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At least 271 records · Page 15Linked to original sources
PubMed2003

Transthoracic echocardiography in rats. Evalution of commonly used indices of left ventricular dimensions, contractile performance, and hypertrophy in a genetic model of hypertrophic heart failure (SHHF-Mcc-facp-Rats) in comparison with Wistar rats during aging.

Two-weekly echocardiographic examinations were conducted in nine SHHF-Mc-fa(cp) rats in comparison with eight age-matched Wistar rats. In the SHHF-rats, characterized by progressive LV-dilation and decreasing contractile function between 77-87 weeks of age, left ventricular (LV) hypertrophy was most sensitively demonstrated by increased LV-mass-index (p < 0.001). LV-areas and area-ejection fraction (EF) (2D-images) discriminated more sensitively in the early stages than M-mode-derived diameters and fractional shortening (FS); midwall shortening was the most sensitive parameter of reduced systolic function. Post-mortem measurements showed an excellent correlation with calculated LV-mass (r = 0.91). Post-mortem LV-volumes correlated significantly with diastolic LV-diameters, LV-areas, and calculated LV-volumes (r = 0.56-0.59). Mean within-subject standard deviations in controls were 0.5-0.6 mm (LV-diameters), 3.1-4.6 mm(2) (LV-areas), approximately 10% of the mean for FS, area-EF and midwall shortening, and approximately 20% for wall thickness and LV-mass. The data might be used to choose the most sensitive parameters, and to estimate sample size for echocardiographic investigations in rats.

Aging↗
PubMed2003

Alcoholism-related phenotypes and genetic variants of the CB1 receptor.

OBJECTIVE: Neurotransmitter release of GABAergic and glutamatergic neurons may be significantly influenced by cannabinoid CB1 receptors located at presynaptic nerve terminals. GABA and glutamate have been reported to be involved in the pathogenesis of severe alcohol withdrawal-induced seizures and delirium tremens. The aim of this study is to test the potential influence of a bi-allelic cannabinoid receptor gene (CNR1) polymorphism (G1359A) on severe alcohol withdrawal syndromes. METHODS: Based upon a sample size estimation, 196 subjects meeting DSM IV and ICD10 criteria for alcohol dependence and 210 non-alcoholic controls were recruited for study. CB1 polymorphisms were determined using polymerase chain reaction (PCR). History of alcohol withdrawal-induced delirium tremens, seizures and other alcohol withdrawal-related phenotypes were obtained using the SSAGA (Semi-Structured Assessment of Genetics in Alcoholism). Data were corroborated with information from the inpatients' clinical files. RESULTS: Allele frequencies of the CNR1 G1359A polymorphism were within the range reported by previous studies. After correcting for multiple testing, no association of the A- or G-allele of CNR1 polymorphism with a history of alcohol withdrawal-induced seizures was detected. In addition, no significant relationships with other alcoholism-related phenotypes were found. CONCLUSION: This study failed to confirm an earlier report of a potential role of a CNR1 polymorphism in the pathogenesis of delirium tremens.

Adult↗
PubMed1994

The efficacy of oral splints in the treatment of myofascial pain of the jaw muscles: a controlled clinical trial.

Oral splints are widely used in the treatment of myofascial pain of masticatory muscles, even though their mechanism of action is unknown. The present study evaluated the therapeutic efficacy of splints using a parallel, randomized, controlled and blind design. Following a sample size estimation, 63 subjects were recruited and assigned to 3 groups: (1) passive control: full occlusal splint worn only 30 min at each appointment; (2) active control: palatal splint worn 24 h/day; and (3) treatment: full occlusal splint worn 24 h/day. On each of 7 visits over 10 weeks, subjects rated on 100 mm visual analogue scales their pain intensity and unpleasantness at rest and after experimental mastication. The effect of pain on the quality of life was also rated on category scales. All pain ratings decreased significantly with time, and quality of life improved for all 3 groups. However, there were no significant differences between groups in any of the variables. These data suggest that the gradual reduction in the intensity and unpleasantness of myofascial pain, as well as the improvement of quality of life during the trial, was non-specific and not related to the type of treatment.

Adolescent↗
PubMed2006

Statistical power and analytical quantification.

It is suggested that power analysis should be formally incorporated into quantification experiment reports in order to substantiate the conclusions derived from experimental data more effectively. The article addressed the issues of power analysis calculation, sample size estimation and appropriate data reporting in quantitative analytical comparisons. Illustrative examples from the literature are used to show how the described power analysis theory could be applied in practice.

