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Objectives/Background: Despite the high prevalence of sleep disturbance, stress, and depressive symptoms among patients with episodic migraine, there has been limited prospective research examining how these comorbid symptoms relate to future headache risk. Methods: We conducted an a priori secondary analysis of a prospective cohort study of 98 adults with episodic migraine recruited through Harvard‐affiliated medical centers and local college student clinics in Boston, MA. At baseline, participants completed validated questionnaires on sleep quality, stress, and depressive symptoms. Over the next 6 weeks, they recorded headaches on twice‐daily diaries. We conducted time‐to‐event analyses to evaluate whether these baseline symptoms were associated with headache recurrence. Results: At baseline, 45/98 (46%) participants had poor sleep quality, 51/98 (52%) reported moderate/high stress levels, and 18/98 (18%) had high depressive symptom scores. Over 4,406 person‐days, we observed 823 discrete headaches. In multivariable models, the hazard ratios for headache recurrence were: 1.22 (95% CI 1.02, 1.46) for people with baseline poor sleep, 1.12 (95% CI 0.93, 1.35) for those with baseline moderate/high stress compared to lower levels, and 1.31 (95% CI 1.05, 1.65) for the combination of poor sleep and moderate/high stress compared to the combination of good sleep and low stress. There was no association between depression scores and headache risk. Conclusion: Among patients with episodic migraine, poor sleep was associated with a higher rate of headache recurrence over the next 6 weeks, especially among those with coexisting moderate/high stress. [ABSTRACT FROM AUTHOR]

Objective: Hypertensive disorders of pregnancy (HDPs) increase cardiovascular disease (CVD) risk. Pregnancy morbidities, including preeclampsia and CVD, are common in systemic lupus erythematosus (SLE). Possible connections are important to explore. In a population‐based cohort, we investigated whether HDPs are associated with a higher risk of cardiovascular outcomes separately in women with SLE and those without SLE to examine the role of SLE. Methods: We identified first singleton births in the Medical Birth Register (1987–2012) among mothers with SLE and a large general population comparison group. Discharge diagnoses for HDPs, cardiovascular outcomes, and hypertension in the National Patient Register were identified using International Classification of Diseases codes. We estimated adjusted hazard ratios and 95% confidence intervals of the association between HDPs and outcomes in separate models in women with and without SLE. We then evaluated additive and multiplicative effect modification using relative excess risk due to interaction and Cox models jointly accounting for SLE and HDPs, respectively. Mediation analysis estimated the proportion of the association between SLE and outcome explained by HDPs. Results: HDPs were more common in pregnant women with SLE (20% versus 7%). In SLE, HDPs were associated with a 2‐fold higher rate of cardiovascular outcomes and a 3‐fold higher rate of incident hypertension. HDPs mediated 20% of the latter association. In women without SLE, HDPs were associated with higher incidence of hypertension later in life. Conclusion: In women with SLE and those without SLE, HDPs were associated with a 3‐fold higher rate of hypertension. In SLE, women with HDPs developed cardiovascular outcomes twice as often as women without HDPs. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of routine exercise with headache frequency, intensity, and duration among adults with episodic migraine (EM). Background: A comprehensive management plan for EM must aim at reducing disability and cost of care; to do so requires optimizing acute and preventive medications, and behavior changes. Prophylactic medication use is associated with adverse events and contraindications with comorbidities. Aerobic exercise is reported to decrease migraine frequency. However, no study has evaluated a potential synergistic relation between regular exercise and preventive medication use among patients with EM. Design and Methods: This was a secondary analysis of data from a prospective cohort study of adults with EMs. In that study, adults with EM (using International Classification of Headache Disorders‐3 criteria confirmed by study physicians) were recruited from three academic medical centers in Boston, MA. At baseline, participants provided information on exercise, clinical and demographic characteristics, and lifestyle behaviors. We prospectively collected daily information on headaches and health behavior over at least 6 weeks using electronic questionnaires from 94 participants. We assessed the association between baseline self‐reported moderate‐vigorous exercise at least three times per week, at baseline, and prospectively recorded headache frequency, intensity, and duration. We further assessed whether these associations differed by the prevalent use of prophylactic migraine medication. Results: Data from 94 of 98 eligible participants were used in the analysis as 4 participants had missing data on routine exercise frequency or intensity at baseline. On average, patients who reported moderate‐vigorous exercise at least three times per week at enrollment had 1.5 fewer headache days per month (−1.5 headache days/month; 95% confidence interval [CI] −3.1 to 0.1) compared to less exercise; this was not statistically significant (p = 0.066). The association between exercise and headache days per month varied by baseline use of migraine prophylaxis (p‐value of interaction = 0.009). Among those who reported regular use of migraine prophylaxis, a report of moderate‐vigorous exercise at least three times per week was associated with 5.1 fewer headache days (−5.1: 95% CI −8.2 to −2.0; p = 0.001) compared to those who reported lower levels of exercise. However, among those not using migraine prophylaxis, we observed only 0.4 fewer headache days per month (−0.4: 95% CI −2.2 to 1.3; p = 0.636) associated with moderate‐vigorous exercise at least three times/week, a result that was not statistically significant. There was no association of self‐reported moderate‐vigorous exercise at least three times a week with headache intensity or duration. Conclusion: In patients with EM, those who reported moderate‐vigorous exercise at least three times per week had fewer headache days per month, though not statistically significant. This association was significantly stronger in those who used prophylactic medication for migraines. Exercise appeared not to be associated with the severity or duration of headaches. Routine moderate‐vigorous exercise may be an important adjunctive strategy for improving headache burden in patients eligible for migraine prophylaxis. [ABSTRACT FROM AUTHOR]

