Showing papers on "Placebo published in 2003"
TL;DR: The reductions in major cardiovascular events with atorvastatin are large, given the short follow-up time, and may have implications for future lipid-lowering guidelines.
3,436 citations
TL;DR: The addition of adalimumab at a dosage of 20 mg, 40 mg, or 80 mg administered subcutaneously every other week to long-term MTX therapy in patients with active RA provided significant, rapid, and sustained improvement in disease activity over 24 weeks compared with MTX plus placebo.
Abstract: Objective
To evaluate the efficacy and safety of adalimumab (D2E7), a fully human monoclonal tumor necrosis factor α antibody, in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA) despite treatment with MTX.
Methods
In a 24-week, randomized, double-blind, placebo-controlled study, 271 patients with active RA were randomly assigned to receive injections of adalimumab (20 mg, 40 mg, or 80 mg subcutaneously) or placebo every other week while continuing to take their long-term stable dosage of MTX. The primary efficacy end point was the American College of Rheumatology criteria for 20% improvement (ACR20) at 24 weeks.
Results
An ACR20 response at week 24 was achieved by a significantly greater proportion of patients in the 20-mg, 40-mg, and 80-mg adalimumab plus MTX groups (47.8%, 67.2%, and 65.8%, respectively) than in the placebo plus MTX group (14.5%) (P < 0.001). ACR50 response rates with the 20-mg, 40-mg, and 80-mg adalimumab dosages (31.9%, 55.2%, and 42.5%, respectively) were significantly greater than that with placebo (8.1%) (P = 0.003, P < 0.001, and P < 0.001, respectively). The 40-mg and 80-mg doses of adalimumab were associated with an ACR70 response (26.9% and 19.2%, respectively) that was statistically significantly greater than that with placebo (4.8%) (P < 0.001 and P = 0.020). Responses were rapid, with the greatest proportion of adalimumab-treated patients achieving an ACR20 response at the first scheduled visit (week 1). Adalimumab was safe and well tolerated; comparable numbers of adalimumab-treated patients and placebo-treated patients reported adverse events.
Conclusion
The addition of adalimumab at a dosage of 20 mg, 40 mg, or 80 mg administered subcutaneously every other week to long-term MTX therapy in patients with active RA provided significant, rapid, and sustained improvement in disease activity over 24 weeks compared with MTX plus placebo.
1,813 citations
TL;DR: Fetal nigral transplantation currently cannot be recommended as a therapy for PD based on results, and Stratification based on disease severity showed a treatment effect in milder patients.
Abstract: Thirty-four patients with advanced Parkinson's disease participated in a prospective 24-month double-blind, placebo-controlled trial of fetal nigral transplantation. Patients were randomized to receive bilateral transplantation with one or four donors per side or a placebo procedure. The primary end point was change between baseline and final visits in motor component of the Unified Parkinson's Disease Rating Scale in the practically defined off state. There was no significant overall treatment effect (p = 0.244). Patients in the placebo and one-donor groups deteriorated by 9.4 +/- 4.25 and 3.5 +/- 4.23 points, respectively, whereas those in the four-donor group improved by 0.72 +/- 4.05 points. Pairwise comparisons were not significant, although the four-donor versus placebo groups yielded a p value of 0.096. Stratification based on disease severity showed a treatment effect in milder patients (p = 0.006). Striatal fluorodopa uptake was significantly increased after transplantation in both groups and robust survival of dopamine neurons was observed at postmortem examination. Fifty-six percent of transplanted patients developed dyskinesia that persisted after overnight withdrawal of dopaminergic medication ("off"-medication dyskinesia). Fetal nigral transplantation currently cannot be recommended as a therapy for PD based on these results.
1,417 citations
TL;DR: Short-term TNF&agr; antagonism with infliximab did not improve and high doses (10 mg/kg) adversely affected the clinical condition of patients with moderate-to-severe chronic heart failure.
Abstract: Background– Preclinical and preliminary clinical data have suggested that tumor necrosis factor-α (TNFα) may play a role in the evolution and progression of heart failure and that inhibition of TNFα may favorably modify the course of the disease. We evaluated the efficacy and safety of infliximab, a chimeric monoclonal antibody to TNFα, in patients with moderate-to-severe heart failure. Methods and Results– One hundred fifty patients with stable New York Heart Association class III or IV heart failure and left ventricular ejection fraction ≤35% were randomly assigned to receive placebo (n=49), infliximab 5 mg/kg (n=50), or infliximab 10 mg/kg (n=51) at 0, 2, and 6 weeks after randomization and were followed-up prospectively for 28 weeks. Neither dose of infliximab improved clinical status at 14 weeks, the primary endpoint of the study, despite suppression of inflammatory markers (C-reactive protein and interleukin-6) and a modest increase in ejection fraction in the patients receiving 5 mg/kg ( P =0.013). Furthermore, after 28 weeks, 13, 10, and 20 patients were hospitalized for any reason in the placebo, 5 mg/kg infliximab, and 10 mg/kg infliximab groups, respectively. The combined risk of death from any cause or hospitalization for heart failure through 28 weeks was increased in the patients randomized to 10 mg/kg infliximab (hazard ratio 2.84, 95% confidence interval 1.01 to 7.97; nominal P =0.043). Conclusions– Short-term TNFα antagonism with infliximab did not improve and high doses (10 mg/kg) adversely affected the clinical condition of patients with moderate-to-severe chronic heart failure.
