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PubMed2001

Effects of covariance model assumptions on hypothesis tests for repeated measurements: analysis of ovarian hormone data and pituitary-pteryomaxillary distance data.

In the analysis of repeated measurements, multivariate methods which account for the correlations among the observations from the same experimental unit are widely used. Two commonly-used multivariate methods are the unstructured multivariate approach and the mixed model approach. The unstructured multivariate approach uses MANOVA types of models and does not require assumptions on the covariance structure. The mixed model approach uses multivariate linear models with random effects and requires covariance structure assumptions. In this paper, we describe the characteristics of tests based on these two methods of analysis and investigate the performance of these tests. We focus particularly on tests for group effects and parallelism of response profiles.

Adolescent↗
PubMed2001

CYP gene polymorphisms and early menarche.

Early age at menarche is a risk factor for breast cancer. A previous study reported a significant positive association between the CYP3A4*1B variant allele and early puberty. We investigated whether polymorphisms of the CYP3A4, CYP17, CYP1B1, and CYP1A2 genes predict the age at onset of menarche. Five hundred eighty-three nulliparous women between ages 17 and 35, of various ethnic backgrounds, completed a questionnaire that included information about menstrual history. Samples of DNA were provided and used to genotype these women for polymorphic variants in the four genes. There was no significant difference in mean age at menarche between women who carried two variant CYP17 A2 alleles (12.5 years) and women who carried one or no variant allele (12.5 years) (P = 0.8, adjusted for ethnic group and year of birth). Similar results were found for the CYP1B1*3 variant allele and for the CYP1A2*1F variant allele. Women who carried two variant CYP3A4*1B alleles had an earlier mean age at menarche (12.0 years) than women who carried one or no variant allele (12.6 years) (P = 0.02). However, after adjusting for ethnic group and year of birth, no significant differences in mean age at menarche were found. The polymorphic variants of the CYP3A4, CYP17, CYP1B1, and CYP1A2 genes are unlikely to influence age of menarche.

Adolescent↗
PubMed2005

Development of reaching in infancy.

The development of reaching for stationary objects was studied longitudinally in 12 human infants: 5 from the time of reach onset to 5 months of age, 5 from 6 to 20 months of age, and 2 from reach onset to 20 months of age. We used linear mixed-effects statistical modeling and found a gradual slowing of reach speed and a more rapid decrease of movement jerk with increasing age. The elbow was essentially locked during early reaching, but was prominently used by 6 months. Differences between infants were distributed normally and no evidence of different types of reachers was found. The current work combined with other longitudinal studies of infant reaching shows that the increase in skill over the first 2 years of life is seen, not by an increase in reaching speed, but by an increase in reach smoothness. By the end of the second year, the overall speed profile of reaching is approaching the typical adult profile where an early acceleration of the hand brings the hand to the region of the target with a smooth transition to a lower-speed phase where grasp is accomplished.

Age Factors↗
PubMed2005

The impact of the VF-14 index, a perceived visual function measure, in the routine management of cataract patients.

BACKGROUND: Evidence about the impact of routine feedback of patient-reported outcomes is contradictory, and there is limited information regarding its use in the routine management of cataract patients. METHODS: The VF-14 Index was used to assess the visual function of 833 consecutive cataract patients, attending 19 ophthalmologists from public and private hospitals and primary care practices in Spain, in 1999-2000. In this before/after trial, the intervention included (1) an educational session, and (2) the provision of the VF-14 scores of all subsequent patients to the ophthalmologist. Mixed effects linear and logistic models were constructed to assess the effect on the process (correlation between patients' and physicians' assessments of visual function, appropriateness of surgery recommendation) and the outcome of care (satisfaction). RESULTS: The adjusted regression coefficient for the VF-14 score significantly increased after the intervention as a predictor of the ophthalmologist's assessment of visual function (beta coefficient: control 0.10 vs. intervention 0.35, p < 0.05). The intervention did not increase the probability of an appropriate medical decision (OR = 0.90; 95% CI: 0.42; 2,69) and it did not change patient satisfaction with care. CONCLUSIONS: Routine provision of education and feedback on the patient's VF-14 Index score significantly increases agreement between patients' and physicians' assessments of functional capacity. The lack of a beneficial effect on management or outcome suggests the need for a more intense intervention to change medical practice.

Aged↗
PubMed2004

One-year follow-up study of blood pressure and dietary patterns in dietary approaches to stop hypertension (DASH)-sodium participants.

