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Randomization
Kinds of Randomization Terms modified by Randomization Selected AbstractsTrials update in walesCYTOPATHOLOGY, Issue 2007A. Fiander Three ongoing studies will be presented and discussed. Prevalence of Human Papillomavirus Infection in a South Wales Screening population Methods: A total of 10 000 consecutive, anonymous liquid based cytology screening samples were collected over a five month period in 2004. Age, cytology result and social deprivation score was provided for each specimen. The methodology was chosen to ensure inclusion of all women attending routine cervical screening, avoiding potential constraints associated with obtaining individual informed consent. The liquid based cytology samples were processed and reported by the receiving cytology laboratory and the residual specimens sent to the HPV Research Laboratory, Wales College of Medicine, where they were processed and stored at -80°C until analysis. High risk and low risk HPV Typing was undertaken using PCR , EIA (Jacobs et al 1997). Full high risk typing was performed on HPV positive specimens. Results: The study population had a mean age of 38 years with 92% negative, 5% borderline and 3% dyskaryotic cytology. The average social deprivation score was 17.4 (based upon the Welsh Index of multiple deprivation). The following results will be presented: HPV prevalence by age. HPV prevalence by cytology result. Type specific HPV prevalence in single and multiple infection. Conclusion: This study represents the largest type specific HPV Prevalence Study in the UK to date. As such it will form a useful base line against which to access performance of marketed HPV tests and evaluating the impact following implementation of HPV vaccination. [Funded by Welsh Office for Research and Development] CRISP , 1 Study (Cervical Randomized Intervention Study Protocol -1) Background: Indole-3-carbinol (I3C) and Diindolylmethane (DIM) are found in cruciferous vegetables and have been identified as compounds that could potentially prevent or halt carcinogenesis. I3C spontaneously forms DIM in vivo during acid digestion. I3C has been shown to prevent the development of cervical cancer in HPV 16 transgenic mice and both I3C and DIM have been shown to promote cell death in cervical cancer cell models. DIM is the major active bi-product of I3C and preliminary data indicate that DIM is active in cervical dysplasia and may be better tolerated than I3C. Aim: To investigate chemoprevention of high grade cervical neoplasia using Diindolylmethane (DIM) supplementation in women with low grade cytological abnormalities on cervical cytology. Objectives: To observe any reduction in the prevalence of histological proven high-grade cervical intraepithelial neoplasia (CIN) after 6 months of supplementation. ,,To observe any reduction in the prevalence of cytological abnormalities. ,,To observe any changes in the clinical appearance of the cervix. To assess acceptability and monitor any side effects of DIM supplementation. ,,To assess whether any benefit is seen in relation to Human Papillomavirus (HPV) status including HPV Type, Viral load and integration. Methods: This is a double blind randomized placebo-controlled trial involving 600,700 women with low grade cytological abnormalities on a cervical smear. Randomization is in the ratio of 2 : 1 in favour of active medication. Women with first mildly dyskaryotic smear or second borderline smear are eligible. They are asked to take two capsules daily for 6 months. At the end of 6 months they undergo repeat cervical cytology, HPV testing and colposcopy. Results: A progress report will be given for this ongoing study. [Funded: - Cancer Research UK] Type Specific HPV Infection in Welsh Cervical Cancers Background: Whilst there have been numerous studies of HPV infection associated with cervical cancer and on prevalence of Human Papillomavirus in diverse populations there have been no studies of these variables in the same population. Against a background of prophylactic HPV vaccination it is important to assess potential protection against cervical cancer within a given population. The most comprehensive analysis of HPV type specific cervical cancer is a meta-analysis published by the IARC in 2003. This however included only three UK based studies, totalling 118 cases, 75 of which were only investigated by HPV type PCR for four high risk types. None of this data was presented with associated population based prevalence data. Therefore, the research objectives for this study in combination with the first study above, are as follows: To determine the frequency of specific HPV types in cervical cancers in Wales. To compare the distribution of specific HPV types amongst cervical cancers with their prevalence in the general population. This will allow accurate delineation of the relationship between prevalence of specific HPV types in the general population and their association with clinically relevant disease. This information is a pre-requisite to assess the potential impact of prophylactic vaccination against HPV infection in Wales. Methods: Welsh Cervical Cancer specimens from 2000,2005 will be identified from pathology departments within Wales. The pathology of each tumour will be reviewed by a single Gynaecological Pathologist. The age of the patient and pathological features of the tumour will be noted. DNA will be extracted from the paraffin sections and HPV typed by PCR-EIA. Results: A progress report will be given for this ongoing study. [Funded by Welsh Office for Research and Development] [source] Extended cognitive behavior therapy for cigarette smoking cessationADDICTION, Issue 8 2008Joel D. Killen ABSTRACT Primary aim Examine the effectiveness of extended cognitive behavior therapy (CBT) in promoting longer-term smoking abstinence. Design Open-label treatment phase followed by extended treatment phase. Randomization conducted prior to entry into open-label treatment phase; analysis based on intention-to-treat to avoid threat of selection bias. Setting Community smoking cessation clinic. Participants A total of 304 adult smokers (,18 years of age; ,10 cigarettes/day). Intervention Open-label (8 weeks): all participants received bupropion SR, nicotine patch, CBT. Extended treatment (12 weeks): participants received either CBT + voicemail monitoring and telephone counseling or telephone-based general support. Measurements Seven-day point prevalence abstinence, expired-air carbon monoxide. Results At week 20 follow-up, CBT produced a higher 7-day point prevalence abstinence rate: 45% versus 29%, P = 0.006; at 52 weeks the difference in abstinence rates (31% versus 27%) was not significant. History of depression was a moderator of treatment. Those with a positive history had a better treatment response at 20 weeks when assigned to the less intensive telephone support therapy (P < 0.05). Conclusion The superiority of CBT to 20 weeks suggests that continued emphasis on the development of cognitive and behavioral strategies for maintaining non-smoking during an extended treatment phase may help smokers to maintain abstinence in the longer term. At present, the minimum duration of therapy is unknown. [source] Treatment of intermediate- and high-grade non-Hodgkin's lymphoma using CEOP versus CNOPEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2002A Hellenic Co-operative Oncology Group Study Abstract:Introduction: During the last few years epirubicin (E) and mitoxantrone (M) (Novantrone) have been used in the treatment of non-Hodgkin's lymphoma (NHL), because of their favorable principal profile. In