Migraine and cardiovascular disease: a population-based study.

OBJECTIVES: Although the relationship between migraine and cardiovascular disease (CVD) has been studied, several questions remain unanswered. Herein we contrast the rate of diagnosed CVD as well as of risk factors for CVD in individuals with migraine with and without aura (MA and MO) and in controls. METHODS: In this case-control study, migraineurs (n = 6,102) and controls (n = 5,243) were representative of the adult US population. Headache diagnosis was formally assigned using a validated mailed questionnaire which also obtained details on treatment, comorbidities, and other variables. CVD events were obtained based on self-reported medical diagnosis. Risk factors for CVD and modified Framingham scores were computed. RESULTS: In unadjusted analyses, migraine overall and MA were associated with myocardial infarction, stroke, and claudication, and MO was associated with myocardial infarction and claudication. Migraineurs were more likely than controls to have a medical diagnosis of diabetes (12.6% vs 9.4%, odds ratio [OR] 1.4, 95% confidence interval [CI] 1.2-1.6), hypertension (33.1% vs 27.5%, OR 1.4, 95% CI 1.3-1.6), and high cholesterol (32.7% vs 25.6%, OR 1.4, 95% CI 1.3-1.5). Risk was highest in MA, but remained elevated in MO. Framingham scores were significantly higher in MO and MA than in controls. After adjustments (gender, age, disability, treatment, CVD risk factors), migraine remained significantly associated with myocardial infarction (OR 2.2, 95% CI 1.7-2.8), stroke (OR 1.5, 95% CI 1.2-2.1), and claudication (OR 2.69, 95% CI 1.98-3.23). CONCLUSION: Both migraine with and without aura are associated with cardiovascular disease (CVD) and with risk factors for CVD. However, since our sample size is large, the clinical relevance of the differences is yet to be established.

Migraine and cardiovascular disease: possible mechanisms of interaction.

Migraine, especially migraine with aura (MA), is an established risk factor for ischemic lesions of the brain. Recent evidence has also linked migraine to a broader range of ischemic vascular disorders including angina, myocardial infarction, coronary revascularization, claudication, and cardiovascular mortality. The mechanisms which link migraine to ischemic vascular disease remain uncertain and are likely to be complex. Cortical spreading depression, the presumed substrate of aura, may directly predispose to brain lesions and that would explain why MA is consistently demonstrated as a risk factor for cerebral ischemia, while for migraine without aura (MO), the evidence is less consistent. Additionally, individuals with migraine have a higher prevalence of risk factors known to be associated with cardiovascular disease (CVD), including hypertension, diabetes, and hyperlipidemia. The increased prevalence of CVD risk factors is also higher for MA than for MO. Since the evidence linking migraine and CVD is getting robust, neurologists should be aware of this association. Individuals with MO seem to be at little increased risk of CVD. MA is associated with an increased risk of ischemic stroke and likely also for other ischemic CVD events. Accordingly, heightened vigilance is recommended for modifiable cardiovascular risk factors in migraineurs, especially with MA. Ultimately, it will be important to determine whether MA is a modifiable risk factor for CVD and if preventive medications for migraine or antiplatelet therapy might reduce the risk of CVD in patients with MA.

Exposure to rizatriptan during pregnancy: post-marketing experience up to 30 June 2004.

Merck & Co., Inc. evaluates outcomes of the use of rizatriptan during pregnancy through a Pregnancy Registry in the United States (US) and spontaneous reports for pregnancies reported from sources outside the US. Review of the outcomes of 25 prospective pregnancy reports in the Pregnancy Registry and reports from other sources does not suggest that treatment with rizatriptan predisposes patients to spontaneous abortions or congenital anomalies. However, the number of reports is small. Healthcare providers in the United States are encouraged to report any prenatal exposure to rizatriptan by calling the Pregnancy Registry at +1 (800) 986 8999 or visiting the Registry's website at http://www.merckpregnancyregistries.com.

