Note: This page contains sample records for the topic study group trial from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: August 15, 2014.
1

International Pediatric MS Study Group Clinical Trials Summit  

PubMed Central

Objective: Pediatric studies for new biological agents are mandated by recent legislation, necessitating careful thought to evaluation of emerging multiple sclerosis (MS) therapies in children with MS. Challenges include a small patient population, the lack of prior randomized clinical trials, and ethical concerns. The goal of this meeting was to assess areas of consensus regarding clinical trial design and outcome measures among academic experts involved in pediatric MS care and research. Methods: The Steering Committee of the International Pediatric MS Study Group identified key focus areas for discussion. A total of 69 meeting attendees were assembled, including 35 academic experts. Regulatory and pharmaceutical representatives also attended, and provided input, which informed academic expert consensus decisions. Results: The academic experts agreed that clinical trials were necessary in pediatric MS to obtain pharmacokinetic, safety and efficacy data, and regulatory approval allowing for greater medication access. The academic experts agreed that relapse was an appropriate primary outcome measure for phase III pediatric trials. An international standardized cognitive battery was identified. The pros and cons of various trial designs were discussed. Guidelines surrounding MRI studies, pharmacokinetics, pharmacodynamics, and registries were developed. The academic experts agreed that given the limited subject pool, a stepwise approach to the launch of clinical trials for the most promising medications is necessary in order to ensure study completion. Alternative approaches could result in unethical exposure of patients to trial conditions without gaining knowledge. Conclusion: Consensus points for conduct of clinical trials in the rare disease pediatric MS were identified amongst a panel of academic experts, informed by regulatory and industry stakeholders.

Tardieu, Marc; Amato, Maria Pia; Banwell, Brenda; Bar-Or, Amit; Ghezzi, Angelo; Kornberg, Andrew; Krupp, Lauren B.; Pohl, Daniela; Rostasy, Kevin; Tenembaum, Silvia; Waubant, Emmanuelle; Wassmer, Evangeline

2013-01-01

2

'Putting Life in Years' (PLINY) telephone friendship groups research study: pilot randomised controlled trial  

PubMed Central

Background Loneliness in older people is associated with poor health-related quality of life (HRQoL). We undertook a parallel-group randomised controlled trial to evaluate the effectiveness and cost-effectiveness of telephone befriending for the maintenance of HRQoL in older people. An internal pilot tested the feasibility of the trial and intervention. Methods Participants aged >74 years, with good cognitive function, living independently in one UK city were recruited through general practices and other sources, then randomised to: (1) 6 weeks of short one-to-one telephone calls, followed by 12 weeks of group telephone calls with up to six participants, led by a trained volunteer facilitator; or (2) a control group. The main trial required the recruitment of 248 participants in a 1-year accrual window, of whom 124 were to receive telephone befriending. The pilot specified three success criteria which had to be met in order to progress the main trial to completion: recruitment of 68 participants in 95 days; retention of 80% participants at 6 months; successful delivery of telephone befriending by local franchise of national charity. The primary clinical outcome was the Short Form (36) Health Instrument (SF-36) Mental Health (MH) dimension score collected by telephone 6 months following randomisation. Results We informed 9,579 older people about the study. Seventy consenting participants were randomised to the pilot in 95 days, with 56 (80%) providing valid primary outcome data (26 intervention, 30 control). Twenty-four participants randomly allocated to the research arm actually received telephone befriending due to poor recruitment and retention of volunteer facilitators. The trial was closed early as a result. The mean 6-month SF-36 MH scores were 78 (SD 18) and 71 (SD 21) for the intervention and control groups, respectively (mean difference, 7; 95% CI, -3 to 16). Conclusions Recruitment and retention of participants to a definitive trial with a recruitment window of 1 year is feasible. For the voluntary sector to recruit sufficient volunteers to match demand for telephone befriending created by trial recruitment would require the study to be run in more than one major population centre, and/or involve dedicated management of volunteers. Trial registration ISRCTN28645428.

2014-01-01

3

Comparison of Immunologic Assays for Detecting Immune Responses in HIV Immunotherapeutic Studies: AIDS Clinical Trials Group Trial A5181?  

PubMed Central

This study was designed to evaluate which of several T-cell-specific, immune response assays are the most relevant in measuring the key characteristics of an effective immune response to HIV-1. Using 5 HIV-1 antigens as stimulants, we assessed lymphocyte proliferation, supernatant gamma interferon (IFN-?) cytokine production (CP), single-cell IFN-? production by enzyme-linked immunospot (ELISPOT) assay, with and without Epstein-Barr virus-transformed B-lymphoblastoid cell lines (B-LCLs), and intracellular cytokine production (ICC) for IFN-? and interleukin 2 (IL-2) by flow cytometry. We used these to compare specimens from HIV-1-infected subjects who were virally suppressed with a stable antiretroviral therapy (ART) regimen (group A) with specimens from subjects not on ART but with HIV-1 viremia of <3,000 copies/ml (group B). The lymphocyte proliferation assay (LPA) did not significantly differentiate between the two groups. Using fresh peripheral blood mononuclear cells (PBMCs), the CP and ELISPOT assays for IFN-? detected the greatest differences between the two groups, specific for three of the five HIV-1 antigens, whereas significant differences were seen only in response to one antigen when cryopreserved cells were used. The strongest correlations were seen between the CP and ELISPOT assays. The ELISPOT B-LCL assay showed a cell concentration-dependent increase in IFN-? production compared to that shown by the standard ELISPOT assay but did not differentiate between the groups. In the ICC assay, greater numbers of IFN-?-producing T cells were seen in group B, and little or no detectable IL-2 production was seen in both groups. These studies highlight complexities of immunologic monitoring of T-cell responses in multisite clinical trials in HIV infection and outline considerations for optimizing these efforts.

Macatangay, Bernard J. C.; Zheng, Lu; Rinaldo, Charles R.; Landay, Alan L.; Pollard, Richard B.; Pahwa, Savita; Lederman, Michael M.; Bucy, R. Pat

2010-01-01

4

The effectiveness of a health promotion with group intervention by clinical trial. Study protocol  

PubMed Central

Background The promotion of health and the interventions in community health continue to be one of the pending subjects of our health system. The most prevalent health problems (cardiovascular diseases, cancer, diabetes...) are for the most part related to life habits. We propose a holistic and integral approach as the best option for tackling behavior and its determinants. The research team has elaborated the necessary educational material to realize group teaching, which we call "Health Workshops". The goal of the present study is to evaluate the effectiveness of these Health Workshops in the following terms: Health Related Quality of Life (HRQOL), incorporate and maintain a balanced diet, do physical activity regularly, maintain risk factors such as tension, weight, cholesterol within normal limits and diminish cardiovascular risk. Methods/Design Controlled and random clinical testing, comparing a group of persons who have participated in the Health Workshops with a control group of similar characteristics who have not participated in the Health Workshops. Field of study: the research is being done in Health Centers of the city of Barcelona, Spain. Population studied: The group is composed of 108 persons that are actually doing the Health Workshops, and 108 that are not and form the control group. They are assigned at random to one group or the other. Data Analysis: With Student's t-distribution test to compare the differences between numerical variables or their non parametric equivalent if the variable does not comply with the criteria of normality. (Kolmogorov-Smirnof test). Chi-square test to compare the differences between categorical variables and the Logistic Regression Model to analyze different meaningful variables by dichotomous analysis related to the intervention. Discussion The Health Workshop proposed in the present study constitutes an innovative approach in health promotion, placing the emphasis on the person's self responsibility for his/her own health. The rhythm of a weekly session during 8 weeks with recommended activities to put into practice, as well as the support of the group is an opportunity to incorporate healthy habits and make a commitment to self-care. The sheets handed out are a Health Manual that can always be consulted after the workshop ends. Trial registration Clinical Trials.gov Identifier: NCT01440738

2012-01-01

5

A randomised controlled trial of group debriefing  

Microsoft Academic Search

There has never been published a randomised controlled trial of group debriefing. In this study we employed an analogue study with students to conduct the first such trial. Sixty-four participants were shown a stressful video of paramedics attending to injured and dead victims of a road traffic accident. Half the participants were subsequently debriefed and half were provided with tea

Grant J. Devilly; Rachid Annab

2008-01-01

6

Neoadjuvant clinical trials for the treatment of primary breast cancer: the experience of the German study groups.  

PubMed

The advantages of neoadjuvant chemotherapy are the ability to 1) increase the rate of breast conservation and improve operability, 2) to reduce mortality by recognizing resistance mechanisms early, and 3) to investigate the activity of new agents by assessing the pathological complete response rate as a surrogate marker for clinical efficacy. The German Breast Group (GBG) is a cooperative study group which focuses on neoadjuvant therapy for breast cancer. This group cooperates closely with the German Gynecological Oncology Working Group-Breast (AGO-B). Additionally, these two German study groups maintain close ties with other national and international study groups, such as the Breast International Group (BIG), Austrian Breast and Colorectal Cancer Study Group (ABCSG), Central European Cooperative Oncology Group (CECOG), International Cooperative Cancer Group (ICCG) and National Surgical Adjuvant Breast Project (NSABP). A series of clinical trials evaluating the role of neoadjuvant therapy in women with primary breast cancer have been designed, performed and published over the last 10 years. This article summarizes the results of the neoadjuvant trials that have been conducted by the German study groups, outlines ongoing clinical research projects, and discusses concepts for future clinical trials. PMID:22246608

Untch, Michael; Loibl, Sibylle; Konecny, Gottfried E; von Minckwitz, Gunter

2012-02-01

7

Disappointment and adherence among parents of newborns allocated to the control group: a qualitative study of a randomized clinical trial  

PubMed Central

Background When a child participates in a clinical trial, informed consent has to be given by the parents. Parental motives for participation are complex, but the hope of getting a new and better treatment for the child is important. We wondered how parents react when their child is allocated to the control group of a randomized controlled trial, and how it will affect their future engagement in the trial. Methods We included parents of newborns randomized to the control arm in the Danish Calmette study at Rigshospitalet in Copenhagen. The Calmette study is a randomized clinical trial investigating the non-specific effects of early BCG-vaccine to healthy neonates. Randomization is performed immediately after birth and parents are not blinded to the allocation. We set up a semi-structured focus group with six parents from four families. Afterwards we telephone-interviewed another 19 mothers to achieve saturation. Thematic analysis was used to identify themes across the data sets. Results The parents reported good understanding of the randomization process. Their most common reaction to allocation was disappointment, though relief was also seen. A model of reactions to being allocated to the control group was developed based on the participants’ different positions along two continuities from ‘Our participation in trial is not important’ to ‘Our participation in trial is important’, and ‘Vaccine not important to us’ to ‘Vaccine important to us’. Four very disappointed families had thought of getting the vaccine elsewhere, and one had actually had their child vaccinated. All parents involved in the focus group and the telephone interviews wanted to participate in the follow-ups planned for the Calmette study. Conclusions This study identified an almost universal experience of disappointment among parents of newborns who were randomized to the control group, but also a broad expression of understanding and accepting the idea of randomization. The trial staff might use the model of reactions in understanding the parents’ disappointment and in this way support their motives for participation. A generalized version might be applicable across randomized controlled trials at large. Trial registration The Calmette study is registered in EudraCT (https://eudract.ema.europa.eu/) with trial number 2010-021979-85.

2014-01-01

8

Recruitment strategies in the women's health trial: feasibility study in minority populations. WHT:FSMP Investigators Group. Women's Health Trial:Feasibility Study in Minority Populations.  

PubMed

The Women's Health Trial:Feasibility Study in Minority Populations (WHT:FSMP) examined the feasibility of recruiting postmenopausal women from a broad range of racial and socioeconomic backgrounds into a primary prevention trial requiring marked reductions in dietary fat. Postmenopausal women aged 50-79 yr who had no history of cardiovascular disease or cancer and who consumed 36% or more total energy from fat qualified to participate. We randomized the women into dietary intervention (60%) or control (40%) groups; we aimed to randomize 750 women in 18 months in each of the three clinical centers. All centers achieved goals for randomization based on ethnicity, and two centers exceeded overall recruitment goals. The greatest source of randomized participants was mass mailing, followed by items in the media, referrals, and community outreach. Recruitment yields were generally similar for the ethnic groups but lower for less-educated participants. The experience of WHT:FSMP indicates that postmenopausal women from the African-American, Hispanic, and non-Hispanic white communities can be recruited into dietary intervention studies for the prevention of disease. PMID:9741867

Lewis, C E; George, V; Fouad, M; Porter, V; Bowen, D; Urban, N

1998-10-01

9

Determinants of patient recruitment in a multicenter clinical trials group: trends, seasonality and the effect of large studies. | accrualnet.cancer.gov  

Cancer.gov

The authors developed a model that adequately predicted five-year enrollment trends based on patient enrollment during the first 32 quarters. The study identified key trends and determinants of enrollment in a large multicenter clinical trials group. This information can be used to assess a clinical trials group’s performance over time and plan the strategic development and incorporation of future trials in its program. The predictors and the modeling process may be adapted to other groups and settings.

10

Histiocytosis X: clinical trial of chlorambucil: a report from Childrens Cancer Study Group.  

PubMed

A prospective study for histiocytosis X was designed to determine whether "good risk" patients, ie, those without evidence of dysfunction of liver, lung, or hemopoietic system, would respond to single agent therapy; in this case chlorambucil (CMB) used in a dose of 5 mgm/m2/day. If there was no response after an adequate trial period, treatment was initiated with four drugs using a combination of prednisone, vinblastine, cyclophosphamide and methotrexate. There were 26 evaluable patients, 57% of whom were less than two years of age at onset of therapy. There were three complete and four partial responses to CMB for a response rate of 26.9%. Sixteen patients received an adequate trial of four-drug therapy with three complete and two partial responses for a response rate of 33%. These responses were inferior to those previously reported for either single agents or combined therapy in histiocytosis X. PMID:396466

Lahey, M E; Heyn, R M; Newton, W A; Shore, N; Smith, W B; Leikin, S; Hammond, D

1979-01-01

11

International Prostate Screening Trials Evaluation Group (IPSTEG)  

Cancer.gov

Key Programs International Prostate Screening Trials Evaluation Group (IPSTEG) Background Information The International Prostate Screening Trial Evaluation Group (IPSTEG) is a collaboration between the researchers in Europe and North America conducting

12

Immunoprophylaxis against klebsiella and pseudomonas aeruginosa infections. The Federal Hyperimmune Immunoglobulin Trial Study Group.  

PubMed

To determine if passive immunization could decrease the incidence or severity of Klebsiella and Pseudomonas aeruginosa infections, patients admitted to intensive care units of 16 Department of Veterans Affairs and Department of Defense hospitals were randomized to receive either 100 mg/kg intravenous hyperimmune globulin (IVIG), derived from donors immunized with a 24-valent Klebsiella capsular polysaccharide plus an 8-valent P. aeruginosa O-polysaccharide-toxin A conjugate vaccine, or an albumin placebo. The overall incidence and severity of vaccine-specific Klebsiella plus Pseudomonas infections were not significantly different between the groups receiving albumin and IVIG. There was some evidence that IVIG may decrease the incidence (2.7% albumin vs. 1.2% IVIG) and severity (1.0% vs. 0.3%) of vaccine-specific Klebsiella infections, but these reductions were not statistically significant. The trial was stopped because it was statistically unlikely that IVIG would be protective against Pseudomonas infections at the dosage being used. Patients receiving IVIG had more adverse reactions (14.4% vs. 9.2%). PMID:8769611

Donta, S T; Peduzzi, P; Cross, A S; Sadoff, J; Haakenson, C; Cryz, S J; Kauffman, C; Bradley, S; Gafford, G; Elliston, D; Beam, T R; John, J F; Ribner, B; Cantey, R; Welsh, C H; Ellison, R T; Young, E J; Hamill, R J; Leaf, H; Schein, R M; Mulligan, M; Johnson, C; Abrutyn, E; Griffiss, J M; Slagle, D

1996-09-01

13

Phase I Trial of Rosiglitazone in FSGS: I. Report of the FONT Study Group  

PubMed Central

Background and objectives: Patients with primary focal segmental glomerulosclerosis (FSGS) who are resistant to standard therapy are at high risk for progressive chronic kidney disease. Prevention of renal fibrosis represents a promising strategy to slow or halt kidney function decline. This paper presents the results of a Phase I clinical trial of rosiglitazone, a thiazolidinedione, that exerts antifibrotic effects in animal models of FSGS. The primary goal was assessment of safety, tolerability, and pharmacokinetics (PK) of rosiglitazone. Design, setting, participants, & measurements; Eleven patients, including eight boys/men and three girls/women, with mean age 15 ± 6 yr and estimated GFR 131 ± 62 ml/min/1.73 m2, received rosiglitazone, 3 mg/m2/d for 16 wk. PK was assessed twice, after the initial dose and after attaining steady state, in a General Clinical Research Center. Results: There were no serious adverse events or cardiovascular complications. Rosiglitazone was well tolerated by all patients, as judged by the Treatment Satisfaction Questionnaire for Medication. The PK studies indicated that the area under the curve was decreased by 40 to 50% and oral clearance of rosiglitazone was increased by 250 to 300% in patients with resistant FSGS compared with healthy controls and patients with nonproteinuric stage 2 chronic kidney disease. Conclusions: Rosiglitazone therapy was safe and well tolerated. PK assessment of potential novel therapies for resistant FSGS is necessary to define appropriate dosing regimens. There is rationale to evaluate the efficacy of rosiglitazone as an antifibrotic agent for resistant FSGS in Phase II/III clinical trials.

Joy, Melanie S.; Gipson, Debbie S.; Dike, Mary; Powell, Leslie; Thompson, Amber; Vento, Suzanne; Eddy, Allison; Fogo, Agnes B.; Kopp, Jeffrey B.; Cattran, Daniel; Trachtman, Howard

2009-01-01

14

The MATISSE study: a randomised trial of group art therapy for people with schizophrenia  

Microsoft Academic Search

BACKGROUND: Art Therapy has been promoted as a means of helping people who may find it difficult to express themselves verbally engage in psychological treatment. Group Art Therapy has been widely used as an adjunctive treatment for people with schizophrenia but there have been few attempts to examine its effects and cost effectiveness has not been examined. The MATISSE study

Mike J Crawford; Helen Killaspy; Eleftheria Kalaitzaki; Barbara Barrett; Sarah Byford; Sue Patterson; Tony Soteriou; Francis A O'Neill; Katie Clayton; Anna Maratos; Thomas R Barnes; David Osborn; Tony Johnson; Michael King; Peter Tyrer; Diana Waller

2010-01-01

15

Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial.  

PubMed

The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370 patients were centrally randomly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation. The hypothesis was that consolidation therapy would prolong progression-free survival (PFS). The PFS after randomization was 27 months for the bortezomib group compared with 20 months for the control group (P = .05). Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after randomization (P = .007). No difference in overall survival was seen. Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality-of-life (QOL) questionnaires, whereas no other major differences in QOL were recorded between the groups. Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response (VGPR) but not for patients in the ? VGPR category at randomization. Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL. This trial was registered at www.clinicaltrials.gov as #NCT00417911. PMID:23616624

Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind; Lenhoff, Stig; Laane, Edward; Remes, Kari; Steingrimsdottir, Hlif; Abildgaard, Niels; Ahlberg, Lucia; Blimark, Cecilie; Dahl, Inger Marie; Forsberg, Karin; Gedde-Dahl, Tobias; Gregersen, Henrik; Gruber, Astrid; Guldbrandsen, Nina; Haukås, Einar; Carlson, Kristina; Kvam, Ann Kristin; Nahi, Hareth; Lindås, Roald; Andersen, Niels Frost; Turesson, Ingemar; Waage, Anders; Westin, Jan

2013-06-01

16

Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial  

PubMed Central

The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370 patients were centrally randomly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation. The hypothesis was that consolidation therapy would prolong progression-free survival (PFS). The PFS after randomization was 27 months for the bortezomib group compared with 20 months for the control group (P = .05). Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after randomization (P = .007). No difference in overall survival was seen. Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality-of-life (QOL) questionnaires, whereas no other major differences in QOL were recorded between the groups. Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response (VGPR) but not for patients in the ? VGPR category at randomization. Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL. This trial was registered at www.clinicaltrials.gov as #NCT00417911.

Gimsing, Peter; Hjertner, Oyvind; Lenhoff, Stig; Laane, Edward; Remes, Kari; Steingrimsdottir, Hlif; Abildgaard, Niels; Ahlberg, Lucia; Blimark, Cecilie; Dahl, Inger Marie; Forsberg, Karin; Gedde-Dahl, Tobias; Gregersen, Henrik; Gruber, Astrid; Guldbrandsen, Nina; Haukas, Einar; Carlson, Kristina; Kvam, Ann Kristin; Nahi, Hareth; Lindas, Roald; Andersen, Niels Frost; Turesson, Ingemar; Waage, Anders; Westin, Jan; Gregersen, Henrik; Frost Andersen, Niels; Gimsing, Peter; Toffner-Clausen, Nilsaage; Abildgaard, Niels; Laane, Edward; Silvennoinen, Raija; Remes, Kari; Steingrimsdottir, Hlif; Lindas, Roald; Gedde-Dahl, Tobias; Guldbrandsen, Nina; Kristin Kvam, Ann; Haukas, Einar; Marie Dahl, Inger; Hjertner, Oyvind; Waage, Anders; Blimark, Cecilie; Mellqvist, Ulf-Henrik; Westin, Jan; Ahlberg, Lucia; Lenhoff, Stig; Turesson, Ingemar; Linder, Olle; Gruber, Astrid; Nahi, Hareth; Forsberg, Karin; Carlson, Kristina

2013-01-01

17

Recruitment activities for a nationwide, population-based, group-randomized trial: the VA MI-Plus study  

PubMed Central

Background The Veterans Health Administration (VHA) oversees the largest integrated healthcare system in the United States. The feasibility of a large-scale, nationwide, group-randomized implementation trial of VHA outpatient practices has not been reported. We describe the recruitment and enrollment of such a trial testing a clinician-directed, Internet-delivered intervention for improving the care of postmyocardial infarction patients with multiple comorbidities. Methods With a recruitment goal of 200 eligible community-based outpatient clinics, parent VHA facilities (medical centers) were recruited because they oversee their affiliated clinics and the research conducted there. Eligible facilities had at least four VHA-owned and -operated primary care clinics, an affiliated Institutional Review Board (IRB), and no ongoing, potentially overlapping, quality-improvement study. Between December 2003 and December 2005, in two consecutive phases, we used initial and then intensified recruitment strategies. Results Overall, 48 of 66 (73%) eligible facilities were recruited. Of the 219 clinics and 957 clinicians associated with the 48 facilities, 168 (78%) clinics and 401 (42%) clinicians participated. The median time from initial facility contact to clinic enrollment was 222 days, which decreased by over one-third from the first to the second recruitment phase (medians: 323 and 195 days, respectively; p < .001), when more structured recruitment with physician recruiters was implemented and a dedicated IRB manager was added to the coordinating center staff. Conclusions Large group-randomized trials benefit from having dedicated physician investigators and IRB personnel involved in recruitment. A large-scale, nationally representative, group-randomized trial of community-based clinics is feasible within the VHA or a similar national healthcare system.

2011-01-01

18

Factors affecting baseline quality of life in two international adjuvant breast cancer trials. International Breast Cancer Study Group (IBCSG).  

PubMed Central

Quality of life (QL) is used to assess treatments in clinical trials but may be influenced by other factors. We analysed the impact of biomedical, sociodemographic and cultural factors on baseline QL indicators in two International Breast Cancer Study Group trials. Patients with stage II breast cancer were randomized within 6 weeks of primary surgery to various adjuvant treatments. They were asked to assess five indicators of QL at baseline. QL forms were available for 1231 (83%) of the 1475 premenopausal and 989 (82%) of the 1212 post-menopausal patients, who were from nine countries and spoke seven languages. Culture (defined as language/country groups) had a statistically significant impact on baseline QL measures. Premenopausal patients with poor prognostic factors showed a tendency to report worse QL, with oestrogen receptor status as an independent predictor for mood (P = 0.0005). Older post-menopausal patients reported better emotional wellbeing (P = 0.002), mood (P = 0.002), and less effort to cope (P = 0.0009) compared with younger post-menopausal patients. Co-morbidity, type of surgery, treatment assignment and sociodemographic factors showed a statistically significant impact in post-menopausal patients only. Cultural and biomedical factors influenced baseline QL and should be considered when evaluating the impact of treatment on QL in international breast cancer clinical trials.

Bernhard, J.; Hurny, C.; Coates, A. S.; Peterson, H. F.; Castiglione-Gertsch, M.; Gelber, R. D.; Galligioni, E.; Marini, G.; Thurlimann, B.; Forbes, J. F.; Goldhirsch, A.; Senn, H. J.; Rudenstam, C. M.

1998-01-01

19

MAVIDOS Maternal Vitamin D Osteoporosis Study: study protocol for a randomized controlled trial. The MAVIDOS Study Group  

PubMed Central

MAVIDOS is a randomised, double-blind, placebo-controlled trial (ISRCTN82927713, registered 2008 Apr 11), funded by Arthritis Research UK, MRC, Bupa Foundation and NIHR. Background Osteoporosis is a major public health problem as a result of associated fragility fractures. Skeletal strength increases from birth to a peak in early adulthood. This peak predicts osteoporosis risk in later life. Vitamin D insufficiency in pregnancy is common (31% in a recent Southampton cohort) and predicts reduced bone mass in the offspring. In this study we aim to test whether offspring of mothers supplemented with vitamin D in pregnancy have higher bone mass at birth than those whose mothers were not supplemented. Methods/Design Women have their vitamin D status assessed after ultrasound scanning in the twelfth week of pregnancy at 3 trial centres (Southampton, Sheffield, Oxford). Women with circulating 25(OH)-vitamin D levels 25-100 nmol/l are randomised in a double-blind design to either oral vitamin D supplement (1000 IU cholecalciferol/day, n = 477) or placebo at 14 weeks (n = 477). Questionnaire data include parity, sunlight exposure, dietary information, and cigarette and alcohol consumption. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH)-vitamin D, PTH and biochemistry. At delivery venous umbilical cord blood is collected, together with umbilical cord and placental tissue. The babies undergo DXA assessment of bone mass within the first 14 days after birth, with the primary outcome being whole body bone mineral content adjusted for gestational age and age. Children are then followed up with yearly assessment of health, diet, physical activity and anthropometric measures, with repeat assessment of bone mass by DXA at age 4 years. Discussion As far as we are aware, this randomised trial is one of the first ever tests of the early life origins hypothesis in human participants and has the potential to inform public health policy regarding vitamin D supplementation in pregnancy. It will also provide a valuable resource in which to study the influence of maternal vitamin D status on other childhood outcomes such as glucose tolerance, blood pressure, cardiovascular function, IQ and immunology.

2012-01-01

20

Analytic methods for individually randomized group treatment trials and group-randomized trials when subjects belong to multiple groups.  

PubMed

Participants in trials may be randomized either individually or in groups and may receive their treatment either entirely individually, entirely in groups, or partially individually and partially in groups. This paper concerns cases in which participants receive their treatment either entirely or partially in groups, regardless of how they were randomized. Participants in group-randomized trials are randomized in groups, and participants in individually randomized group treatment trials are individually randomized, but participants in both types of trials receive part or all of their treatment in groups or through common change agents. Participants who receive part or all of their treatment in a group are expected to have positively correlated outcome measurements. This paper addresses a situation that occurs in group-randomized trials and individually randomized group treatment trials-participants receive treatment through more than one group. As motivation, we consider trials in The Childhood Obesity Prevention and Treatment Research Consortium, in which each child participant receives treatment in at least two groups. In simulation studies, we considered several possible analytic approaches over a variety of possible group structures. A mixed model with random effects for both groups provided the only consistent protection against inflated type I error rates and did so at the cost of only moderate loss of power when intraclass correlations were not large. We recommend constraining variance estimates to be positive and using the Kenward-Roger adjustment for degrees of freedom; this combination provided additional power but maintained type I error rates at the nominal level. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24399701

Andridge, Rebecca R; Shoben, Abigail B; Muller, Keith E; Murray, David M

2014-06-15

21

Industrial Genotoxicology Group collaborative trial to investigate cell cycle parameters in human lymphocyte cytogenetics studies.  

PubMed

Human lymphocyte cultures have been used for many years for assessing the in vitro clastogenic potential of test substances. In these assays the harvest time should be based on the cell cycle time in order to ensure that cells are sampled at an appropriate time for the detection of clastogenic effects. The sources of variation in the cell cycle time in routine cytogenetic assays have not been well studied. Consequently 13 laboratories, all members of the Industrial Genotoxicology Group, participated in a collaborative study to measure the variation in cell cycle time in cultured human peripheral blood lymphocytes under various conditions. The study was performed in two phases, spaced 6 months apart. The average generation time (AGT) was measured by the incorporation of bromodeoxyuridine. Very similar AGTs were found in the presence and absence of S9 mix. The mean AGT (mean of four donors) in each laboratory varied from 11.2 to 17.1 h, indicating there is significant variability in cell cycle times of human peripheral blood lymphocytes between laboratories. There was greater variation between laboratories than within laboratories. A comparison of AGT values at 72 h performed in experiments at least 6 months apart indicated good reproducibility in most laboratories. The study indicates that a 24 h post-treatment harvest may result in the analysis of very few first division cells unless very significant cell cycle delay is induced by the test substance. It was also found that a post-harvest time equivalent to 1.5 cell cycles will result in an approximately equal mixture of first and second division cells and therefore should by suitable for assessing both the induction of chromosome aberrations and polyploidy. PMID:9175642

Henderson, L; Jones, E; Brooks, T; Chételat, A; Ciliutti, P; Freemantle, M; Howard, C A; Mackay, J; Phillips, B; Riley, S; Roberts, C; Wotton, A K; van de Waart, E J

1997-05-01

22

Mediation and spillover effects in group-randomized trials: a case study of the 4Rs educational intervention  

PubMed Central

Peer influence and social interactions can give rise to spillover effects in which the exposure of one individual may affect outcomes of other individuals. Even if the intervention under study occurs at the group or cluster level as in group-randomized trials, spillover effects can occur when the mediator of interest is measured at a lower level than the treatment. Evaluators who choose groups rather than individuals as experimental units in a randomized trial often anticipate that the desirable changes in targeted social behaviors will be reinforced through interference among individuals in a group exposed to the same treatment. In an empirical evaluation of the effect of a school-wide intervention on reducing individual students’ depressive symptoms, schools in matched pairs were randomly assigned to the 4Rs intervention or the control condition. Class quality was hypothesized as an important mediator assessed at the classroom level. We reason that the quality of one classroom may affect outcomes of children in another classroom because children interact not simply with their classmates but also with those from other classes in the hallways or on the playground. In investigating the role of class quality as a mediator, failure to account for such spillover effects of one classroom on the outcomes of children in other classrooms can potentially result in bias and problems with interpretation. Using a counterfactual conceptualization of direct, indirect and spillover effects, we provide a framework that can accommodate issues of mediation and spillover effects in group randomized trials. We show that the total effect can be decomposed into a natural direct effect, a within-classroom mediated effect and a spillover mediated effect. We give identification conditions for each of the causal effects of interest and provide results on the consequences of ignoring “interference” or “spillover effects” when they are in fact present. Our modeling approach disentangles these effects. The analysis examines whether the 4Rs intervention has an effect on children's depressive symptoms through changing the quality of other classes as well as through changing the quality of a child's own class.

VanderWeele, Tyler J.; Hong, Guanglei; Jones, Stephanie M.; Brown, Joshua L.

2013-01-01

23

Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials  

PubMed Central

This study investigated the impact of comorbidity in 555 patients with chronic lymphocytic leukemia enrolled in two trials of the German Chronic Lymphocytic Leukemia Study Group on first-line treatment with fludarabine plus cyclophosphamide, fludarabine, or chlorambucil. Patients with two or more comorbidities and patients with less than two comorbidities differed in overall survival (71.7 versus 90.2 months; P<0.001) and progression-free survival (21.0 versus 31.5 months; P<0.01). After adjustment for other prognostic factors and treatment, comorbidity maintained its independent prognostic value in a multivariate Cox regression analysis. Chronic lymphocytic leukemia was the major cause of death in patients with two or more comorbidities. Disease control in patients with two or more comorbidities was better with fludarabine plus cyclophosphamide than with fludarabine treatment, but not with fludarabine compared to chlorambucil treatment. These results give insight into interactions between comorbidity and therapy of chronic lymphocytic leukemia and suggest that durable control of the hematologic disease is most critical to improve overall outcome of patients with increased comorbidity. The registration numbers of the trials reported are NCT00276848 and NCT00262795.

Goede, Valentin; Cramer, Paula; Busch, Raymonde; Bergmann, Manuela; Stauch, Martina; Hopfinger, Georg; Stilgenbauer, Stephan; Dohner, Hartmut; Westermann, Anne; Wendtner, Clemens M.; Eichhorst, Barbara; Hallek, Michael

2014-01-01

24

Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials.  

PubMed

This study investigated the impact of comorbidity in 555 patients with chronic lymphocytic leukemia enrolled in two trials of the German Chronic Lymphocytic Leukemia Study Group on first-line treatment with fludarabine plus cyclophosphamide, fludarabine, or chlorambucil. Patients with two or more comorbidities and patients with less than two comorbidities differed in overall survival (71.7 versus 90.2 months; P<0.001) and progression-free survival (21.0 versus 31.5 months; P<0.01). After adjustment for other prognostic factors and treatment, comorbidity maintained its independent prognostic value in a multivariate Cox regression analysis. Chronic lymphocytic leukemia was the major cause of death in patients with two or more comorbidities. Disease control in patients with two or more comorbidities was better with fludarabine plus cyclophosphamide than with fludarabine treatment, but not with fludarabine compared to chlorambucil treatment. These results give insight into interactions between comorbidity and therapy of chronic lymphocytic leukemia and suggest that durable control of the hematologic disease is most critical to improve overall outcome of patients with increased comorbidity. The registration numbers of the trials reported are NCT00276848 and NCT00262795. PMID:24584349

Goede, Valentin; Cramer, Paula; Busch, Raymonde; Bergmann, Manuela; Stauch, Martina; Hopfinger, Georg; Stilgenbauer, Stephan; Döhner, Hartmut; Westermann, Anne; Wendtner, Clemens M; Eichhorst, Barbara; Hallek, Michael

2014-06-01

25

Significant Increase in Breast Conservation in 16 Years of Trials Conducted by the Austrian Breast & Colorectal Cancer Study Group  

PubMed Central

Objective To confirm evidence that breast-conserving treatment (BCT) does not impair the prognosis in breast cancer patients as compared to mastectomy and to argue that it be regarded as the treatment of choice in stage I and II disease. Summary Background Data Scientifically, survival rates in breast cancer have been shown to be stage-dependent, but independent of the extent of surgical breast tissue removal, as long as the resection margins are free of tumor infiltration. Methods Between 1984 and 1997, six different trials conducted by the Austrian Breast & Colorectal Cancer Study Group accrued a total of 4,259 women with hormone-responsive disease. The authors selected and compared three patient groups (n = 3,316) according to pathologic stage, age, and the surgical procedure applied. Results Over this interval, the BCT rate in the premenopausal node-positive subgroup experienced a highly significant increase from 27.2% to 73.2% overall. In the group of postmenopausal node-negative patients, the BCT rate grew significantly by 37.3% to 77.3% in total. With an overall BCT rate growing from 22.5% to 56.8% in postmenopausal node-positive women, those presenting with T1 tumors saw a significant increase from 35.1% to 65.9%. Mortality and local recurrence rates proved stable or even decreased considerably over time and in all subgroups. Conclusions The presented outcome of BCT rates, significantly improved over this 16-year period and in no way counterbalanced by higher local recurrence or death rates, reflects an excellent example of surgical quality control. BCT can safely be regarded as the standard of therapy for T1 and increasingly for T2 disease. Especially in multi-institutional adjuvant breast cancer trials, the highest priority should be given to breast-conserving procedures.

Jakesz, Raimund; Samonigg, Hellmut; Gnant, Michael; Kubista, Ernst; Depisch, Dieter; Kolb, Roland; Mlineritsch, Brigitte; Mischinger, Hans-Jorg; Menzel, Rainer-Christian; Steindorfer, Peter; Kwasny, Werner; Tausch, Christoph; Stierer, Michael; Taucher, Susanne; Seifert, Michael; Hausmaninger, Hubert

2003-01-01

26

Use of Brief Instructional Trials to Identify Small Group Reading Strategies: A Two Experiment Study  

Microsoft Academic Search

The Instructional Hierarchy (IH) has proven useful for understanding the functional properties of empirically valid instructional\\u000a strategies. Investigators have relied heavily on the IH as a heuristic in conceptualizing instructional components used in\\u000a brief experimental analyses. To date, only one investigation has applied brief experimental analysis results to small group\\u000a reading interventions. The purpose of this paper is to describe

Merilee McCurdy; Edward Daly; Valerie Gortmaker; Christine Bonfiglio; Michael Persampieri

2007-01-01

27

Defining Responses to Therapy and Study Outcomes in Clinical Trials of Invasive Fungal Diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer Consensus Criteria  

PubMed Central

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

Segal, Brahm H.; Herbrecht, Raoul; Stevens, David A.; Ostrosky-Zeichner, Luis; Sobel, Jack; Viscoli, Claudio; Walsh, Thomas J.; Maertens, Johan; Patterson, Thomas F.; Perfect, John R.; Dupont, Bertrand; Wingard, John R.; Calandra, Thierry; Kauffman, Carol A.; Graybill, John R.; Baden, Lindsey R.; Pappas, Peter G.; Bennett, John E.; Kontoyiannis, Dimitrios P.; Cordonnier, Catherine; Viviani, Maria Anna; Bille, Jacques; Almyroudis, Nikolaos G.; Wheat, L. Joseph; Graninger, Wolfgang; Bow, Eric J.; Holland, Steven M.; Kullberg, Bart-Jan; Dismukes, William E.; De Pauw, Ben E.

2009-01-01

28

Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999.  

PubMed

We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS)+/-s.e. was 67.2+/-2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0+/-1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because >60% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate- or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8 mg/m(2) had no advantage over prednisolone 60 mg/m(2) in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to <2% in the last two trials. Secondary brain tumors developed in 12 patients at 8-22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies. PMID:20033052

Tsuchida, M; Ohara, A; Manabe, A; Kumagai, M; Shimada, H; Kikuchi, A; Mori, T; Saito, M; Akiyama, M; Fukushima, T; Koike, K; Shiobara, M; Ogawa, C; Kanazawa, T; Noguchi, Y; Oota, S; Okimoto, Y; Yabe, H; Kajiwara, M; Tomizawa, D; Ko, K; Sugita, K; Kaneko, T; Maeda, M; Inukai, T; Goto, H; Takahashi, H; Isoyama, K; Hayashi, Y; Hosoya, R; Hanada, R

2010-02-01

29

Phase II trial with S-1 in chemotherapy-na??ve patients with gastric cancer. A trial performed by the EORTC Early Clinical Studies Group (ECSG)  

Microsoft Academic Search

S-1 is a new oral fluorinated pyrimidine derivate, in which the oral 5-fluorouracil (5-FU) prodrug, tegafur, was combined with two 5-FU-modulating substances, 5-chloro-2,4-dihydroxypyridine (gimeracil), and potassium oxonate (oteracil), at a molar ratio of 1:0.4:1. The final mechanism of action is exerted by 5-FU. The present study is the first European phase II trial of S-1 in gastric cancer. The primary

P Chollet; P Schöffski; K Weigang-Köhler; J. H. M Schellens; H Cure; N Pavlidis; V Grünwald; R De Boer; J Wanders; P Fumoleau

2003-01-01

30

CYP2D6 Metabolism and Patient Outcome in the Austrian Breast and Colorectal Cancer Study Group Trial (ABCSG) 8  

PubMed Central

Background Controversy exists regarding CYP2D6 genotype and tamoxifen efficacy. Methods A matched case-control study was conducted utilizing the Austrian Breast and Colorectal Cancer Study Group Trial 8 that randomized post-menopausal women with estrogen receptor positive breast cancer to tamoxifen for 5 years (Arm A) or tamoxifen for 2 years followed by anastrozole for 3 years (Arm B). Cases had disease recurrence, contralateral breast cancer, second non-breast cancer, or died. For each case, controls were identified from the same treatment arm of similar age, surgery/radiation, and TNM stage. Genotyping was performed for alleles associated with no (PM; *3, *4, *6); reduced (IM; *10, and *41); and extensive (EM: absence of these alleles) CYP2D6 metabolism. Findings The common CYP2D6 *4 allele was in Hardy Weinberg Equilibrium. In Arm A during the first 5 years of therapy, women with 2 poor alleles (PM/PM: OR=2.45, 95% CI: 1.05–5.73, p=0.04) and women with one poor allele (PM/IM or PM/EM: OR=1.67, 95% CI: 0.95–2.93, p=0.07) had a higher likelihood of an event than women with two extensive alleles (EM/EM). In years 3–5 when patients remained on tamoxifen (Arm A) or switched to anastrozole (Arm B), PM/PM tended towards a higher likelihood of a disease event relative to EM/EM (OR= 2.40, 95% CI: 0.86–6.66, p=0.09) among women on Arm A but not among women on Arm B (OR= 0.28; 95% CI: 0.03–2.30). Conclusion In ABCSG8, the negative effects of reduced CYP2D6 metabolism were observed only during the period of tamoxifen administration, and not after switching to anastrozole.

Goetz, Matthew P.; Suman, Vera J.; Hoskin, Tanya L.; Gnant, Michael; Filipits, Martin; Safgren, Stephanie L.; Kuffel, Mary; Jakesz, Raimund; Rudas, Margaretha; Greil, Richard; Dietze, Otto; Lang, Alois; Offner, Felix; Reynolds, Carol A.; Weinshilboum, Richard M.; Ames, Matthew M.; Ingle, James N.

2012-01-01

31

The effect of participatory women's groups on birth outcomes in Bangladesh: does coverage matter? Study protocol for a randomized controlled trial  

PubMed Central

Background Progress on neonatal survival has been slow in most countries. While there is evidence on what works to reduce newborn mortality, there is limited knowledge on how to deliver interventions effectively when health systems are weak. Cluster randomized trials have shown strong reductions in neonatal mortality using community mobilisation with women's groups in rural Nepal and India. A similar trial in Bangladesh showed no impact. A main hypothesis is that this negative finding is due to the much lower coverage of women's groups in the intervention population in Bangladesh compared to India and Nepal. For evidence-based policy making it is important to examine if women's group coverage is a main determinant of their impact. The study aims to test the effect on newborn and maternal health outcomes of a participatory women's group intervention with a high population coverage of women's groups. Methods A cluster randomised trial of a participatory women's group intervention will be conducted in 3 districts of rural Bangladesh. As we aim to study a women's group intervention with high population coverage, the same 9 intervention and 9 control unions will be used as in the 2005-2007 trial. These had been randomly allocated using the districts as strata. To increase coverage, 648 new groups were formed in addition to the 162 existing groups that were part of the previous trial. An open cohort of women who are permanent residents in the union in which their delivery or death was identified, is enrolled. Women and their newborns are included after birth, or, if a woman dies during pregnancy, after her death. Excluded are women who are temporary residents in the union in which their birth or death was identified. The primary outcome is neonatal mortality in the last 24 months of the study. A low cost surveillance system will be used to record all birth outcomes and deaths to women of reproductive age in the study population. Data on home care practices and health care use are collected through interviews. Trial registration ISRCTN: ISRCTN01805825

2011-01-01

32

Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG)  

Microsoft Academic Search

Because nodular lymphocyte-predomi- nant Hodgkin lymphoma (NLPHL) ex- press CD20, rituximab may be used as a nonmutagenic treatment option to avoid late toxicities in this rather indolent en- tity. Between 1999 and 2004, the German Hodgkin Study Group (GHSG) investi- gated the activity of rituximab (375 mg\\/m2 in 4 doses) in a phase 2 trial in 21 relapsed or refractory

Holger Schulz; Ute Rehwald; Franck Morschhauser; Thomas Elter; Christoph Driessen; Thomas Rudiger; Peter Borchmann; Roland Schnell; Volker Diehl; Andreas Engert; Marcel Reiser

2007-01-01

33

A group-randomized tobacco trial among 30 Pacific Northwest colleges: Results from the Campus Health Action on Tobacco study  

PubMed Central

Introduction: We conducted a group-randomized trial to increase smoking cessation and decrease smoking onset and prevalence in 30 colleges and universities in the Pacific Northwest. Methods: Random samples of students, oversampling for freshmen, were drawn from the participating colleges; students completed a questionnaire that included seven major areas of tobacco policies and behavior. Following this baseline, the colleges were randomized to intervention or control. Three interventionists developed Campus Advisory Boards in the 15 intervention colleges and facilitated intervention activities. The freshmen cohort was resurveyed 1 and 2 years after the baseline. Two-years postrandomization, new cross-sectional samples were drawn, and students were surveyed. Results: At follow-up, we found no significant overall differences between intervention and control schools when examining smoking cessation, prevalence, or onset. There was a significant decrease in prevalence in private independent colleges, a significant increase in cessation among rural schools, and a decrease in smoking onset in urban schools. Discussion: Intervention in this college population had mixed results. More work is needed to determine how best to reach this population of smokers.

McLerran, Dale; Livaudais, Jennifer C.; Coronado, Gloria D.

2010-01-01

34

SWIFT trial of delayed elective intervention v conservative treatment after thrombolysis with anistreplase in acute myocardial infarction. SWIFT (Should We Intervene Following Thrombolysis?) Trial Study Group.  

PubMed Central

OBJECTIVE--To see whether early elective angiography with a view to coronary angioplasty or bypass grafting of a stenosed infarct related vessel would improve outcome in acute myocardial infarction treated by thrombolysis with anistreplase. DESIGN--Randomised study of two treatment strategies with analysis of results over 12 months. SETTING--21 district hospitals and regional cardiac centres in Britain and Ireland. SUBJECTS--800 of 993 patients presenting with clinical and electrocardiographic features of acute myocardial infarction up to three hours after the onset of major symptoms. TREATMENT STRATEGIES--Intravenous anistreplase 30 units followed by a standard regimen of heparin, warfarin, and timolol and (in patients so randomised) early angiography plus appropriate intervention. MAIN OUTCOME MEASURE--Death or reinfarction within 12 months. RESULTS--397 patients were randomised to receive early angiography plus appropriate intervention (coronary angioplasty in 169 cases, coronary grafting in 59) and 403 patients to receive conservative care (of these, 12 had angioplasty and seven bypass grafting during the initial admission). By 12 months mortality (5.8% (23 patients) in the intervention group v 5.0% (20) in the conservative care group; p = 0.6) and rates of reinfarction (15.1% (60 patients) v 12.9% (52); p = 0.4) were similar in the two groups. No significant differences in rates of angina or rest pain were found at 12 months. Left ventricular ejection fraction at three and 12 months was the same in both groups. Median hospital stay was longer in the intervention group (11 days v 10 days; p less than 0.0001). CONCLUSION--For most patients given thrombolytic treatment for acute myocardial infarction a strategy of angiography and intervention is appropriate only when required for clinical indications.

1991-01-01

35

Improved Neuropsychological and Neurological Functioning Across Three Antiretroviral Regimens in Diverse Resource-Limited Settings: AIDS Clinical Trials Group Study A5199, the International Neurological Study  

PubMed Central

Background.?AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. Methods.?Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. Results.?The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). Conclusions.?The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization –recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. Clinical trials registration. ?NCT00096824.

Robertson, K.; Jiang, H.; Kumwenda, J.; Supparatpinyo, K.; Evans, S.; Campbell, T. B.; Price, R.; Tripathy, S.; Kumarasamy, N.; La Rosa, A.; Santos, B.; Silva, M. T.; Montano, S.; Kanyama, C.; Faesen, S.; Murphy, R.; Hall, C.; Marra, C. M.; Marcus, C.; Berzins, B.; Allen, R.; Housseinipour, M.; Amod, F.; Sanne, I.; Hakim, J.; Walawander, A.; Nair, A.

2012-01-01

36

The effects and costs of the universal parent group program - all children in focus: a study protocol for a randomized wait-list controlled trial  

PubMed Central

Background In recent decades, parents have been involved in programs that aim to improve parenting style and reduce child behavior problems. Research of preventive parenting programs has shown that these interventions generally have a positive influence on both parents and children. However, to our knowledge there is a gap in the scientific literature when it comes to randomized controlled trials of brief, manual-based structured programs which address general parenting among the population, and focus on promoting health. A four-session universal health promotion parent group program named All Children in Focus was developed. It aims at promoting parental competence and children’s positive development with the parent–child relationship as the target. There is currently no randomized controlled trial existing of the program. Methods/Design A prospective multicenter randomized wait-list controlled trial is being conducted. Approximately 600 parents with children ranging in age from 3–12 years have been recruited in eleven municipalities and city districts in the County of Stockholm, Sweden. Parents are randomized at baseline to an intervention group, which receives the program directly, or to a waiting-list control group, which participates in the program six months later. Changes in parenting and child health and development are assessed with measures immediately post-intervention and six months after the baseline. Observations of a minor group of parents and children are conducted to explore possible relations between parental reports and observed behaviors, as well as changes in the interaction between parent and child. Further, data collected within the evaluation will also be applied to evaluate the possible cost-effectiveness of the program. Discussion This paper describes a study protocol of a randomized controlled trial. Except for the quantitative outcome measures to evaluate the effectiveness of All Children in Focus, this protocol also describes health economic and qualitative analyses to deepen the knowledge of the program. We further discuss some issues regarding the implementation of the program in municipalities and city districts. Trial registration Current Controlled Trials ISRCTN70202532

2013-01-01

37

Studies of the Ocular Complications of AIDS (SOCA) in Collaboration with the AIDS Clinical Trials Group (ACTG) Protocol 350 Ganciclovir Cidofovir CMV Retinitis Trial (GCCRT) Data Collection Forms (as of 24 September 1999).  

National Technical Information Service (NTIS)

This document contains the study data collection forms for the Ganciclovir Cidofovir CMV Retinitis Trial (GCCRT). The GCCRT was a Phase IV, randomized, multicenter trial conducted by the Studies of the Ocular Complications of AIDS (SOCA) in collaboration ...

1999-01-01

38

Early autologous stem cell transplantation for chronic lymphocytic leukemia: long-term follow-up of the German CLL Study Group CLL3 trial.  

PubMed

The CLL3 trial was designed to study intensive treatment including autologous stem cell transplantation (autoSCT) as part of first-line therapy in patients with chronic lymphocytic leukemia (CLL). Here, we present the long-term outcome of the trial with particular focus on the impact of genomic risk factors, and we provide a retrospective comparison with patients from the fludarabine-cyclophosphamide-rituximab (FCR) arm of the German CLL Study Group (GCLLSG) CLL8 trial. After a median observation time of 8.7 years (0.3-12.3 years), median progression-free survival (PFS), time to retreatment, and overall survival (OS) of 169 evaluable patients, including 38 patients who did not proceed to autoSCT, was 5.7, 7.3, and 11.3 years, respectively. PFS and OS were significantly reduced in the presence of 17p- and of an unfavorable immunoglobulin heavy variable chain mutational status, but not of 11q-. Five-year nonrelapse mortality was 6.5%. When 110 CLL3 patients were compared with 126 matched patients from the FCR arm of the CLL8 trial, 4-year time to retreatment (75% vs 77%) and OS (86% vs 90%) was similar despite a significant benefit for autoSCT in terms of PFS. In summary, early treatment intensification including autoSCT can provide very effective disease control in poor-risk CLL, although its clinical benefit in the FCR era remains uncertain. The trial has been registered with www.clinicaltrials.gov as NCT00275015. PMID:22490331

Dreger, Peter; Döhner, Hartmut; McClanahan, Fabienne; Busch, Raymonde; Ritgen, Matthias; Greinix, Hildegard; Fink, Anna-Maria; Knauf, Wolfgang; Stadler, Michael; Pfreundschuh, Michael; Dührsen, Ulrich; Brittinger, Günter; Hensel, Manfred; Schetelig, Johannes; Winkler, Dirk; Bühler, Andreas; Kneba, Michael; Schmitz, Norbert; Hallek, Michael; Stilgenbauer, Stephan

2012-05-24

39

Phase 2 Trial of Pemetrexed in Children and Adolescents with Refractory Solid Tumors: a Children's Oncology Group Study  

PubMed Central

Background Pemetrexed is a multi-targeted antifolate that inhibits key enzymes involved in nucleotide biosynthesis. We performed a phase 2 trial of pemetrexed in children with refractory or recurrent solid tumors, including CNS tumors, to estimate the response rate and further define its toxicity profile. Procedure Pemetrexed, at a dose of 1910 mg/m2, was administered as a 10-minute intravenous infusion every 21 days. Patients also received vitamin B12, daily multivitamin supplementation, and dexamethasone. A two-stage design (10 + 10) was employed in each of the following disease strata: osteosarcoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET, and non-brainstem high-grade glioma. Results Seventy-two eligible subjects (39 males) were enrolled. Median age was 11 years (range 3–23). Sixty-eight were evaluable for response. The median number of cycles administered was 2 (range 1–13). No complete or partial responses were observed. Stable disease, for a median of 5 (range 4–13) cycles, was observed in 5 patients (ependymoma, Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma; n=1 each). Neutropenia (44%), anemia (35%), and elevated alanine transaminase (35%) attributable to pemetrexed were the most commonly recurring toxicities observed in patients receiving multiple cycles. Other toxicities attributed to pemetrexed occurring in ?10% of cycles included thrombocytopenia (30%), fatigue (18%), nausea (14), hyperglycemia (13%), rash (11%), vomiting (13%), and hypophosphatemia (11%). Conclusions Pemetrexed, administered as an intravenous infusion every 21 days, was tolerable in children and adolescents with refractory solid tumors, including CNS tumors, but did not show evidence of objective anti-tumor activity in the childhood tumors studied.

Warwick, Anne B.; Malempati, Suman; Krailo, Mark; Melemed, Allen; Gorlick, Richard; Ames, Matthew M.; Safgren, Stephanie L.; Adamson, Peter C.; Blaney, Susan M.

2012-01-01

40

Comparison of usual podiatric care and early physical therapy intervention for plantar heel pain: study protocol for a parallel-group randomized clinical trial  

PubMed Central

Background A significant number of individuals suffer from plantar heel pain (PHP) and many go on to have chronic symptoms and continued disability. Persistence of symptoms adds to the economic burden of PHP and cost-effective solutions are needed. Currently, there is a wide variation in treatment, cost, and outcomes of care for PHP with limited information on the cost-effectiveness and comparisons of common treatment approaches. Two practice guidelines and recent evidence of effective physical therapy intervention are available to direct treatment but the timing and influence of physical therapy intervention in the multidisciplinary management of PHP is unclear. The purpose of this investigation is to compare the outcomes and costs associated with early physical therapy intervention (ePT) following initial presentation to podiatry versus usual podiatric care (uPOD) in individuals with PHP. Methods A parallel-group, block-randomized clinical trial will compare ePT and uPOD. Both groups will be seen initially by a podiatrist before allocation to a group that will receive physical therapy intervention consisting primarily of manual therapy, exercise, and modalities, or podiatric care consisting primarily of a stretching handout, medication, injections, and orthotics. Treatment in each group will be directed by practice guidelines and a procedural manual, yet the specific intervention for each participant will be selected by the treating provider. Between-group differences in the Foot and Ankle Ability Measure 6 months following the initial visit will be the primary outcome collected by an independent investigator. In addition, differences in the European Quality of Life – Five Dimensions, Numeric Pain Rating Scale, Global Rating of Change (GROC), health-related costs, and cost-effectiveness at 6 weeks, 6 months, and 1 year will be compared between groups. The association between successful outcomes based on GROC score and participant expectations of recovery generally, and specific to physical therapy and podiatry treatment, will also be analyzed. Discussion This study will be the first pragmatic trial to investigate the clinical outcomes and cost-effectiveness of ePT and uPOD in individuals with PHP. The results will serve to inform clinical practice decisions and management guidelines of multiple disciplines. Trial registration ClinicalTrials.gov: NCT01865734

2013-01-01

41

Are people with negative diabetes screening tests falsely reassured? Parallel group cohort study embedded in the ADDITION (Cambridge) randomised controlled trial  

PubMed Central

Objective To assess whether receiving a negative test result at primary care based stepwise diabetes screening results in false reassurance. Design Parallel group cohort study embedded in a randomised controlled trial. Setting 15 practices (10 screening, 5 control) in the ADDITION (Cambridge) trial. Participants 5334 adults (aged 40-69) in the top quarter for risk of having undiagnosed type 2 diabetes (964 controls and 4370 screening attenders). Main outcome measures Perceived personal and comparative risk of diabetes, intentions for behavioural change, and self rated health measured after an initial random blood glucose test and at 3-6 and 12-15 months later (equivalent time points for controls). Results A linear mixed effects model with control for clustering by practice found no significant differences between controls and people who screened negative for diabetes in perceived personal risk, behavioural intentions, or self rated health after the first appointment or at 3-6 months or 12-15 months later. After the initial test, people who screened negative reported significantly (but slightly) lower perceived comparative risk (mean difference ?0.16, 95% confidence interval ?0.30 to ?0.02; P=0.04) than the control group at the equivalent time point; no differences were evident at 3-6 and 12-15 months. Conclusions A negative test result at diabetes screening does not seem to promote false reassurance, whether this is expressed as lower perceived risk, lower intentions for health related behavioural change, or higher self rated health. Implementing a widespread programme of primary care based stepwise screening for type 2 diabetes is unlikely to cause an adverse shift in the population distribution of plasma glucose and cardiovascular risk resulting from an increase in unhealthy behaviours arising from false reassurance among people who screen negative. Trial registration Current controlled trials ISRCTN99175498.

