Sudden Cardiac Arrest Survivors Research Articles

Early repolarization with horizontal ST segment may be associated with aborted sudden cardiac arrest: a retrospective case control study

BackgroundRisk stratification of the early repolarization pattern (ERP) is needed to identify malignant early repolarization. J-point elevation with a horizontal ST segment was recently suggested as a malignant feature of the ERP. In this study, the prevalence of the ERP with a horizontal ST segment was examined among survivors of sudden cardiac arrest (SCA) without structural heart disease to evaluate the value of ST-segment morphology in risk stratification of the ERP.MethodsWe reviewed the data of 83 survivors of SCA who were admitted from August 2005 to August 2010. Among them, 25 subjects without structural heart disease were included. The control group comprised 60 healthy subjects who visited our health promotion center; all control subjects were matched for age, sex, and underlying disease (diabetes mellitus, hypertension). Early repolarization was defined as an elevation of the J point of at least 0.1 mV above the baseline in at least two continuous inferior or lateral leads that manifested as QRS slurring or notching. An ST-segment pattern of <0.1 mV within 100 ms after the J point was defined as a horizontal ST segment.ResultsThe SCA group included 17 men (64%) with a mean age of 49.7 ± 14.5 years. The corrected QTc was not significantly different between the SCA and control groups (432.7 ± 37.96 vs. 420.4 ± 26.3, respectively; p = 0.089). The prevalence of ERP was not statistically different between the SCA and control groups (5/25, 20% vs. 4/60, 6.7%, respectively; p = 0.116). The prevalence of early repolarization with a horizontal ST segment was more frequent in the SCA than in the control group (20% vs. 3.3%, respectively; p = 0.021). Four SCA subjects (16%) and one control subject (1.7%) had a J-point elevation of >2 mm (p = 0.025). Four SCA subjects (16%) and one (1.7%) control subject had an ERP in the inferior lead (p = 0.025).ConclusionThe prevalence of ERP with a horizontal ST segment was higher in patients with aborted SCA than in matched controls. This result suggests that ST morphology has value in the recognition of malignant early repolarization.

Total Subcutaneous Defibrillators: The Current Status and Future Prospect of a New Technology

Implantable cardioverter-defibrillators (ICDs) constitute an effective therapy for protection against death in survivors of sudden cardiac arrest and in those at risk for sudden cardiac death based on poor left ventricular function. In this article, the authors discuss the totally subcutaneous ICD (SC-ICD) system that was designed to provide an alternative to transvenous electrodes in patients who do not require cardiac pacing. The authors also discuss the promises and shortcomings of this new device technology compared with the conventional transvenous implantable defibrillator system and review the experience up-to-date with the SC-ICD.

Early repolarization in children with unexplained syncope

Introduction: It has traditionally been believed that early repolarization (ER) is benign. Significant association between ER and sudden cardiac arrest due to idiopathic ventricular fibrillation was recently found in a large cohort of adult survivors of sudden cardiac arrest. In some prior studies, unexplained syncope has been linked to risk of sudden death, but the mechanisms remain speculative.We assessed herein the prevalence of ER in children referred to our center for unexplained syncope. Methods: We evaluated retrospectively electrocardiograms from such children (n = 29; mean age, 12.1 years; range, 7-18 years) for presence of ER, which was defined as an elevation of the QRS-ST junction (J-point) in at least 2 leads of at least 1 mm (0.1 mV) above the baseline level. The anterior precordial leads (V1-V3) were excluded from the analysis to avoid inclusion of patients with right ventricular dysplasia or Brugada syndrome. Agematched children (n = 33; mean age, 12.3 years; range, 7-16 years) with noncardiac chest pain were included as controls. Results: Early repolarization was detected in 45% (13/29) of children with unexplained syncope vs 24% (8/33) in the chest pain group. Among children with syncope, ER was far more frequent in males than in females (8/12 vs 5/ 17, respectively). Echocardiography showed normal functional and structural findings in all children. Conclusion: In this relatively small-scale retrospective study of children with unexplained syncope with otherwise normal cardiac findings, we found particularly among those of male gender a greater prevalence of ER than in controls (noncardiac chest pain).With view to earlier findings of Haisaguerre et al (NEJM 2008), this intriguing association warrants further prospective studies addressing its precise clinical implication and underlying mechanisms. (Less)

