Showing papers on "Randomized controlled trial published in 2001"
TL;DR: The revised CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.
4,977 citations
TL;DR: The Consort Statement as mentioned in this paper is a group of scientists and editors developed to improve the quality of reporting of randomized, controlled trials (RCTs) by providing guidance to authors about how to improve their reporting of their trials.
Abstract: Overwhelming evidence now indicates that the quality of reporting of randomized, controlled trials (RCTs) is less than optimal. Recent methodologic analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which boast the elimination of systematic error as their primary hallmark. Systematic error in RCTs reflects poor science, and poor science threatens proper ethical standards. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have adopted the CONSORT statement. The CONSORT statement facilitates critical appraisal and interpretation of RCTs by providing guidance to authors about how to improve the reporting of their trials. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the CONSORT statement. The meaning and rationale for each checklist item are presented. For most items, at least one published example of good reporting and, where possible, references to relevant empirical studies are provided. Several examples of flow diagrams are included. The CONSORT statement, this explanatory and elaboration document, and the associated Web site (http://www.consort -statement.org) should be helpful resources to improve reporting of randomized trials.
3,647 citations
TL;DR: The revised CONSORT statement as discussed by the authors is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results, which can be achieved only through complete transparency from authors.
Abstract: To comprehend the results of a randomized controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Consolidated Standards of Reporting Trials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this article incorporates new evidence and addresses some criticisms of the original statement. The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results, and Comment. The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage of participants through an RCT. The revised flow diagram depicts information from 4 stages of a trial (enrollment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, according to each intervention group, included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis. In sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.
2,955 citations
TL;DR: In temporal-lobe epilepsy, surgery is superior to prolonged medical therapy, and Randomized trials of surgery for epilepsy are feasible and appear to yield precise estimates of treatment effects.
Abstract: Background Randomized trials of surgery for epilepsy have not been conducted, because of the difficulties involved in designing and implementing feasible studies. The lack of data supporting the therapeutic usefulness of surgery precludes making strong recommendations for patients with epilepsy. We conducted a randomized, controlled trial to assess the efficacy and safety of surgery for temporal-lobe epilepsy. Methods Eighty patients with temporal-lobe epilepsy were randomly assigned to surgery (40 patients) or treatment with antiepileptic drugs for one year (40 patients). Optimal medical therapy and primary outcomes were assessed by epileptologists who were unaware of the patients' treatment assignments. The primary outcome was freedom from seizures that impair awareness of self and surroundings. Secondary outcomes were the frequency and severity of seizures, the quality of life, disability, and death. Results At one year, the cumulative proportion of patients who were free of seizures impairing awarenes...
2,923 citations
TL;DR: The revised CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.
Abstract: To comprehend the results of a randomized controlled trial (RCT), readers must understand its design, conduct, analysis and interpretation. That goal can only be achieved through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Consolidated Standards of Reporting Trials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this paper incorporates new evidence and addresses some criticisms of the original statement.
2,444 citations
TL;DR: Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes and the MIRACL study are studied.
Abstract: Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study : A randomized controlled trial.
2,273 citations
TL;DR: Evidence supports the effectiveness of self-management training in type 2 diabetes, particularly in the short term, and further research is needed to assess the effectiveness on sustained glycemic control, cardiovascular disease risk factors, and ultimately, microvascular and cardiovascular disease and quality of life.
Abstract: OBJECTIVE —To systematically review the effectiveness of self-management training in type 2 diabetes. RESEARCH DESIGN AND METHODS —MEDLINE, Educational Resources Information Center (ERIC), and Nursing and Allied Health databases were searched for English-language articles published between 1980 and 1999. Studies were original articles reporting the results of randomized controlled trials of the effectiveness of self-management training in people with type 2 diabetes. Relevant data on study design, population demographics, interventions, outcomes, methodological quality, and external validity were tabulated. Interventions were categorized based on educational focus (information, lifestyle behaviors, mechanical skills, and coping skills), and outcomes were classified as knowledge, attitudes, and self-care skills; lifestyle behaviors, psychological outcomes, and quality of life; glycemic control; cardiovascular disease risk factors; and economic measures and health service utilization. RESULTS —A total of 72 studies described in 84 articles were identified for this review. Positive effects of self-management training on knowledge, frequency and accuracy of self-monitoring of blood glucose, self-reported dietary habits, and glycemic control were demonstrated in studies with short follow-up ( CONCLUSIONS —Evidence supports the effectiveness of self-management training in type 2 diabetes, particularly in the short term. Further research is needed to assess the effectiveness of self-management interventions on sustained glycemic control, cardiovascular disease risk factors, and ultimately, microvascular and cardiovascular disease and quality of life.
1,886 citations
TL;DR: Exercise training reduces HbA1c by an amount that should decrease the risk of diabetic complications, but no significantly greater change in body mass was found when exercise groups were compared with control groups.
