Showing papers on "Randomized controlled trial published in 2000"

Randomized, controlled trials, observational studies, and the hierarchy of research designs.

Abstract: Background In the hierarchy of research designs, the results of randomized, controlled trials are considered to be evidence of the highest grade, whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects. We used published meta-analyses to identify randomized clinical trials and observational studies that examined the same clinical topics. We then compared the results of the original reports according to the type of research design. Methods A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of randomized, controlled trials and meta-analyses of either cohort or case–control studies that assessed the same intervention. For each of five topics, summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual randomized, controlled trials and the individual observational studies. Results For the five clinical topics and 99 r...

A comparison of observational studies and randomized, controlled trials.

Abstract: Background For many years it has been claimed that observational studies find stronger treatment effects than randomized, controlled trials We compared the results of observational studies with those of randomized, controlled trials Methods We searched the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition We then searched the Medline and Cochrane data bases to identify all the randomized, controlled trials and observational studies comparing the same treatments for these conditions For each treatment, the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis-of-variance procedure and then compared with the combined magnitude of the effects in the randomized, controlled trials that evaluated the same treatment Results There were 136 reports about 19 diverse treatments, such as calcium-channel-blocker therapy for coronary artery disease, appendectomy, and interventions for subfertility In most cases, the estimates of the treatment effects from observational studies and randomized, controlled trials were similar In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the randomized, controlled trials Conclusions We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in randomized, controlled trials

Design and Analysis of Cluster Randomization Trials in Health Research

Abstract: Acknowledgements. Preface. 1. Introduction. 1.1 Why randomize clusters? 1.2 What is the impact of cluster randomization on the design and analysis of a trial? 1.3 Quantifying the effect of clustering. 1.4 Randomized versus non-randomized comparisons. 1.5 The unit of inference. 1.6 Terminology: what's in a name? 2. The historical development of cluster randomized trials. 2.1 Randomized trials before 1950. 2.2 Cluster randomized trials between 1950 and 1978. 2.3 Cluster randomized trails since 1978. 3. Issues arising in the planning of cluster randomization trials. 3.1 Selecting interventions. 3.2 Setting eligibility criteria. 3.3 Measuring subject response. 3.4 The most commonly used experimental designs. 3.5 Factorial and crossover designs. 3.6 Selecting an experimental design. 3.7 The importance of cluster-level replication. 3.8 Strategies for conducting successful trials. 4. The role of informed consent and other ethical issues. 4.1 The risk of harm. 4.2 Informed consent. 4.3 Subject blindness and informed consent. 4.4 Randomized consent designs. 4.5 Ethical issues and trial monitoring. 5. Sample size estimation for cluster randomization designs. 5.1 General issues of sample size estimation. 5.2 The completely randomized design. 5.3 The matched-pair design. 5.4 The stratified design. 5.5 Issues involving losses to follow-up. 5.6 Strategies for achieving desired power. 6. Analysis of binary outcomes. 6.1 Selecting the unit of analysis. 6.2 The completely randomized design. 6.3 The matched-pair design. 6.4 The stratified design. 7. Analysis of quantitative outcomes. 7.1 The completely randomized design. 7.2 The matched-pair design. 7.3 The stratified design. 8. Analysis of count, time to event and categorical outcomes. 8.1 Count and time to event data. 8.2 Categorical data. 9. Reporting of cluster randomization trials. 9.1 Reporting of study design. 9.2 Reporting of study results. References. Index.

Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis

Abstract: Background Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value. Methods We conducted a randomized, double-blind trial of 383 patients who had a first acute clinical demyelinating event (optic neuritis, incomplete transverse myelitis, or a brain-stem or cerebellar syndrome) and evidence of prior subclinical demyelination on magnetic resonance imaging (MRI) of the brain. After initial treatment with corticosteroids, 193 patients were randomly assigned to receive weekly intramuscular injections of 30 μg of interferon beta-1a and 190 were assigned to receive weekly injections of placebo. The study end points were the development of clinically definite multiple sclerosis and changes in findings on MRI of the brain. The trial was stopped after a preplanned interim efficacy analysis. Results During three years of follow-up, the cumulative probability of ...

A randomized, wait-list controlled clinical trial: the effect of a mindfulness meditation-based stress reduction program on mood and symptoms of stress in cancer outpatients.

