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PubMed1979

Hydrallazine with beta-blocker and diuretic in the treatment of hypertension. A double-blind crossover study.

Thirty-seven hypertensive patients were treated with cyclopenthiazide, oxprenolol and hydrallazine. Blood pressure was controlled in 31 patients and a subsequent double-blind crossover study in 27 patients comparing hydrallazine with placebo confirmed the efficacy of hydrallazine in combination with diuretic and beta-adrenergic-blocking agent. The combination was effective in patients with renal hypertension and renal impairment. No adverse effects on renal function were observed. Patients who were slow acetylators had significantly better blood pressure control and more side effects. In view of the frequency of hydrallazine related side effects, prior institution of beta-adrenergic blocking drugs is desirable.

Adult↗
PubMed1983

Failure of oral inosiplex treatment of recurrent herpes simplex virus infections.

A compound, a mixture of acedoben, dimepranol, and inosine (inosiplex) was used to treat recurrent local herpes simplex virus (HSV) infections in a double-blind placebo-controlled crossover study. Altogether, 58 patients with a history of frequently recurrent HSV infections were examined. Eighteen selected patients participated in the drug trial. Ten patients received both inosiplex and placebo, three received only inosiplex, and five received only the placebo. Three patients received both placebo and inosiplex twice. No substantial differences between the treatments with inosiplex or placebo could be seen in the frequency of occurrence or healing of the local lesions, nor in the results of these patients' immunologic studies. An evident placebo effect was observed, since only 15 (26%) of the 58 subjects examined continued to have an often relapsing form of the disease when followed up regularly.

Administration, Oral↗
PubMed1990

A randomised double-blind placebo-controlled crossover add-on trial of lamotrigine in patients with treatment-resistant partial seizures.

Efficacy and safety of lamotrigine (LTG) as add-on therapy was assessed in a randomised double-blind placebo-controlled trial of this drug in 23 adult patients with refractory partial seizures. Fifteen patients showed an improvement on LTG treatment, with a greater than 50% decrease in total seizure count in 7 patients. Fourteen patients experienced fewer simple and complex partial seizures, with 8 patients benefitting by more than a 50% decrease in seizure frequency. The drug was well tolerated over the 2 month treatment period. The plasma concentration of concomitant antiepileptic drugs remained unchanged. No haematological or chemical abnormalities were noted.

Adolescent↗
PubMed2000

Inhaled steroids for episodic viral wheeze of childhood.

BACKGROUND: Recurrent episodic wheeze in association with viral upper respiratory tract infection (URTI) is a specific clinical illness distinct from persistent atopic asthma. OBJECTIVES: The objective of this review was to identify whether corticosteroid treatment, given episodically or daily, is beneficial to children with viral episodic wheeze. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) of corticosteroid treatment versus placebo in children under 17 years of age who suffer from 'episodic viral wheeze', which is defined by wheeze in association with coryzal symptoms with minimal or no intercurrent lower respiratory tract symptoms. DATA COLLECTION AND ANALYSIS: Trial quality was assessed independently by two reviewers. Study authors were contacted for missing information. Studies were categorised according to whether treatment was given episodically or daily (maintenance). The primary outcome was episodes requiring oral corticosteroids. Secondary outcomes addressed episode severity, frequency and duration and parental treatment preference. MAIN RESULTS: Five randomised controlled trials in children with a history of mild episodic viral wheeze were identified. Most of the children had previously required no or infrequent oral corticosteroids and had very infrequent hospital admissions. There were three studies of preschool children given episodic high dose inhaled corticosteroid (1.6 - 2.25 mg per day), two using a crossover and one a parallel design. The two studies of maintenance corticosteroid (400 micrograms per day) were parallel in design, one of pre-school children the other of children aged 7 -9 years. Results from the two cross-over studies of episodic high dose inhaled corticosteroids showed a reduced requirement for oral corticosteroids (Relative risk (RR)=0.53, 95% CI: 0.27, 1.04). In these 2 double blind studies, this treatment was preferred by the children's parents over placebo (RR=0.64, 95% CI: 0.48,0.87). Maintenance low dose inhaled corticosteroids did not show any clear reduction over placebo in the proportion of episodes requiring oral corticosteroids (N=2 trials, RR=0.82, 95%CI: 0.23,2.90) or in those requiring hospital admission (N=1 trial, RR=0.21, 95% CI: 0.01,4.11). REVIEWER'S CONCLUSIONS: Episodic high dose inhaled corticosteroids provide a partially effective strategy for the treatment of mild episodic viral wheeze of childhood. There is no current evidence to favour maintenance low dose inhaled corticosteroids in the prevention and management of episodic mild viral induced wheeze.