Determinants of migraine-specific quality of life.

This paper reports an analysis of two randomized controlled trials of rizatriptan, in which the 24-h Migraine Quality of Life QuestionnaireCopyright was used to assess migraine-specific quality of life in patients receiving acute treatment. The objective of the analysis was to determine which clinical effects of a migraine medication, as measured by traditional clinical trial endpoints, contribute to a better short-term health-related quality of life. The results demonstrate that patients who experience complete pain relief and are able to function at their normal ability within 2 h and experience no headache recurrence have the highest migraine-specific quality of life scores. Patients who were satisfied with medication at 2 h had higher migraine-specific quality of life scores than those who were not satisfied. In conclusion, migraine therapy that provides rapid, complete, and sustained pain relief, with restoration of functional ability, has the most beneficial impact on short-term health-related quality of life for migraineurs.

Patient satisfaction with rizatriptan versus other triptans: direct head-to-head comparisons.

This study summarises the impact of treatment with rizatriptan 10 mg versus other 5-HT 1B/1D receptor agonists (triptans) on patient satisfaction with medication. Rizatriptan is a potent, selective 5-HT1B/1D receptor agonist shown to be fast, effective and well tolerated in the acute treatment of migraine. We investigated patients' overall satisfaction with treatment in studies in which direct comparisons with other triptans were made. Data from five double-blind, placebo-controlled trials in which rizatriptan 10 mg was compared with another triptan were included in the analysis. Rizatriptan 10 mg was compared with sumatriptan 100 mg in one parallel study (n = 916), sumatriptan 50 mg in two crossover studies (n = 1599), naratriptan 2.5 mg in one parallel study (n = 502), and zolmitriptan 2.5 mg in one parallel study (n = 701). Satisfaction was reported by patients on a seven-point scale ranging from 'completely satisfied, couldn't be better' to 'completely dissatisfied, couldn't be worse' at 2 hours after dosing. The percent of patients in the top two 'satisfied' categories (completely or very satisfied) were analysed. More patients on rizatriptan 10 mg were completely or very satisfied compared with sumatriptan 100 mg (33% vs 26%, p < 0.05), sumatriptan 50 mg (40% vs 35%, p < 0.05), naratriptan 2.5 mg (33% vs 19%, p < 0.01), and zolmitriptan 2.5 mg (38% vs 30%, p < 0.05). In all five studies more patients treated with rizatriptan 10 mg or other triptans were completely or very satisfied with treatment than patients receiving placebo (p < 0.001, except naratriptan vs placebo p = 0.004). The results, combined with the superior efficacy profile (fast, effective, well tolerated) of rizatriptan 10 mg, should enhance the treatment of migraine headache and lead to improved therapeutic intervention in clinical practice.

Preference comparison of rizatriptan ODT 10-mg and sumatriptan 50-mg tablet in migraine.

