Novel emboli protection system during cardiac surgery: a multi-center, randomized, clinical trial.

BACKGROUND Stroke is a major cause of morbidity and mortality during open-heart surgery. Up to 60% of intraoperative cerebral events are emboli induced. This randomized, controlled, multicenter trial is the first human study evaluating the safety and efficacy of a novel aortic cannula producing simultaneous forward flow and backward suction for extracting solid and gaseous emboli from the ascending aorta and aortic arch upon their intraoperative release. METHODS Sixty-six patients (25 females; 68±10 years) undergoing elective aortic valve replacement surgery, with or without coronary artery bypass graft surgery, were randomized to the use of the CardioGard (CardioGard Medical, Or-Yehuda, Israel) Emboli Protection cannula ("treatment") or a standard ("control") aortic cannula. The primary endpoint was the volume of new brain lesions measured by diffusion-weighted magnetic resonance imaging (DW-MRI), performed preoperatively and postoperatively. Device safety was investigated by comparisons of complications rate, namely neurologic events, stroke, renal insufficiency and death. RESULTS Of 66 patients (34 in the treatment group), 51 completed the presurgery and postsurgery MRI (27 in the treatment group). The volume of new brain lesion for the treatment group was (mean±standard error of the mean) 44.00±64.00 versus 126.56±28.74 mm3 in the control group (p=0.004). Of the treatment group, 41% demonstrated new postoperative lesions versus 66% in the control group (p=0.03). The complication rate was comparable in both groups. CONCLUSIONS The CardioGard cannula is safe and efficient in use during open-heart surgery. Efficacy was demonstrated by the removal of a substantial amount of emboli, a significant reduction in the volume of new brain lesions, and the percentage of patients experiencing new brain lesions.

Increased sleep need and daytime sleepiness 6 months after traumatic brain injury: a prospective controlled clinical trial.

Post-traumatic sleep-wake disturbances are common after acute traumatic brain injury. Increased sleep need per 24 h and excessive daytime sleepiness are among the most prevalent post-traumatic sleep disorders and impair quality of life of trauma patients. Nevertheless, the relation between traumatic brain injury and sleep outcome, but also the link between post-traumatic sleep problems and clinical measures in the acute phase after traumatic brain injury has so far not been addressed in a controlled and prospective approach. We therefore performed a prospective controlled clinical study to examine (i) sleep-wake outcome after traumatic brain injury; and (ii) to screen for clinical and laboratory predictors of poor sleep-wake outcome after acute traumatic brain injury. Forty-two of 60 included patients with first-ever traumatic brain injury were available for follow-up examinations. Six months after trauma, the average sleep need per 24 h as assessed by actigraphy was markedly increased in patients as compared to controls (8.3 ± 1.1 h versus 7.1 ± 0.8 h, P < 0.0001). Objective daytime sleepiness was found in 57% of trauma patients and 19% of healthy subjects, and the average sleep latency in patients was reduced to 8.7 ± 4.6 min (12.1 ± 4.7 min in controls, P = 0.0009). Patients, but not controls, markedly underestimated both excessive sleep need and excessive daytime sleepiness when assessed only by subjective means, emphasizing the unreliability of self-assessment of increased sleep propensity in traumatic brain injury patients. At polysomnography, slow wave sleep after traumatic brain injury was more consolidated. The most important risk factor for developing increased sleep need after traumatic brain injury was the presence of an intracranial haemorrhage. In conclusion, we provide controlled and objective evidence for a direct relation between sleep-wake disturbances and traumatic brain injury, and for clinically significant underestimation of post-traumatic sleep-wake disturbances by trauma patients.

Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial

IMPORTANCE High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. OBJECTIVE To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. DESIGN, SETTING, AND PARTICIPANTS The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. INTERVENTIONS HSCT vs intravenous pulse cyclophosphamide. MAIN OUTCOMES AND MEASURES The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. RESULTS A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. CONCLUSIONS AND RELEVANCE Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN54371254.

The effects of erythritol air-polishing powder on microbiologic and clinical outcomes during supportive periodontal therapy: Six-month results of a randomized controlled clinical trial.