2009-01-01

42

Evaluating a community-based early childhood education and development program in Indonesia: study protocol for a pragmatic cluster randomized controlled trial with supplementary matched control group  

PubMed Central

Background This paper presents the study protocol for a pragmatic cluster randomized controlled trial (RCT) with a supplementary matched control group. The aim of the trial is to evaluate a community-based early education and development program launched by the Government of Indonesia. The program was developed in collaboration with the World Bank with a total budget of US$127.7 million, and targets an estimated 738,000 children aged 0 to 6 years living in approximately 6,000 poor communities. The aim of the program is to increase access to early childhood services with the secondary aim of improving school readiness. Methods/Design The study is being conducted across nine districts. The baseline survey contained 310 villages, of which 100 were originally allocated to the intervention arm, 20 originally allocated to a 9-month delay staggered start, 100 originally allocated to an 18-month delay staggered start and 90 allocated to a matched control group (no intervention). The study consists of two cohorts, one comprising children aged 12 to 23 months and the other comprising children aged 48 to 59 months at baseline. The data collection instruments include child observations and task/game-based assessments as well as a questionnaire suite, village head questionnaire, service level questionnaires, household questionnaire, and child caretaker questionnaire. The baseline survey was conducted from March to April 2009, midline was conducted from April to August 2010 and endline conducted early 2013. The resultant participation rates at both the district and village levels were 90%. At the child level, the participation rate was 99.92%. The retention rate at the child level at midline was 99.67%. Discussion This protocol paper provides a detailed record of the trial design including a discussion regarding difficulties faced with compliance to the randomization, compliance to the dispersion schedule of community block grants, and procurement delays for baseline and midline data collections. Considering the execution of the program and the resultant threats to the study, we discuss our analytical plan and intentions for endline data collection. Trials registration Current Controlled Trials ISRCTN76061874

2013-01-01

43

Effectiveness and cost-effectiveness of a group-based pain self-management intervention for patients undergoing total hip replacement: feasibility study for a randomized controlled trial  

PubMed Central

Background Total hip replacement (THR) is a common elective surgical procedure and can be effective for reducing chronic pain. However, waiting times can be considerable. A pain self-management intervention may provide patients with skills to more effectively manage their pain and its impact during their wait for surgery. This study aimed to evaluate the feasibility of conducting a randomized controlled trial to assess the effectiveness and cost-effectiveness of a group-based pain self-management course for patients undergoing THR. Methods Patients listed for a THR at one orthopedic center were posted a study invitation pack. Participants were randomized to attend a pain self-management course plus standard care or standard care only. The lay-led course was delivered by Arthritis Care and consisted of two half-day sessions prior to surgery and one full-day session after surgery. Participants provided outcome and resource-use data using a diary and postal questionnaires prior to surgery and one month, three months and six months after surgery. Brief telephone interviews were conducted with non-participants to explore barriers to participation. Results Invitations were sent to 385 eligible patients and 88 patients (23%) consented to participate. Interviews with 57 non-participants revealed the most common reasons for non-participation were views about the course and transport difficulties. Of the 43 patients randomized to the intervention group, 28 attended the pre-operative pain self-management sessions and 11 attended the post-operative sessions. Participant satisfaction with the course was high, and feedback highlighted that patients enjoyed the group format. Retention of participants was acceptable (83% of recruited patients completed follow-up) and questionnaire return rates were high (72% to 93%), with the exception of the pre-operative resource-use diary (35% return rate). Resource-use completion rates allowed for an economic evaluation from the health and social care payer perspective. Conclusions This study highlights the importance of feasibility work prior to a randomized controlled trial to assess recruitment methods and rates, barriers to participation, logistics of scheduling group-based interventions, acceptability of the intervention and piloting resource use questionnaires to improve data available for economic evaluations. This information is of value to researchers and funders in the design and commissioning of future research. Trial registration Current Controlled Trials ISRCTN52305381.

2014-01-01

44

Effectiveness of group acceptance and commitment therapy for fibromyalgia: a 6-month randomized controlled trial (EFFIGACT study).  

PubMed

In the last decade, there has been burgeoning interest in the effectiveness of third-generation psychological therapies for managing fibromyalgia (FM) symptoms. The present study examined the effectiveness of acceptance and commitment therapy (ACT) on functional status as well as the role of pain acceptance as a mediator of treatment outcomes in FM patients. A total of 156 patients with FM were enrolled at primary health care centers in Zaragoza, Spain. The patients were randomly assigned to a group-based form of ACT (GACT), recommended pharmacological treatment (RPT; pregabalin + duloxetine), or wait list (WL). The primary end point was functional status (measured with the Fibromyalgia Impact Questionnaire, FIQ). Secondary end points included pain catastrophizing, pain acceptance, pain, anxiety, depression, and health-related quality of life. The differences between groups were calculated by linear mixed-effects (intention-to-treat approach) and mediational models through path analyses. Overall, GACT was statistically superior to both RPT and WL immediately after treatment, and improvements were maintained at 6months with medium effect sizes in most cases. Immediately after treatment, the number needed to treat for 20% improvement compared to RPT was 2 (95% confidence interval 1.2-2.0), for 50% improvement 46, and for achieving a status of no worse than mild impaired function (FIQ total score <39) also 46. Unexpectedly, 4 of the 5 tested path analyses did not show a mediation effect. Changes in pain acceptance only mediated the relationship between study condition and health-related quality of life. These findings are discussed in relation to previous psychological research on FM treatment. PMID:24378880

Luciano, Juan V; Guallar, José A; Aguado, Jaume; López-Del-Hoyo, Yolanda; Olivan, Bárbara; Magallón, Rosa; Alda, Marta; Serrano-Blanco, Antoni; Gili, Margalida; Garcia-Campayo, Javier

2014-04-01

45

Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97.  

PubMed

In this study, the long-term outcome of 1818 patients treated in five consecutive clinical trials (the cooperative study group for childhood acute lymphoblastic leukaemia (COALL) 82, 85, 89, 92 and 97) from 24 cooperating centres in Germany is reported. The probability of event-free survival (pEFS) improved significantly from the first two trials conducted in the 1980s (COALL 82 and COALL 85) to the three trials conducted in the 1990s (COALL 89, 92 and 97) (P=0.001). Through all COALL studies, age > or =10 years and initial white blood cell count (WBC) > or =50 x 10(9)/l and pro-B immunophenotype were of significant prognostic relevance. A refinement of risk assessment has been achieved by in vitro drug sensitivity testing in COALL 92 and 97. In patients with very sensitive leukaemic cells, therapy could be reduced without loss of efficacy. In COALL 97, a further improvement in risk stratification was gained by the molecular assessment of minimal residual disease (MRD) under treatment, which proved to have a superior prognostic effect when compared with in vitro drug sensitivity testing. Importantly, the gradual reduction in central nervous system (CNS) irradiation led to a decreased incidence of brain tumours as a second malignancy. In general, the prevention of treatment-related late effects will be one of the major issues in future studies. It remains to be shown whether prolonged infusions of anthracyclines, which have been implemented into the COALL studies after equal efficacy compared with short-time infusions was confirmed, will be associated with fewer cardiac late effects. Another way to prevent late effects may be a more refined risk assessment allowing for a reduction in cumulative treatment burden. A great challenge in the future will be to improve the overall treatment results, which very likely can only be achieved by the identification of molecularly defined subgroups to which novel, rational therapeutic strategies can be applied. PMID:20016530

Escherich, G; Horstmann, M A; Zimmermann, M; Janka-Schaub, G E

2010-02-01

46

Effectiveness and cost-effectiveness of a novel, group self-management course for adults with chronic musculoskeletal pain: study protocol for a multicentre, randomised controlled trial (COPERS)  

PubMed Central

Introduction Chronic musculoskeletal pain is a common condition that often responds poorly to treatment. Self-management courses have been advocated as a non-drug pain management technique, although evidence for their effectiveness is equivocal. We designed and piloted a self-management course based on evidence for effectiveness for specific course components and characteristics. Methods/analysis COPERS (coping with persistent pain, effectiveness research into self-management) is a pragmatic randomised controlled trial testing the effectiveness and cost-effectiveness of an intensive, group, cognitive behavioural-based, theoretically informed and manualised self-management course for chronic pain patients against a control of best usual care: a pain education booklet and a relaxation CD. The course lasts for 15?h, spread over 3?days, with a –2?h follow-up session 2?weeks later. We aim to recruit 685 participants with chronic musculoskeletal pain from primary, intermediate and secondary care services in two UK regions. The study is powered to show a standardised mean difference of 0.3 in the primary outcome, pain-related disability. Secondary outcomes include generic health-related quality of life, healthcare utilisation, pain self-efficacy, coping, depression, anxiety and social engagement. Outcomes are measured at 6 and 12?months postrandomisation. Pain self-efficacy is measured at 3?months to assess whether change mediates clinical effect. Ethics/dissemination Ethics approval was given by Cambridgeshire Ethics 11/EE/046. This trial will provide robust data on the effectiveness and cost-effectiveness of an evidence-based, group self-management programme for chronic musculoskeletal pain. The published outcomes will help to inform future policy and practice around such self-management courses, both nationally and internationally. Trial registration ISRCTN24426731.

Carnes, Dawn; Taylor, Stephanie JC; Homer, Kate; Eldridge, Sandra; Bremner, Stephen; Pincus, Tamar; Rahman, Anisur; Underwood, Martin

2013-01-01

47

Attitudes toward participation in breast cancer randomized clinical trials in the African-American community: a focus group study. | accrualnet.cancer.gov  

Cancer.gov

Focus groups revealed that African-American women are largely positive about breast cancer clinical research, with more than half reporting that they would be interested in participating in a hypothetical trial. Several major issues that influenced these women’s willingness, or unwillingness, to participate in trials were identified. Insights gained may help researchers develop protocols and recruitment procedures that are culturally sensitive and relevant to this population.

48

Do randomized clinical trials with inadequate blinding report enhanced placebo effects for intervention groups and nocebo effects for placebo groups? A protocol for a meta-epidemiological study of PDE-5 inhibitors  

PubMed Central

Background Patients’ expectations of treatment effects may contribute to positive (placebo) and negative (nocebo) outcomes. The effect of patient expectations may be pronounced in subjectively assessed conditions, such as male erectile dysfunction. The aim of this project is to examine the magnitude of expectancy in trials of phosphodiesterase-5 inhibitors. We hypothesize that randomized controlled trials with inadequate blinding will report enhanced placebo effects for intervention groups and nocebo effects for placebo groups, compared with adequately blinded studies. Methods/design We will quantify the magnitude of expectancy by comparing the effect estimates of trials with inadequate and adequate blinding. Blinding will be assessed using four domains from the Cochrane ‘risk-of-bias’ tool: allocation concealment; blinding of patient; caregiver; and outcome assessor. Our secondary aim is to identify factors that can modify expectations, such as prior experience with the intervention and drug side effects. We will perform an electronic search using a combination of controlled vocabulary and free text words in the following databases: MEDLINE, EMBASE, CENTRAL, and a clinical trials register. We will include randomized controlled trials, with either parallel or crossover design, that compare one phosphodiesterase-5 inhibitor with a placebo. The study’s primary aim should be to investigate the efficacy of phosphodiesterase-5 inhibitors for treating male erectile dysfunction. Screening will take place at two levels: abstracts and titles, followed by full text reports. Two reviewers will independently extract data on the primary outcome and assess risk of bias. We will meta-analyze treatment effects, if appropriate, to assess the magnitude of enhanced placebo effects and nocebo effects in intervention and placebo groups, respectively. We will explore possible mediators of placebo and nocebo effects with subgroup and meta-regression analyses. Discussion Treatments may confer significant costs and risk of adverse effects; it is important, therefore, to determine whether the effects of treatments are larger than expectancy alone. If treatment expectations can be used in a non-deceptive way to produce clinically advantageous outcomes, then it may be possible to incorporate such mechanisms into evidence-based healthcare decision-making.

2012-01-01

49

Key treatment questions in childhood acute lymphoblastic leukemia: results in 5 consecutive trials performed by the ALL-BFM study group from 1981 to 2000.  

PubMed

Between 1981 and 2000, 6 609 children (<18 years of age) were treated in 5 consecutive trials of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria, and Switzerland. Probability of 10-year event-free survival (survival) improved from 65% (77%) in study ALL-BFM 81-78% (85%) in ALL-BFM 95. In parallel to relapse reduction, major efforts focused on reducing acute and late toxicity through advanced risk adaptation of treatment. The major findings derived from these ALL-BFM trials were as follows: 1) preventive cranial radiotherapy could be safely reduced to 12 Gy in T-ALL and high-risk ALL patients and eliminated in non-high-risk non-T-ALL patients, if it was replaced by high-dose and intrathecal methotrexate; 2) omission of delayed reintensification severely impaired outcome of low-risk patients; 3) 6 months less maintenance therapy caused an increase in systemic relapses; 4) slow response to an initial 7-day prednisone window was identified as adverse prognostic factor; 5) condensed induction therapy resulted in a significant improvement of outcome; 6) the daunorubicin dose in induction could be safely reduced in low-risk patients; 7) intensification of consolidation/reintensification treatment led to considerable improvement of outcome in high-risk patients. PMID:23700060

Schrappe, M; Möricke, A; Reiter, A; Henze, G; Welte, K; Gadner, H; Ludwig, W-D; Ritter, J; Harbott, J; Mann, G; Klingebiel, T; Gruhn, B; Niemeyer, C; Kremens, B; Niggli, F; Debatin, K-M; Ratei, R; Stanulla, M; Beier, R; Cario, G; Schrauder, A; Zimmermann, M

2013-05-01

50

Peer support for family carers of people with dementia, alone or in combination with group reminiscence in a factorial design: study protocol for a randomised controlled trial  

PubMed Central

Background Peer support interventions can improve carer wellbeing and interventions that engage both the carer and person with dementia can have significant mutual benefits. Existing research has been criticised for inadequate rigour of design or reporting. This paper describes the protocol for a complex trial that evaluates one-to-one peer support and a group reminiscence programme, both separately and together, in a factorial design. Design A 2 × 2 factorial multi-site randomised controlled trial of individual peer support and group reminiscence interventions for family carers and people with dementia in community settings in England, addressing both effectiveness and cost-effectiveness. Discussion The methods described in this protocol have implications for research into psychosocial interventions, particularly complex interventions seeking to test both individual and group approaches. Trial Registration ISRCTN37956201

2011-01-01

51

Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC clinical trials group BR24 study.  

PubMed

PURPOSE This phase II/III double-blind study assessed efficacy and safety of cediranib with standard chemotherapy as initial therapy for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Paclitaxel (200 mg/m(2)) and carboplatin (area under the serum concentration-time curve 6) were given every 3 weeks, with daily oral cediranib or placebo at 30 mg (first 45 patients received 45 mg). Progression-free survival (PFS) was the primary outcome of the phase II interim analysis; phase III would proceed if the hazard ratio (HR) for PFS < or = 0.77 and toxicity were acceptable. Results A total of 296 patients were enrolled, 251 to the 30-mg cohort. The phase II interim analysis demonstrated a significantly higher response rate (RR) for cediranib than for placebo, HR of 0.77 for PFS, no excess hemoptysis, and a similar number of deaths in each arm. The study was halted to review imbalances in assigned causes of death. In the primary phase II analysis (30-mg cohort), the adjusted HR for PFS was 0.77 (95% CI, 0.56 to 1.08) with a higher RR for cediranib than for placebo (38% v 16%; P < .0001). Cediranib patients had more hypertension, hypothyroidism, hand-foot syndrome, and GI toxicity. Hypoalbuminemia, age > or = 65 years, and female sex predicted increased toxicity. Survival update (N = 296) 10 months after study unblinding favored cediranib over placebo (median of 10.5 months v 10.1 months; HR, 0.78; 95% CI, 0.57 to 1.06; P = .11). Causes of death in the cediranib 30-mg cohort were NSCLC (81%), protocol toxicity +/- NSCLC (13%), and other (6%); for the placebo group, they were 98%, 0%, and 2%, respectively. CONCLUSION The addition of cediranib to carboplatin/paclitaxel results in improved response and PFS, but does not appear tolerable at a 30-mg dose. Consequently, the National Cancer Institute of Canada Clinical Trials Group and the Australasian Lung Cancer Trials Group initiated a randomized, double-blind, placebo-controlled trial of cediranib 20 mg with carboplatin and paclitaxel in advanced NSCLC. PMID:19917841

Goss, Glenwood D; Arnold, Andrew; Shepherd, Frances A; Dediu, Mircea; Ciuleanu, Tudor-Eliade; Fenton, David; Zukin, Mauro; Walde, David; Laberge, Francis; Vincent, Mark D; Ellis, Peter M; Laurie, Scott A; Ding, Keyue; Frymire, Eliot; Gauthier, Isabelle; Leighl, Natasha B; Ho, Cheryl; Noble, Jonathan; Lee, Christopher W; Seymour, Lesley

2010-01-01

52

A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: The Japan clinical oncology group study  

Microsoft Academic Search

Objective: To determine whether postoperative adjuvant chemotherapy confers a survival benefit on patients with esophageal squamous cell carcinoma undergoing radical surgery, we undertook a cooperative, prospective randomized controlled trial. Methods: A total of 205 patients underwent transthoracic esophagectomy with lymphadenectomy at eleven institutions between December 1988 and July 1991. These patients were prospectively randomized into two groups (100 patients underwent

Nobutoshi Ando; Toshifumi Iizuka; Teruo Kakegawa; Kaichi Isono; Hiroshi Watanabe; Hiroko Ide; Otsuo Tanaka; Masayuki Shinoda; Wataru Takiyama; Masaki Arimori; Kaoru Ishida; Shoichiro Tsugane

1997-01-01

53

Fatigue in patients with cancer: results with National Cancer Institute of Canada Clinical Trials Group studies employing the EORTC QLQ-C30  

Microsoft Academic Search

The purpose of this study was to examine the factors which affect the level of fatigue among patients participating in clinical\\u000a trials in which this symptom had been assessed with the EORTC QLQ-C30. Data were assembled from 2390 patients in ten clinical\\u000a trials in which the QLQ-C30 had been used to assess baseline and on-study quality of life. The relationship

Joseph L. Pater; Benny Zee; Michael Palmer; Dianne Johnston; David Osoba

1997-01-01

54

Go4it; study design of a randomised controlled trial and economic evaluation of a multidisciplinary group intervention for obese adolescents for prevention of diabetes mellitus type 2  

PubMed Central

Background In the Netherlands, the first adolescents with diabetes mellitus type 2 as a result of obesity have recently been diagnosed. Therefore, it is very important that programs aiming at the prevention of type 2 diabetes of obese adolescents are developed and evaluated. Methods Go4it is a multidisciplinary group treatment that focuses on: 1) increasing awareness of the current dietary and physical activity behaviour (i.e. energy balance behaviour), 2) improving diet, 3) decreasing sedentary behaviour, 4) increasing levels of physical activity, and 5) coping with difficult situations. Go4it consists of 7 sessions with an interval of 2–3 weeks. The effectiveness of the multidisciplinary group treatment compared with usual care (i.e. referral to a dietician) was evaluated in a randomised controlled trial. We examined effects on BMI(sds), body composition, energy expenditure, glucose tolerance and insulin resistance (primary outcome measure), as well as dietary and physical activity behaviour and quality of life. An economic evaluation from a societal perspective was conducted alongside the randomised trial to evaluate the cost-effectiveness of the multidisciplinary treatment program vs. usual care. Discussion In this paper we described a multidisciplinary treatment program (Go4it) for obese adolescents and the design of a randomised controlled trial and economic evaluation to evaluate its effectiveness and cost-effectiveness. Trial registration Netherlands Trial Register (ISRCTN27626398).

Hofsteenge, Geesje H; Chinapaw, Marijke JM; Weijs, Peter JM; van Tulder, Maurits W; Delemarre-van de Waal, Henriette A

2008-01-01

55

Phase I Three-Dimensional Conformal Radiation Dose Escalation Study in Newly Diagnosed Glioblastoma: Radiation Therapy Oncology Group Trial 98-03  

SciTech Connect

Purpose: To evaluate in a Phase I trial the feasibility and toxicity of dose-escalated three-dimensional conformal radiotherapy (3D-CRT) concurrent with chemotherapy in patients with primary supratentorial glioblastoma (GBM). Methods and Materials: A total of 209 patients were enrolled. All received 46 Gy in 2-Gy fractions to the first planning target volume (PTV{sub 1}), defined as the gross tumor volume (GTV) plus 1.8 cm. A subsequent boost was given to PTV{sub 2}, defined as GTV plus 0.3 cm. Patients were stratified into two groups (Group 1: PTV{sub 2} <75 cm{sup 3}; Group 2: PTV{sub 2} {>=}75 cm{sup 3}). Four RT dose levels were evaluated: 66, 72, 78, and 84 Gy. Carmustine 80 mg/m{sup 2} was given during RT, then every 8 weeks for 6 cycles. Pretreatment characteristics were well balanced. Results: Acute and late Grade 3/4 RT-related toxicities were no more frequent at higher RT dose or with larger tumors. There were no dose-limiting toxicities (acute Grade {>=}3 irreversible central nervous system toxicities) observed on any dose level in either group. On the basis of the absence of dose-limiting toxicities, dose was escalated to 84 Gy in both groups. Late RT necrosis was noted at 66 Gy (1 patient), 72 Gy (2 patients), 78 Gy (2 patients), and 84 Gy (3 patients) in Group 1. In Group 2, late RT necrosis was noted at 78 Gy (1 patient) and 84 Gy (2 patients). Median time to RT necrosis was 8.8 months (range, 5.1-12.5 months). Median survival in Group 1 was 11.6-19.3 months. Median survival in Group 2 was 8.2-13.9 months. Conclusions: Our study shows the feasibility of delivering higher than standard (60 Gy) RT dose with concurrent chemotherapy for primary GBM, with an acceptable risk of late central nervous system toxicity.

Tsien, Christina [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States)], E-mail: ctsien@umich.edu; Moughan, Jennifer [Radiation Therapy Oncology Group, Philadelphia, PA (United States); Michalski, Jeff M. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Gilbert, Mark R. [Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Purdy, James [University of California-Davis Medical Center, Sacramento, CA (United States); Simpson, Joseph [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Kresel, John J. [Arizona Oncology Services and Barrows Neurological Institute, Phoenix, AZ (United States); Curran, Walter J. [Thomas Jefferson University, Philadelphia, PA (United States); Diaz, Aidnag [University of Texas Health Science Center, San Antonio, TX (United States); Mehta, Minesh P. [University of Wisconsin, Madison, WI (United States)

2009-03-01

56

Effective components of feedback from Routine Outcome Monitoring (ROM) in youth mental health care: study protocol of a three-arm parallel-group randomized controlled trial  

PubMed Central

Background Routine Outcome Monitoring refers to regular measurements of clients’ progress in clinical practice, aiming to evaluate and, if necessary, adapt treatment. Clients fill out questionnaires and clinicians receive feedback about the results. Studies concerning feedback in youth mental health care are rare. The effects of feedback, the importance of specific aspects of feedback, and the mechanisms underlying the effects of feedback are unknown. In the present study, several potentially effective components of feedback from Routine Outcome Monitoring in youth mental health care in the Netherlands are investigated. Methods/Design We will examine three different forms of feedback through a three-arm parallel-group randomized controlled trial. 432 children and adolescents (aged 4 to 17 years) and their parents, who have been referred to mental health care institution Pro Persona, will be randomly assigned to one of three feedback conditions (144 participants per condition). Randomization will be stratified by age of the child or adolescent and by department. All participants fill out questionnaires at the start of treatment, one and a half months after the start of treatment, every three months during treatment, and at the end of treatment. Participants in the second and third feedback conditions fill out an additional questionnaire. In condition 1, clinicians receive basic feedback regarding clients’ symptoms and quality of life. In condition 2, the feedback of condition 1 is extended with feedback regarding possible obstacles to a good outcome and with practical suggestions. In condition 3, the feedback of condition 2 is discussed with a colleague while following a standardized format for case consultation. The primary outcome measure is symptom severity and secondary outcome measures are quality of life, satisfaction with treatment, number of sessions, length of treatment, and rates of dropout. We will also examine the role of being not on track (not responding to treatment). Discussion This study contributes to the identification of effective components of feedback and a better understanding of how feedback functions in real-world clinical practice. If the different feedback components prove to be effective, this can help to support and improve the care for youth. Trial registration Dutch Trial Register NTR4234

2014-01-01

57

Epirubicin-vinorelbine vs FEC100 for node-positive, early breast cancer: French Adjuvant Study Group 09 trial  

PubMed Central

The aim of the study was to compare our reference adjuvant chemotherapy, FEC100 (fluorouracil 500?mg?m?2, epirubicin 100?mg?m?2 and cyclophosphamide 500?mg?m?2, six cycles every 21 days), to an epirubicin–vinorelbine (Epi-Vnr) combination for early, poor-prognosis breast cancer patients. Patients (482) were randomised to receive FEC100, or Epi-Vnr (epirubicin 50?mg?m?2 day 1 and vinorelbine 25?mg?m?2, days 1 and 8, six cycles every 21 days). The 7-year disease-free survival rates were 59.4 and 58.8%, respectively (P=0.47). The relative dose intensity of planned epirubicin doses was 89.1% with FEC100 and 88.9% with Epi-Vnr. There were significantly more grades 3–4 neutropenia (P=0.009) with Epi-Vnr, and significantly more nausea-vomiting (P<0.0001), stomatitis (P=0.0007) and alopecia (P<0.0001) with FEC100. No cases of congestive heart failure were reported, whereas four decreases in left ventricular ejection fraction occurred after FEC100 and five after Epi-Vnr. One case of acute myeloblastic leukaemia was registered in the FEC100 arm. After 7 years of follow-up, there was no difference between treatment arms. Epi-Vnr regimen provided a good efficacy in such poor-prognosis breast cancer patients, and could be an alternative to FEC100, taking into account respective safety profiles of both regimens.

Kerbrat, P; Roche, H; Bonneterre, J; Veyret, C; Lortholary, A; Monnier, A; Fumoleau, P; Fargeot, P; Namer, M; Chollet, P; Goudier, M-J; Audhuy, B; Simon, H; Montcuquet, P; Eymard, J-C; Walter, S; Clavere, P; Guastalla, J-P

2007-01-01

58

Para-aortic irradiation for stage I testicular seminoma: results of a prospective study in 675 patients. A trial of the German testicular cancer study group (GTCSG).  

PubMed

A prospective nonrandomised trial was performed in order to evaluate tumour control and toxicity of low-dose adjuvant radiotherapy in stage I seminoma with treatment portals confined to the para-aortic lymph nodes. Between April 1991 and March 1994, 721 patients were enrolled for the trial by 48 centres in Germany. Patients with pure seminoma and no evidence of lymph node involvement or distant metastases received 26 Gy prophylactic limited para-aortic radiotherapy. Disease-free survival at 5 years was the primary end point. With a median follow-up of 61 months, 675 patients with follow-up investigations were evaluable for this analysis. Kaplan-Meier estimates of disease-free and disease-specific survival were 95.8% (95% CI: 94.2-97.4) and 99.6% (95% CI: 99.2-100%) at 5 years and 94.9% (95% CI: 92.5-97.4%) and 99.6% (95% CI: 99.2-100%) at 8 years, respectively. A total of 26 patients relapsed. All except two were salvaged from relapse. In all, 21 recurrences were located in infradiaphragmatic lymph nodes without any 'in-field' relapse. Nausea and diarrhoea grade 3 were observed in 4.0 and 1.0% of the patients, respectively. Grade 3 late effects have not been observed so far. The results of our trial lend further support to the concept of limited para-aortic irradiation as the recently defined new standard of radiotherapy in stage I seminoma. There is no obvious compromise in disease-specific or disease-free survival compared to more extensive hockey-stick portals, which were used as standard portals at the time this study was initiated. PMID:15150576

Classen, J; Schmidberger, H; Meisner, C; Winkler, C; Dunst, J; Souchon, R; Weissbach, L; Budach, V; Alberti, W; Bamberg, M

2004-06-14

59

Web-Based, Cross-Group Registration for Clinical Trials Piloted for NCI's Cooperative Group Members Cancer Trial Support Unit Could Expand to Other Physicians in 2001  

Cancer.gov

Oncologists who belong to the National Cancer Institute's (NCI's) Cooperative Groups can now register online for selected phase III studies in a pilot project intended to streamline and simplify many of the tasks associated with clinical trials.

60

Planning and analyzing adaptive group sequential survival trials.  

PubMed

The use of adaptive methods has experienced increasing interest in the current literature on group sequential designs. Group sequential analysis in survival trials usually apply the error spending function approach due to the unpredictable amount of information available in an interim analysis. An alternative way is to apply adaptive methods where additionally the maximum amount of information and other designing parameters can be changed based on the information available at the interim stage. In this paper, it is shown how the inverse normal method can be used within a survival design using the log-rank test for comparing two survival functions. This method allows for many kinds of design modifications. In case of no modifications, the inverse normal method coincides with the commonly used analysis strategy. It is straightforward to specify effect estimates. Confidence intervals for the hazard ratio that can be calculated at each stage of the trial and intervals that can only be computed by the end of the trial are proposed. The latter also enables the calculation of median unbiased estimates. Overall p-values can be defined analogously. Properties of the analyses techniques are investigated and compared with alternative approaches. It is shown that the proposed analysis technique might help to rescue an underpowered study and opens the way to other types of changes in design. The proposed technique is implemented in the software ADDPLAN Adaptive Design, Plans and Analyses (http://www.addplan.com). PMID:16972724

Wassmer, Gernot

2006-08-01

61

The ACTIVATE study: results from a group-randomized controlled trial comparing a traditional worksite health promotion program with an activated consumer program.  

PubMed

PURPOSE. This study compares a traditional worksite-based health promotion program with an activated consumer program and a control program DESIGN. Group randomized controlled trial with 18-month intervention. SETTING. Two large Midwestern companies. SUBJECTS. Three hundred and twenty employees (51% response). INTERVENTION. The traditional health promotion intervention offered population-level campaigns on physical activity, nutrition, and stress management. The activated consumer intervention included population-level campaigns for evaluating health information, choosing a health benefits plan, and understanding the risks of not taking medications as prescribed. The personal development intervention (control group) offered information on hobbies. The interventions also offered individual-level coaching for high risk individuals in both active intervention groups. MEASURES. Health risk status, general health status, consumer activation, productivity, and the ability to evaluate health information. ANALYSIS. Multivariate analyses controlled for baseline differences among the study groups. RESULTS. At the population level, compared with baseline performance, the traditional health promotion intervention improved health risk status, consumer activation, and the ability to recognize reliable health websites. Compared with baseline performance, the activated consumer intervention improved consumer activation, productivity, and the ability to recognize reliable health websites. At the population level, however, only the activated consumer intervention improved any outcome more than the control group did; that outcome was consumer activation. At the individual level for high risk individuals, both traditional health coaching and activated consumer coaching positively affected health risk status and consumer activation. In addition, both coaching interventions improved participant ability to recognize a reliable health website. Consumer activation coaching also significantly improved self-reported productivity. CONCLUSION. An effective intervention can change employee health risk status and activation both at the population level and at the individual high risk level. However, program engagement at the population level was low, indicating that additional promotional strategies, such as greater use of incentives, need to be examined. Less intensive coaching can be as effective as more intensive, albeit both interventions produced modest behavior change and retention in the consumer activation arm was most difficult. Further research is needed concerning recruitment and retention methods that will enable populations to realize the full potential of activated consumerism. PMID:22040398

Terry, Paul E; Fowles, Jinnet Briggs; Xi, Min; Harvey, Lisa

2011-01-01

62

Pediatric Oncology Group (POG) studies of acute myeloid leukemia (AML): a review of four consecutive childhood AML trials conducted between 1981 and 2000  

Microsoft Academic Search

From 1981 to 2000, a total of 1823 children with acute myeloid leukemia (AML) enrolled on four consecutive Pediatric Oncology Group (POG) clinical trials. POG 8101 demonstrated that the induction rate associated with the 3+7+7 combination of daunorubicin, Ara-C, and 6-thioguanine (DAT) was greater than that associated with an induction regimen used to treat acute lymphoblastic leukemia (82 vs 61%;

Y Ravindranath; M Chang; C P Steuber; D Becton; G Dahl; C Civin; B Camitta; A Carroll; S C Raimondi; H J Weinstein

2005-01-01

63

A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery  

Microsoft Academic Search

Objective: A prospective randomized trial was performed to investigate the prognostic advantage of postoperative adjuvant chemotherapy in patients with resected stage I–II non-small cell lung cancer (NSCLC). Patients and methods: From March 1992 to December 1994, 221 patients with completely resected stage I–II primary NSCLC were enrolled and randomly assigned to two groups, as follows: 2-year oral administration of Uracil

Chiaki Endo; Yasuki Saito; Hiroshi Iwanami; Takao Tsushima; Tadashi Imai; Mitsuo Kawamura; Takashi Kondo; Kaoru Koike; Masashi Handa; Ryuzo Kanno; Shigefumi Fujimura

2003-01-01

64

Is chemotherapy necessary for premenopausal women with lower-risk node-positive, endocrine responsive breast cancer? 10-year update of International Breast Cancer Study Group Trial 11-93  

PubMed Central

Introduction International Breast Cancer Study Group (IBCSG) Trial 11-93 is the largest trial evaluating the role of the addition of chemotherapy to ovarian function suppress/ablation (OFS) and tamoxifen in premenopausal patients with endocrine-responsive early breast cancer. Methods IBCSG Trial 11-93 is a randomized trial comparing 4 cycles of adjuvant chemotherapy (AC: doxorubicin or epirubicin, plus cyclophosphamide) added to OFS and five years of tamoxifen versus OFS and tamoxifen without chemotherapy in premenopausal patients with node-positive, endocrine-responsive early breast cancer. 174 pts were randomized from May, 1993 to Nov, 1998. The trial was closed before the target accrual was reached due to low accrual rate. Results Patients randomized tended to have lower risk node-positive disease and the median age was 45. After 10 years median follow up, there remains no difference between the two randomized treatment groups for disease-free (hazard ratio=1.02 (0.57-1.83); p=0.94) or overall survival (hazard ratio=0.97 (0.44-2.16); p=0.94). Conclusion This trial, although small, offers no evidence that AC chemotherapy provides additional disease control for premenopausal patients with lower-risk node-positive endocrine-responsive breast cancer who receive adequate adjuvant endocrine therapy. A large trial is needed to determine whether chemotherapy adds benefit to endocrine therapy for this population.

Thurlimann, Beat; Price, Karen N.; Gelber, Richard D.; Holmberg, Stig B.; Crivellari, Diana; Colleoni, Marco; Collins, John; Forbes, John F.; Castiglione-Gertsch, Monica; Coates, Alan S.; Goldhirsch, Aron

2010-01-01

65

The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial  

PubMed Central

Background Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder.

2013-01-01

66

Fosinopril attenuates clinical deterioration and improves exercise tolerance in patients with heart failure. Fosinopril Efficacy/Safety Trial (FEST) Study Group.  

PubMed

This study was a 12-week, double-blind, placebo-controlled, multinational trial of fosinopril in 308 patients with mild to moderately severe heart failure (New York Heart Association [NYHA] functional class IIS 17%, IIM 48%, and III 35%; mean ejection fraction [+/-SD] 26.5% [+/-6.9%]; bicycle exercise duration 1 to 11 min). An initial dose of 10 mg once daily was titrated as tolerated to 40 mg once daily. Patients all received diuretic therapy; digoxin was optional. The primary endpoint was maximal bicycle exercise time; a secondary endpoint was occurrence of the following prospectively defined, ordered clinical events indicative of worsening heart failure: death, study discontinuation, hospitalization, emergency room visits, and need for supplemental diuretic. At study endpoint (last value obtained for each patient), bicycle exercise time increased more with fosinopril (38.1 s) than with placebo (23.5 s) (P = 0.101 by ANCOVA and 0.010 by prospectively defined dropout-adjusted endpoint analysis). More patients remained free of clinical events indicative of worsening heart failure when treated with fosinopril (89%) than with placebo (75%), and the worst events of fosinopril-treated patients tended to be less severe than those of placebo patients (P = 0.001). Analysis of the occurrence of individual clinical events showed that the need for supplemental diuretic was markedly reduced with fosinopril (8% vs 20%, of patients, P = 0.002), as were hospitalizations (3% vs 12% of patients, P = 0.002) and study discontinuations (2% vs 12% of patients, P < 0.001) for worsening heart failure; the two groups had similar incidences of death (3% of patients in the fosinopril group vs 2% in the placebo group, P = 0.723). In addition, symptoms of dyspnoea (P = 0.017), fatigue (P = 0.019), and NYHA functional class (P = 0.008) improved with fosinopril relative to placebo. In conclusion, fosinopril, at an initial dose of 10 mg once daily, subsequently titrated as tolerated to 40 mg once daily, increased exercise tolerance and reduced the frequency of clinical events indicative of worsening heart failure. PMID:8682023

Erhardt, L; MacLean, A; Ilgenfritz, J; Gelperin, K; Blumenthal, M

1995-12-01

67

Independent but Coordinated Trials: Insights from the Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group  

PubMed Central

Background The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the “Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.” Purpose We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. Methods The Collaborative Research Group consists of three individual studies: “Be Fit, Be Well“(Washington University in St. Louis/Harvard University), “POWER Hopkins” (Johns Hopkins), and “POWER-UP” (University of Pennsylvania). There are a total of 15 participating clinics with ~1,100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. Results The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. Limitations The challenges of the organizational design include the complex decision making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols. Conclusions The POWER Trials Collaborative Research Group is a case study of an alternative organizational model to conduct independent, yet coordinated trials. Such a model is increasingly being used in NHLBI supported trials , especially given the interest in comparative effectiveness research. Nevertheless, the ultimate utility of this model will not be fully understood until the trials are completed.

Yeh, Hsin-Chieh; Clark, Jeanne M.; Emmons, Karen M.; Moore, Renee H.; Bennett, Gary G; Warner, Erica T.; Sarwer, Davis B.; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A.; Wells, Barbara; Wadden, Thomas A.; Colditz, Graham A.; Appel, Lawrence J.

2011-01-01

68

A randomized controlled trial of group Stepping Stones Triple P: a mixed-disability trial.  

PubMed

Stepping Stones Triple P (SSTP) is a parenting program designed for families of a child with a disability. The current study involved a randomized controlled trial of Group Stepping Stones Triple P (GSSTP) for a mixed-disability group. Participants were 52 families of children diagnosed with an Autism Spectrum Disorder, Down syndrome, Cerebral Palsy, or an intellectual disability. The results demonstrated significant improvements in parent-reported child behavior, parenting styles, parental satisfaction, and conflict about parenting. Results among participants were similar despite children's differing impairments. The intervention effect was maintained at 6-month follow-up. The results indicate that GSSTP is a promising intervention for a mixed-disability group. Limitations of the study, along with areas for future research, are also discussed. PMID:24033239

Roux, Gemma; Sofronoff, Kate; Sanders, Matthew

2013-09-01

69

Phase II study of interleukin-12 for treatment of plateau phase multiple myeloma (E1A96): A trial of the Eastern Cooperative Oncology Group?  

PubMed Central

The Eastern Cooperative Oncology Group (ECOG) conducted a phase II trial of interleukin-12 (IL-12) for plateau phase multiple myeloma. Patients were initially treated with IL-12 250 ng/kg I.V. daily for 5 days every 3 weeks. The trial was modified due to toxicity after the first 16 patients. IL-12 was given 300 ng/kg subcutaneously twice weekly for 24 weeks. Of 48 eligible patients, there were 4 objective responses (8.3%), all CR. The median survival and progression-free survival were 42.8 and 11.4 months. Unacceptable grade 3 or 4 non-hematologic toxicity (31% with IL-12 subcutaneously and 63% with IL-12 intravenously) was observed.

Lacy, Martha Q.; Jacobus, Susanna; Blood, Emily A.; Kay, Neil E.; Rajkumar, S. Vincent; Greipp, Philip R.

2014-01-01

70

Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study. HANE Trial Research Group.  

PubMed Central

OBJECTIVE: To compare the effectiveness and tolerability of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in patients with mild to moderate hypertension. DESIGN: Randomised multicentre trial over 48 weeks with double blind comparison of treatments. SETTING: 48 centres in four countries. PATIENTS: 868 patients with essential hypertension (diastolic blood pressure 95-120 mm Hg) INTERVENTIONS: Initial treatment (step 1) consisted of 12.5 mg hydrochlorothiazide (n = 215), 25 mg atenolol (n = 215), 10 mg nitrendipine (n = 218), or 5 mg enalapril (n = 220) once daily. If diastolic blood pressure was not reduced to < 90 mm Hg within four weeks, doses were increased to 25 mg, 50 mg, 20 mg, 10 mg, respectively, once daily (step 2) and after two more weeks to twice daily (step 3). The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure. MAIN OUTCOME MEASURES: Blood pressure by means of an automatic device with repeated measurements. RESULTS: After eight weeks the response rate for atenolol (63.7%) was significantly higher than for enalapril (50.0%), hydrochlorothiazide (44.7%), or nitrendipine (44.5%). After one year atenolol was still more effective (48.0%) than hydrochlorothiazide (35.4%) and nitrendipine (32.9%), but not significantly better than enalapril (42.7%). The treatment related dropout rate was higher (P < 0.001) in the nitrendipine group (n = 28). CONCLUSIONS: There is no evidence of superiority for antihypertensive effectiveness or tolerability of the "new" classes of antihypertensives (calcium channel blockers and angiotensin converting enzyme inhibitors). As these drugs are now widely used as treatment of first choice, our results further emphasise the need for studies confirming that they also reduce morbidity and mortality, as has been shown for diuretics and beta blockers.

Philipp, T.; Anlauf, M.; Distler, A.; Holzgreve, H.; Michaelis, J.; Wellek, S.

1997-01-01

71

Study protocol for a group randomized controlled trial of a classroom-based intervention aimed at preventing early risk factors for drug abuse: integrating effectiveness and implementation research  

PubMed Central

Background While a number of preventive interventions delivered within schools have shown both short-term and long-term impact in epidemiologically based randomized field trials, programs are not often sustained with high-quality implementation over time. This study was designed to support two purposes. The first purpose was to test the effectiveness of a universal classroom-based intervention, the Whole Day First Grade Program (WD), aimed at two early antecedents to drug abuse and other problem behaviors, namely, aggressive, disruptive behavior and poor academic achievement. The second purpose--the focus of this paper--was to examine the utility of a multilevel structure to support high levels of implementation during the effectiveness trial, to sustain WD practices across additional years, and to train additional teachers in WD practices. Methods The WD intervention integrated three components, each previously tested separately: classroom behavior management; instruction, specifically reading; and family-classroom partnerships around behavior and learning. Teachers and students in 12 schools were randomly assigned to receive either the WD intervention or the standard first-grade program of the school system (SC). Three consecutive cohorts of first graders were randomized within schools to WD or SC classrooms and followed through the end of third grade to test the effectiveness of the WD intervention. Teacher practices were assessed over three years to examine the utility of the multilevel structure to support sustainability and scaling-up. Discussion The design employed in this trial appears to have considerable utility to provide data on WD effectiveness and to inform the field with regard to structures required to move evidence-based programs into practice. Trial Registration Clinical Trials Registration Number: NCT00257088

Poduska, Jeanne; Kellam, Sheppard; Brown, C Hendricks; Ford, Carla; Windham, Amy; Keegan, Natalie; Wang, Wei

2009-01-01

72

Exploring recruitment barriers and facilitators in early cancer detection trials: the use of pre-trial focus groups  

PubMed Central

Background Recruiting to randomized controlled trials is fraught with challenges; with less than one third recruiting to their original target. In preparation for a trial evaluating the effectiveness of a blood test to screen for lung cancer (the ECLS trial), we conducted a qualitative study to explore the potential barriers and facilitators that would impact recruitment. Methods Thirty two people recruited from community settings took part in four focus groups in Glasgow and Dundee (UK). Thematic analysis was used to code the data and develop themes. Results Three sub-themes were developed under the larger theme of recruitment strategies. The first of these themes, recruitment options, considered that participants largely felt that the invitation to participate letter should come from GPs, with postal reminders and face-to-face reminders during primary care contacts. The second theme dealt with understanding randomization and issues related to the control group (where bloods were taken but not tested). Some participants struggled with the concept or need for randomization, or for the need for a control group. Some reported that they would not consider taking part if allocated to the control group, but others were motivated to take part even if allocated to the control group by altruism. The final theme considered perceived barriers to participation and included practical barriers (such as flexible appointments and reimbursement of travel expenses) and psychosocial barriers (such as feeling stigmatized because of their smoking status and worries about being coerced into stopping smoking). Conclusions Focus groups provided useful information which resulted in numerous changes to proposed trial documentation and processes. This was in order to address participants information needs, improve comprehension of the trial documentation, enhance facilitators and remove barriers to participation. The modifications made in light of these findings may enhance trial recruitment and future trials may wish to consider use of pretrial focus groups.

2014-01-01

73

A Phase I/II trial of radiotherapy concurrent with TS-1 plus cisplatin in patients with clinically resectable type 4 or large type 3 gastric cancer: Osaka Gastrointestinal Cancer Chemotherapy Study Group OGSG1205.  

PubMed

A Phase I/II trial of radiotherapy administered concurrently with TS-1 plus cisplatin has been initiated in Japanese patients with clinical resectable type 4 or large type 3 gastric cancer. The aim of this trial is to determine the recommended dose of TS-1 and cisplatin combined with radiotherapy at a fixed dose in the Phase I study, and to evaluate the efficacy and safety in the Phase II study. The primary endpoint for Phase II is the pathological complete response rate, assessed using surgically resected specimens. Secondary endpoints are the response rate, progression-free survival, overall survival, operation transitional rate, R0 resection rate, rate of treatment completion, rate of down-staging and rates of postoperative complications and adverse events. In Phase II, a total of 30 patients will be enrolled in the Osaka Gastrointestinal Cancer Chemotherapy Study Group trial over a period of 6 years. PMID:23447812

Imano, Motohiro; Furukawa, Hiroshi; Yokokawa, Masaki; Nishimura, Yasumasa; Kurokawa, Yukinori; Satoh, Taroh; Sakai, Daisuke; Yasuda, Takushi; Imamoto, Haruhiko; Tujinaka, Toshimasa; Shimokawa, Toshio; Shiozaki, Hitoshi

2013-04-01

74

Interlaboratory variability of CD8 subset measurements by flow cytometry and its applications to multicenter clinical trials. NAID/NICHD Women and Infants Transmission Study Group.  

PubMed Central

Recent studies have demonstrated the utility of measuring subsets of CD8+ T cells as prognostic markers in epidemiology cohort studies of human immunodeficiency virus (HIV)-infected patients. Most of these studies evaluating the value of CD8+ T-cell subsets have been performed at single centers, and few data are available on variability in the measurement of the CD8+ cell populations in multicenter trials. In the current study, we addressed this question by evaluating interlaboratory variability from the five laboratories enrolled in the Women and Infants Transmission Study sponsored by the National Institutes of Health. This study evaluated 35 HIV-positive and 28 HIV-negative proficiency testing samples sent to the laboratories for evaluation. The study focused on the robust coefficient of variation (RCV) for CD38 (11%), HLA-DR (21%), and CD57 (15%) expression on the CD8+ population. Data from the current study indicated that the variability in these measurements is greater than that for CD3+ CD4+ (RCV, 5%) and CD3+ CD8+ (RCV, 5%) cells. Knowledge of the variability of the CD8+ subset measurements should guide investigators in the design and analysis of clinical trials and epidemiology studies. Ability to obtain improved interlaboratory agreement on CD8+ subset measurements will facilitate further evaluation of these markers in HIV studies.

Landay, A L; Brambilla, D; Pitt, J; Hillyer, G; Golenbock, D; Moye, J; Landesman, S; Kagan, J

1995-01-01

75

Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer  

PubMed Central

Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy.

Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Ohlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

2010-01-01

76

A phase III randomized trial of postoperative pelvic irradiation in stage IB cervical carcinoma with poor prognostic features: Follow-up of a gynecologic oncology group study  

SciTech Connect

Purpose: To investigate, in a phase III randomized trial, whether postoperative external-beam irradiation to the standard pelvic field improves the recurrence-free interval and overall survival (OS) in women with Stage IB cervical cancers with negative lymph nodes and certain poor prognostic features treated by radical hysterectomy and pelvic lymphadenectomy. Methods and Materials: Eligible patients had Stage IB cervical cancer with negative lymph nodes but with 2 or more of the following features: more than one third (deep) stromal invasion, capillary lymphatic space involvement, and tumor diameter of 4 cm or more. The study group included 277 patients: 137 randomized to pelvic irradiation (RT) and 140 randomized to observation (OBS). The planned pelvic dose was from 46 Gy in 23 fractions to 50.4 Gy in 28 fractions. Results: Of the 67 recurrences, 24 were in the RT arm and 43 were in the OBS arm. The RT arm showed a statistically significant (46%) reduction in risk of recurrence (hazard ratio [HR] = 0.54, 90% confidence interval [CI] = 0.35 to 0.81, p = 0.007) and a statistically significant reduction in risk of progression or death (HR = 0.58, 90% CI = 0.40 to 0.85, p = 0.009). With RT, 8.8% of patients (3 of 34) with adenosquamous or adenocarcinoma tumors recurred vs. 44.0% (11 of 25) in OBS. Fewer recurrences were seen with RT in patients with adenocarcinoma or adenosquamous histologies relative to others (HR for RT by histology interaction = 0.23, 90% CI = 0.07 to 0.74, p = 0.019). After an extensive follow-up period, 67 deaths have occurred: 27 RT patients and 40 OBS patients. The improvement in overall survival (HR = 0.70, 90% CI = 0.45 to 1.05, p = 0.074) with RT did not reach statistical significance. Conclusions: Pelvic radiotherapy after radical surgery significantly reduces the risk of recurrence and prolongs progression-free survival in women with Stage IB cervical cancer. RT appears to be particularly beneficial for patients with adenocarcinoma or adenosquamous histologies. Circumstances that may have influenced the overall survival differences are considered.

Rotman, Marvin [Department of Radiation Oncology, SUNY Downstate Medical Center, Brooklyn, NY (United States)]. E-mail: mrotman@downstate.edu; Sedlis, Alexander [Department of Obstetrics and Gynecology, SUNY Downstate Medical Center, Brooklyn, NY (United States); Piedmonte, Marion R. [Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY (United States); Bundy, Brian [Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY (United States); Lentz, Samuel S. [Section on Gynecologic Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Muderspach, Laila I. [Women's and Children's Hospital, Keck School of Medicine, University of Southern California, Los Angeles, CA (United States); Zaino, Richard J. [Department of Pathology, Milton S. Hershey Medical Center of Pennsylvania State University, Hershey, PA (United States)

2006-05-01

77

Choosing a Control Group in Effectiveness Trials of Behavioral Drug Abuse Treatments  

PubMed Central

Effectiveness trials are an important step in the scientific process of developing and evaluating behavioral treatments. The focus on effectiveness research presents a different set of requirements on the research design when compared with efficacy studies. The choice of a control condition has many implications for a clinical trial's internal and external validity. The purpose of this manuscript is to provide a discussion of the issues involved in choosing a control group for effectiveness trials of behavioral interventions in substance abuse treatment. The authors provide a description of four trial designs and a discussion of the advantages and disadvantages of each.

Brigham, Gregory S.; Feaster, Daniel J.; Wakim, Paul G.; Dempsey, Catherine L.

2009-01-01

78

Prostate Cancer Clinical Trials Group: The University of Michigan Site.  

National Technical Information Service (NTIS)

Our efforts over this reporting period (April 1, 2010 to March 31, 2011) was on proposing three new concepts and accruing to six DOD-PCCTC trials including two that stem from major contributions by our group c09-057 is a randomized, double-blind, placebo-...

M. Hussain

2011-01-01

79

Prostate Cancer Clinical Trials Group: The University of Michigan Site.  

National Technical Information Service (NTIS)

Our efforts over this reporting period (April 1, 2011 to March 31, 2012) were on proposing one new concept , finishing development of another concept and accruing to six DOD-PCCTC trials including two that stem from major contributions by our group. c11-0...

M. Hussain

2012-01-01

80

GRIN: "GRoup versus INdividual physiotherapy following lower limb intra-muscular Botulinum Toxin-A injections for ambulant children with cerebral palsy: an assessor-masked randomised comparison trial": study protocol  

PubMed Central

Background Cerebral palsy is the most common cause of physical disability in childhood. Spasticity is a significant contributor to the secondary impairments impacting functional performance and participation. The most common lower limb spasticity management is focal intramuscular injections of Botulinum Toxin-Type A accompanied by individually-delivered (one on one) physiotherapy rehabilitation. With increasing emphasis on improving goal-directed functional activity and participation within a family-centred framework, it is timely to explore whether physiotherapy provided in a group could achieve comparable outcomes, encouraging providers to offer flexible models of physiotherapy delivery. This study aims to compare individual to group-based physiotherapy following intramuscular Botulinum Toxin-A injections to the lower limbs for ambulant children with cerebral palsy aged four to fourteen years. Methods/Design An assessor-masked, block randomised comparison trial will be conducted with random allocation to either group-based or individual physiotherapy. A sample size of 30 (15 in each study arm) will be recruited. Both groups will receive six hours of direct therapy following Botulinum Toxin-A injections in either an individual or group format with additional home programme activities (three exercises to be performed three times a week). Study groups will be compared at baseline (T1), then at 10 weeks (T2, efficacy) and 26 weeks (T3, retention) post Botulinum Toxin-A injections. Primary outcomes will be caregiver/s perception of and satisfaction with their child’s occupational performance goals (Canadian Occupational Performance Measure) and quality of gait (Edinburgh Visual Gait Score) with a range of secondary outcomes across domains of the International Classification of Disability, Functioning and Health. Discussion This paper outlines the study protocol including theoretical basis, study hypotheses and outcome measures for this assessor-masked, randomised comparison trial comparing group versus individual models of physiotherapy following intramuscular injections of Botulinum Toxin-A to the lower limbs for ambulant children with cerebral palsy. Trial registration ACTRN12611000454976

2014-01-01

81

Tobacco Assessment in Actively Accruing National Cancer Institute Cooperative Group Program Clinical Trials  

PubMed Central

Purpose Substantial evidence suggests that tobacco use has adverse effects on cancer treatment outcomes; however, routine assessment of tobacco use has not been fully incorporated into standard clinical oncology practice. The purpose of this study was to evaluate tobacco use assessment in patients enrolled onto actively accruing cancer clinical trials. Methods Protocols and forms for 155 actively accruing trials in the National Cancer Institute's (NCI's) Clinical Trials Cooperative Group Program were evaluated for tobacco use assessment at enrollment and follow-up by using a structured coding instrument. Results Of the 155 clinical trials reviewed, 45 (29%) assessed any form of tobacco use at enrollment, but only 34 (21.9%) assessed current cigarette use. Only seven trials (4.5%) assessed any form of tobacco use during follow-up. Secondhand smoke exposure was captured in 2.6% of trials at enrollment and 0.6% during follow-up. None of the trials assessed nicotine dependence or interest in quitting at any point during enrollment or treatment. Tobacco status assessment was higher in lung/head and neck trials as well as phase III trials, but there was no difference according to year of starting accrual or cooperative group. Conclusion Most actively accruing cooperative group clinical trials do not assess tobacco use, and there is no observable trend in improvement over the past 8 years. Failure to incorporate standardized tobacco assessments into NCI-funded Cooperative Group Clinical Trials will limit the ability to provide evidence-based cessation support and will limit the ability to accurately understand the precise effect of tobacco use on cancer treatment outcomes.