OBJECTIVE: To compare the proportion of patients who prefer rizatriptan orally disintegrating tablet (ODT) 10-mg to sumatriptan 50-mg tablet. BACKGROUND: Migraineurs express treatment preference based on a variety of attributes including the speed of pain relief and medication formulation. Rizatriptan ODT is an orally disintegrating formulation of rizatriptan, a selective 5-HT1B/1D receptor agonist. This study was conducted to determine patient preference between rizatriptan ODT 10-mg and sumatriptan 50-mg tablet for the acute treatment of migraine. METHODS: This was a multicenter, randomized, open-label, two-period crossover study conducted in the United States with 524 enrolled patients. Patients treated a single moderate or severe headache in each treatment period. Patients treated one migraine with either rizatriptan ODT 10-mg or sumatriptan 50-mg tablet, then treated a second migraine with the alternate therapy. Patients completed diary assessments at baseline, and 30, 45, 60, 90, and 120 minutes postdose and rated headache severity on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). At the final study visit following treatment of their second migraine, patients expressed preference for one of the two study medications by completing an interviewer-administered Global Preference Question and then responded to a self-administered series of questions to capture their most important reason for preferring one study medication over the other. Safety measurements were recorded through standard adverse experience reporting. RESULTS: Three hundred eighty-six patients treated two migraine attacks. For those patients who expressed a preference for either rizatriptan ODT or sumatriptan (n = 374), the percentage of patients who preferred rizatriptan ODT 10-mg (57%, n = 213) was significantly greater than those who preferred sumatriptan 50-mg tablet (43%, n = 161) (P<.01). For those patients who treated two migraine attacks and had drug severity measures for both attacks (n = 384), a significantly greater percentage of patients reported pain relief after taking rizatriptan ODT than sumatriptan at the 45- and 60-minute time points (38% versus 29% and 58% versus 49%, respectively) (P<.01). In addition, a significantly greater percentage of patients taking rizatriptan ODT reported a pain-free status at the 60- and 120-minute time points (23% versus 17% [P<.05] and 60% versus 52% [P<.01], respectively). Both rizatriptan ODT and sumatriptan were well tolerated. CONCLUSIONS: A significantly greater proportion of patients preferred rizatriptan ODT 10-mg to sumatriptan 50-mg tablet for the acute treatment of migraine. Efficacy and safety data are consistent with the preference findings.

Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years.

BACKGROUND: The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma, although very young patients may have difficulty using inhalers, and dose delivery can be variable. Moreover, reduced compliance with inhaled therapy relative to orally administered therapy has been reported. One potential advantage of montelukast is the ease of administering a once-daily chewable tablet; additionally, no tachyphylaxis or change in the safety profile has been evidenced after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years, respectively. To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool children. OBJECTIVE: Our primary objective was to determine the safety profile of montelukast, an oral leukotriene receptor antagonist, in preschool children with persistent asthma. Secondarily, the effect of montelukast on exploratory measures of asthma control was also studied. DESIGN AND STATISTICAL ANALYSIS: We conducted a double-blind, multicenter, multinational study at 93 centers worldwide: including 56 in the United States, and 21 in countries in Africa, Australia, Europe, North America, and South America. In this study, we randomly assigned 689 patients (aged 2-5 years) to 12 weeks of treatment with placebo (228 patients) or 4 mg of montelukast as a chewable tablet (461 patients) after a 2-week placebo baseline period. Patients had a history of physician-diagnosed asthma requiring use of beta-agonist and a predefined level of daytime asthma symptoms. Caregivers answered questions twice daily on a validated, asthma-specific diary card and, at specified times during the study, completed a validated asthma-specific quality-of-life questionnaire. Physicians and caregivers completed a global evaluation of asthma control at the end of the study. Efficacy end points included: daytime and overnight asthma symptoms, daily use of beta-agonist, days without asthma, frequency of asthma attacks, number of patients discontinued because of asthma, need for rescue medication, physician and caregiver global evaluations of change, asthma-specific caregiver quality of life, and peripheral blood eosinophil counts. Although exploratory, the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding. At screening and at study completion, a complete physical examination was performed. Routine laboratory tests were drawn at screening and weeks 6 and 12, and submitted to a central laboratory for analysis. Adverse effects were collected from caregivers at each clinic visit. An intention-to-treat approach, including all patients with a baseline measurement and at least 1 postrandomization measurement, was performed for all efficacy end points. An analysis-of-variance model with terms for treatment, study center and stratum (inhaled/nebulized corticosteroid use, cromolyn use, or none) was used to estimate treatment group means and between-group differences and to construct 95% confidence intervals. Treatment-by-age, -sex, -race, -radioallergosorbent test, -stratum, and -study center interactions were evaluated by including each term separately. Fisher's exact test was used for between-group comparisons of the frequency of asthma attacks, discontinuations from the study because of worsening asthma, need for rescue medication, and the frequencies of adverse effects. Because of an imbalance in baseline values for eosinophil counts for the 2 treatment groups, an analysis of covariance was performed on the eosinophil change from baseline with the patient's baseline as covariate. STUDY PARTICIPANTS: Of the 689 patients enrolled, approximately 60% were boys and 60% were white. Patients were relatively evenly divided by age: 21%, 24%, 30%, and 23% were aged 2, 3, 4, and 5 years, respectively. For 77% of the patients, asthma symptoms first developed during the first 3 years of life. During the placebo baseline period, patients had asthma symptoms on 6.1 days/week and used beta-agonist on 6.0 days/week. RESULTS: In over 12 weeks of treatment of patients aged 2 to 5 years, montelukast administered as a 4-mg chewable tablet produced significant improvements compared with placebo in multiple parameters of asthma control including: daytime asthma symptoms (cough, wheeze, trouble breathing, and activity limitation); overnight asthma symptoms (cough); the percentage of days with asthma symptoms; the percentage of days without asthma; the need for beta-agonist or oral corticosteroids; physician global evaluations; and peripheral blood eosinophils. The clinical benefit of montelukast was evident within 1 day of starting therapy. Improvements in asthma control were consistent across age, sex, race, and study center, and whether or not patients had a positive radioallergosorbent test. Montelukast demonstrated a consistent effect regardless of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy. Caregiver global evaluations, the percentage of patients experiencing asthma attacks, and improvements in quality-of-life scores favored montelukast, but were not significantly different from placebo. There were no clinically meaningful differences between treatment groups in overall frequency of adverse effects or of individual adverse effects, with the exception of asthma, which occurred significantly more frequently in the placebo group. There were no significant differences between treatment groups in the frequency of laboratory adverse effects or in the frequency of elevated serum transaminase levels. Approximately 90% of the patients completed the study. CONCLUSIONS: Oral montelukast (4-mg chewable tablet) administered once daily is effective therapy for asthma in children aged 2 to 5 years and is generally well tolerated without clinically important adverse effects. Similarly, in adults and children aged 6 to 14 years, montelukast improves multiple parameters of asthma control. Thus, this study confirms and extends the benefit of montelukast to younger children with persistent asthma.