particular, M has less severe non-hematological toxicity. Patients and methods: A randomized multicenter phase III study was conducted in order to compare the efficacy and toxicity of CEOP and CNOP in intermediate- and high-grade NHL. CEOP (arm A) consisted of cyclophosphamide 1000 mg m,2, vincristine 2 mg, E 70 mg m,2 on day 1 and prednisone 60 mg on days 1,7. The CNOP regimen (arm B) was identical to CEOP except for replacement of E by M at a dose of 12 mg m,2. Randomization was stratified according to stages I,IV. From September 1993 to March 1999, 249 patients registered for the trial. Patient characteristics were equally distributed in the two arms, except for age and International Prognostic Index (IPI) groups. Results: There were no significant differences between the two groups in the rates of complete (CR) and partial response (PR). The overall response rate was 78% in arm A (57% CR, 21% PR) and 82% in arm B (60% CR, 22% PR). With a median follow-up time of 47.3 months, the median survival was not reached in arm A, while it was 39.5 months in arm B (P = 0.09). Three-year survival rates were 62.5% for CEOP and 51.5% for CNOP. There was no significant difference regarding the time to progression between the two groups (29.7 vs. 18.5 months); furthermore the median duration of CRs was 71.6 and 49 months for CEOP and CNOP, respectively (P = 0.07). The therapeutic efficacies of both regimens were equivalent among the four IPI groups. More alopecia was observed in arm A. WHO grade >2 neutropenia was more frequent in arm B. Supportive treatment with G-CSF was given to 22 and 24 patients, respectively. Conclusion: There were no significant differences in terms of overall response rates, overall survival and time to progression between CEOP and CNOP in the treatment of intermediate- and high-grade NHL. Patients with low or low intermediate IPI risk treated with either CEOP or CNOP showed significantly better survival, response rates and time to progression than those with high intermediate or high IPI risk. Therefore, new improved therapeutic approaches should be developed for the treatment of high IPI risk patients. [source] Randomization in psychiatric intervention research in the general practice settingINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2000CM Van Der Feltz-Cornelis Faculty of Medicine Abstract Most studies of psychiatric interventions in general practice settings conform only in part to the requirements of randomization, placebo control and blinding as formulated by the Cochrane Collaboration. It is possible, nonetheless, to develop experimental research designs that are sufficiently near to this standard. These must deal with certain methodological issues specific to psychiatric research. This article discusses scientific standards of psychiatric research with special consideration of interventions in general practice settings. These issues are accompanied by concrete examples and suggestions on how to confront the problems. In psychiatric intervention research, equivalence studies with single-blind outcome assessment, a tested and ethically justified method, are generally used in place of placebo-controlled studies. The article also examines randomization procedures in greater depth. Randomization can be applied across trial subjects or across doctors' practices. Practical consequences of randomizing across subjects, and specific implementations of it such as crossover and pre-post designs in general practice settings, are clarified. Overall, a research design using randomization across doctors' practices is judged preferable to one that randomizes across trial subjects. One potential problem is that the control group may become too small, especially when considerable effects are expected from the intervention being studied. One might consider making the control condition smaller in the first place, or, if indicated on ethical grounds, performing an intermediate analysis and then breaking off the study as soon as a statistically significant effect has been demonstrated. Multilevel statistical techniques offer new opportunities for analysis within such designs. Copyright © 2000 Whurr Publishers Ltd. [source] Effect of Metoprolol on Quality of Life in the Prevention of Syncope TrialJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2009Ph.D., ROBERT S. SHELDON M.D. Introduction: Vasovagal syncope is common, often recurrent, and reduces quality of life. No therapies have proven useful to improve quality of life in adequately designed randomized clinical trials. Beta-blockers have mixed evidence for effectiveness in preventing syncope. Methods: The Prevention of Syncope Trial was a randomized, placebo-controlled, double-blind, multinational, clinical trial that tested the hypothesis that metoprolol improves quality of life in adult patients with vasovagal syncope in a 1-year observation period. Randomization was stratified in strata of patients <42 and ,42 years old. The quality of life questionnaires Short Form-36 (SF-36) and Euroqol EQ-5D were completed at baseline and after 6 and 12 months of treatment by 204, 132, and 121 patients, respectively. Results: There were 208 patients, mean age 42 ± 18, of whom 134 (64%) were females. All had positive tilt tests. There was no improvement in quality of life during the trial in the entire group or in either treatment arm. Patients in the metoprolol treatment arm did not have improved quality of life compared to the patients in the placebo arm using either the SF-36 or EQ5D after either 6 or 12 months. Finally, there was no improvement in quality of life associated with metoprolol use in patients either <42 or ,42 years of age. Conclusion: Metoprolol does not improve quality of life in patients with recurrent vasovagal syncope and a positive tilt test. [source] Bilaminar techniques for the treatment of recession-type defects.JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2003A comparative clinical study Abstract Objectives: Complete root coverage is the primary objective to be accomplished when treating gingival recessions in patients with aesthetic demands. Furthermore, in order to satisfy patient demands fully, root coverage should be accomplished by soft tissue, the thickness and colour of which should not be distinguishable from those of adjacent soft tissue. The aim of the present split-mouth study was to compare the treatment outcome of two surgical approaches of the bilaminar procedure in terms of (i) root coverage and (ii) aesthetic appearance of the surgically treated sites. Material and Methods: Fifteen young systemically and periodontally healthy subjects with two recession-type defects of similar depth affecting contralateral teeth in the aesthetic zone of the maxilla were enrolled in the study. All recessions fall into Miller class I or II. Randomization for test and control treatment was performed by coin toss immediately prior to surgery. All defects were treated with a bilaminar surgical technique: differences between test and control sites resided in the size, thickness and positioning of the connective tissue graft. The clinical re-evaluation was made 1 year after surgery. Results: The two bilaminar techniques resulted in a high percentage of root coverage (97.3% in the test and 94.7% in the control group) and complete root coverage (gingival margin at the cemento-enamel junction (CEJ)) (86.7% in the test and 80% in the control teeth), with no statistically significant difference between them. Conversely, better aesthetic outcome and post-operative course were indicated by the patients for test compared to control sites. Conclusions: The proposed modification