Diagnosing coronary artery disease by sound analysis from coronary stenosis induced turbulent blood flow: diagnostic performance in patients with stable angina pectoris.

Optimizing risk assessment may reduce use of advanced diagnostic testing in patients with symptoms suggestive of stable coronary artery disease (CAD). Detection of diastolic murmurs from post-stenotic coronary turbulence with an acoustic sensor placed on the chest wall can serve as an easy, safe, and low-cost supplement to assist in the diagnosis of CAD. The aim of this study was to evaluate the diagnostic accuracy of an acoustic test (CAD-score) to detect CAD and compare it to clinical risk stratification and coronary artery calcium score (CACS). We prospectively enrolled patients with symptoms of CAD referred to either coronary computed tomography or invasive coronary angiography (ICA). All patients were tested with the CAD-score system. Obstructive CAD was defined as more than 50 % diameter stenosis diagnosed by quantitative analysis of the ICA. In total, 255 patients were included and obstructive CAD was diagnosed in 63 patients (28 %). Diagnostic accuracy evaluated by receiver operating characteristic curves was 72 % for the CAD-score, which was similar to the Diamond-Forrester clinical risk stratification score, 79 % (p = 0.12), but lower than CACS, 86 % (p < 0.01). Combining the CAD-score and Diamond-Forrester score, AUC increased to 82 %, which was significantly higher than the standalone CAD-score (p < 0.01) and Diamond-Forrester score (p < 0.05). Addition of the CAD-score to the Diamond-Forrester score increased correct reclassification, categorical net-reclassification index = 0.31 (p < 0.01). This study demonstrates the potential use of an acoustic system to identify CAD. The combination of clinical risk scores and an acoustic test seems to optimize patient selection for diagnostic investigation.

Interrater reliability of diagnostic methods in traditional Indian ayurvedic medicine.

This study assesses the interrater reliability of Ayurvedic pulse (nadi), tongue (jivha), and body constitution (prakriti) assessments. Fifteen registered Ayurvedic doctors with 3-15 years of experience independently examined twenty healthy subjects. Subjects completed self-assessment questionnaires and software analyses for prakriti assessment. Weighted kappa statistics for all 105 pairs of doctors were computed for the pulse, tongue, and prakriti data sets. According to the Landis-Koch scale, the pairwise kappas ranged from poor to slight, slight to fair, and fair to moderate for pulse, tongue, and prakriti assessments, respectively. The average pairwise kappa for pulse, tongue, and prakriti was 0.07, 0.17, and 0.28, respectively. For each data set and pair of doctors, the null hypothesis of random rating was rejected for just twelve pairs of doctors for prakriti, one pair of doctors for pulse examination, and no pairs of doctors for tongue assessment. Thus, the results demonstrate a low level of reliability for all types of assessment made by doctors. There was significant evidence against random rating by software and questionnaire use and by the diagnosis preferred by the majority of doctors. Prakriti assessment appears reliable when questionnaire and software assessment are used, while other diagnostic methods have room for improvement.

Attitudes of COPD patients towards tele-rehabilitation: a cross-sector case study.

The aim of this paper is to describe patients' attitudes towards tele-rehabilitation in the Danish TELEKAT (for Telehomecare, Chronic Patients and the Integrated Healthcare System) project, in order to better understand patients' behavior when performing tele-rehabilitation activities in home surroundings. A total of 111 COPD patients were included in the study, and they were randomized into an intervention group (n = 60) and a control group (n = 51). However, a non-randomized design was used to analyze the qualitative perspectives of the patients' attitudes towards tele-rehabilitation. From the intervention group, 22 COPD patients were selected for qualitative interviews and participant observation in their homes. The theoretical framework for this study is based on learning theory and the "communities of practice" approach inspired by Etienne Wenger. COPD patients exhibit four types of attitudes about their tele-rehabilitation: indifference, learning as part of situations in everyday life, feeling of security and motivation for performing physical training. The patients express the view that they circulate between these attitudes depending on their physical and emotional state as they perform their training. The COPD patients and healthcare professionals have created a community of tele-rehabilitation across sectors, exchanging experiences, stories and strategies for how to manage rehabilitation in home surroundings.