1,404 citations
TL;DR: The results suggest that the preventive effect of lactobacillus GG on atopic eczema extends beyond infancy, and not just during the first 2 years of life.
1,345 citations
TL;DR: Etroetin beta corrects anaemia but does not improve cancer control or survival among patients with head and neck cancer and patients receiving curative cancer treatment and given erythropoietin should be studied in carefully controlled trials.
1,216 citations
TL;DR: In this article, a randomized, double-blind, parallel-group, placebo-controlled study with inhaled long-acting β 2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone.
1,184 citations
TL;DR: The treatment of psoriasis with etanercept led to a significant reduction in the severity of disease over a period of 24 weeks, paralleled by improvements in global assessments by physicians and the patients and in quality-of-life measures.
Abstract: Background Inflammatory cytokines such as tumor necrosis factor (TNF) have been implicated in the pathogenesis of psoriasis. We evaluated the safety and efficacy of etanercept, a TNF antagonist, for the treatment of plaque psoriasis. Methods In this 24-week, double-blind study, 672 patients underwent randomization and 652 either received placebo or received etanercept subcutaneously at a low dose (25 mg once weekly), a medium dose (25 mg twice weekly), or a high dose (50 mg twice weekly). After 12 weeks, patients in the placebo group began twice-weekly treatment with 25 mg of etanercept. The primary measure of clinical response was the psoriasis area-and-severity index. Results At week 12, there was an improvement from base line of 75 percent or more in the psoriasis area-and-severity index in 4 percent of the patients in the placebo group, as compared with 14 percent of those in the low-dose–etanercept group, 34 percent in the medium-dose–etanercept group, and 49 percent in the high-dose–etanercept group...
1,121 citations
TL;DR: Evidence for benefit from nicotine replacement therapy in hospital patients is inconclusive, although the results of a trial reported in this issue of Thorax give cause for optimism and should stimulate further studies.
Abstract: Evidence for benefit from nicotine replacement therapy in hospital patients is inconclusive, although the results of a trial reported in this issue of Thorax give cause for optimism and should stimulate further studies.
Most smokers become nicotine dependent and, when they stop smoking, experience withdrawal symptoms and craving. Nicotine replacement therapy (NRT) reduces these unpleasant symptoms and, theoretically, should decrease the risk of relapse. Smoking cessation is properly defined as validated sustained abstinence from cigarettes and/or other tobacco products for at least 6 months, but preferably for 1 year. This editorial includes evidence only from those studies which have applied such a definition and which have specified their settings and populations.
NRT is available as chewing gum, transdermal patches, sublingual tablets, lozenges, inhalation cartridges and nasal spray. In specialised cessation clinics1–8 and in primary care,9,10 prospective randomised clinical trials have shown that NRT, used as an adjunct to advice and support, results in better cessation rates than does advice and support alone. In the clinics success rates with NRT tend to be higher (11–30%) and more consistent than in primary care, where some studies have found no significant difference from placebo.11–14 One study in primary care showed 8% success with nicotine chewing gum compared with 4% with advice plus leaflet, but there was no placebo controlled arm.15 Two studies of transdermal nicotine in primary care have shown success rates of around 10%, which were superior to those with placebo (around 6%).9,10 The benefit for transdermal nicotine in cessation clinics6–8 and in primary care9,10 is thus clear, whereas nicotine chewing gum,1–5 inhaler,16,17 …
1,097 citations
TL;DR: Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms, a pattern which continued for the study duration.
