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Study Medication (study + medication)

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Medical Sciences	100%

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Neurology	23%
Cardiovascular Disease	10%
13 Other Subdomains	67%

Selected Abstracts

Once-daily OROS®,hydromorphone for the management of chronic nonmalignant pain: a dose-conversion and titration study

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2007
M. Wallace
Summary Background:, The use of opioid analgesics for patients with chronic nonmalignant pain is becoming more widely accepted, and long-acting formulations are an important treatment option. Aim:, To assess conversion to extended-release OROS® hydromorphone from previous stable opioid agonist therapy in patients with chronic nonmalignant pain of moderate-to-severe intensity. Methods:, In this open-label multicentre trial, patients were stabilised on their previous opioid therapy before being switched to OROS® hydromorphone at a ratio of 5 : 1 (morphine sulphate equivalent to hydromorphone hydrochloride). The OROS® hydromorphone dose was titrated over 3,16 days to achieve effective analgesia, and maintenance treatment continued for 14 days. Results:, Study medication was received by 336 patients; 66% completed all study phases. Stabilisation of OROS® hydromorphone was achieved by 94.6% of patients, the majority in two or fewer titration steps (mean time, 4.2 days). Mean pain intensity scores, as determined by the Brief Pain Inventory, decreased during OROS® hydromorphone treatment (p , 0.001). The percentage of patients rating their pain relief as ,good' or ,complete' increased, and the use of rescue analgesics for breakthrough pain decreased. The interference of pain with everyday activities (e.g. walking or work), and the effects on mood and enjoyment of life, also improved during the study (all p < 0.001). OROS® hydromorphone was well tolerated, and adverse events were those expected for opioid agonist therapy. Conclusion:, Patients with chronic nonmalignant pain who had been receiving opioid therapy easily underwent conversion to OROS® hydromorphone, with no loss of efficacy or increase in adverse events. [source]

The use of high resolution computerized tomography (HRCT) of the chest in evaluating the effect of tobramycin solution for inhalation in cystic fibrosis lung disease,

PEDIATRIC PULMONOLOGY, Issue 5 2010
Samya Z. Nasr MD
Abstract Objectives To compare the usefulness of HRCT of the chest versus spirometric measures (PFTs) in evaluating the effect of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF). Methods Thirty-two CF patients with mostly mild lung disease age ,6 years, were enrolled in a double-blind, placebo-controlled pilot study. Patients were chronically colonized with Pseudomonas aeruginosa for at least 6 months prior to and at enrollment. If patients were on TSI, they were taken off for at least 3 months prior to enrollment. Duration was 6 months; 31 subjects completed the study. HRCT and PFTs were evaluated at baseline, after 28 days of treatment and at the end of the study. Study medication was administered as 5,ml nebulized treatment twice a day for 28 days followed by 28 days off (one cycle). Study consisted of three cycles. Two radiologists scored all films using a validated system. A total HRCT score consists of the sum of subscores: linear opacities, hyperinflation, nodular opacities, peribronchial thickening, mucous plugging, and bronchiectasis; each subscore could range from 0 to 80, with potential total scores varying from 0 to 480. The percent of the maximum possible HRCT score was then calculated and used for all comparisons. Results Using two tailed paired t -test, the percent maximum HRCT score decreased by 1.4,±,2.6% (mean,±,SD) (P,=,0.049) and 0.3,±,2.8% (P,=,0.63) for the TSI group and decreased by 0.1,±,1.5% (P,=,0.74) and increased by 0.6,±,1.8% (P,=,0.23) for the placebo group between visits 1 and 2, and visits 1 and 3, respectively. The data were then analyzed using a mixed model utilizing changes in scores over the durations of the study for each group. The change of HRCT score for the TSI group was ,0.24/day (P,=,0.02) and ,0.03/day (P,=,0.22), and for the control group the change was ,0.01 (P,=,0.93) and 0.02 (P,=,0.29) between visits 1 and 2, and visits 1 and 3 respectively. FEF25,75% and FEV1% changes were not statistically significant using both analyses. Conclusion HRCT seems to be more sensitive in detecting treatment effect than PFT in CF patients with mild lung disease, especially following the first treatment period (visit 2). Total HRCT score showed some improvement at the end of the study, though not statistically significant. This is probably due to obtaining the HRCT an average of 30 days after completion of the TSI treatment, and selection of study population with mostly mild lung disease. This could indicate that the most significant improvement in the total HRCT score in this patient population occurs after the first treatment period with TSI. Pediatr Pulmonol. 2010; 45:440,449. © 2010 Wiley-Liss, Inc. [source]

Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependence

ADDICTION, Issue 1 2010
Marie Longo
ABSTRACT Aim To investigate the safety and efficacy of once-daily supervised oral administration of sustained-release dexamphetamine in people dependent on methamphetamine. Design Randomized, double-blind, placebo-controlled trial. Participants Forty-nine methamphetamine-dependent drug users from Drug and Alcohol Services South Australia (DASSA) clinics. Intervention Participants were assigned randomly to receive up to 110 mg/day sustained-release dexamphetamine (n = 23) or placebo (n = 26) for a maximum of 12 weeks, with gradual reduction of the study medication over an additional 4 weeks. Medication was taken daily under pharmacist supervision. Measurements Primary outcome measures included treatment retention, measures of methamphetamine consumption (self-report and hair analysis), degree of methamphetamine dependence and severity of methamphetamine withdrawal. Hair samples were analysed for methamphetamine using liquid chromatography-mass spectrometry. Findings Treatment retention was significantly different between groups, with those who received dexamphetamine remaining in treatment for an average of 86.3 days compared with 48.6 days for those receiving placebo (P = 0.014). There were significant reductions in self-reported methamphetamine use between baseline and follow-up within each group (P < 0.0001), with a trend to a greater reduction among the dexamphetamine group (P = 0.086). Based on hair analysis, there was a significant decrease in methamphetamine concentration for both groups (P < 0.0001). At follow-up, degree of methamphetamine dependence was significantly lower in the dexamphetamine group (P = 0.042). Dexamphetamine maintenance was not associated with serious adverse events. Conclusions The results of this preliminary study have demonstrated that a maintenance pharmacotherapy programme of daily sustained-release amphetamine dispensing under pharmacist supervision is both feasible and safe. The increased retention in the dexamphetamine group, together with the general decreases in methamphetamine use, degree of dependence and withdrawal symptom severity, provide preliminary evidence that this may be an efficacious treatment option for methamphetamine dependence. [source]

Long-Term, Open-Label Safety Study of Oral Almotriptan 12.5 mg for the Acute Treatment of Migraine in Adolescents

HEADACHE, Issue 5 2010
Frank Berenson MD
(Headache 2010;50:795-807) Objectives., This study evaluated the long-term safety of oral almotriptan 12.5 mg for the treatment of multiple migraine episodes in adolescents over a 12-month period. Efficacy outcomes were assessed as a secondary objective. Methods., Adolescent migraineurs aged 12-17 years were enrolled in this 12-month, open-label study (Study ID CR002827). Patients were instructed to record their assessments on paper headache records whenever they experienced a migraine headache that they treated with study medication. Safety was assessed descriptively and assessments included adverse event (AE) recording, change in laboratory values, vital signs, and electrocardiogram parameters. Efficacy outcomes were assessed descriptively and outcomes included rates for 2- and 24-hour pain relief and sustained pain relief, 2- and 24-hour pain-free and sustained pain-free, and presence of migraine-associated symptoms of photophobia, phonophobia, nausea and vomiting. Results., Overall, 67.1% of patients reported ,1 AE over the course of the trial, 7.6% had an AE judged by the study investigator to be related to treatment with almotriptan, 2.4% discontinued because of an AE, and 1.9% reported serious AEs. The most commonly reported treatment-related AEs (occurring in ,1% of patients) were nausea (1.4%) and somnolence (1.4%). Pain relief responses for treated migraines of moderate or severe intensity at baseline were 61.7% and 68.6%, at 2 and 24 hours, respectively; the sustained pain relief rate was 55.5%. Pain-free responses were reported for 40.5% of all treated migraines at 2 hours and 65.9% of treated migraines at 24 hours; the sustained pain-free rate was 38.4%. The proportion of migraines that achieved the pain relief, sustained pain relief, pain-free and sustained pain-free endpoints were similar in the 12- to 14-year and 15- to 17-year age groups. Treating with almotriptan 12.5 mg when headache pain was mild was associated with higher rates of pain relief and pain-free at 2 and 24 hours, and sustained pain relief and sustained pain-free, compared with treatment initiated when pain was severe. Conclusions., Almotriptan 12.5 mg was well tolerated in this adolescent population over a 12-month period. No unexpected safety or tolerability concerns were revealed over the course of this study. The results are consistent with almotriptan 12.5 mg being effective for the acute treatment of pain and symptoms associated with migraine in both younger and older adolescents. [source]

