Bettina F

2018-04-01

Long-QT syndrome (LQTS), an inherited cardiac repolarization disorder, is an important cause of fetal and neonatal mortality. Detecting LQTS prenatally is challenging. A fetal heart rate (FHR) less than third percentile for gestational age is specific for LQTS, but the sensitivity is only ≈50%. Left ventricular isovolumetric relaxation time (LVIRT) was evaluated as a potential diagnostic marker for fetal LQTS. LV isovolumetric contraction time, LV ejection time, LVIRT, cycle length, and FHR were measured using pulsed Doppler waveforms in fetuses. Time intervals were expressed as percentages of cycle length, and the LV myocardial performance index was calculated. Single measurements were stratified by gestational age and compared between LQTS fetuses and controls. Receiver-operator curves were performed for FHR and normalized LVIRT (N-LVIRT). A linear mixed-effect model including multiple measurements was used to analyze trends in FHR, N-LVIRT, and LV myocardial performance index. There were 33 LQTS fetuses and 469 controls included. In LQTS fetuses, the LVIRT was prolonged in all gestational age groups ( P <0.001), as was the N-LVIRT. The best cutoff to diagnose LQTS was N-LVIRT ≥11.3 at ≤20 weeks (92% sensitivity, 70% specificity). Simultaneous analysis of N-LVIRT and FHR improved the sensitivity and specificity for LQTS (area under the curve=0.96; 95% confidence interval, 0.82-1.00 at 21-30 weeks). N-LVIRT, LV myocardial performance index, and FHR trends differed significantly between LQTS fetuses and controls through gestation. The LVIRT is prolonged in LQTS fetuses. Findings of a prolonged N-LVIRT and sinus bradycardia can improve the prenatal detection of fetal LQTS. © 2018 American Heart Association, Inc.

Obstructive Sleep Apnea in Patients with Congenital Long QT Syndrome: Implications for Increased Risk of Sudden Cardiac Death.

PubMed

Shamsuzzaman, Abu S; Somers, Virend K; Knilans, Timothy K; Ackerman, Michael J; Wang, Yu; Amin, Raouf S

2015-07-01

Congenital long QT syndrome (LQTS) is a familial arrhythmogenic cardiac channelopathy characterized by prolonged ventricular repolarization and increased risk of torsades de pointes-mediated syncope, seizures, and sudden cardiac death (SCD). QT prolongation corrected for heart rate (QTc) is an important diagnostic and prognostic feature in LQTS. Obstructive sleep apnea (OSA) has been increasingly implicated in the pathogenesis of cardiovascular disease, including arrhythmias and SCD. We tested the hypothesis that the presence of concomitant OSA in patients with LQTS is associated with increased QT intervals, both during sleep and while awake. Polysomnography with simultaneous overnight 12-lead electrocardiography (ECG) was recorded in 54 patients with congenital LQTS and 67 control subjects. OSA was diagnosed as apnea-hypopnea index (AHI) ≥ 5 events/h for adults and AHI > 1 event/h for children. RR and QT intervals were measured from the 12-lead surface ECG. QTc was determined by the Bazett formula. Respiratory disturbance index, AHI, and arousal index were significantly increased in patients with LQTS and with OSA compared to those without OSA and control subjects. QTc during different sleep stages and while awake was also significantly increased in patients with LQTS and OSA compared to those without OSA. Severity of OSA in patients with LQTS was directly associated with the degree of QTc. The presence and severity of obstructive sleep apnea (OSA) in patients with congenital long QT syndrome (LQTS) is associated with increased QT prolongation corrected for heart rate, which is an important biomarker of sudden cardiac death (SCD). Treatment of OSA in LQTS patients may reduce QT prolongation, thus reducing the risk of LQT-triggered SCD. © 2015 Associated Professional Sleep Societies, LLC.

Confronting the ’Essence of Decision’: Canada and the Cuban Missile Crisis

DTIC Science & Technology

2010-11-01

des mesures de guerre approuvé comme la principale cause du délai prolongé que l’on a connu. La présente étude a démontré que des ... du contrôle civil de l’armée. En réalité, cette hypothèse comprend deux volets. D’une part, de quelles mesures disposaient le MDN et la haute...vastes forces en devenir, s’est installée dans les processus nationaux de planification stratégique et de reconnaissance de la

Role of Country of Birth, Testing Site, and Neighborhood Characteristics on Nonlinkage to HIV Care Among Latinos.

PubMed

Sheehan, Diana M; Cosner, Chelsea; Fennie, Kristopher P; Gebrezgi, Merhawi T; Cyrus, Elena; Maddox, Lorene M; Levison, Julie H; Spencer, Emma C; Niyonsenga, Theophile; Trepka, Mary Jo

2018-04-01

The objective of this study was to estimate disparities in linkage to human immunodeficiency virus (HIV) care among Latinos by country/region of birth, HIV testing site, and neighborhood characteristics. A retrospective study was conducted using Florida HIV surveillance records of Latinos/Hispanics aged ≥13 diagnosed during 2014-2015. Linkage to HIV care was defined as a laboratory test (HIV viral load or CD4) within 3 months of HIV diagnosis. Multi-level Poisson regression models were used to estimate adjusted prevalence ratios (aPR) for nonlinkage to care. Of 2659 Latinos, 18.8% were not linked to care within 3 months. Compared with Latinos born in mainland United States, those born in Cuba [aPR 0.60, 95% confidence interval (CI) 0.47-0.76] and Puerto Rico (aPR 0.61, 95% CI 0.41-0.90) had a decreased prevalence of nonlinkage. Latinos diagnosed at blood banks (aPR 2.34, 95% CI 1.75-3.12), HIV case management and screening facilities (aPR 1.76, 95% CI 1.46-2.14), and hospitals (aPR 1.42, 95% CI 1.03-1.96) had an increased prevalence of nonlinkage compared with outpatient general, infectious disease, and tuberculosis/sexually transmitted diseases/family planning clinics. Latinos who resided in the lowest (aPR 1.57, 95% CI 1.19-2.07) and third lowest (aPR 1.33, 95% CI 1.01-1.76) quartiles of neighborhood socioeconomic status compared with the highest quartile were at increased prevalence. Latinos who resided in neighborhoods with <25% Latinos also had increased prevalence of nonlinkage (aPR 1.23, 95% CI 1.01-1.51). Testing site at diagnosis may be an important determinant of HIV care linkage among Latinos due to neighborhood or individual-level resources that determine location of HIV testing.

Is self interdental cleaning associated with dental plaque levels, dental calculus, gingivitis and periodontal disease?

PubMed

Crocombe, L A; Brennan, D S; Slade, G D; Loc, D O

2012-04-01

To ascertain whether interdental cleaning behaviours of Australian adults were associated with lower levels of plaque, gingivitis and periodontal disease. Data were obtained from the National Survey of Adult Oral Health 2004-06. Outcome variables were three indicators of oral hygiene outcomes (the presence or not of dental plaque, dental calculus and gingivitis) and two of periodontal disease (the presence or not of at least one tooth with a periodontal pocket or clinical attachment loss of ≥ 4 mm). The independent variable was classified into the following three groups: regularly clean interproximally 'at least daily' (daily+); 'less than daily' (< daily); and 'do not regularly clean interproximally' (reference group). Poisson regression with robust variance estimation was used to calculate prevalence ratios (PRs) and 95% confidence intervals (95% CIs) relative to the reference group, adjusted for covariates. Regular self interdental cleaning was associated with less dental plaque (< daily, PR = 0.89, 95% CI = 0.84, 0.95; and daily+, PR = 0.89, 95% CI = 0.82, 0.96), less dental calculus (< daily, PR = 0.88, 95% CI = 0.80, 0.97; and daily+, PR = 0.79, 95% CI = 0.70, 0.89) and lower levels of moderate/severe gingivitis (daily+, PR = 0.85, 95% CI = 0.77, 0.94). Periodontal pocketing was less likely for the < daily group (PR = 0.61, 95% CI = 0.46, 0.82), but was not associated with daily+ cleaning (PR = 0.99, 95% CI = 0.663, 1.49). There was not a significant association between interdental cleaning and clinical attachment loss (< daily, PR = 0.90, 95% CI = 0.77, 1.05; and daily+, PR = 1.17, 95% CI = 0.95, 1.44). Regular interdental cleaning was associated with better oral hygiene outcomes, such as dental plaque and gingivitis, although there was no significant association between regular interdental cleaning and clinical attachment loss. © 2011 John Wiley & Sons A/S.

ESRD among Immigrants to Ontario, Canada: A Population-Based Study.

PubMed

Perl, Jeffrey; McArthur, Eric; Tan, Vivian S; Nash, Danielle M; Garg, Amit X; Harel, Ziv; Li, Alvin H; Sood, Manish M; Ray, Joel G; Wald, Ron

2018-05-02

Background The epidemiology of ESRD requiring maintenance dialysis (ESRD-D) in large, diverse immigrant populations is unclear. Methods We estimated ESRD-D prevalence and incidence among immigrants in Ontario, Canada. Adults residing in Ontario in 2014 were categorized as long-term Canadian residents or immigrants according to administrative health and immigration datasets. We determined ESRD-D prevalence among these adults and calculated age-adjusted prevalence ratios (PRs) comparing immigrants to long-term residents. Among those who immigrated to Ontario between 1991 and 2012, age-adjusted ESRD-D incidence was calculated by world region and country of birth, with immigrants from Western nations as the referent group. Results Among 1,902,394 immigrants and 8,860,283 long-term residents, 1700 (0.09%) and 8909 (0.10%), respectively, presented with ESRD-D. Age-adjusted ESRD-D prevalence was higher among immigrants from sub-Saharan Africa (PR, 2.17; 95% confidence interval [95% CI], 1.84 to 2.57), Latin America and the Caribbean (PR, 2.11; 95% CI, 1.90 to 2.34), South Asia (PR, 1.45; 95% CI, 1.32 to 1.59), and East Asia and the Pacific (PR, 1.34; 95% CI, 1.22 to 1.46). Immigrants from Somalia (PR, 4.18; 95% CI, 3.11 to 5.61), Trinidad and Tobago (PR, 2.88; 95% CI, 2.23 to 3.73), Jamaica (PR, 2.88; 95% CI, 2.40 to 3.44), Sudan (PR, 2.84; 95% CI, 1.53 to 5.27), and Guyana (PR, 2.69; 95% CI, 2.19 to 3.29) had the highest age-adjusted ESRD-D PRs relative to long-term residents. Immigrants from these countries also exhibited higher age-adjusted ESKD-D incidence relative to Western Nations immigrants. Conclusions Among immigrants in Canada, those from sub-Saharan Africa and the Caribbean have the highest ESRD-D risk. Tailored kidney-protective interventions should be developed for these susceptible populations. Copyright © 2018 by the American Society of Nephrology.

A comparison of the results obtained with traditional phlebotomy and with therapeutic erythrocytapheresis in patients with erythrocytosis

PubMed Central

Vecchio, Sisto; Leonardo, Patrizia; Musuraca, Vittoria; D'Ettoris, Anna Rita; Geremicca, Walter

2007-01-01

Background Phlebotomy is the most commonly treatment used for erythrocytosis and polycythaemia. After the introduction in the medical practice of cell separators, erythrocytapheresis has been also introduced. The aim of the study was to compare the clinical results of the two kinds of treatment. Patients and methods We analysed 98 patients affected by different forms of erythrocytosis, divided into three treatment groups: 1) patients undergoing phlebotomy; 2) patients treated only with therapeutic erythrocytapheresis; 3) patients who underwent phlebotomy treatment for a certain period and who were then switched to apheresis treatment. The haematocrit in these patients was maintained at about 45% and they were treated when the haematocrit exceeded the critical threshold of 50%. Results The interval between two therapeutic interventions was assumed as indicator. In 80% of the patients treated only with phlebotomy the interval was between 20 days and 2 months, in subjects treated with only erythrocytapheresis the intevals were between 2 and 7 months. In the third group of patients, the switch from phlebotomy to erythrocytapheresis considerably prolonged the interval. Conclusions The data showed that erythrocytapheresis was clearly superior to traditional phlebotomy in terms of prolonging the period between one treatment and another, independently of the type of erythrocytosis and of the treatment group. PMID:19204747

A comparative dose-effect study with cardiac glycosides assessing cardiac and extracardiac responses in normal subjects.

PubMed

Alken, R G; Belz, G G

1984-01-01

We tested the hypothesis that differences exist in the pharmacodynamic pattern of different cardiac glycosides. We conducted a randomized, placebo-controlled study in normal volunteers and evaluated the effects of weekly increased oral dosing of digoxin (n = 10; from 0.25 to 1.0 mg/day), meproscillarin (n = 10; from 0.5 to 2.0 mg/day), and placebo (n = 5). To determine the glycoside effects, corrected electromechanical systole (QS2c) was used to measure inotropy and the PQ interval to test dromotropy. Red-green discrimination and critical flicker fusion (CFF) assessed visual functions. Subjective complaints were collected using rating lists. Both glycosides dose dependently shortened QS2c and prolonged PQ interval. PQ prolongations over +20 ms occurred in seven of 10 digoxin subjects, in two of 10 meproscillarin, and in one of five placebo. Equi-inotropic response, identified at 12 ms mean QS2c shortening, revealed the relative potency of digoxin to be 2.4 times higher than meproscillarin; this ratio increased to sevenfold for equi-effective negative dromotropic effects at 12 ms mean PQ prolongation. Each drug was associated with a dominant subjective complaint: digoxin with anergy and meproscillarin with diarrhea. Red-green discrimination was better under meproscillarin and CFF was depressed by digoxin. The results indicate that pharmacodynamic differences exist between cardiac glycosides. A differential use of various glycosides should be considered and tested clinically.

Homogenous photocatalytic decontamination of prion infected stainless steel and titanium surfaces.

PubMed

Berberidou, Chrysanthi; Xanthopoulos, Konstantinos; Paspaltsis, Ioannis; Lourbopoulos, Athanasios; Polyzoidou, Eleni; Sklaviadis, Theodoros; Poulios, Ioannis

2013-01-01

Prions are notorious for their extraordinary resistance to traditional methods of decontamination, rendering their transmission a public health risk. Iatrogenic Creutzfeldt-Jakob disease (iCJD) via contaminated surgical instruments and medical devices has been verified both experimentally and clinically. Standard methods for prion inactivation by sodium hydroxide or sodium hypochlorite have failed, in some cases, to fully remove prion infectivity, while they are often impractical for routine applications. Prion accumulation in peripheral tissues and indications of human-to-human bloodborne prion transmission, highlight the need for novel, efficient, yet user-friendly methods of prion inactivation. Here we show both in vitro and in vivo that homogenous photocatalytic oxidation, mediated by the photo-Fenton reagent, has the potential to inactivate the pathological prion isoform adsorbed on metal substrates. Photocatalytic oxidation with 224 μg mL(-1) Fe (3+), 500 μg mL(-1) h(-1) H 2O 2, UV-A for 480 min lead to 100% survival in golden Syrian hamsters after intracranial implantation of stainless steel wires infected with the 263K prion strain. Interestingly, photocatalytic treatment of 263K infected titanium wires, under the same experimental conditions, prolonged the survival interval significantly, but failed to eliminate infectivity, a result that we correlate with the increased adsorption of PrP(Sc) on titanium, in comparison to stainless steel. Our findings strongly indicate that our, user--and environmentally--friendly protocol can be safely applied to the decontamination of prion infected stainless steel surfaces.

Mammalian enabled (Mena) is a critical regulator of cardiac function

PubMed Central

Aguilar, Frédérick; Belmonte, Stephen L.; Ram, Rashmi; Noujaim, Sami F.; Dunaevsky, Olga; Protack, Tricia L.; Jalife, Jose; Todd Massey, H.; Gertler, Frank B.

2011-01-01

Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena−/−) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena−/− mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena−/− hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena−/− mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction. PMID:21335464

Mammalian enabled (Mena) is a critical regulator of cardiac function.

PubMed

Aguilar, Frédérick; Belmonte, Stephen L; Ram, Rashmi; Noujaim, Sami F; Dunaevsky, Olga; Protack, Tricia L; Jalife, Jose; Todd Massey, H; Gertler, Frank B; Blaxall, Burns C

2011-05-01

Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.

ECG-ViEW II, a freely accessible electrocardiogram database

PubMed Central

Park, Man Young; Lee, Sukhoon; Jeon, Min Seok; Yoon, Dukyong; Park, Rae Woong

2017-01-01

The Electrocardiogram Vigilance with Electronic data Warehouse II (ECG-ViEW II) is a large, single-center database comprising numeric parameter data of the surface electrocardiograms of all patients who underwent testing from 1 June 1994 to 31 July 2013. The electrocardiographic data include the test date, clinical department, RR interval, PR interval, QRS duration, QT interval, QTc interval, P axis, QRS axis, and T axis. These data are connected with patient age, sex, ethnicity, comorbidities, age-adjusted Charlson comorbidity index, prescribed drugs, and electrolyte levels. This longitudinal observational database contains 979,273 electrocardiograms from 461,178 patients over a 19-year study period. This database can provide an opportunity to study electrocardiographic changes caused by medications, disease, or other demographic variables. ECG-ViEW II is freely available at http://www.ecgview.org. PMID:28437484

Evaluation of the electromechanical properties of the cardiovascular system after prolonged weightlessness

NASA Technical Reports Server (NTRS)

Bergman, S. A., Jr.; Johnson, R. L.; Hoffler, G. W.

1977-01-01

Devices and techniques for measuring and analyzing systolic time intervals and quantitative phonocardiograms were initiated during Apollo 17. The data show that the systolic time interval from Apollo 17 crewmen remained elevated longer postflight than the response criteria of heart rate, blood pressure, and percent change in leg volume all of which had returned to preflight levels by the second day postflight. Although the systolic time interval values were only slightly outside the preflight fiducial limits, this finding suggested that: the analysis of systolic time intervals may help to identify the mechanisms of postflight orthostatic intolerance by virtue of measuring ventricular function more directly and, the noninvasive technique may prove useful in determining the extent and duration of cardiovascular instability after long duration space flight. The systolic time intervals obtained on the Apollo 17 crewmen during lower body negative pressure were similar to those noted in patients with significant heart disease.

Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.

PubMed

Durairaj, Chandrasekar; Ruiz-Garcia, Ana; Gauthier, Eric R; Huang, Xin; Lu, Dongrui R; Hoffman, Justin T; Finn, Richard S; Joy, Anil A; Ettl, Johannes; Rugo, Hope S; Zheng, Jenny; Wilner, Keith D; Wang, Diane D

2018-03-01

The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia's correction (QTcF), Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent.

The QT interval in lightning injury with implications for the cessation of metabolism hypothesis

NASA Technical Reports Server (NTRS)

Andrews, Christopher J.; Colquhoun, David M.; Darveniza, Mat

1991-01-01

An hypothesis is presented to provide an alternative to the Cessation of Metabolism hypothesis often invoked in lightning injury. Cessation of Metabolism has been proposed to explain the observation of good recovery after a prolonged period in cardiac arrest in some lightning injured patients. Reevaluation of EEGs from lightning injured patients show a high incidence of QT prolongation. Reexamination of the cases used to support Cessation of Metabolism also reveals little evidence to justify the hypothesis. The finding of QT prolongation coupled with the hyperadrenergic state said to exist in lightning injury, may promote a state of episodic induction of and recovery from Torsade de Pointes Ventricular Tachycardia (VT). Histological examination of the myocardium supports the new hypothesis. This the first concerted description of lightning injury as one of the general causes of QT prolongation. It appears to occur frequently after lightning injury, is a prerequisite of and predisposes to episodes of Torsade de Pointes VT. These electrocardiographic abnormalities explain Cessation of Metabolism and recognition may change management and lead to greater survival.

Effects of intervals between jumps or bouts on osteogenic response to loading.

PubMed

Umemura, Yoshihisa; Sogo, Naota; Honda, Akiko

2002-10-01

Prolonged loading repetitions can diminish the mechanosensitivity of bones, and increased intervals between loading might restore sensitivity. This study was designed to investigate the effects of intervals between loadings or bouts on osteogenic response. Forty female Fisher 344 rats aged 5 wk were divided into a control group and three exercise groups: 20 jumps in a single bout with a 3-s (S3) or 30-s (S30) jump interval, or 20 jumps in 2 bouts (10 x 2) separated by a 6-h interval with a 3-s jump interval (D3). After 8 wk of training, the bone masses per body weight of the femur and tibia were significantly greater in the three exercise groups than in the control group, and these values were also greater in S30 than in S3, although they were at the same level in D3 and S3. These data suggest that a longer interval (30 s) between individual loading had more effective anabolic effects on bone than a shorter interval (3 s).

A question about the potential cardiac toxicity of escitalopram.

PubMed

Howland, Robert H

2012-04-01

Previous reviews have focused on the potential cardiac toxicity of the racemic drug citalopram (Celexa(®)). Evaluating the safety of escitalopram (Lexapro(®)) is an important issue to consider, since it is the S-enantiomer of citalopram. Escitalopram has a small effect on the QTc interval. A prolonged QTc was seen in 2% to 14% of escitalopram overdose cases, without serious cardiac sequelae. The QTc prolongation effect of citalopram in beagle dogs has been attributed to the minor metabolite racemic didemethylcitalopram (DDCT). Whether the escitalopram minor metabolite S-DDCT has this effect is not known. Concentrations of S-DDCT are lower than DDCT, but for a broad range of doses of escitalopram and citalopram, the S-DDCT and DDCT concentrations are well below the QTc prolonging concentrations reported in dogs. There is no strong evidence from human and animal studies that the cardiac safety of escitalopram is significantly superior to that of citalopram. Copyright 2012, SLACK Incorporated.

Risk management of QTc-prolongation in patients receiving haloperidol: an epidemiological study in a University hospital in Belgium.

PubMed

Vandael, Eline; Vandenberk, Bert; Vandenberghe, Joris; Spriet, Isabel; Willems, Rik; Foulon, Veerle

2016-04-01

Many drugs, including haloperidol, are linked with a risk of QTc-prolongation, which can lead to Torsade de Pointes and sudden cardiac death. To investigate the prevalence of concomitant risk factors for QTc-prolongation in patients treated with haloperidol, and the use of safety measures to minimize this risk. University Hospitals of Leuven, Belgium. Methods A retrospective epidemiological study was performed. On 15 consecutive Mondays, all patients with a prescription for haloperidol were included. A risk score for QTc-prolongation, inspired by the pro-QTc score of Haugaa et al., was calculated based on gender, comorbidities, lab results and concomitant QTc-prolonging drugs (each factor counting for one point). Available electrocardiograms before and during the treatment of haloperidol were registered. Management of the risk of QTc-prolongation. Two hundred twenty-two patients were included (59.0 % men, median age 77 years) of whom 26.6 % had a risk score of ≥4 (known to significantly increase the mortality). Overall, 24.3 % received haloperidol in combination with other drugs with a known risk of Torsade de Pointes. Half of the patients had an electrocardiogram in the week before the start of haloperidol; only in one-third a follow-up electrocardiogram during haloperidol treatment was performed. Of the patients with a moderately (n = 41) or severely (n = 14) prolonged QTc-interval before haloperidol, 48.8 % and 42.9 % respectively had a follow-up electrocardiogram. In patients with a risk score ≥4, significantly more electrocardiograms were taken before starting haloperidol (p = 0.020). Although many patients had risk factors for QTc-prolongation (including the use of other QTc-prolonging drugs) or had a prolonged QTc on a baseline electrocardiogram, follow-up safety measures were limited. Persistent efforts should be taken to develop decision support systems to manage this risk.

Recurring patterns of atrial fibrillation in surface ECG predict restoration of sinus rhythm by catheter ablation.

PubMed

Di Marco, Luigi Yuri; Raine, Daniel; Bourke, John P; Langley, Philip

2014-11-01

Non-invasive tools to help identify patients likely to benefit from catheter ablation (CA) of atrial fibrillation (AF) would facilitate personalised treatment planning. To investigate atrial waveform organisation through recurrence plot indices (RPI) and their ability to predict CA outcome. One minute 12-lead ECG was recorded before CA from 62 patients with AF (32 paroxysmal AF; 45 men; age 57±10 years). Organisation of atrial waveforms from i) TQ intervals in V1 and ii) QRST suppressed continuous AF waveforms (CAFW), were quantified using RPI: percentage recurrence (PR), percentage determinism (PD), entropy of recurrence (ER). Ability to predict acute (terminating vs. non-terminating AF), 3-month and 6-month postoperative outcome (AF vs. AF free) were assessed. RPI either by TQ or CAFW analysis did not change significantly with acute outcome. Patients arrhythmia-free at 6-month follow-up had higher organisation in TQ intervals by PD (p<0.05) and ER (p<0.005) and both were significant predictors of 6-month outcome (PD (AUC=0.67, p<0.05) and ER (AUC=0.72, p<0.005)). For paroxysmal AF cases, all RPI predicted 3-month (AUC(ER)=0.78, p<0.05; AUC(PD)=0.79, p<0.05; AUC(PR)=0.80, p<0.01) and 6-month (AUC(ER)=0.81, p<0.005; AUC(PD)=0.75, p<0.05; AUC(PR)=0.71, p<0.05) outcome. CAFW-derived RPIs did not predict acute or postoperative outcomes. Higher values of any RPI from TQ (values greater than 25th percentile of preoperative distribution) were associated with decreased risk of AF relapse at follow-up (hazard ratio ≤0.52, all p<0.05). Recurring patterns from preprocedural 1-minute recordings of ECG TQ intervals were significant predictors of CA 6-month outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association of Hormone-Related Characteristics and Breast Cancer Risk by Estrogen Receptor/Progesterone Receptor Status in the Shanghai Breast Cancer Study

PubMed Central

Bao, Ping-Ping; Shu, Xiao Ou; Gao, Yu-Tang; Zheng, Ying; Cai, Hui; Deming, Sandra L.; Ruan, Zhi-Xian; Gu, Kai; Lu, Wei; Zheng, Wei

2011-01-01

Etiologic differences between subtypes of breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status are not well understood. The authors evaluated associations of hormone-related factors with breast cancer subtypes in a population-based case-control study involving 1,409 ER-positive (ER+)/PR-positive (PR+) cases, 712 ER-negative (ER−)/PR-negative (PR−) cases, 301 ER+/PR− cases, 254 ER−/PR+ cases, and 3,474 controls aged 20–70 years in Shanghai, China (phase I, 1996–1998; phase II, 2002–2005). Polytomous logistic regression and Wald tests for heterogeneity across subtypes were conducted. Breast cancer risks associated with age at menarche, age at menopause, breastfeeding, age at first livebirth, waist-to-hip ratio, and oral contraceptive use did not differ by hormone receptor status. Among postmenopausal women, higher parity (≥2 children vs. 1) was associated with reduced risk (odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.52, 0.91) and higher body mass index (BMI; weight (kg)/height (m)2) with increased risk (highest quartile: OR = 2.40, 95% CI: 1.65, 3.47) of the ER+/PR+ subtype but was unrelated to the ER−/PR− subtype (for parity, Pheterogeneity = 0.02; for BMI, Pheterogeneity < 0.01). Hormone replacement therapy (OR = 2.25, 95% CI: 1.40, 3.62) and alcohol consumption (OR = 1.59, 95% CI: 1.01, 2.51) appeared to be preferentially associated with the ER+/PR− subtype. These findings indicate that BMI, parity, hormone replacement therapy, and alcohol consumption may play different roles in subtypes of breast cancer. More research is needed to better understand the etiology of 2 relatively rare subtypes, ER+/PR− tumors and ER−/PR+ tumors. PMID:21768404

Predictors of Recall Certainty of Dates of Analgesic Medication Use in Pregnancy

PubMed Central

Radin, Rose G.; Mitchell, Allen A.; Werler, Martha M.

2012-01-01

Purpose Recalled dates of medication use are difficult to validate, particularly for over-the-counter (OTC) medications. We evaluated mothers’ recall certainty as an approximation of the accuracy of their recalled exposures. Methods We used data from the Slone Epidemiology Center Birth Defects Study collected by retrospective interview of women about pregnancy medication use. For each medication reported, women were asked to report the dates of their use and how certain they were of their reported dates. For this analysis, 32,107 reports from 14,577 analgesic users were categorized as ‘high’ or ‘low’ recall certainty if they considered a reported date as exact or estimated, respectively. Patterns of analgesic use, maternal demographics, and health behaviors were explored as predictors of high recall certainty of dates of analgesic use. We used log-binomial regression with the generalized estimating equations extension to account for multiple reports per subject in estimating prevalence ratios (PR) and 95% confidence intervals. Results Relative to episodes of short-term routine use (≥4 times/week for ≤30 days), high recall certainty was more likely for episodes of a single dose (prescription PR=1.92 (1.61, 2.27); OTC PR=3.65 (3.03, 4.40)) and less likely for episodes of occasional use (prescription PR=0.10 (0.05, 0.18); OTC PR=0.65 (0.53, 0.79)). The association of chronic routine use with high recall certainty was inverse among prescription analgesics and positive among OTC analgesics (prescription PR=0.56 (0.40, 0.80); OTC PR=2.46 (1.92, 3.42)). Conclusions Some characteristics that were associated with recall accuracy in previous studies were also associated with recall certainty in this study. PMID:22674801

[External workplace violence against doctors in hospital services in Lima Metropolitana, Peru 2014].

PubMed

Tuya-Figueroa, Ximena; Mezones-Holguin, Edward; Monge, Eduardo; Arones, Ricardo; Mier, Milagros; Saravia, Mercedes; Torres, Jose; Mayta-Tristán, Percy

2016-01-01

. To calculate the frequency and factors associated with external workplace violence (EWV) against doctors in health inpatient services in the metropolitan area of Lima (Spanish: Lima Metropolitana), Peru. . A cross-sectional analytic study, which included doctors from the Ministry of Health (MINSA), Social Security (EsSalud), and the private subsector, was carried out. The frequency of EWV was measured throughout the entire professional practice during the previous 12 months and during the last month. Variables related to the doctor, assailant, and health service were measured. Raw and adjusted prevalence ratios (PR) were calculated by means of a Poisson-family generalized linear model with non-parametric bootstrapping. . A total of 406 doctors participated; 31.5% were victims of EWV at least once during their professional practice, with 19.9% over the past 12 months and 7.6% during the last month. The chances of being threatened in the last 12 months increased if the doctor was male (adjusted PR [aPR]: 1.7; 95% confidence interval [CI] = 1.1- 2.8), had graduated from a Peruvian university outside of the metropolitan area of Lima (aPR: 1.5; 95% CI = 1.1-2.4), worked at MINSA (aPR: 7.9; 95% CI = 2.24-50.73) or EsSalud (RR: 8.68; 95% CI = 2.26-56.17), and worked in the emergency (aPR: 1.9; 95% CI = 1.2-3.6) or operating room (aPR: 1.6; 95% CI = 1.1-2.3). Age, years of professional practice, or being a medical resident were not associated with EWV. . In the hospitals studied, a large number of doctors have been victims of EWV. Working in public services increases the possibility of violence. Implementation of support, identification, and primary prevention strategies in hospitals is recommended.