Administration, Inhalation↗
PubMed1997

Analysis of sleep EEG microstructure in subchronic paroxetine treatment of healthy subjects.

Paroxetine is a selective and potent serotonin reuptake inhibitor and its efficacy for the treatment of depression has been proven. Under acute and subchronical treatment regimens, disturbances of the regular sleep pattern are a reported side effect of the drug. The present study was therefore performed to investigate the impact of subchronic treatment with the selective serotonin reuptake inhibitor paroxetine on the microstructure of the sleep EEG. The study especially addressed the question of subchronic effects of paroxetine medication (30 mg/day) in eight healthy male volunteers in a double blind, placebo-controlled crossover design. Conventional sleep EEG parameters and a spectral power analysis for different sleep stages after 4 weeks of treatment were computed. Additionally, the correlation of certain EEG rhythms across the night was calculated in order to detect subtle dynamical EEG alterations, not necessarily obvious when regarding conventional EEG analysis. Although we could not detect any alterations of the spectral power values in certain frequency bands either during NREM nor during REM sleep following subchronic paroxetine medication, the dynamical EEG attributes across the night revealed a significant enhancement of the correlation between certain EEG rhythms mainly during NREM sleep.

Adult↗
PubMed1982

Topical glyceryl trinitrate as adjunctive treatment in Raynaud's disease.

The effects of topical glyceryl trinitrate in Raynaud's disease were compared with those of placebo in a double-blind, crossover trial in 17 patients with bilateral Raynaud's disease and an associated collagen disease, who were receiving oral sympatholytic agents at the maximum levels they could tolerate. 1% glyceryl trinitrate ointment or a placebo of lanolin was applied to one hand only for 6 weeks, then patients changed to the other preparation for 6 weeks. The results were evaluated every 2 weeks. The frequency of attacks, severity of attacks, and size of ulcers in the treated hand were significantly lower when the patients were using glyceryl trinitrate ointment than when they were using placebo. The treatment of Raynaud's disease may be improved by using topical glyceryl trinitrate ointment as an adjunct to a basic regimen of oral sympatholytic agents. Glyceryl trinitrate ointment may obviate the need for more aggressive treatment, such as intraarterial reserpine, in selected patients.

Administration, Topical↗
PubMed2004

Gabapentin is a first line drug for the treatment of neuropathic pain in spinal cord injury.

STUDY DESIGN: Prospective, randomized, double blind, placebo-controlled, crossover clinical trial. OBJECTIVES: To determine the efficacy of gabapentin in the treatment of neuropathic pain related to spinal cord injury. SUMMARY OF BACKGROUND DATA: Neuropathic pain is initiated or caused by a primary lesion or dysfunction in the nervous system. Neuropathic pain associated with spinal cord injury is quite refractory, and current treatments are not effective. Gabapentin, an anticonvulsant, has become the first choice in the treatment of neuropathic pain. The place of gabapentin in the treatment of spinal cord injury-related neuropathic pain was questioned in only a few recent reports; however, they are retrospectively designed, nonstandardized, and uncontrolled studies, or involve a very small series of patients using less than optimum doses. METHODS: A total of 18-week study period included a 4-week medication/placebo titration period. This was followed by a 4-week stable dosing period when the patients continued to receive maximum tolerated doses, a 2-week washout period, then a crossover of 4 weeks of medication/placebo titration, and another 4 weeks of stable dosing period. Twenty paraplegic patients (female/male: 7/13) with complete spinal cord injury at the thoracic and lumbar level, aged between 20 and 65 years, with neuropathic pain for more than 6 months were recruited for the study. RESULTS: All patients completed the study. Gabapentin reduced the intensity as well as the frequency of pain, relieved all neuropathic pain descriptors except the itchy, sensitive, dull, and cold types, and improved the quality of life (P < 0.05). CONCLUSIONS: Gabapentin can be added to the list of first-line medications for the treatment of chronic neuropathic pain in spinal cord injury patients. It is a promising new agent and offers advantages over currently available treatments.