Abstract: The large-scale Women's Health Initiative has confirmed that, in postmenopausal women, combined estrogen/ progestin therapy entails an increased risk of invasive breast cancer. The investigators have now explored this relationship in detail, characterizing the cancers that developed and seeking to learn whether hormonal effects on the mammogram can influence diagnosis. A total of 16,608 postmenopausal women 50 to 79 years of age, all with an intact uterus, were randomly assigned to receive active treatment (0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate daily in a single tablet) or placebo. The participants, seen at 40 clinical centers, were to be followed from 1993 to 1998 by annual clinical breast examinations and mammograms, but the trial was ended after a mean interval of 5.2 years. Intent-to-treat analyses demonstrated a hazard ratio of 1.24 for both total cancers and invasive cancers in women given hormone therapy compared with the placebo group. There was some suggestion of an increased risk for in situ breast cancer in hormone-treated women. An increased risk of breast cancer in treated women emerged after 3 years in those not receiving hormones previously and after 2 years in previously treated women. The findings were similar when women in specific risk categories were analyzed, and race and ethnicity were not significant factors. Invasive cancers associated with combined hormone therapy were larger than those in placebo recipients, more likely to be node-positive, and diagnosed when more advanced. There was, however, no difference in tumor grade or in the distribution of histologic types of breast cancer. After the first year, hormone-treated women more often had abnormal or highly suspicious mammograms than did those given placebo. In this prospective, randomized trial, combined estrogen/progestin treatment of postmenopausal women increased both breast cancer risk and the frequency of abnormal mammograms requiring medical assessment. In addition, cancers in treated women were more advanced when diagnosed than was the case for placebo recipients.
967 citations
TL;DR: The results of this study indicate that rofecoxib or low-dose naproxen does not slow cognitive decline in patients with mild-to-moderate AD.
Abstract: ContextLaboratory evidence that inflammatory mechanisms contribute to neuronal
injury in Alzheimer disease (AD), along with epidemiological evidence, suggests
that nonsteroidal anti-inflammatory drugs (NSAIDs) may favorably influence
the course of the disease.ObjectiveTo determine whether treatment with a selective cyclooxygenase (COX)
-2 inhibitor (rofecoxib) or a traditional nonselective NSAID (naproxen) slows
cognitive decline in patients with mild-to-moderate AD.DesignMulticenter, randomized, double-blind, placebo-controlled, parallel
group trial, with 1-year exposure to study medications.SettingForty ambulatory treatment centers affiliated with the Alzheimer's Disease
Cooperative Study consortium.ParticipantsParticipants with mild-to-moderate AD (Mini-Mental State Examination
score of 13-26) were recruited from December 1999 to November 2000 using clinic
populations, referrals from community physicians, and local advertising. Stable
use of cholinesterase inhibitors, estrogen, low-dose aspirin, and vitamin
E was allowed. Participants with inflammatory diseases that might respond
to the study medications were excluded. Of 474 participants screened, 351
were enrolled.InterventionsOnce-daily rofecoxib, 25 mg, or twice-daily naproxen sodium, 220 mg,
or placebo.Main Outcome MeasuresThe primary outcome measure was the 1-year change in the Alzheimer Disease
Assessment Scale-Cognitive (ADAS-Cog) subscale score. Secondary outcome measures
included the Clinical Dementia Rating scale sum-of-boxes, the Neuropsychiatric
Inventory, the Quality of Life-AD, and the time to attainment of significant
end points (4-point decline from baseline ADAS-Cog score, 1-step worsening
on the global Clinical Dementia Rating scale, 15-point decline on the ADCS
activities of daily living inventory, institutionalization, or death).ResultsThe 1-year mean (SD) change in ADAS-Cog scores in participants treated
with naproxen (5.8 [8.0]) or rofecoxib (7.6 [7.7]) was not significantly different
from the change in participants treated with placebo (5.7 [8.2]). Results
of secondary analyses showed no consistent benefit of either treatment. Fatigue,
dizziness, and hypertension were more commonly reported in the active drug
groups, and more serious adverse events were found in the active treatment
group than in the placebo group.ConclusionThe results of this study indicate that rofecoxib or low-dose naproxen
does not slow cognitive decline in patients with mild-to-moderate AD.
TL;DR: Among postmenopausal women aged 65 years or older, estrogen plus progestin did not improve cognitive function when compared with placebo, and timing of prior hormone therapy initiation with respect to the final menstrual period did not affect the results.
