Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials.

Importance: Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important. Objective: To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy. Data Sources: A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials. Study Selection: Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up. Data Extraction and Synthesis: Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials. Main Outcomes and Measures: The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups. Results: A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups. Conclusions and Relevance: Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.

Durability of blood pressure reduction after ultrasound renal denervation: three-year follow-up of the treatment arm of the randomised RADIANCE-HTN SOLO trial.

BACKGROUND: While the blood pressure (BP)-lowering effect of renal denervation (RDN) has been established, long-term durability is a key prerequisite for a broader clinical implementation. AIMS: Our aims were to assess the long-term durability of the office BP (OBP)-lowering efficacy, antihypertensive medication (AHM) use, and safety of ultrasound RDN (uRDN). METHODS: Four weeks after withdrawal of AHM, patients with untreated daytime ambulatory BP ≥135/85 mmHg and <170/105 mmHg were randomised to uRDN (n=74) or sham (n=72) in the RADIANCE-HTN SOLO trial. Initiation of AHM was encouraged for home BP >135/85 mmHg following primary endpoint ascertainment at 2 months. Patients and physicians were unblinded at 6 months.  Results: Fifty-one of 74 patients (age: 53.9±11 years; 67% men) originally randomised to uRDN completed the 36-month follow-up. Initial screening OBP upon study entry was 145/92±14/10 mmHg on a mean of 1.2 AHM (range: 0-2.0). Baseline OBP after AHM washout was 154/99±13/8 mmHg. At 36 months, patients were on an average of 1.3 AHM (range: 0-3.0) with 8 patients on no AHM. OBP decreased by 18/11±15/9 mmHg from baseline to 36 months (p<0.001 for both). Overall, OBP control (<140/90 mmHg) improved from 29.4% at screening to 45.1% at 36 months (p=0.059). For patients uncontrolled at screening (n=36), systolic OBP decreased by 10.8 mmHg (p<0.001) at 36 months on similar AHM (p=0.158). CONCLUSIONS: The safety and effectiveness of uRDN was durable to 36 months, with reduced OBP and improved OBP control despite a similar starting medication burden. No new uRDN-related long-term safety concerns were identified.

What contributes to good outcomes? The perspective of young people on short-term psychoanalytic psychotherapy for depressed adolescents.

Depression is the fourth leading cause of adolescent illness and disability worldwide. A growing evidence base demonstrates that Short Term Psychoanalytic Psychotherapy [STPP] is an efficacious treatment for moderate to severe adolescent depression. However, with research in its infancy, key factors contributing to efficacy are unknown. Service users' lived experiences provide valuable insight in this area. This study aimed to elucidate what adolescents value in treatment by inductively exploring lived experiences of STPP. Five adolescents with the largest reduction in depressive symptoms scores between baseline and end of treatment, who had taken part in a large-scale randomized controlled trial, were sampled. In-depth interviews carried out soon after the end of therapy were analysed using Interpretative Phenomenological Analysis. Three superordinate themes were identified: "Therapy as a Transformational Process", "Explorative and Exposing: The Therapeutic Space" and "Being Heard and Working Together: The Therapeutic Relationship". Adolescents valued a process of collaborative exploration with the therapist which when it was achieved was felt to facilitate a deep-rooted transformation in self-perception. Additionally, they described how an adjustment was needed to the particular frame of a psychoanalytic therapy. However, not all participants with a good treatment outcome experienced therapy in this way, suggesting a potential gap between the quantitative assessment of outcomes, and the way young people experience and understand the change process. Clinical implications and directions for research are discussed.

The experience of sleep problems for adolescents with depression in short-term psychological therapy.

A growing body of literature demonstrates a strong relationship between sleep disturbances and depression in adolescence. In spite of this, few studies have explored how adolescents with depression experience sleep problems. The present study aimed to qualitatively explore the experience of sleep problems in adolescents with depression, including their understanding of how a psychological therapy impacted on these sleep difficulties. The sample included 12 adolescents with sleep disturbances who had been offered treatment for depression through a large, multi-centre, randomised controlled trial. Semi-structured interviews conducted after treatment and 1-year post treatment were analysed using thematic analysis. Two main themes were identified. Both themes demonstrated how an overarching desire to escape impacted the adolescents' sleep in distinct ways; 'thinking about the 'bad stuff'' was characterised by ruminative thinking, which prevented sleep, whereas 'sleep as an escape' indicated a desire to sleep excessively due to feelings of helplessness. Overall, the findings demonstrate a nuanced relationship between sleep and depression in adolescence, and imply that the underlying meaning of the sleep difficulties for each young person should be considered in the delivery of therapy for adolescent depression.