Abstract: ContextExercise is widely perceived to be beneficial for glycemic control and
weight loss in patients with type 2 diabetes. However, clinical trials on
the effects of exercise in patients with type 2 diabetes have had small sample
sizes and conflicting results.ObjectiveTo systematically review and quantify the effect of exercise on glycosylated
hemoglobin (HbA1c) and body mass in patients with type 2 diabetes.Data SourcesDatabase searches of MEDLINE, EMBASE, Sport Discuss, Health Star, Dissertation
Abstracts, and the Cochrane Controlled Trials Register for the period up to
and including December 2000. Additional data sources included bibliographies
of textbooks and articles identified by the database searches.Study SelectionWe selected studies that evaluated the effects of exercise interventions
(duration ≥8 weeks) in adults with type 2 diabetes. Fourteen (11 randomized
and 3 nonrandomized) controlled trials were included. Studies that included
drug cointerventions were excluded.Data ExtractionTwo reviewers independently extracted baseline and postintervention
means and SDs for the intervention and control groups. The characteristics
of the exercise interventions and the methodological quality of the trials
were also extracted.Data SynthesisTwelve aerobic training studies (mean [SD], 3.4 [0.9] times/week for
18 [15] weeks) and 2 resistance training studies (mean [SD], 10 [0.7] exercises,
2.5 [0.7] sets, 13 [0.7] repetitions, 2.5 [0.4] times/week for 15 [10] weeks)
were included in the analyses. The weighted mean postintervention HbA1c was lower in the exercise groups compared with the control groups
(7.65% vs 8.31%; weighted mean difference, −0.66%; P<.001). The difference in postintervention body mass between exercise
groups and control groups was not significant (83.02 kg vs 82.48 kg; weighted
mean difference, 0.54; P = .76).ConclusionExercise training reduces HbA1c by an amount that should
decrease the risk of diabetic complications, but no significantly greater
change in body mass was found when exercise groups were compared with control
groups.
1,660 citations
TL;DR: The authors' experimental intervention increased the duration and degree (exclusivity) of breastfeeding and decreased the risk of gastrointestinal tract infection and atopic eczema in the first year of life.
Abstract: This paper summarizes the objectives, design, follow-up, and data validation of a cluster-randomized trial of a breastfeeding promotion intervention modeled on the WHO/UNICEF Baby-Friendly Hospital Initiative (BFHI). Thirty-four hospitals and their affiliated polyclinics in the Republic of Belarus were randomized to receive BFHI training of medical, midwifery, and nursing staffs (experimental group) or to continue their routine practices (control group). All breastfeeding mother-infant dyads were considered eligible for inclusion in the study if the infant was singleton, bom at 237 weeks gestation, weighed ≥2500 grams at birth, and had a 5-minute Apgar score ≥5, and neither mother nor infant had a medical condition for which breastfeeding was contraindicated. One experimental and one control site refused to accept their randomized allocation and dropped out of the trial. A total of 17,795 mothers were recruited at the 32 remaining sites, and their infants were followed up at 1, 2, 3, 6, 9, and 12 months of age. To our knowledge, this is the largest randomized trial ever undertaken in area of human milk and lactation. Monitoring visits of all experimental and control maternity hospitals and polyclinics were undertaken prior to recruitment and twice more during recruitment and follow-up to ensure compliance with the randomized allocation. Major study outcomes include the occurrence of ≥1 episode of gastrointestinal infection, ≥2 respiratory infections, and the duration of breastfeeding, and are analyzed according to randomized allocation (“intention to treat”). One of the 32 remaining study sites was dropped from the trial because of apparently falsified follow-up data, as suggested by an unrealistically low incidence of infection and unrealistically long duration of breastfeeding, and as confirmed by subsequent data audit of polyclinic charts and interviews with mothers of 64 randomly-selected study infants at the site. Smaller random audits at each of the remaining sites showed extremely high concordance between the PROBIT data forms and both the polyclinic charts and maternal interviews, with no evident difference in under- or over-reporting in experimental vs control sites. Of the 17,046 infants recruited from the 31 participating study sites, 16,491 (96.7%) completed the study and only 555 (3.3%) were lost to follow-up. PROBIT’s results should help inform decision making for clinicians, hospitals, industry, and governments concerning the support, protection, and promotion of breastfeeding.
1,578 citations
01 Nov 2001
TL;DR: At 1 year, participants in the Chronic Disease Self-Management Program experienced statistically significant improvements in health behaviors, self-efficacy, and health status and had fewer visits to the emergency department and had less ED visits.
