Metformin is comparable to insulin for pharmacotherapy in gestational diabetes mellitus: A network meta-analysis evaluating 6046 women.

CONTEXT: The comparative efficacy of gestational diabetes (GDM) treatments lack conclusive evidence for choice of first-line treatment. OBJECTIVES: The aim of this study was to compare the efficacy of metformin and glibenclamide to insulin using a core outcome set (COS) to unify outcomes across trials investigating the treatment of gestational diabetes mellitus. STUDY DESIGN: A network meta-analysis (NMA) was conducted. DATA-SOURCE: PubMed, Embase, and Cochrane Controlled Register of Trials were searched from inception to January 2020. STUDY SELECTION: RCTs that enrolled pregnant women who were diagnosed with GDM and that compared the efficacy of different pharmacological interventions for the treatment of GDM were included. META-ANALYSIS: A generalized pairwise modelling framework was employed. RESULTS: A total of 38 RCTs with 6046 participants were included in the network meta-analysis. Compared to insulin, the estimated effect of metformin indicated improvements for weight gain (WMD -2·39 kg; 95% CI -3·31 to -1·46), maternal hypoglycemia (OR 0.34; 95% CI 0.12 to 0·97) and LGA (OR 0.61; 95% CI 0.38 to 0·98). There were also improvements in estimated effects for neonatal hypoglycemia (OR 0.48; 95% CI 0.19 to 1·25), pregnancy induced hypertension (OR 0.63; 95% CI 0.37 to 1·06), and preeclampsia (OR 0.74; 95% CI 0.538 to 1·04), though with limited evidence against our model hypothesis of equivalence with insulin for these outcomes. CONCLUSION: Metformin is, at least, comparable to insulin for the treatment of GDM. Glibenclamide appears less favorable, in comparison to insulin, than metformin.

Ultrasound controlled paclitaxel releasing system-A novel method for improving the availability of coronary artery drug coated balloon.

OBJECTIVES: The aim of this study is to improve local-drug delivery efficiency and tissue absorption using the ultrasound (US)-responsible drug coating based on a newly developed US-controlled paclitaxel release balloon. BACKGROUND: Low availability of the drug coating remains a major concern of the current drug coated balloon (DCB). The goal of this study is to develop a method to use an US-responsible paclitaxel-loaded microcapsules (PM) as the main content of balloon drug coating to enhance bioavailability of DCB. METHODS: An US-controlled paclitaxel release balloon is designed and fabricated based on the US-responsible paclitaxel-loaded poly (lactic-co-glycolic acid) (PLGA) microcapsules. Rapid exchange percutaneous transluminal coronary angioplasty (PTCA) balloon catheters were coated with the PM. The deployment processes of the paclitaxel-loaded microcapsules coated balloons (PMCB) under US, PMCB without US and a homogenous matrix of paclitaxel and iopromide coated balloon (PICB) were then placed in healthy and stent implanted porcine coronary arteries. RESULTS: In vitro release assay demonstrated an ability of US (1 MHz, 1.22 W/cm2 , 1 minute) to affect the release kinetics of paclitaxel from PM by inducing a 76 ± 5.4% increase in the rate of release. The paclitaxel content in target vessels are 203 ± 37 µg/g for PMCB under US, 85 ± 23 µg/g for PMCB without US, and 107 ± 31 µg/g for PICB 1-hr post-surgery. The availability of the drug for the PMCB reaches 27% under US. CONCLUSIONS: The US-controlled paclitaxel release balloon significantly improved the drug content of the target vessels in the porcine model.

Safety and efficacy of leadless pacemaker retrieval.

BACKGROUND AND OBJECTIVES: The success rate of leadless cardiac pacemaker (LP) retrieval remains a major concern for this disruptive technology. The present paper performed a systematic review of the safety and feasibility of the retrieval of LPs. METHODS: Primary publications that performed LP retrieval were collected and included five animal experiments and two worldwide retrieval experiences in human. The procedural details, such as indication, days post implantation, extraction success rate, and complications, were described. The present paper analyzed factors affecting the retrieval and management of the nonfunctional devices. RESULTS: Retrieval animal models was possible at least up to 2.5 years post implantation, and data from humans suggest that removal of a device that was implanted longer (eg, 4 years and 9 months for Nanostim; 4 years for Micra) could be performed within a reasonable safety profile. The fixed mechanism, implant site, and encapsulation of the LP systems may affect the retrieval process. CONCLUSIONS: A high success rate in the relatively chronic retrieval of LPs was demonstrated, which promotes the extensive use of these devices in the treatment arrhythmia in the future.

