Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PLACEBOS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,261 records · Page 70Linked to original sources
PubMed2002

Noninvasive ventilation for acute respiratory failure: a prospective randomised placebo-controlled trial.

The aim of the present study was to clarify whether the known effects of noninvasive positive-pressure ventilation (NPPV) in patients with respiratory failure are real or due to placebo effects and whether early application of NPPV in the emergency department leads to rapid improvement of the patients condition and outcome. A prospective randomised placebo-controlled study was conducted in 20 patients with severe acute respiratory failure (ARF) secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute pulmonary oedema, not improving under conventional medical therapy and on the edge of intubation. Patients received either conventional medical therapy plus two-level NPPV (hi-level NPPV) or conventional medical therapy plus "placebo" NPPV. The main outcome measures involved the need for endotracheal intubation in the bi-level NPPV arm and in the placebo arm after crossing over to active NPPV. Morbidity, length of stay, mortality and the effect of the ventilatory mode on clinical, arterial-blood gas parameters, and the sternocleidomastoid muscles electromyogram (EMG) activity were also measured. The 10 patients in the active NPPV group rapidly improved and none needed intubation. Placebo NPPV resulted in no change in the clinical condition of patients that continued to worsen and the 10 patients were crossed over to active NPPV. Three patients were intubated. No differences in terms of morbidity, length of stay or mortality between the two groups were observed. Active NPPV (but not placebo NPPV) led to a rapid and significant improvement in the clinical parameters, pH and the carbon dioxide tension in arterial blood and to a decrease in respiratory frequency and sternocleidomastoid EMG activity. Early application of bi-level noninvasive positive-pressure ventilation in patients with severe acute respiratory failure, due to chronic obstructive pulmonary disease and acute pulmonary oedema, leads to a rapid improvement in clinical status and blood gases. Noninvasive positive-pressure ventilation had no placebo effect.

Acute Disease↗
PubMed2002

Effects of formoterol and ipratropium bromide in COPD: a 3-month placebo-controlled study.

The aim of this study was to compare the effects of formoterol, ipratropium bromide and a placebo on walking distance, lung function, symptoms and quality of life (QoL) in chronic obstructive pulmonary disease (COPD) patients. A total of 183 patients (mean age 64 yrs, 86 female) with moderate-to-severe nonreversible COPD participated in this randomised, double-blind, parallel-group study. After a 2-week placebo run-in, patients were randomised to formoterol Turbuhaler 18 microg b.i.d. (delivered dose), ipratropium bromide 80 microg t.i.d. via a pressurised metered dose inhaler, or placebo for 12 weeks. Inhaled short-acting beta2-agonists were allowed as relief medication and inhaled glucocorticosteroids were allowed at a constant dose. The primary variable was walking distance in the shuttle walking test (SWT). Baseline mean SWT distance was 325 m, mean forced expiratory volume in one second (FEV1) was 40% predicted. Clinically significant improvements in SWT (>30 m) were seen in 41, 38 and 30% of formoterol, ipratropium and placebo patients, respectively (not significant). Mean increases from run-in were 19, 17 and 5 m in the formoterol, ipratropium and placebo groups, respectively. Both active treatments significantly improved FEV1, forced vital capacity, peak expiratory flow and daytime dyspnoea score compared with placebo. Formoterol reduced relief medication use compared with placebo. Neither active treatment improved QoL. Formoterol and ipratropium improved airway function and symptoms, without significant improvements in the shuttle walking test.

Adrenergic beta-Agonists↗
PubMed2004

Efficacy of quetiapine for the treatment of schizophrenia: a combined analysis of three placebo-controlled trials.