Abstract: CONTEXT. For patients with chronic disease, there is growing interest in "self-man- agement" programs that emphasize the patients' central role in managing their ill- ness. A recent randomized clinical trial demonstrated the potential of self-manage- ment to improve health status and reduce health care utilization in patients with chronic diseases. OBJECTIVE. To evaluate outcomes of a chronic disease self-management program in a "real-world" setting. STUDY DESIGN. Before-after cohort study. PATIENTS AND SETTING. Of the 613 patients from various Kaiser Permanente hospitals and clinics recruited for the study, 489 had complete baseline and follow-up data. INTERVENTION. The Chronic Disease Self-Management Program is a 7-week, small- group intervention attended by people with different chronic conditions. It is taught largely by peer instructors from a highly structured manual. The program is based on self-efficacy theory and emphasizes problem solving, decision making, and confi- dence building. MAIN OUTCOME MEASURES. Health behavior, self-efficacy (confidence in ability to deal with health problems), health status, and health care utilization, assessed at baseline and at 12 months by self-administered questionnaires. RESULTS. At 1 year, participants in the program experienced statistically significant improvements in health behaviors (exercise, cognitive symptom management, and communication with physicians), self-efficacy, and health status (fatigue, shortness of breath, pain, role function, depression, and health distress) and had fewer visits to the emergency department (ED) (0.4 visits in the 6 months prior to baseline, compared with 0.3 in the 6 months prior to follow-up; P = 0.05). There were slightly fewer out- patient visits to physicians and fewer days in hospital, but the differences were not statistically significant. Results were of about the same magnitude as those observed in a previous randomized, controlled trial. Program costs were estimated to be about $200 per participant. CONCLUSIONS. We replicated the results of our previous clinical trial of a chronic dis- ease self-management program in a "real-world" setting. One year after exposure to the program, most patients experienced statistically significant improvements in a variety of health outcomes and had fewer ED visits.
1,386 citations
TL;DR: The aim of this study was to establish an experimental procedure that can be used as a guide for the design of future studies on randomized trials of this type.
Abstract: OBJECTIVES: Delirium (or acute confusional state) affects 35% to 65% of patients after hip-fracture repair, and has been independently associated with poor functional recovery. We performed a randomized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture. DESIGN: Prospective, randomized, blinded. SETTING: Inpatient academic tertiary medical center. PARTICIPANTS: 126 consenting patients 65 and older (mean age 79 6 8 years, 79% women) admitted emergently for surgical repair of hip fracture. MEASUREMENTS: Detailed assessment through interviews with patients and designated proxies and review of medical records was performed at enrollment to ascertain prefracture status. Subjects were then randomized to proactive geriatrics consultation, which began preoperatively or within 24 hours of surgery, or “usual care.” A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol. To ascertain study outcomes, all subjects underwent daily, blinded interviews for the duration of their hospitalization, including the Mini-Mental State Examination (MMSE), the Delirium Symptom Interview (DSI), and the Memorial Delirium Assessment Scale (MDAS). Delirium was diagnosed using the Confusion Assessment Method (CAM) algorithm. RESULTS: The 62 patients randomized to geriatrics consultation were not significantly different ( P . .1) from the 64 usual-care patients in terms of age, gender, prefracture dementia, comorbidity, type of hip fracture, or type of surgical repair. Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively. A mean of 10 recommendations were made throughout the duration of the hospitalization, with 77% adherence by the orthopedics team. Delirium occurred in 20 ⁄62 (32%) intervention patients, versus 32 ⁄ 64 (50%) usual-care patients ( P 5 .04), representing a relative risk of 0.64 (95% confidence interval (CI) 5 0.37‐0.98) for the consultation group. One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group. There was an even greater reduction in cases of severe delirium, occurring in 7⁄60 (12%) of intervention patients and 18 ⁄62 (29%) of usual-care patients, with a relative risk of 0.40 (95% CI 5 0.18‐0.89). Despite this reduction in delirium, length of stay did not significantly differ between intervention and usual-care groups (median 6 interquartile range 5 5 6 2 days in both groups), likely because protocols and pathways predetermined length of stay. In subgroup analyses, geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living (ADL) functional impairment. CONCLUSIONS: Proactive geriatrics consultation was successfully implemented with good adherence after hipfracture repair. Geriatrics consultation reduced delirium by over one-third, and reduced severe delirium by over one-half. Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients. J Am Geriatr Soc 49:516‐522, 2001.
TL;DR: Interim CIGTS outcomes do not support altering current treatment approaches to open-angle glaucoma, and aggressive treatment aimed at substantial reduction in IOP from baseline is used, loss of VF can be seen to be minimal in general.
TL;DR: The use of CONSORT does indeed help to improve the quality of reports of RCTs and is enhanced by continuous monitoring of the biomedical literature; this monitoring allows CONSORT to be modified depending on the merits of maintaining or dropping current items and including new items.
Abstract: To comprehend the results of a randomized, controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Con solidated S tandards o f R eporting T rials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this paper incorporates new evidence and addresses some criticisms of the original statement. The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results, and Discussion. The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage of participants through an RCT. The revised flow diagram depicts information from four stages of a trial (enrollment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, for each intervention group, that are included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis. In sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.
TL;DR: In this paper, a systematic review and meta-regression analysis of randomised controlled trials obtained from five electronic databases (Medline, Embase, Sports Discus, PsycLIT, Cochrane Library) and through contact with experts in the field, bibliographic searches, and hand searches of recent copies of relevant journals was conducted.
