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At least 829 records · Page 46Linked to original sources
PubMed1999

Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter Selective Lymphadenectomy Trial Group.

OBJECTIVE: To evaluate the multicenter application of intraoperative lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection (LM/SL/SCLND) for the management of early-stage melanoma. SUMMARY BACKGROUND DATA: The multidisciplinary technique of LM/SL/SCLND has been widely adopted, but not validated in a multicenter trial. The authors began the international Multicenter Selective Lymphadenectomy Trial (MSLT) 5 years ago to evaluate the survival of patients with early-stage primary melanoma after wide excision alone versus wide excision plus LM/SL/SCLND. This study examined the accuracy of LM/SL/SCLND in the MSLT, using the experience of the organizing center (John Wayne Cancer Institute [JWCI]) as a standard for comparison. METHODS: Before entering patients into the randomization phase, each center in the MSLT was required to finish a 30-case learning phase with complete nuclear medicine, pathology, and surgical review. Selection of MSLT patients in the LM/SL/SCLND treatment arm was based on complete pathologic and surgical data. The comparison group of JWCI patients was selected using these criteria: primary cutaneous melanoma having a thickness > or =1 mm with a Clark level > or =III, or a thickness <1 mm with a Clark level > or =IV (MSLT criterion); LM/SL performed between June 1, 1985, and December 30, 1998; and patient not entered in the MSLT. The accuracy of LM/SL/SCLND was determined by comparing the rates of sentinel node (SN) identification and the incidence of SN metastases in the MSLT and JWCI groups. RESULTS: There were 551 patients in the MSLT group and 584 patients in the JWCI group. In both groups, LM performed with blue dye plus a radiocolloid was more successful (99.1 %) than LM performed with blue dye alone (95.2%) (p = 0.014). After a center had completed the 30-case learning phase, the success of SN identification in the MSLT group was independent of the center's case volume or experience in the MSLT. CONCLUSIONS: Lymphatic mapping and sentinel lymphadenectomy can be successfully learned and applied in a standardized fashion with high accuracy by centers worldwide. Successful SN identification rates of 97% can be achieved, and the incidence of nodal metastases approaches that of the organizing center. A multidisciplinary approach (surgery, nuclear medicine, and pathology) and a learning phase of > or =30 consecutive cases per center are sufficient for mastery of LM/SL in cutaneous melanoma. Lymphatic mapping performed using blue dye plus radiocolloid is superior to LM using blue dye alone.

Adolescent↗
PubMed2002

Randomized, placebo-controlled trial of dietary supplementation of alpha-tocopherol on mutagen sensitivity levels in melanoma patients: a pilot trial.

We evaluated the effects of vitamin E (dl-alpha-tocopherol) on mutagen sensitivity levels in a randomized placebo-controlled pilot trial. In brief, a dietary supplement of 1000 mg/day vitamin E or a placebo was randomly administered for 3 months to melanoma outpatients clinically free of the disease. Plasma vitamin E and mutagen sensitivity levels were measured at baseline and at the end of the trial after 3 months. At baseline, we found no significant differences in plasma vitamin E and mutagen sensitivity levels between the two groups. We also measured dietary intake at baseline and found dietary vitamin E to be a poor predictor of plasma levels of vitamin E. After 3 months of supplementation, we found that plasma levels of alpha-tocopherol increased significantly (P = 0.0005) in the vitamin E compared to the placebo group. We also found a non-significant, but consistent decrease in plasma gamma-tocopherol concentrations in the vitamin E supplemented compared to the placebo group. We did not find any significant difference between the vitamin E and placebo groups in mutagen sensitivity levels either at baseline or after 3 months of supplementation. We conclude that short term vitamin E supplementation, although it causes increased blood levels of alpha-tocopherol, does not provide protection against bleomycin-induced chromosome damage.

Adult↗
PubMed2005

Randomized, controlled clinical trial of point-of-care limited ultrasonography assistance of central venous cannulation: the Third Sonography Outcomes Assessment Program (SOAP-3) Trial.