Abstract: ContextObservational studies have suggested that postmenopausal hormone treatment
may improve cognitive function, but data from randomized clinical trials have
been sparse and inconclusive The Women's Health Initiative Memory Study (WHIMS)
is an ancillary study of the Women's Health Initiative (WHI) hormone therapy
trials On July 8, 2002, the estrogen plus progestin therapy in the WHI trial
was discontinued because of certain increased health risks for womenObjectiveTo determine whether estrogen plus progestin therapy protects global
cognitive function in older postmenopausal womenDesign, Setting, and ParticipantsA randomized, double-blind, placebo-controlled clinical trial, WHIMS
is an ancillary study of geographically diverse, community-dwelling women
aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen
plus progestin trial that started in June 1995 Of 4894 eligible postmenopausal
women aged 65 years or older and free of probable dementia at baseline, 4532
(926%) were enrolled in the estrogen plus progestin component of WHIMS A
total of 4381 participants (967%) provided at least 1 valid cognitive function
score between June 1995 and July 8, 2002InterventionsParticipants received either 1 daily tablet containing 0625 mg of conjugated
equine estrogen with 25 mg of medroxyprogesterone acetate (n = 2145) or matching
placebo (n = 2236)Main Outcome MeasureGlobal cognitive function measured annually with the Modified Mini-Mental
State ExaminationResultsThe Modified Mini-Mental State Examination mean total scores in both
groups increased slightly over time (mean follow-up of 42 years) Women in
the estrogen plus progestin group had smaller average increases in total scores
compared with women receiving placebo (P = 03),
but these differences were not clinically important Removing women by censoring
them after adjudicated dementia, mild cognitive impairment, or stroke, and
nonadherence to study protocol, did not alter the findings Prior hormone
therapy use and duration of prior use did not affect the interpretation of
the results, nor did timing of prior hormone therapy initiation with respect
to the final menstrual period More women in the estrogen plus progestin group
had a substantial and clinically important decline (≥2 SDs) in Modified
Mini-Mental State Examination total score (67%) compared with the placebo
group (48%) (P = 008)ConclusionsAmong postmenopausal women aged 65 years or older, estrogen plus progestin
did not improve cognitive function when compared with placebo While most
women receiving estrogen plus progestin did not experience clinically relevant
adverse effects on cognition compared with placebo, a small increased risk
of clinically meaningful cognitive decline occurred in the estrogen plus progestin
group
TL;DR: Azithromycin treatment was associated with improvement in clinically relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa.
Abstract: ContextTreatment strategies for cystic fibrosis (CF) lung disease include antibiotics,
mucolytics, and anti-inflammatory therapies. Increasing evidence suggests
that macrolide antibiotics might be beneficial in patients with CF.ObjectiveTo determine if an association between azithromycin use and pulmonary
function exists in patients with CF.Design and SettingA multicenter, randomized, double-blind, placebo-controlled trial conducted
from December 15, 2000, to May 2, 2002, at 23 CF care centers in the United
States.ParticipantsOf the 251 screened participants with a diagnosis of CF, 185 (74%) were
randomized. Eligibility criteria included age 6 years or older, infection
with Pseudomonas aeruginosa for 1 or more years,
and a forced expiratory volume in 1 second (FEV1) of 30% or more.
Participants were stratified by FEV1 (≥60% predicted vs <60%
predicted), weight of less than 40 kg vs 40 kg or more, and CF center.InterventionThe active group (n = 87) received 250 mg (weight <40 kg) or 500
mg (weight ≥40 kg) of oral azithromycin 3 days a week for 168 days; placebo
group (n = 98) received identically packaged tablets.Main Outcome MeasuresChange in FEV1 from day 0 to completion of therapy at day
168 and determination of safety. Secondary outcomes included pulmonary exacerbations
and weight gain.ResultsThe azithromycin group had a mean 0.097-L (SD, 0.26) increase in FEV1 at day 168 compared with 0.003 L (SD, 0.23) in the placebo group (mean
difference, 0.094 L; 95% confidence interval [CI], 0.023-0.165; P = .009). Nausea occurred in 17% more participatns in the azithromycin
group (P = .01), diarrhea in 15% more (P = .009), and wheezing in 13% more (P = .007).
Participants in the azithromycin group had less risk of experiencing an exacerbation
than participants in the placebo group (hazard ratio, 0.65; 95% CI, 0.44-0.95; P = .03) and weighed at the end of the study an average
0.7 kg more than participants receiving placebo (95% CI, 0.1-1.4 kg; P = .02).ConclusionAzithromycin treatment was associated with improvement in clinically
relevant end points and should be considered for patients with CF who are
6 years or older and chronically infected with P aeruginosa.
TL;DR: A role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease is suggested and all treatments were well tolerated.
Abstract: The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).
In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/formoterol (Symbicort®) 160/4.5 µg (delivered dose), budesonide 200 µg (metered dose), formoterol 4.5 µg or placebo. Severe exacerbations and FEV1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever β2‐agonist and safety variables were recorded.
Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever β2‐agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated.
These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease.
This study was supported by AstraZeneca.
TL;DR: Olanzapine is more effective than placebo, and combined olanzapine-fluoxetine isMore effective than olanZapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms.
Abstract: Background Despite the longer duration of the depressive phase in bipolar disorder and the frequent clinical use of antidepressants combined with antipsychotics or mood stabilizers, relatively few controlled studies have examined treatment strategies for bipolar depression. Objective To examine the use of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Design Double-blind, 8-week, randomized controlled trial. Setting Eighty-four sites (inpatient and outpatient) in 13 countries. Patients A total of 833 randomized adults with bipolar I depression with a Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 20. Intervention Patients were randomly assigned to receive placebo (n = 377); olanzapine, 5 to 20 mg/d (n = 370); or olanzapine-fluoxetine combination, 6 and 25, 6 and 50, or 12 and 50 mg/d (n = 86). Main Outcome Measure Changes in MADRS total scores using mixed-effects model repeated-measures analyses. Results During all 8 study weeks, the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs the placebo group ( P Conclusions Olanzapine is more effective than placebo, and combined olanzapine-fluoxetine is more effective than olanzapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms.
