Development of a clinical prediction model for the postthrombotic syndrome in a prospective cohort of patients with proximal deep vein thrombosis.

Essentials We developed a prediction model for postthrombotic syndrome (PTS) after deep vein thrombosis (DVT). High risk predictors were iliac vein DVT, BMI>35 and moderate-severe Villalta category. Patients with a score ≥4 had an odds ratio of 5.9 (95% CI 2.1-16.6) for PTS. SOX-PTS score may select DVT patients for close monitoring or aggressive strategies to treat DVT. SUMMARY: Background Postthrombotic syndrome (PTS) is a chronic complication that develops in 20-50% of patients after deep vein thrombosis (DVT). Although individual risk factors for PTS have been characterized, the ability to predict which DVT patients are likely to develop PTS remains limited. Objective To develop a clinical prediction score for PTS in patients with DVT. Methods The derivation cohort consisted of participants in the SOX Trial, a randomized double-blind placebo-controlled trial of elastic compression stockings versus placebo stockings worn for 2 years after DVT to prevent PTS in patients with a first proximal DVT, enrolled in 24 community and tertiary-care hospitals from 2004 to 2010. Multivariable logistic regression analysis of baseline characteristics was performed. The outcome was the occurrence of PTS, diagnosed starting from 6 months or later according to Ginsberg's criteria. Results Seven hundred and sixty-two patients were included in the analysis. The median follow-up was 728 days. The model includes three independent predictors, and has a range of possible scores from 0 to 5. High-risk predictors were: index DVT in the iliac vein; body mass index of ≥ 35 kg m-2 ; and moderate-severe Villalta severity category at DVT diagnosis. As compared with patients with a score of 0, those with a score of ≥ 4 had an odds ratio of 5.9 (95% confidence interval 2.1-16.6) for developing PTS. Conclusions To our knowledge, this is the first clinical prediction score for PTS. We identified three independent predictors that, when combined, predicted PTS risk after a first proximal DVT. The SOX-PTS score requires external validation before it can be considered for clinical use.

Side effects of hyperbaric oxygen therapy in children with cerebral palsy.

BACKGROUND: This article reports the side effects observed in a double-blind placebo-controlled multi-center randomized clinical trial carried out to assess the efficacy and safety of hyperbaric oxygen (HBO2) therapy in children with cerebral palsy. Intention-to-treat analysis did not prove to have a beneficial effect. MATERIAL AND METHODS: 111 children aged 3 to 12 years were included and followed for 8 weeks. They all received 40 compressions of 1 hour (5 days per week). In the treated group (n=57), HBO2 sessions consisted of an exposure to 100% oxygen at 1.75 atmosphere absolute (atm abs) while children in the control group (n=54) received air at 1.3 atm abs. A physician carried out a general health surveillance including an ear examination prior to and immediately following each session. All clinical events occurring during the course of the study were recorded. FINDINGS: Events were classified in 3 categories: Events related to pressure/volume changes, events related to oxygen toxicity, and other events. No events due to oxygen toxicity were noted. Only middle ear barotrauma significantly differed according to the groups (50% in HBO2 session group versus 27.8% in control group). Other events were rare and equivalent in both groups. CONCLUSION: Short-term exposure to HBO2 at medium level pressure (1.75 atm abs) was responsible for a significant increase of middle ear barotrauma compared to children that received very low external pressure (1.3 atm abs).

A multicenter, randomized, double-blinded trial of pyridostigmine in postpolio syndrome.