Pediatric asthma assessment: validation of 2 symptom diaries.

Accurate assessment of the value of asthma interventions in pediatric clinical trials is an essential step toward the improvement of the treatment of this disorder in children. Conventional pulmonary function measures can be infeasible and unreliable in younger children, particularly for use in multisite studies. As an alternative or supplemental approach, diary questionnaires completed by the patients or their caregivers may provide valuable data regarding the efficacy of asthma interventions in pediatric clinical trials. These questionnaires, however, have routinely not been validated for use in pediatric populations. Two pediatric diary questionnaires (the child-completed Pediatric Asthma Diary [PAD] and the parent/caregiver-completed Pediatric Asthma Caregiver Diary [PACD]) were designed to evaluate asthma symptoms in children aged 6 to 14 years and 2 to 5 years, respectively. The validity of these diary questionnaires was evaluated in 2 separate prospective studies that included children who were divided into 2 asthma groups: stable (requiring no additional asthma medication) and unstable (requiring either an increase in or the addition of asthma medication). Both scales displayed significant discriminant validity, construct validity, and responsiveness to change in asthma therapy. Only the PACD detected differences between groups in nighttime symptoms, such as awakenings caused by asthma. These validity studies suggest that diary questionnaires such as the PAD and PACD can be valuable as an alternative for the evaluation of interventions in pediatric asthma when pulmonary function testing is inappropriate or as an adjunct to such objective measures.

The multinational impact of migraine symptoms on healthcare utilisation and work loss.