We sought to develop a semiautomated screening approach using electronic healthcare data to identify drug–drug interactions (DDIs) that result in clinical outcomes. Using a case‐crossover design with 30‐day hazard and referent windows, we evaluated codispensed drugs (potential precipitants) in 7,801 patients who experienced rhabdomyolysis while on cytochrome P450 (CYP)3A4‐metabolized statins and in 15,147 who experienced bleeding while on dabigatran. Estimates of direct associations between precipitant drugs and outcomes were used to adjust for bias and precipitants' direct effects. The P values were adjusted for multiple testing using the false discovery rate (FDR). From among 460 drugs codispensed with statins, 1 drug (clarithromycin) generated an alert (adjusted odds ratio (OR) 5.83, FDR < 0.05). From among 485 drugs codispensed with dabigatran, 2 drugs (naproxen and enoxaparin, ORs 2.50 and 2.75; FDR < 0.05) generated an alert. All three signals reflected known pharmacologic interactions, confirming the potential of case‐crossover–based approaches for DDI screening in electronic healthcare data. [ABSTRACT FROM AUTHOR]

Objective: Higher traffic-related air pollution has been associated with higher body mass index (BMI) among children. However, few studies have assessed the associations among adults.Methods: Participants (N = 2,372) from the Framingham Offspring and Third Generation cohorts who underwent multidetector-computed tomography scans (2002-2005) were included. Residential-based proximity to the nearest major roadway and 1-year average levels of fine particulate matter (PM2.5 ) air pollution were estimated. BMI was measured at Offspring examination 7 (1998-2001) and Third Generation examination 1 (2002-2005); subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured using multidetector-computed tomography. Linear regression models were used for continuous BMI, SAT, and VAT and logistic models for the binary indicator of obesity (BMI ≥30 kg/m2 ), adjusting for demographic variables, individual- and area-level measures of socioeconomic position, and clinical and lifestyle factors.Results: Participants who lived 60 m from a major roadway had 0.37 kg/m2 higher BMI (95% CI: 0.10 to 0.65 kg/m2 ), 78.4 cm3 higher SAT (95% CI: 4.5 to 152.3 cm3 ), and 41.8 cm3 higher VAT (95% CI: -4.7 to 88.2 cm3 ) than those who lived 440 m away.Conclusions: Living closer to a major roadway was associated with higher overall and abdominal adiposity. [ABSTRACT FROM AUTHOR]

