Pharmacokinetics of rosuvastatin when coadministered with rifampicin in healthy males: a randomized, single-blind, placebo-controlled, crossover study

BACKGROUND: Rifampicin (rifampin) has been reported to have drug-drug interaction with several 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors due to its ability to influence the function of cytochrome P450 enzymes or transporters. Rosuvastatin is absorbed from the blood into the liver by organic anion transporting polypeptide 1B1 and is then metabolized by cytochrome P450 isozyme 2C9. OBJECTIVE: The aim of this study was to examine the effect of rifampicin on the pharmacokinetics of rosuvastatin. METHODS: This was a randomized, single-blind, placebo-controlled, crossover study, with a 4-week washout period. Healthy male volunteers were treated for 6 days with rifampicin 450 mg or placebo once daily. On days 0 and 7, a single oral dose of rosuvastatin 20 mg was administered. Plasma concentrations of rosuvastatin were measured by liquid chromatography-tandem mass spectrometry. RESULTS: A total of 18 healthy Chinese male volunteers (mean [SD] age, 21 [2] years; weight, 62 [7] kg; and body mass index was within the normal range [22.0-24.0 kg/m2]) were included in the study. The plasma concentrations of rosuvastatin were not significantly changed by pretreatment with rifampicin, although there was considerable interindividual variation in the plasma concentration of rosuvastatin. During the rifampicin phase, the AUC(0-infinity) of rosuvastatin decreased in 10 and increased in 8 of the 18 subjects. In 3 of the 8 subjects, the AUC(0-infinity) of rosuvastatin during the rifampicin phase was > or = 50% compared with the placebo phase; and only 1 increased by more than double (183%). Of those in the decreased group (n = 10), the AUC(0-infinity) values were decreased by >50% in 3 subjects and were not decreased by >30% in the remaining 7 subjects. The mean AUC(0-infinity) of rosuvastatin was 95.8% (110.4 [41.4] vs 115.3 [30.9] ng/mL . h(-1)) of the corresponding value during the placebo phase (P = NS). There was no statistically significant difference in either C(max) or t(1/2) of rosuvastatin between the rifampicin-treated and placebo groups (18.5 [6.3] vs 16.5 [5.5] ng/mL; 12.8 [3.0] vs 13.3 [2.8] h). The oral clearance of rosuvastatin was not significantly affected by rifampicin pretreatment either (0.4 [0.3] vs 0.3 [0.2] L . h; P = 0.072). CONCLUSION: The pharmacokinetics of rosuvastatin were not significantly changed by coadministration of rifampicin in this small group of healthy male volunteers.     

Needle acupuncture in tension-type headache: a randomized, placebo-controlled study

A study with needle acupuncture was performed in tension-type headache employing a new placebo acupuncture METHOD: Sixty-nine patients (mean age 48.1 years, SD = 14.1) fulfilling the International Headache Society criteria for tension-type headache were randomly assigned to verum or placebo condition. No significant differences between placebo and verum with respect to visual analogue scale and frequency of headache attacks could be observed immediately, 6 weeks and 5 months after the end of treatment. There was a significant but weak improvement in quality of life parameters (clinical global impressions, Nottingham Health Profile) after verum treatment. In decision tree analyses, the changes in clinical global impressions and headache frequency depended significantly on primary headache frequency with a limit value of 24.5 days headache per month. High values in the von Zerssen Depression Score resulted in high mean visual analogue scale values.     

Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study

The aim of this study was to evaluate the efficacy and tolerability of topiramate for the prevention of chronic migraine in a randomized, double-blind, placebo-controlled trial. Chronic migraine is a common form of disabling headache presenting in headache subspecialty practice. Preventive treatments are essential for chronic migraine management, although there are few or no controlled empirical trial data on their use in this patient population. Topiramate is approved for the prophylaxis of migraine headache in adults. Patients (18-65 years) who experienced chronic migraine (defined as > or =15 monthly migraine days) for > or =3 months prior to trial entry and had > or =12 migraine days during the 4-week (28-day) baseline phase were randomized to topiramate or placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly) to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200 mg/day, according to patient need. Existing migraine preventive treatments, except for antiepileptic drugs, were continued throughout the trial. The primary efficacy measure was the change in number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population, which consisted of all patients who received at least one dose of study medication and had one outcome assessment during the double-blind phase. Health-related quality of life was evaluated with the Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was assessed by adverse event (AE) reports and early trial discontinuations. Eighty-two patients were screened. Thirty-two patients in the intent-to-treat population (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most patients (78%) met the definition for acute medication overuse at baseline. The mean duration of treatment was 100 and 92 days for topiramate- and placebo-treated patients, respectively. Study completion rates for topiramate- and placebo-treated patients were 75% and 52%, respectively. Topiramate significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7, P < 0.05). No significant intergroup differences were found for MSQ and HIT-6. MIDAS showed improvement with the topiramate treatment group (P = 0.042 vs. placebo). Treatment emergent adverse events were reported by 75% of topiramate-treated patients (37%, placebo). The most common AEs, paraesthesia, nausea, dizziness, dyspepsia, fatigue, anorexia and disturbance in attention, were reported by 53%, 9%, 6%, 6%, 6%, 6% and 6% of topiramate-treated patients, respectively, vs. 7%, 0%, 0%, 0%, 0%, 4% and 4% of placebo-treated patients. This randomized, double-blind, placebo-controlled trial demonstrates that topiramate is effective and reasonably well tolerated when used for the preventive treatment of chronic migraine, even in the presence of medication overuse.     

Factors that influence the applicability of sham needle in acupuncture trials: two randomized, single-blind, crossover trials with acupuncture-experienced subjects

OBJECTIVES: In recent years the retractable type of sham needle has been anticipated to be a possible solution for masking patients in acupuncture research. However, this needle has been intended mainly for acupuncture-na?ve subjects. The authors' goal in this study was to assess the validity of the retractable type of sham needle. METHODS: The authors conducted two randomized, single-blind, crossover trials with acupuncture-experienced subjects. Different acupuncture points were used in each trial (a LI-4 trial and a BL-23 trial). The subjects received two sessions of different stimulations in each trial. A Park Sham Needle was used in one session, a genuine acupuncture needle in the other. RESULTS: In the LI-4 trial, all of the 21 subjects (100%) felt penetration with the genuine needle, but only 7 of the 20 subjects (35%) felt a similar sensation with the sham needle (P=0.0002). Fifteen of the 21 subjects (71%) felt a dull sensation with the genuine needle, but only 4 of the 20 subjects (20%) felt a similar sensation with the sham needle (P=0.01). In the BL-23 trial, 14 of the 20 subjects (70%) felt penetration with the genuine needle and 10 of the 20 subjects (50%) felt "penetration" with the sham needle (P=0.39). Eight of the 20 subjects (40%) felt a dull sensation with the genuine needle and 2 of the 20 subjects (10%) did with the sham needle (P=0.109). CONCLUSIONS: Potential factors that influence the applicability of "placebo" needling include not only inter-tester variability but also the patient's knowledge and experience of acupuncture, acupuncture point selection, the visual impact of needling, and so on.     

Sumatriptan-naproxen and butalbital: a double-blind, placebo-controlled crossover study