Adolescents' experiences of brief psychosocial intervention for depression: An interpretative phenomenological analysis of good-outcome cases.

BACKGROUND: Brief psychosocial intervention (BPI) is a treatment for adolescent depression that has recently demonstrated clinical effectiveness in a controlled trial. The aim of this study is to explore experiences of adolescents with major depression receiving BPI treatment in the context of good treatment outcomes. METHOD: A subsample of five interviews from a larger study of adolescents' experiences of BPI was purposively selected, focusing on good-outcome cases. Interviews were analysed using interpretative phenomenological analysis to provide a richer understanding of participants' experiences of overcoming depression in the BPI group. RESULTS: Four central themes were identified: 'Being heard and feeling safe', 'Collaborative working enhancing therapy', 'Gaining a different perspective on one's self and relationships' and 'A positive therapeutic relationship'. CONCLUSION: BPI is a novel approach with promising clinical effectiveness. Utilising adolescents' experiences has revealed potential psychological mechanisms of good treatment response to BPI. Overall implications for clinical practice with depressed adolescents are discussed.

The therapeutic relationship in Cognitive Behaviour Therapy with depressed adolescents: A qualitative study of good-outcome cases.

OBJECTIVES: This paper aimed to explore client experiences of the therapeutic relationship among adolescents with good outcomes after receiving Cognitive Behaviour Therapy (CBT) for moderate to severe depression. DESIGN: This was a qualitative study employing Interpretative Phenomenological Analysis (IPA). METHODS: As part of a randomized clinical trial, 77 adolescents with moderate to severe depression were interviewed using a semi-structured interview, which was audio-recorded. Five of these interviews, with adolescents aged 14-18 years who completed CBT and had good outcomes, were purposively sampled and analysed using IPA. RESULTS: The findings indicated that a positive therapeutic relationship was fostered with therapists who respected the adolescents' autonomy and sense of individuality, while offering experiences of emotional closeness and connection. This was achieved by balancing the dual roles of being 'friendly' and affable, with being a 'professional expert' thereby embodying a collaborative and egalitarian approach. CONCLUSIONS: The therapeutic relationship in CBT can help to motivate adolescents to engage with cognitively and emotionally challenging tasks. By providing an understanding of what helps and hinders the development of a positive therapeutic relationship, the current findings offer important insight into how therapists can foster positive relationships with depressed adolescents. This knowledge will make it more likely that adolescents will engage in the treatment process and in turn experience greater therapeutic gains. PRACTITIONER POINTS: Offers a detailed phenomenological analysis of what fostered a positive therapeutic relationship in good outcome CBT, and what was experienced as harmful from the adolescents' perspective. Provides support that the therapeutic relationship is crucial in CBT; a respectful and understanding relationship provides a platform for the adolescent to carry out CBT activities and tasks.

Long-term Outcomes of Balloon Dilation for Persistent Eustachian Tube Dysfunction.

OBJECTIVE: To gather long-term follow-up data on the efficacy of balloon dilation for treating patients with persistent Eustachian tube dysfunction (ETD). STUDY DESIGN: Extended follow-up study of the treatment arm of a prospective, multicenter, randomized controlled trial. SETTING: Tertiary care academic center and private practice. PATIENTS: Patients diagnosed with medically refractory persistent ETD. INTERVENTIONS: Balloon dilation of the Eustachian tube. MAIN OUTCOME MEASURES: The endpoints were the mean change from baseline in the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) score, revision dilation rate, changes in assessments of middle ear function, and patient satisfaction. RESULTS: A total of 47 participants enrolled in the extended follow-up study. Mean follow-up was 29.4 months (range, 18-42 mo). There was a statistically significant mean (SD) change from baseline in the overall ETDQ-7 score (-2.5 ±â€Š1.2; p < 0.0001). A reduction of one or more in their overall ETDQ-7 score was observed by 93.6% (44/47) participants. The revision dilation rate was 2.1% (1/47). Among participants with abnormal baseline middle ear assessments, 76.0% had normalized tympanic membrane position (p < 0.0001), 62.5% had normalization of tympanogram type (p < 0.001), and 66.7% had positive Valsalva maneuvers (p < 0.0001). Participant satisfaction was 83.0% at long-term follow-up. CONCLUSIONS: Balloon dilation results in durable improvements in symptoms and middle ear assessments for patients with persistent Eustachian tube dysfunction at mean follow-up of longer than 2 years.