of the bilaminar technique improved the aesthetic outcome. The reduced size and minimal thickness of connective tissue graft, together with its positioning apical to the CEJ, facilitated graft coverage by means of the coronally advanced flap. Zusammenfassung Hintergrund: Die vollständige Deckung der Wurzeloberfläche ist das primäre Ziel, das bei der Therapie von fazialen Rezessionen bei Patienten mit ästhetischen Ansprüchen erreicht werden soll. Weiterhin sollte die Rezessionsdeckung, wenn sie den Ansprüchen des Patienten vollends entsprechen soll, mit einer Dicke und Farbe der Gingiva erreicht werden, die nicht vom benachbarten Gewebe zu unterscheiden sind. Zielsetzung: Vergleich der Therapieergebnisse von 2 chirurgischen Varianten der zweischichtigen Technik im Halbseitenversuch hinsichtlich (1) Rezessionsdeckung und (2) ästhetischer Erscheinung der chirurgisch behandelten Stellen. Material und Methoden: 15 junge und parodontal gesunde Personen mit jeweils 2 Rezessionsdefekten ähnlicher Größe an kontralateralen Zähnen im ästhetischen Bereich des Oberkiefers wurden in die Studie aufgenommen. Alle Rezessionen gehörten in die Miller-Klassen I oder II. Die Randomisierung für die Test- und Kontrollbehandlung erfolgte unmittelbar präoperativ durch Münzwurf. Alle Defekte wurden nach einer zweischichtigen chirurgischen Technik behandelt: Die Unterschiede zwischen Test- und Kontrollstellen bestanden in Größe, Dicke und Positionierung des Bindegewebstransplantates. Die klinische Nachuntersuchung erfolgte 1 Jahr postoperativ. Ergebnisse: Beide zweischichtigen Techniken führten zu einem hohen Prozentsatz von Wurzeldeckung (Test: 97,3%; Kontrolle: 94,7%) und kompletter Wurzeldeckung (Gingivarand an der Schmelz-Zement-Grenze [SZG]) (Test: 86,7%; Kontrolle: 80%) ohne statistisch signifikante Unterschiede zwischen beiden Gruppen. Allerdings wurden mit der Testtherapie bessere ästhetische Ergebnisse erzielt als mit der Kontrollbehandlung. Schlussfolgerung: Die vorgestellte Modifikation der zweischichtigen Technik verbesserte die ästhetischen Ergebnisse. Die reduzierte Größe und minimale Dicke des Bindegewebstransplantates zusammen mit seiner Positionierung apikal der SZG erleichterten eine Deckung mittels eines koronalen Verschiebelappens. Résumé Objectif: Un recouvrement complet de la racine est le premier objectif lorsque l'on traite des récessions gingivales chez les patients ayant une demande esthétique. De plus, afin de satisfaire totalement la demande du patient, cette couverture radiculaire doit aussi être réalisé par des tissus mous de couleur et d'épaisseur qui ne se distinguent pas des tissus mous adjacents. Le but de cette étude en bouche séparée était de comparer le devenir de deux approches chirurgicales de la technique bilaminaire pour (i) le recouvrement de la racine et (ii) l'apparence esthétique des sites traités chirurgicalement. Matériel et Méthodes: 15 sujets jeunes et indemnes de maladie parodontale et systèmique présentant deux récessions de profondeur similaires sur des dents contralatérales dans des zones esthétiques du maxillaire furent enrollés dans cette étude. Toutes les récessions étaient des classes I ou II de Miller. La répartition pour les traitements test ou contrôle fut tirée à pile ou face juste avant la chirurgie. Toutes les lésions furent traitées par la technique bilaminaire, la différence entre les groupes résidant dans la taille, l'épaisseur et le positionnement du greffon de tissus conjonctif. La réévaluation clinique fut faite un an après la chirurgie. Résultats: Les deux techniques bilaminaires ont entrainé un fort pourcentage de recouvrement radiculaire (97.3% pour le groupe test et 94.7% pour le groupe contrôle) et le recouvrement complet (gencive marginale au niveau de la CEJ) (86.7% dans le groupe test et 80% pour le groupe contrôle) sans différence statistiquement significative entre elles. Par contre, un meilleur rendu esthétique et suites post opératoires furent rapportés par les patients pour le traitement test. Conclusions: La modification proposée de cette technique bilaminaire améliore le devenir esthétique. La taille réduite et l'épaisseur minimale greffon conjonctif et son positionnement apical au CEJ, ont facilité le recouvrement du greffon par le lambeau déplacé coronairement. [source] Randomization of Amyloid-,-Peptide(1-42) Conformation by Sulfonated and Sulfated Nanoparticles Reduces Aggregation and CytotoxicityMACROMOLECULAR BIOSCIENCE, Issue 10 2010Ana M. Saraiva Abstract The amyloid-, peptide (A,) plays a central role in the mechanism of Alzheimer's disease, being the main constituent of the plaque deposits found in AD brains. A, amyloid formation and deposition are due to a conformational switching to a ,-enriched secondary structure. Our strategy to inhibit A, aggregation involves the re-conversion of A, conformation by adsorption to nanoparticles. NPs were synthesized by sulfonation and sulfation of polystyrene, leading to microgels and latexes. Both polymeric nanostructures affect the conformation of A, inducing an unordered state. Oligomerization was delayed and cytotoxicity reduced. The proper balance between hydrophilic moieties and hydrophobic chains seems to be an essential feature of effective NPs. [source] FDA report: Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease,,§AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Min Lu On June 30, 2009, the United States Food and Drug Administration (FDA) approved ferumoxytol (FerahemeÔ injection, AMAG Pharmaceuticals), an iron-containing product for intravenous (IV) administration, for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). The safety and efficacy of ferumoxytol were assessed in three randomized, open-label, controlled clinical trials. Two trials evaluated patients with nondialysis dependent CKD and a third trial assessed patients undergoing hemodialysis. Randomization was either to ferumoxytol or oral iron. Ferumoxytol was administered as two 510 mg IV injections, separated by 3,8 days. Oral iron, Ferro-Sequels®, was administered at a dose of 100 mg twice daily for 21 days. In all three clinical trials, ferumoxytol administration increased the mean blood hemoglobin (Hgb) concentrations by ,1.0 g/dL over the 35 day period, a mean increase that was greater than what was observed in patients receiving oral iron. Patients receiving ferumoxytol also had increases in blood transferrin saturation (TSAT) and ferritin values. For the proposed ferumoxytol dosing regimen, 4.9% of patients had serum ferritin ,800 ng/mL and TSAT ,50% post-treatment. The most important ferumoxytol safety concerns were hypersensitivity reactions and/or hypotension. Anaphylaxis or anaphylactoid reactions were reported in 0.2% of subjects, and other adverse reactions potentially associated with hypersensitivity (e.g., pruritus, rash, urticaria, or wheezing) were reported in 3.7%. Hypotension was observed in 1.9%, including three patients with serious hypotensive reactions. Ferumoxytol administration may transiently affect the diagnostic ability of magnetic resonance imaging and the drug label provides further information regarding this effect. Am. J. Hematol. 