Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial

Background:

Spasticity is a common and poorly controlled symptom of multiple sclerosis. Our objective was to determine the short-term effect of smoked cannabis on this symptom.

Methods:

We conducted a placebo-controlled, crossover trial involving adult patients with multiple sclerosis and spasticity. We recruited participants from a regional clinic or by referral from specialists. We randomly assigned participants to either the intervention (smoked cannabis, once daily for three days) or control (identical placebo cigarettes, once daily for three days). Each participant was assessed daily before and after treatment. After a washout interval of 11 days, participants crossed over to the opposite group. Our primary outcome was change in spasticity as measured by patient score on the modified Ashworth scale. Our secondary outcomes included patients’ perception of pain (as measured using a visual analogue scale), a timed walk and changes in cognitive function (as measured by patient performance on the Paced Auditory Serial Addition Test), in addition to ratings of fatigue.

Results:

Thirty-seven participants were randomized at the start of the study, 30 of whom completed the trial. Treatment with smoked cannabis resulted in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo (p < 0.0001). In addition, treatment reduced pain scores on a visual analogue scale by an average of 5.28 points more than placebo (p = 0.008). Scores for the timed walk did not differ significantly between treatment and placebo (p = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo (p = 0.003). No serious adverse events occurred during the trial.

Interpretation:

Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact.Spasticity is a common and disabling symptom that remains a substantial problem for many patients with multiple sclerosis. Some patients have adverse effects from conventional antispasticity medications; for others, spasticity persists despite treatment. A report from the Institute of Medicine in the United States concluded that the active compounds of cannabis (marijuana) are potentially effective in treating neurologic conditions and “should be tested rigorously in clinical trials.”¹ There is evidence that the cannabinoid receptors CB₁ and CB₂ may be involved in the control of spasticity in multiple sclerosis² and that the endogenous ligand of CB₁, anandamide, is itself an effective antispasticity agent.³ CB₁ receptors are primarily presynaptic; their activation inhibits calcium influx and glutamate release, and reduces neuronal excitability by activating somatic and dendritic potassium channels.⁴Although many patients with multiple sclerosis endorse smoking cannabis as therapy, evidence that it relieves spasticity is largely anecdotal, as most trials focus on orally administered cannabinoids. We sought to assess the safety and efficacy of smoked cannabis versus placebo in patients with multiple sclerosis who have treatment-resistant spasticity.     

Acupuncture for chronic prostatitis/chronic pelvic pain syndrome: study protocol for a randomized controlled trial

Background

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition affecting men of all ages. Acupuncture may be an effective treatment option for CP/CPPS, but evidence is limited. We propose to evaluate the effectiveness of acupuncture in a rigorously conducted trial.

Methods

Ten hospitals will recruit 440 participants with CP/CPPS in China from October 2017 to December 2019. Participants will be randomly allocated to acupuncture or sham acupuncture with a 1:1 ratio using computerized simple random sampling. The whole study consists of 2-week baseline, 8-week treatment, and 24-week follow up. Twenty 30-mintute sessions of acupuncture or sham acupuncture treatment will be provided between week 1 and 8. The two co-primary outcomes are the proportion of responders at week 8 and week 32. Secondary outcomes include proportion of responders in the two groups at different time points; change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score; change in the NIH-CPSI subscales; change in the International Prostate Symptom Score; change in the Hospital Anxiety and Depression Scale; expectation assessments; proportions of participants in each response category of the Global Response Assessment; change in the International Index of Erectile Function 5; change in the five-level EuroQol five-dimensional questionnaire and a visual analogue scale; and changes in peak and average urinary flow rate.

Discussion

This study will provide robust evidence on whether acupuncture is effective for relieving symptoms of CP/CPPS.

Trials registration

ClinicalTrials.gov, NCT03213938. Registered on 5 July 2017.

