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Results for “randomized crossover trial”

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PubMed2003

The effects of sodium oxybate on clinical symptoms and sleep patterns in patients with fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) is associated with the sleep phenomenon of alpha intrusion, and with low growth hormone secretion. Sodium oxybate has been shown to increase both slow-wave sleep and growth hormone levels. This double blind, randomized, placebo controlled crossover trial was conducted to evaluate the effects of sodium oxybate on the subjective symptoms of pain, fatigue, and sleep quality and the objective polysomnographic (PSG) sleep variables of alpha intrusion, slow-wave (stage 3/4) sleep, and sleep efficiency in patients with FM. METHODS: Patients received either 6.0 g/day sodium oxybate or placebo for 1 month, with an intervening 2 week washout period. Efficacy measures included PSG evaluations, tender point index (TPI), and subjective measurements from daily diary entries. Safety measures included clinical laboratory values, vital signs, and adverse events. RESULTS: Twenty-four female patients were included in the study; 18 completed the trial. TPI was decreased from baseline by 8.5, compared with an increase of 0.4 for placebo (p = 0.0079). Six of the 7 pain/fatigue scores (overall pain, pain at rest, pain during movement, end of day fatigue, overall fatigue, and morning fatigue) were relieved by 29% to 33% with sodium oxybate, compared with 6% to 10% relief with placebo (p < 0.005). Alpha intrusion, sleep latency, and rapid-eye-movement sleep were significantly decreased, while slow-wave (stage 3/4) sleep was significantly increased, compared with placebo (p < 0.005). Two of the 5 subjective sleep related variables were significantly different from placebo: morning alertness (improved by 18% with sodium oxybate, compared with 2% for placebo; p = 0.0033) and quality of sleep (improved by 33% and 10%, respectively; p = 0.0003). CONCLUSION: Sodium oxybate effectively reduced the symptoms of pain and fatigue in patients with FM, and dramatically reduced the sleep abnormalities (alpha intrusion and decreased slow-wave sleep) associated with the nonrestorative sleep characteristic of this disorder.

Adjuvants, Anesthesia↗

PubMed1992

Prospective randomized comparison of high-frequency oscillatory and conventional ventilation in respiratory distress syndrome.

A prospective randomized trial with a crossover design was conducted to compare the efficacy and safety of two distinct strategies of high-frequency oscillatory ventilation (HFOV) to conventional intermittent mandatory ventilation (CV) in the management of respiratory distress syndrome. Only premature neonates with a birth weight less than 1.751 kg were eligible for enrollment into the study. Of 83 patients studied, 26 patients were assigned to CV-only, 27 to HFOV for 72 hours followed by CV (HFOV/CV), and 30 to HFOV-only until extubation. There was no difference among the three groups with respect to the incidence of pulmonary airleak, intraventricular hemorrhage, or death. The highest incidence of chronic lung disease was in the CV-only group. Although both HFOV groups had a lower incidence of chronic lung disease assessed at 30 days and 36 weeks postconception age, the difference was statistically significant only between the CV-only and HFOV-only groups (65% vs 30% at 30 days; P = .008; 38% vs 10% at 36 weeks postconception age, P = .013). These results suggest that use of HFOV as the predominant mode of ventilation in the management of respiratory distress syndrome is as safe as CV and can contribute to a decreased incidence of chronic lung disease. Furthermore, a short (72-hour) period of HFOV support does not provide the same advantage as continuous HFOV.

Analysis of Variance↗

PubMed1999

Norditropin SimpleXx: a liquid human growth hormone formulation, a pen system and an auto-insertion device.