Acetates↗
PubMed1995

Molecular analysis of nondisjunction in Down syndrome patients with and without atrioventricular septal defects.

BACKGROUND: Congenital heart disease is common in Down syndrome patients, with atrioventricular septal defects accounting for a majority of the abnormalities. The molecular mechanisms of meiotic nondisjunction resulting in Down syndrome were studied for associations with the presence of atrioventricular septal defects. METHODS AND RESULTS: Twenty highly polymorphic chromosome 21 microsatellite markers were used to genotype two groups of patients (group 1: Down syndrome with atrioventricular septal defects, n = 43; and group 2: Down syndrome without cardiac defects, n = 51) to determine (1) the parental origin of the extra chromosome, (2) the stage of meiotic nondisjunction resulting in the trisomy, (3) the presence or absence of disomic homozygosity or heterozygosity, and (4) the degree of recombination in the nondisjoined chromosomes. The parental origin of the nondisjoined chromosome was maternal in 86.2% of the families, with no significant differences between groups. The most centromeric marker was nonreduced, indicating a meiosis I nondisjunction in 76.5% of maternally derived trisomies, and reduced, indicating a meiosis II nondisjunction in 76.9% of paternally derived trisomies, with no significant differences between groups. There were no significant differences in the proportion of reduced markers at any locus between groups. The distribution of the number of crossovers was significantly different between groups (chi 2 = 14.12, P < .001), with less recombination observed in group 1. CONCLUSIONS: In Down syndrome patients, no association was found between the presence of an atrioventricular septal defect and the parent of origin, stage of meiotic nondisjunction, or disomic homozygosity or heterozygosity. A significant association was found between the presence of an atrioventricular septal defect and reduced frequency of recombination.

Case-Control Studies↗
PubMed2005

Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy.

BACKGROUND: Vasodilatory therapy of Raynaud's phenomenon represents a difficult clinical problem because treatment often remains inefficient and may be not tolerated because of side effects. METHODS AND RESULTS: To investigate the effects of sildenafil on symptoms and capillary perfusion in patients with Raynaud's phenomenon, we performed a double-blinded, placebo-controlled, fixed-dose, crossover study in 16 patients with symptomatic secondary Raynaud's phenomenon resistant to vasodilatory therapy. Patients were treated with 50 mg sildenafil or placebo twice daily for 4 weeks. Symptoms were assessed by diary cards including a 10-point Raynaud's Condition Score. Capillary flow velocity was measured in digital nailfold capillaries by means of a laser Doppler anemometer. While taking sildenafil, the mean frequency of Raynaud attacks was significantly lower (35+/-14 versus 52+/-18, P=0.0064), the cumulative attack duration was significantly shorter (581+/-133 versus 1046+/-245 minutes, P=0.0038), and the mean Raynaud's Condition Score was significantly lower (2.2+/-0.4 versus 3.0+/-0.5, P=0.0386). Capillary blood flow velocity increased in each individual patient, and the mean capillary flow velocity of all patients more than quadrupled after treatment with sildenafil (0.53+/-0.09 versus 0.13+/-0.02 mm/s, P=0.0004). Two patients reported side effects leading to discontinuation of the study drug. CONCLUSIONS: Sildenafil is an effective and well-tolerated treatment in patients with Raynaud's phenomenon.