Efficacy of Eletriptan in Migraine-Related Functional Impairment: Functional and Work Productivity Outcomes

HEADACHE, Issue 5 2007
Stephen D. Silberstein MD
Objective.,To provide a multidimensional assessment of the extent of functional impairment during an acute migraine attack, and of the improvement in functioning in response to treatment, using 4 concurrently administered scales: the 7-item work productivity questionnaire (PQ-7), the functional assessment in migraine (FAIM) activities and participation (FAIM-A&P) subscale, the FAIM-impact of migraine on mental functioning (FAIM-IMMF) subscale, and the traditional 4-point global functional impairment scale (FIS). Methods.,Outpatients with an International Classification of Headache Disorders diagnosis of migraine were randomized to double-blind treatment of a single attack with either oral eletriptan 20 mg (n = 192) once-daily, eletriptan 40 mg (N = 213) once-daily, or placebo (n = 208). Patients were encouraged to take study medication as soon as they were sure they were experiencing a typical migraine headache, after the aura phase (if present) had ended. Patients with moderate-to-severe functional impairment were identified on each of the 4 disability scales, and 2-hour functional response was compared between treatments. Results.,At baseline, the PQ-7 and FAIM-IMMF items that assessed ability to perform tasks requiring concentration, sustained work or attention, and ability to think quickly or spontaneously, were especially sensitive to the effects of mild headache pain, with 27% to 48% of patients (n = 92-112) reporting moderate-to-severe impairment. Only 11.3% of patients (n = 112) reported this level of impairment due to mild pain on the FIS. Functional response at 2 hours was significantly higher on eletriptan 40 mg versus placebo on the FAIM-A&P (63% vs 36%; n = 218; P < .0001); on the PQ-7 (56% vs 34%; n = 116; P= .0052); and on the FAIM-IMMF (50% vs 34%; n = 215; P= .017). These rates were all lower than the functional response rates on the FIS for eletriptan 40 mg (75%) and eletriptan 20 mg (70%) versus placebo (45%; P < .001). Conclusions.,In this exploratory analysis, use of multidimensional scales was found to provide a sensitive measure of headache-related functional impairment, especially for detecting clinically meaningful cognitive effects, and for detecting drug versus placebo differences. [source]

Long-Term Migraine Prevention With Topiramate: Open-Label Extension of Pivotal Trials

HEADACHE, Issue 7 2006
Alan Rapoport MD
Objective.,To demonstrate that topiramate is an effective and generally well-tolerated migraine preventive therapy when used for up to 14 months. Background.,Topiramate 100 and 200 mg/d significantly reduced mean monthly migraine frequency during 2 large, 26-week, randomized, placebo-controlled trials. Only a small number of clinical trials have examined the long-term (,1 year) effectiveness and safety of migraine preventive therapies. Methods.,Five hundred sixty-seven patients with an established history of migraine with or without aura were enrolled in this 8-month, open-label extension of 2 large (49 US and 52 US and Canadian medical centers), randomized, double-blind, placebo-controlled, parallel group, 26-week trials of identical design. To be eligible for the open-label extension, patients were required to have either completed the double-blind phase of the 2 pivotal migraine prevention trials or withdrew after 4 weeks due to lack of efficacy. All eligible patients, regardless of type or dose of study medication (topiramate or placebo) received in the double-blind phase, were titrated to a clinically effective dose of open-label topiramate based on physician judgment of patient response. Efficacy of topiramate was measured as the change in mean monthly migraine frequency. Results.,The mean topiramate dose during the open-label extension phase was 124.7 mg/d and 150.3 mg/d for patients on placebo (n = 159) or topiramate (n = 408), respectively, during the double-blind phase (N = 567, 91% female, mean age 39.4 years). Patients on topiramate for up to 14 months had 2.2 ± 2.4 (mean ± SD) migraines per month after completion of the open-label extension phase (3.4 ± 2.6 at double-blind endpoint). Patients on topiramate during the open-label extension phase only (placebo during the double-blind phase) had 3.0 ± 2.9 migraines per month at open-label extension endpoint (4.9 ± 3.0 migraines per month at double-blind endpoint). Discontinuation rates due to adverse events during the double-blind phase were 22.2% for patients on topiramate and 11.0% for patients on placebo. Discontinuation rates due to adverse events during the open-label extension phase were 8.6% for those patients who had already received topiramate during the double-blind phase and 20.9% for those patients who had previously received placebo. Conclusions.,Patients receiving topiramate experienced a sustained reduction in migraine frequency for up to 14 months. The effectiveness and safety of topiramate was consistent with that observed during 2 26-week pivotal trials. [source]

Early Intervention With Almotriptan Improves Sustained Pain-free Response in Acute Migraine

HEADACHE, Issue 10 2003
Ninan T. Mathew MD
Objective.,To determine whether treatment of migraine with almotriptan, when pain intensity is mild, improves 1- and 2-hour pain-free and sustained pain-free rates compared with treatment when pain intensity is moderate or severe. Methods.,This was a post hoc analysis derived from an open-label, multicenter, long-term study of the safety, tolerability, and efficacy of almotriptan 12.5 mg. Patients who met International Headache Society criteria for migraine with or without aura were eligible. Patients were instructed to take a single dose of almotriptan 12.5 mg at the onset of a migraine attack. Rescue medication could be taken if migraine pain had not disappeared at 2 hours. A second dose of almotriptan 12.5 mg could be taken if head pain recurred within 24 hours of the initial dose. Patients reported the intensity of pain at baseline and at 1 and 2 hours postmedication using a 4-point scale: no pain, mild, moderate, or severe pain. They also reported recurrence of pain (return of moderate or severe pain within 2 to 24 hours of taking the study medication) and use of rescue medication. Rescue medication consisted of supplemental analgesics taken for pain relief at 2 to 24 hours postdose. Ergotamines and other 5-HT1B/1D agonists were excluded as rescue medications. Based on these patient-reported end points, sustained pain-free rates, defined as pain-free at 2 hours with no recurrence from 2 to 24 hours and no use of rescue medication, were calculated. Results.,A higher proportion of migraine attacks of mild intensity were pain-free at 1 hour (35.3%) compared with attacks of moderate or severe intensity (7.5%) (P < .001). Two-hour pain-free rates also were significantly higher with mild intensity pain (76.9%) compared to moderate or severe intensity (43.9%) (P < .001). In addition, recurrence rates and use of rescue medication were reduced when attacks were treated during mild pain. Recurrence was 12.9% for mild pain versus 25.0% for moderate or severe pain (P < .001), and use of rescue medication was 9.4% for mild pain versus 17.2% for moderate or severe pain (P < .001). Sustained pain-free rates were nearly twice as high when attacks were treated during mild intensity pain (66.6%) compared with attacks treated during moderate or severe pain (36.6%) (P < .001). Conclusion.,Treatment with almotriptan 12.5 mg during migraine attacks of mild pain intensity improves 1- and 2-hour pain-free and sustained pain-free responses. [source]