TL;DR: Treatment of postherpetic neuralgia with pregabalin is safe, efficacious in relieving pain and sleep interference, and associated with greater global improvement than treatment with placebo.
Abstract: Objective: To evaluate the efficacy and safety of pregabalin in the treatment of postherpetic neuralgia (PHN). Methods: The authors conducted a multicenter, parallel-group, double-blind, placebo-controlled, 8-week, randomized clinical trial in PHN, defined as pain for 3 or more months following herpes zoster rash healing. Patients (n = 173) were randomized to treatment with pregabalin or placebo. Patients randomized to pregabalin received either 600 mg/day (creatinine clearance > 60 mL/min) or 300 mg/day (creatinine clearance 30 to 60 mL/min). The primary efficacy measure was the mean of the last seven daily pain ratings. Secondary endpoints included additional pain ratings, sleep interference, quality of life, mood, and patient and clinician ratings of global improvement. Results: Pregabalin-treated patients had greater decreases in pain than patients treated with placebo (endpoint mean scores 3.60 vs 5.29, p = 0.0001). Pain was significantly reduced in the pregabalin-treated patients after the first full day of treatment and throughout the study, and significant improvement on the McGill Pain Questionnaire total, sensory, and affective pain scores was also found. The proportions of patients with ≥30% and ≥50% decreases in mean pain scores were greater in the pregabalin than in the placebo group (63% vs 25% and 50% vs 20%, p = 0.001). Sleep also improved in patients treated with pregabalin compared to placebo ( p = 0.0001). Both patients and clinicians were more likely to report global improvement with pregabalin than placebo ( p = 0.001). Given the maximal dosage studied, pregabalin had acceptable tolerability compared to placebo despite a greater incidence of side effects, which were generally mild to moderate in intensity. Conclusions: Treatment of PHN with pregabalin is safe, efficacious in relieving pain and sleep interference, and associated with greater global improvement than treatment with placebo.
TL;DR: Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity in a high-risk population.
TL;DR: Treatment with cannabinoids did not have a beneficial effect on spasticity when assessed with the Ashworth scale, but objective improvement in mobility and patients' opinion of an improvement in pain suggest cannabinoids might be clinically useful.
TL;DR: Long-term, once-daily treatment with low-dose budesonide decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset.
TL;DR: The effects of opposing verbal suggestions on experimental ischemic arm pain in healthy volunteers and on motor performance in Parkinsonian patients are analyzed and found that verbally induced expectations of analgesia/hyperalgesia and motor improvement/worsening antagonized completely the effects of a conditioning procedure.
Abstract: The placebo and nocebo effect is believed to be mediated by both cognitive and conditioning mechanisms, although little is known about their role in different circumstances. In this study, we first analyzed the effects of opposing verbal suggestions on experimental ischemic arm pain in healthy volunteers and on motor performance in Parkinsonian patients and found that verbally induced expectations of analgesia/hyperalgesia and motor improvement/worsening antagonized completely the effects of a conditioning procedure. We also measured the effects of opposing verbal suggestions on hormonal secretion and found that verbally induced expectations of increase/decrease of growth hormone (GH) and cortisol did not have any effect on the secretion of these hormones. However, if a preconditioning was performed with sumatriptan, a 5-HT1B/1D agonist that stimulates GH and inhibits cortisol secretion, a significant increase of GH and decrease of cortisol plasma concentrations were found after placebo administration, although opposite verbal suggestions were given. These findings indicate that verbally induced expectations have no effect on hormonal secretion, whereas they affect pain and motor performance. This suggests that placebo responses are mediated by conditioning when unconscious physiological functions such as hormonal secretion are involved, whereas they are mediated by expectation when conscious physiological processes such as pain and motor performance come into play, even though a conditioning procedure is performed.
TL;DR: It is shown that teriparatide treatment results in an increase in bone mineral density and is a potentially useful therapy for osteoporosis in men.
Abstract: Teriparatide [rhPTH(1-34)] increases bone mineral density and reduces the risk of vertebral fracture in women. We randomized 437 men with spine or hip bone mineral density more than 2 SD below the young adult male mean to daily injections of placebo, teriparatide 20 microg, or teriparatide 40 microg. All subjects also received supplemental calcium and vitamin D. The study was stopped after a median duration of 11 months because of a finding of osteosarcomas in rats in routine toxicology studies. Biochemical markers of bone formation increased early in the course of therapy and were followed by increases in indices of osteoclastic activity. Spine bone mineral density was greater than in placebo subjects after 3 months of teriparatide therapy, and by the end of therapy it was increased by 5.9% (20 microg) and 9.0% (40 microg) above baseline (p < 0.001 vs. placebo for both comparisons). Femoral neck bone mineral density increased 1.5% (20 microg; p = 0.029) and 2.9% (40 microg; p < 0.001), and whole body bone mineral content increased 0.6% (20 microg; p = 0.021) and 0.9% (40 microg;p = 0.005) above baseline in the teriparatide subjects. There was no change in radial bone mineral density in the teriparatide groups. Bone mineral density responses to teriparatide were similar regardless of gonadal status, age, baseline bone mineral density, body mass index, smoking, or alcohol intake. Subjects experienced expected changes in mineral metabolism. Adverse events were similar in the placebo and 20-microg groups, but more frequent in the 40-microg group. This study shows that teriparatide treatment results in an increase in bone mineral density and is a potentially useful therapy for osteoporosis in men.