Objectives.— The primary objective was to compare the efficacy of a sumatriptan and naproxen combination medication (SumaRT/Nap—85 mg sumatriptan and 500 mg naproxen sodium), a butalbital‐containing combination medication (BCM—50 mg butalbital, 325 mg acetaminophen, 40 mg caffeine), and placebo when used to treat moderate to severe migraine headache pain in subjects who used BCMs in the past. Background.— Despite the lack of Food and Drug Administration approval and the absence of placebo‐controlled trials to demonstrate efficacy, butalbital‐containing medications are among the most commonly prescribed acute migraine treatments in the United States. Butalbital‐containing medications are associated with serious and undesirable side effects, and have been linked to the chronification of migraine and development of medication‐overuse headaches. This study compares the relative efficacy, safety, and tolerability of a fixed dose SumaRT/Nap versus a BCM and placebo. Methods.— Enrolled subjects were required to have treated at least 1 migraine with a butalbital medication in the past. Enrolled subjects treated 3 moderate to severe migraines using each of the 3 study treatments once in a randomized sequence. The primary endpoint compared SumaRT/Nap versus BCM for sustained pain freedom at 2‐24 hours without the use of any rescue medication. This study combines data from 2 identical outpatient, randomized, multicenter, double‐blind, double‐dummy, 3 attack crossover studies in adult migraineurs (International Classification of Headache Disorders, 2nd edition). Results.— A total of 442 subjects treated at least 1 attack with study medication. The majority of the treated subjects were female (88%) with a mean age 43 years, who reported that their migraines had a severe impact on their lives (78% with Headache Impact Test‐6 of >59). At screening, 88% of subjects reported current butalbital use; 68% had used butalbital for more than 6 weeks; and 82% reported satisfaction with butalbital. Across treatment groups, 28‐29% of subjects took study medication within 15 minutes of migraine onset, 34‐37% of subjects took study medication >15 minutes to 2 hours after onset, and 32‐36% of subjects took study medication more than 2 hours after onset. This study did not detect a difference at the nominal 0.05 level in percent sustained pain‐free between SumaRT/Nap (8%), BCM (6%), and placebo (3%). SumaRT/Nap was superior to BCM for pain free at 2, 4, 6, 8, 24, 48 hours (P ≤ .044); pain relief (mild or no pain) at 2, 4, 6, 8, 24, 48 hours (P ≤ .01); sustained pain relief 2‐24 hours (P < .001); migraine free (pain free with no nausea, photophobia, or phonophobia) at 4, 6, 8, 24, 48 hours (P ≤ .046); and complete symptom free (migraine free with no neck/sinus pain) at 4, 6, 8, 48 hours (P ≤ .031). Adverse event incidence was similar for all treatments (10%, 12%, and 9% for placebo, SumaRT/Nap, and BCM, respectively). Nausea was the most frequent adverse event (2%, 2%, and <1% for placebo, SumaRT/Nap, and BCM, respectively). Five serious adverse events were reported by 3 subjects: viral meningitis and colon neoplasm (placebo); chest pain and hypertension 17 days postdose (SumaRT/Nap); and breast cancer (BCM). Investigators judged no serious adverse events related to study medication. Conclusions.— This study primarily included subjects whose migraines significantly impacted their lives. Before the study, these subjects used butalbital‐containing medications as part of their current migraine treatment regimen and were satisfied with it, suggesting they were butalbital responders who had found a workable treatment strategy for themselves. When treated with SumaRT/Nap versus BCM in this study, however, a significant proportion of subjects reported better treatment outcomes for themselves for both migraine pain and associated symptoms. Use of SumaRT/Nap was also associated with less rescue medication use and a longer time before use of rescue medication compared with both BCM and placebo.     

Irbesartan reduces the albumin excretion rate in microalbuminuric type 2 diabetic patients independently of hypertension: a randomized double-blind placebo-controlled crossover study

OBJECTIVE: ACE inhibitors delay the progression from incipient to overt diabetic nephropathy and reduce albumin excretion rate (AER), independently of blood pressure. Angiotensin II type 1 receptor antagonists produce similar effects on microalbuminuria and mean arterial pressure. The aim of this study was to evaluate the effect of irbesartan on microalbuminuria and blood pressure in hypertensive and normotensive type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Sixty-four microalbuminuric hypertensive (group 1) and 60 microalbuminuric normotensive (group 2) type 2 diabetic male patients, matched for age, BMI, HbA(1c), and diabetes duration, were enrolled. Each group was divided into two subgroups receiving either irbesartan (150 mg b.i.d. orally) or placebo for 60 days. After 15 days of washout, irbesartan was given to the subgroups who had received the placebo, and vice versa, in a randomized double-blind crossover study. RESULTS: In microalbuminuric hypertensive type 2 diabetic subjects, irbesartan reduced 24-h mean systolic and diastolic pressure and AER. In microalbuminuric normotensive type 2 diabetic patients, irbesartan reduced AER. CONCLUSIONS: These results indicate the beneficial effects of irbesartan on AER in type 2 diabetic subjects, independently of its antihypertensive effects.     

Effects of a concomitant single oral dose of rifampicin on the pharmacokinetics of pravastatin in a two-phase,randomized, single-blind,placebo-controlled,crossover study in healthy Chinese male subjects