BACKGROUND: Postpoliomyelitis syndrome (PPS) is likely due to degeneration and dysfunction of terminal axons of enlarged postpolio motor units. Age-related decline in growth hormone and insulin-like growth factor (IGF-I) may be a contributing factor. Neuromuscular junction abnormalities and decreased IGF-I levels may respond to the anticholinesterase pyridostigmine, with consequent improvement in strength, fatigue, and quality of life. OBJECTIVES: To determine the effect of pyridostigmine in PPS on health-related quality of life, isometric muscle strength, fatigue, and serum IGF-I levels; and to assess the safety of pyridostigmine in PPS. METHODS: The study was a multicenter, randomized, double-blinded, placebo-controlled trial of a 6-month course of pyridostigmine 60 mg three times per day in 126 PPS patients. The primary data analysis compared mean changes of outcomes between treatment and control groups at 6 months using an intention to treat approach. Secondary analyses included a comparison of outcomes at 6 and 10 weeks, and in compliant patients. RESULTS: The study showed no significant differences in pyridostigmine and placebo-treated patients with regard to changes in quality of life, isometric strength, fatigue, and IGF-I serum levels at 6 months in the primary analysis and in compliant patients. There were no differences in outcomes at 6 and 10 weeks between groups. However, very weak muscles (1 to 25% predicted normal at baseline) were somewhat stronger (p = 0.10, 95% CI of difference -9.5 to 73.3%), and in compliant patients IGF-I was somewhat increased (p = 0.15, 95% CI of difference -6.4 to 44.8 ng/mL) at 6 months with the medication. Pyridostigmine was generally well tolerated. CONCLUSIONS: This study showed no significant differences between pyridostigmine and placebo-treated PPS patients on measures of quality of life, isometric strength, fatigue, and serum IGF-I.

A randomized comparison of the effect of four antihypertensive monotherapies on the subjective quality of life in previously untreated asymptomatic patients: field trial in general practice. The OCAPI Study Group. Optimiser le Choix d'un Anti-hypertenseur de Première Intention.

OBJECTIVE: To assess the equivalence of four antihypertensive treatments in patients with mild-to- moderate hypertension, and to compare the effects of those drugs on the subjective quality of life and clinical safety. DESIGN, SETTING AND PATIENTS: 653 patients aged > or = 18 years with untreated hypertension were randomly allocated to receive a combination of two diuretics (altizide and spironolactone), a beta-blocker (bisoprolol), a calcium antagonist (verapamil), or an angiotensin converting enzyme (ACE) inhibitor (enalapril). Follow-up lasted for 1 year. MAIN OUTCOME MEASURES: A composite outcome of the following measures was used to define success: attendance at the 12-month visit; at least nine supine DBP measurements during the study; and median supine DBP < 90 mmHg and a reduction of at least 10 mmHg compared with the baseline value. Failure was defined as one or more of those criteria not being fulfilled. Equivalence was concluded if the 95% confidence interval for the success rates differed between two groups by less than +/- 10%. Clinical safety and subjective quality of life were also assessed. RESULTS: No statistically significant differences in the change in DBP or systolic blood pressure were observed between the groups. The success rates were 43.9, 42.0, 32.5 and 43.9% in diuretic, beta-blocker, calcium antagonist and ACE inhibitor groups, respectively. Equivalence between the treatments could not be concluded, although analysis with a larger equivalence interval showed that some comparisons indicated equivalence. Significant improvement in satisfaction was observed for certain items for subjective quality of life at 1 month in the calcium antagonist treatment group, and significant differences in the responses to the clinical safety questionnaire were observed after 1-month follow-up in calcium antagonist and beta-blocker groups. Differences were no longer significant after 9 months. CONCLUSIONS: These results do not provide evidence on the basis of efficacy of blood pressure lowering or ability to increase short-term (1-year) safety and quality of life favouring any particular treatment among the studied drugs for newly diagnosed patients with mild-to-moderate hypertension.

Efficacy of acebutolol after acute myocardial infarction (the APSI trial). The APSI Investigators.