Abnormalities of the QT interval in primary disorders of autonomic failure

NASA Technical Reports Server (NTRS)

Choy, A. M.; Lang, C. C.; Roden, D. M.; Robertson, D.; Wood, A. J.; Robertson, R. M.; Biaggioni, I.

1998-01-01

BACKGROUND: Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. SUBJECTS AND METHODS: Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. RESULTS: Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P < .05 and P < .01, respectively). A similar but not significant trend was observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P < .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not have significantly different RR, QT, QTc intervals, or QTc dispersion when compared with controls. CONCLUSIONS: Patients with primary autonomic failure who have combined parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not solely caused by lesions of the sympathetic nervous system, and that the parasympathetic nervous system is likely to have a modulatory role in ventricular repolarization.

Dispersion of the corrected QT interval in the electrocardiogram of the ex-prisoners of war.

PubMed

Corović, Naima; Duraković, Zijad; Misigoj-Duraković, Marjeta

2003-04-01

The study of electrocardiograms (ECGs) was performed in a subgroup of 181 men, ex-prisoners of war with mean age 35.8+/-11.0 years and mean duration of imprisonment 164.5+/-87.1 days, chosen at random from the total sample of released prisoners (N=1458). The control group was pair-matched. The analysis of ECGs was done according to the Minnesota code, and Bazett's formula gave the values of the corrected QT interval (QT(c)). The dispersion of the QT(c) interval is determined by the difference between the longest and the shortest measured QT(c) interval in each ECG lead. The results of descriptive statistics in the group of ex-prisoners showed the range of QT(c) dispersion of 8.0-122.0 ms (mean 52.4+/-21.6 ms), while in the control group the range was 6.0-72.0 ms (mean 30.4+/-13.8 ms) (df=360, t=11.536; P<0.001). The QT(c) interval from 422.0 to 480.0 ms had 60.2% ex-prisoners and 30.4% controls, while a QT(c) interval over 480.0 ms had 19.3% ex-prisoners and 1.10% controls (P<0.0001). In the ex-prisoners group, the QT(c) dispersion over 50 ms was present in 51.4%; of those, a dispersion of 95 ms and more was found in 3.9%, while in the controls a QT(c) dispersion over 50 ms was found in 8.3%, but a dispersion of 95 ms and more was not recorded (P<0.0001). The odds ratio estimated for the prolonged QT(c) interval was 8.467 and for enlarged QT(c) dispersion it was 11.695 in the ex-prisoners versus controls (P<0.001). In conclusion, persons exposed to long-term maltreatment in detention camps have significantly greater QT(c) dispersion, as well as a higher relative risk of prolonged QT(c) interval and greater QT(c) dispersion than a control group.

Tachycardia-dependent augmentation of "notched J waves" in a general patient population without ventricular fibrillation or cardiac arrest: not a repolarization but a depolarization abnormality?

PubMed

Aizawa, Yoshifusa; Sato, Masahito; Kitazawa, Hitoshi; Aizawa, Yoshiyasu; Takatsuki, Seiji; Oda, Eiji; Okabe, Masaaki; Fukuda, Keiichi

2015-02-01

J waves can be observed in individuals of the general population, but electrocardiographic characteristics are poorly understood. The purpose of this study was to examine the J-wave dynamicity in a general patient population. The responses of J waves (>0.1 mV above the isoelectric line in 2 contiguous leads) to varying RR intervals were analyzed. Patients with aborted sudden cardiac death, documented ventricular fibrillation, or a family history of sudden cardiac death were excluded. The J-wave amplitude was measured at baseline, in beats with short RR intervals in conducted atrial premature beats (APBs) or atrial stimulation during the electrophysiology study, and in the beats next to APBs with prolonged RR intervals. Mainly notched J waves were identified in 94 of 701 (24.5%) general patients (13.4%), and APBs were present in 23 of 94 (24.5%) patients. The mean baseline amplitude of J waves was 0.20 ± 0.06 mV at the baseline RR interval of 853 ± 152 ms, 0.25 ± 0.11 mV at the RR interval in the conducted APB of 545 ± 133 ms (P = .0018), and 0.19 ± 0.08 mV at the RR interval of 1146 ± 314 ms (P = .3102). The clinical characteristics were not different between patients with and without tachycardia-dependent augmentation of J waves. Augmentation of J waves was confirmed by the electrophysiology study: 0.28 ± 0.12 mV vs 0.42 ± 0.11 mV at baseline and in the beats of atrial stimulation, respectively (P = .0001). However, no bradycardia-dependent augmentation (>0.05 mV) was observed. Such tachycardia-dependent augmentation can represent depolarization abnormality rather than repolarization abnormality. J waves in a general patient population were augmented at shorter RR intervals, but not at prolonged RR intervals. Mechanistically, conduction delay is most likely responsible for this. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

[Complete atrioventricular block in Duchenne muscular dystrophy].

PubMed

Kuru, Satoshi; Tanahashi, Tamotsu; Matsumoto, Shinjirou; Kitamura, Tetsuya; Konagaya, Masaaki

2012-01-01

We report a case of complete atrioventricular (AV) block in a 40-year-old patient with Duchenne muscular dystrophy (DMD). While he was bed-ridden and required mechanical ventilation, his cardiac involvement was mild. He had the deletion of exon 45-52 in the dystrophin gene. He underwent transient complete AV block and came to require pacemaker implantation due to recurrence of complete AV block ten days after the first attack. Electrophysiological study revealed mild prolonged AH and HV interval. Although DMD patients with AV block have been rarely reported so far, attention should be paid to AV block for patients who prolonged their lives.

Perioperative management of patients with congenital or acquired disorders of the QT interval.

PubMed

O'Hare, M; Maldonado, Y; Munro, J; Ackerman, M J; Ramakrishna, H; Sorajja, D

2018-04-01

QT prolongation can be attributable to various causes that can be categorised as acquired or congenital. Arrhythmias related to QT prolongation can result in clinical presentations, such as syncope and sudden cardiac death. The perioperative period presents a number of issues that may affect a patient's risk of developing polymorphic ventricular tachycardia or torsades de pointes. Although most patients may have an unremarkable perioperative course, some may have complications; this review article aims to help clinicians avoid potential complications, and to help them address treatment for perioperative issues that may occur. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

High level of oxygen treatment causes cardiotoxicity with arrhythmias and redox modulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapalamadugu, Kalyan C.; Panguluri, Siva K.; Bennett, Eric S.

2015-01-01

Hyperoxia exposure in mice leads to cardiac hypertrophy and voltage-gated potassium (Kv) channel remodeling. Because redox balance of pyridine nucleotides affects Kv function and hyperoxia alters cellular redox potential, we hypothesized that hyperoxia exposure leads to cardiac ion channel disturbances and redox changes resulting in arrhythmias. In the present study, we investigated the electrical changes and redox abnormalities caused by 72 h hyperoxia treatment in mice. Cardiac repolarization changes were assessed by acquiring electrocardiogram (ECG) and cardiac action potentials (AP). Biochemical assays were employed to identify the pyridine nucleotide changes, Kv1.5 expression and myocardial injury. Hyperoxia treatment caused marked bradycardia,more » arrhythmia and significantly prolonged (ms) the, RR (186.2 ± 10.7 vs. 146.4 ± 6.2), PR (46.8 ± 3.1 vs. 39.3 ± 1.6), QRS (10.8 ± 0.6 vs. 8.5 ± 0.2), QTc (57.1 ± 3.5 vs. 40 ± 1.4) and JT (13.4 ± 2.1 vs. 7.0 ± 0.5) intervals, when compared with normoxia group. Hyperoxia treatment also induced significant increase in cardiac action potential duration (APD) (ex-APD{sub 90}; 73.8 ± 9.5 vs. 50.9 ± 3.1 ms) and elevated levels of serum markers of myocardial injury; cardiac troponin I (TnI) and lactate dehydrogenase (LDH). Hyperoxia exposure altered cardiac levels of mRNA/protein expression of; Kv1.5, Kvβ subunits and SiRT1, and increased ratios of reduced pyridine nucleotides (NADH/NAD and NADPH/NADP). Inhibition of SiRT1 in H9C2 cells using Splitomicin resulted in decreased SiRT1 and Kv1.5 expression, suggesting that SiRT1 may mediate Kv1.5 downregulation. In conclusion, the cardiotoxic effects of hyperoxia exposure involve ion channel disturbances and redox changes resulting in arrhythmias. - Highlights: • Hyperoxia treatment leads to arrhythmia with prolonged QTc and action potential duration. • Hyperoxia treatment alters cardiac pyridine nucleotide [NAD(P)H/NAD(P)] levels. • SiRT1 and Kv1.5 are co-regulated in hyperoxic heart injury. • Hyperoxia may lead to cardiotoxicity.« less

Differences in Awareness of Pre-exposure Prophylaxis and Post-exposure Prophylaxis Among Groups At-Risk for HIV in New York State: New York City and Long Island, NY, 2011-2013.

PubMed

Walters, Suzan M; Rivera, Alexis V; Starbuck, Lila; Reilly, Kathleen H; Boldon, Nyasha; Anderson, Bridget J; Braunstein, Sarah

2017-07-01

Pre-exposure prophylaxis (PrEP) to reduce the risk of HIV was approved in 2012 and post-exposure prophylaxis (PEP) in 2005. We report the differences in awareness of PrEP/PEP and factors associated with awareness by examining 3 risk groups (men who have sex with men (MSM), people who inject drugs, and high-risk heterosexuals). National HIV Behavioral Surveillance system data collected in New York City (NYC) and Long Island, NY in 2011-2013 were used. Logistic regressions by region were developed to estimate adjusted associations [Adjusted Odds Ratios (AOR)] and determine differences in awareness of PrEP/PEP. Awareness of PrEP/PEP was low for all groups. In multivariate analysis controlling for sociodemographic factors, noninjection drug use, HIV status, and exposure to HIV prevention, males who inject drugs in NYC had significantly decreased odds of PrEP/PEP awareness [AOR: 0.45; confidence interval (CI): 0.25 to 0.81] compared with MSM. MSM aged 18-29 years had increased awareness of PrEP (AOR: 2.94; 95% CI 1.11 to 7.80). On Long Island, females who inject drugs (AOR: 0.18; 95% CI: 0.05 to 0.62), males who inject drugs (AOR: 0.14; 95% CI: 0.05 to 0.39), female heterosexuals (AOR: 0.25; 95% CI: 0.11 to 0.59), and male heterosexuals (AOR: 0.32; 95% CI: 0.14 to 0.73) had significantly decreased odds of PrEP/PEP awareness. Black MSM had increased awareness of PrEP (AOR: 4.08 CI:1.21 to 13.73). Large proportions of groups at-risk for HIV were unaware of PrEP/PEP. When comparing risk groups to MSM, we found MSM to have greater awareness in both regions. On Long Island, people who inject drugs and heterosexuals were far less likely to have PrEP/PEP awareness than in NYC. On Long Island, Black MSM had increased PrEP awareness and in NYC MSM aged 18-29 had increased PrEP awareness. These findings suggest that awareness may be spreading through networks and highlight the importance of targeted educational and prevention efforts by group and region.

Perceived discrimination and smoking among rural-to-urban migrant women working as restaurant/hotel workers and sex workers in China

PubMed Central

Shin, Sanghyuk S.; Wan, Xia; Wang, Qian; Raymond, H. Fisher; Liu, Huilin; Ding, Ding; Yang, Gonghuan; Novotny, Thomas E.

2013-01-01

Background Smoking may be a coping mechanism for psychosocial stress caused by discrimination. Methods We conducted a cross-sectional survey of rural-to-urban migrant women working as restaurant/hotel workers (RHWs) and those working as sex workers (FSWs) in 10 Chinese cities to investigate whether perceived discrimination is associated with smoking. We interviewed RHWs at medical examination clinics and FSWs at entertainment venues. Modified Poisson regression was used to estimate prevalence ratios. Results Of the 1696 RHWs and 532 FSWs enrolled, 155 (9.1%) and 63 (11.8%) reported perceived discrimination, respectively. Perceived discrimination was independently associated with ever tried smoking (prevalence ratio [PR], 1.71; 95% confidence interval [CI], 1.31–2.23) and current smoking (PR, 2.52; 95% CI, 1.32–4.79) among RHWs and ever tried smoking (PR, 1.36; 95% CI, 1.16–1.61) and current smoking (PR, 1.63; 95% CI, 1.28–2.06) among FSWs. Discussion Perceived discrimination is associated with higher prevalence of smoking among rural-to-urban migrant women in China. PMID:22389186

Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin.

PubMed

Richter, C; Schnabel, A; Csernok, E; De Groot, K; Reinhold-Keller, E; Gross, W L

1995-07-01

In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality.

Prevalence of UTI among Iranian infants with prolonged jaundice, and its main causes: A systematic review and meta-analysis study.

PubMed

Tola, H H; Ranjbaran, M; Omani-Samani, R; Sadeghi, M

2018-04-01

An extremely variable and high prevalence of urinary tract infection (UTI) in infants with prolonged jaundice has been reported in Iran. However, there is no research from the area that has attempted to estimate pooled prevalence of UTI from considerably diverse evidence. Therefore, this systematic review and meta-analysis study aimed to estimate the prevalence of UTI in infants with prolonged jaundice who were admitted into clinics or hospitals in Iran. A systematic review and meta-analysis was conducted of published articles on UTI prevalence in infants with prolonged jaundice in Iran. Electronic databases were searched, including Web of Sciences, PubMed/Medline, Scopus, Iranian Scientific Information Database (SID) and Iranmedex, for both English and Persian language articles published between January, 2000 and March, 2017. All possible combinations of the following keywords were used: jaundice, icterus, hyperbilirubinemia during infancy, infection and neonatal. Nine studies that reported prevalence of UTI in infants with prolonged jaundice were included. The overall prevalence of UTI was estimated using random-effects meta-analysis models. A total of 1750 infants were pooled to estimate the overall prevalence of UTI in infants with prolonged jaundice. The prevalence reported by the studies included in this literature review was extremely variable and ranged 0.6-53.9%. The overall prevalence was 11% (95% Confidence Interval (CI): 5.0-18.0), and Escherichia coli was found to be the main cause of UTI. The overall prevalence of UTI was 11%, and E. coli was the main cause of UTI in infants with prolonged jaundice. Screening of UTI should be considered for infants with prolonged jaundice. Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Validation of Open-Heart Intraoperative Risk score to predict a prolonged intensive care unit stay for adult patients undergoing cardiac surgery with cardiopulmonary bypass

PubMed Central

Tribuddharat, Sirirat; Sathitkarnmanee, Thepakorn; Ngamsaengsirisup, Kriangsak; Wongbuddha, Chawalit

2018-01-01

Background A prolonged stay in an intensive care unit (ICU) after cardiac surgery with cardiopulmonary bypass (CPB) increases the cost of care as well as morbidity and mortality. Several predictive models aim at identifying patients at risk of prolonged ICU stay after cardiac surgery with CPB, but almost all of them involve a preoperative assessment for proper resource management, while one – the Open-Heart Intraoperative Risk (OHIR) score – focuses on intra-operative manipulatable risk factors for improving anesthetic care and patient outcome. Objective We aimed to revalidate the OHIR score in a different context. Materials and methods The ability of the OHIR score to predict a prolonged ICU stay was assessed in 123 adults undergoing cardiac surgery (both coronary bypass graft and valvular surgery) with CPB at two tertiary university hospitals between January 2013 and December 2014. The criteria for a prolonged ICU stay matched a previous study (ie, a stay longer than the median). Results The area under the receiver operating characteristic curve of the OHIR score to predict a prolonged ICU stay was 0.95 (95% confidence interval 0.90–1.00). The respective sensitivity, specificity, positive predictive value, and accuracy of an OHIR score of ≥3 to discriminate a prolonged ICU stay was 93.10%, 98.46%, 98.18%, and 95.9%. Conclusion The OHIR score is highly predictive of a prolonged ICU stay among intraopera-tive patients undergoing cardiac surgery with CPB. The OHIR comprises of six risk factors, five of which are manipulatable intraoperatively. The OHIR can be used to identify patients at risk as well as to improve the outcome of those patients. PMID:29379295

PK/PD Modelling of the QT Interval: a Step Towards Defining the Translational Relationship Between In Vitro, Awake Beagle Dogs, and Humans.

PubMed

Marostica, Eleonora; Van Ammel, Karel; Teisman, Ard; Gallacher, David; Van Bocxlaer, Jan; De Ridder, Filip; Boussery, Koen; Vermeulen, An

2016-07-01

Inhibiting the human ether-a-go-go-related gene (hERG)-encoded potassium ion channel is positively correlated with QT-interval prolongation in vivo, which is considered a risk factor for the occurrence of Torsades de Pointes (TdP). A pharmacokinetic/pharmacodynamic model was developed for four compounds that reached the clinic, to relate drug-induced QT-interval change in awake dogs and humans and to derive a translational scaling factor a 1. Overall, dogs were more sensitive than humans to QT-interval change, an a 1 of 1.5 was found, and a 10% current inhibition in vitro produced a higher percent QT-interval change in dogs as compared to humans. The QT-interval changes in dogs were predictive for humans. In vitro and in vivo information could reliably describe the effects in humans. Robust translational knowledge is likely to reduce the need for expensive thorough QT studies; therefore, expanding this work to more compounds is recommended.

Effects of home-based pulmonary rehabilitation with a metronome-guided walking pace in chronic obstructive pulmonary disease.

PubMed

Lee, Sung-soon; Kim, Changhwan; Jin, Young-Soo; Oh, Yeon-Mok; Lee, Sang-Do; Yang, Yun Jun; Park, Yong Bum

2013-05-01

Despite documented efficacy and recommendations, pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) has been underutilized. Home-based PR was proposed as an alternative, but there were limited data. The adequate exercise intensity was also a crucial issue. The aim of this study was to investigate the effects of home-based PR with a metronome-guided walking pace on functional exercise capacity and health-related quality of life (HRQOL) in COPD. The subjects participated in a 12-week home-based PR program. Exercise intensity was initially determined by cardiopulmonary exercise test, and was readjusted (the interval of metronome beeps was reset) according to submaximal endurance test. Six-minute walk test, pulmonary function test, cardiopulmonary exercise test, and St. George's Respiratory Questionnaire (SGRQ) were done before and after the 12-week program, and at 6 months after completion of rehabilitation. Thirty-three patients participated in the program. Six-minute walking distance was significantly increased (48.8 m; P = 0.017) and the SGRQ score was also improved (-15; P < 0.001) over the six-month follow-up period after rehabilitation. There were no significant differences in pulmonary function and peak exercise parameters. We developed an effective home-based PR program with a metronome-guided walking pace for COPD patients. This rehabilitation program may improve functional exercise capacity and HRQOL.

Association between the Frequency of Protein-Rich Food Intakes and Kihon-Checklist Frailty Indices in Older Japanese Adults: The Kyoto-Kameoka Study.

PubMed

Yamaguchi, Miwa; Yamada, Yosuke; Nanri, Hinako; Nozawa, Yoshizu; Itoi, Aya; Yoshimura, Eiichi; Watanabe, Yuya; Yoshida, Tsukasa; Yokoyama, Keiichi; Goto, Chiho; Ishikawa-Takata, Kazuko; Kobayashi, Hisamine; Kimura, Misaka

2018-01-13

We aimed to investigate whether frequencies of protein-rich food intake were associated with frailty among older Japanese adults. A cross-sectional study was conducted in 2011 among 3843 men and 4331 women in a population-based cohort of Kameoka city, Kyoto Prefecture, Japan. Frailty was assessed by the weighted score based on the 25-item Kihon-Checklist. The frequency of protein-rich food intake was examined as "seafood", "meat", "dairy products", "eggs", and "soy products". The outcome of frailty was analyzed with a multiple logistic regression model using the frequency of protein-rich food intake. When compared to the first quartile, it was observed that there was a significant association between the lower adjusted prevalence ratio (PR) for frailty and the frequency of seafood intake in the fourth quartile among men (PR 0.64, 95% confidence interval (CI), 0.42, 0.99) and from the second quartile to the third quartile among women (PR 0.61, 95% CI, 0.43, 0.85; PR 0.64, 95% CI, 0.46, 0.91). The frequency of dairy products intake in the third quartile among women was significantly associated with a lower PR for frailty ( p -value = 0.013). Our findings suggest that the consumption of seafood and dairy products may help older adults in maintaining their independence.

Association between the Frequency of Protein-Rich Food Intakes and Kihon-Checklist Frailty Indices in Older Japanese Adults: The Kyoto-Kameoka Study

PubMed Central

Yamaguchi, Miwa; Nozawa, Yoshizu; Itoi, Aya; Yoshimura, Eiichi; Watanabe, Yuya; Yoshida, Tsukasa; Yokoyama, Keiichi; Goto, Chiho; Ishikawa-Takata, Kazuko; Kobayashi, Hisamine; Kimura, Misaka

2018-01-01

We aimed to investigate whether frequencies of protein-rich food intake were associated with frailty among older Japanese adults. A cross-sectional study was conducted in 2011 among 3843 men and 4331 women in a population-based cohort of Kameoka city, Kyoto Prefecture, Japan. Frailty was assessed by the weighted score based on the 25-item Kihon-Checklist. The frequency of protein-rich food intake was examined as “seafood”, “meat”, “dairy products”, “eggs”, and “soy products”. The outcome of frailty was analyzed with a multiple logistic regression model using the frequency of protein-rich food intake. When compared to the first quartile, it was observed that there was a significant association between the lower adjusted prevalence ratio (PR) for frailty and the frequency of seafood intake in the fourth quartile among men (PR 0.64, 95% confidence interval (CI), 0.42, 0.99) and from the second quartile to the third quartile among women (PR 0.61, 95% CI, 0.43, 0.85; PR 0.64, 95% CI, 0.46, 0.91). The frequency of dairy products intake in the third quartile among women was significantly associated with a lower PR for frailty (p-value = 0.013). Our findings suggest that the consumption of seafood and dairy products may help older adults in maintaining their independence. PMID:29342873

Differences between African-American adolescent females with and without human papillomavirus infection.

PubMed

Seth, Puja; Wingood, Gina M; Diclemente, Ralph J; Crosby, Richard A; Salazar, Laura F; Rose, Eve S; Sales, Jessica M

2011-03-01

An important policy question is whether high-risk populations can be identified and prioritised for human papillomavirus (HPV) immunisation. Data collection included an audio computer-assisted survey interview and testing of Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, and HPV among 295 African-American adolescent females. The results indicated that 43.1% tested positive for HPV. Logistic regression analyses indicated that HPV prevalence was not associated with other sexually transmissible infections (prevalence ratio (PR)=0.85, 95% confidence interval (CI)=0.51-1.41), unprotected vaginal sex (PR=1.04, 95% CI=0.56-1.92), having sex with an older male partner (PR=1.12, 95% CI=0.64-1.96), and having a casual partner (PR=0.89, 95% CI=0.54-1.48). Additionally, t-tests indicated that HPV prevalence was not associated with frequency of vaginal sex (t=0.17, P=0.87), protected sex (t=-0.16, P=0.87), number of recent (t=0.40, P=0.69) or lifetime (t=1.45, P=0.15) sexual partners. However, those testing positive for HPV were younger (t=1.97, P=0.05) and reported current use of birth control pills (PR=2.38, 95% CI=1.00-5.63). It may not be possible to identify those with elevated risk of HPV acquisition. Thus, HPV vaccination, regardless of risk indicators, may be the most efficacious public health strategy.

Leisure-time physical activity and breast cancer risk by hormone receptor status: effective life periods and exercise intensity.

PubMed

Suzuki, Reiko; Iwasaki, Motoki; Kasuga, Yoshio; Yokoyama, Shiro; Onuma, Hiroshi; Nishimura, Hideki; Kusama, Ritsu; Shimazu, Taichi; Tsugane, Shoichiro

2010-11-01

Physical activity may decrease breast cancer risk. However, it is unclear what intensity of exercise and during which life periods this effect on decreasing risk is efficiently expressed, and whether the associations differ by the estrogen-/progesterone- receptor (ER/PR) status of tumors. We investigated associations between age- and intensity-specific leisure-time physical activity and ER/PR-defined breast cancer risk. We conducted a hospital-based case-control study in Nagano, Japan. Subjects were 405 cases newly diagnosed (>99% known ER/PR) from 2001 to 2005, who were age-/area-matched with 405 controls. Activity was assessed with a self-reported questionnaire which considered intensity level (moderate and/or strenuous) at different ages (at 12 and 20 years, and in the previous 5 years). Odds ratios (ORs) and 95% confidence intervals were calculated using logistic regression. Strenuous but not moderate physical activity at age 12 was inversely associated with pre- and postmenopausal breast cancer risk across ER/PR subtypes [overall OR(≥ 5 days/week vs. none) = 0.24 (0.14-0.43)]. Moderate physical activity in the previous 5 years was significantly associated with a decrease in risk for postmenopausal ER + PR + tumors only [OR(≥ 1 day/week vs. none) = 0.35 (0.18-0.67)]. Strenuous activity in teens and moderate activity after menopause may contribute to a reduction in breast cancer risk.

Recent Transmission of Tuberculosis - United States, 2011-2014.

PubMed

Yuen, Courtney M; Kammerer, J Steve; Marks, Kala; Navin, Thomas R; France, Anne Marie

2016-01-01

Tuberculosis is an infectious disease that may result from recent transmission or from an infection acquired many years in the past; there is no diagnostic test to distinguish the two causes. Cases resulting from recent transmission are particularly concerning from a public health standpoint. To describe recent tuberculosis transmission in the United States, we used a field-validated plausible source-case method to estimate cases likely resulting from recent transmission during January 2011-September 2014. We classified cases as resulting from either limited or extensive recent transmission based on transmission cluster size. We used logistic regression to analyze patient characteristics associated with recent transmission. Of 26,586 genotyped cases, 14% were attributable to recent transmission, 39% of which were attributable to extensive recent transmission. The burden of cases attributed to recent transmission was geographically heterogeneous and poorly predicted by tuberculosis incidence. Extensive recent transmission was positively associated with American Indian/Alaska Native (adjusted prevalence ratio [aPR] = 3.6 (95% confidence interval [CI] 2.9-4.4), Native Hawaiian/Pacific Islander (aPR = 3.2, 95% CI 2.3-4.5), and black (aPR = 3.0, 95% CI 2.6-3.5) race, and homelessness (aPR = 2.3, 95% CI 2.0-2.5). Extensive recent transmission was negatively associated with foreign birth (aPR = 0.2, 95% CI 0.2-0.2). Tuberculosis control efforts should prioritize reducing transmission among higher-risk populations.

Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: a report from the Children's Oncology Group.

PubMed

Villablanca, Judith G; London, Wendy B; Naranjo, Arlene; McGrady, Patrick; Ames, Matthew M; Reid, Joel M; McGovern, Renee M; Buhrow, Sarah A; Jackson, Hollie; Stranzinger, Enno; Kitchen, Brenda J; Sondel, Paul M; Parisi, Marguerite T; Shulkin, Barry; Yanik, Gregory A; Cohn, Susan L; Reynolds, C Patrick

2011-11-01

To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma. Patients received 7 days of fenretinide: 2,475 mg/m(2)/d divided TID (<18 years) or 1,800 mg/m(2)/d divided BID (≥18 years) every 21 days for a maximum of 30 courses. Patients with stable or responding disease after course 30 could request additional compassionate courses. Best response by course 8 was evaluated in stratum 1 (measurable disease on CT/MRI ± bone marrow and/or MIBG avid sites) and stratum 2 (bone marrow and/or MIBG avid sites only). Sixty-two eligible patients, median age 5 years (range 0.6-19.9), were treated in stratum 1 (n = 38) and stratum 2 (n = 24). One partial response (PR) was seen in stratum 2 (n = 24 evaluable). No responses were seen in stratum 1 (n = 35 evaluable). Prolonged stable disease (SD) was seen in 7 patients in stratum 1 and 6 patients in stratum 2 for 4 to 45+ (median 15) courses. Median time to progression was 40 days (range 17-506) for stratum 1 and 48 days (range 17-892) for stratum 2. Mean 4-HPR steady-state trough plasma concentrations were 7.25 μmol/L (coefficient of variation 40-56%) at day 7 course 1. Toxicities were mild and reversible. Although neither stratum met protocol criteria for efficacy, 1 PR + 13 prolonged SD occurred in 14/59 (24%) of evaluable patients. Low bioavailability may have limited fenretinide activity. Novel fenretinide formulations with improved bioavailability are currently in pediatric phase I studies. ©2011 AACR

Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: A report from the Children’s Oncology Group NSC #374551; IND# 40294

PubMed Central

Villablanca, Judith G.; London, Wendy B.; Naranjo, Arlene; McGrady, Patrick; Ames, Matthew M.; Reid, Joel M.; McGovern, Renee M.; Buhrow, Sarah A.; Jackson, Hollie; Stranzinger, Enno; Kitchen, Brenda J.; Sondel, Paul M.; Parisi, Marguerite T.; Shulkin, Barry; Yanik, Gregory A.; Cohn, Susan L.; Reynolds, C. Patrick

2011-01-01

Purpose To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma. Experimental Design Patients received 7 days of fenretinide: 2475 mg/m2/day divided TID (<18 years) or 1800 mg/m2/day divided BID (≥18 years) every 21 days for a maximum of 30 courses. Patients with stable or responding disease after course 30 could request additional compassionate courses. Best response by course 8 was evaluated in Stratum 1 (measurable disease on CT/MRI +/− bone marrow and/or MIBG avid sites) and Stratum 2 (bone marrow and/or MIBG avid sites only). Results Sixty-two eligible patients, median age 5 years (range 0.6–19.9), were treated in Stratum 1 (n=38) and Stratum 2 (n=24). One partial response (PR) was seen in Stratum 2 (n=24 evaluable). No responses were seen in Stratum 1 (n=35 evaluable). Prolonged stable disease (SD) was seen in 7 patients in Stratum 1 and 6 patients in Stratum 2 for 4–45+ (median 15) courses. Median time to progression was 40 days (range 17–506) for Stratum 1 and 48 days (range 17–892) for Stratum 2. Mean 4-HPR steady state trough plasma concentrations were 7.25 µM (coefficient of variation 40–56%) at day 7 course 1. Toxicities were mild and reversible. Conclusions Although neither stratum met protocol criteria for efficacy, 1 PR + 13 prolonged SD occurred in 14/59 (24%) of evaluable patients. Low bioavailability may have limited fenretinide activity. Novel fenretinide formulations with improved bioavailability are currently in pediatric Phase I studies. PMID:21908574

Radionuclide gastric emptying studies in patients with anorexia nervosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Domstad, P.A.; Shih, W.J.; Humphries, L.