Radiofrequency Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation: Meta-analysis of Safety and Efficacy.

BACKGROUND: Radiofrequency ablation (RFA) and antiarrhythmic drugs (AADs) are the main treatments used for atrial fibrillation (AF). In recent years, a number of articles comparing the 2 treatments have begun to emerge. Though, the influence of follow-up time in the meta-analysis was not considered in these articles. However, more recently, large-scale clinical trial articles have included follow-up with the patients up to 5 years after treatment. Therefore, the aim of this study was to assess the impact of variable follow-up times on the recurrence of AF by observing both the short-term and long-term efficacy and safety of catheter ablation and AADs for the treatment of AF. METHODS AND RESULTS: The primary investigators of eligible randomized controlled trials were invited to contribute standardized outcome data. Random effect summary estimates were calculated as standardized mean differences and odds ratios with 95% confidence intervals for continuous and binary outcomes. In this study, 9 randomized controlled trials (n = 1542 patients) were included. The rate of recurrence of AF with no limit on follow-up time, >12 months, >18 months, >24 months, >30 months, and approximately 36 months was compared. Furthermore, the gap between the RFA and AAD groups in the recurrence rate of AF was found to decrease inversely to follow-up time. When the follow-up time reached 24 months, the difference between RFA and AAD was relatively stable with an odds ratio of 0.45 (95% confidence interval: 0.32-0.62). Overall, RFA decreased adverse events in the remaining trials; however, AAD performed better in terms of safety and had fewer adverse events with RFA usually causing more serious complications. CONCLUSION: RFA is more advantageous in terms of recurrence rate of AF than drug therapy. In addition, the analysis suggests that this effect persists during long-term follow-up; however, these benefits appear to decrease with longer follow-up time. Finally, AAD performed better in terms of safety and had fewer adverse events.

Hypertrophic cardiomyopathy-linked variants of cardiac myosin-binding protein C3 display altered molecular properties and actin interaction.

The most common inherited cardiac disorder, hypertrophic cardiomyopathy (HCM), is characterized by thickening of heart muscle, for which genetic mutations in cardiac myosin-binding protein C3 (c-MYBPC3) gene, is the leading cause. Notably, patients with HCM display a heterogeneous clinical presentation, onset and prognosis. Thus, delineating the molecular mechanisms that explain how disparate c-MYBPC3 variants lead to HCM is essential for correlating the impact of specific genotypes on clinical severity. Herein, five c-MYBPC3 missense variants clinically associated with HCM were investigated; namely V1 (R177H), V2 (A216T), V3 (E258K), V4 (E441K) and double mutation V5 (V3 + V4), all located within the C1 and C2 domains of MyBP-C, a region known to interact with sarcomeric protein, actin. Injection of the variant complementary RNAs in zebrafish embryos was observed to recapitulate phenotypic aspects of HCM in patients. Interestingly, V3- and V5-cRNA injection produced the most severe zebrafish cardiac phenotype, exhibiting increased diastolic/systolic myocardial thickness and significantly reduced heart rate compared with control zebrafish. Molecular analysis of recombinant C0-C2 protein fragments revealed that c-MYBPC3 variants alter the C0-C2 domain secondary structure, thermodynamic stability and importantly, result in a reduced binding affinity to cardiac actin. V5 (double mutant), displayed the greatest protein instability with concomitant loss of actin-binding function. Our study provides specific mechanistic insight into how c-MYBPC3 pathogenic variants alter both functional and structural characteristics of C0-C2 domains leading to impaired actin interaction and reduced contractility, which may provide a basis for elucidating the disease mechanism in HCM patients with c-MYBPC3 mutations.

Measuring medical students' professional competencies in a problem-based curriculum: a reliability study.