Reliability studies of diagnostic methods in Indian traditional Ayurveda medicine: An overview.

Recently, a need to develop supportive new scientific evidence for contemporary Ayurveda has emerged. One of the research objectives is an assessment of the reliability of diagnoses and treatment. Reliability is a quantitative measure of consistency. It is a crucial issue in classification (such as prakriti classification), method development (pulse diagnosis), quality assurance for diagnosis and treatment and in the conduct of clinical studies. Several reliability studies are conducted in western medicine. The investigation of the reliability of traditional Chinese, Japanese and Sasang medicine diagnoses is in the formative stage. However, reliability studies in Ayurveda are in the preliminary stage. In this paper, examples are provided to illustrate relevant concepts of reliability studies of diagnostic methods and their implication in practice, education, and training. An introduction to reliability estimates and different study designs and statistical analysis is given for future studies in Ayurveda.

Intrarater and interrater reliability of pulse examination in traditional Indian Ayurvedic medicine.

BACKGROUND: In Ayurveda, pulse examination (nadipariksha) is an important tool to assess the status of three doshas: vata, pitta, and kapha. Long historical use has been seen as a documentation of its efficacy; however, there is a lack of a quantitative measure of the reliability of the pulse examination method. The objective of this study was to test the intrarater and interrater reliability of pulse examination in Ayurveda. METHODS: Fifteen registered Ayurvedic doctors with 3-15 years of experience examined the pulse of 20 healthy volunteers twice, for a total of 600 examinations. The examinations were performed blind and in a random order. Only the current status of dosha-specific methods of pulse examination were considered. Cohen's weighted κ statistic was used as a measure of intrarater and interrater reliability, and a hypothesis of homogeneous diagnosis (random rating) was tested. Following this, we tested whether proportions of ratings were equal between doctors. RESULTS: According to the Landis and Koch scale, the level of reliability ranged from poor to moderate. It was observed that the doctors more frequently diagnosed a combination of two doshas than a single dosha. The κ values were generally larger for experienced doctors (p = 0.04). CONCLUSION: Experience and proper training have important roles in pulse examination.

Cost-utility analysis of a telerehabilitation program: a case study of COPD patients.

OBJECTIVE: The present study seeks to conduct cost-utility analysis (CUA) of the Danish TELEKAT (Telehomecare, Chronic Patients and the Integrated Healthcare System) project. The TELEKAT project seeks to test and develop a preventive home monitoring concept across sectors for chronic obstructive pulmonary disease (COPD) patients. The concept of the TELEKAT project is to reduce admissions by enabling the COPD patients to conduct self-monitoring and maintain rehabilitation activities in their own home. COPD patients with severe and very severe COPD were included in the study. SUBJECTS AND METHODS: This economic evaluation follows international guidelines for the conduction of a CUA alongside a clinical randomized controlled trial. The analysis is based on a health sector perspective. RESULTS: The mean incremental cost efficiency ratio, located in the southeast quadrant, shows that telerehabilitation is less costly and more effective than the rehabilitation given to the control group. The telerehabilitation program produces more value for money and generates savings on healthcare budgets. CONCLUSIONS: The telerehabilitation program appears to be more cost-effective than the conventional rehabilitation program for COPD patients. Further studies of cost-effectiveness with a focus on large-scale studies are needed.

Repeatability of Pulse Diagnosis and Body Constitution Diagnosis in Traditional Indian Ayurveda Medicine.

In Ayurveda, pulse diagnosis and body constitution diagnosis have a long historical use; still, there is lack of quantitative measure of the reliability of these diagnostic methods. Reliability means consistency of information. Consistent diagnosis leads to consistent treatment and is important for clinical practice, education, and research. The objective of this study is to study the methodology to evaluate the test-retest reliability (repeatability) of pulse diagnosis and body constitution diagnosis. A double-blinded, controlled, clinical trial was conducted in Copenhagen. The same doctor, an expert in Ayurvedic pulse diagnosis, examined the pulse and body constitution of 17 healthy participants twice, in random order without seeing them. A metric on pulse and body constitution variables was developed. Cohen's weighted kappa statistic was used as a measure of intra-rater reliability. Permutation tests were used to test the hypothesis of homogeneous diagnosis (ie, the doctor's diagnosis does not depend on the subject). The hypothesis of homogeneous classification was rejected on the 5% significance level (P values of .02 and .001, respectively, for pulse and body constitution diagnosis). According to the Landis and Koch scale, values of the weighted kappa for pulse diagnosis (P = .42) and body constitution diagnosis (P = .65) correspond to "moderate" and "substantial" agreement, respectively. There was a reasonable level of consistency between 2 pulse and body constitution diagnoses. Further studies are required to quantify inter-subject and intra-subject agreement for greater understanding of reliability of pulse and body constitution diagnosis.