Almotriptan Reduces the Incidence of Migraine-Associated Symptoms: A Pooled Analysis

HEADACHE, Issue 2002
Roger Cady MD
Objectives.,Evaluate the reduction in migraine-associated symptoms after administration of a single oral dose of almotriptan. Methods.,This pooled analysis (N=1773) used data from three randomized, placebo-controlled, phase III trials (studies A, B, and C) to determine the incidence of migraine-associated symptoms (defined as nausea, vomiting, photophobia, and phonophobia) 2 hours after a single oral dose of study medication (almotriptan, sumatriptan, or placebo). Outcome data was extracted from studies A and B for placebo and the almotriptan 6.25-mg and 12.5-mg groups, and from study C for placebo, almotriptan 12.5-mg, and sumatriptan 100-mg groups. Results.,The incidence of nausea, photophobia, and phonophobia at 2 hours after dosing with study medication was significantly reduced (all P < .05) with almotriptan 6.25 mg or 12.5 mg compared with placebo. The percentage of patients with vomiting was lower with both doses of almotriptan in studies A and B compared with placebo, although differences were significant only for the 6.25-mg dose in study A (P < .001). For study C, the incidence of nausea, vomiting, photophobia, and phonophobia was similar for almotriptan and sumatriptan and lower than with placebo at 2 hours after dosing. Significant reductions (all P < .05) versus placebo were observed in the incidence of vomiting and phonophobia with almotriptan 12.5 mg, and photophobia and phonophobia with sumatriptan 100 mg. Conclusion.,Almotriptan provides relief from migraine-associated symptoms of nausea, vomiting, photophobia, and phonophobia, and thus represents an attractive treatment option for a wide spectrum of migraine symptomatology. [source]

Almotriptan Increases Pain-Free Status in Patients With Acute Migraine Treated in Placebo-Controlled Clinical Trials

HEADACHE, Issue 2002
FRCP(C), Ninan T. Mathew MD
Objectives.,Evaluate the efficacy of a single oral dose of almotriptan in achieving pain-free status during treatment of acute migraine attacks. Methods.,This pooled analysis (N=1321) used data from two randomized, placebo-controlled, phase III trials (studies A and B) to determine the proportion of patients with migraine achieving pain-free status 2 hours after a single oral dose of study medication (almotriptan or placebo). Pain was assessed using a 4-point integer scale (0=no headache, 3=severe headache), and recorded in a patient self-assessment booklet. Results.,The proportion of patients pain-free at 2 hours after study medication was significantly greater with almotriptan 6.25 mg (both studies P,.002) and almotriptan 12.5 mg (both studies P,.001) than with placebo. In study A, 11.6% of patients taking almotriptan 12.5 mg versus 2.5% of patients receiving placebo were pain-free at 1 hour (P=.016). At 1.5 hours, 26.8% of patients taking almotriptan 12.5 mg versus 8.8% receiving placebo (P=.001) were pain-free, and at 2 hours, 38.4% on almotriptan versus 11.3% on placebo were pain-free (P<.001). In study B, 23.8% of patients taking almotriptan 12.5 mg were free from pain at 1.5 hours versus 10.2% receiving placebo (P<.001). At 2 hours, 39.2% taking almotriptan 12.5 mg versus 15.3% receiving placebo were pain-free (P<.001). Increases in pain-free status with almotriptan generally occurred in a dose-dependent manner. Conclusion.,Compared with placebo, almotriptan 12.5 mg significantly increases the proportion of patients who are pain-free by as early as 1 hour, and consistently by 1.5 hours, after a single dose. [source]

Treatment satisfaction and efficacy of the rapid release formulation of sumatriptan 100 mg tablets utilising an early intervention paradigm in patients previously unsatisfied with sumatriptan

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 12 2008
L. C. Newman
Summary Aims:, To evaluate treatment satisfaction, efficacy and functional ability of the rapid release formulation of sumatriptan 100 mg tablets (sumatriptan RT 100 mg) in an early intervention paradigm in patients who were dissatisfied with low-dose sumatriptan and not completely satisfied with their current migraine regimen. Methods:, Experienced migraineurs who reported a mild migraine pain phase, dissatisfaction with the previous sumatriptan treatment and some dissatisfaction with their current treatment regimen had no experience with sumatriptan at the 100 mg dose were enrolled in an open-label, single group study. Subjects were instructed to treat four migraine attacks within 30 min of the onset of mild pain. Treatment satisfaction was measured with the Patient Perception of Migraine Questionnaire Revised version (PPMQ-R) questionnaire. Results:, More than half of the subjects were either very satisfied or satisfied with the efficacy of early intervention sumatriptan RT 100 mg after each attack and at the follow-up study visit. The mean total PPMQ-R score was 75.2 out of 100. Between 63% and 73% of subjects were pain-free within 4 h of dosing. Between 79% and 90% of subjects reported an ability to function normally within 4 h of taking the study medication. Conclusion:, Subjects who were previously unsatisfied with lower doses of sumatriptan and less than very satisfied with their current treatment regimen were more likely to be satisfied or very satisfied with sumatriptan RT 100 mg in an early intervention paradigm. Results were consistent across four migraine attacks and at a follow-up visit. The treatment satisfaction results corresponded with positive results on efficacy measures and a functional status measure. [source]

Endogenous Estrogen Levels and the Effects of Ultra-Low-Dose Transdermal Estradiol Therapy on Bone Turnover and BMD in Postmenopausal Women,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2007
Alison J Huang
Abstract In a randomized controlled trial of a 0.014 mg/d transdermal estradiol patch, serum bone turnover markers decreased to a greater degree in postmenopausal women with lower versus higher endogenous estradiol levels. This suggests that the protective effects of ultra-low-dose estrogen therapy on the postmenopausal skeletal health may depend critically on women's endogenous estrogen levels before treatment. Introduction: Postmenopausal women with very low or undetectable estradiol levels have lower BMD, increased bone turnover, and increased risk of hip and vertebral fracture. We assessed whether the effects of ultra-low-dose 0.014 mg/d transdermal estradiol (Menostar; Berlex, Montvale, NJ, USA) on bone turnover and BMD are influenced by endogenous estradiol levels. Materials and Methods: We analyzed data from postmenopausal women (mean age, 66 yr) randomized to an 0.014-mg/d transdermal estradiol patch or placebo in the ultra-low-dose transdermal estrogen (ULTRA) trial. The free estradiol index (FEI), calculated as the ratio of total estradiol (by mass spectometry) to sex hormone-binding globulin (SHBG; by immunoradiometric assay) × 100, was used to estimate bioavailable estradiol at baseline. Among the 382 women who adhered to ,80% of study medication, we examined change in serum osteocalcin and bone-specific alkaline phosphatase levels at 12 mo and total hip and lumbar spine BMD at 24 mo in each quintile of FEI. Results: Compared with women in the highest quintile of FEI, those in the lowest quintile of FEI had a 26% greater reduction in bone-specific alkaline phosphatase and 15% greater reduction in osteocalcin in response to ultra-low estradiol treatment (p for trend across quintiles < 0.05). There was a trend toward greater improvement in total hip BMD (p = 0.06) but not spine BMD (p = 0.90) in those with lower versus higher FEI levels. Conclusions: The beneficial effects of ultra-low-dose 0.014-mg/d transdermal estrogen therapy on skeletal health may depend critically on women's endogenous estrogen levels before treatment. [source]

Original Paper: Telmisartan Effects on Insulin Resistance in Obese or Overweight Adults Without Diabetes or Hypertension