Adult↗
PubMed1996

Grain dust and endotoxin inhalation challenges produce similar inflammatory responses in normal subjects.

STUDY OBJECTIVE: To compare the physiologic and inflammatory response following inhalation of corn dust extract (CDE) and lipopolysaccharide (LPS) solutions in normal subjects. DESIGN: Randomized, double-blind crossover design. PARTICIPANTS: Fourteen healthy, nonatopic, nonasthmatic, never-smoking volunteers. INTERVENTIONS: On separate visits, subjects underwent a series of four inhalation challenges to LPS or CDE, each containing either a high (6 micrograms/mL) or low (0.9 microgram/mL) endotoxin concentration, and administered at equal Xolumes. RESULTS: Chest tightness, cough, dyspnea, and sputum production were experienced following both LPS and CDE exposures and with similar frequency at both high and low endotoxin concentrations. LPS and CDE inhalations caused acute declines in FEV1, and the changes in FEV1 from baseline following exposure to both inhalants were not significantly different at both high and low endotoxin concentrations. Following exposure to the high-endotoxin LPS and CDE, no consistent differences in total cell and cytokine (tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], IL-6, IL-8) concentrations were seen between exposures, although the neutrophil concentration was greater following the LPS exposure (p = 0.01). BAL cellularity and cytokine concentrations following the low-endotoxin LPS and CDE exposure revealed no differences, except for IL-1 beta, which was greater following LPS exposure (p = 0.05). The high-endotoxin LPS and CDE exposures resulted in greater increases in BAL neutrophils and cytokines in comparison to its respective low-endotoxin exposure. CONCLUSIONS: At exposure levels of endotoxin, LPS and CDE result in similar symptoms, changes in airflow, and increases in BAL inflammatory cells and mediators. Moreover, the physiologic and inflammatory response to LPS and CDE appears to be related to the exposure level of endotoxin.

Adult↗
PubMedDate not supplied

A double-blind crossover trial comparing human insulin (recombinant DNA) with animal insulins in the treatment of previously insulin-treated diabetic patients.

Ninety-four diabetic patients established on treatment with pork (N = 47) or beef insulin (N = 47) took part in a double-blind crossover trial in which 6-wk treatment periods of their animal insulin were compared with similar periods on human insulin (recombinant DNA). Six patients withdrew during the trial--in three cases for hypoglycemia while taking human insulin. In patients initially treated with beef insulin there was no significant change in the mean blood glucose, the 'M' index, the total daily insulin dose, or the frequency of hypoglycemic attacks after the change to human insulin. Home blood glucose sample values were greater before the morning and evening insulin injection on human insulin (morning: 12.8 mmol/L [beef] versus 14.2 mmol/L [human insulin] [P less than 0.05]; evening: 10.0 mmol/L versus 11.6 mmol/L [P = 0.05]). In pork insulin-treated patients greater values while on human insulin were found for mean glucose (9.0 mmol/L [pork] versus 9.7 mmol/L [human insulin], P = 0.05), 'M' index (65.0 [pork] versus 79.6 [human insulin], P less than 0.025), and total daily insulin dose (50.9 U/day [pork] versus 52.5 U/day [human insulin], P less than 0.001). The early morning glucose sample was also greater on human insulin (9.6 mmol/L [pork] versus 12.1 mmol/L [human insulin], P less than 0.001). No significant differences in either insulin antibody levels or E. coli protein antibody levels were found between either of the animal-insulin treatment periods and human insulin treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Variables associated with pathologic heart murmurs in primary care consultations].