Patient compliance is of vital importance for the outcome of any medical therapy. Compliance is especially a problem in long-term treatment of non-life threatening diseases, such as growth retardation in children. Until recently, all human growth hormone (hGH) products required a reconstitution process. Norditropin((R)) SimpleXx(TM) is a liquid formulation of the biosynthetic hGH product Norditropin((R)), and, together with an improved NovoPen((R)) 1.5, NordiPen(TM), and an auto-insertion device, PenMate(TM)/NordiPenMate(TM), it has been developed in order to ease the injection process for patients. A randomized, open, multicentre, crossover trial compared Norditropin((R)) SimpleXx(TM)/improved NovoPen((R)) 1.5 with freeze-dried Norditropin((R)) PenSet((R))/Nordiject((R)). A total of 67 children with GH deficiency, aged 5-18 years, were treated with either Norditropin((R)) SimpleXx(TM) for 6 weeks followed by Norditropin((R)) for 6 weeks or the opposite (sequences I and II, respectively). Acceptability/convenience and pain perception were evaluated by questionnaire after each period. The function and handling of the PenMate(TM) were evaluated in a Dutch trial by 27 GH-treated children with intrauterine growth retardation, aged 4-16 years, and their parents. All children were accustomed to using the Nordiject((R)) pen. The evaluation of the PenMate(TM) was based on a questionnaire. A similar trial was conducted in England, in which the NordiPen(TM) and the NordiPenMate(TM) were evaluated by 25 GH-treated children and their parents. Norditropin((R)) SimpleXx(TM) was found to be easier to inject by 64% of the children, and 98% of the children found the system easier to use overall. There was no difference in pain perception between the two administration systems, as judged by questionnaires and visual analogue scale score. Three out of four patients preferred to continue treatment with Norditropin((R)) SimpleXx(TM). The safety profiles of the two systems were similar. In the Dutch trial, the PenMate(TM) was found to be easy and safe to handle, even for very young children (aged 4-5 years). Of patients who took a long time to get used to the injections, 73% found that the new pen would help. A total of 88% of the children would prefer to use the PenMate(TM) in the future. Positive results of the handling tests were also reported in the British trial. The use of Norditropin((R)) SimpleXx(TM) and the auto-insertion device may improve patient compliance.

Adolescent↗

PubMed2001

Acute effects of 3,4-methylenedioxymethamphetamine alone and in combination with ethanol on the immune system in humans.

Cell-mediated immune response and release of cytokines after the administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") alone and in combination with ethanol were assessed in a double blind, randomized, crossover, controlled clinical trial. Six healthy male recreational users of MDMA participated in four different experimental sessions, with a washout interval between sessions of 1 week, in which single oral doses of MDMA (100 mg), ethanol (0.8 g/kg), the combination of both drugs, and placebo were tested. Acute MDMA administration produced a time-dependent immune dysfunction in association with serum concentrations of the drug as well as cortisol stimulation kinetics. Although total leukocyte count remained unchanged, there was a decrease in the CD4 T/CD8 T-cell ratio due to a decrease in both the percentage and absolute number of CD4 T-helper cells and simultaneous increase in natural killer (NK) cells. Ethanol consumption produced a decrease in T-helper cells and B lymphocytes. The combination of MDMA and ethanol caused the highest suppressive effect on CD4 T cells and increasing effect in NK cells. Drugs treatment produced a high increase of immunosuppressive cytokines (transforming growth factor-beta and interleukin-10) and a switch from Th1-type cytokines (interleukin-2 and interferon-gamma) to Th2-type cytokines (interleukin-4 and interleukin-10). Disregulation in the production of pro- and anti-inflammatory cytokines with an unbalance toward anti-inflammatory response was also observed. The immune function shows a trend toward baseline levels at 24 h after MDMA kinetics. This transient defect in immunological homeostasis, if temporarily repeated, might alter the immune response with a risk for the general health status.

Adult↗

PubMed2003

Comparison of 3 vancomycin dosage regimens during hemodialysis with cellulose triacetate dialyzers: post-dialysis versus intradialytic administration.

AIMS: Traditionally, vancomycin is administered following dialysis to minimize drug loss when high-flux membranes are employed. Unfortunately, this approach is extremely inconvenient for patients and staff, requiring the patients to remain in the unit for at least 1 hour following dialysis. This study was designed to evaluate the feasibility of administering vancomycin during hemodialysis. Specifically, this study was designed to compare the pharmacokinetics of vancomycin when administered during the last 1-2 hours of dialysis (i.e. intra-dialytic administration) to that administered after completion of dialysis. MATERIALS AND METHODS: In a randomized, 3-way crossover trial, the pharmacokinetics of vancomycin were evaluated in 9 hemodialysis patients, comparing vancomycin 15 mg/kg following dialysis (Phase I), vancomycin 15 mg/kg during the last hour of hemodialysis (Phase II) or vancomycin 30 mg/kg during the last 2 hours of hemodialysis (Phase III). Vancomycin plasma concentrations were obtained over an 8-day period and subsequent comparisons between the treatment approaches were made with paired t-tests or ANOVA, as appropriate. Dialysate vancomycin concentrations determined on Day 1 and Day 3 of Phases II and III were used to calculate the fraction of vancomycin dose removed, and were compared to plasma data using paired t-tests. RESULTS: Vancomycin was significantly removed (33.4 to 39.5%) during a 3- to 4-hour high-flux dialysis session occurring on Day 3 after vancomycin administration. Mean serum concentrations immediately following intradialytic vancomycin administration of 15 mg/kg over the last hour of dialysis or 30 mg/kg over the last 2 hours of dialysis were initially high (77.7 and 95.5 mcg/ml respectively), but fell to 25.9 and 40.5 mcg/ml, respectively, by 4 hours post-dialysis. Predialysis concentrations on Days 3, 5 and 8 were similar for vancomycin 30 mg/kg administered over the last 2 hours of dialysis as compared with a 15 mg/kg dose given after dialysis. Vancomycin 15 mg/kg over the last hour of dialysis resulted in significantly lower subsequent predialysis concentrations than the other dosing schemes. CONCLUSIONS: Vancomycin administration of 30 mg/kg over the last 2 hours of dialysis achieves serum concentrations similar to conventional dosing of 15 mg/kg after dialysis and would allow dosing on a weekly basis.

