Background Which, medication, if any, to use to prevent the headache of pediatric migraine has not been established. Methods We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment. Results A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P=0.26; topiramate vs. placebo, P=0.48; amitriptyline vs. topiramate, P=0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group had a suicide attempt. Conclusions There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events. (Funded by the National Institutes of Health; CHAMP ClinicalTrials.gov number, NCT01581281 ).
Background Whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy is uncertain. Methods We conducted a multicenter, randomized, controlled trial involving symptomatic patients 45 years of age or older with a meniscal tear and evidence of mild-to-moderate osteoarthritis on imaging. We randomly assigned 351 patients to surgery and postoperative physical therapy or to a standardized physical-therapy regimen (with the option to cross over to surgery at the discretion of the patient and surgeon). The patients were evaluated at 6 and 12 months. The primary outcome was the difference between the groups with respect to the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical-function score (ranging from 0 to 100, with higher scores indicating more severe symptoms) 6 months after randomization. Results In the intention-to-treat analysis, the mean improvement in the WOMAC score after 6 months was 20.9 points (95% confidence interval [CI], 17.9 to 23.9) in the surgical group and 18.5 (95% CI, 15.6 to 21.5) in the physical-therapy group (mean difference, 2.4 points; 95% CI, -1.8 to 6.5). At 6 months, 51 active participants in the study who were assigned to physical therapy alone (30%) had undergone surgery, and 9 patients assigned to surgery (6%) had not undergone surgery. The results at 12 months were similar to those at 6 months. The frequency of adverse events did not differ significantly between the groups. Conclusions In the intention-to-treat analysis, we did not find significant differences between the study groups in functional improvement 6 months after randomization; however, 30% of the patients who were assigned to physical therapy alone underwent surgery within 6 months. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; METEOR ClinicalTrials.gov number, NCT00597012 .).
In a random number generation task, participants are asked to generate a random sequence of numbers, most typically the digits 1 to 9. Such number sequences are not mathematically random, and both extent and type of bias allow one to characterize the brain’s “internal random number generator”. We assume that certain patterns and their variations will frequently occur in humanly generated random number sequences. Thus, we introduce a pattern-based analysis of random number sequences. Twenty healthy subjects randomly generated two sequences of 300 numbers each. Sequences were analysed to identify the patterns of numbers predominantly used by the subjects and to calculate the frequency of a specific pattern and its variations within the number sequence. This pattern analysis is based on the Damerau-Levenshtein distance, which counts the number of edit operations that are needed to convert one string into another. We built a model that predicts not only the next item in a humanly generated random number sequence based on the item’s immediate history, but also the deployment of patterns in another sequence generated by the same subject. When a history of seven items was computed, the mean correct prediction rate rose up to 27% (with an individual maximum of 46%, chance performance of 11%). Furthermore, we assumed that when predicting one subject’s sequence, predictions based on statistical information from the same subject should yield a higher success rate than predictions based on statistical information from a different subject. When provided with two sequences from the same subject and one from a different subject, an algorithm identifies the foreign sequence in up to 88% of the cases. In conclusion, the pattern-based analysis using the Levenshtein-Damarau distance is both able to predict humanly generated random number sequences and to identify person-specific information within a humanly generated random number sequence.
The description of a metabolic network in terms of elementary (flux) modes (EMs) provides an important framework for metabolic pathway analysis. However, their application to large networks has been hampered by the combinatorial explosion in the number of modes. In this work, we develop a method for generating random samples of EMs without computing the whole set.