CONTEXT: A 2001 Agency for Healthcare Research and Quality Evidence Report on patient safety addressed point-of-care limited ultrasonography guidance for central venous cannulation and strongly recommended real-time, dynamic guidance for all central cannulas. However, on the basis of one limited study, the report dismissed static assistance, a "quick look" with ultrasound to confirm vein location before preparing the sterile field, as unhelpful. OBJECTIVE: The objective of this trial was to compare the overall success rate of central cannula placement with use of dynamic ultrasound (D), static ultrasound (S), and anatomical landmarks (LM). DESIGN AND SETTING: A concealed, randomized, controlled, clinical trial conducted from September 2003 to February 2004 in a U.S. urban teaching hospital. PATIENTS: Two-hundred one patients undergoing internal jugular vein central venous cannulation. INTERVENTIONS: Patients were randomly assigned to three groups: 60 to D, 72 to S, and 69 to LM. An iLook25 SonoSite was used for all imaging. MEASUREMENTS AND MAIN RESULTS: Cannulation success, first-attempt success, and number of attempts were noted. Other measures were vein size and clarity of LM. Results, controlled for pretest difficulty assessment, are stated as odds improvement (95% confidence interval) over LM for D and S. D had an odds 53.5 (6.6-440) times higher for success than LM. S had an odds 3 (1.3-7) times higher for success than LM. The unadjusted success rates were 98%, 82%, and 64% for D, S, and LM. For first-attempt success, D had an odds 5.8 (2.7-13) times higher for first success than LM, and S had an odds 3.4 (1.6-7.2) times higher for first success than LM. The unadjusted first-attempt success rates were 62%, 50%, and 23% for D, S, and LM. CONCLUSIONS: Ultrasound assistance was superior to LM techniques. D outperformed S but may require more training and personnel. All central cannula placement should be conducted with ultrasound assistance. The 2001 Agency for Healthcare Research and Quality Evidence Report dismissing static assistance was incorrect.

Aged↗
PubMed2005

A randomized, controlled trial of saphenous vein graft intervention with a filter-based distal embolic protection device: TRAP trial.

The purpose of this prospective, multicenter trial was to evaluate the safety and effectiveness of the TRAP Vascular Filtration System (VFS) to reduce embolic complications during stenting of diseased saphenous vein grafts (SVGs). Patients with SVG lesions were randomly assigned to undergo stenting with or without the TRAP device. The trial was designed to enroll 752 randomized patients. However, the sponsor terminated the study after a total of 467 patients (358 randomized) were enrolled because of poor recruitment once another distal protection device was approved for clinical use. The primary study endpoint, major adverse cardiac events at 30 days, occurred in 17.3% of control patients and 12.7% of patients treated with the TRAP device (P = 0.24). There was a trend toward a lower incidence of myocardial infarction in the TRAP group compared with the control group (16.2% vs 10.5%, P = 0.12). This difference was predominantly due to a lower incidence of moderate-large infarction (CKMB >5x) in the TRAP group. Use of the TRAP VFS during SVG intervention was safe and was associated with a trend toward a lower incidence of adverse events, however, due to low enrollment the study lacked sufficient power to detect a significant benefit with the device.

Aged↗
PubMed1995

Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomised trial. The Scottish Cancer Trials Breast Group.

OBJECTIVE: To determine any cardiac or vascular morbidity associated with long term treatment with tamoxifen given after mastectomy for primary breast cancer. DESIGN: Cohort study using linkage between database of a randomised trial and statistics of Scottish hospital inpatients to identify episodes of cardiac and vascular morbidity. SETTING: NHS hospitals in Scotland. SUBJECTS: 1312 women who had undergone mastectomy for breast cancer and who were randomised either to a treatment group to receive adjuvant tamoxifen or to a control group to be given tamoxifen only on first relapse of disease. Maximum duration of tamoxifen treatment was 14 years. Total woman years of follow up were 9943. MAIN OUTCOME MEASURES: Randomised and observational comparisons of risk (expressed as hazard ratios) of myocardial infarction, other cardiac event, cerebrovascular disease, or thromboembolic event according to treatment allocated and between nonusers, former users, and current users of tamoxifen. RESULTS: Use of tamoxifen was associated with lower rates of myocardial infarction. Hazard ratio for women in control group was 1.92 (95% confidence interval 0.99 to 3.73) compared with women allocated to adjuvant treatment. The association was stronger for current use: hazard ratio for non-users was 3.49 (1.52 to 8.03) compared with current users. Current users of tamoxifen, however, had higher rates of thromboembolic events:hazard ratio for non-users was 0.40 (0.18 to 0.90) compared with current users. CONCLUSIONS: Our results provide further evidence that tamoxifen reduces the risk of myocardial infarction. Thromboembolic events should be carefully monitored in trials of tamoxifen, particularly those of prophylactic treatment, in which tamoxifen is given to healthy women.