TL;DR: Topiramate (up to 300 mg per day) is more efficacious than placebo as an adjunct to standardised medication compliance management in treatment of alcohol dependence.
TL;DR: It is demonstrated that higher SDCs were associated with increased mortality and suggested that the effectiveness of digoxin therapy in men with heart failure and a left ventricular ejection fraction of 45% or less may be optimized in the SDC range of 0.5 to 0.8 ng/mL.
Abstract: ContextThe Digitalis Investigation Group (DIG) trial reported that digoxin
provided no overall mortality benefit and only a modest reduction in hospitalizations
among patients with heart failure and depressed left ventricular systolic
function. The clinical outcomes associated with digoxin therapy at different
serum concentrations in the DIG trial have not been assessed.ObjectiveTo assess variations in serum digoxin concentration (SDC) and their
association with mortality and hospitalization in patients with heart failure.Design, Setting, and PatientsPost hoc analysis of the randomized, double-blinded, placebo-controlled
DIG trial, conducted from August 1991 to December 1995, with the main analysis
restricted to men with a left ventricular ejection fraction of 45% or less
(n = 3782). Patients randomly assigned to receive digoxin were divided into
3 groups based on SDC at 1 month (0.5-0.8 ng/mL, n = 572; 0.9-1.1 ng/mL, n
= 322; and ≥1.2 ng/mL, n = 277) and compared with patients randomly assigned
to receive placebo (n = 2611).Main Outcome MeasureAll-cause mortality at a mean follow-up of 37 months.ResultsHigher SDCs were associated with increased crude all-cause mortality
rates (0.5-0.8 ng/mL, 29.9%; 0.9-1.1 ng/mL, 38.8%; and ≥1.2 ng/mL, 48.0%; P = .006 for trend). Patients with SDCs of 0.5 to 0.8 ng/mL
had a 6.3% (95% confidence interval [CI], 2.1%-10.5%) lower mortality rate
compared with patients receiving placebo. Digoxin was not associated with
a reduction in mortality among patients with SDCs of 0.9 to 1.1 ng/mL (2.6%
increase; 95% CI, − 3.0% to 8.3%), whereas patients with SDCs of 1.2
ng/mL and higher had an 11.8% (95% CI, 5.7%-18.0%) higher absolute mortality
rate than patients receiving placebo. The association between SDC and mortality
persisted after multivariable adjustment (SDC 0.5-0.8 ng/mL hazard ratio [HR]
0.80, 95% CI, 0.68-0.94; SDC 0.9-1.1 ng/mL HR 0.89, 95% CI, 0.74-1.08; SDC
≥1.2 ng/mL HR 1.16, 95% CI, 0.96-1.39; and HR of 1.00 [referent] for placebo).ConclusionsOur findings demonstrate that higher SDCs were associated with increased
mortality and suggest that the effectiveness of digoxin therapy in men with
heart failure and a left ventricular ejection fraction of 45% or less may
be optimized in the SDC range of 0.5 to 0.8 ng/mL.
TL;DR: Both lamotrigine and lithium were superior to placebo for the prevention of relapse or recurrence of mood episodes in patients with bipolar I disorder who had recently experienced a manic or hypomanic episode.
Abstract: Background Lamotrigine has been shown to be an effective treatment for bipolar depression and rapid cycling in placebo-controlled clinical trials. This double-blind, placebo-controlled study was conducted to assess the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of relapse or recurrence of mood episodes in recently manic or hypomanic patients with bipolar I disorder. Methods After an 8- to 16-week open-label phase during which treatment with lamotrigine was initiated and other psychotropic drug regimens were discontinued, patients were randomized to lamotrigine (100-400 mg daily), lithium (0.8-1.1 mEq/L), or placebo as double-blind maintenance treatment for as long as 18 months. Results Of 349 patients who met screening criteria and entered the open-label phase, 175 met stabilization criteria and were randomized to double-blind maintenance treatment (lamotrigine, 59 patients; lithium, 46 patients; and placebo, 70 patients). Both lamotrigine and lithium were superior to placebo at prolonging the time to intervention for any mood episode (lamotrigine vs placebo, P = .02; lithium vs placebo, P = .006). Lamotrigine was superior to placebo at prolonging the time to a depressive episode ( P = .02). Lithium was superior to placebo at prolonging the time to a manic, hypomanic, or mixed episode( P =.006). The most common adverse event reported for lamotrigine was headache. Conclusions Both lamotrigine and lithium were superior to placebo for the prevention of relapse or recurrence of mood episodes in patients with bipolar I disorder who had recently experienced a manic or hypomanic episode. The results indicate that lamotrigine is an effective, well-tolerated maintenance treatment for bipolar disorder, particularly for prophylaxis of depression.