BACKGROUND: We conducted a 12-month follow-up study on participants in the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial to determine the impact of the DASH diet and 150, 100, or 50 mmol/day of sodium after discontinuation of the feeding intervention. METHODS: Upon completion of the trial, 56 of the 113 participants at the clinical center at Duke University entered a longitudinal observational study. Measurements including 24-h ambulatory systolic and diastolic blood pressure (BP), weight, and 24-h urinary electrolytes were obtained at 1, 6, and 12 months after completion of the DASH-Sodium trial. Block food frequency questionnaires were completed at the 12-month visit. Linear mixed-effects regression models were used to analyze the effect of the diet and sodium intake on longitudinal changes in BP during the final feeding period. RESULTS: The DASH participants significantly increased their intakes of fruits or juices and vegetables at 12 months. Control participants had no change in DASH food group intake. Both groups increased sodium intake. Among control participants, systolic and diastolic BP increased 5.33 (95% confidence interval [CI] 0.28, 10.37) and 3.20 mm Hg (95% CI 0.25, 6.16), respectively. Among DASH participants, systolic and diastolic BP increased 3.12 (95% CI -0.44, 6.68) and 0.79 mm Hg (95% CI -1.15, 2.72), respectively. There was a significant effect of the final sodium level by diet on the change in SBP over time (P = .04 for three-way interaction among diet, time of visit, and sodium). CONCLUSIONS: After the feeding intervention, DASH diet participants ate more fruits/vegetables and had sustained reductions in BP despite increased sodium intake.

Adult↗
PubMed2024

Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on the oropharyngeal metagenome in adolescents with cystic fibrosis.

BACKGROUND: Triple modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) improves lung function and impacts upon the respiratory microbiome in people with Cystic fibrosis (pwCF) with advanced lung disease. However, adolescents with cystic fibrosis (CF) are less colonized with bacterial pathogens than adult pwCF but their microbiota already differs from healthy individuals. The aim of this study was to longitudinally analyze the impact of ETI on the respiratory metagenome in adolescents with predominantly mild CF lung disease. METHODS: In this prospective observational study, we included pwCF aged 12-20 years with at least one F508del mutation, who collected oropharyngeal swabs before and after initiation of ETI therapy twice per week to biweekly over three months. We performed whole metagenome shotgun sequencing, followed by host DNA filtering and taxonomic profiling. We used linear and additive mixed effects models adjusted for known confounders and corrected for multiple testing to study longitudinal development of the microbiome. We analyzed bacterial diversity, abundance, and strain-level phylogeny. RESULTS: We analyzed the metagenomic data of 297 swabs of 20 pwCF. Microbiome composition changed after initiation of ETI therapy. We observed a slight diversification of the microbiome over time (Inv Simpson, Coef 0.085, 95 %CI 0.003, 0.17, p = 0.04). Strain-level analysis and clustering showed that strain retention of the most frequent bacterial species is predominant even during ETI therapy. CONCLUSIONS: During three months of ETI therapy, commensal bacteria increased, which may help to prevent overgrowth of bacterial pathogens.

Humans↗
PubMed2005

Modulation of equine articular chondrocyte messenger RNA levels following brief exposures to recombinant equine interleukin-1beta.

The effect of recombinant equine IL-1beta (EqIL-1beta) on steady-state mRNA levels of equine articular chondrocytes in high-density monolayer culture was investigated using a customized cDNA array analysis. Total RNA samples isolated from chondrocytes cultured in media alone or with the addition of 1 ng/ml EqIL-1beta for 1-, 3-, and 6-h durations of exposure were reverse transcribed, radiolabeled, and hybridized to a customized 380-target cDNA array. Means of duplicate log base 2 transformed hybridization signals were normalized to equine glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mean signal intensities. Differentially expressed transcripts were identified using a two-stage mixed linear analysis of variance model (Statistical Analysis Software, Cary, NC). A time-dependent pattern was observed in the number of transcripts increased > or =two-fold in response to EqIL-1beta after 1, 3 and 6h (1, 2 and 109 transcripts, respectively). At 6 h of EqIL-1beta stimulation, signal intensities for 88 cDNA targets with purported function in processes related to cell cycle, intracellular signaling, transcription, translation, extracellular matrix turnover, and inflammation, as well as a number of cDNAs lacking homology to previously reported cDNA sequences, were increased >two-fold and were associated with p<0.05. Principal component analysis identified a vector component ( approximately 10% of the total variation) corresponding to a potential EqIL-1beta co-regulation of cell cycle associated gene transcription. These results support and expand our existing comprehension of the complex role of IL-1 in modulated chondrocyte gene expression and suggest the involvement of specific target gene up-regulation and activation of downstream inflammatory cascade mediators. This study adds to the current understanding of the molecular events associated with an IL-1 induced inflammation and pathobiologic processes that may be associated with the development of equine osteoarthritis.

