Efficacy of bupropion and nortriptyline for smoking cessation among people at risk for or with chronic obstructive pulmonary disease.

BACKGROUND: The observations that smokers with chronic obstructive pulmonary disease (COPD) are at increased risk of depression and that nicotine may have antidepressant effects and regulate mood provide a rationale for the use of antidepressant drugs for smoking cessation in patients with COPD. No clinical trial has studied the efficacy of bupropion hydrochloride and nortriptyline hydrochloride for smoking cessation in this patient population, to our knowledge. METHODS: In a placebo-controlled double-dummy randomized trial, 255 adults at risk for COPD or with COPD were prescribed sustained-release bupropion (bupropion SR) (150 mg twice daily) or nortriptyline (75 mg once daily) for 12 weeks. All patients received smoking cessation counseling. The main outcome measure was prolonged abstinence from smoking from week 4 to week 26 after the target quit date. RESULTS: The use of bupropion SR and nortriptyline resulted in higher prolonged abstinence rates compared with placebo, although only the difference between bupropion SR and placebo was statistically significant (differences with placebo, 13.1% [95% confidence interval, 1.2%-25.1%] for bupropion SR and 10.2% [95% confidence interval, -1.7% to 22.2%] for nortriptyline). In patients with COPD, bupropion SR and nortriptyline seem efficacious in achieving prolonged abstinence (differences with placebo, 18.9% [95% confidence interval, 3.6%-34.2%] for bupropion SR and 12.9% [95% confidence interval, -0.8% to 26.4%] for nortriptyline). In participants at risk for COPD, no statistically significant differences with placebo in prolonged abstinence rates were found. CONCLUSIONS: Bupropion SR treatment is an efficacious aid to smoking cessation in patients with COPD. Nortriptyline treatment seems to be a useful alternative.

Increasing the daily water intake for the prophylactic treatment of headache: a pilot trial.

Dehydration is commonly believed to result in headache, but the effectiveness of increasing the water intake in patients who frequently suffer from headaches has not been studied thus far. In a pilot study, we examined the possible effects and feasibility of increased water intake in headache patients. Eighteen headache patients (all had migraine, two also had tension-type headache) were randomly allocated to placebo medication, or the advice to additionally drink 1.5 l of water per day, for a period of 12 weeks. Effect measurements consisted of a 2 weeks headache diary and the Migraine Specific Quality of Life (MSQOL) questionnaire. The advice to increase the daily fluid intake by 1.5 l increased the fluid intake in the intervention group by approximately 1 l. This reduced the total hours of headache in 2 weeks by 21 h (95% CI: -48 to 5). Mean headache intensity decreased by 13 mm (95% CI: -32 to 5) on a visual analogue scale (VAS). The effects on MSQOL, number of headache episodes, and medication seemed to be small. The data of the present study suggest a reduction in the total number of hours and intensity of headache episodes after increased water intake. Our results seem to justify larger scaled research on the effectiveness of increased water intake in headache patients.

The validity and ethics of giving placebo in a randomized nonpharmacologic trial was evaluated.

OBJECTIVE: When studying the effects of a non-pharmacologic intervention, the choice of a control group is often difficult. In a study on the effectiveness of increased water intake on voiding dysfunction in elderly men we used an unusual design. This article addresses the internal validty and ethics of this design. STUDY DESIGN AND SETTING: The randomized trial we evaluated had a 6-month follow-up period and was carried out among 141 elderly men with moderate lower urinary tract symptoms. The experimental group was given the instruction to drink more water, the control group received placebo medication. The participants were not informed that there was a 50% chance of receiving placebo. We measured whether the prior expectations and preferences were comparable for the two study groups, whether blinding was preserved throughout the study period, and whether the participants considered this design ethical. RESULTS: Prior to randomization, patients had higher expectations for the experimental intervention, but there was not statistically significant difference in their preference. During the study period, two out of 71 patients in the control group unmasked the placebo. In general, both groups fully agreed with the informed consent procedure. CONCLUSION: This design can be considered when the effects of a non-pharmacologic interventions are studied.

Should nortriptyline be used as a first-line aid to help smokers quit? Results from a systematic review and meta-analysis.