OBJECTIVE: To determine the effectiveness of quetiapine (Seroquel) against specific aspects of schizophrenic symptomatology. RESEARCH DESIGN AND METHODS: Combined data from three placebo-controlled, double-blind, randomised trials that had previously demonstrated quetiapine's overall clinical effectiveness and tolerability were analysed. Efficacy assessments evaluated were the Clinical Global Impression (CGI) Severity of Illness score, Brief Psychiatric Rating Scale (BPRS) factors I-V, BPRS positive symptom cluster score and 18 individual BPRS items. The Simpson-Angus Scale (SAS), the Abnormal Involuntary Movements Scale (AIMS), changes in weight and prolactin concentrations and the recording of adverse events comprised the main tolerability measures. RESULTS: Efficacy assessments were available for a total of 426 quetiapine patients (mean age 36.9 years) with a DSM-IIIR diagnosis of schizophrenia; 502 patients were included in the tolerability analyses. The mean quetiapine dose was 300.5 mg/day with a mean maximum dose of 686.0 mg/day. Quetiapine was efficacious across a broad range of symptoms, including depression, anxiety and hostility. Significant improvements compared with placebo were noted for CGI Severity of Illness (p < 0.001) and in 14 of the 18 individual BPRS items (p < 0.001). Positive symptoms also improved (p < 0.01 at Week 2 and p < 0.001 from Week 3); greater improvements were observed in patients who received at least 400 mg/day quetiapine. Quetiapine was generally well tolerated: 4.0% of patients withdrew from treatment due to adverse events compared with 3.0% of placebo patients. Akathisia occurred in 2.0% and 2.5% of quetiapine and placebo patients, respectively. Similar decreases in prolactin levels for quetiapine (-10.0 microg/L) and placebo (-10.9 microg/L) were noted from baseline to end of treatment. Agitation and headache, the most common adverse events, were comparable in the quetiapine and placebo groups (agitation: 19.3% vs. 20.3%, respectively; headache: 19.1% vs. 17.3%, respectively). CONCLUSIONS: The results of this combined analysis confirm the individual findings of the three pivotal studies to demonstrate that quetiapine is effective across several domains of schizophrenia, improving positive, negative and depressive symptoms and reducing agitation, aggression and hostility. Similarly, the analysis reiterated the good tolerability profile of quetiapine, particularly in terms of its placebo-like effects on prolactin levels and incidence of extrapyramidal symptoms (EPS).

Adolescent↗
PubMed2004

Randomized, placebo-controlled comparison of early use of frovatriptan in a migraine attack versus dosing after the headache has become moderate or severe.

OBJECTIVE: To evaluate whether frovatriptan would provide greater relief if given early during a migraine attack. RESEARCH DESIGN AND METHODS: Adults with a history of migraine of at least 1 year, and who had 2-8 headaches in the previous month were recruited from 19 US centres for a prospective, placebo-controlled crossover study over 2 migraine attacks. Dose 1 was taken at the onset of mild migraine headache, Dose 2 was taken at least 2 h later if the headache progressed to moderate/severe. Patients were randomized to receive Dose 1 frovatriptan then Dose 2 placebo or Dose 1 placebo followed by Dose 2 frovatriptan. Treatment order was reversed for the second attack. This schedule enabled a comparison of frovatriptan with placebo and a comparison of early and later treatment with frovatriptan. MAIN OUTCOME MEASURES: Freedom from pain at 2 h for frovatriptan versus placebo as Dose 1; use of Dose 2 and/or rescue medication, pain severity, functional impairment and headache recurrence. RESULTS: In 241 patients who each treated 2 migraine attacks, Dose 1 frovatriptan was more effective than placebo in terms of the proportion of patients who were pain free at 2 h (28% vs 20%, p = 0.04). This benefit was sustained up to 4 h post-dose (p = 0.003). Early use of frovatriptan significantly reduced re-medication (p < 0.001). Twenty-four-hour headache recurrence was low in both early (4%) and later use (6%) groups. Sustained pain-free response occurred in 40% of frovatriptan early use patients compared with 31% of later use patients (p < 0.05). Early use prevented headache progression: 69%-78% had mild/no headache 2-4 h after Dose 1 frovatriptan compared with 54%-63% taking Dose 1 placebo (p < 0.001). Early use reduced pain burden and functional disability (p < or = 0.001). More patients rated early use of frovatriptan as excellent or good (57% vs 46%). CONCLUSIONS: Early use of frovatriptan resulted in a higher, earlier and sustained pain-free response, prevented progression to moderate/severe headache and reduced pain burden and functional disability.

Adult↗
PubMed1995

Effect of low-dose prophylactic dopamine on high-dose cisplatin-induced electrolyte wasting, ototoxicity, and epidermal growth factor excretion: a randomized, placebo-controlled, double-blind trial.

PURPOSE: To evaluate the protective effect of low-dose dopamine given as continuous infusion in patients who undergo chemotherapy with the nephrotoxin cisplatin. PATIENTS AND METHODS: Forty-two patients who received high-dose cisplatin-containing chemotherapy entered a prospective, randomized, double-blind, placebo-controlled trial. Twenty-one patients received dopamine, and 21 received placebo. Patients were to receive either infusional dopamine 2 micrograms/kg/min over 48 hours or placebo. Cisplatin 125 mg/m2 was administered 12 hours after initiating dopamine (group D) or placebo (group P). This schedule was repeated twice, 1 week apart. Measurements of serum creatinine, urinary electrolytes and creatinine, urinary excretion of epidermal growth factor (EGF), ototoxicity, parameters of hematopoietic recovery, and duration of hospitalization were analyzed. RESULTS: We observed an increase in serum creatinine level to a peak of 1.9 mg/dL (range, 0.8 to 7.8) in the dopamine group, in comparison to 1.4 mg/dL (range, 0.9 to 3.3) in the placebo group (P = .04). Urinary magnesium excretion increased and EGF excretion decreased in both groups. Urinary sodium, chloride, and potassium excretion were increased in both groups, but more so in the placebo group. Dopamine had no measurable effect on hearing loss, duration of hospitalization, or hematopoietic recovery. CONCLUSION: The use of prophylactic dopamine increased peak serum creatinine levels relative to placebo and failed to prevent cisplatin-induced renal toxicity or ototoxicity. Determination of whether dopamine could reverse chemotherapy-induced renal damage would require a randomized prospective trial.