Abstract: Objective: To determine the effectiveness of exercise as an intervention in the management of depression. Design: Systematic review and meta-regression analysis of randomised controlled trials obtained from five electronic databases (Medline, Embase, Sports Discus, PsycLIT, Cochrane Library) and through contact with experts in the field, bibliographic searches, and hand searches of recent copies of relevant journals. Main outcome measures: Standardised mean difference in effect size and weighted mean difference in Beck depression inventory score between exercise and no treatment and between exercise and cognitive therapy. Results: All of the 14 studies analysed had important methodological weaknesses; randomisation was adequately concealed in only three studies, intention to treat analysis was undertaken in only two, and assessment of outcome was blinded in only one. The participants in most studies were community volunteers, and diagnosis was determined by their score on the Beck depression inventory. When compared with no treatment, exercise reduced symptoms of depression (standardised mean difference in effect size −1.1 (95% confidence interval −1.5 to −0.6); weighted mean difference in Beck depression inventory −7.3 (−10.0 to −4.6)). The effect size was significantly greater in those trials with shorter follow up and in two trials reported only as conference abstracts. The effect of exercise was similar to that of cognitive therapy (standardised mean difference −0.3 (95% confidence interval −0.7 to 0.1)). Conclusions: The effectiveness of exercise in reducing symptoms of depression cannot be determined because of a lack of good quality research on clinical populations with adequate follow up. What is already known on this topic Depression is common Management is often inadequate and many patients do not comply with antidepressant medication The effect of exercise on depression has been a subject of interest for many years What this study adds Most studies of the effect of exercise on depression are of poor quality, have brief follow up, and are undertaken on non-clinical volunteers Exercise may be efficacious in reducing symptoms of depression in the short term but its effectiveness in clinical populations is unknown A well designed, randomised controlled trial with long term follow up is needed
TL;DR: Use of the Consolidated Standards for Reporting of Trials (CONSORT) statement is associated with improvements in the quality of reports of RCTs.
Abstract: ContextThe Consolidated Standards for Reporting of Trials (CONSORT) statement
was developed to help improve the quality of reports of randomized controlled
trials (RCTs). To date, a paucity of data exists regarding whether it has
achieved this goal.ObjectiveTo determine whether use of the CONSORT statement is associated with
improvement in the quality of reports of RCTs.Design and SettingComparative before-and-after evaluation in which reports of RCTs published
in 1994 (pre-CONSORT) were compared with RCT reports from the same journals
published in 1998 (post-CONSORT). We included 211 reports from BMJ, JAMA, and The Lancet (journals that
adopted CONSORT) as well as The New England Journal of Medicine (a journal that did not adopt CONSORT and was used as a comparator).Main Outcome MeasuresNumber of CONSORT items included in a report, frequency of unclear reporting
of allocation concealment, and overall trial quality score based on the Jadad
scale, a 5-point quality assessment instrument.ResultsCompared with 1994, the number of CONSORT checklist items in reports
of RCTs increased in all 4 journals in 1998, and this increase was statistically
significant for the 3 adopter journals (pre-CONSORT, 23.4; mean change, 3.7;
95% confidence interval [CI], 2.1-5.3). The frequency of unclear reporting
of allocation concealment decreased for each of the 4 journals, and this change
was statistically significant for adopters (pre-CONSORT, 61%; mean change, −22%;
95% CI, −38% to −6%). Similarly, 3 of the 4 journals showed an
improvement in the quality score for reports of RCTs, and this increase was
statistically significant for adopter journals overall (pre-CONSORT, 2.7;
mean change, 0.4; 95% CI, 0.1-0.8).ConclusionUse of the CONSORT statement is associated with improvements in the
quality of reports of RCTs.
TL;DR: Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy in patients with solid or nonmyeloid hematologic malignancies.
Abstract: PURPOSE: This randomized, double-blind, placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements, hematopoietic parameters, quality of life (QOL), and safety in anemic cancer patients receiving nonplatinum chemotherapy. The study also explored a possible relationship between increased hemoglobin and survival. PATIENTS AND METHODS: Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels ≤ 10.5 g/dL, or greater than 10.5 g/dL but ≤ 12.0 g/dL after a hemoglobin decrease of ≥ 1.5 g/dL per cycle since starting chemotherapy, were randomized 2:1 to epoetin alfa 150 to 300 IU/kg (n = 251) or placebo (n = 124) three times per week subcutaneously for 12 to 24 weeks. The primary end point was proportion of patients transfused; secondary end points were change in hemoglobin and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the stud...
TL;DR: For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/d, reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization.
Abstract: CONTEXT
Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events.
OBJECTIVE
To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events.
DESIGN AND SETTING
A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia.
PATIENTS
A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction.
INTERVENTIONS
Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission.
MAIN OUTCOME MEASURES
Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization.
RESULTS
A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12 vs 24 events; P =.045). In the atorvastatin group, mean low-density lipoprotein cholesterol level declined from 124 mg/dL (3.2 mmol/L) to 72 mg/dL (1.9 mmol/L). Abnormal liver transaminases (>3 times upper limit of normal) were more common in the atorvastatin group than in the placebo group (2.5% vs 0.6%; P<.001).
CONCLUSION
For patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin, 80 mg/d, reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization.
TL;DR: In women and men at risk of having a cardiovascular event because of the presence of at least one major risk factor, low-dose aspirin given in addition to treatment of specific risk factors contributes an additional preventive effect, with an acceptable safety profile.