JOURNAL OF CLINICAL HYPERTENSION, Issue 9 2010
Willa Hsueh MD
J Clin Hypertens (Greenwich). 2010;12:746,752. ©2010 Wiley Periodicals, Inc. Angiotensin receptor blockers (ARBs) are antihypertensive agents associated with reduced risk of new-onset diabetes mellitus. The ARB telmisartan is a partial agonist of peroxisome proliferator,activated receptor-gamma (PPAR-,). This study evaluated the effect of telmisartan on insulin resistance, a known target of PPAR-, agonism. Overweight/obese persons with body mass index ,28 kg/m2, waist circumference ,35 inches, and components of the metabolic syndrome without hypertension or diabetes who were not preselected for insulin resistance were enrolled. Patients were randomized to telmisartan or matching placebo for 16 weeks. The primary efficacy measure was changed from baseline in the insulin sensitivity index (SI), calculated from oral glucose tolerance testing. SI was also evaluated in a subset of patients using a hyperinsulinemic euglycemic clamp. Secondary end points included measures of insulin sensitivity and glucose and lipid metabolism. A total of 138 patients were randomized and received ,1 dose of study medication; 128 completed the study. At end point, no significant difference was found between telmisartan and placebo groups regarding change from baseline in SI or in glucose area under the curve. No significant between-group differences were found regarding glucose metabolism or lipoprotein levels. In the population with abdominal obesity and components of the metabolic syndrome, telmisartan did not increase insulin sensitivity. [source]

Amoxicillin plus metronidazole in the treatment of adult periodontitis patients

JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2001
A double-blind placebo-controlled study
Abstract Background, aims: The aim of this double-blind, parallel study was to evaluate the adjunctive effects of systemically administered amoxicillin and metronidazole in a group of adult periodontitis patients who also received supra- and subgingival debridement. Methods: 49 patients with a diagnosis of generalised severe periodontitis participated in the study. Random assignment resulted in 26 patients in the placebo (P) group with a mean age of 40 years and 23 patients in the test (T) group which had a mean age of 45 years. Clinical measurements and microbiological assessments were taken at baseline and 3 months after completion of initial periodontal therapy with additional placebo or antibiotic treatment. Patients received coded study medication of either 375 mg amoxicillin in combination with 250 mg metronidazole or identical placebo tablets, every 8 hours for the following 7 days. Results: At baseline, no statistically significant differences between groups were found for any of the clinical parameters. Except for the plaque, there was a significantly larger change in the bleeding, probing pocket depth (PPD) and clinical attachment level (CAL) in the T-group as compared to the P-group after therapy. The greatest reduction in PPD was found at sites with initial PPD of 7 mm, 2.5 mm in the P-group and 3.2 mm in the T-group. The improvement in CAL was most pronounced in the PPD category 7 mm and amounted to 1.5 mm and 2.0 mm in the P- and T-groups, respectively. No significant decrease was found in the number of patients positive for any of the test species in the P-group. The number of patients positive for Porphyromonas gingivalis, Bacteroides forsythus and Prevotella intermedia in the T-group showed a significant decrease. After therapy there was a significant difference between the P- and the T- group in the remaining number of patients positive for P. gingivalis, B. forsythus and Peptostreptococcus micros. 4 subgroups were created on the basis of the initial microbiological status for P. gingivalis positive (Pg-pos) and negative patients (Pg-neg) in the P- and the T-groups. The difference in reduction of PPD between Pg-pos and Pg-neg patients was particularly evident with respect to the changes in % of sites with a probing pocket depth 5 mm. This % decreased from 45% at baseline to 23% after treatment in the Pg-pos placebo subgroup and decreased from 46% to 11% in the Pg-pos test subgroup (p0.005). In contrast, the changes in the proportions of sites with a probing pocket depth 5 mm in the Pg-neg placebo and Pg-neg test subgroup were similar, from 43% at baseline to 18% after treatment versus 40% to 12%, respectively. Conclusions: This study has shown that systemic usage of metronidazole and amoxicillin, when used in conjunction with initial periodontal treatment in adult periodontitis patients, achieves significantly better clinical and microbiological results than initial periodontal treatment alone. Moreover, this research suggests that especially patients diagnosed with P. gingivalis benefit from antibiotic treatment. Zusammenfassung Zielsetzung: Das Ziel dieser placebokontrollierten Doppelblindstudie mit parallelen Gruppen war es, die zusätzlichen Effekte der systemischen Gabe von Amoxicillin und Metronidazol bei Patienten mit Erwachsenenparodontitis zu untersuchen, bei denen auch eine supra- und subgingivale Instrumentierung durchgeführt worden war. Material und Methoden: 49 Patienten mit einer generalisierten schweren Erwachsenenparodontitis nahmen an der Studie teil. Zufällige Zuweisung der Therapien führte zu 26 Patienten in der Placebo-Gruppe (P) mit einem mittleren Alter von 40 und 23 Patienten in der Test-Gruppe (T) mit einem mittleren Alter von 45 Jahren. Klinische Messungen und mikrobiologische Untersuchungen wurden zu Beginn der Therapie sowie 3 Monate nach parodontaler Initialbehandlung mit zusätzlicher Placebo- bzw. Antibiotikagabe durchgeführt. Nachdem alle Zähne mit pathologisch vertieften Taschen subgingival instrumentiert worden waren, erhielten die Patienten eine kodierte Studienmedikation, die entweder aus 375 mg Amoxicillin und 250 mg Metronidazol oder identisch aussehenden Placebotabletten bestand, die die Patienten für 7 Tage alle 8 Stunden einnehmen sollten. Ergebnisse: Zu Beginn der Studie bestand kein statistisch signifikanter Unterschied zwischen den Versuchsgruppen hinsichtlich klinischer Parameter. Nicht für den Plaque Index, aber für Sondierungsblutung, Sondierungstiefen (ST) und klinische Attachmentlevel (PAL) kam es in der T-Gruppe zu signifikant stärkeren Veränderungen im Vergleich zur P-Gruppe. Die stärkste ST-Reduktion bzw. die größten Attachmentgewinne wurden bei Stellen gefunden, die initial ST 7 mm aufgewiesen hatten: P-Gruppe: ST=2.5 mm, PAL=1.5 mm; T-Gruppe: ST=3.2 mm, PAL=2.0 mm. Für keines der untersuchten Parodontalpathogene wurde eine signifikante Reduktion in der P-Gruppe beobachtet, während sich in der T-Gruppe eine signifikante Reduktion für Porphyromonas gingivalis, Bacteroides forsythus und Prevotella intermedia ergab. Nach Therapie ergab sich ein statistisch signifikanter Unterschied zwischen T- und P-Gruppe hinsichtlich Persistenz von P. gingivalis, B. forsythus und Peptostreptococcus micros. Entsprechend dem initialen mikrobiologischen Status für P. gingivalis wurden 4 Untergruppen gebildet: P. gingivalis positive (Pg+) oder (Pg,) Patienten in der T-bzw. P-Gruppe. Der Unterschied zwischen Pg+ und Pg, Patienten war besonders groß hinsichtlich der Veränderung des %-Anteils der Stellen mit ST5 mm. Dieser verringerte sich in der Pg+ P-Untergruppe von 45% auf 23% und in der Pg+ T-Untergruppe von 46% auf 11% (p0.005). Im Unterschied dazu war die Reduktion des Anteils der ST 5 mm in der Pg, P- und T-Untergruppen gleich: P-Gruppe: 43% auf 18%; T-Gruppe von 40% auf 12%. Schlußfolgerungen: Die systemische Gabe von Amoxicillin und Metronidazol zusätzlich zu subgingivaler Instrumentierung bei Patienten mit Erwachsenenparodontitis führt zu signifikant günstigeren klinischen und mikrobiologischen Ergebnissen als die konventionelle Therapie allein. Insbesondere Patienten mit P. gingivalis scheinen von dieser unterstützenden antibiotischen Therapie zu profitieren. Résumé Le but de cette étude parallèle en double aveugle était d'évaluer les effets supplémentaires apportés par l'administration d'amoxicilline et de metronidazole dans un groupe de patients atteints de parodontite de l'adulte qui ont reçu également un débridement supra et sous gingival. 49 patients présentant un diagnostic de parodontite généralisée sévère participèrent à l'étude. La composition des groupes sélectionnés au hasard, était de 26 patients dans le groupe placebo (P) avec un âge moyen de 40 ans et 23 patients dans le groupe test (T) avec une moyenne d'âge de 45 ans. Des mesures cliniques et des prélèvements microbiologiques étaient réalisés initialement et 3 mois après la fin de la thérapeutique parodontale initiale complétée par un placebo ou un traitement antibiotique. Les patients recevaient des médicaments codés pour l'étude de 375 mg amoxicilline combiné avec 250 mg de metronidazol ou des comprimés placebo identiques, toutes les 8 heures pendant les 7 jours suivants. Initalement, aucune différence statistiquement significative entre les groupes n'était observée, pour aucun des paramètres cliniques. En dehors de la plaque, il y avait une modification plus élevée significative pour le saignement, la profondeur de poche au sondage (PPD) et le niveau clinique d'attache (CAL) dans le groupe T, par rapport au groupe P, après traitement. La plus grande réduction pour PPD était observée pour les sites ayant une profondeur de poche au sondage intiale>ou égale à 7 mm, 2.5 mm dans le groupe P et 3.2 mm dans le groupe T. L'amélioration du CAL était plus prononcée pour la catégorie >ou égale à 7 mm et allait jusqu'à 1.5 et 2.0 mm dans les groupes P et T, respectivement. Aucune diminution significative n'était trouvée pour le nombre de patients positifs pour n'importe quelle espèce test dans le groupe P. Le nomber de patients positifs pour Porphyromonas gingivalis, Bacteroides forsythus et Prevotella intermedia dans le groupe T présentait une diminution significative. Après thérapeutique, il y avait une différence significative entre les groupe P et T, en ce qui concerne le nombre de patients positifs pour P. gingivalis, B. forsythus et Peptostreptococcus micros. 4-sous groupes furent créés sur la base de l'état microbiologique pour les patients positifs àP. gingivalis (Pg-pos), et négatifs (Pg-neg), dans les groupes P et T. La différence de réduction de PPD entre les patients Pg-pos et Pg-neg était particulièrement évidente en ce qui concernait les changements en % de sites présentant une profondeur de poche au sondage >ou égale à 5 mm. Ce % diminuait de 45% initialement à 23% après traitement dans le sous-groupe Pg-pos placebo et de 46% à 11% dans le sous-groupe Pg-pos test (p<0.005). A l'inverse, les changements observés dans les proportions de sites avec une profondeur de poche au sondage >5 mm dans les sous-groupes Pg-neg placebo et Pg-neg test étaient similaires, de 43% initialement à 18% après traitement contre 40% à 12% respectivement. En conclusion, cette étude a montré que l'utilisation systèmique de metronidazole et d'amoxicilline, lorsqu'elle est utilisée en complément du traitement parodontal initial chez des patients atteints de parodontite de l'adulte, donne, de façon significative, de meilleurs résultats cliniques et microbiologiques qu'un traitement parodontal initial seul. De plus, cette recherche suggère que les patients porteurs du P. gingivalis bénéficient particulièrement d'un traitement antibiotique. [source]