Mild induced hypothermia and an urgent invasive coronary strategy: A promising protocol for comatose survivors of sudden cardiac arrest

Context: Montenegro has a low-level HIV epidemic, but the majority of registered HIV cases have been diagnosed in patients between the ages of 20to 34-years-old. Th e aim of this study was to assess the level of HIV-related knowledge, attitudes towards people living with HIV (PLHIV) and sexual behaviour among youth aged 15-24 in Montenegro. Methods: A nationally representative cross-sectional survey assessed 1164 young people aged 15-24. Th e data were collected in December 2009 using face-to-face interviewing for topics concerning HIV-related awareness and attitudes, whereas a self-administered questionnaire covered topics related to sexual experiences and behaviour. Results: In general, the level of HIV-related knowledge and accepting attitudes towards people living with HIV were unsatisfactory. Of the surveyed population, slightly more than half reported current sexual activity. Th e reported level of sexual risk behaviour diff ered signifi cantly according to participant sex and region. Early sexual initiation and not using condoms during the fi rst episodes of sexual intercourse were found to be signifi cant predictors of more frequent sexual risk behaviour. Conclusions: Despite the relatively high awareness pertaining to routes of HIV transmission, the surveyed population reported misconceptions related to HIV transmission. A significant proportion of young people have engaged in risky sexual behaviours. Th ese results strongly support the introduction of secondary school curriculum related to HIV/STI prevention as well other risk behaviours observed in this age cohort.

Experiences of sudden cardiac arrest survivors regarding prognostication and advance care planning

Objective We sought to better understand SCA survivors’ beliefs about complex issues that arise in the immediate post-arrest period and explore advance care planning. Specifically, we wished to explore four themes: (1) patient and family perception of medical providers’ prognostication in the immediate post-arrest phase; (2) patient definitions of death; (3) use of advance directives (ADs); and (4) perceptions of health and organ donation. Methods We conducted a qualitative study of adult arrest survivors using semi-structured telephone interviews. Participants were recruited from a nonprofit national organization for SCA. Results Nine of 11 subjects contacted completed the survey. In the immediate post-arrest phase, subjects believed that medical professionals made errors in giving poor prognosis early in the course of resuscitation. While some subjects felt they had experienced “death,” some subjects felt the term “death” was an inappropriate term to describe their experience. The majority of the subjects did not have an AD prior to their SCA and no subjects reported having a conversation about ADs with their medical team. While the majority of subjects classified their health as “very good” or “excellent,” few subjects were registered organ donors, citing comorbidities and skepticism about future resuscitative efforts as rationale. Conclusions Our study elucidated the attitudes and experiences of SCA survivors. Variability in prognostication timing and inconsistency in describing SCA can complicate discussions between the medical team and families. AD and organ donation discussions may help to provide sensitive care concordant with a patient's wishes.

Testing an Exercise Intervention to Improve Aerobic Conditioning and Autonomic Function after an Implantable Cardioverter Defibrillator (ICD)

Implantable cardioverter defibrillators (ICDs) are an increasingly common treatment for survivors of sudden cardiac arrest or others with life-threatening ventricular arrhythmias. Health-care providers are often reluctant to prescribe exercise for this group because of the belief that it will provoke ventricular arrhythmias and cardiac arrest; patients are often afraid to exercise because of concern over receiving an ICD shock. A social cognitive theory-driven exercise intervention aimed at stabilizing cardiac arrhythmias and reducing ICD shocks by increasing parasympathetic autonomic nervous system control is described. The exercise intervention has two phases that include an 8-week aerobic conditioning component followed by a 16-week exercise maintenance component. The aerobic exercise intervention is expected to have significant impact on cardiopulmonary function, ventricular arrhythmias, cardiac autonomic function, and self-efficacy in persons who have an ICD. The exercise intervention is currently being tested using a randomized clinical trial format, the results of which will be available in 2012. The exercise after ICD trial is one of the first clinical trials to test the effects of aerobic exercise on cardiopulmonary outcomes after receiving an ICD for primary or secondary prevention of sudden cardiac arrest.

Unexplained sudden cardiac death—back to clinical evaluation

The diagnosis of unexplained cardiac arrest could soon become obsolete, as so-called molecular autopsy can now be used to identify its underlying causes. The current view of this subject is discussed, and some personal opinions are presented on the assessment of survivors of sudden cardiac arrest and relatives of individuals who do not survive.