OBJECTIVES: The objective of this paper is to evaluate the efficacy of nortriptyline for smoking cessation compared to placebo and bupropion sustained release. DATA SOURCES: Randomized trials were identified by (1) checking electronic and (2) online publicly accessible registers of clinical trials; (3) searching references of identified studies and screening abstract books of conferences and symposia, and (4) personal communication with the first authors of identified papers. REVIEW METHODS: We included randomized trials in which nortriptyline was compared to placebo or bupropion hydrochloride SR. The main clinical outcome measure was (at least) 6-month prolonged abstinence, confirmed with a biochemical test. To investigate the efficacy of nortriptyline in time, we calculated the percentage of smokers who relapsed in time. RESULTS: We identified five randomized trials, including 861 smokers. Compared to placebo medication, nortriptyline resulted in significantly higher prolonged abstinence rates after at least 6 months [relative risk (RR) = 2.4, 95% CI 1.7-3.6; RD = 0.11, 95% CI 0.07-0.15]. The difference in efficacy between nortriptyline and placebo was highest in the first months after the target quit date. However, the number of people who remained abstinent decreased substantially and significantly faster over time in the nortriptyline group. Although bupropion resulted in higher abstinence rates compared with nortriptyline, the difference was not statistically significant (RR = 1.7, 95% CI 0.7-4.1). CONCLUSION: This systematic review and meta-analysis shows that the use of nortriptyline for smoking cessation resulted in higher prolonged abstinence rates after at least 6 months compared to placebo treatment. Furthermore, the use of nortriptyline for smoking cessation is well tolerated and safe. As a result, we believe health care professionals should be recommended to prescribe nortriptyline as a first-line therapy for smoking cessation, also because of the much lower cost of nortriptyline compared to bupropion SR.

Prevalence and characteristics of headache in Dutch schoolchildren.

The aim of this study was to determine whether there has been an increase in headache prevalence in Dutch children and to compare headache characteristics of children with low, medium and high headache severity.A sample of 2358 schoolchildren between the ages of 10 and 17 years filled out Waters' Headache Questionnaire and the Paediatric Pain Assessment Tool. Results showed that 21% of the boys and 26% of the girls at elementary school, and 14% of the boys and 28% of the girls at high school reported weekly headaches. When compared to figures from a previous study in the Netherlands published in 1985, the prevalence of weekly headaches in 10-17-year-olds has increased by 6%. In boys at elementary school, the prevalence of headaches with a frequency of a few times a week has doubled. Children with low, medium and high headache severity differed with respect to all headache characteristics, i.e. pain quality, accompanying symptoms, warning signals, location, onset, impact of headache, family occurrence, perceived cause, medical consultation, and school absence.

[Roaming through methodology. XXIII. The need for randomization and blinding in therapeutic investigations]. / Dwalingen in de methodologie. XXIII. De noodzaak van randomiseren en blinderen in therapeutisch onderzoek.

After the start of a treatment patients often get better. This may be due to the treatment or other circumstances. There may be errors in the execution of the study, the disease may disappear spontaneously, effective co-interventions may be present and possibly there are also placebo effects. Most of the time, only sufficiently large randomised, blinded research is useful to estimate the efficacy of drugs and of other treatments. The best comparison is often between the new treatment and the best available one, not the sham treatment.

The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial.

