Ovarian hormones, age and pubertal development and their association with days of headache onset in girls with migraine: An observational cohort study.

Background Fifty-three percent of adolescent girls report headaches at the onset of menses, suggesting fluctuations of ovarian hormones trigger migraine during puberty. Aims To determine if urinary metabolites of estrogen and progesterone are associated with days of headache onset (HO) or severity in girls with migraine. Methods This was a pilot study and included 34 girls with migraine balanced across three age strata (pre-pubertal (8-11), pubertal (12-15), and post-pubertal (16-17) years of age). They collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide (E1G) and pregnandiol glucuronide (PdG) and the daily change was calculated (ΔE1G, ΔPdG). Pubertal development was assessed by age, pubertal development score (PDS), and menstrual cycle variance. The primary outcome measures were HO days and headache severity. Generalized linear mixed models were used, and included the hormonal variables and three different representations of pubertal development as covariates. Results Models of HO days demonstrate a significant age*PdG interaction (OR 0.85 [95% CI 0.75, 0.97]) for a 1 standard deviation increase in PdG and three-year increase in age. A separate model showed a significant PDS*PdG interaction (OR -0.85 [95% CI; 0.76, 0.95]). ΔPDG was associated with headache severity in unadjusted models ( p < 0.017). Conclusion Age and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine.

Symptoms of premenstrual syndrome and their association with migraine headache.

OBJECTIVES: To determine the association between the severity of premenstrual (PMS) symptoms and headache outcome measures during natural menstrual cycles and after medical oophorectomy. BACKGROUND: Premenstrual syndrome may occur in 64% of those with pure menstrual migraine and 33% of those with menstrually related migraine. Few past studies have examined the relationship between the severity of PMS symptoms and migraine headache. METHODS: Data were obtained from a 6.5-month randomized-controlled trial examining the role of medical oophorectomy in the prevention of migraine headache and later divided into two data sets for analysis purposes. The menstrual cycle data set was composed of data from three natural menstrual cycles obtained from 21 participants during lead-in and placebo run-in phases. Each menstrual cycle was subdivided into seven 3-day intervals based on urine hormone metabolites. The medical oophorectomy data set included data from a 2-month treatment period in which a medical oophorectomy was induced by gonadotropin-releasing hormone agonists (GnRHa) and participants were randomized to transdermal estradiol or a matching placebo (GnRHa/estradiol and GnRHa/placebo groups, respectively). All participants completed a daily diary recording the severity of PMS symptoms and headache outcome measures. The primary outcome measures were the PMS index (mean of the daily PMS severity scores) and the headache index (mean of the headache severity scores). Pearson correlation coefficients were used to assess the degree of association between the outcome measures. RESULTS: Menstrual Cycle Data Set.-The PMS index was significantly correlated with the headache index during native menstrual cycles (correlation coefficient of 0.47; P < .05) and during all seven intervals of the menstrual cycle (correlation coefficients of 0.39 to 0.65; all P values < .05). Medical Oophorectomy Data Set.-Correlation coefficients between the PMS and headache indices were 0.58 and 0.47 for the GnRHa/estradiol (n = 9) and GnRHa/placebo groups, respectively (P-values of <.05). CONCLUSIONS: Moderate correlations exist within female migraineurs between the severity of PMS symptoms and headache outcome measures throughout natural menstrual cycles as well as after medical oophorectomy. Our data would suggest that the presence and severity of headache might modulate PMS symptoms in female migraineurs.

Health values of patients coinfected with HIV/hepatitis C: are two viruses worse than one?

OBJECTIVES: We sought to assess health values of patients coinfected with HIV/hepatitis C (HCV) and compare them with those of patients singly infected with HIV or HCV and to characterize and assess the relationship of clinical and nonhealth-related factors with health values. SUBJECTS: We studied a total of 203 subjects infected with HIV, HCV, or both. MEASURES: We assessed rating scale (RS), time tradeoff (TTO), and standard gamble (SG) values, and we explored associations of health values with the Mental Component Summary (MCS) and Physical Component Summary (PCS) of the SF-12; number of bothersome symptoms from the HIV Symptoms Index; spirituality, as assessed by the Functional Assessment of Chronic Illness Therapy, Spiritual Well-being scale; as well as with a number of demographic, clinical, and psychosocial characteristics. RESULTS: Of the 203 subjects, 59 (29%) had HIV monoinfection, 69 (34%) had HCV monoinfection, and 75 (37%) were coinfected. The mean (SD) health values for the cohort were: RS = 0.69 (0.23), TTO= 0.88 (0.24), and SG = 0.78 (0.30). Infection type was related, albeit differently, to TTO values (mean values for patients with coinfection = 0.82; HIV = 0.91; and HCV = 0.91 [P < 0.05]) and SG values (coinfection = 0.77; HIV = 0.70; and HCV = 0.87; P < 0.05). In multivariable models, RS scores were significantly associated with sexual orientation, PCS scores, MCS scores, symptoms, and spirituality (adjusted R = 0.61); TTO with symptoms and spirituality (adjusted R = 0.23); and SG with infection type, PCS scores, and symptoms (adjusted R = 0.24). CONCLUSIONS: Health values and their correlates varied by method of assessment. Health values appear to be driven more by symptoms, health status, and spirituality than by number of viral infections.

Defining the relationship between ovarian hormones and migraine headache.