Cardiopulmonary resuscitation – automated external defibrillation programs for children and adolescents: Is public access defibrillation directed at our youth justifiable?

Cardiopulmonary resuscitation – automated external defibrillation programs for children and adolescents: Is public access defibrillation directed at our youth justifiable?

Scandinavian Clinical practice guidelines for therapeutic hypothermia and post‐resuscitation care after cardiac arrest

Sudden cardiac arrest survivors suffer from ischaemic brain injury that may lead to poor neurological outcome and death. The reperfusion injury that occurs is associated with damaging biochemical reactions, which are suppressed by mild therapeutic hypothermia (MTH). In several studies MTH has been proven to be safe, with few complications and improved survival, and is recommended by the International Liaison of Committee on Resuscitation. The aim of this paper is to recommend clinical practice guidelines for MTH treatment after cardiac arrest from the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI). Relevant studies were identified after two consensus meetings of the SSAI Task Force on Therapeutic Hypothermia (SSAITFTH) and via literature search of the Cochrane Central Register of Controlled Trials and Medline. Evidence was assessed and consensus opinion was used when high-grade evidence (Grade of Recommendation, GOR) was unavailable. A management strategy was developed as a consensus from the evidence and the protocols in the participating countries. Although proven beneficial only for patients with initial ventricular fibrillation (GOR A), the SSAITFTH also recommend MTH after restored spontaneous circulation, if active treatment is chosen, in patients with initial pulseless electrical activity and asystole (GOR D). Normal ethical considerations, premorbid status, total anoxia time and general condition should decide whether active treatment is required or not. MTH should be part of a standardized treatment protocol, and initiated as early as possible after indication and treatment have been decided (GOR E). There is insufficient evidence to make definitive recommendations among techniques to induce MTH, and we do not know the optimal target temperature, duration of cooling and rewarming time. New studies are needed to address the question as to how MTH affects, for example, prognostic factors.

Long-term cognitive outcome in teenage survivors of arrhythmic cardiac arrest

Sudden cardiac arrest (SCA) can be the first sign of ventricular arrhythmia in teenagers. Neurocognitive problems are common after successful resuscitation. We studied cognitive function in teenage survivors of SCA, including emotional status and coping ability. Ten SCA survivors, aged 11-19 years, had neuropsychological tests within a few weeks of resuscitation. Awareness status, orientation, episodic and semantic memory, basic auditory-visual functions, praxis and speech, short-term memory, ability to learn new verbal and visual material were assessed. These tests were repeated at about 6 months. Eight patients had an initial assessment; one boy remained in a coma and one was making simple emotional contact, revealing intensified mixed aphasia and dyskinesia. Six patients had severe disturbances of memory, motor functions and praxis. After 6 months, four patients had no neurocognitive disturbance. Four patients had memory impairment making school education difficult. Two patients were totally dependent on caregivers. Because of the absence of symptoms before SCA, and amnesia relating to the SCA episodes, patients had problems accepting their heart problems and limitations resulting from it. Teenagers surviving SCA have significant neurcognitive and psychological problems. They need psychological care and guidance in understanding their condition.

Reliability and Validity of the Self-Efficacy Expectations and Outcome Expectations After Implantable Cardioverter Defibrillator Implantation Scales

The purpose of this study was to assess the reliability and validity characteristics of two new scales that measure self-efficacy expectations (Self-Efficacy Expectations After Implantable Cardioverter Defibrillator Implantation Scale [SE-ICD]) and outcome expectations (Outcome Expectations After ICD Implantation Scale [OE-ICD]) in survivors ( N = 168) of sudden cardiac arrest, all of whom received an ICD. Cronbach's α reliability demonstrated good internal consistency (SE-ICD α = .93 and OE-ICD α = .81). Correlations with other self-efficacy instruments (general self-efficacy and social self-efficacy) were consistently high. The instruments were responsive to change across time with effect sizes of .46 for SE-ICD and .26 for OE-ICD. These reliable, valid, and responsive instruments for measurement of self-efficacy expectations and outcome expectations after an ICD can be used in research and clinical settings.