Adult↗

PubMed2003

Greater rise in fat oxidation with medium-chain triglyceride consumption relative to long-chain triglyceride is associated with lower initial body weight and greater loss of subcutaneous adipose tissue.

OBJECTIVE: Medium-chain triglyceride (MCT) consumption has been shown to increase energy expenditure (EE) and lead to greater losses of the adipose tissue in animals and humans. The objective of this research was to examine the relationship between body composition and thermogenic responsiveness to MCT treatment. DESIGN: Randomized, crossover, controlled feeding trial, with diets rich in either MCT or long-chain triglyceride (LCT) (as olive oil) for periods of 4 weeks each. SUBJECTS: A total of 19 healthy overweight men aged (x+/-s.e.m.) 44.5+/-2.5 y with a body mass index of 27.8+/-0.5 kg/m(2). MEASUREMENTS: EE and body composition were measured using indirect calorimetry and magnetic resonance imaging, respectively, at the baseline and end point of each feeding period. EE was measured for 30 min before consumption of a standard meal and for 5.5 h following the meal. RESULTS: Body weight (BW) decreased (P<0.05) by 1.03+/-0.25 kg with MCT consumption compared to 0.62+/-0.29 kg with LCT consumption. The difference in average EE between MCT and LCT consumptions was related to initial BW, such that men with lower initial BW had a greater rise in EE with MCT consumption relative to LCT on day 28 (r=-0.472, P=0.04) but not day 2 (r=-0.368, P=0.12). Similar results were obtained with fat oxidation on day 28 (r=-0.553, P=0.01). The greater rise in fat oxidation with MCT compared to LCT consumption on day 2 tended to be related to greater loss of BW after MCT vs LCT consumption (r=-0.4075, P=0.08). CONCLUSION: These data suggest that shunting of dietary fat towards oxidation results in diminished fat storage, as reflected by the loss of BW and subcutaneous adipose tissue. Furthermore, MCT consumption may stimulate EE and fat oxidation to a lower extent in men of greater BW compared to men of lower BW, indicative of the lower responsiveness to a rapidly oxidized fat by overweight men.International

Adipose Tissue↗

PubMed2004

Time/duration effectiveness of sildenafil versus tadalafil in the treatment of erectile dysfunction in male spinal cord-injured patients.

STUDY DESIGN: A randomized, blinded, crossover clinical trial comparing sildenafil versus tadalafil for erectile dysfunction (ED) in male spinal cord-injured (SCI) patients. OBJECTIVES: To compare the safety, time/duration effectiveness, and the impact on the quality of life (QoL) of tadalafil 10 mg versus sildenafil 50 mg. SETTING: Neurourology Section, Careggi Hospital, Florence, Italy. METHODS: During a screening (visit 1), a diary card was distributed, in which the subjects assessed, after each attempt at intercourse the quality of their erection, responding (Yes/No) to both Sexual Encounter Profile Questions 2 (SEP2) and 3 (SEP3). The subjects made at least four attempts at intercourse. At visit 2, 15 patients (group 1) were assigned sildenafil and 15 (group 2) started with tadalafil. Responses to baseline International Index of Erectile Function 5 items (IIEF-5), Questions 13-14 (IIEF 15 items) and SEP diary were recorded. Patients attempted intercourse on four separate occasions: within 4 h of taking the first tablet, within 12 h for the second tablet, 24 h for the third, and the fourth from 24 to 36 h. At visit 3, the investigators evaluated the effectiveness with the same measures used at baseline. After a wash-out period, at visit 4, Group 1 was given tadalafil, and Group 2 was given sildenafil. Patients were required to observe the same criteria in taking the four tablets as in visit 2. After 4 weeks (visit 5), we evaluated the patients as we did in visit 3. RESULTS: Overall, 28 patients completed the study. No subjects discontinued the drugs due to drawbacks. Tadalafil allowed a majority of men in this trial to achieve both normal sexual functioning up to 24 h postdosing compared to sildenafil (P<0.01) and improved overall sex life satisfaction as well as sexual relations with partner. CONCLUSION: Based on these data, tadalafil may have the potential to become an important treatment option for ED in SCI patients. SPONSORSHIP: This study was not sponsored.