Adult↗
PubMed1996

Randomized double-blind prospective trial to evaluate the effects of sargramostim versus placebo in a moderate-dose fluorouracil, doxorubicin, and cyclophosphamide adjuvant chemotherapy program for stage II and III breast cancer.

PURPOSE: To determine the effects of sargramostim (recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) on the incidence, duration, and complications of myelosuppression after moderate-dose fluorouracil, doxorubicin, cyclophosphamide (FAC) adjuvant chemotherapy in patients with node-positive breast cancer. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled study, 142 women with stage II and III breast cancer were to receive four 21-day cycles of chemotherapy that consisted of fluorouracil 600 mg/ m2 intravenously (IV), doxorubicin 60 mg/m2 IV, and cyclophosphamide 750 mg/m2 IV on day 1, followed by placebo or GM-CSF 250 micrograms/m2/d daily subcutaneously (SC) on days 3 through 15. All patients received prophylactic ciprofloxacin by mouth when the absolute neutrophil count (ANC) was less than 1,000/microL. RESULTS: Eighty-six percent of GM-CSF patients (n = 62) and 96% of placebo patients (n = 69) completed four assessable cycles of treatment on study. Overall, the median duration of severe neutropenia (ANC < 500/microL) was 2.8 days with GM-CSF and 6.8 days with placebo (P < .001); the duration of ANC less than 1,000/microL was 6.0 versus 9.1 days, respectively (P < .001). Hospitalizations for febrile neutropenia were uncommon in either group: GM-CSF, six; placebo, eight. The only other difference in hematologic toxicity was grade 3/4 thrombocytopenia observed with greater frequency in GM-CSF patients than placebo patients in cycles 3 and 4. GM-CSF increased mean the FAC dose-intensity among patients who completed two or more cycles (P < .001). GM-CSF was generally well tolerated and associated with more injection-site reactions, but less mucositis than placebo. There were no deaths on study. CONCLUSION: GM-CSF significantly enhanced ANC recovery after FAC chemotherapy; it decreased the incidence and duration of associated neutropenia and moderately increased the dose-intensity of adjuvant chemotherapy. Whether these effects will ultimately translate into improved long-term outcome remains to be determined.

Adolescent↗
PubMed2002

Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial.

PURPOSE: We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of oxaliplatin-induced neurotoxicity. PATIENTS AND METHODS: Fifty-two patients treated with a bimonthly oxaliplatin-based regimen were randomized to receive GSH (1,500 mg/m(2) over a 15-minute infusion period before oxaliplatin) or normal saline solution. Clinical neurologic evaluation and electrophysiologic investigations were performed at baseline and after four (oxaliplatin dose, 400 mg/m(2)), eight (oxaliplatin dose, 800 mg/m(2)), and 12 (oxaliplatin dose, 1,200 mg/m(2)) cycles of treatment. RESULTS: At the fourth cycle, seven patients showed clinically evident neuropathy in the GSH arm, whereas 11 patients in the placebo arm did. After the eighth cycle, nine of 21 assessable patients in the GSH arm suffered from neurotoxicity compared with 15 of 19 in the placebo arm. With regard to grade 2 to 4 National Cancer Institute common toxicity criteria, 11 patients experienced neuropathy in the placebo arm compared with only two patients in the GSH arm (P =.003). After 12 cycles, grade 2 to 4 neurotoxicity was observed in three patients in the GSH arm and in eight patients in the placebo arm (P =.004). The neurophysiologic investigations (sural sensory nerve conduction) showed a statistically significant reduction of the values in the placebo arm but not in the GSH arm. The response rate was 26.9% in the GSH arm and 23.1% in the placebo arm, showing no reduction in activity of oxaliplatin. CONCLUSION: This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaliplatin.

Adult↗
PubMed1996

The placebo effect in pain reduction: the influence of conditioning experiences and response expectancies.