A randomized, placebo-controlled trial was carried out to determine the effectiveness of acebutolol in preventing late death in high-risk patients surviving an acute myocardial infarction (MI). The average 1-year mortality rate in placebo groups of 9 trials of beta blockers in post-MI patients was 7.2% compared with 17% in a nonselected cohort of patients who had survived at least 7 days after an MI. The mandate for this trial was based on the fact that high-risk patients whose mortality rate exceeds 20% have not been enrolled in significant numbers in previous trials. It remains to be proved whether beta-blocking therapy in this patient population is beneficial. Selection of high-risk patients for inclusion in the trial was based on an algorithm set up from the Essai de Prevention Secondaire de l'Infarctus du Myocarde Registry. At the time of the second interim analysis, the mortality rate in the placebo group was 12%, lower than expected (greater than or equal to 20%). The trial was stopped; at that time, 309 patients had been allocated to placebo and 298 patients to acebutolol therapy. After 318 days, there were 17 deaths in the acebutolol-treated group and 34 in the placebo group, a reduction in total mortality of 48% (p = 0.019). There were 30 vascular deaths in the placebo group and 12 in the acebutolol group. Thus, cardiovascular mortality with acebutolol was reduced by 58% (p = 0.006). The incidence of all cardiovascular-related deaths was lower in the acebutolol-treated group. The total reduction in mortality did not appear to be correlated with secondary risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of nonspecific immunity to reduce the risk of recurrent infections in children attending day-care centers. The Epicrèche Research Group.

A randomized, double blind, placebo-controlled clinical trial was performed in 423 children attending day-care centers to assess whether stimulating nonspecific immunity would reduce the incidence of recurrent infections. The drug used for the trial (Imocur) is an extract obtained from eight different species of bacteria. At the end of the total follow-up period (3 months with treatment and 4.5 months without), the risk for > or = 4 episodes of upper respiratory infections was not significantly lower in the treated group than in the placebo group (26.7% vs. 33.8%, relative risk, 0.79; 95% confidence interval, 0.59 to 1.06). In an exploratory analysis limited to the 3-month treatment period, however, we observed a 48% reduction in the risk of presenting > or = 3 episodes of upper respiratory infections: 9.5% vs. 18.3%, respectively, in the treatment group and the placebo group (relative risk, 0.52; 95% confidence interval, 0.31 to 0.86). Similar results were found for the risk of > or = 1 episode of gastroenteritis. We also observed a strong correlation between the drug efficacy and age; this observation is coherent with the underlying pathophysiologic model in which the immune system matures with age.

Serum insulin-like growth factor-I (IGF-I) does not correlate positively with isometric strength, fatigue, and quality of life in post-polio syndrome.

OBJECTIVES AND BACKGROUND: To determine if serum insulin-like growth factor-I (IGF-I) levels are associated with strength, body mass index (BMI), fatigue, or quality of life in post-poliomyelitis syndrome (PPS). PPS is likely due to a distal disintegration of enlarged post-polio motor units as a result of terminal axonal sprouting. Age-related decline in growth hormone and IGF-I (which support terminal axonal sprouts) is proposed as a contributing factor. METHODS: As part of the North American Post-Poliomyelitis Pyridostigmine Study (NAPPS), baseline data on maximum voluntary isometric contraction (MVIC), BMI, subjective fatigue (fatigue severity scale, Hare fatigue symptom scale), health-related quality of life (short form health survey-36; SF-36), and serum IGF-I levels were gathered on 112 PPS patients. Pearson correlation coefficients were calculated to evaluate the association between serum IGF-I and MVIC in 12 muscles, BMI, two fatigue scales, and SF-36 scale scores. RESULTS: There is a significant inverse correlation of IGF-I levels with MVIC in left ankle dorsiflexors (r=-0.30, P<0.01), and left and right knee extensors (r=-0.22, -0.25, P=<0.01, 0.01), but no significant correlations in other muscles. When men and women were evaluated separately, inverse correlations of IGF-I levels with MVIC were found only in men. IGF-I correlated inversely with BMI (r=-0.32, P=0006) and age (r=-0.32, P=0.0005). IGF-I did not correlate with the fatigue or SF-36 scales. CONCLUSIONS: In this exploratory study, we found that contrary to our expectations, IGF-I did not correlate positively with strength. IGF-I correlated negatively with strength in several lower extremity muscles, BMI, and age. IGF-I is likely not an important factor in the pathogenesis of fatigue and in determining quality of life in PPS, but its role on strength should be studied further.

