Treating adolescent drug abuse: a randomized trial comparing multidimensional family therapy and cognitive behavior therapy

Aim To examine the efficacy of two adolescent drug abuse treatments: individual cognitive behavioral therapy (CBT) and multidimensional family therapy (MDFT). Design A 2 (treatment condition) x 4 (time) repeated‐measures intent‐to‐treat randomized design. Data were gathered at baseline, termination, 6 and 12 months post‐termination. Analyses used latent growth curve modeling. Setting Community‐based drug abuse clinic in the northeastern United States. Participants A total of 224 youth, primarily male (81%), African American (72%), from low‐income single‐parent homes (58%) with an average age of 15 years were recruited into the study. All youth were drug users, with 75% meeting DSM‐IV criteria for cannabis dependence and 13% meeting criteria for abuse. Measurements Five outcomes were measured: (i) substance use problem severity; (ii) 30‐day frequency of cannabis use; (iii) 30‐day frequency of alcohol use; (iv) 30‐day frequency of other drug use; and (v) 30‐day abstinence. Findings Both treatments produced significant decreases in cannabis consumption and slightly significant reductions in alcohol use, but there were no treatment differences in reducing frequency of cannabis and alcohol use. Significant treatment effects were found favoring MDFT on substance use problem severity, other drug use and minimal use (zero or one occasion of use) of all substances, and these effects continued to 12 months following treatment termination. Conclusion Both interventions are promising treatments. Consistent with previous controlled trials, MDFT is distinguished by the sustainability of treatment effects.     

Quality of life on antihypertensive therapy: a randomized double-blind controlled trial of captopril and atenolol

A randomized double-blind study lasting 2 months was performed with either 25 mg captopril twice a day or 50 mg atenolol once a day in 125 patients with established diastolic hypertension (diastolic blood pressure greater than 95 mmHg) identified during a population screening programme of subjects aged less than 65 years. Quality of life was assessed from self-completed questionnaires. A significant fall in diastolic blood pressure occurred with both captopril (106.7 +/- 7.0 to 98.6 +/- 8.6 mmHg) and atenolol (107.4 +/- 7.5 to 98.2 +/- 8.1 mmHg) but there was no difference between the two drugs in the size of the fall. A measure of the number of symptomatic complaints, the symptom complaint rate, decreased with both drugs, by 1.3% for captopril and 3.1% for atenolol, but the difference between the drugs was not significant [1.8%; 95% confidence interval (Cl) - 1.3%, 4.9%]. There was a significant increase in the reporting of cough and runny nose in those on captopril compared with atenolol. A health index increased by 1.1% with captopril in comparison with no change on atenolol (difference 1.1%; 95% Cl - 2.0%, 4.2%). Psychological well-being was measured using the Symptom Rating Test. The improvement in total score was 1.4% with captopril and 2.3% with atenolol. The difference of 0.9% was not statistically significant (95% Cl - 1.2%, 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulse pressure changes with six classes of antihypertensive agents in a randomized, controlled trial

Pulse pressure has been more strongly associated with cardiovascular outcomes, especially myocardial infarction and heart failure, than has systolic, diastolic, or mean arterial pressure in a variety of populations. Little is known, however, of the comparative effects of various classes of antihypertensive agents on pulse pressure. In retrospective analyses of the Veterans Affairs Single-Drug Therapy for Hypertension Study, we compared changes in pulse pressure with 6 classes of antihypertensive agents: 1292 men with diastolic blood pressure of 95 to 109 mm Hg on placebo were randomized to receive hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, prazosin, or placebo. Drug doses were titrated to achieve a goal diastolic blood pressure of <90 mm Hg during a 4- to 8-week medication titration phase. Pulse pressure change (placebo subtracted) was assessed from baseline to the end of the 3-month titration and 1-year maintenance. Mean baseline systolic, diastolic, and pulse pressures were 152, 99, and 53 mm Hg, respectively. Reductions in pulse pressure during titration were greater (P<0.001) with clonidine (6.7 mm Hg) and hydrochlorothiazide (6.2 mm Hg) than with captopril (2.5 mm Hg), diltiazem (1.6 mm Hg), and atenolol (1.4 mm Hg); reduction with prazosin (3.9 mm Hg) was similar to all but clonidine. After 1 year, pulse pressure was reduced significantly more (P<0.001) with hydrochlorothiazide (8.6 mm Hg) than with captopril and atenolol (4.1 mm Hg with both); clonidine (6.3 mm Hg), diltiazem (5.5 mm Hg), and prazosin (5.0 mm Hg) were intermediate. These data show that classes of antihypertensive agents differ in their ability to reduce pulse pressure. Whether these differences affect rates of cardiovascular events remains to be determined.     

Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial

BACKGROUND: In a phase II study, etanercept (recombinant human tumor necrosis factor receptor [p75]:Fc fusion protein) safely produced rapid, dose-dependent improvement in rheumatoid arthritis over 3 months. OBJECTIVE: To confirm the benefit of etanercept therapy of longer duration and simplified dosing in patients with rheumatoid arthritis. DESIGN: Randomized, double-blind, placebo-controlled trial with blinded joint assessors. SETTING: 13 North American centers. PATIENTS: 234 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs. INTERVENTION: Twice-weekly subcutaneous injections of etanercept, 10 or 25 mg, or placebo for 6 months. MEASUREMENTS: The primary end points were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 3 and 6 months. Other end points were 70% ACR responses at 3 and 6 months and other measures of disease activity at 3 and 6 months. RESULTS: Etanercept significantly reduced disease activity in a dose-related fashion. At 3 months, 62% of the patients receiving 25 mg of etanercept and 23% of the placebo recipients achieved 20% ACR response (P < 0.001). At 6 months, 59% of the 25-mg group and 11% of the placebo group achieved a 20% ACR response (P < 0.001); 40% and 5%, respectively, achieved a 50% ACR response (P < 0.01). The respective mean percentage reduction in the number of tender and swollen joints at 6 months was 56% and 47% in the 25-mg group and 6% and -7% in the placebo group (P < 0.05). Significantly more etanercept recipients achieved a 70% ACR response, minimal disease status (0 to 5 affected joints), and improved quality of life. Etanercept was well tolerated, with no dose-limiting toxic effects. CONCLUSIONS: Etanercept can safely provide rapid, significant, and sustained benefit in patients with active rheumatoid arthritis.     

Triple therapy in early active rheumatoid arthritis: a randomized, single-blind, controlled trial comparing step-up and parallel treatment strategies

OBJECTIVE: The Tight Control of Rheumatoid Arthritis study previously demonstrated that an intensive step-up disease-modifying antirheumatic drug (DMARD) treatment strategy targeting persistent disease activity was superior to routine care in the management of early rheumatoid arthritis (RA). We undertook this study to test the hypothesis that early parallel triple therapy achieves better outcomes than step-up therapy within an intensive disease management regimen. METHODS: Ninety-six patients with early RA (mean disease duration 11.5 months) were randomized to receive step-up therapy (sulfasalazine [SSZ] monotherapy, then after 3 months, methotrexate [MTX] was added, and when the maximum tolerated dosage of MTX was reached, hydroxychloroquine [HCQ] was added) or parallel triple therapy (SSZ/MTX/HCQ). All patients were assessed monthly for 12 months. If their disease activity score in 28 joints (DAS28) was > or =3.2, the dosage of DMARDs was increased according to protocol, and swollen joints were injected with triamcinolone acetonide (maximum dosage 80 mg per month). A metrologist who was blinded to the treatment allocation performed assessments every 3 months. The primary outcome measure was the mean decrease in the DAS28 score at 12 months. RESULTS: Both groups showed substantial improvements in disease activity and functional outcome. At 12 months, the mean decrease in the DAS28 score was -4.0 (step-up therapy group) versus -3.3 (parallel therapy group) (P = 0.163). No significant differences in the percentages of patients with DAS28 remission (step-up therapy group 45% versus parallel triple therapy group 33%), DAS28 good response (60% versus 41%, respectively), or American College of Rheumatology criteria for 20% improvement (ACR20) (77% versus 76%, respectively), ACR50 (60% versus 51%, respectively), or ACR70 (30% versus 20%, respectively) responses were seen. Radiologic progression was similar in both groups. CONCLUSION: This study confirms that highly effective control of disease activity can be achieved using conventional DMARDs as part of an intensive disease management strategy. Within this setting, step-up therapy is at least as effective as parallel triple therapy.     