Adult↗
PubMed1998

Economic evaluation and randomised controlled trial of extracorporeal membrane oxygenation: UK collaborative trial. The Extracorporeal Membrane Oxygenation Economics Working Group.

OBJECTIVE: To compare the resource implications and short term outcomes of extracorporeal membrane oxygenation and conventional management for term babies with severe respiratory failure. DESIGN: Cost effectiveness evaluation alongside a randomised controlled trial. SETTING: 55 approved recruiting hospitals in the United Kingdom. These hospitals provided conventional management, but infants randomised to extracorporeal membrane oxygenation were transferred to one of five specialist centres. SUBJECTS: 185 mature newborn infants (gestational age at birth >35 weeks, birth weight >2 kg) with severe respiratory failure (oxygenation index >40) recruited between 1993 and 1995. The commonest diagnoses were persistent pulmonary hypertension due to meconium aspiration, congenital diaphragmatic hernia, isolated persistent fetal circulation, sepsis, and idiopathic respiratory distress syndrome. MAIN OUTCOME MEASURE: Cost effectiveness based on survival at 1 year of age without severe disability. RESULTS: 63 (68%) of the 93 infants randomised to extracorporeal membrane oxygenation survived to 1 year compared with 38 (41%) of the 92 infants who received conventional management. Of those that survived, one infant in each arm was lost to follow up and the proportion with disability at 1 year was similar in the two arms of the trial. One child in each arm had severe disability. The estimated additional cost of extracorporeal membrane oxygenation per additional surviving infant without severe disability was 51 222 pounds and the cost per surviving infant with no disability was 75 327 pounds. CONCLUSIONS: Extracorporeal membrane oxygenation for term neonates with severe respiratory failure would increase overall survival without disability. Although the policy will increase costs of neonatal health care, it is likely to be as cost effective as other life extending technologies.

Cost-Benefit Analysis↗
PubMedDate not supplied

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series.

OBJECTIVE: To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. DESIGN: Randomised, double blind, placebo controlled, parallel group, multicentre study. SETTING: Four general practices and a hospital ear, nose, and throat outpatient department. PARTICIPANTS: 51 patients with perennial allergic rhinitis. INTERVENTION: Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. MAIN OUTCOME MEASURES: Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. RESULTS: Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). CONCLUSION: The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo.

Adolescent↗
PubMed2002

Local warming and insertion of peripheral venous cannulas: single blinded prospective randomised controlled trial and single blinded randomised crossover trial.

OBJECTIVE: To determine whether local warming of the lower arm and hand facilitates peripheral venous cannulation. DESIGN: Single blinded prospective randomised controlled trial and single blinded randomised crossover trial. SETTING: Neurosurgical unit and haematology ward of university hospital. PARTICIPANTS: 100 neurosurgical patients and 40 patients with leukaemia who required chemotherapy. INTERVENTIONS: Neurosurgical patients' hands and forearms were covered for 15 minutes with a carbon fibre heating mitt. Patients were assigned randomly to active warming at 52 degrees C or passive insulation (heater not activated). The same warming system was used for 10 minutes in patients with leukaemia. They were assigned randomly to active warming or passive insulation on day 1 and given alternative treatment during the subsequent visit. MAIN OUTCOME MEASURES: PRIMARY: success rate for insertion of 18 gauge cannula into vein on back of hand. SECONDARY: time required for successful cannulation. RESULTS: In neurosurgical patients, it took 36 seconds (95% confidence interval 31 to 40 seconds) to insert a cannula in the active warming group and 62 (50 to 74) seconds in the passive insulation group (P=0.002). Three (6%) first attempts failed in the active warming group compared with 14 (28%) in the passive insulation group (P=0.008). The crossover study in patients with leukaemia showed that insertion time was reduced by 20 seconds (8 to 32, P=0.013) with active warming and that failure rates at first attempt were 6% with warming and 30% with passive insulation (P<0.001). CONCLUSIONS: Local warming facilitates the insertion of peripheral venous cannulas, reducing both time and number of attempts required. This may decrease the time staff spend inserting cannulas, reduce supply costs, and improve patient satisfaction.