1987-05-01

To evaluate gastric emptying in anorexia nervosa patients, 26 patients (17 females, two males, ranging in age from 13 to 40 yr) with upper GI symptoms ingested 150-200 microCi (/sup 99m/Tc)triethelenetetraamine polysterene resin in cereal and were imaged in the supine position. Data were accumulated at 5 min intervals to obtain the gastric emptying time (GET). The results of the studies were divided into three categories: prolonged, 13 patients; rapid, 11; and normal 3. Twelve of 13 patients with prolonged GET were given 10 mg metoclopramide i.v. injections; nine of the 12 patients had a good response and three hadmore » no response. Five of the nine patients underwent metoclopramide therapy and four of the patients showed benefit from the therapy. One patient discontinued metoclopramide therapy because of somnolence. Although all patients had subjective symptoms of gastric dysfunction, our results indicated only 50% had objectively prolonged GET, and another 50% showed normal or even rapid GET. Therefore, this radionuclide study enables quantitatively objective documentation of gastric emptying, separation of those patients with rapid or normal GET from those with prolonged GET, thereby avoiding the possible side effects from metoclopramide medication, and prediction of effectiveness of metoclopramide therapy in patients with prolonged GET.« less

Evidence for a postreproductive phase in female false killer whales Pseudorca crassidens.

PubMed

Photopoulou, Theoni; Ferreira, Ines M; Best, Peter B; Kasuya, Toshio; Marsh, Helene

2017-01-01

A substantial period of life after reproduction ends, known as postreproductive lifespan (PRLS), is at odds with classical life history theory and its causes and mechanisms have puzzled evolutionary biologists for decades. Prolonged PRLS has been confirmed in only two non-human mammals, both odontocete cetaceans in the family Delphinidae. We investigate the evidence for PRLS in a third species, the false killer whale, Pseudorca crassidens , using a quantitative measure of PRLS and morphological evidence from reproductive tissues. We examined specimens from false killer whales from combined strandings (South Africa, 1981) and harvest (Japan 1979-80) and found morphological evidence of changes in the activity of the ovaries in relation to age. Ovulation had ceased in 50% of whales over 45 years, and all whales over 55 years old had ovaries classified as postreproductive. We also calculated a measure of PRLS, known as postreproductive representation (PrR) as an indication of the effect of inter-population demographic variability. PrR for the combined sample was 0.14, whereas the mean of the simulated distribution for PrR under the null hypothesis of no PRLS was 0.02. The 99th percentile of the simulated distribution was 0.08 and no simulated value exceeded 0.13. These results suggest that PrR was convincingly different from the measures simulated under the null hypothesis. We found morphological and statistical evidence for PRLS in South African and Japanese pods of false killer whales, suggesting that this species is the third non-human mammal in which this phenomenon has been demonstrated in wild populations. Nonetheless, our estimate for PrR in false killer whales (0.14) is lower than the single values available for the short-finned pilot whale (0.28) and the killer whale (0.22) and is more similar to working Asian elephants (0.13).

Identification of Risk Factors for the Development of Pressure Ulcers Despite Standard Screening Methodology and Prophylaxis in Trauma Patients.

PubMed

Raff, Lauren A; Waller, Holly; Griffin, Russell L; Kerby, Jeffrey D; Bosarge, Patrick L

2016-07-01

To present information about a study of risk factors for development of pressure ulcers (PrUs) in trauma patients. This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Describe the previous PrU research, scope of the problem, and methodology of the study.2. Explain the results of the study identifying PrU risk factors for trauma patients. Pressure ulceration prevention has been emphasized  over the past several years in inpatient hospital settings with  subsequent decreases in the development of pressure ulcers (PrUs).  However, there remains a subset of trauma and burn patients  that develop PrUs despite standard screening methodology and  prophylaxis. This study determines the conditions that predict  development of pressure ulcers (PrUs) despite conventional  prophylaxis and screening.  Demographic and PrU data were collected over a  5-year period from June 2008 to May 2013. Patients diagnosed  with PrUs upon arrival in the trauma bay were excluded from  analysis. An ordinal logistic regression of PrU stage was used to  estimate odds ratios (ORs) and associated 95% confidence intervals  (CIs) for the association between characteristics of interest and  odds of a PrU. A backward selection process was used to select the  most parsimonious model.  During the study period, 14,616 trauma patients were  admitted and had available data. A total of 124 patients (0.85%) that met inclusion criteria went on to develop PrUs during their hospital course. Factors associated with the development of PrUs included spine Abbreviated Injury Scale (AIS) >3 (OR, 5.72; CI, 3.63-9.01), mechanical ventilation (OR, 1.95; CI, 1.23-3.10) and age 40 to 64 (OR, 2.09; CI, 1.24-3.52) and age ≥ 65 (OR, 4.48; CI, 2.52-7.95). Interestingly, head injury AIS >3 was protective from the development of PrUs (OR, 0.56; CI, 0.32-0.96). Hypotension and shock defined as systolic BP <90 mm Hg and base deficit less than -6 were not associated with the development of PrUs. In addition, body mass index was not associated with PrU development.  Spinal injuries, older than age 40, and mechanical  ventilation predict the development of PrUs for a subset of  patients, despite conventional prophylaxis and screening. Advanced  prevention methods, such as low-air-loss mattresses for these patient  subgroups should be considered immediately upon identification  of these risk factors during the hospital course.

Work-family conflict and prolonged fatigue among Japanese married male physicians.

PubMed

Ohta, Hiroshi; Wada, Koji; Kawashima, Masatoshi; Arimatsu, Mayuri; Higashi, Toshiaki; Yoshikawa, Toru; Aizawa, Yoshiharu

2011-12-01

Fatigue experienced by physicians may not only endanger their own health but may also affect the safety of patients. Such fatigue may be associated with the work environment and personal factors such as work-family conflict (WFC). This study aimed to determine the association between WFC and prolonged fatigue among Japanese married male physicians. Physicians who graduated from a Japanese medical school answered a mailed anonymous self-report questionnaire. For assessment of WFC and prolonged fatigue, the Japanese versions of the WFC scale and the Checklist of Individual Strength questionnaire (CIS) were used. Prolonged fatigue was defined as the upper quartile of total CIS scores. The WFC scale comprises six dimensions. Total scores were divided into tertiles: low, intermediate, and high levels of WFC. A multiple logistic regression analysis was performed to examine the association between WFC and prolonged fatigue. A total of 540 male physicians answered the questionnaire, and the data of 444 married male physicians were analyzed. The data were then adjusted for age and work condition factors. Prolonged fatigue was significantly associated with high strain-based work interference with family (WIF; corrected odds ratio, 5.56; 95% confidence interval, 2.55-12.1), intermediate strain-based WIF (2.53, 1.25-5.10), high time-based family interference with work (FIW; 1.92, 1.08-3.40), and there was a weak association with high strain-based FIW (1.93, 0.98-3.83). Employers should take measures to improve working conditions in hospitals, and give physicians the opportunity to learn how to cope with WFC. These measures could ultimately help prevent prolonged fatigue.

Prolonged methylprednisolone therapy after the pulse treatment for patients with moderate-to-severe paraquat poisoning: A retrospective analysis.

PubMed

Gao, Jie; Feng, ShunYi; Wang, Jian; Yang, SiYuan; Li, Yong

2017-06-01

This retrospective study aims to evaluate the effect of prolonged methylprednisolone (MP) therapy on the mortality of patients with moderate-to-severe paraquat (PQ) poisoning after the pulse treatment.We performed a retrospective analysis of patients with acute moderate-to-severe PQ poisoning that were admitted to the emergency department from May 2012 to August 2016. Out of 138 patients, 60 were treated with pulse treatment (15 mg kg day MP for 3 days) and 78 were treated with prolonged MP therapy after pulse treatment (15 mg kg day MP for 3 days; afterward, the dosage was reduced in half every 2 days, and the MP therapy was terminated until 0.47 mg kg day). Kaplan-Meier method was used to compare the mortality between the 2 groups. Cox proportional hazard models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI).The mortality of the prolonged MP therapy after pulse treatment group was lower than that of the pulse group (47.4% vs 63.3%; log-rank tests, P  =  .003). According to the multivariate Cox analysis, the prolonged MP therapy after pulse treatment was significantly associated with a lower mortality risk (HR: 0.31, 95% CI: 0.19-0.52, P < .001) compared with the pulse group. In addition, the prolonged MP therapy after pulse treatment caused more incidences of leucopenia than the pulse treatment alone (25.6% vs 11.7%, P  =  .04).The prolonged MP therapy after pulse treatment can reduce the mortality of moderate-to-severe PQ poisoning patients.

Low extracellular potassium prolongs repolarization and evokes early afterdepolarization in human induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Kuusela, Jukka; Larsson, Kim; Shah, Disheet; Prajapati, Chandra; Aalto-Setälä, Katriina

2017-06-15

Long QT syndrome (LQTS) is characterized by a prolonged QT-interval on electrocardiogram and by increased risk of sudden death. One of the most common and potentially life-threatening electrolyte disturbances is hypokalemia, characterized by low concentrations of K + Using a multielectrode array platform and current clamp technique, we investigated the effect of low extracellular K + concentration ([K + ] Ex ) on the electrophysiological properties of hiPSC-derived cardiomyocytes (CMs) generated from a healthy control subject (WT) and from two symptomatic patients with type 1 of LQTS carrying G589D (LQT1A) or IVS7-2A>G mutation (LQT1B) in KCNQ1 The baseline prolongations of field potential durations (FPDs) and action potential durations (APDs) were longer in LQT1-CMs than in WT-CMs. Exposure to low [K + ] Ex prolonged FPDs and APDs in a concentration-dependent fashion. LQT1-CMs were found to be more sensitive to low [K + ] Ex compared to WT-CMs. At baseline, LQT1A-CMs had more prolonged APDs than LQT1B-CMs, but low [K + ] Ex caused more pronounced APD prolongation in LQT1B-CMs. Early afterdepolarizations in the action potentials were observed in a subset of LQT1A-CMs with further prolonged baseline APDs and triangular phase 2 profiles. This work demonstrates that the hiPSC-derived CMs are sensitive to low [K + ] Ex and provide a platform to study acquired LQTS. © 2017. Published by The Company of Biologists Ltd.

Dietary fat intake and development of specific breast cancer subtypes.

PubMed

Sieri, Sabina; Chiodini, Paolo; Agnoli, Claudia; Pala, Valeria; Berrino, Franco; Trichopoulou, Antonia; Benetou, Vassiliki; Vasilopoulou, Effie; Sánchez, María-José; Chirlaque, Maria-Dolores; Amiano, Pilar; Quirós, J Ramón; Ardanaz, Eva; Buckland, Genevieve; Masala, Giovanna; Panico, Salvatore; Grioni, Sara; Sacerdote, Carlotta; Tumino, Rosario; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Peeters, Petra H M; van Gils, Carla H; Bueno-de-Mesquita, H Bas; van Kranen, Henk J; Key, Timothy J; Travis, Ruth C; Khaw, Kay Tee; Wareham, Nicholas J; Kaaks, Rudolf; Lukanova, Annekatrin; Boeing, Heiner; Schütze, Madlen; Sonestedt, Emily; Wirfält, Elisabeth; Sund, Malin; Andersson, Anne; Chajes, Veronique; Rinaldi, Sabina; Romieu, Isabelle; Weiderpass, Elisabete; Skeie, Guri; Dagrun, Engeset; Tjønneland, Anne; Halkjær, Jytte; Overvard, Kim; Merritt, Melissa A; Cox, David; Riboli, Elio; Krogh, Vittorio

2014-04-09

We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and saturated fat were associated with greater risk of ER(+)PR(+) disease (HR = 1.20, 95% confidence interval [CI] = 1.00 to 1.45; HR = 1.28, 95% CI = 1.09 to 1.52; highest vs lowest quintiles) but not ER(-)PR(-) disease. High saturated fat was statistically significantly associated with greater risk of HER2(-) disease. High saturated fat intake particularly increases risk of receptor-positive disease, suggesting saturated fat involvement in the etiology of this BC subtype. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Are obesity and overweight associated with gingivitis occurrence in Brazilian schoolchildren?

PubMed

Nascimento, Gustavo G; Seerig, Lenise M; Vargas-Ferreira, Fabiana; Correa, Fernanda O B; Leite, Fábio R M; Demarco, Flávio F

2013-12-01

This cross-sectional study aimed to assess the relationship between weight status and gingival inflammation in Brazilian schoolchildren aged 8- to 12-year old, when controlling for potential confounders. Overall, 1211 children aged 8- to 12-year old from public and private schools in Southern Brazil were selected by a two-stage cluster method. Questionnaires were used to assess socio-demographic data and oral hygiene habits. Oral examination evaluated presence of plaque and gingival bleeding. Anthropometric measures were collected to obtain body mass index. Multivariate Poisson regression was used for data analysis (Prevalence Ratio/95% Confidence Interval). Prevalence of gingivitis was 44.0%. Mean and median values of gingival bleeding sites were 3.10 and 2.0 respectively. Obese/overweight children totalized 34.6%. In multivariate adjusted analysis, sex (PR 0.86; 95%CI 0.75;0.98), maternal schooling (PR 1.09; 95% CI 1.01;1.18), plaque (PR 1.37; 95% CI 1.26;1.50), dental caries experience (PR 1.16; 95% CI 1.01;1.36) and bleeding during tooth brushing (PR 1.27; 95% CI 1.11;1.48) were associated with the outcome. In the sex-stratified analysis, overweight/obese boys presented a greater risk for gingivitis (PR 1.22 95% CI 1.01;1.48). Gingivitis was not associated with obesity/overweight in the total sample. Gender differences seem to influence the relationship between gingivitis and obesity/overweight; a stronger association was noted among boys than girls. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Racial Disparities in Short Sleep Duration by Occupation and Industry

PubMed Central

Jackson, Chandra L.; Redline, Susan; Kawachi, Ichiro; Williams, Michelle A.; Hu, Frank B.

2013-01-01

Short sleep duration, which is associated with increased morbidity and mortality, has been shown to vary by occupation and industry, but few studies have investigated differences between black and white populations. By using data from a nationally representative sample of US adult short sleepers (n = 41,088) in the National Health Interview Survey in 2004–2011, we estimated prevalence ratios for short sleep duration in blacks compared with whites for each of 8 industry categories by using adjusted Poisson regression models with robust variance. Participants' mean age was 47 years; 50% were women and 13% were black. Blacks were more likely to report short sleep duration than whites (37% vs. 28%), and the black-white disparity was widest among those who held professional occupations. Adjusted short sleep duration was more prevalent in blacks than whites in the following industry categories: finance/information/real estate (prevalence ratio (PR) = 1.44, 95% confidence interval (CI): 1.30, 1.59); professional/administrative/management (PR = 1.30, 95% CI: 1.18, 1.44); educational services (PR = 1.39, 95% CI: 1.25, 1.54); public administration/arts/other services (PR = 1.30, 95% CI: 1.21, 1.41); health care/social assistance (PR = 1.23, 95% CI: 1.14, 1.32); and manufacturing/construction (PR = 1.14, 95% CI: 1.07, 1.20). Short sleep generally increased with increasing professional responsibility within a given industry among blacks but decreased with increasing professional roles among whites. Our results suggest the need for further investigation of racial/ethnic differences in the work-sleep relationship. PMID:24018914

The pregnancy-related anxiety scale: A validity examination using Rasch analysis.

PubMed

Brunton, Robyn J; Dryer, Rachel; Krägeloh, Chris; Saliba, Anthony; Kohlhoff, Jane; Medvedev, Oleg

2018-04-27

Pregnancy-related anxiety is increasingly recognised as a common condition that is associated with many deleterious outcomes for both the mother and infant (e.g., preterm birth, postnatal depression). Limitations in the psychometric properties and/or breadth of existing scales for pregnancy-related anxiety highlight the need for a psychometrically sound measure to facilitate effective screening and possible early interventions. The recently developed Pregnancy-related Anxiety Scale (PrAS) was evaluated using Rasch analysis to explore how the scale's psychometric properties could be fine-tuned. A sample of 497 pregnant women completed the PrAS. Data were subjected to Rasch analysis, and the resulting scale structure examined using Confirmatory Factor Analysis. After minor modifications, the Rasch model with 33-items and 8-factors demonstrated good fit, unidimensionality and excellent targeting and internal consistency. Confirmatory Factor Analysis confirmed the final structure, and Cronbach's alpha demonstrated excellent reliability. The use of the same sample for all analyses was a potential limitation due to the possibility of sample-specific influences. The Rasch analysis further supports the internal construct validity of the PrAS. Ordinal to interval score conversions provide added precision to the analysis of the PrAS scores. The Rasch results, together with previous validation evidence, point to the PrAS as a comprehensive and psychometrically sound screening scale for pregnancy-related anxiety. The PrAS offers clinicians the ability to screen for pregnancy-related anxiety. The subscales provide additional insights into a woman's pregnancy-related anxiety and her specific areas of concern, enabling more targeted interventions. Copyright © 2018 Elsevier B.V. All rights reserved.

Racial disparities in short sleep duration by occupation and industry.

PubMed

Jackson, Chandra L; Redline, Susan; Kawachi, Ichiro; Williams, Michelle A; Hu, Frank B

2013-11-01

Short sleep duration, which is associated with increased morbidity and mortality, has been shown to vary by occupation and industry, but few studies have investigated differences between black and white populations. By using data from a nationally representative sample of US adult short sleepers (n = 41,088) in the National Health Interview Survey in 2004-2011, we estimated prevalence ratios for short sleep duration in blacks compared with whites for each of 8 industry categories by using adjusted Poisson regression models with robust variance. Participants' mean age was 47 years; 50% were women and 13% were black. Blacks were more likely to report short sleep duration than whites (37% vs. 28%), and the black-white disparity was widest among those who held professional occupations. Adjusted short sleep duration was more prevalent in blacks than whites in the following industry categories: finance/information/real estate (prevalence ratio (PR) = 1.44, 95% confidence interval (CI): 1.30, 1.59); professional/administrative/management (PR = 1.30, 95% CI: 1.18, 1.44); educational services (PR = 1.39, 95% CI: 1.25, 1.54); public administration/arts/other services (PR = 1.30, 95% CI: 1.21, 1.41); health care/social assistance (PR = 1.23, 95% CI: 1.14, 1.32); and manufacturing/construction (PR = 1.14, 95% CI: 1.07, 1.20). Short sleep generally increased with increasing professional responsibility within a given industry among blacks but decreased with increasing professional roles among whites. Our results suggest the need for further investigation of racial/ethnic differences in the work-sleep relationship.

Exploring the Correlates to Depression in Elder Abuse Victims: Abusive Experience or Individual Characteristics?

PubMed

Santos, Ana João; Nunes, Baltazar; Kislaya, Irina; Gil, Ana Paula; Ribeiro, Oscar

2017-09-01

Depression and depressive symptoms have been studied both as risk factors and consequences of elder abuse, even though the most common cross-sectional design of the studies does not allow inferring cause or consequence relationships. This study estimates the proportion of older adults who screened positive for depressive symptoms among those self-reporting elder abuse and examines whether individual characteristics and/or abusive experience aspects are associated with self-reported depressive symptoms. Participants were 510 older adults self-reporting experiences of abuse in family setting enrolled in the cross-sectional victims' survey of the Aging and Violence Study. Depressive symptoms were assessed through the abbreviated version of the Geriatric Depression Scale (GDS-5). Poisson regression was used to determine the prevalence ratio (PR) of screening depressive symptoms according to individual and abusive experience covariates: sex, age group, cohabitation, perceived social support, chronic diseases, functional status, violence type, perpetrator, and number of conducts. Women (PR = 1.18, 95% confidence interval [CI] = [1.04, 1.35]) individuals perceiving low social support level (PR = 1.36, 95% CI = [1.16, 1.60]) and with long-term illness (PR = 1.17, 95% CI = [1.02, 1.33]) were found to be associated with increased risk for screening depressive symptoms. In regard to abusive experience, only the number of abusive conducts increased the PR (PR = 1.07, 95% CI = [1.05, 1.09]). Routine screening for elder abuse should include psychological well-being assessment. Interventions toward risk alleviation for both mental health problems and elder abuse should target women perceiving low social support level and with long-term illness.

Human Tuberculosis Caused by Mycobacterium bovis in the United States, 2006-2013.

PubMed

Scott, Colleen; Cavanaugh, Joseph S; Pratt, Robert; Silk, Benjamin J; LoBue, Philip; Moonan, Patrick K

2016-09-01

Using genotyping techniques that have differentiated Mycobacterium bovis from Mycobacterium tuberculosis since 2005, we review the epidemiology of human tuberculosis caused by M. bovis in the United States and validate previous findings nationally. All tuberculosis cases with a genotyped M. tuberculosis complex isolate reported during 2006-2013 in the United States were eligible for analysis. We used binomial regression to identify characteristics independently associated with M. bovis disease using adjusted prevalence ratios (aPRs) and corresponding 95% confidence intervals (CIs). During 2006-2013, the annual percentages of tuberculosis cases attributable to M. bovis remained consistent nationally (range, 1.3%-1.6%) among all tuberculosis cases (N = 59 273). Compared with adults 25-44 years of age, infants aged 0-4 years (aPR, 1.9 [95% CI, 1.4-2.8]) and children aged 5-14 years (aPR, 4.0 [95% CI, 3.1-5.3]) had higher prevalences of M. bovis disease. Patients who were foreign-born (aPR, 1.4 [95% CI, 1.2-1.7]), Hispanic (aPR, 3.9 [95% CI, 3.0-5.0]), female (aPR, 1.4 [95% CI, 1.3-1.6]), and resided in US-Mexico border counties (aPR, 2.0 [95% CI, 1.7-2.4]) also had higher M. bovis prevalences. Exclusively extrapulmonary disease (aPR, 3.7 [95% CI, 3.3-4.2]) or disease that was both pulmonary and extrapulmonary (aPR, 2.4 [95% CI, 2.1-2.9]) were associated with a higher prevalence of M. bovis disease. Children, foreign-born persons, Hispanics, and females are disproportionately affected by M. bovis, which was independently associated with extrapulmonary disease. Targeted prevention efforts aimed at Hispanic mothers and caregivers are warranted. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Behaviors Associated With a Risk of HIV Transmission From HIV-Positive Street Youth to Non–Street Youth in Ukraine

PubMed Central

Nerlander, Lina M.C.; Zapata, Lauren B.; Yorick, Roman; Skipalska, Halyna; Smith, Ruben A.; Kissin, Dmitry M.; Jamieson, Denise J.; Vitek, Charles R.; Hillis, Susan D.

2017-01-01

Background Little is known about the extent to which HIV-infected street youth (living part or full time on the streets) exhibit behaviors associated with HIV transmission in their interactions with youth not living on the streets (“non–street youth”). We aimed to determine prevalences and predictors of such “bridging behaviors”: inconsistent condom use and needle sharing between HIV-positive street youth and non–street youth. Methods A total of 171 street youth in 3 Ukrainian cites were identified as HIV infected after testing of eligible participants aged 15 to 24 years after random selection of venues. Using data from these youth, we calculated prevalence estimates of bridging behaviors and assessed predictors using logistic regression. Results Overall, two-thirds of HIV-infected street youth exhibited bridging behaviors; subgroups with high prevalences of bridging included females (78.3%) and those involved in transactional sex (84.2%). In multivariable analysis, inconsistent condom use with non–street youth was associated with being female (adjusted prevalence ratio [aPR], 1.2; 95% confidence interval [CI], 1.1–1.4), working (aPR, 1.2; 95% CI, 1.03–1.4), multiple partners (aPR, 1.4; 95% CI, 1.2–1.6), and “never” (aPR, 1.4; 95% CI, 1.1–1.6) or “sometimes” (aPR, 1.3; 95% CI, 1.02–1.8) versus “always” sleeping on the street. Needle sharing with non–street youth was associated with being male (aPR, 1.4; 95% CI, 1.02–2.0), orphaned (aPR, 2.3; 95% CI, 1.8–3.0), and 2 years or less living on the streets (aPR, 1.8; 95% CI, 1.5–2.1). Conclusions Bridging behaviors between HIV-infected street youth and non–street youth are common. Addressing the comprehensive needs of street and other at-risk youth is a critical prevention strategy. PMID:26267878

Gender differences in the association between lifestyle behaviors and diabetes distress in a community sample of adults with type 2 diabetes.

PubMed

Lipscombe, Carla; Smith, Kimberley J; Gariepy, Geneviève; Schmitz, Norbert

2016-03-01

The present study examined the association between moderate and severe diabetes distress (DD) and lifestyle behaviors (physical activity, smoking, alcohol consumption) in a community sample of adults with type 2 diabetes mellitus (T2DM). A total of 1971 adults with T2DM were recruited using mixed methods sampling. Participants were considered eligible if they had a doctor diagnosis of T2DM (≤10 years), were insulin naïve, aged 40-75 years, and were from Quebec, Canada. Participants provided information on DD, lifestyle behaviors, sociodemographic, and diabetes-related factors. Multinomial logistic regressions examined the association between moderate and severe DD and each lifestyle behavior, according to gender. Effect estimates can be interpreted as probability ratios (PR). In females, physical inactivity was associated with an increased likelihood of moderate distress (PR 2.2; 95% confidence interval [CI] 1.49-3.24) and severe distress (PR 1.80; 95% CI 1.00-3.24). In males, only severe distress was associated with physical inactivity (PR 1.92; 95% CI 1.00-3.66). Current smoking was associated with a greater probability of severe distress in males (PR 3.0; 95% CI 1.54-5.84) and females (PR 1.32; 95% CI 0.67-2.60); however this effect was stronger in males. No association was found between alcohol consumption and DD in females. In males, frequent alcohol consumption was associated with a reduced probability of moderate (PR 0.56; 95% CI 0.34-0.91) and severe distress (PR 0.47; 95% CI 0.21-1.06). The findings of this study suggest important gender differences in the association between DD and lifestyle behaviors. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Sex Hormones and the QT Interval: A Review

PubMed Central

Sedlak, Tara; Shufelt, Chrisandra; Iribarren, Carlos

2012-01-01

Abstract A prolonged QT interval is a marker for an increased risk of ventricular tachyarrhythmias. Both endogenous and exogenous sex hormones have been shown to affect the QT interval. Endogenous testosterone and progesterone shorten the action potential, and estrogen lengthens the QT interval. During a single menstrual cycle, progesterone levels, but not estrogen levels, have the dominant effect on ventricular repolarization in women. Studies of menopausal hormone therapy (MHT) in the form of estrogen-alone therapy (ET) and estrogen plus progesterone therapy (EPT) have suggested a counterbalancing effect of exogenous estrogen and progesterone on the QT. Specifically, ET lengthens the QT, whereas EPT has no effect. To date, there are no studies on oral contraception (OC) and the QT interval, and future research is needed. This review outlines the current literature on sex hormones and QT interval, including the endogenous effects of estrogen, progesterone, and testosterone and the exogenous effects of estrogen and progesterone therapy in the forms of MHT and hormone contraception. Further, we review the potential mechanisms and pathophysiology of sex hormones on the QT interval. PMID:22663191

CYP2C19 variation, not citalopram dose nor serum level, is associated with QTc prolongation.

PubMed

Kumar, Yingying; Kung, Simon; Shinozaki, Gen

2014-12-01

Recently, a FDA Safety Communication warned of a dose-dependent risk for QTc prolongation with citalopram, which is metabolized by CYP2C19 of the cytochrome P450 system. We investigate associations between citalopram and escitalopram dose, serum concentration, CYP2C19 phenotype, and QTc. We undertook a retrospective chart review of citalopram or escitalopram patients with the inclusion criteria of consistent medication dose, CYP2C19 phenotype (extensive metabolizers [EM], intermediate metabolizers [IM], poor metabolizers [PM]), and QTc interval on ECG. We further identified 42 citalopram users with citalopram serum concentration measurements and ECG. Regression and one-way ANOVA were used to examine the relationship between citalopram dose, citalopram serum concentration, CYP2C19 phenotype, and QTc interval. Of 75 citalopram patients, the EM group had significantly shorter QTc intervals than a combined IM+PM group (427.1±23.6 ms vs. 440.1±26.6 ms, one-tailed t-test, p=0.029). In the 80 escitalopram cohort, there was no significant difference in QTc between phenotype groups. There was no statistical correlation between citalopram (p=0.62) or escitalopram (p=0.30) dose and QTc. QTc was not associated with citalopram serum level (p=0.45). In contrast to the FDA warning, this study found no association between citalopram/escitalopram dose and QTc. However, PM of the drug tended to have longer QTc intervals. Our findings suggest cytochrome P450 genotyping in select patients may be helpful to guide medication optimization while limiting harmful effects. © The Author(s) 2014.