OBJECTIVE: (1) To determine whether the attack characteristics of migraine differ between different intervals of the menstrual cycle; (2) To ascertain whether the "rate of change,""magnitude of change," or "total burden" of urinary hormone metabolites correlates with headaches outcome measures during different intervals of the menstrual cycle. BACKGROUND: The mechanisms through which migraines are influenced by ovarian hormones remain unclear. No previous studies until now have identified "hormonally defined" time intervals within the female menstrual cycle and compared headache outcome measures among these intervals in female migraineurs. METHOD: Daily headache diary data were obtained from 21 female migraineurs during three native menstrual cycles. Daily urine samples were collected and later assayed for estrogen and progesterone metabolites. Seven 3-day time intervals were identified within each menstrual cycle based on urine hormone measurements. Primary (headache index) and secondary (disability index, headache severity, and headache frequency) outcome measures were compared between intervals using the mixed model approach. "Rates of change,""magnitude of change," and the "total burden" of ovarian hormones were estimated from urine hormone metabolites and correlated with headache outcome measures. RESULTS: The headache index was significantly different across different intervals of the menstrual cycle (P values <.001) and was higher during menstrual intervals (first 6 days of the menstrual cycle) than during mid-cycle and mid-luteal intervals (P < .002). Similarly, secondary outcome measures were highest during the menstrual intervals. "Higher burdens" of urinary progesterone metabolites were positively correlated with headache outcome measures during the luteal intervals of the menstrual cycle. "Rates of change" and the "magnitude of change" of urinary hormone metabolites did not correlate with headache outcome measures. CONCLUSIONS: Migraine headache is more severe, disabling, and frequent during the menstrual intervals of the female reproductive cycle than during mid-luteal or mid-cycle intervals. Progesterone metabolites may play a role in modulating migraine headaches during luteal intervals of the menstrual cycle.

Medical oophorectomy with and without estrogen add-back therapy in the prevention of migraine headache.

OBJECTIVES: To determine the preventive benefit of "medical oophorectomy" and transdermal estradiol in women with migraine. BACKGROUND: Epidemiological studies have demonstrated that declines in serum estrogen levels occurring during normal menstrual cycles can trigger headache in women with migraine. Prior to this study, no randomized controlled trials have evaluated whether minimizing these hormonal changes pharmacologically can prevent headache. METHODS: Twenty-one women with regular menstrual cycles and a diagnosis of migraine headache were enrolled. After a 2.5-month placebo run-in phase, all patients received a subcutaneous goserelin implant (a gonadotropin-releasing hormone agonist) to induce a medical oophorectomy. One month later, while continuing goserelin, participants were randomized to receive a transdermal patch containing 100 microg of estradiol-17beta (gonadotropin-releasing hormone agonist/estradiol group, n = 9) or a placebo patch (gonadotropin-releasing hormone agonist/placebo group, n = 12) during a 2-month treatment phase. The primary outcome measure was the headache index, which was defined as the mean of pain severity ratings (0 to 10 scale) recorded three times per day by daily diary. Secondary outcome measures included headache disability, headache severity, headache frequency, and the percentage of headaches with a pain severity rating of 7 or greater. RESULTS: The headache index was significantly lower during the treatment period in the gonadotropin-releasing hormone agonist/estradiol group than in the gonadotropin-releasing hormone agonist/placebo group (P =.025). Similar improvements were observed in the gonadotropin-releasing hormone agonist/estradiol group for all secondary outcome measures with the exception of headache frequency, which was unchanged between the groups. Within the gonadotropin-releasing hormone agonist/estradiol group, there was a 33.7% reduction (95% confidence interval, -64.4 to -3.0) in the headache index during the treatment phase when compared with the placebo run-in phase; no difference was seen between those phases within the gonadotropin-releasing hormone agonist/placebo group. CONCLUSIONS: Minimization of hormonal fluctuations with gonadotropin-releasing hormone agonist therapy alone is inadequate to prevent headache in women who are premenopausal with migraine. The addition of transdermal estradiol to existing gonadotropin-releasing hormone agonist therapy provides a modest preventive benefit.

Weaning success among ventilator-dependent patients in a rehabilitation facility.

OBJECTIVES: To determine outcomes of difficult-to-wean, ventilator-dependent patients transferred from intensive care units to rehabilitation hospitals and to determine predictors of weaning success in such patients. DESIGN: A retrospective cohort study. SETTING: A rehabilitation facility. PARTICIPANTS: One hundred forty-five difficult-to-wean patients (55.2% men; 83.4% white; mean age +/- standard deviation, 65.8 +/- 16.4y) transferred to a rehabilitation facility between July 1994 and June 1996. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographic and clinical data, including variables identified previously as predictive of weaning success among highly selected populations. RESULTS: Patients' Gillespie categories (reason for ventilator dependency) included "other medical conditions" (eg, pneumonia, neurologic) in 42.1% of the cases, postoperative in 24.8%, previous lung disease (eg, chronic obstructive pulmonary disease, interstitial lung disease) in 15.2%, trauma in 11.7%, respiratory failure with multisystem failure in 3.4%, and uncomplicated acute lung injury (acute respiratory distress syndrome) in 2.8%. Of 145 patients, 50.3% were completely weaned, 4.8% were partially weaned, and 44.8% remained ventilator dependent. In a stepwise multivariable logistic regression analysis, significant predictors of weaning success included white race (odds ratio [OR] = 3.4), serum albumin level (OR = 2.1g/dL), and blood urea nitrogen (BUN) level (OR = .97mg/dL); in addition, compared with postoperative patients, patients with "other medical conditions" (OR = .15) or previous lung disease (OR = .08) were less likely to be weaned (area under receiver operating characteristic curve = .76). Among 31 long-term survivors who were interviewed at least 6 months after discharge from the rehabilitation facility, 58.1% rated their health-related quality of life as good or better. CONCLUSIONS: Half of the patients admitted to a rehabilitation facility were weaned from their ventilators. Predictors of weaning success included race, BUN level, albumin level, and reason for ventilator dependency.