We investigated the role of conditioning experiences and response expectancies in the generation of placebo effects. On 3 sequential days (Test 1, Experimental Session, Test 2), 66 female undergraduates were presented with a series of pain stimuli. For the experimental group, placebo administration (analgesic cream) was paired with a decrease in the painful stimulus. Two control groups were used to explore the relative contributions of verbally induced expectancies and contingent unconditional stimulus experiences per se. The results show that placebo-induced pain reduction can he obtained as a result or a conditioning procedure, independent of verbally induced expectancies. Mere verbal persuasion was not sufficient to elicit placebo-induced pain reduction. Irrespective of the experimental manipulations, the placebo effect was related to both reduced pain expectations and reduced fear of pain. Although conditioned placebo responses were evident at the subjective level, no placebo effects emerged at the physiological level.

Journal Article↗
PubMed1996

A double-blind, placebo-controlled study of vigabatrin three g/day in patients with uncontrolled complex partial seizures. Vigabatrin Protocol 024 Investigative Cohort.

This study compared the efficacy and tolerability of vigabatrin 3/day as add-on therapy with that of placebo in patients with focal epilepsy whose complex partial seizures were difficult to control with established antiepilepsy drug therapy. We enrolled 203 patients; 182 (90 placebo; 92 vigabatrin) received drug therapy under double-blind conditions. We increased the daily dosage to 2.5 g/day during a 4-week titration segment and maintained it at 3 g/day during the 12-week maintenance segment. By analyses we found a statistically significant lower frequency of seizures (complex seizures plus partial seizures secondarily generalized) at the end of the study for patients receiving vigabatrin than for those receiving placebo. The median monthly frequency was reduced by three seizures per 28 days in the placebo group (baseline, 8.3; end of study, 7.5) (p = 0.0002). Therapeutic success (a 50% reduction from baseline in mean monthly seizure frequency) was attained in 40 of the vigabatrin patients (43%) compared with 17 of those treated with placebo (19%) (p < 0.001). Vigabatrin significantly increased the mean number of seizure-free days per 28 days (2.2 days) compared with placebo (0.5 days) (p = 0.0024). Mean trough serum vigabatrin concentration during therapy was 8.6 +/- 7.7 micrograms/ml. The oral clearance of vigabatrin was determined to be 7.8 L/hr, and the elimination half-life was 8.4 hours. No clinically important changes in MRI, evoked potential, or other laboratory tests were noted during vigabatrin treatment. The results of this study indicate that 3 g/day vigabatrin is more effective than placebo as add-on therapy. Vigabatrin was well tolerated, compliance was high with twice-daily administration, and therapy did not result in clinically relevant drug interactions.

Adolescent↗
PubMed1999

A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures. Topiramate YTC Study Group.

BACKGROUND AND OBJECTIVE: Topiramate is effective as adjunctive treatment of partial-onset seizures in adults. The efficacy and safety of topiramate as adjunctive therapy for the treatment of primary generalized tonic-clonic (PGTC) seizures were investigated in a randomized, double-blind, placebo-controlled study. METHODS: Eighty patients, 3 to 59 years old, who experienced three or more PGTC seizures during an 8-week baseline phase were randomly assigned to treatment with either topiramate (n = 39) or placebo (n = 41). Topiramate was titrated to target doses of approximately 6 mg/kg/day over 8 weeks and maintained for another 12 weeks. RESULTS: The median percentage reduction from baseline in PGTC seizure rate was 56.7% for topiramate patients and 9.0% for placebo patients (p = 0.019). The proportion of patients with 50% or higher reduction in PGTC seizure rate was 22/39 (56%) and 8/40 (20%) for the topiramate and placebo groups, respectively (p = 0.001). The median percentage reduction in the rate of all generalized seizures was 42.1% for topiramate patients and 0.9% for placebo patients (p = 0.003). The proportions of patients with 50% or higher reductions in generalized seizure rate were 18/39 (46%) and 7/41 (17%) for the topiramate and placebo groups, respectively (p = 0.003). The most common adverse events were somnolence, fatigue, weight loss, difficulty with memory, and nervousness. Treatment-limiting adverse events occurred in one patient in the topiramate group (anorexia and weight loss) and one in the placebo group (granulocytopenia and thrombocytopenia). CONCLUSION: Topiramate is well-tolerated and effective for the adjunctive treatment of PGTC seizures.

Adolescent↗
PubMed1992

A randomized, blinded, placebo-controlled evaluation of calcium chloride and epinephrine for inotropic support after emergence from cardiopulmonary bypass.