2010. Published 2010 Wiley-Liss, Inc. [source] Placebo-controlled trial of rituximab in IgM anti,myelin-associated glycoprotein antibody demyelinating neuropathy,ANNALS OF NEUROLOGY, Issue 3 2009Marinos C. Dalakas MD Objective Report a double-blind, placebo-controlled study of rituximab in patients with anti,MAG demyelinating polyneuropathy (A-MAG-DP). Methods Twenty-six patients were randomized to four weekly infusions of 375mg/m2 rituximab or placebo. Sample size was calculated to detect changes of ,1 Inflammatory Neuropathy Course and Treatment (INCAT) leg disability scores at month 8. IgM levels, anti-MAG titers, B cells, antigen-presenting cells, and immunoregulatory T cells were monitored every 2 months. Results Thirteen A-MAG-DP patients were randomized to rituximab and 13 to placebo. Randomization was balanced for age, electrophysiology, disease duration, disability scores, and baseline B cells. After 8 months, by intention to treat, 4 of 13 rituximab-treated patients improved by ,1 INCAT score compared with 0 of 13 patients taking placebo (p = 0.096). Excluding one rituximab-randomized patient who had normal INCAT score at entry, and thus could not improve, the results were significant (p = 0.036). The time to 10m walk was significantly reduced in the rituximab group (p = 0.042) (intention to treat). Clinically, walking improved in 7 of 13 rituximab-treated patients. At month 8, IgM was reduced by 34% and anti-MAG titers by 50%. CD25+CD4+Foxp3+ regulatory cells significantly increased by month 8. The most improved patients were those with high anti-MAG titers and most severe sensory deficits at baseline. Interpretation Rituximab is the first drug that improves some patients with A-MAG-DP in a controlled study. The benefit may be exerted by reducing the putative pathogenic antibodies or by inducing immunoregulatory T cells. The results warrant confirmation with a larger trial. Ann Neurol 2009;65:286,293 [source] Effect of hyaluronic acid in symptomatic hip osteoarthritis: A multicenter, randomized, placebo-controlled trial,ARTHRITIS & RHEUMATISM, Issue 3 2009Pascal Richette Objective To evaluate the efficacy and tolerability of a single intraarticular (IA) injection of hyaluronic acid (HA) for the treatment of hip osteoarthritis (OA). Methods A multicenter, randomized, parallel-group, placebo-controlled trial was conducted over 3 months. Patients (older than 30 years) with symptomatic hip OA (pain score of >40 mm on a visual analog scale [VAS]) and a Kellgren/Lawrence grade of 2 or 3 were randomly assigned to receive 1 fluoroscopically guided IA injection of HA (2.5 ml) or placebo (2.5 ml). Patients were followed up for 3 months. The main outcome measure was pain score on a VAS (100 mm) at month 3 compared with baseline. Secondary outcome measures were the proportion of responders defined by Osteoarthritis Research Society International criteria; Western Ontario and McMaster Universities Osteoarthritis Index subscores for pain, stiffness, and disability; and patient and physician global assessment. Randomization was computer generated. HA and placebo preparations were placed in numbered identical containers, and syringes were covered with masking tape. Physicians assessing outcomes were blinded with regard to group assignment. Results Eighty-five patients were randomized to the HA group (n = 42) or placebo group (n = 43). Baseline characteristics were similar between the 2 groups. At 3 months, the decrease in pain score did not differ between the HA and placebo groups in the intent-to-treat analysis (mean ± SD decrease 7.8 ± 24.9 mm with HA versus 9.1 ± 27.4 mm with placebo; P = 0.98). The responder rates were 33.3% and 32.6% in the HA and placebo groups, respectively (P = 0.94). Other secondary end points did not differ between the groups, nor did use of rescue medication or frequency of adverse events. Conclusion Our findings indicate that a single IA injection of HA is no more effective than placebo in treating the symptoms of hip OA. [source] Adaptive Randomization for Multiarm Comparative Clinical Trials Based on Joint Efficacy/Toxicity OutcomesBIOMETRICS, Issue 3 2009Yuan Ji Summary We present an outcome-adaptive randomization (AR) scheme for comparative clinical trials in which the primary endpoint is a joint efficacy/toxicity outcome. Under the proposed scheme, the randomization probabilities are unbalanced adaptively in favor of treatments with superior joint outcomes characterized by higher efficacy and lower toxicity. This type of scheme is advantageous from the patients' perspective because on average, more patients are randomized to superior treatments. We extend the approximate Bayesian time-to-event model in Cheung and Thall (2002,,Biometrics,58, 89,97) to model the joint efficacy/toxicity outcomes and perform posterior computation based on a latent variable approach. Consequently, this allows us to incorporate essential information about patients with incomplete follow-up. Based on the computed posterior probabilities, we propose an AR scheme that favors the treatments with larger joint probabilities of efficacy and no toxicity. We illustrate our methodology with a leukemia trial that compares three treatments in terms of their 52-week molecular remission rates and 52-week toxicity rates. [source] Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: an open, randomized effectiveness study mimicking clinical practice.BIPOLAR DISORDERS, Issue 5 2010The 6th trial of the Danish University Antidepressant Group (DUAG-6) Licht RW, Nielsen JN, Gram LF, Vestergaard P, Bendz H. Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: an open, randomized effectiveness study mimicking clinical practice. The 6th trial of the Danish University Antidepressant Group (DUAG-6). Bipolar Disord 2010: 12: 483,493. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives:, In industry-generated pivotal studies, lamotrigine has been found to be superior to placebo and comparable to lithium in the maintenance treatment of bipolar I disorder. Here, we directly compared lamotrigine to lithium under conditions similar to clinical routine conditions. Methods:, Adult bipolar I disorder patients with at least two episodes within the last five years and an index episode requiring treatment were randomized to lithium (n = 78; doses adjusted to obtain serum levels of 0.5,1.0 mmol/L) or to lamotrigine (n = 77; up-titrated to 400 mg/day) as maintenance treatments. Randomization took place when clinically appropriate, and comedication was allowed within the first six months after randomization. The patients were enrolled from March 2001 to December 2005, and observations were censored December 2006, allowing a subgroup of patients to be followed for more than five years. The primary outcome measure was time to predefined endpoints indicating insufficient maintenance treatment, and the major secondary outcome measure was time to any study endpoint. Data were analyzed primarily by Cox proportional regression models. Results:, For the primary outcome measure, the crude Hazard Rate Ratio (HRR) (lamotrigine relative to lithium) was 0.92 [95% confidence interval (CI): 0.60,1.40]. When the primary endpoints were broken down by polarity, the HRRs (lamotrigine relative to lithium) for mania and depression were, respectively, 1.91 (95% CI: 0.73,5.04) and 0.69 (95% CI: 0.41,1.22). There was no between-group difference in terms of staying in study [HRR: 0.85 (95% CI: 0.61,1.19)]. Most treatment failures occurred within the first 1.5 years of treatment, and, among patients followed for at least five years, practically no patients were maintained successfully on monotherapy with either of the drugs. The lithium-treated patients reported diarrhea, tremor, polyuria, and thirst more frequently. Two cases, probably lamotrigine-related, of benign rash occurred. Conclusions:, No differences in maintenance effectiveness between lithium and lamotrigine could be demonstrated. Lamotrigine was better tolerated than lithium, but apparently this did not influence the outcome. [source] Sleep quality and respiratory function in children with severe cerebral palsy using night-time