Arm↗
PubMed2005

Effect of multivitamin and multimineral supplements on morbidity from infections in older people (MAVIS trial): pragmatic, randomised, double blind, placebo controlled trial.

OBJECTIVE: To examine whether supplementation with multivitamins and multiminerals influences self reported days of infection, use of health services, and quality of life in people aged 65 or over. DESIGN: Randomised, placebo controlled trial, with blinding of participants, outcome assessors, and investigators. SETTING: Communities associated with six general practices in Grampian, Scotland. PARTICIPANTS: 910 men and women aged 65 or over who did not take vitamins or minerals. INTERVENTIONS: Daily multivitamin and multimineral supplementation or placebo for one year. MAIN OUTCOME MEASURES: Primary outcomes were contacts with primary care for infections, self reported days of infection, and quality of life. Secondary outcomes included antibiotic prescriptions, hospital admissions, adverse events, and compliance. RESULTS: Supplementation did not significantly affect contacts with primary care and days of infection per person (incidence rate ratio 0.96, 95% confidence interval 0.78 to 1.19 and 1.07, 0.90 to 1.27). Quality of life was not affected by supplementation. No statistically significant findings were found for secondary outcomes or subgroups. CONCLUSION: Routine multivitamin and multimineral supplementation of older people living at home does not affect self reported infection related morbidity. TRIAL REGISTRATION: ISRCTN: 66376460.

Aged↗
PubMed2005

Randomised controlled trial of prevention of falls in people aged > or =75 with severe visual impairment: the VIP trial.

OBJECTIVES: To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision. DESIGN: Randomised controlled trial. SETTING: Dunedin and Auckland, New Zealand. PARTICIPANTS: 391 women and men aged > or =75 with visual acuity of 6/24 or worse who were living in the community; 92% (361 of 391) completed one year of follow-up. INTERVENTIONS: Participants received a home safety assessment and modification programme delivered by an occupational therapist (n = 100), an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation (n = 97), both interventions (n = 98), or social visits (n = 96). MAIN OUTCOME MEASURES: Numbers of falls and injuries resulting from falls, costs of implementing the home safety programme. RESULTS: Fewer falls occurred in the group randomised to the home safety programme but not in the exercise programme (incidence rate ratios 0.59 (95% confidence interval 0.42 to 0.83) and 1.15 (0.82 to 1.61), respectively). However, within the exercise programme, stricter adherence was associated with fewer falls (P = 0.001). A conservative analysis showed neither intervention was effective in reducing injuries from falls. Delivering the home safety programme cost NZ650 dollars (234 pounds sterling, 344 euros, US432 dollars) (at 2004 prices) per fall prevented. CONCLUSION: The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision. The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group, possibly due to low levels of adherence. Trial registration number ISRCTN15342873.

Accidental Falls↗
PubMed2005

Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial.

OBJECTIVE: To determine if the macrolide clarithromycin affects mortality and cardiovascular morbidity in patients with stable coronary heart disease. DESIGN: Centrally randomised multicentre trial. All parties at all stages were blinded. Analyses were by intention to treat. SETTING: Five Copenhagen University cardiology departments and a coordinating centre. PARTICIPANTS: 13,702 patients aged 18 to 85 years who had a discharge diagnosis of myocardial infarction or angina pectoris in 1993-9 and alive in August 1999 were invited by letter; 4373 were randomised. INTERVENTIONS: Two weeks' treatment with clarithromycin 500 mg/day or matching placebo. MAIN OUTCOME MEASURES PRIMARY OUTCOME: composite of all cause mortality, myocardial infarction, or unstable angina pectoris during three years' follow-up. Secondary outcome: composite of cardiovascular mortality, myocardial infarction, or unstable angina pectoris. The outcomes were obtained from Danish registers and were blindly assessed by the event committee. RESULTS: 2172 participants were randomised to clarithromycin and 2201 to placebo. We found no significant effects of clarithromycin on the primary outcome (hazard ratio 1.15, 95% confidence interval 0.99 to 1.34) or secondary outcome (1.17, 0.98 to 1.40). Mortality was significantly higher in the clarithromycin arm (1.27, 1.03 to 1.54; P = 0.03) as a result of significantly higher cardiovascular mortality (1.45, 1.09 to 1.92; P = 0.01). CONCLUSIONS: Short term clarithromycin in patients with stable coronary heart disease may cause significantly higher cardiovascular mortality. The long term safety of clarithromycin in patients with stable ischaemic heart disease should be examined. Trial registration ClinicalTrials.gov NCT00121550.