OBJECTIVES To characterize the physical characteristics of a new low abrasive erythritol powder (EPAP) and to evaluate its influence on the clinical and microbiologic parameters over a period of 6 months in patients undergoing supportive periodontal therapy (SPT). METHOD AND MATERIALS Prior to the clinical application, the particle size and abrasion level of EPAP were compared to glycine air-polishing powder (GPAP) ex vivo. Subsequently, 40 chronic periodontitis patients previously enrolled in SPT were randomly assigned into two groups for the treatment with subgingival EPAP or repeated scaling and root planing (SRP). At baseline (BL), bleeding on probing positive (BOP+) sites with probing pocket depth (PPD) of ≥ 4 mm but no detectable calculus were defined as study sites. During SPT, these sites were either treated by EPAP or SRP at BL, 3, and 6 months (3M, 6M). When indicated, additional SRP was provided. Plaque Index, BOP, PPD, clinical attachment level (CAL), and subgingival plaque were evaluated at BL and 6M. RESULTS EPAP yielded lower abrasiveness and smaller particle sizes when compared to GPAP. In 38 patients completing the study, EPAP and SRP resulted in significant reductions of BOP% (EPAP, 40.45%; SRP, 42.53%), PPD (EPAP, -0.67; SRP, -0.68), and increase of CAL (EPAP, 0.48; SRP, 0.61) while at 6M no statistically significant between-group differences were observed (P > .05). Microbiologic evaluation revealed minor shifts in the composition of the subgingival biofilm without influence on periodontopathogenic bacteria. CONCLUSION The subgingival use of EPAP by means of an air-polishing device may be considered safe and may lead to comparable clinical and microbiologic outcomes to those obtained with SRP. CLINICAL RELEVANCE The subgingival use of EPAP appears to represent a promising modality for the removal of subgingival biofilm during SPT.

Pulmonary Vein Isolation Versus Defragmentation: The CHASE-AF Clinical Trial

BACKGROUND Long-term success rates using ablation for persistent atrial fibrillation (AF) are disappointing and usually do not exceed 60%. OBJECTIVES This study sought to compare arrhythmia-free survival between pulmonary vein isolation (PVI) and a stepwise approach (full defrag) consisting of PVI, ablation of complex fractionated electrograms, and additional linear ablation lines in the setting of atrial tachycardias (AT) in patients with persistent AF after PVI. METHODS From November 2010 to February 2013, 205 patients (151 men; 61.7 ± 10.2 years of age) underwent de novo ablation for persistent AF. Subsequently, patients were prospectively randomized to either PVI alone (n = 78) or full defrag (n = 75), with 52 patients not randomized due to AF termination with the original PVI. The primary endpoint was recurrence of any AT after a blanking period of 3 months. RESULTS During the entire study, 241 ablations were performed (mean: 1.59 in the PVI-alone group, 1.55 in the full-defrag group). With the stepwise approach, termination of AF occurred in 45 (60%) patients. However, arrhythmia-free survival did not differ whether patients underwent single or multiple procedures (p = 0.468). Procedure duration, fluoroscopy time, and radiofrequency duration were significantly longer in the full-defrag group (all p < 0.001). CONCLUSIONS A stepwise approach aimed at AF termination does not seem to provide additional benefit over PVI alone in patients with persistent AF, but it is associated with significantly longer procedural and fluoroscopic duration as well as radiofrequency application time. (The Randomized Catheter Ablation of Persist End Atrial Fibrillation Study [CHASE-AF]; NCT01580124).

Antiplatelet therapy duration following bare metal or drug-eluting coronary stents: the dual antiplatelet therapy randomized clinical trial

IMPORTANCE Despite antirestenotic efficacy of coronary drug-eluting stents (DES) compared with bare metal stents (BMS), the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Although dual antiplatelet therapy (DAPT) beyond 1 year provides ischemic event protection after DES, ischemic event risk is perceived to be less after BMS, and the appropriate duration of DAPT after BMS is unknown. OBJECTIVE To compare (1) rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE; composite of death, myocardial infarction, or stroke) after 30 vs 12 months of thienopyridine in patients treated with BMS taking aspirin and (2) treatment duration effect within the combined cohorts of randomized patients treated with DES or BMS as prespecified secondary analyses. DESIGN, SETTING, AND PARTICIPANTS International, multicenter, randomized, double-blinded, placebo-controlled trial comparing extended (30-months) thienopyridine vs placebo in patients taking aspirin who completed 12 months of DAPT without bleeding or ischemic events after receiving stents. The study was initiated in August 2009 with the last follow-up visit in May 2014. INTERVENTIONS Continued thienopyridine or placebo at months 12 through 30 after stent placement, in 11,648 randomized patients treated with aspirin, of whom 1687 received BMS and 9961 DES. MAIN OUTCOMES AND MEASURES Stent thrombosis, MACCE, and moderate or severe bleeding. RESULTS Among 1687 patients treated with BMS who were randomized to continued thienopyridine vs placebo, rates of stent thrombosis were 0.5% vs 1.11% (n = 4 vs 9; hazard ratio [HR], 0.49; 95% CI, 0.15-1.64; P = .24), rates of MACCE were 4.04% vs 4.69% (n = 33 vs 38; HR, 0.92; 95% CI, 0.57-1.47; P = .72), and rates of moderate/severe bleeding were 2.03% vs 0.90% (n = 16 vs 7; P = .07), respectively. Among all 11,648 randomized patients (both BMS and DES), stent thrombosis rates were 0.41% vs 1.32% (n = 23 vs 74; HR, 0.31; 95% CI, 0.19-0.50; P < .001), rates of MACCE were 4.29% vs 5.74% (n = 244 vs 323; HR, 0.73; 95% CI, 0.62-0.87; P < .001), and rates of moderate/severe bleeding were 2.45% vs 1.47% (n = 135 vs 80; P < .001). CONCLUSIONS AND RELEVANCE Among patients undergoing coronary stent placement with BMS and who tolerated 12 months of thienopyridine, continuing thienopyridine for an additional 18 months compared with placebo did not result in statistically significant differences in rates of stent thrombosis, MACCE, or moderate or severe bleeding. However, the BMS subset may have been underpowered to identify such differences, and further trials are suggested. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00977938.

Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

BACKGROUND Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. METHODS In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). RESULTS Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. CONCLUSIONS Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. CLINICAL TRIALS REGISTRATION ISRCT 72102977.

Non-surgical treatment of pain associated with posterior tibial tendon dysfunction: study protocol for a randomised clinical trial

BACKGROUND Symptoms associated with pes planovalgus or flatfeet occur frequently, even though some people with a flatfoot deformity remain asymptomatic. Pes planovalgus is proposed to be associated with foot/ankle pain and poor function. Concurrently, the multifactorial weakness of the tibialis posterior muscle and its tendon can lead to a flattening of the longitudinal arch of the foot. Those affected can experience functional impairment and pain. Less severe cases at an early stage are eligible for non-surgical treatment and foot orthoses are considered to be the first line approach. Furthermore, strengthening of arch and ankle stabilising muscles are thought to contribute to active compensation of the deformity leading to stress relief of soft tissue structures. There is only limited evidence concerning the numerous therapy approaches, and so far, no data are available showing functional benefits that accompany these interventions. METHODS After clinical diagnosis and clarification of inclusion criteria (e.g., age 40-70, current complaint of foot and ankle pain more than three months, posterior tibial tendon dysfunction stage I & II, longitudinal arch flattening verified by radiography), sixty participants with posterior tibial tendon dysfunction associated complaints will be included in the study and will be randomly assigned to one of three different intervention groups: (i) foot orthoses only (FOO), (ii) foot orthoses and eccentric exercise (FOE), or (iii) sham foot orthoses only (FOS). Participants in the FOO and FOE groups will be allocated individualised foot orthoses, the latter combined with eccentric exercise for ankle stabilisation and strengthening of the tibialis posterior muscle. Participants in the FOS group will be allocated sham foot orthoses only. During the intervention period of 12 weeks, all participants will be encouraged to follow an educational program for dosed foot load management (e.g., to stop activity if they experience increasing pain). Functional impairment will be evaluated pre- and post-intervention by the Foot Function Index. Further outcome measures include the Pain Disability Index, Visual Analogue Scale for pain, SF-12, kinematic data from 3D-movement analysis and neuromuscular activity during level and downstairs walking. Measuring outcomes pre- and post-intervention will allow the calculation of intervention effects by 3×3 Analysis of Variance (ANOVA) with repeated measures. DISCUSSION The purpose of this randomised trial is to evaluate the therapeutic benefit of three different non-surgical treatment regimens in participants with posterior tibial tendon dysfunction and accompanying pes planovalgus. Furthermore, the analysis of changes in gait mechanics and neuromuscular control will contribute to an enhanced understanding of functional changes and eventually optimise conservative management strategies for these patients. TRIAL REGISTRATION ClinicalTrials.gov Protocol Registration System: ClinicalTrials.gov ID NCT01839669.