OBJECTIVES: To evaluate the efficacy, the dose-dependence, and the durability of the effect of the ginkgo biloba special extract EGb 761 (ginkgo) in older people with dementia or age-associated memory impairment. DESIGN: A 24-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. SETTING: Homes for the elderly in the southern part of the Netherlands. PARTICIPANTS: Older persons with dementia (either Alzheimer's dementia or vascular dementia; mild to moderate degree) or age-associated memory impairment (AAMI). 214 Participants were recruited from 39 homes for the elderly. INTERVENTION: The participants were allocated randomly to treatment with EGb 761 (2 tablets per day, total dosage either 240 (high dose) or 160 (usual dose) mg/day) or placebo (0 mg/d). The total intervention period was 24 weeks. After 12 weeks of treatment, the initial ginkgo users were randomized once again to either continued ginkgo treatment or placebo treatment. Initial placebo use was prolonged after 12 weeks. MEASUREMENTS: Outcomes were assessed after 12 and 24 weeks of intervention. Outcome measures included neuropsychological testing (trail-making speed (NAI-ZVT-G), digit memory span (NAI-ZN-G), and verbal learning (NAI-WL)), clinical assessment (presence and severity of geriatric symptoms (SCAG), depressive mood (GDS), self-perceived health and memory status (report marks)), and behavioral assessment (self-reported level of instrumental daily life activities). RESULTS: An intention-to-treat analysis showed no effect on each of the outcome measures for participants who were assigned to ginkgo (n = 79) compared with placebo (n = 44) for the entire 24-week period. After 12 weeks of treatment, the combined high dose and usual dose ginkgo groups (n = 166) performed slightly better with regard to self-reported activities of daily life but slightly worse with regard to self-perceived health status compared with the placebo group (n = 48). No beneficial effects of a higher dose or a prolonged duration of ginkgo treatment were found. We could not detect any subgroup that benefited from ginkgo. Ginkgo use was also not associated with the occurrence of (serious) adverse events. CONCLUSIONS: The results of our trial suggest that ginkgo is not effective as a treatment for older people with mild to moderate dementia or age-associated memory impairment. Our results contrast sharply with those of previous ginkgo trials.

Randomized clinical trial on the use of antispasmodic drugs in barium enema: impact on radiological practice.

PURPOSE: To assess the willingness of radiologists to change their practice when the results of a randomized clinical trial (RCT) on the use of antispasmodic drugs in barium enema are presented. MATERIALS AND METHODS: During the years 1994 and 1995 two postal questionnaires were sent to 481 practicing radiologists who were all members of the Netherlands Society of Radiology. In the first questionnaire the respondents were asked to give the characteristics of their practices in performing daily barium enema. The data from this questionnaire was used as a reference. The second questionnaire was sent to the respondents together with an abstract on the randomized clinical trial supporting the use of antispasmodic drugs in barium enema. We also indicated a preference for Buscopan over Glucagon as the antispasmodic drug. The willingness to change prescription habits was measured by comparing the data of the two questionnaires. RESULTS: Of 481 practicing radiologists, 312 responded to the first questionnaire and gave information of their prescription habits (response rate 64%). These 312 responders were sent an abstract of the RCT and were asked to fill out a second questionnaire to determine their willingness to change their practice. Two hundred and sixty-seven radiologists responded (response rate 86%). A significant number of 119 (51%) were willing to increase the use of antispasmodic drugs. A significant number of 128 (55%) chose to increase the use of Buscopan, while a significant number of 81 (32%) were willing to decrease the use of Glucagon. CONCLUSION: Direct exposure to the results of an RCT recommending the use of antispasmodic drugs in barium enema, especially Buscopan, is likely to increase its use by practicing radiologists.

Recurrent headache, coping, and quality of life in children: a review.

OBJECTIVES: To clarify the concepts of coping with pain and quality of life (QoL) and to present a literature review of the strategies that children with recurrent headaches use to cope with their pain, the impact of recurrent headaches on children's QoL, and the influence of personal and situational variables on headache, coping, and QoL in children. METHODS: The literature search encompassed published articles that were found by means of a CD-ROM search of MEDLINE (1966 to December 1998) and PsycLIT (1974 to December 1998) and the snowball method. RESULTS: In pediatric headache research, only three studies have been found in which children report the use of various coping strategies, and only two studies considered QoL. Demographic factors and psychological variables such as depression, anger, and anxiety influence headache prevalence. The impact of headache-related variables such as headache type, severity, perceived cause, and prior experience on QoL has only been studied in adults. CONCLUSIONS: More research on coping and QoL is needed in pediatric headache. The conceptual model that is presented in this article may serve as a guide.

Balneotherapy for rheumatoid arthritis and osteoarthritis.