An injectable implant to stimulate the sphenopalatine ganglion for treatment of acute ischaemic stroke up to 24 h from onset (ImpACT-24B): an international, randomised, double-blind, sham-controlled, pivotal trial.

BACKGROUND: Sphenopalatine ganglion stimulation increased cerebral collateral blood flow, stabilised the blood-brain barrier, and reduced infarct size, in preclinical models of acute ischaemic stroke, and showed potential benefit in a pilot randomised trial in humans. The pivotal ImpACT-24B trial aimed to determine whether sphenopalatine ganglion stimulation 8-24 h after acute ischaemic stroke improved functional outcome. METHODS: ImpACT-24B is a randomised, double-blind, sham-controlled, pivotal trial done at 73 centres in 18 countries. It included patients (men aged 40-80 years and women aged 40-85 years) with anterior-circulation acute ischaemic stroke, not undergoing reperfusion therapy. Enrolled patients were randomly assigned via web-based randomisation to receive active sphenopalatine ganglion stimulation (intervention group) or sham stimulation (sham-control group) 8-24 h after stroke onset. Patients, clinical care providers, and all outcome assessors were masked to treatment allocation. The primary efficacy endpoint was the difference between active and sham groups in the proportion of patients whose 3-month level of disability improved above expectations. This endpoint was evaluated in the modified intention-to-treat (mITT) population (defined as all patients who received one active or sham treatment session) and the population with confirmed cortical involvement (CCI) and was analysed using the Hochberg multi-step procedure (significance in both populations if p<0·05 in both, and in one population if p<0·025 in that one). Safety endpoints at 3 months were all serious adverse events (SAEs), SAEs related to implant placement or removal, SAEs related to stimulation, neurological deterioration, and mortality. All patients who underwent an attempted sphenopalatine ganglion stimulator or sham stimulator placement procedure were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00826059. FINDINGS: Between June 10, 2011, and March 7, 2018, 1078 patients were enrolled and randomly assigned to either the intervention or the sham-control group. 1000 patients received at least one session of sphenopalatine ganglion stimulation or sham stimulation and entered the mITT population (481 [48%] received sphenopalatine ganglion stimulation, 519 [52%] were sham controls), among whom 520 (52%) patients had CCI on imaging. The proportion of patients in the mITT population whose 3-month disability level was better than expected was 49% (234/481) in the intervention group versus 45% (236/519) in the sham-control group (odds ratio 1·14, 95% CI 0·89-1·46; p=0·31). In the CCI population, the proportion was 50% (121/244) in the intervention group versus 40% (110/276) in the sham-control group (1·48, 1·05-2·10; p=0·0258). There was an inverse U-shaped dose-response relationship between attained sphenopalatine ganglion stimulation intensity and the primary outcome in the CCI population: the proportion with favourable outcome increased from 40% to 70% at low-midrange intensity and decreased back to 40% at high intensity stimulation (p=0·0034). There were no differences in mortality or SAEs between the intervention group (n=536) and the sham-control group (n=519) in the safety population. INTERPRETATION: Sphenopalatine ganglion stimulation is safe for patients with acute ischaemic stroke 8-24 h after onset, who are ineligible for thrombolytic therapy. Although not reaching significance, the trial's results support that, among patients with imaging evidence of cortical involvement at presentation, sphenopalatine ganglion stimulation is likely to improve functional outcome. FUNDING: BrainsGate Ltd.

Meaning and medication: a thematic analysis of depressed adolescents' views and experiences of SSRI antidepressants alongside psychological therapies.