TL;DR: In this article, a pooled analysis of individual patient data from seven phase 3 randomized trials (involving 3351 patients) in which the effects of postoperative fluorouracil plus leucovorin (five trials) or fluorourocil plus levamisole (two trials) were compared with surgery alone in patients with stage II or III colon cancer was performed.
Abstract: Background Adjuvant chemotherapy is standard treatment for patients with resected colon cancer who are at high risk for recurrence, but the efficacy and toxicity of such treatment in patients more than 70 years of age are controversial Methods We performed a pooled analysis, based on the intention to treat, of individual patient data from seven phase 3 randomized trials (involving 3351 patients) in which the effects of postoperative fluorouracil plus leucovorin (five trials) or fluorouracil plus levamisole (two trials) were compared with the effects of surgery alone in patients with stage II or III colon cancer The patients were grouped into four age categories of equal size, and analyses were repeated with 10-year age ranges (≤50, 51 to 60, 61 to 70, and >70 years), with the same conclusions The toxic effects measured in all trials were nausea or vomiting, diarrhea, stomatitis, and leukopenia Patients in the fluorouracil-plus-leucovorin and fluorouracil-plus-levamisole groups were combined for the ef
TL;DR: Subcutaneous etanercept at a dose of 25 mg twice weekly is safe, but not effective, for the treatment of patients with moderate to severe Crohn's disease.
TL;DR: Adjuvant hormonal therapy should be offered only to women whose tumors express hormone receptor protein in tumor tissues, and quality of life needs to be evaluated in selected randomized clinical trials to examine the impact of the major acute and long-term side effects of adjuvant treatments.
Abstract: Objective Our goal was to provide health-care providers, patients, and the general public with an assessment of currently available data regarding the use of adjuvant therapy for breast cancer. Participants The participants included a non-Federal, non-advocate, 14-member panel representing the fields of oncology, radiology, surgery, pathology, statistics, public health, and health policy as well as patient representatives. In addition, 30 experts in medical oncology, radiation oncology, biostatistics, epidemiology, surgical oncology, and clinical trials presented data to the panel and to a conference audience of 1000. Evidence The literature was searched with the use of MEDLINE(TM) for January 1995 through July 2000, and an extensive bibliography of 2230 references was provided to the panel. Experts prepared abstracts for their conference presentations with relevant citations from the literature. Evidence from randomized clinical trials and evidence from prospective studies were given precedence over clinical anecdotal experience. Consensus process The panel, answering predefined questions, developed its conclusions based on the evidence presented in open forum and the scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately after its release at the conference and was updated with the panel's final revisions. The statement is available at http://consensus.nih.gov. Conclusions The panel concludes that decisions regarding adjuvant hormonal therapy should be based on the presence of hormone receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered only to women whose tumors express hormone receptor protein. Because adjuvant polychemotherapy improves survival, it should be recommended to the majority of women with localized breast cancer regardless of lymph node, menopausal, or hormone receptor status. The inclusion of anthracyclines in adjuvant chemotherapy regimens produces a small but statistically significant improvement in survival over non-anthracycline-containing regimens. Available data are currently inconclusive regarding the use of taxanes in adjuvant treatment of lymph node-positive breast cancer. The use of adjuvant dose-intensive chemotherapy regimens in high-risk breast cancer and of taxanes in lymph node-negative breast cancer should be restricted to randomized trials. Ongoing studies evaluating these treatment strategies should be supported to determine if such strategies have a role in adjuvant treatment. Studies to date have included few patients older than 70 years. There is a critical need for trials to evaluate the role of adjuvant chemotherapy in these women. There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary cancer. Currently, the role of postmastectomy radiotherapy for patients with one to three positive lymph nodes remains uncertain and should be tested in a randomized controlled trial. Individual patients differ in the importance they place on the risks and benefits of adjuvant treatments. Quality of life needs to be evaluated in selected randomized clinical trials to examine the impact of the major acute and long-term side effects of adjuvant treatments, particularly premature menopause, weight gain, mild memory loss, and fatigue. Methods to support shared decision-making between patients and their physicians have been successful in trials; they need to be tailored for diverse populations and should be tested for broader dissemination.
TL;DR: Lumbar fusion in a well-informed and selected group of patients with severe CLBP can diminish pain and decrease disability more efficiently than commonly used nonsurgical treatment.