     

Effectiveness of massage therapy for subacute low-back pain: a randomized controlled trial

BACKGROUND: The effectiveness of massage therapy for low-back pain has not been documented. This randomized controlled trial compared comprehensive massage therapy (soft-tissue manipulation, remedial exercise and posture education), 2 components of massage therapy and placebo in the treatment of subacute (between 1 week and 8 months) low-back pain. METHODS: Subjects with subacute low-back pain were randomly assigned to 1 of 4 groups: comprehensive massage therapy (n = 25), soft-tissue manipulation only (n = 25), remedial exercise with posture education only (n = 22) or a placebo of sham laser therapy (n = 26). Each subject received 6 treatments within approximately 1 month. Outcome measures obtained at baseline, after treatment and at 1-month follow-up consisted of the Roland Disability Questionnaire (RDQ), the McGill Pain Questionnaire (PPI and PRI), the State Anxiety Index and the Modified Schober test (lumbar range of motion). RESULTS: Of the 107 subjects who passed screening, 98 (92%) completed post-treatment tests and 91 (85%) completed follow-up tests. Statistically significant differences were noted after treatment and at follow-up. The comprehensive massage therapy group had improved function (mean RDQ score 1.54 v. 2.86-6.5, p < 0.001), less intense pain (mean PPI score 0.42 v. 1.18-1.75, p < 0.001) and a decrease in the quality of pain (mean PRI score 2.29 v. 4.55-7.71, p = 0.006) compared with the other 3 groups. Clinical significance was evident for the comprehensive massage therapy group and the soft-tissue manipulation group on the measure of function. At 1-month follow-up 63% of subjects in the comprehensive massage therapy group reported no pain as compared with 27% of the soft-tissue manipulation group, 14% of the remedial exercise group and 0% of the sham laser therapy group. INTERPRETATION: Patients with subacute low-back pain were shown to benefit from massage therapy, as regulated by the College of Massage Therapists of Ontario and delivered by experienced massage therapists.     

Effectiveness of focused structural massage and relaxation massage for chronic low back pain: protocol for a randomized controlled trial

Background

Hypertension affects 29% of the adult U.S. population and is a leading cause of heart disease, stroke, and kidney failure. Despite numerous effective treatments, only 53% of people with hypertension are at goal blood pressure. The chronic care model suggests that blood pressure control can be achieved by improving how patients and physicians address patient self-care.

Methods and design

This paper describes the protocol of a nested 2 × 2 randomized controlled trial to test the separate and combined effects on systolic blood pressure of a behavioral intervention for patients and a quality improvement-type intervention for physicians. Primary care practices were randomly assigned to the physician intervention or to the physician control condition. Physician randomization occurred at the clinic level. The physician intervention included training and performance monitoring. The training comprised 2 internet-based modules detailing both the JNC-7 hypertension guidelines and lifestyle modifications for hypertension. Performance data were collected for 18 months, and feedback was provided to physicians every 3 months. Patient participants in both intervention and control clinics were individually randomized to the patient intervention or to usual care. The patient intervention consisted of a 6-month behavioral intervention conducted by trained interventionists in 20 group sessions, followed by 12 monthly phone contacts by community health advisors. Follow-up measurements were performed at 6 and 18 months. The primary outcome was the mean change in systolic blood pressure at 6 months. Secondary outcomes were diastolic blood pressure and the proportion of patients with adequate blood pressure control at 6 and 18 months.

Discussion

Overall, 8 practices (4 per treatment group), 32 physicians (4 per practice; 16 per treatment group), and 574 patients (289 control and 285 intervention) were enrolled. Baseline characteristics of patients and providers and the challenges faced during study implementation are presented. The HIP interventions may improve blood pressure control and lower cardiovascular disease risk in a primary care practice setting by addressing key components of the chronic care model. The study design allows an assessment of the effectiveness and cost of physician and patient interventions separately, so that health care organizations can make informed decisions about implementation of 1 or both interventions in the context of local resources.

Trial registration

ClinicalTrials.gov identifier NCT00201136     

Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial.