Background: Pravastatin is a potent cholesterol-lowering agent; ~34% of an oral dose of pravastatin is eliminated unchanged through biliary and urinary excretion. Rifampicin is an inducer of drug metabolism enzymes, and it affects the activities of transporters involved in pravastatin disposition. Drug-drug interaction between rifampicin and pravastatin is possible because of the effects of rifampicin on the activities of drug transporters.Objective: This study was designed to investigate the effects of a single oral dose of rifampicin on the pharmacokinetics of pravastatin.Methods: Healthy Chinese male volunteers were recruited for this 2-phase, single-blind, placebo-controlled, crossover study. The subjects were randomly divided into 2 groups to receive either rifam-picin or placebo concomitantly with pravastatin. All subjects received a 20-mg oral dose of pravastatin on days 1 and 9, separated by an 8-day washout period. Subjects in the rifampicin group received a single 600-mg oral dose of rifampicin on day 1 and placebo on day 9; those in the placebo group received placebo on day 1 and a single 600-mg oral dose of rifampicin on day 9. High-performance liquid chromatography-tandem mass spectrometry was used to determine plasma concentrations of pravastatin for up to 12 hours after administration.Results: Twelve volunteers participated in the study (6 per group). The mean (SD) age of the subjects was 20 (2) years (range, 18–25 years). The mean height of the subjects was 174 (4) cm (range, 168–180 cm), and the mean weight was 69.2 (3.7) kg (range, 65–77 kg). The mean pharmacokinetic parameters for pravastatin that changed significantly were as follows (rifampicin and placebo groups, respectively): C_max (315.7 [227.2] and 115.8 [77.5] ng · mL^?1 [P = 0.009]); AUC_0–12 (604.8 [73.3] and 259.0 [133.4] ng · h · mL^?1 [P < 0.001]); AUC_0–∞) (623.3 [248.8] and 275.1 [58.5] ng · h · mL^?1 [P < 0.001]); and apparent oral clearance (CL/F) (0.52 [0.18] and 1.30 [0.58] L · h^?1 · kg^?1 [P < 0.001]). No significant changes in the T_max or t_½ of pravastatin were observed. All subjects tolerated pravastatin well during both phases of the study, with or without coadministration of rifampicin. None of the subjects withdrew from the study.Conclusion: Coadministration of a single oral dose of rifampicin significantly increased the plasma concentration of pravastatin in this group of healthy Chinese male subjects.     

Pharmacokinetic and pharmacodynamic effects of midodrine on blood pressure, the autonomic nervous system, and plasma natriuretic peptides: a prospective, randomized, single-blind, two-period, crossover, placebo-controlled study

BACKGROUND: Midodrine is an alpha-agonist prodrug of desglymidodrine (DGM) that has been reported to be of clinical benefit in patients with neurocardiogenic syncope. Its effects may be mediated not only by its hypertensive properties but also by its neurohumoral influences independent of blood pressure (BP). OBJECTIVE: The present study aimed to simultaneously characterize the effects of midodrine on BP, plasma catecholamines, plasma atrial natriuretic peptide (ANP), and power spectral analysis of heart rate (HR) in healthy volunteers. METHODS: This was a prospective, randomized, single-blind, 2-period, crossover study in which a single, oral, 5-mg dose of midodrine was compared with placebo. The washout period between midodrine and placebo was 1 week. The study parameters included plasma DGM (as measured by high-performance liquid chromatography [HPLC]); systolic and diastolic BP (as measured with an oscillometric monitor); HR; plasma catecholamines (measured by HPLC); plasma ANP, also known as venous return (measured by a radio-immunoassay); and low- and high-frequency HR variation (calculated from computerized 5-minute electrocardiographic recordings). All study parameters were measured simultaneously 12 times just before and over a period of 8 hours after drug administration. RESULTS: Fifteen healthy nonsmoking male subjects (14 white, 1 black; mean [SD] age, 28.6 [4.7] years; weight, 74.5 [16.4] kg; seated BP, 109.9 [9.0]/73.6 [9.5] mm Hg; seated HR, 63.8 [8.4] bpm) were randomized. No significant effects of midodrine on BP were observed. At Cmax, midodrine decreased norepinephrine from 188.4 (30.6) to 162.5 (29.8) pg/mL (P = 0.011) and HR from 57.2 (7.3) to 54.9 (6.6) bpm (P = 0.022). A significant correlation was found between DGM concentration and HR ( varphi -0.61; P = 0.014). A DGM-related increase in plasma ANP (+29.6 [90.0] fmoL/mL) was observed. CONCLUSION: This study in healthy male volunteers found that midodrine has sympatholytic influences that are independent of BP but related to augmented venous return.     