BACKGROUND: Identification and assessment of professional competencies for medical students is challenging. We have recently developed an instrument for assessing the essential professional competencies for medical students in Problem-Based Learning (PBL) programs by PBL tutors. This study aims to evaluate the reliability and validity of professional competency scores of medical students using this instrument in PBL tutorials. METHODS: Each group of seven to eight students in PBL tutorials (Year 2, n = 46) were assessed independently by two faculty members. Each tutor assessed students in his/her group every five weeks on four occasions. The instrument consists of ten items, which measure three main competency domains: interpersonal, cognitive and professional behavior. Each item is scored using a five-point Likert scale (1 = poor, 5 = exceptional). Reliability of professional competencies scores was calculated using G-theory with raters nested in occasions. Furthermore, criterion-related validity was measured by testing the correlations with students' scores in written examination. RESULTS: The overall generalizability coefficient (G) of the professional competency scores was 0.80. Students' professional competencies scores (universe scores) accounted for 27% of the total variance across all score comparisons. The variance due to occasions accounted for 10%, while the student-occasion interaction was zero. The variance due to raters to occasions represented 8% of the total variance, and the remaining 55% of the variance was due to unexplained sources of error. The highest reliability measured was the interpersonal domain (G = 0.84) and the lowest reliability was the professional behavior domain (G = 0.76). Results from the decision (D) study suggested that an adequate dependability (G = 0.71) can be achieved by using one rater for five occasions. Furthermore, there was a positive correlation between the written examination scores and cognitive competencies scores (r = 0.46, P < 0.01), but not with the other two competency domains (interpersonal and professionalism). CONCLUSIONS: This study demonstrates that professional competency assessment scores of medical students in PBL tutorials have an acceptable reliability. Further studies for validating the instrument are required before using it for summative evaluation of students by PBL tutors.

Meta-analysis of the incidence of lead dislodgement with conventional and leadless pacemaker systems.

INTRODUCTION: Leadless cardiac pacemaker (LCP) implantation using a transcatheter was recently developed to avoid pocket- and lead-related complications. Although a LCP has an active fixation mechanism using tines or a helix, LCP and lead dislodgement issues remain a major safety concern for patients. This article reviews the literature to determine the incidence of lead and LCP dislodgement. METHODS AND RESULTS: A total of 18 studies which included 17,321 patients undergoing conventional single- or dual-chamber pacemaker implantation and three studies which included 2,116 patients undergoing LCP device implantation were reviewed. The incidence of lead dislodgement ranged from 1% to 2.69% in individual studies with a mean of 1.63%, weighted mean of 1.71%, and median of 1.60 %. There was a relatively higher lead dislodgement rate between atrial and ventricular electrodes (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.9-6.70; P  =  0.6; I2   =  0%), and between magnetic resonance imaging conditional and conventional leads (OR, 2.79; 95% CI, 1.30-5.99; P  =  0.16; I2   =  46%). The use of active fixation leads (OR, 1.06; 95% CI, 0.66-1.70; P  =  0.29; I2   =  20%) showed no significant difference in dislodgement risk compared to passive fixation leads. The incidence of LCP device dislodgement was 0%, 0.13%, and 1% in three leadless pacemaker studies. CONCLUSIONS: The incidence rates of conventional pacemaker lead dislodgement vary in individual studies with an overall high incidence. Use of the currently available LCP systems appears to result in a lower rate of device dislodgement. This may reflect the effectiveness of this novel technology and the fixation design of LCP devices.

Solely abluminal drug release from coronary stents could possibly improve reendothelialization.