OBJECTIVE: To compare self-reported healthcare resource utilisation, paid work loss, unpaid work loss and loss of effectiveness at work due to migraine in a clinic-based adult migraine population. METHODS: The Migraine Background Questionnaire (MBQ) was translated and pilot-tested for use in 25 countries. The questionnaire was then self-administered by patients at a screening visit for 3 phase III clinical trials of rizatriptan [a selective serotonin (5-hydroxytryptamine) 5-HT1B/1D receptor agonist] in 23 US and 78 non-US sites. PARTICIPANTS: Persons 18 to 65 years of age with at least a 6-month history of moderate to severe migraines prior to the screening visit were surveyed. RESULTS: A total of 2670 persons (54.7% Europe, 16.5% Latin America, 23.1% North America, 5.5% other countries) completed the MBQ and had responses which could be analysed. On average, each patient reported 2.78 doctor visits, 0.53 emergency room visits and 0.06 hospitalisations related to migraine per year. Patients self-reported being only 46% effective while on the job with migraine symptoms. Extrapolation of patient self-reported work and productivity loss for the last 4 weeks to an annual basis suggested that clinic-based patients with migraine lose 19.5 workday equivalents (8.3 days due to absenteeism, 11.2 days due to reduced workday equivalents) due to migraine per year. In the US, the annual employer cost of this total migraine-related work loss is estimated to be $US3309 (2000 values) per patient with migraine. The levels of self-reported healthcare resources utilised for migraine and work loss were generally consistent across geographic regions. CONCLUSIONS: The impact of migraine symptoms on healthcare resource utilisation and work loss was similar across most measures in Europe, Latin America, North America and other countries. Total migraine-related work loss due to absenteeism and reduced workday equivalents accounts for most of the economic burden of migraine, regardless of country, in a clinic-based migraine population.

Development of a brief 24-hour adolescent migraine functioning questionnaire.

The objective was to develop a brief questionnaire to assess short-term functioning decrements in adolescents with acute migraine. One hundred twenty-three potential items were generated by literature review and by interviewing adolescent migraineurs and migraine specialists. To reduce the items, 127 adolescents were asked to identify which items affected their daily functioning in the 24 hours following onset of a migraine, and to rate them on a 5-point scale from "not very important" to "extremely important." Reduction to an 18-item questionnaire was performed by evaluating subject-perceived importance (number of times an item was chosen times mean importance score) in combination with principal components factor analysis. Five domains were identified: (1) activities, (2) social functioning, (3) cognitive functioning, (4) migraine headache symptoms, and (5) emotional functioning. Questions regarding school loss and school performance during a migraine were added to the final questionnaire as a separate outcome measure. The correlation between the five domains as measured by the Spearman correlation coefficient ranged from 0.17 to 0.49 suggesting some, but minimal, overlap. Cronbach alpha for individual domains ranged from.50 to.84. The questionnaire was pilot-tested in 12 adolescent migraineurs to determine ease of administration and comprehension and revised to improve clarity.

Randomised comparison of losartan vs. captopril on quality of life in elderly patients with symptomatic heart failure: the losartan heart failure ELITE quality of life substudy.

OBJECTIVE: To measure health-related quality-of-life (HRQoL) in elderly symptomatic heart failure patients following treatment with an angiotensin II receptor antagonist (losartan) vs. an angiotensin-converting-enzyme (ACE) inhibitor (captopril). METHODS: Patients (age > or = 65 years) were randomised to losartan, titrated to 50 mg once daily, or captopril, titrated to 50 mg three times daily, as tolerated. Sickness Impact Profile (SIP) and Minnesota Living with Heart Failure (LIhFE) questionnaires were administered at baseline, weeks 12 and 48. Composite hypothesis testing of change in HRQoL from baseline for completers, and withdrawal for unfavourable events (death, clinical/laboratory adverse experience) was used to account for differential dropout rates. RESULTS: In 203 patients completing the substudy (week 48), significant and comparable improvements in HRQoL from baseline were observed for both treatment groups (p < or = 0.001). Although there was a trend favouring losartan vs. captopril for the composite HRQoL endpoint (unadjusted p = 0.018, one-sided), this was not considered significant after adjusting for multiple testing. Significantly more captopril patients in the substudy subset withdrew for unfavourable reasons (19.6 vs. 10.9%, p = 0.038). CONCLUSIONS: Significant improvements in HRQoL were observed in elderly patients with symptomatic heart failure treated with losartan and captopril long-term. A trend favouring losartan in the composite measure of drug tolerability/quality of life was not significant, but losartan was generally better tolerated than captopril in that significantly fewer losartan patients discontinued therapy.