postural equipment: a pilot studyACTA PAEDIATRICA, Issue 11 2009Catherine M Hill Abstract Background:, Night-time postural equipment (NTPE) prevents contractures and hip subluxation in children with severe physical disabilities. However, impact on sleep quality and respiratory function has not been objectively studied. Methods:, Ten children with severe cerebral palsy (CP), mean age of 10.9 (range: 5.3,16.7) years, were recruited from a community population. Polysomnography was undertaken on two nights, once with the child sleeping in their NTPE and once sleeping unsupported. Randomization to first night condition controlled for first night effects. Results:, Night-time postural equipment use was associated with higher mean overnight oxygen saturation for three children but lower values for six children compared with sleeping unsupported. There were no differences in sleep quality between the conditions. The study group had lower overnight oxyhaemoglobin saturation values, less rapid eye movement (REM) sleep and higher arousal indices compared with typically developing children. Conclusion:, This pilot study indicated that children with severe CP risk respiratory compromise in sleep irrespective of positioning. Further study will determine if the observed trend for mean overnight oxygen saturation to be lower within positioning equipment reflects random night-to-night variation or is related to equipment use. We suggest that respiratory function is assessed when determining optimal positioning for children using night-time positioning equipment. [source] Step-forward Randomization in Multicenter Emergency Treatment Clinical TrialsACADEMIC EMERGENCY MEDICINE, Issue 6 2010Wenle Zhao PhD Abstract The authors present a new centralized randomization method for multicenter emergency treatment clinical trials. With this step-forward method, treatment randomization for the next subject is performed immediately after the enrollment of the current subject. This design ensures the readiness of the treatment assignment for each subject at the point of study enrollment, and it simultaneously provides effective control on treatment assignments balance and distributions of covariates. The authors also discuss procedures of the step-forward randomization method along with its implementation for two National Institute of Neurological Disorders and Stroke,funded multicenter acute stroke trials, one double-blinded and one open-labeled. Advantages and limitations are presented based on experience gained in these two trials. ACADEMIC EMERGENCY MEDICINE 2010; 17:659,665 © 2010 by the Society for Academic Emergency Medicine [source] Reverse Auctions with Multiple Reinforcement Learning Agents,DECISION SCIENCES, Issue 1 2008Subhajyoti Bandyopadhyay ABSTRACT Reverse auctions in business-to-business (B2B) exchanges provide numerous benefits to participants. Arguably the most notable benefit is that of lowered prices driven by increased competition in such auctions. The competition between sellers in reverse auctions has been analyzed using a game-theoretic framework and equilibria have been established for several scenarios. One finding of note is that, in a setting in which sellers can meet total demand with the highest-bidding seller being able to sell only a fraction of the total capacity, the sellers resort to a mixed-strategy equilibrium. Although price randomization in industrial bidding is an accepted norm, one might argue that in reality managers do not utilize advanced game theory calculations in placing bids. More likely, managers adopt simple learning strategies. In this situation, it remains an open question as to whether the bid prices converge to the theoretical equilibrium over time. To address this question, we model reverse-auction bidding behavior by artificial agents as both two-player and n -player games in a simulation environment. The agents begin the game with a minimal understanding of the environment but over time analyze wins and losses for use in determining future bids. To test for convergence, the agents explore the price space and exploit prices where profits are higher, given varying cost and capacity scenarios. In the two-player case, the agents do indeed converge toward the theoretical equilibrium. The n -player case provides results that reinforce our understanding of the theoretical equilibria. These results are promising enough to further consider the use of artificial learning mechanisms in reverse auctions and other electronic market transactions, especially as more sophisticated mechanisms are developed to tackle real-life complexities. We also develop the analytical results when one agent does not behave strategically while the other agent does and show that our simulations for this environment also result in convergence toward the theoretical equilibrium. Because the nature of the best response in the new setting is very different (pure strategy as opposed to mixed), it indicates the robustness of the devised algorithm. The use of artificial agents can also overcome the limitations in rationality demonstrated by human managers. The results thus have interesting implications for designing artificial agents in automating bid responses for large numbers of bids where human intervention might not always be possible. [source] Clinical trials methodology: randomization, intent-to-treat, and random-effects regressionDEPRESSION AND ANXIETY, Issue 8 2009David C. Atkins First page of article [source] Clinical trials and statistical analyses: what should dermatologists look for in a report?DERMATOLOGIC THERAPY, Issue 3 2009Mohamed Alosh ABSTRACT Clinicians need to evaluate the quality of individual clinical studies and synthesize the information from multiple clinical studies to provide insights in selecting appropriate therapies for patients. Understanding the key statistical principles that underlie a clinical trial and how they may be implemented can help clinicians properly interpret the efficacy and safety findings of clinical trials. Several factors should be considered when evaluating clinical studies reported in the literature, as important differences might exist among reported studies, thereby impacting the reliability of their findings. Studies vary in terms of study design, conduct, analysis, and presentation of findings. The key features to consider when evaluating clinical trials are inferential intent (exploratory versus confirmatory), choice of control group, randomization, extent of blinding, prespecification of analyses, appropriate handling of missing data, and multiple end points. Making comparisons across studies is extremely difficult and rarely statistically justified. However, this article will point out issues to keep in mind when evaluating multiple studies, such as variations in design and study populations. [source] Early detection of relapse in panic disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2004M. R. Mavissakalian Objective:, To explore predictive models of relapsing based on change in symptoms at a time when panic disorder patients are still in remission following discontinuation of antidepressants. Method:, Forty-seven subjects, who were randomized to double-blind placebo and who had valid data at four time points: pretreatment, randomization to placebo substitution, an assessment on placebo prior to the last assessment or relapse and their last assessment (relapsers n = 15, non-relapsers n = 32) were studied using descriptive, growth curve analysis and logistic regression methodologies. Results:, Measures of generalized anxiety, fearfulness and disability at work and at home were better