Carbolines↗

PubMed1997

Effects of substituting dietary soybean protein and oil for milk protein and fat in subjects with hypercholesterolemia.

OBJECTIVES: To determine whether, in individuals with hypercholesterolemia, substituting dietary soybean products for cows' milk products improves the plasma lipid profile and whether any change in the profile is due partially to soy oil. DESIGN: Randomized 3-treatment crossover trial. SETTING: Family practice clinics and an outpatient clinic in London, Ont. PARTICIPANTS: Seventeen healthy men and 17 healthy women with elevated plasma levels of total and low-density-lipoprotein (LDL) cholesterol and with normal plasma levels of triglycerides. INTERVENTIONS: Participants incorporated into their normal diet either 2% cows' milk products, soybean products or a combination of skim milk products and soy oil, each over period of 4 weeks, with 22-week wash-out periods. Plasma lipid profile, blood pressure and body weight were assessed after each dietary and wash-out period. OUTCOME MEASURES: Plasma levels of total and lipoprotein cholesterol, plasma levels of triglycerides, apolipoprotein B and A1 levels, blood pressure and plasma lipid peroxidation. RESULTS: The change in diet had no effect on body mass index, levels of apolipoproteins B and A1 and most plasma lipids. During the soybean period, the subjects' mean level of high-density-lipoprotein (HDL) cholesterol increased 9% (p < 0.04) and their mean LDL/HDL cholesterol ratio decreased 14% (p < 0.007). These effects were less pronounced during the skim milk/soy oil period. In the 24 subjects with the highest initial LDL cholesterol level and LDL/HDL cholesterol ratio, the mean LDL cholesterol level decreased 11% after the soybean period. In all subjects, changes in the LDL/HDL cholesterol ratio induced by a soybean diet were negatively correlated with the initial LDL/HDL cholesterol ratio and positively correlated with the initial HDL cholesterol level. CONCLUSIONS: In people with hypercholesterolemia, the plasma lipid profile improved after treatment with a soybean-product diet, and this improvement was partially due to soy oil. The degree of responsiveness was associated with initial risk factors for coronary artery disease.

Adult↗

PubMedDate not supplied

Generation of TNFalpha and interleukin-6 by peritoneal macrophages after overnight dwells with bicarbonate- or lactate-buffered dialysis fluid.

OBJECTIVE: In order to evaluate the biocompatibility profile of a newly designed peritoneal dialysis fluid (PDF), we evaluated peritoneal leukocyte (PMphi) cytokine release following overnight in vivo dwells using standard, lactate-buffered, single-chamber bag PDF (Lac-PDF) and purely bicarbonate-buffered, double-chamber bag PDF containing 34 (Bic-PDF) or 39 (Bic Hi-PDF) mmol/L bicarbonate. DESIGN: A randomized, open, crossover clinical trial with single weekly test dwells was performed in stable, long-term continuous ambulatory PD patients (n = 8). During 8-hour overnight dwells, PMphi were exposed to different PDF containing 1.5% glucose. After drainage, peritoneal cells were isolated and incubated with RPMI 1640 medium for 2 or 3 hours, with and without stimulation by lipopolysaccharide (LPS). Ex vivo release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 was measured by specific ELISA technique. RESULTS: After pre-exposure to Lac-PDF, PMphi generated 242 +/- 279 pg TNFalpha/10(6) cells and 157 +/- 105 pg IL-6/10(6) cells. When pre-exposed to Bic-PDF and Bic Hi-PDF, TNFa and IL-6 production of PMphi was not significantly different from Lac-PDF. After LPS stimulation (100 ng/mL), PMD secretion of TNFalpha and IL-6 pre-exposed to three PDF revealed no significant differences between groups: TNFalpha was 2,864 +/- 1,216, 2,910 +/- 1,202, and 3,291 +/- 558 pg/10(6) cells after overnight dwells with Lac-PDF, Bic-PDF, and Bic Hi-PDF, respectively. Comparably, LPS-stimulated (100 pg/ mL) PMphi showed IL-6 secretion of 891 +/- 335, 1,380 +/- 1,149, and 1,442 +/- 966 pg/10(6) cells for Lac-PDF, Bic-PDF, and Bic Hi-PDF. CONCLUSION: After long-term overnight dwells, initial pH, the different buffers, and varying glucose degradation product levels of PDF do not strongly affect PMphi function with respect to cytokine release. The lack of significant differences between fluids may result from the complete dialysate equilibration achieved during the overnight intraperitoneal dwell.