Initial management of immune thrombocytopenic purpura in adults: a randomized controlled trial comparing intermittent anti-D with routine care

We conducted a randomized clinical trial in adults with a new diagnosis of ITP and a platelet count <30000/muL to test the hypothesis that initial intermittent treatment with anti-D may avoid or defer the need for splenectomy when compared to current routine care (glucocorticoid treatment, followed by splenectomy). Splenectomy was to be performed in the anti-D group if patients failed to respond to three consecutive anti-D treatments given within 10 days. The incidences of splenectomy were 14 of 37 (38%) in the routine care group and 14 of 33 (42%) in the anti-D group (absolute risk reduction = 4.6% in favor of the routine care group, 95% CI, -18.4 to 27.6%). However, splenectomy was performed prematurely, not according to the protocol, in 11 of 14 patients in the anti-D group. The median time to splenectomy was 36 days (range, 9-78) in the routine care group and 112 days (range, 19-558) in the anti-D group (P = 0.045 at 100 days after randomization, P = 0.840 at 1 year after randomization, using log-rank analysis). Patients in the anti-D group were treated with prednisone for fewer days (70 days) compared to the routine care group (112 days, P = 0.01). No major bleeding events occurred. In this study, initial treatment of patients with intermittent anti-D initially deferred splenectomy. Whether our aggressive regimen of anti-D could have prevented splenectomy if it had been adhered to in all patients remains uncertain. However, compliance with this anti-D regimen was not feasible for many patients and/or their physicians.     

Predictors of failure to initiate randomized treatment in a large trial of antihypertensive drug therapy in the aged

BACKGROUND: The identification of factors that contribute to noncompliance with trial drug initiation where virtually complete compliance might be expected, may help identify patients whose management is least likely to comply with clinical guidelines and study protocols. METHODS: Examination of cross-sectional and longitudinal data arising from the Second Australian National Blood Pressure Study. Prevalence rate ratios (RR) and 95% confidence intervals (CI) estimated from log-binomial models were used to assess associations between subject characteristics and whether the randomized drug was prescribed at trial randomization. The study population consisted of 6083 hypertensive Australians aged 65 to 84 years. RESULTS: After adjusting for each variable in a multivariate model the following were significant predictors of failure to prescribe RR (95% CI): not previously prescribed antihypertensive drugs 2.89 (2.52-3.32); lower systolic blood pressure (BP) 1.51 (1.59-1.43) or diastolic BP 1.18 (1.22-1.13); younger age 80 to 84 v 65 to 79 years 0.75 (0.59-0.95); total cholesterol >or=6.6 v 相似文献   

Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid

Intrahepatic cholestasis of pregnancy (ICP) is characterized by troublesome maternal pruritus, elevated serum bile acids (> or =10 micromol/L) and increased fetal risk. Recently we determined a cutoff level of serum bile acids, > or =40 micromol/L, to be associated with impaired fetal outcome. We have now studied the effects of ursodeoxycholic acid (UDCA) and dexamethasone on pruritus, biochemical markers of cholestasis, and fetal complication rates in a double-blind, placebo-controlled trial. For this purpose, 130 women with ICP were randomly allocated to UDCA (1 g/day for three weeks), or dexamethasone (12 mg/day for 1 week and placebo during weeks 2 and 3), or placebo for 3 weeks. Pruritus and biochemical markers of cholestasis were analyzed at inclusion and after 3 weeks of treatment. Fetal complications (spontaneous preterm delivery; asphyxial events; and meconium staining of amniotic fluid, placenta, and membranes) were registered at delivery. An intention-to-treat analysis showed significant reduction of alanine aminotransferase (ALT) (P = .01) and bilirubin (P = .002) in the UDCA group only. In a subgroup analysis of ICP women with serum bile acids > or =40 micromol/L at inclusion (n = 34), UDCA had significant effects on pruritus (-75%), bile acids (-79%), ALT (-80%), and bilirubin (-50%) as well, but not on fetal complication rates. Dexamethasone yielded no alleviation of pruritus or reduction of ALT and was less effective than UDCA at reducing bile acids and bilirubin. In conclusion, 3 weeks of UDCA treatment improved some biochemical markers of ICP irrespective of disease severity, whereas significant relief from pruritus and marked reduction of serum bile acids were only found in patients with severe ICP.     