Chemistry Techniques, Analytical↗
PubMed2005

A cross-sectional analysis demonstrated the healthy volunteer effect in smokers.

OBJECTIVE: This cross-sectional descriptive analysis sought to determine if a healthy volunteer effect can be demonstrated among smokers selected to participate in a dietary intervention trial. STUDY DESIGN AND SETTING: Body mass index (BMI), body fat, physical activity, dietary intake, and plasma concentration of antioxidant nutrients and carotenoids were assessed cross-sectionally, at the time of enrollment into a dietary intervention trial, among 136 adult smokers. RESULTS: Mean BMI was below national age- and gender-specific averages as was prevalence of overweight and obesity. Physical activity was reported to average 15.4 h/wk. Compared with other sample populations of smokers, our smokers reported lower total fat and cholesterol intakes, higher vitamin C and beta-carotene intakes, and generally equal vitamin E intakes. Plasma ascorbic acid, alpha-tocopherol, alpha- and beta-carotene, and beta-cryptoxanthin concentrations were higher than those of smokers surveyed by NHANES III. CONCLUSION: These findings suggest that a "healthy volunteer effect" can be described among adult smokers. Future dietary intervention trials among smokers should cautiously estimate sample size because smokers electing to participate may report healthier dietary patterns than other smokers. Screening criteria regarding baseline micronutrient status of smokers should be evaluated given that intervention effects may be dependent on overall health status.

Adolescent↗
PubMed2006

Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer.

In vivo MRI-derived measurements of human cerebral cortex thickness are providing novel insights into normal and abnormal neuroanatomy, but little is known about their reliability. We investigated how the reliability of cortical thickness measurements is affected by MRI instrument-related factors, including scanner field strength, manufacturer, upgrade and pulse sequence. Several data processing factors were also studied. Two test-retest data sets were analyzed: 1) 15 healthy older subjects scanned four times at 2-week intervals on three scanners; 2) 5 subjects scanned before and after a major scanner upgrade. Within-scanner variability of global cortical thickness measurements was <0.03 mm, and the point-wise standard deviation of measurement error was approximately 0.12 mm. Variability was 0.15 mm and 0.17 mm in average, respectively, for cross-scanner (Siemens/GE) and cross-field strength (1.5 T/3 T) comparisons. Scanner upgrade did not increase variability nor introduce bias. Measurements across field strength, however, were slightly biased (thicker at 3 T). The number of (single vs. multiple averaged) acquisitions had a negligible effect on reliability, but the use of a different pulse sequence had a larger impact, as did different parameters employed in data processing. Sample size estimates indicate that regional cortical thickness difference of 0.2 mm between two different groups could be identified with as few as 7 subjects per group, and a difference of 0.1 mm could be detected with 26 subjects per group. These results demonstrate that MRI-derived cortical thickness measures are highly reliable when MRI instrument and data processing factors are controlled but that it is important to consider these factors in the design of multi-site or longitudinal studies, such as clinical drug trials.

Aged↗
PubMed2006

Standardized data collection for multi-center clinical studies of severe malaria in African children: establishing the SMAC network.

The Severe Malaria in African Children (SMAC) network was established to conduct mortality-based trials. Although falciparum malaria kills more than one million children each year, single centers cannot enroll enough patients to detect reductions of 20-30% in mortality rates. Our aim was to quantify and describe severe malaria across a variety of epidemiological settings so that we could design intervention studies with more precise sample size estimates. We used a standardized surveillance mechanism to capture clinical, laboratory and outcome data on all parasitemic children admitted to hospital. Between December 2000 and December 2003, 20333 patients were enrolled at five sites. The frequency of severe malaria syndromes (cerebral malaria, severe malarial anemia and acidosis) differed between sites, as did the syndrome-specific mortality rates. Intervention studies targeted at reducing mortality in one or a combination of severe malaria syndromes would require 3-4 years to complete within the existing network. These data provide more accurate estimates of the disease burden of children hospitalized for malaria in sub-Saharan Africa. Networks are required to recruit enough patients for mortality-based studies and to encompass the epidemiological diversity of malaria in sub-Saharan Africa. SMAC represents the first effort to develop this capacity.

Africa South of the Sahara↗
PubMed2005

Evaluation of the clinical efficacy of prokinetic drugs in the management of post-operative ileus: can retrospective data help us?