Adult↗

PubMed2002

Correlation and predictive performances of saliva and plasma nicotine concentration on tobacco withdrawal-induced craving.

AIMS: To investigate whether saliva is a useful alternative to plasma for routine monitoring of nicotine and evaluate the predictive performances of saliva and plasma concentration on craving estimated by a Tiffany Questionnaire on Smoking Urge-Brief Form. METHODS: Thirteen healthy smokers were enrolled in a randomized, two period, crossover trial. Linear and power models were evaluated to predict the plasma nicotine concentrations from the saliva measurements, whereas a population PK/PD indirect response model was used to predict craving using either saliva or plasma nicotine concentration as the independent variable. RESULTS: The results of the analysis revealed that the power model was preferred over the linear one. The bias on the predicted plasma concentrations was of 0.47 ng ml-1 with a 95% confidence interval of [-0.57, 1.52] and a precision of 5.68 ng ml-1. The placebo effect model was initially fitted to data, then the indirect response approach (with inhibition in k(in)) was used to model the craving scores using plasma and saliva nicotine concentrations as independent variables. The two indirect response PK/PD models based on saliva and plasma nicotine concentrations, adequately described the onset, extent, and duration of craving. The maximal inhibition I(max) was 0.722 and 1 for saliva and plasma concentrations while the estimated nicotine concentrations giving 50% of the maximal inhibition were 269 ng ml-1 and 24.3 ng ml-1 for saliva and plasma, respectively. CONCLUSIONS: A good correlation between plasma and saliva nicotine concentrations has been found using a power model. Comparable values of bias and precision on the model-predicted craving indicate that plasma and saliva concentration can equally well be used to predict the onset of tobacco withdrawal induced craving. Analysis of saliva definitely offers a potentially more attractive way to assess nicotine concentration values, as samples can be collected easily and noninvasively. In addition, saliva sampling avoids the pain and discomfort involved in venepuncture. In studies that assess psychological measures, such as subjective mood, blood collection could present a possible confounding factor because of the anxiety and pain that accompanies it. For these reasons saliva can reasonably be considered as the ideal sampling site for all clinical studies conducted for the evaluation of the potential activity of drugs on nicotine deprivation symptoms.

Adult↗

PubMed1997

Anesthetic effects of tiletamine-zolazepam, alone or in combination with butorphanol, in goats.

OBJECTIVE: To evaluate anesthetic effects of tiletamine-zolazepam (TZ), alone or in combination with butorphanol, in goats undergoing laparotomy for embryo collection. DESIGN: Randomized clinical trial with crossover design. ANIMALS: 9 adult female goats. PROCEDURE: Goats were anesthetized twice: once with TZ (5.5 mg/kg [2.5 mg/lb] of body weight, i.v.) and once with tiletamine-zolazepam and butorphanol (0.1 mg/kg [0.045 mg/lb], i.v.). Additional doses of TZ (0.5 to 1.0 mg/kg [0.23 to 0.45 mg/lb], i.v.] were administered as needed to maintain a surgical anesthetic plane. Time to sternal recumbency was recorded, and quality of induction was scored. Arterial pressures, heart rate, respiratory rate, and rectal temperature were recorded every 5 minutes; arterial blood samples were collected every 30 minutes. Oxygen was insufflated if estimated saturation of hemoglobin in peripheral arterial blood with oxygen was < 90%; intermittent positive-pressure ventilation was performed if goats became apneic. Muscle relaxation, quality of anesthesia, and eye signs were scored every 15 minutes during anesthesia. Anesthesia time was recorded, and quality of recovery and degree of postoperative analgesia were scored. Plasma cortiso concentration was measured before induction, immediately after extubation, and 2 hours after extubation. RESULTS: Induction was rapid and smooth. Five goats regurgitated, 3 required supplemental oxygen, and 1 required intermittent positive-pressure ventilation, but none of the goats became hypotensive. Muscle relaxation and quality of anesthesia were adequate. Goats recovered from anesthesia without complications. We did not detect any significant differences between anesthetic regimens for any of the variables measured, except bicarbonate concentration and base excess. CLINICAL IMPLICATIONS: TZ at a dose of 5.5 mg/kg was satisfactory for anesthetic induction in goats; additional doses can be given to extend anesthesia time, but addition of butorphanol at a dose of 0.1 mg/kg to this regimen does not seem to provide any measurable benefit. An oxygen source and a means of assisting ventilation should be available.