BACKGROUND: Adolescence is a key period of risk for the emergence of Major Depressive Disorder (MDD). The prescription of selective serotonin re-uptake inhibitors (SSRIs) for the treatment of depression in adolescents is an issue of worldwide controversy, and evidence regarding their safety and efficacy is inconclusive. In the UK, NICE guidelines have recently recommended offering SSRIs to adolescents alongside psychological therapy or on their own if therapy is refused. Thus, SSRIs are increasingly becoming a major component of treatment for adolescents. This study qualitatively explored adolescents' views and experiences of SSRIs within their accounts of engaging in a psychological therapy for depression, particularly focusing on meanings they attached to medication-use. METHODS: The qualitative study reports data from semi-structured interviews conducted 12-months post-treatment with 12 adolescents who were clinically referred and treated for depression as part of the IMPACT trial. The interviews were analysed using Thematic Analysis. RESULTS: Four themes were identified: 'a perceived threat to autonomy', 'a sign of severity', 'a support, not a solution', and 'an ongoing process of trial and error'. CONCLUSIONS: This study highlights the value of bringing adolescents' voices into the broader debate on the use of antidepressants in their age group and in the development of future guidelines. Future implications for research and clinical practice are discussed.

'Shutting the World Out': An Interpretative Phenomenological Analysis Exploring the Paternal Experience of Parenting a Young Adult with a Developmental Disability.

BACKGROUND: An in-depth exploration of the experience of midlife fathers of developmentally disabled young adults (aged 19-32 years) was motivated by a dearth of research in this area (McKnight, PsyPAG Quarterly, 94, 2015, 10). METHOD: Five fathers participated in semi-structured interviews which were subjected to interpretative phenomenological analysis (Smith, Flowers and Larkin, 2009, Interpretative Phenomenological Analysis: Theory, Method, and Research. London: Sage). RESULTS: The final thematic structure comprises four inter-related themes. They demonstrate a high degree of concern for children's well-being; the joy adult children confers on their father's lives as well as the difficulties men experience in response to the limited opportunities available to their offspring. Importantly findings also illustrate the way in which men struggle to contend with painful emotions. CONCLUSIONS: Societal conceptions of masculinity, fatherhood and disability necessarily influence the way fathers experience the world (Yarwood, Fathering, 9, 2011, 150). It is imperative that service providers recognize the particular challenges faced by fathers, seeking ways to better engage and support them.

Laparoscopic Hiatal Hernia Repair in 221 Patients: Outcomes and Experience.

BACKGROUND AND OBJECTIVES: Hiatal hernia is a common condition often associated with symptomatic gastroesophageal reflux disease (GERD). The objectives of this study were to examine the efficacy and safety of laparoscopic hiatal hernia repair (LHHR) with biologic mesh to reduce and/or alleviate GERD symptoms and associated hiatal hernia recurrence. METHODS: We retrospectively reviewed consecutive LHHR procedures with biologic mesh performed by a single surgeon from July 2009 to October 2014. The primary efficacy outcome measures were relief from GERD symptoms, as measured according to the GERD-health-related quality-of-life (GERD-HRQL) scale and hiatal hernia recurrence. A secondary outcome measure was overall safety of the procedure. RESULTS: A total of 221 patients underwent LHHR with biologic mesh during the study period, and pre- and postoperative GERD-HRQL studies were available for 172 of them. At baseline (preoperative), the mean GERD-HRQL score for all procedures was 18.5 ± 14.4. At follow-up (mean, 14.5 ± 11.0 months [range, 2.0-56.0]), the score showed a statistically significant decline to a mean of 4.4 ± 7.5 (P < .0001). To date, 8 patients (3.6%, 8/221) have had a documented anatomic hiatal hernia recurrence. However, a secondary hiatal hernia repair reoperation was necessary in only 1 patient. Most complications were minor (dysphagia, nausea and vomiting). However, there was 1 death caused by a hemorrhage that occurred 1 week after surgery. CONCLUSIONS: Laparoscopic hiatal hernia repair using biologic mesh, both with and without a simultaneous bariatric or antireflux procedure, is an efficacious and safe therapeutic option for management of hiatal hernia, prevention of recurrence, and relief of symptomatic GERD.

'Well the Future, that is Difficult': A Hermeneutic Phenomenological Analysis Exploring the Maternal Experience of Parenting a Young Adult with a Developmental Disability.