Coordination of primary health care for back pain. A randomized controlled trial.

STUDY DESIGN: A randomized controlled trial comparing usual care with a program for the coordination of primary health care (CORE) for the treatment of subacute low-back pain patients. OBJECTIVES: To measure the effectiveness of the CORE program as a mean for implementing clinical practice guidelines for low-back pain in an urban community. SUMMARY OF BACKGROUND DATA: Clinical practice guidelines have been developed for primary care physicians and patients on the clinical management of low-back pain. The implementation of the guidelines in a large community is difficult with the multiplicity of medical and nonmedical back care providers and products. The CORE program was designed to make the guidelines fit in this complex environment. METHODS: One hundred ten workers compensated for low-back pain for 4 to 8 weeks in metropolitan Montreal were randomized in two groups: usual care (N = 56) and the CORE program (N = 54). Coordination of primary health care was performed by two primary care physicians and a nurse in liaison with the treating physicians, and included a complete examination, recommendations for the clinical management, and support to carry out the recommendations. All workers were followed for 6 months. Back pain and functional status were assessed at baseline, 3 months, and 6 months. RESULTS: In the 6-month follow-up, the CORE group returned to work 6.6 days (standard error = 8.9) quicker than the control group, a difference that was not statistically significant. However, the CORE group showed a sustained improvement in pain and functional status with two-fold differences at the end of the 6 months of follow-up. This represented nine points on the Oswestry scale (P = 0.02) and 12 points on the Quebec Back Pain Disability Scale (P = 0.01). The CORE group also used three times less specialized imaging tests of the spine at 3 months (P < 0.01) and exercised twice as much at 6 months (P < 0.05) than the controls. CONCLUSIONS: The therapeutic results for workers with low-back pain could be improved by implementing the clinical practice guidelines with primary care physicians in a large community, without delaying the return to work. The CORE intervention for back pain patients is highly relevant to primary care practice. It is simple in its application, flexible to accommodate physicians' and- patients' preferences in health care, and it is effective on patients' clinical outcome.

Promotion of breastfeeding intervention trial (PROBIT): a cluster-randomized trial in the Republic of Belarus. Design, follow-up, and data validation.

This paper summarizes the objectives, design, follow-up, and data validation of a cluster-randomized trial of a breastfeeding promotion intervention modeled on the WHO/UNICEF Baby-Friendly Hospital Initiative (BFHI). Thirty-four hospitals and their affiliated polyclinics in the Republic of Belarus were randomized to receive BFHI training of medical, midwifery, and nursing staffs (experimental group) or to continue their routine practices (control group). All breastfeeding mother-infant dyads were considered eligible for inclusion in the study if the infant was singleton, born at > or = 37 weeks gestation, weighed > or = 2500 grams at birth, and had a 5-minute Apgar score > or = 5, and neither mother nor infant had a medical condition for which breastfeeding was contraindicated. One experimental and one control site refused to accept their randomized allocation and dropped out of the trial. A total of 17,795 mothers were recruited at the 32 remaining sites, and their infants were followed up at 1, 2, 3, 6, 9, and 12 months of age. To our knowledge, this is the largest randomized trial ever undertaken in area of human milk and lactation. Monitoring visits of all experimental and control maternity hospitals and polyclinics were undertaken prior to recruitment and twice more during recruitment and follow-up to ensure compliance with the randomized allocation. Major study outcomes include the occurrence of > or = 1 episode of gastrointestinal infection, > or = 2 respiratory infections, and the duration of breastfeeding, and are analyzed according to randomized allocation ("intention to treat"). One of the 32 remaining study sites was dropped from the trial because of apparently falsified follow-up data, as suggested by an unrealistically low incidence of infection and unrealistically long duration of breastfeeding, and as confirmed by subsequent data audit of polyclinic charts and interviews with mothers of 64 randomly-selected study infants at the site. Smaller random audits at each of the remaining sites showed extremely high concordance between the PROBIT data forms and both the polyclinic charts and maternal interviews, with no evident difference in under- or over-reporting in experimental vs control sites. Of the 17,046 infants recruited from the 31 participating study sites, 16,491 (96.7%) completed the study and only 555 (3.3%) were lost to follow-up. PROBIT's results should help inform decision-making for clinicians, hospitals, industry, and governments concerning the support, protection, and promotion of breastfeeding.