A randomized, controlled trial of banding ligation plus drug therapy versus drug therapy alone in the prevention of esophageal variceal rebleeding

Background & Aims:  Both medications with beta-blockers and isosorbide-5-mononitrate and endoscopic variceal ligation have been proven plausible in the prevention of variceal rebleeding. However, the relative efficacy and safety of the combined treatment for preventing rebleeding remains unresolved.
Methods:  Patients with history of esophageal variceal bleeding were enrolled. Emergency ligation was performed in patients with acute variceal bleeding. After hemodynamic stability, eligible patients were randomized to either the Medication group, using nadolol plus isorsorbide-5-mononitrate, or the Combined group, receiving banding ligation in addition to medications. Patients in the two groups with rebleeding from esophageal varices were treated with band ligation. The end points were rebleeding from varices or death.
Results:  After a median follow up of 23 months, recurrent upper gastrointestinal bleeding developed in 51% in the Medication group and 38% in the Combined group ( P  = 0.21). Recurrent bleeding from esophageal varices occurred in 26 patients (43%) in the Medication group and in 16 patients (26%) in the Combined group ( P  = 0.07). Recurrent bleeding from gastroesophageal varices occurred in 48% of Medication group and 28% of Combined group ( P  = 0.05). The frequency of adverse effects and mortality rates were similar between both groups ( P  = 0.28).
Conclusions:  Combined ligation with medications was marginally more effective than medication alone in the prevention of gastroesophageal variceal rebleeding with similar adverse effects and mortality.     

TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis: a randomized controlled trial

Prevention of variceal rebleeding is mandatory in cirrhotic patients. We compared the efficacy, safety, and cost of transjugular intrahepatic portosystemic shunt (TIPS) versus pharmacologic therapy in preventing variceal rebleeding in patients with advanced cirrhosis. A total of 91 Child-Pugh class B/C cirrhotic patients surviving their first episode of variceal bleeding were randomized to receive TIPS (n = 47) or drug therapy (propranolol + isosorbide-5-mononitrate) (n = 44) to prevent variceal rebleeding. Mean follow-up was 15 months. Rebleeding occurred in 6 (13%) TIPS-treated patients versus 17 (39%) drug-treated patients (P =.007). The 2-year rebleeding probability was 13% versus 49% (P =.01). A similar number of reinterventions were required in the 2 groups; these were mainly angioplasty +/- restenting in the TIPS group (90 of 98) and endoscopic therapy for rebleeding in the medical group (45 of 62) (not significant). Encephalopathy was more frequent in TIPS than in drug-treated patients (38% vs. 14%, P =.007). Child-Pugh class improved more frequently in drug-treated than in TIPS-treated patients (72% vs. 45%; P =.04). The 2-year survival probability was identical (72%). The identified cost of therapy was double for TIPS-treated patients. In summary, medical therapy was less effective than TIPS in preventing rebleeding. However, it caused less encephalopathy, identical survival, and more frequent improvement in Child-Pugh class with lower costs than TIPS in high-risk cirrhotic patients. This suggests that TIPS should not be used as a first-line treatment, but as a rescue for failures of medical/endoscopic treatments (first-option therapies).     

The effects of drug therapy on radiographic progression of rheumatoid arthritis. results of a 36-week randomized trial comparing methotrexate and auranofin

Objective. To determine the effects of drug therapy (methotrexate [MTX] versus auranofin [AUR]) on radiographic progression in patients with active rheumatoid arthritis (RA). Methods. We conducted a 9-month randomized, multicenter, double-blind trial comparing MTX and AUR. Standardized radiographs of the hands and wrists were obtained at baseline and at completion of the study. Four experienced bone radiologists graded the radiographs for erosions, joint space narrowing, erosion healing, and reparative bone formation. Results. Two hundred eighty-one patients were enrolled in the study. Radiographs were available on 167 of the 183 who completed the trial. After 9 months of therapy, there was a significantly greater worsening of the erosion score in the AUR group (mean ± SEM change of 1.67 ± 0.4) compared with the change in the MTX group (0.60 ± 0.3) (P = 0.040). There was also a significantly greater worsening of the joint space narrowing score in the AUR group compared with the MTX group (1.36 ± 0.3 versus 0.42 ± 0.2) (P = 0.007). There was no difference demonstrated between groups in healing of erosions or in reparative bone formation. Conclusion. The rate of radiographic progression in patients with RA, as measured by erosion score and joint space narrowing score, was demonstrated to be lower in those treated with MTX, as compared with AUR, over a 36-week period.     

