Cardiac arrhythmias six months following traumatic spinal cord injury

ObjectiveTo investigate the incidence of cardiac arrhythmias at six months following traumatic spinal cord injury (SCI) and to compare the prevalence of arrhythmias between participants with cervical and thoracic SCI.DesignA prospective observational study using continuous twenty-four-hour Holter monitoring.SettingInpatient rehabilitation unit of a university research hospital and patient home setting.ParticipantsFifty-five participants with acute traumatic SCI were prospectively included. For each participant, the SCI was characterized according to the International Standards for Neurological Classification of SCI by the neurological level and severity according to the American Spinal Injury Association Impairment Scale.Outcome measuresComparisons between demographic characteristics and arrhythmogenic occurrences as early as possible after SCI (4 ± 2 days) followed by 1, 2, 3, 4 weeks and 6 month time points of Holter monitoring.ResultsBradycardia (heart rate [HR] <50 bpm) was present in 29% and 33% of the participants with cervical (C1–C8) and thoracic (T1–T12) SCI six months after SCI, respectively. The differences in episodes of bradycardia between the two groups were not significant (P < 0.54). The mean maximum HR increased significantly from 4 weeks to 6 months post-SCI (P < 0.001), however mean minimum and maximum HR were not significantly different between the groups at the six-month time point. There were no differences in many arrhythmias between recording periods or between groups at six months.ConclusionsAt the six-month timepoint following traumatic SCI, there were no significant differences in occurrences of arrhythmias between participants with cervical and thoracic SCI compared to the findings observed in the first month following SCI.     

Obesity and estrogen as risk factors for gastroesophageal reflux symptoms

Context  Gastroesophageal reflux and obesity are both increasing in prevalence. The scientific evidence for an association between these conditions is sparse and contradictory. A difference between sexes concerning this relation has been proposed. Objective  To evaluate the relation between body mass and gastroesophageal reflux symptoms and determine how this relation is influenced by female sex hormones. Design  Population-based, cross-sectional, case-control study. Setting  Two consecutive public health surveys within the county of Nord-Trondelag, Norway, conducted in 1984-1986 and 1995-1997. Participants  Among 65 363 adult participants in the second survey, 3113 individuals who reported severe heartburn or regurgitation during the last 12 months were defined as cases, whereas 39 872 persons without reflux symptoms were defined as controls. Main Outcome Measure  Risk of reflux, estimated using multivariate logistic regression, with odds ratios (ORs) and 95% confidence intervals (CIs) as measures of association. Results  There was a dose-response association between increasing body mass index (BMI) and reflux symptoms in both sexes (P for trend <.001), with a significantly stronger association in women (P<.001). Compared with those with a BMI less than 25, the risk of reflux was increased significantly among severely obese (BMI >35) men(OR, 3.3; 95% CI, 2.4-4.7) and women (OR, 6.3; 95% CI, 4.9-8.0). The association between BMI and reflux symptoms was stronger among premenopausal women compared with postmenopausal women (P<.001), although use of postmenopausal hormone therapy increased the strength of the association (P<.001). Reduction in BMI was associated with decreased risk of reflux symptoms. Conclusions  There is a significant association between body mass and symptoms of gastroesophageal reflux. The association is stronger among women, especially premenopausally, and use of hormone therapy strengthens the association, suggesting that estrogens may play an important role in the etiology of reflux disease.      

Comparison of different stepwise screening strategies for type 2 diabetes: Finding from Danish general practice,Addition-DK

AimTo examine attendance, number of people with T2DM and costs of three different stepwise screening strategies for T2DM in general practice (GP).MethodsDiabetes risk questionnaires were mailed to individuals aged 40–69 years from 45 general practices in 2001–2002 and individuals at high risk for T2DM, were asked to contact their GP to arrange a screening test. In 2005–2006, 26 general practices were randomised into two different opportunistic screening programmes (OP-direct and OP-subsequent) and risk questionnaires were distributed to individuals aged 40–69 years during GP consultations. In the OP-direct approach, high-risk individuals were offered to start the screening during the actual consultation while high-risk individuals in the OP-subsequent approach, were invited to a screening test at a later date. We report attendance, number of people with T2DM and costs of each screening approach.ResultsThe mail-distributed approach identified 0.8% of the target population with T2DM, the OP-direct approach and the OP-subsequent approach, 0.9% and 0.5% respectively. Cost per person with T2DM was in the mail-distributed approach: € 1058, OP-direct approach: € 707 and the OP-subsequent approach: € 727.ConclusionThis study indicates that opportunistic screening identifies the same level of unknown diabetes as a mail-distributed approach but with lower costs.     

Multiple doses of pegylated long‐acting growth hormone are well tolerated in healthy male volunteers and possess a potential once‐weekly treatment profile

Objectives Recombinant human growth hormone (rhGH) replacement therapy in children and adults currently requires daily subcutaneous injections for several years or lifelong. The current study examined safety, tolerability, pharmacokinetic and pharmacodynamic response parameters after single and multiple doses of a long‐acting rhGH preparation (NNC126‐0083). Design Randomized, double‐blinded, placebo‐controlled, multiple‐dose, dose‐escalating (0·02, 0·04, 0·08 and 0·16 mg protein/kg), sequential dose group trial. Subjects Forty adult Japanese healthy male volunteers (aged 20–45; body mass index: 18·0–27·0 kg/m²). Five groups (n = 8) were randomized to receive multiple doses of NNC126‐0083 (n = 6) or placebo (n = 2). Methods Primary outcome was safety, and tolerability of multiple doses of NNC126‐0083 compared with placebo. Blood samples for the assessment of pharmacokinetics (PK) and pharmacodynamics response [insulin‐like growth factor I (IGF‐I) and IGF binding protein 3 (IGFBP‐3)] were taken after multiple ascending doses. Results NNC126‐0083 was well tolerated and not associated with any local injection‐site reactions or lipoatrophy. Following administration, NNC126‐0083 levels increased rapidly and remained elevated for several days, returning to baseline before each weekly injection. Steady‐state PK was achieved after the third dosing. A more than dose‐proportional exposure was observed at the highest NNC126‐0083 dose (0·16 mg protein/kg). A strong dose‐dependent pharmacodynamic response in circulating concentrations of both IGF‐I and IGFBP‐3 compared with placebo (P < 0·0001) was observed during the administration of all doses. Conclusions Multiple administration of NNC126‐0083 in healthy male volunteers indicates that NNC126‐0083 has the potential for an efficacious, well‐tolerated, once‐weekly rhGH compound in the treatment of GH deficiency.     