Malaria surveillance-response strategies in different transmission zones of the People's Republic of China: preparing for climate change

PubMed Central

2012-01-01

Background A sound understanding of malaria transmission patterns in the People’s Republic of China (P.R. China) is crucial for designing effective surveillance-response strategies that can guide the national malaria elimination programme (NMEP). Using an established biology-driven model, it is expected that one may design and refine appropriate surveillance-response strategies for different transmission zones, which, in turn, assist the NMEP in the ongoing implementation period (2010–2020) and, potentially, in the post-elimination stage (2020–2050). Methods Environmental data obtained from 676 locations across P.R. China, such as monthly temperature and yearly relative humidity (YRH), for the period 1961–2000 were prepared. Smoothed surface maps of the number of months suitable for parasite survival derived from monthly mean temperature and YRH were generated. For each decade, the final malaria prediction map was overlaid by two masked maps, one showing the number of months suitable for parasite survival and the other the length of YRH map in excess of 60%. Results Considering multiple environmental factors simultaneously, the environmental variables suitable for malaria transmission were found to have shifted northwards, which was especially pronounced in northern P.R. China. The unstable suitable regions (transmission periods between five and six months) showed increased transmission intensity due to prolonged suitable periods, especially in the central part of the country. Conclusion Adequate and effective surveillance-response strategies for NMEP should be designed to achieve the goal of malaria elimination in P.R. China by 2020, especially in the zones predicted to be the most vulnerable for climate change. PMID:23256579

New Insight in Loss of Gut Barrier during Major Non-Abdominal Surgery

PubMed Central

Derikx, Joep P. M.; van Waardenburg, Dick A.; Thuijls, Geertje; Willigers, Henriëtte M.; Koenraads, Marianne; van Bijnen, Annemarie A.; Heineman, Erik; Poeze, Martijn; Ambergen, Ton; van Ooij, André; van Rhijn, Lodewijk W.; Buurman, Wim A.

2008-01-01

Background Gut barrier loss has been implicated as a critical event in the occurrence of postoperative complications. We aimed to study the development of gut barrier loss in patients undergoing major non-abdominal surgery. Methodology/Principal Findings Twenty consecutive children undergoing spinal fusion surgery were included. This kind of surgery is characterized by long operation time, significant blood loss, prolonged systemic hypotension, without directly leading to compromise of the intestines by intestinal manipulation or use of extracorporeal circulation. Blood was collected preoperatively, every two hours during surgery and 2, 4, 15 and 24 hours postoperatively. Gut mucosal barrier was assessed by plasma markers for enterocyte damage (I-FABP, I-BABP) and urinary presence of tight junction protein claudin-3. Intestinal mucosal perfusion was measured by gastric tonometry (PrCO2, Pr-aCO2-gap). Plasma concentration of I-FABP, I-BABP and urinary expression of claudin-3 increased rapidly and significantly after the onset of surgery in most children. Postoperatively, all markers decreased promptly towards baseline values together with normalisation of MAP. Plasma levels of I-FABP, I-BABP were significantly negatively correlated with MAP at ½ hour before blood sampling (−0.726 (p<0.001), −0.483 (P<0.001), respectively). Furthermore, circulating I-FABP correlated with gastric mucosal PrCO2, Pr-aCO2-gap measured at the same time points (0.553 (p = 0.040), 0.585 (p = 0.028), respectively). Conclusions/Significance This study shows the development of gut barrier loss in children undergoing major non-abdominal surgery, which is related to preceding hypotension and mesenterial hypoperfusion. These data shed new light on the potential role of peroperative circulatory perturbation and intestinal barrier loss. PMID:19088854

An antibiotic recipe for an arrhythmic disaster.

PubMed

McCutcheon, Keir; Manga, Pravin

2015-01-01

We describe the case of a patient who developed torsade de pointes during temporary pacemaker insertion after administration of intravenous erythromycin. The case highlights the dangers of administering drugs that prolong the QT interval in patients with complete atrioventricular block, and we discuss the underlying pathophysiological recipe that can lead to a potential arrhythmic disaster.

Long QT syndrome unmasked in an adult subject presenting with excited delirium.

PubMed

Bozeman, William P; Ali, Karim; Winslow, James E

2013-02-01

Excited delirium is increasingly recognized as a risk factor for sudden death, though the specific pathophysiology of these deaths is typically unclear. We describe a survivor of excited delirium that displayed a transient severe prolongation of the QT interval, suggesting unmasking of long QT syndrome as a possible mechanism of sudden death. A 30-year-old man was arrested by police for violent assaultive behavior. Officers at the scene noted confusion, nonsensical speech, sweating, and bizarre agitated behavior; he was transported to the Emergency Department for medical evaluation of possible excited delirium. His initial electrocardiogram revealed a markedly prolonged corrected QT interval of over 600 ms. Intravenous hydration and sodium bicarbonate were administered, with normalization of the QT; he was admitted and recovered uneventfully. We discuss the possible association between long QT syndrome and unexplained sudden deaths seen with excited delirium. Sodium bicarbonate may be considered when long QT syndrome is identified during or after agitated delirium, though its routine use cannot be recommended based on a case report. Copyright © 2013 Elsevier Inc. All rights reserved.

Does prolonged β-lactam infusions improve clinical outcomes compared to intermittent infusions? A meta-analysis and systematic review of randomized, controlled trials

PubMed Central

2011-01-01

Background The emergence of multi-drug resistant Gram-negatives (MDRGNs) coupled with an alarming scarcity of new antibiotics has forced the optimization of the therapeutic potential of available antibiotics. To exploit the time above the minimum inhibitory concentration mechanism of β-lactams, prolonging their infusion may improve outcomes. The primary objective of this meta-analysis was to determine if prolonged β-lactam infusion resulted in decreased mortality and improved clinical cure compared to intermittent β-lactam infusion. Methods Relevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL. Heterogeneity was assessed qualitatively, in addition to I2 and Chi-square statistics. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using Mantel-Haenszel random-effects models. Results Fourteen randomized controlled trials (RCTs) were included. Prolonged infusion β-lactams were not associated with decreased mortality (n= 982; RR 0.92; 95% CI:0.61-1.37) or clinical cure (n = 1380; RR 1.00 95% CI:0.94-1.06) compared to intermittent infusions. Subgroup analysis for β-lactam subclasses and equivalent total daily β-lactam doses yielded similar results. Most studies had notable methodological flaws. Conclusions No clinical advantage was observed for prolonged infusion β-lactams. The limited number of studies with MDRGNs precluded evaluation of prolonged infusion of β-lactams for this subgroup. A large, multicenter RCT with critically ill patients infected with MDRGNs is needed. PMID:21696619

Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa.

PubMed

Haberer, Jessica E; Baeten, Jared M; Campbell, James; Wangisi, Jonathan; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Psaros, Christina; Safren, Steven A; Ware, Norma C; Thomas, Katherine K; Donnell, Deborah; Krows, Meighan; Kidoguchi, Lara; Celum, Connie; Bangsberg, David R

2013-01-01

Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation. Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants--all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%-100%, p<0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%-100%) by unannounced pill counts and 97.2% (90.6%-100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort. The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary.

Antiretroviral Prescription and Viral Suppression in a Representative Sample of HIV-Infected Persons in Care in 4 Large Metropolitan Areas of the United States, Medical Monitoring Project, 2011-2013.

PubMed

Wohl, Amy Rock; Benbow, Nanette; Tejero, Judith; Johnson, Christopher; Scheer, Susan; Brady, Kathleen; Gagner, Alexandra; Hughes, Alison; Eberhart, Michael; Mattson, Christine; Skarbinski, Jacek

2017-10-01

Comparisons of antiretroviral therapy (ART) prescription and viral suppression among people in HIV care across US metropolitan areas are limited. Medical Monitoring Project, 2011-2013, data were used to describe and compare associations between sociodemographics and ART prescription and viral suppression for persons receiving HIV care. Chicago, Los Angeles County (LAC), Philadelphia, and San Francisco in the United States. Bivariate and multivariable methods were used. The proportion of patients prescribed ART (91%-93%) and virally suppressed (79%-88%) was consistent although more persons were virally suppressed in San Francisco compared with the other areas, and a smaller proportion was virally suppressed in Philadelphia compared with Chicago. In the combined cohort, persons aged 30-49 years were less likely than persons 50+ (adjusted prevalence ratio (aPR) -0.97, confidence interval (CI): 0.94 to 0.99); persons reporting non-injection drug use were less likely than non-users (aPR = 0.94, CI: 0.90 to 0.98); and Hispanics were more likely than whites (aPR - 1.04, CI: 1.01 to 1.08) to be prescribed ART. Blacks (aPR = 0.93; CI: 0.87 to 0.99) and homeless persons (aPR = 0.87; CI: 0.80 to 0.95) were less likely to be virally suppressed in the combined cohort. In LAC, persons aged 30-49 years were less likely than those 50+ to be prescribed ART (aPR = 0.94, CI: 0.90 to 0.98). Younger persons (18-29) (aPR = 0.77; CI: 0.60 to 0.99) and persons with less than a high school education (aPR = 0.80; CI: 0.67 to 0.95) in Philadelphia, blacks (aPR = 0.90; CI: 0.83 to 0.99) and men who have sex with women only (aPR = 0.89; CI: 0.80 to 0.99) in Chicago, and homeless individuals in LAC (aPR = 0.80; CI: 0.67 to 0.94) were less likely to be virally suppressed. Data highlight the need to increase ART prescription to achieve viral suppression among younger persons, noninjection drug users, blacks, and homeless persons in US metropolitan areas and underscores the importance of region-specific strategies for affected subgroups.

Intermittent fasting promotes prolonged associative interactions during synaptic tagging/capture by altering the metaplastic properties of the CA1 hippocampal neurons.

PubMed

Dasgupta, Ananya; Kim, Joonki; Manakkadan, Anoop; Arumugam, Thiruma V; Sajikumar, Sreedharan

2017-12-19

Metaplasticity is the inherent property of a neuron or neuronal population to undergo activity-dependent changes in neural function that modulate subsequent synaptic plasticity. Here we studied the effect of intermittent fasting (IF) in governing the interactions of associative plasticity mechanisms in the pyramidal neurons of rat hippocampal area CA1. Late long-term potentiation and its associative mechanisms such as synaptic tagging and capture at an interval of 120 min were evaluated in four groups of animals, AL (Ad libitum), IF12 (daily IF for 12 h), IF16 (daily IF for 16 h) and EOD (every other day IF for 24 h). IF had no visible effect on the early or late plasticity but it manifested a critical role in prolonging the associative interactions between weak and strong synapses at an interval of 120 min in IF16 and EOD animals. However, both IF12 and AL did not show associativity at 120 min. Plasticity genes such as Bdnf and Prkcz, which are well known for their expressions in late plasticity and synaptic tagging and capture, were significantly upregulated in IF16 and EOD in comparison to AL. Specific inhibition of brain derived neurotropic factor (BDNF) prevented the prolonged associativity expressed in EOD. Thus, daily IF for 16 h or more can be considered to enhance the metaplastic properties of synapses by improving their associative interactions that might translate into animprovedmemoryformation. Copyright © 2017. Published by Elsevier Inc.

Comparable Effects of High-Intensity Interval Training and Prolonged Continuous Exercise Training on Abdominal Visceral Fat Reduction in Obese Young Women.

PubMed

Zhang, Haifeng; Tong, Tom K; Qiu, Weifeng; Zhang, Xu; Zhou, Shi; Liu, Yang; He, Yuxiu

2017-01-01

This study compared the effect of prolonged moderate-intensity continuous training (MICT) on reducing abdominal visceral fat in obese young women with that of work-equivalent (300 kJ/training session) high-intensity interval training (HIIT). Forty-three participants received either HIIT ( n = 15), MICT ( n = 15), or no training (CON, n = 13) for 12 weeks. The abdominal visceral fat area (AVFA) and abdominal subcutaneous fat area (ASFA) of the participants were measured through computed tomography scans preintervention and postintervention. Total fat mass and the fat mass of the android, gynoid, and trunk regions were assessed through dual-energy X-ray absorptiometry. Following HIIT and MICT, comparable reductions in AVFA (-9.1, -9.2 cm 2 ), ASFA (-35, -28.3 cm 2 ), and combined AVFA and ASFA (-44.7, -37.5 cm 2 , p > 0.05) were observed. Similarly, reductions in fat percentage (-2.5%, -2.4%), total fat mass (-2.8, -2.8 kg), and fat mass of the android (-0.3, -0.3 kg), gynoid (-0.5, -0.7 kg), and trunk (-1.6, -1.2 kg, p > 0.05) regions did not differ between HIIT and MICT. No variable changed in CON. In conclusion, MICT consisting of prolonged sessions has no quantitative advantage, compared with that resulting from HIIT, in abdominal visceral fat reduction. HIIT appears to be the predominant strategy for controlling obesity because of its time efficiency.

Protective effects of pseudoginsenoside-F11 on methamphetamine-induced neurotoxicity in mice.

PubMed

Wu, Chun Fu; Liu, Yan Li; Song, Ming; Liu, Wen; Wang, Jin Hui; Li, Xian; Yang, Jing Yu

2003-08-01

In the present study, pseudoginsenoside-F(11) (PF(11)), a saponin that existed in American ginseng, was studied on its protective effect on methamphetamine (MA)-induced behavioral and neurochemical toxicities in mice. MA was intraperitoneally administered at the dose of 10 mg/kg four times at 2-h intervals, and PF(11) was orally administered at the doses of 4 and 8 mg/kg two times at 4-h intervals, 60 min prior to MA administration. The results showed that PF(11) did not significantly influence, but greatly ameliorated, the anxiety-like behavior induced by MA in the light-dark box task. In the forced swimming task, PF(11) significantly shortened the prolonged immobility time induced by MA. In the appetitively motivated T-maze task, PF(11) greatly shortened MA-induced prolonged latency and decreased the error counts. Similar results were also observed in the Morris water maze task. PF(11) significantly shortened the escape latency prolonged by MA. There were significant decreases in the contents of dopamine (DA), 3,4-dihydroxyphenacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoacetic acid (5-HIAA) in the brain of MA-treated mice. PF(11) could partially, but significantly, antagonize MA-induced decreases of DA. The above results demonstrate that PF(11) is effective in protection of MA-induced neurotoxicity and also suggest that natural products, such as ginseng, might be potential candidates for the prevention and treatment of the neurological disorders induced by MA abuse.

Prolongation of Off-Cycle Interval by Finasteride Is Not Associated with Survival Improvement in Intermittent Androgen Deprivation Therapy in LNCaP Tumor Model

PubMed Central

Wang, Yujuan; Gupta, Shubham; Hua, Vi; Ramos-Garcia, Raquel; Shevrin, Daniel; Jovanovic, Borko D.; Nelson, Joel B

2009-01-01

BACKGROUND We have previously reported that finasteride administration in intermittent androgen deprivation therapy (IADT) can improve survival of nude mice bearing LNCaP xenograft tumors when the duration of off-cycle in IADT was fixed. A recent retrospective study showed that addition of finasteride doubled the duration of the off-cycle, without changing progression to castration resistance. In view of the above difference, we attempted to investigate the relationship of 5α-reductase inhibition with the off-cycle interval and overall survival in a murine model. METHODS Subcutaneous LNCaP tumors were established in nude mice (Balb/C-Nu). After the tumors reached a size of 0.5 cm in diameter, the mice were castrated and followed up for 2 weeks after which they were randomized to continuous androgen deprivation (CAD), CAD plus finasteride, IADT, and IADT plus finasteride. The off-cycle was discontinued when the tumor volume was doubled. Subsequent cycles were carried out similarly. RESULTS Use of finasteride during the off-cycle of IADT doubled the first off-cycle duration. However, prolongation of the off-cycle by finasteride did not translate into an increase in overall survival. CONCLUSIONS The survival advantage of IADT+F over IADT that we previously reported was lost when the off-cycle prolongation by finasteride was allowed. Maximum possible lengthening of the off-cycle by 5α-reductase inhibition is not associated with survival improvement in this animal model. PMID:19739129

Mixed Lineage Kinase 3 deficiency delays viral clearance in the lung and is associated with diminished influenza-induced cytopathic effect in infected cells

PubMed Central

Desmet, Emily A.; Hollenbaugh, Joseph A.; Sime, Patricia J.; Wright, Terry W.; Topham, David J.; Sant, Andrea J.; Takimoto, Toru; Dewhurst, Stephen; Maggirwar, Sanjay B.

2010-01-01

Influenza virus leads to acute respiratory disease resulting in seasonal epidemics and periodic pandemics. Little is known about the signaling events that regulate host defense to influenza. One particular pathway, the c-Jun amino-terminal kinase (JNK) cascade is activated following influenza infection and blocking JNK leads to enhanced viral replication. We hypothesize that Mixed Lineage Kinase 3 (MLK3), an upstream regulator of JNK, is involved in the host response to influenza. To test this, wild-type and MLK3−/− mice were infected with pathogenic strain of influenza A virus, A/PR/8/34 (PR8). Although, cellular and humoral immune responses were similar between wild-type and MLK3−/− hosts, the viral load in the lungs was comparatively higher in MLK3−/− mice at day 8 post infection. Consistent with this, MLK3−/− murine lung fibrobalsts had prolonged survival and increased virion production following infection compared to wild-type. These findings support a role for MLK3 in viral production during influenza infection. PMID:20185156

Subclinical ketosis in post-partum dairy cows fed a predominantly pasture-based diet: defining cut-points for diagnosis using concentrations of beta-hydroxybutyrate in blood and determining prevalence.

PubMed

Compton, C W R; Young, L; McDougall, S

2015-09-01

Firstly, to define, in dairy cows in the first 5 weeks post-calving fed a predominantly pasture-based diet, cut-points of concentrations of beta-hydroxybutyrate (BHBA) in blood, above which there were associations with purulent vaginal discharge (PVD), reduced pregnancy rates (PR) and decreased milk production, in order to better define subclinical ketosis (SCK) in such cattle; and secondly, to determine the prevalence, incidence and risk factors for SCK. An observational field study was conducted in 565 cows from 15 spring-calving and predominantly pasture-fed dairy herds in two regions of New Zealand during the 2010- 2011 dairy season. Within each herd, a cohort of randomly selected cows (approximately 40 per herd) was blood sampled to determine concentrations of BHBA on six occasions at weekly intervals starting within 5 days of calving. The key outcome variables were the presence/absence of PVD at 5 weeks post-calving, PR after 6 weeks (6-week PR) and after the completion of the breeding season (final PR), and mean daily milk solids production. Two cut-points for defining SCK were identified: firstly concentration of BHBA in blood≥1.2 mmol/L within 5 days post-calving, which was associated with an increased diagnosis of PVD (24 vs. 8%); and secondly concentration of BHBA in blood≥1.2 mmol/L at any stage within 5 weeks post-calving, which was associated with decreased 6-week PR (78 vs. 85%). The mean herd-level incidence of SCK within 5 weeks post-calving was 68 (min 12; max 100)% and large variations existed between herds in peak prevalence of SCK and the interval post-calving at which such peaks occurred. Cows>8 years of age and cows losing body condition were at increased risk of SCK within 5 weeks of calving. Cows with concentration of BHBA in blood≥1.2 mmol/L in early lactation had a higher risk of PVD and lower 6-week PR. Cow and herd-level prevalence of SCK varied widely in early lactation. Subclinical ketosis is common and is significantly associated with reproductive performance in mainly pasture-fed New Zealand dairy cattle. Controlling SCK may therefore result in improvements in herd reproductive performance. However considerable variation exists among herds in the incidence of SCK and in the timing of peak prevalence which means that herd-specific monitoring programmes are required to define herd SCK status accurately.

Breastfeeding: patterns, correlates, and fertility effects.

PubMed

Jain, A K; Bongaarts, J

1981-03-01

Paper based on data generated by the World Fertility Survey in 8 countries: Bangladesh, Indonesia, Sri Lanka, Jordan, Peru, Guyana, Colombia, and Panama. The authors address the following issues, among others: the prevalence and duration of breastfeeding; variations in the duration of breastfeeding among different subgroups, classified by age, parity, woman's education, etc,; the key determinants of breastfeeding; and the effect of breastfeeding on fertility. The large majority of women in all the countries breastfed their last 2 children, the number who did not ranging from 2 to 18%. Duration ranged from 9 months (Panama) to 29 months (Bangladesh). Key determinants were women's education, place of residence, husband's occupation, and survival status of the child--consistent for all 8 countries. Women with more education and those living in urban areas breastfeed for shorter periods. Sex of child, age and parity of mother, and mother's work experience showed no independent effect on duration of breastfeeding. Although breastfeeding is not used for family limitation, the possibility that it is used to prolong birth intervals cannot be ruled out. Average length of last closed birth interval increased with prolonged breastfeeding in all 8 countries. 1 month of breastfeeding adds an average of 0.4 months to the birth interval, although there was considerable variation among the countries. To what extent these variations may be due to differences in reporting errors or to other factors could not be determined.

Eribulin mesylate (halichondrin B Analog E7389) in platinum-resistant and platinum-sensitive ovarian cancer: a two-cohort, phase II study

PubMed Central

Hensley, Martee L.; Kravetz, Sara; Jia, Xiaoyu; Iasonos, Alexia; Tew, William; Pereira, Lauren; Sabbatini, Paul; Whalen, Christin; Aghajanian, Carol A.; Zarwan, Corinne; Berlin, Suzanne

2011-01-01

Background Eribulin mesylate is a tubulin inhibitor with activity superior to paclitaxel in NIH:OVCAR-3 human epithelial ovarian cancer xenograft models. We sought to assess the efficacy of eribulin in platinum-resistant and platinum-sensitive recurrent ovarian cancer. Methods Patients with recurrent measurable epithelial ovarian cancer, ≤2 prior cytotoxic regimens, and adequate organ function were enrolled into two separate cohorts: 1) Platinum resistant (progression-free interval from last platinum-based therapy <6 months); and 2) Platinum sensitive (progression-free interval from last platinum-based therapy ≥6 months). Treatment: Eribulin 1.4 mg/m2 over 15 minutes by vein on days 1 and 8, every 21 days. Efficacy was determined by objective response by computed tomography. Results Platinum-resistant cohort: Thirty-seven patients enrolled. Thirty-six patients were evaluable for response and toxicity. Two patients achieved partial response (PR, 5.5%). Sixteen (44%) had a best response of stable disease. Median progression-free survival was 1.8 months (95% confidence interval, 1.4–2.8 months). Platinum-sensitive cohort: Thirty-seven patients enrolled, and all were evaluable for response. Seven patients achieved partial response (PR, 19%). Median progression-free survival was 4.1 months (95% confidence interval, 2.8–5.8 months). The major toxicity was grade 3 or 4 neutropenia (42% in platinum-resistant patients; 54% in platinum-sensitive patients). Conclusions Eribulin achieved objective response in 5.5% of women with platinum-resistant recurrent ovarian cancer and in 19% of women with platinum-sensitive disease. Median progression-free survival was 1.8 months in the platinum-resistant group and 4.1 months in the platinum-sensitive group. PMID:21935916

Electroconvulsive therapy-induced Wolff-Parkinson-White syndrome: a case report.

PubMed

Enomoto, Shingo; Yoshino, Aihide; Takase, Bonpei; Kuwahara, Tatsuro; Tatsuzawa, Yasutaka; Nomura, Soichiro

2013-01-01

Wolff-Parkinson-White (WPW) syndrome is characterized by premature ventricular excitation due to the presence of an abnormal accessory pathway. Electrocardiography (ECG) of patients with WPW syndrome portrays a short PR interval and a wide QRS interval with a delta wave. Herein, we report the case of a patient with schizophrenia who developed a wide QRS interval with a delta wave immediately following electroconvulsive therapy (ECT). Initially, the delta wave disappeared within 2 days after ECT. However, the duration of the delta wave increased exponentially to 4 months when ECT was repeated. Although the patient's cardiocirculatory dynamics remained normal, we continued to monitor her ECG until the delta wave disappeared because WPW syndrome can lead to serious arrhythmia. Copyright © 2013 Elsevier Inc. All rights reserved.

Stability and accuracy of total and free PSA values in samples stored at room temperature.

PubMed

Forde, J C; Blake, O; Crowley, V E; Lynch, T H

2016-11-01

In 2010, an estimated 476,076 total PSA tests were performed in Ireland, at a cost of €3.6 million with the majority ordered by general practitioners. We aimed to replicate storage conditions at room temperature and see if prolonged storage affected total and free PSA values. Blood samples were taken from 20 male patients in four VACUETTE ® Serum Separator tubes (Greiner-Bio-One, Austria) and stored at room temperature (22 °C) for different time intervals (4, 8, 24, 48 h) before being centrifuged and analyzed. Total PSA (tPSA) and free PSA (fPSA) values were determined using the Tosoh AIA 1800 assay (Tokyo, Japan). Mean tPSA values were measured at 4, 8, 24 and 48 h with values of 7.9, 8.1, 7.8 and 8.0 μg/L, respectively. Values ranged from -1.26 to +2.53 % compared to the initial 4 h interval reading, indicating tPSA remained consistent at room temperature. The tPSA showed no significance between groups (ANOVA, p = 0.283). Mean fPSA values at 4, 8, 24 and 48 h were 2.05, 2.04, 1.83, 1.82 μg/L, respectively. At 24 and 48 h there was 10.73 and 11.22 % reduction, respectively, in fPSA compared to the 4-h time interval, indicating prolonged storage resulted in reduced fPSA values. After 24 h, there was an 8.8 % reduction in the free/total PSA %. The fPSA showed significant differences between groups (ANOVA, p = 0.024). Our recommendation is that samples that have been stored for prolonged amounts of time (greater than 24 h) should not be used for free PSA testing.

Elevated Plasma Moxifloxacin Concentrations and SLCO1B1 g.−11187G>A Polymorphism in Adults with Pulmonary Tuberculosis

PubMed Central

Gelfond, Jon; Johnson-Pais, Teresa L.; Engle, Melissa; Peloquin, Charles A.; Johnson, John L.; Sizemore, Erin E.; Mac Kenzie, William R.

2018-01-01

ABSTRACT Moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals and bactericidal activity against Mycobacterium tuberculosis. However, moxifloxacin plasma concentrations are variable between patients. We evaluated whether human gene polymorphisms affect moxifloxacin plasma concentrations in tuberculosis patients from two geographic regions. We enrolled a convenience sample of 49 adults with drug-sensitive pulmonary tuberculosis from Africa and the United States enrolled in two treatment trials of moxifloxacin as part of multidrug therapy. Pharmacokinetic parameters were evaluated by noncompartmental techniques. Human single-nucleotide polymorphisms of transporter genes were evaluated by analysis of covariance (ANCOVA) on moxifloxacin exposure and the peak (maximum) concentration (Cmax). The moxifloxacin area under the concentration-time curve from 0 to 24 h (AUC0–24) and Cmax were significantly increased by the drug milligram-per-kilogram dosage and the genotype of variant g.−11187G>A in the SLCO1B1 gene (rs4149015) but not by geographic region. The median moxifloxacin AUC0–24 was 46% higher and the median Cmax was 30% higher in 4 (8%) participants who had the SLCO1B1 g.−11187 AG genotype than in 45 participants who had the wild-type GG genotype (median AUC0–24 from the model, 34.4 versus 23.6 μg · h/ml [P = 0.005, ANCOVA]; median Cmax from the model, 3.5 versus 2.7 μg/ml [P = 0.009, ANCOVA]). Because moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals and prolonged QTc intervals are associated with cardiac arrhythmia, further study is needed to evaluate the risk associated with the SLCO1B1 g.−11187G>A variant. (This study has been registered at ClinicalTrials.gov under identifier NCT00164463.) PMID:29463526

Tp-Te interval predicts heart rate reduction after fingolimod administration in patients with multiple sclerosis.

PubMed

Tocci, Giuliano; Giuliani, Manuela; Canichella, Flaminia; Timpano, Jacopo; Presta, Vivianne; Francia, Pietro; Musumeci, Maria Beatrice; Fubelli, Federica; Pozzilli, Carlo; Volpe, Massimo; Ferrucci, Andrea

2016-10-15

FTY720 (Fingolimod) is an immunosuppressive drug, which provides favourable effects in patients with multiple sclerosis (MS), albeit it induces heart rate (HR) and blood pressure (BP) reductions. Therefore, we tested potential factors able to predict HR response in MS patients treated with fingolimod. We analysed patients with MS followed at our Neurology Outpatient Clinic from May 2013 to June 2015. All patients underwent BP measurements and 12-lead ECG before and 6-h after drug administration. At these time intervals, conventional and new ECG indexes for cardiac damage, including Tp-Te interval, were measured. Univariate and multivariate analyses were performed to test the outcome of HR reduction more than median difference between baseline and final observations. 69 outpatients with MS (46 males, age 35.1±9.4years, BP 119.0±12.7/73.0±9.3mmHg, HR 73.5±11.4bpm) were included. No relevant adverse reactions were reported. Fingolimod induced progressive systolic (P=0.024) and diastolic (P<0.001) BP, as well as HR (P<0.001) reductions compared to baseline. Prolonged PQ (150.4±19.5 vs. 157.0±19.5ms; P<0.001), QT (374.9±27.0 vs. 400.0±25.8ms; P<0.001), Tp-Te (1.8±0.3 vs. 1.9±0.3mm; P=0.021), and reduced QTc (414.4±24.4 vs. 404.5±24.5ms; P<0.001) intervals were also recorded at final observation. Baseline HR, QT and Tp-Te intervals provided prognostic information at univariate analysis, although Tp-Te interval resulted the best independent predictor for HR reduction at multivariate analysis [0.057 (0.005-0.660); P=0.022]. This study firstly demonstrates that prolonged Tp-Te interval may identify those MS patients treated with fingolimod at higher risk of having significant, asymptomatic HR reduction during clinical observation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Feasibility of noninvasive fetal electrocardiographic monitoring in a clinical setting.

PubMed

Arya, Bhawna; Govindan, Rathinaswamy; Krishnan, Anita; Duplessis, Adre; Donofrio, Mary T

2015-06-01

Cardiac rhythm is an essential component of fetal cardiac evaluation. The Monica AN24 is a fetal heart rate monitor that may provide a quick, inexpensive modality for obtaining a noninvasive fetal electrocardiogram (fECG) in a clinical setting. The fECG device has the ability to acquire fECG signals and allow calculation of fetal cardiac time intervals between 16- and 42-week gestational age (GA). We aimed to demonstrate the feasibility of fECG acquisition in a busy fetal cardiology clinic using the Monica fetal heart rate monitor. This is a prospective observational pilot study of fECG acquired from fetuses referred for fetal echocardiography. Recordings were performed for 5-15 min. Maternal signals were attenuated and fECG averaged. fECG and fetal cardiac time intervals (PR, QRS, RR, and QT) were evaluated by two cardiologists independently and inter-observer reliability was assessed using intraclass coefficient (ICC). Sixty fECGs were collected from 50 mothers (mean GA 28.1 ± 6.1). Adequate signal-averaged waveforms were obtained in 20 studies with 259 cardiac cycles. Waveforms could not be obtained between 26 and 30 weeks. Fetal cardiac time intervals were measured and were reproducible for PR (ICC = 0.89; CI 0.77-0.94), QRS (ICC = 0.79; CI 0.51-0.91), and RR (ICC = 0.77; CI 0.53-0.88). QT ICC was poor due to suboptimal T-wave tracings. Acquisition of fECG and measurement of fetal cardiac time intervals is feasible in a clinical setting between 19- and 42-week GA, though tracings are difficult to obtain, especially between 26 and 30 weeks. There was high reliability in fetal cardiac time intervals measurements, except for QT. The device may be useful for assessing atrioventricular/intraventricular conduction in fetuses from 20 to 26 and >30 weeks. Techniques to improve signal acquisition, namely T-wave amplification, are ongoing.