Abstract: Objective: The objective of this study was to assess the effects of participation in a mindfulness meditation‐ based stress reduction program on mood disturbance and symptoms of stress in cancer outpatients. Methods: A randomized, wait-list controlled design was used. A convenience sample of eligible cancer patients enrolled after giving informed consent and were randomly assigned to either an immediate treatment condition or a wait-list control condition. Patients completed the Profile of Mood States and the Symptoms of Stress Inventory both before and after the intervention. The intervention consisted of a weekly meditation group lasting 1.5 hours for 7 weeks plus home meditation practice. Results: Ninety patients (mean age, 51 years) completed the study. The group was heterogeneous in type and stage of cancer. Patients’ mean preintervention scores on dependent measures were equivalent between groups. After the intervention, patients in the treatment group had significantly lower scores on Total Mood Disturbance and subscales of Depression, Anxiety, Anger, and Confusion and more Vigor than control subjects. The treatment group also had fewer overall Symptoms of Stress; fewer Cardiopulmonary and Gastrointestinal symptoms; less Emotional Irritability, Depression, and Cognitive Disorganization; and fewer Habitual Patterns of stress. Overall reduction in Total Mood Disturbance was 65%, with a 31% reduction in Symptoms of Stress. Conclusions: This program was effective in decreasing mood disturbance and stress symptoms in both male and female patients with a wide variety of cancer diagnoses, stages of illness, and ages. Key words: meditation, cancer, stress, mood, intervention, mindfulness. ANOVA 5 analysis of variance; MANOVA 5 multiple analysis of variance; POMS 5 Profile of Mood States; SOSI 5 Symptoms of Stress Inventory.

Randomized Intergroup Trial of Cisplatin–Paclitaxel Versus Cisplatin–Cyclophosphamide in Women With Advanced Epithelial Ovarian Cancer: Three-Year Results

Abstract: BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.

Estrogen Replacement Therapy for Treatment of Mild to Moderate Alzheimer Disease: A Randomized Controlled Trial

Abstract: ContextSeveral reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women.ObjectiveTo determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD.DesignThe Alzheimer's Disease Cooperative Study, a randomized, double-blind, placebo-controlled clinical trial conducted between October 1995 and January 1999.SettingThirty-two study sites in the United States.ParticipantsA total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy.InterventionsParticipants were randomized to estrogen, 0.625 mg/d (n = 42), or 1.25 mg/d (n = 39), or to identically appearing placebo (n = 39). One subject withdrew after randomization but before receiving medication; 97 subjects completed the trial.Main Outcome MeasuresThe primary outcome measure was change on the Clinical Global Impression of Change (CGIC) 7-point scale, analyzed by intent to treat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and language), motor function, and activities of daily living; compared by the combined estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follow-up.ResultsThe CGIC score for estrogen vs placebo was 5.1 vs 5.0 (P = .43); 80% of participants taking estrogen vs 74% of participants taking placebo worsened (P = .48). Secondary outcome measures also showed no significant differences, with the exception of the Clinical Dementia Rating Scale, which suggested worsening among patients taking estrogen (mean posttreatment change in score for estrogen, 0.5 vs 0.2 for placebo; P = .01).ConclusionsEstrogen replacement therapy for 1 year did not slow disease progression nor did it improve global, cognitive, or functional outcomes in women with mild to moderate AD. The study does not support the role of estrogen for the treatment of this disease. The potential role of estrogen in the prevention of AD, however, requires further research.

A 5-month, randomized, placebo-controlled trial of galantamine in AD

Abstract: Objective: To investigate the efficacy and tolerability of galantamine, using a slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to moderate AD. Methods: A 5-month multicenter, placebo-controlled, double-blind trial. Following a 4-week placebo run-in, patients were randomized to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations and adverse event monitoring were carried out. Results: After 5 months, the galantamine–placebo differences on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for the 24 mg/day group ( p Conclusions: Galantamine 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with placebo. Slow dose escalation appears to enhance the tolerability of galantamine, minimizing the incidence and severity of adverse events.