Peters, Erica N.; Torres, Essie; Toll, Benjamin A.; Cummings, K. Michael; Gritz, Ellen R.; Hyland, Andrew; Herbst, Roy S.; Marshall, James R.; Warren, Graham W.

2012-01-01

82

White Paper of the PhRMA Working Group on Adaptive Dose-Ranging Studies Innovative Approaches for Designing and Analyzing Adaptive Dose-Ranging Trials  

Microsoft Academic Search

1. BACKGROUND In the spring of 2005, the Pharmaceutical Innovation Steering Committee (PISC) of PhRMA formed several working groups to look into different drivers of the decreasing success rates observed in drug development programs across the pharmaceutical industry, identified in a previous survey conducted by a consulting group. Among those was the Adaptive Dose-Ranging Designs (initially called Rolling Dose Studies)

Björn Bornkamp; Frank Bretz; Alex Dmitrienko; Eli Lilly; Greg Enas; Brenda Gaydos; Chyi-Hung Hsu; Franz König; Michael Krams; Qing Liu; Beat Neuenschwander; Tom Parke; José Pinheiro; Amit Roy; Bristol-Myers Squibb; Rick Sax; Frank Shen

83

Facilitating Teacher Study Groups  

ERIC Educational Resources Information Center

Although literacy coaching means many different things, all coaching initiatives have one common commitment: the goal of building teacher expertise. In the authors' work as coaches and with coaches, they have relied on teacher study groups as a main strategy for accomplishing this task. Their understanding of the potential for study groups has…

Walpole, Sharon; Beauchat, Katherine A.

2008-01-01

84

Patient Reported Outcomes of a Randomized, Placebo-Controlled Trial of Bevacizumab in the Front-Line Treatment of Ovarian Cancer: A Gynecologic Oncology Group Study  

PubMed Central

Purpose To analyze quality of life (QOL) in a randomized, placebo-controlled phase III trial concluding that the addition of concurrent and maintenance bevacizumab (Arm 3) to carboplatin and paclitaxel prolongs progression-free survival in front-line treatment of advanced ovarian cancer compared to chemotherapy alone (Arm 1) or chemotherapy with bevacizumab in cycles 2–6 only (Arm 2). Patients and Methods The Trial Outcome Index of the Functional Assessment of Cancer Therapy-Ovary (FACT-O TOI) was used to assess QOL before cycles 1, 4, 7, 13, and 21; and 6 months after completing study therapy. Differences in QOL scores were assessed using a linear mixed model, adjusting for baseline score, and age. The significance level was set at 0.0167 to account for multiple comparisons. Results 1693 patients were queried. Arm 2 (p<0.001) and Arm 3 (p<0.001) reported lower QOL scores than those in Arm 1. The treatment differences were observed mainly at cycle 4, when the patients receiving bevacizumab (Arm 2 and Arm 3) reported 2.72 points (98.3% CI: 0.88 ~ 4.57; effect size=0.18) and 2.96 points (98.3% CI: 1.13~4.78; effect size=0.20) lower QOL respectively, than those in Arm 1. The difference in QOL scores between Arm 1 and Arm 3 remained statistically significant up to cycle 7. The percentage of patients who reported abdominal discomfort dropped over time, without significant differences among study arms. Conclusion The small QOL difference observed during chemotherapy did not persist during maintenance bevacizumab.

Monk, Bradley J.; Huang, Helen Q.; Burger, Robert A.; Mannel, Robert S.; Homesley, Howard D.; Fowler, Jeffrey; Greer, Benjamin E.; Boente, Matthew; Liang, Sharon X.; Wenzel, Lari

2014-01-01

85

Erectile dysfunction is frequent in systemic sclerosis and associated with severe disease: a study of the EULAR Scleroderma Trial and Research group  

PubMed Central

Introduction Erectile dysfunction (ED) is common in men with systemic sclerosis (SSc) but the demographics, risk factors and treatment coverage for ED are not well known. Method This study was carried out prospectively in the multinational EULAR Scleroderma Trial and Research database by amending the electronic data-entry system with the International Index of Erectile Function-5 and items related to ED risk factors and treatment. Centres participating in this EULAR Scleroderma Trial and Research substudy were asked to recruit patients consecutively. Results Of the 130 men studied, only 23 (17.7%) had a normal International Index of Erectile Function-5 score. Thirty-eight per cent of all participants had severe ED (International Index of Erectile Function-5 score ? 7). Men with ED were significantly older than subjects without ED (54.8 years vs. 43.3 years, P < 0.001) and more frequently had simultaneous non-SSc-related risk factors such as alcohol consumption. In 82% of SSc patients, the onset of ED was after the manifestation of the first non-Raynaud's symptom (median delay 4.1 years). ED was associated with severe cutaneous, muscular or renal involvement of SSc, elevated pulmonary pressures and restrictive lung disease. ED was treated in only 27.8% of men. The most common treatment was sildenafil, whose efficacy is not established in ED of SSc patients. Conclusions Severe ED is a common and early problem in men with SSc. Physicians should address modifiable risk factors actively. More research into the pathophysiology, longitudinal development, treatment and psychosocial impact of ED is needed.

2012-01-01

86

Phase II Trial of Hydroxyurea, Dacarbazine (DTIC), and Etoposide (VP-16) in Mixed Mesodermal Tumors of the Uterus: A Gynecologic Oncology Group Study  

Microsoft Academic Search

Objective: The purpose of this study was to evaluate the efficacy of this three-drug regimen—hydroxyurea, dacarbazine (DTIC), and etoposide (VP-16)—in patients with advanced or recurrent mixed mesodermal tumors (MMT) of the uterus who had not undergone previous chemotherapy. The study was performed as a groupwide phase II study of the Gynecologic Oncology Group. Study Design: Thirty-three evaluable patients received hydroxyurea

John L. Currie; John A. Blessing; Ramon McGehee; John T. Soper; Michael Berman

1996-01-01

87

The reliability, validity and responsiveness of the International Restless Legs Syndrome Study Group rating scale and subscales in a clinical-trial setting  

Microsoft Academic Search

Patients and methodsTo assess the reliability, validity, and responsiveness of the International Restless Legs Syndrome Study Group's rating scale (the International Restless Legs Scale (IRLS)) (V2.0), using pooled data from two matching, placebo-controlled studies of ropinirole for treating Restless Legs Syndrome (RLS).

Linda Abetz; Robert Arbuckle; Richard P. Allen; Diego Garcia-Borreguero; Wayne Hening; Arthur S. Walters; Elena Mavraki; Jeffrey M. Kirsch

2006-01-01

88

Report From the Working Group Conference on Multisite Trial Design for Cognitive Remediation in Schizophrenia  

PubMed Central

The National Institute of Mental Health (NIMH)-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Project and related efforts have stimulated the initiation of several studies of pharmacologic treatments for cognitive impairment in schizophrenia. Cognitive remediation may provide an excellent platform for the provision of new learning opportunities and the acquisition of new skills for patients who are engaged in pharmacologic trials to improve cognition. However, it is not clear how a cognitive remediation intervention would be employed in multisite clinical trials. A meeting of experts on cognitive remediation and related methodological topics was convened to address the feasibility and study design issues for the development of a multisite trial of cognitive remediation in schizophrenia called the Cognitive Remediation in the Schizophrenia Trials Network study. This report details the findings from this meeting, which included the following 4 conclusions. (1) A multisite trial of a cognitive remediation intervention using a network of diverse research sites would be of great scientific value. (2) Various interventions could be employed for this multisite trial. (3) Programs that do not address key motivational and interpersonal aspects of cognitive remediation may benefit from supplementation with “bridging groups” that allows patients to meet with others and to apply their newly acquired cognitive skills to everyday life. (4) Before a multisite efficacy trial is initiated, a pilot study could demonstrate the feasibility of conducting a trial using a cognitive remediation intervention.

Keefe, Richard S. E.; Vinogradov, Sophia; Medalia, Alice; Silverstein, Steven M.; Bell, Morris D.; Dickinson, Dwight; Ventura, Joseph; Marder, Stephen R.; Stroup, T. Scott

2011-01-01

89

Comparative Evaluation of the Safety and Efficacy of Long-Term Use of Imidafenacin and Solifenacin in Patients with Overactive Bladder: A Prospective, Open, Randomized, Parallel-Group Trial (the LIST Study)  

PubMed Central

Objectives. Overactive bladder (OAB) is a chronic disease, but comparative trials of anticholinergics, which are commonly used for treatment of OAB, have generally been performed for up to 12 weeks only. There is no comparative study of a long-term intervention. Methods. We conducted a 52-week prospective randomized comparative study to evaluate the efficacy and tolerability of two anticholinergics. Results. Forty-one Japanese patients with untreated OAB were randomly assigned to imidafenacin and solifenacin groups. There was no difference in OABSS and KHQ scores between the two groups, but the severity and incidence of adverse events caused by the anticholinergics showed increased differences between the groups with time. The severity of dry mouth and the incidence of constipation were significantly lower in the imidafenacin group (P = 0.0092 and P = 0.0013, resp.). Conclusions. This study is the first long-term trial to show differences in the properties of anticholinergics that were not detected in short-term studies. Since OAB is a chronic disease, we conclude that imidafenacin is preferable to solifenacin from a perspective of safety.

Zaitsu, Masayoshi; Mikami, Koji; Ishida, Noriko; Takeuchi, Takumi

2011-01-01

90

Phase III Trial of Weekly Methotrexate or Pulsed Dactinomycin for Low-Risk Gestational Trophoblastic Neoplasia: A Gynecologic Oncology Group Study  

PubMed Central

Purpose There is no consensus on the best regimen for the primary treatment of low-risk gestational trophoblastic neoplasia (GTN). Patients and Methods Two commonly used single-drug regimens were compared with respect to the proportion of patients meeting the criteria for a complete response (CR) in a randomized phase III trial conducted by the Gynecologic Oncology Group. Eligibility was purposefully broad to maximize the generalizability of the results and included patients with a WHO risk score of 0 to 6 and patients with metastatic disease (limited to lung lesions < 2 cm, adnexa, or vagina) or choriocarcinoma. Results Two hundred forty women were enrolled, and 216 were deemed eligible. Biweekly intravenous dactinomycin 1.25 mg/m2 was statistically superior to weekly intramuscular (IM) methotrexate 30 mg/m2 (CR: 70% v 53%; P = .01). Similarly, in patients with low-risk GTN as defined before the 2002 WHO risk score revisions (risk score of 0 to 4 and excluding choriocarcinoma), response was 58% and 73% in the methotrexate and dactinomycin arms, respectively (P = .03). Both regimens were less effective if the WHO risk score was 5 or 6 or if the diagnosis was choriocarcinoma (CR: 9% and 42%, respectively). There were two potential recurrences; one at 4 months (dactinomycin) and one at 22 months (methotrexate). Not all patients completed follow-up. Both regimens were well tolerated. Conclusion The biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN, a generally curable disease.

Osborne, Raymond J.; Filiaci, Virginia; Schink, Julian C.; Mannel, Robert S.; Alvarez Secord, Angeles; Kelley, Joseph L.; Provencher, Diane; Scott Miller, David; Covens, Allan L.; Lage, Janice M.

2011-01-01

91

Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.  

PubMed

Stavudine (d4T) was, until recently, one of the most widely prescribed antiretroviral drugs worldwide. While there has been a major shift away from d4T use in resource-limited countries, a large number of patients have previously received (or continue to receive) d4T, and many have developed peripheral neuropathy. The identification of genetic predictors of increased risk might suggest novel therapeutic targets for such patients. In AIDS Clinical Trials Group protocol 384, antiretroviral-naïve patients were randomized to d4T/didanosine (ddI)- or zidovudine/lamivudine-containing regimens. Data from d4T/ddI recipients were analyzed for genome-wide associations (approximately 1 million genetic loci) with new onset distal sensory peripheral neuropathy. Analyses involved 254 patients (49 % White, 34 % Black, 17 % Hispanic), comprising 90 peripheral neuropathy cases (32 grade 1, 35 grade 2, 23 grade 3) and 164 controls. After correcting for multiple comparisons, no polymorphism was consistently associated with neuropathy among all patients, among White, Black, and Hispanic patients analyzed separately, both in genome-wide analyses (threshold, P?

Leger, Paul D; Johnson, Daniel H; Robbins, Gregory K; Shafer, Robert W; Clifford, David B; Li, Jun; McLaren, Paul J; Haas, David W

2014-06-01

92

A phase II trial of combination of CPT-11 and cisplatin for advanced non-small-cell lung cancer. CPT-11 Lung Cancer Study Group.  

PubMed Central

A phase I trial of the combination of irinotecan (CPT-11) with cisplatin in advanced non-small cell lung cancer (NSCLC) showed a very promising response rate of 54% in previously untreated NSCLC patients. This study was conducted to confirm the activity and toxicities of CPT-11 and cisplatin combination for previously untreated NSCLC in a multi-institutional phase II study. Seventy patients with stage IIIB or IV NSCLC received CPT-11 60 mg m(-2) intravenously (i.v.) on days 1, 8 and 15, and cisplatin 80 mg m(-2) (i.v.) on day 1 every 4 weeks. Assessments were made of response, survival and toxicities. Sixty-nine were eligible, and evaluable for toxicities and survival, and 64 patients evaluable for response. Thirty-three patients (52%; 95% confidence interval 39-64%) achieved an objective response, with one complete response (2%) and 32 partial responses (50%). The median duration of response was 19 weeks and the overall median survival time was 44 weeks. The 1-year survival rate was 33%. The major toxic effects were leucopenia and diarrhoea. Grade 3 or 4 leucopenia, neutropenia, and diarrhoea occurred in 32 patients (46%), 53 patients (80%), and 13 patients (19%) respectively. A combination of CPT-11 and cisplatin is very effective against non-small-cell lung cancer with acceptable toxicities.

Masuda, N.; Fukuoka, M.; Fujita, A.; Kurita, Y.; Tsuchiya, S.; Nagao, K.; Negoro, S.; Nishikawa, H.; Katakami, N.; Nakagawa, K.; Niitani, H.

1998-01-01

93

Randomized clinical trial: group counseling based on tinnitus retraining therapy.  

PubMed

The main component of tinnitus retraining therapy (TRT) is structured counseling. We conducted a randomized clinical trial to test the hypothesis that group educational counseling based on TRT principles would effectively treat veterans who have clinically significant tinnitus. Veterans with clinically significant tinnitus were randomized into one of three groups: educational counseling, traditional support, and no treatment. Subjects in the first two groups attended four 1.5 h group sessions each week. All subjects completed outcome questionnaires at baseline and at 1, 6, and 12 mo. A total of 269 subjects participated: 94 in the educational counseling group, 84 in the traditional support group, and 91 in the no-treatment group. Statistical analyses showed that educational counseling provided significantly more benefit than either traditional support or no treatment, as measured by the Tinnitus Severity Index. Results suggest that group educational counseling can significantly benefit many tinnitus patients and could be integral to a "progressive intervention" approach to tinnitus clinical management. PMID:17551855

Henry, James A; Loovis, Carl; Montero, Melissa; Kaelin, Christine; Anselmi, Kathryn-Anne; Coombs, Rebecca; Hensley, June; James, Kenneth E

2007-01-01

94

A Phase II Study of Intensity Modulated Radiation Therapy to the Pelvis for Postoperative Patients With Endometrial Carcinoma: Radiation Therapy Oncology Group Trial 0418  

SciTech Connect

Purpose: To determine the feasibility of pelvic intensity modulated radiation therapy (IMRT) for patients with endometrial cancer in a multi-institutional setting and to determine whether this treatment is associated with fewer short-term bowel adverse events than standard radiation therapy. Methods: Patients with adenocarcinoma of the endometrium treated with pelvic radiation therapy alone were eligible. Guidelines for target definition and delineation, dose prescription, and dose-volume constraints for the targets and critical normal structures were detailed in the study protocol and a web-based atlas. Results: Fifty-eight patients were accrued by 25 institutions; 43 were eligible for analysis. Forty-two patients (98%) had an acceptable IMRT plan; 1 had an unacceptable variation from the prescribed dose to the nodal planning target volume. The proportions of cases in which doses to critical normal structures exceeded protocol criteria were as follows: bladder, 67%; rectum, 76%; bowel, 17%; and femoral heads, 33%. Twelve patients (28%) developed grade {>=}2 short-term bowel adverse events. Conclusions: Pelvic IMRT for endometrial cancer is feasible across multiple institutions with use of a detailed protocol and centralized quality assurance (QA). For future trials, contouring of vaginal and nodal tissue will need continued monitoring with good QA and better definitions will be needed for organs at risk.

Jhingran, Anuja, E-mail: ajhingra@mdanderson.org [University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Winter, Kathryn [RTOG Statistical Center, Philadelphia, Pennsylvania (United States)] [RTOG Statistical Center, Philadelphia, Pennsylvania (United States); Portelance, Lorraine [University of Miami, Miami, Florida (United States)] [University of Miami, Miami, Florida (United States); Miller, Brigitte [Carolinas Medical Center North East, Concord, North Carolina (United States)] [Carolinas Medical Center North East, Concord, North Carolina (United States); Salehpour, Mohammad [University of Texas MD Anderson Cancer Center, Houston, Texas (United States)] [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gaur, Rakesh [St. Luke's Hospital, Kansas City, Missouri (United States)] [St. Luke's Hospital, Kansas City, Missouri (United States); Souhami, Luis [McGill University Health Centre, Montreal, Quebec (Canada)] [McGill University Health Centre, Montreal, Quebec (Canada); Small, William [Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illionis (United States)] [Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illionis (United States); Berk, Lawrence [H. Lee Moffitt Cancer Center, Tampa, Florida (United States)] [H. Lee Moffitt Cancer Center, Tampa, Florida (United States); Gaffney, David [Huntsman Cancer Hospital, Salt Lake City, Utah (United States)] [Huntsman Cancer Hospital, Salt Lake City, Utah (United States)

2012-09-01

95

Characteristics of control group participants who increased their physical activity in a cluster-randomized lifestyle intervention trial  

Microsoft Academic Search

BACKGROUND: Meaningful improvement in physical activity among control group participants in lifestyle intervention trials is not an uncommon finding, and may be partly explained by participant characteristics. This study investigated which baseline demographic, health and behavioural characteristics were predictive of successful improvement in physical activity in usual care group participants recruited into a telephone-delivered physical activity and diet intervention trial,

Lauren A Waters; Marina M Reeves; Brianna S Fjeldsoe; Elizabeth G Eakin

2011-01-01

96

Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efavirenz in healthy volunteers: AIDS Clinical Trials Group study A5267  

PubMed Central

Background Drug-drug interactions complicate management of co-infection with HIV-1 and Mycobacterium tuberculosis. Bedaquiline (formerly TMC207), an investigational agent for the treatment of tuberculosis, is metabolized by cytochrome P450 (CYP) 3A which may be induced by the antiretroviral drug efavirenz. Methods This was a Phase I pharmacokinetic drug interaction trial. Each healthy volunteer received two 400 mg doses of bedaquiline, the first alone, and the second with concomitant steady-state efavirenz. Plasma pharmacokinetic sampling for bedaquiline and its N-monodesmethyl metabolite (M2) was performed over 14 days after each bedaquiline dose. Steady-state efavirenz pharmacokinetics were also determined. Efavirenz metabolizer status was based on CYP2B6 composite 516/983 genotype. Results Thirty-three of 37 enrolled subjects completed the study. Geometric mean ratios (GMR) for bedaquiline with efavirenz versus bedaquiline alone were 0.82 (90% CI 0.75 to 0.89) for the 14-day area under the concentration-time curve (AUC0-336h) and 1.00 (90% CI 0.88 to 1.13) for the maximum concentration (Cmax). For M2, the GMR was 1.07 (90% CI 0.97 to 1.19) for AUC0-336h and 1.89 (90% CI 1.66 to 2.15) for Cmax. There were no Grade 3 or 4 clinical adverse events. One subject developed asymptomatic Grade 3 serum transaminase elevation, prompting study drug discontinuation. Efavirenz concentrations stratified by CYP2B6 genotype were similar to historical data. Conclusions Single-dose bedaquiline was well-tolerated alone and with steady-state efavirenz. The effect of efavirenz on bedaquiline concentrations is unlikely to be clinically significant.

Dooley, Kelly E; Park, Jeong-Gun; Swindells, Susan; Allen, Reena; Haas, David W.; Cramer, Yoninah; Aweeka, Francesca; Wiggins, Ilene; Gupta, Amita; Lizak, Patricia; Qasba, Sonia; van Heeswijk, Rolf; Flexner, Charles

2012-01-01

97

Multiple fixed doses of "Seroquel" (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group.  

PubMed

Five fixed doses of the atypical antipsychotic "Seroquel" (quetiapine) were evaluated to delineate a dose-response relationship, as measured by changes from baseline in Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), and Modified Scale for the Assessment of Negative Symptoms (SANS) summary scores, and to compare efficacy and tolerability opposite placebo and haloperidol. Three hundred sixty-one patients from 26 North American centers entered this double-blind, placebo-controlled trial with acute exacerbation of chronic schizophrenia (DSM-III-R). Patients who completed a single-blind, placebo washout phase were randomized to double-blind treatment with quetiapine (75, 150, 300, 600, or 750 mg daily), haloperidol (12 mg daily), or placebo and evaluated weekly for 6 weeks. At end point, significant differences (p < 0.05, analysis of covariance) in adjusted mean changes from baseline were identified between the four highest doses of quetiapine and placebo for BPRS total, BPRS positive-symptom cluster, and CGI Severity of Illness item scores and between quetiapine 300 mg and placebo for SANS summary score. Differences between quetiapine and haloperidol were not significant. Dose-response modeling showed significant linear and quadratic functions of quetiapine dose for all primary efficacy variables. Notably, no significant safety concerns were identified as dose increased. Quetiapine was no different from placebo across the dose range studied regarding incidence of extrapyramidal symptoms or change in prolactin concentrations. Quetiapine is well tolerated and clinically effective in the treatment of schizophrenia. It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day and in reducing negative symptoms at a dose of 300 mg/day. PMID:9270900

Arvanitis, L A; Miller, B G

1997-08-15

98

Weight and Lean Body Mass Change with Antiretroviral Initiation and Impact on Bone Mineral Density: AIDS Clinical Trials Group Study A5224s  

PubMed Central

Objective To compare the effect initiating different antiretroviral therapy (ART) regimens have on weight, body mass index (BMI), and lean body mass (LBM) and explore how changes in body composition are associated with bone mineral density (BMD). Methods A5224s was a substudy of A5202, a prospective trial of 1857 ART-naïve participants randomized to blinded abacavir-lamivudine (ABC/3TC) or tenofovir DF-emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV/r). All subjects underwent dual-energy absorptiometry (DXA) and abdominal CT for body composition. Analyses used 2-sample t-tests and linear regression. Results A5224s included 269 subjects: 85% male, 47% white non-Hispanic, median age 38 years, HIV-1 RNA 4.6 log10 copies/mL, and CD4 233 cells/µL. Overall, significant gains occurred in weight, BMI, and LBM at 96 weeks post randomization (all p<0.001). Assignment to ATV/r (vs EFV) resulted in significantly greater weight (mean difference 3.35 kg) and BMI gain (0.88 kg/m2; both p=0.02), but not LBM (0.67 kg; p=0.15), while ABC/3TC and TDF/FTC were not significantly different (p?0.10). In multivariable analysis, only lower baseline CD4 count and higher HIV-1 RNA were associated with greater increase in weight, BMI, or LBM. In multivariable analyses, increased LBM was associated with an increased hip BMD. Conclusions ABC/3TC vs. TDF/FTC did not differ in change in weight, BMI, or LBM; ATV/r vs. EFV resulted in greater weight and BMI gain but not LBM. A positive association between increased LBM and increased hip BMD should be further investigated through prospective interventional studies to verify the impact of increased LBM on hip BMD.

Erlandson, Kristine Mace; Kitch, Douglas; Tierney, Camlin; Sax, Paul E.; Daar, Eric S.; Tebas, Pablo; Melbourne, Kathleen; Ha, Belinda; Jahed, Nasreen C.; Mccomsey, Grace A.

2014-01-01

99

Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group  

PubMed Central

Background About one half of adults with acute lymphoblastic leukemia are not cured of the disease and ultimately die. The objective of this study was to explore the factors influencing the outcome of adult patients with relapsed acute lymphoblastic leukemia. Design and Methods We analyzed the characteristics, the outcome and the prognostic factors for survival after first relapse in a series of 263 adult patients with acute lymphoblastic leukemia (excluding those with mature B-cell acute lymphoblastic leukemia) prospectively enrolled in four consecutive risk-adapted PETHEMA trials. Results The median overall survival after relapse was 4.5 months (95% CI, 4–5 months) with a 5-year overall survival of 10% (95% CI, 8%–12%); 45% of patients receiving intensive second-line treatment achieved a second complete remission and 22% (95% CI, 14%–30%) of them remained disease free at 5 years. Factors predicting a good outcome after rescue therapy were age less than 30 years (2-year overall survival of 21% versus 10% for those over 30 years old; P<0.022) and a first remission lasting more than 2 years (2-year overall survival of 36% versus 17% among those with a shorter first remission; P<0.001). Patients under 30 years old whose first complete remission lasted longer than 2 years had a 5-year overall survival of 38% (95% CI, 23%–53%) and a 5-year disease-free survival of 53% (95% CI, 34%–72%). Conclusions The prognosis of adult patients with acute lymphoblastic leukemia who relapse is poor. Those aged less than 30 years with a first complete remission lasting longer than 2 years have reasonable possibilities of becoming long-term survivors while patients over this age or those who relapse early cannot be successfully rescued using the therapies currently available.

Oriol, Albert; Vives, Susana; Hernandez-Rivas, Jesus-Maria; Tormo, Mar; Heras, Inmaculada; Rivas, Concepcion; Bethencourt, Concepcion; Moscardo, Federico; Bueno, Javier; Grande, Carlos; del Potro, Eloy; Guardia, Ramon; Brunet, Salut; Bergua, Juan; Bernal, Teresa; Moreno, Maria-Jose; Calvo, Carlota; Bastida, Pilar; Feliu, Evarist; Ribera, Josep-Maria

2010-01-01

100

A phase II trial of gemcitabine and capecitabine in patients with unresectable or metastatic gallbladder cancer or cholangiocarcinoma: Southwest Oncology Group Study S0202  

PubMed Central

SUMMARY Background Patients with gallbladder cancer or cholangiocarcinoma usually present with advanced disease and limited treatment options. Based on the common embryologic origin of the exocrine pancreas and gallbladder, coupled with data demonstrating effectiveness of gemcitabine in pancreatic carcinoma, this trial was pursued. The aim was to test the combination of gemcitabine 1,000 mg/m2 IV over 100 minutes on days 1 and 8, and capecitabine 650 mg/m2 BID PO days 1–14, administered every 21 days, in the treatment of patients in this population. Patients and Methods The primary objective of this study was to assess the response rate (confirmed complete and partial responses) of gemcitabine and capecitabine used in incurable biliary neoplasms. Secondary objectives included overall survival and toxicities. A two-stage design was used to detect a difference in the null hypothesis of 5% response probability and the alternative 20% response probability. If at least one response occurred after the first 20 patients, another 20 were to be accrued. Results The study accrued 57 patients from September 2003 until April 2005. Three patients were ineligible, and two others received no treatment. Characteristics of analyzable patients: 35 (67%) cholangiocarcinoma, 17 (33%) gallbladder cancer; PS 0 (18 pts), 1 (26 pts), 2 (8 pts); 26 (50%) male; median age 58.8 years (29.5–85.6). Among 51 patients evaluated for toxicity, 6 experienced grade 4 toxicities: 1 thrombosis/embolism and muscle pain, 1 fatigue and 4 neutropenia, one of whom also had grade 4 leukopenia and grade 4 thrombocytopenia. Among 52 patients, there were 7 confirmed partial responses for a confirmed response probability of 13% (95% CI: 6% to 26%). Six patients had an unconfirmed partial response for an overall response probability of 25% (95% CI: 14% to 39%). Twelve patients (23%) demonstrated stable disease. The 6 month overall survival was 55% (95% CI: 41%–69%), and median survival was 7 months (95% CI: 5 – 8 mo.). Conclusions The combination of gemcitabine and capecitabine is a well tolerated regimen with activity in patients with advanced gallbladder cancer and cholangiocarcinoma.

Iqbal, Syma; Rankin, Cathryn; Lenz, Heinz-Josef; Gold, Philip J.; Ahmad, Syed A.; El-Khoueiry, Anthony B.; Messino, Michael J.; Holcombe, Randall F.; Blanke, Charles D.

2012-01-01

101

Extended Adjuvant Therapy With Anastrozole Among Postmenopausal Breast Cancer Patients: Results From the Randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a  

Microsoft Academic Search

Results ABCSG Trial 6a included 856 patients. At a median follow-up of 62.3 months, women who received anas- trozole (n = 387) had a statistically significantly reduced risk of recurrence (locoregional recurrence, con- tralateral breast cancer, or distant metastasis) compared with women who received no further treatment (n = 469; hazard ratio = 0.62; 95% CI = 0.40 to 0.96,

Raimund Jakesz; Richard Greil; Michael Gnant; Marianne Schmid; Werner Kwasny; Ernst Kubista; Brigitte Mlineritsch; Christoph Tausch; Michael Stierer; Friedrich Hofbauer; Karl Renner; Christian Dadak; Ernst Rücklinger; Hellmut Samonigg

102

The potential risk of neoadjuvant chemotherapy in breast cancer patients—results from a prospective randomized trial of the Austrian Breast and Colorectal Cancer Study Group (ABCSG-07)  

Microsoft Academic Search

Purpose To evaluate the impact that pre- and postoperatively administered chemotherapy with cyclophosphamide, methotrexate and fluorouracil\\u000a (CMF) and postoperative chemotherapy vs. postoperative chemotherapy alone have on long-term prognosis. Patients and Methods The ABCSG conducted a nationwide randomized phase III trial in high-risk endocrine non-responsive breast cancer patients\\u000a comparing pre- and postoperative chemotherapy containing CMF as preoperative treatment vs. postoperative chemotherapy

Susanne Taucher; Guenther G. Steger; Raimund Jakesz; Christoph Tausch; Viktor Wette; Walter Schippinger; Werner Kwasny; Georg Reiner; Richard Greil; Peter Dubsky; Sabine Poestlberger; Joerg Tschmelitsch; Hellmut Samonigg; Michael Gnant

2008-01-01

103

Hyperbaric Oxygen Therapy for Radionecrosis of the Jaw: A Randomized, Placebo-Controlled, Double-Blind Trial From the ORN96 Study Group  

Microsoft Academic Search

Purpose To determine the efficacy and safety of hyperbaric oxygen therapy (HBO) for overt mandibular osteoradionecrosis. Patients and Methods This prospective, multicenter, randomized, double-blind, placebo-controlled trial was con- ducted at 12 university hospitals. Ambulatory adults with overt osteoradionecrosis of the mandible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute atmosphere for 90 minutes or a placebo, and

Djillali Annane; Joel Depondt; Philippe Aubert; Maryvonne Villart; Philippe Gajdos; Sylvie Chevret

2004-01-01

104

Multicenter phase II trial of neoadjuvant exemestane for postmenopausal patients with hormone receptor-positive, operable breast cancer: Saitama Breast Cancer Clinical Study Group (SBCCSG-03)  

Microsoft Academic Search

This multicenter phase II trial evaluated the efficacy and tolerability of 4 months of neoadjuvant exemestane in 44 postmenopausal\\u000a patients with estrogen receptor (ER)-positive and\\/or progesterone receptor-positive, stage II to IIIB breast cancer measuring\\u000a ?3 cm. Pathological response was assessed by a central review board using response criteria proposed by the Japanese Breast\\u000a Cancer Society. Clinical response [complete or partial response (PR)

Hiroyuki Takei; Kimito Suemasu; Kenichi Inoue; Tsuyoshi Saito; Katsuhiko Okubo; Junichi Koh; Kazuhiko Sato; Hitoshi Tsuda; Masafumi Kurosumi; Toshio Tabei

2008-01-01

105

A Randomized Controlled Trial of Cognitive Behavioral Group Therapy for Bipolar Disorder  

Microsoft Academic Search

Background: This study evaluated the effectiveness of adjunctive cognitive behavioral group therapy (CBGT) to prevent recurrence of episodes in euthymic patients with bipolar disorder. Methods: A randomized controlled single-blind trial was conducted with 50 patients with bipolar disorder types I and II followed up for at least 12 months in an outpatient service and whose disease was in remission. An

B. C. Gomes; L. N. Abreu; E. Brietzke; S. C. Caetano; A. Kleinman; F. G. Nery; B. Lafer

2011-01-01

106

Increasing the Degrees of Freedom in Future Group Randomized Trials: The "df*" Method Revisited  

ERIC Educational Resources Information Center

Background: This article revisits an article published in Evaluation Review in 2005 on sample size estimation and power analysis for group-randomized trials. With help from a careful reader, we learned of an important error in the spreadsheet used to perform the calculations and generate the results presented in that article. As we studied the…

Murray, David M.; Blitstein, Jonathan L.; Hannan, Peter J.; Shadish, William R.

2012-01-01

107

Considerations for Designing Group Randomized Trials of Professional Development with Teacher Knowledge Outcomes  

ERIC Educational Resources Information Center

Despite recent shifts in research emphasizing the value of carefully designed experiments, the number of studies of teacher professional development with rigorous designs has lagged behind its student outcome counterparts. We outline a framework for the design of group randomized trials (GRTs) with teachers' knowledge as the outcome and…

Kelcey, Ben; Phelps, Geoffrey

2013-01-01

108

Using Multilevel Mixtures to Evaluate Intervention Effects in Group Randomized Trials  

ERIC Educational Resources Information Center

There is evidence to suggest that the effects of behavioral interventions may be limited to specific types of individuals, but methods for evaluating such outcomes have not been fully developed. This study proposes the use of finite mixture models to evaluate whether interventions, and, specifically, group randomized trials, impact participants…

Van Horn, M. Lee; Fagan, Abigail A.; Jaki, Thomas; Brown, Eric C.; Hawkins, J. David; Arthur, Michael W.; Abbott, Robert D.; Catalano, Richard F.

2008-01-01

109

Phase I safety and pharmacokinetics study of micronized atovaquone in human immunodeficiency virus-infected infants and children. Pediatric AIDS Clinical Trials Group.  

PubMed

A phase I dose-escalating safety and pharmacokinetic study evaluated an oral suspension of micronized atovaquone (m-atovaquone) in infants and children stratified into age groups from 1 month to 12 years of age. Dosages of 10, 30, and 45 mg/kg of body weight/day were evaluated as single daily doses over a period of 12 days. Steady-state concentrations in plasma were determined on day 12, and single postdose concentrations were measured on days 1, 3, 5, 7, 9, 13, 15, 18, 21, and 24. Prior studies with adults suggest that the average plasma atovaquone concentration of 15 micrograms/ml is associated with therapeutic success in more than 95% of patients with Pneumocystis carinii pneumonitis. The results showed m-atovaquone to be safe and well tolerated. Dosages of 30 mg/kg/day were adequate to achieve an average steady-state concentration of greater than 15 micrograms/ml in children ages 1 to 3 months and 2 to 12 years, but a dosage of 45 mg/kg/day was needed to reach this concentration in infants 3 to 24 months of age. The oral suspension of atovaquone is safe and well tolerated in children. A single daily dose of 30 mg/kg provides bioavailability considered adequate for therapy of P. carinii pneumonia, but infants between 3 and 24 months of age may require a dosage of 45 mg/kg/day. PMID:9624466

Hughes, W; Dorenbaum, A; Yogev, R; Beauchamp, B; Xu, J; McNamara, J; Moye, J; Purdue, L; van Dyke, R; Rogers, M; Sadler, B

1998-06-01

110

Phase II Trial in Japan of Sequential Administration of Weekly Paclitaxel Followed by FEC as Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer [KBCSG0206 Trial: Kinki Breast Cancer Study Group (KBCSG)  

Microsoft Academic Search

Objective: We conducted a phase II trial in Japan to evaluate the efficacy and tolerability of weekly paclitaxel followed by fluorouracil, epirubicin, and cyclophosphamide (FEC) as neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (LABC). Methods: Patients with clinical stage IIIA–IIIB breast cancer received NAC consisting of 12 once-a-week cycles of paclitaxel followed by 4 once-every-third-week cycles of FEC. Results:

Tetsuya Taguchi; Norikazu Masuda; Takahiro Nakayama; Kazuyoshi Motomura; Fumine Tsukamoto; Kenzo Shimazu; Takashi Nomura; Takashi Morimoto; Hiroshi Yamamoto; Kazuyuki Wakita; Yoshiaki Nakano; Kohri Yoneda; Hideo Inaji; Yuichi Takatsuka; Shinzaburo Noguchi

2010-01-01

111

The ANU WellBeing study: a protocol for a quasi-factorial randomised controlled trial of the effectiveness of an Internet support group and an automated Internet intervention for depression  

PubMed Central

Background Recent projections suggest that by the year 2030 depression will be the primary cause of disease burden among developed countries. Delivery of accessible consumer-focused evidenced-based services may be an important element in reducing this burden. Many consumers report a preference for self-help modes of delivery. The Internet offers a promising modality for delivering such services and there is now evidence that automated professionally developed self-help psychological interventions can be effective. By contrast, despite their popularity, there is little evidence as to the effectiveness of Internet support groups which provide peer-to-peer mutual support. Methods/Design Members of the community with elevated psychological distress were randomised to receive one of the following: (1) Internet Support Group (ISG) intervention, (2) a multi-module automated psychoeducational and skills Internet Training Program (ITP), (3) a combination of the ISG and ITP, or (4) an Internet Attention Control website (IAC) comprising health and wellbeing information and question and answer modules. Each intervention was 12 weeks long. Assessments were conducted at baseline, post-intervention, 6 and 12 months to examine depressive symptoms, social support, self-esteem, quality of life, depression literacy, stigma and help-seeking for depression. Participants were recruited through a screening postal survey sent to 70,000 Australians aged 18 to 65 years randomly selected from four rural and four metropolitan regions in Australia. Discussion To our knowledge this study is the first randomised controlled trial of the effectiveness of a depression ISG. Trial registration Current Controlled Trials ISRCTN65657330.

2010-01-01

112

Phase I/II Trial of Erlotinib and Temozolomide With Radiation Therapy in the Treatment of Newly Diagnosed Glioblastoma Multiforme: North Central Cancer Treatment Group Study N0177  

PubMed Central

Purpose Epidermal growth factor receptor (EGFR) amplification in glioblastoma multiforme (GBM) is a common occurrence and is associated with treatment resistance. Erlotinib, a selective EGFR inhibitor, was combined with temozolomide (TMZ) and radiotherapy (RT) in a phase I/II trial. Patients and Methods Adults not taking enzyme-inducing anticonvulsants after resection or biopsy of GBM were treated with erlotinib (150 mg daily) until progression. Erlotinib was delivered alone for 1 week, then concurrently with TMZ (75 mg mg/m2 daily) and RT (60 Gy), and finally, concurrently with up to six cycles of adjuvant TMZ (200 mg/m2 daily for 5 days every 28 days). The primary end point was survival at 1 year. Results Ninety-seven eligible patients were accrued with a median follow-up time of 22.2 months. By definition, the primary end point was successfully met with a median survival time of 15.3 months. However, there was no sign of benefit in overall survival when comparing N0177 with the RT/TMZ arm of the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981/22981 (recursive partitioning analysis [RPA] class III, 19 v 21 months; RPA class IV, 16 v 16 months; RPA class V, 8 v 10 months, respectively). Presence of diarrhea, rash, and EGFRvIII, p53, phosphatase and tensin homolog (PTEN), combination EGFR and PTEN, and EGFR amplification status were not predictive (P > .05) of survival. Conclusion Although the primary end point was successfully met using nitrosourea-based (pre-TMZ) chemotherapy era historic controls, there was no sign of benefit compared with TMZ era controls. Analyses of molecular subsets did not reveal cohorts of patients sensitive to erlotinib. TMZ chemotherapy combined with RT resulted in improved outcomes compared with historical controls who received nitrosourea-based chemotherapies.

Brown, Paul D.; Krishnan, Sunil; Sarkaria, Jann N.; Wu, Wenting; Jaeckle, Kurt A.; Uhm, Joon H.; Geoffroy, Francois J.; Arusell, Robert; Kitange, Gaspar; Jenkins, Robert B.; Kugler, John W.; Morton, Roscoe F.; Rowland, Kendrith M.; Mischel, Paul; Yong, William H.; Scheithauer, Bernd W.; Schiff, David; Giannini, Caterina; Buckner, Jan C.

2008-01-01

113

Effects of a low-fat high-carbohydrate diet on plasma sex hormones in premenopausal women: results from a randomized controlled trial. Canadian Diet and Breast Cancer Prevention Study Group.  

PubMed Central

We are conducting a long-term randomized controlled trial to determine if intervention with a low-fat high-carbohydrate diet reduces breast cancer risk. The present study examines the effects of 2 years of dietary intervention on serum sex hormone levels in premenopausal women. Subjects with extensive mammographic densities were enrolled in a dietary intervention trial. The intervention involved intensive individual counselling aimed at reducing total dietary fat to 15% of calories. Control subjects received general advice about diet but were not counselled to change their fat intake. Serum sex hormone levels were measured in 220 premenopausal subjects at entry and 2 years after randomization. Two years after randomization oestradiol levels were 20% (70 pmol l(-1)) lower (P = 0.04) and progesterone levels were 35% (1.0 nmol l(-1)) lower (P = 0.004) and follicle-stimulating hormone (FSH) levels were 7% (1 IU) higher (P = 0.38) in the intervention group than in the control group. The FSH-oestradiol ratio was 13% higher in the intervention group (P = 0.18). Samples analysed accounting for the timing of the blood sample in relation to the menstrual cycle showed that, in the intervention group, oestradiol and progesterone levels were lower and FSH levels higher in subjects with blood samples taken more than 30 days after the last menstrual period. Because of the strong evidence linking ovarian hormonal activity to breast cancer risk, these results suggest that a low-fat high-carbohydrate diet may reduce risk of breast cancer by reducing exposure to ovarian hormones that are a stimulus to cell division in the breast.

Boyd, N. F.; Lockwood, G. A.; Greenberg, C. V.; Martin, L. J.; Tritchler, D. L.

1997-01-01

114

Go4it; study design of a randomised controlled trial and economic evaluation of a multidisciplinary group intervention for obese adolescents for prevention of diabetes mellitus type 2  

Microsoft Academic Search

BACKGROUND: In the Netherlands, the first adolescents with diabetes mellitus type 2 as a result of obesity have recently been diagnosed. Therefore, it is very important that programs aiming at the prevention of type 2 diabetes of obese adolescents are developed and evaluated. METHODS: Go4it is a multidisciplinary group treatment that focuses on: 1) increasing awareness of the current dietary

Geesje H Hofsteenge; Marijke JM Chinapaw; Peter JM Weijs; Maurits W van Tulder; Henriette A Delemarre-van de Waal

2008-01-01

115

Living with diabetes: a group-based self-management support programme for T2DM patients in the early phases of illness and their partners, study protocol of a randomised controlled trial  

PubMed Central

Background The present article presents the protocol for a randomised controlled trial to test the effectiveness of a group-based self-management support programme for recently diagnosed type 2 diabetes mellitus (T2DM) patients (one to three years post-diagnosis) and their partners. The course aims to support T2DM patients and their partners in successfully integrating diabetes care into their daily lives and hereby enhance self-management and diabetes-specific health-related quality of life. The content of the course is based on the Common-Sense Model of Self-Regulation (CSM). Furthermore, principles from the Social Cognitive Theory (SCT) and social support theories are integrated. Methods/Design We aim to recruit 160 recently diagnosed T2DM patients and their partners from general practices in six different regions in the Netherlands. Patients need to be diagnosed with T2DM for one to three years and have to experience some degree of diabetes-related difficulties, as measured with a three-item screener. Participating patients and their partners are randomly allocated to the intervention or control condition. Participants in the intervention condition receive three monthly group sessions and a booster session three months later. Participants in the control condition receive a single information meeting. Data will be collected at baseline (T0), directly after the programme (T1) and six months post-programme (T2), including: self-management, diabetes-specific health-related quality of life, illness perceptions, attitudes, social support and empowerment. A three-level multilevel model will be used to compare change-scores between the conditions (intervention/control) on each outcome. Discussion Our study will be the first to determine whether a group-based support programme based on the CSM is effective in enhancing self-management and diabetes-specific health-related quality of life in recently diagnosed T2DM patients. The important role of patients’ partners in effective diabetes care is also acknowledged in the study. Trial registration Netherlands National Trial Register (NTR) NTR3302.

2014-01-01

116

A Phase I Trial and Pharmacokinetic Study of Aflibercept (VEGF Trap) in Children with Refractory Solid Tumors: A Children's Oncology Group Phase I Consortium Report  

PubMed Central

Background Aflibercept is a novel decoy receptor that efficiently neutralizes circulating vascular endothelial growth factor (VEGF). A pediatric phase 1 trial was performed to define the dose limiting toxicities (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of aflibercept. Methods Cohorts of 3–6 children with refractory solid tumors received aflibercept intravenously over 60 minutes every 14 days, at 2.0, 2.5 or 3.0 mg/kg/dose. PK sampling and analysis of peripheral blood biomarkers were performed with the initial dose. Results 21 eligible patients were enrolled; 18 were fully evaluable for toxicity. One of 6 patients receiving 2.0 mg/kg/dose developed dose-limiting intra-tumoral hemorrhage and 2 of 6 receiving 3.0 mg/kg/dose developed either dose-limiting tumor pain or tissue necrosis. None of the 6 patients receiving 2.5 mg/kg/dose developed DLT, defining this as the MTD. The most common non-dose limiting toxicities were hypertension and fatigue. Three patients with hepatocellular carcinoma, hepatoblastoma and clear cell sarcoma had stable disease for >13 weeks. At the MTD, the ratio of free to bound aflibercept serum concentration was 2.10 on day 8, but only 0.44 by day 15. A rapid decrease in VEGF (p<0.05) and increase in PlGF (p<0.05) from baseline was observed in response to aflibercept by day 2. Conclusion The aflibercept MTD in children of 2.5 mg/kg/dose every 14 days is lower that the adult recommended dose of 4.0 mg/kg. This dose achieves, but does not sustain, free aflibercept concentrations in excess of bound. Tumor pain and hemorrhage may be evidence of anti-tumor activity, but were dose-limiting.

Bender, Julia Glade; Blaney, Susan M.; Borinstein, Scott; Reid, Joel M.; Baruchel, Sylvain; Ahern, Charlotte; Ingle, Ashish M.; Yamashiro, Darrell J.; Chen, Alice; Weigel, Brenda; Adamson, Peter C.; Park, Julie R.

2012-01-01

117

Phase I/II trial of gemcitabine plus oral TS-1 in elderly patients with advanced non-small cell lung cancer: Thoracic oncology research group study 0502.  

PubMed

A phase I/II trial of TS-1 combined with gemcitabine was designed to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients older than 70 years of age received TS-1 orally b.i.d. on days 1-14 and gemcitabine intravenously on days 8 and 15 every 4 weeks. In phase I (n=22), each cohort received escalating doses of TS-1 (30-40 mg/m(2) b.i.d.) and gemcitabine (800-1000 mg/m(2)); MTD was 40 mg/m(2) b.i.d. TS-1 and 1000 mg/m(2) gemcitabine; RD was 30 mg/m(2) b.i.d. TS-1 and 1000 mg/m(2) gemcitabine. Dose-limiting toxicities included a grade 3 infection, skin toxicity, and stomatitis. In phase II (n=37), the overall response rate was 27% (90% confidence interval (CI): 15-42%) and the median time to progression and overall survival were 4.2 months (90% CI: 3.2-5.7) and 12.9 months (90% CI: 10.4-14.7), respectively. The most common grade 3 or higher toxicity was neutropenia (45.9%), and thrombocytopenia was observed in 13.5% of patients. Two cases each of grade 3 pneumonitis and skin toxicity were observed, but nonhematological toxicities occurred at generally low frequencies. TS-1 with gemcitabine is a promising doublet regimen in elderly patients with advanced NSCLC with acceptable toxicities. PMID:20153912

Seto, Takashi; Yamanaka, Takeharu; Wasada, Izumi; Seki, Nobuhiko; Okamoto, Hiroaki; Ogura, Takashi; Shibuya, Masahiko; Takiguchi, Yuichi; Shinkai, Tetsu; Masuda, Noriyuki; Ichinose, Yukito; Eguchi, Kenji; Watanabe, Koshiro

2010-08-01

118

A phase II study of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) with G-CSF for breast cancer patients with visceral metastases or hormone-independent tumors: a trial of the Japan Clinical Oncology Group.  

PubMed

To evaluate the efficacy and toxicity of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) therapy, a phase II study of EPI, 130 mg/m2, plus CPA, 1000 mg/m2, with G-CSF every 3 weeks was carried out for 51 advanced or recurrent breast cancer patients by the Japan Clinical Oncology Group (JCOG). Fifty out of the 51 patients who were eligible for our criteria were treated with this regimen as first-line chemotherapy for visceral metastases or hormone-independent tumors. In this trial, 203 cycles were administered with an average of four cycles per patients. In 50 patients who were evaluable for response, there were 7 complete (CR) and 25 partial responses (PR) with an overall response rate of 64% (95% confidence interval, 50.1-75.9%). Symptomatic and hematological acute toxicity more than grade 3 occurred frequently; however, no treatment-related death occurred. The incidence of toxicities (> or = grade 3) was as follows: leukopenia 98%, thrombocytopenia 42%, nausea/vomiting 56% and hair loss 12%. In each cycle, daily administration of 2 micrograms/kg G-CSF (granulocyte-colony stimulating factor) was given on days 2-15 subcutaneously. The incidence of cardiotoxicity was low. Arrhythmia (< or = grade 2) was observed in 8% and a slight decrease of ejection fraction index (< or = grade 2) was observed in 2% in this trial. The median follow-up period for patients was 37.2 (24.6-51.5) months and the median survival period was 17.4 months. These data indicate that high-dose EPI + CPA combination chemotherapy was effective and well tolerated for breast cancer patients with visceral metastases or hormone-independent tumors. A randomized trial of high-dose EPI vs conventional chemotherapy is required to ascertain the usefulness of this regimen. PMID:9390210

Takashima, S; Saeki, T; Adachi, I; Watanabe, T; Sasaki, Y; Murai, H; Tabei, T; Ogita, M; Sano, M; Kanda, K; Shimoyama, M

1997-10-01

119

Rationale and study protocol for the supporting children's outcomes using rewards, exercise and skills (SCORES) group randomized controlled trial: A physical activity and fundamental movement skills intervention for primary schools in low-income communities  

PubMed Central

Background Many Australian children are insufficiently active to accrue health benefits and physical activity (PA) levels are consistently lower among youth of low socio-economic position. PA levels decline dramatically during adolescence and evidence suggests that competency in a range of fundamental movement skills (FMS) may serve as a protective factor against this trend. Methods/design The Supporting Children’s Outcomes Using Rewards Exercise and Skills (SCORES) intervention is a multi-component PA and FMS intervention for primary schools in low-income communities, which will be evaluated using a group randomized controlled trial. The socio-ecological model provided a framework for the 12-month intervention, which includes the following components: teacher professional learning, student leadership workshops (including leadership accreditation and rewards, e.g., stickers, water bottles), PA policy review, PA equipment packs, parental engagement via newsletters, FMS homework and a parent evening, and community partnerships with local sporting organizations. Outcomes will be assessed at baseline, 6- and 12-months. The primary outcomes are PA (accelerometers), FMS (Test of Gross Motor Development II) and cardiorespiratory fitness (multi-stage fitness test). Secondary outcomes include body mass index [using weight (kg)/height (m2)], perceived competence, physical self-esteem, and resilience. Individual and environmental mediators of behavior change (e.g. social support and enjoyment) will also be assessed. The System for Observing Fitness Instruction Time will be used to assess the impact of the intervention on PA within physical education lessons. Statistical analyses will follow intention-to-treat principles and hypothesized mediators of PA behavior change will be explored. Discussion SCORES is an innovative primary school-based PA and FMS intervention designed to support students attending schools in low-income communities to be more skilled and active. The findings from the study may be used to guide teacher pre-service education, professional learning and school policy in primary schools. Trial registration Australian New Zealand Clinical Trials Registry No: ACTRN12611001080910

2012-01-01

120

A randomised control trial for the effectiveness of group interpersonal psychotherapy for postnatal depression  

Microsoft Academic Search

This study is a randomised controlled trial comparing outcomes from an 8-week Interpersonal Psychotherapy group (IPT-G) for\\u000a postnatal depression with ‘treatment as usual’ (TAU), conducted in a routine community setting in the Australian Capital Territory\\u000a (ACT). Eligible women were recruited and randomly assigned to either IPT-G or TAU conditions. This study compared outcomes\\u000a on such variables as depressive symptoms, marital

Rhiannon Mulcahy; Rebecca E. Reay; Ross B. Wilkinson; Cathy Owen

2010-01-01

121

Randomized trial comparing intravenous immunoglobulin with methylprednisolone pulse therapy in acute idiopathic thrombocytopenic purpura. Danish I.T.P. Study Group.  

PubMed

Forty-three children with newly diagnosed idiopathic thrombocytopenic purpura (ITP), platelet count (PC) below 20 x 10(9)l-1, and either continued bleeding or failure to show a spontaneous rise in the PC after a 3 day observation period were randomized to treatment with either intravenous immunoglobulin (IVIG) infusions 1 g kg-1 (n = 23) or intravenous methylprednisolone pulse therapy (MPPT) 30 mg kg-1 (n = 20) on two consecutive days. After 72 h, IVIG had induced greater platelet responses (mean PC 188 x 10(9) versus 77 x 10(9)l-1, 2p < 0.001) and raised the PC to a haemostatically safe level above 50 x 10(9)l-1 more frequently (91 versus 50%, one-sided exact p = 0.003). Children responding poorly were then given the alternative treatment in addition. After 6 days, a normal PC of over 150 x 10(9)l-1 had been obtained more frequently in the group given first-line IVIG (70 versus 50%, p = 0.16). The relapse rates during 6 months of follow-up were not significantly different (26 versus 40%, p = 0.26). Cross-over treatment in 11 children with relapse confirmed the superior response to IVIG. The treatment given was restricted to the two initial infusions more often in the IVIG group (70 versus 35%, p = 0.05). These results indicate that IVIG may be preferable to MPPT as the initial treatment for ITP. PMID:8863869

Rosthøj, S; Nielsen, S; Pedersen, F K

1996-08-01

122

Combined immunization of infants with oral and inactivated poliovirus vaccines: results of a randomized trial in The Gambia, Oman, and Thailand. WHO Collaborative Study Group on Oral and Inactivated Poliovirus Vaccines.  

PubMed Central

To assess an immunization schedule combining oral (OPV) and inactivated poliovirus vaccines (IPV), we conducted a clinical trial in the Gambia, Oman, and Thailand. Children were randomized to receive one of the following schedules: OPV at birth, 6, 10, and 14 weeks of age; OPV at birth followed by both OPV and IPV at 6, 10, and 14 weeks of age: or placebo at birth followed by IPV at 6, 10, and 14 weeks of age. A total of 1685 infants were enrolled; 24-week serum specimens were available for 1291 infants (77%). Across the study sites at 24 weeks of age, the proportion of seropositive children in the combined schedule group was 95-99% for type 1, 99-100% for type 2, and 97-100% for type 3. In the Gambia and Oman, the combined schedule performed significantly better than OPV for type 1 (95-97% versus 88-90%) and type 3 (97-99% versus 72-73%). In the Gambia and Oman, seroprevalences in the IPV group were lower for type 1 (significantly lower in the Gambia); significantly lower for type 2; and significantly higher for type 3, compared with the OPV group. In Thailand, the IPV group had significantly lower proportions of children who were seropositive for each of the three types, compared with the OPV group. The responses to OPV in the Gambia, Oman, and Thailand were consistent with previous studies from these countries. IPV given at 6, 10, and 14 weeks of age provided inadequate serological protection against poliovirus, especially type 1. The combined schedule provided the highest levels of serum antibody response, with mucosal immunity equivalent to that produced by OPV alone.