Animals↗
PubMedDate not supplied

Medium term planning of biopharmaceutical manufacture with uncertain fermentation titers.

The growing trend of employing multiproduct manufacturing facilities along with the randomness inherent in the biopharmaceutical manufacturing environment is creating significant scheduling and planning challenges for the biopharmaceutical industry. This work focuses on capturing the effect of uncertainty in fermentation titers when optimizing the planning of biopharmaceutical manufacturing campaigns. A mixed integer linear programming (MILP) model based on previous work is derived via chance constrained programming (CCP). The methodology is applied to two illustrative examples, and the results are compared with those from the deterministic model and a multiscenario model accompanied by an iterative construction algorithm. The computational results indicate that the proposed methodology offers significant improvements in solution quality over the compared approaches and presents an opportunity for biopharmaceutical manufacturers to make better medium term planning decisions, particularly under uncertain manufacturing conditions.

Algorithms↗
PubMed2001

Liability of commercial and social hosts for alcohol-related injuries: a national survey of accountability norms and judgments.

Legal standards for liability of commercial sellers and social providers of alcoholic beverages are affected by social norms concerning accountability and responsibility. Using a nationwide probability sample telephone survey of 7,021 U.S. residents, we conducted a randomized experiment in which each subject was asked to respond to multiple vignettes. The vignettes told stories of drinking situations, systematically varying dimensions concerning age of drinker, commercial versus social settings, amount of alcohol consumed, history of previous behavior, and seriousness of damage or injury following drinking. Analyses involved linear mixed (i.e., random effects) model regressions, using responses to vignettes as the outcome variable, controlling for a series of sociodemographic, behavioral, and attitudinal measures. Results showed that age of drinker (young), setting (bar), and previous behavior (history of irresponsibility) were most strongly associated with harsher judgments of civil liability. Citizens' multiple standards for assigning legal liability and implications for public policy are discussed.

Journal Article↗
PubMed2003

Associations between prenatal and postnatal growth and adult body size and composition.

BACKGROUND: Adult body size and composition (ABSC) measures are associated with work capacity and productivity, reproductive performance, and chronic disease risk. Growth failure in early childhood may have important long-term consequences through its influence on ABSC. OBJECTIVE: We assessed associations between prenatal and postnatal growth (0-2 y of age) and ABSC. DESIGN: We included 267 singletons from a prospective study carried out between 1969 and 1977 in 4 ladino Guatemalan villages. We used data from that study and from a follow-up study conducted in 1998-1999 (when the subjects were 21-27 y of age) to determine associations of birth weight, length at 15 d of age, ponderal index, and length at 2 y of age with adult height, weight, fat-free mass (FFM), fat mass, percentage of body fat, and waist-to-hip ratio. Multivariate linear regression analyses with mixed models were carried out to account for sibling clustering. Two-stage least-squares analyses were used to separate specific effects of prenatal and postnatal growth. RESULTS: Birth weight, length at 15 d of age, and length at 2 y of age were positively associated with height, weight, and FFM in both sexes (P < 0.05). Prenatal growth and postnatal growth were equally important determinants of height, weight, and FFM. Weak positive associations of postnatal growth with adult fat mass and percentage of body fat were found in both sexes, whereas similar associations for prenatal growth were found in women only. Growth in early childhood was not related to waist-to-hip ratio. CONCLUSIONS: Growth retardation in early childhood was associated with shortness and less FFM in adulthood. Preventing growth failure in utero and preventing growth failure during the first 2 y of life are equally important for ABSC.

Adipose Tissue↗
PubMed1996

Longitudinal changes in smell identification.