Supraventricular tachyarrhythmia as a cause of sudden cardiac arrest

Supraventricular tachyarrhythmias (SVTA) are an accepted cause of cardiac arrest in patients with Wolff-Parkinson-White syndrome (WPW) and hypertrophic cardiomyopathy but their participation in other conditions is less well understood. The purpose of the study was to examine the role of SVTA in sudden cardiac arrest (SCA) by comprehensive evaluation of patients successfully resuscitated from SCA. A total of 169 survivors of SCA in the absence of acute myocardial infarction underwent systematic evaluation that included echocardiography, Holter monitoring, coronary angiography and electrophysiological study (EPS) with additional testing in selected cases using provocative drug testing with isoproterenol, ajmaline or ergonovine. SVTA was found as the only possible cause or as the cause facilitating SCA in 29 patients: (1) 3 had a WPW syndrome related to accessory pathway with short refractory period; (2) for 12 patients, SVTA was the cause of cardiovascular collapse; heart disease (HD) was present in 11 cases, but disappeared in two of four with dilated cardiomyopathy after the restoration of sinus rhythm; (3) in 14 patients, SVTA degenerated either in a VF or ventricular tachycardia (VT); HD was present in 12 cases, but disappeared in one; two had no HD and recurrent similar arrhythmia was documented by cardiac defibrillator in one of them. SVTA induced coronary ischemia was the main cause of SCA. Rapid SVTA was a cause of SCA, either by cardiovascular collapse or by the degeneration in VT or VF. The complication generally occurred in patients with advanced HD or with rapid SVTA-induced cardiomyopathy and rarely in patients without HD. The incidence of SVTA as the only cause or the facilitating cause of SCAs is probably underestimated, because it is difficult to prove.

High acceptance of a home AED programme by survivors of sudden cardiac arrest and their families

The feasibility and acceptance of providing sudden cardiac arrest survivors with life supporting first aid training and automated external defibrillators (AEDs) at their homes is unknown. Preliminary experiences are reported here. Trained medical students provided life supporting first aid courses including AED training to cardiac arrest survivors. Patients were asked to invite relatives and friends to such training sessions at their home. Laerdal Little Anne and Heartstart AED Trainer were used. An AED was placed at the patients' disposal. A refresher course took place 1 year later. Questionnaires were used to evaluate the project. Since 1999, 88 families have been trained and provided with an AED. Immediately after the training 90% (66% "agree", 24% "maybe yes") believed they would perform first aid correctly, 1 year later 98% did so (68% "agree", 29% "maybe yes") (p=0.03). Families considered feeling much safer having an AED at home. The handling of an AED was regarded to be easy and AEDs would even be used on strangers. Only on one occasion an AED was used in a real emergency situation. Providing patients and relatives with life support first aid and AED training at their homes is feasible and has raised no major objections by the family members. All have considered handling of an AED much simpler than providing basic life support and therefore none think that it would be a major problem to use it in case of an emergency. This still has to be proven.

Heart Rate Variability and 24-hour Minimum Heart Rate

Heart rate variability (HRV) indices based on 24-hr electrocardiograph recordings have been used in clinical research studies to assess the aggregate activity of the autonomic nervous system. Although 24-hr HRV is generally considered noninvasive, use in research protocols typically involves considerable data collection and processing expenses and substantial participant burden. The purposes of this research methods evaluation were to describe the relationships between 24-hr minimum heart rate (HR) and several 24-hr time domain HRV indices (Ln SDNN, Ln SDANN, Ln SDNNIDX, Ln RMSSD, and Logit50) across several research data sets (normal women, normal men, children enrolled in a study of recurrent abdominal pain, women with irritable bowel syndrome, sudden cardiac arrest survivors, and heart failure patients) and to explore the possibility that 24-hr minimum HR might serve as a simpler alternative or adjunct to HRV measures in some situations. The correlations of global HRV measures (e.g., Ln SDNN, Ln SDANN) with 24-hr minimum HR were consistently larger (typical r approximately -.80) than with average HR (typical r approximately -.50). In repeated measurements, change in minimum HR was also correlated with change in general HRV (typical r approximately -.60). However, modest differentiation of minimum HR and HRV measures was noted in patients taking certain classes of cardiac medications (e.g., anti-arrhythmics, beta blockers). Twenty-four-hour minimum HR is correlated with general time domain HRV measures and might be useful as a simpler proxy, surrogate, or auxiliary variable in some clinical research applications, especially those in which participants are not receiving cardiac medications.