BACKGROUND: Balneotherapy (hydrotherapy or spa therapy) for patients with arthritis is one of the oldest forms of therapy. One of the aims of balneotherapy is to soothe the pain and as a consequence to relieve patients' suffering and make them feel well. OBJECTIVES: To perform a systematic review to assess the effects of balneotherapy for rheumatoid arthritis and osteoarthritis. SEARCH STRATEGY: Using the Cochrane search strategy, studies were found by screening: 1) The Medline CD-ROM database from 1966 to June 1999 and 2) the database from the Cochrane Field 'Rehabilitation and Related Therapies', which contains also studies published in journals not covered by Medline. Also, 3) reference checking and 4) personal communications with authors was carried out to retrieve eligible studies. To perform an adequate assessment of the methodological quality the languages of the publications had to be: Dutch, English, French or German. Date of the most recent literature search: June, 1999 SELECTION CRITERIA: Studies were eligible if they were randomized controlled trials (RCT) comparing balneotherapy with any intervention or with no intervention. Patients included had rheumatoid arthritis (RA), osteoarthritis (OA) or some other form of arthritis. Trials incorporating patients with definite or classical rheumatoid arthritis (RA) as defined by the American Rheumatism Association Criteria (ARA) (Ropes 1958) (these criteria have changed over time) or by the criteria of Steinbrocker (1949) were regarded as a separate group. At least one of the WHO/ILAR core set of endpoints for RA clinical trials had to be the main outcome measures. DATA COLLECTION AND ANALYSIS: A criteria list used to assess the methodological quality was the one developed at the Department of Epidemiology at the Maastricht University, called "the Maastricht list". The quality scores and data abstraction of the studies were carried out independently by two reviewers (HdV, RdB). Disagreements were solved by consensus. MAIN RESULTS: Ten trials with 607 patients were included in this review. Most trials reported positive findings, but were methodologically flawed to some extent. A 'quality of life' outcome was reported by two trials. Just one of the randomized trials mentioned an intention-to-treat analysis and only three performed a comparison of effects between groups. Pooling of the data was not performed, because of heterogeneity of the studies, multiple outcome measurements, and, apart from two studies, the overall data presentation was too scarce to enable pooling of the data. REVIEWER'S CONCLUSIONS: One cannot ignore the positive findings reported in most trials. However the scientific evidence is weak because of the poor methodological quality, the absence of an adequate statistical analysis, and the absence, for the patient, of most essential outcome measures (pain, quality of life), Therefore, the noted "positive findings" should be viewed with caution. Because of the methodological flaws an answer about the efficacy of balneotherapy cannot be provided at this time. Flaws found in the reviewed studies could be avoided in future trials.

No effect of bipolar interferential electrotherapy and pulsed ultrasound for soft tissue shoulder disorders: a randomised controlled trial.

OBJECTIVE: To assess the efficacy of bipolar interferential electrotherapy (ET) and pulsed ultrasound (US) as adjuvants to exercise therapy for soft tissue shoulder disorders (SD). METHODS: Randomised placebo controlled trial with a two by two factorial design plus an additional control group in 17 primary care physiotherapy practices in the south of the Netherlands. Patients with shoulder pain and/or restricted shoulder mobility, because of a soft tissue impairment without underlying specific or generalised condition, were enrolled if they had not recovered after six sessions of exercise therapy in two weeks. They were randomised to receive (1) active ET plus active US; (2) active ET plus dummy US; (3) dummy ET plus active US; (4) dummy ET plus dummy US; or (5) no adjuvants. Additionally, they received a maximum of 12 sessions of exercise therapy in six weeks. Measurements at baseline, 6 weeks and 3, 6, 9, and 12 months later were blinded for treatment. OUTCOME MEASURES: recovery, functional status, chief complaint, pain, clinical status, and range of motion. RESULTS: After written informed consent 180 patients were randomised: both the active treatments were given to 73 patients, both the dummy treatments to 72 patients, and 35 patients received no adjuvants. Prognosis of groups appeared similar at baseline. Blinding was successfully maintained. At six weeks seven patients (20%) without adjuvants reported very large improvement (including complete recovery), 17 (23%) and 16 (22%) with active and dummy ET, and 19 (26%) and 14 (19%) with active and dummy US. These proportions increased to about 40% at three months, but remained virtually stable thereafter. Up to 12 months follow up the 95% CI for differences between groups for all outcomes include zero. CONCLUSION: Neither ET nor US prove to be effective as adjuvants to exercise therapy for soft tissue SD.

A patient-specific approach for measuring functional status in low back pain.