OBJECTIVES: To compare a new stent with an asymmetric coating, eluting the drug to the abluminal surface, to a stent with a conventional coating eluting the drug both to the luminal and the abluminal side. BACKGROUND: Stents with asymmetric coating, eluting the drug to the vessel wall (BPSES-A), could potentially give faster reendothelialization after percutaneous coronary interventions (PCI) and decrease in in-stent thrombosis and late restenosis. METHODS: BPSES-A, conventional coated stents (BPSES-C), biodegradable polymer stents without drug (BPS, for control), and bare metal stents (BMS, for control) were implanted into the coronary arteries of 38 pigs (75 stents). Pigs were sacrificed after 4, 12, and 24 weeks. Quantitative coronary angiography was used to compare in-stent late lumen loss (LLL) and electron microscopy was used to reveal levels of reendothelialization. RESULTS: The stents were all successfully implanted. LLL of BPSES-A, BPSES-C, BMS, and BPS were 0.56 ± 0.51, 0.60 ± 0.58, 0.89 ± 0.43, and 1.68 ± 0.30 mm, respectively, after 4 weeks. LLL of BPSES-A and BPSES-C were 0.63 ± 0.53 and 0.69 ± 0.24 mm, respectively, after 12 weeks. LLL of BPSES-A, BPSES-C, and BMS were 0.42 ± 0.15 m, 0.56 ± 0.28 mm, and 0.99 ± 0.13 mm, respectively, after 24 weeks. The scaling of reendothelialization was as follows: after 4 weeks BMS > = BPS > BPSES-A > BPSES-C, after 12 weeks BPSES-A > BPSES-C, and after 24 weeks BMS > BPSES-A > BPSES-C. Reendothelialization was better in BPSES-A than BPSES-C (P < 0.05). There was no correlation between LLL and reendothelialization (P = 0.42). CONCLUSION: Asymmetric coating of coronary stents might be helpful to improve reendothelialization. © 2016 Wiley Periodicals, Inc.

Personalized Telehealth in the Future: A Global Research Agenda.

As telehealth plays an even greater role in global health care delivery, it will be increasingly important to develop a strong evidence base of successful, innovative telehealth solutions that can lead to scalable and sustainable telehealth programs. This paper has two aims: (1) to describe the challenges of promoting telehealth implementation to advance adoption and (2) to present a global research agenda for personalized telehealth within chronic disease management. Using evidence from the United States and the European Union, this paper provides a global overview of the current state of telehealth services and benefits, presents fundamental principles that must be addressed to advance the status quo, and provides a framework for current and future research initiatives within telehealth for personalized care, treatment, and prevention. A broad, multinational research agenda can provide a uniform framework for identifying and rapidly replicating best practices, while concurrently fostering global collaboration in the development and rigorous testing of new and emerging telehealth technologies. In this paper, the members of the Transatlantic Telehealth Research Network offer a 12-point research agenda for future telehealth applications within chronic disease management.

HEALTH PROFESSIONALS' USER EXPERIENCE OF THE INTELLIGENT BED IN PATIENTS' HOMES.

BACKGROUND: The intelligent bed is a medical bed with several home healthcare functions. It includes, among others, an "out of bed" detector, a moisture detector, and a catheter bag detector. The design purpose of the intelligent bed is to assist patients in their daily living, facilitate the work of clinical staff, and improves the quality of care. The aim of this sub-study of the iCare project was to explore how health professionals (HPs) experience and use the intelligent bed in patients' homes. METHODS: The overall research design is inspired by case study methodology. A triangulation of data collection techniques has been used: log book, documentation study, participant observations (n = 45 hr), and qualitative interviews (n = 23). The data have been analyzed by means of Nvivo 9.0. FINDINGS: We identified several themes: HP transformation from passive technology recipient to innovator; individualized care; work flow redesign; and sensor technology intruding on patient privacy. CONCLUSIONS: It is suggested that functions of the intelligent bed can result in more individualized care, workflow redesign, and time savings for the health professionals in caring for elderly patients. However, the technology intruded on patients' privacy.

Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management.

Several drugs used in the treatment of mental diseases are associated with an increased risk of sudden cardiac death (SCD). A general cause-relationship between the intake of these drugs and SCD is unattainable, but numerous case reports of drug-induced malignant arrhythmia and epidemiological studies, associating the use of specific drugs with SCD, strongly support the presence of an increased risk. Whereas the absolute risk of drug-induced life-threatening arrhythmia may be relatively low, even small increments in risk of SCD may have a major health impact considering that millions of patients are treated with psychotropics. In subgroups of pre-disposed patients, e.g. patients with cardiac diseases or other co-morbidities, the elderly or patients treated with other negatively interacting drugs, the absolute risk of drug-induced arrhythmia may be considerable. On the other hand, several of the major mental disorders are associated with a large risk of suicide if untreated. The observed risk of malignant arrhythmia associated with treatment with psychotropic drugs calls for clinical guidelines integrating the risk of the individual drug and other potentially interacting risk factors. In this review, data from various authorities on the risk of arrhythmia associated with psychotropic medications were weighted and categorized into three risk categories. Additionally, we suggest a clinically applicable algorithm to reduce the risk of malignant arrhythmia in patients to be treated with psychotropic medications. The algorithm integrates the risk categories of the individual drugs and pre-disposing risk factors and suggests a prudent follow-up for patients with an increased risk. We believe this clinically manageable guideline might improve safety in the many and rapidly increasing number of patients on psychotropic drugs.