TL;DR: Lamotrigine and lithium were superior to placebo for the prevention of mood episodes in bipolar I patients, with lamot Rigine predominantly effective against depression and lithium predominantly effectiveagainst mania.
Abstract: Background The anticonvulsant lamotrigine was previously shown to be effective for bipolar depression. This study assessed the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of mood episodes in bipolar disorder. Method During an 8- to 16-week open-label phase, lamotrigine (titrated to 200 mg/day) was added to current therapy for currently or recently depressed DSM-IV-defined bipolar I outpatients (N = 966) and concomitant drugs were gradually withdrawn. Patients stabilized on open-label treatment (N = 463) were then randomly assigned to lamotrigine (50, 200, or 400 mg/day; N = 221), lithium (0.8-1.1 mEq/L; N = 121), or placebo (N = 121) monotherapy for up to 18 months. The primary outcome measure was time from randomization to intervention (addition of pharmacotherapy) for any mood episode (depressive, manic, hypomanic, or mixed). Data were gathered from September 1997 to August 2001. Results Time to intervention for any mood episode was statistically superior (p = .029) for both lamotrigine and lithium compared with placebo-median survival times were 200, 170, and 93 days, respectively. Intervention for depression was more frequent than for mania by a factor of nearly 3:1. Lamotrigine was statistically superior to placebo at prolonging the time to intervention for a depressive episode (p = .047). The proportions of patients who were intervention-free for depression at 1 year were lamotrigine 57%, lithium 46%, and placebo 45%. Lithium was statistically superior to placebo at prolonging the time to intervention for a manic or hypomanic episode (p = .026). The proportions of patients who were intervention-free for mania at 1 year were lamotrigine 77%, lithium 86%, and placebo 72%. Headache was the most frequent adverse event for all 3 treatment groups. Conclusion Lamotrigine and lithium were superior to placebo for the prevention of mood episodes in bipolar I patients, with lamotrigine predominantly effective against depression and lithium predominantly effective against mania.
TL;DR: In this article, the effectiveness and safety of fluoride toothpastes in the prevention of dental caries in children was evaluated in randomized or quasi-randomized controlled trials with blind outcome assessment.
Abstract: BACKGROUND: Fluoride toothpastes have been widely used for over three decades and remain a benchmark intervention for the prevention of dental caries OBJECTIVES: To determine the effectiveness and safety of fluoride toothpastes in the prevention of caries in children and to examine factors potentially modifying their effect SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (May 2000), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2000), MEDLINE (1966 to January 2000), plus several other databases We handsearched journals, reference lists of articles and contacted selected authors and manufacturers SELECTION CRITERIA: Randomized or quasi-randomized controlled trials with blind outcome assessment, comparing fluoride toothpaste with placebo in children up to 16 years during at least one year The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS) DATA COLLECTION AND ANALYSIS: Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party Authors were contacted for missing data The primary measure of effect was the prevented fraction (PF) that is the difference in caries increments between the treatment and control groups expressed as a percentage of the increment in the control group Random effects meta-analyses were performed where data could be pooled Potential sources of heterogeneity were examined in random effects meta-regression analyses MAIN RESULTS: Seventy-four studies were included For the 70 that contributed data for meta-analysis (involving 42,300 children) the D(M)FS pooled PF was 24% (95% confidence interval (CI), 21 to 28%; p<00001) This means that 16 children need to brush with a fluoride toothpaste (rather than a non-fluoride toothpaste) over three years to prevent one D(M)FS in populations with caries increment of 26 D(M)FS per year In populations with caries increment of 11 D(M)FS per year, 37 children will need to use a fluoride toothpaste for three years to avoid one D(M)FS There was clear heterogeneity, confirmed statistically (p<00001) The effect of fluoride toothpaste increased with higher baseline levels of D(M)FS, higher fluoride concentration, higher frequency of use, and supervised brushing, but was not influenced by exposure to water fluoridation There is little information concerning the deciduous dentition or adverse effects (fluorosis) REVIEWER'S CONCLUSIONS: Supported by more than half a century of research, the benefits of fluoride toothpastes are firmly established Taken together, the trials are of relatively high quality, and provide clear evidence that fluoride toothpastes are efficacious in preventing caries
TL;DR: In this article, the clinical efficacy and safety of cognitive-behavioral therapy (CBT) against education (EDU) and desipramine (DES) against placebo (PLA) in female patients with moderate to severe functional bowel disorders (irritable bowel syndrome, functional abdominal pain, painful constipation, and unspecified FBD).