BACKGROUND: Cross-sectional studies have demonstrated that olfactory function diminishes with increasing age, which may impact on the safety and quality of life of older persons. To date, however, there have been no published longitudinal studies on olfaction. The purpose of this study was to examine the influence of age and gender on smell identification over a 3-year period in a group of generally healthy men and women. METHODS: Males (n = 85) and females (n = 76) between the ages of 19 and 95 years were administered the University of Pennsylvania Smell Identification Test (SIT) over a 3-year span as part of the oral physiology component of the Baltimore Longitudinal Study of Aging. A linear mixed-effects regression model was used to determine how longitudinal changes in SIT scores differ with respect to gender, history of medical problems, and use of prescription medications. RESULTS: Over the 3-year period, SIT scores diminished progressively with increased age. Women and men in the eighth decade of life experienced a decline of greater than one SIT point per year. Females consistently performed better than males in smell identification. Similar results were obtained regardless of medical problems or medication usage. CONCLUSIONS: These results extend the conclusions of previous cross-sectional olfactory studies and indicate that smell identification deteriorates progressively with greater age. Furthermore, age-related declines in olfaction occur even in the absence of overt medical problems.

Adult↗
PubMed2006

Daily affect in Parkinson disease is responsive to life events and motor symptoms.

OBJECTIVE: The aims of this study were to examine the daily affective experiences of patients with Parkinson disease (PD) and to determine their association with daily events and motor symptoms. Specifically, it was intended to test the hypothesis that PD, even in the absence of depression, is associated with anhedonia. METHOD: Nondepressed male subjects with PD (N=24) and a comparison group of healthy elderly males (N=23) completed daily affect rating scales and, for the patients with PD, a supplemental self-assessment questionnaire of PD-related symptoms for 4 consecutive weeks. The effect of daily events and PD-related symptoms on daily affect was examined using linear and logistic mixed regression models. RESULTS: Overall, patients with PD reported significantly less positive and more negative affect than healthy peers over time. There were similar, and expected, associations between negative events and affect in both groups. Although patients with PD reported far fewer positive events than control subjects, they reported as great an improvement in affect in response to them. Regarding self-reported PD-related symptoms, only increasing severity of core motor symptoms was independently associated with worse affect. CONCLUSIONS: Although the conclusions of this study are tempered by a comparison group that is not optimal, our results suggest that patients with PD do not demonstrate anhedonia in response to positive life events. The gross intergroup difference in daily events suggests the potential value of interventions that emphasize daily engagement in positive experiences to improve positive affective tone.

Affect↗
PubMed2005

Topiramate improves health-related quality of life when used to prevent migraine.

OBJECTIVE: To assess changes in health-related quality of life (HRQoL) measures among patients receiving topiramate (TPM) 100 mg/d in two divided doses for migraine prevention in three randomized, double-blind, placebo-controlled, 26-week trials with similar protocols and study populations. BACKGROUND: Migraine substantially impairs HRQoL and work productivity before, during, and after attacks. Approximately 50% of patients with migraine could be recommended for preventive therapies, yet only 3% to 5% of patients receive them. TPM is an effective and generally well-tolerated migraine prophylactic (preventive) therapy for adults, as demonstrated in several randomized, double-blind, placebo-controlled trials. The most common adverse events in double-blind, placebo-controlled studies of TPM in migraine prevention are paresthesia, fatigue, anorexia, nausea, taste alteration, and diarrhea. DESIGN AND METHODS: The Migraine-Specific Questionnaire (MSQ, version 2.1) was used to assess the effect of TPM 100 mg/d on the functionality and HRQoL of randomized intent-to-treat (ITT) and study-completer populations pooled from three randomized, double-blind, placebo-controlled trials. MSQ scores (0 to 100, higher score indicates better functioning) were assessed for the following three domains: role restriction (examines the degree to which performance of daily activities is limited by migraine), role prevention (examines the degree to which performance of daily activities is interrupted by migraine), and emotional function (examines feelings of frustration and helplessness due to migraine). Between-group differences from baseline in mean MSQ domain scores for TPM 100 mg/d and placebo were compared using a mixed-effects model with piecewise linear regression. Effect sizes were calculated to estimate the magnitude of change in HRQoL that can be associated with TPM therapy. RESULTS: TPM 100 mg/d significantly improved all three MSQ domains compared with placebo for both the ITT (TPM, n = 372; placebo, n = 362) and study-completer (TPM, n = 220; placebo, n = 216) populations (P < .001 for all three domains, both populations). Effect sizes for TPM 100 mg/d varied from 0.40 to 0.78, indicating that the changes in MSQ scores for TPM 100 mg/d were moderate and may be clinically significant. CONCLUSION: TPM 100 mg/d has been shown to be effective in the prevention of migraine headache in adults. As the MSQ results from the three randomized, placebo-controlled trials indicate, HRQoL is significantly improved for up to 6 months following initiation of treatment.