BACKGROUND: The predominant focus of extant literature exploring maternal experience of developmental disability has been stress, adaptation, efficacy of interventions and the burden of care. Most studies involve mothers of children, with scant attention given to what life is like later. This study qualitatively explores the experience of mothers of young adults (aged 19-28). MATERIALS AND METHODS: Semi-structured interviews conducted with six women aged 48-60 were transcribed and analysed using interpretative phenomenological analysis. RESULTS: Three themes illustrate how mothers are confronted with their adult children's continuing need for support and how a lack of trust in social care creates anxiety about the future, increasing awareness of mortality. CONCLUSIONS: Vulnerability represents a useful concept for understanding these findings theoretically. Galvin & Todres' (2013) conceptual framework for the humanization of care provides the opportunity to prioritize the needs of individuals by highlighting dimensions of existence which confer meaning.

Disposition to home or acute rehabilitation is associated with a favorable clinical outcome in the SENTIS trial.

OBJECTIVE: To explore the impact of stroke severity and discharge disposition on 90-day outcomes in US patients enrolled in the SENTIS trial. METHODS: SENTIS is a previously published prospective randomized controlled trial. We analyzed the demographic information, National Institutes of Health Stroke Scores (NIHSS) on day 4, discharge disposition and 90-day modified Rankin Score (mRS). Univariate models were constructed to determine the impact of discharge disposition on 90-day outcomes as well as the association of the day 4 NIHSS with outcomes. RESULTS: A total of 292 patients with a mean age of 65 ± 14 years were analyzed. Discharge disposition was distributed as follows: 153 (52.1%) to an inpatient rehabilitation facility (IRF), 111 (38.0%) to home and 28 (9.6%) to a skilled nursing facility (SNF). Only 2 out of 28 patients (7.1%) discharged to a SNF achieved a 90-day mRS ≤ 2 compared with 60/153 (39.2%) in the IRF group (OR 8.39 (95% CI 1.92 to 36.64), p = 0.0047). This association persisted after adjusting for age and admission NIHSS. Only 3 of 50 patients (6%) with a NIHSS of ≥ 14 at day 4 achieved a mRS 0-2 at day 90. CONCLUSIONS: This analysis shows that discharge to an IRF is associated with better neurological outcomes than discharge to a SNF. Additionally, patients with a NIHSS of ≥ 14 at day 4 are unlikely to achieve independent function.

A comparison between the HeRO graft and conventional arteriovenous grafts in hemodialysis patients.

Venous stenosis and occlusion are a major cause of vascular access dysfunction and failure. The HeRO Graft bypasses occlusion and traverses stenosis with outflow directly into the central venous circulation. A randomized, multicenter study was conducted to evaluate the efficacy and safety of the HeRO Graft relative to conventional AV grafts. The design was to enroll 143 patients in a 2:1 randomization ratio between HeRO and conventional AV control groups. Data on 72 subjects (52 HeRO Graft and 20 AV graft controls) were obtained. The HeRO Graft and control cohorts were comparable in baseline characteristics. Adequacy of dialysis, bacteremia rates, and adverse events were consistent between groups. Twelve month Kaplan-Meier estimates for primary and secondary patency rates were 34.8% and 67.6% in the HeRO Graft cohort, and 30.6% and 58.4% in the control cohort. There was no statistical difference in terms of patency between groups. The rates of intervention were 2.2/year for HeRO Graft and 1.6/year for the control (p = 0.100). Median days to loss of secondary patency was 238 for HeRO Graft versus 102 for the control (p = 0.032). The HeRO Graft appears to provide similar patency, adequacy of dialysis, and bacteremia rates to those of conventional AV grafts.

Prospective comparison of discrimination algorithms to prevent inappropriate ICD therapy: primary results of the Rhythm ID Going Head to Head Trial.

