Screening for abdominal aortic aneurysms: single centre randomised controlled trial

Objective To determine whether screening Danish men aged 65 or more for abdominal aortic aneurysms reduces mortality.Design Single centre randomised controlled trial.Setting All five hospitals in Viborg County, Denmark.Participants All 12 639 men born during 1921-33 and living in Viborg County. In 1994 we included men born 1921-9 (64-73 years). We also included men who became 65 during 1995-8.Interventions Men were randomised to the intervention group (screening by abdominal ultrasonography) or control group. Participants with an abdominal aortic aneurysm > 5 cm were referred for surgical evaluation, and those with smaller aneurysms were offered annual scans.Outcome measures Specific mortality due to abdominal aortic aneurysm, overall mortality, and number of planned and emergency operations for abdominal aortic aneurysms.Results 4860 of 6333 men were screened (attendance rate 76.6%). 191 (4.0% of those screened) had abdominal aortic aneurysms. The mean follow-up time was 52 months. The screened group underwent 75% (95% confidence interval 51% to 91%) fewer emergency operations than the control group. Deaths due to abdominal aortic aneurysms occurred in nine patients in the screened group and 27 in the control group. The number needed to screen to save one life was 352. Specific mortality was significantly reduced by 67% (29% to 84%). Mortality due to non-abdominal aortic aneurysms was non-significantly reduced by 8%. The benefits of screening may increase with time.Conclusion Mass screening for abdominal aortic aneurysms in Danish men aged 65 or more reduces mortality.     

Efficacy of a small single dose of oral dexamethasone for outpatient croup: a double blind placebo controlled clinical trial.

OBJECTIVE--To assess the efficacy of a single dose of oral dexamethasone 0.15 mg/kg in children with mild croup not admitted to hospital. DESIGN--Double blind, randomised, placebo controlled clinical trial. SETTING--The emergency department of a tertiary paediatric hospital. SUBJECTS--100 children aged 4-122 months presenting with mild croup. INTERVENTION--A single oral dose of dexamethasone 0.15 mg/kg or placebo. MAIN OUTCOME MEASURE--Return to medical care with ongoing croup. RESULTS--Baseline characteristics of the two treatment groups were similar. Eight children (all from the placebo group) returned to medical care with ongoing croup, one being admitted. There was no reported difference in duration of croup symptoms, duration of viral symptoms, or rate of return to medical care for other reasons. CONCLUSION--Oral dexamethasone in a dose of 0.15 mg/kg is effective in reducing return to medical care with ongoing croup in children with mild croup.     

Radiotherapy in small cell cancer of the lung treated with combination chemotherapy: a controlled trial.

Three hundred and seventy one patients with extensive or limited small cell cancer of the lung took part in a randomised trial to evaluate irradiation of the primary tumour in patients treated with combination chemotherapy. They were randomly allocated to treatment either with chemotherapy alone (198) or with both chemotherapy and radiotherapy (173). All 371 initially received 12 weeks of chemotherapy after which they were categorised according to response. Only those with stable or responding disease continued with their allotted treatment. Thus 144 received chemotherapy alone and 135 received both chemotherapy and radiotherapy. The design of the study permitted analysis of the effect of radiotherapy according to initial extent of disease and quality of early response to chemotherapy. Radiotherapy (40 Gy (4000 rad), one fraction a day over 20 days) did not improve the survival of patients in any category of initial extent of disease or early response to chemotherapy and was not effective in preventing local relapse.     

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.     

Screening the elderly in the community: controlled trial of dependency surveillance using a questionnaire administered by volunteers.

OBJECTIVE--To test the benefits of regular surveillance of the elderly at home using an activities of daily living questionnaire administered by volunteers. DESIGN--Randomised controlled study. PATIENTS--539 Subjects aged 75 and over from two general practices. INTERVENTION--All subjects were visited at the beginning and end of the study by volunteers, who completed a scored activity of daily living questionnaire. The study group were revisited at regular intervals. Individuals with an increase in score greater than 5 were referred to their general practitioners. All interactions with social services and health authorities were recorded for both groups. MAIN OUTCOME MEASURES--Mortality, activity of daily living score, total number of days in institutions, geriatric and psychogeriatric service contacts, primary health care team contacts, use of community support services. RESULTS--The study group were admitted to hospital more often than the controls (335 occasions v 252), but the control group spent 33% more days in institutions, mainly in long term admissions to residential accommodation. The number of falls reported in the control group doubled (from 17 before the first interview to 36 before the last) and in the study group remained unchanged (12 before both interviews). The study group received community support services sooner than the control group. There was no difference between the groups in mortality or activity of daily living score. CONCLUSION--Regular visiting of old people at home by non-professional volunteers using a simple activity of daily living questionnaire is a practical way of identifying problems and initiating action for this group.     