Adolescent↗
PubMed1993

Loss of quality adjusted days as a trial endpoint: effect of early thrombolytic treatment in suspected myocardial infarction. Grampion Region Early Anistreplase Trial (GREAT).

STUDY OBJECTIVES: (1) To measure the quality of life and the loss of quality adjusted days (QADS) after suspected acute myocardial infarction in patients who received thrombolytic treatment either at home or in hospital. (2) To compare the loss of QADS as a trial endpoint with the conventional endpoints of mortality and Q-wave infarction. DESIGN: Randomised double blind parallel group trial of anistreplase (30 U given intravenously) and placebo given either at home or in hospital. SETTING: Rural practices in Grampian admitting patients to teaching hospitals in Aberdeen. PATIENTS: A total of 311 patients with suspected acute myocardial infarction and no contraindications to thrombolytic treatment seen at home within four hours of the onset of symptoms. MEASUREMENTS AND MAIN RESULTS: Loss of quality adjusted days (QADS) in the first 100 days after suspected myocardial infarction (365 QADS = 1 QALY) was the main outcome measure. Compared with later administration in hospital, anistreplase at home resulted in a relative reduction of mortality of 49% (95% confidence interval 3.95%, 2p = 0.04), and a relative reduction of 26% in the proportion of survivors with infarction who had Q-waves (95% CI 7.44%, 2p = 0.007). During the 100 day follow up, the median loss of QADS was 25 for all patients. This loss was significantly greater in those who died than in survivors (65 v 18, 2p < 0.001), and in survivors with infarction than in survivors without infarction (26 v 13, 2p < 0.01). However, there was no significant difference in loss of QADS in those with infarction with or without Q-waves (29 v 21, NS), and the median loss of QADS was not significantly different in those who had thrombolytic treatment at home or in hospital (median difference 0, 95% CI -5, +4 QADS). CONCLUSIONS: Loss of QADS had two serious limitations as an outcome measure: it was less sensitive than mortality and it failed to reflect physiological benefit. Palliative treatment with no physiological effect would have resulted in a greater gain in QADS (or QALYs) than did early thrombolytic treatment. Extreme caution is required in accepting a gain in QALYs as a valid outcome measure for health care.

Anistreplase↗
PubMed1998

The clinical trial protocol of the Metrifonate in Alzheimer's Trial (MALT).

The promising results of early trials in Alzheimer's disease with the acetylcholinesterase inhibitor metrifonate prompted initiation of the Metrifonate in ALzheimer's Trial (MALT). MALT is an international, randomized, double-blind, placebo-controlled, parallel-group study which was designed to determine, over a 26-week period, the efficacy, tolerability and safety of two doses of metrifonate in patients with probable Alzheimer's disease. A total of 605 patients were randomized to receive either a daily dose of oral metrifonate 40/50 mg (n = 200, by body weight <65 kg/> or =65 kg) or metrifonate 60/80 mg (n = 197, by body weight <65 kg/> or = 65 kg). Patients were assessed in the key symptom domains of Alzheimer's disease, i.e. cognition, behavioural and psychiatric disturbances, activities of daily living and global function. In summary, administration of metrifonate for 26 weeks to the intent-to-treat population significantly benefited cognitive performance, global function and certain aspects of behaviour and functional ability compared with placebo. These efficacy results were associated with high levels of acetylcholinesterase inhibition and a good safety and tolerability profile. The protocol of MALT is discussed here. Full results of the study will be available in a separate publication.

Aged↗
PubMed2000

Randomized trial of contrast media utilization in high-risk PTCA: the COURT trial.