predictors of relapse than measures of panic and anxiety sensitivity. Logistic regression models using any one of these four general variables and its linear change correctly predicted relapse for 78.7,84.4% of the study subjects. Conclusion:, It is possible to gauge, with a fair degree of accuracy, the probability of relapsing in panic disorder patients who have discontinued serotonergic antidepressants 2 months prior to the return of panic. [source] Twice daily biphasic insulin aspart improves postprandial glycaemic control more effectively than twice daily NPH insulin, with low risk of hypoglycaemia, in patients with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 6 2003J. S. Christiansen Objective:, Biphasic insulin aspart 30 (BIAsp30) is a dual release formulation, containing 30% soluble and 70% protamine-crystallized insulin aspart. This study compared the glycaemic control and safety profiles achieved with either twice daily BIAsp30 or NPH insulin in patients with type 2 diabetes not optimally controlled by oral hypoglycaemic agents (OHAs), NPH insulin or a combination of both. Methods:, In this 16-week multinational, parallel-group, double-blind trial, 403 such patients were randomized to receive either BIAsp30 or NPH insulin immediately before breakfast and evening meals. OHAs were discontinued at randomization. Efficacy was assessed by glycosylated haemoglobin (HbA1c) and self-recorded daily 8-point blood glucose (BG) profiles. Hypoglycaemic and other adverse events were the chosen safety parameters. Results:, HbA1c concentration decreased by >0.6% (p < 0.0001 vs. baseline) in both groups, with metabolic control continuing to improve throughout the trial without reaching a stable level. Patients who switched from once or twice daily NPH monotherapy to twice daily BIAsp30 achieved a significantly greater reduction in HbA1c (0.78%) than those randomized to twice daily NPH insulin (0.58%; p = 0.03). BIAsp30 decreased mean daily postprandial glycaemic exposure to a greater extent than NPH insulin (mean difference = 0.69 mmol/l; p < 0.0001), reflecting greater decreases in the postbreakfast and postdinner increments (of 1.26 and 1.33 mmol/l, respectively), although postlunch increment was relatively increased (by 0.56 mmol/l). Despite the greater reduction in overall postprandial glycaemic exposure in the BIAsp30 group, the overall safety profile of BIAsp30 was equivalent to that of NPH insulin with <2% of patients experiencing major hypoglycaemia, and approximately 33% reporting minor hypoglycaemic episodes, in both groups. Conclusion:, Twice daily BIAsp30 reduced postprandial glucose exposure to a significantly greater extent than NPH insulin and was at least as effective at reducing HbA1c in patients with type 2 diabetes. Both insulins were well tolerated. In patients poorly controlled on OHAs or NPH alone, glycaemic control can be improved by switching to twice daily BIAsp30, without increasing hypoglycaemic risk. [source] An Emergency Department Intervention to Increase Booster Seat Use for Lower Socioeconomic FamiliesACADEMIC EMERGENCY MEDICINE, Issue 4 2006Michael A. Gittelman MD Abstract Objectives: To evaluate the effectiveness of booster seat education within an emergency department (ED) setting for families residing in lower socioeconomic neighborhoods. Methods: This was a prospective, randomized study of families with children aged 4 to 7 years and weighing 40 to 80 lb who presented to a pediatric ED without a booster seat and resided in lower socioeconomic communities. Subjects were randomly assigned to one of three groups: 1) received standard discharge instructions, 2) received five-minute booster seat training, and 3) received five-minute booster seat training and free booster seat with installation. Automobile restraint practices were obtained initially and by telephone at one month. Results: A total of 225 children were enrolled. Before randomization in the study, 79.6% of parents reported that their child was usually positioned in the car with a lap/shoulder belt and 13.3% with a lap belt alone. Some parents (16.4%) had never heard of a booster seat, and 44.9% believed a lap belt was sufficient restraint. A total of 147 parents (65.3%) were contacted for follow-up at one month. Only one parent (1.3%) in the control group and four parents (5.3%) in the education group purchased and used a booster seat after their ED visit, while 55 parents (98.2%) in the education and installation group reported using the booster seat; 42 (75.0%) of these parents reported using the seat 100% of the time. Conclusions: Education in a pediatric ED did not convince parents to purchase and use booster seats; however, the combination of education with installation significantly increased booster seat use in this population. [source] Human Patient Simulation Is Effective for Teaching Paramedic Students Endotracheal IntubationACADEMIC EMERGENCY MEDICINE, Issue 9 2005FRCPC, Robert E. Hall BSc Abstract Objectives: The primary purpose of this study was to determine whether the endotracheal intubation (ETI) success rate is different among paramedic students trained on a human patient simulator versus on human subjects in the operating room (OR). Methods: Paramedic students (n= 36) with no prior ETI training received identical didactic and mannequin teaching. After randomization, students were trained for ten hours on a patient simulator (SIM) or with 15 intubations on human subjects in the OR. All students then underwent a formalized test of 15 intubations in the OR. The primary outcome was the rate of successful intubation. Secondary outcomes were the success rate at first attempt and the complication rate. The study was powered to detect a 10% difference for the overall success rate (,= 0.05, ,= 0.20). Results: The overall intubation success rate was 87.8% in the SIM group and 84.8% in the OR group (difference of 3.0% [95% confidence interval {CI} =,4.2% to 10.1%; p = 0.42]). The success rate on the first attempt was 84.4% in the SIM group and 80.0% in the OR group (difference of 4.4% [95% CI =,3.4% to 12.3%; p = 0.27]). The complication rate was 6.3% in the SIM group and 4.4% in the OR group (difference of 1.9% [95% CI =,2.9% to 6.6%; p = 0.44]). Conclusions: When tested in the OR, paramedic students who were trained in ETI on a simulator are as effective as students who trained on human subjects. The results support using simulators to teach ETI. [source] A systematic review of the effectiveness of smoking relapse prevention interventions for abstinent smokersADDICTION, Issue 8 2010Shade Agboola ABSTRACT Aims To carry out a systematic review of the effectiveness of relapse prevention interventions (RPIs) among abstinent smokers who had completed an initial course of treatment or who had abstained unassisted, pooling only outcome data from similar follow-up time points. Methods We used the same search strategy as was used in Cochrane reviews of RPIs to identify randomized trials of behavioural and pharmacological studies of smoking RPIs published up to July 2008. Abstinence from smoking was defined as either continuous abstinence or point prevalence abstinence, measured at three follow-up time points: short term (1,3 months post randomization), medium term (6,9 months) and long term (12,18 months). Abstinence among pregnant/postpartum women was also measured at delivery or the last follow-up prior to delivery. Random effect meta-analysis was used to estimate pooled odds ratios (OR) with 95% confidence intervals (CI). Results Thirty-six studies randomizing abstainers were included. Self-help materials appeared to be effective in preventing relapse