La medicina ayurvédica lleva mucho tiempo utilizando el diagnóstico mediante el pulso y la constitución corporal; no obstante, se sigue careciendo de medidas cuantitativas de la fiabilidad de estos métodos diagnósticos, la cual implica uniformidad de la información. Un diagnóstico coherente lleva a un tratamiento uniforme y resulta de gran importancia para la práctica clínica, la educación y la investigación.El objetivo de este estudio, un ensayo clínico controlado doble ciego llevado a cabo en Copenhagen, es analizar la metodología para evaluar la fiabilidad (repetibilidad) del diagnóstico mediante el pulso y la constitución corporal. El mismo médico, un experto en el diagnóstico ayurvédico mediante el pulso, examinó en dos ocasiones el pulso y la constitución corporal de 17 participantes sanos, en orden aleatorio y sin verlos. Se desarrolló una escala de medida de las variables de pulso y constitución corporal. Como método de la fiabilidad en el mismo evaluador se usó el valor estadístico kappa ponderada de Cohen y se usaron pruebas de permutación para probar la hipótesis de la homo-geneidad del diagnóstico (es decir, el diagnóstico del médico no depende del paciente).La hipótesis de la homogeneidad de la clasificación se rechazó al nivel de significación del 5 % (P valor de 0,02 y 0,001, respectivamente, para el diagnóstico medi-ante el pulso y la constitución corporal). Conforme a las escalas de Landis y Koch, los valores de kappa ponderada para el diagnóstico mediante el pulso (P = 0,42) y medi-ante la constitución corporal (P = 0,65) se corresponden con una concordancia "moderada" y "sustancial", respectivamente.Se produjo un nivel de uniformidad razonable entre los dos diagnósticos mediante constitución corporal y pulso, aunque se requieren más estudios para cuantificar la concordancia inter e intrapacientes con el objetivo de obtener una mayor comprensión de la fiabilidad.

Assessing QT interval prolongation and its associated risks with antipsychotics.

Several antipsychotics are associated with the ventricular tachycardia torsade de pointes (TdP), which may lead to sudden cardiac death (SCD), because of their inhibition of the cardiac delayed potassium rectifier channel. This inhibition extends the repolarization process of the ventricles of the heart, illustrated as a prolongation of the QT interval on a surface ECG. SCD in individuals receiving antipsychotics has an incidence of approximately 15 cases per 10,000 years of drug exposure but the exact association with TdP remains unknown because the diagnosis of TdP is uncertain. Most patients manifesting antipsychotic-associated TdP and subsequently SCD have well established risk factors for SCD, i.e. older age, female gender, hypokalaemia and cardiovascular disease. QT interval prolongation is the most widely used surrogate marker for assessing the risk of TdP but it is considered somewhat imprecise, partly because QT interval changes are subject to measurement error. In particular, drug-induced T-wave changes (e.g. flattening of the T-wave) may complicate the measurement of the QT interval. Furthermore, the QT interval depends on the heart rate and a corrected QT (QTc) interval is often used to compensate for this. Several correction formulas have been suggested, with Bazett's formula the most widely used. However, Bazett's formula overcorrects at a heart rate above 80 beats per minute and, therefore, Fridericia's formula is considered more appropriate to use in these cases. Several other surrogate markers for TdP have been developed but none of them is clinically implemented yet and QT interval prolongation is still considered the most valid surrogate marker. Although automated QT interval determination may offer some assistance, QT interval determination is best performed by a cardiologist skilled in its measurement. A QT interval >500 ms markedly increases the risk for TdP and SCD, and should lead to discontinuation of the offending drug and, if present, correction of underlying electrolyte disturbances, particularly serum potassium and magnesium derangements. Before prescribing antipsychotics that may increase the QTc interval, the clinician should ask about family and personal history of SCD, presyncope, syncope and cardiac arrhythmias, and recommend cardiology consultation if history is positive.