Sumatriptan and corneal reflexes in headache-free migraine patients: a randomized and placebo-controlled crossover study

A temporary sensitization of central trigeminal neurones in migraine patients during acute attacks has been described in previous studies using the electrically evoked nociceptive blink reflex. The cornea is innervated by small myelinated A-delta and unmyelinated C-fibres only. Stimulation with air puffs activates peripheral nociceptors and allows the investigation of peripheral trigeminal nerve structures. Our objective was to investigate whether corneal reflex examinations with air puff stimulation detect abnormalities in migraineurs during their pain-free interval and if the corneal reflex may be modulated by the administration of an oral triptan. After validation of the nociceptive air puff technique by investigating the corneal reflexes before and after a local anaesthesia of the cornea, we recorded corneal reflexes in 25 migraineurs during their pain-free period and 25 healthy controls before and after the oral administration of 100 mg sumatriptan in a randomized, placebo-controlled, crossover study. Baseline response areas under the curve (AUCs) and latencies of the R2 components of the corneal reflexes did not show any significant differences between patients and controls. Patients did not show any significant differences regarding their headache and non-headache side. The use of an oral triptan had no significant influence on latencies or AUCs in both patients and controls. Our data suggest that there is no facilitation of the trigeminal system in the headache-free interval among patients with migraine. The stable corneal reflexes after the oral administration of 100 mg sumatriptan suggest that there was no inhibition of the trigeminal system, both in patients during their headache-free period and in healthy controls.     

Bioequivalence of two commercial preparations of trimethoprim/sulfamethoxazole: a randomized, single-dose, single-blind, crossover trial

BACKGROUND: Trimethoprim/sulfamethoxazole (TMP/SMX) is a combination of 2 antimicrobial agents that act synergistically, sequentially blocking 2 chemical reactions essential to bacterial survival. TMP/SMX is effective against organisms that are resistant to its separate components. OBJECTIVE: The objective of this study was to compare the bioavailability of 2 commercial preparations of T:MP/SMX 40/200 mg per 5-ml, oral suspension, used in Mexico for the treatment of bacterial infection. METHODS: This study used a single-dose, randomized,single-blind, 2 x 2 crossover (2 dosing periods x 2 treatments) design to compare the 2 preparations. Healthy male volunteers aged 18 to 55 years received the trial and reference preparations in randomized sequence, under fasting conditions, with a 7-day washout period between dosing periods. Each preparation was administered as a single-dose 10-ml, oral suspension delivering 80 tng of TMP and 400 mg of SMX (equivalent to 2 doses of TMP/SMX 40/200 rig per 5 ml.). Pharmacokinetic (PK) parameters of C(max) AUC(0-t), and AUC(0-1) were determined for each component of each preparation. Schuirmann's unilateral double t test was performed. Null hypotheses indicating bioin-equivalence (P > 0.05) were rejected. Bioequivalence was determined if the quotient of the parameters of C(max), AUC(0-t), and AUC(0-infinity) were between 80% and 125%, at a power of 80% (alpha > 0.08). RESULT: Twenty-three of the 24 enrolled subjects completed the study. The subjects were all Hispanic, the mean (SD) age was 25 (6) years, and the mean (SD) body mass index was 22.54 (2.59) kg/m(2). Plasma concentration-time values of TMP and SMX were similar with both preparations. The null hypotheses of Schuirmann's unilateral double t test were rejected, and results of the analyses of the PK parameters obtained 95% CIs within the predetermined range of bioequivalence (80%-125 degrees 10). The trial and reference preparations were statistically interchangeable and appeared to be bioequivalent. CONCLUSIONS: Based on similar PK profiles and statistical analyses, the trial and reference preparations were statistically interchangeable and appeared to be bioequivalent in this population of 23 healthy male volunteers in Mexico.     

Pharmacology and tolerability of a single dose of exenatide in adolescent patients with type 2 diabetes mellitus being treated with metformin: A randomized,placebo-controlled,single-blind,dose-escalation,crossover study