Cognitive-behavioral therapy for somatization disorder: a randomized controlled trial

BACKGROUND: Patients diagnosed as having somatization disorder (SD) who present with a lifetime history of multiple, medically unexplained physical symptoms represent a significant challenge to health care providers. To date, no psychotherapeutic or pharmacologic intervention has been found to produce clinically meaningful improvement in symptoms or functioning of patients with SD. We examined the efficacy of cognitive-behavioral therapy (CBT) for SD. METHODS: Eighty-four participants meeting criteria for SD were randomly assigned to 1 of 2 conditions: (1) standard medical care augmented by a psychiatric consultation intervention or (2) a 10-session, manualized, individually administered CBT regimen added to the psychiatric consultation intervention. Assessments were conducted at baseline and 3, 9, and 15 months after baseline. The primary outcome measure was the severity scale of the Clinical Global Impression Scale for Somatization Disorder (CGI-SD). Secondary outcome measures were responder status as determined by clinical ratings, self-reported measures of physical functioning and somatic symptoms, and health care utilization assessed via medical records. RESULTS: Fifteen months after baseline, somatization symptoms were significantly less severe in the group treated with CBT (0.84 points on the CGI-SD 7-point scale) (P<.001). Patients treated with CBT also were significantly more likely to be rated as either very much improved or much improved than patients treated with only augmented standard medical care (40% [n = 17] vs 5% [n = 2]). Cognitive-behavioral therapy was associated with greater improvements in self-reported functioning and somatic symptoms and a greater decrease in health care costs. CONCLUSION: For patients diagnosed as having SD, CBT may produce clinical benefits beyond those that result from the current state-of-the-art treatment.     

Primary prophylaxis of variceal hemorrhage: a randomized controlled trial comparing band ligation,propranolol, and isosorbide mononitrate

BACKGROUND & AIMS: This randomized controlled trial compared variceal band ligation (VBL), propranolol (PPL), and isosorbide-5-mononitrate (ISMN) in the prevention of first esophageal variceal bleed. METHODS: Over a 6-year period, 172 patients with cirrhosis, grade II or III esophageal varices that had never bled, were recruited; 44 into VBL, 66 into PPL, and 62 into ISMN. Baseline patient characteristics: age, 55 +/- 11 years; Child-Pugh score, 8 +/- 2; 65% alcohol-induced cirrhosis; follow-up period, 19.7 +/- 17.6 months (range, 0.13-72.1 months), were comparable in the 3 groups. RESULTS: On intention-to-treat analysis, variceal bleeding occurred in 7% of patients randomized to VBL, 14% to PPL, and 23% to ISMN. The 2-year actuarial risks for first variceal bleed were 6.2% (95% confidence interval [CI], 0.0%-15.0%) for VBL, 19.4% (95% CI, 0.1%-32.4%) for PPL, and 27.7% (95% CI, 14.2%-41.2%) for ISMN. A significant number of patients reported side effects with drug treatment (45% PPL and 42% ISMN vs. 2% VBL; P = 0.00), resulting in withdrawal from treatment in 30% of PPL and 21% of ISMN patients. There were no statistically significant differences in mortality rates in the 3 groups. In as-treated analysis, there was a statistically significant difference in actuarial risk for bleeding at 2 years between VBL and ISMN (7.5%, 95% CI, 2.5%-10.6% vs. 33.0%, 95% CI, 15%-49%, respectively, log rank test P = 0.03) but not between VBL and PPL. CONCLUSIONS: VBL was equivalent to PPL and superior to ISMN in preventing first variceal bleed. The side-effect profile for pharmacotherapy was considerable.