Analgesics, Opioid↗

PubMed2005

Treatment of vasodepressor carotid sinus syndrome with midodrine: a randomized, controlled pilot study.

OBJECTIVES: To evaluate the efficacy of treatment of the vasodepressor form of carotid sinus hypersensitivity (carotid sinus syndrome (CSS)) with midodrine. DESIGN: A prospective, double-blind, randomized, controlled trial of crossover design. SETTING: A dedicated outpatient facility with access to tilt-table, digital arterial photoplethysmography, and 24-hour ambulatory blood pressure (BP) monitoring equipment. PARTICIPANTS: Ten older adults (4 male, 6 female, mean age 75, range 66-86 years) with a history of unexplained syncope who displayed an asymptomatic decrease in systolic BP (SBP) of more than 50 mmHg or a symptomatic decrease of more than 30 mmHg within 30 seconds of carotid sinus massage (CSM). MEASUREMENTS: Symptom reproduction and BP and heart rate changes were evaluated after CSM in supine and semierect positions on the right and then left sides. These measurements were performed on the final day of placebo and active-treatment phases. Ambulatory 24-hour BP monitoring took place on the penultimate and final days of each treatment phase. RESULTS: Eight patients were symptomatic after their initial CSM. The mean+/-standard deviation SBP decrease after initial CSM was 54+/-22 mmHg. Initial mean 24-hour ambulatory BP was 127/70+/-7/5 mmHg. Eight patients reported symptoms after CSM at the end of the placebo phase. The mean SBP decrease at the end of the placebo phase was 49+/-12 mmHg. The mean 24-hour ambulatory BP was 127/69+/-9/7 mmHg. One patient reported symptoms after CSM at the end of the active-treatment phase. The mean SBP decrease at the end of the active-treatment phase was 36+/-9 mmHg. The mean 24-hour ambulatory BP at the end of the treatment phase was 133/75+/-7/6 mmHg. The differences in symptom reporting and mean SBP decrease after CSM were both significant (P<.01 and P=.03, respectively). CONCLUSION: The results of this pilot study suggest that treatment of vasodepressor CSS with midodrine significantly reduced the rate of symptom reporting and attenuated SBP decreases after CSM but increased mean 24-hour ambulatory BP.

Accidental Falls↗

PubMed1998

Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: the DELTA Study, protocol 1.

Few well-controlled diet studies have investigated the effects of reducing dietary saturated fatty acid (SFA) intake in premenopausal and postmenopausal women or in blacks. We conducted a multicenter, randomized, crossover-design trial of the effects of reducing dietary SFA on plasma lipids and lipoproteins in 103 healthy adults 22 to 67 years old. There were 46 men and 57 women, of whom 26 were black, 18 were postmenopausal women, and 16 were men > or =40 years old. All meals and snacks, except Saturday dinner, were prepared and served by the research centers. The study was designed to compare three diets: an average American diet (AAD), a Step 1 diet, and a low-SFA (Low-Sat) diet. Dietary cholesterol was constant. Diet composition was validated and monitored by a central laboratory. Each diet was consumed for 8 weeks, and blood samples were obtained during weeks 5 through 8. The compositions of the three diets were as follows: AAD, 34.3% kcal fat and 15.0% kcal SFA; Step 1, 28.6% kcal fat and 9.0% kcal SFA; and Low-Sat, 25.3% kcal fat and 6.1% kcal SFA. Each diet provided approximately 275 mg cholesterol/d. Compared with AAD, plasma total cholesterol in the whole group fell 5% on Step 1 and 9% on Low-Sat. LDL cholesterol was 7% lower on Step 1 and 11% lower on Low-Sat than on the AAD (both P<.01). Similar responses were seen in each subgroup. HDL cholesterol fell 7% on Step 1 and 11% on Low-Sat (both P<.01). Reductions in HDL cholesterol were seen in all subgroups except blacks and older men. Plasma triglyceride levels increased approximately 9% between AAD and Step 1 but did not increase further from Step 1 to Low-Sat. Changes in triglyceride levels were not significant in most subgroups. Surprisingly, plasma Lp(a) concentrations increased in a stepwise fashion as SFA was reduced. In a well-controlled feeding study, stepwise reductions in SFA resulted in parallel reductions in plasma total and LDL cholesterol levels. Diet effects were remarkably similar in several subgroups of men and women and in blacks. The reductions in total and LDL cholesterol achieved in these different subgroups indicate that diet can have a significant impact on risk for atherosclerotic cardiovascular disease in the total population.