BACKGROUND: Previous in vitro and in vivo studies have suggested an association between thrombus-related events and type of contrast media. Low osmolar contrast agents appear to improve the safety of diagnostic and coronary artery interventional procedures. However, no data are available on PTCA outcomes with an isosmolar contrast agent. METHODS AND RESULTS: A multicenter prospective randomized double-blind trial was performed in 856 high-risk patients undergoing coronary artery intervention. The objective was to compare the isosmolar nonionic dimer iodixanol (n=405) with the low osmolar ionic agent ioxaglate (n=410). A composite variable of in-hospital major adverse clinical events (MACE) was the primary end point. A secondary objective was to evaluate major angiographic and procedural events during and after PTCA. The composite in-hospital primary end point was less frequent in those receiving iodixanol compared with those receiving ioxaglate (5.4% versus 9.5%, respectively; P=0.027). Core laboratory defined angiographic success was more frequent in patients receiving iodixanol (92.2% versus 85. 9% for ioxaglate, P=0.004). There was a trend toward lower total clinical events at 30 days in patients randomized to iodixanol (9.1% versus 13.2% for ioxaglate, P=0.07). Multivariate predictors of in-hospital MACE were use of ioxaglate (P=0.01) and treatment of a de novo lesion (P=0.03). CONCLUSIONS: In this contemporary prospective multicenter trial of PTCA in the setting of acute coronary syndromes, there was a low incidence of in-hospital clinical events for both treatment groups. The cohort receiving the nonionic dimer iodixanol experienced a 45% reduction in in-hospital MACE when compared with the cohort receiving ioxaglate.

Aged↗
PubMed1997

Determining the trough-to-peak ratio in parallel-group trials. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

We explored how in parallel-group trials interindividual variability, correction for placebo effects, and smoothing of blood pressure profiles can be handled in measuring the trough-to-peak ratio in 244 individuals with isolated systolic hypertension (> or = 60 years) enrolled in the placebo-controlled Systolic Hypertension in europe Trial. Net treatment effects were computed by subtracting the mean changes from baseline during placebo (n = 133) from those during active treatment (n = 111). At entry, systolic/diastolic pressures averaged 176/86 mm Hg in the clinic and 149/80 mm Hg on 24-hour ambulatory monitoring. With corrections applied for baseline and placebo, nitrendipine (10 to 40 mg/d), with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d), reduced (P < .001) these blood pressure values by 16.6/7.3 and 9.8/4.7 mm Hg, respectively. The net trough-to-peak ratios were first determined from blood pressure profiles (12 hours) with 1-hour precision, synchronized by the morning and evening doses of the double-blind medication. According to the usual approach, disregarding interindividual variability, the systolic/diastolic net trough-to-peak ratios were 0.46/0.40 in the morning and 0.77/0.99 in the evening. In individual subjects, the baseline-adjusted trough-to-peak ratios were nonnormally distributed. We therefore used a nonparametric technique to calculate the net trough-to-peak ratios from the results in individual subjects. In the morning, these ratios averaged 0.25 systolic (95% confidence interval, 0.09 to 0.41) and 0.15 diastolic (95% confidence interval, 0.00 to 0.31) and in the evening, 0.19 and 0.36 (95% confidence intervals, 0.00 to 0.38 and 0.14 to 0.56), respectively. When the blood pressure profiles were smoothed by substituting the 1-hour averages by moving or fixed 2-hour averages or by Fourier modeling, the trough-to-peak ratios remained unchanged after the morning dose (0.20/0.13, 0.20/0.14, and 0.16/0.21, respectively) but tended to increase in the evening (0.32/0.38, 0.28/0.40, and 0.48/0.49). In conclusion, the parallel-group analysis proposed makes it possible for one to correct the trough-to-peak ratio for baseline as well as placebo, to account for interindividual variability, and to calculate a confidence interval for the net trough-to-peak ratio. Accounting for interindividual variability reduces the trough-to-peak ratio. Smoothing affects the individualized net trough-to-peak ratios in an unpredictable way and should therefore be avoided.

Aged↗
PubMed2003

Rational Prescribing in Primary Care (RaPP-trial). A randomised trial of a tailored intervention to improve prescribing of antihypertensive and cholesterol-lowering drugs in general practice [ISRCTN48751230].