OBJECTIVE--To evaluate the acceptability and efficacy of adding cognitive behaviour therapy to the medical care of patients presenting with the chronic fatigue syndrome. DESIGN--Randomised controlled trial with final assessment at 12 months. SETTING--An infectious diseases outpatient clinic. SUBJECTS--60 consecutively referred patients meeting consensus criteria for the chronic fatigue syndrome. INTERVENTIONS--Medical care comprised assessment, advice, and follow up in general practice. Patients who received cognitive behaviour therapy were offered 16 individual weekly sessions in addition to their medical care. MAIN OUTCOME MEASURES--The proportions of patients (a) who achieved normal daily functioning (Karnofsky score 80 or more) and (b) who achieved a clinically significant improvement in functioning (change in Karnofsky score 10 points or more) by 12 months after randomisation. RESULTS--Only two eligible patients refused to participate. All randomised patients completed treatment. An intention to treat analysis showed that 73% (22/30) of recipients of cognitive behaviour therapy achieved a satisfactory outcome as compared with 27% (8/30) of patients who were given only medical care (difference 47 percentage points; 95% confidence interval 24 to 69). Similar differences were observed in subsidiary outcome measures. The improvement in disability among patients given cognitive behaviour therapy continued after completion of therapy. Illness beliefs and coping behaviour previously associated with a poor outcome changed more with cognitive behaviour therapy than with medical care alone. CONCLUSION--Adding cognitive behaviour therapy to the medical care of patients with the chronic fatigue syndrome is acceptable to patients and leads to a sustained reduction in functional impairment.     

Acupuncture for migraine prophylaxis: a randomized controlled trial

Background:

Acupuncture is commonly used to treat migraine. We assessed the efficacy of acupuncture at migraine-specific acupuncture points compared with other acupuncture points and sham acupuncture.

Methods:

We performed a multicentre, single-blind randomized controlled trial. In total, 480 patients with migraine were randomly assigned to one of four groups (Shaoyang-specific acupuncture, Shaoyang-nonspecific acupuncture, Yangming-specific acupuncture or sham acupuncture [control]). All groups received 20 treatments, which included electrical stimulation, over a period of four weeks. The primary outcome was the number of days with a migraine experienced during weeks 5–8 after randomization. Our secondary outcomes included the frequency of migraine attack, migraine intensity and migraine-specific quality of life.

Results:

Compared with patients in the control group, patients in the acupuncture groups reported fewer days with a migraine during weeks 5–8, however the differences between treatments were not significant (p > 0.05). There was a significant reduction in the number of days with a migraine during weeks 13–16 in all acupuncture groups compared with control (Shaoyang-specific acupuncture v. control: difference –1.06 [95% confidence interval (CI) –1.77 to –0.5], p = 0.003; Shaoyang-nonspecific acupuncture v. control: difference –1.22 [95% CI –1.92 to –0.52], p < 0.001; Yangming-specific acupuncture v. control: difference –0.91 [95% CI –1.61 to –0.21], p = 0.011). We found that there was a significant, but not clinically relevant, benefit for almost all secondary outcomes in the three acupuncture groups compared with the control group. We found no relevant differences between the three acupuncture groups.

Interpretation:

Acupuncture tested appeared to have a clinically minor effect on migraine prophylaxis compared with sham acupuncture.

Trial Registration:

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00599586","term_id":"NCT00599586"}}NCT00599586About 6%–8% of men and 16%–18% of women in the United States and England experience migraines, with or without an aura.^1,2 A prevalence of 1% has been reported in mainland China,³ compared with 4.7% in Hong Kong and 9.1% in Taiwan.^4,5 A recent Cochrane meta-analysis suggests that acupuncture as migraine prophylaxis is safe and effective and should be considered as a treatment option for willing patients.⁶Although the specific effects acupuncture are controversial, acupuncture, as it is currently practised, clearly differentiates between real acupuncture points and nonacupuncture points. The Chinese Government launched the National Basic Research Program to obtain more data about the specificity of acupuncture points.⁷Trials from Italy and Brazil^8,9 showed that acupuncture was more effective than sham acupuncture in preventing migraines, but other trials have reported no differences.^10–13 There is no evidence that one acupuncture strategy is more effective than another for treating migraines. According to acupuncture theory, a headache on the lateral side is usually defined as a Shaoyang headache. In Jinkuiyi,¹⁴ migraines are said to affect the yang meridians (including the Taiyang, Yangming and Shaoyang meridians). In Lingshu,¹⁵ the Shaoyang meridians are said to go through the lateral side of the body, therefore the Shaoyang meridians are thought to be superior for treating migraines. Some points on the Shaoyang meridians are regarded as being more specific for migraines than other points.¹⁶Our aim was to investigate whether acupuncture at specific acupuncture points was more efficacious in preventing migraine than sham acupuncture at nonacupuncture points. We also investigated whether the efficacy varied when acupuncture points along different meridians or points along the same meridian were used.     