Adolescent↗
PubMed1998

Intraarterial vs intravenous administration of antivenin for the treatment of Crotalidae atrox envenomation: a pilot study.

OBJECTIVE: Standard therapy for significant snake envenomation includes antivenin. i.v. administration is currently the only recommended route. Intraarterial (i.a.) administration has potential advantages over i.v. that could improve outcome. To study this, the authors compared i.v. and i.a. antivenin administrations for the treatment of experimental snake envenomations. METHODS: 14 adult female swine were anesthetized and prepared with femoral artery and ear vein catheters, and baseline hoof, forearm, and thigh circumference and volume displacement measurements were taken. Crotalidae atrox venom was injected into the subcutaneous tissue of the hoof. The doses of venom were 4.75, 9.50, 19.00, 37.90, 47.30, 56.90, and 66.40 mg. Immediately following injection of venom, polyvalent antivenin (Crotalidae) (0.285 mg/10 mL saline) was infused over 30 minutes into the femoral artery (i.a. group) or ear vein (i.v. group). As a control, 10 mL of saline was infused into the ear vein (i.a. group) or femoral artery (i.v. group). Measurements were recorded up to 48 hours. Linear mixed-effect regression models were used for each measurement and to compare the i.a. and i.v. groups. RESULTS: Venom dose and time after administrations were associated with increased circumferences and increased volumes (p < 0.05). i.v. administration was associated with larger hoof (1.26 cm) and forearm (0.42 cm) sizes and volume displacement (21.71 mL) when compared with i.a. administration ( p < 0.05). CONCLUSION: i.a. antivenin results in a modest but significant decrease in tissue edema when compared with i.v..

Animals↗
PubMed2005

Accelerated longitudinal decline of aerobic capacity in healthy older adults.

BACKGROUND: The ability of older persons to function independently is dependent largely on the maintenance of sufficient aerobic capacity and strength to perform daily activities. Although peak aerobic capacity is widely recognized to decline with age, its rate of decline has been estimated primarily from cross-sectional studies that may provide misleading, overly optimistic estimates of aging changes. METHODS AND RESULTS: To determine longitudinal rate of change in aerobic capacity and the influence of age, gender, and physical activity on these changes, we performed serial measurements of peak treadmill oxygen consumption (peak VO2) in 375 women and 435 men ages 21 to 87 years from the Baltimore Longitudinal Study of Aging, a community-dwelling cohort free of clinical heart disease, over a median follow-up period of 7.9 years. A linear mixed-effects regression model was used to calculate the predicted longitudinal 10-year rate of change in peak VO2, expressed in milliliters per minute, for each age decade from the 20s through the 70s after adjustment for self-reported leisure-time physical activity. A longitudinal decline in peak VO2 was observed in each of the 6 age decades in both sexes; however, the rate of decline accelerated from 3% to 6% per 10 years in the 20s and 30s to >20% per 10 years in the 70s and beyond. The rate of decline for each decade was larger in men than in women from the 40s onward. Similar longitudinal rates of decline prevailed when peak VO2 was indexed per kilogram of body weight or per kilogram of fat-free mass and in all quartiles of self-reported leisure-time physical activity. When the components of peak VO2 were examined, the rate of longitudinal decline of the oxygen pulse (ie, the O2 utilization per heart beat) mirrored that of peak VO2, whereas the longitudinal rate of heart rate decline averaged only 4% to 6% per 10 years, and accelerated only minimally with age. CONCLUSIONS: The longitudinal rate of decline in peak VO2 in healthy adults is not constant across the age span in healthy persons, as assumed by cross-sectional studies, but accelerates markedly with each successive age decade, especially in men, regardless of physical activity habits. The accelerated rate of decline of peak aerobic capacity has substantial implications with regard to functional independence and quality of life, not only in healthy older persons, but particularly when disease-related deficits are superimposed.

Adult↗
PubMed2004

A pilot study of brief interpersonal psychotherapy for depression among women.

A matched-case-control study compared eight-week outcomes between a group of 16 depressed women who received brief (eight-session) interpersonal psychotherapy and a group of 16 who received a selective serotonin reuptake inhibitor (sertraline). Women who met DSM-IV criteria for major depression and who had a score above 15 on the Hamilton Rating Scale for Depression were treated openly with brief interpersonal psychotherapy and were matched on key variables with women being treated with sertraline. Linear mixed-effects regression models were used to compare groups on measures of symptoms and functioning during eight weeks of treatment. Both groups improved significantly over time, with large effect sizes. However, contrary to expectations, the women who received psychotherapy improved more quickly than those who received sertraline.