Objective: This study assessed the pharmacokinetics, pharmacodynamics, and tolerability of single doses of exenatide in adolescent patients with type 2 diabetes mellitus (T2DM).Methods: This was a randomized, single-blind, dose-escalation, crossover study in adolescent (age 10–16 years) patients with T2DM who were being treated with diet and exercise or a stable dose of metformin, a sulfonylurea, or a combination of metformin and a sulfonylurea for at least 3 months before screening. Eligible patients were allocated to receive single subcutaneous doses of exenatide 2.5 μg, exenatide 5 μg, and placebo, each followed by a standardized meal, on 3 separate days (maximum interval between first and third doses, 5 weeks). Exenatide 2.5 μg always preceded exenatide 5 μg in each treatment sequence. The primary end points were the pharmacokinetics and safety profile of exenatide; secondary end points included postprandial plasma glucose, serum insulin, and plasma glucagon concentrations.Results: The study enrolled 13 adolescent patients with T2DM (7 females, 6 males; mean [SD] age, 15 [1] years; body mass index, 32.5 [5.0] kg/m²; glycosylated hemoglobin, 8.2% [1.5%]). After administration of exenatide 5 μg, the geometric mean (SE) exenatide AUC_0?∞ and C_max were 339.5 (39.6) pg · h/mL and 85.1 (11.5) pg/mL, respectively (n = 12). The exenatide AUC appeared to be dose dependent, although exenatide was not quantifiable in all patients at the 2.5-μg dose; after administration of exenatide 2.5-μg, the geometric mean AUC_0?∞) was 159.2 (23.1) pg · h/mL (n = 6) and the geometric mean C_max was 56.3 (10.1) pg/mL (n = 9). Both exenatide doses were associated with significant reductions in postprandialplasma glucose excursions compared with placebo (P < 0.01); the incremental mean (SE) AUC_15–360min was ?3465.6 (1587.3) mg · min/dL for exenatide 2.5 pg, ?4422.2 (2434.4) mg · min/dL for exenatide 5 μg, and 3457.4 (1615.5) mg · min/dL for placebo. The 2 exenatide doses were also associated with significant reductions in postprandial plasma glucagon concentrations compared with placebo (P < 0.01); the respective incremental mean values for AUC_15–180min were 125.5 (658.4), ?1403.8 (632.1), and 1843.1 (540.6) pg · min/mL. There were no significant differences in serum insulin concentrations between exenatide and placebo. Exenatide was generally well tolerated, with no hypoglycemic events recorded during the study.Conclusions: In these adolescent patients with T2DM, administration of single 2.5- and 5-μg doses of exenatide were associated with dose-dependent increases in plasma exenatide concentrations and improved postprandial glucose concentrations compared with placebo. Both doses appeared to be well tolerated. ClinicalTrials.gov Identifier: NCT00254254.     

Effects of acupuncture as a treatment for hyperventilation syndrome: a pilot, randomized crossover trial

BACKGROUND: Sustained and subtle hyperventilation can result in a wide variety of symptoms, leading to a chronic condition that has been termed hyperventilation syndrome (HVS). Treatment options include physiotherapy, in the form of breathing retraining (BR), but additional approaches aim to reduce the anxiety that is recognized as being a frequent component of this condition. OBJECTIVES: The aim of this study was to evaluate whether acupuncture is an appropriate treatment for HVS to reduce anxiety, and whether a crossover trial is an appropriate study design to evaluate acupuncture in this condition. DESIGN: A single-blind crossover trial was carried out comparing the effects of 4 weeks (30 minutes twice weekly) acupuncture and BR on patients with HVS. SUBJECTS: Ten (10) patients diagnosed with HVS were recruited to the trial and randomized into two groups. Both groups received acupuncture and BR with a washout period of 1 week. OUTCOME MEASURES: The primary outcome measure used was the Hospital Anxiety and Depression (HAD) Scale. Other outcome measures used were the Nijmegen questionnaire and Medical Research Council Dyspnea scale. RESULTS: The results showed statistically significant treatment differences between acupuncture and breathing retraining, in favor of acupuncture. Reductions were found in the HAD A (anxiety) (p = 0.02) and Nijmegen (symptoms) (p = 0.03) scores. There was no statistical evidence of any carryover effects. However, when graphically examining individual anxiety scores, in those who received acupuncture first, there was a reduction in anxiety levels which persisted through the washout period, suggesting that there may have been some carryover effect from this treatment. CONCLUSIONS: This study suggests that acupuncture may be beneficial in the management of HVS in terms of reducing anxiety levels and symptom severity. However, there may be some carryover effect, after acupuncture treatment, which went undetected because the small sample size. This preliminary study provides the basis for a larger, sufficiently powered and methodologically sound trial.     