Mutations in Danish patients with long QT syndrome and the identification of a large founder family with p.F29L in KCNH2.

BACKGROUND: Long QT syndrome (LQTS) is a cardiac ion channelopathy which presents clinically with palpitations, syncope or sudden death. More than 700 LQTS-causing mutations have been identified in 13 genes, all of which encode proteins involved in the execution of the cardiac action potential. The most frequently affected genes, covering > 90% of cases, are KCNQ1, KCNH2 and SCN5A. METHODS: We describe 64 different mutations in 70 unrelated Danish families using a routine five-gene screen, comprising KCNQ1, KCNH2 and SCN5A as well as KCNE1 and KCNE2. RESULTS: Twenty-two mutations were found in KCNQ1, 28 in KCNH2, 9 in SCN5A, 3 in KCNE1 and 2 in KCNE2. Twenty-six of these have only been described in the Danish population and 18 are novel. One double heterozygote (1.4% of families) was found. A founder mutation, p.F29L in KCNH2, was identified in 5 "unrelated" families. Disease association, in 31.2% of cases, was based on the type of mutation identified (nonsense, insertion/deletion, frameshift or splice-site). Functional data was available for 22.7% of the missense mutations. None of the mutations were found in 364 Danish alleles and only three, all functionally characterised, were recorded in the Exome Variation Server, albeit at a frequency of < 1:1000. CONCLUSION: The genetic etiology of LQTS in Denmark is similar to that found in other populations. A large founder family with p.F29L in KCNH2 was identified. In 48.4% of the mutations disease causation was based on mutation type or functional analysis.

Long pacing pulses reduce phrenic nerve stimulation in left ventricular pacing.

INTRODUCTION: Phrenic nerve stimulation is a major obstacle in cardiac resynchronization therapy (CRT). Activation characteristics of the heart and phrenic nerve are different with higher chronaxie for the heart. Therefore, longer pulse durations could be beneficial in preventing phrenic nerve stimulation during CRT due to a decreased threshold for the heart compared with the phrenic nerve. We investigated if long pulse durations decreased left ventricular (LV) thresholds relatively to phrenic nerve thresholds in humans. METHODS AND RESULTS: Eleven patients, with indication for CRT and phrenic nerve stimulation at the intended pacing site, underwent determination of thresholds for the heart and phrenic nerve at different pulse durations (0.3-2.9 milliseconds). The resulting strength duration curves were analyzed by determining chronaxie and rheobase. Comparisons for those parameters were made between the heart and phrenic nerve, and between the models of Weiss and Lapicque as well. In 9 of 11 cases, the thresholds decreased faster for the LV than for the phrenic nerve with increasing pulse duration. In 3 cases, the thresholds changed from unfavorable for LV stimulation to more than a factor 2 in favor of the LV. The greatest change occurred for pulse durations up to 1.5 milliseconds. The chronaxie of the heart was significantly higher than the chronaxie of the phrenic nerve (0.47 milliseconds vs. 0.22 milliseconds [P = 0.029, Lapicque] and 0.79 milliseconds vs. 0.27 milliseconds [P = 0.033, Weiss]). CONCLUSION: Long pulse durations lead to a decreased threshold of the heart relatively to the phrenic nerve and may prevent stimulation of the phrenic nerve in a clinical setting.

Cascade screening in families with inherited cardiac diseases driven by cardiologists: feasibility and nationwide outcome in long QT syndrome.