Objective: The aim of this work was to assess efficacy and tolerability of simvastatin plus vitamin D for migraine prevention in adults with episodic migraine.Methods: We performed a randomized, double-blind, placebo-controlled trial with a 12-week baseline period and 24-week intervention period in 57 adults with episodic migraine. Participants were randomly assigned to simvastatin 20 mg tablets twice-daily plus vitamin D3 1,000 international units capsules twice-daily or matching placebo tablets and capsules.Results: Compared to placebo, participants using simvastatin plus vitamin D3 demonstrated a greater decrease in number of migraine days from the baseline period to intervention weeks 1 to 12: a change of -8.0 (interquartile range [IQR]: -15.0 to -2.0) days in the active treatment group versus +1.0 (IQR: -1.0 to + 6.0) days in the placebo group, p < 0.001; and to intervention weeks 13 to 24: a change of -9.0 (IQR: -13 to -5) days in the active group versus +3.0 (IQR: -1.0 to + 5.0) days in the placebo group, p < 0.001. In the active treatment group, 8 patients (25%) experienced 50% reduction in the number of migraine days at 12 weeks and 9 (29%) at 24 weeks postrandomization. In comparison, only 1 patient (3%) in the placebo group (p = 0.03) experienced such a reduction. Adverse events were similar in both active treatment and placebo groups.Interpretation: The results demonstrate that simvastatin plus vitamin D is effective for prevention of headache in adults with episodic migraine. Given statins' ability to repair endothelial dysfunction, this economical approach may also reduce the increased risk for vascular diseases among migraineurs. [ABSTRACT FROM AUTHOR]

Purpose This study aims to explore the influence of gestational age at enrollment, and enrollment before or after prenatal screening, on the estimation of drug effects in pregnancy exposure registries. Methods We assessed the associations between first trimester antiepileptic drug (AED) exposure and risk of spontaneous abortion and major congenital malformations in the North American AED Registry (1996-2013). We performed logistic regression analyses, conditional or unconditional on gestational age at enrollment, to estimate relative risk (RR) for first trimester AED users compared with non-users. We also compared first trimester users of valproic acid and lamotrigine. Analyses were repeated in women who enrolled before prenatal screening. Results Enrollment occurred earlier among 7029 AED users than among 581 non-users; it was similar among AEDs. Comparing AED users with non-users, RR (95% confidence interval) of spontaneous abortion ( n = 359) decreased from 5.1 (2.3-14.1) to 2.0 (0.9-5.6) after conditioning on gestational week at enrollment and to 1.9 (0.8-5.4) upon further restriction to before-screening enrollees. RR of congenital malformations ( n = 216) changed from 3.1 (1.4-8.5) to 3.2 (1.4-9.0) after conditioning on gestational week at enrollment and to 2.0 (0.7-10.1) upon further restriction to before-screening enrollees. When comparing valproic acid users and lamotrigine users, the RR of congenital malformations was not substantially changed by conditioning or restricting. Conclusions Spontaneous abortion rates were sensitive to gestational age at enrollment. Estimates of congenital malformation risks for AED users relative to non-users were sensitive to before/after-screening enrollment. This difference was not apparent between active drugs, likely due to similar gestational age at enrollment. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