Pramipexole vs Levodopa as initial treatment for Parkinson disease: A randomized controlled trial

Abstract: CONTEXT Pramipexole and levodopa both ameliorate the motor symptoms of early Parkinson disease (PD), but no controlled studies have compared long-term outcomes after initiating dopaminergic therapy with pramipexole vs levodopa. OBJECTIVE To compare the development of dopaminergic motor complications after initial treatment of early PD with pramipexole vs levodopa. DESIGN Multicenter, parallel-group, double-blind, randomized controlled trial. SETTING Academic movement disorders clinics at 22 sites in the United States and Canada. PATIENTS Three hundred one patients with early PD who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997. INTERVENTIONS Subjects were randomly assigned to receive pramipexole, 0.5 mg 3 times per day, with levodopa placebo (n = 151); or carbidopa/levodopa, 25/100 mg 3 times per day, with pramipexole placebo (n = 150). For patients with residual disability, the dosage was escalated during the first 10 weeks. From week 11 to month 23.5, investigators were permitted to add open-label levodopa to treat continuing or emerging disability. MAIN OUTCOME MEASURES Time to the first occurrence of any of 3 dopaminergic complications: wearing off, dyskinesias, or on-off motor fluctuations; changes in scores on the Unified Parkinson's Disease Rating Scale (UPDRS), assessed at baseline and follow-up evaluations; and, in a subgroup of 82 subjects evaluated at baseline and 23.5 months, ratio of specific to nondisplaceable striatal iodine 123 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) uptake on single photon emission computed tomography imaging of the dopamine transporter. RESULTS Initial pramipexole treatment resulted in significantly less development of wearing off, dyskinesias, or on-off motor fluctuations (28%) compared with levodopa (51%) (hazard ratio, 0.45; 95% confidence interval [CI], 0. 30-0.66; P<.001). The mean improvement in total UPDRS score from baseline to 23.5 months was greater in the levodopa group than in the pramipexole group (9.2 vs 4.5 points; P<.001). Somnolence was more common in pramipexole-treated patients than in levodopa-treated patients (32.4% vs 17.3%; P =.003), and the difference was seen during the escalation phase of treatment. In the subgroup study, patients treated initially with pramipexole (n = 39) showed a mean (SD) decline of 20.0% (14.2%) in striatal beta-CIT uptake compared with a 24.8% (14.4%) decline in subjects treated initially with levodopa (n = 39; P =.15). CONCLUSIONS Fewer patients receiving initial treatment for PD with pramipexole developed dopaminergic motor complications than with levodopa therapy. Despite supplementation with open-label levodopa in both groups, the levodopa-treated group had a greater improvement in total UPDRS compared with the pramipexole group. JAMA. 2000;284:1931-1938.

An Introduction To Instrumental Variables For epidemiologists

Abstract: Instrumental-variable (IV) methods were invented over 70 years ago, but remain uncommon in epidemiology. Over the past decade or so, non-parametric versions of IV methods have appeared that connect IV methods to causal and measurement-error models important in epidemiological applications. This paper provides an introduction to those developments, illustrated by an application of IV methods to non-parametric adjustment for non-compliance in randomized trials.

The triple P-positive parenting program: a comparison of enhanced, standard, and self-directed behavioral family intervention for parents of children with early onset conduct problems.

Abstract: Three variants of a behavioral family intervention (BFI) program known as Triple P were compared using 305 preschoolers at high risk of developing conduct problems. Families were randomly assigned to enhanced BFI (EBFI), standard BFI (SBFI), self-directed BFI (SDBFI), or wait list (WL). At postintervention, the 2 practitioner-assisted conditions were associated with lower levels of parent-reported disruptive child behavior, lower levels of dysfunctional parenting, greater parental competence, and higher consumer satisfaction than the SDBFI and WL conditions. Overall, children in EBFI showed greater reliable improvement than children in SBFI, SDBFI, and WL. By 1-year follow-up, children in all 3 conditions achieved similar levels of clinically reliable change in observed disruptive behavior. However, the EBFI and SBFI conditions showed greater reliable improvement on parent-observed disruptive child behavior.

High- and Low-Dose Interferon Alfa-2b in High-Risk Melanoma: First Analysis of Intergroup Trial E1690/S9111/C9190

Abstract: PURPOSE: Pivotal trial E1684 of adjuvant high-dose interferon alfa-2b (IFNα2b) therapy in high-risk melanoma patients demonstrated a significant relapse-free and overall survival (RFS and OS) benefit compared with observation (Obs). PATIENTS AND METHODS: A prospective, randomized, three-arm, intergroup trial evaluated the efficacy of high-dose IFNα2b (HDI) for 1 year and low-dose IFNα2b (LDI) for 2 years versus Obs in high-risk (stage IIB and III) melanoma with RFS and OS end points. RESULTS: A total of 642 patients were enrolled (608 patients eligible), of whom a majority (75%) had nodal metastasis (50% had nodal recurrence). Unlike E1684, E1690 allowed entry of patients with T4 (> 4 mm) deep primary tumors, regardless of nodal dissection, and 25% of the patients entered onto this trial had deep primary tumors (compared with 11% in E1684). At 52 months’ median follow-up, HDI demonstrated an RFS benefit exceeding that of LDI compared with Obs. The 5-year estimated RFS rates for the HDI, LDI, and Obs arms ...

Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas

Abstract: Background The risks of colorectal cancer and adenoma, the precursor lesion, are believed to be influenced by dietary factors. Epidemiologic evidence that cereal fiber protects against colorectal cancer is equivocal. We conducted a randomized trial to determine whether dietary supplementation with wheat-bran fiber reduces the rate of recurrence of colorectal adenomas. Methods We randomly assigned 1429 men and women who were 40 to 80 years of age and who had had one or more histologically confirmed colorectal adenomas removed within three months before recruitment to a supervised program of dietary supplementation with either high amounts (13.5 g per day) or low amounts (2 g per day) of wheat-bran fiber. The primary end point was the presence or absence of new adenomas at the time of follow-up colonoscopy. Subjects and physicians, including colonoscopists, were unaware of the group assignments. Results Of the 1303 subjects who completed the study, 719 had been randomly assigned to the high-fiber group and ...

Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes

Abstract: Background Evidence suggests that physiologic pacing (dual-chamber or atrial) may be superior to single-chamber (ventricular) pacing because it is associated with lower risks of atrial fibrillation, stroke, and death. These benefits have not been evaluated in a large, randomized, controlled trial. Methods At 32 Canadian centers, patients without chronic atrial fibrillation who were scheduled for a first implantation of a pacemaker to treat symptomatic bradycardia were eligible for enrollment. We randomly assigned patients to receive either a ventricular pacemaker or a physiologic pacemaker and followed them for an average of three years. The primary outcome was stroke or death due to cardiovascular causes. Secondary outcomes were death from any cause, atrial fibrillation, and hospitalization for heart failure. Results A total of 1474 patients were randomly assigned to receive a ventricular pacemaker and 1094 to receive a physiologic pacemaker. The annual rate of stroke or death due to cardiovascular cause...

A Controlled Trial of a Critical Pathway for Treatment of Community-Acquired Pneumonia

Abstract: ContextLarge variations exist among hospitals in the use of treatment resources for community-acquired pneumonia (CAP). Lack of a common approach to the diagnosis and treatment of CAP has been cited as an explanation for these variations.ObjectiveTo determine if use of a critical pathway improves the efficiency of treatment for CAP without compromising the well-being of patients.DesignMulticenter controlled clinical trial with cluster randomization and up to 6 weeks of follow-up.SettingNineteen teaching and community hospitals in Canada.PatientsA total of 1743 patients with CAP presenting to the emergency department at 1 of the participating institutions between January 1 and July 31, 1998.InterventionHospitals were assigned to continue conventional management (n = 10) or implement the critical pathway (n = 9), which consisted of a clinical prediction rule to guide the admission decision, levofloxacin therapy, and practice guidelines.Main Outcome MeasuresEffectiveness of the critical pathway, as measured by health-related quality of life on the Short-Form 36 Physical Component Summary (SF-36 PCS) scale at 6 weeks; and resource utilization, as measured by the number of bed days per patient managed (BDPM).ResultsQuality of life and the occurrence of complications, readmission, and mortality were not different for the 2 strategies; the 1-sided 95% confidence limit of the between-group difference in the SF-36 PCS change score was 2.4 points, which was within a predefined 3-point boundary for equivalence. Pathway use was associated with a 1.7-day reduction in BDPM (4.4 vs 6.1 days; P = .04) and an 18% decrease in the admission of low-risk patients (31% vs 49%; P = .01). Although inpatients at critical pathway hospitals had more severe disease, they required 1.7 fewer days of intravenous therapy (4.6 vs 6.3 days; P = .01) and were more likely to receive treatment with a single class of antibiotic (64% vs 27%; P<.001).ConclusionIn this study, implementation of a critical pathway reduced the use of institutional resources without causing adverse effects on the well-being of patients.

A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities.