OBJECTIVES: We assessed the outcome of cascade screening of families with congenital long QT syndrome (LQTS) in Danish heart centers. METHODS: Affected family members were identified through systematic family screening. RESULTS: In total, 228 affected relatives were identified from 90 families. A disease-causing mutation useful for presymptomatic genetic testing was found in 82% of probands. Two-thirds of affected relatives fulfilled electrocardiographic criteria for the diagnosis, whereas diagnosis was based on genetic findings in only one-third. The majority of affected relatives were asymptomatic. Symptomatic relatives and probands most often presented with syncope, followed by aborted cardiac arrest and sudden cardiac death. A serious cardiac event (SCE, such as syncope, aborted cardiac arrest or cardiac arrest) was reported by 32% of affected relatives and 87% of probands (p < 0.0001). Fifty-two percent of affected relatives were on ß-blockers and 11% had an implantable cardioverter defibrillator (ICD), as compared to 88 and 49% of probands (p < 0.0001). Appropriate ICD therapy was given to 13% of affected relatives and to 27% of probands (p = 0.1). CONCLUSIONS: Clinically driven cascade screening of Danish LQTS families identified 2-3 affected relatives per proband. Affected relatives had milder disease courses, but SCEs in a subset strongly support screening. Danish cardiologists have adopted cascade screening of LQTS families according to specific Danish guidelines.

Clinical refinement of the automatic lung parameter estimator (ALPE).

The automatic lung parameter estimator (ALPE) method was developed in 2002 for bedside estimation of pulmonary gas exchange using step changes in inspired oxygen fraction (FIO2). Since then a number of studies have been conducted indicating the potential for clinical application and necessitating systems evolution to match clinical application. This paper describes and evaluates the evolution of the ALPE method from a research implementation (ALPE1) to two commercial implementations (ALPE2 and ALPE3). A need for dedicated implementations of the ALPE method was identified: one for spontaneously breathing (non-mechanically ventilated) patients (ALPE2) and one for mechanically ventilated patients (ALPE3). For these two implementations, design issues relating to usability and automation are described including the mixing of gasses to achieve FIO2 levels, and the automatic selection of FIO2. For ALPE2, these improvements are evaluated against patients studied using the system. The major result is the evolution of the ALPE method into two dedicated implementations, namely ALPE2 and ALPE3. For ALPE2, the usability and automation of FIO2 selection has been evaluated in spontaneously breathing patients showing that variability of gas delivery is 0.3 % (standard deviation) in 1,332 breaths from 20 patients. Also for ALPE2, the automated FIO2 selection method was successfully applied in 287 patient cases, taking 7.2 ± 2.4 min and was shown to be safe with only one patient having SpO2 < 86 % when the clinician disabled the alarms. The ALPE method has evolved into two practical, usable systems targeted at clinical application, namely ALPE2 for spontaneously breathing patients and ALPE3 for mechanically ventilated patients. These systems may promote the exploration of the use of more detailed descriptions of pulmonary gas exchange in clinical practice.

Patients' use of self-monitored readings for managing everyday life with COPD: a qualitative study.

OBJECTIVE: Effects of self-monitoring depend on how patients engage with readings and how this engagement is used for managing chronic disease. This article reports on a study of how chronic obstructive pulmonary disease (COPD) patients made use of readings during 16 weeks of self-monitoring. PATIENTS AND METHODS: Semistructured interviews were conducted with 22 COPD patients three times each: at the beginning, halfway through, and after the monitoring device was collected. Spouses of nine interviewees were present during one or more interviews. The analysis of how patients used self-monitored readings was based on critical psychology. RESULTS: Patients used readings to monitor bodily condition, to judge whether and when to contact health professionals, to communicate with health professionals about health management, to revise planned activities, to engage close relatives, and to motivate exercise and other health behavior. Self-monitoring can produce a sense of security as readings provide grounds for explaining symptoms and widen the scope of possibilities for taking action. Patients experienced readings as encouraging, reassuring, depressing, worrisome, and at times disturbing. A few patients involved themselves with readings in ways that are emotionally challenging and contrary to medical advice. Reasons for not making use of self-monitoring include good health or not regarding monitoring as relevant at the time. CONCLUSIONS: Results can qualify the support health professionals offer in relation to patients' self-monitoring and self-management.

Efficacy and safety of vernakalant in patients with atrial flutter: a randomized, double-blind, placebo-controlled trial.