GFR, Mortality and ICD Therapy After ICD Generator Replacement Background Impaired renal function is associated with increased mortality among patients with implantable cardioverter-defibrillators (ICDs). The relationship between renal function at time of ICD generator replacement and subsequent appropriate ICD therapies is not known. Methods and Results We identified 441 patients who underwent first ICD generator replacement between 2000 and 2011 and had serum creatinine measured within 30 days of their procedure. Patients were divided into tertiles based on estimated glomerular filtration rate (eGFR). Adjusted Cox proportional hazard and competing risk models were used to assess relationships between eGFR and subsequent mortality and appropriate ICD therapy. Median eGFR was 37.6, 59.3, and 84.8 mL/min/1.73 m2 for tertiles 1-3, respectively. Five-year Kaplan-Meier survival probability was 34.8%, 61.4%, and 84.5% for tertiles 1-3, respectively (P < 0.001). After multivariable adjustment, compared to tertile 3, worse eGFR tertile was associated with increased mortality (HR 2.84, 95% CI [1.36-5.94] for tertile 2; HR 3.84, 95% CI [1.81-8.12] for tertile 1). At 5 years, 57.0%, 58.1%, and 60.2% of patients remained free of appropriate ICD therapy in tertiles 1-3, respectively (P = 0.82). After adjustment, eGFR tertile was not associated with future appropriate ICD therapy. Results were unchanged in an adjusted competing risk model accounting for death. Conclusions At time of first ICD generator replacement, lower eGFR is associated with higher mortality, but not with appropriate ICD therapies. The poorer survival of ICD patients with reduced eGFR does not appear to be influenced by arrhythmia status, and there is no clear proarrhythmic effect of renal dysfunction, even after accounting for the competing risk of death. [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose The role of administrative databases for research on drug safety during pregnancy can be limited by their inaccurate assessment of the timing of exposure, as the gestational age at birth is typically unavailable. Therefore, we sought to develop and validate algorithms to estimate the gestational age at birth using information available in these databases. Methods Using a population-based cohort of 286,432 mother-child pairs in British Columbia (1998-2007), we validated an ICD-9/10-based preterm-status indicator and developed algorithms to estimate the gestational age at birth on the basis of this indicator, maternal age, singleton/multiple status, and claims for routine prenatal care tests. We assessed the accuracy of the algorithm-based estimates relative to the gold standard of the clinical gestational age at birth recorded in the delivery discharge record. Results The preterm-status indicator had specificity and sensitivity of 98% and 91%, respectively. Estimates from an algorithm that assigned 35 weeks of gestational age at birth to deliveries with the preterm-status indicator and 39 weeks to those without them were within 2 weeks of the clinical gestational age at birth in 75% of preterm and 99% of term deliveries. Conclusions Subtracting 35 weeks (245 days) from the date of birth in deliveries with codes for preterm birth and 39 weeks (273 days) in those without them provided the optimal estimate of the beginning of pregnancy among the algorithms studied. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the association between residential distance to nearest major roadway, as a marker of long-term exposure to traffic pollution, and cognitive function in older adults. Design Prospective cohort study with median follow-up of 16.8 months. Setting Community. Participants Seven hundred sixty-five community-dwelling seniors. Measurements The Mini- Mental State Examination, Hopkins Verbal Learning Test- Revised ( HVLT- R), Trail Making Test ( TMT), category and letter fluency tests, and Clock-in-the- Box Test were administered during home visits on two occasions. The residential distance to the nearest major roadway was calculated, and generalized estimating equations were used to evaluate the association between performance on each test and residential distance to nearest major roadway, adjusting for participant demographics, education, socioeconomic status, and past medical history. Results Shorter distance to major roadway was associated with statistically significantly poorer performance on the immediate and delayed recall components of the HVLT- R, TMT Part B, TMT delta, and letter and category fluency tests. Generally, participants residing less than 100 m from a major roadway performed worst. Performance improved monotonically with increasing distance. Conclusion In this cohort of community-dwelling older adults, residential proximity to a major roadway was associated with poorer performance on cognitive tests of verbal learning and memory, psychomotor speed, language, and executive functioning. If causal, these results add to the growing evidence that living near major roadways is associated with adverse health outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose Although chronic use of diuretics has been implicated as a risk factor for falls, it is unknown whether changes in diuretic drugs are associated with an acutely elevated risk of falls. We evaluated the relationship between change in a diuretic prescription (new prescription or increased dose) and the occurrence of documented falls among nursing home residents. Methods Participants of the cohort were 1785 long-term care residents of two large nursing homes (2005-2010; Boston, MA). A self-matched, case-crossover analysis was used to examine whether there is an acutely increased risk of falling in the day following a diuretic drug change compared with days without a diuretic drug change. Odds ratios with 95% confidence intervals were calculated using conditional logistic regression models. Results During a mean follow-up of 8.4 months, 1181 participants experienced an incident fall. Nine participants experienced a diuretic change on the day before the fall. The odds of falling one day following a change in a diuretic was elevated (OR = 2.08; 95%CI = 0.89, 4.86). The association was stronger and reached nominal statistical significance when loop diuretics were examined separately (OR = 2.46; 95%CI = 1.02, 5.92). We estimated that, for every 271 loop diuretic drug changes, one excess fall occurred. Conclusions Nursing home residents are at an increased risk of falls in the day following a new prescription or increased dose of a loop diuretic drug. Extra precautions should be taken immediately following a loop diuretic drug change in an effort to prevent falls. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Inhibitors of myostatin, a negative regulator of skeletal muscle mass, are being developed to mitigate aging-related muscle loss. Knock-out (KO) mouse studies suggest myostatin also affects adiposity, glucose handling and cardiac growth. However, the cardiac consequences of inhibiting myostatin remain unclear. Myostatin inhibition can potentiate cardiac growth in specific settings ( Morissette et al., 2006) , a concern because of cardiac hypertrophy is associated with adverse clinical outcomes. Therefore, we examined the systemic and cardiac effects of myostatin deletion in aged mice (27–30 months old). Heart mass increased comparably in both wild-type (WT) and KO mice. Aged KO mice maintained twice as much quadriceps mass as aged WT; however, both groups lost the same percentage (36%) of adult muscle mass. Dual-energy X-ray absorptiometry revealed increased bone density, mineral content, and area in aged KO vs. aged WT mice. Serum insulin and glucose levels were lower in KO mice. Echocardiography showed preserved cardiac function with better fractional shortening (58.1% vs. 49.4%, P = 0.002) and smaller left ventricular diastolic diameters (3.41 vs. 2.71, P = 0.012) in KO vs. WT mice. Phospholamban phosphorylation was increased 3.3-fold in KO hearts ( P < 0.05), without changes in total phospholamban, sarco(endo)plasmic reticulum calcium ATPase 2a or calsequestrin. Aged KO hearts showed less fibrosis by Masson’s Trichrome staining. Thus, myostatin deletion does not affect aging-related increases in cardiac mass and appears beneficial for bone density, insulin sensitivity and heart function in senescent mice. These results suggest that clinical interventions designed to inhibit skeletal muscle mass loss with aging could have beneficial effects on other organ systems as well. [ABSTRACT FROM AUTHOR]