1996-01-01

123

Systematic review of clinical trials of cervical manipulation: control group procedures and pain outcomes  

Microsoft Academic Search

OBJECTIVE: To characterize the types of control procedures used in controlled clinical trials of cervical spine manipulation and to evaluate the outcomes obtained by subjects in control groups so as to improve the quality of future clinical trials METHODS: A search of relevant clinical trials was performed in PubMed 1966-May 2010 with the following key words: \\

Howard Vernon; Aaron Puhl; Christine Reinhart

2011-01-01

124

Study Groups: Conduit for Reform.  

ERIC Educational Resources Information Center

This conference presentation describes study groups as a mechanism for changing teacher behavior. The history of study groups is discussed, beginning with the first American study groups organized by Benjamin Franklin; the Chautauqua Literary and Scientific Circle; the waning of study groups in the early 20th century as college enrollment…

Makibbin, Shirley S.; Sprague, Marsha M.

125

Safety and acceptability of vaginal disinfection with benzalkonium chloride in HIV infected pregnant women in west Africa: ANRS 049b phase II randomized, double blinded placebo controlled trial. DITRAME Study Group  

PubMed Central

OBJECTIVES: To study the tolerance and acceptability in Africa of a perinatal intervention to prevent vertical HIV transmission using benzalkonium chloride disinfection. DESIGN: A randomized, double blinded phase II trial. SETTING: Prenatal care units in Abidjan (Cote d'Ivoire) and Bobo-Dioulasso (Burkina Faso). PATIENTS: Women accepting testing and counselling who were seropositive for HIV-1 and under 37 weeks of pregnancy were eligible. A total of 108 women (54 in each group) enrolled from November 1996 to April 1997, with their informed consent. INTERVENTION: Women self administered daily a vaginal suppository of 1% benzalkonium chloride or matched placebo from 36 weeks of pregnancy, and a single intrapartum dose. The neonate was bathed with 1% benzalkonium chloride solution or placebo within 30 minutes after birth. MAIN OUTCOME MEASURES: Adverse events were recorded weekly, with a questionnaire and speculum examination in women through delivery, and examination of the neonate through day 30. The incidence of genital signs and symptoms in the women and cutaneous or ophthalmological events in newborns were compared between groups on an intent to treat basis. RESULTS: The median duration of prepartum treatment was 21 days (range 0-87 days). Compliance was 87% for prepartum and 69% for intrapartum treatment, and 88% for the neonatal bath, without differences between the two groups. In women, the most frequent event was leucorrhoea; the incidence of adverse events did not differ between treatment groups. In children, the incidence of dermatitis and conjunctivitis did not differ between the benzalkonium chloride and placebo groups (p = 0.16 and p = 0.29, respectively). CONCLUSION: Vaginal disinfection with benzalkonium chloride is a feasible and well tolerated intervention in west Africa. Its efficacy in preventing vertical HIV transmission remains to be demonstrated. ???

Msellati, P.; Meda, N.; Leroy, V.; Likikouet, R.; Van de Perre, P.; Cartoux, M.; Bonard, D.; Ouangre, A.; Combe, P.; Gautier-Charpenti..., L.; Sylla-Koko, F.; Lassalle, R.; Dosso, M.; Welffens-Ekra, C.; Dabis, F.; Mandelbrot, L.

1999-01-01

126

Community mobilisation with women's groups facilitated by Accredited Social Health Activists (ASHAs) to improve maternal and newborn health in underserved areas of Jharkhand and Orissa: study protocol for a cluster-randomised controlled trial  

PubMed Central

Background Around a quarter of the world's neonatal and maternal deaths occur in India. Morbidity and mortality are highest in rural areas and among the poorest wealth quintiles. Few interventions to improve maternal and newborn health outcomes with government-mandated community health workers have been rigorously evaluated at scale in this setting. The study aims to assess the impact of a community mobilisation intervention with women's groups facilitated by ASHAs to improve maternal and newborn health outcomes among rural tribal communities of Jharkhand and Orissa. Methods/design The study is a cluster-randomised controlled trial and will be implemented in five districts, three in Jharkhand and two in Orissa. The unit of randomisation is a rural cluster of approximately 5000 population. We identified villages within rural, tribal areas of five districts, approached them for participation in the study and enrolled them into 30 clusters, with approximately 10 ASHAs per cluster. Within each district, 6 clusters were randomly allocated to receive the community intervention or to the control group, resulting in 15 intervention and 15 control clusters. Randomisation was carried out in the presence of local stakeholders who selected the cluster numbers and allocated them to intervention or control using a pre-generated random number sequence. The intervention is a participatory learning and action cycle where ASHAs support community women's groups through a four-phase process in which they identify and prioritise local maternal and newborn health problems, implement strategies to address these and evaluate the result. The cycle is designed to fit with the ASHAs' mandate to mobilise communities for health and to complement their other tasks, including increasing institutional delivery rates and providing home visits to mothers and newborns. The trial's primary endpoint is neonatal mortality during 24 months of intervention. Additional endpoints include home care practices and health care-seeking in the antenatal, delivery and postnatal period. The impact of the intervention will be measured through a prospective surveillance system implemented by the project team, through which mothers will be interviewed around six weeks after delivery. Cost data and qualitative data are collected for cost-effectiveness and process evaluations. Study registration ISRCTN: ISRCTN31567106

2011-01-01

127

Frequent Hemodialysis Network (FHN) randomized trials: Study design  

Microsoft Academic Search

Observational studies suggest improvements with frequent hemodialysis (HD), but its true efficacy and safety remain uncertain. The Frequent Hemodialysis Network Trials Group is conducting two multicenter randomized trials of 250 subjects each, comparing conventional three times weekly HD with (1) in-center daily HD and (2) home nocturnal HD. Daily HD will be delivered for 1.5–2.75 h, 6 days\\/week, with target

R S Suri; A X Garg; G M Chertow; N W Levin; M V Rocco; T Greene; G J Beck; J J Gassman; P W Eggers; R A Star; D B Ornt; A S Kliger

2007-01-01

128

Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983–1995  

Microsoft Academic Search

Since 1968, the Children's Cancer Group (CCG) has treated more than 16 000 children with acute lymphoblastic leukemia (ALL). Herein, we report improvements obtained in CCG trials during two successive series of studies (1983–1988 and 1989–1995). Overall, 10-year EFS was 62% ± 10% for the 1983–1988 series and 72% ± 1% for the 1988–1995 series (P < 0.0001). Five-year cumulative

PS Gaynon; ME Trigg; NA Heerema; MG Sensel; HN Sather; GD Hammond; WA Bleyer

2000-01-01

129

Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983- 1995  

Microsoft Academic Search

Since 1968, the Children's Cancer Group (CCG) has treated more than 16 000 children with acute lymphoblastic leukemia (ALL). Herein, we report improvements obtained in CCG trials during two successive series of studies (1983-1988 and 1989- 1995). Overall, 10-year EFS was 62% ? 10% for the 1983-1988 series and 72% ? 1% for the 1988-1995 series (P , 0.0001). Five-year

PS Gaynon; ME Trigg; NA Heerema; MG Sensel; HN Sather; GD Hammond; WA Bleyer

2000-01-01

130

A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study  

Microsoft Academic Search

Background. Despite their low risk for recurrence, many women with endometrial adenocarcinoma receive postoperative radiation therapy (RT). This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics (FIGO) stages IB, IC, and II (occult disease).Methods. Four hundred forty-eight consenting patients with

Henry M Keys; James A Roberts; Virginia L Brunetto; Richard J Zaino; Nick M Spirtos; Jeffrey D Bloss; Andrew Pearlman; Mitchell A Maiman; Jeffrey G Bell

2004-01-01

131

Central nervous system-directed therapy in the treatment of childhood acute lymphoblastic leukemia and studies of neurobehavioral outcome: children’s cancer group trials  

Microsoft Academic Search

Long-term survival rates in childhood acute lymphoblastic leukemia (ALL) have improved due, in part, to the introduction and\\u000a subsequent refinements in central nervous system (CNS)-directed therapy. Studies of cognitive, motor, and behavioral functioning,\\u000a which characterize the patterns and severity of CNS sequelae, are being used increasingly as measurable treatment endpoints.\\u000a This paper summarizes the advances in CNS-directed therapy derived from

Thomas A. Kaleita

2002-01-01

132

Adaptive vs. group sequential self-designing trials.  

PubMed

This is a discussion of the paper. 'Repeated Confidence Intervals in Self-Designing Clinical Trials and Switching between Non-Inferiority and Superinferiority' by Joachim Hartung and Guido Knapp, appearing in this special issue on adaptive designs. PMID:16972723

Mehrotra, Devan V; Fan, Xiaoyin

2006-08-01

133

Neurohormonal activation in patients with mild or moderately severe congestive heart failure and effects of ramipril. The Ramipril Trial Study Group.  

PubMed Central

OBJECTIVES--To describe neurohormonal activation in patients with mild or moderate heart failure and how it may be modified by treatment with ramipril. SETTING--Cardiology departments at 24 hospitals in Denmark, Finland, Norway, and Sweden. PATIENTS--223 patients with mild or moderately severe congestive heart failure who were taking diuretics with or without digitalis. DESIGN--Randomised, double bind, multicentre, placebo controlled comparison of ramipril and placebo. Venous blood samples were drawn at rest, before blind treatment, and after 12 weeks of treatment with the study drug. A probability prediction score for mortality derived by stepwise linear discriminant from neurohormone data in the first cooperative north Scandinavian enalapril survival study (CONSENSUS I) was used to assess combined activity of the different neurohormonal systems. RESULTS--Plasma concentrations of atrial natriuretic peptide were raised at baseline but angiotensin II, aldosterone, and noradrenaline concentrations were within normal limits. There was, however, a wide interindividual variation. Plasma noradrenaline concentration and prediction score were higher among patients with class III congestive heart failure according to the New York Heart Association's classification than among patients with class II congestive heart failure (P < 0.05). There was a modest but significant inverse correlation between exercise duration at baseline and plasma noradrenaline concentration (r = -0.21, P = 0.0023), aldosterone concentration (r = -0.14, P = 0.04), and prediction score (r = -0.24, P = 0.0004). Prediction score at baseline was significantly higher among those who died (n = 10) than among survivors (P = 0.03). Angiotensin converting enzyme activity was suppressed and plasma concentrations of aldosterone and atrial natriuretic peptide were reduced after 12 weeks of treatment with ramipril compared with placebo. In patients with the most pronounced neurohormonal activation at baseline (highest third of noradrenaline concentration or prediction score), noradrenaline concentration and prediction score were significantly lower after 12 weeks of taking ramipril compared with placebo. Patients with a prediction score in the highest third at baseline had a higher heart rate than to those in the lowest third (P = 0.003). CONCLUSIONS--Neurohormonal activation is associated with the degree of symptoms and the severity of disease in mild or moderately severe congestive heart failure. Treatment with ramipril attenuates neurohormonal activation. This effect is most pronounced among patients with the highest circulating concentrations of neurohormones before the start of treatment.

Sigurdsson, A; Amtorp, O; Gundersen, T; Nilsson, B; Remes, J; Swedberg, K

1994-01-01

134

A Phase I Trial and Pharmacokinetic Study of Sorafenib in Children with Refractory Solid Tumors or Leukemias: A Children's Oncology Group Phase I Consortium Report  

PubMed Central

Purpose To determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of sorafenib in children with refractory extracranial solid tumors and evaluate the tolerability of the solid tumor MTD in children with refractory leukemias. Experimental Design Sorafenib was administered orally every 12 hours for consecutive 28-day cycles. Pharmacokinetics (day 1 and steady-state) and pharmacodynamics were conducted during cycle 1. Results Of 65 patients enrolled, 60 were eligible. In the solid tumor cohort (n = 49), 4 of 6 patients experienced a DLT [hypertension, pain, rash/urticaria, thrombocytopenia, alanine aminotransferase (ALT)/ aspartate aminotransferase (AST)] at the starting dose (150 mg/m2/dose) which resulted in de-escalation to 105 mg/m2/dose. After eligibility criteria modification and dose re-escalation, the MTD was 200 mg/m2/ dose for solid tumors and 150 mg/m2/dose for leukemias. Sorafenib exposure was highly variable between patients but was within the ranges reported in adults. The apparent sorafenib clearance increased with patient age. Diarrhea, rash, fatigue, and increased ALT/AST were the most common sorafenib-related toxicities. Stable disease for 4 or more cycles was observed in 14 solid tumor patients, and 2 patients with acute myeloid leukemia (AML) and FLT3 internal tandem duplication (FLT3ITD) experienced a decrease in bone marrow blasts to less than 5%. Conclusions The recommended phase II dose of sorafenib administered every 12 hours continuously for children with solid tumors is 200 mg/m2/dose and 150 mg/m2/dose for children with leukemias. Sorafenib toxicities and distribution in children are similar to adults. The activity of sorafenib in children with AML and FLT3ITD is currently being evaluated, and a phase II study for select solid tumors is ongoing.

Widemann, Brigitte C.; Kim, AeRang; Fox, Elizabeth; Baruchel, Sylvain; Adamson, Peter C.; Ingle, Ashish M.; Bender, Julia Glade; Burke, Michael; Weigel, Brenda; Stempak, Diana; Balis, Frank M.; Blaney, Susan M.

2012-01-01

135

Quality Assessment for Therapeutic Drug Monitoring in AIDS Clinical Trials Group (ACTG 5146): A Multicenter Clinical Trial  

PubMed Central

In a randomized trial, AIDS Clinical Trials Group (ACTG) protocol 5146 (A5146) investigated the use of TDM to adjust doses of HIV-1 protease inhibitors (PIs) in patients with prior virologic failure on PI-based therapy who were starting a new PI-based regimen. The overall percentage of “PI trough repeats”, such as rescheduled visits or redrawn PI trough specimens, increased from 2% to 5% to 10% as the process progressed from the clinical sites, the PSL, and the study team, respectively. Cumulatively, this represents a 17% rate of failure to obtain adequate PI trough sample. While targeting a turn-around of ? 7 days from sample receipt to a drug concentration report, 12% of the received specimens required a longer period to report concentrations. The implementation of dosing changes in the TDM arm were achieved within ?7 days for 56% of the dose change events, and within ?14 days for 77% of dose change events. This quality assurance analysis provides a valuable summary of the specific points in the TDM process that could be improved during a multicenter clinical trial including: [1] shortening the timeline of sample shipment from clinical site to the lab, [2] performing the collection of PI trough specimen within the targeted sampling window by careful monitoring of the last dose times and collection times by the clinicians [3] increasing patient adherence counseling to reduce the number of samples that are redrawn due to suspecting inconsistent adherence, and [4] decreasing the time to successful TDM-based dose adjustment. The application of some of these findings may also be relevant to single center studies or clinical TDM programs within a hospital.

DiFrancesco, Robin; Rosenkranz, Susan; Mukherjee, A. Lisa; Demeter, Lisa M.; Jiang, Hongyu; DiCenzo, Robert; Dykes, Carrie; Rinehart, Alex; Albrecht, Mary; Morse, Gene D.

2010-01-01

136

ACTG 196: Aids Clinical Trials Group (on CD-ROM).  

National Technical Information Service (NTIS)

The efficacy and safety of clarithromycin, 500 mg BID, rifabutin, 300-450 mg QD, and the combination for prevention of Mycobacterium avium complex (MAC) disease were compared in a randomized, double-blinded, placebo-controlled trial in patients with AIDS ...

2005-01-01

137

Group art therapy as an adjunctive treatment for people with schizophrenia: multicentre pragmatic randomised trial  

PubMed Central

Objectives To evaluate the clinical effectiveness of group art therapy for people with schizophrenia and to test whether any benefits exceed those of an active control treatment. Design Three arm, rater blinded, pragmatic, randomised controlled trial. Setting Secondary care services across 15 sites in the United Kingdom. Participants 417 people aged 18 or over, who had a diagnosis of schizophrenia and provided written informed consent to take part in the study. Interventions Participants, stratified by site, were randomised to 12 months of weekly group art therapy plus standard care, 12 months of weekly activity groups plus standard care, or standard care alone. Art therapy and activity groups had up to eight members and lasted for 90 minutes. In art therapy, members were given access to a range of art materials and encouraged to use these to express themselves freely. Members of activity groups were offered various activities that did not involve use of art or craft materials and were encouraged to collectively select those they wanted to pursue. Main outcome measures The primary outcomes were global functioning, measured using the global assessment of functioning scale, and mental health symptoms, measured using the positive and negative syndrome scale, 24 months after randomisation. Main secondary outcomes were levels of group attendance, social functioning, and satisfaction with care at 12 and 24 months. Results 417 participants were assigned to either art therapy (n=140), activity groups (n=140), or standard care alone (n=137). Primary outcomes between the three study arms did not differ. The adjusted mean difference between art therapy and standard care at 24 months on the global assessment of functioning scale was ?0.9 (95% confidence interval ?3.8 to 2.1), and on the positive and negative syndrome scale was 0.7 (?3.1 to 4.6). Secondary outcomes did not differ between those referred to art therapy or those referred to standard care at 12 or 24 months. Conclusions Referring people with established schizophrenia to group art therapy as delivered in this trial did not improve global functioning, mental health, or other health related outcomes. Trial registration Current Controlled Trials ISRCTN46150447.

2012-01-01

138

Rationale and design of the HepZero study: a prospective, multicenter, international, open, randomized, controlled clinical study with parallel groups comparing heparin-free dialysis with heparin-coated dialysis membrane (Evodial) versus standard care: study protocol for a randomized controlled trial  

PubMed Central

Background Anticoagulation for chronic dialysis patients with contraindications to heparin administration is challenging. Current guidelines state that in patients with increased bleeding risks, strategies that can induce systemic anticoagulation should be avoided. Heparin-free dialysis using intermittent saline flushes is widely adopted as the method of choice for patients at risk of bleeding, although on-line blood predilution may also be used. A new dialyzer, Evodial (Gambro, Lund, Sweden), is grafted with unfractionated heparin during the manufacturing process and may allow safe and efficient heparin-free hemodialysis sessions. In the present trial, Evodial was compared to standard care with either saline flushes or blood predilution. Methods The HepZero study is the first international (seven countries), multicenter (10 centers), randomized, controlled, open-label, non-inferiority (and if applicable subsequently, superiority) trial with two parallel groups, comprising 252 end-stage renal disease patients treated by maintenance hemodialysis for at least 3 months and requiring heparin-free dialysis treatments. Patients will be treated during a maximum of three heparin-free dialysis treatments with either saline flushes or blood predilution (control group), or Evodial. The first heparin-free dialysis treatment will be considered successful when there is: no complete occlusion of air traps or dialyzer rendering dialysis impossible; no additional saline flushes to prevent clotting; no change of dialyzer or blood lines because of clotting; and no premature termination (early rinse-back) because of clotting. The primary objectives of the study are to determine the effectiveness of the Evodial dialyzer, compared with standard care in terms of successful treatments during the first heparin-free dialysis. If the non-inferiority of Evodial is demonstrated then the superiority of Evodial over standard care will be tested. The HepZero study results may have major clinical implications for patient care. Trial registration ClinicalTrials.gov NCT01318486

2013-01-01

139

Hanford Waste Tank Grouping Study  

Microsoft Academic Search

This letter report discusses the progress and accomplishments of the Tank Grouping Study in FY96. Forty-one single-shell tanks (SSTs) were included in the FY95. In FY96, technical enhancements were also made to data transformations and tank grouping methods. The first focus of the FY96 effort was a general tank grouping study in which the 41 SSTs were grouped into classes

K. M. Remund; B. C. Simpson

1996-01-01

140

Innovative study design for paediatric clinical trials  

Microsoft Academic Search

Purpose  Despite representing a fundamental step towards the efficacious and safe utilisation of drugs in the paediatric population,\\u000a the conduct of clinical trials in children poses several problems. Methodological issues and ethical concerns represent the\\u000a major obstacles that have traditionally limited paediatric research. The randomised clinical trial, mainstay of clinical studies\\u000a to assess the effects of any therapeutic intervention, shows some

Paola Baiardi; Carlo Giaquinto; Silvia Girotto; Cristina Manfredi; Adriana Ceci

2011-01-01

141

Long-term results of International Breast Cancer Study Group Trial VIII: adjuvant chemotherapy plus goserelin compared with either therapy alone for premenopausal patients with node-negative breast cancer  

PubMed Central

Background: The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy (goserelin), chemotherapy [cyclophosphamide, methotrexate and fluorouracil (CMF)], and chemoendocrine therapy (CMF followed by goserelin) for pre/perimenopausal women with lymph-node-negative breast cancer. Patients and methods: From 1990 to 1999, 1063 patients were randomized to receive (i) goserelin for 24 months (n = 346), (ii) six courses of ‘classical’ CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or (iii) six courses of CMF plus 18 months goserelin (CMF? goserelin; n = 357). Tumors were classified as estrogen receptor (ER) negative (19%), ER positive (80%), or ER unknown (1%); 19% of patients were younger than 40. Median follow-up was 12.1 years. Results: For the ER-positive cohort, sequential therapy provided a statistically significant benefit in disease-free survival (DFS) (12-year DFS = 77%) compared with CMF alone (69%) and goserelin alone (68%) (P = 0.04 for each comparison), due largely to the effect in younger patients. Patients with ER-negative tumors whose treatment included CMF had similar DFS (12-year DFS CMF = 67%; 12-year DFS CMF? goserelin = 69%) compared with goserelin alone (12-year DFS = 61%, P= NS). Conclusions: For pre/perimenopausal women with lymph-node-negative ER-positive breast cancer, CMF followed by goserelin improved DFS in comparison with either modality alone. The improvement was the most pronounced in those aged below 40, suggesting an endocrine effect of prolonged CMF-induced amenorrhea.

Karlsson, P.; Sun, Z.; Braun, D.; Price, K. N.; Castiglione-Gertsch, M.; Rabaglio, M.; Gelber, R. D.; Crivellari, D.; Collins, J.; Murray, E.; Zaman, K.; Colleoni, M.; Gusterson, B. A.; Viale, G.; Regan, M. M.; Coates, A. S.; Goldhirsch, A.

2011-01-01

142

Metabolic deterioration of the sedentary control group in clinical trials.  

PubMed

Randomized clinical trials of exercise training regimens in sedentary individuals have provided a mechanistic understanding of the long-term health benefits and consequences of physical activity and inactivity. The sedentary control periods from these trials have provided evidence of the progressive metabolic deterioration that results from as little as 4-6 mo of continuing a physically inactive lifestyle. These clinical trials have also demonstrated that only a modest amount of physical activity is required to prevent this metabolic deterioration, and this amount of physical activity is consistent with current physical activity recommendations (150 min/wk of moderate intensity physical activity). These recommendations have been issued to the general population for a vast array of health benefits. While greater adherence to these recommendations should result in substantial improvements in the health of the population, these recommendations still remain inadequate for many individuals. An individual's physical activity requirements are influenced by such factors as an individual's diet, nonexercise physical activity patterns, genetic profile, and medications. Improving the understanding of how these factors influence an individual's physical activity requirements will help advance the field and help move the field toward the development of more personalized physical activity recommendations. PMID:21778417

Patel, Mahesh J; Slentz, Cris A; Kraus, William E

2011-10-01

143

Promoting walking as an adjunct intervention to group cognitive behavioral therapy for anxiety disorders--a pilot group randomized trial.  

PubMed

A group randomized trial of adding a home-based walking program to a standard group cognitive behavioral therapy (GCBT+EX) was compared with groups receiving GCBT and educational sessions (GCBT+ED). The study was implemented in an outpatient clinic providing GCBT for clients diagnosed with panic disorder, generalized anxiety disorder or social phobia. Pre- and post-treatment measures included the self-report depression, anxiety, and stress scale (DASS-21) and measures of physical activity. From January 2004 to May 2005, six groups were allocated to GCBT+EX (n=38) and five to GCBT+ED (n=36). Analysis of covariance for completed cases (GCBT+EX, n=21; GCBT+ED, n=20), adjusting for the group design, baseline DASS-21 scores, and anxiety diagnosis showed significant effect for GCBT+EX on depression, anxiety, and stress (regression coefficients=-6.21, -3.41, and -5.14, respectively, p<0.05) compared to the GCBT+ED. The potential of exercise interventions as adjunct to GCBT for anxiety disorder needs to be further explored. PMID:17988832

Merom, Dafna; Phongsavan, Philayrath; Wagner, Renate; Chey, Tien; Marnane, Claire; Steel, Zachary; Silove, Derrick; Bauman, Adrian

2008-08-01

144

Randomized Phase II Study of Pemetrexed, Carboplatin, and Thoracic Radiation With or Without Cetuximab in Patients With Locally Advanced Unresectable Non-Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 30407  

PubMed Central

Purpose Cancer and Leukemia Group B conducted a randomized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy (TRT). Patients and Methods Patients with unresectable stage III non–small-cell lung cancer (NSCLC) were randomly assigned to carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2) every 21 days for four cycles and TRT (70 Gy; arm A) or the same treatment with cetuximab administered concurrent only with TRT (arm B). Patients in both arms received up to four cycles of pemetrexed as consolidation therapy. The primary end point was the 18-month overall survival (OS) rate; if the 18-month OS rate was ? 55%, the regimen(s) would be considered for further study. Results Of the 101 eligible patients enrolled (48 in arm A and 53 in arm B), 60% were male; the median age was 66 years (range, 32 to 81 years); 44% and 35% had adenocarcinoma and squamous carcinoma, respectively; and more patients enrolled onto arm A compared with arm B had a performance status of 0 (58% v 34%, respectively; P = .04). The 18-month OS rate was 58% (95% CI, 46% to 74%) in arm A and 54% (95% CI, 42% to 70%) in arm B. No significant difference in OS between patients with squamous and nonsquamous NSCLC was observed (P = .667). The toxicities observed were consistent with toxicities associated with concurrent chemoradiotherapy. Conclusion The combination of pemetrexed, carboplatin, and TRT met the prespecified criteria for further evaluation. This regimen should be studied further in patients with locally advanced unresectable nonsquamous NSCLC.

Govindan, Ramaswamy; Bogart, Jeffrey; Stinchcombe, Thomas; Wang, Xiaofei; Hodgson, Lydia; Kratzke, Robert; Garst, Jennifer; Brotherton, Timothy; Vokes, Everett E.

2011-01-01

145

Placebo group improvement in trials of pharmacotherapies for alcohol use disorders: A multivariate meta-analysis examining change over time  

PubMed Central

Objective Placebo group improvement in pharmacotherapy trials has been increasing over time across several pharmacological treatment areas. However, it is unknown to what degree increasing improvement has occurred in pharmacotherapy trials for alcohol use disorders or what factors may account for placebo group improvement. This meta-analysis of 47 alcohol pharmacotherapy trials evaluated (1) the magnitude of placebo group improvement, (2) the extent to which placebo group improvement has been increasing over time, and (3) several potential moderators that might account for variation in placebo group improvement. Method Random-effects univariate and multivariate analyses were conducted that examined the magnitude of placebo group improvement in the 47 studies and several potential moderators of improvement: (a) publication year, (b) country in which the study was conducted, (c) outcome data source/type, (d) number of placebo administrations, (e) overall severity of study participants, and (f) additional psychosocial treatment. Results Substantial placebo group improvement was found overall and improvement was larger in more recent studies. Greater improvement was found on moderately subjective outcomes, with more frequent administrations of the placebo, and in studies with greater participant severity of illness. However, even after controlling for these moderators, placebo group improvement remained significant, as did placebo group improvement over time. Conclusion Similar to previous pharmacotherapy placebo research, substantial pre- to post-test placebo group improvement has occurred in alcohol pharmacotherapy trials, an effect that has been increasing over time. However, several plausible moderator variables were not able to explain why placebo group improvement has been increasing over time.

Del Re, AC; Maisel, Natalya; Blodgett, Janet; Wilbourne, Paula; Finney, John

2014-01-01

146

Impact of glycine-containing ORS solutions on stool output and duration of diarrhoea: a meta-analysis of seven clinical trials. The International Study Group on Improved ORS.  

PubMed Central

The results are described of a meta-analysis of seven randomized trials that compared the clinical effects of the standard solution of WHO oral rehydration salts (ORS), containing 20 milligrams of glucose, and experimental ORS solutions, containing glycine, on 643 children with acute noncholera diarrhoea. The availability of data on individual patients in each trial permitted the scope of the meta-analysis to be enhanced because the data could be pooled after adjusting for differences in baseline patient characteristics; also, the statistical strategy in terms of data quality, post-randomization exclusion of patients, and regression modelling could be standardized for all trials. The results of the analysis showed that neither stool output nor duration of diarrhoea was reduced by the experimental formulations. Only for weight gain was there a statistically significant difference between the treatment groups (those given the WHO-ORS solution gained less weight). This probably reflects transient excess fluid retention within the gut lumen or tissues of the patients who received the glycine-containing solutions. ORS formulations that contain glycine are therefore not clinically superior to the WHO-ORS solution.

1991-01-01

147

Group sequential t-test for clinical trials with small sample sizes across stages  

Microsoft Academic Search

Interim analyses are often applied in clinical trials for various reasons. To assess the effect of a clinical treatment, the group sequential t-test with a fixed number of interim analyses is frequently used in clinical trials. The existing critical values used in group sequential t-tests are obtained from normal approximations of t-statistics. In practice, however, normal approximation is not accurate

Jun Shao; Huaibao Feng

2007-01-01

148

Cooperative group clinical trials in general thoracic surgery: report from the 2012 Robert Ginsberg Clinical Trials Meeting of the General Thoracic Surgical Club.  

PubMed

At the 25th Annual General Thoracic Surgical Club meeting in March 2012, the major cooperative groups presented updates on clinical trials at the Robert Ginsberg Clinical Trials Meeting. There were 57 members in attendance. Representatives from the Radiation Treatment Oncology Group (RTOG), American College of Surgeons Oncology Group (ACOSOG), Cancer and Leukemia Group B (CALGB), Southwest Oncology Group (SWOG), National Cancer Institute of Canada Clinical Trials Group (NCIC), and the Eastern Cooperative Oncology Group (ECOG) presented an overview of trials currently accruing or in development. These include oncologic trials that thoracic surgeons are currently accruing patients to in North America. The purpose of this review is to centralize the information to assist surgeons enrolling patients into oncologic clinical trials in thoracic surgery. PMID:23336898

Allen, Mark S; Wigle, Dennis A

2013-02-01

149

Compliance with Therapeutic Guidelines in Radiation Therapy Oncology Group Prospective Gastrointestinal Clinical Trials  

PubMed Central

Background This report analyzes the adherence to radiation therapy protocol guidelines in contemporary Radiation Therapy Oncology Group (RTOG) gastrointestinal trials. We aim to provide insight into current standards and compliance of radiation therapy field design and administration. Methods From 1994 to 2006, the Gastrointestinal Cancer Committee of the RTOG initiated and completed 15 phase I-III clinical trials utilizing radiation therapy in the multimodality treatment of gastrointestinal cancers. In each protocol, details for planning and executing radiation therapy were outlined and each protocol contained scoring criteria for these components of radiation therapy, characterized according to per-protocol, variation acceptable and deviation unacceptable. Review of treatment planning and implementation was performed in all studies following therapy completion. Results Radiation therapy planning and implementation was reviewed in 2,309 of 2,312 (99.9%) patients. The mean rate of compliance over all for the 15 protocols was 65% (total of the 2,309 analyzed patients). The mean variation acceptable rate was 21% whereas the mean deviation unacceptable rate was 5%. The mean “other” rate (no RT given or incomplete RT due to death, progression or refusal) was 8%. Two of the 15 trials (13%) had deviation unacceptable rates > 10%. In four studies incorporating pre-treatment review of radiation therapy planning and treatment, compliance with protocol therapy was enhanced. Conclusion The fidelity of radiation planning and execution detailed in protocol to actual therapy is heterogeneous, with a mean per-protocol rate of 65%. As clinical trials evolve, available technology should permit efficient pre-treatment review processes, thus facilitating compliance to protocol therapy. These analyses should also permit prospective analysis of outcome measures by compliance to therapy.

Willett, Christopher G.; Moughan, Jennifer; O'Meara, Elizabeth; Galvin, James M.; Crane, Christopher H.; Winter, Kathryn; Manfredi, Denise; Rich, Tyvin A.; Rabinovitch, Rachel; Lustig, Robert; Machtay, Mitchell; Curran, Walter J

2014-01-01

150

Radiotherapy Protocol Deviations and Clinical Outcomes: A Meta-analysis of Cooperative Group Clinical Trials  

PubMed Central

Background Noncompliance with radiotherapy (RT) protocol guidelines has been linked to inferior clinical outcomes. We performed a meta-analysis of cooperative group trials to examine the association between RT quality assurance (QA) deviations and disease control and overall survival (OS). Methods We searched MEDLINE and the Cochrane Central Register of Controlled Trials for multi-institutional trials that reported clinical outcomes in relation to RT QA results. Hazard ratios (HRs) describing the association between RT protocol noncompliance and patient outcomes were extracted directly from the original studies or calculated from survival curves. Inverse variance meta-analyses were performed to assess the association between RT QA deviations and OS. A second meta-analysis tested the association between RT QA deviations and secondary outcomes, including local or locoregional control, event-free survival, and relapse. Random-effects models were used in cases of statistically significant (P < .10) effect heterogeneity. The Egger test was used to detect publication bias. All statistical tests were two-sided. Results Eight studies (four pediatric, four adult) met all inclusion criteria and were incorporated into this analysis. The frequency of RT QA deviations ranged from 8% to 71% (median = 32%). In a random-effects model, RT deviations were associated with a statistically significant decrease in OS (HR of death = 1.74, 95% confidence interval [CI] = 1.28 to 2.35; P < .001). A similar effect was seen for secondary outcomes (HR of treatment failure = 1.79, 95% CI = 1.15 to 2.78; P = .009). No evidence of publication bias was detected. Conclusion In clinical trials, RT protocol deviations are associated with increased risks of treatment failure and overall mortality.

2013-01-01

151

Experiences of being a control group: lessons from a UK-based randomized controlled trial of group singing as a health promotion initiative for older people.  

PubMed

Existing randomized controlled trials within the health field suggest that the concept of randomization is not always well understood and that feelings of disappointment may occur when participants are not placed in their preferred arm. This may affect a study's rigour and ethical integrity if not addressed. We aimed to test whether these issues apply to a healthy volunteer sample within a health promotion trial of singing for older people. Written comments from control group participants at two points during the trial were analysed, together with individual semi-structured interviews with a small sample (n = 11) of this group. We found that motivation to participate in the trial was largely due to the appeal of singing and disappointment resulted from allocation to the control group. Understanding of randomization was generally good and feelings of disappointment lessened over time and with a post-research opportunity to sing. Findings suggest that measures should be put in place to minimize the potential negative impacts of randomized controlled trials in health promotion research. PMID:23648336

Skingley, Ann; Bungay, Hilary; Clift, Stephen; Warden, June

2013-05-01

152

DEMOGRAPHIC AND HEALTH FACTORS ASSOCIATED WITH ENROLLMENT IN POST-TRIAL STUDIES: THE WOMEN'S HEALTH INITIATIVE HORMONE THERAPY TRIALS  

PubMed Central

Background After clinical trials end, continued follow-up of the assembled cohort often is desirable for additional research. Factors influencing participants’ decisions to consent to additional follow-up and how these shape post-trial cohorts have not been broadly studied. Purpose We examined how two re-enrollment campaigns and the passage of time altered features of the post-trial cohorts compared with the original Women’s Health Initiative Hormone Therapy clinical trials. Methods We examined associations that markers of socio-demography, health, lifestyle and on-trial experiences had with re-enrollment and contrasted the characteristics of successive post-trial cohorts with those of the original enrollees. Results The post-trial enrollment campaigns re-enrolled 81.1% and 82.5% of available women, respectively. Women who re-enrolled tended to have better health characteristics than those not re-enrolled. Compared to women of comparable age in the original cohort, women retained for the second post-trial follow-up less often had a history of cardiovascular disease [odds ratio OR=0.36], hypertension [OR=0.57], diabetes [OR=0.59], or measured cognitive deficit [OR=0.40]. These women more often had graduated from high school [OR=1.72] and had participated in other WHI trials [OR=1.76]. Limitations We have examined experience with creating follow-up cohorst from participants in a single study. Thus, our findings may not apply to other cohorts and protocols. Conclusions Post-trial enrollment in follow-up studies can be successful; however the characteristics of the resulting cohort may differ substantially from the originally assembled group of trial participants. Collection during the original trial of potential predictors of differential re-enrollment may facilitate re-enrollment.

Espeland, Mark A.; Pettinger, Mary; Falkner, Karen L.; Shumaker, Sally A.; Limacher, Marian; Thomas, Fridtjof; Weaver, Kathryn E.; Stefanick, Marcia L.; McQuellon, Cynthia; Hunt, Julie R.; Johnson, Karen C.

2014-01-01

153

Safety and acceptability of vaginal disinfection with benzalkonium chloride in HIV infected pregnant women in west Africa: ANRS 049b phase II randomized, double blinded placebo controlled trial. DITRAME Study Group  

Microsoft Academic Search

OBJECTIVES: To study the tolerance and acceptability in Africa of a perinatal intervention to prevent vertical HIV transmission using benzalkonium chloride disinfection. DESIGN: A randomized, double blinded phase II trial. SETTING: Prenatal care units in Abidjan (Côte d'Ivoire) and Bobo-Dioulasso (Burkina Faso). PATIENTS: Women accepting testing and counselling who were seropositive for HIV-1 and under 37 weeks of pregnancy were

P. Msellati; N. Meda; V. Leroy; R. Likikouet; P. Van de Perre; M. Cartoux; D. Bonard; A. Ouangre; P. Combe; L. Gautier-Charpentier; F. Sylla-Koko; R. Lassalle; M. Dosso; C. Welffens-Ekra; F. Dabis; L. Mandelbrot

1999-01-01

154

ALTS Trial Design and Study Centers  

Cancer.gov

Epidemiologic, virologic and molecular studies have clearly demonstrated that human papillomavirus (HPV) is the central cause of cervical cancer. The motivation for the ALTS trial was to use the information we have gained about the role of HPV to design better treatment and prevention strategies to reduce the burden of cervical cancer and its precursors.

155

Generation of "Virtual" Control Groups for Single Arm Prostate Cancer Adjuvant Trials  

PubMed Central

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies.

Koziol, James A.; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M.; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-guo; McLaren, Christine E.; Gurley, Michael J.; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W.; Mercola, Dan

2014-01-01

156

A review of methods for ensuring the comparability of comparison groups in randomized clinical trials.  

PubMed

While different design features of medical studies ostensibly serve different functions, many fall under the umbrella of methods aimed at ensuring the comparability of the comparison groups. Randomization rightly occupies the top spot in the hierarchy of design types, as it eliminates some biases (that is, systematic differences in comparison groups) that no other design can claim to eliminate. It is often assumed, and sometimes even asserted explicitly, that randomization by itself suffices to ensure that the comparison groups are sufficiently comparable that they would differ only randomly, but two points need to be made in this context. First, the assertion is not true. Second, even if it were true, it would still not be a cause for complacency, because even random baseline imbalances can wreck havoc on the valid interpretation of randomized clinical trials. Additional methods, beyond randomization, are therefore seen to be essential to the design of a good randomized clinical trial. Such methods include masking, allocation concealment, restrictions on the randomization, adjustment for prognostic variables, and the intent-to-treat approach to data analysis. Masking aims to ensure that those individuals in any one group formed by randomization are treated as similarly as possible subsequent to randomization as those in any other group formed by randomization. In contrast, allocation concealment and restricted randomization aim to create groups that start off as comparable. Adjustment for prognostic variables aims to change the comparison groups themselves to make them comparable. For example, one might find gender to be both predictive of outcome and unbalanced across treatment groups, and so one would compare the treatment groups not overall but rather first only among females and second only among males. The intent-to-treat approach aims to keep similar groups similar by not allowing for patient selection based on post-randomization outcomes (including failure to comply with the protocol). The key to understanding masking, allocation concealment, and randomization is to recognize that none of them are binary phenomena, even though they are often incorrectly understood to be. So one must question how these methods are actually carried out, rather than contenting oneself with the vague statement that these methods were performed. This review will shed light on the distinction between the process and the outcome of each of these methods (masking, allocation concealment, and randomization), and will also consider issues related to adjustment for prognostic covariates. PMID:18393784

Berger, Vance W

2006-01-01

157

Effects of group prenatal care on psychosocial risk in pregnancy: results from a randomised controlled trial.  

PubMed

Few interventions have succeeded in reducing psychosocial risk among pregnant women. The objective of this study was to determine whether an integrated group prenatal care intervention already shown to improve perinatal and sexual risk outcomes can also improve psychosocial outcomes compared to standard individual care. This randomised controlled trial included pregnant women ages 14-25 from two public hospitals (N = 1047) who were randomly assigned to standard individual care, group prenatal care or integrated group prenatal care intervention (CenteringPregnancy Plus, CP+). Timing and content of visits followed obstetrical guidelines, from 18-week gestation through birth. Each 2-h group prenatal care session included physical assessment, education/skills building and support via facilitated discussion. Using intention-to-treat models, there were no significant differences in psychosocial function; yet, women in the top tertile of psychosocial stress at study entry did benefit from integrated group care. High-stress women randomly assigned to CP+ reported significantly increased self-esteem, decreased stress and social conflict in the third trimester of pregnancy; social conflict and depression were significantly lower 1-year postpartum (all p-values < 0.02). CP+ improved psychosocial outcomes for high-stress women. This 'bundled' intervention has promise for improving psychosocial outcomes, especially for young pregnant women who are traditionally more vulnerable and underserved. PMID:21318932

Ickovics, Jeannette R; Reed, Elizabeth; Magriples, Urania; Westdahl, Claire; Schindler Rising, Sharon; Kershaw, Trace S

2011-02-01

158

Effects of group prenatal care on psychosocial risk in pregnancy: Results from a randomised controlled trial  

PubMed Central

Few interventions have succeeded in reducing psychosocial risk among pregnant women. The objective of this study was to determine whether an integrated group prenatal care intervention already shown to improve perinatal and sexual risk outcomes can also improve psychosocial outcomes compared to standard individual care. This randomised controlled trial included pregnant women ages 14–25 from two public hospitals (N = 1047) who were randomly assigned to standard individual care, group prenatal care or integrated group prenatal care intervention (CenteringPregnancy Plus, CP+). Timing and content of visits followed obstetrical guidelines, from 18-week gestation through birth. Each 2-h group prenatal care session included physical assessment, education/skills building and support via facilitated discussion. Using intention-to-treat models, there were no significant differences in psychosocial function; yet, women in the top tertile of psychosocial stress at study entry did benefit from integrated group care. High-stress women randomly assigned to CP+ reported significantly increased self-esteem, decreased stress and social conflict in the third trimester of pregnancy; social conflict and depression were significantly lower 1-year postpartum (all p-values <0.02). CP+ improved psychosocial outcomes for high-stress women. This ‘bundled’ intervention has promise for improving psychosocial outcomes, especially for young pregnant women who are traditionally more vulnerable and underserved.

Ickovics, Jeannette R.; Reed, Elizabeth; Magriples, Urania; Westdahl, Claire; Rising, Sharon Schindler; Kershaw, Trace S.

2012-01-01

159

Recruiting ethnic minority participants to a clinical trial: a qualitative study  

PubMed Central

Objectives To compare the motives and experiences of different ethnic groups participating in a randomised double blind placebo-controlled trial of montelukast in preschool wheeze, and to assess parents’ or guardians’ understanding of trial procedures and their implications, including the collection of genetic material. Design Qualitative interviews with parents or guardians. Setting Interviews occurred in the homes of London children recruited to a national multicentre clinical trial following primary and secondary care attendance with wheeze. Participants 42 parents (20 of Bangladeshi origin, 10 white UK, 12 other ethnicities) of preschool children enrolled in a clinical trial. Results Bangladeshi families were relatively reluctant to participate in the qualitative study, despite strong engagement with the parent study. Anxiety related to wheezing was a common primary motive for trial enrolment. Parents viewed the trial as a route to improved treatment. Verbal delivery of trial information appeared more effective than study literature, especially for Bangladeshi families, with low parental literacy and high levels of trust in medical professionals potential contributors to this effect. All ethnic groups expressed a low understanding and/or retention of essential study concepts such as randomisation and genetic testing. Conclusions Bangladeshi families are particularly motivated to participate in clinical trials despite variable comprehension of study concepts. This motivation is more strongly contingent on strong researcher-subject rapport than on the quality of study literature. Trial teams seeking to recruit from South Asian populations should emphasise face-to-face verbal explanation of trial concepts and procedures and consider modified trial literature.

MacNeill, Virginia; Nwokoro, Chinedu; Griffiths, Chris; Grigg, Jonathan; Seale, Clive

2013-01-01

160

Group therapy for adolescents with repeated self harm: randomised controlled trial with economic evaluation  

Microsoft Academic Search

Objective To examine the effectiveness and cost-effectiveness of group therapy for self harm in young people.Design Two arm, single (assessor) blinded parallel randomised allocation trial of a group therapy intervention in addition to routine care, compared with routine care alone. Randomisation was by minimisation controlling for baseline frequency of self harm, presence of conduct disorder, depressive disorder, and severity of

J M Green; A J Wood; M J Kerfoot; G Trainor; C Roberts; J Rothwell; A Woodham; E Ayodeji; B Barrett; S Byford; R Harrington

2011-01-01

161

Impact of Ultrahigh Baseline PSA Levels on Biochemical and Clinical Outcomes in Two Radiation Therapy Oncology Group Prostate Clinical Trials  

Microsoft Academic Search

Purpose: To assess ultrahigh (UH; prostate-specific antigen [PSA]levels {>=}50 ng\\/ml) patient outcomes by comparison to other high-risk patient outcomes and to identify outcome predictors. Methods and Materials: Prostate cancer patients (PCP) from two Phase III Radiation Therapy Oncology Group clinical trials (studies 9202 and 9413) were divided into two groups: high-risk patients with and without UH baseline PSA levels. Predictive

George Rodrigues; Kyounghwa Bae; Mack Roach; Colleen Lawton; Bryan Donnelly; David Grignon; Gerald Hanks; Arthur Porter; Herbert Lepor; Howard Sandler

2011-01-01

162

Placebo-Controlled Trial to Determine the Effectiveness of a Urea/Lactic Acid-Based Topical Keratolytic Agent for Prevention of Capecitabine-Induced Hand-Foot Syndrome: North Central Cancer Treatment Group Study N05C5  

PubMed Central

Purpose Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine for which no effective preventative treatment has been definitively demonstrated. This trial was conducted on the basis of preliminary data that a urea/lactic acid–based topical keratolytic agent (ULABTKA) may prevent HFS. Patients and Methods A randomized, double-blind phase III trial evaluated 137 patients receiving their first ever cycle of capecitabine at a dose of either 2,000 or 2,500 mg/m2 per day for 14 days. Patients were randomly assigned to a ULABTKA versus a placebo cream, which was applied to the hands and feet twice per day for 21 days after the start of capecitabine. Patients completed an HFS diary (HFSD) daily. HFS toxicity grade (Common Terminology Criteria for Adverse Events [CTCAE] v3.0) was also collected at baseline and at the end of each cycle. The primary end point was the incidence of moderate/severe HFS symptoms in the first treatment cycle, based on the patient-reported HFSD. Results The percentage of patients with moderate/severe HFS symptoms was not different between groups, being 13.6% in the ULABTKA arm and 10.2% in the placebo arm (P = .768 by Fisher's exact test). The odds ratio was 1.37 (95% CI, 0.37 to 5.76). Cycle 1 CTCAE skin toxicity was higher in the ULABTKA arm but not significantly so (33% v 27%; P = .82). No significant differences were observed in other toxicities between groups. Conclusion These data do not support the efficacy of a ULABTKA cream for preventing HFS symptoms in patients receiving capecitabine.

Wolf, Sherry L.; Qin, Rui; Menon, Smitha P.; Rowland, Kendrith M.; Thomas, Sachdev; Delaune, Robert; Christian, Diana; Pajon, Eduardo R.; Satele, Daniel V.; Berenberg, Jeffrey L.; Loprinzi, Charles L.

2010-01-01

163

Stimulant Abuser Groups to Engage in 12-Step (STAGE-12): A Multisite Trial in the NIDA Clinical Trials Network  

PubMed Central

Aims The study evaluated the effectiveness of an 8-week combined group plus individual 12-step facilitative intervention on stimulant drug use and 12-step meeting attendance and service. Design Multisite randomized controlled trial, with assessments at baseline, mid-treatment, end of treatment, and 3- and 6-month post-randomization follow-ups (FU). Setting Intensive outpatient substance treatment programs. Participants Individuals with stimulant use disorders (n = 471) randomly assigned to treatment as usual (TAU) or TAU into which the STAGE-12 intervention was integrated. Measurements Urinalysis and self-reports of substance use and 12-step attendance and activities. Intervention Group sessions focused on increasing acceptance of 12-step principles; individual sessions incorporated an intensive referral procedure connecting participants to 12-step volunteers. Findings Compared to TAU, STAGE-12 participants had significantly greater odds of self-reported stimulant abstinence during the active 8-week treatment phase; however, among those who had not achieved abstinence during this period, STAGE-12 participants had more days of use. STAGE-12 participants had lower ASI Drug Composite scores at and a significant reduction from baseline to the 3-month FU, attended 12-step meetings on a greater number of days during the early phase of active treatment, engaged in more other types of 12-step activities throughout the active treatment phase and the entire FU period, and had more days of self-reported service at meetings from mid-treatment through the 6-month FU. Conclusions The present findings are mixed with respect to the impact of integrating the STAGE-12 intervention into intensive outpatient drug treatment compared to TAU on stimulant drug use. However, the results more clearly indicate that individuals in STAGE-12 had higher rates of 12-step meeting attendance and were engaged in more related activities throughout both the active treatment phase and the entire 6-month follow-up period than did those in TAU.

Donovan, Dennis M.; Daley, Dennis C.; Brigham, Gregory S.; Hodgkins, Candace C.; Perl, Harold I.; Garrett, Sharon; Doyle, Suzanne; Floyd, Anthony S.; Knox, Patricia C.; Botero, Christopher; Kelly, Thomas; Killeen, Therese; Hayes, Carole; Baumhofer, Nicole Kau'i; Seamans, Cindy; Zammarelli, Lucy

2012-01-01

164

A North Central Cancer Treatment Group Phase II Trial of Topotecan in Relapsed Gliomas  

Microsoft Academic Search

Current systemic treatment options for patientswith relapsed gliomas are limited. Thetopoisomerase I inhibitor topotecan has demonstrated broadantitumor activity in both preclinicalstudies as well as a number of phase I and II trials in humans.Studies in primates have shown goodcerebrospinal fluid levels of topotecan following systemicadministration. We therefore performed this phase II trial in patients who developed evidence of progressive glioma

Patrick A. Burch; Albert M. Bernath; Terrence L. Cascino; Bernd W. Scheithauer; Paul Novotny; Suresh Nair; Jan C. Buckner; Delano M. Pfeifle; John W. Kugler; Loren K. Tschetter

2000-01-01

165

Acute toxicity and cost analysis of a phase III randomized trial of accelerated and conventional radiotherapy for squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group study.  

PubMed

The primary purpose of the present analysis was to assess the feasibility and acute toxicity of a pure accelerated fractionation regimen in a cooperative group setting. This analysis included the first 320 patients entered on to the Trans-Tasman Radiation Oncology Group (TROG) randomized controlled trial which compared accelerated radiotherapy (ART) with conventional radiotherapy (CRT) in stage III and IV squamous cell carcinoma (SCC) of the head and neck. Patients were randomized to either 59.4 Gy in 33 fractions over 24 days (ART) or to 70 Gy 35 fractions over 49 days (CRT) after being stratified for site and stage. Accrual began in 1991 and the trial was closed on 3 April 1998 with the targeted 350 patients. The 3-year survival for the whole group was 54%, and the 3-year disease-free survival was 41%. Toxicity data were available on 303 patients (148 ART; 155 CRT). Mucosal toxicity was worse in the accelerated arm, and it peaked approximately 3 weeks earlier than the conventional arm. Skin toxicity was equivalent but occurred approximately 7 days earlier in the accelerated arm. Acute effects in both arms healed completely. Hospitalization was more common in the ART arm (71 vs 52 patients; P = 0.01) but the total bed days in hospital was not greatly different (1707 bed days for ART and 1607 bed days for CRT). Patients were more likely to require nasogastric (NG) feeding in the ART arm (49 vs 33 patients; P = 0.02). There were 1157 NG feeding days for ART and 1154 NG feeding days for CRT. The average cost of radiation treatment per patient including hospitalization, NG feeding and accommodation was $11,750 in the ART arm and $11,587 in the CRT arm. The accelerated arm has been shown to be a tolerable, practical and cost-equivalent regimen. The assessment of the therapeutic ratio of this accelerated protocol (ART) will be determined when the analysis of late effects and loco-regional control is made when the data are more mature. PMID:10901965

Poulsen, M; Denham, J; Spry, N; Lamb, D; Peters, L; Krawitz, H; Penniment, M; Williamson, S; Tripcony, L

1999-11-01

166

Pilot study evaluating broccoli sprouts in advanced pancreatic cancer (POUDER trial) - study protocol for a randomized controlled trial  

PubMed Central

Background Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies with marked resistance to chemo- and radiotherapy. PDA-cancer stem cells (CSCs) are not targeted by current therapies and may be a reason for poor prognosis. Studies indicate that diets rich in cabbage, broccoli, and cauliflower offer cancer preventative and therapeutic benefits. Recent experimental studies have confirmed these findings and demonstrated that isothiocyanate, sulforaphane, and the polyphenol, quercetin, effectively reduced tumor growth and enhanced the sensitivity of the cancer cells to current chemotherapeutics. The aim of the present study is to test the feasibility of a randomized controlled trial on the application of freeze-dried broccoli sprouts in patients with advanced PDA. Methods and study design The study is designed as a prospective randomized, double-blinded pilot trial with a treatment and a placebo-controlled arm in a single center setting. A total number of forty patients (18 years or older) in two parallel groups with advanced, surgically non-resectable PDA under palliative chemotherapy are planned for recruitment. Patients in the treatment group will receive fifteen capsules of the study substance per day (90 mg of active sulforaphane) during the chemotherapy treatment course. Patients in the placebo group will receive the same capsule size and portion distribution with inactive substances (mainly methylcellulose). The follow-up duration is one year. Feasibility of the study substance, adverse effects, and patient compliance, as well as levels of serum tumor markers (CEA, CA 19-9), quality of life, and patient overall survival rates will be assessed at defined points of time. Discussion The POUDER trial is expected to transfer promising experimental and epidemiological data into a clinical pilot study to assess the effectiveness of broccoli sprout extracts in the treatment of advanced PDA. The study objectives will provide data on the clinical feasibility and acceptability of a supportive treatment option accompanying palliative chemotherapy. Based on these results, future clinical studies to create further evidence in this field are possible. Trial registration The POUDER trial has been registered at ClinicalTrials.gov with an ID NCT01879878 and WHO with an ID U1111-1144-2013 on June 13th 2013.

2014-01-01

167

Effect of physical training on urinary incontinence: a randomized parallel group trial in nursing homes  

PubMed Central

Background Residents in nursing homes (NHs) are often frail older persons who have impaired physical activity. Urinary incontinence (UI) is a common complaint for residents in NHs. Reduced functional ability and residence in NHs are documented to be risk factors for UI. Objective To investigate if an individualized training program designed to improve activity of daily living (ADL) and physical capacity among residents in nursing homes has any impact on UI. Materials and methods This randomized controlled trial was a substudy of a Nordic multicenter study. Participants had to be >65 years, have stayed in the NH for more than 3 months and in need of assistance in at least one ADL. A total of 98 residents were randomly allocated to either a training group (n = 48) or a control group (n = 50) after baseline registrations. The training program lasted for 3 months and included accommodated physical activity and ADL training. Personal treatment goals were elicited for each subject. The control group received their usual care. The main outcome measure was UI as measured by a 24-hour pad-weighing test. There was no statistically significant difference between the groups on this measure at baseline (P = 0.15). Changes were calculated from baseline to 3 months after the end of the intervention. Results Altogether, 68 participants were included in the analysis, 35 in the intervention group and 33 in the control group. The average age was 84.3 years. The 3 months’ postintervention adjusted mean difference between groups according to amount of leakage was 191 g (P = 0.03). This result was statistically significant after adjusting for baseline level, age, sex, and functional status. The leakage increased in residents not receiving the experimental intervention, while UI in the training group showed improvement. Conclusion The intervention group had significant better results compared with the control group after an individualized training program designed to improve ADL and physical capacity. Further studies are needed to evaluate the effect of a goal-oriented physical training program toward NH residents UI complaints.