at long-term follow up in initially unaided quitters (pooled OR 1.52; 95% CI 1.15 to 2.01, I2 = 0%, NNT = 11, 3 studies). Other behavioural interventions for relapse prevention appeared effective in the short term only. There were positive results for the use of pharmacotherapies for relapse prevention. Bupropion was effective at long-term follow-up (pooled OR 1.49; 95% CI 1.10 to 2.01; I2 = 0%; NNT = 11; 4 studies). Nicotine replacement therapy (NRT) was effective at medium-term (pooled OR 1.56; 95% CI 1.16 to 2.11; I2 = 37%; NNT = 14; 4 trials) and long-term follow-ups (pooled OR 1.33; 95% CI 1.08 to 1.63; I2 = 0%; NNT = 20; 4 trials). Single trials of extended treatment of Varenicline and rimonabant were also found to be effective at short-term and medium-term follow-ups. Conclusions Self-help materials appear to prevent relapse in initially unaided quitters. Use of NRT, bupropion and varenicline appears to be effective in preventing relapse following an initial period of abstinence or an acute treatment episode. There is currently no good evidence that behavioural support prevents relapse after initial unaided abstinence or following an acute treatment period. [source] Spatial distribution and environmental correlates of Australian snubfin and Indo-Pacific humpback dolphinsECOGRAPHY, Issue 3 2006Guido J. Parra We present data on the spatial distribution of Australian snubfin and humpback dolphins using boat-based line transect surveys in three adjacent bays located in the Far Northern Section of the Great Barrier Reef Marine Park, northeast Queensland. We used Geographic Information Systems (GIS), and both randomization and Mantel tests to examine the relationship between the spatial distribution of the dolphins and three simple, readily quantified, environmental variables: distance to land, distance to river mouth, and water depth. Mantel tests allowed us to make clear inferences about the correlation of the species' distributions with environmental variables, while taking into account spatial autocorrelation and intercorrelation among variables. Randomization tests indicated snubfin and humpback dolphins occur closer to land than would be expected at random. Two-sample randomization tests indicated snubfin dolphins were found closer to river mouths than were humpback dolphins. Taking spatial autocorrelation into account, Mantel tests indicated all environmental variables were correlated with the spatial distribution of snubfin and humpback dolphins. Interspecific differences in spatial distribution appeared to be related to proximity to river mouths. Preference by snubfin and humpback dolphins for nearshore, estuarine waters is likely related to the productivity of these tropical coastal areas. This spatial analysis suggests that existing protected areas in this region may not include the most critical habitats for snubfin and humpback dolphins. The techniques used here shown relationships between the spatial distribution of the dolphins and environmental features that should facilitate their management and conservation. [source] An Evaluation of a Blind Rotational Technique for Selective Mainstem IntubationACADEMIC EMERGENCY MEDICINE, Issue 10 2004Aaron E. Bair MD Abstract Objectives: Although rare, massive hemoptysis and major bronchial disruptions are associated with high mortality. Selective ventilation of the uninvolved lung can increase the likelihood of survival. Specialized devices used for single lung ventilation are often not readily available and can be difficult to place in the emergency department. The authors evaluated a blind rotational technique for selective mainstem intubation using either a standard endotracheal tube (ET) or a directional-tip endotracheal tube (DTET). Methods: This was a prospective, randomized trial on 25 human cadavers. The desired side of mainstem intubation was determined by randomization. Each cadaver was used for four ET, four DTET, and four control intubations. In the ET group, the trachea was intubated. The tube was then rotated 90° in the direction of the desired placement and advanced until resistance was met. In the DTET group, the technique was identical, except the trigger was activated to flex the tip during advancement. In the control group, an ET was advanced in neutral alignment until resistance was met. A bronchoscopist blinded to the desired placement determined tube position. Comparison testing was performed using Pearson's chi-square test. Results: When attempting to intubate the left mainstem, use of the ET with the rotational technique was successful 72.3% of the time (95% confidence interval [95% CI] = 57% to 84%). Intubation of the left mainstem using the DTET was successful 68.5% of the time (95% CI = 54% to 81%; p = 0.67). Attempts to selectively intubate the right mainstem using the rotational technique were highly successful in both groups: 94% for the ET (95% CI = 84% to 99%) versus 97.8% for the DTET (95% CI = 89% to 100%). Among controls, the right mainstem was intubated 93% of the time (95% CI = 86% to 97%). Conclusions: In a cadaveric model, the left mainstem bronchus can be selectively intubated with moderate reliability using this rotational technique. Use of a DTET confers no significant advantage. The ability to generalize these findings to living subjects is unknown. [source] School-based alcohol education: results of a cluster-randomized controlled trialADDICTION, Issue 3 2009Matthis Morgenstern ABSTRACT Objective This study aimed to examine the effects of a school-based alcohol education intervention. Design Two-arm three-wave cluster-randomized controlled trial, with schools as the unit for randomization. Surveys were conducted prior to intervention implementation, then 4 and 12 months after baseline. Setting A total of 30 public schools in Schleswig-Holstein, Germany. Participants Baseline data were obtained from 1686 7th graders. The retention rate was 85% over 12 months. Intervention The intervention consisted of four interactive lessons conducted by teachers, booklets for students and booklets for parents. Measures Knowledge, attitudes, life-time alcohol consumption (ever use alcohol without parental knowledge, ever been drunk and ever binge drinking) and past-month alcohol use. Results Intention-to-treat analyses revealed that intervention status was associated with more general knowledge about alcohol and lower levels of life-time binge drinking. No effects were found with respect to students' self-reported attitudes, intentions to drink, life-time alcohol use and past-month alcohol use. Conclusions The results indicate that this brief school-based intervention had a small short-term preventive effect on alcohol misuse. [source] Linking opioid-dependent hospital patients to drug treatment: health care use and costs 6 months after randomizationADDICTION, Issue 12 2006Paul G. Barnett ABSTRACT Aims To conduct an economic evaluation of the first 6 months' trial of treatment vouchers and case management for opioid-dependent hospital patients. Design Randomized clinical trial and evaluation of administrative data. Setting Emergency department, wound clinic, in-patient units and methadone clinic in a large urban public hospital. Participants The study randomized 126 opioid-dependent drug users seeking medical care. Interventions Participants were randomized among four groups. These received vouchers for 6 months of methadone treatment, 6 months of case management, both these interventions, or usual care. Findings During the first 6 months of this study, 90% of those randomized to vouchers alone enrolled in methadone maintenance, significantly more than the 44% enrollment