TL;DR: Atomoxetine appears to be an efficacious treatment for adult ADHD, and its lack of abuse potential may be an advantage for many patients.
TL;DR: It is demonstrated that brief periods (<20 minutes) of a low‐level vibration applied during quiet standing can effectively inhibit bone loss in the spine and femur, with efficacy increasing significantly with greater compliance, particularly in those subjects with lower body mass.
Abstract: A 1-year prospective, randomized, double-blind, and placebo-controlled trial of 70 postmenopausal women demonstrated that brief periods (<20 minutes) of a low-level (0.2g, 30 Hz) vibration applied during quiet standing can effectively inhibit bone loss in the spine and femur, with efficacy increasing significantly with greater compliance, particularly in those subjects with lower body mass.
Introduction: Indicative of the anabolic potential of mechanical stimuli, animal models have demonstrated that short periods (<30 minutes) of low-magnitude vibration (<0.3g), applied at a relatively high frequency (20–90 Hz), will increase the number and width of trabeculae, as well as enhance stiffness and strength of cancellous bone. Here, a 1-year prospective, randomized, double-blind, and placebo-controlled clinical trial in 70 women, 3–8 years past the menopause, examined the ability of such high-frequency, low-magnitude mechanical signals to inhibit bone loss in the human.
Materials and Methods: Each day, one-half of the subjects were exposed to short-duration (two 10-minute treatments/day), low-magnitude (2.0 m/s2 peak to peak), 30-Hz vertical accelerations (vibration), whereas the other half stood for the same duration on placebo devices. DXA was used to measure BMD at the spine, hip, and distal radius at baseline, and 3, 6, and 12 months. Fifty-six women completed the 1-year treatment.
Results and Conclusions: The detection threshold of the study design failed to show any changes in bone density using an intention-to-treat analysis for either the placebo or treatment group. Regression analysis on the a priori study group demonstrated a significant effect of compliance on efficacy of the intervention, particularly at the lumbar spine (p = 0.004). Posthoc testing was used to assist in identifying various subgroups that may have benefited from this treatment modality. Evaluating those in the highest quartile of compliance (86% compliant), placebo subjects lost 2.13% in the femoral neck over 1 year, whereas treatment was associated with a gain of 0.04%, reflecting a 2.17% relative benefit of treatment (p = 0.06). In the spine, the 1.6% decrease observed over 1 year in the placebo group was reduced to a 0.10% loss in the active group, indicating a 1.5% relative benefit of treatment (p = 0.09). Considering the interdependence of weight, the spine of lighter women (<65 kg), who were in the highest quartile of compliance, exhibited a relative benefit of active treatment of 3.35% greater BMD over 1 year (p = 0.009); for the mean compliance group, a 2.73% relative benefit in BMD was found (p = 0.02). These preliminary results indicate the potential for a noninvasive, mechanically mediated intervention for osteoporosis. This non-pharmacologic approach represents a physiologically based means of inhibiting the decline in BMD that follows menopause, perhaps most effectively in the spine of lighter women who are in the greatest need of intervention.
TL;DR: Aripiprazole (20 and 30 mg/d) and risperidone (6 mg/D) were significantly better than placebo on all efficacy measures as mentioned in this paper.
Abstract: Background: Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors. This multicenter trial examined the efficacy, safety, and tolerability of aripiprazole in patients with acute exacerbation of schizophrenia or schizoaffective disorder. Methods: In this 4-week double-blind study, 404 patients were randomized to 20 mg/d (n=101) or 30 mg/d (n=101)ofaripiprazole,placebo(n=103),or6mg/dofrisperidone (n=99). Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores and ClinicalGlobalImpressionscores.Safetyandtolerabilityevaluations included extrapyramidal symptoms and effects on weight, prolactin, and corrected QT (QTc) interval. Results: Aripiprazole (20 and 30 mg/d) and risperidone (6 mg/d) were significantly better than placebo on all efficacy measures. Separation from placebo occurred at week 1 for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole. There were no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales. Meanprolactinlevelsdecreasedwitharipiprazolebutsignificantlyincreased5-foldwithrisperidone.Meanchange in QTc interval did not differ significantly from placebo with any active treatment group. Aripiprazole and risperidone groups showed a similar lowincidence of clinically significant weight gain. Conclusions: Aripiprazole is effective, safe, and well toleratedforthepositiveandnegativesymptomsinschizophreniaandschizoaffectivedisorder.Itisthefirstnon-D2receptorantagonistwithclearantipsychoticeffectsandrepresents a novel treatment development for psychotic disorders. Arch Gen Psychiatry. 2003;60:681-690