The objectives of the study were to determine whether retrospective data can be used to answer questions about the efficacy of prokinetic agents when used to treat horses with post-operative ileus (POI). We describe prevalence and mortality of POI with reference to treatment with four prokinetic agents. By combining data from two Hospitals a study population of 55 horses with POI following pedunculated lipoma obstruction (PLO) was established. Univariable and multivariable associations were determined between short term survival and potential explanatory variables. With death as outcome in multivariable models, breed and hospital were significantly associated with outcome but the use of prokinetic agents was not (P=0.15). However, sample size estimates indicate the low power of this study to detect differences in outcome. It was not possible definitively to evaluate the efficacy of prokinetics as treatment for POI following PLO using retrospective data. The data were suggestive of limited efficacy of prokinetics as treatment for POI. It is postulated that the identified association between hospital and survival reflects differences in clinician decision making. The study highlights the need for further prospective studies using randomised clinical trials to evaluate accurately the efficacy of prokinetic agents. This report illustrates difficulties with performing retrospective analysis of clinical data to determine the efficacy of treatment regimes.

Animals↗
PubMed2002

Tezosentan in patients with acute heart failure and acute coronary syndromes: design of the Randomized Intravenous Tezosentan study (RITZ-4).

BACKGROUND: Endothelin-1 is the most potent known endogenous vasoconstrictor. It is released during ischemia, and elevated levels have been demonstrated in hypertension, myocardial infarction, and heart failure. Tezosentan is a dual endothelin receptor antagonist, and it has improved cardiac output and reduced pulmonary and systemic vascular resistance in experimental animal models and in initial human acute decompensated heart failure studies. METHODS: The Randomized Intravenous TeZosentan (RITZ-4) study was a multicenter, randomized, double-blind, placebo-controlled trial of tezosentan in patients with acute heart failure associated with acute coronary syndrome. The estimated sample size was 200 patients. Patients with evidence of acute heart failure and acute coronary syndrome were eligible for the study. Eligible patients were randomly assigned to tezosentan or matching placebo. The primary end point was the composite of death, worsening heart failure, recurrent ischemia, and recurrent or new myocardial infarction within 72 hours after the start of study drug treatment. Secondary end points included all-cause death and hospitalization at 30 days, and length of initial hospital stay. RESULTS: Enrollment was completed in February 2001, with 193 patients enrolled. CONCLUSIONS: The RITZ-4 study evaluated an important population in which few data are available to guide medical management. RITZ-4 will provide valuable safety and efficacy data with the novel compound tezosentan in patients with acute heart failure and acute coronary syndrome.

Acute Disease↗
PubMed1999

Modelling MRI enhancing lesion counts in multiple sclerosis using a negative binomial model: implications for clinical trials.

In multiple sclerosis (MS) the number of new enhancing lesions seen on monthly magnetic resonance imaging (MRI) scans is the most widely used response variable in MRI-monitored studies of experimental treatments. However, no statistical model has been proposed to describe the distribution of the number of such lesions across MS patients. This article briefly summarizes the statistical models for counted data. The negative binomial (NB) model is proposed to fit the number of new enhancing lesions counted in a set of 56 untreated MS patients followed for 9 months. It is shown that the large variability present in this data set is better addressed by the NB model (residual deviance=66.6, 54 degrees of freedom) than by the Poisson model (residual deviance=1830.1, 55 degrees of freedom). Applications of the parametrization of lesion counts are discussed, and an example related to computer simulations for the sample size estimation is presented.

Adolescent↗
PubMed1999

Pharmacokinetics during pregnancy: evidence-based maternal dose formulation.

OBJECTIVE: To review the literature regarding how drug pharmacokinetics differ between pregnant and nongravid women. DATA SOURCES: Articles published between 1963 and 1997 were retrieved from the database of the National Library of Medicine for review, using the key words "pregnancy," "pharmacokinetics," and "human." Additional articles and book chapters were identified from the bibliographies of articles retrieved. METHODS OF STUDY SELECTION: Articles had to include primary data that were not previously published. Data abstracted from articles meeting the inclusion criteria included: sample size, estimated gestational age, area under the curve, volume of distribution, maximum plasma concentration, steady-state concentration, half-life, time to maximum plasma concentration, clearance, and data from nonpregnant controls. TABULATION, INTEGRATION, AND RESULTS: Of more than 1000 articles published, 61 articles and book chapters reported relevant pharmacokinetic data, such as those listed, based on primary data. Only two studies synthesized pharmacokinetic data into guidelines for individualized clinical regimens. CONCLUSION: Available data regarding the pharmacokinetics of therapeutic regimens during pregnancy do not provide clinically relevant guidelines for the formulation of therapy for individual patients. Pharmacokinetic investigations during pregnancy that produce evidence-based guidelines for treating individual patients were identified as a major area of need. Minimum requirements are recommended for reporting pharmacokinetic studies in obstetrics.