Case-Control Studies↗
PubMed2004

The efficacy of two methods of ankle immobilization in reducing gastrocnemius, soleus, and peroneal muscle activity during stance phase of gait.

BACKGROUND: Immobilization to limit muscle activity is a common therapeutic and posttreatment event. There are potential time and resource savings if a prefabricated boot can replace a custom applied cast. The purpose of this study was to determine if muscle activity reduction is similar using a fiberglass cast versus a prefabricated (Aircast FoamWalker) boot. METHODS: Surface EMG data were recorded from the gastrocnemius, soleus, and peroneals of 12 normal adults while walking barefoot, in a fiberglass cast with a cast shoe (cast), and while wearing an Aircast FoamWalker (boot). Subjects walked at their self-selected speed for 10 trials in each condition, and the order of barefoot, cast, and boot was randomly assigned. The data were rectified, integrated across stance phase and normalized to a percent of each subject's barefoot mean integrated EMG (iEMG) value. For each muscle, a linear mixed-effects statistical model (subject by trial by condition) was utilized to determine if iEMG activity levels were reduced by immobilization compared to barefoot walking. RESULTS: Activity for all muscles was significantly lower in the boot compared with barefoot (p <.05). The cast iEMG levels were significantly different from barefoot for the soleus and peroneals (p <.05). Gastrocnemius activity was significantly decreased in the boot when compared with the cast (p <.0001). The greater reduction in iEMG levels for the boot indicates that it is superior to a fiberglass cast in reducing gastrocnemius muscle activity during the stance phase of gait. CONCLUSIONS: The data show that a prefabricated boot is as effective as a custom applied cast in reducing soleus and peroneal muscle iEMG during stance phase. The boot was more effective in reducing gastrocnemius activity when compared to the cast. CLINICAL RELEVANCE: This study suggests that a prefabricated boot may be used in place of a custom cast when the goal of treatment is to limit muscle activity of the leg.

Adult↗
PubMed2006

The impact of migraine on daily activities: effect of topiramate compared with placebo.

OBJECTIVE: Assess the impact of migraine preventive therapy on patient-reported routine daily activities using the Migraine Specific Questionnaire (MSQ) and the Medical Outcomes Study Short Form-36 (SF-36) in patients with migraine who participated in a 26-week, randomized, double-blind, placebo-controlled trial of topiramate for migraine prevention. METHODS: Patients were required to have 3-12 migraines and < or = 15 headache days/month during the baseline phase. Patients who failed > 2 adequate regimens of migraine preventive therapy were excluded. MSQ and SF-36 data were collected at baseline, weeks 8, 16, and 26 from 469 patients receiving either topiramate 50, 100, or 200 mg/day or placebo. Patients entered a double-blind, 8-week titration period followed by an 18-week maintenance period. Two activity-related MSQ domains (Role Restrictive [RR] and Role Prevention [RP]) and two activity-related SF-36 domains (Role Physical [SF-36-RP] and Vitality [SF-36-VT]) were prospectively designated as the outcome measures. Changes in MSQ and SF-36 scores during the double-blind phase relative to prospective baseline scores were compared between topiramate- and placebo-treated groups. Specifically, a mixed-effect piecewise linear regression model was used to estimate average domain score over time, and areas under the domain-over-time curve (AUC) were compared using a 2-sided t-test, with multiplicity adjustment. RESULTS: In the intent-to-treat population (N = 469), topiramate (all doses) significantly improved mean MSQ-RR domain scores versus placebo (topiramate 50 mg/day, p = 0.035; topiramate 100 mg/day; p < 0.001; topiramate 200 mg/day, p = 0.001). Topiramate-associated improvements in mean MSQ-RP domain scores were significant versus placebo only for topiramate 100 mg/day (p = 0.045). SF-36-RP and SF-36-VT domain scores improved (not significant versus placebo) for topiramate 100 and 200 mg/day. Changes in these MSQ and SF-36 domain scores significantly correlated with changes in mean monthly migraine frequency. CONCLUSION: Improvements in patient-reported outcomes specific for migraine (measured by the MSQ) were significantly better for patients receiving topiramate than for those receiving placebo. Improvements in the prospectively selected MSQ and SF-36 domains were significantly correlated with the decrease in mean monthly migraine frequency observed with topiramate treatment.

Activities of Daily Living↗