Psychoanalytic and cognitive-behavior therapy of chronic depression: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Despite limited effectiveness of short-term psychotherapy for chronic depression, there is a lack of trials of long-term psychotherapy. Our study is the first to determine the effectiveness of controlled long-term psychodynamic and cognitive-behavioral (CBT) treatments and to assess the effects of preferential vs. randomized assessment. Methods / Design: Patients are assigned to treatment according to their preference or randomized (if they have no clear preference). Up to 80 sessions of psychodynamic or psychoanalytically oriented treatments (PAT) or up to 45 sessions of CBT are offered during the first year in the study. After the first year, PAT can be continued according to the "naturalistic", usual way of treating such patients within the system of German health care system (normally 240 up to 300 sessions), CBT therapists may extend their treatment up to 80 sessions, but focus mainly on maintenance and relapse prevention. We plan to recruit a total of 240 patients (60 per arm). A total of 11 assessments are conducted throughout treatment and up to 3 years after initiation of treatment. The primary outcome measures are the QIDS (independent clinician rating) and the BDI after year 1, 2 and 3. DISCUSSION: We combine an RCT and a naturalistic approach in order to investigate, how effectively chronic depression can be treated on an outpatient basis by the two forms of treatment reimbursed in the German health care system and we will determine the effects of treatment preference vs. randomization.     

Hyoscine butylbromide versus acetaminophen for nonspecific colicky abdominal pain in children: a randomized controlled trial

BACKGROUND:Less than two-thirds of children with abdominal pain in the emergency department receive analgesia. We sought to determine whether hyoscine butylbromide was superior to acetaminophen for children with nonspecific colicky abdominal pain.METHODS:We randomly allocated children aged 8–17 years with nonspecific colicky abdominal pain who presented to the pediatric emergency department of London Health Sciences Centre, London, Ontario to receive hyoscine butylbromide, 10 mg given orally, or acetaminophen, 15 mg/kg given orally (maximum 975 mg). We considered the minimal clinically important difference for the primary outcome (self-reported pain at 80 min) to be 13 mm on a 100 mm visual analogue scale. Secondary outcomes included administration of rescue analgesia, adverse effects and pain score less than 30 mm at 80 minutes.RESULTS:A total of 236 participants (120 in the hyoscine butylbromide group and 116 in the acetaminophen group) were included in the trial. The mean visual analogue scale scores at 80 minutes were 29 mm (standard deviation [SD] 26 mm) and 30 mm (SD 29 mm) with hyoscine butylbromide and acetaminophen, respectively (adjusted difference 1, 95% confidence interval −7 to 7). Rescue analgesia was administered to 4 participants (3.3%) in the hyoscine butylbromide group and 1 participant (0.9%) in the acetaminophen groups (p = 0.2). We found no significant differences in rates of adverse effects between hyoscine butylbromide (32/116 [27.6%]) and acetaminophen (28/115 [24.3]) (p = 0.5); no serious adverse effects were observed. The proportion with a pain score less than 30 mm at 80 minutes was 66 (55.0%) with hyoscine butylbromide and 63 (54.3%) with acetaminophen (p = 0.9).INTERPRETATION:Hyoscine butylbromide was not superior to acetaminophen in this setting. Both agents were associated with clinically important pain reduction, and either can be considered for children presenting to the emergency department with nonspecific colicky abdominal pain. Trial registration: Clinicaltrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT02582307","term_id":"NCT02582307"}}NCT02582307