Forty hemodynamically stable patients were randomized to receive an intravenous bolus of either calcium chloride (5 mg/kg) (n = 20) or placebo (n = 20) (phase I). Six minutes later, they received either an epinephrine (30 ng.kg-1.min-1) (n = 20) or placebo (n = 20) infusion (phase II). Hemodynamic and ionized calcium measurements were obtained in phase I at baseline and at 3 and 6 min after the bolus, and in phase II, at 3 and 6 min (study times 9 and 12 min) after initiation of the infusion. Compared with placebo, calcium did not significantly increase cardiac index but significantly increased mean arterial pressure. Calcium improved cardiac index from 2.46 +/- 0.12 (mean +/- SEM) to 2.74 +/- 0.12 L.min-1.m-2; likewise, placebo improved cardiac index from 2.51 +/- 0.15 to 2.74 +/- 0.15 L.min-1.m-2. Mean arterial blood pressure increased with calcium from 74 +/- 2 to 82 +/- 3 mm Hg compared with a placebo change of 74 +/- 2 to 76 +/- 2 mm Hg. Patients who received the epinephrine infusion (n = 20) demonstrated a significant increase in cardiac index at time 12 min compared with patients receiving only placebo (n = 20). Cardiac index of the epinephrine group increased from 2.56 +/- 0.15 to 2.92 +/- 0.22 L.min-1.m-2, whereas in the placebo group it decreased from 2.86 +/- 0.13 to 2.78 +/- 0.12 L.min-1.m-2. Prior administration of calcium did not alter the subsequent response to epinephrine (n = 10) compared with patients receiving epinephrine alone (n = 10). We conclude that cardiac index improves with time without drug therapy after bypass. Calcium chloride increases mean arterial blood pressure but not cardiac index immediately after cardiopulmonary bypass, whereas low-dose epinephrine significantly increases both cardiac index and mean arterial blood pressure without causing tachycardia in these patients. Calcium chloride (5 mg/kg) did not augment or inhibit the hemodynamic response to an epinephrine infusion.

Calcium↗
PubMed2004

The safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial.

UNLABELLED: A noninvasive method of delivery of parenteral opioids for management of acute pain may offer logistic advantages for patients and nursing staff. A patient-controlled transdermal system (PCTS) under development consists of a preprogrammed, self-contained drug-delivery system that uses electrotransport technology (E-TRANS, ALZA Corp, Mountain View, CA) to deliver 40 micro g of fentanyl HCl over 10 min per on-demand dose for patient-controlled analgesia (PCA). In this randomized, double-blinded, placebo-controlled trial we compared the efficacy and safety of on-demand fentanyl HCl PCTS 40 microg against placebo for postoperative pain up to 24 h after major abdominal, orthopedic, or thoracic surgery in 205 patients. The primary efficacy measurement was the percentage of patients withdrawn from the study because of inadequate analgesia after completing at least 3 h of treatment. Secondary efficacy measures included mean pain intensity (using visual analog scales), patient global assessments, and investigator global assessments. Of 189 patients considered evaluable for efficacy, 25% of patients in the fentanyl HCl PCTS 40 microg group withdrew because of inadequate analgesia, compared with 40.4% of the placebo group (P < 0.05). Use of fentanyl HCl PCTS 40 micro g was associated with lower VAS scores and higher mean patient and investigator global assessment scores compared with placebo. No patient experienced clinically relevant respiratory depression. This study showed that a fentanyl HCl PCTS 40 microg for PCA was superior to placebo and well tolerated for the control of moderate to severe postoperative pain for up to 24 h after major surgery. IMPLICATIONS: This multicenter, randomized, double-blinded, placebo-controlled trial showed that an on-demand fentanyl HCl patient-controlled transdermal system (PCTS) was superior to placebo and well tolerated for the control of moderate to severe postoperative pain for up to 24 h after major surgery. This fentanyl HCl PCTS is a preprogrammed, needle free, self-contained drug-delivery system that uses electrotransport technology (iontophoresis) to deliver 40 microg of fentanyl per on-demand dose.

Acute Disease↗
PubMed2005

A double-blind comparison of intravenous ondansetron and placebo for preventing postoperative emesis in 1- to 24-month-old pediatric patients after surgery under general anesthesia.