Background Sciatica can be disabling, and evidence regarding medical treatments is limited. Pregabalin is effective in the treatment of some types of neuropathic pain. This study examined whether pregabalin may reduce the intensity of sciatica. Methods We conducted a randomized, double-blind, placebo-controlled trial of pregabalin in patients with sciatica. Patients were randomly assigned to receive either pregabalin at a dose of 150 mg per day that was adjusted to a maximum dose of 600 mg per day or matching placebo for up to 8 weeks. The primary outcome was the leg-pain intensity score on a 10-point scale (with 0 indicating no pain and 10 the worst possible pain) at week 8; the leg-pain intensity score was also evaluated at week 52, a secondary time point for the primary outcome. Secondary outcomes included the extent of disability, back-pain intensity, and quality-of-life measures at prespecified time points over the course of 1 year. Results A total of 209 patients underwent randomization, of whom 108 received pregabalin and 101 received placebo; after randomization, 2 patients in the pregabalin group were determined to be ineligible and were excluded from the analyses. At week 8, the mean unadjusted leg-pain intensity score was 3.7 in the pregabalin group and 3.1 in the placebo group (adjusted mean difference, 0.5; 95% confidence interval [CI], -0.2 to 1.2; P=0.19). At week 52, the mean unadjusted leg-pain intensity score was 3.4 in the pregabalin group and 3.0 in the placebo group (adjusted mean difference, 0.3; 95% CI, -0.5 to 1.0; P=0.46). No significant between-group differences were observed with respect to any secondary outcome at either week 8 or week 52. A total of 227 adverse events were reported in the pregabalin group and 124 in the placebo group. Dizziness was more common in the pregabalin group than in the placebo group. Conclusions Treatment with pregabalin did not significantly reduce the intensity of leg pain associated with sciatica and did not significantly improve other outcomes, as compared with placebo, over the course of 8 weeks. The incidence of adverse events was significantly higher in the pregabalin group than in the placebo group. (Funded by the National Health and Medical Research Council of Australia; PRECISE Australian and New Zealand Clinical Trials Registry number, ACTRN12613000530729 .).
INTRODUCTION: Cupping is used in various traditional medicine forms to relieve pain in musculoskeletal diseases. The aim of this study was to investigate the effectiveness of cupping in relieving the symptoms of knee osteoarthritis (OA). METHODS: In a two-group, randomized controlled exploratory pilot study patients with a clinically and radiological confirmed knee OA (Kellgren-Lawrence Grading Scale: 2-4) and a pain intensity > 40 mm on a 100 mm visual analogue scale (VAS) were included. 40 Patients were randomized to either 8 sessions of pulsatile dry cupping within 4 weeks or no intervention (control). Paracetamol was allowed on demand for both groups. Outcomes were the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, the pain intensity on a VAS (0 mm = no pain to 100 mm = maximum intensity) and Quality of Life (SF-36) 4 and 12 weeks after randomization. Use of Paracetamol was documented within the 4-week treatment period. Analyses were performed by analysis of covariance adjusting for the baseline value for each outcome. RESULTS: 21 patients were allocated to the cupping group (5 male; mean age 68 +/- SD 7.2) and 19 to the control group (8 male; 69 +/- 6.8). After 4 weeks the WOMAC global score improved significantly more in the cupping group with a mean of 27.7 (95% confidence interval 22.1; 33.3) compared to 42.2 (36.3; 48.1) in the control group (p = 0.001). After 12 weeks the WOMAC global score were still significantly different in favor for cupping (31.0 (24.9; 37.2) vs. 40.8 (34.4; 47.3) p = 0.032), however the WOMAC subscores for pain and stiffness were not significant anymore. Significantly better outcomes in the cupping group were also observed for pain intensity on VAS and for the SF-36 Physical Component Scale compared to the control group after 4 and 12 weeks. No significant difference was observed for the SF-36 Mental Component Scale and the total number of consumed Paracetamol tablets between both groups (mean 9.1, SD +/- 20.0 vs. 11.5 +/- 15.9). CONCLUSION: In this exploratory study dry cupping with a pulsatile cupping device relieved symptoms of knee OA compared to no intervention. Further studies comparing cupping with active treatments are needed.Trial registrationClinicaltrials.gov Identifier: NCT01057043.