Naltrexone Is Associated With Reduced Drinking by Alcohol Dependent Patients Receiving Antidepressants for Mood and Anxiety Symptoms: Results From VA Cooperative Study No. 425, "Naltrexone in the Treatment of Alcoholism"

ALCOHOLISM, Issue 1 2008
John H. Krystal
Background:, It is not clear whether naltrexone is effective in reducing alcohol consumption among patients with clinically significant mood symptoms and whether naltrexone favorably interacts with antidepressant medications when they are co-prescribed. Methods:, This study reflects a secondary analysis of the first 13 weeks of VA CSP #425, a study that evaluated the efficacy of naltrexone 50 mg/d in 627 alcohol dependent military veterans receiving Twelve Step Facilitation therapy at 20 VA Medical Centers. This study included patients with comorbid mood and anxiety disorders, providing they did not need treatment for these comorbid conditions at the time of study entry. Sixty patients developed sufficiently severe mood symptoms while on study medication that they required antidepressant treatment. This analysis evaluated whether the efficacy of naltrexone and placebo was influenced by the prescription of antidepressant medications to some study patients for their mood and anxiety symptoms. Results:, In patients randomized to placebo (n = 209), prescription of antidepressants was associated with a significantly higher percentage of drinking days (lsmean = 24.4, se = 4.85 vs. lsmean = 12.9, se = 1.69, p = 0.02). Although the group of patients receiving naltrexone (n = 418) was larger than the group assigned to placebo, there were no significant differences in drinking-related outcomes in the groups who did or did not receive antidepressants (lsmean = 11.5, se = 1.18 vs. lsmean = 12.9, se = 1.69, p = 0.47). Among the group of patients receiving antidepressants, naltrexone prescription was associated with a reduction in the percent drinking days compared to placebo [lsmean = 10.1, se = 3.47 vs. lsmean = 24.4, se = 4.85, F(1,556) = 5.84, p = 0.02]. Conclusions:, Further investigation will be needed to determine whether naltrexone is efficacious among depressed alcohol dependent patients and whether naltrexone and antidepressant medications show interactive efficacy for treating alcohol dependence. [source]

Effectiveness and safety of a prevention-of-flare-progression strategy with pimecrolimus cream 1% in the management of paediatric atopic dermatitis

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 11 2008
B Sigurgeirsson
Abstract Objective, This study was performed to investigate the efficacy and safety of a prevention-of-flare-progression strategy with pimecrolimus cream 1% in children and adolescents with atopic dermatitis (AD). Methods, A 26-week multi-centre, randomized, double-blind, vehicle-controlled study was conducted in 521 patients aged 2,17 years, with a history of mild or moderate AD, who were clear/almost clear of disease before randomization to pimecrolimus cream 1% (n = 256) or vehicle cream (n = 265). Twice-daily treatment with study medication was started at the first signs and/or symptoms of recurring AD. If, despite the application of study medication for at least 3 days, AD worsened (as confirmed by the investigator), treatment with a moderately potent topical corticosteroid (TCS) was allowed in both groups. The primary efficacy end point was the number of days on study without TCS use for a flare. Results, The mean number of TCS-free days was significantly higher (P < 0.0001) in the pimecrolimus cream 1% group (160.2 days) than in the control group (137.7 days). On average, patients on pimecrolimus cream 1% experienced 50% fewer flares requiring TCSs (0.84) than patients on vehicle cream (1.68) (P < 0.0001). Patients on pimecrolimus cream 1% also had fewer unscheduled visits (87) than patients on vehicle cream (246). Conclusions, In children and adolescents with a history of mild or moderate AD but free/almost free of signs or symptoms of the disease, early treatment of subsequent AD exacerbations with pimecrolimus cream 1% prevented progression to flares requiring TCS, leading to fewer unscheduled visits and reducing corticosteroid exposure. [source]

Equivalence of hydroxyethyl starch HES 130/0.