Prognostic value of estrogen receptor and progesterone receptor tumor expression in Danish ovarian cancer patients: from the 'MALOVA' ovarian cancer study.

PubMed

Høgdall, Estrid V S; Christensen, Lise; Høgdall, Claus K; Blaakaer, Jan; Gayther, Simon; Jacobs, Ian J; Christensen, Ib Jarle; Kjaer, Susanne K

2007-11-01

Estrogen and progesterone are important hormones secreted by the ovary acting through specific receptors. Tumor tissue expression profiles of these have demonstrated prognostic value in malignancies such as breast, uterine and prostate cancer. In this study, including tissue samples from 773 Danish patients with an ovarian tumor, we evaluated whether estrogen receptor (ER) and progesterone receptor (PR) expression correlated with clinico-pathological parameters, and a possible prognostic impact on ovarian cancer (OC) patients was investigated. Using tissue array and immunohistochemistry, we analyzed the ER and PR expression levels in tissues from 582 women with OC and 191 women with low malignancy potential (LMP) ovarian tumors. Our results demonstrated that ER was expressed in 30 of the 191 LMP tumors (16%) and in 207 of the 582 OC (36%). PR was expressed in 38 LMP tumors (20%) and in 115 OC (20%). For both tumor types an excess of positive tumors was found in the serous compared to the mucinous subtype (p< or =0.00001). The frequency of ER expression-positive OC increased with increasing FIGO stage (p=0.0003), and the frequency of PR-positive tumors increased with increasing histological grade (p=0.0006). In a Cox survival analysis, a tissue ER and PR expression 10% or higher was found to imply an independent significant advantageous course of patient disease-specific survival (ER: hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.63-0.99; PR: HR, 0.69; 95% CI, 0.51-0.94) together with FIGO stage, residual tumor after primary surgery, age at diagnosis and other histological types vs. serous adenocarcinoma. The histological grade of tumor was found to have no independent prognostic value. The prognostic value of ER and PR was found additive with a HR for patients with high ER and PR expression of 0.48 (95% CI, 0.31-0.74) compared to patients with <10% expression for both receptors. In conclusion, our results predict that an elevated expression of ER and PR, alone and in combination, point to a favorable outcome for patients with OC.

Bicarbonate refractory QRS prolongation and left bundle-branch block following escitalopram and lamotrigine overdose: A case report and literature review of toxic left bundle-branch block.

PubMed

Farkas, A N; Marcott, M; Yanta, J H; Pizon, A F

2018-05-02

Toxic prolongation of the QRS interval most often results from blockade of cardiac voltage-gated sodium channels and manifests on electrocardiogram with a right bundle-branch block-like morphology. Rarely, a left bundle-branch block (LBBB) morphology has been reported. We report a case of transient LBBB resultant from ingestion of lamotrigine and citalopram which was refractory to sodium bicarbonate therapy and eventually resolved spontaneously. Cases of toxic LBBB are less likely to respond to bicarbonate therapy, suggesting that this finding is due to a mechanism other than sodium channel blockade. © 2018 John Wiley & Sons Ltd.

Prolonged treatment with transcutaneous electrical nerve stimulation (TENS) modulates neuro-gastric motility and plasma levels of vasoactive intestinal peptide (VIP), motilin and interleukin-6 (IL-6) in systemic sclerosis.

PubMed

McNearney, Terry A; Sallam, Hanaa S; Hunnicutt, Sonya E; Doshi, Dipti; Chen, Jiande D Z

2013-01-01

We assessed the effects of transcutaneous electrical nerve stimulation (TENS) on neurogastric functioning in scleroderma patients. Seventeen SSc patients underwent 30 min TENS treatment >10Hz at GI acupuncture points PC6 and ST36, once (acute TENS) and then after two weeks of TENS sessions for 30 min twice daily (prolonged TENS). Data collected at Visits 1 and 2 included gastric myoelectrical activity (GMA) by surface electrogastrography (EGG), heart rate variability (HRV) by surface electrocardiography (EKG), GI specific symptoms and health related SF-36 questionnaires. Plasma VIP, motilin and IL-6 levels were determined. Statistical analyses were performed by Student's t-test, Spearman Rank and p-values <0.05 were considered significant. 1. Only after prolonged TENS, the percentages of normal slow waves and average slow wave coupling (especially channels 1, 2 reflecting gastric pacemaker and corpus regions) were significantly increased; 2. the percentage of normal slow waves was significantly correlated to sympathovagal balance; 3. Mean plasma VIP and motilin levels were significantly decreased after acute TENS, (vs. baseline), generally maintained in the prolonged TENS intervals. Compared to baseline, mean plasma IL-6 levels were significantly increased after acute TENS, but significantly decreased after prolonged TENS. 4. After prolonged TENS, the frequency of awakening due to abdominal pain and abdominal bloating were significantly and modestly decreased, respectively. In SSc patients, two weeks of daily TENS improved patient GMA scores, lowered plasma VIP, motilin and IL-6 levels and improved association between GMA and sympathovagal balance. This supports the therapeutic potential of prolonged TENS to enhance gastric myoelectrical functioning in SSc.

Effects of an Extended Cage-change Interval on Ammonia Levels and Reproduction in Mongolian Gerbils (Meriones unguiculatus).

PubMed

McCullagh, Elizabeth A; McCullagh, Peter; Klug, Achim; Leszczynski, Jori K; Fong, Derek L

2017-11-01

Prompted by the cage cleanliness of Mongolian gerbils (Meriones unguiculatus), we evaluated a prolonged cage-change interval. We compared the effects of a 2-wk and 6-wk cage-change schedule on ammonia levels, temperature, humidity, and reproductive performance in breeding pairs housed in IVC. We hypothesized that ammonia levels would remain below our threshold for cage changing and that reproductive performance would not be affected. Although ammonia levels increased over time, they remained low (less than 5 ppm) over the 6-wk period. In addition, the 6-wk cage-change interval did not significantly influence reproductive parameters, such as average pup weaning weight, number of litters, and number of pups per litter. We conclude that an extended cage-change interval (6-wk) can be used for gerbils without significant increases in intracage ammonia levels or effects on reproduction.

Prolonged breast-feeding and mortality up to two years post-partum among HIV-positive women in Zambia

PubMed Central

Kuhn, Louise; Kasonde, Prisca; Sinkala, Moses; Kankasa, Chipepo; Semrau, Katherine; Vwalika, Cheswa; Tsai, Wei-Yann; Aldrovandi, Grace M.; Thea, Donald M.

2005-01-01

Background A previously reported association between prolonged lactation and maternal mortality has generated concern that breast-feeding may be detrimental for HIV-positive women. Methods As part of a trial conducted in Lusaka, Zambia, 653 HIV-positive women were randomly assigned either to a counseling program that encouraged abrupt cessation of breast-feeding at 4 months (group A) or to a program that encouraged prolonged breast-feeding for the duration of the woman’s own informed choice (group B). We examined whether mortality up to 2 years post-partum increased with breast-feeding for a longer duration. Results There was no difference in mortality 12 months after delivery between 326 HIV-positive women randomly assigned to short breast-feeding [group A: 4.93%; 95% confidence interval (CI), 2.42–7.46] versus 327 women assigned to long breast-feeding (group B: 4.89%; 95% CI, 2.38–7.40). Analysis based on actual practice, rather than random assignment, also demonstrated no increased mortality due to breast-feeding. Conclusions Although HIV-related mortality was high in this cohort of untreated HIV-positive women, prolonged lactation was not associated with increased mortality. PMID:16184038

Soil-transmitted helminth infection and nutritional status among urban slum children in Kenya.

PubMed

Suchdev, Parminder S; Davis, Stephanie M; Bartoces, Monina; Ruth, Laird J; Worrell, Caitlin M; Kanyi, Henry; Odero, Kennedy; Wiegand, Ryan E; Njenga, Sammy M; Montgomery, Joel M; Fox, LeAnne M

2014-02-01

To evaluate the nutritional impact of soil-transmitted helminth (STH) infection, we conducted a cross-sectional survey of 205 pre-school (PSC) and 487 school-aged children (SAC) randomly selected from the surveillance registry of the Centers for Disease Control and Prevention of the Kibera slum in Kenya. Hemoglobin, iron deficiency (ID), vitamin A deficiency (VAD), inflammation, malaria, anthropometry, and STH ova were measured. Poisson regression models evaluated associations between STH and malnutrition outcomes and controlled for confounders. Approximately 40% of PSC and SAC had STH infection, primarily Ascaris and Trichuris; 2.9% of PSC and 1.1% of SAC had high-intensity infection. Malnutrition prevalence among PSC and SAC was anemia (38.3% and 14.0%, respectively), ID (23.0% and 5.0%, respectively), VAD (16.9% and 4.5%, respectively), and stunting (29.7% and 16.9%, respectively). In multivariate analysis, STH in PSC was associated with VAD (prevalence ratio [PR] = 2.2, 95% confidence interval = 1.1-4.6) and ID (PR = 3.3, 95% confidence interval = 1.6-6.6) but not anemia or stunting. No associations were significant in SAC. Integrated deworming and micronutrient supplementation strategies should be evaluated in this population.

[Effect of PMU hepatic arterial chemotherapy for liver metastases of gastric cancer. Hokuriku Cisplatin Round-table Conference].

PubMed

Sakuma, H; Matsuki, N; Katayama, K; Hirosawa, H; Tomita, F; Takano, N; Tanaka, T; Sawa, T; Ueno, K; Uogishi, M

1989-08-01

We performed PMU hepatic arterial chemotherapy (a combination therapy consisting of intra-hepatic arterial infusion of CDDP and MMC, oral administration of UFT) in 20 patients with gastric cancer and liver metastases. In this method, 1-6 courses of one infusion of CDDP at 70-100 mg/body and MMC of 10 mg/body into the proper hepatic artery were administered at intervals of 3-4 weeks. UFT of 300-400 mg/day was orally administered with the infusion. The primary response for hepatic metastatic lesions was observed in one case of CR, 14 cases of PR, 4 cases of NC, and one case of PD. The efficacy for CR and PR was high at 75%. The median disease-free interval was 56 weeks in responders. The 50% survival period was 11.1 months; one-year survival rate, 42.1%; two-year survival rate, 12.3%; the longest survival period was 108 weeks. Mild and transient side effects were recognized in 17 cases (85%): gastrointestinal symptoms, sense of general malaise, fever, leukocytopenia, and elevated BUN. Thus, the results indicated that this combination chemotherapy was effective for liver metastases of gastric cancer.

The prevalence of actinic cheilitis in farmers in a semi-arid northeastern region of Brazil.

PubMed

Martins-Filho, Paulo Ricardo Saquete; Da Silva, Luiz Carlos Ferreira; Piva, Marta Rabello

2011-09-01

Actinic cheilitis (AC) is a potentially malignant disorder of the lip caused by chronic exposure to solar radiation. Despite being a relatively common lesion in tropical countries, the data related to AC prevalence in Brazil are sparse, particularly in regions with high levels of ultraviolet radiation. To estimate AC prevalence among farmers in a semiarid northeastern Brazil. Cross-sectional study was carried out involving a representative sample (n = 240) of the farm workers. Sociodemographic, clinical, and histopathological variables were analyzed. AC prevalence was 16.7% [95% confidence interval (CI): 12.0% to 21.4%]. The disease was more prevalent in males [prevalence ratio (PR) = 2.72; 95% CI: 1.52-4.90], fair-skinned farmers (PR = 2.07; 95% CI: 1.00-4.30), age over 50 years (PR = 2.91; 95% CI: 1.40-6.04), daily exposure time more than eight hours (PR = 1.84; 95% CI: 1.03-3.27), and among smokers/ex-smokers (PR = 2.17; 95% CI: 1.22-3.87). Mantel-Haenszel test showed a positive relationship between cumulative exposure time and development of AC (P < 0.001). Two cases were diagnosed as microinvasive squamous cell carcinoma. Our results suggest that farmers in this semiarid area have a high risk of lip cancer and indicate the need for health public programs in the early detection of AC and education to teach the population about precautions to be taken during sun exposure. © 2011 The International Society of Dermatology.

Post-exposure prophylaxis awareness and use among men who have sex with men in London who use geosocial-networking smartphone applications.

PubMed

Goedel, William C; Hagen, Daniel; Halkitis, Perry N; Greene, Richard E; Griffin-Tomas, Marybec; Brooks, Forrest A; Hickson, DeMarc; Duncan, Dustin T

2017-05-01

The number of new HIV infections continues to be on the rise in many high-income countries, most notably among men who have sex with men (MSM). Despite recent attention to the use of antiretroviral medications as pre-exposure prophylaxis (PrEP) among MSM, considerably less research has been devoted to examining the awareness and use of post-exposure prophylaxis (PEP). Based on a convenience sample of 179 self-reported HIV-uninfected MSM using a geosocial-networking smartphone application, this study is among the first to examine the awareness and use of PEP and their demographic and behavioral correlates among MSM in London. Most respondents (88.3%) had heard of PEP, where 27.4% reported having used it. In multivariable models, the disclosure of one's sexual orientation to their general practitioner (Prevalence ratio [PR]: 3.49; 95% confidence interval (CI): 1.14, 10.70; p = .029) and reporting one's HIV status as negative (rather than unknown) (PR: 11.49; 95% CI: 1.68, 76.92; p = .013) were associated with having heard of PEP; while the recent use of club drugs (PR: 3.02; 95% CI: 1.42, 6.43; p = .004) was associated with having ever used PEP. High awareness and use in this sample suggest that PEP is a valuable risk-reduction strategy that should be capitalized on, be it in addition to or in the absence of PrEP.

Post-exposure prophylaxis awareness and use among men who have sex with men in London who use geosocial-networking smartphone applications

PubMed Central

Goedel, William C.; Hagen, Daniel; Halkitis, Perry N.; Greene, Richard E.; Griffin-Tomas, Marybec; Brooks, Forrest A.; Hickson, DeMarc; Duncan, Dustin T.

2017-01-01

The number of new HIV infections continues to be on the rise in many high-income countries, most notably among men who have sex with men (MSM). Despite recent attention to the use of antiretroviral medications as pre-exposure prophylaxis (PrEP) among MSM, considerably less research has been devoted to examining the awareness and use of post-exposure prophylaxis (PEP). Based on a convenience sample of 179 self-reported HIV-uninfected MSM using a geosocial-networking smartphone application, this study is among the first to examine the awareness and use of PEP and their demographic and behavioral correlates among MSM in London. Most respondents (88.3%) had heard of PEP, where 27.4% reported having used it. In multivariable models, the disclosure of one’s sexual orientation to their general practitioner (Prevalence ratio [PR]: 3.49; 95% confidence interval (CI): 1.14, 10.70; p = .029) and reporting one’s HIV status as negative (rather than unknown) (PR: 11.49; 95% CI: 1.68, 76.92; p = .013) were associated with having heard of PEP; while the recent use of club drugs (PR: 3.02; 95% CI: 1.42, 6.43; p = .004) was associated with having ever used PEP. High awareness and use in this sample suggest that PEP is a valuable risk-reduction strategy that should be capitalized on, be it in addition to or in the absence of PrEP. PMID:27910722

[Repeated pregnancy among adolescents and social vulnerability in Rio de Janeiro (RJ, Brazil): data analysis of Information System on Live Births].

PubMed

da Silva, Katia Silveira; Rozenberg, Riva; Bonan, Claudia; Chuva, Vânia Cristina Costa; da Costa, Simoni Furtado; Gomes, Maria Auxiliadora de Souza Mendes

2011-05-01

Repeated pregnancy (RP) among adolescents is seldom researched in Brazil, even tough the debate on the reproductive rights is important for this extract of population. A transversal study was developed with data from the Declaration of Live Births of adolescent mothers, living in Rio de Janeiro (RJ, Brazil), in 2005. The aim was to estimate the magnitude and features associated with RP. Prevalence ratios (PR) of RP, with 95% confidence interval (CI) for selected variables, were estimated through log-binomial multivariate regression. Among 12,168 adolescents, a RP prevalence of 29.1% was identified and the principal factors associated were: age 15-19 anos (PR=5.42; RI 95% 3.72-7.81); not doing prenatal consultation (RP=2.36; CI 95% 2.16-2.58); educational status<4 anos (PR=1.48; CI 95% 1.25-1.76); housewife job (PR=1.8; CI 95% 1.57-2.15) or other (PR=1.9; CI 95%; 1.73-2.10). Giving birth by cesarean section and low birth weight were negatively associated to repeated pregnancy with RP equal to 0,94 (CI 95%; 0,86-0,99) and 0.69 (CI 95%; 0.62-0.77). The adolescents with RP had worst socioeconomic and assistance indicators than those on their first pregnancy. Specific social policies for adolescent mothers, in vulnerable situation, will enable them to have better conditions to exercise their reproductive rights.

Prevalence and factors associated with latent tuberculosis infection in an indigenous population in the Brazilian Amazon.

PubMed

Malacarne, Jocieli; Rios, Diana Patricia Giraldo; Silva, Cosme Marcelo Furtado Passos da; Braga, José Ueleres; Camacho, Luiz Antonio Bastos; Basta, Paulo Cesar

2016-01-01

Recent studies have shown a high incidence and prevalence of latent tuberculosis infection (LTBI) in indigenous populations around the World. We aimed to estimate the prevalence and annual risk of infection (ARI) as well as to identify factors associated with LTBI in an indigenous population from the Brazilian Amazon. We conducted a cross-sectional study in 2011. We performed tuberculin skin tests (TSTs), smears and cultures of sputum samples, and chest radiographs for individuals who reported cough for two or more weeks. Associations between LTBI (TST ≥5mm) and socio-demographic, clinical, and epidemiological characteristics were investigated using Poisson regression with robust variance. Prevalence ratio (PR) was used as the measure of association. We examined 263 individuals. The prevalence of LTBI was 40.3%, and the ARI was 2.4%. Age ≥15 years [PR=5.5; 95% confidence interval (CI): 3.5-8.6], contact with tuberculosis (TB) patients (PR=3.8; 95% CI: 1.2-11.9), previous TB history (PR=1.4; 95% CI: 1.2-1.7), and presence of Bacillus Calmette-Guérin (BCG) scar (PR=1.9, 95% CI: 1.2-2.9) were associated with LTBI. Although some adults may have been infected years prior, the high prevalence of infection and its strong association with age ≥15 years, history of TB, and recent contact with TB patients suggest that the TB transmission risk is high in the study area.

Recent Transmission of Tuberculosis — United States, 2011–2014

PubMed Central

Yuen, Courtney M.; Kammerer, J. Steve; Marks, Kala; Navin, Thomas R.; France, Anne Marie

2016-01-01

Tuberculosis is an infectious disease that may result from recent transmission or from an infection acquired many years in the past; there is no diagnostic test to distinguish the two causes. Cases resulting from recent transmission are particularly concerning from a public health standpoint. To describe recent tuberculosis transmission in the United States, we used a field-validated plausible source-case method to estimate cases likely resulting from recent transmission during January 2011–September 2014. We classified cases as resulting from either limited or extensive recent transmission based on transmission cluster size. We used logistic regression to analyze patient characteristics associated with recent transmission. Of 26,586 genotyped cases, 14% were attributable to recent transmission, 39% of which were attributable to extensive recent transmission. The burden of cases attributed to recent transmission was geographically heterogeneous and poorly predicted by tuberculosis incidence. Extensive recent transmission was positively associated with American Indian/Alaska Native (adjusted prevalence ratio [aPR] = 3.6 (95% confidence interval [CI] 2.9–4.4), Native Hawaiian/Pacific Islander (aPR = 3.2, 95% CI 2.3–4.5), and black (aPR = 3.0, 95% CI 2.6–3.5) race, and homelessness (aPR = 2.3, 95% CI 2.0–2.5). Extensive recent transmission was negatively associated with foreign birth (aPR = 0.2, 95% CI 0.2–0.2). Tuberculosis control efforts should prioritize reducing transmission among higher-risk populations. PMID:27082644

Nonprescribed use of tranquilizers and use of other drugs among Brazilian students.

PubMed

Opaleye, Emérita S; Ferri, Cleusa P; Locatelli, Danilo P; Amato, Tatiana C; Noto, Ana R

2014-01-01

To describe patterns of nonprescribed use of tranquilizers by students aged 10 to 18 years and assess the sociodemographic characteristics of these adolescents and their use of other substances. A randomized and stratified sample of 47,979 students from state and private schools of the 27 Brazilian state capitals completed a self-report questionnaire. Poisson regression was used to estimate the associations between tranquilizer use and sociodemographic factors, as well as the use of other psychotropic substances. The lifetime prevalence of nonprescribed use of tranquilizers was 3.9%. Use was most common among girls, wealthier adolescents, and those from private schools. An association was found between use of tranquilizers and lifetime use of alcohol (prevalence ratio [PR] = 3.15; 95% confidence intervals [95%CI] 2.58-3.85), tobacco (PR = 2.61; 95%CI 2.31-2.95), illicit drugs (PR = 3.70; 95%CI 3.19-4.29), and other prescription drugs (PR = 7.03; 95%CI 6.18-7.99). As the number of substances adolescents reported having used increased, so did the nonprescribed use of tranquilizers. Nonprescribed use of tranquilizers by adolescents might indicate the use of other substances, including high-risk combinations such as tranquilizers and alcohol. The risks of this association should be addressed during the early stages of drug prevention programs.

The association between major birth defects and preterm birth.

PubMed

Honein, Margaret A; Kirby, Russell S; Meyer, Robert E; Xing, Jian; Skerrette, Nyasha I; Yuskiv, Nataliya; Marengo, Lisa; Petrini, Joann R; Davidoff, Michael J; Mai, Cara T; Druschel, Charlotte M; Viner-Brown, Samara; Sever, Lowell E

2009-03-01

To evaluate the association between preterm birth and major birth defects by maternal and infant characteristics and specific types of birth defects. We pooled data for 1995-2000 from 13 states with population-based birth defects surveillance systems, representing about 30% of all U.S. births. Analyses were limited to singleton, live births from 24-44 weeks gestational age. Overall, birth defects were more than twice as common among preterm births (24-36 weeks) compared with term births (37-41 weeks gestation) (prevalence ratio [PR] = 2.65, 95% confidence interval [CI] 2.62-2.68), and approximately 8% of preterm births had a birth defect. Birth defects were over five times more likely among very preterm births (24-31 weeks gestation) compared with term births (PR = 5.25, 95% CI 5.15-5.35), with about 16% of very preterm births having a birth defect. Defects most strongly associated with very preterm birth included central nervous system defects (PR = 16.23, 95% CI 15.49-17.00) and cardiovascular defects (PR = 9.29, 95% CI 9.03-9.56). Birth defects contribute to the occurrence of preterm birth. Research to identify shared causal pathways and risk factors could suggest appropriate interventions to reduce both preterm birth and birth defects.

Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin.

PubMed Central

Richter, C; Schnabel, A; Csernok, E; De Groot, K; Reinhold-Keller, E; Gross, W L

1995-01-01

In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality. PMID:7621588

A detailed description of the short-term musculoskeletal and cognitive effects of prolonged standing for office computer work.

PubMed

Baker, Richelle; Coenen, Pieter; Howie, Erin; Lee, Jeremy; Williamson, Ann; Straker, Leon

2018-07-01

Due to concerns about excessive sedentary exposure for office workers, alternate work positions such as standing are being trialled. However, prolonged standing may have health and productivity impacts, which this study assessed. Twenty adult participants undertook two hours of laboratory-based standing computer work to investigate changes in discomfort and cognitive function, along with muscle fatigue, movement, lower limb swelling and mental state. Over time, discomfort increased in all body areas (total body IRR [95% confidence interval]: 1.47[1.36-1.59]). Sustained attention reaction time (β = 18.25[8.00-28.51]) deteriorated, while creative problem solving improved (β = 0.89[0.29-1.49]). There was no change in erector spinae, rectus femoris, biceps femoris or tibialis anterior muscle fatigue; low back angle changed towards less  lordosis, pelvis movement increased, lower limb swelling increased and mental state decreased. Body discomfort was positively correlated with mental state. The observed changes suggest replacing office work sitting with standing should be done with caution. Practitioner Summary: Standing is being used to replace sitting by office workers; however, there are health risks associated with prolonged standing. In a laboratory study involving 2 h prolonged standing discomfort increased (all body areas), reaction time and mental state deteriorated while creative problem-solving improved. Prolonged standing should be undertaken with caution.

Work-related asthma, financial barriers to asthma care, and adverse asthma outcomes: asthma call-back survey, 37 states and District of Columbia, 2006 to 2008.

PubMed

Knoeller, Gretchen E; Mazurek, Jacek M; Moorman, Jeanne E

2011-12-01

Proper asthma management and control depend on patients having affordable access to healthcare yet financial barriers to asthma care are common. To examine associations of work-related asthma (WRA) with financial barriers to asthma care and adverse asthma outcomes. Cross-sectional, random-digit-dial survey conducted in 37 states and District of Columbia. A total of 27,927 ever-employed adults aged ≥18 years with current asthma. Prevalence ratios (PR) for the associations of WRA with financial barriers to asthma care and of WRA with adverse asthma outcomes stratified by financial barriers. Persons with WRA were significantly more likely than those with non-WRA to have at least 1 financial barrier to asthma care [PR, 1.66; 95% confidence interval (CI), 1.43-1.92]. Individuals with WRA were more likely to experience adverse asthma outcomes such as asthma attack (PR, 1.31; 95% CI, 1.22-1.40), urgent treatment for worsening asthma (PR, 1.57; 95% CI, 1.39-1.78), asthma-related emergency room visit (PR, 1.69; 95% CI, 1.41-2.03), and very poorly controlled asthma (PR, 1.54; 95% CI: 1.36-1.75). After stratifying for financial barriers to asthma care, the associations did not change. Financial barriers to asthma care should be considered in asthma management, and individuals with WRA are more likely to experience financial barriers. However, individuals with WRA are more likely to experience adverse asthma outcomes than individuals with non-WRA, regardless of financial barriers. Additional studies are needed to identify medical, behavioral, occupational, or environmental factors associated with adverse asthma outcomes among individuals with WRA.

[Mass media influence and risk of developing eating disorders in female students from Lima, Peru].

PubMed

Lazo Montoya, Yessenia; Quenaya, Alejandra; Mayta-Tristán, Percy

2015-12-01

Eating disorders (EDs) are a public health problem, and their relationship to mass media is still controversial. To assess whether there is an association between models of body image shown in mass media and the risk of developing EDs among female adolescent students from Lima, Peru. Cross-sectional study conducted in three schools located in the district of La Victoria, Lima, Peru. The risk of developing EDs was measured using the Eating Attitudes Test-26 (EAT-26), while mass media influence was measured using the Sociocultural Attitudes Towards Appearance Questionnaire-3 (SATAQ-3), which was categorized into tertiles both in the overall score and its subscales (information, pressure, general internalization, and athletic internalization). Adjusted prevalence ratios (aPR) for EDs were estimated. Four hundred and eighty-three students were included, their median age was 14 ? 3 years old. A risk of developing an ED was observed in 13.9% of them. Students who are more influenced by mass media (upper tertile of the SATAQ-3) have a higher probability of having a risk of developing an ED (aPR: 4.24; 95% confidence interval |-CI-|: 2.10-8.56), as well as those who have a greater access to information (PR: 1.89; 95% CI: 1.09-3.25), suffer more pressure (PR: 4.97; 95% CI: 2.31-10.69), show a greater general internalization (PR: 5.00; 95% CI: 2.39-10.43), and show a greater level of athletic internalization (PR: 4.35; 95% CI: 2.19-8-66). The greater the influence of mass media, the greater the probability of having a risk of developing an ED among female students from Lima, Peru.

Characteristics and Risk Behaviors of Men Who Have Sex With Men and Women Compared With Men Who Have Sex With Men-20 US Cities, 2011 and 2014.

PubMed

Shadaker, Shaun; Magee, Matthew; Paz-Bailey, Gabriela; Hoots, Brooke E

2017-07-01

Men who have sex with men (MSM) are heterogeneous with respect to sexual behavior. We examined differences in sex behaviors between men who have sex with men and women (MSMW) and men who have sex with men only (MSMO). Data for this analysis were from MSM who participated in National HIV Behavioral Surveillance in 2011 and 2014. We used the combined years to evaluate demographic and behavioral differences between MSMW and MSMO. Using log-linked Poisson regression models, adjusted prevalence ratios (aPR) were calculated for behavioral outcomes. Overall, 2042 (11.9%) participants were classified as MSMW. MSMW were less likely than MSMO to have condomless sex with male partners [aPR 0.77; 95% confidence interval (CI): 0.74 to 0.81] and to have been diagnosed with another sexually transmitted disease (aPR 0.83; 95% CI: 0.72 to 0.95). MSMW were more likely than MSMO to have given money or drugs for sex (aPR 2.85; 95% CI: 2.52 to 3.24) or received money or drugs for sex (aPR 2.64; 95% CI: 2.37 to 2.93) and to ever have injected drugs (aPR 2.05; 95% CI: 1.80 to 2.34). MSMW had more total sex partners (median 6, interquartile range: 4-11 vs. 3, 2-8), casual sex partners (5, 2-10 vs. 3, 1-7), and condomless sex partners (2, 1-4 vs. 1, 0-2) in the last 12 months (P < 0.01 for all comparisons). MSMW have distinct sexual risk behaviors from MSMO and may contribute to HIV transmission among women. MSMW could benefit from tailored interventions to reduce HIV risk behaviors.

Individual and contextual factors related to binge drinking among adolescents in Spain: a multilevel approach.