Abdominal pain is reported by a third of school-aged children¹ and accounts for several visits daily in most emergency departments.^2–5 Although the use of analgesia to treat acute abdominal pain is well-supported,^6,7 there is little evidence to guide the management of nonspecific abdominal pain in the emergency department,⁸ which accounts for two-thirds of cases of abdominal pain presenting to the emergency department.^8,9 Acetaminophen is the most commonly used World Health Organization Step 1 analgesic.¹⁰ In children, it is effective for many painful conditions,^11,12 but data supporting its use for abdominal pain are lacking.^13,14 Despite strong advocacy by the American Academy of Pediatrics¹⁵ for adequate pain management, less than two-thirds of children with abdominal pain in the emergency department receive analgesia,^16,17 and roughly half experience ongoing pain after discharge. ¹⁸ Children with nonspecific abdominal pain are less likely than those with a specific cause to receive analgesia.⁵ Available analgesic options for children with nonspecific abdominal pain in the emergency department may result in greater adherence to the American Academy of Pediatrics recommendations.Hyoscine butylbromide is orally administered and available in most Canadian emergency departments. We surmised that it may be effective for colicky abdominal pain owing to its antispasmodic properties.¹⁹ Ten placebo-controlled studies involving 3699 adults with functional abdominal pain showed hyoscine butylbromide to be beneficial, without serious adverse effects.^20–29 In the only pediatric study, hyoscine butylbromide, 10 mg given orally, was found to be beneficial compared to a homeopathic preparation in 204 children, with no serious adverse effects.³⁰ We sought to determine whether hyoscine butylbromide was superior to acetaminophen in relieving pain among children presenting to the emergency department with nonspecific colicky abdominal pain.     

Parent-only treatment for childhood obesity: a randomized controlled trial

Parent-only (PO) treatments for childhood obesity are feasible, more cost-effective and potentially easier to disseminate. The objective of this study was to determine whether a PO treatment is not inferior to a parent + child (PC) treatment for childhood obesity. Eighty parent-child dyads with an 8-12 year old overweight or obese child (>85th BMI-P) were recruited and randomized into PO or PC treatment for childhood obesity. Parents or parent-child dyads attended 5-month treatment groups. Child and parent body size, child caloric intake, and child physical activity were assessed at baseline, post-treatment, and 6-months follow-up. Noninferiority testing using mixed linear models was used to compare PO treatment with PC treatment. Results showed that the PO group was not inferior to the PC group in terms of child weight loss. Results also showed that the PO group was not inferior to the PC group in terms of parent weight loss and child physical activity, but not child caloric intake. This study suggests that a PO treatment could provide similar results to PC in child weight loss and other relevant outcomes, and potentially could be more cost-effective and easier to disseminate. Although further research is needed, this study suggests that PO groups are a viable method for providing childhood obesity treatment.     

Immediate and short-term pain relief by acute sciatic nerve press: a randomized controlled trial

Background

Despite much research, an immediately available, instantly effective and harmless pain relief technique has not been discovered. This study describes a new manipulation: a "2-minute sciatic nerve press", for rapid short-term relief of pain brought on by various dental and renal diseases.

Methods

This randomized, single-blind, placebo-controlled trial ran in three hospitals in Anhui Province, China, with an enrollment of 66 out of 111 solicited patients aged 16 to 74 years. Patients were recruited sequentially, by specific participating physicians at their clinic visits to three independent hospitals. The diseases in enrolled dental patients included dental caries, periodontal diseases and dental trauma. Renal diseases in recruits included kidney infections, stones and some other conditions. Patients were randomly assigned to receive the "2-minute sciatic nerve press" or the "placebo press". For the "2-minute sciatic nerve press", pressure was applied simultaneously to the sciatic nerves at the back of the thighs, using the fists while patients lay prone. For the "placebo press", pressure was applied simultaneously to a parallel spot on the front of the thighs, using the fists while patients lay supine. Each fist applied a pressure of 11 to 20 kg for 2 minutes, after which, patients arose to rate pain.

Results

The "2-minute sciatic nerve press" produced greater pain relief than the "placebo press". Within the first 10 minutes after sciatic pressure, immediate pain relief ratings averaged 66.4% (p < 0.001) for the dental patients, versus pain relief of 20% for the placebo press, and, 52.2% (p < 0.01) for the renal patients, versus relief of 14% for the placebo press, in median. The method worked excellently for dental caries and periodontal diseases, but poorly for dental trauma. Forty percent of renal patients with renal colic did not report any pain relief after the treatment.