Analgesics↗
PubMed1996

Completeness of reporting of trials published in languages other than English: implications for conduct and reporting of systematic reviews.

BACKGROUND: Lately, the number of systematic reviews published has increased substantially. Many systematic reviews exclude trials published in languages other than English. However, there is little empirical evidence to support this action. We looked for differences in the completeness of reporting between trials published in other languages and those published in English, to see whether the exclusion of trials published in other languages is justified. METHODS: We compared completeness of reporting, design characteristics, and analytical approaches of 133 randomised controlled trials (RCTs) published in English between 1989 and 1994 and 96 published in French, German, Italian, or Spanish during the same time. RCTs were identified by hand searching of journals (seven in English and six in the other languages). FINDINGS: We found no significant differences between trials published in English and other-language trials for any single item in the completeness of reporting scale (randomisation, double-blinding, withdrawals), or for the overall score (percentage of maximum possible score 51.0% for trials in English, 46.2% for trials in other languages; 95% CI for difference -1.1 to 10.5). Other-language trials were more likely than English-language trials to have adult participants, to use two or more interventions, and to compare two or more active treatments without an untreated control group. Trials in other languages were less likely to report a clearly prespecified primary outcome or any rationale for sample size estimation. INTERPRETATION: These results provide evidence for inclusion of all trial reports, irrespective of the language in which they are published, in systematic reviews. Their inclusion is likely to increase precision and may reduce systematic errors. We hope that our findings will prove useful to those developing guidelines and policies for the conduct of reporting of systematic reviews.

Adult↗
PubMed2003

What we have learned about conducting randomized controlled trials in the NICHD MFMU network.

The National Institute of Child Health and Human Development (NICHD) created the NICHD Maternal Fetal Medicine Units Network in 1986 to conduct randomized trials and observational studies in perinatal medicine to improve adverse pregnancy and infant outcomes. From 1986 to 2002, the Network has started 16 randomized trials. Five of the trials are described, with particular attention given to difficult issues that arose, such as feasibility, sample size estimation, randomization in very high risk pregnancies, changing clinical practice, importance of the study question to the investigators, and lack of recruitment. Changes that the Network group made to their organization and methodology as a result of these issues are described, together with their application to some of the other trials proposed and conducted by the group.

Dystocia↗
PubMed2000

Prevention of recurrent depressive episodes with milnacipran: consequences on quality of life.

BACKGROUND: Depression is now seen as a chronic disabling condition that spans the patient's lifetime and creates significant medical, economic and quality of life consequences. METHODS: 500 depressed patients were treated with milnacipran for 6 months. A total of 214 recovered patients were randomised to receive either milnacipran (50 mg bid) or a matching placebo for a 1-year recurrence prevention phase. Recurrence rate was the primary criteria; quality of life (QoL) consequences were evaluated through a shortened version of the French Sickness Impact Profile (SIP), the Depression Impact Profile (DIP). RESULTS: Milnacipran demonstrated its ability to reduce recurrences (Odds-Ratio=1.5; P<0.05), with a more marked effect in recovered patients with few residual symptoms (Odds-Ratio=3.0). Responders who continued treatment with milnacipran had a dramatic improvement in their quality of life, although patients with residual symptoms still experienced some deterioration in their QoL (recreation, emotional, social, alertness and home assistance scores). Even recovered patients having zero scores on the Hamilton Depression Rating Scale-21 items (HDRS) had some QoL deterioration. The DIP emotional score was found to be more predictive of recurrence than the HDRS. Overall, the QoL was improved for those in the milnacipran group in comparison to placebo on the mobility, communication, psycho-social and total scores. LIMITATIONS: The QoL evaluation was a secondary criteria; no a priori sample size estimate was performed. The choice of a generic QoL instrument might have reduced the sensitivity to clinical changes in depression. CONCLUSIONS: Prevention of recurrence in MDD with milnacipran contributes to an improvement in the QoL.

Adolescent↗
PubMed2001

Gemcitabine plus vinorelbine yields better survival outcome than vinorelbine alone in elderly patients with advanced non-small cell lung cancer. A Southern Italy Cooperative Oncology Group (SICOG) phase III trial.