PubMed

Teixidó-Compañó, Ester; Sordo, Luis; Bosque-Prous, Marina; Puigcorbé, Susanna; Barrio, Gregorio; Brugal, M Teresa; Belza, María José J; Espelt, Albert

2018-01-15

The aim of this study was to estimate the prevalence of binge drinking by regions in Spain and assess the effect of individual and contextual factors related to this drinking pattern in adolescents. A cross-sectional study was performed with data from the 2014 Spanish School Survey on Drug Use (ESTUDES) in students aged 14-18 years (N = 34,259). The outcome was binge drinking in adolescents during the last 30 days. Individual independent variables were socioeconomic variables and variables related to access to alcohol and its availability. Contextual variables consisted of adult alcohol consumption, public policies on alcohol, and socioeconomic factors. Multilevel Poisson regression models with robust variance were estimated, obtaining prevalence ratios (PR) and their 95% confidence intervals.  The results showed that the prevalence of youth binge drinking by region of residence was similar for both sexes (r = 0.72). At the individual level, binge drinking was mainly associated with the perception of easy access to alcohol (PR: 1.38; 95% CI: 1.23-1.55), consumption in open areas [(PR: 3.82; 95% CI: 3.44-4.24) < once a month and (PR: 6.57; 95% CI: 5.85-7.37) ≥ once a month], at least one parent allowing alcohol consumption (PR: 1.42; 95% CI: 1.37-1.47), and receiving >30 euros weekly (PR :1.51; 95% CI: 1.37-1.67). Contextual variables were not associated with youth binge drinking when individual variables were considered. In conclusion, youth binge drinking was associated with individual variables related to high alcohol accessibility and availability, regardless of contextual variables. These variables explained the variability in binge drinking among Spanish regions.

Negative self-perception of smile associated with malocclusions among Brazilian adolescents.

PubMed

Moura, Cristiano; Cavalcanti, Alessandro Leite; Gusmão, Estela Santos; Soares, Renata de Souza Coelho; Moura, Fabiana Torres Cavalcante; Santillo, Patrícia Morgana Hordonho

2013-08-01

This study estimated the prevalence of negative self-perception of smile because of occlusion abnormalities and investigated their association according to standard clinical criteria. The sample consisted of 1290 randomly selected Brazilian adolescent boys and girls aged 12-16 years. The outcome of interest was dissatisfaction with smile, and data were collected using a standardized questionnaire. Occlusion characteristics were assessed using the dental aesthetic index (DAI). The other study variables were gender, age, and use of dental services. A chi-square test and Poisson multiple regression were used for statistical analysis. Of the 1290 students interviewed and examined, 539 (41.8 per cent) were dissatisfied with their smile; of these, 373 (69.2 per cent) assigned their dissatisfaction to the presence of an occlusal abnormality, and 166 (30.8 per cent) reported reasons other than occlusal abnormalities for their negative self-perception of their smile. In multivariate analysis, the following variables were associated with the outcome of interest: maxillary anterior irregularity [prevalence ratio (PR) = 1.40; 95 per cent confidence interval (CI) = 1.29-1.80], incisal spacing (PR = 1.37; 95 per cent CI = 1.19-1.57), vertical open bite (PR = 1.34; 95 per cent CI = 1.15-1.55), mandibular anterior irregularity (PR = 1.29; 95 per cent CI = 1.14-1.46), permanent anterior teeth missing (PR = 1.21; 95 per cent CI = 1.05-1.39), and incisal diastema (PR = 1.14; 95 per cent CI = 1.01-1.31). The negative self-perception of smile was statistically associated with severity of occlusal disorders according to the DAI scores, which suggests that self-perception should be used together with standard clinical criteria when decisions about orthodontic treatments are made in public health care systems.

Sexually Transmitted Infection Prevention With Long-Acting Reversible Contraception: Factors Associated With Dual Use.

PubMed

Thompson, Erika L; Vamos, Cheryl A; Griner, Stacey B; Logan, Rachel; Vázquez-Otero, Coralia; Daley, Ellen M

2017-07-01

Long-acting reversible contraception (LARC) is extremely effective in preventing pregnancy; however, it does not provide sexually transmitted infection (STI) prevention. Therefore, dual use is recommended for the prevention of STIs, in addition to pregnancy, by using LARC methods with condoms. This study assessed factors associated with LARC only use and dual-LARC and condom use among college women. The National College Health Assessment-II Fall 2012 to 2013 was used for this analysis. The analytic sample was restricted to women who used a LARC method (ie, intrauterine device or implant) (N = 1658). The main outcome was dual method use, LARC and condom, at last sex. An adjusted logistic regression model assessed sociodemographic factors (age, relationship, race), health care utilization (routine gynecological examination), and sexual behavior (number of partners) as factors associated with dual condom-LARC use at the last time of vaginal-sex. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated. Among women reporting LARC use, 24% used a condom. Dual users were less likely to have only 1 sexual partner (adjusted PR [aPR], 0.66; 95% CI, 0.54-0.81) and be in a relationship. Dual users were more likely than LARC-only users to be Hispanic (aPR, 1.34; 95% CI, 1.01-1.78), black (aPR, 1.40; 95% CI, 1.07-1.83), and biracial/multiracial (aPR, 1.38; 95% CI, 1.10-1.73). These findings illustrate differences between dual-condom LARC and LARC-only college users. It is likely that relationship status and number of partners influences perceived risk for STIs and decision making for dual use among this population.

Evaluation of factors associated with severe and frequent back pain in high school athletes.

PubMed

Noll, Matias; Silveira, Erika Aparecida; Avelar, Ivan Silveira de

2017-01-01

Several studies have shown that half of all young athletes experience back pain (BP). However, high intensity and frequency of BP may be harmful, and the factors associated with BP severity have not been investigated in detail. Here, we investigated the factors associated with a high intensity and high frequency of BP in high school athletes. We included 251 athletes (173 boys and 78 girls [14-20 years old]) in this cross-sectional study. The dependent variables were a high frequency and high intensity of BP, and the independent variables were demographic, socioeconomic, psychosocial, hereditary, anthropometric, behavioural, and postural factors and the level of exercise. The effect measure is presented as prevalence ratio (PR) with 95% confidence interval (CI). Of 251 athletes, 104 reported BP; thus, only these athletes were included in the present analysis. Results of multivariable analysis showed an association between high BP intensity and time spent using a computer (PR: 1.15, CI: 1.01-1.33), posture while writing (PR: 1.41, CI: 1.27-1.58), and posture while using a computer (PR: 1.39, CI: 1.26-1.54). Multivariable analysis also revealed an association of high BP frequency with studying in bed (PR: 1.19, CI: 1.01-1.40) and the method of carrying a backpack (PR: 1.19, CI: 1.01-1.40). In conclusion, we found that behavioural and postural factors are associated with a high intensity and frequency of BP. To the best of our knowledge, this study is the first to compare different intensities and frequencies of BP, and our results may help physicians and coaches to better understand BP in high school athletes.

Evaluation of factors associated with severe and frequent back pain in high school athletes

PubMed Central

Noll, Matias; Silveira, Erika Aparecida; de Avelar, Ivan Silveira

2017-01-01

Several studies have shown that half of all young athletes experience back pain (BP). However, high intensity and frequency of BP may be harmful, and the factors associated with BP severity have not been investigated in detail. Here, we investigated the factors associated with a high intensity and high frequency of BP in high school athletes. We included 251 athletes (173 boys and 78 girls [14–20 years old]) in this cross-sectional study. The dependent variables were a high frequency and high intensity of BP, and the independent variables were demographic, socioeconomic, psychosocial, hereditary, anthropometric, behavioural, and postural factors and the level of exercise. The effect measure is presented as prevalence ratio (PR) with 95% confidence interval (CI). Of 251 athletes, 104 reported BP; thus, only these athletes were included in the present analysis. Results of multivariable analysis showed an association between high BP intensity and time spent using a computer (PR: 1.15, CI: 1.01–1.33), posture while writing (PR: 1.41, CI: 1.27–1.58), and posture while using a computer (PR: 1.39, CI: 1.26–1.54). Multivariable analysis also revealed an association of high BP frequency with studying in bed (PR: 1.19, CI: 1.01–1.40) and the method of carrying a backpack (PR: 1.19, CI: 1.01–1.40). In conclusion, we found that behavioural and postural factors are associated with a high intensity and frequency of BP. To the best of our knowledge, this study is the first to compare different intensities and frequencies of BP, and our results may help physicians and coaches to better understand BP in high school athletes. PMID:28222141

Systematic review with meta-analysis: the comparative effectiveness of aspirin vs. screening for colorectal cancer prevention.

PubMed

Emilsson, L; Holme, Ø; Bretthauer, M; Cook, N R; Buring, J E; Løberg, M; Adami, H-O; Sesso, H D; Gaziano, M J; Kalager, M

2017-01-01

Both aspirin use and screening with flexible sigmoidoscopy or guaiac faecal occult blood testing (FOBT) may reduce mortality from colorectal cancer, but comparative effectiveness of these interventions is unknown. To compare aspirin to guaiac FOBT screening with regard to incidence and mortality of colorectal cancer in a network meta-analysis. We searched Medline, EMBASE and the COCHRANE central register (CENTRAL) for relevant randomised trials identified until 31 October 2015. Randomised trials in average-risk populations that reported colorectal cancer mortality, colorectal cancer incidence, or both, with a minimum follow-up of 2 years, and more than 100 randomised individuals were included. Three investigators independently extracted data. We calculated relative risks [RR with 95% predictive intervals (PrIs)] for the comparison of the interventions by frequentist network meta-analyses. The effect of aspirin on colorectal cancer mortality was similar to FOBT (RR 1.03; 95% PrI 0.76-1.39) and flexible sigmoidoscopy (RR 1.16; 95% PrI 0.84-1.60). Aspirin was more effective than FOBT (RR 0.36; 95% PrI 0.22-0.59) and flexible sigmoidoscopy (RR 0.37; 95% PrI 0.22-0.62) in preventing death from or cancer in the proximal colon. Aspirin was equally effective as screening in reducing colorectal cancer incidence, while flexible sigmoidoscopy was superior to FOBT (RR 0.84; 95% PrI 0.72-0.97). Low-dose aspirin seems to be equally effective as flexible sigmoidoscopy or guaiac FOBT screening to reduce colorectal cancer incidence and mortality, and more effective for cancers in the proximal colon. A randomised comparative effectiveness trial of aspirin vs. screening is warranted. © 2016 John Wiley & Sons Ltd.

Update on the evaluation of a new drug for effects on cardiac repolarization in humans: issues in early drug development

PubMed Central

Salvi, Vaibhav; Karnad, Dilip R; Panicker, Gopi Krishna; Kothari, Snehal

2010-01-01

Following reports of death from cardiac arrhythmias with drugs like terfenadine and cisapride, the International Conference for Harmonization formulated a guidance (E14) document. This specifies that all new drugs must undergo a ‘thorough QT/QTc’ (TQT) study to detect drug-induced QT prolongation, a surrogate marker of ventricular tachycardia, especially torsades de pointes (TdPs). With better understanding of data from several completed TQT studies, regulatory requirements have undergone some changes since the E14 guidance was implemented in October 2005. This article reviews the implications of the E14 guidance and the changes in its interpretation including choice of baseline QT, demonstration of assay sensitivity, statistical analysis of the effect of new drug and positive control, and PK-PD modelling. Some issues like use of automated QT measurements remain unresolved. Pharmaceutical companies too are modifying Phase 1 studies to detect QTc liability early in order to save time and resources. After the E14 guidance, development of several drugs that prolong QTc by >5 ms is being abandoned by sponsors. However, all drugs that prolong the QT interval do not increase risk of TdP. Researchers in regulatory agencies, academia and industry are working to find better biomarkers of drug-induced TdP which could prevent many useful drugs from being prematurely abandoned. Drug-induced TdP is a rare occurrence. With fewer drugs that prolong QT interval reaching the licensing stage, knowing which of these drugs are torsadogenic is proving to be elusive. Thus, paradoxically, the effectiveness of the E14 guidance itself has made prospective validation of new biomarkers difficult. This article is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010 PMID:19775279

In Silico QT and APD Prolongation Assay for Early Screening of Drug-Induced Proarrhythmic Risk.

PubMed

Romero, Lucia; Cano, Jordi; Gomis-Tena, Julio; Trenor, Beatriz; Sanz, Ferran; Pastor, Manuel; Saiz, Javier

2018-04-23

Drug-induced proarrhythmicity is a major concern for regulators and pharmaceutical companies. For novel drug candidates, the standard assessment involves the evaluation of the potassium hERG channels block and the in vivo prolongation of the QT interval. However, this method is known to be too restrictive and to stop the development of potentially valuable therapeutic drugs. The aim of this work is to create an in silico tool for early detection of drug-induced proarrhythmic risk. The system is based on simulations of how different compounds affect the action potential duration (APD) of isolated endocardial, midmyocardial, and epicardial cells as well as the QT prolongation in a virtual tissue. Multiple channel-drug interactions and state-of-the-art human ventricular action potential models ( O'Hara , T. , PLos Comput. Biol. 2011 , 7 , e1002061 ) were used in our simulations. Specifically, 206.766 cellular and 7072 tissue simulations were performed by blocking the slow and the fast components of the delayed rectifier current ( I Ks and I Kr , respectively) and the L-type calcium current ( I CaL ) at different levels. The performance of our system was validated by classifying the proarrhythmic risk of 84 compounds, 40 of which present torsadogenic properties. On the basis of these results, we propose the use of a new index (Tx) for discriminating torsadogenic compounds, defined as the ratio of the drug concentrations producing 10% prolongation of the cellular endocardial, midmyocardial, and epicardial APDs and the QT interval, over the maximum effective free therapeutic plasma concentration (EFTPC). Our results show that the Tx index outperforms standard methods for early identification of torsadogenic compounds. Indeed, for the analyzed compounds, the Tx tests accuracy was in the range of 87-88% compared with a 73% accuracy of the hERG IC 50 based test.

Endoscopic Cold Incision, Balloon Dilation, Mitomycin C Application, and Steroid Injection for Adult Laryngotracheal Stenosis

PubMed Central

Parker, Noah P.; Bandyopadhyay, Dipankar; Misono, Stephanie; Goding, George S.

2017-01-01

Objectives/Hypothesis To describe the presentation, stenosis characteristics, etiological differences, and outcomes of adult laryngotracheal stenosis treated with endoscopic cold incision, balloon dilation, topical mitomycin C application, and steroid injection. Study Design Retrospective chart review. Methods Demographic and clinical data were extracted for patients treated between March 2000 and December 2010. Prolonged intubation and idiopathic patient data were utilized for comparative analysis. Results Eighty patients (65 females; 15 males; 220 procedures; 2.9 years mean follow-up) presented with dyspnea (81%) and/or exercise intolerance (40%). Most commonly, etiologies were idiopathic (53 of 80; 66%) or prolonged intubation (14 of 80; 18%). Mean procedures per patient and interval between procedures were 2.8 procedures and 405 days, respectively. Mean stenosis length and distance from the caudal phonating edge of the true vocal folds were 9 mm and 19 mm. Complication, tracheotomy, and open-procedure rates were 1.8%, 1.4%, and 10.0%, respectively. Patients with more than two procedures demonstrated a mean 4-mm reduction in stenosis length and a 2-mm cephalad progression of stenosis over time. More caudal stenoses required more frequent procedures. Procedures were less frequent as more procedures were performed. Stenosis characteristics, interval between procedures, and total procedures were similar between idiopathic patients with or without intubation histories, but different between idiopathic and prolonged intubation patients. Conclusions This procedure was shown to be a viable option in adult laryngotracheal stenosis. Repeat dilation was likely, but was performed without adversely affecting stenosis characteristics. Stenoses farther from the vocal folds required procedures more frequently. Idiopathic patients with a history of brief, elective intubation had stenosis characteristics and responses to therapy similar to idiopathic patients without an intubation history. Both idiopathic groups together demonstrated stenosis characteristics and responses to therapy dissimilar to patients with a history of prolonged intubation. PMID:23086662

Is there a prognostic relevance of electrophysiological studies in bundle branch block patients?

PubMed

Bogossian, Harilaos; Frommeyer, Gerrit; Göbbert, Kornelius; Hasan, Fuad; Nguyen, Quy Suu; Ninios, Ilias; Mijic, Dejan; Bandorski, Dirk; Hoeltgen, Reinhard; Seyfarth, Melchior; Lemke, Bernd; Eckardt, Lars; Zarse, Markus

2017-08-01

The present European guidelines suggest a diagnostic electrophysiological (EP) study to determine indication for cardiac pacing in patients with bundle branch block and unexplained syncope. We evaluated the prognostic relevance of an EP study for mortality and the development of permanent complete atrioventricular (AV) block in patients with symptomatic bifascicular block and first-degree AV block. The HV interval is a poor prognostic marker to predict the development of permanent AV block in patients with symptomatic bifascicular block (BFB) and AV block I°. Thirty consecutive patients (mean age, 74.8 ± 8.6 years; 25 males) with symptomatic BFB and first-degree AV block underwent an EP study before device implantation, according to current guidelines. For 53 ± 31 months, patients underwent yearly follow-up screening for syncope or higher-degree AV block. Thirty patients presented with prolonged HV interval during the EP study (mean, 82.2 ± 20.1 ms; range, 57-142 ms), classified into 3 groups: group 1, <70 ms (mean, 62 ± 4 ms; range, 57-67 ms; n = 7), group 2, >70 to ≤100 ms (mean, 80 ± 8 ms; range, 70-97 ms; n = 18), and group 3, >100 ms (mean, 119 ± 14 ms; range, 107-142 ms; n = 5). According to the guidelines, patients in groups 2 and 3 received a pacemaker. The length of the HV interval was not associated with the later development of third-degree AV block or with increased mortality. Our present study suggests that an indication for pacemaker implantation based solely on a diagnostic EP study with prolongation of the HV interval is not justified. © 2017 Wiley Periodicals, Inc.

Population pharmacokinetics and pharmacodynamics of escitalopram in overdose and the effect of activated charcoal

PubMed Central

van Gorp, Freek; Duffull, Stephen; Hackett, L Peter; Isbister, Geoffrey K

2012-01-01

AIMS To describe the pharmacokinetics and pharmacodynamics (PKPD) of escitalopram in overdose and its effect on QT prolongation, including the effectiveness of single dose activated charcoal (SDAC). METHODS The data set included 78 escitalopram overdose events (median dose, 140 mg [10–560 mg]). SDAC was administered 1.0 to 2.6 h after 12 overdoses (15%). A fully Bayesian analysis was undertaken in WinBUGS 1.4.3, first for a population pharmacokinetic (PK) analysis followed by a PKPD analysis. The developed PKPD model was used to predict the probability of having an abnormal QT as a surrogate for torsade de pointes. RESULTS A one compartment model with first order input and first-order elimination described the PK data, including uncertainty in dose and a baseline concentration for patients taking escitalopram therapeutically. SDAC reduced the fraction absorbed by 31% and reduced the individual predicted area under the curve adjusted for dose (AUCi/dose). The absolute QT interval was related to the observed heart rate with an estimated individual heart rate correction factor (α = 0.35). The heart rate corrected QT interval (QTc) was linearly dependent on predicted escitalopram concentration [slope = 87 ms/(mg l–1)], using a hypothetical effect-compartment (half-life of effect-delay, 1.0h). Administration of SDAC significantly reduced QT prolongation and was shown to reduce the risk of having an abnormal QT by approximately 35% for escitalopram doses above 200 mg. CONCLUSIONS There was a dose-related lengthening of the QT interval that lagged the increase in drug concentration. SDAC resulted in a moderate reduction in fraction of escitalopram absorbed and reduced the risk of the QT interval being abnormal. PMID:21883384

Effect of hyperventilation on rate corrected QT interval of children.

PubMed

Kannivelu, Arivalagan; Kudumula, Vikram; Bhole, Vinay

2013-02-01

Hyperventilation is known to cause ST segment changes and QT variability in adults, but this has not been systematically studied in children. To investigate the effect of hyperventilation on rate corrected QT interval (QTc) in children. 25 children (male=10) with a median age of 14 (range 8.3-17.6) years were asked to hyperventilate for 1 min before exercise testing using the modified Bruce protocol. Mean QTc at rest, after hyperventilation, at peak exercise and at 1 min of recovery was 425(±31), 460(±30), 446(±38) and 420(±32) ms, respectively. Mean increase (95% CI) in QTc after hyperventilation was 35(19 to 51) ms (p<0.001), while there was minimal difference between QT interval at rest and after hyperventilation (mean QT 352(±41) vs 357(±44) ms). In six children, there were abnormalities in T wave morphology following hyperventilation. The QTc increment following hyperventilation was more pronounced in children with resting QTc <440 ms (n=14, mean increment (95% CI): 55 (33 to 78) ms) compared to children with QTc ≥440 ms (n=11, mean increment (95% CI): 9 (-4 to 22) ms) (p=0.001). QTc prolongation following hyperventilation was seen in children with both low and intermediate probability of long QT syndrome (LQTS). Peak exercise and early recovery did not cause a statistically significant change in QTc in either of these groups. Hyperventilation produces repolarisation abnormalities, including prolongation of QTc and T wave abnormalities in children with low probability of LQTS. The likely mechanism is delayed adaptation of QT interval with increased heart rate. Thus, a hyperventilation episode can be misdiagnosed as LQTS, especially in an emergency department.

Maternal obesity, environmental factors, cesarean delivery and breastfeeding as determinants of overweight and obesity in children: results from a cohort.

PubMed

Portela, Daniel S; Vieira, Tatiana O; Matos, Sheila Ma; de Oliveira, Nelson F; Vieira, Graciete O

2015-04-15

Overweight and obesity are a public health problem with a multifactorial aetiology. The objective of this study was to evaluate risk factors for overweight and obesity in children at 6 years of age, including type of delivery and breastfeeding. This study relates to a cohort of 672 mother-baby pairs who have been followed from birth up to 6 years of age. The sample included mothers and infants seen at all ten maternity units in a large Brazilian city. Genetic, socioeconomic, demographic variables and postnatal characteristics were analyzed. The outcome analyzed was overweight and/or obesity defined as a body mass index greater than or equal to +1 z-score. The sample was stratified by breastfeeding duration, and a descriptive analysis was performed using a hierarchical logistic regression. P-values of <0.05 were considered significant. Prevalence rates (PR) of overweight and obesity among the children were 15.6% and 12.9%, respectively. Among the subset of breastfed children, factors associated with the outcome were maternal overweight and/or obesity (PR 1.92; 95% confidence interval "95% CI" 1.15-3.24) and lower income (PR 0.50; 95% CI 0.29-0.85). Among children who had not been breastfed or had been breastfed for shorter periods (less than 12 months), predictors were mothers with lower levels of education (PR 0.39; 95% CI 0.19-0.78), working mothers (PR 1.83; 95% CI 1.05-3.21), caesarean delivery (PR 1.98; 95% CI 1.14 - 3.50) and maternal obesity (PR 3.05; 95% CI 1.81 - 5.25). Maternal obesity and caesarean delivery were strongly associated with childhood overweight and/or obesity. Lower family income and lower levels of education were identified as protective factors. Breastfeeding duration appeared to modify the association between overweight/obesity and the other predictors studied.

No Evidence of Sexual Risk Compensation in the iPrEx Trial of Daily Oral HIV Preexposure Prophylaxis

PubMed Central

Marcus, Julia L.; Glidden, David V.; Mayer, Kenneth H.; Liu, Albert Y.; Buchbinder, Susan P.; Amico, K. Rivet; McMahan, Vanessa; Kallas, Esper Georges; Montoya-Herrera, Orlando; Pilotto, Jose; Grant, Robert M.

2013-01-01

Objective Preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) reduced HIV acquisition in the iPrEx trial among men who have sex with men and transgender women. Self-reported sexual risk behavior decreased overall, but may be affected by reporting bias. We evaluated potential risk compensation using biomarkers of sexual risk behavior. Design and methods Sexual practices were assessed at baseline and quarterly thereafter; perceived treatment assignment and PrEP efficacy beliefs were assessed at 12 weeks. Among participants with ≥1 follow-up behavioral assessment, sexual behavior, syphilis, and HIV infection were compared by perceived treatment assignment, actual treatment assignment, and perceived PrEP efficacy. Results Overall, acute HIV infection and syphilis decreased during follow-up. Compared with participants believing they were receiving placebo, participants believing they were receiving FTC/TDF reported more receptive anal intercourse partners prior to initiating drug (12.8 vs. 7.7, P = 0.04). Belief in receiving FTC/TDF was not associated with an increase in receptive anal intercourse with no condom (ncRAI) from baseline through follow-up (risk ratio [RR] 0.9, 95% confidence interval [CI]: 0.6–1.4; P = 0.75), nor with a decrease after stopping study drug (RR 0.8, 95% CI: 0.5–1.3; P = 0.46). In the placebo arm, there were trends toward lower HIV incidence among participants believing they were receiving FTC/TDF (incidence rate ratio [IRR] 0.8, 95% CI: 0.4–1.8; P = 0.26) and also believing it was highly effective (IRR 0.5, 95% CI: 0.1–1.7; P = 0.12). Conclusions There was no evidence of sexual risk compensation in iPrEx. Participants believing they were receiving FTC/TDF had more partners prior to initiating drug, suggesting that risk behavior was not a consequence of PrEP use. PMID:24367497

The association between temporomandibular disorders and suicide ideation in a representative sample of the South Korean population.

PubMed

Han, Don-Hun

2014-01-01

To investigate in a representative sample of South Koreans (1) the prevalence of and associations between general pain, temporomandibular disorders (TMD), and suicide ideation (SI), and (2) whether the associations between general pain, TMD, and SI differ according to cancer history. Data were from the Fourth Korean National Health and Nutrition Examination Survey (KNHANES IV; N = 16,658). KNHANES IV participants provided reports regarding their cancer history, EQ-5D (a measure of health status from the EuroQoL Group), and TMD symptoms including clicking of one or both temporomandibular joints, pain, and mouth-opening limitation (MOL). Participants were assessed for any SI over the last 12 months, as a dependent variable. The independent variables were pain/discomfort (EQ-PD) reported by the subjects on the EQ-5D, severe TMD (tenderness or reduced jaw mobility once or more per week), and total TMD (occurrence of clicking, tenderness on palpation, or reduced jaw mobility [opening < 30 mm] once or more per week). Demographic information (age and gender), socioeconomic status (income, education, occupation, and marital status), behavioral factors (smoking and binge drinking), and cancer history were evaluated as covariates. The association of TMD with SI was assessed by the prevalence ratio (PR) and 95% confidence intervals. In fully adjusted models, elevated PRs for SI were observed for each pain condition (PR = 1.26 for total TMD, PR = 1.35 for severe TMD, and PR = 1.75 for EQ-PD). In the subgroup analyses by cancer history, the PRs were higher in the cancer history (+) group; the order of magnitude was severe TMD (PR = 2.20), EQ-PD (PR = 2.16), and total TMD (PR = 2.02). Pain conditions, including TMD pain, might aggravate SI among those with a cancer history. These findings add to a growing body of evidence indicating that TMD warrants further attention in relation to suicide.

Racial/Ethnic Disparities in Short Sleep Duration by Occupation: The Contribution of Immigrant Status

PubMed Central

Jackson, Chandra L.; Hu, Frank B.; Redline, Susan; Williams, David R.; Mattei, Josiemer; Kawachi, Ichiro

2016-01-01

Sleep duration, associated with increased morbidity/mortality, has been shown to vary by race and occupation. Few studies have examined the additional influence of immigrant status. Using a nationally-representative sample of 175,244 US adults from the National Health Interview Survey from 2004-2011, we estimated prevalence ratios (PRs) for short sleep duration (<7 hours/per day) among US- and non-US born Blacks and Latinos by occupation compared to their White counterparts using adjusted Poisson regression models with robust variance. Non-US born participants’ mean age was 46 years, 55% were men, 58% were Latino, and 65% lived in the US ≥15 years. Short sleep prevalence was highest among US- and non-US born Blacks in all occupations, and the prevalence generally increased with increasing professional/management roles in Blacks and Latinos while it decreased among Whites. Adjusted short sleep was more prevalent in US-born Blacks compared to Whites in professional/management (PR=1.52 [95% confidence interval (CI): 1.42-1.63]), support services (PR=1.31 [95% CI: 1.26-1.37]), and laborers (PR=1.11 [95% CI: 1.06-1.16]). The Black-White comparison was even higher for non-US born Black laborers (PR=1.50 [95% CI: 1.24-1.80]). Similar for non-US born Latinos, Latinos born in the US had a higher short sleep prevalence in professional/management (PR=1.14 [95% CI: 1.04-1.24]) and support services (PR=1.06 [95% CI: 1.01-1.11]), but a lower prevalence among laborers (PR=0.77 [95% CI: 0.74-0.81]) compared to Whites. Short sleep varied within and between immigrant status for some ethnicities in particular occupations, further illuminating the need for tailored interventions to address sleep disparities among US workers. PMID:25108693

Derivation and validation of the prolonged length of stay score in acute stroke patients.

PubMed

Koton, S; Bornstein, N M; Tsabari, R; Tanne, D

2010-05-11

Length of stay (LOS) is the main cost-determining factor of hospitalization of stroke patients. Our aim was to derive and validate a simple score for the assessment of the risk of prolonged LOS for acute stroke patients in a national setting. Ischemic stroke (IS) and intracerebral hemorrhage (ICH) patients in the National Acute Stroke Israeli Surveys (NASIS 2004 and 2007) were included. Predictors of prolonged LOS (LOS > or =7 days) in the NASIS 2004 (n = 1,700) were identified with logistic regression analysis and used for the derivation of the Prolonged Length of Stay (PLOS) score. The score was validated in the NASIS 2007 (n = 1,648). Median (interquartile range) LOS was 6 (3-10) days in the derivation cohort (42.3% prolonged LOS) and 5 (3-8) in the validation cohort (35.7% prolonged LOS). The derivation cohort included 54.8% men, 90.8% IS and 9.2% ICH, with a mean (SD) age of 71.2 (12.5) years. Stroke severity was the strongest multivariable predictor of prolonged LOS: odds ratio (95% confidence interval [CI]) increased from 2.6 (2.0-3.3) for NIH Stroke Scale score (NIHSS) 6-10 to 4.9 (3.0-8.0) for NIHSS 16-20, compared with NIHSS < or =5. Stroke severity and type, decreased level of consciousness on admission, history of congestive heart failure, and prior atrial fibrillation were used for the derivation of the PLOS score (c statistics 0.692, 95% CI 0.666-0.718). The score performed similarly well in the validation cohort (c statistics 0.680, 95% CI 0.653-0.707). A simple prolonged length of stay score, based on available baseline information, may be useful for tailoring policy aimed at better use of resources and optimal discharge planning of acute stroke patients.