Prevalence of diastolic dysfunction as a possible cause of dyspnea in the elderly

PURPOSE: Symptoms in patients with heart failure and preserved left ventricular ejection fraction may be caused by isolated diastolic dysfunction. The purpose of this study was to assess the prevalence of diastolic dysfunction as a potential cause of dyspnea in a sample of elderly subjects, as well as of isolated diastolic dysfunction as a potential cause of dyspnea in a subgroup with a preserved left ventricular ejection fraction and normal lung function. METHODS: A total of 152 subjects with dyspnea underwent echocardiography, electrocardiography, and lung function testing. Subjects with normal lung function test results (n = 60) underwent cardiac magnetic resonance imaging, chest radiography, bicycle exercise tests, and blood tests. Left ventricular diastolic function was assessed by a variety of echocardiographic/Doppler techniques. RESULTS: Of 129 subjects with dyspnea, 81 (63%) had signs of lung disease or 'obvious' cardiac disease. In the remaining 48 subjects, 32 (67%) had a potential cardiac/noncardiac cause of dyspnea. In all subjects with dyspnea, 1% to 11% had diastolic dysfunction, and in the 48 remaining subjects, 0% to 10% had isolated diastolic dysfunction, depending on the definition used. CONCLUSION: The frequency of diastolic dysfunction was low in the sample of elderly subjects with dyspnea as well as in the subgroup of persons with no signs of lung disease, left ventricular systolic dysfunction, atrial fibrillation, or valvular heart disease. Diastolic dysfunction was infrequent as a possible cause of dyspnea, and coexisting potential causes of dyspnea were often present.     

Modeling Dynamic Contrast-Enhanced MRI Data with a Constrained Local AIF

Purpose

This study aims to develop a constrained local arterial input function (cL-AIF) to improve quantitative analysis of dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) data by accounting for the contrast-agent bolus amplitude error in the voxel-specific AIF.

Procedures

Bayesian probability theory-based parameter estimation and model selection were used to compare tracer kinetic modeling employing either the measured remote-AIF (R-AIF, i.e., the traditional approach) or an inferred cL-AIF against both in silico DCE-MRI data and clinical, cervical cancer DCE-MRI data.

Results

When the data model included the cL-AIF, tracer kinetic parameters were correctly estimated from in silico data under contrast-to-noise conditions typical of clinical DCE-MRI experiments. Considering the clinical cervical cancer data, Bayesian model selection was performed for all tumor voxels of the 16 patients (35,602 voxels in total). Among those voxels, a tracer kinetic model that employed the voxel-specific cL-AIF was preferred (i.e., had a higher posterior probability) in 80 % of the voxels compared to the direct use of a single R-AIF. Maps of spatial variation in voxel-specific AIF bolus amplitude and arrival time for heterogeneous tissues, such as cervical cancer, are accessible with the cL-AIF approach.

Conclusions

The cL-AIF method, which estimates unique local-AIF amplitude and arrival time for each voxel within the tissue of interest, provides better modeling of DCE-MRI data than the use of a single, measured R-AIF. The Bayesian-based data analysis described herein affords estimates of uncertainties for each model parameter, via posterior probability density functions, and voxel-wise comparison across methods/models, via model selection in data modeling.

     

Impact of transducer frequency setting on speckle tracking measures

Speckle tracking echocardiography is an emerging technique, which is currently being included in clinical guidelines. We sought to investigate the impact of transducer frequency settings on speckle tracking derived measures. The study comprised of 22 subjects prospectively enrolled for a randomized controlled trial (LOOP-study, Clinicaltrials.gov:NCT02036450). Patients were above 70 years of age with increased risk of stroke, and had an echocardiogram performed, which included focused images of the left ventricle. Focused images were obtained with the transducer frequency set at both 1.7/3.3 and 1.5/3.0 MHz. The images were obtained immediately after each other at the exact same position for the two settings. Speckle tracking was performed in three apical projections, allowing for acquisition of layered global longitudinal strain (GLS) and strain rate measures. Concordance between the frequency settings was tested for endo-, mid-, and epicardial GLS and strain rates by coefficients of variation, bias coefficients and visually displayed by Bland–Altman plots. Bland–Altman plots did not reveal any significant over- or underestimation of any speckle tracking measure. Bias coefficients showed that none of the measurements differed significantly between the two settings (bias for GLS_endo?=???0.07?±?2.94, p?=?0.91; GLS_mid?=?0.02?±?2.70, p?=?0.98, GLS_epi?=?0.07?±?2.53, p?=?0.90). Coefficients of variation were as follows: GLS_endo?=?15.11%, GLS_mid?=?15.28%, GLS_epi?=?17.26%, systolic strain rate?=?15.66%, early diastolic strain rate?=?38.46%, late diastolic strain rate?=?11%. Changing between transducer frequency settings does not systematically derange speckle tracking measures. One can safely reduce the transducer frequency without compromising the validity of speckle tracking derived measures.