Effect of intravenous omega-3 fatty acid infusion and hemodialysis on fatty acid composition of free fatty acids and phospholipids in patients with end-stage renal disease.

BACKGROUND: Patients treated with hemodialysis (HD) have been reported to have decreased levels of ω-3 polyunsaturated fatty acids (PUFAs) in plasma and cells. The aim of this study was to investigate the effect of ω-3 PUFAs administered intravenously during HD, as well as the effect of HD treatment, on the fatty acid composition of plasma free fatty acids (FFAs), plasma phospholipids, and platelet phospholipids. METHODS: Forty-four HD patients were randomized to groups receiving either a single dose of a lipid emulsion containing 4.1 g of ω-3 PUFAs or placebo (saline) administered intravenously during HD. Blood was drawn immediately before (baseline) and after (4 hours) HD and before the next HD session (48 hours). Fatty acid composition was measured using gas chromatography. RESULTS: The increase in ω-3 FFAs was greater in the ω-3 PUFA group compared with the placebo group, whereas the increase in total FFAs was similar between the 2 groups. In the ω-3 PUFA group, ω-3 PUFAs in plasma phospholipids were higher after 48 hours than at baseline, and in platelet phospholipids, ω-3 PUFAs increased after 4 hours. In the placebo group, no changes were observed in ω-3 PUFAs in plasma and platelet phospholipids. CONCLUSIONS: Intravenous ω-3 PUFAs administered during HD caused a transient selective increase in ω-3 FFA concentration. Furthermore, ω-3 PUFAs were rapidly incorporated into platelets, and the content of ω-3 PUFAs in plasma phospholipids increased after 48 hours.

Remote monitoring of implantable-cardioverter defibrillators: results from the Reliability of IEGM Online Interpretation (RIONI) study.

AIMS: Intracardiac electrograms (IEGMs) recorded by implantable cardioverter-defibrillators (ICDs) are essential for arrhythmia diagnosis and ICD therapy assessment. Short IEGM snapshots showing 3-10 s before arrhythmia detection were added to the Biotronik Home Monitoring system in 2005 as the first-generation IEGM Online. The RIONI study tested the primary hypothesis that experts' ratings regarding the appropriateness of ICD therapy based on IEGM Online and on standard 30 s IEGM differ in <10% of arrhythmia events. METHODS AND RESULTS: A total of 619 ICD patients were enrolled and followed for 1 year. According to a predefined procedure, 210 events recorded by the ICDs were selected for evaluation. Three expert board members rated the appropriateness of ICD therapy and classified the underlying arrhythmia using coded IEGM Online and standard IEGM to avoid bias. The average duration of IEGM Online was 4.4±1.5 s. According to standard IEGM, the underlying arrhythmia was ventricular in 135 episodes (64.3%), supraventricular in 53 episodes (25.2%), oversensing in 17 episodes (8.1%), and uncertain in 5 episodes (2.4%). The expert board's rating diverged between determinable IEGM Online tracings and standard IEGM in 4.6% of episodes regarding the appropriateness of ICD therapy (95% CI up to 8.0%) and in 6.6% of episodes regarding arrhythmia classification (95% CI up to 10.5%). CONCLUSION: By enabling accurate evaluation of the appropriateness of ICD therapy and the underlying arrhythmia, the first-generation IEGM Online provided a clinically effective basis for timely interventions and for optimized patient management schemes, which was comparable with current IEGM recordings.

Marine n-3 polyunsaturated fatty acids in patients with end-stage renal failure and in subjects without kidney disease: a comparative study.