Retrievability of implant-supported crowns when using three different cements: a controlled clinical trial

PURPOSE The purpose of this study was to analyze the removal of implant-supported crowns retained by three different cements using an air-accelerated crown remover and to evaluate the patients' response to the procedure. MATERIALS AND METHODS This controlled clinical trial was conducted with 21 patients (10 women, 11 men; mean age: 51 ± 10.2 years) who had received a total of 74 implants (all placed in the posterior zone of the mandible). Four months after implant surgery, the crowns were cemented on standard titanium abutments of different heights. Three different cements (two temporary: Harvard TEMP and Improv; and one definitive: Durelon) were used and randomly assigned to the patients. Eight months later, one blinded investigator removed all crowns. The number of activations of the instrument (CORONAflex, KaVo) required for crown removal was recorded. The patients completed a questionnaire retrospectively to determine the impact of the procedure and to gauge their subjective perception. A linear regression model and descriptive statistics were used for data analysis. RESULTS All crowns could be retrieved without any technical complications or damage. Both abutment height (P = .019) and cement type (P = .004) had a significant effect on the number of activations, but the type of cement was more important. An increased total number of activations had no or only a weak correlation to the patients' perception of concussion, noise, pain, and unwillingness to use the device. CONCLUSIONS Cemented implant crowns can be removed, and the application of an air-accelerated device is a practicable method. A type of cement with appropriate retention force has to be selected. The impact on the patients' subjective perception should be taken into account.

A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus: The RESERVOIR Clinical Trial.

OBJECTIVES The aim of this study was to compare the efficacy of amphilimus-eluting stents (AES) with that of everolimus-eluting stents (EES) in patients with diabetes mellitus (DM). BACKGROUND The AES is a polymer-free drug-eluting stent that elutes sirolimus formulated with an amphiphilic carrier from laser-dug wells. This technology could be associated with a high efficacy in patients with DM. METHODS This was a multicenter, randomized, noninferiority trial. Patients with DM medically treated with oral glucose-lowering agents or insulin and de novo coronary lesions were randomized in a 1:1 fashion to AES or EES. The primary endpoint was the neointimal (NI) volume obstruction assessed by optical coherence tomography at 9-month follow-up. RESULTS A total of 116 lesions in 112 patients were randomized. Overall, 40% were insulin-treated patients, with a median HbA1c of 7.3% (interquartile range: 6.7% to 8.0%). The primary endpoint, NI volume obstruction, was 11.97 ± 5.94% for AES versus 16.11 ± 18.18% for EES, meeting the noninferiority criteria (p = 0.0003). Pre-specified subgroup analyses showed a significant interaction between stent type and glycemic control (p = 0.02), with a significant reduction in NI hyperplasia in the AES group in patients with the higher HbA1c (p = 0.03). By quantitative coronary angiography, in-stent late loss was 0.14 ± 0.24 for AES versus 0.24 ± 0.57 mm for EES (p = 0.27), with a larger minimal lumen diameter at follow-up for AES (p = 0.02), mainly driven by 2 cases of occlusive restenosis in the EES group. CONCLUSIONS AES are noninferior to EES for the coronary revascularization of patients with DM. These results suggest a high efficacy of the AES and may support the potential benefit of this stent in patients with DM. (A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus [RESERVOIR]; NCT01710748).

Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial.

BACKGROUND REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding. METHODS We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13,200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions. FINDINGS 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio [OR] 1·05, 95% CI 0·80-1·39; p=0·72). Major bleeding was similar between treatment groups (seven [<1%] of 1605 receiving REG1 vs two [<1%] of 1601 treated with bivalirudin; OR 3·49, 95% CI 0·73-16·82; p=0·10), but major or minor bleeding was increased with REG1 (104 [6%] vs 65 [4%]; 1·64, 1·19-2·25; p=0·002). INTERPRETATION The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin. FUNDING Regado Biosciences Inc.

A Single-blinded, Randomized Clinical Trial of How to Implement an Evidence-based Treatment for Generalized Anxiety Disorder [IMPLEMENT] — Effects of Three Different Strategies of Implementation