OBJECTIVE: To assess the existence of variables associated to pathological murmurs in infancy. DESIGN: Retrospective crossover study. SETTING: Paediatrics clinic at Carrus Health Centre, Elche. PARTICIPANTS: 109 cases of children with a cardiac murmur recorded between 1987 and 1991 were studied. MEASUREMENTS AND MAIN RESULTS: The percentage of children with pathological cardiac murmurs was 10.1. An association of pathology to younger age at diagnosis (p = 0.006) and to the intensity of the murmurs (p = 0.001) was found. CONCLUSIONS: The frequency of pathological murmurs in our study is similar to that in other series consulted. The age of diagnosis and the intensity of the murmur appear to be variables associated to pathology in children, which should be borne in mind in Primary Care clinics.

Child↗
PubMed1985

Propranolol-verapamil versus propranolol-nifedipine in severe angina pectoris of effort: a randomized, double-blind, crossover study.

To compare a propranolol-verapamil with a propranolol-nifedipine combination in patients with severe angina of effort, 16 patients (11 men and 5 women, aged 56 +/- 8 years [mean +/- standard deviation]) with more than 5 episodes/week of angina and a positive exercise tolerance test despite propranolol (229 +/- 44 mg/day [range 180 to 360]) were maintained on this dose of propranolol and, in addition, received verapamil (360 mg/day) and nifedipine (60 mg/day) for 3 weeks each in a double-blind, randomized fashion. In comparison with propranolol alone, anginal frequency and nitroglycerin usage were reduced by propranolol-verapamil but not by propranolol-nifedipine. Exercise time (standard Bruce protocol) was similar for the 2 combinations (6.4 +/- 2.0 minutes with propranolol-verapamil, 6.6 +/- 2.1 minutes with propranolol-nifedipine, difference not significant), but the magnitude of ST-segment depression at peak exercise was less (p less than 0.05) during propranolol-verapamil (0.03 +/- 0.06 mV) than during propranolol alone (0.18 +/- 0.07 mV) and propranolol-nifedipine (0.08 +/- 0.07 mV). Left ventricular ejection fraction at rest was higher (p less than 0.05) with propranolol-nifedipine (0.62 +/- 0.10) than with propranolol-verapamil (0.58 +/- 0.10), but neither differed from ejection fraction at rest with propranolol alone (0.59 +/- 0.08). Ejection fraction at peak exercise was similar during all 3 periods. In 2 patients, verapamil caused weakness, lightheadedness, and severe sinus bradycardia (40 to 48 beats/min), and the dosage was reduced (blindly) to 240 mg/day, with the alleviation of bradycardia and associated symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1984

Failure of transdermal nitroglycerin to improve chronic stable angina: a randomized, placebo-controlled, double-blind, double crossover trial.

We assessed the effect of transdermal nitroglycerin (NTG-TTS), releasing 5 mg/24 hr, in 11 patients with chronic stable angina during a randomized, placebo-controlled, double-blind, double crossover trial of four 1-week periods. All patients had a positive exercise test and coronary artery disease prior to entry into the study. Efficacy was assessed weekly by anginal diaries, ambulatory ST segment recordings, and computerized exercise testing 2 to 4 hours after renewal of NTG-TTS. One patient withdrew in the first week (placebo) and was excluded from all analysis. The weekly frequency of anginal attacks was 9 +/- 11 (mean +/- SD) and 9 +/- 10 during the 2 placebo weeks and 11 +/- 14 and 9 +/- 11 during NTG-TTS; the time to 1 mm ST segment depression (seconds) was 268 +/- 178 and 303 +/- 217 with placebo and 228 +/- 221 and 285 +/- 178 with NTG-TTS; exercise duration (seconds) was 375 +/- 230 and 467 +/- 254 during placebo and was 394 +/- 233 and 412 +/- 236 during NTG-TTS. The weekly number of episodes of ST depression was 11 +/- 9 and 8 +/- 5 during placebo and 8 +/- 5 and 9 +/- 7 during NTG-TTS. Our study failed to show any consistent differences in patients treated with placebo or NTG-TTS.

Administration, Topical↗
PubMed1998

Use of the InteliSite capsule to study ranitidine absorption from various sites within the human intestinal tract.

