Larger RCT Research Articles

Does Helica treatment of early endometriosis confer short- and long-term benefits in terms of pain relief and sub-fertility?

Early-stage endometriosis is a known contributing factor for chronic pelvic pain and sub-fertility. To determine whether Helica Thermal Coagulation is an effective short- and long-term treatment for endometriosis-associated chronic pelvic pain and sub-fertility. Thirty six patients were followed up from 6 weeks to 1 year post-Helica treatment of early endometriosis. Pain relief was assessed subjectively. Eight of the women suffered from sub-fertility in addition to pelvic pain, while three patients suffered from sub-fertility alone. Ninety-three percent were pain free at 6 weeks, 75 % were pain free at 6 months and 37.5 % remained pain free at 1-year follow-up. Of those who continued to have pain at 1-year follow-up, three had repeated Helica treatment, two had hysterectomy and bilateral salpingoopherectomy, and the rest were commenced on different hormonal treatment to control endometriosis. Ten women (62 %) conceived within 1 year of treatment. Helica coagulation seems to be an effective way of treating early endometriosis-associated pelvic pain and sub-fertility. However, its effects only seem to be short term, with a decline in symptom relief and pregnancy rate over the 12-month post-operative period. Larger RCT are required.

FRI0455 High intensity aerobic exercise in ankylosing spondylitis reduces arterial stiffness: results from a randomized controlled trial

BackgroundPatients with ankylosing spondylitis (AS) are at increased risk of cardiovascular disease (CVD). However, we do not know etiological mechanism or how to reduce risk. Exercise is known to reduce...

Maternal iron status and depressive symptoms in rural Bangladesh

Iron deficiency and maternal depression are prevalent in developing countries like Bangladesh. Our aim was two‐fold: 1) determine the relationship between iron status and maternal depressive symptoms; 2) assess the Center for Epidemiological Studies Depression Scale (CESD) in women of rural Bangladesh. Mother‐infant dyads taken from a larger RCT (Chang et al., 2010) to improve diarrhea and anemia in rural Bangladesh were analyzed. Depressive symptoms were collected at baseline (n=113), 3 mo (n=319), and 6 mo (n=328). Maternal ferritin and transferrin receptor were collected between baseline and 3 mo (n=307) and at 6 mo (n=108). Factor analysis of CESD structure resulted in a 3‐factor solution: interpersonal difficulty/somatic inhibition, depressed affect, and well‐being. We found a 70.3% prevalence of high depressive symptoms (CESD ≥ 16) but low prevalence (11.2%) of iron depletion (ferritin < 20 ng/mL). Nonetheless, iron depleted (ID) women had higher depressive symptoms than iron sufficient (IS) women at every time point (ANOVA, p<0.04). Multivariate regression adjusted for covariates (child age & sex, WAZ, assets), revealed that body iron at 6 mo (assessed with Cook's equation) was related to the “depressed affect” factor scores at 6 mo (p<0.048). This relationship between iron depletion and CESD symptomatology warrants validation of CESD factor structure and cutoff point in Bangladesh.Grant Funding Source: USAID to the Johns Hopkins Global Research Activity Cooperative Agreement

Abstract TP319: Randomized Pilot Trial of Usual Care versus LIFE (Lifestyle Intervention using Functional Exercise to Reduce Falls) in Those with Mild Stroke

Purpose/Objectives: Falls are a health concern post-stroke with 30% of those who return home reporting loss of balance in the first month. Individuals with “mild” stroke are especially vulnerable as they are often discharged home quickly without exposure to balance improvement/falls prevention programs. It is important to identify effective interventions that can be offered in the naturalistic home setting. We assessed, for individuals with a first mild stroke, the impact of a home-based falls prevention program - LiFE (Lifestyle Intervention using Functional Exercise) vs STRUCTURED vs CONTROL intervention on rate of falls (self-report) and secondary outcomes including static and dynamic balance, etc.. This pilot RCT data is from a larger RCT (n=317) comparing these three interventions in older individuals (>70) at high risk for falls. Methods: Three group parallel RCT with all interventions taught at home. The LiFE group received teaching on principles of balance and strength training; applied while the individual performed common daily activities. STRUCTURED received balance and lower limb strength exercises while CONTROLS received gentle exercise. Blind assessments of the main outcomes of interest were performed before randomisation, after intervention (six months) and at one year (follow-up). Results: Of 39 participants 14 were randomized to LiFE; 14 to STRUCTURED; and, 11 to CONTROL. There were fewer fallers in the group receiving LiFE (n=6/14) vs the other two groups: (RR = 0.67; LiFE vs CONTROL); but not between STRUCTURED vs CONTROL (RR= 1.01). However, when number of falls was analyzed, LiFE had the greatest number - 26 vs 13 vs 20 - STRUCTURED and CONTROL respectively. Further data exploration revealed that LiFE was the only group with participants (n=3) who had >5 falls. Conclusion: Although LiFE was associated with a reduction in fallers; there was a disconcertingly higher rate of frequent falls in a few participants. These findings, while on a small sample, suggest that LiFE, which requires judgment and problem solving, may be suitable for a specified sub-set. The LiFE intervention “how to” and patient selection criteria will be discussed during the presentation.