Abstract: Background Controversy persists about the use of right unilateral (RUL) and bilateral (BL) electroconvulsive therapy (ECT). While RUL ECT results in less severe short-term and long-term cognitive effects, there is concern that it is less efficacious than BL ECT. Methods In a double-blind study, 80 depressed patients were randomized to RUL ECT, with electrical dosages 50%, 150%, or 500% above the seizure threshold, or BL ECT, with an electrical dosage 150% above the threshold. Depression severity and cognitive functioning were assessed before, during, immediately after, and 2 months after ECT. Compared with baseline, responders had at least a 60% reduction in symptom scores 1 week after ECT, and were monitored for relapse for 1 year. Results High-dosage RUL and BL ECT were equivalent in response rate (65%) and approximately twice as effective as low-dosage (35%) or moderate-dosage (30%) unilateral ECT. During the week after the randomized phase, BL ECT resulted in greater impairment than any dosage of unilateral ECT in several measures of anterograde and retrograde memory. Two months after ECT, retrograde amnestic deficits were greatest among patients treated with BL ECT. Thirty-three (53%) of the 62 patients who responded to ECT relapsed, without treatment group differences. The relapse rate was greater in patients who had not responded to adequate pharmacotherapy prior to ECT and who had more severe depressive symptoms after ECT. Conclusion Right unilateral ECT at high dosage is as effective as a robust form of BL ECT, but produces less severe and persistent cognitive effects.

Preoperative radiotherapy for resectable rectal cancer: A meta-analysis.

Abstract: ContextThe benefit of adjuvant radiotherapy for resectable rectal cancer has been extensively studied, but data on survival are still equivocal despite a reduction in the rate of local recurrence.ObjectiveTo assess the effectiveness of preoperative radiotherapy followed by surgery in the reduction of overall and cancer-related mortality and in the prevention of local recurrence and distant metastases.Data SourcesComputerized bibliographic searches of MEDLINE and CANCERLIT (1970 to December 1999), including non-English sources, were supplemented with hand searches of reference lists. The medical subject headings used were rectal cancer, radiotherapy, surgery, RCT, randomized, and clinical trial.Study SelectionStudies were included if they were randomized controlled trials (RCTs) comparing preoperative radiotherapy plus surgery with surgery alone and if they included patients with resectable histologically proven rectal adenocarcinoma, without metastatic disease. Fourteen RCTs were analyzed.Data ExtractionData on population, intervention, and outcomes were extracted from each RCT according to the intention-to-treat method by 3 independent observers and combined using the DerSimonian and Laird method.Data SynthesisRadiotherapy plus surgery compared with surgery alone significantly reduced the 5-year overall mortality rate (odds ratio [OR] 0.84; 95% confidence interval [CI], 0.72-0.98; P = .03), cancer-related mortality rate (OR, 0.71; 95% CI, 0.61-0.82; P<.001), and local recurrence rate (OR, 0.49; 95% CI, 0.38-0.62; P<.001). No reduction was observed in the occurrence of distant metastases (OR, 0.93; 95% CI, 0.73-1.18; P = .54).ConclusionsIn patients with resectable rectal cancer, preoperative radiotherapy significantly improved overall and cancer-specific survival compared with surgery alone. The magnitude of the benefit is relatively small and criteria are needed to identify patients most likely to benefit from adjuvant radiotherapy.

A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication.

Abstract: Background Research evidence supports the efficacy of cognitive-behavioral therapy in the treatment of drug-refractory positive symptoms of schizophrenia. Although the cumulative evidence is strong, early controlled trials showed methodological limitations. Methods A randomized controlled design was used to compare the efficacy of manualized cognitive-behavioral therapy developed particularly for schizophrenia with that of a nonspecific befriending control intervention. Both interventions were delivered by 2 experienced nurses who received regular supervision. Patients were assessed by blind raters at baseline, after treatment (lasting up to 9 months), and at a 9-month follow-up evaluation. Patients continued to receive routine care throughout the study. An assessor blind to the patients' treatment groups rated the technical quality of audiotaped sessions chosen at random. Analysis was by intention to treat. Results Ninety patients received a mean of 19 individual treatment sessions over 9 months, with no significant between-group differences in treatment duration. Both interventions resulted in significant reductions in positive and negative symptoms and depression. At the 9-month follow-up evaluation, patients who had received cognitive therapy continued to improve, while those in the befriending group did not. These results were not attributable to changes in prescribed medication. Conclusion Cognitive-behavioral therapy is effective in treating negative as well as positive symptoms in schizophrenia resistant to standard antipsychotic drugs, with its efficacy sustained over 9 months of follow-up.