OBJECTIVE: Patients with end-stage renal disease treated with chronic hemodialysis (HD) are reported to have low levels of marine n-3 polyunsaturated fatty acids (PUFA) in plasma and cell membranes compared with healthy subjects. The aim of this study was to investigate whether n-3 PUFA levels in plasma and cells are lower in HD patients as compared with subjects without kidney disease. RESEARCH DESIGN: A comparative study was carried out. SETTING: This study was carried out at the Departments of Nephrology and Cardiology, Aalborg Hospital, Aarhus University Hospital, Denmark. PARTICIPANTS: This study consisted of 2 study populations comprising HD patients and 5 study populations comprising subjects without kidney disease. INTERVENTION: The fatty acid distribution in plasma phospholipids and platelet phospholipids was measured using gas chromatography. MAIN OUTCOME MEASURE: Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) levels in plasma or serum phospholipids and platelet phospholipids in HD patients were compared with n-3 PUFA levels in subjects without kidney disease. RESULTS: EPA and DHA were lower and AA/EPA was higher in plasma/serum phospholipids in HD patients than in subjects without kidney disease. Similarly, higher AA and AA/EPA and lower EPA and DHA levels were found in platelet phospholipids of HD patients. Adjustment for gender, age, and habitual intake of fish and fish oil supplements did not change these results. CONCLUSION: HD patients have lower n-3 PUFA levels in plasma and cells compared with subjects without kidney disease.

Empowering patients with COPD using Tele-homecare technology.

This paper discusses how a tele-rehabilitation program using home tele-monitoring may empower patients with chronic obstructive pulmonary disease (COPD). The paper is based on preliminary findings from an ongoing research and innovation project, called "Tele-homecare, chronic patients and the integrated healthcare system" (the TELEKAT project) that employs triple interventions related to patients, professionals, and the organization of care. The ways COPD patients make use of home tele-monitoring in the TELEKAT project points to the relevance of a concept of empowerment rooted in ideologies of social action, and focusing on the improvement of both personal and social conditions at the intersection of individual, organizational and community development.

Intravenous infusion of n-3 polyunsaturated fatty acids and inducibility of ventricular tachycardia in patients with implantable cardioverter defibrillator.

AIMS: Marine n-3 polyunsaturated fatty acids (PUFA) may have antiarrhythmic effects. The aim of this study was to investigate the effect of intravenously administered n-3 PUFA on the inducibility of ventricular tachycardia (VT) in patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: In a randomized, placebo-controlled cross-over study, patients with an ICD underwent two electrophysiological studies using the stimulation possibilities in the ICD preceded by intravenous infusion of either a lipid emulsion delivering 3.9 g n-3 PUFA or placebo (0.9% saline). The level of stimulation required to induce sustained monomorphic VT was ranked in order from least to most aggressive, and non-inducibility was ranked highest. The content of n-3 PUFA in plasma free fatty acids (FFA), plasma phospholipids, and platelet phospholipids was measured by gas chromatography. Eight patients were included, and six of these completed the study. The content of n-3 PUFA as FFA and in platelet phospholipids increased more after n-3 PUFA infusion than after placebo (P<0.001). Of the five patients who were inducible after placebo, two were no longer inducible after n-3 PUFA infusion and another two required stronger stimulation to induce VT. The difference in the stimulation required after placebo and after n-3 PUFA was borderline significant (P=0.063, Wilcoxon signed-rank test). CONCLUSION: Intravenous n-3 PUFA tended to decrease VT inducibility, but a larger study is warranted.

Quantitative analysis of T-wave morphology increases confidence in drug-induced cardiac repolarization abnormalities: evidence from the investigational IKr inhibitor Lu 35-138.

This study investigates repolarization changes induced by a new candidate drug to determine whether a composite electrocardiographic (ECG) measure of T-wave morphology could be used as a reliable marker to support the evidence of abnormal repolarization, which is indicated by QT interval prolongation. Seventy-nine healthy subjects were included in this parallel study. After a baseline day during which no drug was given, 40 subjects received an I(Kr)-blocking antipsychotic compound (Lu 35-138) on 7 consecutive days while 39 subjects received placebo. Resting ECGs were recorded and used to determine a combined measure of repolarization morphology (morphology combination score [MCS]), based on asymmetry, flatness, and notching. Replicate measurements were used to determine reliable change and study power for both measures. Lu 35-138 increased the QTc interval with corresponding changes in T-wave morphology as determined by MCS. For subjects taking Lu 35-138, T-wave morphology was a more reliable indicator of I(Kr) inhibition than QTcF (chi(2) = 20.3, P = .001). At 80% study power for identifying a 5-millisecond placebo-adjusted change from baseline for QTcF, the corresponding study power for MCS was 93%. As a covariate to the assessment of QT interval liability, MCS offered important additive information to the effect of Lu 35-138 on cardiac repolarization.