Adult↗

PubMed1989

The performance of the two-stage analysis of two-treatment, two-period crossover trials.

In the two-treatment, two-period crossover trial, patients are randomly allocated either to one group that receives treatment A followed by treatment B, or to another group that receives the treatments in the reverse order. Grizzle first proposed a two-stage procedure for analysing the data from such a trial. This paper examines the long-run sampling properties of this procedure, in terms of mean square error of point estimates, coverage probability of confidence intervals and actual significance level of hypothesis tests for the differences between the effects of the two treatments. The advantages of incorporating baseline observations into the analysis are also explored. Because the preliminary test for carryover is highly correlated with the analysis of data from the first period only, actual significance levels are higher than nominal levels even when there is no differential carryover. When carryover is present, the nominal level very seriously understates the actual level, and this becomes even worse when baseline observations are ignored. Increasing sample size only exacerbates the problem since this adverse behaviour then occurs at smaller values of the carryover effect. It is concluded that the two-stage analysis is too potentially misleading to be of practical use.

Analysis of Variance↗

PubMed1994

Nitrovasodilator effects on intraocular pressure and outflow facility in monkeys.

The nitrovasodilators nitroglycerin (NTG) and hydralazine (HZN) were investigated for their effects on intraocular pressure (IOP) and outflow facility in the cynomolgus monkey eye in vivo. Fifty microliters of 0.1% HZN were administered topically in masked, randomized, crossover, placebo controlled trials, and by intracameral perfusion. Both NTG and HZN decreased IOP (mean IOP decrease with NTG 4.40 +/- 2.11 (S.E.M.) (+/- 4.7, S.D.) mmHg, P < 0.01, n = 5, with HZN 3.15 +/- 0.85 (S.E.M.) (+/- 2.3, S.D.) mmHg, P = 0.01, n = 7). Outflow facility increased by 92% (P < 0.05) after intracameral bolus injection of 10(-3) mol l-1 NTG, but not at lower doses. Intracameral HZN caused a significant increase in facility of outflow of 28% (P < 0.05) when perfused at a constant concentration of 10(-5) mol l-1, but not at certain other concentrations. These results demonstrate the capacity for topically applied NTG and HZN to reduce IOP in the living primate eye. They further suggest that, at certain drug doses, but not others, the IOP reduction may be mediated, in part, by an action on the outflow apparatus.

Animals↗

PubMed2006

Does having a computerized prosthetic knee influence cognitive performance during amputee walking?

OBJECTIVE: To compare objective cognitive performance and perception of cognitive burden during walking tasks using 2 different prosthetic knees: a computerized hydraulic knee (Otto Bock C-leg) and a noncomputerized hydraulic knee (Ossur Mauch SNS). DESIGN: Two-group crossover trial, with participants randomly assigned to order of prosthesis. Participants completed assessments under 2 conditions, a self-selected speed walk and a controlled speed walk, on 2 separate occasions (precrossover, postcrossover). SETTING: Veterans Health Administration hospital. PARTICIPANTS: Eight transfemoral amputees. INTERVENTION: Computerized versus noncomputerized prosthetic knee. MAIN OUTCOME MEASURES: Objective cognitive performance measures included verbal fluency (Controlled Oral Word Association Test, Category Test), attention and working memory (serial subtraction), and walking speed during cognitive tasks. Measures of perceived cognitive burden included subjective attentional requirements of walking and cognitive tasks and subjective general cognitive burden of prosthesis. RESULTS: There were no significant differences in objective cognitive performance on any task between prostheses, nor did walking speed vary by prosthesis during the free-speed walk. Participants reported that walking required less attention while wearing the C-leg and that the C-leg was less of a cognitive burden than the noncomputerized prosthesis. CONCLUSIONS: In nondemanding walking conditions with experienced amputees, participants reported that the more costly C-leg required less cognitive attention than the noncomputerized knee. However, this subjective experience did not translate to improved performance on neuropsychologic screening instruments or on walking speed. Noncomputerized prostheses may be adequate for a majority of amputees, and further research is needed to identify particular groups of amputees (ie, new amputees, amputees with complex physical or cognitive demands) who may benefit from computerized prostheses.