BACKGROUND: Despite long-standing calls to disseminate evidence-based treatments for generalized anxiety (GAD), modest progress has been made in the study of how such treatments should be implemented. The primary objective of this study was to test three competing strategies on how to implement a cognitive behavioral treatment (CBT) for out-patients with GAD (i.e., comparison of one compensation vs. two capitalization models). METHODS: For our three-arm, single-blinded, randomized controlled trial (implementation of CBT for GAD [IMPLEMENT]), we recruited adults with GAD using advertisements in high-circulation newspapers to participate in a 14-session cognitive behavioral treatment (Mastery of your Anxiety and Worry, MAW-packet). We randomly assigned eligible patients using a full randomization procedure (1:1:1) to three different conditions of implementation: adherence priming (compensation model), which had a systematized focus on patients' individual GAD symptoms and how to compensate for these symptoms within the MAW-packet, and resource priming and supportive resource priming (capitalization model), which had systematized focuses on patients' strengths and abilities and how these strengths can be capitalized within the same packet. In the intention-to-treat population an outcome composite of primary and secondary symptoms-related self-report questionnaires was analyzed based on a hierarchical linear growth model from intake to 6-month follow-up assessment. This trial is registered at ClinicalTrials.gov (identifier: NCT02039193) and is closed to new participants. FINDINGS: From June 2012 to Nov. 2014, from 411 participants that were screened, 57 eligible participants were recruited and randomly assigned to three conditions. Forty-nine patients (86%) provided outcome data at post-assessment (14% dropout rate). All three conditions showed a highly significant reduction of symptoms over time. However, compared with the adherence priming condition, both resource priming conditions indicated faster symptom reduction. The observer ratings of a sub-sample of recorded videos (n = 100) showed that the therapists in the resource priming conditions conducted more strength-oriented interventions in comparison with the adherence priming condition. No patients died or attempted suicide. INTERPRETATION: To our knowledge, this is the first trial that focuses on capitalization and compensation models during the implementation of one prescriptive treatment packet for GAD. We have shown that GAD related symptoms were significantly faster reduced by the resource priming conditions, although the limitations of our study included a well-educated population. If replicated, our results suggest that therapists who implement a mental health treatment for GAD might profit from a systematized focus on capitalization models. FUNDING: Swiss Science National Foundation (SNSF-Nr. PZ00P1_136937/1) awarded to CF. KEYWORDS: Cognitive behavioral therapy; Evidence-based treatment; Implementation strategies; Randomized controlled trial

Multilevel analysis for a longitudinal clinical trial

This study applies the multilevel analysis technique to longitudinal data of a large clinical trial. The technique accounts for the correlation at different levels when modeling repeated blood pressure measurements taken throughout the trial. This modeling allows for closer inspection of the remaining correlation and non-homogeneity of variance in the data. Three methods of modeling the correlation were compared. ^

Hepatitis B vaccination of high risk pregnant women: A clinical trial at Parkland Memorial Hospital

Hepatitis B infection is a major public health problem of global proportions. It is estimated that 2 billion people worldwide are infected by the Hepatitis B virus (HBV) at some point, and 350 million are chronic carriers. The Centers for Disease Control and Prevention (CDC) report an incidence in the United States of 140,000–320,000 infections each year (asymptomatic and symptomatic), and estimate 1–1.25 million people are chronically infected. Hepatitis B and its chronic complications (cirrhosis of the liver, liver failure, hepatocellular carcinoma) responsible for 4,000–5,000 deaths in America each year. ^ One quarter of those who become chronic carriers develop progressive liver disease, and chronic HBV infection is thought to be responsible for 60 million cases of cirrhosis worldwide, surpassing alcohol as a cause of liver disease. Since there are few treatment options for the person chronically infected with Hepatitis B, and what is available is expensive, prevention is clearly best strategy for combating this disease. ^ Since the approval of the Hepatitis B vaccine in 1981, national and international vaccination campaigns have been undertaken for the prevention of Hepatitis B. Despite encouraging results, however, studies indicate that prevalence rates of Hepatitis B infection have not been significantly reduced in certain high risk populations because vaccination campaigns targeting those groups do not exist and opportunities for vaccination by individual physicians in clinical settings are often missed. Many of the high-risk individuals who go unvaccinated are women of childbearing age, and a significant proportion of these women become infected with the Hepatitis B virus (HBV) during pregnancy. Though these women are often seen annually or for prenatal care (because of the close spacing of their children and their high rate of fertility), the Hepatitis B vaccine series is seldom recommended by their health care provider. In 1993, ACOG issued a statement recommending Hepatitis B vaccination of pregnant women who were defined as high-risk by diagnosis of a sexually transmitted disease. ^ Hepatitis B vaccine has been extensively studied in the non-pregnant population. The overall efficacy of the vaccine in infants, children and adults is greater than 90%. In the small clinical trials to date, the vaccine seemed to be effective in those pregnant women receiving 3 doses; however, by using the usual 0, 1 and 6 month regimen, most pregnant women were unable to complete a full series during pregnancy. There is data now available supporting the use of an "accelerated" dosing schedule at 0, 1 and 4 months. This has not been evaluated in pregnant women. A clinical trial proving the efficacy of the 0, 1, 4 schedule and its feasibility in this population would add significantly to the body of research in this area, and would have implications for public health policy. Such a trial was undertaken in the Parkland Memorial Hospital Obstetrical Infectious Diseases clinic. In this study, the vaccine was very well tolerated with no major adverse events reported, 90% of fully vaccinated patients achieved immunity, and only Body Mass Index (BMI) was found to be a significant factor affecting efficacy. This thesis will report the results of the trial and compare it to previous trials, and will discuss barriers to implementation, lessons learned and implications for future trials. ^