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2003
HES 200/0.
Background:, Hydroxyethyl starch solutions (HES) are increasingly used for the compensation of surgical blood loss. The objective of this clinical trial was to compare a novel 6% HES 130/0.4 solution with a favourable pharmacological profile and a standard 6% HES 200/0.5 solution for maintenance of haemodynamic stability in major gynaecological surgery. Methods:, Sixty female patients aged 18,80 years undergoing major gynaecological surgery with indication for perioperative colloidal volume replacement were enrolled in this prospective, randomized double-blinded clinical study. The administration of study medication was dependent on individual requirements to maintain haemodynamic stability. The amount of study medication required from induction of anaesthesia until 6 h postoperatively served as the primary investigative parameter. Results:, The two one-sided test procedure by Westlake demonstrated equivalence of mean infused volumes between HES 130/0.4 and HES 200/0.5 during the study period (1224 ± 544 ml and 1389 ± 610 ml, respectively, P < 0.05). Perioperatively, haemodynamics did not differ significantly between treatment groups. While none of the mean values of coagulation parameters shifted outside the normal range, the degree of haemodilution revealed reduced haematocrit values in HES 200/0.5 treated patients at 6 h postoperatively (P < 0.05). Moreover, prothrombin time (PT) was higher and consequently international normalized ratio (INR) was lower at the same time point for patients who received HES 130/0.4 (P < 0.05). Conclusion:, This clinical trial demonstrated therapeutic equivalence of this novel low-substituted HES 130/0.4 solution and a standard HES 200/0.5 solution for perioperative volume replacement. Moreover, both HES preparations were equally well-tolerated and safe. [source]

(204) Rofecoxib Was More Effective than Codeine with Acetaminophen in the Treatment of Acute Pain

PAIN MEDICINE, Issue 3 2001
David J. Chang
Rofecoxib (VIOXX®) is a selective inhibitor of cyclo-oxygenase-2 and is indicated for the treatment of acute pain. Prior acute pain studies showed similar analgesic efficacy of rofecoxib 50 mg compared with analgesics doses of non-selective NSAIDs. We performed a randomized, double-blind trial to evaluate the efficacy and safety of rofecoxib, a standard fixed formulation of codeine with acetaminophen, and placebo in the treatment of acute pain. Three-hundred ninety-three patients with moderate or severe pain after surgical extraction of at least two 3rd molars were randomized to receive a single dose of rofecoxib 50 mg (n = 182), codeine 60 mg with acetaminophen 600 mg (n = 180), or placebo (n = 31). Efficacy was assessed at 11 pre-specified time points after dosing by pain relief and pain intensity scores. Patient global assessment of study medication was also performed. Baseline characteristics were similar among the groups. The mean age was 21 years; 69.0% were female; and 78.6% had a pain intensity score of "moderate." For the primary endpoint, total pain relief over 6 hours, rofecoxib was more effective than codeine/acetaminophen (p < 0.001) and placebo (p < 0.001). Proportion of patients who rated the study medication as good, very good, or excellent at 6 hours was 64.6% on rofecoxib, 36.4% on codeine/acetaminophen, and 10.3% on placebo (rofecoxib> codeine/acetaminophen; p < 0.001). The time to rescue medication was longer for rofecoxib compared to codeine/acetaminophen (p < 0.001). More patients on codeine/acetaminophen experienced clinical adverse events than rofecoxib (p < 0.05). Patients receiving codeine/acetaminophen versus rofecoxib had higher incidences of nausea (25.0% vs 6.0%; p < 0.001) and vomiting (18.3% vs 3.8%; p < 0.001). In this study, rofecoxib had superior efficacy and gastrointestinal safety compared to codeine/acetaminophen, which provides support for the use of rofecoxib as an alternative option to opioid analgesics in the treatment of acute post-surgical pain. [source]

Randomized Controlled Trial of Tacrolimus Versus Microemulsified Cyclosporin (TMC) in Liver Transplantation: Poststudy Surveillance to 3 Years

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2007
J. G. O'Grady
The 1-year results of the tacrolimus versus microemulsified cyclosporin (TMC) study found a benefit with tacrolimus immunosuppression after primary liver transplants in adults with respect to freedom from graft loss and immunological failure. The integrity of the randomization process was preserved for a further 2 years for poststudy surveillance. The data after 3 years confirms the significant difference between tacrolimus and cyclosporin with tacrolimus less likely to meet the composite primary endpoint (log rank p = 0.01; relative risk 0.75; 95% CI 0.60,0.95; p = 0.016). However, freedom from death or retransplantation no longer achieves statistical significance (relative risk 0.79; 95% CI 0.62,1.02; p = 0.065). A total of 62.1% of patients randomized to tacrolimus were alive at 3 years with their original graft and still on their allocated study medication, as compared with only 41.6% in the cyclosporin limb (p < 0.001). No difference was detected between tacrolimus and cyclosporin in hepatitis-C-positive patients with the available data. The TMC study confirms after 3 years of follow-up the benefits of tacrolimus-based immunosuppression over cyclosporin using C0 monitoring. [source]

Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis,

ANNALS OF NEUROLOGY, Issue 2 2009
Sanne Piepers MD
Objective To determine whether valproic acid (VPA), a histone deacetylase inhibitor that showed antioxidative and antiapoptotic properties and reduced glutamate toxicity in preclinical studies, is safe and effective in amyotrophic lateral sclerosis (ALS) using a sequential trial design. Methods Between April 2005 and January 2007, 163 ALS patients received VPA 1,500mg or placebo daily. Primary end point was survival. Secondary outcome measure was decline of functional status measured by the revised ALS Functional Rating Scale. Analysis was by intention to treat and according to a sequential trial design. This trial was registered with ClinicalTrials.gov (number NCT00136110). Results VPA did not affect survival (cumulative survival probability of 0.72 in the VPA group [standard error (SE), 0.06] vs 0.88 in the placebo group [SE, 0.04] at 12 months, and 0.59 in the VPA group [SE, 0.07] vs 0.68 in the placebo group [SE, 0.08] at 16 months) or the rate of decline of functional status. VPA intake did not cause serious adverse reactions. Interpretation Our finding that VPA, at a dose used in epilepsy, does not show a beneficial effect on survival or disease progression in patients with ALS has implications for future trials with histone deacetylase inhibitors in ALS and other neurodegenerative diseases. The use of a sequential trial design allowed inclusion of only half the number of patients required for a classic trial design and prevented patients from unnecessarily continuing potentially harmful study medication. Ann Neurol 2009;66:227,234 [source]

Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: A double-blind, randomized, placebo-controlled trial

ARTHRITIS & RHEUMATISM, Issue 5 2007
Henrike van Dongen
Objective To determine whether patients with undifferentiated arthritis (UA; inflammatory, nontraumatic arthritis that cannot be diagnosed using current classification criteria) benefit from treatment with methotrexate (MTX). Methods The PRObable rheumatoid arthritis: Methotrexate versus Placebo Treatment (PROMPT) study was a double-blind, placebo-controlled, randomized, multicenter trial involving 110 patients with UA who fulfilled the American College of Rheumatology (ACR) 1958 criteria for probable RA. Treatment started with MTX (15 mg/week) or placebo tablets, and every 3 months the dosage was increased if the Disease Activity Score was >2.4. After 12 months, the study medication was tapered and discontinued. Patients were followed up for 30 months. When a patient fulfilled the ACR criteria for RA (primary end point), the study medication was changed to MTX. Joint damage was scored on radiographs of the hands and feet. Results In 22 of the 55 patients (40%) in the MTX group, UA progressed to RA compared with 29 of 55 patients (53%) in the placebo group. However, in the MTX group, patients fulfilled the ACR criteria for RA at a later time point than in the placebo group (P = 0.04), and fewer patients showed radiographic progression over 18 months (P = 0.046). Conclusion This study provides evidence for the efficacy of MTX treatment in postponing the diagnosis of RA, as defined by the ACR 1987 criteria, and retarding radiographic joint damage in UA patients. [source]

The effect of therapeutic glucocorticoids on the adrenal response in a randomized controlled trial in patients with rheumatoid arthritis,