Vinsnes, Anne G; Helbostad, Jorunn L; Nyr?nning, Signe; Harkless, Gene E; Granbo, Randi; Seim, Arnfinn

2012-01-01

168

Generation of "virtual" control groups for single arm prostate cancer adjuvant trials.  

PubMed

It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies. PMID:24465467

Jia, Zhenyu; Lilly, Michael B; Koziol, James A; Chen, Xin; Xia, Xiao-Qin; Wang, Yipeng; Skarecky, Douglas; Sutton, Manuel; Sawyers, Anne; Ruckle, Herbert; Carpenter, Philip M; Wang-Rodriguez, Jessica; Jiang, Jun; Deng, Mingsen; Pan, Cong; Zhu, Jian-Guo; McLaren, Christine E; Gurley, Michael J; Lee, Chung; McClelland, Michael; Ahlering, Thomas; Kattan, Michael W; Mercola, Dan

2014-01-01

169

Pragmatic randomised controlled trial of group psychoeducation versus group support in the maintenance of bipolar disorder  

Microsoft Academic Search

Background  Non-didactically delivered curriculum based group psychoeducation has been shown to be more effective than both group support\\u000a in a specialist mood disorder centre in Spain (with effects lasting up to five years), and treatment as usual in Australia.\\u000a It is unclear whether the specific content and form of group psychoeducation is effective or the chance to meet and work collaboratively

Richard K Morriss; Fiona Lobban; Steven Jones; Lisa Riste; Sarah Peters; Christopher Roberts; Linda Davies; Debbie Mayes

2011-01-01

170

A randomized controlled trial of ecological momentary intervention plus brief group therapy for generalized anxiety disorder.  

PubMed

Momentary intervention has been proposed as a cost-effective, generalizable, and ecologically valid method to increase the efficiency of face-to-face cognitive-behavioral therapy (CBT). The purpose of the current pilot study was to evaluate the efficacy of a six-session palmtop computer-assisted Group CBT for generalized anxiety disorder (GAD) (CAGT6) in comparison with a six-session Group CBT for GAD without the computer (CBGT6) and typical (12 session) Group CBT for GAD (CBGT12) in a randomized controlled trial. Thirty-four individuals with a primary diagnosis of GAD were randomized to one of the three conditions and completed measures of GAD and anxiety before therapy, after therapy, and at 6-, and 12-month follow-ups. Results indicated that CAGT6 was superior to CBGT6 at posttreatment, but not significantly different from CBGT12. At 6- and 12-month follow-ups, CAGT6 was neither significantly different from CBGT6, nor from CBGT12. Percentages of individuals achieving reliable change on two of the three GAD measures favored CAGT6 over CBGT6 at posttreatment, suggesting promise for the added value of the mobile technology. PMID:24059730

Newman, Michelle G; Przeworski, Amy; Consoli, Andrés J; Taylor, C Barr

2014-06-01

171

Prevention of abdominal wound infection (PROUD trial, DRKS00000390): study protocol for a randomized controlled trial  

PubMed Central

Background Wound infection affects a considerable portion of patients after abdominal operations, increasing health care costs and postoperative morbidity and affecting quality of life. Antibacterial coating has been suggested as an effective measure to decrease postoperative wound infections after laparotomies. The INLINE metaanalysis has recently shown the superiority of a slowly absorbable continuous suture for abdominal closure; with PDS plus® such a suture has now been made available with triclosan antibacterial coating. Methods/Design The PROUD trial is designed as a randomised, controlled, observer, surgeon and patient blinded multicenter superiority trial with two parallel groups and a primary endpoint of wound infection during 30 days after surgery. The intervention group will receive triclosan coated polydioxanone sutures, whereas the control group will receive the standard polydioxanone sutures; abdominal closure will otherwise be standardized in both groups. Statistical analysis is based on intention-to-treat population via binary logistic regression analysis, the total sample size of n = 750 is sufficient to ensure alpha = 5% and power = 80%, an interim analysis will be carried out after data of 375 patients are available. Discussion The PROUD trial will yield robust data to determine the effectiveness of antibacterial coating in one of the standard sutures for abdominal closure and potentially lead to amendment of current guidelines. The exploration of clinically objective parameters as well as quality of life holds immediate relevance for clinical management and the pragmatic trial design ensures high external validity. Trial Registration The trial protocol has been registered with the German Clinical Trials Register (DRKS00000390).

2011-01-01

172

An effective group psychoeducational intervention for improving compliance with vaginal dilation: A randomized controlled trial  

SciTech Connect

Purpose: Although vaginal dilation is often recommended to minimize or prevent vaginal scarring after pelvic radiotherapy, compliance with this recommendation has historically been very low. Therefore, effective intervention strategies are needed to enhance compliance with vaginal dilation after radiotherapy for gynecologic cancer. Methods and Materials: This study was a randomized controlled clinical trial of a psychoeducational intervention specifically designed to increase compliance with vaginal dilation. The information-motivation-behavioral skills model of enhancing compliance with behavioral change was the basis for the intervention design. Forty-two sexually active women, 21 to 65 years of age, diagnosed with Stages Ic-III cervical or endometrial cancer, who received pelvic radiotherapy, were randomized to either the experimental psychoeducational group or the information-only control group. Assessment via questionnaire occurred before treatment and at 6-week, 6-month, 12-month, 18-month, and 24-month follow-up. Assessment via interview also occurred at 6-month, 12-month, 18-month, and 24-month follow-up. Results: The psychoeducational intervention was successful in increasing compliance with vaginal dilation. Conclusions: This study is the first randomized controlled study to demonstrate the effectiveness of an intervention in increasing compliance with the use of vaginal dilators.

Jeffries, Sherryl A. [Department of Psychosocial Resources, Tom Baker Cancer Centre, Calgary, Alberta (Canada); Calgary Health Region Chronic Pain Centre, Calgary, Alberta (Canada); Robinson, John W. [Department of Psychosocial Resources, Tom Baker Cancer Centre, Calgary, Alberta (Canada) and Program in Clinical Psychology, University of Calgary, Calgary, Alberta (Canada) and Faculty of Medicine, Department of Oncology, University of Calgary, Calgary, Alberta (Canada)]. E-mail: johnrobi@cancerboard.ab.ca; Craighead, Peter S. [Faculty of Medicine, Department of Oncology, University of Calgary, Calgary, Alberta (Canada); Department of Radiation Oncology, Tom Baker Cancer Centre, Calgary, Alberta (Canada); Keats, Melanie R. [Faculty of Kinesiology, University of Calgary, Calgary, Alberta (Canada)

2006-06-01

173

What to Do when Data Are Missing in Group Randomized Controlled Trials. NCEE 2009-0049  

ERIC Educational Resources Information Center

This NCEE Technical Methods report examines how to address the problem of missing data in the analysis of data in Randomized Controlled Trials (RCTs) of educational interventions, with a particular focus on the common educational situation in which groups of students such as entire classrooms or schools are randomized. Missing outcome data are a…

Puma, Michael J.; Olsen, Robert B.; Bell, Stephen H.; Price, Cristofer

2009-01-01

174

Pathological prognostic factors in the second British Stomach Cancer Group trial of adjuvant therapy in resectable gastric cancer  

Microsoft Academic Search

The second British Stomach Cancer Group trial was a prospective randomised controlled trial of adjuvant radiotherapy or cytotoxic chemotherapy after gastrectomy for adenocarcinoma. It recruited between 1981 and 1986. No survival advantage has been demonstrated for the patients receiving either type of adjuvant therapy compared with those undergoing surgery alone. We report on 436 patients randomised into the trial together

CC-W Yu; DA Levison; JA Dunn; LC Ward; M Demonakou; WH Allum; MT Hallisey

1995-01-01

175

How to design the control group in randomized controlled trials of acupuncture?  

PubMed

In evidence-based medicine, randomized controlled trials (RCTs) are the preferred method for evaluating the efficacy of interventions. In regard to acupuncture RCTs, the most difficult issues are the design of the control group and implementation of the principle of "double-blinding." We compared the advantages and limitations associated with different control group designs in acupuncture RCTs, to assist researchers in this field. PMID:22829860

Lin, Jaung-Geng; Chen, Chao-Hsun; Huang, Yu-Che; Chen, Yi-Hung

2012-01-01

176

Disappointment and drop-out rate after being allocated to control group in a smoking cessation trial. | accrualnet.cancer.gov  

Cancer.gov

Some patients assigned to clinical trial control groups are disappointed at not participating in the intervention group. This disappointment is often given as the reason patients withdraw from trials. In this study, patients who said they were very disappointed also said that they had not received understandable information provided during the consent process. The authors provide suggestions for addressing patients’ needs to lower drop-out rates. It is especially important to make sure that patients understand randomization prior to enrollment.

177

Multifamily Group Psychoeducation and Cognitive Remediation for First-Episode Psychosis: A Randomized Controlled Trial  

PubMed Central

Background Multifamily group psychoeducation (MFG) has been shown to reduce relapse rates among individuals with first-episode psychosis. However, given the cognitive demands associated with participating in this intervention (e.g., learning and applying a structured problem-solving activity), the cognitive deficits that accompany psychotic disorders may limit the ability of certain individuals to benefit from this intervention. Thus, the goal of this study is to examine whether individuals with first-episode psychosis who participate simultaneously in MFG and cognitive remediation--an intervention shown to improve cognitive functioning among individuals with psychotic disorders--will be less likely to experience a relapse than individuals who participate in MFG alone. Methods/Design Forty individuals with first-episode psychosis and their caregiving relative will be recruited to participate in this study. Individuals with first-episode psychosis will be randomized to one of two conditions: (i) MFG with concurrent participation in cognitive remediation or (ii) MFG alone. The primary outcome for this study is relapse of psychotic symptoms. We will also examine secondary outcomes among both individuals with first-episode psychosis (i.e., social and vocational functioning, health-related quality of life, service utilization, independent living status, and cognitive functioning) and their caregiving relatives (i.e., caregiver burden, anxiety, and depression) Discussion Cognitive remediation offers the possibility of ameliorating a specific deficit (i.e., deficits in cognitive functioning) that often accompanies psychotic symptoms and may restrict the magnitude of the clinical benefits derived from MFG. Trial Registration ClinicalTrials (NCT): NCT01196286

2011-01-01

178

Sexual assault resistance education for university women: study protocol for a randomized controlled trial (SARE trial).  

PubMed

BACKGROUND: More than one in six women will be sexually assaulted in their lifetimes, most by men they know. The situation on university campuses is even more startling, with as many as 1 in 4 female students being victims of rape or attempted rape. The associated physical and mental health effects are extensive and the social and economic costs are staggering. The aim of this randomized controlled trial is to determine whether a novel, small-group sexual assault resistance education program can reduce the incidence of sexual assault among university-attending women, when compared to current university practice of providing informational brochures. METHODS: The trial will evaluate a theoretically and empirically sound four-unit, 12-hour education program that has been demonstrated in pilot studies to have short-term efficacy. Three of the four units provide information, skills, and practice aimed at decreasing the time needed for women to assess situations with elevated risk of acquaintance sexual assault as dangerous and to take action, reducing emotional obstacles to taking action, and increasing the use of the most effective methods of verbal and physical self-defense. The fourth unit focuses on facilitating a stronger positive sexuality from which women may resist sexual coercion by male intimates more successfully. The trial will extend the pilot evaluations by expanding the participant pool and examining the long term efficacy of the program. A total of 1716 first-year female students (age 17 to 24 years) from three Canadian universities will be enrolled. The primary outcome is completed sexual assault, measured by The Sexual Experiences Survey - Short Form Victimization instrument. Secondary outcomes include changes in knowledge, attitudes, and skills related to the process of sexual assault resistance. Outcomes will be measured at baseline, 1 week, 6, 12, 18, and 24 months. DISCUSSION: The results of the trial will be used to produce a maximally effective sexual assault resistance education program that can be adopted by universities, to assess whether aspects of the program need to be strengthened, and also to indicate how long the effects of the program last and at which point in time refresher sessions may be necessary.Trial registration: ClinicalTrials.gov NCT01338428. PMID:23702221

Senn, Charlene Y; Eliasziw, Misha; Barata, Paula C; Thurston, Wilfreda E; Newby-Clark, Ian R; Radtke, H Lorraine; Hobden, Karen L

2013-05-23

179

Pain and Emotional Well-Being Outcomes in Southwest Oncology Group-Directed Intergroup Trial S0205: A Phase III Study Comparing Gemcitabine Plus Cetuximab Versus Gemcitabine As First-Line Therapy in Patients With Advanced Pancreas Cancer  

PubMed Central

Purpose S0205 was a randomized clinical trial that compared the therapeutic impact of gemcitabine versus gemcitabine plus cetuximab. Study results for patient-reported health-related quality of life (HRQL) outcomes are reported. Patients and Methods Patients completed the Brief Pain Inventory and a measure of emotional well-being (each measured on a 0 to 10 scale) at baseline and at weeks 5, 9, 13, and 17 postrandom assignment. Worst pain status was classified as palliated (worst pain scores < 5 maintained for 2 consecutive cycles) or not palliated (remaining patients) and tested with a ?2 test. Change in emotional well-being and worst pain (exploratory analysis) were assessed over 17 weeks using generalized estimating equations with inverse probability of censoring weights. Results Seven hundred twenty of 766 enrolled patients contributed baseline HRQL data. The two treatment arms did not differ statistically in the percentage of patients with successful worst pain palliation. Longitudinal analyses showed significantly improved emotional well-being for patients on both arms by weeks 13 and 17 (P < .01 and P < .001). An exploratory longitudinal analysis of worst pain showed significant decreases at all time points for both arms (P < .01 and P < .001). Significant treatment arm differences for either worst pain or emotional well-being were not observed at any of the assessment times. Conclusion We observed palliated pain and improved well-being for patients on this trial. However, these improvements were similar in both treatment arms, suggesting that the addition of cetuximab did not contribute to improvement in these HRQL outcomes.

Moinpour, Carol M.; Vaught, Nancy L.; Goldman, Bryan; Redman, Mary W.; Philip, Philip A.; Millwood, Barbara; Lippman, Scott M.; Seay, Thomas E.; Flynn, Patrick J.; O'Reilly, Eileen M.; Rowland, Kendrith M.; Wong, Ralph P.; Benedetti, Jacqueline; Blanke, Charles D.

2010-01-01

180

Multicenter phase II clinical trial of nilotinib for patients with imatinib-resistant or -intolerant chronic myeloid leukemia from the East Japan CML study group evaluation of molecular response and the efficacy and safety of nilotinib  

PubMed Central

Background Nilotinib is a second-generation tyrosine kinase inhibitor that exhibits significant efficacy as first- or second-line treatment in patients with chronic myeloid leukemia (CML). We conducted a multicenter Phase II Clinical Trial to evaluate the safety and efficacy of nilotinib among Japanese patients with imatinib-resistant or -intolerant CML-chronic phase (CP) or accelerated phase (AP). Results We analyzed 49 patients (33 imatinib-resistant and 16 imatinib-intolerant) treated with nilotinib 400 mg twice daily. The major molecular response (MMR) rate was 47.8% at 12 months among 35 patients who did not demonstrate an MMR at study entry. Somatic BCR-ABL1 mutations (Y253H, I418V, and exon 8/9 35-bp insertion [35INS]) were detected in 3 patients at 12 months or upon discontinuation of nilotinib. Although 75.5% of patients were still being treated at 12 months, nilotinib treatment was discontinued because of progressing disease in 1 patient, insufficient effect in 2, and adverse events in 9. There was no statistically significant correlation between MMR and trough concentrations of nilotinib. Similarly, no correlation was observed between trough concentrations and adverse events, except for pruritus and hypokalemia. Hyperbilirubinemia was frequently observed (all grades, 51.0%; grades 2–4, 29%; grades 3–4, 4.1%). Hyperbilirubinemia higher than grade 2 was significantly associated with the uridine diphosphate glucuronosyltransferase (UGT)1A9 I399C/C genotype (P?=?0.0086; Odds Ratio, 21.2; 95% Confidence Interval 2.2–208.0). Conclusions Nilotinib was efficacious and well tolerated by patients with imatinib-resistant or -intolerant CML-CP/AP. Hyperbilirubinemia may be predicted before nilotinib treatment, and may be controlled by reducing the daily dose of nilotinib in patients with UGT1A9 polymorphisms. Trial registration clinicaltrials.gov: UMIN000002201

2014-01-01

181

Effectiveness of a group diabetes education programme in underserved communities in South Africa: pragmatic cluster randomized control trial  

PubMed Central

Background Diabetes is an important contributor to the burden of disease in South Africa and prevalence rates as high as 33% have been recorded in Cape Town. Previous studies show that quality of care and health outcomes are poor. The development of an effective education programme should impact on self-care, lifestyle change and adherence to medication; and lead to better control of diabetes, fewer complications and better quality of life. Methods Trial design: Pragmatic cluster randomized controlled trial Participants: Type 2 diabetic patients attending 45 public sector community health centres in Cape Town Interventions: The intervention group will receive 4 sessions of group diabetes education delivered by a health promotion officer in a guiding style. The control group will receive usual care which consists of ad hoc advice during consultations and occasional educational talks in the waiting room. Objective: To evaluate the effectiveness of the group diabetes education programme Outcomes: Primary outcomes: diabetes self-care activities, 5% weight loss, 1% reduction in HbA1c. Secondary outcomes: self-efficacy, locus of control, mean blood pressure, mean weight loss, mean waist circumference, mean HbA1c, mean total cholesterol, quality of life Randomisation: Computer generated random numbers Blinding: Patients, health promoters and research assistants could not be blinded to the health centre’s allocation Numbers randomized: Seventeen health centres (34 in total) will be randomly assigned to either control or intervention groups. A sample size of 1360 patients in 34 clusters of 40 patients will give a power of 80% to detect the primary outcomes with 5% precision. Altogether 720 patients were recruited in the intervention arm and 850 in the control arm giving a total of 1570. Discussion The study will inform policy makers and managers of the district health system, particularly in low to middle income countries, if this programme can be implemented more widely. Trial register Pan African Clinical Trial Registry PACTR201205000380384

2012-01-01

182

Patterns of missing mini mental status exam (MMSE) in radiation therapy oncology group (RTOG) brain cancer trials  

Microsoft Academic Search

The Mini Mental Status Exam (MMSE) instrument has been commonly used in the Radiation Therapy Oncology Group (RTOG) to assess\\u000a mental status in brain cancer patients. Evaluating patient factors in relation to patterns of incomplete MMSE assessments\\u000a can provide insight into predictors of missingness and optimal MMSE collection schedules in brain cancer clinical trials.\\u000a This study examined eight RTOG brain

K. Bae; D. W. Bruner; S. Baek; B. Movsas; B. W. Corn; J. J. Dignam

183

Altering School Climate through School-Wide Positive Behavioral Interventions and Supports: Findings from a Group-Randomized Effectiveness Trial  

Microsoft Academic Search

Positive Behavioral Interventions and Supports (PBIS) is a universal, school-wide prevention strategy that is currently implemented\\u000a in over 7,500 schools to reduce disruptive behavior problems. The present study examines the impact of PBIS on staff reports\\u000a of school organizational health using data from a group-randomized controlled effectiveness trial of PBIS conducted in 37\\u000a elementary schools. Longitudinal multilevel analyses on data

Catherine P. Bradshaw; Christine W. Koth; Leslie A. Thornton; Philip J. Leaf

2009-01-01

184

Results of a randomized trial comparing sequential intravenous/oral treatment with ciprofloxacin plus metronidazole to imipenem/cilastatin for intra-abdominal infections. The Intra-Abdominal Infection Study Group.  

PubMed Central

OBJECTIVE: In a randomized, double-blind, multicenter trial, ciprofloxacin/metronidazole was compared with imipenem/cilastatin for treatment of complicated intra-abdominal infections. A secondary objective was to demonstrate the ability to switch responding patients from intravenous (IV) to oral (PO) therapy. SUMMARY BACKGROUND DATA: Intra-abdominal infections result in substantial morbidity, mortality, and cost. Antimicrobial therapy often includes a 7- to 10-day intravenous course. The use of oral antimicrobials is a recent advance due to the availability of agents with good tissue pharmacokinetics and potent aerobic gram-negative activity. METHODS: Patients were randomized to either ciprofloxacin plus metronidazole intravenously (CIP/MTZ IV) or imipenem intravenously (IMI IV) throughout their treatment course, or ciprofloxacin plus metronidazole intravenously and treatment with oral ciprofloxacin plus metronidazole when oral feeding was resumed (CIP/MTZ IV/PO). RESULTS: Among 671 patients who constituted the intent-to-treat population, overall success rates were as follows: 82% for the group treated with CIP/MTZ IV; 84% for the CIP/MTZ IV/PO group; and 82% for the IMI IV group. For 330 valid patients, treatment success occurred in 84% of patients treated with CIP/MTZ IV, 86% of those treated with CIP/MTZ IV/PO, and 81% of the patients treated with IMI IV. Analysis of microbiology in the 30 patients undergoing intervention after treatment failure suggested that persistence of gram-negative organisms was more common in the IMI IV-treated patients who subsequently failed. Of 46 CIP/MTZ IV/PO patients (active oral arm), treatment success occurred in 96%, compared with 89% for those treated with CIP/MTZ IV and 89% for those receiving IMI IV. Patients who received intravenous/oral therapy were treated, overall, for an average of 8.6 +/- 3.6 days, with an average of 4.0 +/- 3.0 days of oral treatment. CONCLUSIONS: These results demonstrate statistical equivalence between CIP/MTZ IV and IMI IV in both the intent-to-treat and valid populations. Conversion to oral therapy with CIP/MTZ appears as effective as continued intravenous therapy in patients able to tolerate oral feedings.

Solomkin, J S; Reinhart, H H; Dellinger, E P; Bohnen, J M; Rotstein, O D; Vogel, S B; Simms, H H; Hill, C S; Bjornson, H S; Haverstock, D C; Coulter, H O; Echols, R M

1996-01-01

185

Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design  

PubMed Central

Background Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question. Methods/design We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs’). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials. Discussion To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.

2013-01-01

186

Cost effectiveness of group follow-up after structured education for type 1 diabetes: a cluster randomised controlled trial  

PubMed Central

Background This study examines the cost effectiveness of group follow-up after participation in the Dose Adjustment for Normal Eating (DAFNE) structured education programme for type 1 diabetes. Methods Economic evaluation conducted alongside a cluster randomised controlled trial involving 437 adults with type 1 diabetes in Ireland. Group follow-up involved two group education ‘booster’ sessions post-DAFNE. Individual follow-up involved two standard one-to-one hospital clinic visits. Incremental costs, quality-adjusted life years (QALYs) gained and cost effectiveness were estimated at 18 months. Uncertainty was explored using sensitivity analysis and by estimating cost effectiveness acceptability curves. Results Group follow-up was associated with a mean reduction in QALYs gained of 0.04 per patient (P value, 0.052; 95% CI, ?0.08 to 0.01, intra-class correlation (ICC), 0.033) and a mean reduction in total healthcare costs of €772 (P value, 0.020; 95% CI, ?1,415 to ?128: ICC, 0.016) per patient. At alternative threshold values of €5,000, €15,000, €25,000, €35,000, and €45,000, the probability of group follow-up being cost effective was estimated to be 1.000, 0.762, 0.204, 0.078, and 0.033 respectively. Conclusions The results do not support implementation of group follow-up as the sole means of follow-up post-DAFNE. Given the reported cost savings, future studies should explore the cost effectiveness of alternative models of group care for diabetes. Trial registration Current Controlled Trials ISRCTN79759174 (assigned: 9 February 2007).

2014-01-01

187

Biomarkers of sarcopenia in clinical trials-recommendations from the International Working Group on Sarcopenia.  

PubMed

Sarcopenia, the age-related skeletal muscle decline, is associated with relevant clinical and socioeconomic negative outcomes in older persons. The study of this phenomenon and the development of preventive/therapeutic strategies represent public health priorities. The present document reports the results of a recent meeting of the International Working Group on Sarcopenia (a task force consisting of geriatricians and scientists from academia and industry) held on June 7-8, 2011 in Toulouse (France). The meeting was specifically focused at gaining knowledge on the currently available biomarkers (functional, biological, or imaging-related) that could be utilized in clinical trials of sarcopenia and considered the most reliable and promising to evaluate age-related modifications of skeletal muscle. Specific recommendations about the assessment of aging skeletal muscle in older people and the optimal methodological design of studies on sarcopenia were also discussed and finalized. Although the study of skeletal muscle decline is still in a very preliminary phase, the potential great benefits derived from a better understanding and treatment of this condition should encourage research on sarcopenia. However, the reasonable uncertainties (derived from exploring a novel field and the exponential acceleration of scientific progress) require the adoption of a cautious and comprehensive approach to the subject. PMID:22865205

Cesari, Matteo; Fielding, Roger A; Pahor, Marco; Goodpaster, Bret; Hellerstein, Marc; van Kan, Gabor A; Anker, Stefan D; Rutkove, Seward; Vrijbloed, J Willem; Isaac, Maria; Rolland, Yves; M'rini, Christine; Aubertin-Leheudre, Mylène; Cedarbaum, Jesse M; Zamboni, Mauro; Sieber, Cornell C; Laurent, Didier; Evans, William J; Roubenoff, Ronenn; Morley, John E; Vellas, Bruno

2012-09-01

188

Structural aberrations affecting the MYC locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL).  

PubMed

Recent retrospective studies of heterogeneously treated patients have suggested that chromosomal aberrations of the MYC gene locus indicate an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL). Here, we investigated the prognostic impact of MYC aberrations analyzed by interphase fluorescence in situ hybridization in 177 patients with de novo DLBCL treated within the two prospective, randomized trials non-Hodgkin's lymphoma NHL-B1 and NHL-B2. MYC aberrations were detected in 14 DLBCL (7.9%). In a univariate analysis compared with MYC-negative DLBCL, MYC-positive cases showed a significantly shorter overall survival (OS) (P=0.047) and relevantly, though not significantly, shorter event-free survival (EFS) (P=0.062). In a Cox model adjusted for the international prognostic index, the presence of a MYC gene rearrangement was the strongest statistically independent predictor of OS (relative risk 3.4, P=0.004) and EFS (relative risk 2.5, P=0.015), and this also held true when the cell-of-origin signature detected by immunohistochemistry was included in the model. PMID:18754028

Klapper, W; Stoecklein, H; Zeynalova, S; Ott, G; Kosari, F; Rosenwald, A; Loeffler, M; Trümper, L; Pfreundschuh, M; Siebert, Reiner

2008-12-01

189

Targeting young drinkers online: the effectiveness of a web-based brief alcohol intervention in reducing heavy drinking among college students: study protocol of a two-arm parallel group randomized controlled trial  

Microsoft Academic Search

Background  The prevalence of heavy drinking among college students and its associated health related consequences highlights an urgent\\u000a need for alcohol prevention programs targeting 18 to 24 year olds. Nevertheless, current alcohol prevention programs in the\\u000a Netherlands pay surprisingly little attention to the drinking patterns of this specific age group. The study described in\\u000a this protocol will test the effectiveness of

Carmen V Voogt; Evelien AP Poelen; Marloes Kleinjan; Lex ACJ Lemmers; Rutger CME Engels

2011-01-01

190

Effectiveness of Peer-Led Dissonance-Based Eating Disorder Prevention Groups: Results from Two Randomized Pilot Trials  

PubMed Central

Objective The present preliminary trials tested whether undergraduate peer leaders can effectively deliver a dissonance-based eating disorder prevention program, which could facilitate broad dissemination of this efficacious intervention. Method In Study 1, female undergraduates (N = 171) were randomized to peer-led groups, clinician-led groups, or an educational brochure control condition. In Study 2, which improved a design limitation of Study 1 by using completely parallel outcome measures across conditions, female undergraduates (N = 148) were randomized to either immediate peer-led groups or a waitlist control condition. Results In Study 1, participants in peer- and clinician-led groups showed significantly greater pre-post reductions in risk factors and eating disorder symptoms than controls (M d = .64 and .98 respectively), though clinician- versus peer-led groups had higher attendance and competence rating, and produced stronger effects at posttest (M d = .32) and at 1-year follow-up (M d = .26). In Study 2, participants in peer-led groups showed greater pre-post reductions in all outcomes than waitlist controls (M d = .75). Conclusions Results provide novel evidence that dissonance-based eating disorder prevention groups led by undergraduate peers are feasible and produce greater reductions in eating disorder risk factors and symptoms than minimal-intervention control conditions, but indicate that effects are smaller for peer- versus clinician-led groups.

Rohde, Paul; Durant, Shelley; Shaw, Heather; Wade, Emily

2014-01-01

191

The NSABP Study of Tamoxifen and Raloxifene (STAR) trial  

PubMed Central

In the Study of Tamoxifen and Raloxifene (STAR) trial, postmenopausal women at increased risk of breast cancer received either oral tamoxifen (20 mg/day) or raloxifene (60 mg/day) over 5 years. There were an equal number of cases of invasive breast cancer in women assigned to tamoxifen and raloxifene. There were fewer cases of noninvasive breast cancer in the tamoxifen group than in the raloxifene group (risk ratio [RR]: 1.40; 95% confidence interval [CI]: 0.98–2.02). There were more cases of uterine cancer with tamoxifen than with raloxifene (RR: 0.62; 95% CI: 0.35–1.08). Thromboembolic events occurred less often in the raloxifene group (RR: 0.70; 95% CI: 0.54–0.91) and there were fewer cataracts and cataract surgeries in the women taking raloxifene (RR: 0.79; 95% CI: 0.68–0.92). The STAR trial has shown that raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of adverse events but a nonstatistically significant higher risk of noninvasive breast cancer. The risk of other cancers, fractures, ischemic heart disease and stroke is similar for both drugs.

Vogel, Victor G

2009-01-01

192

A randomized phase III trial of adjuvant chemotherapy with UFT for completely resected pathological stage I non-small-cell lung cancer: the West Japan Study Group for Lung Cancer Surgery (WJSG)--the 4th study  

Microsoft Academic Search

Purpose: To examine the efficacy of UFT, an oral 5-fluorouracil derivative agent, as post-operative adjuvant therapy for pathologic (p-) stage I non-small-cell lung cancer (NSCLC), because a previous randomized study had suggested it was efficacious for early-stage NSCLC patients. Patients and methods: Patients with completely resected p-stage I, adenocarcinoma or squamous cell carcinoma were eligible. A total of 332 patients

M. Nakagawa; F. Tanaka; N. Tsubota; M. Ohta; M. Takao; H. Wada

2005-01-01

193

The EHR solution to clinical trial recruitment in physician groups. | accrualnet.cancer.gov  

Cancer.gov

This article was written by the president and founder of the Holston Medical Group and explains his company’s success with an electronic health record (EHR). The EHR is used among 102 providers in 26 locations and has been used to enroll thousands of patients in more than 250 clinical trials. The Holston Medical Group has determined that the use of the EHR Web-based technology can significantly streamline patient recruitment, speed monitoring, and help to prevent protocol failure—all while increasing revenue stream.

194

Radiotherapy in pediatric medulloblastoma: Quality assessment of Pediatric Oncology Group Trial 9031  

SciTech Connect

Purpose: To evaluate the potential influence of radiotherapy quality on survival in high-risk pediatric medulloblastoma patients. Methods and Materials: Trial 9031 of the Pediatric Oncology Group (POG) aimed to study the relative benefit of cisplatin and etoposide randomization of high-risk patients with medulloblastoma to preradiotherapy vs. postradiotherapy treatment. Two-hundred and ten patients were treated according to protocol guidelines and were eligible for the present analysis. Treatment volume (whole brain, spine, posterior fossa, and primary tumor bed) and dose prescription deviations were assessed for each patient. An analysis of first site of failure was undertaken. Event-free and overall survival rates were calculated. A log-rank test was used to determine the significance of potential survival differences between patients with and without major deviations in the radiotherapy procedure. Results: Of 160 patients who were fully evaluable for all treatment quality parameters, 91 (57%) had 1 or more major deviations in their treatment schedule. Major deviations by treatment site were brain (26%), spinal (7%), posterior fossa (40%), and primary tumor bed (17%). Major treatment volume or total dose deviations did not significantly influence overall and event-free survival. Conclusions: Despite major treatment deviations in more than half of fully evaluable patients, underdosage or treatment volume misses were not associated with a worse event-free or overall survival.

Miralbell, Raymond [Quality Assurance Review Committee, Providence, RI (United States) and Department of Radiation Oncology, University Hospital, Geneva (Switzerland)]. E-mail: Raymond.Miralbell@hcuge.ch; Fitzgerald, T.J. [Quality Assurance Review Committee, Providence, RI (United States); Laurie, Fran [Quality Assurance Review Committee, Providence, RI (United States); Kessel, Sandy [Quality Assurance Review Committee, Providence, RI (United States); Glicksman, Arvin [Quality Assurance Review Committee, Providence, RI (United States); Friedman, Henry S. [Pediatric Neuro-Oncology Division, Duke South Hospital, Durham, NC (United States); Urie, Marcia [Quality Assurance Review Committee, Providence, RI (United States); Kepner, James L. [Roswell Park Cancer Institute, Buffalo, NY (United States); Zhou Tianni [Operations Center, Children's Oncology Group, Arcadia, CA (United States); Chen Zhengjia [Operations Center, Children's Oncology Group, Arcadia, CA (United States); Barnes, Pat [Department of Radiology, Stanford University, Stanford, CA (United States); Kun, Larry [Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, TN (United States); Tarbell, Nancy J. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)

2006-04-01

195

Phase II clinical trial of capecitabine in ovarian carcinoma recurrent 6–12 months after completion of primary chemotherapy, with exploratory TS, DPD, and TP correlates: a Gynecologic Oncology Group study  

Microsoft Academic Search

Purpose.A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of capecitabine in women with measurable platinum-sensitive ovarian cancer or platinum-sensitive primary peritoneal cancer and to explore the ability of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) to predict response and toxicities.

Agustin A. Garcia; John A. Blessing; Heinz-Josef Lenz; Kathleen M. Darcy; Robert S. Mannel; David Scott Miller; Nader Husseinzadeh

2005-01-01

196

The relaxation exercise and social support trial-resst: study protocol for a randomized community based trial  

PubMed Central

Background Studies suggests a possible link between vaginal discharge and common mental distress, as well as highlight the implications of the subjective burden of disease and its link with mental health. Methods/Design This is a community-based intervention trial that aims to evaluate the impact of a psycho-social intervention on medically unexplained vaginal discharge (MUVD) in a group of married, low-income Lebanese women, aged 18-49, and suffering from low to moderate levels of anxiety and/or depression. The intervention consisted of 12 sessions of structured social support, problem solving techniques, group discussions and trainer-supervised relaxation exercises (twice per week over six weeks). Women were recruited from Hey el Selloum, a southern disadvantaged suburb of Beirut, Lebanon, during an open recruitment campaign. The primary outcome was self-reported MUVD, upon ruling out reproductive tract infections (RTIs), through lab analysis. Anxiety and/or depression symptoms were the secondary outcomes for this trial. These were assessed using an Arabic validated version of the Hopkins Symptoms Checklist-25 (HSCL-25). Assessments were done at baseline and six months using face-to face interviews, pelvic examinations and laboratory tests. Women were randomized into either intervention or control group. Intent to treat analysis will be used. Discussion The results will indicate whether the proposed psychosocial intervention was effective in reducing MUVD (possibly mediated by common mental distress). Trial Registration The trial is registered at the Wellcome Trust Registry, ISRCTN assigned: ISRCTN: ISRCTN98441241

2011-01-01

197

Nitrates and bone turnover (NABT) - trial to select the best nitrate preparation: study protocol for a randomized controlled trial  

PubMed Central

Background Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study. Methods and design This will be an open-label randomized, controlled trial conducted at Women’s College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the ‘multiple comparisons with the best’ approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Discussion Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures. Trial registration ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742.

2013-01-01

198

Behavioral risk assessment in HIV Vaccine Trials Network (HVTN) clinical trials: a qualitative study exploring HVTN staff perspectives.  

PubMed

In HIV vaccine trials, the collection and analysis of participant behavior data associated with risk of acquiring HIV-infection is important for a number of reasons. Although the rationale for behavioral risk assessment in HIV vaccine clinical trials is clear, consistent collection of behavioral data over time and across protocols has been challenging for the HIV Vaccine Trials Network (HVTN). Integrating biomedical and behavioral research within the same preventive vaccine clinical trial has proven difficult. The HVTN conducted an internal landscape analysis to: (1) evaluate the challenges of behavioral risk assessment in HIV vaccine trials and observational studies; (2) explore the impact of the Step Study on behavioral risk assessment measures; and (3) identify strategies to overcome existing challenges and improve the quality of data resulting from behavioral risk analysis. These analyses of behavioral risk within the HVTN revealed several challenges and recommendations for improved behavioral risk data collection in future protocols. The recommendations for improvement include: (1) establishment of protocol-specific behavioral risk working groups that include social and behavioral experts; (2) provision of behavioral rationale and objectives to the development team; (3) creation of a template for geographic- and population-specific assessment of low and high risk behaviors; and (4) pilot testing of behavioral risk assessments. Results also underscored the need for routinely conducted analyses of behavioral data. PMID:23859840

Andrasik, Michele Peake; Karuna, Shelly T; Nebergall, Michelle; Koblin, Beryl A; Kublin, Jim G

2013-09-13

199

Summary of ceftaroline fosamil clinical trial studies and clinical safety.  

PubMed

In October 2010, the new cephalosporin, ceftaroline fosamil, was approved by the US Food and Drug Administration for therapy of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSIs). The active metabolite, ceftaroline, demonstrates in vitro activity against typical bacterial pathogens most often associated with CABP or ABSSSIs, including resistant Gram-positive pathogens such as multidrug-resistant Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus. The efficacy and safety of ceftaroline fosamil was assessed in 2 large phase 3 programs of randomized, double-blind, clinical trials for CABP and ABSSSIs. For both indications, therapy with ceftaroline fosamil was observed to be noninferior to the comparator agents (ceftriaxone for CABP and vancomycin plus aztreonam for ABSSSIs) at both a standard test of cure assessment time (8-15 days after discontinuation of study drug) and an early assessment time point (day 3 or 4 of study). In the integrated analysis of the trials for CABP (FOCUS 1 and 2), clinical cure rates for the ceftaroline group were numerically higher than those for the ceftriaxone group (for the clinically evaluable population 84.3% vs 77.7%; difference: 6.6%; 95% confidence interval, 1.6%-11.8%). Among patients with CABP caused by S. pneumoniae, clinical cure rates were markedly higher in the ceftaroline treatment group than in the ceftriaxone treatment group (59 of 69 [85.5%] vs 48 of 70 [68.6%], respectively). For the ABSSSI studies (CANVAS 1 and 2), microbiologically evaluable (ME) success rates were similar between the treatment groups. Notably, the clinical cure rates in ME patients with methicillin-resistant S. aureus ABSSSIs were 142 of 152 (93.4%) and 115 of 122 (94.3%), for ceftaroline and vancomycin plus aztreonam, respectively, and did not differ from those achieved in infections due to methicillin-susceptible S. aureus (93.0%-94.5%). Ceftaroline fosamil was well tolerated, with a safety profile similar to the comparator agents used in these phase 3 trials. PMID:22903949

File, Thomas M; Wilcox, Mark H; Stein, Gary E

2012-09-01

200

TrialNet Information for Study Participants  

MedlinePLUS

... Join Where do I go? TrialNet Locations Can Type 1 Diabetes Be Prevented? You Can Help Answer This Question! If someone in your family has type 1 diabetes, you and other family members may be at ...

201

Effectiveness of a psycho-educational group program for major depression in primary care: a randomized controlled trial  

PubMed Central

Background Studies show the effectiveness of group psychoeducation in reducing symptoms in people with depression. However, few controlled studies that have included aspects of personal care and healthy lifestyle (diet, physical exercise, sleep) together with cognitive-behavioral techniques in psychoeducation are proven to be effective. The objective of this study is to assess the effectiveness of a psychoeducational program, which includes aspects of personal care and healthy lifestyle, in patients with mild/moderate depression symptoms in Primary Care (PC). Methods In a randomized, controlled trial, 246 participants over 20 years old with ICD-10 major depression were recruited through nurses/general practitioners at 12 urban Primary Care Centers (PCCs) in Barcelona. The intervention group (IG) (n=119) received a group psychoeducational program (12 weekly, 1.5 h sessions led by two nurses) and the control group (CG) (n=112) received usual care. Patients were assessed at baseline and at, 3, 6 and 9 months. The main outcome measures were the BDI, EQ-5D and remission based upon the BDI. Results 231 randomized patients were included, of whom 85 had mild depression and 146 moderate depression. The analyses showed significant differences between groups in relation to remission of symptoms, especially in the mild depression group with a high rate of 57% (p=0.009) at post-treatment and 65% (p=0.006) at 9 month follow up, and only showed significant differences on the BDI at post-treatment (p=0.016; effect size Cohen’s d’=.51) and at 6 and 9 month follow-up (p= 0.048; d’=.44). In the overall and moderate sample, the analyses only showed significant differences between groups on the BDI at post-treatment, p=0.02 (d’=.29) and p=0.010 (d’=.47), respectively. The psychoeducation group improved significantly on the EQ-5D at short and long-term. Conclusions This psychoeducational intervention is a short and long-term effective treatment for patients with mild depression symptoms. It results in a high remission rate, is recommended in PC and can be carried out by nurses with previous training. In moderate patients, group psychoeducation is effective in the short-term. Trial registration Clinical Trials.gov identifier NCT00841737

2012-01-01

202

The Thrombolysis in Myocardial Infarction (TIMI) Study Group experience.  

PubMed

The Thrombolysis in Myocardial Infarction (TIMI) study group, an academic research organization, was formed in 1984 with initial support from the National Heart, Lung, and Blood Institute. Its initial goal was to compare the effects of the then-new thrombolytic agent, recombinant tissue plasminogen activator, with streptokinase. The TIMI study group has remained active since then and has completed 50 multicenter clinical trials. The TIMI network now collaborates with more than 1000 separate sites in 45 countries on 5 continents. In addition to thrombolytic agents, TIMI has studied antithrombotic, antiplatelet, anti-ischemic, lipid lowering, and anti-inflammatory drugs. TIMI has also established robust biomarker and pharmacogenetics programs, and has devised a panel of risk assessment scores that are widely used. TIMI is currently conducting 7 large trials worldwide on novel agents designed to reduce the morbidity and mortality of a variety of cardiovascular disorders. PMID:22901500

Braunwald, Eugene; Sabatine, Marc S

2012-10-01

203

Reducing prescribing of highly anticholinergic antidepressants for elderly people: randomised trial of group versus individual academic detailing  

PubMed Central

Objective To compare the effect of individual educational visits versus group visits using academic detailing to discuss prescribing of highly anticholinergic antidepressants in elderly people. Design Randomised controlled trial with three arms (individual visits, group visits, and a control arm). Setting Southwest Netherlands. Participants 190 general practitioners and 37 pharmacists organised in 21 peer review groups were studied using a database covering all prescriptions to people covered by national health insurance in the area (about 240?000). Intervention All general practitioners and pharmacists in both intervention arms were offered two educational visits. For physicians in groups randomised to the individual visit arm, 43 of 70 general practitioners participated; in the group visit intervention arm, five of seven groups (41 of 52 general practitioners) participated. Main outcome measures Numbers of elderly people (?60 years) with new prescriptions of highly anticholinergic antidepressants and less anticholinergic antidepressants. Results An intention to treat analysis found a 26% reduction in the rate of starting highly anticholinergic antidepressants in elderly people (95% confidence interval ?4% to 48%) in the individual intervention arm and 45% (8% to 67%) in the group intervention arm. The use of less anticholinergic antidepressants increased by 40% (6% to 83%) in the individual intervention arm and 29% (?7% to 79%) in the group intervention arm. Conclusions Both the individual and the group visits decreased the use of highly anticholinergic antidepressants and increased the use of less anticholinergic antidepressant in elderly people. These approaches are practical means to improve prescribing by continuing medical education.

van Eijk, Martine E C; Avorn, Jerry; Porsius, Arijan J; de Boer, Anthonius

2001-01-01

204

Phase II clinical trial of capecitabine in ovarian carcinoma recurrent 6–12 months after completion of primary chemotherapy with exploratory TS DPD and TP correlates: a Gynecologic Oncology Group study  

Microsoft Academic Search

Abstract Purpose. A phase II trial was conducted to evaluate the anti-tumor activity and adverse effects of capecitabine in women,with measurable platinum-sensitive ovarian cancer or platinum-sensitive primary peritoneal cancer and to explore the ability of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) to predict response and toxicities. Experimental design. Patients were treated with a daily starting dose

Agustin A. Garcia; John A. Blessing; Heinz-josef Lenz; Kathleen M. Darcy; Robert S. Mannel; David Scott Miller; Nader Husseinzadeh

205

The danger of trial-by-trial knowledge of results in perceptual averaging studies  

Microsoft Academic Search

Revived interest in “intuitive statistics” (Peterson & Beach, 1967) is evident in recent studies concerning the ability of\\u000a observers to estimate mean size for ensembles of lines or of circles. To put the recent studies in context, and to highlight\\u000a a potential danger in providing trial-by-trial knowledge of results (KOR), brief contact with previous research is made and\\u000a a new

Ben Bauer

2009-01-01

206

Clinical trials transparency and the Trial and Experimental Studies Transparency (TEST) act.  

PubMed

Clinical trial research is the cornerstone for successful advancement of medicine that provides hope for millions of people in the future. Full transparency in clinical trials may allow independent investigators to evaluate study designs, perform additional analysis of data, and potentially eliminate duplicate studies. Current regulatory system and publishers rely on investigators and pharmaceutical industries for complete and accurate reporting of results from completed clinical trials. Legislation seems to be the only way to enforce mandatory disclosure of results. The Trial and Experimental Studies Transparency (TEST) Act of 2012 was introduced to the legislators in the United States to promote greater transparency in research industry. Public safety and advancement of science are the driving forces for the proposed policy change. The TEST Act may benefit the society and researchers; however, there are major concerns with participants' privacy and intellectual property protection. PMID:24440100

Logvinov, Ilana

2014-03-01

207

The Effectiveness of an Online Support Group for Members of the Community with Depression: A Randomised Controlled Trial  

PubMed Central

Background Internet support groups (ISGs) are popular, particularly among people with depression, but there is little high quality evidence concerning their effectiveness. Aim The study aimed to evaluate the efficacy of an ISG for reducing depressive symptoms among community members when used alone and in combination with an automated Internet-based psychotherapy training program. Method Volunteers with elevated psychological distress were identified using a community-based screening postal survey. Participants were randomised to one of four 12-week conditions: depression Internet Support Group (ISG), automated depression Internet Training Program (ITP), combination of the two (ITP+ISG), or a control website with delayed access to e-couch at 6 months. Assessments were conducted at baseline, post-intervention, 6 and 12 months. Results There was no change in depressive symptoms relative to control after 3 months of exposure to the ISG. However, both the ISG alone and the combined ISG+ITP group showed significantly greater reduction in depressive symptoms at 6 and 12 months follow-up than the control group. The ITP program was effective relative to control at post-intervention but not at 6 months. Conclusions ISGs for depression are promising and warrant further empirical investigation. Trial Registration Controlled-Trials.com ISRCTN65657330

Griffiths, Kathleen M.; Mackinnon, Andrew J.; Crisp, Dimity A.; Christensen, Helen; Bennett, Kylie; Farrer, Louise

2012-01-01

208

Randomised trials of STD treatment for HIV prevention: report of an international workshop. HIV/STD Trials Workshop Group.  

PubMed Central

Three community trials of the impact of STD treatment interventions on HIV incidence in rural populations have been completed or are in progress in Uganda and Tanzania. Investigators from these trials met for a joint technical workshop in Baltimore in May 1996. This report summarises the consensus of the workshop, with the aim of providing useful input to research on HIV intervention strategies. Issues discussed include: (i) the role of community randomised trials; (ii) strategies for STD management; (iii) epidemiological and statistical issues in the design and analysis of community randomised trials; (iv) diagnostic methods for STDs in population surveys; (v) treatment regimens for STDs in rural Africa; and (vi) ethical issues in community trials.

Hayes, R; Wawer, M; Gray, R; Whitworth, J; Grosskurth, H; Mabey, D

1997-01-01

209

Group therapy for adolescents with repeated self harm: randomised controlled trial with economic evaluation  

PubMed Central

Objective To examine the effectiveness and cost-effectiveness of group therapy for self harm in young people. Design Two arm, single (assessor) blinded parallel randomised allocation trial of a group therapy intervention in addition to routine care, compared with routine care alone. Randomisation was by minimisation controlling for baseline frequency of self harm, presence of conduct disorder, depressive disorder, and severity of psychosocial stress. Participants Adolescents aged 12-17 years with at least two past episodes of self harm within the previous 12 months. Exclusion criteria were: not speaking English, low weight anorexia nervosa, acute psychosis, substantial learning difficulties (defined by need for specialist school), current containment in secure care. Setting Eight child and adolescent mental health services in the northwest UK. Interventions Manual based developmental group therapy programme specifically designed for adolescents who harm themselves, with an acute phase over six weekly sessions followed by a booster phase of weekly groups as long as needed. Details of routine care were gathered from participating centres. Main outcome measures Primary outcome was frequency of subsequent repeated episodes of self harm. Secondary outcomes were severity of subsequent self harm, mood disorder, suicidal ideation, and global functioning. Total costs of health, social care, education, and criminal justice sector services, plus family related costs and productivity losses, were recorded. Results 183 adolescents were allocated to each arm (total n=366). Loss to follow-up was low (<4%). On all outcomes the trial cohort as a whole showed significant improvement from baseline to follow-up. On the primary outcome of frequency of self harm, proportional odds ratio of group therapy versus routine care adjusting for relevant baseline variables was 0.99 (95% confidence interval 0.68 to 1.44, P=0.95) at 6 months and 0.88 (0.59 to 1.33, P=0.52) at 1 year. For severity of subsequent self harm the equivalent odds ratios were 0.81 (0.54 to1.20, P=0.29) at 6 months and 0.94 (0.63 to 1.40, P=0.75) at 1 year. Total 1 year costs were higher in the group therapy arm (£21?781) than for routine care (£15?372) but the difference was not significant (95% CI ?1416 to 10782, P=0.132). Conclusions The addition of this targeted group therapy programme did not improve self harm outcomes for adolescents who repeatedly self harmed, nor was there evidence of cost effectiveness. The outcomes to end point for the cohort as a whole were better than current clinical expectations. Trial registration ISRCTN 20496110

2011-01-01

210

Design of tumor biomarker-monitoring trials: a proposal by the European Group on Tumor Markers.  

PubMed

A major application of tumor biomarkers is in serial monitoring of cancer patients, but there are no published guidelines on how to evaluate biomarkers for this purpose. The European Group on Tumor Markers has convened a multidisciplinary panel of scientists to develop guidance on the design of such monitoring trials. The panel proposes a 4-phase model for biomarker-monitoring trials analogous to that in use for the investigation of new drugs. In phase I, biomarker kinetics and correlation with tumor burden are assessed. Phase II evaluates the ability of the biomarker to identify, exclude, and/or predict a change in disease status. In phase III, the effectiveness of tumor biomarker-guided intervention is assessed by measuring patient outcome in randomized trials. Phase IV consists of an audit of the long-term effects after biomarker monitoring has been included into standard patient care. Systematic well-designed evaluations of biomarkers for monitoring may provide a stronger evidence base that might enable their earlier use in evaluating responses to cancer therapy. PMID:23034139

Sölétormos, György; Duffy, Michael J; Hayes, Daniel F; Sturgeon, Catharine M; Barak, Vivian; Bossuyt, Patrick M; Diamandis, Eleftherios P; Gion, Massimo; Hyltoft-Petersen, Per; Lamerz, Rolf M; Nielsen, Dorte L; Sibley, Paul; Tholander, Bengt; Tuxen, Malgorzata K; Bonfrer, Johannes M G

2013-01-01

211

Phase II Selection Design Trial of Concurrent Chemotherapy and Cetuximab Versus Chemotherapy Followed by Cetuximab in Advanced-Stage Non-Small-Cell Lung Cancer: Southwest Oncology Group Study S0342  

PubMed Central

Purpose Randomized clinical trials failed to show a survival benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus concurrent chemotherapy in patients with metastatic non–small-cell lung cancer (NSCLC), with preclinical data suggesting potential negative interactions. In contrast, pilot trials of the EGFR-targeted antibody, cetuximab, plus chemotherapy suggested enhanced antitumor activity. This randomized phase II trial was designed to select a cetuximab plus chemotherapy regimen for phase III evaluation. Patients and Methods Treatment-naive patients with advanced-stage NSCLC were randomly assigned to receive paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxel-carboplatin for four cycles followed by cetuximab. Results Of 242 patients enrolled, 224 were eligible and assessable for response (106 and 118 patients in the concurrent and sequential arms, respectively). With a median follow-up time of 32 months, the median overall survival was 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P = .57); 1-year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35% to 53%), respectively. Response rates and progression-free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm (15% v 5% in the sequential arm; P = .036). Conclusion Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxel/carboplatin plus cetuximab was chosen.

Herbst, Roy S.; Kelly, Karen; Chansky, Kari; Mack, Philip C.; Franklin, Wilbur A.; Hirsch, Fred R.; Atkins, James N.; Dakhil, Shaker R.; Albain, Kathy S.; Kim, Edward S.; Redman, Mary; Crowley, John J.; Gandara, David R.

2010-01-01

212

THE COOPERATIVE INTERNATIONAL NEUROMUSCULAR RESEARCH GROUP DUCHENNE NATURAL HISTORY STUDY: GLUCOCORTICOID TREATMENT PRESERVES CLINICALLY MEANINGFUL FUNCTIONAL MILESTONES AND REDUCES RATE OF DISEASE PROGRESSION AS MEASURED BY MANUAL MUSCLE TESTING AND OTHER COMMONLY USED CLINICAL TRIAL OUTCOME MEASURES  

PubMed Central

Introduction Glucocorticoid (GC) therapy in Duchenne muscular dystrophy (DMD) has altered disease progression, necessitating contemporary natural history studies. Methods The Cooperative Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 DMD males, ages 2–28 years. A comprehensive battery of measures was obtained. Results A novel composite functional “milestone” scale scale showed clinically meaningful mobility and upper limb abilities were significantly preserved in GC-treated adolescents/young adults. Manual muscle test (MMT)-based calculations of global strength showed that those patients <10 years of age treated with steroids declined by 0.4±0.39 MMT unit/year, compared with ?0.4±0.39 MMT unit/year in historical steroid-naive subjects. Pulmonary function tests (PFTs) were relatively preserved in steroid-treated adolescents. The linearity and magnitude of decline in measures were affected by maturational changes and functional status. Conclusions In DMD, long-term use of GCs showed reduced strength loss and preserved functional capabilities and PFTs compared with previous natural history studies performed prior to the widespread use of GC therapy.

HENRICSON, ERIK K.; ABRESCH, R. TED; CNAAN, AVITAL; HU, FENGMING; DUONG, TINA; ARRIETA, ADRIENNE; HAN, JAY; ESCOLAR, DIANA M.; FLORENCE, JULAINE M.; CLEMENS, PAULA R.; HOFFMAN, ERIC P.; McDONALD, CRAIG M.

2014-01-01

213

Maintenance Cognitive Stimulation Therapy (CST) in practice: study protocol for a randomized controlled trial  

PubMed Central

Background Cognitive Stimulation Therapy (CST) is a psychosocial evidence-based group intervention for people with dementia recommended by the UK NICE guidelines. In clinical trials, CST has been shown to improve cognition and quality of life, but little is known about the best way of ensuring implementation of CST in practice settings. A recent pilot study found that a third of people who attend CST training go on to run CST in practice, but staff identified a lack of support as a key reason for the lack of implementation. Methods/design There are three projects in this study: The first is a pragmatic multi-centre, randomised controlled trial (RCT) of staff training, comparing CST training and outreach support with CST training only; the second, the monitoring and outreach trial, is a phase IV trial that evaluates implementation of CST in practice by staff members who have previously had the CST manual or attended training. Centres will be randomised to receive outreach support. The primary outcome measure for both of these trials is the number of CST sessions run for people with dementia. Secondary outcomes include the number of attenders at sessions, job satisfaction, dementia knowledge and attitudes, competency, barriers to change, approach to learning and a controllability of beliefs and the level of adherence. Focus groups will assess staff members’ perceptions of running CST groups and receiving outreach support. The third study involves monitoring centres running groups in their usual practice and looking at basic outcomes of cognition and quality of life for the person with dementia. Discussion These studies assess the effects of outreach support on putting CST into practice and running groups effectively in a variety of care settings with people with dementia; evaluate the effectiveness of CST in standard clinical practice; and identify key factors promoting or impeding the successful running of groups. Trial registration Clinical trial ISRCTN28793457.