AIMS: Vernakalant is a novel, relatively atrial-selective antiarrhythmic agent for conversion of atrial fibrillation (AF) to sinus rhythm. This study examined the safety and efficacy of vernakalant in converting atrial flutter (AFL) to sinus rhythm. METHODS AND RESULTS: This was a phase 2/3, randomized, double-blind, placebo-controlled trial. Adults with AFL received either a 10 min infusion of 3.0 mg/kg vernakalant (n = 39) or placebo (n = 15). If AFL or AF persisted at the end of a 15 min observation period, a second 10 min infusion of 2.0 mg/kg vernakalant or placebo was administered. The primary efficacy outcome was the proportion of patients who had treatment-induced conversion of AFL to sinus rhythm for a minimum duration of 1 min within 90 min after the start of the first infusion. No patient in the placebo group met the primary outcome. Only one patient receiving vernakalant (1 of 39, 3%) converted to sinus rhythm. A reduced mean absolute ventricular response rate occurred within 50 min in patients receiving vernakalant (mean change from baseline -8.2 b.p.m.) vs. patients receiving placebo (-0.2 b.p.m.) (P = 0.037). A post-hoc analysis revealed that vernakalant increased AFL cycle length by an average of 55 ms, whereas the AFL cycle length was unchanged in the placebo group (P < 0.001). There was no occurrence of 1 : 1 atrio-ventricular conduction. Dysgeusia and sneezing were the most common treatment-related adverse events, consistent with previous reports. CONCLUSION: Vernakalant did not restore sinus rhythm in patients with AFL. Vernakalant modestly slowed AFL and ventricular response rates, and was well tolerated.

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.

Clinical impact of home telemonitoring on patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide. A complication of COPD is exacerbations that result in increased utilization of healthcare services, readmissions to the hospital, and a decline in health-related quality of life. Home telehealth has been shown both to improve health-related quality of life and to reduce admission rates. Using clinical data from a home telemonitoring group, this study sought to investigate the clinical impact of telemonitoring. SUBJECTS AND METHODS: Fifty-seven subjects with COPD were included in a 4-month telemonitoring project. Differences between the clinical parameters during the first and last months of participation in the project were tested for significance, and the levels for the first month versus the difference were tested for correlation. RESULTS: Significant declines were observed in prescriptions for antibiotics and steroids (p=0.03), clinical consultations (p=0.05), mean systolic blood pressure (p<0.001), standard deviation of systolic blood pressure (p=0.03), and mean diastolic blood pressure (p=0.02). No significant differences were observed for mean of oxygen saturation (p=0.77), standard deviation of oxygen saturation (p=0.36), mean of forced expiratory volume in 1 s (p=0.17), mean of forced vital capacity (p=0.29), mean of pulse rate (p=0.78), standard deviation of pulse rate (p=0.57), and standard deviation of diastolic blood pressure (p=0.27). CONCLUSIONS: The results suggest that telemonitoring improves the condition of the patient by lowering the blood pressure, the number of prescribed antibiotics and steroids, and the number of clinical consultations.

Coronary Artery Disease Detected by Low Frequency Heart Sounds.

OBJECTIVES: Previous studies have observed an increase in low frequency diastolic heart sounds in patients with coronary artery disease (CAD). The aim was to develop and validate a diagnostic, computerized acoustic CAD-score based on heart sounds for the non-invasive detection of CAD. METHODS: Prospective study enrolling 463 patients referred for elective coronary angiography. Pre-procedure non-invasive recordings of heart sounds were obtained using a novel acoustic sensor. A CAD-score was defined as the power ratio between the 10-90 Hz frequency spectrum and the 90-300 Hz frequency spectrum of the mid-diastolic heart sound. Quantitative coronary angiography analysis was performed by a blinded core laboratory and patients grouped according to the results: obstructive CAD defined by the presence of at least one ≥ 50% stenosis, non-obstructive CAD as patients with a maximal stenosis in the 25-50% interval and non-CAD as no coronary lesions exceeding 25%. We excluded patients with potential confounders or incomplete data (n = 245). To avoid over-fitting the final cohort of 218 patients was randomly divided into to a training group for development (n = 127) and a validation group (n = 91). RESULTS: In both the training and the validation group the CAD-score was significantly increased in CAD patients compared to non-CAD patients (p < 0.0001). In the validation group the area under the receiver-operating curve was 77% (95% CI 63-91%). Sensitivity was 71% (95% CI 59-82%) and specificity 64% (95% CI 45-83%). CONCLUSION: The acoustic CAD-score is a new, inexpensive, non-invasive method to detect CAD, which may supplement clinical risk stratification and reduce the need for subsequent non-invasive and invasive testing.