OBJECTIVE: This phase III study was aimed at evaluating whether the addition of gemcitabine (G) to vinorelbine (V) could improve the survival and quality of life (QoL) of elderly patients with advanced NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC, aged >or=70 years, were randomly allocated to receive V 30 mg/m(2) on days 1 and 8 every 3 weeks or G 1200 mg/m(2) plus V 30 mg/m(2) on days 1 and 8 every 3 weeks. Survival was the main end point of the study. The estimated sample size was 120 patients per arm, but an interim analysis of survival was planned on the first 60 patients per arm. RESULTS: In May 1999, an interim analysis was performed with the survival data of the first 120 eligible patients (V(arm)=60, G+V(arm)=60). Forty-nine patients had stage IIIB disease and 71 patients stage IV disease, median potential follow-up of 14 months (range; 3-22), 93 patients had died (G+V(arm)=41, V(arm)=52). Median survival time (MST) was 29 weeks and projected 1-year survival was 30% in the G+V(arm); these values were 18 weeks and 13% in the V(arm). At multivariate Cox analysis, the risk of death in the G+V(arm) compared with V(arm) was 0.48 (95% C1=0.29-0.79; P<0.01). Combination therapy was also associated with a clear delay in symptom and QoL deterioration. The ORR was 22 and 15% in the G+V and V(arms), respectively. Toxicity was not irrelevant in both arms. CONCLUSIONS: G+V treatment is associated with a significantly better survival than V alone in elderly NSCLC patients. The magnitude of the difference justifies the early closure of the study. The G+V regimen is now the SICOG reference regimen in this type of patients.

Aged↗
PubMed2000

The phase II/III transition. Toward the proof of efficacy in cancer clinical trials.

Few phase III investigations show a benefit for an experimental treatment when compared to a standard therapy or placebo. This illustrates the need for more reliable estimates of treatment effects from the phase II investigations used to design the more definitive phase III trials. In this manuscript, we examine four aspects of phase II clinical trial designs: (1) selecting endpoints; (2) defining the patient population for evaluation; (3) determining a level of activity that would justify a phase III trial; and (4) estimating sample sizes. In each area, problems with the conventional approaches are discussed and alternatives for the successful transition of phase II results to a phase III setting are suggested. An application of the design for patients with androgen-independent prostate cancer is illustrated.

Antineoplastic Agents↗
PubMed2000

Design and analysis of three treatment equivalence trials.

We consider design and analysis of clinical trials aimed at demonstrating equivalence of three treatments. We discuss analysis methods that require demonstrating that each pair of treatments has an unimportant difference. The critical values that we provide are smaller than the standard normal critical values, pointing out that the adjustment is counter to the usual multiplicity adjustments. Special issues in demonstrating equivalence of three rather than two treatments are discussed. We propose some conservative criteria for estimating sample size. Procedures for choosing pairs of treatments that are equivalent to each other, even when all three treatments are not shown equivalent, are also discussed along with implications for control of type I errors. We also demonstrate the methods with data from the literature.

Clinical Trials as Topic↗
PubMed1997

Short-term effects of blood pressure control and antihypertensive drug regimen on glomerular filtration rate: the African-American Study of Kidney Disease and Hypertension Pilot Study.

The African-American Study of Kidney Disease and Hypertension pilot study randomized 94 nondiabetic black men and women (mean age, 53 years; 75% male) with presumed hypertensive nephrosclerosis and a baseline glomerular filtration rate (GFR) of 25 to 70 mL/min/1.73 m2 (mean, 52.3 mL/min/1.73 m2) to blood pressure control at either a low mean arterial pressure (MAP) goal of < or = 92 mm Hg or a usual MAP goal of 102 to 107 mm Hg and an antihypertensive drug regimen that included either a calcium antagonist (amlodipine), a beta-blocker (atenolol), or an angiotensin-converting enzyme (ACE) inhibitor (enalapril). After 3 months of follow-up (n = 90), the mean GFR was similar (53.0 mL/min/1.73 m2 v 53.7 mL/min/1.73 m2) to the baseline levels in participants randomized to the low MAP group (n = 44), whereas the mean GFR increased by 3.9 mL/min/1.73 m2 (P = 0.02) in participants randomized to the usual MAP group (n = 46). During the same period of time, the mean GFR increased significantly in participants randomized to the calcium channel blocker regimen (n = 28) (5.7 mL/min/ 1.73 m2; P = 0.01) but not in participants randomized to the beta-blocker regimen (n = 31) (1.7 mL/min/1.73 m2; P = 0.10) or the ACE inhibitor regimen (n = 31) (1.1 mL/min/1.73 m2; P = 0.52). Changes in GFR at 3 months were significantly different among the three treatment groups (P = 0.04). We conclude that the magnitude of short-term effects of blood pressure control and antihypertensive drug regimens on GFR should be considered when estimating sample size for clinical trials designed to evaluate the effects of these interventions on long-term changes in GFR slope.

Adolescent↗