Adult↗

PubMed2000

Treadmill training with body weight support: its effect on Parkinson's disease.

OBJECTIVE: To test whether body weight-supported treadmill training (BWSTT) is effective in improving functional outcome of patients with Parkinson's disease. DESIGN: Prospective crossover trial. Patients were randomized to receive either a 4-week program of BWSTT with up to 20% of their body weight supported followed by 4 weeks of conventional physical therapy (PT), or the same treatments in the opposite order. Medications for parkinsonism were not modified throughout the study. SETTING: Inpatient rehabilitation unit for neurologic diseases. SUBJECTS: Ten patients (5 men, 5 women) with Hoehn and Yahr stage 2.5 or 3 parkinsonism; mean age 67.6 years, mean duration of Parkinson's disease 4.2 years. MAIN OUTCOME MEASURES: The Unified Parkinson's Disease Rating Scale (UPDRS), ambulation endurance and speed (sec/10 m), and number of steps for 10-meter walk. RESULTS: The mean total UPDRS before/after BWSTT was 31.6/25.6, and before/after PT was 29.1/28.0. Analysis of covariance for improvement of UPDRS demonstrated a significant effect of type of therapy (F(1, 16) = 42.779, p < .0001) but not order of therapy (F(1, 16) = 0.157, p = .697 1). Patients also had significantly greater improvement with BWSTT than with PT in ambulation speed (BWSTT, before/after = 10.0/8.3; PT, 9.5/8.9), and number of steps (BWSTT, 22.3/19.6; PT, 21.5/20.8). CONCLUSIONS: In persons with Parkinson's disease, treadmill training with body weight support produces greater improvement in activities of daily living, motor performance, and ambulation than does physical therapy.

Aged↗

PubMed2001

Erythromycin increases plasma concentrations of alpha-dihydroergocryptine in humans.

OBJECTIVE: Our objective was to investigate the potential for relevant pharmacotherapeutic interaction between cytochrome P4503A4 (CYP3A4)-inhibiting agents such as erythromycin and the dopamine agonist alpha-dihydroergocryptine (DHEC). METHODS: The study was carried out as a single-center, controlled, nonblinded, 2-way crossover clinical trial with randomly allocated period-balanced sequences, investigating two treatments of a single oral dose of 10 mg DHEC (on the morning of day 1), once administered alone (reference), once along with a 4-day treatment (days -2 to 1) of 500 mg erythromycin 3 times daily. Periods were separated by a washout of at least 14 days. Nine healthy white male volunteers, 22 to 42 years old, with a body weight range of 58 to 90 kg (body mass index, 20.2-25.1 kg x m(-2)) began the study. One subject discontinued prematurely, and 8 concluded the study in accordance with the study protocol. RESULTS: The plasma and urinary pharmacokinetics of DHEC and its metabolites were characterized by a large variability. Concomitant treatment with erythromycin led to respective increases of 9.5 (95% confidence interval [CI], 6.5 to 13.9) and 16.5 (95% CI, 8.7 to 31.5) times the maximum observed plasma drug concentration and the area under the time course of the plasma concentrations up to the last quantifiable concentration after dosing of unchanged DHEC (determined by radioimmunoassay). The 24-hour urinary excretion was on average 11 times larger (95% CI, 5.9 to 20.7). Qualitatively similar findings were recorded for the total of DHEC plus metabolites (as determined by enzyme immunoassay). CONCLUSIONS: The concomitant use of erythromycin or similarly CYP3A4-inhibiting agents along with direct dopaminergic agonists such as the ergoline DHEC may cause a clinically relevant increase in pharmacokinetic exposure, which may induce exaggerated dopaminergic effects.

Administration, Oral↗