BACKGROUND: Activities and their importance for daily living vary widely between patients. Patient-specific measurement of functional status means that the evaluation is focused on activities that an individual patient selected as main complaints. OBJECTIVE: To develop and to evaluate a patient-specific approach for measuring functional status in low back pain. STUDY DESIGN: A cohort of 150 patients was measured at baseline and 12 weeks later. METHODS: The feasibility of the patient-specific approach was evaluated in patients with nonspecific low back pain. We used effect size statistics to evaluate responsiveness in terms of sensitivity to change and specificity to change. RESULTS: The selection procedure for the main complaint was feasible but labor intensive. The patient-specific approach was able to detect changes in complaints that were highly relevant for the patients. The patient-specific approach appeared to be more sensitive to change but less specific to change compared with other instruments. CONCLUSIONS: On the basis of this study it would be valuable to apply the patient-specific approach in future studies, also with the aim of further evaluation. In the meantime a number of practical problems of the method need to be resolved.

Optimization of placebos for double-blind clinical trials. Experience with a phytopharmaceutical.

The maintenance of double-blind conditions in placebo-controlled trials depends on the quality of the placebo preparation. The placebo should match the active substance-containing preparation as closely as possible, but it must not contain any substances that might themselves be pharmacologically active. Active substances characterized by a particular colour, taste, smell or other easily perceptible properties constitute a challenge to researchers. The way of developing a placebo that matches a phytopharmaceutical to a satisfactory extent is described and discussed.

Low-level laser therapy in ankle sprains: a randomized clinical trial.

OBJECTIVE: To test the efficacy of low-level laser therapy on lateral ankle sprains as an addition to a standardized treatment regimen, a trial was conducted in which high-dose laser (5J/cm2), low-dose laser (0.5J/cm2), and placebo laser therapy (0J/cm2) at skin level were compared. DESIGN: Randomized, double-blind, controlled clinical trial with a follow-up of 1 year. Patients, therapists, assessors, and analysts were blinded to the assigned treatment. SETTING: An ambulatory care setting. PATIENTS: After informed consent and verification of exclusion criteria, 217 patients with acute lateral ankle sprains were randomized to three groups from September 1, 1993, through December 31, 1995. INTERVENTIONS: Twelve treatments of 904nm laser therapy in 4 weeks as an adjunct to a standardized treatment regimen of 4 weeks of brace therapy combined with standardized home exercises and advice. The laser therapy device used was a 904nm Ga-As laser, with 25-watt peak power and 5,000 or 500Hz frequency, a pulse duration of 200nsec, and an irradiated area of 1cm2. PRIMARY OUTCOME MEASURES: Pain and function as reported by the patient. RESULTS: Intention-to-treat analysis of the short-term results showed no statistically significant difference on the primary outcome measure, pain (p = .41), although the placebo group showed slightly less pain. Function was significantly better in the placebo group at 10 days (p = .01) and 14 days (p = .03) after randomization. The placebo group also performed significantly better on days of sick leave (p = .02) and at some points for hindrance in activities in daily life and pressure pain, as well as subjective recovery (p = .05). Intention-to-treat analysis showed that total days of absenteeism from work and sports were remarkably lower in the placebo group than in the laser groups, ranging from 3.7 to 5.3 and 6 to 8 days, respectively. The total number of relapses at 1 year in the low-dose laser group (n = 22) was significantly higher (p = .04) than in the other two groups (high laser, n = 13; placebo, n = 13). Subgroup analysis to correct for possible confounders did not alter these findings. CONCLUSIONS: Neither high- nor low-dose laser therapy is effective in the treatment of lateral ankle sprains.

Abdominal symptoms and food intolerance related to gallstones.

We have evaluated the association between gallstones and abdominal symptoms, comparing two different study designs. We asked questions on abdominal pain, dyspeptic symptoms, and food intolerance in (1) surgery patients referred for conditions unrelated to gallstones, screened by ultrasound (screening study, n = 892, 63 with gallstones); and in (2) symptomatic patients referred for gallbladder ultrasound (clinical study, n = 336, 71 with gallstones). Gallstones were associated with mid upper abdominal pain in the screening study, and with mid upper abdominal pain, biliary pain, and colic (each independently) in the clinical study. When these symptoms were absent (and only dyspeptic symptoms or food intolerance was present), gallstones were not more common than expected from the general population prevalence (estimated from the screening study). When upper abdominal pain symptoms are accounted for, other symptoms (dyspeptic; food intolerance; pain related to food intake) have no additional diagnostic value. The results are discussed, contrasting different types of studies.