Conclusion

Two minutes of pressure on both sciatic nerves can produce immediate significant conduction analgesia, providing a convenient, safe and powerful way to overcome clinical pain brought on by dental diseases and renal diseases for short term purposes.

Trial registration

ACTR 12606000439549     

siRNA relieves chronic neuropathic pain

Double stranded, short interfering RNAs (siRNA) of 21–22 nt length initiate a sequence-specific, post-trancriptional gene silencing in animals and plants known as RNA interference (RNAi). Here we show that RNAi can block a pathophysiological pain response and provide relief from neuropathic pain in a rat disease model by down regulating an endogenous, neuronally expressed gene. Rats, intrathecally infused with a 21 nt siRNA perfectly complementary to the pain-related cation-channel P2X₃, showed diminished pain responses compared to missense (MS) siRNA-treated and untreated controls in models of both agonist-evoked pain and chronic neuropathic pain. This form of delivery caused no adverse effects in any of the animals receiving P2X₃ siRNA, MS siRNA or vehicle. Molecular analysis of tissues revealed that P2X₃ mRNA expressed in dorsal root ganglia, and P2X₃ protein translocated into the dorsal horn of the spinal cord, were significantly diminished. These observations open a path toward use of siRNA as a genetic tool for drug target validation in the mammalian central nervous system, as well as for proof of concept studies and as therapeutic agents in man.     

Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

Background

Acute exacerbations contribute to the morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations.

Methods

Stable patients with COPD were randomized in a double-blind, placebo-controlled trial to receive moxifloxacin 400 mg PO once daily (N = 573) or placebo (N = 584) once a day for 5 days. Treatment was repeated every 8 weeks for a total of six courses. Patients were repeatedly assessed clinically and microbiologically during the 48-week treatment period, and for a further 24 weeks'' follow-up.

Results

At 48 weeks the odds ratio (OR) for suffering an exacerbation favoured moxifloxacin: per-protocol (PP) population (N = 738, OR 0.75, 95% confidence interval (CI) 0.565-0.994, p = 0.046), intent-to-treat (ITT) population (N = 1149, OR 0.81, 95% CI 0.645-1.008, p = 0.059), and a post-hoc analysis of per-protocol (PP) patients with purulent/mucopurulent sputum production at baseline (N = 323, OR 0.55, 95% CI 0.36-0.84, p = 0.006).There were no significant differences between moxifloxacin and placebo in any pre-specified efficacy subgroup analyses or in hospitalization rates, mortality rates, lung function or changes in St George''s Respiratory Questionnaire (SGRQ) total scores. There was, however, a significant difference in favour of moxifloxacin in the SGRQ symptom domain (ITT: -8.2 vs -3.8, p = 0.009; PP: -8.8 vs -4.4, p = 0.006). Moxifloxacin treatment was not associated with consistent changes in moxifloxacin susceptibility. There were more treatment-emergent, drug related adverse events with moxifloxacin vs placebo (p < 0.001) largely due to gastrointestinal events (4.7% vs 0.7%).

Conclusions

Intermittent pulsed therapy with moxifloxacin reduced the odds of exacerbation by 20% in the ITT population, by 25% among the PP population and by 45% in PP patients with purulent/mucopurulent sputum at baseline. There were no unexpected adverse events and there was no evidence of resistance development.

Trial registration

ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00473460","term_id":"NCT00473460"}}NCT00473460 (ClincalTrials.gov).     

Amantadine for dyskinesias in Parkinson's disease: a randomized controlled trial

Background

Dyskinesias are some of the major motor complications that impair quality of life for patients with Parkinson''s disease. The purpose of the present study was to investigate the efficacy of amantadine in Parkinson''s disease patients suffering from dyskinesias.

Methods

In this multi-center, double-blind, randomized, placebo-controlled, cross-over trial, 36 patients with Parkinson''s disease and dyskinesias were randomized, and 62 interventions, which included amantadine (300 mg /day) or placebo treatment for 27 days, were analyzed. At 15 days after washout, the treatments were crossed over. The primary outcome measure was the changes in the Rush Dyskinesia Rating Scale (RDRS) during each treatment period. The secondary outcome measures were changes in the Unified Parkinson''s Disease Rating Scale part IVa (UPDRS-IVa, dyskinesias), part IVb (motor fluctuations), and part III (motor function).