Determinants of Recurrent Ventricular Arrhythmia or Death in 300 Consecutive Patients with Ischemic Heart Disease Who Experienced Aborted Sudden Death: Data from the Leiden Out‐of‐Hospital Cardiac Arrest Study

Evaluation of the relation between clinical characteristics and incidence of recurrent ventricular arrhythmias (VAs) or death during long-term follow-up in a cohort of 300 consecutive ischemic heart disease (IHD) patients who had survived an episode of sudden cardiac arrest (SCA). Survivors of life-threatening VA are at high risk for recurrent events. A total of 300 consecutive survivors of SCA with IHD were included in a standardized screening and evaluation protocol. Multivariable Cox regression analysis was performed to determine the relation between clinical variables at baseline and the incidence of recurrent VA, all-cause mortality and the composite of both (composite endpoint). The presenting arrhythmia was VT in 156 (52%) patients and VF in 144 (48%) patients. Revascularization was performed in 78 (26%) patients and an ICD was implanted in 216 (72%) patients. During follow-up (mean 30 +/- 21 months) 37 (12%) patients died and 88 (29%) patients experienced a recurrence. Advanced age (adjusted hazard ratio (HR) 2.0; 1.2-3.3), history of heart failure (HR 1.8; 1.2-2.6), and amiodarone use (HR 3.1; 2.1-4.6) were independent predictors for the composite endpoint. VT as presenting arrhythmia was an independent predictor for all-cause mortality only (HR 2.4; 1.2-4.8). A decreased risk of recurrences was determined by beta-blocker use (HR 0.5; 0.4-0.8) and coronary revascularization (HR 0.3; 0.2-0.6). In a cohort of 300 consecutive survivors of SCA the incidence of recurrent VA and death is dependent on patient age, history of heart failure, and use of amiodarone. In contrast, use of beta-blockers and aggressive coronary revascularization improve the outcome.

Domains of concern of intimate partners of sudden cardiac arrest survivors after ICD implantation.

There is limited research that describes the experiences of intimate partners of sudden cardiac arrest (SCA) survivors. The purposes of this article are to (1) describe the domains of concern of intimate partners of SCA survivors during the first year after internal cardioverter defibrillator (ICD) implantation and (2) outline strategies used by partners of SCA survivors in dealing with the concerns and demands of recovery in the first year after ICD implantation. This is a secondary analysis of interview data collected for the primary study "Family Experiences Following Sudden Cardiac Arrest." A grounded theory method was used to identify experiences of SCA survivors and their family members from hospitalization through the first year after ICD implantation. Data were collected from the SCA survivor and one intimate partner at 5 times: hospital discharge, and at 1, 3, 6, and 12 months postdischarge. Eight Domains of Concern were identified for intimate partners following SCA and ICD implantation during the first year. These included (1) Care of the survivor, (2) My (partner) self-care, (3) Relationship, (4) ICD, (5) Money, (6) Uncertain future, (7) Health care providers, and (8) Family. Five categories of strategies to deal with the Domains of Concerns were identified (1) Care of the survivor, (2) My (partner) self-care, (3) Relationship, (4) Uncertain future, and (5) Controlling the environment. Nursing intervention programs should include the intimate partner of SCA survivors and contain education and support in the following areas: (1) information on the function of the ICD, (2) normal progression of physical and emotional recovery experiences, (3) safety and maintenance of the ICD, (4) activities of daily living after an ICD, (5) strategies to assist with the survivors care, and (6) strategies to assist with partner self care.

Recall and recognition in mild hypoxia: using covariance structural modeling to test competing theories of explicit memory

To test theories of explicit memory in amnesia, we examined the effect of hypoxia on memory performance in a group of 56 survivors of sudden cardiac arrest. Structural equation modeling revealed that a single-factor explanation of recall and recognition was insufficient to account for performance, thus contradicting single-process models of explicit memory. A dual-process model of recall in which two processes (e.g., declarative memory and controlled search) contribute to recall performance, whereas only one process (e.g., declarative memory) underlies recognition performance, also failed to explain the results adequately. In contrast, a dual-process model of recognition provided an acceptable account of the data. In this model, two processes—recollection and familiarity—underlie recognition memory, whereas only the recollection process contributes to free recall. The best-fitting model was one in which hypoxia and aging led to deficits in recollection, but left familiarity unaffected. Moreover, a controlled search process was correlated with recollection, but was not associated with familiarity or the severity of hypoxia. The results support models of explicit memory in which recollection depends on the hippocampus and frontal lobes, whereas familiarity-based recognition relies on other brain regions.