The article presents a study on the validity assessment of occupational exposures reported by uninjured workers at a Midwestern meatpacking plant. It notes that the methods used to assess the level of agreement between self-reports and direct observations of workers were kappas and intraclass correlation coefficients. Results show varied self-reported exposures among meatpacking workers. Accordingly, the study sheds light on understanding and preventing occupational injury.

The article presents a case study on obesity and C-reactive protein (CRP) levels among white, black, and Hispanic U.S. adults. In the study, the sex-specific multivariable models of the association of body mass index (BMI) or waist circumference of participants were fitted with log CRP levels. The researchers conclude that higher body mass index (BMI) and larger waist circumference were linked to higher CRP levels in ethnic groups for men and women.

OBJECTIVES: To evaluate several aspects of the relationship between alcohol use and coronary heart disease in older adults, including beverage type, mediating factors, and type of outcome. DESIGN: Prospective cohort study. SETTING: Four U.S. communities. PARTICIPANTS: Four thousand four hundred ten adults aged 65 and older free of cardiovascular disease at baseline. MEASUREMENTS: Risk of incident myocardial infarction or coronary death according to self-reported consumption of beer, wine, and spirits ascertained yearly. RESULTS: During an average follow-up period of 9.2 years, 675 cases of incident myocardial infarction or coronary death occurred. Compared with long-term abstainers, multivariate relative risks of 0.90 (95% confidence interval (CI)=0.71–1.14), 0.93 (95% CI=0.73–1.20), 0.76 (95% CI=0.53–1.10), and 0.58 (95% CI=0.39–0.86) were found in consumers of less than one, one to six, seven to 13, and 14 or more drinks per week, respectively ( P for trend=.007). Associations were similar for secondary coronary outcomes, including nonfatal and fatal events. No strong mediators of the association were identified, although fibrinogen appeared to account for 9% to 10% of the relationship. The associations were statistically similar for intake of wine, beer, and liquor and generally similar in subgroups, including those with and without an apolipoprotein E4 allele. CONCLUSION: In this population, consumption of 14 or more drinks per week was associated with the lowest risk of coronary heart disease, although clinicians should not recommend moderate drinking to prevent coronary heart disease based on this evidence alone, because current National Institute on Alcohol Abuse and Alcoholism guidelines suggest that older adults limit alcohol intake to one drink per day. [ABSTRACT FROM AUTHOR]