Electroacupuncture in fibromyalgia: results of a controlled trial.

OBJECTIVE--To determine the efficacy of electroacupuncture in patients with fibromyalgia, a syndrome of unknown origin causing diffuse musculoskeletal pain. DESIGN--Three weeks'' randomised study with blinded patients and evaluating physician. SETTING--University divisions of physical medicine and rehabilitation and rheumatology, Geneva. PATIENTS--70 patients (54 women) referred to the division for fibromyalgia as defined by the American College of Rheumatology. INTERVENTIONS--Patients were randomised to electroacupuncture (n = 36) or a sham procedure (n = 34) by means of an electronic numbers generator. MAIN OUTCOME MEASURES--Pain threshold, number of analgesic tablets used, regional pain score, pain recorded on visual analogue scale, sleep quality, morning stiffness, and patient''s and evaluating physician''s appreciation. RESULTS--Seven of the eight outcome parameters showed a significant improvement in the active treatment group whereas none were improved in the sham treatment group. Differences between the groups were significant for five of the eight outcome measures after treatment. CONCLUSIONS--Electroacupuncture is effective in relieving symptoms of fibromyalgia. Its potential in long term management should now be studied.     

Remedial therapy after stroke: a randomised controlled trial.

Of 1094 patients with a confirmed stroke admitted to Northwick Park, a district general hospital, 364 (33%) died while in hospital, 215 (20%) were fully recovered when discharged, and 329 (30%) were too frail or too ill from diseases other than stroke to be considered for active rehabilitation. Only 121 (11%) were suitable for intensive treatment. They and 12 patients referred direct to outpatients were allocated at random to one of three different courses of rehabilitation. Intensive was compared with conventional rehabilitation and with a third regimen which included no routine rehabilitation, but under which patients were encouraged to continue with exercises taught while in hospital and were regularly seen at home by a health visitor. Progress at three months and 12 months was measured by an index of activities of daily living. Improvement was greatest in those receiving intensive treatment, intermediate in those receiving conventional treatment, and least in those receiving no routine treatment. Decreasing intensity of treatment was associated with a significant increase in the proportions of patients who deteriorated and in the extent to which they deteriorated. Probably only a few stroke patients, mostly men, are suitable for intensive outpatient rehabilitation, but for those patients the treatment is effective and realistic.     

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.     

Cimetidine for recurrent ulcer after vagotomy or gastrectomy: a randomised controlled trial.

In a randomised controlled trial cimetidine 1 g daily for six weeks was compared with placebo in the treatment of recurrent ulcers after gastrectomy or vagotomy for duodenal ulcer. Healing, assessed endoscopically, was seen in seven out of 12 patients given cimetidine and in five out of 12 controls. Four of the controls whose ulcers did not heal were subsequently treated with cimetidine, and in two the ulcers healed after six weeks. Pain recorded by the patient and consumption of alkalis were each slightly but not significantly less in the cimetidine-treated patients. When cimetidine is to be used for recurrent ulceration probably the dosage and duration of treatment should be increased.     

Transurethral microwave treatment for benign prostatic hypertrophy: a randomised controlled clinical trial.

OBJECTIVES--To determine whether transurethral microwave treatment for patients with benign prostatic hypertrophy provides significant symptomatic relief, a reduction in residual urine volumes, and improvements in flow rates compared with sham treatment. DESIGN--Prospective double blind randomised study with follow up at three months. SETTING--Department of Urology in a London teaching hospital. PATIENTS--40 men completed the study: 22 received microwave treatment and 18 received sham treatment. Entry criteria were symptoms of prostatism of at least six months'' duration, a total symptom score > 14, and a peak urine flow rate < 15 ml/s or a residual urine volume > 50 ml. Exclusion criteria were prostatic cancer, a residual urine volume > 200 ml, a very large prostate, an obstructing middle lobe, acute urinary retention, impaired renal function, coexisting urinary tract disease, and previous prostatic surgery. INTERVENTIONS--A single 90 minute transurethral microwave treatment or sham treatment. OUTCOME MEASURES--Patients'' symptoms (including daytime frequency and nocturia) recorded in a self assessment symptom score questionnaire, peak urinary flow rates, and residual urine volumes. RESULTS--The mean total symptom scores of the patients who received microwave treatment fell from 30 to 11 compared with a fall from 31 to 26 for patients who received sham treatment (p < 0.001). Among patients who received microwave treatment daytime frequency fell from 9.4 to 5.5 voids a day and night time frequency from 3.5 to 1.6 voids a night; residual urine volumes fell from 104 ml to 52 ml; and peak urine flow rates increased by 2.3 ml/s. In the control group there was no improvement in any of these features. Treatment preserved sexual function and antegrade ejaculation. CONCLUSIONS--For selected patients with prostatism microwave treatment is effective and has few side effects.     