Abstract: STUDY DESIGN A randomized controlled multicenter study with a 2-year follow-up by an independent observer. OBJECTIVES To determine whether fusion of the lower lumbar spine could reduce pain and diminish disability more effectively when compared with nonsurgical treatment in patients with severe chronic low back pain (CLBP). SUMMARY OF BACKGROUND DATA The reported results after fusion surgery on patients with CLBP vary considerably, and the evidence of treatment efficacy is weak in the absence of randomized controlled studies. PATIENTS AND METHODS A total of 294 patients referred to 19 spinal centers from 1992 through 1998 were randomized blindly into four treatment groups. Patients aged 25-65 years with CLBP for at least 2 years and with radiologic evidence of disc degeneration at L4-L5, L5-S1, or both were eligible to participate in the study. The surgical group (n=222) included three different fusion techniques, not analyzed separately in this study. Patients in the nonsurgical group (n=72) were treated with different kinds of physical therapy. The surgical group comprised 49.5% men, and the mean age was 43 years. The corresponding figures for the nonsurgical group were 48.6% and 44 years. The patients had suffered from low back pain for a mean of 7.8 and 8.5 years and been on sick leave due to back pain for a mean of 3.2 and 2.9 years, respectively. The Visual Analogue Scale (VAS) was used to measure pain. The Oswestry Low Back Pain Questionnaire, the Million Score and the General Function Score (GFS) were used to measure disability. The Zung Depression Scale was used to measure depressive symptoms. The overall result was assessed by the patient and by an independent observer. Records from the Swedish Social Insurance were used to evaluate work disability. Patients who changed groups were included in the analyses of significance according to the intention-to-treat principle. RESULTS At the 2-year follow-up 289 of 294 (98%) patients, including 25 who had changed groups, were examined. Back pain was reduced in the surgical group by 33% (64 to 43), compared with 7% (63 to 58) in the nonsurgical group (P=0.0002). Pain improved most during the first 6 months and then gradually deteriorated. Disability according to Oswestry was reduced by 25% (47 to 36) compared with 6% (48 to 46) among nonsurgical patients (P=0.015), according to Million by 28% (64 to 46) compared with 8% (66 to 60) (P=0.004), and accordingtoGFS by 31% (49 to 34) compared with 4% (48 to 46) (P=0.005). The depressive symptoms, according to Zung, were reduced by 20% (39 to 31) in the surgical group compared with 7% (39 to 36) in the nonsurgical group (P=0.123). In the surgical group 63% (122/195) rated themselves as "much better" or "better" compared with 29% (18/62) in the nonsurgical group (P<0.0001). The "net back to work rate" was significantly in favor of surgical treatment, or 36% vs. 13% (P=0.002). The early complication rate in the surgical group was 17%. CONCLUSION Lumbar fusion in a well-informed and selected group of patients with severe CLBP can diminish pain and decrease disability more efficiently than commonly used nonsurgical treatment.
TL;DR: Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences thanmedical management and normal activity alone.
Abstract: Study Design. A randomized clinical trial with 1-year and 3-year telephone questionnaire follow-ups. Objective. To report a specific exercise intervention’s long-term effects on recurrence rates in acute, first-episode low back pain patients. Summary of Background Data. The pain and disability associated with an initial episode of acute low back pain (LBP) is known to resolve spontaneously in the short-term in the majority of cases. However, the recurrence rate is high, and recurrent disabling episodes remain one of the most costly problems in LBP. A deficit in the multifidus muscle has been identified in acute LBP patients, and does not resolve spontaneously on resolution of painful symptoms and resumption of normal activity. Any relation between this deficit and recurrence rate was investigated in the long-term. Methods. Thirty-nine patients with acute, first-episode LBP were medically managed and randomly allocated to either a control group or specific exercise group. Medical management included advice and use of medications. Intervention consisted of exercises aimed at rehabilitating the multifidus in cocontraction with the transversus abdominis muscle. One year and three years after treatment, telephone questionnaires were conducted with patients. Results. Questionnaire results revealed that patients from the specific exercise group experienced fewer recurrences of LBP than patients from the control group. One year after treatment, specific exercise group recurrence was 30%, and control group recurrence was 84% (P , 0.001). Two to three years after treatment, specific exercise group recurrence was 35%, and control group recurrence was 75% (P , 0.01). Conclusion. Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences than medical management and normal activity alone. [Key Words: multifidus, low back pain, rehabilitation]
TL;DR: Supportive-expressive group therapy does not prolong survival in women with metastatic breast cancer, but it improves mood and the perception of pain, particularly in women who are initially more distressed.
Abstract: Background Supportive–expressive group therapy has been reported to prolong survival among women with metastatic breast cancer. However, in recent studies, various psychosocial interventions have not prolonged survival. Methods In a multicenter trial, we randomly assigned 235 women with metastatic breast cancer who were expected to survive at least three months in a 2:1 ratio to an intervention group that participated in weekly supportive–expressive group therapy (158 women) or to a control group that received no such intervention (77 women). All the women received educational materials and any medical or psychosocial care that was deemed necessary. The primary outcome was survival; psychosocial function was assessed by self-reported questionnaires. Results Women assigned to supportive–expressive therapy had greater improvement in psychological symptoms and reported less pain (P=0.04) than women in the control group. A significant interaction of treatment-group assignment with base-line psychological scor...
TL;DR: There is little evidence for dose-response effects of physical activity and exercise, though this is largely because of a lack of studies rather than a lacks of evidence.