in those randomized to case management without vouchers (P < 0.001). The direct costs of substance abuse treatment, including case management, was $4040 for those who received vouchers, $4177 for those assigned to case management and $5277 for those who received the combination of both interventions. After 3 months, the vouchers alone group used less heroin than the case management alone group. The difference was not significant at 6 months. There were no significant differences in other health care costs in the 6 months following randomization. Conclusion Vouchers were slightly more effective but no more costly than case management during the initial 6 months of the study. Vouchers were as effective and less costly than the combination of case management and vouchers. The finding that vouchers dominate is tempered by the possibility that case management may lower medical care costs. [source] Bootstrap calibration to improve the reliability of tests to compare sample means and variancesENVIRONMETRICS, Issue 8 2001R. I. C. Chris Francis Abstract The comparison of several sample means to see whether they differ significantly is a common analysis, which is not straightforward when the samples may be from non-normal distributions with different variances. A recent study found that a randomization test that attempts to approximate the distribution of F -statistics from one- and two-factor analysis of variance in the presence of unequal population variances was the best of 12 alternative tests considered. However, it sometimes suffered from excess size with data from extremely non-normal distributions. In the present article a method for improving the robustness of the test by bootstrap calibration is described for one-factor analysis of variance, and shown to be effective by a simulation study. The method is also applied with Levene's test for unequal variance by randomization. In this case the test is very robust without calibration, and calibration does not improve it. Copyright © 2001 John Wiley & Sons, Ltd. [source] Cocaine Rapid Efficacy Screening Trial (CREST): a paradigm for the controlled evaluation of candidate medications for cocaine dependenceADDICTION, Issue 2005Deborah B. Leiderman ABSTRACT Aim Development of effective medications for the treatment of cocaine dependence remains a major priority for the National Institute on Drug Abuse (NIDA) at the National Institutes of Health. The Cocaine Rapid Efficacy Screening Trial (CREST) paradigm was developed by the Division of Treatment Research and Development (DT R&D) at NIDA with the goal of enhancing pilot clinical trial validity when systematically assessing a range of medications and drug classes for potential utility in treatment of cocaine dependence. Design CREST utilizes a randomized, controlled, parallel group, blinded methodology for comparing one or more marketed medications against a standard, pharmaceutical grade placebo. The trial design is comprised of a flexible 2,4-week screening/baseline period followed by randomization to an 8-week treatment period. Measures Standard measures of outcomes for the CREST included urinary benzoylecgonine (primary metabolite of cocaine), retention, cocaine craving, depression, clinical global impression and HIV-risk behaviors. In order to facilitate comparisons of data from the CREST studies across sites, drug classes and time, standardized procedures, measures and psychosocial counseling were used. Results A total of 19 medications were evaluated in out-patient treatment research clinics in Boston, Cincinnati, Los Angeles, New York and Philadelphia. Conclusions Findings supported decisions to move forward three medications (cabergoline, reserpine, tiagabine) using full-scale, adequately powered, randomized placebo-controlled trial designs. Lessons learned from the CREST experience continue to shape cocaine pharmacotherapy trial design and execution. [source] Advanced Statistics:Statistical Methods for Analyzing Cluster and Cluster-randomized DataACADEMIC EMERGENCY MEDICINE, Issue 4 2002Robert L. Wears MD Abstract. Sometimes interventions in randomized clinical trials are not allocated to individual patients, but rather to patients in groups. This is called cluster allocation, or cluster randomization, and is particularly common in health services research. Similarly, in some types of observational studies, patients (or observations) are found in naturally occurring groups, such as neighborhoods. In either situation, observations within a cluster tend to be more alike than observations selected entirely at random. This violates the assumption of independence that is at the heart of common methods of statistical estimation and hypothesis testing. Failure to account for the dependence between individual observations and the cluster to which they belong can have profound implications on the design and analysis of such studies. Their p-values will be too small, confidence intervals too narrow, and sample size estimates too small, sometimes to a dramatic degree. This problem is similar to that caused by the more familiar "unit of analysis error" seen when observations are repeated on the same subjects, but are treated as independent. The purpose of this paper is to provide an introduction to the problem of clustered data in clinical research. It provides guidance and examples of methods for analyzing clustered data and calculating sample sizes when planning studies. The article concludes with some general comments on statistical software for cluster data and principles for planning, analyzing, and presenting such studies. [source] New Beverage for Cardiovascular Health, Proposal Based on Oriental and Occidental Food Culture from a World-Wide Epidemiological StudyGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2008Emilio Hideyuki Moriguchi Objectives: To investigate whether combined isoflavones and antioxidants in oriental and occidental drinks reduce the risk of cardiovascular disease (CVD) in high-risk Japanese immigrants living in Brazil. Materials and methods: From among over 100 Japanese immigrants thirty-seven females aged 45,60 years in Porto Alegre, Brazil, were randomized after informed consent into two groups to drink 200 ml of whole soy cell juice (S) containing 7.5 g soy protein and 10 mg of isoflavones (aglycone) in peach juice or placebo peach juice (P) with 80 Kcal for 12 weeks. Health survey including 24-hour urine (24 U) examination were carried out before the randomization and after the double blind placebo controlled intervention study. Results: Both weight and body mass index (BMI) were significantly (p < 0.05, 0.01) decreased from the baseline only in the S group. Systolic blood pressure (SBP) was decreased significantly (p < 0.05) from the baseline in the S group with elevated 24 U isoflavone excretion (>10 µmol), and there was a significant (p < 0.05) inter-group difference between the S and P groups after intervention. Total and low density lipoprotein (LDL)-cholesterol (C) decreased significantly (p < 0.05) in the S group from the baseline and there was a significant difference (p < 0.05) between the S and P groups after intervention. HbA1c and atherogenic index (non-high density lipoprotein (HDL)-C/HDL-C) were significantly (p < 0.05) decreased in both groups. Conclusions: Soy isoflavones combined with fruit antioxidants, the combination of which might potentiate local nitric oxide (NO) affect, decreased SBP, total cholesterol and LDL-C. Peach juice itself improved blood glucose levels and the atherogenic index of the high-risk Japanese population in Brazil. [source] | ||||||||||||||||||||||||||||||||||||||||||||||