To assess the cross-sectional and longitudinal associations between alcohol consumption and risk of falls in older adults. Cross-sectional and longitudinal analyses. Four U.S. communities. A total of 5,841 older adults enrolled in the Cardiovascular Health Study, an ongoing, population-based, prospective cohort study, participated. Self-reported alcohol consumption at baseline, self-reported frequent falls at baseline, and the 4-year risk of falls of participants who denied frequent falls at baseline. Cross-sectional analysis indicated an apparent inverse association between alcohol consumption and risk of frequent falls (adjusted odds ratio in consumers of 14 or more drinks per week=0.41; 95% confidence interval (CI)=0.14–1.17; P for trend=.06), but longitudinal analysis indicated a similar 4-year risk of falls in abstainers and light to moderate drinkers but a 25% higher risk in consumers of 14 or more drinks per week (95% CI=3–52%; P for trend=.07). Similar results were found in analyses stratified by age, sex, race, and physical activity. Consumption of 14 or more drinks per week is associated with an increased risk of subsequent falls in older adults. Cross-sectional studies may fail to identify this risk of heavier drinking, perhaps because older adults at risk for falls decrease their alcohol use over time or because heavier drinkers at risk for falls tend not to enroll in cohort studies. However, because this study relied upon annual reporting of falls, further prospective studies should be conducted to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: We developed a source documentation approach that identified fluoride content of drinking water at the state or local level to estimate fluoride concentrations from public water systems. We then compared estimates from this approach with estimates obtained from a single source, the 1992 Centers for Disease Control and Prevention (CDC) Fluoridation Census.Methods: We used residential histories from a case-control study. For each residence we attempted to determine fluoride concentrations using the 1992 CDC Fluoridation Census. For the source documentation method we utilized multiple sources from state and local contacts to verify and collect additional data. We compared the fluoride estimates obtained by the two methods.Results: When fluoride values were found using both methods, there was good correlation (Kendall's tau = 0.85; 95% confidence interval = 0.79, 0.90) and concordance was 96 percent. We obtained over 99 percent of the fluoride values needed using source documentation as compared to 49 percent of the values needed when we used a single publication. When fluoride values were missing using the 1992 CDC Fluoridation Census, 21 percent had source documentation estimates of at least 0.7 ppm.Conclusions: Researchers need to consider limitations of using a secondary data source to estimate fluoride in drinking water, particularly in studies where exposure to fluoride is the primary exposure of interest. [ABSTRACT FROM AUTHOR]

TWA and Post-MI Arrhythmia. Introduction: This is the first study to assess T wave alternans (TWA) analyzed from routine ambulatory electrocardiograms (AECGs) to identify postmyocardial infarction (post-MI) patients at increased risk for arrhythmic events. Methods and Results: The new method of modified moving average (MMA) analysis was used to measure TWA magnitude in 24-hour AECGs from ATRAMI, a prospective study of 1,284 post-MI patients. Using a nested case-control approach, we defined cases as patients who experienced cardiac arrest due to documented ventricular fibrillation or arrhythmic death during the follow-up period of 21 ± 8 months . We analyzed 15 cases and 29 controls matched for sex, age, site of MI, left ventricular ejection fraction, thrombolysis, and beta-blockade therapy. TWA was reported as the maximum 15-second value at three predetermined times associated with cardiovascular stress: maximum heart rate, 8:00 A.M., and maximum ST segment deviation. TWA increased significantly from baseline in both leads at each time point (P ≪ 0.01) in cases and controls. TWA in V[sub 5] increased more in cases than controls during peak heart rate (P = 0.005) and at 8:00 A.M. (P = 0.02) . A 4- to 7-fold higher odds of life-threatening arrhythmias was predicted by TWA level above the 75th percentile during maximum heart rate in leads V[sub 1] (odds ratio [OR] 4.2, 95% confidence interval [CI]: 1.1–16.3, P = 0.04 ) and V[sub 5] (OR 7.9, 95% CI: 1.9–33.1, P = 0.005) . TWA at 8:00 A.M. also predicted risk in leads V[sub 1] (OR = 5.0, 95% CI: 1.2–20.5, P = 0.02) and V[sub 5] (OR = 4.2, 95% CI: 1.1–16.3, P = 0.04) . Conclusion: TWA measurement from routine 24-hour AECGs is a promising approach for risk stratification for cardiac arrest and arrhythmic death in relatively low-risk post-MI patients. (J Cardiovasc Electrophysiol, Vol. 14, pp. 705-711, July 2003). [ABSTRACT FROM AUTHOR]