Risk factors of prolonged mechanical ventilation following open heart surgery: what has changed over the last decade?

PubMed

Siddiqui, Muhammad-Mujtaba Ali; Paras, Iftikhar; Jalal, Anjum

2012-09-01

To identify the risk factors for prolonged invasive mechanical ventilation after open heart surgery in Pakistan. This study is based on retrospective analysis of database. We conducted study of all patients who underwent open heart surgery at CPE Institute of Cardiology, Multan from March 2009 to May 2011. The data was retrieved from the database in the form of electronic spreadsheet which was then analyzed using SPSS software. The patients with incomplete data entries were removed from the analysis resulting in a set of 1,617 patients. The data of each patient consisted of 65 preoperative, operative and postoperative variables. The data was summarized as means, medians and standard deviations for numeric variables and frequencies and percentages or categoric variables. These risk factors were compared using Chi-sqaure test. Their ODDs ratios and 95% confidence intervals of ODD's Ratios and P values were calculated. Out of a total of 1,617 patients, 77 patients (4.76%) had prolonged ventilation for a cumulated duration of more than over 24 hours. Preoperative renal failure, emphysema, low EF (<30%), urgent operation, preoperative critical state, prolonged bypass time, prolonged cross clamp time, complex surgical procedures and peri-operative myocardial infarction were found to be risk factors for PIMV. Old age, female gender, advanced ASA class, advanced NYHA class, diabetes mellitus, smoking, history of COPD, redo surgery, left main stenosis, obesity and use of intra-aortic balloon pump were not found to have significant ODDs ratios for PIMV. The patients with prolonged ventilation had significantly high mortality i.e. 32.47% while the normal ventilation group had 0.32% overall mortality. Many of the previously considered risk factors for prolonged ventilation after open heart study are no more significant risk factors. However, prolonged ventilation continues to be associated with very high mortality.

A clinical prediction model for prolonged air leak after pulmonary resection.

PubMed

Attaar, Adam; Winger, Daniel G; Luketich, James D; Schuchert, Matthew J; Sarkaria, Inderpal S; Christie, Neil A; Nason, Katie S

2017-03-01

Prolonged air leak increases costs and worsens outcomes after pulmonary resection. We aimed to develop a clinical prediction tool for prolonged air leak using pretreatment and intraoperative variables. Patients who underwent pulmonary resection for lung cancer/nodules (from January 2009 to June 2014) were stratified by prolonged parenchymal air leak (>5 days). Using backward stepwise logistic regression with bootstrap resampling for internal validation, candidate variables were identified and a nomogram risk calculator was developed. A total of 2317 patients underwent pulmonary resection for lung cancer/nodules. Prolonged air leak (8.6%, n = 200) was associated with significantly longer hospital stay (median 10 vs 4 days; P < .001). Final model variables associated with increased risk included low percent forced expiratory volume in 1 second, smoking history, bilobectomy, higher annual surgeon caseload, previous chest surgery, Zubrod score >2, and interaction terms for right-sided thoracotomy and wedge resection by thoracotomy. Wedge resection, higher body mass index, and unmeasured percent forced expiratory volume in 1 second were protective. Derived nomogram discriminatory accuracy was 76% (95% confidence interval [CI], 0.72-0.79) and facilitated patient stratification into low-, intermediate- and high-risk groups with monotonic increase in observed prolonged air leaks (2.0%, 8.9%, and 19.2%, respectively; P < .001). Patients at intermediate and high risk were 4.80 times (95% CI, 2.86-8.07) and 11.86 times (95% CI, 7.21-19.52) more likely to have prolonged air leak compared with patients at low risk. Using readily available candidate variables, our nomogram predicts increasing risk of prolonged air leak with good discriminatory ability. Risk stratification can support surgical decision making, and help initiate proactive, patient-specific surgical management. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Identifying Patients at Higher Risk of Prolonged Air Leak After Lung Resection.

PubMed

Gilbert, Sebastien; Maghera, Sonam; Seely, Andrew J; Maziak, Donna E; Shamji, Farid M; Sundaresan, Sudhir R; Villeneuve, Patrick J

2016-11-01

Predictive models of prolonged air leak have relied on information not always available preoperatively (eg, extent of resection, pleural adhesions). Our objective was to construct a model to identify patients at increased risk of prolonged air leak using preoperative factors exclusively. From 2012 to 2014, data on consecutive patients undergoing pulmonary resection were collected prospectively. Prolonged air leak was defined as lasting longer than 7 days and requiring hospitalization. Factors associated with the primary outcome (p < 0.2) were included in a multivariate model. Regression coefficients were used to develop a weighted risk score for prolonged air leak. Of 225 patients, 8% (18/225) experienced a prolonged air leak. Male gender (p = 0.08), smoking history (p = 0.03), body mass index (BMI) 25 or below (p < 0.01), Medical Research Council (MRC) dyspnea score above 1 (p = 0.06), and diffusion capacity for carbon monoxide below 80% (Dlco) (p = 0.01) were selected for inclusion in the final model. Weighted scores were male gender (1 point), BMI 25 or below (0.5 point), smoker (2 points), Dlco% below 80% (2 points), and MRC dyspnea score above 1 (1 point). The area under the receiver operating characteristic curve was 0.8 (95% confidence interval [CI] = 0.7 to 0.9]. An air leak score above 4 points offered the best combination of sensitivity (83% [95% CI = 58 to 96]) and specificity (65% [95% CI = 58 to 71]). A subgroup of lung resection patients at higher risk for a prolonged air leak can be effectively identified with the use of widely available, preoperative factors. The proposed scoring system is simple, is clinically relevant to the informed consent, and allows preoperative patient selection for interventions to reduce the risk of prolonged air leak. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Electrophysiologic effects of a novel selective adenosine A1 agonist (CVT-510) on atrioventricular nodal conduction in humans.

PubMed

Lerman, B B; Ellenbogen, K A; Kadish, A; Platia, E; Stein, K M; Markowitz, S M; Mittal, S; Slotwiner, D J; Scheiner, M; Iwai, S; Belardinelli, L; Jerling, M; Shreeniwas, R; Wolff, A A

2001-07-01

CVT-510, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside, is a selective A(1)-adenosine receptor agonist with potential potent antiarrhythmic effects in tachycardias involving the atrioventricular (AV) node. This study, the first in humans, was designed to determine the effects of CVT-510 on AV nodal conduction and hemodynamics. Patients in sinus rhythm with normal AV nodal function at electrophysiologic study (n = 32) received a single intravenous bolus of CVT-510. AH and HV intervals were measured during sinus rhythm and during atrial pacing at 1, 5, 10, 15, 20, 30, 45, and 60 minutes after the bolus. Increasing doses of CVT-510 (0.3 to 10 microg/kg) caused a dose-dependent increase in the AH interval. At 1 minute, a dose of 10 microg/kg increased the AH interval during sinus rhythm from 93 +/- 23 msec to 114 +/- 37 msec, p = 0.01 and from 114 +/- 31 msec to 146 +/- 44 msec during atrial pacing at 600 msec, p = 0.003). The AH interval returned to baseline by 20 minutes. CVT-510 at doses of 0.3 to 10 microg/kg had no effect on sinus rate, HV interval, or systemic blood pressure, and was not associated with serious adverse effects. At doses of 15 and 30 microg/kg, CVT-510 produced transient second/third degree AV heart block in all four patients treated. One of these patients also had a prolonged sedative effect that was reversed with aminophylline. CVT-510 promptly prolongs AV nodal conduction and does not affect sinus rate or blood pressure. Selective stimulation of the A(1)-adenosine receptor by CVT-510 may be useful for immediate control of heart rate in atrial fibrillation/flutter and to convert paroxysmal supraventricular tachycardia to sinus rhythm, while avoiding vasodilatation mediated by the A(2)-adenosine receptor, as well as the vasodepressor and negative inotropic effects associated with beta-adrenergic receptor blockade and/or calcium channel blockers.

International perspective on nanotechnology papers, patents, and NSF awards (2000-2016)

NASA Astrophysics Data System (ADS)

Zhu, Hongyi; Jiang, Shan; Chen, Hsinchun; Roco, Mihail C.

2017-11-01

This paper presents the development of nanotechnology between 2000 and 2016 as reflected in the Web of Science papers, United States Patent and Trademark Office (USPTO), World International Property Organization (WIPO) patents, and National Science Foundation (NSF) awards, with a special reference to the United States (US), European Union (EU27), P.R. China, Japan, and South Korea. The field of nanotechnology is branching out into novel scientific and technology platforms, and it is increasingly difficult to separate foundational nanoscale components from divergent application areas. The average global growth rate has been sustained at about 15% for both papers and patents in the selected interval. The growth rates among regions are non-uniform. P.R. China and South Korea have increased faster in both the numbers and quality of their scientific publications, and currently P.R. China has the largest volume of nanotechnology publications and South Korea the most publications per capita in the field of nanotechnology. The US, EU27, and Japan are maintaining leadership in the upstream, better cited, conceptual components of nanotechnology research and development.

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

PubMed Central

Öztürk, T.; Ağdanlı, D.; Bayturan, Ö.; Çıkrıkcı, C.; Keleş, G.T.

2015-01-01

Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation. PMID:25714880

Electrocardiographic Predictors of Incident Atrial Fibrillation

PubMed Central

Nguyen, Kaylin T.; Vittinghoff, Eric; Dewland, Thomas A.; Mandyam, Mala C.; Stein, Phyllis K.; Soliman, Elsayed Z.; Heckbert, Susan R.; Marcus, Gregory M.

2017-01-01

Atrial fibrillation (AF) is likely secondary to multiple different pathophysiological mechanisms that are increasingly, but incompletely understood. Motivated by the hypothesis that 3 previously described electrocardiographic (ECG) predictors of AF identify distinct AF mechanisms, we sought to determine if these ECG findings independently predict incident disease. Among Cardiovascular Health Study participants without prevalent AF, we determined whether left anterior fascicular block (LAFB), a prolonged QTC, and atrial premature complexes (APCs) each predicted AF after adjusting for each other. We then calculated the attributable risk in the exposed for each ECG marker. LAFB and QTC intervals were assessed on baseline 12-lead ECG (n=4,696). APC count was determined using 24-hour Holter recordings obtained in a random subsample (n=1,234). After adjusting for potential confounders and each ECG marker, LAFB (hazard ratio [HR. 2.1, 95% confidence interval [CI. 1.1–3.9, p=0.023), a prolonged QTC (HR 2.5, 95% CI 1.4–4.3, p=0.002), and every doubling of APC count (HR 1.2, 95% CI 1.1–1.3, p<0.001) each remained independently predictive of incident AF. The attributable risk of AF in the exposed was 35% (95% CI 13–52%) for LAFB, 25% (95% CI 0.6–44%) for a prolonged QTC, and 34% (95% CI 26–42%) for APCs. In conclusion, in a community-based cohort, 3 previously established ECG-derived AF predictors were each independently associated with incident AF, suggesting they may represent distinct mechanisms underlying the disease. PMID:27448684

Comparable Effects of High-Intensity Interval Training and Prolonged Continuous Exercise Training on Abdominal Visceral Fat Reduction in Obese Young Women

PubMed Central

Zhang, Haifeng; Tong, Tom K.; Qiu, Weifeng; Zhang, Xu; Zhou, Shi

2017-01-01

This study compared the effect of prolonged moderate-intensity continuous training (MICT) on reducing abdominal visceral fat in obese young women with that of work-equivalent (300 kJ/training session) high-intensity interval training (HIIT). Forty-three participants received either HIIT (n = 15), MICT (n = 15), or no training (CON, n = 13) for 12 weeks. The abdominal visceral fat area (AVFA) and abdominal subcutaneous fat area (ASFA) of the participants were measured through computed tomography scans preintervention and postintervention. Total fat mass and the fat mass of the android, gynoid, and trunk regions were assessed through dual-energy X-ray absorptiometry. Following HIIT and MICT, comparable reductions in AVFA (−9.1, −9.2 cm2), ASFA (−35, −28.3 cm2), and combined AVFA and ASFA (−44.7, −37.5 cm2, p > 0.05) were observed. Similarly, reductions in fat percentage (−2.5%, −2.4%), total fat mass (−2.8, −2.8 kg), and fat mass of the android (−0.3, −0.3 kg), gynoid (−0.5, −0.7 kg), and trunk (−1.6, −1.2 kg, p > 0.05) regions did not differ between HIIT and MICT. No variable changed in CON. In conclusion, MICT consisting of prolonged sessions has no quantitative advantage, compared with that resulting from HIIT, in abdominal visceral fat reduction. HIIT appears to be the predominant strategy for controlling obesity because of its time efficiency. PMID:28116314

Disparities and Trends in Door-to-Needle Time: The FL-PR CReSD Study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities).

PubMed

Oluwole, Sofia A; Wang, Kefeng; Dong, Chuanhui; Ciliberti-Vargas, Maria A; Gutierrez, Carolina M; Yi, Li; Romano, Jose G; Perez, Enmanuel; Tyson, Brittany Ann; Ayodele, Maranatha; Asdaghi, Negar; Gardener, Hannah; Rose, David Z; Garcia, Enid J; Zevallos, Juan Carlos; Foster, Dianne; Robichaux, Mary; Waddy, Salina P; Sacco, Ralph L; Rundek, Tatjana

2017-08-01

In the United States, about half of acute ischemic stroke patients treated with tPA (tissue-type plasminogen activator) receive treatment within 60 minutes of hospital arrival. We aimed to determine the proportion of patients receiving tPA within 60 minutes (door-to-needle time [DTNT] ≤60) and 45 minutes (DTNT ≤45) of hospital arrival by race/ethnicity and sex and to identify temporal trends in DTNT ≤60 and DTNT ≤45. Among 65 654 acute ischemic stroke admissions in the National Institute of Neurological Disorders and Stroke-funded FL-PR CReSD study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities) from 2010 to 2015, we included 6181 intravenous tPA-treated cases (9.4%). Generalized estimating equations were used to determine predictors of DTNT ≤60 and DTNT ≤45. DTNT ≤60 was achieved in 42% and DTNT ≤45 in 18% of cases. After adjustment, women less likely received DTNT ≤60 (odds ratio, 0.81; 95% confidence interval, 0.72-0.92) and DTNT ≤45 (odds ratio, 0.73; 95% confidence interval, 0.57-0.93). Compared with Whites, Blacks less likely had DTNT ≤45 during off hours (odds ratio, 0.68; 95% confidence interval, 0.47-0.98). Achievement of DTNT ≤60 and DTNT ≤45 was highest in South Florida (50%, 23%) and lowest in West Central Florida (28%, 11%). In the FL-PR CReSD, achievement of DTNT ≤60 and DTNT ≤45 remains low. Compared with Whites, Blacks less likely receive tPA treatment within 45 minutes during off hours. Treatment within 60 and 45 minutes is lower in women compared with men and lowest in West Central Florida compared with other Florida regions and Puerto Rico. Further research is needed to identify reasons for delayed thrombolytic treatment in women and Blacks and factors contributing to regional disparities in DTNT. © 2017 American Heart Association, Inc.

Prolonged Screen Viewing Times and Sociodemographic Factors among Pregnant Women: A Cross-Sectional Survey in China

PubMed Central

Liu, Dengyuan; Rao, Yunshuang; Zeng, Huan; Zhang, Fan; Wang, Lu; Xie, Yaojie; Sharma, Manoj; Zhao, Yong

2018-01-01

Objectives: This study aimed to assess the prevalence of prolonged television, computer, and mobile phone viewing times and examined related sociodemographic factors among Chinese pregnant women. Methods: In this study, a cross-sectional survey was implemented among 2400 Chinese pregnant women in 16 hospitals of 5 provinces from June to August in 2015, and the response rate of 97.76%. We excluded women with serious complications and cognitive disorders. The women were asked about their television, computer, and mobile phone viewing during pregnancy. Prolonged television watching or computer viewing was defined as spending more than two hours on television or computer viewing per day. Prolonged mobile phone viewing was watching more than one hour on mobile phone per day. Results: Among 2345 pregnant women, about 25.1% reported prolonged television viewing, 20.6% reported prolonged computer viewing, and 62.6% reported prolonged mobile phone viewing. Pregnant women with long mobile phone viewing times were likely have long TV (Estimate = 0.080, Standard Error (SE) = 0.016, p < 0.001) and computer viewing times (Estimate = 0.053, SE = 0.022, p = 0.015). Pregnant women with long TV (Estimate = 0.134, SE = 0.027, p < 0.001) and long computer viewing times (Estimate = 0.049, SE = 0.020, p = 0.015) were likely have long mobile phone viewing times. Pregnant women with long TV viewing times were less likely to have long computer viewing times (Estimate = −0.032, SE = 0.015, p = 0.035), and pregnant women with long computer viewing times were less likely have long TV viewing times (Estimate = −0.059, SE = 0.028, p = 0.035). Pregnant women in their second pregnancy had lower prolonged computer viewing times than those in their first pregnancy (Odds Ratio (OR) 0.56, 95% Confidence Interval (CI) 0.42–0.74). Pregnant women in their second pregnancy were more likely have longer prolonged mobile phone viewing times than those in their first pregnancy (OR 1.25, 95% CI 1.01–1.55). Conclusions: The high prevalence rate of prolonged TV, computer, and mobile phone viewing times was common for pregnant women in their first and second pregnancy. This study preliminarily explored the relationship between sociodemographic factors and prolonged screen time to provide some indication for future interventions related to decreasing screen-viewing times during pregnancy in China. PMID:29495439

Factors associated to inpatient mortality rates in type-2-diabetic patients: a cross-sectional analytical study in three Peruvian hospitals.

PubMed

Atamari-Anahui, Noé; Martinez-Ninanqui, Franklin W; Paucar-Tito, Liz; Morales-Concha, Luz; Miranda-Chirau, Alejandra; Gamarra-Contreras, Marco Antonio; Zea-Nuñez, Carlos Antonio; Mejia, Christian R

2017-12-05

Diabetes mortality has increased in recent years. In Peru, there are few studies on in-hospital mortality due to type 2 diabetes in the provinces. To determine factors associated to hospital mortality in patients with diabetes mellitus type 2 in three hospitals from Cusco-Peru. An analytical cross-sectional study was performed. All patients with diabetes mellitus type 2 hospitalized in the city of Cusco during the 2016 were included. Socio-educational and clinical characteristics were evaluated, with "death" as the variable of interest. The crude (cPR) and adjusted (aPR) prevalence ratios were estimated using generalized linear models with Poisson family and log link function, with their respective 95% confidence intervals (95% CI). The values p <0.05 were considered significant. A total of 153 patients were studied; 33.3% (51) died in the hospital. The mortality rate increased when the following factors were associated: age of the patients increased the mortality rate by one-year increments (aPR: 1.02; CI95%: 1.01-1.03; p<0.001); to have been admitted by the emergency service (aPR: 1.93; CI95%: 1.34-2.77; p<0.001); being a patient who is readmitted to the hospital (aPR: 2.01; CI95%: 1.36-2.98; p<0.001); and patients who have had a metabolic in-hospital complication (aPR: 1.61; CI95%: 1.07-2.43; p=0.024) or renal in-hospital complications (aPR: 1.47; CI95%: 1.30-1.67; p<0.001). Conversely, the mortality rate was reduced when admission was due to a urinary tract infection (aPR: 0.50; CI95%: 0.35-0.72; p<0.001); adjusted by seven variables. A third of hospitalized diabetes mellitus type 2 patients died during the study period. Mortality was increased as age rises, patients admitted through emergency rooms, patients who were readmitted to the hospital, and patients who had metabolic or renal complications. Patients admitted for a urinary tract infection had a lower mortality rate.

Adult body size and physical activity in relation to risk of breast cancer according to tumor androgen receptor status.

PubMed

Zhang, Xuehong; Eliassen, A Heather; Tamimi, Rulla M; Hazra, Aditi; Beck, Andrew H; Brown, Myles; Collins, Laura C; Rosner, Bernard; Hankinson, Susan E

2015-06-01

Obesity and physical activity have been hypothesized to affect breast cancer risk partly via the androgen signaling pathway. We conducted the first study to evaluate these associations by tumor androgen receptor (AR) status. Height, weight, and physical activity were assessed using questionnaires in the Nurses' Health Study. AR, estrogen receptor (ER), and progesterone receptor (PR) status were determined using immunohistochemistry on tumor tissue and medical/pathology reports. A total of 1,701 AR(+) and 497 AR(-) cases were documented during 26 years of follow-up of 103,577 women. After adjusting for ER/PR status and other risk factors, the relative risks (RR) and 95% confidence intervals (95% CI) for every 5 kg/m(2) increase in body mass index (BMI) were 1.07 (1.01-1.13) for AR(+) and 1.16 (1.05-1.29) for AR(-) tumors (P-heterogeneity = 0.17). The RRs (95% CIs) per 5 hours of brisk walking/week were 0.87 (0.73-1.04) for AR(+) and 0.67 (0.45-0.99) for AR(-) tumors (P-heterogeneity = 0.22). Further, BMI, but not physical activity, associations differed significantly across ER/PR/AR subtypes (P-heterogeneity = 0.04 and 0.63, respectively). The RRs (95% CIs) for 5 kg/m(2) increase in BMI were 1.23 (1.04-1.45) for ER(+)PR(+)AR(-), 1.19 (1.01-1.39) for ER(-)PR(-)AR(-), 1.15 (1.08-1.23) for ER(+)PR(+)AR(+), and 0.88 (0.75-1.03) for ER(+)PR(-)AR(+) tumors. Higher BMI was associated with an increased risk of both AR(+) and AR(-) breast tumors in postmenopausal women, whereas physical activity, including brisk walking, was associated with a reduced risk of both subtypes. In addition, a significant positive association was observed between higher BMI and ER(-)PR(-)AR(-) tumors. The similar associations observed by AR status suggest that mechanisms other than androgen signaling underlie these two breast cancer risk factors. ©2015 American Association for Cancer Research.

Fetal electrocardiogram (ECG) for fetal monitoring during labour.

PubMed

Neilson, James P

2015-12-21

Hypoxaemia during labour can alter the shape of the fetal electrocardiogram (ECG) waveform, notably the relation of the PR to RR intervals, and elevation or depression of the ST segment. Technical systems have therefore been developed to monitor the fetal ECG during labour as an adjunct to continuous electronic fetal heart rate monitoring with the aim of improving fetal outcome and minimising unnecessary obstetric interference. To compare the effects of analysis of fetal ECG waveforms during labour with alternative methods of fetal monitoring. The Cochrane Pregnancy and Childbirth Group's Trials Register (latest search 23 September 2015) and reference lists of retrieved studies. Randomised trials comparing fetal ECG waveform analysis with alternative methods of fetal monitoring during labour. One review author independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. One review author assessed the quality of the evidence using the GRADE approach. Seven trials (27,403 women) were included: six trials of ST waveform analysis (26,446 women) and one trial of PR interval analysis (957 women). The trials were generally at low risk of bias for most domains and the quality of evidence for ST waveform analysis trials was graded moderate to high. In comparison to continuous electronic fetal heart rate monitoring alone, the use of adjunctive ST waveform analysis made no obvious difference to primary outcomes: births by caesarean section (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.96 to 1.08; six trials, 26,446 women; high quality evidence); the number of babies with severe metabolic acidosis at birth (cord arterial pH less than 7.05 and base deficit greater than 12 mmol/L) (average RR 0.72, 95% CI 0.43 to 1.20; six trials, 25,682 babies; moderate quality evidence); or babies with neonatal encephalopathy (RR 0.61, 95% CI 0.30 to 1.22; six trials, 26,410 babies; high quality evidence). There were, however, on average fewer fetal scalp samples taken during labour (average RR 0.61, 95% CI 0.41 to 0.91; four trials, 9671 babies; high quality evidence) although the findings were heterogeneous and there were no data from the largest trial (from the USA). There were marginally fewer operative vaginal births (RR 0.92, 95% CI 0.86 to 0.99; six trials, 26,446 women); but no obvious difference in the number of babies with low Apgar scores at five minutes or babies requiring neonatal intubation, or babies requiring admission to the special care unit (RR 0.96, 95% CI 0.89 to 1.04, six trials, 26,410 babies; high quality evidence). There was little evidence that monitoring by PR interval analysis conveyed any benefit of any sort. The modest benefits of fewer fetal scalp samplings during labour (in settings in which this procedure is performed) and fewer instrumental vaginal births have to be considered against the disadvantages of needing to use an internal scalp electrode, after membrane rupture, for ECG waveform recordings. We found little strong evidence that ST waveform analysis had an effect on the primary outcome measures in this systematic review.There was a lack of evidence showing that PR interval analysis improved any outcomes; and a larger future trial may possibly demonstrate beneficial effects.There is little information about the value of fetal ECG waveform monitoring in preterm fetuses in labour. Information about long-term development of the babies included in the trials would be valuable.

Logistic regression analysis of risk factors for prolonged pulmonary recovery in children from aspirated foreign body.

PubMed

Hidaka, Hiroshi; Obara, Taku; Kuriyama, Shinichi; Kurosawa, Shin; Katori, Yukio; Kobayashi, Toshimitsu

2013-10-01

Foreign body aspiration is a life-threatening emergency for children. Fried chicken is commonly available all over the world, but no cases have previously been reported addressing this food as a tracheobronchial foreign body. We report an extremely rare case of tracheobronchial aspiration of fried chicken complicated by severe bronchitis and postoperative atelectasis. To clarify predisposing factors related to bronchopulmonary complications, we also reviewed paediatric cases of tracheobronchial foreign bodies treated in our department over the past 14 years. We retrospectively reviewed a total of 77 cases of tracheobronchial foreign bodies from 1988 to 2011. The main outcome measure was duration of hospitalisation, reflecting postoperative therapy. Logistic regression analyses were conducted to determine risk factors for longer hospitalisation. Age, sex, and interval between the aspiration episode and bronchoscopy were not significantly associated with longer hospitalisation. Regarding kinds of foreign bodies, higher rates of longer hospitalisation were noted for patients who had aspirated peanut or animal material, as compared to patients who had aspirated non-organic material (odds ratio, 5.80; 95% confidence interval, 1.12-30.43). In terms of predicting the risk of pulmonary complications, the type of foreign body aspirated offers a more meaningful factor than the interval between aspiration and operation. Specifically, peanuts or animal material containing oils appear to be associated with a more prolonged pulmonary recovery even after retrieval of the foreign body. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Pregnancy and contraceptive use among women participating in the FEM-PrEP trial.

PubMed

Callahan, Rebecca; Nanda, Kavita; Kapiga, Saidi; Malahleha, Mookho; Mandala, Justin; Ogada, Teresa; Van Damme, Lut; Taylor, Douglas

2015-02-01

Pregnancy among study participants remains a challenge for trials of new HIV prevention agents despite promotion and provision of contraception. We evaluated contraceptive use, pregnancy incidence, and study drug adherence by contraceptive method among women enrolled in the FEM-PrEP trial of once-daily oral tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) for HIV prevention. We required women to be using effective non-barrier contraception at enrollment. At each monthly follow-up visit, women were counseled on contraceptive use and tested for pregnancy. TDF-FTC adherence was determined by measuring plasma drug concentrations at 4-week intervals. We used Cox proportional hazards models to assess factors associated with incident pregnancy and multivariate logistic regression to examine the relationship between contraceptive method used at enrollment and TDF-FTC adherence. More than half of women were not using effective contraception before enrollment. Ninety-eight percent of these women adopted either injectable (55%) or oral (43%) contraceptives. The overall pregnancy rate was 9.6 per 100 woman-years. Among injectable users and new users of combined oral contraceptives (COCs), the rates were 1.6 and 35.1, respectively. New users of injectables had significantly greater odds of adhering to TDF-FTC than new COC users [odds ratio (95% confidence interval): 4.4 (1.7 to 11.6), P = 0.002], existing COC users [3.1 (1.3 to 7.3), P = 0.01], and existing injectable users [2.4 (1.1 to 5.6), P = 0.04]. Women using COCs during FEM-PrEP, particularly new adopters, were more likely to become pregnant and less likely to adhere to study product than injectable users. HIV prevention trials should consider requiring long-acting methods, including injectables, for study participation.

Effect of HIV Infection on Human Papillomavirus Types Causing Invasive Cervical Cancer in Africa

PubMed Central

de Vuyst, Hugo; Tenet, Vanessa; Plummer, Martyn; Tully, Stephen; Franceschi, Silvia

2016-01-01

Objectives: HIV infection is known to worsen the outcome of cervical human papillomavirus (HPV) infection and may do so differentially by HPV type. Design: Twenty-one studies were included in a meta-analysis of invasive cervical cancers (ICC) among women infected with HIV in Africa. Method: Type-specific HPV DNA prevalence was compared with data from a similar meta-analysis of HIV-negative ICC using prevalence ratios (PR). Results: HPV detection was similar in 770 HIV-positive (91.2%) and 3846 HIV-negative (89.6%) ICC, but HIV-positive ICC harbored significantly more multiple HPV infections (PR = 1.75, 95% confidence intervals: 1.18 to 2.58), which were significantly more prevalent in ICC tested from cells than from biopsies. HPV16 was the most frequently detected type in HIV-positive ICC (42.5%), followed by HPV18 (22.2%), HPV45 (14.4%), and HPV35 (7.1%). Nevertheless, HIV-positive ICC were significantly less frequently infected with HPV16 than HIV-negative ICC (PR = 0.88, 95% confidence intervals: 0.79 to 0.99). Other high-risk types were significantly more prevalent in HIV-positive ICC, but only for HPV18 was there a significantly higher prevalence of both single and multiple infections in HIV-positive ICC. Increases for other high-risk types were primarily accounted for by multiple infections. The proportion of HPV-positive ICC estimated attributable to HPV16/18 (71.8% in HIV positive, 73.4% in HIV negative) or HPV16/18/31/33/45/52/58 (88.8%, 89.5%) was not affected by HIV. Conclusions: HIV alters the relative carcinogenicity of HPV types, but prophylactic HPV16/18 vaccines may nevertheless prevent a similar proportion of ICC, irrespective of HIV infection. PMID:27331659

Factors associated with the contraindicated use of oral contraceptives in Brazil

PubMed Central

Corrêa, Daniele Aparecida Silva; Felisbino-Mendes, Mariana Santos; Mendes, Mayara Santos; Malta, Deborah Carvalho; Velasquez-Melendez, Gustavo

2016-01-01

ABSTRACT OBJECTIVE To estimate the prevalence of the contraindicated use of oral contraceptives and the associated factors in Brazilian women. METHODS 20,454 women who answered the VIGITEL survey in 2008 also participated in this study, of which 3,985 reported using oral contraceptives. We defined the following conditions for the contraindicated use of contraceptives: hypertension; cardiovascular diseases such as heart attack, stroke/cerebrovascular accident; diabetes mellitus; being smoker and 35 years old or older. We estimated the prevalence and 95% confidence intervals of contraindicated use in users of oral contraceptives and the factors associated with contraindication by prevalence ratio and 95% confidence intervals. RESULTS In the total population, 21% (95%CI 19.7–21.9) of women showed some contraindication to the use of oral contraceptives, of which 11.7% (95%CI 10.6–13.7) belonged to the group of users of oral contraceptives. The most frequent contraindication in users of oral contraceptives was hypertension (9.1%). The largest proportion of women with at least one contraindication was aged between 45 and 49 years (45.8%) and with education level between zero and eight years (23.8%). The prevalence of contraindication to oral contraceptives was higher in women less educated (zero to eight years of study) (PR = 2.46; 95%CI 1.57–3.86; p < 0.05) and with age between 35-44 years (PR = 4.00; 95%CI 2.34–6.83) and 45-49 years (PR = 5.59; 95%CI 2.90–10.75). CONCLUSIONS Age greater than or equal to 35 and low education level were demographic and iniquity factors, respectively, in the contraindicated use of oral contraceptives. PMID:28099550

Effect of Mobile Phone Radiofrequency Electromagnetic Fields on.