PURPOSE: The purpose of this study was to evaluate the extent of ranitidine absorption from an externally activated drug-delivery system in two distinct regions of the intestine (jejunum and ileum) in healthy human volunteers. This investigation also was designed to evaluate the utility of the InteliSite capsule for studying regional intestinal drug absorption in humans. METHODS: The intestinal absorption of ranitidine from the jejunum and ileum was compared in eight, healthy volunteers in this open-label, two-way crossover study. In two of the eight volunteers, absorption from the colon also was studied. Subjects swallowed the capsule containing ranitidine solution (121 mg) and 100 microCi of 99mTc-DTPA. The endcap of the capsule contained 20 microCi of (111)In-DTPA. At the desired intestinal site, the capsule was activated by the application of an external RF magnetic signal (6.78 MHz operating frequency) and the ranitidine solution was released. Blood samples were collected from a forearm vein for 12 hours after capsule activation. RESULTS: The capsule released the ranitidine solution when activated in the jejunum, ileum and colon (visualized by the gamma camera). There was no difference in the extent of ranitidine absorption or ranitidine pharmacokinetics when the capsule was activated in the jejunum or ileum. CONCLUSIONS: This study demonstrates the utility of a novel, externally activated drug-delivery system to assess site-specific intestinal drug absorption in humans. Results indicate that use of the InteliSite capsule method to evaluate site-specific intestinal ranitidine absorption in humans yields data similar to that obtained previously by means of oral intubation studies.

Adult↗
PubMed1999

Oral desmopressin for nocturnal polyuria in elderly subjects: a double-blind, placebo-controlled randomized exploratory study.

OBJECTIVE: To evaluate the decrease in nocturnal diuresis, nocturnal polyuria and the safety of oral desmopressin in elderly subjects with nocturia. SUBJECTS AND METHODS: After being identified using a population-based questionnaire, subjects were included in the study if they; (i) were healthy and free from medication with possible influence on the diuresis or voiding pattern; (ii) had an increased nocturnal frequency (>/=2 nocturnal voids/night, as reported before screening); (iii) had a nocturnal urinary output of >/=0.9 mL/min; (iv) completed and responded to an initial dose-titration study. Twelve men and five women (mean age 67.7 years, sd 4.6 years) met these criteria and were treated with oral desmopressin or placebo at bedtime for 2 weeks on each medication in a randomized, double-blind, crossover design. RESULTS: Subjects treated with desmopressin had a significantly reduced nocturnal diuresis of 0.59 mL/min compared with those on placebo (95% confidence interval, CI, 0.33-0.85). The 24-h diuresis was unaffected by desmopressin treatment. Patients treated with desmopressin had fewer micturitions at night than had those on placebo (1.1 and 1.7, respectively; P<0.001; mean difference=0.59; 95% CI, 0.32-0.85). The reduction in nocturnal diuresis was dependent on the baseline level of night-time diuresis (r=0.886; r2=0.785; P<0.0001) and the nocturnal part of the baseline 24 h-diuresis (r=0.708; r2=0.502; P<0.001). After desmopressin treatment was withdrawn, diuresis returned to the levels before treatment. The time from falling asleep to first awakening was improved by 1.4 h in patients treated with desmopressin. There was no change in body weight or ankle circumference during desmopressin treatment. Overall, the treatment was well tolerated and no serious adverse events were observed. CONCLUSION: Desmopressin was effective in reducing nocturnal diuresis and nocturnal voids in polyuric elderly subjects, with no significant adverse events or inconvenience to the patient. The length of uninterrupted sleep was also improved.

Administration, Oral↗
PubMed2004

Comparison of bronchoprotective and bronchodilator effects of a single dose of formoterol delivered by hydrofluoroalkane and chlorofluorocarbon aerosols and dry powder in a double blind, placebo-controlled, crossover study.