Electric convulsion therapy in depression: a double-blind controlled trial.

The therapeutic effect of simulated and real bilateral electric convulsion therapy was examined in a double-blind, randomised trial on 22 patients with a primary depressive illness. Each treatment was given twice weekly for three weeks and the results assessed by the psychiatrist using a visual analogue rating scale, nurses using a nine-point rating scale, and the patients themselves using the Beck Depression Inventory. With all three methods of assessment patients given the real treatment substantially improved (p less than 0.001), whereas those given simulated treatment showed little change. Three weeks after substituting real treatment for simulated, however, these patients were also significantly improved (psychiatrist''s rating p less than 0.001; nurses'' rating p less than 0.005; Beck inventory p less than 0.005). These findings confirm the value of electric convulsion therapy in severe depressive illness and strongly suggest that the convulsion is important for the therapeutic effect.     

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     

Smoked cannabis for chronic neuropathic pain: a randomized controlled trial

Background

Chronic neuropathic pain affects 1%–2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood.

Methods

Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events.

Results

We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02–1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough.

Conclusion

A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063)Chronic neuropathic pain has a prevalence of 1%–2%,¹ and treatment options are limited.² Pharmacotherapy includes anticonvulsants, antidepressants, opioids and local anesthetics,^3,4 but responses vary and side effects limit compliance.Cannabis sativa has been used to treat pain since the third millennium BC.⁵ An endogenous pain-processing system has been identified, mediated by endogenous cannabinoid ligands acting on specific cannabinoid receptors.⁶ These findings, coupled with anecdotal evidence of the analgesic effects of smoked cannabis,⁷ support a reconsideration of cannabinoid agents as analgesics.Oral cannabinoids such as tetrahydrocannabinol, cannabidiol and nabilone have, alone and in combination, shown efficacy in central^8,9 and peripheral¹⁰ neuropathic pain, rheumatoid arthritis¹¹ and fibromyalgia.¹²The analgesic effects of smoked cannabis remain controversial, although it is used by 10%–15% of patients with chronic noncancer pain¹³ and multiple sclerosis.¹⁴ Clinical trials are needed to evaluate these effects, given that the risks and benefits of inhaled cannabinoids may differ from oral agents. To date, three small clinical trials of the analgesic efficacy of smoked cannabis have been reported.^15–17 All studies were conducted in residential laboratories, and participants smoked multiple doses of the drug at each time point. No study adequately reported data related to adverse events.We conducted a clinical trial using a standardized single-dose delivery system to explore further the safety and efficacy of smoked cannabis in outpatients with chronic neuropathic pain.     

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).     

Care in a birth room versus a conventional setting: a controlled trial.

A controlled clinical trial was carried out to assess whether a birth room setting would influence the care of mothers and newborns. Of the 163 low-risk women enrolled, 49 (30%) manifested some prenatal risk and were excluded. The remaining 114 were allocated by strict alternation to a birth room or a conventional setting. Of the 56 women allocated to the birth room, 63% of the primiparas and 19% of the multiparas were later transferred. The numbers in the two settings who had oxytocin stimulation, epidural anesthesia, forceps delivery or cesarean section did not show statistically significant differences. The episiotomy rates were slightly lower in the birth room than in the conventional setting, and the rates of an intact perineum were higher in the birth room. Neither the Apgar scores nor the morbidity rates of the infants showed statistically significant differences related to the setting to which the mother had been allocated, although more infants from the conventional setting were admitted to a special care unit. Both "experimental" groups of women less often received routine perineal shaving, enemas or intravenous infusions than did an obstetrically similar nonexperimental comparison group. Despite the apparent inability in this setting for the birth room to influence the rate of major obstetric procedures (except for episiotomy) and outcomes, the authors believe that a birth room is desirable in tertiary care centres as well as in community hospitals.     

Streptokinase in central retinal vein occlusion: a controlled clinical trial.

Forty patients with central retinal vein occlusion were allocated at random either to a treatment group given streptokinase followed by anticoagulatns or to a control group given no specific treatment. The two groups, which were each of 20 patients, were broadly similar in respect of clinical and laboratory values and similar in their initial visual acuity. At follow-up ("final" vision) the visual acuity in the treated group was significantly better than in the untreated group. Only one treated patient developed thrombotic glaucoma compared with four controls. Streptokinase may, however, have been responsible for vitreous haemorrhage (and permanent loss of vision) in three patients and hence probably has only a limited role in the treatment of central retinal vein occlusion.