ARONSON, D., et al.: Effects of Sulfonylurea Hypoglycemic Agents and Adenosine Triphosphate Dependent Potassium Channel Antagonists on Ventricular Arrhythmias in Patients with Decompensated Heart Failure. --> Hypoglycemic sulfonylureas block cardiac ATP‐sensitive potassium channels (KATP). The opening of these channels in cardiomyocytes can induce arrhythmias. In animal studies, sulfonylureas exert an antiarrhythmic effect on the ischemic myocardium, but data on human arrhythmic events are lacking. The study population included 207 patients (age 61 ± 14 years) admitted for decompensated CHF. The severity of ventricular arrhythmias was assessed by 24‐hour Holter monitoring. None of the patients were on parenteral vasoactive therapy or antiarrhythmics during Holter recording. Diabetic patients comprised 48% of the study population, and 34% of diabetic patients were prescribed sulfonylureas. The mean hourly ventricular pairs (3.6 ± 0.5vs1.8 ± 0.3, P = 0.03), the mean hourly repetitive ventricular beats (5.7 ± 1.0vs2.6 ± 0.1, P = 0.03), and the frequency of ventricular tachycardia episodes per 24 hours (4.7 ± 0.8vs2.2 ± 0.4, P = 0.03) were significantly lower in patients with diabetes who were receiving sulfonylureas compared with nondiabetics. No significant difference occurred between patients with diabetes who were not receiving sulfonylureas and nondiabetic patients. Multivariate regression revealed a negative independent relationship between sulfonylurea therapy and hourly ventricular pairs(P = 0.03),the mean hourly repetitive ventricular beats(P = 0.03),and ventricular tachycardia episodes(P = 0.04). In a multiple logistic regression, sulfonylurea therapy was a negative predictor of repetitive ventricular beats (P = 0.01,adjusted OR, 0.31; 95% CI, 0.12–0.78). Concomitant sulfonylurea therapy may reduce the occurrence of complex ventricular ectopy in the setting of severe CHF. These results suggest that cardiac KATP channel activation may be involved in the genesis of ventricular arrhythmias in CHF. (PACE 2003; 26:1254–1261) [ABSTRACT FROM AUTHOR]

Endothelin-1 (ET-1) can modulate central and peripheral sympathetic outflow. However, if increased ET-1 levels contribute to autonomic perturbations in the setting of congestive heart failure (CHF) is not known. The purpose of this study was to determine if increased ET-1 levels contribute to the depressed HRV in patients with CHF. Sixty-four patients were admitted to the hospital for treatment of decompensated CHF (mean age 59 ± 12 years, NYHA Classes III [72%] and IV [28%]). Time and frequency-domain HRV measures were obtained from 24-hour Holter recordings. Neurohormonal activation was assessed by measuring plasma renin activity (PRA), aldosterone, norepinephrine, and ET-1 levels. Among the time-domain HRV indices, ET-1 correlated negatively with the standard deviation of RR intervals (SDNN) (r = -0.38. P = 0.002) and standard deviation of all 5-minute mean RR intervals (SDANN5) (r = -0.48, P < 0.0001), but not with time-domain indices indicative of parasympathetic modulation. Among the frequency-domain HRV indices. ET-1 correlated negatively with the total power (r = -0.32. P = 0.01) and ultralow frequency power (ULF) (r = -0.43, P = 0.0004), but not with indices of parasympathetic (high frequency) or sympathovagal (low frequency) modulation. Using multiple linear regression, adjusting for clinical parameters, drug therapies, and other neurohormones, the strong negative relationship between ET-1 and SDNN (P = 0.027), SDANN5 (P = 0.002), and ULF power (P = 0.017) persisted. In conclusion. ET-1 may play an important role in the autonomic dysfunction characteristic of CHF. The correlation between ET-1 levels and prognostically important indices of overall HRV suggests that these HRV measures are better markers of neurohormonal activation in CHF, which may partially account for their greater discriminatory power for risk stratification. [ABSTRACT FROM AUTHOR]

Introduction: Increased local and systemic elaboration of cytokines have an important role in the pathogenesis of congestive heart failure (CHF) through diverse mechanisms. Because cytokines are known to act at the neuronal level in both the peripheral and central nervous system, we sought to determine whether increased cytokine levels are associated with the autonomic dysfunction that characterizes CHF. Methods and Results: We studied 64 patients admitted for decompensated CHF (mean age 59 ± 12 years). Autonomic function was assessed using time- and frequency-domain heart rate variability (HRV) measures, obtained from 24-hour Holter recordings. In addition, norepinephrine, tumor necrosis factor-a (TNF-α), and interleukin-6 (IL-6) were measured in all patients. TNF-α levels did not correlate with any of the HRV measures. IL-6 inversely correlated with the time-domain parameters of standard deviation of RR intervals (SDNN) (r = -0.36, P = 0.004) and standard deviation of all 5-minute mean RR intervals (SDANN) (r = -0.39, P = 0.001), and with the frequency-domain parameters of total power (TP) (r = -0.37, P = 0.003) and ultralow-frequency (ULF) power (r = -0.43, P = 0.001). No correlation was found between IL-6 and indices of parasympathetic modulation. Using multiple linear regression models, adjusting for clinical variables and drug therapies, the strong inverse relationship between IL-6 and SDNN (P = 0.006), SDANN (P = 0.001), TP (P = 0.04), and ULF power (P = 0.0007) persisted. Conclusion: Reduction of long-term HRV indices is associated with increased levels of IL-6 in patients with decompensated heart failure. The ability of long-term HRV parameters to better reflect activation of diverse hormonal systems may explain their greater prognostic power for risk stratification in patients with CHF. [ABSTRACT FROM AUTHOR]

The article offers information on attribution of sleep disturbances as a trigger of migraine has conducted a prospective cohort study adults with episodic migraine to examine the bidirectional, temporal associations between migraine onset and sleep duration, quality, and fragmentation. Topics include the strong bidirectional associations between sleep duration and quality and next-day migraine, and the clinicians should avoid attributing migraine attacks solely to sleep problems.