Results

RDRS improved in 64% and 16% of patients treated with amantadine or placebo, respectively, with significant differences between treatments. The adjusted odds-ratio for improvement by amantadine was 6.7 (95% confidence interval, 1.4 to 31.5). UPDRS-IVa was improved to a significantly greater degree in amantadine-treated patients [mean (SD) of 1.83 (1.56)] compared with placebo-treated patients [0.03 (1.51)]. However, there were no significant effects on UPDRS-IVb or III scores.

Conclusions

Results from the present study demonstrated that amantadine exhibited efficacious effects against dyskinesias in 60–70% of patients.

Trial Registration

UMIN Clinical Trial Registry UMIN000000780     

Determining optimal approaches for weight maintenance: a randomized controlled trial

Background

Weight regain often occurs after weight loss in overweight individuals. We aimed to compare the effectiveness of 2 support programs and 2 diets of different macronutrient compositions intended to facilitate long-term weight maintenance.

Methods

Using a 2 × 2 factorial design, we randomly assigned 200 women who had lost 5% or more of their initial body weight to an intensive support program (implemented by nutrition and activity specialists) or to an inexpensive nurse-led program (involving “weigh-ins” and encouragement) that included advice about high-carbohydrate diets or relatively high-monounsaturated-fat diets.

Results

In total, 174 (87%) participants were followed-up for 2 years. The average weight loss (about 2 kg) did not differ between those in the support programs (0.1 kg, 95% confidence interval [CI] −1.8 to 1.9, p = 0.95) or diets (0.7 kg, 95% CI −1.1 to 2.4, p = 0.46). Total and low-density lipoprotein (LDL) cholesterol levels were significantly higher among those on the high-monounsaturated-fat diet (total cholesterol: 0.17 mmol/L, 95% CI 0.01 to 0.33; p = 0.040; LDL cholesterol: 0.16 mmol/L, 95% CI 0.01 to 0.31; p = 0.039) than among those on the high-carbohydrate diet. Those on the high-monounsaturated-fat diet also had significantly higher intakes of total fat (5% total energy, 95% CI 3% to 6%, p < 0.001) and saturated fat (2% total energy, 95% CI 1% to 2%, p < 0.001). All of the other clinical and laboratory measures were similar among those in the support programs and diets.

Interpretation

A relatively inexpensive program involving nurse support is as effective as a more resource-intensive program for weight maintenance over a 2-year period. Diets of different macronutrient composition produced comparable beneficial effects in terms of weight loss maintenance. ClinicalTrials.gov trial register no. NCT00128336.Increasing rates of overweight and obesity and the co-morbidities associated with excess adiposity have been reported in affluent and developing countries worldwide.^1,2 Many different dietary and exercise regimens have been shown to be effective in the short term in reducing body weight and improving cardiovascular risk factors and blood glucose in overweight and obese adults.^3–8 Weight regain typically occurs after intentional weight loss.^9,10 There are relatively few examples in the literature of lifestyle interventions that have produced long-term benefits in terms of maintenance of weight loss, improved risk-factor status or reduced rates of type 2 diabetes, the most immediate co-morbidity of obesity.^11,12 These trials involved intensive and costly interventions.In the present study, we compared the effectiveness of an intensive program led by health professionals (dietician and exercise specialist) and a more simple, relatively inexpensive nurse-coordinated program for people attempting to maintain weight loss. Additionally, we compared 2 of the most widely recommended nutritional approaches for weight management (high-carbohydrate and high-monounsaturated-fat diets).     