[Example of a phase IV trial involving several physicians and aiming at answering a scientific question: EOL]. / Exemple d'un essai de phase IV impliquant de nombreux médecins et visant a répondre à une question scientifique: EOL.

The aim of this trial was to test the hypothesis that a reduced number of doses improves compliance in current medical practice. Compliance with twice a day dosage was compared with compliance with three doses a day. Two bioequivalent presentations of nicardipine were used, the regular presentation (t.i.d.) and the slow-release (b.i.d.). The trial was controlled, randomized, open, in two parallel groups: (1)'t.i.d.' group: one tablet of regular nicardipine, 20 mg, three times a day, three months; (2) 'b.i.d.' group: one capsule of slow-release nicardipine, twice a day, three months. 2651 general practitioners randomized 7274 hypertensive patients. The primary criterion was documented in 93.7 per cent of the cases at the end of the trial. The remaining 6.3 per cent comprised treatment withdrawal (2.8 per cent) and patients lost to follow-up (3.5 per cent). The primary criterion study was compliance, assessed by a self-questionnaire filled in by the patient and a standardised interview by the physician. Compliance was slightly better in the b.i.d. group than in the t.i.d. group (p < 0.001). Remaining pill count was also used but it was a failure. A random sample of investigators made on-site visits. Discordant data were infrequent and were limited to dates of visits. Difficulties with on-site visits were mostly due to a rather frequent lack of source records.

[Monitoring of clinical trials and interim analysis. 1. Monitoring committee]. / Surveillance d'essais cliniques et analyses intermédiaires. 1. Les comités de surveillance.

In order to fulfil the ethical principles linked to the protection of patients randomized in a controlled clinical trial, monitoring procedures need to be set up. In this context, a committee of experts, called the data monitoring committee is in charge of reviewing regularly unblinded data to assess the quality and the relevance of the trial, to evaluate the evidence of an emerging treatment difference and to control the rate of occurrence of serious adverse events. After each meeting, the monitoring committee reports to the steering committee its recommendation to continue or to stop the trial prematurely. Protocol modifications might be proposed as well. Illustrated with several examples, this article reviews different situations a monitoring committee might have to tackle with.

[Monitoring of clinical trials and interim analysis. 2. Statistic methods]. / Surveillance d'essais cliniques et analyses intermédiaires. 2. Méthodes statistiques.

Although the decision to continue or to stop prematurely a clinical trial is not solely based on statistical tests, they bring useful objective arguments to the data monitoring board. However, the multiple use of statistical tests leads to increase the risk of false positive conclusions in favor of one of the treatments, and several methods have been developed to address this problem. This article presents the four major strategies that are being used for monitoring clinical trials, as well as the rationale for planning and using such statistical monitoring procedures.

Graduated compression stockings to treat acute leg pain associated with proximal DVT. A randomised controlled trial.

Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30-40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.

Effect of treatment gaps in elderly patients with dementia treated with cholinesterase inhibitors.