Lumbar spinal stenosis: conservative or surgical management?: A prospective 10-year study.

Abstract: Study design A cohort of 100 patients with symptomatic lumbar spinal stenosis, characterized in a previous article, were given surgical or conservative treatment and followed for 10 years. Objectives To identify the short- and long-term results after surgical and conservative treatment, and to determine whether clinical or radiologic predictors for the treatment result can be defined. Summary of background data Surgical decompression has been considered the rational treatment. However, clinical experience indicates that many patients do well with conservative treatment. Methods In this study, 19 patients with severe symptoms were selected for surgical treatment and 50 patients with moderate symptoms for conservative treatment, whereas 31 patients were randomized between the conservative (n = 18) and surgical (n = 13) treatment groups. Pain was decisive for the choice of treatment group. All patients were observed for 10 years by clinical evaluation and questionnaires. The results, evaluated by patient and physician, were rated as excellent, fair, unchanged, or worse. Results After a period of 3 months, relief of pain had occurred in most patients. Some had relief earlier, whereas for others it took 1 year. After a period of 4 years, excellent or fair results were found in half of the patients selected for conservative treatment, and in four fifths of the patients selected for surgery. Patients with an unsatisfactory result from conservative treatment were offered delayed surgery after 3 to 27 months (median, 3.5 months). The treatment result of delayed surgery was essentially similar to that of the initial group. The treatment result for the patients randomized for surgical treatment was considerably better than for the patients randomized for conservative treatment. Clinically significant deterioration of symptoms during the final 6 years of the follow-up period was not observed. Patients with multilevel afflictions, surgically treated or not, did not have a poorer outcome than those with single-level afflictions. Clinical or radiologic predictors for the final outcome were not found. There were no dropouts, except for 14 deaths. Conclusions The outcome was most favorable for surgical treatment. However, an initial conservative approach seems advisable for many patients because those with an unsatisfactory result can be treated surgically later with a good outcome.

Effectiveness of Manual Physical Therapy and Exercise in Osteoarthritis of the Knee: A Randomized, Controlled Trial

Abstract: Background: Few investigations include both subjective and objective measurements of the effectiveness of treatments for osteoarthritis of the knee. Beneficial interventions may decrease the disability associated with osteoarthritis and the need for more invasive treatments. Objective: To evaluate the effectiveness of physical therapy for osteoarthritis of the knee, applied by experienced physical therapists with formal training in manual therapy. Design: Randomized, controlled clinical trial. Setting: Outpatient physical therapy department of a large military medical center. Patients: 83 patients with osteoarthritis of the knee who were randomly assigned to receive treatment (n = 42; 15 men and 27 women [mean age, 60 ± 11 years]) or placebo (n = 41; 19 men and 22 women [mean age, 62 ± 10 years]). Intervention: The treatment group received manual therapy, applied to the knee as well as to the lumbar spine, hip, and ankle as required, and performed a standardized knee exercise program in the clinic and at home. The placebo group had subtherapeutic ultrasound to the knee at an intensity of 0.1 W/cm 2 with a 10% pulsed mode. Both groups were treated at the clinic twice weekly for 4 weeks. Measurements: Distance walked in 6 minutes and sum of the function, pain, and stiffness subscores of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). A tester who was blinded to group assignment made group comparisons at the initial visit (before initiation of treatment), 4 weeks, 8 weeks, and 1 year. Results: Clinically and statistically significant improvements in 6-minute walk distance and WOMAC score at 4 weeks and 8 weeks were seen in the treatment group but not the placebo group. By 8 weeks, average 6-minute walk distances had improved by 13.1 % and WOMAC scores had improved by 55.8% over baseline values in the treatment group (P < 0.05). After controlling for potential confounding variables, the average distance walked in 6 minutes at 8 weeks among patients in the treatment group was 170 m (95% Cl, 71 to 270 m) more than that in the placebo group and the average WOMAC scores were 599 mm higher (95% Cl, 197 to 1002 mm). At 1 year, patients in the treatment group had clinically and statistically significant gains over baseline WOMAC scores and walking distance; 20% of patients in the placebo group and 5% of patients in the treatment group had undergone knee arthroplasty. Conclusions: A combination of manual physical therapy and supervised exercise yields functional benefits for patients with osteoarthritis of the knee and may delay or prevent the need for surgical intervention.