UNLABELLED: We assessed the efficacy and safety of ondansetron (0.1 mg/kg IV) prophylactically administered before surgery for prevention of postoperative vomiting (POV) in a double-blind, placebo-controlled study of 670 pediatric patients, 1- to 24-mo-old, undergoing elective surgery under general anesthesia. The study enrolled 335 children in each treatment group (ondansetron versus placebo). Significantly fewer children treated with ondansetron exhibited emesis or discontinued the study prematurely after surgery (ondansetron, 11%; placebo, 28%; odds ratio = 0.33; P < 0.0001). The number required to treat prophylactically with ondansetron to prevent POV was approximately six. Ondansetron treatment also resulted in fewer patients requiring rescue medication or assumed to have had rescue upon early discontinuation from the study during the postoperative period (ondansetron, 5%; placebo, 10%) and less emesis (0 of 6) after rescue medication when compared with placebo (7 of 21). The incidence of POV and other antiemetic effects of ondansetron were similar in children aged 1-12 mo and 13-24 mo and in children prospectively expected or not expected to require opioids as part of their anesthetic or analgesic management. Ondansetron was well tolerated; the incidence of adverse events considered possibly related to study drug was similar between treatment groups (ondansetron, 1.8%; placebo, 1.5%). IMPLICATIONS: This prospective, randomized, double-blind, placebo-controlled study establishes the efficacy and tolerability of IV ondansetron (0.1 mg/kg) in the prevention of postoperative emesis in 1- to 24-mo-old pediatric patients undergoing elective surgery under general anesthesia.

Anesthesia, General↗
PubMed2006

An iontophoretic fentanyl patient-activated analgesic delivery system for postoperative pain: a double-blind, placebo-controlled trial.

An iontophoretic fentanyl HCl patient-activated transdermal system (fentanyl HCl PATS) is under development for the treatment of acute postoperative pain. The fentanyl HCl PATS is a needle-free, credit card-sized, preprogrammed system that is applied to the patient's upper outer arm or chest. The fentanyl HCl PATS was demonstrated to be superior to placebo in a previous trial; however, the randomization scheme used and the lack of control of entry pain level may have contributed to the lack of robust findings. We compared the fentanyl HCl PATS with placebo for acute postoperative pain management in a larger trial that addressed the limitations of the previous study. Adult patients admitted to the postanesthesia care unit after major surgery were titrated to comfort with opioids and randomized 1:1 to receive the fentanyl HCl PATS 40 microg or placebo for 24 hours. Supplemental IV fentanyl was available to patients upon request in both treatment groups for the first 3 hours after enrollment. The primary efficacy end-point was the percentage of patients who discontinued participation in the study because of inadequate analgesia. Pain intensity scores, patient global assessments (PGA), and investigator global assessments (IGA) were collected. Four-hundred-eighty-four patients (PATS, n = 244; placebo, n = 240) were enrolled. Fewer patients receiving the fentanyl HCl PATS discontinued because of inadequate analgesia compared with placebo (28.7% versus 60.0%; P < 0.0001). Mean last pain intensity scores were 3.5 and 5.4 for the fentanyl HCl PATS and placebo groups, respectively. Patients (73.4%, PGA) and investigators (72.1%, IGA) considered the fentanyl HCl PATS a good or excellent method of pain control. Treatment-related adverse events were similar between groups. This study demonstrated the superiority of the iontophoretic fentanyl HCl PATS over placebo for acute postoperative pain management.

Analgesia, Patient-Controlled↗
PubMed2004

Clodronate reduces vertebral fracture risk in women with postmenopausal or secondary osteoporosis: results of a double-blind, placebo-controlled 3-year study.

UNLABELLED: The efficacy of oral clodronate 800 mg daily to reduce vertebral fractures was studied in 593 women with postmenopausal or secondary osteoporosis. The incidence of vertebral fractures was significantly reduced by 46%. The effect was not modified by the underlying cause of osteoporosis or other baseline factors including bone mineral density, QUS, weight, and smoking. INTRODUCTION: This study aimed to determine if the bisphosphonate, clodronate (Bonefos), reduced the incidence of vertebral fractures in osteoporotic women. MATERIALS AND METHODS: Women fulfilling the WHO criteria for osteoporosis at the lumbar spine (T-score </= -2.5) and/or with at least one prevalent vertebral fracture were recruited to a 3-year double-blind, placebo-controlled study. A total of 593 patients were randomized to two strata comprised of women with postmenopausal osteoporosis (I, n = 483) and secondary osteoporosis (II, n = 110). They received either clodronate 800 mg daily orally (n = 292) or an identical placebo (n = 301). All patients received a calcium supplement of 500 mg daily. BMD was measured at 6, 12, 24, and 36 months, and lateral spine radiographs were obtained at baseline and annually thereafter for vertebral morphometry. RESULTS: Treatment with clodronate was associated with a significant increase in mean spine BMD over 3 years (percent change from baseline, 4.35 +/- 6.34% versus 0.64 +/- 6.02% in the placebo group, p < 0.0001). At the hip, clodronate maintained total BMD, whereas a significant decrease was observed in the placebo group (percent change from baseline 0.70 +/- 5.67% versus -3.03 +/- 6.32% in the placebo group, p < 0.0001). The changes at the spine and hip were similar in both strata. Incident vertebral fractures at 3 years were observed in 63 women in the placebo group and 33 patients receiving clodronate (relative risk, 0.54; 95% CI, 0.37-0.80; p = 0.001). Clodronate significantly reduced vertebral fracture risk in both strata and in women with or without prior vertebral fracture at baseline. Nonvertebral osteoporosis-associated fractures occurred in 21 women in the placebo group and in 14 women treated with clodronate. Treatment was well tolerated, with no significant difference in adverse event rates, including esophagitis, during clodronate treatment. CONCLUSION: We conclude that clodronate 800 mg daily is a safe and effective treatment to reduce fracture risk in women with osteoporosis, regardless of causation.