Design and Methods for a Comparative Effectiveness Pilot Study: Virtual World vs. Face-to-Face Diabetes Self-Management.

BackgroundType 2 diabetes (diabetes) is a serious threat to public health in the United States and disproportionally affects many racial/ethnic minority groups, including African Americans. Limited access to treatment and high attrition rates further contribute to health disparities in diabetes-related morbidity and mortality among minorities. Greater opportunities for increasing access and decreasing barriers to treatment are needed. Technology-based interventions have potential for accomplishing this goal but evidence of feasibility and potential effectiveness is lacking, especially for populations that traditionally have limited educational attainment and low computer literacy.ObjectiveThis paper describes the design and methods of a pilot randomized clinical trial that will compare the feasibility and potential efficacy of delivering a diabetes self-management intervention via a virtual world vs. a face-to-face format.MethodsStudy participants (n=100) will be African American women with uncontrolled type 2 diabetes recruited from primary care practices and affiliated health centers at a large safety net hospital in Massachusetts. Participants will be randomized into a virtual world-based (VW) intervention condition or a face-to-face control condition. Both conditions provide the same theory-based curriculum and equivalent exposure to the self-management program (eight group sessions), and both will be delivered by a single intervention team (a dietitian and a diabetes educator). Assessments will be conducted at baseline and 4 months. Feasibility will be determined by evaluating the degree to which participants engage in the VW-based intervention compared to face to face (number of sessions completed). Potential efficacy will be determined by comparing change in physiological (glycemic control) and behavioral (self-reported dietary intake, physical activity, blood glucose self-monitoring, and medication adherence) outcomes between the experimental and control groups.ResultsThe primary outcomes of interest are feasibility of the VW intervention and its potential efficacy on glucose control and diabetes self-management behaviors, compared to the face-to-face condition. Analysis will use a two-sample Kolmogorov-Smirnov test for changes in variable distribution. P values will be calculated using binomial tests for proportions and t tests for continuous variables.ConclusionsIf the intervention is found to be feasible and promising, it will be tested in a larger RCT.

Properties of the Achievement of Therapeutic Objectives Scale (ATOS): A Generalizability Theory study

The psychometric properties of the process instrument Achievement of Therapeutic Objectives Scale (ATOS) were examined in this study. Generalizability Theory (GT) was used to evaluate variability attached to several possible sources of error. A random sample of 24 psychotherapy sessions was selected from a larger RCT trial including Cluster C patients and rated in different rating conditions (rating all scales versus rating a subgroup of the scales). Two G-study designs were used to compute variance components and generalizability coefficients. The results provided evidence that the ATOS is sensitive to differences among patients and to differences among subscales within patients (i.e., to different constructs within the ATOS). Rating condition contributed much to variability in scores when the ATOS scales were examined separately, but this variability was negligible when all scales were included in the same analysis. There was little variability due to raters, which indicates that adequately trained raters are able to apply the ATOS without contributing to measurement error.