BACKGROUND: The underlying reasons for differences between clinical practice and systematically developed guidelines vary from one clinical problem to another. It is therefore logical to tailor strategies to support the implementation of guidelines to address identified barriers to change. The objective of this trial is to evaluate the effects of a tailored intervention to support the implementation of systematically developed guidelines for the use of antihypertensive and cholesterol-lowering drugs for the primary prevention of cardiovascular disease. METHODS/DESIGN: Unblinded, cluster-randomised trial. 150 general practices will be recruited from two geographical areas in Norway, and randomised to the intervention or control group (passive dissemination of guidelines). Outcomes will be measured for all eligible patients seen in the participating practices during one year after the intervention. A multifaceted intervention has been tailored to address identified barriers to change. Key components are an educational outreach visit with audit and feedback, and computerised reminders. Pharmacists will conduct the visits. During the outreach visit the main recommendations will be presented and software will be installed that links to the electronic medical record systems used in the participating practices. The software will perform an audit that will be fed back during the visit, present pop-up reminders for patients with high blood pressure or cholesterol, and provide a cardiovascular risk calculator and patient education material. The main outcomes are the proportions of 1) first time prescriptions for hypertension where thiazides are not prescribed, 2) patients not assessed for cardiovascular risk before prescribing antihypertensive or cholesterol-lowering drugs, and 3) patients treated for hypertension or high cholesterol for three months or more who have not achieved recommended treatment goals.

Anticholesteremic Agents↗
PubMed2001

A multicentre randomized controlled trial of leisure therapy and conventional occupational therapy after stroke. TOTAL Study Group. Trial of Occupational Therapy and Leisure.

OBJECTIVE: To evaluate the effects of leisure therapy and conventional occupational therapy (OT) on the mood, leisure participation and independence in activities of daily living (ADL) of stroke patients 6 and 12 months after hospital discharge. DESIGN: Multicentre randomized controlled trial. SETTING AND PARTICIPANTS: Four hundred and sixty-six stroke patients from five UK centres. MAIN OUTCOME MEASURES: The General Health Questionnaire (12 item), the Nottingham Extended ADL Scale and the Nottingham Leisure Questionnaire, assessed by post, with telephone clarification. RESULTS: Four hundred and forty (94%) and 426 (91%) subjects were alive at 6 and 12 months, respectively. Three hundred and seventy-four (85% of survivors) and 311 (78% of survivors) responded at 6 and 12 month follow-up respectively. At six months and compared to the control group, those allocated to leisure therapy had nonsignificantly better GHQ scores (-1.2: 95% CI -2.9, +0.5), leisure scores (+0.7, 95% CI -1.1, +2.5) and Extended ADL scores (+0.4: 95% CI -3.8, +4.5): the ADL group had nonsignificantly better GHQ scores (-0.1: 95% CI -1.8, +1.7) and Extended ADL scores (+1.4: 95% CI -2.9, +5.6) and nonsignificantly worse leisure scores (-0.3: 95% CI -2.1, +1.6). The results at 12 months were similar. CONCLUSION: In contrast to the findings of previous smaller trials, neither of the additional OT treatments showed a clear beneficial effect on mood, leisure activity or independence in ADL measured at 6 or 12 months.

Activities of Daily Living↗
PubMed2002

Rationale and design of a clinical trial of a low-molecular-weight heparin in preventing clinically important venous thromboembolism in medical patients: the prospective evaluation of dalteparin efficacy for prevention of venous thromboembolism in immobilized patients trial (the PREVENT study).

The utility of low-molecular-weight heparin (LMWH) in the prophylaxis of venous thromboembolic disease has been examined using the surrogate endpoint of venographically identified thrombi. The largest portion of these thrombi were asymptomatic calf-vein thrombi. The clinical relevance of this observation is a matter of debate. The present study is designed to evaluate the impact of an LMWH on clinically important endpoints. The current study is a randomized, prospective, double-blinded, multicenter, multinational, controlled clinical trial comparing dalteparin with placebo in moderately high-risk hospitalized medical patients. A total of 3300 patients will be randomized to receive either 5,000 IU per day of dalteparin or placebo for 14 days. Patients will undergo appropriate evaluation for any symptomatic episodes and all patients will undergo a bilateral compression ultrasound (CUS) on day 21 to search for asymptomatic proximal thrombi. The primary endpoint is the combination of objectively confirmed symptomatic deep vein thrombi (DVT), fatal or non-fatal pulmonary emboli, all proximal DVT, and sudden death. This study will be the first study to examine clinically important endpoints in evaluating the effect of a LMWH in hospitalized medical patients. This study also is the first study to use CUS rather than venography in concordance with contemporary medical practice. This trial is thus designed to address this important question in a clinically relevant manner.

Adult↗