BACKGROUND: In response to the phasing out of chlorofluorocarbon (CFC) inhalers, a metered dose hydrofluoroalkane (HFA) formulation, Modulite (Chiesi Farmaceutici S.p.A, Parma, Italy), to be delivered with a pressurized metered dose inhaler (pMDI), has been developed. Modulite is a HFA formulation technology that has been designed to provide stable and uniform dose delivery of HFA-based formulations to enable an easy transition from CFC to HFA inhalers. OBJECTIVES: The aim of this study was to compare the bronchoprotective and bronchodilator effects of a single dose of 12 microg of formoterol from the HFA Modulite inhaler with the Foradil Aerolizer (dry powder inhaler, DPI) and the Foradil CFC inhalers (Novartis Health Consumer, Basel, Switzerland). METHODS: This was a double blind, double dummy, randomized, placebo-controlled, crossover study conducted in 38 subjects with mild to moderate asthma (mean forced expiratory volume in 1 s [FEV1] 87.5% predicted). The primary endpoint was methacholine challenge provocative dose required for 20% fall in the FEV1 (PD20) 90 min post dose. Bronchodilation was assessed with spirometry (FEV1, FVC, FEF25-75) and impulse oscillometry (resistance at 5 and 20 Hz, reactance at 5 Hz and resonant frequency) over the 90 min post dose. In a subset of 12 subjects formoterol plasma levels, serum potassium and glucose were determined up to 480 min post dose. RESULTS: The three formoterol formulations demonstrated significant (P < or = 0.05) improvements in bronchoprotection compared to placebo and non-inferiority of the HFA preparation compared to the CFC and DPI preparations was demonstrated. Geometric mean PD20 values were 0.51 mg with HFA, 0.62 mg with DPI, 0.62 mg with CFC and 0.2 mg with placebo. The log transformed mean differences in PD20 doubling dose between HFA and (a) DPI was -0.28 (95% CI -0.84-0.29, P = 0.57) (b) CFC was -0.28 (95% CI -0.84-0.28, P = 0.57) and (c) placebo was 1.38 (95% CI 0.82-1.94, P < 0.001). Serum potassium, glucose and formoterol plasma profiles were comparable for the CFC, HFA and DPI devices. CONCLUSION: Our findings of similar efficacy, pharmacokinetics and systemic effects of the HFA formoterol inhaler compared to the CFC and DPI preparations supports the potential use of this novel formulation in the treatment of asthma.

Administration, Inhalation↗
PubMed2004

Safety of botulinum toxin type A: a systematic review and meta-analysis.

OBJECTIVE: To define quantitatively the safety and tolerability profile of botulinum toxin type A (BTX-A) across all common therapeutic indications. The review was limited to the evaluation of the safety profile of one preparation of BTX-A (BOTOX) because distinct formulations of BTX-A are associated with different clinical profiles, requiring separate consideration for an analysis of safety. RESEARCH DESIGN AND METHODS: We identified randomized controlled trials of BTX-A through searches of the MEDLINE, EMBASE, and Cochrane Controlled Trial databases for the years 1966-2003. Studies were double-blind, randomized, crossover, or of parallel group design. The search strategy included the terms 'botulinum toxin', 'therapeutic use', 'randomized controlled trial', 'controlled clinical trial', 'randomized clinical trial', and 'placebo controlled trial'. Only randomized controlled trials of at least 7 days duration that reported adverse events were included in the analysis. MAIN OUTCOME MEASURE: Safety was assessed by means of a meta-analysis of the number and frequency of adverse events. RESULTS: Thirty-six studies involving 2309 subjects met the inclusion criteria. These reported on 1425 subjects receiving BTX-A treatment. No study reported any severe adverse events. The meta-analysis of any mild to moderate adverse events showed a rate of roughly 25% in the BTX-A-treated group (353/1425 patients) compared with 15% in the control group (133/884 patients, p < 0.001). Focal weakness was the only adverse event that occurred significantly more often with BTX-A treatment than control. CONCLUSION: The results of this meta-analysis and experience from long-term, open-label investigations demonstrate that the formulation of BTX-A evaluated here has a favorable safety and tolerability profile across a broad spectrum of therapeutic uses.

Botulinum Toxins, Type A↗