Abstract: Purpose: The purpose of this study was to examine the scientific evidence for a dose-response relation of physical activity with depressive and anxiety disorders. Methods: Computer database searches of MEDLINE, PsychLit, and Internet and personal retrieval systems to locate population studies, randomized controlled trials (RCTs), observational studies, and consensus panel judgments were conducted. Results: Observational studies demonstrate that greater amounts of occupational and leisure time physical activity are generally associated with reduced symptoms of depression. Quasi-experimental studies show that light-, moderate-, and vigorous-intensity exercise can reduce symptoms of depression. However, no RCTs have varied frequency or duration of exercise and controlled for total energy expenditure in studies of depression or anxiety. Quasi-experimental and RCTs demonstrate that both resistance training and aerobic exercise can reduce symptoms of depression. Finally, the relation of exercise dose to changes in cardiorespiratory fitness is equivocal with some studies showing that fitness is associated with reduction of symptoms and others that have demonstrated reduction in symptoms without increases in fitness. Conclusion: All evidence for dose-response effects of physical activity and exercise come from B and C levels of evidence. There is little evidence for dose-response effects, though this is largely because of a lack of studies rather than a lack of evidence. A dose-response relation does, however, remain plausible.
TL;DR: Women and elderly persons remain underrepresented in published trial literature relative to their disease prevalence because safety and efficacy can vary as a function of sex and age, and these enrollment biases undermine efforts to provide evidence-based care to all cardiac patients.
Abstract: ContextElderly persons and women were underrepresented in randomized controlled
trials (RCTs) prior to 1990. Since then, efforts have been made to correct
these biases, but their effect is unclear.ObjectiveTo determine whether the percentage of elderly persons and women in
published clinical trials of acute coronary syndromes has increased and how
this enrollment compared with disease prevalence.Data SourcesThe MEDLINE and Cochrane databases were searched for English-language
articles from January 1966 to March 2000 regarding myocardial infarction,
unstable angina, or acute coronary syndromes. Additional data sources included
meta-analyses, review articles, and cardiology textbooks. Estimates of community-based
myocardial infarction rates came from the National Registry of Myocardial
Infarction and the Worcester Heart Study.Study SelectionPublished RCTs of acute coronary syndrome patients were included and
trials enrolling 50 patients or fewer, those without clinical end points,
papers published in a language other than English, and unpublished manuscripts
were excluded. Of 7645 studies identified, 593 RCTs were selected for review.Data ExtractionThe RCTs were abstracted by 2 of the authors for year of publication,
source of support (ie, funding), pharmacotherapy, study phase, number of study
sites, trial location, number of patients, mean age of the study population,
and any age exclusion criteria for enrollment.Data SynthesisThe number of published RCTs with explicit age exclusions has declined
from 58% during 1966-1990 to 40% during 1991-2000. Trial enrollment of patients
aged 75 years or older increased from 2% for studies published during 1966-1990
to 9% during 1991-2000, but remains well below their representation among
all patients with myocardial infarction (37%) in the United States. Enrollment
of women has risen from 20% for studies published between 1966-1990 to 25%
during 1991-2000, but remains well below their proportion of all patients
with myocardial infarction (43%) in the United States.ConclusionsAttempts at making cardiovascular RCTs more inclusive appear to have
had limited success; thus, women and elderly persons remain underrepresented
in published trial literature relative to their disease prevalence. Because
safety and efficacy can vary as a function of sex and age, these enrollment
biases undermine efforts to provide evidence-based care to all cardiac patients.
TL;DR: Despite good correlation between randomized trials and nonrandomized studies-in particular, prospective studies-discrepancies beyond chance do occur and differences in estimated magnitude of treatment effect are very common.
Abstract: ContextThere is substantial debate about whether the results of nonrandomized
studies are consistent with the results of randomized controlled trials on
the same topic.ObjectivesTo compare results of randomized and nonrandomized studies that evaluated
medical interventions and to examine characteristics that may explain discrepancies
between randomized and nonrandomized studies.Data SourcesMEDLINE (1966–March 2000), the Cochrane Library (Issue 3, 2000),
and major journals were searched.Study SelectionForty-five diverse topics were identified for which both randomized
trials (n = 240) and nonrandomized studies (n = 168) had been performed and
had been considered in meta-analyses of binary outcomes.Data ExtractionData on events per patient in each study arm and design and characteristics
of each study considered in each meta-analysis were extracted and synthesized
separately for randomized and nonrandomized studies.Data SynthesisVery good correlation was observed between the summary odds ratios of
randomized and nonrandomized studies (r = 0.75; P<.001); however, nonrandomized studies tended to show
larger treatment effects (28 vs 11; P = .009). Between-study
heterogeneity was frequent among randomized trials alone (23%) and very frequent
among nonrandomized studies alone (41%). The summary results of the 2 types
of designs differed beyond chance in 7 cases (16%). Discrepancies beyond chance
were less common when only prospective studies were considered (8%). Occasional
differences in sample size and timing of publication were also noted between
discrepant randomized and nonrandomized studies. In 28 cases (62%), the natural
logarithm of the odds ratio differed by at least 50%, and in 15 cases (33%),
the odds ratio varied at least 2-fold between nonrandomized studies and randomized
trials.ConclusionsDespite good correlation between randomized trials and nonrandomized
studies—in particular, prospective studies—discrepancies beyond
chance do occur and differences in estimated magnitude of treatment effect
are very common.