A Randomised Placebo-controlled Double-blind Trial to Evaluate Lipid-lowering Pharmacotherapy on Proteolysis and Inflammation in Abdominal Aortic Aneurysms

Objectives: Modulation of abdominal aortic aneurysm (AAA) expansion by HMG-CoA reductase inhibitors (statins) might be linked to reducing IL-6 and MMP-9, which may be consequent on reducing plasma cholesterol. Ezetimibe is a novel cholesterol absorption inhibitor used in combination with statins. This pilot study compared the biological effects of ezetimibe combination therapy with simvastatin alone on parameters relevant to aneurysm expansion including cytokines and proteolytic enzymes. Design: Randomised placebo-controlled double-blind trial. Materials & Methods: Eighteen patients scheduled for elective open AAA repair were randomised to simvastatin 40 mg plus ezetimibe 10 mg (n = 9), or simvastatin 40 mg plus placebo (n = 9), for 32.5 days (IQR 28–50.5) until the day of surgery. Total concentrations of TNF-α, IL-1β, IL-6, IL-8, IL-10, MMPs-1, -2, -3, -8, -9, -12, -13, TIMP-1 and -2 were measured in plasma, aortic wall homogenates and tissue culture explants. Results: Two patients in the placebo arm did not undergo open repair precluding aortic samples. Ezetimibe was associated with a significant reduction in aortic wall MMP-9 (p = 0.02) and aortic wall IL-6 (p = 0.02), associated with a reduction in plasma lipids. Conclusions: These results suggest that ezetimibe combination therapy reduces aortic wall proteolysis and inflammation, key processes that drive AAA expansion. A larger RCT is justified focussing on aneurysm growth rates in small AAA.

A Randomised Placebo-controlled Double-blind Trial to Evaluate Lipid-lowering Pharmacotherapy on Proteolysis and Inflammation in Abdominal Aortic Aneurysms

Objectives Modulation of abdominal aortic aneurysm (AAA) expansion by HMG-CoA reductase inhibitors (statins) might be linked to reducing IL-6 and MMP-9, which may be consequent on reducing plasma cholesterol. Ezetimibe is a novel cholesterol absorption inhibitor used in combination with statins. This pilot study compared the biological effects of ezetimibe combination therapy with simvastatin alone on parameters relevant to aneurysm expansion including cytokines and proteolytic enzymes. Design Randomised placebo-controlled double-blind trial. Materials & Methods Eighteen patients scheduled for elective open AAA repair were randomised to simvastatin 40 mg plus ezetimibe 10 mg ( n = 9), or simvastatin 40 mg plus placebo ( n = 9), for 32.5 days (IQR 28–50.5) until the day of surgery. Total concentrations of TNF-α, IL-1β, IL-6, IL-8, IL-10, MMPs-1, -2, -3, -8, -9, -12, -13, TIMP-1 and -2 were measured in plasma, aortic wall homogenates and tissue culture explants. Results Two patients in the placebo arm did not undergo open repair precluding aortic samples. Ezetimibe was associated with a significant reduction in aortic wall MMP-9 ( p = 0.02) and aortic wall IL-6 ( p = 0.02), associated with a reduction in plasma lipids. Conclusions These results suggest that ezetimibe combination therapy reduces aortic wall proteolysis and inflammation, key processes that drive AAA expansion. A larger RCT is justified focussing on aneurysm growth rates in small AAA.

Survival after trimodality therapy for malignant pleural mesothelioma: Radical Pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy

Introduction The role of surgery in the management of malignant pleural mesothelioma (MPM) is controversial and there are no established guidelines. We describe the feasibility and long-term outcomes associated with Radical Pleurectomy (RP) as surgical therapy modality in a standardized trimodality therapy concept of MPM. Methods From November 2002 to October 2007, 35 out of 102 consecutive patients with MPM were enrolled in our prospective database. They underwent trimodality therapy, including RP followed by 4 cycles of chemotherapy with Cisplatin (75 mg/m 2)/Pemetrexed (500 mg/m 2) and radiotherapy 4–6 weeks after operation. Results Median age was 65 years. Nineteen patients were in advanced stages III and IV (54.3%). Tumor histology was epithelial in 27 patients (77.1%). Macroscopic complete resection could be achieved in 18 patients (51.4%). Surgical morbidity/mortality and trimodality treatment-related mortality were 20.0%, 2.9% and 5.8%, respectively. Thirty-three patients completed the trimodality therapy. Median follow-up was 21.7 months. Overall median survival was 30.0 months. One-, 2-, and 3-year-survival were 69%, 50% and 31%, respectively. Advanced stages III/IV ( p = 0.06), macroscopic incomplete resections ( p = 0.001), non-epithelial histology ( p = 0.55) and nodal metastases ( p = 0.19) were associated with poorer survival. Conclusions The trimodality therapy concept with RP demonstrates promising results in terms of long-term survival, morbidity and mortality. We propose that a surgical philosophy of limiting the procedure related morbidity while achieving comparable cytoreductive results allows patients to maintain physiological reserve to be eligible for multimodality treatment options in the long-term. The observed and theoretical benefits of this trimodality treatment approach warrant confirmation in larger RCT.