Determinants of patient satisfaction with migraine therapy.

Determinants of patient satisfaction with migraine treatment are not well understood. The objective of this study was to evaluate which treatment outcomes influence patient satisfaction with treatment. Analyses were performed on data from 1506 migraineurs from two clinical trials of rizatriptan for treatment of migraine. Satisfaction with treatment was assessed 2 h after initial treatment and prior to use of rescue therapy. Over 90% of patients who were pain-free at 2 h were at least somewhat satisfied with treatment compared with <10% of patients with moderate or severe pain. Only 60-70% of patients with mild pain at 2 h experienced some level of satisfaction with treatment. For patients with mild pain at 2 h, results showed subjects who reported severe pain at baseline, absence of associated symptoms at 2 h and pain relief within the first 90 min had at least a 76% probability of being at least somewhat satisfied. This probability decreased with the presence of associated symptoms, slower pain relief and moderate baseline pain intensity. Fast, complete pain relief is one important factor in determining short-term patient satisfaction with treatment.

Impact of migraine and migraine therapy on productivity and quality of life.

Migraine is an expensive disorder in terms of lost productivity and its deleterious impact on health-related quality of life (QOL). In addition to lost wages and productivity due to absenteeism, many patients with migraine also experience reduced productivity while at work and disruption of their family, social, and leisure activities. Even a migraine of moderate intensity can impair function and productivity, which emphasizes the importance of therapy that achieves complete, as opposed to partial, pain relief. Rapid onset of complete relief with abatement of migraine-associated symptoms has been reported to be most relevant for patient QOL and satisfaction with migraine therapy. Several instruments have been developed for measuring health-related QOL. Both general and migraine-specific instruments have been useful in assessing the impact of migraine and migraine therapy on health-related QOL; migraine-specific instruments may be more sensitive in measuring the effects of pharmacologic intervention. Compared with placebo, rizatriptan improved productivity in migraine patients. Compared with usual care, rizatriptan had favorable effects on all five domains of the 24-Hour Migraine Quality of Life questionnaire.

Validation of a pediatric asthma caregiver diary.

BACKGROUND: Young children are generally not able to consistently and reliably perform tests of airway function, and normative values are not available. Reliable and valid measures of parental reporting of asthma symptoms and functioning are needed to determine the efficacy of asthma interventions. OBJECTIVE: A pediatric asthma caregiver diary was developed and validated for use in interventional asthma studies. METHODS: A 3-week prospective study of 125 caregiver parents and their children, aged 2 to 5 years, with persistent asthma was conducted. At baseline, children were classified as either stable (no change to anti-inflammatory therapy) or unstable (anti-inflammatory therapy added or increased). RESULTS: A symptom scale and day without asthma symptoms (DWAS) were defined from pediatric asthma caregiver diary questions. The scale and DWAS statistically differentiated between the stable and unstable groups at week 1 and detected change between the 2 groups (P <.01). On average, caregivers reported low symptom scores. However, the frequency of DWAS was only 43% of days in the stable group and 22% in the unstable group. CONCLUSION: The pediatric asthma caregiver diary scale and DWAS have acceptable measurement characteristics for use in clinical trials of children with asthma symptoms. The DWAS indicates an opportunity for improvement in asthma control in this population.

Trends in persistent proteinuria in adult-onset diabetes: a population-based study.