Temporal patterns in long-term survival after resuscitation from out-of-hospital cardiac arrest.

During the past quarter century, advances in treatment of cardiovascular disease have occurred that might potentially benefit survivors of sudden cardiac arrest (SCA). Little is known, however, about the temporal patterns in long-term survival among persons resuscitated from SCA. We hypothesized that long-term survival would improve over time and that this temporal pattern would be most evident for cardiac causes of death. The investigation was a retrospective cohort study of survival among persons who were discharged alive from the hospital after resuscitation from out-of-hospital SCA due to heart disease in King County, Wash, between May 1, 1976, and December 31, 2001 (n=2035). Calendar time was divided into four 5-year intervals: 1976 to 1980, 1981 to 1985, 1986 to 1990, and 1991 to 1995, and one 6-year interval, 1996 to 2001. Age-adjusted survival curves were constructed, and Cox proportional-hazards regression was used to compute hazard ratios (HRs) for the association between mortality and time period. During 11 201 person-years of follow-up, 1334 persons died. Compared with the initial time period, the HR for total mortality was 0.86 (95% confidence interval, 0.73 to 1.01) for 1981 to 1985, 0.82 (0.69 to 0.96) for 1986 to 1990, 0.66 (0.55 to 0.79) for 1991 to 1995, and 0.58 (0.47 to 0.71) for 1996 to 2001 (HR for trend=0.87 [0.84 to 0.91] for each successive time period). In analyses that assessed cardiac mortality, an even stronger temporal association was evident (HR for trend=0.79 [0.75 to 0.84]). Long-term survival after resuscitation from SCA improved steadily over time in this cohort. To continue this trend, future studies should identify circumstances in which proven treatments are underutilized as well as investigate new therapies that might benefit survivors of SCA.

Long-Term Follow-Up of Sudden Cardiac Arrest Survivors and Electrophysiologically Guided Antiarrhythmic Therapy

Sudden cardiac arrest survivors have a high risk of suffering from recurrent arrhythmic events. Recent studies have shown that these patients have a significantly decreased mortality rate, if they are supplied with an implantable cardioverter/defibrillator (ICD). The aim of this study was to evaluate the long-term prognosis of patients with electrophysiologically guided antiarrhythmic drug therapy in comparison to patients with ICD. 204 consecutive survivors of sudden cardiac arrest were enrolled in this study. All patients were examined with an initial electrophysiologic study (EPS) with programmed ventricular stimulation. Patients were treated with antiarrhythmic drugs (if the inducible tachycardia was suppressed) or with the implantation of an ICD. The maximal follow-up period was 120 months, the mean period was 53.3 ± 31.4 months (ICD) versus 60.3 ± 35.5 months (EPS, nonsignificant). Patients with ICD showed an overall mortality rate of 14.6%, whereas EPS-guided patients had a mortality rate of 43.2% (p < 0.001). The cardiac and arrhythmogenic mortality rates were significantly lower in the ICD group (12 vs. 43%, p < 0.01, and 1 vs. 16%, p < 0.001, respectively). A reduction of the mortality risk was observed in the ICD group by up to 61% (all-cause mortality), 52% (cardiac mortality) and 97.2% (arrhythmogenic mortality). In arrhythmic event survivors with ICD, arrhythmic and overall mortality rates are significantly lower compared to patients with an EPS-guided drug therapy. In the secondary prevention of sudden cardiac death, ICD should be the first choice of antiarrhythmic therapy.

Theoretical development of nursing interventions for sudden cardiac arrest survivors using social cognitive theory.

This article discusses the theoretical development of a nursing intervention program to enhance recovery over the first year following sudden cardiac arrest. Concepts from social cognitive theory and domains of concern following sudden cardiac arrest underpin a tailored and standardized nursing intervention. The nursing intervention program is designed for delivery by means of telephone and through the mail. Testing of the nursing intervention program is underway using a clinical trial design.