2012-01-01

214

Acupuncture for low back pain due to spondylolisthesis: study protocol for a randomized controlled pilot trial  

PubMed Central

Background Spondylolisthesis is the major cause of refractory low back pain. There are many studies of the surgical treatment of spondylolisthesis, but few of conservative treatments. There is also no optimal conservative treatment protocol, however, low back pain caused by low-grade spondylolisthesis is controlled with non-surgical pain management. Acupuncture has become a useful method for treating low back pain, but there has not been any study of its efficacy in relation to spondylolisthesis. This study was designed to establish the feasibility of a randomized controlled trial and the safety of acupuncture for low back pain due to low-grade spondylolisthesis. Methods/Design The study is a randomized controlled pilot clinical trial of five weeks duration. Fourteen patients will be recruited and randomly allocated to two groups: an acupuncture plus interlaminar epidural steroid injection group (experimental group), and an interlaminar epidural steroid injection group (control group). All patients will be administered an interlaminar epidural steroid injection once a week for three weeks (three injections in total), but only the experimental group will receive additional treatment with three acupuncture sessions a week for three weeks (nine acupuncture sessions in total). The primary outcome will be measured by the visual analogue scale (VAS). Our primary end point is three-week VAS. The secondary outcome will be measured using the PainVision system, the short-form McGill Pain Questionnaire, and the Oswestry Disability Index. Assessments will be made at baseline and at one, three and five weeks thereafter (that is, the five-week assessment will be made two weeks after treatment cessation). Discussion This randomized controlled pilot trial will inform the design of a further full-scale trial. The outcomes will provide some resources for incorporating acupuncture into existing pain management methods such as interlaminar epidural steroid injection in low-grade spondylolisthesis. Trial registration This trial is registered with the US National Institutes of Health Clinical Trials registry: NCT01909284.

2014-01-01

215

Multiplex genomic profiling of non-small cell lung cancers from the LETS phase III trial of first-line S-1/carboplatin versus paclitaxel/carboplatin: results of a West Japan Oncology Group study  

PubMed Central

Archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected from advanced NSCLC patients enrolled in LETS phase III trial comparing first-line S-1/carboplatin with paclitaxel/carboplatin and subjected to multiplex genotyping for 214 somatic hotspot mutations in 26 genes (LungCarta Panel) and 20 major variants of ALK, RET, and ROS1 fusion genes (LungFusion Panel) with the Sequenom MassARRAY platform. MET amplification was evaluated by fluorescence in situ hybridization. A somatic mutation in at least one gene was identified in 48% of non–squamous cell carcinoma and 45% of squamous cell carcinoma specimens, with EGFR (17%), TP53 (11%), STK11 (9.8%), MET (7.6%), and KRAS (6.2%). Mutations in EGFR or KRAS were associated with a longer or shorter median overall survival, respectively. The LungFusion Panel identified ALK fusions in six cases (2.5%), ROS1 fusions in five cases (2.1%), and a RET fusion in one case (0.4%), with these three types of rearrangement being mutually exclusive. Nine (3.9%) of 229 patients were found to be positive for de novo MET amplification. This first multiplex genotyping of NSCLC associated with a phase III trial shows that MassARRAY-based genetic testing for somatic mutations and fusion genes performs well with nucleic acid derived from FFPE specimens of NSCLC tissue.

Okamoto, Isamu; Sakai, Kazuko; Morita, Satoshi; Yoshioka, Hiroshige; Kaneda, Hiroyasu; Takeda, Koji; Hirashima, Tomonori; Kogure, Yoshihito; Kimura, Tatsuo; Takahashi, Toshiaki; Atagi, Shinji; Seto, Takashi; Sawa, Toshiyuki; Yamamoto, Masashi; Satouchi, Miyako; Okuno, Motoyasu; Nagase, Seisuke; Takayama, Koichi; Tomii, Keisuke; Maeda, Tadashi; Oizumi, Satoshi; Fujii, Shinji; Akashi, Yusaku; Nishino, Kazumi; Ebi, Noriyuki; Nakagawa, Kazuhiko; Nakanishi, Yoichi; Nishio, Kazuto

2014-01-01

216

Multiplex genomic profiling of non-small cell lung cancers from the LETS phase III trial of first-line S-1/carboplatin versus paclitaxel/carboplatin: results of a West Japan Oncology Group study.  

PubMed

Archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected from advanced NSCLC patients enrolled in LETS phase III trial comparing first-line S-1/carboplatin with paclitaxel/carboplatin and subjected to multiplex genotyping for 214 somatic hotspot mutations in 26 genes (LungCarta Panel) and 20 major variants of ALK, RET, and ROS1 fusion genes (LungFusion Panel) with the Sequenom MassARRAY platform. MET amplification was evaluated by fluorescence in situ hybridization. A somatic mutation in at least one gene was identified in 48% of non-squamous cell carcinoma and 45% of squamous cell carcinoma specimens, with EGFR (17%), TP53 (11%), STK11 (9.8%), MET (7.6%), and KRAS (6.2%). Mutations in EGFR or KRAS were associated with a longer or shorter median overall survival, respectively. The LungFusion Panel identified ALK fusions in six cases (2.5%), ROS1 fusions in five cases (2.1%), and a RET fusion in one case (0.4%), with these three types of rearrangement being mutually exclusive. Nine (3.9%) of 229 patients were found to be positive for de novo MET amplification. This first multiplex genotyping of NSCLC associated with a phase III trial shows that MassARRAY-based genetic testing for somatic mutations and fusion genes performs well with nucleic acid derived from FFPE specimens of NSCLC tissue. PMID:24810493

Okamoto, Isamu; Sakai, Kazuko; Morita, Satoshi; Yoshioka, Hiroshige; Kaneda, Hiroyasu; Takeda, Koji; Hirashima, Tomonori; Kogure, Yoshihito; Kimura, Tatsuo; Takahashi, Toshiaki; Atagi, Shinji; Seto, Takashi; Sawa, Toshiyuki; Yamamoto, Masashi; Satouchi, Miyako; Okuno, Motoyasu; Nagase, Seisuke; Takayama, Koichi; Tomii, Keisuke; Maeda, Tadashi; Oizumi, Satoshi; Fujii, Shinji; Akashi, Yusaku; Nishino, Kazumi; Ebi, Noriyuki; Nakagawa, Kazuhiko; Nakanishi, Yoichi; Nishio, Kazuto

2014-04-30

217

From Planning to Implementation: An Examination of Changes in the Research Design, Sample Size, and Precision of Group Randomized Trials Launched by the Institute of Education Sciences  

ERIC Educational Resources Information Center

This article examines changes in the research design, sample size, and precision between the planning phase and implementation phase of group randomized trials (GRTs) funded by the Institute of Education Sciences. Thirty-eight GRTs funded between 2002 and 2006 were examined. Three studies revealed changes in the experimental design. Ten studies

Spybrook, Jessaca; Puente, Anne Cullen; Lininger, Monica

2013-01-01

218

Second-Order Interactions with the Treatment Groups in Controlled Clinical Trials  

PubMed Central

Abstract Summary The occurrence of significant second-order interactions for group characteristics was examined using real data in a randomized controlled trial (RCT). The interactions exist in all RCTs; they could be easily overlooked when using the simple randomization or stratification methods, but could become more obvious when minimization methods are used. Using real data from an RCT, the minimization method enabled balancing the distributions of the four selected stratified factors. Analyses for 3-way second-order interactions including 6 additional potential confounding variables (for a total of 10 variables) presented 8 significant second-order interactions with the treatment groups. Interaction effects need to be evaluated when treatment effects are examined to maximize the power of the treatment effects in any RCTs. A stepwise regression method with piecewise linear functions would be useful to select the significant variables with interaction effects affecting the treatment outcomes in RCTs. Additional ways to handle interaction effects in RCTs are presented in this paper.

Shiao, Shyang-Yun Pamela K.; Ahn, Chul W.; Akazawa, Kouhei

2007-01-01

219

Inadequate Dissemination of Phase I Trials: A Retrospective Cohort Study  

PubMed Central

Background Drug development is ideally a logical sequence in which information from small early studies (Phase I) is subsequently used to inform and plan larger, more definitive studies (Phases II–IV). Phase I trials are unique because they generally provide the first evaluation of new drugs in humans. The conduct and dissemination of Phase I trials have not previously been empirically evaluated. Our objective was to describe the initiation, completion, and publication of Phase I trials in comparison with Phase II–IV trials. Methods and Findings We reviewed a cohort of all protocols approved by a sample of ethics committees in France from January 1, 1994 to December 31, 1994. The comparison of 140 Phase I trials with 304 Phase II–IV trials, showed that Phase I studies were more likely to be initiated (133/140 [95%] versus 269/304 [88%]), more likely to be completed (127/133 [95%] versus 218/269 [81%]), and more likely to produce confirmatory results (71/83 [86%] versus 125/175 [71%]) than Phase II–IV trials. Publication was less frequent for Phase I studies (21/127 [17%] versus 93/218 [43%]), even if only accounting for studies providing confirmatory results (18/71 [25%] versus 79/125 [63%]). Conclusions The initiation, completion, and publications of Phase I trials are different from those of other studies. Moreover, the results of these trials should be published in order to ensure the integrity of the overall body of scientific knowledge, and ultimately the safety of future trial participants and patients.

Decullier, Evelyne; Chan, An-Wen; Chapuis, Francois

2009-01-01

220

Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Long-Acting Methylphenidate for Cancer-Related Fatigue: North Central Cancer Treatment Group NCCTG-N05C7 Trial  

PubMed Central

Purpose Fatigue is one of the most common symptoms experienced by patients with cancer. This trial was developed to evaluate the efficacy of long-acting methylphenidate for improving cancer-related fatigue and to assess its toxicities. Patients and Methods Adults with cancer were randomly assigned in a double-blinded manner to receive methylphenidate (target dose, 54 mg/d) or placebo for 4 weeks. The Brief Fatigue Inventory was the primary outcome measure, while secondary outcome measures included a Symptom Experience Diary (SED), the Short Form-36 (SF-36) Vitality Subscale, a linear analog self-assessment, the Pittsburgh Sleep Quality Index, and the Subject Global Impression of Change. Results In total, 148 patients were enrolled. Using an area under the serum concentration-time curve analysis, there was no evidence that methylphenidate, as compared with placebo, improved the primary end point of cancer-related fatigue in this patient population (P = .35). Comparisons of secondary end points, including clinically significant changes in quality-of-life variables and cancer-related fatigue change from baseline, were similarly negative. However, a subset analysis suggested that patients with more severe fatigue and/or with more advanced disease did have some fatigue improvement with methylphenidate (eg, in patients with stage III or IV disease, the mean improvement in usual fatigue was 19.7 with methylphenidate v 2.1 with placebo; P = .02). There was a significant difference in self-reported toxicities (SED), with increased levels of nervousness and appetite loss in the methylphenidate arm. Conclusion This clinical trial was unable to support the primary prestudy hypothesis that the chosen long-acting methylphenidate product would decrease cancer-related fatigue.

Moraska, Amanda R.; Sood, Amit; Dakhil, Shaker R.; Sloan, Jeff A.; Barton, Debra; Atherton, Pamela J.; Suh, Jason J.; Griffin, Patricia C.; Johnson, David B.; Ali, Aneela; Silberstein, Peter T.; Duane, Steven F.; Loprinzi, Charles L.

2010-01-01

221

IMMUNOCHEMICAL STUDIES ON BLOOD GROUPS  

PubMed Central

The immunochemical properties of purified A1 and A2 glycoproteins have been compared to ascertain whether their antigenic determinants differ. Quantitative precipitin and complement-fixation studies using several anti-A sera as well as purified ?G anti-A antibodies clearly showed a specificity difference. This was also supported by absorption studies: A2 substance specifically removed antibodies reacting with A2 substance leaving anti-A1 activity. A1 substance was more effective than A2 substance in dissolving an A1 anti-A1-specific precipitate. Purified ?M anti-A hemolyzed A1 cells more readily than A2 cells. Inhibition studies using mono- and difucosyl type 2 A-active oligosaccharides showed that type 2 difucosyl receptors are present in A2 substance. The structural basis for the specificity difference between A1 and A2 would appear to be that A2 substances lack type 1 A determinants; this would account for the observed higher H and Leb activity in A2 substances.

Moreno, Carlos; Lundblad, Arne; Kabat, Elvin A.

1971-01-01

222

Effects of Neuraxial Blockade May Be Difficult To Study Using Large Randomized Controlled Trials: The PeriOperative Epidural Trial (POET) Pilot Study  

PubMed Central

Background Early randomized controlled trials have suggested that neuraxial blockade may reduce cardiorespiratory complications after non-cardiothoracic surgery, but recent larger trials have been inconclusive. We conducted a pilot study to assess the feasibility of conducting a large multicentre randomized controlled trial in Canada. Methodology/Principal Findings After Research Ethics Board approvals from the participating institutions, subjects were recruited if they were ?45 years old, had an expected hospital stay ?48 hours, were undergoing a noncardiothoracic procedure amenable to epidural analgesia, met one of six risk criteria, and did not have contraindications to neuraxial blockade. After informed consent, subjects were randomly allocated to combined epidural analgesia (epidural group) and neuraxial anesthesia, with or without general anesthesia, or intravenous opioid analgesia (IV group) and general anesthesia. The primary outcomes were the rate of recruitment and the percents of eligible patients recruited, crossed over, and followed completely. Feasibility targets were defined a priori. A blinded, independent committee adjudicated the secondary clinical outcomes. Subjects were followed daily while in hospital and then at 30 days after surgery. Analysis was intention-to-treat. Over a 15-month period, the recruitment rate was 0.5±0.3 (mean±SEM) subjects per week per centre; 112/494 (22.7%) eligible subjects were recruited at four tertiary-care teaching hospitals in Canada. Thirteen (26.5%) of 49 subjects in the epidural group crossed over to the IV group; seven (14.3%) were due to failed or inadequate analgesia or complications from epidural analgesia. Five (9.8%) of 51 subjects in the IV group crossed over to the epidural group but none were due to inadequate analgesia or complications. Ninety-eight (97.0%) of 101 subjects were successfully followed up until 30 days after their surgery. Conclusion/Significance Of the criteria we defined for the feasibility of a full-scale trial, only the follow-up target was met. The other feasibility outcomes did not meet our preset criteria for success. The results suggest that a large multicentre trial may not be a feasible design to study the perioperative effects of neuraxial blockade. Trial Registration ClinicalTrials.gov NCT 0221260 Controlled-Trials.com ISRCTN 35629817

Choi, Peter T.; Beattie, W. Scott; Bryson, Gregory L.; Paul, James E.; Yang, Homer

2009-01-01

223

Design paper: The CapOpus trial: A randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis  

PubMed Central

Background A number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders. There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis. Objectives The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual. Design The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are primarily recruited through early-psychosis detection teams, community mental health centers, and assertive community treatment teams. Patients are randomized to one of two treatment arms, both lasting six months: 1) specialized addiction treatment plus treatment as usual or 2) treatment as usual. The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy, and incorporates both the family and the case manager of the patient. The primary outcome measure will be changes in amount of cannabis consumption over time. Other outcome measures will be psychosis symptoms, cognitive functioning, quality of life, social functioning, and cost-benefit analyses. Trial registration ClinicalTrials.gov NCT00484302.

Hjorth?j, Carsten; Fohlmann, Allan; Larsen, Anne-Mette; Madsen, Mette TR; Vesterager, Lone; Gluud, Christian; Arendt, Mikkel C; Nordentoft, Merete

2008-01-01

224

Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy  

PubMed Central

The popularity of oxytocin (OT) has grown exponentially during the past decade, and so has the number of OT trials in healthy and clinical groups. We take stock of the evidence from these studies to explore potentials and limitations of pharmacotherapeutic applications. In healthy participants, intranasally administered OT leads to better emotion recognition and more trust in conspecifics, but the effects appear to be moderated by context (perceived threat of the ‘out-group'), personality and childhood experiences. In individuals with untoward childhood experiences, positive behavioral or neurobiological effects seem lowered or absent. In 19 clinical trials, covering autism, social anxiety, postnatal depression, obsessive-compulsive problems, schizophrenia, borderline personality disorder and post-traumatic stress, the effects of OT administration were tested, with doses ranging from 15?IU to more than 7000?IU. The combined effect size was d=0.32 (N=304; 95% confidence interval (CI): 0.18–0.47; P<0.01). However, of all disorders, only studies on autism spectrum disorder showed a significant combined effect size (d=0.57; N=68; 95% CI: 0.15–0.99; P<0.01). We hypothesize that for some of the other disorders, etiological factors rooted in negative childhood experiences may also have a role in the diminished effectiveness of treatment with OT.

Bakermans-Kranenburg, M J; van IJzendoorn, M H

2013-01-01

225

HealthWorks: results of a multi-component group-randomized worksite environmental intervention trial for weight gain prevention  

PubMed Central

Background U.S. adults are at unprecedented risk of becoming overweight or obese, and most scientists believe the primary cause is an obesogenic environment. Worksites provide an opportunity to shape the environments of adults to reduce obesity risk. The goal of this group-randomized trial was to implement a four-component environmental intervention at the worksite level to positively influence weight gain among employees over a two-year period. Environmental components focused on food availability and price, physical activity promotion, scale access, and media enhancements. Methods Six worksites in a U.S. metropolitan area were recruited and randomized in pairs at the worksite level to either a two-year intervention or a no-contact control. Evaluations at baseline and two years included: 1) measured height and weight; 2) online surveys of individual dietary intake and physical activity behaviors; and 3) detailed worksite environment assessment. Results Mean participant age was 42.9 years (range 18-75), 62.6% were women, 68.5% were married or cohabiting, 88.6% were white, 2.1% Hispanic. Mean baseline BMI was 28.5 kg/m2 (range 16.9-61.2 kg/m2). A majority of intervention components were successfully implemented. However, there were no differences between sites in the key outcome of weight change over the two-year study period (p = .36). Conclusions Body mass was not significantly affected by environmental changes implemented for the trial. Results raise questions about whether environmental change at worksites is sufficient for population weight gain prevention. Trial Registration ClinicalTrials.gov: NCT00708461

2012-01-01

226

Randomized Trial of Three Child/Parent Training Groups for ADHD Children.  

ERIC Educational Resources Information Center

The present study examined the effectiveness of a multimodal intervention for young children with ADHD. Fifty families were randomly assigned to three treatment conditions: (1) child group training only (N=18); (2) child and parent group training only (N=14); and (3) child and parent group training and parent/teacher consultation (N=18). Child,…

Reddy, Linda; Braunstein, Dania; Springer, Craig; Bartik, Celina; Hauch, Yvonne; Hall, Tara; Benisz, Becky; Gioia, Lauren

227

Report of the Public Cryptography Study Group.  

National Technical Information Service (NTIS)

The study group has recommended that a voluntary system of prior review of cryptology manuscripts be instituted on an experimental basis. The group accepted as a working premise the National Security Agency's (NSA) concern that some information contained ...

1981-01-01

228

An Examination of the Precision and Technical Accuracy of the First Wave of Group-Randomized Trials Funded by the Institute of Education Sciences  

ERIC Educational Resources Information Center

This article examines the power analyses for the first wave of group-randomized trials funded by the Institute of Education Sciences. Specifically, it assesses the precision and technical accuracy of the studies. The authors identified the appropriate experimental design and estimated the minimum detectable standardized effect size (MDES) for each…

Spybrook, Jessaca; Raudenbush, Stephen W.

2009-01-01

229

Longitudinal Effects of Coping on Outcome in a Randomized Controlled Trial of a Group Intervention for HIV-Positive Adults with AIDS-Related Bereavement  

ERIC Educational Resources Information Center

This study examined the longitudinal effects of coping on outcome one year following completion of a randomized, controlled trial of a group coping intervention for AIDS-related bereavement. Bereaved HIV-positive participants (N = 267) were administered measures of grief, psychiatric distress, quality of life, and coping at baseline,…

Hansen, Nathan B.; Tarakeshwar, Nalini; Ghebremichael, Musie; Zhang, Heping; Kochman, Arlene; Sikkema, Kathleen J.

2006-01-01

230

Effect of cow's milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes. Finnish Trial to Reduce IDDM in the Genetically at Risk Study Group.  

PubMed

Type 1 diabetes is considered to be a T-cell-mediated autoimmune disease in which insulin-producing beta-cells are destroyed. Immunity to insulin has been suggested to be one of the primary autoimmune mechanisms leading to islet cell destruction. We have previously shown that the first immunization to insulin occurs by exposure to bovine insulin (BI) in cow's milk (CM) formula. In this study, we analyzed the development of insulin-specific T-cell responses by proliferation test, emergence of insulin-binding antibodies by enzyme immunoassay, and insulin autoantibodies by radioimmunoassay in relation to CM exposure and family history of type 1 diabetes in infants with a first-degree relative with type 1 diabetes and increased genetic risk for the disease. The infants were randomized to receive either an adapted CM-based formula or a hydrolyzed casein (HC)-based formula after breast-feeding for the first 6-8 months of life. At the age of 3 months, both cellular and humoral responses to BI were higher in infants exposed to CM formula than in infants fully breast-fed (P = 0.015 and P = 0.007). IgG antibodies to BI were higher in infants who received CM formula than in infants who received HC formula at 3 months of age (P = 0.01), but no difference in T-cell responses was seen between the groups. T-cell responses to BI at 9 months of age (P = 0.05) and to human insulin at 12 (P = 0.014) and 24 months of age (P = 0.009) as well as IgG antibodies to BI at 24 months of age (P = 0.05) were lower in children with a diabetic mother than in children with a diabetic father or a sibling, suggesting possible tolerization to insulin by maternal insulin therapy. The priming of insulin-specific humoral and T-cell immunity occurs in early infancy by dietary insulin, and this phenomenon is influenced by maternal type 1 diabetes. PMID:11016449

Paronen, J; Knip, M; Savilahti, E; Virtanen, S M; Ilonen, J; Akerblom, H K; Vaarala, O

2000-10-01

231

Effectiveness and cost-effectiveness of meaning-centered group psychotherapy in cancer survivors: protocol of a randomized controlled trial  

PubMed Central

Background Meaning-focused coping may be at the core of adequate adjustment to life after cancer. Cancer survivors who experience their life as meaningful are better adjusted, have better quality of life and psychological functioning. Meaning-Centered Group Psychotherapy for Cancer Survivors (MCGP-CS) was designed to help patients to sustain or enhance a sense of meaning and purpose in their lives. The aim of the proposed study is to evaluate the effectiveness and cost-effectiveness of MCGP-CS. Methods/Design Survivors diagnosed with cancer in the last 5 years and treated with curative intent, are recruited via several hospitals in the Netherlands. After screening, 168 survivors are randomly assigned to one of the three study arms: 1. Meaning-Centered Group Psychotherapy (MCGP-CS) 2. Supportive group psychotherapy (SGP) 3. Care as usual (CAU). Baseline assessment takes place before randomisation, with follow up assessments post-intervention and at 3, 6 and 12 months follow-up. Primary outcome is meaning making (PMP, PTGI, SPWB). Secondary outcome measures address quality of life (EORTC-30), anxiety and depression (HADS), hopelessness (BHS), optimism (LOT-R), adjustment to cancer (MAC), and costs (TIC-P, EQ-5D, PRODISQ). Discussion Meaning-focused coping is key to adjustment to life after cancer, however, there is a lack of evidence based psychological interventions in this area. Many cancer survivors experience feelings of loneliness and alienation, and have a need for peer support, therefore a group method in particular, can be beneficial for sustaining or enhancing a sense of meaning. If this MCGP-CS is effective for cancer survivors, it can be implemented in the practice of psycho-oncology care. Trial registration Netherlands Trial Register, NTR3571

2014-01-01

232

Clinical outcome measures for trials in Duchenne muscular dystrophy: report from International Working Group meetings  

PubMed Central

In June 2010, 25 representatives from Europe and the US met in Washington, DC, USA, to discuss clinical outcome measures in Duchenne muscular dystrophy (DMD) in the context of clinical trial design and analysis. The workshop was organized in response to a September 2009 European Medicines Agency meeting where a clear directive was given that an international consensus needs to be developed that provides a foundation for age-appropriate clinical outcome measures for use in clinical trials of emerging therapeutics for DMD. Data were presented from eight multicenter longitudinal datasets, representing nearly 1900 patients over a 20-year time period. This experience confirmed the feasibility of repeated evaluations performed at multiple sites and addressed several core issues in drug development for DMD, such as the ‘new’ natural history in the steroidera, reliability and sensitivity of specific outcome measures, as well as disease staging and patient selection. These data form a valuable asset for academic investigators, pharmaceutical sponsors and regulatory agencies involved in DMD therapeutics. The group remains committed working together on a number of collaborative goals to support the therapeutics development effort in this orphan disease and to make these data available to stakeholders working in the field.

Bushby, Kate; Connor, Edward

2012-01-01

233

Prognostic impact of day 15 blast clearance in risk-adapted remission induction chemotherapy for younger patients with acute myeloid leukemia: long-term results of the multicenter prospective LAM-2001 trial by the GOELAMS study group  

PubMed Central

Early response to chemotherapy has a major prognostic impact in acute myeloid leukemia patients treated with a double induction strategy. Less is known about patients treated with standard-dose cytarabine and anthracycline. We designed a risk-adapted remission induction regimen in which a second course of intermediate-dose cytarabine was delivered after standard “7+3” only if patients had 5% or more bone marrow blasts 15 days after chemotherapy initiation (d15-blasts). Of 823 included patients, 795 (96.6%) were evaluable. Five hundred and forty-five patients (68.6%) had less than 5% d15-blasts. Predictive factors for high d15-blasts were white blood cell count (P<0.0001) and cytogenetic risk (P<0.0001). Patients with fewer than 5% d15-blasts had a higher complete response rate (91.7% vs. 69.2%; P<0.0001) and a lower induction death rate (1.8% vs. 6.8%; P=0.001). Five-year event-free (48.4% vs. 25%; P<0.0001), relapse-free (52.7% vs. 36.9%; P=0.0016) and overall survival (55.3% vs. 36.5%; P<0.0001) were significantly higher in patients with d15-blasts lower than 5%. Multivariate analyses identified d15-blasts and cytogenetic risk as independent prognostic factors for the three end points. Failure to achieve early blast clearance remains a poor prognostic factor even after early salvage. By contrast, early responding patients have a favorable outcome without any additional induction course. (ClinicalTrials.gov identifier NCT01015196)

Bertoli, Sarah; Bories, Pierre; Bene, Marie C.; Daliphard, Sylvie; Lioure, Bruno; Pigneux, Arnaud; Vey, Norbert; Delaunay, Jacques; Leymarie, Vincent; Luquet, Isabelle; Blanchet, Odile; Cornillet-Lefebvre, Pascale; Hunault, Mathilde; Bouscary, Didier; Fegueux, Nathalie; Guardiola, Philippe; Dreyfus, Francois; Harousseau, Jean Luc; Cahn, Jean Yves; Ifrah, Norbert; Recher, Christian

2014-01-01

234

Prognostic impact of day 15 blast clearance in risk-adapted remission induction chemotherapy for younger patients with acute myeloid leukemia: long-term results of the multicenter prospective LAM-2001 trial by the GOELAMS study group.  

PubMed

Early response to chemotherapy has a major prognostic impact in acute myeloid leukemia patients treated with a double induction strategy. Less is known about patients treated with standard-dose cytarabine and anthracycline. We designed a risk-adapted remission induction regimen in which a second course of intermediate-dose cytarabine was delivered after standard "7+3" only if patients had 5% or more bone marrow blasts 15 days after chemotherapy initiation (d15-blasts). Of 823 included patients, 795 (96.6%) were evaluable. Five hundred and forty-five patients (68.6%) had less than 5% d15-blasts. Predictive factors for high d15-blasts were white blood cell count (P<0.0001) and cytogenetic risk (P<0.0001). Patients with fewer than 5% d15-blasts had a higher complete response rate (91.7% vs. 69.2%; P<0.0001) and a lower induction death rate (1.8% vs. 6.8%; P=0.001). Five-year event-free (48.4% vs. 25%; P<0.0001), relapse-free (52.7% vs. 36.9%; P=0.0016) and overall survival (55.3% vs. 36.5%; P<0.0001) were significantly higher in patients with d15-blasts lower than 5%. Multivariate analyses identified d15-blasts and cytogenetic risk as independent prognostic factors for the three end points. Failure to achieve early blast clearance remains a poor prognostic factor even after early salvage. By contrast, early responding patients have a favorable outcome without any additional induction course. (ClinicalTrials.gov identifier NCT01015196). PMID:23975179

Bertoli, Sarah; Bories, Pierre; Béné, Marie C; Daliphard, Sylvie; Lioure, Bruno; Pigneux, Arnaud; Vey, Norbert; Delaunay, Jacques; Leymarie, Vincent; Luquet, Isabelle; Blanchet, Odile; Cornillet-Lefebvre, Pascale; Hunault, Mathilde; Bouscary, Didier; Fegueux, Nathalie; Guardiola, Philippe; Dreyfus, François; Harousseau, Jean Luc; Cahn, Jean Yves; Ifrah, Norbert; Récher, Christian

2014-01-01

235

How usual is usual care in pragmatic intervention studies in primary care? An overview of recent trials  

PubMed Central

Background Because pragmatic trials are performed to determine if an intervention can improve current practice, they often have a control group receiving ‘usual care’. The behaviour of caregivers and patients in this control group should be influenced by the actions of researchers as little as possible. Guidelines for describing the composition and management of a usual care control group are lacking. Aim To explore the variety of approaches to the usual care concept in pragmatic trials, and evaluate the influence of the study design on the behaviour of caregivers and patients in a usual care control group. Design of study Review of 73 pragmatic trials in primary care with a usual care control group published between January 2005 and December 2009 in the British Medical Journal, the British Journal of General Practice, and Family Practice. Outcome measures were: description of the factors influencing caregiver and patients in a usual care control group related to an individual randomised design versus cluster randomisation. Results In total, 38 individually randomised trials and 35 cluster randomised trials were included. In most trials, caregivers had the freedom to treat control patients according to their own insight; in two studies, treatment options were restricted. Although possible influences on the behaviour of control caregivers and control patients were more often identified in individually randomised trials, these influences were also present in cluster randomised trials. The description of instructions and information provided to the control group was often insufficient, which made evaluation of the trials difficult. Conclusion Researchers in primary care medicine should carefully consider the design of a usual care control group, especially with regard to minimising the risk of study-induced behavioural change. It is recommended that an adequate description of the information is provided to control caregivers and control patients. A proposal is made for an extension to the CONSORT statement that requires authors to specify details of the usual care control group.

Smelt, Antonia FH; van der Weele, Gerda M; Blom, Jeanet W; Gussekloo, Jacobijn; Assendelft, Willem JJ

2010-01-01

236

Two-group randomised, parallel trial of cognitive and exposure therapies for problem gambling: a research protocol  

PubMed Central

Background Problem gambling is a serious public health concern at an international level where population prevalence rates average 2% or more and occurs more frequently in younger populations. The most empirically established treatments until now are combinations of cognitive and behavioural techniques labelled cognitive behaviour therapy (CBT). However, there is a paucity of high quality evidence for the comparative efficacy of core CBT interventions in treating problem gamblers. This study aims to isolate and compare cognitive and behavioural (exposure-based) techniques to determine their relative efficacy. Methods A sample of 130 treatment-seeking problem gamblers will be allocated to either cognitive or exposure therapy in a two-group randomised, parallel design. Repeated measures will be conducted at baseline, mid and end of treatment (12 sessions intervention period), and at 3, 6 and 12?months (maintenance effects). The primary outcome measure is improvement in problem gambling severity symptoms using the Victorian Gambling Screen (VGS) harm to self-subscale. VGS measures gambling severity on an extensive continuum, thereby enhancing sensitivity to change within and between individuals over time. Discussion This article describes the research methods, treatments and outcome measures used to evaluate gambling behaviours, problems caused by gambling and mechanisms of change. This study will be the first randomised, parallel trial to compare cognitive and exposure therapies in this population. Ethics and dissemination The study was approved by the Southern Adelaide Health Service/Flinders University Human Research Ethics Committee. Study findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN 12610000828022.

Smith, David P; Battersby, Malcolm W; Harvey, Peter W; Pols, Rene G; Ladouceur, Robert

2013-01-01

237

Efficacy of electroacupuncture for symptoms of menopausal transition: study protocol for a randomized controlled trial  

PubMed Central

Background Previous studies have shown that acupuncture can alleviate postmenopausal symptoms, such as hot flashes, but few studies have assessed symptoms during the menopausal transition (MT) period. Thus, the effect of acupuncture upon MT symptoms is unclear. We designed a large-scale trial aimed at evaluating the efficacy of electroacupuncture for MT symptoms compared with sham electroacupuncture and at observing the safety of electroacupuncture. Methods/design In this multicenter randomized controlled trial, 360 women will be randomized to either an electroacupuncture group or a sham electroacupuncture group. During the 8-week-long treatment, a menopause rating scale, average 24-hour hot flash score, Menopause-Specific Quality of Life Questionnaire score, and level of female hormones will be observed. Follow-ups at the 20th and 32nd week will be made. Discussion Though there is no completely inert placebo acupuncture and blinding is difficult in acupuncture trials, the placebo effect of EA can still be partially excluded in this study. For the placebo control, we use non-points and a tailor-made sham needle. This needle is different from a retractable needle, which is usually used for sham acupuncture. The needle in this trial is more simply constructed and more acceptable to Chinese people. We expect to evaluate the efficacy of electroacupuncture for MT symptoms and clarify its effect on these symptoms. Trial registration ClinicalTrials.gov Identifier: NCT01849172 (Date of registration: 05/05/2013).

2014-01-01

238

Design and End Points of Clinical Trials for Patients With Progressive Prostate Cancer and Castrate Levels of Testosterone: Recommendations of the Prostate Cancer Clinical Trials Working Group  

PubMed Central

Purpose To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone. Methods A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data. Results The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as “new lesions” or “no new lesions,” changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group. Conclusion PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit.

Scher, Howard I.; Halabi, Susan; Tannock, Ian; Morris, Michael; Sternberg, Cora N.; Carducci, Michael A.; Eisenberger, Mario A.; Higano, Celestia; Bubley, Glenn J.; Dreicer, Robert; Petrylak, Daniel; Kantoff, Philip; Basch, Ethan; Kelly, William Kevin; Figg, William D.; Small, Eric J.; Beer, Tomasz M.; Wilding, George; Martin, Alison; Hussain, Maha

2014-01-01

239

Study protocol for the nutritional route in oesophageal resection trial: a single-arm feasibility trial (NUTRIENT trial)  

PubMed Central

Introduction The best route of feeding for patients undergoing an oesophagectomy is unclear. Concerns exist that early oral intake would increase the incidence and severity of pneumonia and anastomotic leakage. However, in studies including patients after many other types of gastrointestinal surgery and in animal experiments, early oral intake has been shown to be beneficial and enhance recovery. Therefore, we aim to determine the feasibility of early oral intake after oesophagectomy. Methods and analysis This study is a feasibility trial in which 50 consecutive patients will start oral intake directly following oesophagectomy. Primary outcomes will be the frequency and severity of anastomotic leakage and (aspiration) pneumonia. Clinical parameters will be registered prospectively and nutritional requirements and intake will be assessed by a dietician. Surgical complications will be registered. Ethics and dissemination Approval for this study has been obtained from the Medical Ethical Committee of the Catharina Hospital Eindhoven and the study has been registered at the Dutch Trial Register, NTR4136. Results will be published and presented at international congresses. Discussion We hypothesise that the oral route of feeding is safe and feasible following oesophagectomy, as has been shown previously for other types of gastrointestinal surgery. It is expected that early oral nutrition will result in enhanced recovery. Furthermore, complications related to artificial feeding, such as jejunostomy tube feeding, are believed to be reduced. However, (aspiration) pneumonia and anastomotic leakage are potential risks that are carefully monitored. Trial registration number NTR4136.

Weijs, Teus J; Nieuwenhuijzen, Grard A P; Ruurda, Jelle P; Kouwenhoven, Ewout A; Rosman, Camiel; Sosef, Meindert; v Hillegersberg, Richard; Luyer, Misha D P

2014-01-01

240

Sample size determination in group-sequential clinical trials with two co-primary endpoints.  

PubMed

We discuss sample size determination in group-sequential designs with two endpoints as co-primary. We derive the power and sample size within two decision-making frameworks. One is to claim the test intervention's benefit relative to control when superiority is achieved for the two endpoints at the same interim timepoint of the trial. The other is when superiority is achieved for the two endpoints at any interim timepoint, not necessarily simultaneously. We evaluate the behaviors of sample size and power with varying design elements and provide a real example to illustrate the proposed sample size methods. In addition, we discuss sample size recalculation based on observed data and evaluate the impact on the power and Type I error rate. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24676799

Asakura, Koko; Hamasaki, Toshimitsu; Sugimoto, Tomoyuki; Hayashi, Kenichi; Evans, Scott R; Sozu, Takashi

2014-07-30

241

The Competence Assessment for Standing Trial for Defendants with Mental Retardation (Cast-MR)A Validation Study  

Microsoft Academic Search

The purpose of this study was to develop and validate an instrument for the assessment of competence to stand trial in criminal defendants with mental retardation. Three experiments were conducted on the instrument developed, Competence Assessment for Standing Trial for Defendants with Mental Retardation (CAST-MR). Experiment 1 consisted of three pilot testings with mentally retarded group home residents, Experiment 2

CAROLINE T. EVERINGTON

1990-01-01

242

A Second Validation Study of the Competence Assessment for Standing Trial for Defendants with Mental Retardation (CAST-MR)  

Microsoft Academic Search

This study investigated the reliability and validity of the Competence Assessment for Standing Trial for Defendants with Mental Retardation (CAST-MR) with defendants with mental retardation referred for evaluation of competence to stand trial in the state of Ohio. The CAST-MR demonstrated strong internal consistency and interrater reliability. With respect to the instrument's validity, the group referred as competent had significantly

CAROLINE EVERINGTON; CHARLES DUNN

1995-01-01

243

The Tiotropium Safety and Performance in Respimat(R) Trial (TIOSPIR(R)), a large scale, randomized, controlled, parallel-group trial-design and rationale  

PubMed Central

Background Tiotropium bromide is an effective therapy for COPD patients. Comparing across programs tiotropium Respimat® Soft Mist™ inhaler was at least as efficacious as tiotropium HandiHaler®, however, concerns have been raised about tiotropium’s safety when given via Respimat®. Methods The TIOSPIR® trial (NCT01126437) compares the safety and efficacy of tiotropium Respimat® 5 ?g once daily (marketed) and 2.5 ?g once daily (investigational) with tiotropium HandiHaler® 18 ? once daily (marketed). The hypotheses to be tested are 1). that tiotropium Respimat® 5 ?g once daily and Respimat® 2.5 ?g once daily are non-inferior to HandiHaler® in terms of all-cause mortality, and 2). that tiotropium Respimat® 5 ?g once daily is superior to HandiHaler® in terms of time to first exacerbation. A spirometry substudy evaluates the bronchodilator efficacy. The trial is a randomized, double-blind, double dummy, event-driven, parallel group study. Participants can use any background treatment for COPD except inhaled anticholinergic agents. The study encompasses a wide range of COPD patients, e.g. patients with stable cardiac diseases including arrhythmia can be included. Clinical sites are international and include both primary care as well as specialists. Results To date, over 17,000 participants have been randomized from over 1200 sites in 50 countries with an anticipated treatment duration of 2–3 years. Conclusion TIOSPIR® will provide precise estimates of the relative safety and efficacy of the Respimat® and HandiHaler® formulations of tiotropium, assess potential dose-dependence of important outcomes and provide information on the clinical epidemiology of COPD in a large international patient cohort.

2013-01-01

244

Introduction of online adaptive radiotherapy for bladder cancer through a multicentre clinical trial (Trans-Tasman Radiation Oncology Group 10.01): Lessons learned.  

PubMed

Online adaptive radiotherapy for bladder cancer is a novel radiotherapy technique that was found feasible in a pilot study at a single academic institution. In September 2010 this technique was opened as a multicenter study through the Trans-Tasman Radiation Oncology Group (TROG 10.01 bladder online adaptive radiotherapy treatment). Twelve centers across Australia and New-Zealand registered interest into the trial. A multidisciplinary team of radiation oncologists, radiation therapists and medical physicists represented the trial credentialing and technical support team. To provide timely activation and proper implementation of the adaptive technique the following key areas were addressed at each site: Staff education/training; Practical image guided radiotherapy assessment; provision of help desk and feedback. The trial credentialing process involved face-to-face training and technical problem solving via full day site visits. A dedicated "help-desk" team was developed to provide support for the clinical trial. 26% of the workload occurred at the credentialing period while the remaining 74% came post-center activation. The workload was made up of the following key areas; protocol clarification (36%), technical problems (46%) while staff training was less than 10%. Clinical trial credentialing is important to minimizing trial deviations. It should not only focus on site activation quality assurance but also provide ongoing education and technical support. PMID:23776308

Pham, Daniel; Roxby, Paul; Kron, Tomas; Rolfo, Aldo; Foroudi, Farshad

2013-04-01

245

Introduction of online adaptive radiotherapy for bladder cancer through a multicentre clinical trial (Trans-Tasman Radiation Oncology Group 10.01): Lessons learned  

PubMed Central

Online adaptive radiotherapy for bladder cancer is a novel radiotherapy technique that was found feasible in a pilot study at a single academic institution. In September 2010 this technique was opened as a multicenter study through the Trans-Tasman Radiation Oncology Group (TROG 10.01 bladder online adaptive radiotherapy treatment). Twelve centers across Australia and New-Zealand registered interest into the trial. A multidisciplinary team of radiation oncologists, radiation therapists and medical physicists represented the trial credentialing and technical support team. To provide timely activation and proper implementation of the adaptive technique the following key areas were addressed at each site: Staff education/training; Practical image guided radiotherapy assessment; provision of help desk and feedback. The trial credentialing process involved face-to-face training and technical problem solving via full day site visits. A dedicated “help-desk” team was developed to provide support for the clinical trial. 26% of the workload occurred at the credentialing period while the remaining 74% came post-center activation. The workload was made up of the following key areas; protocol clarification (36%), technical problems (46%) while staff training was less than 10%. Clinical trial credentialing is important to minimizing trial deviations. It should not only focus on site activation quality assurance but also provide ongoing education and technical support.

Pham, Daniel; Roxby, Paul; Kron, Tomas; Rolfo, Aldo; Foroudi, Farshad

2013-01-01

246

The Home-Based Older People's Exercise (HOPE) trial: study protocol for a randomised controlled trial  

PubMed Central

Background Frailty is common in older age, and is associated with important adverse health outcomes including increased risk of disability and admission to hospital or long-term care. Exercise interventions for frail older people have the potential to reduce the risk of these adverse outcomes by increasing muscle strength and improving mobility. Methods/Design The Home-Based Older People's Exercise (HOPE) trial is a two arm, assessor blind pilot randomised controlled trial (RCT) to assess the effectiveness of a 12 week exercise intervention (the HOPE programme) designed to improve the mobility and functional abilities of frail older people living at home, compared with usual care. The primary outcome is the timed-up-and-go test (TUGT), measured at baseline and 14 weeks post-randomisation. Secondary outcomes include the Barthel Index of activities of daily living (ADL), EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life measure and the geriatric depression scale (GDS), measured at baseline and 14 weeks post-randomisation. We will record baseline frailty using the Edmonton Frail Scale (EFS), record falls and document muscle/joint pain. We will test the feasibility of collection of data to identify therapy resources required for delivery of the intervention. Discussion The HOPE trial will explore and evaluate a home-based exercise intervention for frail older people. Although previous RCTs have used operationalised, non-validated methods of measuring frailty, the HOPE trial is, to our knowledge, the first RCT of an exercise intervention for frail older people that includes a validated method of frailty assessment at baseline. Trial registration ISRCTN: ISRCTN57066881

2011-01-01

247

Changes in the Precision of a Study from Planning Phase to Implementation Phase: Evidence from the First Wave of Group Randomized Trials Launched by the Institute of Education Sciences  

ERIC Educational Resources Information Center

The purpose of this study is to extend the work of Spybrook and Raudenbush (2009) and examine how the research designs and sample sizes changed from the planning phase to the implementation phase in the first wave of studies funded by IES. The authors examine the impact of the changes in terms of the changes in the precision of the study from the…

Spybrook, Jessaca; Lininger, Monica; Cullen, Anne

2011-01-01

248

TEACCH-based group social skills training for children with high-functioning autism: a pilot randomized controlled trial  

PubMed Central

Background Although social skills training programs for people with high-functioning autism (HFA) are widely practiced, the standardization of curricula, the examination of clinical effectiveness, and the evaluation of the feasibility of future trials have yet to be done in Asian countries. To compensate for this problem, a Japanese pilot randomized controlled trial (RCT) of the Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH)-based group social skills training for children with HFA and their mothers was conducted. Methods Eleven children with HFA, aged 5–6 years, and their mothers were randomly assigned to the TEACCH program (n=5) or a waiting-list control group (n=6). The program involved comprehensive group intervention and featured weekly 2-hour sessions, totaling 20 sessions over six months. The adaptive behaviors and social reciprocity of the children, parenting stress, and parent–child interactions were assessed using the Strengths and Difficulties Questionnaire (SDQ), Parenting Stress Index (PSI), Beck depression inventory-II (BDI-II), and Interaction Rating Scale (IRS). Results Through this pilot trial, the intervention and evaluation of the program has been shaped. There were no dropouts from the program and the mothers’ satisfaction was high. The outcome measurements improved more in the program group than in the control group, with moderate effect sizes (SDQ, 0.71; PSI, 0.58; BDI-II, 0.40; and IRS, 0.69). This pilot trial also implied that this program is more beneficial for high IQ children and mothers with low stress than for those who are not. Conclusion We have standardized the TEACCH program, confirmed the feasibility of a future trial, and successfully estimated the positive effect size. These findings will contribute to a larger trial in the future and to forthcoming systematic reviews with meta-analyses. Trial registration UMIN000004560

2013-01-01

249

Recruitment to multicentre trials—lessons from UKCTOCS: descriptive study  

Microsoft Academic Search

Objective To describe the factors that contributed to successful recruitment of more than 200 000 women to the UK Collaborative Trial of Ovarian Cancer Screening, one of the largest ever randomised controlled trials.Design Descriptive study.Setting 13 NHS trusts in England, Wales, and Northern Ireland.Participants Postmenopausal women aged 50-74; exclusion criteria included ovarian malignancy, bilateral oophorectomy, increased risk of familial ovarian

Usha Menon; Aleksandra Gentry-Maharaj; Andy Ryan; Aarti Sharma; Matthew Burnell; Rachel Hallett; Sara Lewis; Alberto Lopez; Keith Godfrey; David Oram; Jonathan Herod; Karin Williamson; Mourad Seif; Ian Scott; Tim Mould; Robert Woolas; John Murdoch; Stephen Dobbs; Nazar Amso; Simon Leeson; Derek Cruickshank; Ali McGuire; Stuart Campbell; Lesley Fallowfield; Steve Skates; Mahesh Parmar; Ian Jacobs

2008-01-01

250

A Controlled Trial of Group Cognitive Behavior Therapy for Irish Breast Cancer Patients  

Microsoft Academic Search

The aim of this study was to evaluate a manualized cognitive behavioral group intervention for early-stage breast cancer patients. Sixty-nine women were recruited at an Irish specialist oncology hospital and assigned to a 6-week cognitive behavior therapy (CBT) program or an educational control group. Participants were assessed at baseline, 6 weeks, and 6-month follow-up. Groups × Time (2 × 3)

Aidan McKiernan; Shawn Steggles; Suzanne Guerin; Alan Carr

2010-01-01

251

Community-based group exercise for persons with Parkinson disease: a randomized controlled trial.  

PubMed

The purpose of this study was to compare group boxing training to traditional group exercise on function and quality of life in persons with Parkinson disease (PD). A convenience sample of adults with PD (n = 31) were randomly assigned to boxing training or traditional exercise for 24-36 sessions, each lasting 90 minutes, over 12 weeks. Boxing training included: stretching, boxing (e.g. lateral foot work, punching bags), resistance exercises, and aerobic training. Traditional exercise included: stretching, resistance exercises, aerobic training, and balance activities. Participants were tested before and after completion of training on balance, balance confidence, mobility, gait velocity, gait endurance, and quality of life. The traditional exercise group demonstrated significantly greater gains in balance confidence than the boxing group (p < 0.025). Only the boxing group demonstrated significant improvements in gait velocity and endurance over time with a medium between-group effect size for the gait endurance (d = 0.65). Both groups demonstrated significant improvements with the balance, mobility, and quality of life with large within-group effect sizes (d ? 0.80). While groups significantly differed in balance confidence after training, both groups demonstrated improvements in most outcome measures. Supporting options for long-term community-based group exercise for persons with PD will be an important future consideration for rehabilitation professionals. PMID:23422464

Combs, Stephanie A; Diehl, M Dyer; Chrzastowski, Casey; Didrick, Nora; McCoin, Brittany; Mox, Nicholas; Staples, William H; Wayman, Jessica

2013-01-01

252

Altering school climate through school-wide Positive Behavioral Interventions and Supports: findings from a group-randomized effectiveness trial.  

PubMed

Positive Behavioral Interventions and Supports (PBIS) is a universal, school-wide prevention strategy that is currently implemented in over 7,500 schools to reduce disruptive behavior problems. The present study examines the impact of PBIS on staff reports of school organizational health using data from a group-randomized controlled effectiveness trial of PBIS conducted in 37 elementary schools. Longitudinal multilevel analyses on data from 2,596 staff revealed a significant effect of PBIS on the schools' overall organizational health, resource influence, staff affiliation, and academic emphasis over the 5-year trial; the effects on collegial leadership and institutional integrity were significant when implementation fidelity was included in the model. Trained schools that adopted PBIS the fastest tended to have higher levels of organizational health at baseline, but the later-implementing schools tended to experience the greatest improvements in organizational health after implementing PBIS. This study indicated that changes in school organizational health are important consequences of the PBIS whole-school prevention model, and may in turn be a potential contextual mediator of the effect of PBIS on student performance. PMID:19011963

Bradshaw, Catherine P; Koth, Christine W; Thornton, Leslie A; Leaf, Philip J

2009-06-01

253

Study design considerations in a large COPD trial comparing effects of tiotropium with salmeterol on exacerbations  

PubMed Central

Currently available long-acting inhaled bronchodilators (tiotropium, salmeterol, formoterol) have demonstrated beneficial effects on exacerbations in placebo-controlled trials. However, there have been no direct comparisons of these drugs with exacerbations as the primary outcome and consequently COPD treatment guidelines do not indicate a preference for either bronchodilator. Therefore, an international, randomized, double-blind, double-dummy, parallel-group clinical trial has been designed to investigate the comparative efficacy of 2 long-acting bronchodilators tiotropium 18 ?g daily and salmeterol 50 ?g bid on exacerbations. The trial will include at least 6800 randomized patients with diagnosis of COPD, ? 10 pack-year history of smoking, post-bronchodilator FEV1 ? 70% predicted, and a history of exacerbations in the previous year. The primary endpoint is time to first COPD exacerbation. Secondary endpoints include number of exacerbations and time to premature discontinuation of trial medication. The trial has been designed to address several of the challenges in studying exacerbations in a controlled trial by a symptom and event-based definition of exacerbations, frequent follow-up contacts, selection of time to first event as the primary endpoint and using exposure adjusted analysis when examining number of events. Other challenges in designing exacerbation trials such as differential discontinuation and follow-up of discontinued patients are discussed.

Beeh, Kai-Michael; Hederer, Bettina; Glaab, Thomas; Muller, Achim; Moelken, Maureen Rutten-van; Kesten, Steven; Vogelmeier, Claus

2009-01-01

254

Corticotherapy for traumatic brain-injured Patients - The Corti-TC trial: study protocol for a randomized controlled trial  

PubMed Central

Background Traumatic brain injury (TBI) is a main cause of severe prolonged disability of young patients. Hospital acquired pneumonia (HAP) add to the morbidity and mortality of traumatic brain-injured patients. In one study, hydrocortisone for treatment of traumatic-induced corticosteroid insufficiency (CI) in multiple injured patients has prevented HAP, particularly in the sub-group of patients with severe TBI. Fludrocortisone is recommended in severe brain-injured patients suffering from acute subarachnoid hemorrhage. Whether an association of hydrocortisone with fludrocortisone protects from HAP and improves neurological recovery is uncertain. The aim of the current study is to compare corticotherapy to placebo for TBI patients with CI. Methods The CORTI-TC (Corticotherapy in traumatic brain-injured patients) trial is a multicenter, randomized, placebo controlled, double-blind, two-arms study. Three hundred and seventy six patients hospitalized in Intensive Care Unit with a severe traumatic brain injury (Glasgow Coma Scale ? 8) are randomized in the first 24 hours following trauma to hydrocortisone (200 mg.day-1 for 7 days, 100 mg on days 8-9 and 50 mg on day-10) with fludrocortisone (50 ?g for 10 days) or double placebo. The treatment is stopped if patients have an appropriate adrenal response. The primary endpoint is HAP on day-28. The endpoint of the ancillary study is the neurological status on 6 and 12 months. Discussion The CORTI-TC trial is the first randomized controlled trial powered to investigate whether hydrocortisone with fludrocortisone in TBI patients with CI prevent HAP and improve long term recovery. Trial registration NCT01093261

2011-01-01

255

A Randomized Trial of Contingency Management Delivered in the Context of Group Counseling  

ERIC Educational Resources Information Center

Objective: Contingency management (CM) is efficacious in reducing drug use. Typically, reinforcers are provided on an individual basis to patients for submitting drug-negative samples. However, most treatment is provided in a group context, and poor attendance is a substantial concern. This study evaluated whether adding CM to group-based…

Petry, Nancy M.; Weinstock, Jeremiah; Alessi, Sheila M.

2011-01-01

256

Group-Based Randomized Trial of Contingencies for Health and Abstinence in HIV Patients  

ERIC Educational Resources Information Center

Objective: Contingency management (CM) treatments are usually applied individually for drug abstinence, but CM can also be targeted toward health behaviors and implemented in groups. This study evaluated effects of a group-based CM intervention that focused on reinforcing health behaviors. Method: HIV-positive patients with cocaine or opioid use…

Petry, Nancy M.; Weinstock, Jeremiah; Alessi, Sheila M.; Lewis, Marilyn W.; Dieckhaus, Kevin

2010-01-01

257

Environmental Studies Group. Annual Report for 1978.  

National Technical Information Service (NTIS)

Group projects included radioecological studies of aquatic and terrestrial systems, land management activities, foodstuff monitoring, dust transport studies including fugitive dust measurements and modeling, and several support programs involving evaluati...

D. C. Hunt J. D. Hurley

1980-01-01

258

Roswell Park-led study finds most cancer research trials do not assess participants’ tobacco use  

Cancer.gov

While tobacco use can significantly hamper cancer treatment, few cancer researchers are incorporating tobacco assessment into their clinical studies. That’s the conclusion a group of investigators led by researchers at Roswell Park Cancer Institute drew from a recent survey of cancer clinical trials.

259

Evaluation of support group interventions for children in troubled families: study protocol for a quasi-experimental control group study  

PubMed Central

Background Support groups for children in troubled families are available in a majority of Swedish municipalities. They are used as a preventive effort for children in families with different parental problems such as addiction to alcohol/other drugs, mental illness, domestic violence, divorce situations, or even imprisonment. Children from families with these problems are a well-known at-risk group for various mental health and social problems. Support groups aim at strengthening children’s coping behaviour, to improve their mental health and to prevent a negative psycho-social development. To date, evaluations using a control-group study design are scarce. The aim of the current study is to evaluate the effects of support groups. This paper describes the design of an effectiveness study, initially intended as a randomized controlled trial, but instead is pursued as a quasi-experimental study using a non-randomized control group. Methods/design The aim is to include 116 children, aged 7–13 years and one parent/another closely related adult, in the study. Participants are recruited via existing support groups in the Stockholm county district and are allocated either into an intervention group or a waiting list control group, representing care as usual. The assessment consists of questionnaires that are to be filled in at baseline and at four months following the baseline. Additionally, the intervention group completes a 12-month follow-up. The outcomes include the Strength and Difficulties Questionnaire (SDQ S11-16), the Kids Coping Scale, the “Ladder of life” which measures overall life satisfaction, and “Jag tycker jag är” (I think I am) which measures self-perception and self-esteem. The parents complete the SDQ P4-16 (parent-report version) and the Swedish scale “Familjeklimat” (Family Climate), which measures the emotional climate in the family. Discussion There is a need for evaluating the effects of support groups targeted to children from troubled families. This quasi-experimental study therefore makes an important contribution to this novel field of research. In the article various problems related to pursuing a study with children at risk are discussed. Trial registration ISRCTN52310507

2014-01-01

260

Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov  

PubMed Central

Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency.

Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

2013-01-01

261

Phase II Study of ET743 in Advanced Soft Tissue Sarcomas: A European Organisation for the Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group Trial  

Microsoft Academic Search

Purpose This nonrandomized multicenter phase II study was performed to evaluate the activity and safety of Ecteinascidin (ET-743) administered at a dose of 1.5 mg\\/m 2 as a 24-hour continuous infusion every 3 weeks in patients with pretreated advanced soft tissue sarcoma.

A. Le Cesne; J. Y. Blay; I. Judson; A. Van Oosterom; J. Verweij; J. Radford; P. Lorigan; S. Rodenhuis; I. Ray-Coquard; S. Bonvalot; F. Collin; J. Jimeno; E. Di Paola; M. Van Glabbeke; O. S. Nielsen

2005-01-01

262

Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission – experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG)  

Microsoft Academic Search

Patients with CLL responding to initial chemotherapy with fludarabine alone (F) or in combination with cyclophosphamide (FC) were randomized for treatment with alemtuzumab (30 mg i.v. TIW, 12 weeks) or observation. Of 21 evaluable patients, 11 were randomized to alemtuzumab before the study was stopped due to severe infections in seven of 11 patients. These infections (one life-threatening pulmonary aspergillosis

C-M Wendtner; M Ritgen; C D Schweighofer; G Fingerle-Rowson; H Campe; G Jäger; B Eichhorst; R Busch; H Diem; A Engert; S Stilgenbauer; H Döhner; M Kneba; B Emmerich; M Hallek

2004-01-01

263

The Cessation in Pregnancy Incentives Trial (CPIT): study protocol for a randomized controlled trial  

PubMed Central

Background Seventy percent of women in Scotland have at least one baby, making pregnancy an opportunity to help most young women quit smoking before their own health is irreparably compromised. By quitting during pregnancy their infants will be protected from miscarriage and still birth as well as low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. In the UK, the NICE guidelines: ‘How to stop smoking in pregnancy and following childbirth’ (June 2010) highlighted that little evidence exists in the literature to confirm the efficacy of financial incentives to help pregnant smokers to quit. Its first research recommendation was to determine: Within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit? Design and methods This study is a phase II exploratory individually randomized controlled trial comparing standard care for pregnant smokers with standard care plus the additional offer of financial voucher incentives to engage with specialist cessation services and/or to quit smoking during pregnancy. Participants (n?=?600) will be pregnant smokers identified at maternity booking who, when contacted by specialist cessation services, agree to having their details passed to the NHS Smokefree Pregnancy Study Helpline to discuss the trial. The NHS Smokefree Pregnancy Study Helpline will be responsible for telephone consent and follow-up in late pregnancy. The primary outcome will be self reported smoking in late pregnancy verified by cotinine measurement. An economic evaluation will refine cost data collection and assess potential cost-effectiveness while qualitative research interviews with clients and health professionals will assess the level of acceptance of this form of incentive payment. The research questions are: What is the likely therapeutic efficacy? Are incentives potentially cost-effective? Is individual randomization an efficient trial design without introducing outcome bias? Can incentives be introduced in a way that is feasible and acceptable? Discussion This phase II trial will establish a workable design to reduce the risks associated with a future definitive phase III multicenter randomized controlled trial and establish a framework to assess the costs and benefits of financial incentives to help pregnant smokers to quit. Trial registration Current Controlled Trials ISRCTN87508788

2012-01-01

264

Randomized controlled trial of transdiagnostic group treatments for primary care patients with common mental disorders  

PubMed Central

Background. The purpose was to test the effectiveness of two transdiagnostic group interventions compared to care as usual (CAU) for patients with anxiety, depressive or stress-related disorders within a primary health care context. Objectives. To compare the effects of cognitive-based-behavioural therapy (CBT) and multimodal intervention (MMI) on the quality of life and relief of psychological symptoms of patients with common mental disorders or problems attending primary health care centre. Methods. Patients (n = 278), aged 18–65 years, were referred to the study by the GPs and 245 were randomized to CAU or one of two group interventions in addition to CAU: (i) group CBT administered by psychologists and (ii) group MMI administered by assistant nurses. The primary outcome measure was the Mental Component Summary score of short form 36. Secondary outcome measures were Perceived Stress Scale and Self-Rating Scale for Affective Syndromes. The data were analysed using intention-to-treat with a linear mixed model. Results. On the primary outcome measure, the mean improvement based on mixed model analyses across post- and follow-up assessment was significantly larger for the MMI group than for the CBT (4.0; P = 0.020) and CAU (7.5; P = .001) groups. Participants receiving CBT were significantly more improved than those in the CAU group. On four of the secondary outcome measures, the MMI group was significantly more improved than the CBT and CAU groups. The course of improvement did not differ between the CBT group and the CAU group on these measures. Conclusions. Transdiagnostic group treatment can be effective for patients with common mental disorders when delivered in a primary care setting. The group format and transdiagnostic approach fit well with the requirements of primary care.

Ejeby, Kersti

2014-01-01

265

Exemestane as primary systemic treatment for hormone receptor positive post-menopausal breast cancer patients: a phase II trial of the Austrian Breast and Colorectal Cancer Study Group (ABCSG-17)  

Microsoft Academic Search

Background A multicenter phase II study was conducted to analyze the clinical activity of the steroidal aromatase inhibitor exemestane\\u000a in the neoadjuvant treatment of post-menopausal women with strongly ER- and\\/or PgR- positive operable breast cancer. Patients and methods From September 2000 to December 2003, 80 women were recruited for treatment with exemestane 25 mg once daily for 4 months.\\u000a The primary end-point

Brigitte Mlineritsch; Christoph Tausch; Christian Singer; Gero Luschin-Ebengreuth; Raimund Jakesz; Ferdinand Ploner; Michael Stierer; Elisabeth Melbinger; Christian Menzel; Andrea Urbania; Michael Fridrik; Günther Steger; Peter Wohlmuth; Michael Gnant; Richard Greil

2008-01-01

266

Canadian-led capacity-building in biostatistics and methodology in cardiovascular and diabetes trials: the CANNeCTIN Biostatistics and Methodological Innovation Working Group  

PubMed Central

The Biostatistics and Methodological Innovation Working (BMIW) Group is one of several working groups within the CANadian Network and Centre for Trials INternationally (CANNeCTIN). This programme received funding from the Canadian Institutes of Health Research and the Canada Foundation for Innovation beginning in 2008, to enhance the infrastructure and build capacity for large Canadian-led clinical trials in cardiovascular diseases (CVD) and diabetes mellitus (DM). The overall aims of the BMIW Group's programme within CANNeCTIN, are to advance biostatistical and methodological research, and to build biostatistical capacity in CVD and DM. Our program of research and training includes: monthly videoconferences on topical biostatistical and methodological issues in CVD/DM clinical studies; providing presentations on methods issues at the annual CANNeCTIN meetings; collaborating with clinician investigators on their studies; training young statisticians in biostatistics and methods in CVD/DM trials and organizing annual symposiums on topical methodological issues. We are focused on the development of new biostatistical methods and the recruitment and training of highly qualified personnel - who will become leaders in the design and analysis of CVD/DM trials. The ultimate goal is to enhance global health by contributing to efforts to reduce the burden of CVD and DM.

2011-01-01

267

Acupuncture for acute stroke: study protocol for a multicenter, randomized, controlled trial  

PubMed Central

Background Acupuncture has been widely used as a treatment for stroke in China for more than 3,000 years. However, previous research has not yet shown that acupuncture is effective as a stroke treatment. We report a protocol for a multicenter, randomized, controlled, and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on acute ischemic stroke. Methods/Design In a prospective trial involving three hospitals in the Zhejiang Province (China) 250 patients with a recent (less than 1 week previous) episode of ischemic stroke will be included. Patients will be randomized into two groups: an acupuncture group given scalp acupuncture and electroacupuncture, and a control group given no acupuncture. Eighteen treatment sessions will be performed over a three-week period. The primary outcome will be measured by changes in the National Institutes of Health Stroke Scale score at the one, three, and four-week follow-up. Secondary outcome measures will be: 1) the Fugl-Meyer assessment scale for motor function; 2) the mini-mental state examination and Montreal cognitive assessment for cognitive function; 3) the video-fluoroscopic swallowing study for swallowing ability; and 4) the incidence of adverse events. Discussion This trial is expected to clarify whether or not acupuncture is effective for acute stroke. It will also show if acupuncture can improve motor, cognitive, or swallowing function. Trial registration Chinese Clinical Trial Registry ChiCTR-TRC-12001971.

2014-01-01

268

Quality of Life with Gefitinib in Patients with EGFR-Mutated Non-Small Cell Lung Cancer: Quality of Life Analysis of North East Japan Study Group 002 Trial  

PubMed Central

Background. For non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, first-line gefitinib produced a longer progression-free survival interval than first-line carboplatin plus paclitaxel but did not show any survival advantage in the North East Japan 002 study. This report describes the quality of life (QoL) analysis of that study. Methods. Chemotherapy-naïve patients with sensitive EGFR-mutated, advanced NSCLC were randomized to receive gefitinib or chemotherapy (carboplatin and paclitaxel). Patient QoL was assessed weekly using the Care Notebook, and the primary endpoint of the QoL analysis was time to deterioration from baseline on each of the physical, mental, and life well-being QoL scales. Kaplan–Meier probability curves and log-rank tests were employed to clarify differences. Results. QoL data from 148 patients (72 in the gefitinib arm and 76 in the carboplatin plus paclitaxel arm) were analyzed. Time to defined deterioration in physical and life well-being significantly favored gefitinib over chemotherapy (hazard ratio [HR] of time to deterioration, 0.34; 95% confidence interval [CI], 0.23–0.50; p < .0001 and HR, 0.43; 95% CI, 0.28–0.65; p < .0001, respectively). Conclusion. QoL was maintained much longer in patients treated with gefitinib than in patients treated with standard chemotherapy, indicating that gefitinib should be considered as the standard first-line therapy for advanced EGFR-mutated NSCLC in spite of no survival advantage.

Oizumi, Satoshi; Inoue, Akira; Maemondo, Makoto; Sugawara, Shunichi; Yoshizawa, Hirohisa; Isobe, Hiroshi; Harada, Masao; Kinoshita, Ichiro; Okinaga, Shoji; Kato, Terufumi; Harada, Toshiyuki; Gemma, Akihiko; Saijo, Yasuo; Yokomizo, Yuki; Morita, Satoshi; Hagiwara, Koichi; Nukiwa, Toshihiro

2012-01-01

269

Predictors of accrual success for cooperative group trials: The Cancer and Leukemia Group B (Alliance) experience. | accrualnet.cancer.gov  

Cancer.gov

Gordon DH,Liu Q,Kleinman B,Karrison T,Kelly M,Fleming GF. Alliance for Clinical Trials in Oncology, Chicago, IL; University of Chicago, Chicago, IL. ASCO 2013 Annual Meeting. 2013 May 31. 2013 Jun 04. Chicago, IL.

270

Design, development of water tank-type lung phantom and dosimetric verification in institutions participating in a phase I study of stereotactic body radiation therapy in patients with T2N0M0 non-small cell lung cancer: Japan Clinical Oncology Group trial (JCOG0702)  

PubMed Central

A domestic multicenter phase I study of stereotactic body radiotherapy (SBRT) for T2N0M0 non-small cell lung cancer in inoperable patients or elderly patients who refused surgery was initiated as the Japan Clinical Oncology Group trial (JCOG0702) in Japan. Prior to the clinical study, the accuracy of dose calculation in radiation treatment-planning systems was surveyed in participating institutions, and differences in the irradiating dose between the institutions were investigated. We developed a water tank-type lung phantom appropriate for verification of the exposure dose in lung SBRT. Using this water tank-type lung phantom, the dose calculated in the radiation treatment-planning system and the measured dose using a free air ionization chamber and dosimetric film were compared in a visiting survey of the seven institutions participating in the clinical study. In all participating institutions, differences between the calculated and the measured dose in the irradiation plan were as follows: the accuracy of the absolute dose in the center of the simulated tumor measured using a free air ionization chamber was within 2%, the mean gamma value was ?0.47 on gamma analysis following the local dose criteria, and the pass rate was >87% for 3%/3 mm from measurement of dose distribution with dosimetric film. These findings confirmed the accuracy of delivery doses in the institutions participating in the clinical study, so that a study with integration of the institutions could be initiated.

Nishio, Teiji; Shirato, Hiroki; Ishikawa, Masayori; Miyabe, Yuki; Kito, Satoshi; Narita, Yuichirou; Onimaru, Rikiya; Ishikura, Satoshi; Ito, Yoshinori; Hiraoka, Masahiro

2014-01-01

271

Grouping Multivariate Time Series: A Case Study  

Microsoft Academic Search

We present a case study to demonstrate a process for grouping massive multivariate time series based on nonpara- metric statistical summaries aided by information visualization. We want a method that allows us to quickly find approximate groups in time series, both to identify typical aggregate behaviors and to find aberrant outliers. We use simple statistical summaries to capture the temporal

Tamraparni Dasu; Deborah F. Swayne; David Poole

272

The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up  

PubMed Central

Background: The role of adjuvant dose-intensive chemotherapy and its efficacy according to baseline features has not yet been established. Patients and methods: Three hundred and forty-four patients were randomized to receive seven courses of standard-dose chemotherapy (SD-CT) or three cycles of dose-intensive epirubicin and cyclophosphamide (epirubicin 200 mg/m2 plus cyclophosphamide 4 mg/m2 with filgrastim and progenitor cell support). All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). This paper updates the results and explores patterns of recurrence according to predicting baseline features. Results: At 8.3-years median follow-up, patients assigned DI-EC had a significantly better DFS compared with those assigned SD-CT [8-year DFS percent 47% and 37%, respectively, hazard ratio (HR) 0.76; 95% confidence interval 0.58–1.00; P = 0.05]. Only patients with estrogen receptor (ER)-positive disease benefited from the DI-EC (HR 0.61; 95% confidence interval 0.39, 0.95; P = 0.03). Conclusions: After prolonged follow-up, DI-EC significantly improved DFS, but the effect was observed only in patients with ER-positive disease, leading to the hypothesis that efficacy of DI-EC may relate to its endocrine effects. Further studies designed to confirm the importance of endocrine responsiveness in patients treated with dose-intensive chemotherapy are encouraged.

Colleoni, M.; Sun, Z.; Martinelli, G.; Basser, R. L.; Coates, A. S.; Gelber, R. D.; Green, M. D.; Peccatori, F.; Cinieri, S.; Aebi, S.; Viale, G.; Price, K. N.; Goldhirsch, A.

2009-01-01

273

Can historical controls be used in current clinical trials in osteosarcoma. Metastases and survival in a historical and a concurrent group  

SciTech Connect

A historical group consisting of 35 patients with osteosarcoma was compared to a concurrent group of 23 patients. The treatment for the primary tumors differed only slghtly in the two groups. A more active approach was adopted for treatment of pulmonary metastases in the concurrent group. The percentage of patients not developing metastases and the survival rate in the historical group were approximately one half those for the concurrent group. An analysis of prognostic factors disclosed differences between the two groups as regards the size and histological type of the tumor. The results of the study cast doubt on the suitability of historical controls in current clinical trials conducted to ascertain the effectiveness of adjuvant therapy for osteosarcoma.

Brostroem, L.A. (Karolinska Hospital, Stockholm, Sweden); Aparisi, T.; Ingimarsson, S.; Lagergren, C.; Nilsonne, U.; Strander, H.; Soederberg, G.

1980-12-01

274

The outcome of control groups in clinical trials of conservative treatments for chronic mechanical neck pain: a systematic review  

PubMed Central

Background Chronic neck pain is highly prevalent in Western societies, with about 15% of females and 10% of males suffering with it at any time. The course of untreated chronic neck pain patients in clinical trials has not been well-defined and the placebo effect has not been clarified. Methods A systematic review of RCT's of conservative treatments for chronic mechanical neck pain was conducted. Studies were excluded if they did not include a control group, if they involved subjects with whiplash injuries, a predominance of headache or arm pain associated with chronic neck pain and if only one treatment was reported. Only studies scoring 3–5 out of 5 on the Jadad Scale for quality were included in the final analysis. Data on change in pain scores of subjects in both placebo (PL) as well as no-treatment (NT) control groups were analyzed. Mean changes in pain scores as well as effect sizes were calculated, summarized and compared between these groups. Results Twenty (20) studies, 5 in the NT group and 15 in the PL group, with outcome intervals ranging from 1–52 weeks were included in the final analysis. The mean [95% CI] effect size of change in pain ratings in the no-treatment control studies at outcome points up to 10 weeks was 0.18 [-0.05, 0.41] and for outcomes from 12–52 weeks it was 0.4 [0.12, 0.68]. In the placebo control groups it was 0.50 [0.10, 0.90] at up to 10 weeks and 0.33. [-1.97, 2.66] at 12–24 weeks. None of the comparisons between the no-treatment and placebo groups were statistically significant. Conclusion It appears that the changes in pain scores in subjects with chronic neck pain not due to whiplash who are enrolled in no-treatment and placebo control groups were similarly small and not significantly different. As well, they do not appear to increase over longer-term follow-up.

Vernon, Howard; Humphreys, B Kim; Hagino, Carol

2006-01-01

275

Outcomes of usual chiropractic, harm & efficacy, the ouch study: study protocol for a randomized controlled trial  

PubMed Central

Background Previous studies have demonstrated that adverse events occur during chiropractic treatment. However, because of these studies design we do not know the frequency and extent of these events when compared to sham treatment. The principal aims of this study are to establish the frequency and severity of adverse effects from short term usual chiropractic treatment of the spine when compared to a sham treatment group. The secondary aim of this study is to establish the efficacy of usual short term chiropractic care for spinal pain when compared to a sham intervention. Methods One hundred and eighty participants will be randomly allocated to either usual chiropractic care or a sham intervention group. To be considered for inclusion the participants must have experienced non-specific spinal pain for at least one week. The study will be conducted at the clinics of registered chiropractors in Western Australia. Participants in each group will receive two treatments at intervals no less than one week. For the usual chiropractic care group, the selection of therapeutic techniques will be left to the chiropractors' discretion. For the sham intervention group, de-tuned ultrasound and de-tuned activator treatment will be applied by the chiropractors to the regions where spinal pain is experienced. Adverse events will be assessed two days after each appointment using a questionnaire developed for this study. The efficacy of short term chiropractic care for spinal pain will be examined at two week follow-up by assessing pain, physical function, minimum acceptable outcome, and satisfaction with care, with the use of the following outcome measures: Numerical Rating Scale, Functional Rating Index, Neck Disability Index, Minimum Acceptable Outcome Questionnaire, Oswestry Disability Index, and a global measure of treatment satisfaction. The statistician, outcome assessor, and participants will be blinded to treatment allocation. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000542998

2011-01-01

276

Supportive-expressive and coping group teletherapies for HIV-infected older adults: a randomized clinical trial.  

PubMed

This clinical trial tested whether telephone-administered supportive-expressive group therapy or coping effectiveness training reduce depressive symptoms in HIV-infected older adults. Participants from 24 states (N = 361) completed the Geriatric Depression Scale at pre-intervention, post-intervention, and 4- and 8-month follow-up and were randomized to one of three study arms: (1) 12 weekly sessions of telephone-administered, supportive-expressive group therapy (tele-SEGT; n = 122); (2) 12 weekly sessions of telephone-administered, coping effectiveness training (tele-CET; n = 118); or (3) a standard of care (SOC) control group (n = 121). Tele-SEGT participants reported fewer depressive symptoms than SOC controls at post-intervention (MSEGT = 11.9, MSOC = 14.3) and 4- (MSEGT = 12.5, MSOC = 14.4) and 8-month follow-up (MSEGT = 12.7, MSOC = 14.5) and fewer depressive symptoms than tele-CET participants at post-intervention (MSEGT = 12.4, MCET = 13.6) and 8-month follow-up (MSEGT = 12.7, MCET = 14.1). Tele-CET participants reported no statistically significant differences from SOC controls in GDS values at any assessment period. Tele-SEGT constitutes an efficacious treatment to reduce depressive symptoms in HIV-infected older adults. PMID:23474642

Heckman, Timothy G; Heckman, Bernadette D; Anderson, Timothy; Lovejoy, Travis I; Mohr, David; Sutton, Mark; Bianco, Joseph A; Gau, Jen-Tzer

2013-11-01

277

Mindfulness training improves attentional task performance in incarcerated youth: a group randomized controlled intervention trial  

PubMed Central

We investigated the impact of cognitive behavioral therapy and mindfulness training (CBT/MT) on attentional task performance in incarcerated adolescents. Attention is a cognitive system necessary for managing cognitive demands and regulating emotions. Yet persistent and intensive demands, such as those experienced during high-stress intervals like incarceration and the events leading to incarceration, may deplete attention resulting in cognitive failures, emotional disturbances, and impulsive behavior. We hypothesized that CBT/MT may mitigate these deleterious effects of high stress and protect against degradation in attention over the high-stress interval of incarceration. Using a quasi-experimental, group randomized controlled trial design, we randomly assigned dormitories of incarcerated youth, ages 16–18, to a CBT/MT intervention (youth n = 147) or an active control intervention (youth n = 117). Both arms received approximately 750 min of intervention in a small-group setting over a 3–5 week period. Youth in the CBT/MT arm also logged the amount of out-of-session time spent practicing MT exercises. The Attention Network Test was used to index attentional task performance at baseline and 4 months post-baseline. Overall, task performance degraded over time in all participants. The magnitude of performance degradation was significantly less in the CBT/MT vs. control arm. Further, within the CBT/MT arm, performance degraded over time in those with no outside-of-class practice time, but remained stable over time in those who practiced mindfulness exercises outside of the session meetings. Thus, these findings suggest that sufficient CBT/MT practice may protect against functional attentional impairments associated with high-stress intervals.

Leonard, Noelle R.; Jha, Amishi P.; Casarjian, Bethany; Goolsarran, Merissa; Garcia, Cristina; Cleland, Charles M.; Gwadz, Marya V.; Massey, Zohar

2013-01-01

278

Prevalence of primary outcome changes in clinical trials registered on ClinicalTrials.gov: a cross-sectional study  

PubMed Central

Background: An important principle in the good conduct of clinical trials is that a summary of the trial protocol, with a pre-defined primary outcome, should be freely available before the study commences. The clinical trials registry ClinicalTrials.gov provides one method of doing this, and once the trial is registered, any changes made to the primary outcome are documented. The objectives of this study were: to assess the proportion of registered trials on ClinicalTrials.gov that had the primary outcome changed; to assess when the primary outcome was changed in relation to the listed study start and end dates and to assess whether the primary outcome change had any relation to the study sponsor. Methods: A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 25 October 2012 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. Findings: Our analysis showed that 28229 of 89204 (31.7%) registered studies had their primary outcome changed.  Industry funding was associated with all primary outcome changes, odds ratio (OR)= 1.36, 95% confidence interval (CI)=1.31-1.41, p<0.001; with primary outcome changes after study start date OR=1.37, 95% CI=1.32-1.42, p<0.001; with primary outcome changes after primary completion date OR=1.84, 95% CI=1.75-1.94, p<0.001 and with primary outcome changes after study completion date OR=1.82, 95% CI=1.73-1.91, p<0.001.  Conclusions A significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. These changes are associated with funding source.

Ramagopalan, Sreeram; Skingsley, Andrew P.; Handunnetthi, Lahiru; Klingel, Michelle; Magnus, Daniel; Pakpoor, Julia; Goldacre, Ben

2014-01-01

279

An economic evaluation of Herceptin(R) in adjuvant setting: the Breast Cancer International Research Group 006 trial  

Microsoft Academic Search

Background: Herceptin? (trastuzumab) is a humanized monoclonal antibody that is being tested in the adjuvant setting. Cost implications of using trastuzumab, as administered in the Breast Cancer International Research Group 006 trial, are being calculated. This provides information on the treatment's value for money. Methods: Standard breast cancer treatment models were set up for different subpopulations according to stage (I,

M. Neyt; J. Albrecht; V. Cocquyt

2006-01-01

280

Patient advocates' role in clinical trials: Perspectives from Cancer and Leukemia Group B investigators and advocates. | accrualnet.cancer.gov  

Cancer.gov

Although there is a call for increased involvement of patient advocates in the design of clinical trials and patient recruitment and awareness efforts, little is known about the role and impact of patient advocates. A cooperative group survey of advocates and investigators forms the basis for recommendations.

281

Randomized trials versus observational studies in adolescent pregnancy prevention  

Microsoft Academic Search

The objective of this study is to compare the results of randomized trials and observational studies of interventions to prevent adolescent pregnancy. We identified published and unpublished reports through computerized searches of CATLINE, CINAHL, CONFERENCE PAPERS INDEX, DISSERTATION ABSTRACTS ONLINE, EMBASE, ERIC, MEDLINE, NTIS, POPLINE, PsycINFO, and SOCIOLOGICAL ABSTRACTS; manual searches of eight relevant journals; reference lists from primary articles;

Gordon H. Guyatt; Alba DiCenso; Vern Farewell; Andrew Willan; Lauren Griffith

2000-01-01

282

How Does Tele-Mental Health Affect Group Therapy Process? Secondary Analysis of a Noninferiority Trial  

ERIC Educational Resources Information Center

Objective: Video teleconferencing (VTC) is used for mental health treatment delivery to geographically remote, underserved populations. However, few studies have examined how VTC affects individual or group psychotherapy processes. This study compares process variables such as therapeutic alliance and attrition among participants receiving anger…

Greene, Carolyn J.; Morland, Leslie A.; Macdonald, Alexandra; Frueh, B. Christopher; Grubbs, Kathleen M.; Rosen, Craig S.

2010-01-01

283

Total or Partial Knee Arthroplasty Trial - TOPKAT: study protocol for a randomised controlled trial  

PubMed Central

Background In the majority of patients with osteoarthritis of the knee the disease originates in the medial compartment. There are two fundamentally different approaches to knee replacement for patients with unicompartmental disease: some surgeons feel that it is always best to replace both the knee compartments with a total knee replacement (TKR); whereas others feel it is best to replace just the damaged component of the knee using a partial or unicompartment replacement (UKR). Both interventions are established and well-documented procedures. Little evidence exists to prove the clinical and cost-effectiveness of either management option. This provides an explanation for the high variation in treatment of choice by individual surgeons for the same knee pathology. The aim of the TOPKAT study will be to assess the clinical and cost effectiveness of TKRs compared to UKRs in patients with medial compartment osteoarthritis. Methods/Design The design of the study is a single layer multicentre superiority type randomised controlled trial of unilateral knee replacement patients. Blinding will not be possible as the surgical scars for each procedure differ. We aim to recruit 500 patients from approximately 28 secondary care orthopaedic units from across the UK including district general and teaching hospitals. Participants will be randomised to either UKR or TKR. Randomisation will occur using a web-based randomisation system. The study is pragmatic in terms of implant selection for the knee replacement operation. Participants will be followed up for 5 years. The primary outcome is the Oxford Knee Score, which will be collected via questionnaires at 2 months, 1 year and then annually to 5 years. Secondary outcomes will include cost-effectiveness, patient satisfaction and complications data. Trial registration Current Controlled Trials ISRCTN03013488; ClinicalTrials.gov Identifier: NCT01352247

2013-01-01

284

Fluoxetine for Autistic Behaviors (FAB trial): study protocol for a randomized controlled trial in children and adolescents with autism  

PubMed Central

Background Serotonin reuptake inhibitors (SSRIs) are commonly prescribed off-label for children with autism. To date, clinical trials examining the use of SSRIs in autism have been limited by small sample sizes and inconclusive results. The efficacy and safety of SSRIs for moderating autistic behaviors is yet to be adequately examined to provide evidence to support current clinical practice. The aim of the Fluoxetine for Autistic Behaviors (FAB) study is to determine the efficacy and safety of low dose fluoxetine compared with placebo, for reducing the frequency and severity of repetitive stereotypic behaviors in children and adolescents with an autism spectrum disorder (ASD). The relationship between the effectiveness of fluoxetine treatment and serotonin transporter genotype will also be explored. Methods/Design The FAB study is a multicenter, double-blinded, randomized controlled trial, funded by the Australian Government’s National Health and Medical Research Council (NHMRC) grant. Participants will be aged between 7.5 and 17 years with a confirmed diagnosis of ASD. Eligible participants will be randomized to either placebo or fluoxetine for a 16-week period. Medication will be titrated over the first four weeks. Reponses to medication will be monitored fortnightly using the Clinical Global Impressions Scale (CGI). The primary outcome measure is the Children’s Yale-Brown Obsessive Compulsive Scale-Modified for Pervasive Developmental Disorders (CYBOCS-PDD), administered at baseline and 16 weeks. Secondary outcome measures include the Aberrant Behaviour Scale (ABC), the Spence Children’s Anxiety Scale Parent Report (SCAS-P), and the Repetitive Behaviors Scale (RBS-R), measured at baseline and 16 weeks. Participants will be invited to undergo genetic testing for SLC6A4 allele variants using a cheek swab. Continuous outcomes, including the primary outcome will be compared between the active and placebo groups using unadjusted linear regression. Binary outcomes will be compared using unadjusted logistic regression. Discussion The FAB study is a large clinical trial to specifically investigate the efficacy of low dose fluoxetine for restricted, repetitive, and stereotyped behaviors in ASD. The outcomes of this study will contribute to evidence-based interventions used in clinical practice to assist children with ASD. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12608000173392; registered on 9 April, 2008.

2014-01-01

285

Effectiveness of HIV/STD Sexual Risk Reduction Groups for Women in Substance Abuse Treatment Programs: Results of a NIDA Clinical Trials Network Trial  

PubMed Central

Context Since drug-involved women are among the fastest growing groups with AIDS, sexual risk reduction intervention for them is a public health imperative. Objective Test effectiveness of HIV/STD safer sex skills building (SSB) groups for women in community drug treatment. Design Randomized trial of SSB versus standard HIV/STD Education (HE); assessments at baseline, 3- and 6- months Participants Women recruited from 12 methadone or psychosocial treatment programs in NIDA’s Clinical Trials Network. 515 women with ? one unprotected vaginal or anal sex occasion (USO) with a male partner in the past 6 months were randomized. Interventions In SSB, five 90-minute groups used problem-solving and skills rehearsal to increase HIV/STD risk awareness, condom use and partner negotiation skills. In HE, one 60-minute group covered HIV/STD disease, testing, treatment, and prevention information. Main Outcome Number of USOs at follow up. Results A significant difference in mean USOs was obtained between SSB and HE over time (F=67.2, p<.0001). At 3 months, significant decrements were observed in both conditions. At 6 months SSB maintained the decrease, HE returned to baseline (p<.0377). Women in SSB had 29% fewer USOs than those in HE. Conclusions Skills building interventions can produce ongoing sexual risk reduction in women in community drug treatment.

Tross, Susan; Campbell, Aimee N. C.; Cohen, Lisa R.; Calsyn, Donald; Pavlicova, Martina; Miele, Gloria; Hu, Mei-Chen; Haynes, Louise; Nugent, Nancy; Gan, Weijin; Hatch-Maillette, Mary; Mandler, Raul; McLaughlin, Paul; El-Bassel, Nabila; Crits-Christoph, Paul; Nunes, Edward V.

2009-01-01

286

Efficacy and tolerability of ophthalmic epinastine: A randomized, double-masked, parallel-group, active- and vehicle-controlled environmental trial in patients with seasonal allergic conjunctivitis  

Microsoft Academic Search

Background: Epinastine hydrochloride is an antihistamine with mast cell-stabilizing and anti-inflammatory activity.Objective: The aim of this study was to assess the efficacy and tolerability of ophthalmic epinastine in patients with seasonal allergic conjunctivitis (SAC) exposed to environmental allergens.Methods: This randomized (age-stratified), double-masked, parallel-group, active- and vehicle-controlled, environmental, Phase III clinical trial was conducted at 6 ophthalmology clinics in the United

Scott M. Whitcup; Ron Bradford; John Lue; Rhett M. Schiffman; Mark B. Abelson

2004-01-01

287

Recruiting minority cancer patients into cancer clinical trials: a pilot project involving the Eastern Cooperative Oncology Group and the National Medical Association. | accrualnet.cancer.gov  

Cancer.gov

This paper may be useful for researchers interested in enhancing their interactions with community physicians and increasing the number of minority patients referred to clinical trials. It describes a study conducted by the Eastern Cooperative Oncology Group (ECOG) in collaboration with the National Medical Association (NMA) to better understand barriers and solutions to African-American (AA) accrual and to test several recommended low-cost strategies.

288

Longitudinal Effects of Coping on Outcome in a Randomized Controlled Trial of a Group Intervention for HIV-Positive Adults with AIDS-Related Bereavement  

Microsoft Academic Search

This study examined the longitudinal effects of coping on outcome one year following completion of a randomized, controlled trial of a group coping intervention for AIDS-related bereavement. Bereaved HIV-positive participants (N = 267) were administered measures of grief, psychiatric distress, quality of life, and coping at baseline, post-intervention, and at 4-, 8-, and 12-month follow-ups. Coping strategies directly impacted all outcome variables

Nathan B. Hansen; Nalini Tarakeshwar; Musie Ghebremichael; Heping Zhang; Arlene Kochman; Kathleen J. Sikkema

2006-01-01

289

Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups  

Microsoft Academic Search

Objectives To study the analgesic effect of acupuncture and placebo acupuncture and to explore whether the type of the placebo acupuncture is associated with the estimated effect of acupuncture.Design Systematic review and meta-analysis of three armed randomised clinical trials.Data sources Cochrane Library, Medline, Embase, Biological Abstracts, and PsycLIT.Data extraction and analysis Standardised mean differences from each trial were used to

Matias Vested Madsen; Peter C Gøtzsche; Asbjørn Hróbjartsson

2009-01-01

290

Environmental studies group. Annual report for 1978  

Microsoft Academic Search

Group projects included radioecological studies of aquatic and terrestrial systems, land management activities, foodstuff monitoring, dust transport studies including fugitive dust measurements and modeling, and several support programs involving evaluation of the plant's ambient air samplers and airborne tritium monitoring techniques. Some salient results from the several project reports include determination of an appropriate model for mechanically generated fugitive dust

D. C. Hunt; J. D. Hurley

1980-01-01

291

Clinicians' perceptions of reporting methods for back pain trials: a qualitative study  

PubMed Central

Background How outcomes of clinical trials are reported alters the way treatment effectiveness is perceived: clinicians interpret the outcomes of trials more favourably when results are presented in relative (such as risk ratio) rather than absolute terms (such as risk reduction). However, it is unclear which methods clinicians find easiest to interpret and use in decision making. Aim To explore which methods for reporting back pain trials clinicians find clearest and most interpretable and useful to decision making. Design and setting Indepth interviews with clinicians at clinical practices/research centre. Method Clinicians were purposively sampled by professional discipline, sex, age, and practice setting. They were presented with several different summaries of the results of the same hypothetical trial. Each summary used a different reporting method, and the study explored participants' preferences for each method and how they would like to see future trials reported. Results The 14 clinicians interviewed (comprising GPs, manual therapists, psychologists, a rheumatologist, and surgeons) stated that clinical trial reports were not written with them in mind. They were familiar with mean differences, proportion improved, and numbers needed to treat (NNT), but unfamiliar with standardised mean differences, odds ratios, and relative risks (RRs). They found the proportion improved, RR, and NNT most intuitively understandable, and thought reporting between-group mean differences, RRs, and odds ratios could mislead. Conclusion Clinicians stated that additional reporting methods facilitate the interpretation of trial results, and using a variety of methods would make results easier to interpret in context and incorporate into practice. Authors of future back pain trials should report data in a format that is accessible to clinicians.

Froud, Robert; Underwood, Martin; Carnes, Dawn; Eldridge, Sandra

2012-01-01

292

Etiologic Heterogeneity in Endometrial Cancer: Evidence from a Gynecologic Oncology Group Trial  

PubMed Central

Objective Although the epidemiology of typical endometrial carcinomas (grades 1–2 endometrioid or Type I) is well established, less is known regarding higher grade endometrioid or non-endometrioid carcinomas (Type II). Within a large Gynecologic Oncology Group trial (GOG-210), which included central pathology review, we investigated the etiologic heterogeneity of endometrial cancers by comparing risk factors for different histologic categories. Methods Based on epidemiologic questionnaire data, risk factor associations, expressed as odds ratios (OR) with 95% confidence intervals (CI), were estimated comparing grade 3 endometrioid and Type II cancers (including histologic subtypes) to grades 1–2 endometrioid cancers. Results Compared with 2,244 grades 1–2 endometrioid cancers, women with Type II cancers (321 serous, 141 carcinosarcomas, 77 clear cell, 42 mixed epithelial with serous or clear cell components) were older; more often non-white, multiparous, current smokers; and less often obese. Risk factors for grade 3 endometrioid carcinomas (n=354) were generally similar to those identified for Type II cancers, although patients with grade 3 endometrioid tumors more often had histories of breast cancer without tamoxifen exposure while those with Type II tumors were more frequently treated with tamoxifen. Patients with serous cancers and carcinosarcomas more frequently had breast cancer histories with tamoxifen treatment compared to patients with other tumors. Conclusions Risk factors for aggressive endometrial cancers, including grade 3 endometrioid and non-endometrioid tumors, appear to differ from lower grade endometrioid carcinomas. Our findings support etiologic differences between Type I and II endometrial cancers as well as additional heterogeneity within Type II cancers.

Brinton, Louise A.; Felix, Ashley S.; McMeekin, D. Scott; Creasman, William T.; Sherman, Mark E.; Mutch, David; Cohn, David E.; Walker, Joan L.; Moore, Richard G.; Downs, Levi S.; Soslow, Robert A.; Zaino, Richard

2014-01-01

293

Problem solving treatment and group psychoeducation for depression: multicentre randomised controlled trial  

PubMed Central

Objectives To determine the acceptability of two psychological interventions for depressed adults in the community and their effect on caseness, symptoms, and subjective function. Design A pragmatic multicentre randomised controlled trial, stratified by centre. Setting Nine urban and rural communities in Finland, Republic of Ireland, Norway, Spain, and the United Kingdom. Participants 452 participants aged 18 to 65, identified through a community survey with depressive or adjustment disorders according to the international classification of diseases, 10th revision or Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Interventions Six individual sessions of problem solving treatment (n=128), eight group sessions of the course on prevention of depression (n=108), and controls (n=189). Main outcome measures Completion rates for each intervention, diagnosis of depression, and depressive symptoms and subjective function. Results 63% of participants assigned to problem solving and 44% assigned to prevention of depression completed their intervention. The proportion of problem solving participants depressed at six months was 17% less than that for controls, giving a number needed to treat of 6; the mean difference in Beck depression inventory score was –2.63 (95% confidence interval –4.95 to –0.32), and there were significant improvements in SF-36 scores. For depression prevention, the difference in proportions of depressed participants was 14% (number needed to treat of 7); the mean difference in Beck depression inventory score was –1.50 (–4.16 to 1.17), and there were significant improvements in SF-36 scores. Such differences were not observed at 12 months. Neither specific diagnosis nor treatment with antidepressants affected outcome. Conclusions When offered to adults with depressive disorders in the community, problem solving treatment was more acceptable than the course on prevention of depression. Both interventions reduced caseness and improved subjective function.

Dowrick, Christopher; Dunn, Graham; Ayuso-Mateos, Jose Luis; Dalgard, Odd Steffen; Page, Helen; Lehtinen, Ville; Casey, Patricia; Wilkinson, Clare; Vazquez-Barquero, Jose Luis; Wilkinson, Greg

2000-01-01

294

A randomised controlled study of an audiovisual patient information intervention on informed consent and recruitment to cancer clinical trials. | accrualnet.cancer.gov  

Cancer.gov

This study evaluated audiovisual patient information to determine its effect on refusal rates among 173 cancer patients invited to participate in randomized cancer treatment trials. It also examined the effect of AVPI on anxiety and clinical trials knowledge. The intervention group received information via AVPI and written information, and the control group received only the written information.

295

Mindfulness and Acceptance-Based Group Therapy for Social Anxiety Disorder: An Open Trial  

ERIC Educational Resources Information Center

Mindfulness and Acceptance-Based Group Therapy (MAGT) for Social Anxiety Disorder (SAD) is based largely on Acceptance and Commitment Therapy (ACT; Hayes et al., 1999), with enhanced mindfulness mostly from Mindfulness-Based Cognitive Therapy (MBCT; Segal et al., 2002). The purpose of this study was to assess the feasibility and initial…

Kocovski, Nancy L.; Fleming, Jan E.; Rector, Neil A.

2009-01-01

296

Can Group Interventions Facilitate Forgiveness of an Ex-Spouse?: A Randomized Clinical Trial  

ERIC Educational Resources Information Center

This study evaluated the effectiveness of 2 versions of an 8-session forgiveness group intervention for divorced individuals. Participants (randomized, n = 192; analyzed, n = 149) were randomly assigned to a secular forgiveness condition, a religious forgiveness condition, or a no-intervention comparison condition. Measures of forgiveness and…

Rye, Mark S.; Pargament, Kenneth I.; Pan, Wei; Yingling, David W.; Shogren, Karrie A.; Ito, Masako

2005-01-01

297

No Differences between Group versus Individual Treatment of Childhood Anxiety Disorders in a Randomised Clinical Trial  

ERIC Educational Resources Information Center

Background: The present study compares an individual versus a group format in the delivery of manualised cognitive-behavioural therapy (FRIENDS) for children with anxiety disorders. Clinically referred children (aged 8 to 12) diagnosed with Separation Anxiety Disorder (n = 52), Generalised Anxiety Disorder (n = 37), Social Phobia (n = 22) or…

Liber, Juliette M.; Van Widenfelt, Brigit M.; Utens, Elisabeth M. W. J.; Ferdinand, Robert F.; Van Der Leeden, Adelinde J. M.; Van Gastel, Willemijn; Treffers, Philip D. A.

2008-01-01

298

The Melbourne Diabetes Prevention Study (MDPS): study protocol for a randomized controlled trial  

PubMed Central

Background Worldwide, type 2 diabetes (T2DM) prevalence has more than doubled over two decades. In Australia, diabetes is the second highest contributor to the burden of disease. Lifestyle modification programs comprising diet changes, weight loss and moderate physical activity, have been proven to reduce the incidence of T2DM in high risk individuals. As part of the Council of Australia Governments, the State of Victoria committed to develop and support the diabetes prevention program ‘Life! Taking action on diabetes’ (Life!) which has direct lineage from effective clinical and implementation trials from Finland and Australia. The Melbourne Diabetes Prevention Study (MDPS) has been set up to evaluate the effectiveness and cost-effectiveness of a specific version of the Life! program. Methods/design We intend to recruit 796 participants for this open randomized clinical trial; 398 will be allocated to the intervention arm and 398 to the usual care arm. Several methods of recruitment will be used in order to maximize the number of participants. Individuals aged 50 to 75 years will be screened with a risk tool (AUSDRISK) to detect those at high risk of developing T2DM. Those with existing diabetes will be excluded. Intervention participants will undergo anthropometric and laboratory tests, and comprehensive surveys at baseline, following the fourth group session (approximately three months after the commencement of the intervention) and 12 months after commencement of the intervention, while control participants will undergo testing at baseline and 12 months only. The intervention consists of an initial individual session followed by a series of five structured-group sessions. The first four group sessions will be carried out at two week intervals and the fifth session will occur eight months after the first group session. The intervention is based on the Health Action Process Approach (HAPA) model and sessions will empower and enable the participants to follow the five goals of the Life! program. Discussion This study will determine whether the effect of this intervention is larger than the effect of usual care in reducing central obesity and cardiovascular risk factors and thus the risk of developing diabetes and cardiovascular disease. Also it will evaluate how these two options compare economically. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12609000507280

2013-01-01

299

Treatment of asthma exacerbations with the human-powered nebuliser: a randomised parallel-group clinical trial.  

PubMed

Background:Nebulisers aid the treatment of respiratory diseases, including asthma, but they require electricity and are often cost-prohibitive for low- and middle-income countries.Aims:The aim of this study was to compare a low-cost, human-powered nebuliser compressor with an electric nebuliser compressor for the treatment of mild to moderate asthma exacerbations in adults and children.Methods:This was a non-blinded, parallel-group, equivalence study, with 110 subjects between 6 and 65 years of age, conducted in the emergency department of a district hospital in Ilopango, El Salvador. Participants were assigned by random allocation to receive a 2.5-mg dose of salbutamol from the experimental human-powered nebuliser or the electric nebuliser control. All assigned participants completed treatment and were included in analysis. The study was not blinded as this was clinically unfeasible; however, data analysis was blinded.Results:The mean improvement in peak flow of the experimental and control groups was 37.5 (95% confidence interval (CI) 26.7-48.2) l/min and 38.7 (95% CI, 26.1-51.3) l/min, respectively, with a mean difference of 1.3 (95% CI, -15.1 to 17.7) l/min. The mean improvement in percent-expected peak flow for the experimental and control groups was 12.3% (95% CI, 9.1-15.5%) and 13.8% (95% CI, 9.8-17.9%), respectively, with a mean difference of 1.5% (95% CI, -3.6 to 6.6%).Conclusions:The human-powered nebuliser compressor is equivalent to a standard nebuliser compressor for the treatment of mild-to-moderate asthma. (Funded by the Opus Dean's Fund, Marquette University College of Engineering; ClinicalTrials.gov NCT01795742.). PMID:24965834

Hallberg, Christopher J; Lysaught, M Therese; Najarro, René Antonio; Cea Gil, Fausto; Villatoro, Clara; Diaz de Uriarte, Ana Celia; Olson, Lars E

2014-01-01

300

Clinical trial participants' experiences of completing questionnaires: a qualitative study  

PubMed Central

Objectives To improve clinical study developments for elderly populations, we aim to understand how they transfer their experiences into validated, standardised self-completed study measurement instruments. We analysed how women (mean 78±8?years of age) participating in a randomised controlled trial (RCT) cognised study instruments used to evaluate outcomes of the intervention. Setting The interview study was nested in an RCT on chronic neck pain using common measurement instruments situated in an elderly community in Berlin, Germany, which comprised of units for independent and assisted-living options. Participants The sample (n=20 women) was selected from the RCT sample (n=117, 95% women, mean age 76 (SD±8)?years). Interview participants were selected using a purposive sampling list based on the RCT outcomes. Outcomes We asked participants about their experiences completing the RCT questionnaires. Interviews were analysed thematically, then compared with the questionnaires. Results Interviewees had difficulties in translating complex experiences into a single value on a scale and understanding the relationship of the questionnaires to study aims. Interviewees considered important for the trial that their actual experiences were understood by trial organisers. This information was not transferrable by means of the questionnaires. To rectify these difficulties, interviewees used strategies such as adding notes, adding response categories or skipping an item. Conclusions Elderly interview participants understood the importance of completing questionnaires for trial success. This led to strategies of completing the questionnaires that resulted in ‘missing’ or ambiguous data. To improve data collection in elderly populations, educational materials addressing the differential logics should be developed and tested. Pilot testing validated instruments using cognitive interviews may be particularly important in such populations. Finally, when the target of an intervention is a subjective experience, it seems important to create a method by which participants can convey their personal experiences. These could be nested qualitative studies. Trial registration number ISRCTN77108101807.

Holmberg, Christine; Karner, Julia J; Rappenecker, Julia; Witt, Claudia M

2014-01-01

301

The Counseling Older Adults to Control Hypertension (COACH) Trial: design and methodology of a group-based lifestyle intervention for hypertensive minority older adults  

PubMed Central

The disproportionately high prevalence of hypertension and its associated mortality and morbidity in minority older adults is a major public health concern in the United States. Despite compelling evidence supporting the beneficial effects of therapeutic lifestyle changes on blood pressure reduction, these approaches remain largely untested among minority elders in community-based settings. The Counseling Older Adults to Control Hypertension trial is a two-arm randomized controlled trial of 250 African-American and Latino seniors, 60 years and older with uncontrolled hypertension, who attend senior centers. The goal of the trial is to evaluate the effect of a therapeutic lifestyle intervention delivered via group classes and individual motivational interviewing sessions versus health education, on blood pressure reduction. The primary outcome is change in systolic and diastolic blood pressure from baseline to 12 months. The secondary outcomes are blood pressure control at 12 months; changes in levels of physical activity; body weight; and number of daily servings of fruits and vegetables from baseline to 12 months. The intervention group will receive 12 weekly group classes followed by individual motivational interviewing sessions. The health education group will receive an individual counseling session on healthy lifestyle changes and standard hypertension education materials. Findings from this study will provide needed information on the effectiveness of lifestyle interventions delivered in senior centers. Such information is crucial in order to develop implementation strategies for translation of evidence-based lifestyle interventions to senior centers, where many minority elders spend their time, making the centers a salient point of dissemination.

Ogedegbe, Gbenga; Fernandez, Senaida; Luerassi, Leanne; Silver, Stephanie A.; Kong, Jian; Midberry, Sara; de la Calle, Franze; Plumhoff, Jordan; Sethi, Sheba; Choudhury, Evelyn; Teresi, Jeanne A.

2013-01-01

302

Alcohol email assessment and feedback study dismantling effectiveness for university students (AMADEUS-1): study protocol for a randomized controlled trial  

PubMed Central

Background Alcohol causes huge problems for population health and for society, which require interventions with individuals as well as populations to prevent and reduce harms. Brief interventions can be effective and increasingly take advantage of the internet to reach high-risk groups such as students. The research literature on the effectiveness of online interventions is developing rapidly and is confronted by methodological challenges common to other areas of e-health including attrition and assessment reactivity and in the design of control conditions. Methods/design The study aim is to evaluate the effectiveness of a brief online intervention, employing a randomized controlled trial (RCT) design that takes account of baseline assessment reactivity, and other possible effects of the research process. Outcomes will be evaluated after 3?months both among student populations as a whole including for a randomized no contact control group and among those who are risky drinkers randomized to brief assessment and feedback (routine practice) or to brief assessment only. A three-arm parallel groups trial will also allow exploration of the magnitude of the feedback and assessment component effects. The trial will be undertaken simultaneously in 2 universities randomizing approximately 15,300 students who will all be blinded to trial participation. All participants will be offered routine practice intervention at the end of the study. Discussion This trial informs the development of routine service delivery in Swedish universities and more broadly contributes a new approach to the study of the effectiveness of online interventions in student populations, with relevance to behaviors other than alcohol consumption. The use of blinding and deception in this study raise ethical issues that warrant further attention. Trial registration ISRCTN28328154

2012-01-01

303

Acupuncture for functional dyspepsia: study protocol for a two-center, randomized controlled trial  

PubMed Central

Background Functional dyspepsia (FD) is a common health problem currently without any optimal treatments. Acupuncture has been traditionally sought as a treatment for FD. The aim of this study is to investigate whether acupuncture treatment helps improve symptoms of FD. Methods/design A two-center, randomized, waitlist-controlled trial will be carried out to evaluate whether acupuncture treatment improves FD symptoms. Seventy six participants aged 18 to 75 years with FD as diagnosed by Rome III criteria will be recruited from August 2013 to January 2014 at two Korean Medicine hospitals. They will be randomly allocated either into eight sessions of partially individualized acupuncture treatment over 4 weeks or a waitlist group. The acupuncture group will then be followed-up for 3 weeks with six telephone visits and a final visit will be paid at 8 weeks. The waitlist group will receive the identical acupuncture treatment after a 4-week waiting period. The primary outcome is the proportion of responders with adequate symptom relief and the secondary outcomes include Nepean dyspepsia index, EQ-5D, FD-related quality of life, Beck’s depression inventory, state-trait anxiety inventory questionnaire, and level of ghrelin hormone. The protocol was approved by the participating centers’ Institutional Review Boards. Discussion Results of this trial will help clarify not only whether the acupuncture treatment is beneficial for symptom improvement in FD patients but also to elucidate the related mechanisms of how acupuncture might work. Trial registration ClinicalTrials.gov Identifier: NCT01921504.

2014-01-01

304

Prospective, randomized trial of the biofragmentable anastomosis ring. The BAR Investigational Group.  

PubMed

A randomized trial was undertaken to compare the biofragmental anastomotic ring (BAR) with conventional intraperitoneal colorectal anastomotic techniques. Patients were randomized into one of two schemes: BAR versus sutured or BAR versus stapled anastomosis. There were 782 patients entered into the study and 283 patients (36%) had a sutured anastomosis, 104 patients (13%) had a stapled anastomosis, and 395 (51%) had the BAR. Comparison of the BAR with combined suture and stapled controls revealed no significant differences in wound complication, abscess rate, bleeding, anastomotic leaks, ileus, obstruction, or deaths. There were no differences in return of bowel function, return to normal diet, or hospital stay. Intraoperative difficulties occurred in 46 BAR patients (17%), and this was significantly higher (p less than 0.001) than for sutured (3%) but not for stapled anastomoses (11%). The occurrence of these problems did not adversely effect the outcome. The data suggest that the BAR is a safe, satisfactory alternative to sutured or stapled colorectal anastomoses. PMID:1987848

Bubrick, M P; Corman, M L; Cahill, C J; Hardy, T G; Nance, F C; Shatney, C H

1991-01-01

305

A clinical trial gone awry: the Chocolate Happiness Undergoing More Pleasantness (CHUMP) study  

PubMed Central

The randomized controlled trial is the “gold standard” for evaluating the benefits and harms of interventions. The Chocolate Happiness Undergoing More Pleasantness (CHUMP) study was designed to compare the effects of dark chocolate, milk chocolate and normal chocolate consumption on happiness. Although the intention-to-treat analysis showed that participants who received either dark or milk chocolate were happier than those who received no additional chocolate, the actual-consumption analysis showed that there were no differences between any of the groups. The reason for this result is that many participants switched groups mid-study because of their personal chocolate preferences. Although the CHUMP study was pleasurable, it demonstrated the difficulties associated with performing a truly blinded clinical trial.

Chan, Kevin

2007-01-01

306

A hhase I/II trial to evaluate three-dimensional conformal radiation therapy confined to the region of the lumpectomy cavity for Stage I/II breast carcinoma: Initial report of feasibility and reproducibility of Radiation Therapy Oncology Group (RTOG) Study 0319  

SciTech Connect

Background: This prospective study (Radiation Therapy Oncology Group Study 0319) examines the use of three-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Reproducibility, as measured by technical feasibility, was the primary end point with the goal of demonstrating whether the technique is widely applicable in a multicenter setting before a Phase III trial is undertaken. Methods and Materials: This study was designed such that if fewer than 5 cases out of the first 42 patients evaluable were scored as unacceptable, the treatment would be considered reproducible. Patients received 38.5 Gy in 3.85 Gy/fraction delivered twice daily. The clinical target volume included the lumpectomy cavity plus a 10-15-mm margin bounded by 5 mm within the skin surface and the lung-chest wall interface. The planning target volume (PTV) included the clinical target volume plus a 10-mm margin. Treatment plans were judged as follows: (1) No variations (total coverage), 95% isodose surface covers 100% of the PTV and all specified critical normal tissue dose-volume histogram (DVH) limits met. (2) Minor variation (marginal coverage), 95% isodose surface covers between {>=}95% and <100% of the PTV. No portion of PTV receives <93% of prescription (isocenter) dose. All specified critical normal tissue DVH limits fall within 5% of the guidelines. (3) Major variation (miss), 95% isodose surface covers <95% of the PTV. Portion of PTV receives <93% of prescription isocenter dose. Any critical normal tissue DVH limit exceeds 5% of the specified value. Results: A total of 58 patients were enrolled on this study between 8/15/03 and 4/30/04, 5 of whom were ineligible or did not receive protocol treatment. Two additional patients were excluded, one because the on-study form was not submitted, and the other because no treatment planning material was submitted. This primary end point analysis is based on the first 42 (out of 51) evaluable patients, which were accrued from 17 different institutions (31 centers were credentialed for case enrollment, but because of rapid accrual, not all centers were able to submit cases before trial closure). These 42 patients had the following characteristics: median age was 61 years; 48% had a maximum tumor dimension of <1 cm; 86% had invasive ductal carcinoma; 64% were postmenopausal; the location of tumor was upper outer for 40% and upper central for 21%; 79% had no chemotherapy, and 64% had no hormonal therapy. There were 4 cases with major variations (all 4 related to normal tissue DVHs exceeding 5% of the specified limit). A total of 32 cases with minor variations in treatment plans were detected (16 related to normal tissue DVHs exceeding the specified limits [by {<=}5%], 6 related to suboptimal coverage of the PTV, and 10 related to both). There were 6 cases with no variations. Of the 51 total evaluable patients, 1 additional major variation was noted (PTV receiving <93% of the prescription dose). An additional 5 cases with minor variations in treatment plans were detected (3 related to normal tissue DVHs exceeding the specified limits [by {<=}5%], 1 related to suboptimal coverage of the PTV, and 1 related to both). There were 3 more cases with no variations. Conclusion: Accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy was shown in this preliminary analysis of the first 42 evaluable patients to be technically feasible and reproducible in a multi-institutional trial using exceptionally strict dosimetric criteria.