ARTHRITIS & RHEUMATISM, Issue 5 2006
John R. Kirwan
Objective To measure the effect of low-dose systemic glucocorticoid treatment on the adrenal response to adrenocorticotropic hormone (ACTH) in patients with rheumatoid arthritis (RA). Methods Patients with RA who took part in a randomized double-blind placebo-controlled trial of budesonide (3 mg/day and 9 mg/day) and prednisolone (7.5 mg/day) underwent a short (60-minute) test with injection of ACTH (tetracosactide hexaacetate) at baseline and the day after completing the 3-month treatment program. Plasma cortisol measurements at baseline and 3 months were compared within and between the treatment groups. Individual patients were classified as normal responders to ACTH or as abnormal responders if changes were >2 SD below the pretreatment value in the entire group of study patients. Results Short tests with ACTH injection were performed on 139 patients before beginning the study medication and on 134 patients after cessation of the medication. There were no changes in the placebo group. Mean plasma cortisol levels following treatment were reduced in all active treatment groups. In addition, mean values were significantly reduced for the 30-minute and 60-minute responses to ACTH. The maximum reduction (35%) occurred in the prednisolone group at 60 minutes. Following treatment, 34% of patients taking budesonide 9 mg and 46% of those taking prednisolone 7.5 mg failed to reach the normal maximum cortisol response to ACTH. Four patients failed to achieve the normal percentage increase in cortisol levels, but only 1 patient failed to meet both criteria. Conclusion Low doses of a glucocorticoid resulted in depression of baseline and ACTH-stimulated cortisol levels after 12 weeks of therapy. Although the responsiveness of the hypothalamic,pituitary,adrenal axis in individual patients generally remained within the normal range, these changes should be investigated further. [source]

Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: Results of a two-year, randomized, double-blind, placebo-controlled trial

ARTHRITIS & RHEUMATISM, Issue 5 2002
James R. O'Dell
Objective To compare the efficacy of combination therapy with methotrexate (MTX) and hydroxychloroquine (HCQ), MTX and sulfasalazine (SSZ), and MTX, HCQ, and SSZ in patients with rheumatoid arthritis (RA). Methods RA patients (n = 171) who had not previously been treated with combinations of the study medications were randomized to receive 1 of the 3 treatment combinations in this 2-year, double-blind, placebo-controlled protocol. HCQ was given at a dosage of 200 mg twice a day. The dosage of MTX was accelerated from 7.5 mg/week to 17.5 mg/week in all patients who were not in remission. Similarly, the dosage of SSZ was escalated from 500 mg twice a day to 1 gm twice a day in patients who were not in remission. The primary end point of the study was the percentage of patients who had a 20% response to therapy according to the American College of Rheumatology (ACR) criteria at 2 years. Results Intent-to-treat analysis revealed that patients receiving the triple combination responded best, with 78% achieving an ACR 20% response at 2 years, compared with 60% of those treated with MTX and HCQ (P = 0.05) and 49% of those treated with MTX and SSZ (P = 0.002). Similar trends were seen for the ACR 50% response, with 55%, 40%, and 29% of patients in the 3 treatment groups, respectively, achieving these results at 2 years (P = 0.005 for the triple combination group versus the MTX and SSZ group). All combination treatments were well-tolerated. Fourteen patients (evenly distributed among the 3 groups) withdrew from the protocol because of symptoms that were potentially related to the study medication. Conclusion The triple combination of MTX, SSZ, and HCQ is well-tolerated, and its efficacy is superior to that of the double combination of MTX and SSZ and is marginally superior to that of the double combination of MTX and HCQ. [source]

The role of Lactobacillus casei rhamnosus Lcr35 in restoring the normal vaginal flora after antibiotic treatment of bacterial vaginosis

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2008
L Petricevic
Objective, To evaluate the efficacy of additional topical Lactobacillus casei rhamnosus (Lcr35) subsequent to antibiotic treatment of bacterial vaginosis (BV) to restore the normal vaginal flora. Study design, Single-centre, randomised, observerblinded study. Setting, Population-based study in Vienna over 1 year. Sample, 190 women were enrolled in the study. Methods, Women with Nugent scores between 7 and 10 on initial vaginal swab were randomised to the one of two groups. All women were treated with standard antibiotic therapy for 7 days. Only women in the intervention group received vaginal capsules containing 109 colony-forming units of live Lcr35 for 7 days after antibiotic treatment. Final vaginal swabs for Nugent scoring were taken 4 weeks after the last administration of the study medication. Main outcome measures, The primary efficacy variable was a change in the Nugent score between the baseline and the end of the study of at least 5 grades in each individual woman. Results, Sixty-nine of the 83 women (83%) in the intervention group and 31 of the 88 women (35%) in the control group showed a reduction of the Nugent score by at least 5 grades. The difference in the number of women with improvement was highly significant (P < 0.001). The median difference in Nugent scores between initial and final swabs was 6.61 in the intervention group and 4.13 in the control group (P < 0.001). Conclusion, Our data show that the restoration of the vaginal flora after antibiotic treatment of BV can be significantly enhanced by exogenously applied lactobacilli. [source]

Olanzapine versus Droperidol for the Treatment of Primary Headache in the Emergency Department

ACADEMIC EMERGENCY MEDICINE, Issue 9 2008
Chandler H. Hill MD
Abstract Objectives:, The objective was to determine if there is a difference in pain relief or frequency and severity of side effects in emergency department (ED) patients with primary headache treated with either intramuscular (IM) olanzapine or IM droperidol. Methods:, This was a prospective, randomized nonblinded clinical trial of adult ED patients undergoing treatment for suspected primary headache. Consenting patients were randomized to receive either droperidol 5 mg IM or olanzapine 10 mg IM. Prior to receiving treatment, patients were asked to complete a 100-mm visual analog scale (VAS) describing their pain and a 4-point verbal rating scale (VRS) describing their pain as none, mild, moderate, or severe. Patients also completed a 100-mm VAS describing their level of nausea. Pain and nausea measurements were repeated 30 and 60 minutes after medication administration. Patients also completed the Barnes Akathisia Scale (BAS) 30 and 60 minutes after medication administration. Descriptive statistics were used as appropriate. Pain relief was compared both in terms of the decrease in VAS scores and in the proportion of patients who reported moderate or severe pain whose report later changed to mild or no pain. Results:, One-hundred patients were enrolled; 13 were withdrawn before administration of the study medication, 8 in the droperidol group and 5 in the olanzapine group, leaving 87 patients for analysis. Forty-two patients received droperidol and 45 received olanzapine. In the droperidol group, 35/40 (87.5%) patients who had reported moderate or severe pain at baseline reported mild or no pain at 60 minutes. In the olanzapine group, 38/44 (86.4%) reported this change (p = 0.89). The mean percent change from baseline VAS pain score at 60 minutes was ,37% (95% CI = ,84% to 11%) for droperidol and ,37% (95% CI = ,64% to 10%) for olanzapine (p = 0.30). The mean percent change from baseline for the VAS nausea score was ,59% (95% CI = ,70% to ,47%) for droperidol and ,64% (95% CI = ,77% to ,51%) for olanzapine (p = 0.83). There was no difference in any report of akathisia by the BAS between the groups (p = 0.63). Conclusions:, Both olanzapine and droperidol are effective treatments for primary headaches in the ED. No significant differences were found between the medications in terms of pain relief, antiemetic effect, or akathisia. Olanzapine may be used to treat primary headache and it is an effective alternative to droperidol. [source]

Knowledge of Treatment Group Does Not Bias Assessment of Time to Seizure in an Animal Model of Cocaine Poisoning

ACADEMIC EMERGENCY MEDICINE, Issue 7 2010
Kennon J. Heard MD
ACADEMIC EMERGENCY MEDICINE 2010; 17:E75,E77 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives:, Blinded outcome assessment decreases bias in human clinical trials. The necessity of blinded outcome assessment on animal studies is unknown. The authors determined the effect of knowledge of treatment group on assessment of time to seizure in an animal model of cocaine poisoning. Methods:, Four subjects observed 20 animal experiments where all animals were administered a high dose of cocaine and placebo. For each experiment, two of the observers were told the animal had been treated with placebo and two were told the animal had been treated with a medication expected to delay the onset of seizures. Each observer recorded the time from cocaine administration to onset of seizure. The median time to seizure was compared between observers told the animal received placebo and those told the animal received active treatment. Results:, Seizures were reported by all subjects in 12 animals and by no subjects in five animals, and there was disagreement in three animals. The reported median time to seizure was similar for observers told that the animals were treated with placebo and those told they were treated with study medication. Conclusions:, It is feasible to determine whether unblinded assessments are biased in an animal study. Knowledge of treatment group did not bias the assessment of time to seizure in this animal model. [source]