BACKGROUND: Inappropriate therapy for supraventricular arrhythmias remains a significant source of morbidity in implantable cardioverter-defibrillator (ICD) recipients. OBJECTIVE: The Rhythm ID Goes Head to Head Trial (RIGHT) was designed to compare rhythm discrimination and inappropriate therapies among patients with ICDs from 2 manufacturers. METHODS: Patients with standard ICD indications were randomized to receive a Guidant VITALITY 2 with Rhythm ID or selective Medtronic pulse generators using the Enhanced PR Logic or Wavelet discrimination algorithms. A single- or dual-chamber device was implanted based on clinical indications and programmed in 2 detection zones with detection enhancements enabled for rates between 150 and 200 bpm. Algorithm performance was compared between randomization groups, stratified by single or dual chamber, for the primary end point of first inappropriate therapy (shock or antitachycardia pacing) for supraventricular arrhythmias. RESULTS: There were 1962 patients enrolled and followed for 18.3 ± 9.2 months, with no difference in all-cause mortality between groups. There were 3973 treated episodes where electrograms were available and adjudicated. The primary end point of inappropriate therapy occurred in 246 of 985 VITALITY 2 patients vs 187 of 977 specific Medtronic ICD patients (hazard ratio = 1.34; confidence interval = 1.11-1.62; P = .003). Differences in inappropriate therapy were confined to single-chamber ICDs. Inappropriate shocks were more frequent in VITALITY 2 ICDs (hazard ratio = 1.63; confidence interval = 1.29-2.06; P < .001), with most therapies and performance differences occurring at slower rhythms (rates < 175 bpm). CONCLUSION: Rhythm discrimination performed better in the specific Medtronic than in VITALITY 2 ICDs evaluated, particularly for single-chamber devices. Inappropriate therapies, and differences in performance, may be reduced with the use of rate cutoff above 175 bpm.

Device diagnostics and long-term clinical outcome in patients receiving cardiac resynchronization therapy.

AIMS: This retrospective analysis sought to develop and validate a model using the measured diagnostic variables in cardiac resynchronization therapy (CRT) devices to predict mortality. METHODS AND RESULTS: Data used in this analysis came from two CRT studies: Cardiac Resynchronization Therapy Registry Evaluating Patient Response with RENEWAL Family Devices (CRT RENEWAL) (n = 436) and Heart Failure-Heart Rate Variability (HF-HRV) (n = 838). Patients from CRT RENEWAL were used to create a model for risk of death using logistic regression and to create a scoring system that could be used to predict mortality. Results of both the logistic regression and the clinical risk score were validated in a cohort of patients from the HF-HRV study. Diagnostics significantly improved over time post-CRT implant (all P < 0.001) and were correlated with a trend of decreased risk of death. The regression model classified CRT RENEWAL patients into low (2.8%), moderate (6.9%), and high (13.8%) risk of death based on tertiles of their model predicted risk. The clinical risk score classified CRT RENEWAL patients into low (2.8%), moderate (10.1%), and high (13.4%) risk of death based on tertiles of their score. When both the regression model and the clinical risk score were applied to the HF-HRV study, each was able to classify patients into appropriate levels of risk. CONCLUSION: Device diagnostics may be used to create models that predict the risk of death.

A randomized trial of the effect of automated ventricular capture on device longevity and threshold measurement in pacemaker patients.

BACKGROUND: An automatic capture (AC) algorithm adjusts ventricular pacing output to capture the ventricle while optimizing output to 0.5 V above threshold. AC maintains this output and confirms capture on a beat-to-beat basis in bipolar and unipolar pacing and sensing. OBJECTIVE: To assess the AC algorithm and its impact on device longevity. METHODS: Patients implanted with a pacemaker were randomized 1:1 to have the AC feature on or off for 12 months. Two threshold tests were conducted at each visit- automatic threshold and manual threshold. Average ventricular voltage output and projected device longevity were compared between AC on and off using nonparametric tests. RESULTS: Nine hundred ten patients were enrolled and underwent device implantation. Average ventricular voltage output was 1.6 V for the AC on arm (n = 444) and 3.1 V for the AC off arm (n = 446) (P < 0.001). Projected device longevity was 10.3 years for AC on and 8.9 years for AC off (P < 0.0001), or a 16% increase in longevity for AC on. The proportion of patients in whom there was a difference between automatic threshold and manual threshold of

Clinical and electrical performance of expanded polytetrafluoroethylene-covered defibrillator leads in comparison to traditional leads.