Vicini, Frank [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States)]. E-mail: fvicini@beaumont.edu; Winter, Kathryn M.S. [Department of Statistics, Radiation Therapy Oncology Group (RTOG), Philadelphia, PA (United States); Straube, William [Department of Radiation Oncology, Washington University, St. Louis, MO (United States); Wong, John [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Pass, Helen [Department of Surgery, William Beaumont Hospital, Royal Oak, MI (United States); Rabinovitch, Rachel [University of Colorado Health Sciences Center, Denver, CO (United States); Chafe, Susan [Cross Cancer Institute, University of Alberta, Edmonton, Alberta (Canada); Arthur, Douglas [Virginia Commonwealth University Medical Center, Richmond, VA (United States); Petersen, Ivy [Mayo Clinic, Rochester, MN (United States); McCormick, Beryl [Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

2005-12-01

307

Report of the Public Cryptography Study Group.  

ERIC Educational Resources Information Center

Concerns of the National Security Agency (NSA) that information contained in some articles about cryptography in learned and professional journals and in monographs might be inimical to the national security are addressed. The Public Cryptography Study Group, with one dissenting opinion, recommends that a voluntary system of prior review of…

American Council on Education, Washington, DC.

308

Permissive underfeeding versus target enteral feeding in adult critically ill patients (PermiT Trial): a study protocol of a multicenter randomized controlled trial  

PubMed Central

Background Nutritional support is an essential part of the management of critically ill patients. However, optimal caloric intake has not been systematically evaluated. We aim to compare two strategies of enteral feeding: permissive underfeeding versus target feeding. Method/Design This is an international multi-center randomized controlled trial in critically ill medical- surgical adult patients. Using a centralized allocation, 862 patients will be randomized to permissive underfeeding or target feeding. Patients in the permissive group receive 50% (acceptable range is 40% to 60%) of the calculated caloric requirement, while those in the targeted group receive 100% (acceptable range 70% to 100%) of the calculated caloric requirement. The primary outcome is 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, 28-day, and 180-day mortality as well as health care-associated infections, organ failure, and length of stay in the ICU and hospital. The trial has 80% power to detect an 8% absolute reduction in 90-day mortality assuming a baseline risk of death of 25% at an alpha level of 0.05. Discussion Patient recruitment started in November 2009 and is currently active in five centers. The Data Monitoring Committee advised continuation of the trial after the first interim analysis. The study is expected to finish by November 2013. Trial registration Current Controlled Trials ISRCTN68144998

2012-01-01

309

PREVENTion of a parastomal hernia with a prosthetic mesh in patients undergoing permanent end-colostomy; the PREVENT-trial: study protocol for a multicenter randomized controlled trial  

PubMed Central

Background Parastomal hernia is a common complication of a colostomy. Ultimately, one-third of patients with a parastomal hernia will need surgical correction due to frequent leakage or life-threatening bowel obstruction or strangulation. However, treatment remains a challenge resulting in high recurrence rates. Two single center trials demonstrated that the frequency of parastomal hernias decreases by prophylactic placement of a mesh around the stoma at the time of formation. Unfortunately, both studies were small-sized, single-center studies and with these small numbers less common complications could be missed which were the reasons to initiate a prospective randomized multicenter trial to determine if a retromuscular, preperitoneal mesh at the stoma site prevents parastomal hernia and does not cause unacceptable complications. Methods One hundred and fifty patients undergoing open procedure, elective formation of a permanent end-colostomy will be randomized into two groups. In the intervention group an end-colostomy is created with placement of a preperitioneal, retromuscular lightweight monofilament polypropylene mesh, and compared to a group with a traditional stoma without mesh. Patients will be recruited from 14 teaching hospitals in the Netherlands during a 2-year period. Primary endpoint is the incidence of parastomal hernia. Secondary endpoints are stoma complications, cost-effectiveness, and quality of life. Follow-up will be performed at 3 weeks, 3 months and at 1, 2, and 5 years. To find a difference of 20% with a power of 90%, a total number of 134 patients must be included. All results will be reported according to the CONSORT 2010 statement. Discussion The PREVENT-trial is a multicenter randomized controlled trial powered to determine whether prophylactic placement of a polypropylene mesh decreases the incidence of a parastomal hernia versus the traditional stoma formation without a mesh. Trial registration The PREVENT-trial is registered at: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2018

2012-01-01

310

Mindfulness and Acceptance-Based Group Therapy for Social Anxiety Disorder: An Open Trial  

Microsoft Academic Search

Mindfulness and Acceptance-Based Group Therapy (MAGT) for Social Anxiety Disorder (SAD) is based largely on Acceptance and Commitment Therapy (ACT; Hayes et al., 1999), with enhanced mindfulness mostly from Mindfulness-Based Cognitive Therapy (MBCT; Segal et al., 2002). The purpose of this study was to assess the feasibility and initial effectiveness of MAGT for the treatment of SAD. Forty-two SAD patients

Nancy L. Kocovski; Jan E. Fleming; Neil A. Rector

2009-01-01

311

The prognostic and predictive value of mRNA expression of vascular endothelial growth factor family members in breast cancer: a study in primary tumors of high-risk early breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial  

PubMed Central

Introduction The main prognostic variables in early breast cancer are tumor size, histological grade, estrogen receptor/progesterone receptor (ER/PgR) status, number of positive nodes and human epidermal growth factor receptor 2 (HER2) status. The present study evaluated the prognostic and/or predictive value of vascular endothelial growth factor (VEGF) family members in high-risk early breast cancer patients treated with adjuvant chemo-hormonotherapy. Methods RNA was isolated from 308 formalin-fixed paraffin-embedded primary tumor samples from breast cancer patients enrolled in the HE10/97 trial, evaluating adjuvant dose-dense sequential chemotherapy with epirubicin followed by cyclophosphamide, methotrexate, fluorouracil (CMF) with or without paclitaxel (E-T-CMF versus E-CMF). A fully automated method based on magnetic beads was applied for RNA extraction, followed by one-step quantitative RT-PCR for mRNA analysis of VEGF-A, -B, -C and vascular endothelial growth factor receptor (VEGFR) 1, 2, 3. Results With a median follow-up of 8 years, 109 patients (35%) developed a relapse and 80 patients (26%) died. In high VEGF-C and VEGFR1 mRNA expressing tumors, ER/PgR-negative tumors (Fisher's exact test, P = 0.001 and P = 0.021, respectively) and HER2-positive tumors (P <0.001 and P = 0.028, respectively) were more frequent than in low VEGF-C and VEGFR1 expressing tumors, respectively. From the VEGF family members evaluated, high VEGFR1 mRNA expression (above the 75th percentile) emerged as a significant negative prognostic factor for overall survival (OS; hazard ratio (HR) = 1.60, 95% confidence interval (CI): 1.01 to 2.55, Wald's P = 0.047) and disease-free survival (DFS; HR = 1.67, 95% CI: 1.13 to 2.48, P = 0.010), when adjusting for treatment group. High VEGF-C mRNA expression was predictive for benefit from adjuvant treatment with paclitaxel (E-T-CMF arm) for OS (test for interaction, Wald's P = 0.038), while in multivariate analysis the interaction of VEGF-C with taxane treatment was significant for both OS (Wald's P = 0.019) and DFS (P = 0.041) and continuous VEGF-B mRNA expression values for OS (P = 0.019). Conclusions The present study reports, for the first time, that VEGF-C mRNA overexpression, as assessed by qRT-PCR, has a strong predictive value in high-risk early breast cancer patients undergoing adjuvant paclitaxel-containing treatment. Further studies are warranted to validate the prognostic and/or predictive value of VEGF-B, VEGF-C and VEGFR1 in patients treated with adjuvant therapies and to reveal which members of the VEGF family could possibly be useful markers in identifying patients who will benefit most from anti-VEGF strategies. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12611000506998

2012-01-01

312

Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin Lymphoma Study Group  

Microsoft Academic Search

To determine prognostic factors and treat- ment outcome, patients with primary pro- gressive Hodgkin lymphoma (HD) regis- tered in the database of the German Hodgkin Lymphoma Study Group (GHSG) were analyzed retrospectively. Detailed records from randomized prospective multicenter trials performed between 1988 and 1998 of 3807 patients recruited in these trials were reviewed. The median age of the 206 patients

Andreas Josting; Ulrich Rueffer; Jeremy Franklin; Markus Sieber; Volker Diehl; Andreas Engert

2000-01-01

313

Combined treatment with Dif1stat and diet reduce plasma lipid indicators of moderate hypercholesterolemia more effectively than diet alone: a randomized trial in parallel groups.  

PubMed

An open-labeled randomized trial with parallel groups was carried out to study the effects of Dif1stat (Monascus purpureus-Linear aliphatic alcohols-Niacin) in the treatment of primary moderate hypercholesterolemia. The trial lasted 8 months. The patients, males and females, were assigned to two groups: A (#130), treated with diet, and B (#110) submitted to diet + Dif1stat. After 4 months, group A did not show significant changes in Total cholesterol (TC), LDL-cholesterol (LDLC), HDL-cholesterol (HDLC) or non-HDL-cholesterol (non-HDLC). The same group, showed a reduction in TC (-22%), LDLC (-30%) and non-HDLC (-27%) after 8 months (P < or = 0.001). After 4 months, TC (-21.3%), LDLC (-29%), and non-HDLC (-26%) were significantly lowered in group B (P < or = 0.001). In group B, TC, LDLC and non-HDLC showed a further reduction after 8 months: -29.4, -38 and -37%, respectively (P < or = 0.001). Even triglycerides (TG) decreased significantly (-33%) (P < or = 0.001). After 8 months, group B showed a significant reduction of TG (-33%) (P < or = 0.001), when compared to group A. Some safety parameters were significantly reduced in both groups: AST and gamma-GT in group A after 4 and 8 months, as well as ALT, AST and gamma-GT in group B after 8 months (P < or = 0.001). Dif1stat, given with a suitable diet, was well tolerated in the long-term and induced an anti-atherogenic plasma lipid and lipoprotein profile, in patients with moderate hypercholesterolemia. PMID:19911216

Stefanutti, Claudia; Mazza, Fabio; Vivenzio, Antonio; Di Giacomo, Serafina; Perrone, Giuseppina; Serra, Mariarosaria; Bucci, Antonello

2009-12-01

314

Presentation of continuous outcomes in randomised trials: an observational study  

PubMed Central

Objective To characterise the percentage of available outcome data being presented in reports of randomised clinical trials with continuous outcome measures, thereby determining the potential for incomplete reporting bias. Design Descriptive cross sectional study. Data sources A random sample of 200 randomised trials from issues of 20 medical journals in a variety of specialties during 2007–09. Main outcome measures For each paper’s best reported primary outcome, we calculated the fraction of data reported using explicit scoring rules. For example, a two arm trial with 100 patients per limb that reported 2 sample sizes, 2 means, and 2 standard deviations reported 6/200 data elements (1.5%), but if that paper included a scatterplot with 200 points it would score 200/200 (100%). We also assessed compliance with 2001 CONSORT items about the reporting of results. Results The median percentage of data reported for the best reported continuous outcome was 9% (interquartile range 3–26%) but only 3.5% (3–7%) when we adjusted studies to 100 patients per arm to control for varying study size; 17% of articles showed 100% of the data. Tables were the predominant means of presenting the most data (59% of articles), but papers that used figures reported a higher proportion of data. There was substantial heterogeneity among journals with respect to our primary outcome and CONSORT compliance. Limitations We studied continuous outcomes of randomised trials in higher impact journals. Results may not apply to categorical outcomes, other study designs, or other journals. Conclusions Trialists present only a small fraction of available data. This paucity of data may increase the potential for incomplete reporting bias, a failure to present all relevant information about a study’s findings.

2012-01-01

315

Prednisolone and acupuncture in Bell's palsy: study protocol for a randomized, controlled trial  

PubMed Central

Background There are a variety of treatment options for Bell's palsy. Evidence from randomized controlled trials indicates corticosteroids can be used as a proven therapy for Bell's palsy. Acupuncture is one of the most commonly used methods to treat Bell's palsy in China. Recent studies suggest that staging treatment is more suitable for Bell's palsy, according to different path-stages of this disease. The aim of this study is to compare the effects of prednisolone and staging acupuncture in the recovery of the affected facial nerve, and to verify whether prednisolone in combination with staging acupuncture is more effective than prednisolone alone for Bell's palsy in a large number of patients. Methods/Design In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with prednisolone and/or acupuncture. In total, 1200 patients aged 18 to 75 years within 72 h of onset of acute, unilateral, peripheral facial palsy will be assessed. There are six treatment groups, with four treated according to different path-stages and two not. These patients are randomly assigned to be in one of the following six treatment groups, i.e. 1) placebo prednisolone group, 2) prednisolone group, 3) placebo prednisolone plus acute stage acupuncture group, 4) prednisolone plus acute stage acupuncture group, 5) placebo prednisolone plus resting stage acupuncture group, 6) prednisolone plus resting stage acupuncture group. The primary outcome is the time to complete recovery of facial function, assessed by Sunnybrook system and House-Brackmann scale. The secondary outcomes include the incidence of ipsilateral pain in the early stage of palsy (and the duration of this pain), the proportion of patients with severe pain, the occurrence of synkinesis, facial spasm or contracture, and the severity of residual facial symptoms during the study period. Discussion The result of this trial will assess the efficacy of using prednisolone and staging acupuncture to treat Bell's palsy, and to determine a best combination therapy with prednisolone and acupuncture for treating Bell's palsy. Trial Registration ClinicalTrials.gov: NCT01201642

2011-01-01

316

A new statistical procedure for testing equivalence in two-group comparative bioavailability trials  

Microsoft Academic Search

The clinical problem of testing for equivalence in comparative bioavailability trials is restated in terms of the proper statistical hypotheses. A simple t-test procedure for these hypotheses has been devloped that is more powerful than the methods based on usual (shortest) and symmetric confidence intervals. In this note, this new procedure is explained and an example is given, including the

Walter W. Hauck; Sharon Anderson

1984-01-01

317

A Controlled Trial of Active versus Passive Learning Strategies in a Large Group Setting  

ERIC Educational Resources Information Center

Objective: To compare the effects of active and didactic teaching strategies on learning- and process-oriented outcomes. Design: Controlled trial. Setting: After-hours residents' teaching session. Participants: Family and Community Medicine, Internal Medicine, and Pediatrics residents at two academic medical institutions. Interventions: We…

Haidet, Paul; Morgan, Robert O.; O'Malley, Kimberly; Moran, Betty Jeanne; Richards, Boyd F.

2004-01-01

318

Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials. Advanced Ovarian Cancer Trialists Group.  

PubMed Central

OBJECTIVES--To consider the role of platinum and the relative merits of single agent and combination chemotherapy in the treatment of advanced ovarian cancer. DESIGN--Formal quantitative overview using updated individual patient data from all available randomised trials (published and unpublished). SUBJECTS--8139 patients (6408 deaths) included in 45 different trials. RESULTS--No firm conclusions could be reached. Nevertheless, the results suggest that in terms of survival immediate platinum based treatment was better than non-platinum regimens (overall relative risk 0.93; 95% confidence interval 0.83 to 1.05); platinum in combination was better than single agent platinum when used in the same dose (overall relative risk 0.85; 0.72 to 1.00); and cisplatin and carboplatin were equally effective (overall relative risk 1.05; 0.94 to 1.18). CONCLUSIONS--In the past, randomised clinical trials of chemotherapy in advanced ovarian cancer have been much too small to detect the degree of benefit which this overview suggests is realistic for currently available chemotherapeutic regimens. Hence a new trial comparing cisplatin, doxorubicin, and cyclophosphamide (CAP) with carboplatin has been launched and plans to accrue 2000 patients.

1991-01-01

319

Study protocol of Prednisone in episodic Cluster Headache (PredCH): a randomized, double-blind, placebo-controlled parallel group trial to evaluate the efficacy and safety of oral prednisone as an add-on therapy in the prophylactic treatment of episodic cluster headache with verapamil  

PubMed Central

Background Episodic cluster headache (ECH) is a primary headache disorder that severely impairs patient’s quality of life. First-line therapy in the initiation of a prophylactic treatment is verapamil. Due to its delayed onset of efficacy and the necessary slow titration of dosage for tolerability reasons prednisone is frequently added by clinicians to the initial prophylactic treatment of a cluster episode. This treatment strategy is thought to effectively reduce the number and intensity of cluster attacks in the beginning of a cluster episode (before verapamil is effective). This study will assess the efficacy and safety of oral prednisone as an add-on therapy to verapamil and compare it to a monotherapy with verapamil in the initial prophylactic treatment of a cluster episode. Methods and design PredCH is a prospective, randomized, double-blind, placebo-controlled trial with parallel study arms. Eligible patients with episodic cluster headache will be randomized to a treatment intervention with prednisone or a placebo arm. The multi-center trial will be conducted in eight German headache clinics that specialize in the treatment of ECH. Discussion PredCH is designed to assess whether oral prednisone added to first-line agent verapamil helps reduce the number and intensity of cluster attacks in the beginning of a cluster episode as compared to monotherapy with verapamil. Trial registration German Clinical Trials Register DRKS00004716

2013-01-01

320

Cardiac Home Education and Support Trial (CHEST): A pilot study  

PubMed Central

BACKGROUND: Coronary artery bypass graft (CABG) surgery is performed more frequently in individuals who are older and sicker than in previous years. Increased patient acuity and reduced hospital length of stays leave individuals ill prepared for their recovery. OBJECTIVES: To test the feasibility of a peer support program and determine indicators of the effects of peer support on recovery outcomes of individuals following CABG surgery. METHODS AND RESULTS: A pre-post test pilot randomized clinical trial design enrolled men and women undergoing first-time nonemergency CABG surgery at a single site in Ontario. Patients were randomly assigned to either usual care or peer support. Patients allocated to usual care (n=50) received standard preoperative and postoperative education. Patients in the peer support group (n=45) received individualized education and support via telephone from trained cardiac surgery peer volunteers for eight weeks following hospital discharge. Most (93%) peer volunteers believed they were prepared for their role, with 98% of peer volunteers initiating calls within 72 h of the patient’s discharge. Peer volunteers made an average of 12 calls, less than 30 min in duration over the eight-week recovery period. Patients were satisfied with their peer support (n=45, 98%). The intervention group reported statistical trends toward improved physical function (physical component score) (t [89]=?1.6; P=0.12) role function (t [93]=?1.9; P=0.06), less pain (t [93]=1.30; P=0.20) and improved cardiac rehabilitation enrollment (?2=2.50, P=0.11). CONCLUSIONS: These preliminary results suggest that peer support may improve recovery outcomes following CABG. Data from the present pilot trial also indicate that a home-based peer support intervention is feasible and an adequately powered trial should be conducted.

Parry, Monica; Watt-Watson, Judy; Hodnett, Ellen; Tranmer, Joan; Dennis, Cindy-Lee; Brooks, Dina

2009-01-01

321

Effective Group Training for Patients with Unexplained Physical Symptoms: A Randomized Controlled Trial with a Non-Randomized One-Year Follow-Up  

PubMed Central

Background Although cognitive-behavioral therapy for Unexplained Physical Symptoms (UPS) is effective in secondary care, studies done in primary care produced implementation problems and conflicting results. We evaluated the effectiveness of a cognitive-behavioral group training tailored to primary care patients and provided by a secondary community mental-health service reaching out into primary care. Methodology/Principal Findings The effectiveness of this training was explored in a randomized controlled trial. In this trial, 162 patients with UPS classified as undifferentiated somatoform disorder or as chronic pain disorder were randomized either to the training or a waiting list. Both lasted 13 weeks. The preservation of the training's effect was analyzed in non-randomized follow-ups, for which the waiting group started the training after the waiting period. All patients attended the training were followed-up after three months and again after one year. The primary outcomes were the physical and the mental summary scales of the SF-36. Secondary outcomes were the other SF-36-scales and the SCL-90-R. The courses of the training's effects in the randomized controlled trial and the follow-ups were analyzed with linear mixed modeling. In the randomized controlled trial, the training had a significantly positive effect on the quality of life in the physical domain (Cohen's d?=?0.38;p?=?.002), but this overall effect was not found in the mental domain. Regarding the secondary outcomes, the training resulted in reporting an improved physical (Cohen's d?=?0.43;p?=?0.01), emotional (Cohen's d?=?0.44;p?=?.0.01), and social (Cohen's d?=?0.36;p?=?0.01) functioning, less pain and better functioning despite pain (Cohen's d?=?0.51;p?=?<0.001), less physical symptoms (Cohen's d?=??.23;p?=?0.05) and less sleep difficulties (Cohen's d?=??0.25;p?=?0.04) than time in the waiting group. During the non-randomized follow-ups, there were no relapses. Conclusions/Significance The cognitive-behavioral group training tailored for UPS in primary care and provided by an outreaching secondary mental-health service appears to be effective and to broaden the accessibility of treatment for UPS. Trial Registration TrialRegister.nl NTR1609

Zonneveld, Lyonne N. L.; van Rood, Yanda R.; Timman, Reinier; Kooiman, Cornelis G.; van't Spijker, Adriaan; Busschbach, Jan J. V.

2012-01-01

322

A traditional Chinese medicine versus Western combination therapy in the treatment of rheumatoid arthritis: two-stage study protocol for a randomized controlled trial  

PubMed Central

Background The common randomized controlled trial design has distinct limitations when applied to Chinese medicine, because Chinese medicine identifies and treats 'Chinese medicine patterns' rather than diagnosed diseases. Chinese medicine patterns are a group of associated symptoms, tongue appearances and pulse characteristics. These limitations could be overcome by developing new strategies to evaluate the effect of Chinese medicine. The idea behind pattern-based efficacy evaluations may optimize clinical trial design by identifying the responsiveness-related Chinese medicine patterns. Methods/Design This is a two-stage multi-center trial of Chinese herbal medicine for the management of rheumatoid arthritis. The stage one trial is an open-label trial and aims to explore what groups of Chinese medicine information (such as symptoms) correlates with better efficacy, and the stage two trial is a randomized, controlled, double-blind, double-dummy clinical trial that incorporates the efficacy-related information identified in the stage-one trial into the inclusion criteria. Discussion The indication of a Chinese herbal formula is a specific Chinese medicine pattern and not a single disease and stratifying a disease into several patterns with a group of symptoms is a feasible procedure in clinical trials. This study is the first to investigate whether this approach in the design of Chinese herbal medicine trials can improve responses. Trial registration ChiCTR-TRC-10000989

2011-01-01

323

When Research Meets Reality--Lessons Learned From a Pragmatic Multisite Group-Randomized Clinical Trial on Psychosocial Interventions in the Psychiatric and Addiction Field  

PubMed Central

Research on treatments for patients with co-occurring psychiatric and substance use disorders is of core importance and at the same time highly challenging as it includes patients that are normally excluded from clinical studies. Such research may require methodological adaptations which in turn create new challenges. However, the challenges that arise in such studies are insufficiently discussed in the literature. The aim of this methodology paper is, firstly, to discuss the methodological adaptations that may be required in such research; secondly, to describe how such adaptations created new challenges in a group-randomized clinical trial on Integrated Treatment amongst patients with co-occurring psychiatric and substance use disorders. We also discuss how these challenges might be understood and highlight lessons for future research in this field. Trial registration NCT00447733.

Wusthoff, Linda E.; Waal, Helge; Grawe, Rolf W.

2012-01-01

324

Study protocol: A cluster randomised controlled trial of implementation intentions to reduce smoking initiation in adolescents  

PubMed Central

Background The current literature suggests that forming implementation intentions (simple ‘if-then’ plans) about how to refuse the offer of a cigarette may be an effective intervention to reduce smoking initiation in adolescents. This study is a pragmatic trial to test the effectiveness and cost-effectiveness of such an intervention in reducing smoking initiation in a sample of UK adolescents. Methods/Design A cluster randomised controlled trial with at least 36 schools randomised to receive an implementation intention intervention targeting reducing smoking initiation (intervention group) or increasing homework (control group). Interventions will be conducted at the classroom level and be repeated every six months for four years (eight interventions). Objectively assessed (carbon monoxide monitor) and self-reported smoking plus smoking related cognitions (e.g., smoking intentions, attitudes, norms and self-efficacy) will be assessed at baseline and 12, 24, 36 and 48 months post baseline. Objectively assessed smoking at 48 months post baseline will be the primary outcome variable. Health economic analyses will assess life years gained. Discussion The results of the trial will provide information on the impact of a repeated implementation intention for refusing offers of cigarettes on rates of smoking initiation in adolescents. Trial registration ISRCTN27596806

2013-01-01

325

Renal sympathetic denervation versus antiarrhythmic drugs for drug-resistant hypertension and symptomatic atrial fibrillation (RSDforAF) trial: study protocol for a randomized controlled trial  

PubMed Central

Background Recently, catheter-based renal sympathetic denervation (RSD) has been verified to be safely used to substantially reduce the levels of blood pressure, left ventricular hypertrophy, sleep apnea severity and norepinephrine spillover, and improve glucose tolerance. All these pathological changes are recognized as independent risk factors for the development and recurrence of atrial fibrillation (AF). A randomized, single-blind, parallel-control, multicenter clinical trial is being conducted to compare RSD with antiarrhythmic drugs (AAD) in patients with drug-resistant hypertension and symptomatic AF (RSDforAF trial). Methods/design Patients with drug-resistant hypertension and symptomatic AF will be randomized to RSD and the drug treatment groups. Patients will be followed for 12 months until study closure. Up to 200 patients may be enrolled in six medical centers in China. The primary objective is to study the effects of RSD on AF burden and blood pressure in patients with hypertension and symptomatic AF. Discussion RSDforAF trial will test the hypothesis that RSD is superior to AAD in reducing AF burden and blood pressure in patients with drug-resistant hypertension and symptomatic AF. Trial registration ClinicalTrials.gov, NCT01713270

2013-01-01

326

How to Improve the Implementation of Academic Clinical Pediatric Trials Involving Drug Therapy? A Qualitative Study of Multiple Stakeholders  

PubMed Central

Objective The need for encouraging pediatric drug research is widely recognized. However, hospital-based clinical trials of drug treatments are extremely time-consuming, and delays in trial implementation are common. The objective of this qualitative study was to collect information on the perceptions and experience of health professionals involved in hospital-based pediatric drug trials. Methods Two independent researchers conducted in-depth semi-structured interviews with principal investigators (n?=?17), pharmacists (n?=?7), sponsor representatives (n?=?4), and drug regulatory agency representatives (n?=?3) who participated in institutionally sponsored clinical trials of experimental drugs in pediatric patients between 2002 and 2008. Results Dissatisfaction was reported by 67% (16/24) of principal investigators and pharmacists: all 7 pharmacists felt they were involved too late in the trial implementation process, whereas 11 (65%) principal investigators complained of an excessive regulatory burden and felt they were insufficiently involved in the basic research questions. Both groups perceived clinical trial implementation as burdensome and time-consuming. The sponsor and regulatory agency representatives reported a number of difficulties but were not dissatisfied. Conclusions The heavy burden related to regulatory requirements, and suboptimal communication across disciplines involved, seem to be the main reasons for the major delays in pediatric drug trial implementation. The pharmaceutical aspects are intrinsically tied to trial methodology and implementation and must therefore be examined, in particular by involving Clinical Research Pharmacists at early stages of study conception.

Girard, Delphine; Bourdon, Olivier; Abdoul, Hendy; Prot-Labarthe, Sonia; Brion, Francoise; Tibi, Annick; Alberti, Corinne

2013-01-01

327

The effectiveness of a stratified group intervention using the STarTBack screening tool in patients with LBP - a non randomised controlled trial  

PubMed Central

Background Low back pain (LBP) is costly to society and improving patient outcomes is a priority. Stratifying LBP patients into more homogenous groups is advocated to improve patient outcome. The STarT Back tool, a prognostic screening tool has demonstrated efficacy and greater cost effectiveness in physiotherapy settings. The management of LBP patients in groups is common but to date the utility of the STarT Back tool in group settings has not been explored. The aim of this study is to determine if the implementation of ‘stratified care’ when delivered in a group setting will lead to significantly better physical and psychological outcomes and greater cost effectiveness in LBP patients compared to a bestcare historical control group. Methods/Design This study is a non randomised controlled trial. Low back pain patients recruited from the Waterford Primary Care area (population = 47,000) will be stratified into low, medium or high risk of persisting symptoms using the STarT Back Tool. Low risk patients will be offered a single one off education/exercise class offering positive messages on LBP management in line with recommended guidelines. Medium risk patients will be offered a 12 week group exercise/education intervention addressing their dominant physical obstacles to recovery. A 12 week group cognitive behavioural approach will be delivered to the high risk patients, characterised by the presence of high levels of psychosocial prognostic factors. These patients will be compared with a historical control group where therapists were blinded as to the risk stratification of patients and a generic group intervention was delivered to all patients, irrespective of their initial risk stratification. The primary outcome measure will be disability (Roland Morris Disability Questionnaire). Secondary outcomes will include back pain intensity (Visual Analogue Scale), distress (Distress and Risk Assessment Method), back beliefs (Back Beliefs Questionnaire), health status (Euroqol), global benefit (7 point likert scale), satisfaction (7 point likert scale), cost effectiveness and functional status. Outcome will be measured at baseline, 12 weeks and 6 months. Discussion This paper details the rationale, design, methods, planned analysis and operational aspects of a study examining the utility of the STarT Back Tool as a ‘stratification tool for targeted treatment’ in a group intervention. Trial registration Current controlled trials: ACTRN12613000431729.

2013-01-01

328

Increasing Adherence to Obstructive Sleep Apnea Treatment with a Group Social Cognitive Therapy Treatment Intervention: A Randomized Trial  

PubMed Central

Objective: To examine whether a social cognitive therapy (SCT) intervention increases continuous positive airway pressure (CPAP) use compared to equivalent social interaction (SI) time. Participants: Individuals with obstructive sleep apnea (OSA) referred for CPAP therapy. Intervention: Participants received a 30-min group education session regarding OSA and CPAP. Groups of three to four participants were then randomly assigned to an SCT session or social interaction. Measurements: CPAP usage was assessed at 7 nights, then 1, 3, and 6 months. The two primary outcomes were adherence, usage ? 4 h per night at 6 months, and uptake of CPAP. Questionnaires were given pretreatment and posttreatment. Results: Two hundred six individuals were randomized to SI (n = 97) or SCT (n = 109). CPAP uptake was not different between groups (82% in SI, 88% in SCT groups, P = 0.35). There were no differences between groups in adherence: 63-66% at 1 week, and at 6 months 55-47% (P = 0.36). Higher pretreatment apnea-hypopnea index, higher baseline self-efficacy, and use of CPAP (? 4 h) at 1 week were independent predictors of CPAP adherence at 6 months. CPAP adherence increased by a factor of 1.8 (odds ratio = 1.8, 95% confidence interval 1.1-3.0) for every one-unit increase in self-efficacy. There was no difference between groups postintervention in self-efficacy scores, sleepiness, mood, or sleep quality. Conclusions: In this randomized trial, a single SCT application did not increase adherence when compared with SI time. Although self-efficacy scores prior to CPAP predicted adherence, self-efficacy was not increased by the interventions. Increasing intensity and understanding of SCT interventions may be needed to improve CPAP adherence. Clinical Trials Registration: Australian New Zealand Clinical Trials Registry, ACTRN12607000424404. Citation: Bartlett D; Wong K; Richards D; Moy E; Espie CA; Cistulli PA; Grunstein R. Increasing adherence to obstructive sleep apnea treatment with a group social cognitive therapy treatment intervention: a randomized trial. SLEEP 2013;36(11):1647-1654.

Bartlett, Delwyn; Wong, Keith; Richards, Dianne; Moy, Emma; Espie, Colin A.; Cistulli, Peter A.; Grunstein, Ronald

2013-01-01

329

Methyl group tunnelling studies in calixarenes  

NASA Astrophysics Data System (ADS)

Inelastic neutron scattering has been used to study the tunnelling of methyl groups belonging to several guest molecules (toluene, p-xylene, ?-picoline) incarcerated in a host calixarene matrix. In all the cases investigated, the low temperature neutron spectra show a number of bands which may be interpreted as being due to transitions between tunnel-split librational states of the guest methyl groups. The main line occurs near 0.63meV, very close to the CH 3 quantum free rotor limit. In the toluence complex, the quantum regime persists at least up to 60 K. Effects of coupling between rotational and vibrational modes are discussed. Very subtle structural changes not revealed by diffraction measurements are suggested by the neutron spectroscopy results.

Caciuffo, R.; Amoretti, G.; Carlile, C. J.; Fillaux, F.; Francescangeli, O.; Prager, M.; Ugozzoli, F.

1994-10-01

330

An equivalence evaluation of a nurse-moderated group-based internet support program for new mothers versus standard care: a pragmatic preference randomised controlled trial  

PubMed Central

Background All mothers in South Australia are offered a clinic or home-visit by a Child and Family Health community nurse in the initial postnatal weeks. Subsequent support is available on request from staff in community clinics and from a telephone helpline. The aim of the present study is to compare equivalence of a single clinic-based appointment plus a nurse-moderated group-based internet intervention when infants were aged 0–6 months versus a single home-visit together with subsequent standard services (the latter support was available to mothers in both study groups). Methods/Design The evaluation utilised a pragmatic preference randomised trial comparing the equivalence of outcomes for mothers and infants across the two study groups. Eligible mothers were those whose services were provided by nurses working in one of six community clinics in the metropolitan region of Adelaide. Mothers were excluded if they did not have internet access, required an interpreter, or their nurse clinician recommended that they not participate due to issues such as domestic violence or substance abuse. Randomisation was based on the service identification number sequentially assigned to infants when referred to the Child and Family Health Services from birthing units (this was done by administrative staff who had no involvement in recruiting mothers, delivering the intervention, or analyzing results for the study). Consistent with design and power calculations, 819 mothers were recruited to the trial. The primary outcomes for the trial are parents’ sense of competence and self-efficacy measured using standard self-report questionnaires. Secondary outcomes include the quality of mother-infant relationships, maternal social support, role satisfaction and maternal mental health, infant social-emotional and language development, and patterns of service utilisation. Maternal and infant outcomes will be evaluated using age-appropriate questionnaires when infants are aged <2 months (pre-intervention), 9, 15, and 21 months. Discussion We know of no previous study that has evaluated an intervention that combines the capacity of nurse and internet-based services to improve outcomes for mothers and infants. The knowledge gained from this study will inform the design and conduct of community-based postnatal mother and child support programs. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613000204741

2014-01-01

331

Multiple Hypotheses Testing Procedures in Clinical Trials and Genomic Studies  

PubMed Central

We review and compare multiple hypothesis testing procedures used in clinical trials and those in genomic studies. Clinical trials often employ global tests, which draw an overall conclusion for all the hypotheses, such as SUM test, Two-Step test, Approximate Likelihood Ratio test (ALRT), Intersection-Union Test (IUT), and MAX test. The SUM and Two-Step tests are most powerful under homogeneous treatment effects, while the ALRT and MAX test are robust in cases with non-homogeneous treatment effects. Furthermore, the ALRT is robust to unequal sample sizes in testing different hypotheses. In genomic studies, stepwise procedures are used to draw marker-specific conclusions and control family wise error rate (FWER) or false discovery rate (FDR). FDR refers to the percent of false positives among all significant results and is preferred over FWER in screening high-dimensional genomic markers due to its interpretability. In cases where correlations between test statistics cannot be ignored, Westfall-Young resampling method generates the joint distribution of P-values under the null and maintains their correlation structure. Finally, the GWAS data from a clinical trial searching for SNPs associated with nephropathy among Type 1 diabetic patients are used to illustrate various procedures.

Pan, Qing

2013-01-01

332

Manual and Electroacupuncture for Labour Pain: Study Design of a Longitudinal Randomized Controlled Trial  

PubMed Central

Introduction. Results from previous studies on acupuncture for labour pain are contradictory and lack important information on methodology. However, studies indicate that acupuncture has a positive effect on women's experiences of labour pain. The aim of the present study was to evaluate the efficacy of two different acupuncture stimulations, manual or electrical stimulation, compared with standard care in the relief of labour pain as the primary outcome. This paper will present in-depth information on the design of the study, following the CONSORT and STRICTA recommendations. Methods. The study was designed as a randomized controlled trial based on western medical theories. Nulliparous women with normal pregnancies admitted to the delivery ward after a spontaneous onset of labour were randomly allocated into one of three groups: manual acupuncture, electroacupuncture, or standard care. Sample size calculation gave 101 women in each group, including a total of 303 women. A Visual Analogue Scale was used for assessing pain every 30 minutes for five hours and thereafter every hour until birth. Questionnaires were distributed before treatment, directly after the birth, and at one day and two months postpartum. Blood samples were collected before and after the first treatment. This trial is registered at ClinicalTrials.gov: NCT01197950.

Vixner, Linda; Martensson, Lena B.; Stener-Victorin, Elisabet; Schytt, Erica

2012-01-01

333

Group hypnotherapy versus group relaxation for smoking cessation: an RCT study protocol  

PubMed Central

Background A significant number of smokers would like to stop smoking. Despite the demonstrated efficacy of pharmacological smoking cessation treatments, many smokers are unwilling to use them; however, they are inclined to try alternative methods. Hypnosis has a long-standing reputation in smoking cessation therapy, but its efficacy has not been scientifically proven. We designed this randomised controlled trial to evaluate the effects of group hypnosis as a method for smoking cessation, and we will compare the results of group hypnosis with group relaxation. Methods/Design This is a randomised controlled trial (RCT) to compare the efficacy of a single session of hypnosis with that of relaxation performed in groups of 8-15 smokers. We intend to include at least 220 participants in our trial. The inclusion criteria include smoking at least 5 cigarettes per day, not using other cessation methods and being willing to quit smoking. The intervention is performed by a trained hypnotist/relaxation therapist. Both groups first receive 40 min of mental preparation that is based on motivational interviewing. Then, a state of deep relaxation is induced in the hypnosis condition, and superficial relaxation is induced in the control condition. Suggestions are made in the hypnosis condition that aim to switch the mental self-image of the participants from that of smokers to that of non-smokers. Each intervention lasts for 40 min. The participants also complete questionnaires that assess their smoking status and symptoms of depression and anxiety at baseline, 2 weeks and 6 months post-intervention. In addition, saliva samples are collected to assess cotinine levels at baseline and at 6 months post-intervention. We also assess nicotine withdrawal symptoms at 2 weeks post-intervention. Discussion To the best of our knowledge, this RCT is the first to test the efficacy of group hypnosis versus group relaxation. Issues requiring discussion in the outcome paper include the lack of standardisation of hypnotic interventions in smoking cessation, the debriefing of the participants, the effects of group dynamics and the reasons for dropouts. Trial registration Current Controlled Trials, ISRCTN72839675.

2012-01-01

334

Explaining the impact of a women's group led community mobilisation intervention on maternal and newborn health outcomes: the Ekjut trial process evaluation  

PubMed Central

Background Few large and rigorous evaluations of participatory interventions systematically describe their context and implementation, or attempt to explain the mechanisms behind their impact. This study reports process evaluation data from the Ekjut cluster-randomised controlled trial of a participatory learning and action cycle with women's groups to improve maternal and newborn health outcomes in Jharkhand and Orissa, eastern India (2005-2008). The study demonstrated a 45% reduction in neonatal mortality in the last two years of the intervention, largely driven by improvements in safe practices for home deliveries. Methods A participatory learning and action cycle with 244 women's groups was implemented in 18 intervention clusters covering an estimated population of 114 141. We describe the context, content, and implementation of this intervention, identify potential mechanisms behind its impact, and report challenges experienced in the field. Methods included a review of intervention documents, qualitative structured discussions with group members and non-group members, meeting observations, as well as descriptive statistical analysis of data on meeting attendance, activities, and characteristics of group attendees. Results Six broad, interrelated factors influenced the intervention's impact: (1) acceptability; (2) a participatory approach to the development of knowledge, skills and 'critical consciousness'; (3) community involvement beyond the groups; (4) a focus on marginalized communities; (5) the active recruitment of newly pregnant women into groups; (6) high population coverage. We hypothesize that these factors were responsible for the increase in safe delivery and care practices that led to the reduction in neonatal mortality demonstrated in the Ekjut trial. Conclusions Participatory interventions with community groups can influence maternal and child health outcomes if key intervention characteristics are preserved and tailored to local contexts. Scaling-up such interventions requires (1) a detailed understanding of the way in which context affects the acceptability and delivery of the intervention; (2) planned but flexible replication of key content and implementation features; (3) strong support for participatory methods from implementing agencies.

2010-01-01

335

Phase I Clinical Trial of a Day1, -3, -5 Every 3 WeeksPhase I Clinical Trial of Day1, -3, -5 Every 3 Weeks Schedule with Titanocene Dichloride (MKT 5) in Patients with Advanced Cancer. (Phase I Study Group of the AIO of the German Cancer Society)  

Microsoft Academic Search

Summary Background: Titanocene dichloride (TD) is an organometallic compound with antiproliferative properties in vitro and promising antitumor activity in preclinical in vivo models. The drug interferes with DNA, blocks the S/G2 phase of the cell cycle and shows antiangiogenic properties. The purpose of this study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of a

K. Mross; P. Robben-Bathe; L. Edler; J. Baumgart; W. E. Berdel; H. Fiebig; C. Unger

2000-01-01

336

Phase III randomised controlled trial of neoadjuvant chemotherapy plus radical surgery vs radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan Clinical Oncology Group trial (JCOG 0102)  

PubMed Central

Background: A phase III trial was conducted to determine whether neoadjuvant chemotherapy (NACT) before radical surgery (RS) improves overall survival. Methods: Patients with stage IB2, IIA2, or IIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either BOMP (bleomycin 7?mg days 1–5, vincristine 0.7?mg?m?2 day 5, mitomycin 7?mg?m?2 day 5, cisplatin 14?mg?m?2 days 1–5, every 3 weeks for 2 to 4 cycles) plus RS (NACT group) or RS alone (RS group). Patients with pathological high-risk factors received postoperative radiotherapy (RT). The primary end point was overall survival. Results: A total of 134 patients were randomly assigned to treatment. This study was prematurely terminated at the first planned interim analysis because overall survival in the NACT group was inferior to that in the RS group. Patients who received postoperative RT were significantly lower in the NACT group (58%) than in the RS group (80% P=0.015). The 5-year overall survival was 70.0% in the NACT group and 74.4% in the RS group (P=0.85). Conclusion: Neoadjuvant chemotherapy with BOMP regimen before RS did not improve overall survival, but reduced the number of patients who received postoperative RT.

Katsumata, N; Yoshikawa, H; Kobayashi, H; Saito, T; Kuzuya, K; Nakanishi, T; Yasugi, T; Yaegashi, N; Yokota, H; Kodama, S; Mizunoe, T; Hiura, M; Kasamatsu, T; Shibata, T; Kamura, T

2013-01-01

337

Efficacy of two educational interventions about inhalation techniques in patients with chronic obstructive pulmonary disease (COPD). TECEPOC: study protocol for a partially randomized controlled trial (preference trial)  

PubMed Central

Background Drugs for inhalation are the cornerstone of therapy in obstructive lung disease. We have observed that up to 75?% of patients do not perform a correct inhalation technique. The inability of patients to correctly use their inhaler device may be a direct consequence of insufficient or poor inhaler technique instruction. The objective of this study is to test the efficacy of two educational interventions to improve the inhalation techniques in patients with Chronic Obstructive Pulmonary Disease (COPD). Methods This study uses both a multicenter patients´ preference trial and a comprehensive cohort design with 495 COPD-diagnosed patients selected by a non-probabilistic method of sampling from seven Primary Care Centers. The participants will be divided into two groups and five arms. The two groups are: 1) the patients´ preference group with two arms and 2) the randomized group with three arms. In the preference group, the two arms correspond to the two educational interventions (Intervention A and Intervention B) designed for this study. In the randomized group the three arms comprise: intervention A, intervention B and a control arm. Intervention A is written information (a leaflet describing the correct inhalation techniques). Intervention B is written information about inhalation techniques?plus?training by an instructor. Every patient in each group will be visited six times during the year of the study at health care center. Discussion Our hypothesis is that the application of two educational interventions in patients with COPD who are treated with inhaled therapy will increase the number of patients who perform a correct inhalation technique by at least 25?%. We will evaluate the effectiveness of these interventions on patient inhalation technique improvement, considering that it will be adequate and feasible within the context of clinical practice. Trial registration Current Controlled Trials ISRTCTN15106246

2012-01-01

338

Quality control in multicentric clinical trials. An experience of the EORTC Gynecological Cancer Cooperative Group. | accrualnet.cancer.gov  

Cancer.gov

The authors conducted a data quality study for a European Organization for Research and Treatment of Cancer (EORTC) multicenter randomized phase III treatment trial focusing on cervical cancer. Analysis of the causes of inaccuracies revealed problems in data management, but the investigators also associated some errors with lack of clarity in the protocol and case report forms (CRFs).

339

Acupuncture treatment for pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups  

Microsoft Academic Search

Objectives To study the analgesic effect of acupuncture andplaceboacupunctureandtoexplorewhetherthetype of the placebo acupuncture is associated with the estimated effect of acupuncture. Design Systematic review and meta-analysis of three armed randomised clinical trials. Data sources Cochrane Library, Medline, Embase, Biological Abstracts, and PsycLIT. Data extraction and analysis Standardised mean differencesfromeachtrialwereusedtoestimatetheeffect of acupuncture and placebo acupuncture. The different types of placebo acupuncture

Matias Vested Madsen; P. C Gotzsche; A. Hrobjartsson

2009-01-01

340

Vitamin D supplementation in the management of knee osteoarthritis: study protocol for a randomized controlled trial  

PubMed Central

Background Osteoarthritis (OA) is a common health issue worldwide in the aging population who are also commonly deficient in vitamin D. Our previous study suggested that higher serum 25-(OH)D levels were associated with reduced knee cartilage loss, implying that vitamin D supplementation may prevent the progression of knee OA. The aim of the VItamin D Effects on OA (VIDEO) study is to compare, over a 2- year period, the effects of vitamin D supplementation versus placebo on knee structural changes, knee pain, and lower limb muscle strength in patients with symptomatic knee OA. Methods/design Randomised, placebo-controlled, and double-blind clinical trial aiming to recruit 400 subjects (200 from Tasmania and 200 from Victoria) with both symptomatic knee OA and vitamin D deficiency (serum [25-(OH)D] level of >12.5?nmol/liter and <60?nmol/liter). Participants will be randomly allocated to vitamin D supplementation (50,000?IU compounded vitamin D3 capsule monthly) or identical inert placebo group for 2?years. The primary endpoint is loss of knee cartilage volume measured by magnetic resonance imaging (MRI) and Western Ontario and McMaster Universities Index of OA (WOMAC) knee pain score. The secondary endpoints will be other knee structural changes, and lower limb muscle strength. Several other outcome measures including core muscle images and central blood pressure will be recorded. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modeling analyses. Both intention to treat and per protocol analyses will be utilized. Discussion The trial is designed to test if vitamin D supplementation will reduce loss of knee cartilage volume, prevent the progression of other knee structural abnormalities, reduce knee pain and strengthen lower limb muscle strength, thus modify disease progression in knee OA. Trial registration ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials Registry: ACTRN12610000495022

2012-01-01

341

Usefulness of C-reactive protein testing in acute cough/respiratory tract infection: an open cluster-randomized clinical trial with C-reactive protein testing in the intervention group  

PubMed Central

Background Point of care testing for C-reactive protein (CRP) has shown promise as a measure to reduce unnecessary antibiotic prescribing in respiratory tract infections (RTI), but its use in primary care is still controversial. We aimed to evaluate the effect of CRP testing on the prescription of antibiotics, referral for radiography, and the outcome of patients in general practice with acute cough/RTI. Methods An open-cluster randomized clinical trial was conducted, with CRP testing performed in the intervention group. Antibiotic prescribing and referral for radiography were the main outcome measures. Results A total of 179 patients were included: 101 in the intervention group and 78 in the control group. The two groups were similar in clinical characteristics. In the intervention group, the antibiotic prescribing rate was 37.6%, which was significantly lower than that in the control group (58.9%) (P?=?0.006). Referral for chest X-ray was also significantly lower in the intervention group (55.4%) than in the control group (75.6%) (P?=?0.004). The recovery rate, as recorded by the GPs, was 92.9% and 93.6% in the intervention and control groups, respectively. Conclusion The study showed that CRP testing in patients with acute cough/RTI may reduce antibiotic prescribing and referral for radiography, probably without compromising recovery. Trial registration The trial was registered in the ClinicalTrials.gov Protocol Registration System (identification number: NCT01794819).

2014-01-01

342

Cardiac Improvement During Mechanical Circulatory Support A Prospective Multicenter Study of the LVAD Working Group  

Microsoft Academic Search

Background—Myocardial recovery after left ventricular assist device (LVAD) support has been reported. The LVAD Working Group Recovery Study was a prospective multicenter trial to assess the incidence of myocardial recovery in patients bridged to cardiac transplantation. Methods and Results—After LVAD implantation, patients were evaluated with the use of rest echocardiograms with partial LVAD support and cardiopulmonary exercise testing. Dobutamine echocardiography

Simon Maybaum; Donna Mancini; Steve Xydas; Randall C. Starling; Keith Aaronson; Francis D. Pagani; Leslie W. Miller; Kenneth Margulies; Susan McRee; O. H. Frazier; Guillermo Torre-Amione

2010-01-01

343

Group Music Intervention Reduces Aggression and Improves Self-esteem in Children with Highly Aggressive Behavior: A Pilot Controlled Trial  

PubMed Central

We investigated the effects of group music intervention on aggression and self-esteem in children with highly aggressive behavior. Forty-eight children were allocated to either a music intervention group or an untreated control group. The music intervention group received 50 min of music intervention twice weekly for 15 consecutive weeks. The outcome measures were Child Behavior Checklist Aggression Problems Scale (Parents), Child Aggression Assessment Inventory (Teachers) and Rosenberg Self-esteem Scale. After 15 weeks, the music intervention group showed significant reduction of aggression and improvement of self-esteem compared with the control group. All outcome measures were significantly lower in the music intervention group than prior to treatment, while there was no change in the control group. These findings suggest that music can reduce aggressive behavior and improve self-esteem in children with highly aggressive behavior. Music intervention is an easily accessible therapy for children and as such may be an effective intervention for aggressive behavior. Further more, objective and replicable measures are required from a randomized controlled trial with a larger sample size and active comparable control.

Lee, Myeong Soo; Lee, Jung-Sook

2010-01-01

344

Efficacy and Safety of Lobeglitazone Monotherapy in Patients with Type 2 Diabetes Mellitus over 24-Weeks: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo Controlled Trial  

PubMed Central

Objective The aim of this study was to assess the glucose-lowering and lipid-modifying effects, and safety profile of lobeglitazone, a novel peroxisome proliferator-activated receptor- ? agonist, compared to placebo as a monotherapy in patients with type 2 diabetes. Research Design and Methods In this 24-week, multicenter, randomized, double-blind, parallel-group, placebo controlled study, 173 patients were randomly assigned (a 2?1 ratio) to lobeglitazone 0.5 mg (n?=?115) or matching placebo (n?=?58) orally once daily. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to the end of treatment. The secondary endpoints included various glycemic parameters, lipid parameters and safety profile (ClinicalTrials.gov number NCT01001611). Results At 24 weeks, a significant reduction in HbA1c was observed with lobeglitazone versus placebo (?0.44% vs 0.16%, mean difference ?0.6%, p<0.0001). The goal of HbA1c <7% was achieved significantly more in the lobeglitazone group compared to the placebo group (44% vs 12%, p<0.0001). Markers of insulin resistance were also improved in the lobeglitazone group. In addition, lobeglitazone treatment significantly improved triglycerides, high density lipoprotein cholesterol, small dense low density lipoprotein cholesterol, free fatty acid, and apolipoprotein-B/CIII compared to placebo (p<0.01, respectively). More weight gain was observed in the lobeglitazone group than the placebo group (0.89 kg vs – 0.63 kg, mean difference 1.52 kg, p<0.0001). The safety profile was comparable between the two groups and lobeglitazone was well tolerated. Conclusions Lobeglitazone 0.5 mg showed a favorable balance in the efficacy and safety profile. The results support a potential role of lobeglitazone in treating type 2 diabetes. Trial Registration Clinicaltrials.gov NCT01001611

Kim, Sin Gon; Kim, Doo Man; Woo, Jeong-Taek; Jang, Hak Chul; Chung, Choon Hee; Ko, Kyung Soo; Park, Jeong Hyun; Park, Yong Soo; Kim, Sang Jin; Choi, Dong Seop

2014-01-01

345

Quality Assurance Program for Clinical Measurement of Antiretrovirals: AIDS Clinical Trials Group Proficiency Testing Program for Pediatric and Adult Pharmacology Laboratories  

Microsoft Academic Search

Clinical trials designed to compare antiretroviral regimens, investigate therapeutic drug monitoring, or measure pharmacometrics often include protease inhibitors (PIs), nonnucleoside reverse transcriptase inhib- itors (NNRTIs), and nucleoside reverse transcriptase inhibitors, requiring the measurement of these antiret- rovirals in plasma. Within the adult and pediatric AIDS Clinical Trials Group (ACTG), a network of Phar- macology Support Laboratories (PSLs) is a component

Diane T. Holland; Robin DiFrancesco; Judith Stone; Fayez Hamzeh; James D. Connor; Gene D. Morse

2004-01-01

346

Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid (TPOP): study protocol for a randomized controlled trial  

PubMed Central

Background Preclinical and clinical studies suggest that supplementation with omega-3 fatty acids after trauma might reduce subsequent posttraumatic stress disorder (PTSD). To date, we have shown in an open trial that PTSD symptoms in critically injured patients can be reduced by taking omega-3 fatty acids, hypothesized to stimulate hippocampal neurogenesis. The primary aim of the present randomized controlled trial is to examine the efficacy of omega-3 fatty acid supplementation in the secondary prevention of PTSD following accidental injury, as compared with placebo. This paper describes the rationale and protocol of this trial. Methods/design The Tachikawa Project for Prevention of Posttraumatic Stress Disorder with Polyunsaturated Fatty Acid (TPOP) is a double-blinded, parallel group, randomized controlled trial to assess whether omega-3 fatty acid supplementation can prevent PTSD symptoms among accident-injured patients consecutively admitted to an intensive care unit. We plan to recruit accident-injured patients and follow them prospectively for 12 weeks. Enrolled patients will be randomized to either the omega-3 fatty acid supplement group (1,470 mg docosahexaenoic acid and 147 mg eicosapentaenoic acid daily) or placebo group. Primary outcome is score on the Clinician-Administered PTSD Scale (CAPS). We will need to randomize 140 injured patients to have 90% power to detect a 10-point difference in mean CAPS scores with omega-3 fatty acid supplementation compared with placebo. Secondary measures are diagnosis of PTSD and major depressive disorder, depressive symptoms, physiologic response in the experiment using script-driven imagery and acoustic stimulation, serum brain-derived neurotrophic factor, health-related quality of life, resilience, and aggression. Analyses will be by intent to treat. The trial was initiated on December 13 2008, with 104 subjects randomized by November 30 2012. Discussion This study promises to be the first trial to provide a novel prevention strategy for PTSD among traumatized people. Trial registration ClinicalTrials.gov Identifier NCT00671099

2013-01-01

347

Progressive Staging of Pilot Studies to Improve Phase III Trials for Motor Interventions  

PubMed Central

Based on the suboptimal research pathways that finally led to multicenter randomized clinical trials (MRCTs) of treadmill training with partial body weight support and of robotic assistive devices, strategically planned successive stages are proposed for pilot