Laser acupuncture in children with headache: a double-blind, randomized, bicenter, placebo-controlled trial

To investigate whether laser acupuncture is efficacious in children with headache and if active laser treatment is superior to placebo laser treatment in a prospective, randomized, double-blind, placebo-controlled trial of low level laser acupuncture in 43 children (mean age (SD) 12.3 (+/-2.6) years) with headache (either migraine (22 patients) or tension type headache (21 patients)). Patients were randomized to receive a course of 4 treatments over 4 weeks with either active or placebo laser. The treatment was highly individualised based on criteria of Traditional Chinese medicine (TCM). The primary outcome measure was a difference in numbers of headache days between baseline and the 4 months after randomization. Secondary outcome measures included a change in headache severity using a 10 cm Visual Analogue Scale (VAS) for pain and a change in monthly hours with headache. Measurements were taken during 4 weeks before randomization (baseline), at weeks 1-4, 5-8, 9-12 and 13-16 from baseline. The mean number of headaches per month decreased significantly by 6.4 days in the treated group (p<0.001) and by 1.0 days in the placebo group (p=0.22). Secondary outcome measures headache severity and monthly hours with headache decreased as well significantly at all time points compared to baseline (p<0.001) and were as well significantly lower than those of the placebo group at all time points (p<0.001). We conclude that laser acupuncture can provide a significant benefit for children with headache with active laser treatment being clearly more effective than placebo laser treatment.     

A randomized double-blind placebo-controlled crossover study of subcutaneous sumatriptan in general practice

Objective. To evaluate the therapeutic response to sumatriptan in the acute migraine attack. Material and methods. Two hundred and thirty migraineurs diagnosed by their general practitioners in accordance with their usual practice were included in the study. The patients treated two migraine attacks at home by subcutaneous injection of sumatriptan or placebo for the first attack and the alternative medication, i.e. placebo or sumatriptan, for the second attack (crossover). Following treatment, a neurology resident interviewed and examined the patients, Results. When sumatriptan was compared to placebo, significantly more of the 209 evaluable patients reported headache relief at I h (56% vs 8%, p < 0.001) and 2 h (62% vs 15%, p < 0.001) after the first injection. Resolution of nausea, photophobia, and phonophobia was significantly more common in patients on sumatriptan than in those on placebo ( p < 0.001 for all comparisons). The adverse events were usually transient and of mild or moderate severity; however, three patients withdrew due to adverse events. Ninety-five percent of patients evaluated by a neurology resident met the IHS criteria for migraine. Conclusion. In general practice, sumatriptan taken subcutaneously using an autoinjector at home was an effective and well tolerated acute treatment for migraine.     

Manual laryngeal fixation facilitates tracheal intubation during chest compression: A randomized crossover manikin study

PurposeWe compared the effectiveness of external manual laryngeal fixation (MLF) for tracheal intubation during chest compression using three laryngoscopes, the Macintosh laryngoscope (McL), McGRATH® MAC (McGRGTH), and Pentax-AWS Airwayscope® (AWS) on an adult manikin.MethodsSixteen novice doctors and 15 experienced anesthesiologists performed tracheal intubation during chest compression on an adult manikin using the McL, McGRATH, and AWS with or without MLF. Tracheal intubation time and intubation success rate were measured.ResultsIn the AWS trial, all novice and experienced doctors successfully secured the airway with or without MLF during chest compression. In McL and McGRATH trials, MLF significantly improved the rate of successful intubation during chest compression compared to without MLF for novice doctors. While intubation time did not significantly differ with or without MLF in the AWS trial, MLF significantly shortened intubation time in McL and McGRATH trials for both novice and experienced doctors.ConclusionThese findings suggest that MLF facilitates tracheal intubation with the McL and McGRATH during chest compression.     

Preserved response to diuretics in rosiglitazone-treated subjects with insulin resistance: a randomized double-blind placebo-controlled crossover study

Thiazolidinediones (TZDs) are associated with fluid retention that has been suggested to be resistant to treatment with loop diuretics. This resistance is thought to be caused by upregulation of renal epithelial sodium channels (ENaCs). In this study, we tested whether these mechanisms are of clinical significance. We conducted a well-controlled study in 12 insulin-resistant nondiabetic participants, who received treatment for 9 weeks with either rosiglitazone at a dosage of 4?mg b.i.d. or placebo. The aim of the study was to investigate whether upregulation of ENaCs by rosiglitazone reduces furosemide's natriuretic response and enhances the response to the ENaC inhibitor amiloride. The natriuretic response to furosemide and amiloride and the amount of α-ENaC in urinary exosomes were quantified. Rosiglitazone neither reduced furosemide-induced natriuresis nor changed furosemide's concentration-effect curve. Furthermore, rosiglitazone did not change either amiloride-induced natriuresis nor the amount of urinary α-ENaC. This study challenges previous findings regarding TZD-related ENaC upregulation and suggests that TZD-induced fluid retention should respond normally to loop diuretics.     