Aged↗
PubMed2007

Exercise and calcium combined results in a greater osteogenic effect than either factor alone: a blinded randomized placebo-controlled trial in boys.

UNLABELLED: We examined the combined effects of exercise and calcium on BMC accrual in pre- and early-pubertal boys. Exercise and calcium together resulted in a 2% greater increase in femur BMC than either factor alone and a 3% greater increase in BMC at the tibia-fibula compared with the placebo group. Increasing dietary calcium seems to be important for optimizing the osteogenic effects of exercise. INTRODUCTION: Understanding the relationship between exercise and calcium during growth is important given that the greatest benefits derived from these factors are achieved during the first two decades of life. We conducted a blinded randomized-controlled exercise-calcium intervention in pre- and early-pubertal boys to test the following hypotheses. (1) At the loaded sites (femur and tibia-fibula), exercise and calcium will produce greater skeletal benefits than either exercise or calcium alone. (2) At nonloaded sites (humerus and radius-ulna), there will be an effect of calcium supplementation. MATERIALS AND METHODS: Eighty-eight pre- and early-pubertal boys were randomly assigned to one of four study groups: moderate impact exercise with or without calcium (Ca) (Ex+Ca and Ex+placebo, respectively) or low impact exercise with or without Ca (No-Ex+Ca and No-Ex+Placebo, respectively). The intervention involved 20 minutes of either moderate- or low-impact exercise performed three times a week and/or the addition of Ca-fortified foods using milk minerals (392+/-29 mg/day) or nonfortified foods over 8.5 months. Analysis of covariance was used to determine the main and combined effects of exercise and calcium on BMC after adjusting for baseline BMC. RESULTS: At baseline, no differences were reported between the groups for height, weight, BMC, or bone length. The increase in femur BMC in the Ex+Ca group was approximately 2% greater than the increase in the Ex+placebo, No-Ex+Ca, or No-Ex+Placebo groups (all p<0.03). At the tibia-fibula, the increase in BMC in the Ex+Ca group was approximately 3% greater than the No-Ex+placebo group (p<0.02) and 2% greater than the Ex+Placebo and the No-Ex+Ca groups (not significant). No effect of any group was detected at the humerus, ulna-radius, or lumbar spine for BMC, height, bone area, or volume. CONCLUSIONS: In this group of normally active boys with adequate calcium intakes, additional exercise and calcium supplementation resulted in a 2-3% greater increase in BMC than controls at the loaded sites. These findings strengthen the evidence base for public health campaigns to address both exercise and dietary changes in children for optimizing the attainment of peak BMC.

Bone Density↗
PubMed1993

Amrinone in cardiac surgical patients with left-ventricular dysfunction. A prospective, randomized placebo-controlled trial.