PubMed

Umar, Z U; Abubakar, M B; Ige, J; Igbokwe, U V; Mojiminiyi, F B O; Isezuo, S A

2014-12-29

Since cell phones emit radiofrequency electromagnetic fields (EMFs), this study tested the hypothesis that cell phones placed near the heart may interfere with the electrical rhythm of the heart or affect the blood pressure. Following informed consent, eighteen randomly selected apparently healthy male volunteers aged 21.44 ± 0.53 years had their blood pressure, pulse rates and ECG measured before and after acute exposure to a cell phone. The ECG parameters obtained were: heart rate (HR), QRS complex duration (QRS), PR interval (PR) and Corrected QT interval (QTc). Results are presented as mean ± SEM. Statistical analyses were done using two-tailed paired t test for blood pressure and pulse rate data and one way ANOVA with a post hoc Tukey test for the ECG data. P<0.05 was considered statistically significant. The blood pressure and pulse rates before and after exposure to the cell phone showed no significant difference. The ECG parameters (HR: beats/min, QRS:ms, PR:ms and QTc respectively) did not differ before (66.33 ± 2.50, 91.78 ± 1.36, 151.67 ± 5.39 and 395.44 ± 4.96), during (66.33 ± 2.40, 91.11 ± 1.61, 153.67 ± 5.06 and 394.33 ± 4.05) and after calls (67.22 ± 2.77, 91.11 ± 1.67, 157.44 ± 4.46 and 396.56 ± 4.93) compared to baseline (67.17 ± 2.19, 94.33 ± 1.57, 150.56 ± 4.93 and 399.56 ± 3.88). These results suggest that acute exposure to EMFs from cell phones placed near the heart may not interfere with the electrical activity of the heart or blood pressure in healthy individuals.

Bedaquiline and Delamanid Combination Treatment of 5 Patients with Pulmonary Extensively Drug-Resistant Tuberculosis

PubMed Central

Maryandyshev, Andrey; Pontali, Emanuele; Tiberi, Simon; Akkerman, Onno; Ganatra, Shashank; Sadutshang, Tsetan Dorji; Alffenaar, Jan-Willem; Amale, Rohit; Mullerpattan, Jai; Topgyal, Sonam; Udwadia, Zarir Farokh; Centis, Rosella; D’Ambrosio, Lia; Sotgiu, Giovanni

2017-01-01

We report the experiences of 5 patients taking bedaquiline with delamanid in combination: 1 patient was cured; 3 culture converted, with 2 continuing and 1 changing therapy; and 1 died from respiratory insufficiency. For 2 patients, QT-interval prolongation but no arrhythmias occurred. Use of this therapy is justified for patients with limited options. PMID:28758888

Atypical Findings in Massive Bupropion Overdose: A Case Report and Discussion of Psychopharmacologic Issues.

PubMed

Zhu, Yuanjia; Kolawole, Tiwalola; Jimenez, Xavier F

2016-09-01

Bupropion is an atypical antidepressant that is structurally similar to amphetamines. Its primary toxic effects include seizure, sinus tachycardia, hypertension, and agitation; however, at higher amounts of ingestion, paradoxical cardiac effects are seen. We report the case of a 21-year-old woman who ingested 13.5 g of bupropion, a dose higher than any other previously reported. The patient presented with seizure, sinus tachycardia with prolonged QTc and QRS intervals, dilated pupils, and agitation. Four days after overdose, the patient's sinus tachycardia and prolonged QTc and QRS intervals resolved with symptomatic management, but she soon developed sinus bradycardia, hypotension, and mild transaminitis. With continued conservative management and close monitoring, her sinus bradycardia resolved 8 days after the overdose. The transaminitis resolved 12 days after the overdose. Our findings are consistent with previously reported toxic effects associated with common overdose amounts of bupropion. In addition, we have observed transient cardiotoxicity manifesting as sinus bradycardia associated with massive bupropion overdose. These findings are less frequently reported and must be considered when managing patients with massive bupropion overdose. We review the psychopharmacologic implications of this and comment on previous literature.

Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

PubMed

Pepper, Ruth J; Draibe, Juliana B; Caplin, Ben; Fervenza, Fernando C; Hoffman, Gary S; Kallenberg, Cees G M; Langford, Carol A; Monach, Paul A; Seo, Philip; Spiera, Robert; William St Clair, E; Tchao, Nadia K; Stone, John H; Specks, Ulrich; Merkel, Peter A; Salama, Alan D

2017-01-01

S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV. Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained. Patients were divided into 4 groups: proteinase 3 (PR3)-ANCA with relapse (n = 37), PR3-ANCA without relapse (n = 56), myeloperoxidase (MPO)-ANCA with relapse (n = 6), and MPO-ANCA without relapse (n = 45). Serum S100A8/A9 level decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between patients who experienced a relapse and those who did not in the PR3-ANCA group (P = 0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 level between baseline and month 2 (P = 0.0043) and baseline and month 6 (P = 0.0029). Subgroup analysis demonstrated that patients treated with RTX who had increased levels of S100A8/A9 were at greatest risk of future relapse (P = 0.028). An increase in serum S100A8/A9 level by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with RTX who are at higher risk of relapse by 18 months. Since RTX is increasingly used for remission induction in PR3-ANCA-positive patients experiencing a relapse, S100A8/A9 level may assist in identifying those patients requiring more intensive or prolonged treatment. © 2016, American College of Rheumatology.

[Influence of pacing site on myocardial transmural dispersion of repolarization in intact normal and dilated cardiomyopathy dogs].

PubMed

Bai, Rong; Pu, Jun; Liu, Nian; Lu, Jia-Gao; Zhou, Qiang; Ruan, Yan-Fei; Niu, Hui-Yan; Wang, Lin

2003-12-25

In order to verify the hypothesis that left ventricular epicardial (LV-Epi) pacing and biventricular (BiV) pacing unavoidably influence the myocardial electrophysiological characters and may result in high risk of malignant ventricular arrhythmia, we calculated, in both normal mongrel dogs and dog models with rapid-right-ventricular-pacing induced dilated cardiomyopathy congestive heart failure (DCM-CHF), the monophasic action potential duration (MAPD) and the transmural dispersion of repolarization (TDR) in intracardiac electrogram together with the QT interval and T(peak)-T(end) (T(p(-T(e)) interval in surface electrocardiogram (ECG) during LV-Epi and BiV pacing, compared with those during right ventricular endocardial (RV-Endo) pacing. To prepare the DCM-CHF dog model, rapid right ventricular pacing (250 bpm) was performed for 23.6+/-2.57 days to the dog. All the normal and DCM-CHF dogs were given radio frequency catheter ablation (RFCA) to His bundle with the guide of X-ray fluoroscopy. After the RFCA procedures, the animals were under the situation of complete atrioventricular block so that the canine heart rates could be voluntarily controlled in the following experiments. After a thoracotomy, ECG and monophasic action potentials (MAP) of subendocardial, subepicardial and mid-layer myocardium were recorded synchronously in 8 normal and 5 DCM-CHF dogs during pacing from endocardium of RV apex (RV-Endo), epicardium of LV anterior wall (LV-Epi) and simultaneously both of the above (biventricular, BiV), the later was similar to the ventricular resynchronization therapy to congestive heart failure patients in clinic. The Tp-Te) meant the interval from the peak to the end of T wave, which was a representative index of TDR in surface ECG. The TDR was defined as the difference between the longest and the shortest MAPD of subendocardial, subepicardial and mid-layer myocardium. Our results showed that in normal dogs, pacing participating of LV (LV-Epi, BiV) prolonged MAPD of all the three layers of the myocardium (P<0.05) with the character that mid-layer MAPD was the longest and subepicardial MAPD was the shortest following subendocardial MAPD. At the same time, TDR prolonged from 26.75 ms at RV-Endo pacing to 37.54 ms at BiV pacing and to 47.16 ms at LV-Epi pacing (P<0.001). Meanwhile in surface ECG, BiV and LV-Epi pacing resulted in a longer Tp-Te) interval compared with RV-Endo pacing (P<0.01), without parallel QT interval prolongation. Furthermore, all the DCM-CHF model dogs showed manifestations of congestive heart failure and enlargement of left ventricles. Based on the lengthening of mid-layer MAPD from 257.35 ms to 276.30 ms (P<0.0001) and increase of TDR from 27.58 ms to 33.80 ms (P equals;0.002) in DCM-CHF model due to the structural disorders of myocardium compared with the normal dog, LV-Epi and BiV pacing also led to the effect of prolonging MAPD of three layers of the myocardium and enlarging TDR. From these results we make the conclusions that prolongation of MAPD of subendocardial, subepicardial and mid-layer myocardium and increase in TDR during pacing participating of LV (LV-Epi, BiV) may contribute to the formation of unidirectional block and reentry, which play roles or at least are the high risk factors in the development of malignant ventricular arrhythmia, especially in case of structural disorders of myocardium. These findings must be considered seriously when ventricular resynchronization therapy is performed to congestive heart failure patients.

Fertility after ovarian follicular wave synchronization and fixed-time natural mating compared to random natural mating in dromedary camels (Camelus dromedarius).

PubMed

Nagy, P; Juhasz, J

2012-06-01

The objective of the study was to compare the efficiency of two ovarian follicular wave synchronization protocols coupled with fixed-time natural mating with that of random mating in dromedary camels. Dromedaries were assigned randomly to one of the three treatment groups. Group 1 animals (RM; n = 46) were mated randomly. Group 2 camels (1×GnRH-FTM; n = 46) were given a GnRH analog (Buserelin, 20 μg/animal, i.v.; Receptal, Intervet, Holland) at random, then were mated 14 days later. In Group 3 animals (2×GnRH-FTM; n = 41), random GnRH analog was followed by repeated GnRH injection 14 days later and fixed-time natural mating on Day 28. Transrectal examination and ultrasonography were performed at weekly intervals to evaluate ovarian follicular status, diagnose ovulation and pregnancy. Blood samples were collected for progesterone determination by ELISA to confirm ovulation and pregnancy. All female dromedaries were assigned randomly to one of thirteen fertile bulls and were bred once on Days 1, 14 and 28 in Groups 1-3, respectively. Ovarian follicular status and ovulation rate was similar among groups at the start of the study. Seventy-five of the 133 dromedaries (56.4%) ovulated after random natural mating or random GnRH treatment. Mean length of mating was 386 ± 17.8 (±SEM) seconds. There was no significant difference in mating time among groups and in pregnancy rate among dromedary bulls. In Group 3 (2×GnRH-FTM), ovarian follicular status before mating (P < 0.05), ovulation rate (n = 37, 90.2%, P < 0.001) and pregnancy rate at 21 and 60 days (PR 21 days n = 22, 53.7% and PR 60 days n = 19, 46.3%, P < 0.05) were greater compared to random natural mating (Group 1: OR n = 25, 54.3%, PR 21 days n = 13, 28.3% and PR 60 days n = 12, 26.1%). In Group 2 dromedaries (1×GnRH-FTM), treatment tended to improve follicular status before mating, ovulation rate (n = 34, 73.9%) and pregnancy rate at 21 and 60 days (PR 21 days n = 21, 45.7% and PR 60 days n = 16, 34.8%), but the effect was not significant compared to random natural mating. In conclusion, this is the first study demonstrating that favorable pregnancy rate can be achieved following ovarian follicular wave synchronization with repeated GnRH analog and fixed-time natural mating at 14 days intervals in dromedary camels. Copyright © 2012 Elsevier B.V. All rights reserved.

SLEEP QUALITY AND ITS ASSOCIATION WITH PSYCHOLOGICAL SYMPTOMS IN ADOLESCENT ATHLETES

PubMed Central

Gomes, Gabriel Cordeiro; dos Passos, Muana Hiandra Pereira; Silva, Hítalo Andrade; de Oliveira, Valéria Mayaly Alves; Novaes, Wbinayara Alves; Pitangui, Ana Carolina Rodarti; de Araújo, Rodrigo Cappato

2017-01-01

ABSTRACT Objective: To verify the prevalence of poor sleep quality and its association with personal characteristics and symptoms of depression, anxiety and stress in amateur adolescent athletes. Methods: 309 adolescent athletes aged between 10 and 19 years were enrolled. Data collection included: a structured questionnaire, with personal information; the Pittsburgh Sleep Quality Index (PSQI); and the Depression, Anxiety and Stress Scale (DASS-21). Results are described in mean and standard deviation (numeric variables) and absolute and relative frequencies (categorical variables). For the inferential analysis, Student’s t-test and chi-square test were performed, in addition to Poisson regression. Prevalence ratios (PR) were calculated in a 95% confidence interval (95%CI). Results: The mean age of participants was 14.1±2.1, being 13.8±2.0 and 15.0±2.1, respectively, for those with good and poor sleep quality. Poor sleep quality was recorded in 28.2% (n=87), depression in 26.9% (n=83) and anxiety/stress in 40.1% (n=124). Poor sleep quality was associated with ages between 15 and 19 years (PR 1.24; 95%CI 1.14-1.37), overweight (PR 1.12; 95%CI 1.01-1.24) and psychological symptoms of depression (PR 1.23; 95%CI 1.08-1.40) and anxiety/stress (PR 1.16; 95%CI 1.04-1.28). Conclusions: The presence of overweight and psychological symptoms and the age over 15 years were risk factors for increasing the likelihood of poor sleep quality in adolescent athletes. PMID:28977294

Higher cardiovascular disease prevalence and mortality among younger blacks compared to whites.

PubMed

Jolly, Stacey; Vittinghoff, Eric; Chattopadhyay, Arpita; Bibbins-Domingo, Kirsten

2010-09-01

Blacks have higher rates of cardiovascular disease than whites. The age at which these differential rates emerge has not been fully examined. We examined cardiovascular disease prevalence and mortality among black and white adults across the adult age spectrum and explored potential mediators of these differential disease prevalence rates. We conducted a cross-sectional analysis of National Health and Nutrition Examination Survey data from 1999-2006. We estimated age-adjusted and age-specific prevalence ratios (PR) for cardiovascular disease (heart failure, stroke, or myocardial infarction) for blacks versus whites in adults aged 35 years and older and examined potential explanatory factors. From the National Compressed Mortality File 5-year aggregate file of 1999-2003, we determined age-specific cardiovascular disease mortality rates. In young adulthood, cardiovascular disease prevalence was higher in blacks than whites (35-44 years PR 1.9; 95% confidence interval [CI], 1.1-3.4). The black-white PR decreased with each decade of advancing age (P for trend=.04), leading to a narrowing of the racial gap at older ages (65-74 years PR 1.2; 95% CI, 0.8-1.6; > or =75 years PR 1.0; 95% CI, 0.7-1.4). Clinical and socioeconomic factors mediated some, but not all, of the excess cardiovascular disease prevalence among young to middle-aged blacks. Over a quarter (28%) of all cardiovascular disease deaths among blacks occurred in those aged <65 years, compared with 13% among whites. Reducing black/white disparities in cardiovascular disease will require a focus on young and middle-aged blacks.

Association between risk behaviors and adiposity indicators in adolescents from Southern Brazil: A methodological approach.

PubMed

Silva, Danilo Rp; Ohara, David; Tomeleri, Crisieli M; Batista, Mariana B; Fernandes, Rômulo A; Ronque, Enio Rv; Sardinha, Luís B; Cyrino, Edilson S

2016-09-01

The aim of this study was to analyze the association between risk behaviors and adiposity indicators in adolescents and to discuss some methodological aspects related to this relationship. We evaluated 1,321 adolescents (55.2% female) aged 10-16 years. Relative body fat (%fat) by measurement of triceps and subscapular skinfold thickness and waist circumference (WC) were used as total and central adiposity indicators, respectively. Physical inactivity, time spent in front of the TV, the consumption of soda and/or chocolate, alcohol, and tobacco smoking were analyzed as risk behaviors. Information about the socioeconomic status (categorized into three levels) and nutritional status of the mother (overweight or normal weight) were used as adjustment factors in the analyses of prevalence ratio (PR) of the outcomes and their associated 95% confidence intervals (95% CI). The chi-square test and Poisson regression were used for statistical analyses. Low associations were found between risk behaviors and adiposity indicators. Tobacco smoking was the most positively correlated behavior with adiposity in girls (%fat: PR = 1.61; 95% CI = 1.04-2.47; WC: PR = 1.90; 95% CI = 1.17-3.08) and in adolescents whose mothers were normal weight (%fat: PR = 2.31; 95% CI = 1.33-4.03; WC: PR: 2.31; CI: 1.19-4.46). Additionally, as an important methodological issue, we highlighted the assessment of risk behaviors in adolescents as crucial to producing more robust evidence on the subject. Of the investigated behaviors, we concluded that tobacco smoking is the behavior most associated with adiposity indicators. © The Author(s) 2015.

Severe Hyperkalemia: Can the Electrocardiogram Risk Stratify for Short-term Adverse Events?

PubMed

Durfey, Nicole; Lehnhof, Brian; Bergeson, Andrew; Durfey, Shayla N M; Leytin, Victoria; McAteer, Kristina; Schwam, Eric; Valiquet, Justin

2017-08-01

The electrocardiogram (ECG) is often used to identify which hyperkalemic patients are at risk for adverse events. However, there is a paucity of evidence to support this practice. This study analyzes the association between specific hyperkalemic ECG abnormalities and the development of short-term adverse events in patients with severe hyperkalemia. We collected records of all adult patients with potassium (K+) ≥6.5 mEq/L in the hospital laboratory database from August 15, 2010, through January 30, 2015. A chart review identified patient demographics, concurrent laboratory values, ECG within one hour of K+ measurement, treatments and occurrence of adverse events within six hours of ECG. We defined adverse events as symptomatic bradycardia, ventricular tachycardia, ventricular fibrillation, cardiopulmonary resuscitation (CPR) and/or death. Two emergency physicians blinded to study objective independently examined each ECG for rate, rhythm, peaked T wave, PR interval duration and QRS complex duration. Relative risk was calculated to determine the association between specific hyperkalemic ECG abnormalities and short-term adverse events. We included a total of 188 patients with severe hyperkalemia in the final study group. Adverse events occurred within six hours in 28 patients (15%): symptomatic bradycardia (n=22), death (n=4), ventricular tachycardia (n=2) and CPR (n=2). All adverse events occurred prior to treatment with calcium and all but one occurred prior to K + -lowering intervention. All patients who had a short-term adverse event had a preceding ECG that demonstrated at least one hyperkalemic abnormality (100%, 95% confidence interval [CI] [85.7-100%]). An increased likelihood of short-term adverse event was found for hyperkalemic patients whose ECG demonstrated QRS prolongation (relative risk [RR] 4.74, 95% CI [2.01-11.15]), bradycardia (HR<50) (RR 12.29, 95%CI [6.69-22.57]), and/or junctional rhythm (RR 7.46, 95%CI 5.28-11.13). There was no statistically significant correlation between peaked T waves and short-term adverse events (RR 0.77, 95% CI [0.35-1.70]). Our findings support the use of the ECG to risk stratify patients with severe hyperkalemia for short-term adverse events.

Severe Hyperkalemia: Can the Electrocardiogram Risk Stratify for Short-term Adverse Events?

PubMed Central

Durfey, Nicole; Lehnhof, Brian; Bergeson, Andrew; Durfey, Shayla N.M.; Leytin, Victoria; McAteer, Kristina; Schwam, Eric; Valiquet, Justin

2017-01-01

Introduction The electrocardiogram (ECG) is often used to identify which hyperkalemic patients are at risk for adverse events. However, there is a paucity of evidence to support this practice. This study analyzes the association between specific hyperkalemic ECG abnormalities and the development of short-term adverse events in patients with severe hyperkalemia. Methods We collected records of all adult patients with potassium (K+) ≥6.5 mEq/L in the hospital laboratory database from August 15, 2010, through January 30, 2015. A chart review identified patient demographics, concurrent laboratory values, ECG within one hour of K+ measurement, treatments and occurrence of adverse events within six hours of ECG. We defined adverse events as symptomatic bradycardia, ventricular tachycardia, ventricular fibrillation, cardiopulmonary resuscitation (CPR) and/or death. Two emergency physicians blinded to study objective independently examined each ECG for rate, rhythm, peaked T wave, PR interval duration and QRS complex duration. Relative risk was calculated to determine the association between specific hyperkalemic ECG abnormalities and short-term adverse events. Results We included a total of 188 patients with severe hyperkalemia in the final study group. Adverse events occurred within six hours in 28 patients (15%): symptomatic bradycardia (n=22), death (n=4), ventricular tachycardia (n=2) and CPR (n=2). All adverse events occurred prior to treatment with calcium and all but one occurred prior to K+-lowering intervention. All patients who had a short-term adverse event had a preceding ECG that demonstrated at least one hyperkalemic abnormality (100%, 95% confidence interval [CI] [85.7–100%]). An increased likelihood of short-term adverse event was found for hyperkalemic patients whose ECG demonstrated QRS prolongation (relative risk [RR] 4.74, 95% CI [2.01–11.15]), bradycardia (HR<50) (RR 12.29, 95%CI [6.69–22.57]), and/or junctional rhythm (RR 7.46, 95%CI 5.28–11.13). There was no statistically significant correlation between peaked T waves and short-term adverse events (RR 0.77, 95% CI [0.35–1.70]). Conclusion Our findings support the use of the ECG to risk stratify patients with severe hyperkalemia for short-term adverse events. PMID:28874951

Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.

PubMed

Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L; Couch, Fergus J; Nevanlinna, Heli; Milne, Roger L; Gaudet, Mia; Schmidt, Marjanka K; Broeks, Annegien; Cox, Angela; Fasching, Peter A; Hein, Rebecca; Spurdle, Amanda B; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J; van Leeuwen, Flora E; Andrulis, Irene L; Glendon, Gord; Knight, Julia A; Mulligan, Anna Marie; O'Malley, Frances P; Weerasooriya, Nayana; John, Esther M; Beckmann, Matthias W; Hartmann, Arndt; Weihbrecht, Sebastian B; Wachter, David L; Jud, Sebastian M; Loehberg, Christian R; Baglietto, Laura; English, Dallas R; Giles, Graham G; McLean, Catriona A; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E; Connley, Daniel; Cross, Simon S; Balasubramanian, Sabapathy P; Reed, Malcolm W R; Dörk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Pérez, Jose Ignacio; Menéndez Rodríguez, Primitiva; Zamora, Pilar; Benítez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M; Tapper, William J; Gerty, Sue M; Sawyer, Elinor J; Tomlinson, Ian P; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yang, Show-Lin; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A; Henderson, Brian E; Le Marchand, Loic; Kolonel, Laurence N; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Gronwald, Jacek; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M A; Collée, Margriet; Wang-Gohrke, Shan; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Päivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E; Ørsted, David Dynnes; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Børge G; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E; Hunter, David J; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P E A; Tollenaar, R A E M; Seynaeve, C; Dite, Gillian S; Apicella, Carmel; Hopper, John L; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D; Southey, Melissa C; Humphreys, Manjeet K; Easton, Douglas; Pharoah, Paul; Sherman, Mark E; Garcia-Closas, Montserrat

2011-02-02

Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. In case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors. This study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.

Development of electrocardiogram intervals during growth of FVB/N neonate mice

PubMed Central

2010-01-01

Background Electrocardiography remains the best diagnostic tool and therapeutic biomarker for a spectrum of pediatric diseases involving cardiac or autonomic nervous system defects. As genetic links to these disorders are established and transgenic mouse models produced in efforts to understand and treat them, there is a surprising lack of information on electrocardiograms (ECGs) and ECG abnormalities in neonate mice. This is likely due to the trauma and anaesthesia required of many legacy approaches to ECG recording in mice, exacerbated by the fragility of many mutant neonates. Here, we use a non-invasive system to characterize development of the heart rate and electrocardiogram throughout the growth of conscious neonate FVB/N mice. Results We examine ECG waveforms as early as two days after birth. At this point males and females demonstrate comparable heart rates that are 50% lower than adult mice. Neonatal mice exhibit very low heart rate variability. Within 12 days of birth PR, QRS and QTc interval durations are near adult values while heart rate continues to increase until weaning. Upon weaning FVB/N females quickly develop slower heart rates than males, though PR intervals are comparable between sexes until a later age. This suggests separate developmental events may contribute to these gender differences in electrocardiography. Conclusions We provide insight with a new level of detail to the natural course of heart rate establishment in neonate mice. ECG can now be conveniently and repeatedly used in neonatal mice. This should serve to be of broad utility, facilitating further investigations into development of a diverse group of diseases and therapeutics in preclinical mouse studies. PMID:20735846

Prolonging the duration of masseter muscle reduction by adjusting the masticatory movements after the treatment of masseter muscle hypertrophy with botulinum toxin type a injection.

PubMed

Wei, Jiao; Xu, Hua; Dong, Jiasheng; Li, Qingfeng; Dai, Chuanchang

2015-01-01

Botulinum toxin type A (BTX-A) is widely used for the clinical treatment of masseteric hypertrophy. Until now, few reports have discussed how to prolong the duration of its effectiveness. This study evaluated that purposely adjusting the masticatory movements is possible of postponing the masseter muscle rehypertrophy. Ninety-eight patients were randomly and equally divided into 2 groups, and 35 U BTX-A per side was injected into the masseters. The thickness and volume of the masticatory muscles were measured by ultrasound and computerized tomography, respectively. Patients in Group 1 were instructed to strengthen their masticatory effort during the denervated atrophic stage of the masseter (the interval was evaluated by real-time ultrasound monitoring), whereas patients in Group 2 were not given this instruction. When the masseter muscle began to recover, patients in both groups were instructed to reduce their chewing. The duration of the masseter muscle rehypertrophy was significantly prolonged in Group 1 patients. The thickness and the volume of the other masticatory muscles were significantly increased in Group 1 but were either slightly decreased or insignificantly different in Group 2. Purposely strengthening masticatory muscle movement during the denervated atrophic stage of the masseter can prolong the duration of masseter rehypertrophy.

Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine.

PubMed

Henstra, Marieke; Wong, Liza; Chahbouni, Abdel; Swart, Noortje; Allaart, Cor; Sombogaard, Ferdi

2017-07-01

Ibogaine is an agent that has been evaluated as an unapproved anti-addictive agent for the management of drug dependence. Sudden cardiac death has been described to occur secondary to its use. We describe the clinical effects and toxicokinetics of ibogaine and noribogaine in a single patient. For this purpose, we developed a LC-MS/MS-method to measure ibogaine and noribogaine plasma-concentrations. We used two compartments with first order absorption. The maximum concentration of ibogaine was 1.45 mg/L. Our patient developed markedly prolonged QTc interval of 647ms maximum, several multiple cardiac arrhythmias (i.e., atrial tachycardia and ventricular tachycardia and Torsades des Pointes). QTc-prolongation remained present until 12 days after ingestion, several days after ibogaine plasma-levels were low, implicating clinically relevant noribogaine concentrations long after ibogaine had been cleared from the plasma. The ratio k 12 /k 21 for noribogaine was 21.5 and 4.28 for ibogaine, implicating a lower distribution of noribogaine from the peripheral compartment into the central compartment compared to ibogaine. We demonstrated a linear relationship between the concentration of the metabolite and long duration of action, rather than with parent ibogaine. Therefore, after (prolonged) ibogaine ingestion, clinicians should beware of long-term effects due to its metabolite.

Enzymatic Formulation Capable of Degrading Scrapie Prion under Mild Digestion Conditions

PubMed Central

Okoroma, Emeka A.; Purchase, Diane; Garelick, Hemda; Morris, Roger; Neale, Michael H.; Windl, Otto; Abiola, Oduola O.

2013-01-01

The prion agent is notoriously resistant to common proteases and conventional sterilisation procedures. The current methods known to destroy prion infectivity such as incineration, alkaline and thermal hydrolysis are harsh, destructive, environmentally polluting and potentially hazardous, thus limit their applications for decontamination of delicate medical and laboratory devices, remediation of prion contaminated environment and for processing animal by-products including specified risk materials and carcases. Therefore, an environmentally friendly, non-destructive enzymatic degradation approach is highly desirable. A feather-degrading Bacillus licheniformis N22 keratinase has been isolated which degraded scrapie prion to undetectable level of PrPSc signals as determined by Western Blot analysis. Prion infectivity was verified by ex vivo cell-based assay. An enzymatic formulation combining N22 keratinase and biosurfactant derived from Pseudomonas aeruginosa degraded PrPSc at 65°C in 10 min to undetectable level -. A time-course degradation analysis carried out at 50°C over 2 h revealed the progressive attenuation of PrPSc intensity. Test of residual infectivity by standard cell culture assay confirmed that the enzymatic formulation reduced PrPSc infectivity to undetectable levels as compared to cells challenged with untreated standard scrapie sheep prion (SSBP/1) (p-value = 0.008 at 95% confidence interval). This novel enzymatic formulation has significant potential application for prion decontamination in various environmentally friendly systems under mild treatment conditions. PMID:23874511