Single-dose intravenous tramadol for acute migraine pain in adults: a single-blind, prospective, randomized, placebo-controlled clinical trial

BACKGROUND: Tramadol, an atypical opioid, is a narcotic analgesic used for pain management. A search of the current literature found no studies examining the efficacy of intravenous tramadol on migraine pain. OBJECTIVE: The aim of this study was to investigate the efficacy and tolerability of a single dose of intravenous tramadol hydrogen chloride 100 mg in comparison with placebo in patients presenting with migraine. METHODS: Adult migraineurs admitted consecutively to the emergency department of the Kocaeli University Hospital were enrolled in this single-blind (patients), prospective, randomized, placebo-controlled clinical trial. Patients were randomized to receive a 30-minute infusion of either intravenous tramadol (n = 17; 100 mg in 100-mL saline) or placebo (n = 17; 100-mL saline). Pain response was defined as a decrease of visual analogue scale (VAS) (0-100 mm) score to <50% of the pretreatment (baseline) value and a decrease of 4-point verbal scale (FPVS) score (0 = none, 1 = mild, 2 = moderate, 3 = severe) to mild or none. Pain-free response was defined as a decrease of both VAS and FPVS scores to 0. Pain was assessed at baseline and at 30 minutes and 1 hour after treatment completion. Migraine symptoms (eg, photophobia, phonophobia, nausea, vomiting) and adverse events (AEs) were assessed at the same time. A follow-up was also conducted by phone 24 hours after treatment. RESULTS: Forty-four migraineurs were screened and 34 (28 women and 6 men; mean [SD] age, 39.5 [10.4] years; all were white) were enrolled in the study. Each group contained 11 patients with severe pain and 6 patients with moderate pain at baseline FPVS. At the end of 1 hour, pain response was reported by significantly more patients in the tramadol group than in the placebo group (12 [70.6%] vs 6 [35.3%]; P = 0.040). Pain-free response was reported by 5 (29.4%) patients in the tramadol group and 2 (11.8%) patients in the placebo group, although the difference was not statistically significant. Symptoms associated with migraine were also relieved in all patients reporting pain response. No AEs were observed. However, at the 24-hour follow-up, 1 patient in the tramadol group reported transient blurred vision and dizziness within the day of infusion. Headache recurrence was reported by 2 (16.7%) of the 12 patients with pain response in the tramadol group and 1 (16.7%) of 6 patients with pain response in the placebo group. CONCLUSIONS: Intravenous tramadol appeared to be more effective than placebo in pain response rate at the end of the first hour. The slow infusion of tramadol 100 mg in 100-mL saline solution was well tolerated in this group of adult migraineurs.     

Electronic pain diary: a randomized crossover study

Electronic pain diaries and palm-top computers have become increasingly important in clinical research and practice. In a randomized crossover trial, 24 patients suffering from chronic cancer and non-cancer pain completed both the electronic and the paper version of a pain diary based on the Minimal Documentation System (MIDOS) for pain and symptom assessment. This includes daily assessment of pain on an 11-point numeric rating scale and weekly documentation of a short quality-of-life questionnaire. Of 52 patients seen during the baseline phase of this study, 28 could be enrolled and only 24 patients completed both diary versions. The other patients were either physically or intellectually unable to use a palm-top computer or unwilling to participate in this study. After a total of four weeks, patient satisfaction was remarkably higher for the electronic palm-top version, even though a high number of patients were lacking experience in the use of computers. Obvious differences were observed between the versions. There were higher numbers of missing values in the electronic data, and patients tended to retrospectively fabricate information in the paper version. No significant difference between the electronic and paper diary could be found assessing the documented pain and symptom intensity. The electronic diary was used more frequently and patients said its use supported a more regular pharmacotherapy. We conclude that the use of electronic pain diaries is a valid and feasible method for documenting patients' pain perception, though some patients may not be able to operate such a diary version. Electronic palm-top pain diaries provide a high degree of patient satisfaction and can ease data collection for clinical research and practice.