STUDY OBJECTIVE: To evaluate the efficacy of amrinone for facilitating weaning from cardiopulmonary bypass (CPB). DESIGN: Prospective, randomized, double-blind, placebo-controlled trial with epinephrine as "rescue" therapy. SETTING: Operating room of a large, metropolitan tertiary-care center. PATIENTS: Thirty-nine patients with preoperative left ventricular dysfunction undergoing cardiac surgery. Thirty-three patients underwent aortocoronary bypass grafting; six patients underwent valve replacement for severe mitral or aortic regurgitation. INTERVENTIONS: Patients received either amrinone (1.5 mg/kg loading dose plus 10 micrograms/kg/min maintenance infusion; n = 20) or placebo (n = 19) in a randomized double-blind fashion shortly (median, 10.5 min; range, 2 to 24 min) before separation from CPB. Inotropic drugs (other than the study drug) were withheld prior to separation from CPB unless safety considerations demanded that the protocol be broken. Patients who could not be weaned from CPB, as well as those with a cardiac index of 2.2 L/min/m2 or less after weaning from CPB, received epinephrine (60 to 120 ng/kg/min) by infusion. MEASUREMENTS AND RESULTS: Fourteen of 19 patients receiving placebo but only 1 of the 20 patients receiving amrinone (p = 0.00001) required epinephrine infusion to separate from bypass. The cardiac index of 4 patients receiving placebo (but no patients with amrinone) failed to exceed 2.2 L/min/m2 despite epinephrine infusion, requiring the protocol to be broken (p < 0.08). Blood concentrations of amrinone determined (only in the amrinone group) after separation from CPB confirmed that the dosage of amrinone produced an effective blood concentration. Fourteen of 19 patients receiving placebo and 17 of 20 patients receiving amrinone required an infusion of phenylephrine titrated to maintain systolic blood pressure less than 90 mm Hg. Seven patients (four with amrinone and three with placebo) required antiarrhythmic drug therapy. The outcome at 3 months was similar in the 2 groups. CONCLUSIONS: Amrinone by itself is an effective agent to facilitate weaning from CPB, and therapy with amrinone reduced the need for individualized titration of epinephrine. Amrinone is as effective as individualized titration of epinephrine (after CPB) to improve cardiac function. Patients in the group receiving amrinone had no greater need for vasoconstricting agents than did patients in the group receiving placebo; however, proactive administration of amrinone before separation from CPB appears to offer no greater benefit to high-risk patients than selective administration of drugs (epinephrine) only to those patients who demonstrate the need for drug support at the time of weaning.

Adult↗
PubMed1996

Hemodynamic effects of i.v. milrinone lactate in pediatric patients with septic shock. A prospective, double-blinded, randomized, placebo-controlled, interventional study.

STUDY OBJECTIVE: To determine the hemodynamic effects of i.v. milrinone lactate in pediatric patients with nonhyperdynamic septic shock. Specifically we tested the hypothesis that i.v. milrinone would increase cardiac index by 20% and decrease systemic vascular resistance index by 20% during a 2-h study period. DESIGN: Prospective, double-blinded, randomized, placebo-controlled, descriptive, interventional study. SETTING: Twenty-six-bed pediatric ICU at Children's Medical Center of Dallas and a 10-bed pediatric trauma ICU at Parkland Memorial Hospital. PATIENTS/PARTICIPANTS: Twelve patients (age range, 9 months to 15 years) with nonhyperdynamic septic shock despite administration of catecholamines (cardiac index [CI] normal [3.5 to 5.5 L/min/m2] or low [< or =3.5 L/min/m2]; systemic vascular resistance index [SVRI] normal [800 to 1,600 dyne.s.cm5/m2] or high [> or =1,600 dyne.s.cm5/m2]; and pulmonary capillary wedge pressure [PCWP] normal [8 to 12 mm Hg] or higher) with clinical signs of poor perfusion were enrolled, randomized, and treated in a blinded fashion with i.v. milrinone and placebo. INTERVENTIONS: Patients were randomized into two groups. Group A received a loading dose of 50 micrograms/kg i.v. of milrinone followed by a continuous i.v. infusion of 0.5 microgram/kg/min while group B received an equal volume loading dose and continuous infusion of placebo. After 2 h, group A received an equal-volume loading dose followed by a continuous infusion of placebo while the milrinone infusion continued, while group B received a 50 micrograms/kg loading dose of milrinone followed by a continuous infusion of 0.5 microgram/kg/min while the placebo infusion remained. Outcome variable were measured at baseline, 0.5, 1.0, 2.0, 2.5, 3.0, and 4.0 h. Echocardiographic measurements were taken at baseline, hour 2, and hour 4 in all subjects. No changes in other inotropic or mechanical ventilatory support were allowed during the study period. MEASUREMENTS AND MAIN RESULTS: Milrinone significantly increased CI, stroke volume index (SVI), right and left ventricular stroke work index, and oxygen delivery (Do2) at 0.5, 1.0, and 2.0 h postloading dose (p < 0.05) while significantly decreasing SVRI, pulmonary vascular resistance index, and mean pulmonary arterial pressure at 0.5, 1.0, and 2.0 h postloading dose (p < 0.05). No clinically or statistically significant changes in heart rate, systolic and diastolic BP, mean systemic arterial pressure, or PCWP were observed during milrinone treatment compared to placebo. CONCLUSIONS: CI, SVI, and Do2 significantly increased while SVRI significantly decreased when compared to placebo after i.v. administration of milrinone to pediatric patients with nonhyperdynamic septic shock. No adverse effects were observed. In a volume-resuscitated pediatric patient with septic shock, when administered in addition to catecholamines, milrinone will improve cardiovascular function.

Adolescent↗