Abstract 4066: Response to Symptom Management Intervention among Functionally Impaired Older Adults Following Coronary Artery Bypass Surgery (CABS)

Older adults with poor functioning preoperatively are at risk for delayed recovery following CABS. The purpose of this study was to determine if a symptom management (SM) telehealth intervention was effective in improving early recovery outcomes (physical activity, physiological and psychological functioning) for older adults with impaired functioning prior to CABS. A descriptive, repeated measures design was used in this subanalysis of a larger RCT. Subjects in the parent study (N=232), who met the preoperative impaired functioning criteria [physical component score of Medical Outcomes Study Short-form 36 (MOS SF-36) <50 and a RISKO score of ≥ 6], were included in either the SM intervention group (n=23) or the usual care group (n=31). Methods : Physical activity was measured at baseline using the Modified 7-Day Activity Interview; and at follow-up times by the RT3® accelerometer and an Activity Diary. Physiological and psychosocial functioning was measured by the MOS SF-36. Data was gathered prior to hospital discharge, at 3- and 6-weeks and 3-months after hospital discharge. Findings : Subjects ranged in age from 65– 85 years, with a mean of 71.6 (± 5.1) years. Analysis of covariance with repeated measures was used on physical activity and functioning measures, with preoperative levels used as covariates. There were significant group by time effects, with the SM intervention group as compared to the usual care group having higher levels of physical activity over time for: average daily activity counts [F (3,37)=3.55, p<.05]; levels of estimated energy expenditure (average kcal/kg/day expended) as measured by both the RT3® [F (3,37)=2.89, p<.05] and Activity Diary [F (3,42)=3.01, p<.05]; and average minutes/day in moderate or higher levels of activity [F (3,42)=3.18, p<.05]. Both groups had significantly (p<.05) increased role-physical, mental and social functioning over time. Conclusions : Study findings demonstrated the responsiveness of a subgroup of CABS subjects with impaired preoperative functioning to a SM intervention for older adults. Subjects’ improvements in physical activity functioning can help to decrease their risk for morbidity and mortality that can be associated with poor functioning after cardiac events.

Vitamin K2

Vitamin K2 has been approved for the treatment of osteoporosis in Japan since 1995. Vitamin K2 treatment in osteoporosis has been shown to inhibit the occurrence of new bone fractures and to maintain BMD. The uniqueness of the prevention of bone fractures by vitamin K2 is that there has been no direct evidence of the relationship between increase of BMD and a decrease in the occurrence of bone fractures. A recent systematic review of seven Japanese randomized controlled trials by Cockayne has also shown that supplementation with phytonadione (Vitamin K1) and menaquinone (Vitamin K2) , particularly menaquinone-4, is associated with increased BMD and reduced fracture incidence. To confirm these results, a larger well design RCT using fractures as the primary endpoint is clearly needed.

The effects of group motivational interviewing and externalizing conversations for adolescents with Type-1 diabetes

There is a generally appreciated need for psychosocial interventions to help adolescents with Type-1 diabetes cope more effectively with their diabetes, but guidance literature is scarce. We hypothesized perceptions and coping with diabetes could be changed using group motivational interviewing (MI) and externalizing conversations (EC). This paper reports qualitative research findings from a preliminary study of group MI - EC intervention for adolescents with Type-1 diabetes. Twenty adolescents with poorly controlled diabetes were allocated to treatment and control conditions. Treatment consisted of EC and MI over six 1-h weekly sessions. Control consisted of usual care. Participants completed semi-structured questionnaires assessing their perceptions and management of diabetes before, after and 6 months after the intervention. Questionnaires compiled for the study were analysed using content analysis. The treatment group shifted their perceptions of diabetes. They felt less threatened, had more feelings of control and acceptance. Consequences of having diabetes were seen as having a less restrictive influence on their lifestyle than previously. From this exploratory analysis we tentatively conclude this innovative group intervention led to an adaptive shift in illness perception. We are planning a larger RCT to investigate the relationship between shifts in perception and better diabetes management.