- Experimental brain research. Experimentelle Hirnforschung. Experimentation cerebrale
- Published almost 8 years ago
Successful interaction with the external environment requires a balance between novel or exploratory and routine or exploitative behaviours. This distinction is often expressed in terms of location or orientation of the body relative to surrounding space: functions in which the vestibular system plays an important role. However, the distinction can also be applied to novel versus repetitive production of any behaviour or symbol. Here, we investigated whether vestibular inputs contribute to the balance between novel and routine behaviours, independently of their effects on spatial orienting, by assessing effects of galvanic vestibular stimulation (GVS) on a random number generation task. Right-anodal/left-cathodal GVS, which preferentially activates the left cerebral hemisphere decreased the randomness of the sequence, while left-anodal/right-cathodal GVS, which preferentially activates the right hemisphere increased it. GVS did not induce any spatial biases in locations chosen from the number line. Our results suggest that vestibular stimulation of each hemisphere has a specific effect on the balance between novel and routine actions. We found no evidence for effects of non-specific arousal due to GVS on random number generation, and no evidence for effects on number generation consistent with modulation of spatial attention due to GVS.
OBJECTIVE: To examine whether acupuncture treatment would improve outcome in chronic Achilles tendinopathy. METHODS: A randomized, controlled trial at two centers of 64 randomized patients aged 18 to 70 years with chronic Achilles tendinopathy was conducted from July 2007 to April 2010, with follow-up until October, 2010. These patients were randomly allocated into an acupuncture treatment group (acupuncture group) and an eccentric exercises group (control group). The validated Victorian Institute of Sports Assessment- Achilles (VISA-A) questionnaire was completed at baseline and 8, 16, and 24 weeks. The pain at rest and after activity was accessed at baseline and 8 weeks with Visual Analogue Scale (VAS). RESULTS: After randomization into the acupuncture group or control group, one patient was loss of follow-up. The mean VISA-A score improved significantly after 8 weeks in the acupuncture group to 67.1 points [95% confidence interval (CI), 64.1-70.2] and in the control group to 48.5 points (95% CI, 45.5-51.6) with an additional 18.6 points increase in acupuncture treatment patients (P =0.0000). Acupuncture treatment resulted in a significant increase from baseline in VISA-A of 25.8 after 16 weeks and 28.4 after 24 weeks. Whereas, in the control group the increase from baseline in VISA-A were 10.0 and 16.6 after 16 and 24 weeks, respectively (P =0.0000). The VAS diminished by 2.0 cm after activity, and by 1.5 cm at rest after 8 weeks in the control group. In the acupuncture group, the pain scores diminished significantly more than in the control group, with pain reduction of 3.7 cm after activity (P =0.0000) and 3.2 cm at rest (P =0.0000). CONCLUSION: Acupuncture intervention could improve pain and activity in patients with chronic Achilles tendinopathy compared with eccentric exercises.
The sampling that takes place at all levels of an experimental design must be random if the estimate is to be unbiased in a statistical sense. There are two fundamental ways by which one can make a random sample of the sections and positions to be probed on the sections. Using a card-sampling analogy, one can pick any card at all out of a deck of cards. This is referred to as independent random sampling because the sampling of any one card is made without reference to the position of the other cards. The other approach to obtaining a random sample would be to pick a card within a set number of cards and others at equal intervals within the deck. Systematic sampling along one axis of many biological structures is more efficient than random sampling, because most biological structures are not randomly organized. This article discusses the merits of systematic versus random sampling in stereological studies.
The HCAHPS Survey obtains hospital patients' experiences using four modes: Mail Only, Phone Only, Mixed (mail/phone follow-up), and Touch-Tone (push-button) Interactive Voice Response with option to transfer to live interviewer (TT-IVR/Phone). A new randomized experiment examines two less expensive modes: Web/Mail (mail invitation to participate by Web or request a mail survey) and Speech-Enabled IVR (SE-IVR/Phone; speaking to a voice recognition system; optional transfer to an interviewer). Web/Mail had a 12% response rate (vs. 32% for Mail Only and 33% for SE-IVR/Phone); Web/Mail respondents were more educated and less often Black than Mail Only respondents. SE-IVR/Phone respondents (who usually switched to an interviewer) were less often older than 75 years, more often English-preferring, and reported better care than Mail Only respondents. Concerns regarding inconsistencies across implementations, low adherence to primary modes, or low response rate may limit the applicability of the SE-IVR/Phone and Web/Mail modes in HCAHPS and similar standardized environments.