TL;DR: The Wisconsin CF Neonatal Screening Project as discussed by the authors was designed as a randomized clinical trial to assess the benefits and risks of early diagnosis through screening, and the validity of the randomization method assessed by comparing 16 demographic variables.
Abstract: Objective. Despite its relative frequency among autosomal recessive diseases and the availability of the sweat test, cystic fibrosis (CF) has been difficult to diagnose in early childhood, and delays can lead to severe malnutrition, lung disease, or even death. The Wisconsin CF Neonatal Screening Project was designed as a randomized clinical trial to assess the benefits and risks of early diagnosis through screening. In addition, the incidence of CF was determined, and the validity of our randomization method assessed by comparing 16 demographic variables. Methodology. Immunoreactive trypsinogen analysis was applied to dried newborn blood specimens for recognition of CF risk from 1985 to 1991 and was coupled to DNA-based detection of the ΔF508 mutation from 1991 to 1994. Randomization of 650 341 newborns occurred when their blood specimens reached the Wisconsin screening laboratory. This created 2 groups—an early diagnosis, screened cohort and a standard diagnosis or control group. To avoid selection bias, we devised a unique unblinding method with a surveillance program to completely identify the control subjects. Because sequential analysis of nutritional outcome measures revealed significantly better growth in screened patients during 1996, we accelerated the unblinding and completely identified the control group by April 1998. Having each member of this cohort enrolled and evaluated for at least 1 year and having completed a comprehensive surveillance program, we performed another statistical analysis of anthropometric evaluated indices that includes all CF patients without meconium ileus. Results. The incidence of classical CF, ie, patients diagnosed in this trial with a sweat chloride of 60 mEq/L greater, was 1:4189. By incorporating other CF patients born during the randomization period, including 2 autopsy diagnosed patients and 8 probable patients, we calculate a maximum incidence of 1:3938 (95% confidence interval: 3402–4611). Although there were group differences in the proportion of patients with ΔF508 genotypes and with pancreatic insufficiency, validity of the randomization plan was demonstrated by analyzing 16 demographic variables and finding no significant difference after adjustment for multiple comparisons. Focusing on patients without meconium ileus, we found a marked difference in the mean ± standard deviation age of diagnosis for screened patients (13 ± 37 weeks), compared with the standard diagnosis group (100 ± 117). Anthropometric indices of nutritional status were significantly higher at diagnosis in the screened group, including length/height, weight, and head circumference. During 13 years of study, despite similar nutritional therapy and the inherently better pancreatic status of the control group, analysis of nutritional outcomes revealed significantly greater growth associated with early diagnosis. Most impressively, the screened group had a much lower proportion of patients with weight and height data below the 10th percentile throughout childhood. Conclusions. Although the screened group had a higher proportion of patients with pancreatic insufficiency, their growth indices were significantly better than those of the control group during the 13-year follow-up evaluation and, therefore, this randomized clinical trial of early CF diagnosis must be interpreted as unequivocally positive. Our conclusions did not change when the height and weight data before 4 years of age for the controls detected by unblinding were included in the analysis. Also, comparison of growth outcomes after 4 years of age in all subjects showed persistence of the significant differences. Therefore, selection bias has been eliminated as a potential explanation. In addition, the results show that severe malnutrition persists after delayed diagnosis of CF and that catch-up may not be possible. We conclude that early diagnosis of CF through neonatal screening combined with aggressive nutritional therapy can result in significantly enhanced long-term nutritional status.
TL;DR: It is suggested that alcohol reduction should be recommended as an important component of lifestyle modification for the prevention and treatment of hypertension among heavy drinkers.
Abstract: Alcohol drinking has been associated with increased blood pressure in epidemiological studies. We conducted a meta-analysis of randomized controlled trials to assess the effects of alcohol reductio...
TL;DR: It remains puzzling to me why the investigators restricted the entry criteria and consequently selected a population that was not representative of general clinical practice when excluding patients with frequently coexisting medical conditions such as diabetes, chronic obstructive pulmonary disease, and endocrine diseases.
Abstract: To the Editor:
In their recently published, 1-year prospective, double blind, placebo-controlled study, Winblad et al.1 examined the long-term clinical efficacy and safety of donepezil in mild to moderate AD. I congratulate the investigators for their effort. Unfortunately, it remains puzzling to me why the investigators restricted the entry criteria and consequently selected a population that was not representative of general clinical practice. By excluding patients with frequently coexisting medical conditions such as diabetes, chronic obstructive pulmonary disease, and endocrine diseases, the demonstrable effect of the treatment is not obscured by comorbid conditions and is therefore probably the greatest possible effect that can be observed. One clinical trial revealed that including patients with significant comorbidity reduced the beneficial effect of donepezil by almost 50% of that observed in trials with more rigorous entry criteria.2 In addition, the strict lack of any significant effect at the end point (last observation carried forward; LOCF) on the primary efficacy parameter raises questions. Furthermore, it is questionable whether the magnitude of change taken at its highest value (week 52 [6.2 units or 9.6%]) is detectable by the physician and caregivers. …