OBJECTIVE: To determine the effect of treatment gaps on the risk of institutionalization or death among community-dwelling elderly patients treated with cholinesterase inhibitors (ChIs). METHODS: A survival analysis was conducted among a cohort of community-dwelling elderly patients (age 66+) newly treated with ChIs identified in the Quebec drug claims databases (Régie de l'Assurance Maladie du Québec [RAMQ]) between January 1, 2000, and December 31, 2007. Treatment nonpersistence during the year following ChI initiation was defined as treatment discontinuation or gaps of at least 6 weeks. To account for reverse causality, Cox proportional hazard modeling was conducted only among patients who did not discontinue treatment, in order to assess the association between treatment nonpersistence and institutionalization or death. RESULTS: Among the 24,394 elderly ChI users, 4,108 (16.8) experienced a treatment gap during the year following ChI treatment initiation while 596 (2.4%) discontinued their treatment within the first 3 months (early stoppers) and 4,038 (16.6%) after 3 months of treatment (late stoppers). Of all treated patients, 4,409 (18.1%) were institutionalized or died during follow-up. In patients who did not stop their treatment, the risk of institutionalization or death appeared lower in patients who experienced a treatment gap (hazard ratio 0.91; 95% confidence interval 0.86-0.96). CONCLUSIONS: Our results suggest that, contrary to what was previously reported in clinical trials, treatment gaps do not compromise the outcome of patients treated with ChIs in a real-life setting.

Economic burden and cost determinants of deep vein thrombosis during 2 years following diagnosis: a prospective evaluation.

BACKGROUND: Few studies have evaluated the long-term economic consequences of deep vein thrombosis (DVT). None of them have incorporated prospectively collected clinical data to ensure accurate identification of incident cases of DVT and DVT-related health outcomes of interest, such as post-thrombotic syndrome (PTS). OBJECTIVES: To prospectively quantify medical and non-medical resource use and costs related to DVT during 2 years following diagnosis, and to identify clinical determinants of costs. METHODS: Three hundred and fifty-five consecutive patients with acute DVT were recruited at seven Canadian hospital centers. Resource use and cost information were retrieved from three sources: weekly patient-completed cost diaries, nurse-completed case report forms, and the Quebec provincial administrative healthcare database (RAMQ). RESULTS: The rate of DVT-related hospitalization was 3.5 per 100 patient-years (95% confidence interval [CI] 2.2-4.9). Patients reported a mean (standard deviation) of 15.0 (14.5) physician visits and 0.7 (1.2) other healthcare professional visits. The average cost of DVT was $5180 (95% CI $4344-6017) in Canadian dollars, with 51.6% of costs being attributable to non-medical resource use. Multivariate analysis identified four independent predictors of costs: concomitant pulmonary embolism (relative increase in cost [RIC] 3.16; 95% CI 2.18-4.58), unprovoked DVT (RIC 1.65; 95% CI 1.28-2.13), development of PTS during follow-up (RIC 1.35; 95% CI 1.05-1.74), and management of DVT in the inpatient setting (RIC 1.79; 95% CI 1.33-2.40). CONCLUSIONS: The economic burden of DVT is substantial. The use of measures to prevent the occurrence of PTS and favoring outpatient care of DVT has the potential to diminish costs.

The efficacy and harm of prostaglandin analogues for IOP reduction in glaucoma patients compared to dorzolamide and brimonidine: a systematic review.

AIM: To systematically review the literature on the efficacy and harm of prostaglandin analogues (PGAs) compared to brimonidine and dorzolamide in treating elevated intraocular pressure (IOP). METHODS: Keywords were searched in major literature databases to identify relevant randomised clinical trials (RCTs) of PGAs for ophthalmic use. The study quality of RCTs was assessed using the Jadad scale. Outcomes assessed included reduction in IOP in individual patients, adverse events (AEs) and withdrawals due to AEs. RESULTS: Eight unique RCTs evaluating a total of 1,722 individuals were included in this systematic review. Analysis did not show a significant reduction in the mean IOP from patients receiving latanoprost compared with those receiving brimonidine (WMD = -1.04; p = 0.30). On the other hand, the latanoprost group showed a significant reduction in mean IOP compared to the dorzolamide group (WMD = -2.64; p<0.00001). The number of ocular AEs (excluding hyperaemia) was significantly higher in the brimonidine group compared with the latanoprost group (RR = 0.66; p = 0.0005). CONCLUSION: Latanoprost was found to be significantly superior to dorzolamide but not brimonidine. However, ocular adverse events were significantly fewer in latanoprost users than in brimonide users. Neither travoprost nor bimatoprost was compared to dorzolamide or brimonidine in the present literature.