Identifying drug-induced repolarization abnormalities from distinct ECG patterns in congenital long QT syndrome: a study of sotalol effects on T-wave morphology.

BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal repolarization is therefore warranted. Most drugs associated with risk are inhibitors of the rapidly activating delayed rectifier potassium current (I(Kr)). This current is also inhibited in the congenital type 2 form of the long QT syndrome (LQT2). It is therefore possible that electrocardiographic LQT2 patterns might be used to identify abnormal repolarization patterns induced by drugs. OBJECTIVE: To develop distinct T-wave morphology parameters typical of LQT2 and investigate their use as a composite measure for identification of d,l-sotalol (sotalol)-induced changes in T-wave morphology. METHODS: Three independent study groups were included: a group of 917 healthy subjects and a group of 30 LQT2 carriers were used for the development of T-wave morphology measures. The computerized measure for T-wave morphology (morphology combination score, MCS) was based on asymmetry, flatness and notching, which are typical ECG patterns in LQT2. Blinded to labels, the new morphology measures were tested in a third group of 39 healthy subjects receiving sotalol. Over 3 days the sotalol group received 0, 160 and 320 mg doses, respectively, and a 12-lead Holter ECG was recorded for 22.5 hours each day. Drug-induced prolongation of the heart rate corrected QT interval (QTcF) was compared with changes in the computerized measure for T-wave morphology. Effect sizes for QTcF and MCS were calculated at the time of maximum plasma concentrations and for maximum change from baseline. Accuracy for separating baseline from sotalol recordings was evaluated by area under the receiver operating characteristic curves (AUCs) using all recordings from the time immediately post-dose to maximum change. RESULTS: MCS separated baseline recordings from sotalol treatment with higher accuracy than QTcF for the 160 mg dose: (AUC) 84% versus 72% and for the 320 mg dose: (AUC) 94% versus 87%, p < 0.001. At maximum serum-plasma concentrations and at maximum individual change from baseline, the effect sizes for QTcF were less than half the effect sizes for MCS, p < 0.001. Effect sizes at peak changes of the mean were up to 3-fold higher for MCS compared with QTcF, p < 0.001. In subjects receiving sotalol, T-wave morphology reached similarity to LQT2, whereas QTcF did not. CONCLUSION: Distinct ECG patterns in LQT2 carriers effectively quantified repolarization changes induced by sotalol. Further studies are needed to validate whether this measure has general validity for the identification of drug-induced disturbed repolarization.

n-3 Fatty acids and ventricular arrhythmias in patients with ischaemic heart disease and implantable cardioverter defibrillators.

AIM: To investigate the relationship between serum content of n-3 polyunsaturated fatty acids (PUFA) and the incidence of ventricular arrhythmias in patients with an implantable cardioverter defibrillator (ICD). METHODS: We included 98 patients with ischaemic heart disease and an ICD. The numbers of ventricular fibrillation (VF) and ventricular tachycardia (VT) events were assessed during a 12-month period and related to the concentration of n-3 PUFA in serum phospholipids. RESULTS: Patients with more than one arrhythmic event had significantly lower n-3 PUFA levels compared with patients without arrhythmias (mean 7.1% vs 9.2%, P<0.01). Dividing the patients into quintiles according to their n-3 PUFA level those with the lowest content of n-3 PUFA had more ventricular arrhythmias than patients with the highest concentration of n-3 PUFA (mean 1.3 event vs 0.2 event, P<0.05). CONCLUSION: Patients with a low content of n-3 PUFA in serum had a higher incidence of ventricular arrhythmias compared with patients with high serum levels of n-3 PUFA. The data suggest that the protection offered by n-3 PUFA against sudden cardiac death observed in previous studies is mediated by a direct antiarrhythmic effect of n-3 PUFA.