OBJECTIVE: This study investigates temporal trends in the prevalence and incidence of persistent proteinuria among people with adult-onset diabetes (age > or =40 years). RESEARCH DESIGN AND METHODS: The complete community-based medical records of all Rochester, Minnesota, residents with a diagnosis of diabetes or diabetes-like condition from 1945 through 1989 were reviewed to determine whether they met National Diabetes Data Group (NDDG) criteria. All confirmed diabetes cases residing in Rochester on 1 January 1970 (n = 446), 1980 (n = 647), and/or 1990 (n = 940) were identified. The medical records of these prevalence cases were reviewed from the time of the first laboratory urinalysis value to the last visit, death, or 1 April 1992 (whichever came first) for evidence of persistent proteinuria (two consecutive urinalyses positive for protein, with no subsequent negative values). Similarly, the medical records of all 1970-1989 diabetes incidence cases (n = 1,252) were reviewed to investigate temporal changes in 1) the likelihood of having persistent proteinuria before the date NDDG criteria was met, i.e., baseline; 2) the risk of persistent proteinuria after baseline; and 3) the relative risk of mortality associated with persistent proteinuria. RESULTS: The proportion of diabetes prevalence cases with persistent proteinuria on or before the prevalence date declined from 20% in 1970 to 11% in 1980 and 8% in 1990. Among the 1970-1989 diabetes incidence cases, 77 (6%) had persistent proteinuria on or before baseline; the adjusted odds declined by 50% with each 10-year increase in baseline calendar year (P<0.001). Among individuals free of persistent proteinuria at baseline, 136 subsequently developed persistent proteinuria; the estimated 20-year cumulative incidence was 41% (95% CI 31-59); the adjusted risk did not differ as a function of baseline calendar year. Survival of individuals with persistent proteinuria relative to those without was reduced but did not differ by baseline calendar year. CONCLUSIONS: The prevalence of persistent proteinuria among people with adult-onset diabetes in Rochester, Minnesota, declined 60% between 1970 and 1990. The decline appears because of a decrease in the proportion of diabetes incidence cases with persistent proteinuria before baseline rather than secular declines in the risk of persistent proteinuria after baseline or secular increases in the risk of mortality associated with persistent proteinuria. Similarity over time in age and fasting glucose at baseline, and at prevalence dates, is evidence that earlier detection of diabetes is not the sole explanation for the decline.

Work and productivity loss in the rizatriptan multiple attack study.

The objective of this study was to measure the self-reported effect of acute migraine and its treatment on paid work and productivity loss. Patients self-administered a questionnaire in which the impact of a recent migraine on paid work and productivity activities was assessed. We included the questionnaire in a randomized, double-blind, placebo-controlled, crossover, out-patient study designed to examine the safety and efficacy of rizatriptan (5-HT1B/1D receptor agonist) 10 mg p.o. in patients treating four separate migraine attacks. A total of 407 patients, aged 18-65 years, suffering from moderate to severe migrainous headaches was studied. Patients receiving rizatriptan compared with placebo reported 0.7 fewer hours (P < 0.01) of paid worked missed due to absenteeism, 0.4 fewer hours (P < 0.05) of productive time lost on the job, and 1.1 fewer total hours (P < 0.01) of work loss per migraine attack. Rizatriptan compared with placebo significantly reduced migraine-related work loss associated with absenteeism and decreased effectiveness on the job.

What are minimal important changes for asthma measures in a clinical trial?

In this study, the perceptions of asthmatics to change in their disease was associated with observed changes in clinical asthma measures, in order to identify the threshold where changes in clinical asthma measures are perceivable by patients. The study included 281 asthmatic patients, aged 18-63 yrs, in a randomized, placebo-controlled clinical trial of a leukotriene antagonist. Changes were related in: 1) asthma symptom scores; 2) inhaled beta-agonist use; 3) forced expiratory volume in one second (FEV1); and 4) peak expiratory flow (PEF) to a global question that queried overall change in asthma since starting the study drug. Additional analyses examined differences in the group reporting minimal improvement by treatment (active treatment versus placebo), sex and age groups. The average minimal patient perceivable improvement for each measure was: 1) -0.31 points for the symptom score on a scale of 0-6; 2) -0.81 puffs x day(-1) for inhaled beta-agonist use; 3) 0.23 L for FEV1; and 4) 18.79 L x min(-1) for PEF. In general placebo-treated patients and older patients, who reported minimal improvement, experienced less mean improvement from baseline than active-treated patients and younger patients, who reported minimal improvement. Determining the minimal patient perceivable improvement value for a measure may be helpful to interpret changes. However, interpretation should be carried out cautiously when reporting a single value as a clinically important change.