BACKGROUND: In the event of infection, erosion, or failure, fibrosis of a defibrillation lead can make extraction difficult. In the ENDOTAK RELIANCE G defibrillation lead, coils are covered with expanded polytetrafluoroethylene (ePTFE) to prevent tissue ingrowth. OBJECTIVE: The objective of the REFLEx Study was to evaluate if RELIANCE G defibrillation leads with ePTFE-covered coils are as good as comparative defibrillation leads with respect to electrical performance and termination of spontaneous tachyarrhythmias. METHODS: Patients were randomized to type of defibrillation lead--Guidant RELIANCE G lead or a non-ePTFE-covered lead of choice. Electrical performance success was defined as meeting all minimum standards in the respective manufacturer's manual for amplitude, threshold, and impedance. A noninferiority margin of 5% was prespecified. RESULTS: Electrical performance success at 12 months was 93.0% (280/301) for RELIANCE G and 94.5% (291/308) for comparative leads. The performance success rate for RELIANCE G did not differ significantly from study comparative (P = 0.04, noninferiority). For spontaneous episodes, first shock conversion success rate was 90% for RELIANCE G and 95% for study comparative (P = 0.89, noninferiority). Implant conversion testing was successful in 96.7% (524/542) of RELIANCE G patients and 94.3% (512/543) of comparative patients (chi-square P-value = 0.0784). About 55% (609/1115) of patients completed follow-up through month 12. CONCLUSION: Data from the REFLEx study indicate that ePTFE-covered leads are not inferior to comparative leads with respect to electrical performance and implant conversion testing. We cannot conclude that the first shock conversion efficacy of ePTFE covered leads was statistically noninferior to comparative leads.

Visceral and subcutaneous adiposity measurements in adults: influence of measurement site.

OBJECTIVE: Excess abdominal adiposity is a known risk factor for cardiovascular diseases. Computed tomography can be used to examine the visceral (VAT) and subcutaneous (SAT) components of abdominal adiposity, but it is unresolved whether single-slice or multi-slice protocols are needed. RESEARCH METHOD AND PROCEDURES: Nine computed tomography scans were obtained in the lumbar spine region of 24 adults. The nine slices were obtained at three intervertebral positions (L2-L3, L3-L4, and L4-L5) and at 7 mm above and below these locations. Intra-site and inter-site differences in SAT, VAT, total adipose tissue, and the VAT/SAT ratio were examined using ANOVA and confidence intervals for pairwise differences between means. RESULTS: Intervertebral SAT values increased from 103.1 +/- 50.9 (standard deviation) cm(2) at L2-L3 to 153.3 +/- 68.8 cm(2) at L4-L5, whereas the corresponding VAT values decreased from 164.3 +/- 125.4 to 126.0 +/- 82.7 cm(2). The VAT/SAT ratio was not constant, decreasing from 1.8 +/- 1.4 to 0.9 +/- 0.7. Repeated-measures ANOVA indicated significant inter- and intra-site differences (p

Disadvantages of structured treatment interruption persist in patients with multidrug-resistant HIV-1: final results of the CPCRA 064 study.

BACKGROUND: We report the final results of Community Programs for Clinical Research on AIDS (CPCRA-064) study, a multicenter, prospective, randomized, controlled trial that determines the long-term clinical impact of structured treatment interruption (STI) in patients with multidrug-resistant (MDR) HIV-1. METHODS AND RESULTS: Two hundred seventy-four patients on stable antiretroviral therapy with MDR HIV-1 treatment failure were randomized to a 4-month STI, followed by an optimized antiretroviral regimen (STI arm, n = 140) or an immediate change to an optimized antiretroviral regimen (control arm, n = 134). Main outcome measures were progression of disease or death and changes from baseline in HIV RNA levels (log copies/mL) and CD4 cell counts (cells/mm). The median baseline HIV RNA level was 5.0 log copies/mL, the median CD4 count was 147 cells/mm, and the nadir CD4 count was 32 cells/mm. The median follow-up was 37 months. After the STI period, there were no differences in HIV RNA level responses between treatment arms. Differences in CD4 count responses always favored the control arm, with an advantage of 84 cells from 0 to 4 months (P < 0.0001), 50 cells from 4 to 12 months (P < 0.0001), 45 cells from 12 to 24 months (P = 0.006), and 43 cells after 24 months (P = 0.07). Rates in the STI and control arms for first progression-of-disease event or death were 17.5 and 14.3, respectively (hazard ratio = 1.28; P = 0.22). CONCLUSION: STI before changing regimens in patients with MDR HIV-1 treatment failure has a prolonged negative impact on CD4 cell count recovery and does not confer progression of disease or virologic benefits.