Effect of neurogenic acupoint cupping on high sensitive C-reactive protein and pain perception in female chronic pelvic pain: A randomized controlled trial

Objectives:To determine the effect of neurogenic acupoint dry cupping therapy on high sensitive C-reactive protein (hs-CRP) level, pain perception & intensity, and life impact of pelvic pain in women with chronic pelvic pain (CPP), with regard to the biological and neurophysiological impacts of dry cupping on acupoint.Methods:Thirty women with CPP were randomly divided into two equal groups; the study group received dry cupping on neurogenic acupoints plus lifestyle modifications for 8 weeks (n=15), while the control group received only lifestyle modifications for 8 weeks (n=15). Women were assessed pre- and post-rehabilitation program with the hs-CRP blood test, the short-form McGill Pain Questionnaire (SF-MPQ), and the pelvic pain impact questionnaire (PPIQ).Results:Comparing both groups post-treatment revealed that there were significant reductions in levels of hs-CRP, and scores of SF-MPQ & PPIQ (p<0.05) in the study group compared with the control group. Also, there were significant positive correlations between hs-CRP and both SF-MPQ “Visual Analogue Scale (VAS), Present Pain Intensity (PPI) index & Pain Rating Index (PRI)” and PPIQ (p<0.05).Conclusion:Neurogenic acupoint cupping therapy had significantly improving effects on the degree of inflammation, pain perception & intensity, and life impact of pelvic pain in women with CPP.     

Acute pain therapy in postanesthesia care unit directed by skin conductance: a randomized controlled trial

Background

After surgery, effective and well-directed acute pain therapy is a necessary and integral part of the overall treatment plan. Generally, the assessment of pain intensity depends on a patient’s self-evaluation using scoring systems such as numeric rating scales (NRS, 0 to 10). Recently, a “Pain Monitor” was commercially provided which is based on measurements of fluctuations of skin conductance (NFSC). In this randomized, controlled, single-blind trial, possible benefits of this certain device were studied.

Methods

Postoperative patients (n = 44) were randomly assigned to a test or a control group during their stay in the postanesthesia care unit (PACU). All patients were treated and monitored according to internal hospital standards. Whereas all patients systematically evaluated their pain each 15 min, test group patients were additionally addressed when NFSC exceeded a predefined level. In cases of NRS≥5 during a routine elevation or in between, pain relief was achieved by standard procedures irrespective of group allocation.

Results

During their stay in PACU, both test and control groups experienced a significant decrease in NRS as a consequence of pain therapy. No significant differences in mean NRS or in NFSC values were found between the test and control groups. No correlation was observed between NRS and NFSC.

Conclusion

Postoperative patients experience diverse stressors, such as anxiety, disorientation, shivering, sickness and pain. Although the application of continuous pain monitoring would be meaningful in this clinical setting, the tested device failed to distinguish pain from other stressors in postoperative adult patients.

Trial Registration

German Clinical Trials Register DRKS00000755.     

A multi-centre randomized controlled trial of rehabilitation aimed at improving outdoor mobility for people after stroke: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Up to 42% of all stroke patients do not get out of the house as much as they would like. This can impede a person's quality of life. This study is testing the clinical effectiveness and cost effectiveness of a new outdoor mobility rehabilitation intervention by comparing it to usual care. METHODS: Multi-centre parallel group individually randomised controlled trial. At least 506 participants will be recruited through 15 primary and secondary care settings and will be eligible if they are over 18 years of age, have had a stroke and wish to get out of the house more often. Participants are being randomly allocated to either the intervention group or the control group. Intervention group participants receive up to 12 rehabilitation outdoor mobility sessions over up to 4 months. The main component of the intervention is repeated practice of outdoor mobility with a therapist. Control group participants are receiving the usual intervention for outdoor mobility limitations: verbal advice and provision of leaflets provided over one session. Outcome measures are being collected using postal questionnaires, travel calendars and by independent assessors. The primary outcome measure is the Social Function domain of the SF36v2 quality of life assessment six months after recruitment. The secondary outcome measures include: functional ability, mobility, the number of journeys (monthly travel diaries), satisfaction with outdoor mobility, mood, health-related quality of life, resource use of health and social care. Carer mood is also being collected. The mean Social Function score of the SF-36v2 will be compared between treatment arms using a multiple membership form of mixed effects multiple regression analysis adjusting for centre (as a fixed effect), age and baseline Social Function score as covariates and therapist as a multiple membership random effect. Regression coefficients and 95% confidence intervals will be presented. DISCUSSION: This study protocol describes a pragmatic randomised controlled trial that will hopefully provide robust evidence of the benefit of outdoor mobility interventions after stroke for clinicians working in the community. The results will be available towards the end of 2012.