Fatigue in multiple sclerosis: association with disease-related, behavioural and psychosocial factors.

We determined biopsychosocial correlates of general, physical, and mental fatigue in MS patients, by evaluating the additional contribution of potentially modifiable factors after accounting for non-modifiable disease-related factors. Fifty-three ambulatory MS patients, along with 28 normal controls were recruited for a cross-sectional study. Subjects completed the Multidimensional Fatigue Inventory (MFI) and Fatigue Severity Scale. Potential correlates evaluated were: disease-related factors (disease duration and type, immunomodulating treatment, muscle strength, pain, forced vital capacity (FVC), respiratory muscle strength, body mass index, disability, fibromyalgia), behavioural factors (physical activity, sleep quality) and psychosocial factors (depression, stress, self-efficacy). Multivariate models were calculated for MFI General, Physical, and Mental Fatigue. Age-adjusted multivariate models with non-modifiable factors included the following predictors (P < or = 0.10) of 1) MFI General and Mental Fatigue: none; and 2) MFI Physical Fatigue: FVC and disability. The following potentially modifiable predictors (P < or = 0.10) made an additional contribution to the models 1) MFI General Fatigue: sleep quality, self-efficacy, pain; 2) MFI Physical Fatigue: self-efficacy, physical activity; and 3) MFI Mental Fatigue: stress, self-efficacy. Fatigue in MS is multidimensional. Correlates of general and physical fatigue are disease-related, behavioural and psychosocial factors. Correlates of mental fatigue are psychosocial factors. Potentially modifiable factors account for a considerable portion of fatigue.

Persistency of use of COX-2-specific inhibitors and non-specific non-steroidal anti-inflammatory drugs (NSAIDs) in Quebec.

The effectiveness of pharmacological therapies is dependent in part on patient persistency with the prescribed therapeutic regimen. In the case of non-specific non-steroidal anti-inflammatory drugs (NSAIDs), effectiveness is often compromised by undesirable side-effects, poor compliance or discontinuation of therapy. While patterns of utilization of non-specific NSAIDs have been investigated, few data are available on the patterns of persistency for cyclooxygenase (COX)-2-specific inhibitors. This study used a provincial health-care system database in Quebec, Canada, to determine the duration of treatment in new users of COX-2-specific inhibitors and non-specific NSAIDs over the first 3 months of treatment, and to characterize the factors associated with treatment persistency. Results demonstrate that the median duration of treatment was longer among patients initially prescribed COX-2-specific inhibitors (30 days and 23 days for celecoxib and rofecoxib respectively) than in those prescribed non-selective NSAIDs (10 days). Although the percentage of patients remaining on COX-2-specific drugs declined over the course of treatment, few patients on either celecoxib or rofecoxib switched drugs, either to the other COX-2-specific inhibitor or to non-specific NSAIDs. Factors associated with persistent drug use were: COX-2-specific inhibitors, age, and the use of gastroprotective agents either at treatment initiation or during follow-up. Dosage, chronic disease score and prescriber's specialty were only marginally associated with persistency. Prior use of gastroprotective agents was associated with lower persistency. Although the limitations of this study, which included lack of information on the indication for the prescription and the reason for switch or discontinuation, preclude definite conclusions regarding patterns of use of these drugs, the data suggest that the use of COX-2-specific inhibitors may result in increased persistency with treatment.