Isosorbide dinitrate inhibits platelet adhesion and aggregation in nonthrombolyzed patients with acute myocardial infarction

CLINICAL CARDIOLOGY, Issue 11 2000
Jadwiga Gebalska M.D., Ph.D.
Abstract Background: Apart from their vasodilatator properties, nitrates have been shown to inhibit platelet aggregation. The effects of nitrates on platelet adhesion have not been studied. Nonselected patients with acute myocardial infarction (AMI) have been suggested to gain no benefit from administration of nitrates. However, the importance of nitrates may be greater in a subgroup of nonthrombolyzed patients with AMI. Hypothesis: Isosorbide dinitrate (ISDN) decreases platelet adhesion and aggregation in nonthrombolyzed patients with AMI. Methods: Consecutive 48 men with AMI, not eligible for thrombolytic therapy because of late presentation (> 12 h), were prospectively randomized 2:1 to double-blind ISDN (mean dose 2.4 ± 0.9 mg/h) (n = 33) or placebo (0.9% sodium chloride) (n = 15) infusion. All patients received aspirin. Blood samples were taken at baseline (no study medication) and 3 h into ISDN or placebo infusion. Platelet adhesion to collagen was measured in the ethylene diamine tetraacetic acid (EDTA)-platelet rich plasma by recording changes in light transmission with an optical aggregometer. Platelet aggregation was measured using the Born's method. Results: Isosorbide dinitrate significantly decreased both platelet adhesion and aggregation. No effect was seen in the placebo group. Conclusions: In patients with AMI who do not receive thrombolytic therapy, ISDN effectively inhibits platelet adhesion and aggregation. These effects of nitrates may be of therapeutic and prognostic significance in this group of patients. [source]

Comparison of Topical Anesthetics and Lubricants Prior to Urethral Catheterization in Males: A Randomized Controlled Trial

ACADEMIC EMERGENCY MEDICINE, Issue 6 2004
John Siderias DO
Abstract Although male urethral catheterization in the emergency department (ED) is both common and painful, few studies have evaluated the use of topical anesthesia prior to catheterization. Objectives: To determine whether pretreatment of the urethra with topical lidocaine reduces the pain associated with urethral catheterization. Methods:This was a prospective, double-blind, randomized clinical trial of 36 alert, cooperative male adult patients requiring urethral catheterization, without allergies to the study medications or contraindications to their use, from a suburban university-based ED. Patients in the experimental group had topical lidocaine 2% gel injected in their urethras, whereas control patients received intraurethral lubrication only. Standardized catheterization with a no. 16 Foley was performed followed by pain assessment. The primary outcome measured was pain of catheterization on a 100-mm visual analog scale. Other outcomes included ease of insertion and procedural bleeding. Results: The authors evaluated 36 patients evenly distributed between study groups. Mean age was 62 years (range 22,85). Compared with controls, patients pretreated with lidocaine experienced significantly less pain of catheterization (38 ± 28 mm vs. 58 ± 30 mm; mean difference 20 mm; 95% confidence interval [95% CI] = 0.4 to 32; p = 0.04) and less pain of injection (23 ± 17 mm vs. 40 ± 25 mm; mean difference 17 mm; 95% CI = 3 to 32 mm; p = 0.02). There were no differences in the number of attempts and incidence of adverse events between the groups. Conclusions: Use of topical lidocaine gel reduces the pain associated with male urethral catheterization in comparison with topical lubricants only. [source]

The Impact of Catecholamines on Defibrillation Threshold in Patients with Implanted Cardioverter Defibrillators

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 11 2005
JAMES S. KALUS
Objectives: To determine the effect of physiologic catecholamine concentrations on the defibrillation threshold (DFT) in patients with implanted cardioverter defibrillators. Background: DFT is the minimum energy delivered by an implanted cardioverter defibrillator that successfully converts ventricular fibrillation. DFT testing is performed under conscious sedation. Since activities of daily living enhance sympathetic tone substantially over these nadir levels, it is important to explore the impact of catecholamines on DFT. Methods: In this double-blind study, we determined DFT by the step-down method. Patients (n = 50) were stratified by beta-blocker use and then randomized to a 7-minute infusion of epinephrine, norepinephrine, or placebo. After study infusion, DFT testing was repeated. Changes in DFT with different study medications were compared. Subgroup analyses of the effects of catecholamines on DFT, based on beta-blocker use, were also performed. Results: Norepinephrine reduced DFT from baseline measurements by 22.6% (P = 0.008). Neither epinephrine nor placebo impacted DFT (P = 0.999, P = 0.317, respectively). In the subgroup analyses, DFT was reduced with norepinephrine regardless of beta-blocker use, while epinephrine reduced DFT among those receiving beta-blockers. No change in DFT was observed in either of the placebo subgroups. Conclusions: Elevation of plasma norepinephrine concentrations reduces the DFT, while elevations in epinephrine had no effect. Norepinephrine seems to reduce DFT regardless of beta-blocker therapy but epinephrine's effects are beta-blocker dependent. [source]

Randomized Double-blind Placebo Controlled Crossover Study of Acetaminophen, Ibuprofen, Acetaminophen/Hydrocodone, and Placebo for the Relief of Pain From a Standard Painful Stimulus

ACADEMIC EMERGENCY MEDICINE, Issue 9 2009
James R. Miner MD
Abstract Objectives:, The objective was to compare subjects' change in perceived acute pain from an identical painful stimulus after receiving three separate, commonly used pain medications and placebo. Methods:, This was an institutional review board,approved, randomized, double-blind crossover study of healthy human volunteers. Subjects received 1000 mg of acetaminophen, 800 mg of ibuprofen, the combination of 650 mg of acetaminophen with 10 mg of hydrocodone, or placebo (800 mg of lactose) in a randomized order over four separate occasions each 1 week apart. Prior to receiving the drug on each study day, subjects placed their nondominant hand in a bath of 0°C water for 45 seconds. The bath was divided into two sections; the larger was the reservoir of cooled water monitored at 0°C, and the other half was filled from constant overflow. Water drained from the overflow section into the cooling unit and was then pumped up into the base of the reservoir through a diffusion grid. Subjects completed a 100-mm visual analog scale (VAS) representing perceived pain during the exposure. The cold water exposure and VAS were repeated 1 hour after receiving the study drug, and then subjects were observed for side effects for 4 hours. Data were compared using descriptive statistics, 95% confidence intervals (CIs), and repeated-measures analysis of variance (ANOVA). Results:, Twenty-five subjects were enrolled. The mean VAS preexposure was 56.9 mm (±15.1 mm; range = 5 to 92 mm). The mean decrease in VAS after receiving the study drug for acetaminophen was 10.2% (95% CI = ,1.4 to 20.4), for ibuprofen was ,6.6% (95% CI = ,16.5 to 3.20), for acetaminophen/hydrocodone was 9.5% (95% CI = 1.4 to 20.4), and for placebo was ,6.9% (95% CI = ,15.2 to 1.4). The range in change in pain scores for all agents was ,91.3% to 57.6%. Mild side effects (nausea, dizziness, or somnolence) were reported in 11 subjects (44%) after receiving acetaminophen/hydrocodone; no other side effects were reported. Conclusions:, There was a wide range of changes in pain scores from this identical painful stimulus after receiving the study medications. Acetaminophen and acetaminophen/hydrocodone resulted in a similar decrease in pain (10.2 and 9.5%), while ibuprofen and placebo had a similar lack of effect (,6.6 and ,6.9%). Forty-four percent of subjects receiving acetaminophen/hydrocodone reported mild side effects; no other side effects were seen. In this noninflammatory pain model, the VAS is not able to distinguish differences in pain relief between acetaminophen and acetaminophen/hydrocodone or ibuprofen and placebo. [source]

Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: Results of a two-year, randomized, double-blind, placebo-controlled trial