Validation of a migraine work and productivity loss questionnaire for use in migraine studies.

Migraine symptoms and therapy side effects cause significant functional disability that can result in work and productivity losses. Effective, well-tolerated migraine therapy with rapid onset of relief could decrease work and productivity losses. The Migraine Work and Productivity Loss Questionnaire (MWPLQ) evaluates the impact of migraine and migraine therapy on paid work. Data from a randomized, open-label extension study were collected over 3 months. Migraineurs were randomized to either rizatriptan (5HT1B/1D receptor agonist) or their usual migraine therapy. Data were analyzed from 164 patients who experienced at least one work-related migraine. Internal consistency (Cronbach's alpha) for the work difficulty domains ranged from 0.80 to 0.95. Work loss and work difficulty were moderately correlated (r = 0.39-0.58) with migraine severity and functional ability. Differences were found favoring rizatriptan for absenteeism (1.3 vs 2.4 h), effectiveness at work (62% vs 49%), and difficulty with work-related tasks (p < 0.01). The MWPLQ demonstrated favorable measurement characteristics in this study and could be an important research tool for future evaluations of migraine-related work disability.

Validation of an asthma symptom diary for interventional studies.

OBJECTIVE: The Pediatric Asthma Diary was developed and validated to assess efficacy of interventions in children with asthma. DESIGN, PATIENTS, AND SETTING: Diary validation was performed in a three week, prospective study of 106 children aged 6-14 years with asthma. Children were classified at baseline as either stable (requiring no additional asthma treatment) or new onset/worse (requiring either addition of or increase in anti-inflammatory treatment). RESULTS: A daytime symptom scale and "day without asthma" were defined from diary questions. Both measures demonstrated significant validity and responsiveness to anti-inflammatory treatment. The stable group experienced a higher percentage of days without asthma during week 1 compared with the new onset/worse group (39.6% v 11.6%, respectively). The new onset/worse patients experienced significant improvement in days without asthma (24.5%) compared with stable patients (6.4%). CONCLUSIONS: The Pediatric Asthma Diary daytime symptom scale and day without asthma are acceptable measures for use in asthma intervention studies of children aged 6-14 years.

The migraine work and productivity loss questionnaire: concepts and design.

Our objectives were to: (1) develop a self-report questionnaire for measuring the impact of migraine headache on work; and (2) qualitatively assess aspects of its performance. Two samples of migraine sufferers provided the data. Sample 1 (n = 18) participated in a structured discussion group designed to elicit examples of migraine's on-the-job impact. Sample 2 (n = 11) completed a mail survey and participated in in-depth phone interviews. Interviews addressed item comprehensibility, consistency of interpretation, the cognitive processes by which certain answers were generated and response burden. The participants were currently employed men and women, at least 18 years of age, who met the International Headache Society (IHS) criteria for migraine headache [1]. Discussion group participants indicated that migraine attacks substantially diminished their job performance. Pain, photophobia, phonophobia, mental impairment and fatigue were perceived as interfering with even routine or relatively simple job tasks. The Migraine Work and Productivity Loss Questionnaire, Version 1.0 (MWPLQ) was written. Next, it was assessed in the context of the in-depth interviews. Result indicated that the MWPLQ was comprehended without difficulty, interpreted consistently and easy to complete. Thus, qualitative results provide initial support for the new questionnaire.