Objective: Some evidence suggests that perinatal factors, including birth weight and breastfeeding, may influence the occurrence of autoimmune rheumatic diseases. However, few studies have investigated these factors in patients with systemic lupus erythematosus (SLE). Therefore, we evaluated the role of birth weight, being breastfed, and preterm birth on the incidence of SLE in participants in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII)., Methods: We studied 87,411 NHS participants and 98,413 NHSII participants without SLE at baseline who provided information on perinatal exposures. Among these women, during 26 (NHS) and 14 (NHSII) years of followup, 222 incident SLE cases were confirmed (136 NHS and 86 NHSII) by medical record review using American College of Rheumatology criteria. We used stratified Cox models to estimate the association of perinatal factors with SLE, adjusting for race, early passive cigarette smoke exposure, and parents' occupation. A random-effects meta-analysis was used to compute combined estimates across the 2 cohorts., Results: After adjustment for multiple potential confounders, high birth weight (> or =10 pounds) was associated with increased rates of SLE compared with normal birth weight (7-8.5 pounds; rate ratio [RR] 2.7, 95% confidence interval [95% CI] 1.2-5.9), as was being born > or =2 weeks preterm (RR 1.9, 95% CI 1.2-3.0); however, being breastfed was not (RR 0.8, 95% CI 0.6-1.1)., Conclusion: Birth weight > or =10 pounds and preterm birth were both positively associated with incident SLE among women.

Background: Alcohol intake has been associated with lower platelet activity; however, few large-scale studies have included women, and to our knowledge, the relationship of alcohol intake with measures of platelet activation has not been studied., Methods: We performed a cross-sectional analysis of adults free of cardiovascular disease enrolled in the Framingham Offspring Study. Study physicians assessed alcohol consumption with a standardized questionnaire. We measured platelet activation in response to 1 and 5 microm of adenosine diphosphate (ADP) with a P-selectin assay among 1037 participants and platelet aggregability in response to ADP, epinephrine, and collagen among 2013 participants., Results: Alcohol consumption was inversely associated with P-selectin expression in response to 1 microm ADP (p = 0.007) and 5 microm ADP (p = 0.02) among men but not women. Alcohol consumption was also inversely associated with platelet aggregation induced by ADP among both women (p = 0.04) and men (p trend = 0.008) and by epinephrine among men (p = 0.03), Conclusions: Alcohol consumption is inversely associated with both platelet activation and aggregation, particularly in men. Additional research is needed to determine whether these findings contribute to the contrasting associations of alcohol consumption with risk of thrombotic and hemorrhagic cardiovascular events.

Background: Employees in meat packing experience one of the highest occupational laceration injury rates in the US., Method: A retrospective study was conducted using OSHA 200 injury and illness logs and First Reports of Injury from two large US meat packing plants from 1998 to 2000. The total workers observed during the study period ranged between 2,449 and 2,682 per year., Results: Laceration injury incidence rates in Plant 1 were 14.0 injuries per 200,000 person hours (per 100 workers per year) in 1998, 11.5 in 1999, and 8.3 in 2000, whereas in Plant 2 the overall incidence rate was 3.7 in 1998, 4.8 in 1999, and 3.0 in 2000. Laceration injury rates in Plant 2 were close to the expected OSHA recordable laceration injury rate in 1999 (3.0 per 100 workers per year), but Plant 1 was considerably higher. Plant 1 had a kill support department, and removed animal hides whereas Plant 2 did not. Handheld non-powered tools were the most common contact objects whereas the slaughter department had the highest number of injuries. Finger injuries from a handheld non-powered tool were the most frequent., Conclusions: Findings confirm the high rate of injury from laceration in this industry and indicate hazard varies across time into shift, task being performed, and type of tool being used., ((c) 2005 Wiley-Liss, Inc.)