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Background: Studies on cannabis use and adverse cardiovascular outcomes have reported conflicting results. Research on its relationship to calcified arterial plaque remains limited., Methods: Cross-sectional data from 2152 participants at Exam 6 (2016-2018) in the Multi-Ethnic Study of Atherosclerosis (MESA) were analyzed, including self-reported cannabis smoking patterns and carotid artery calcification (CAC) as measured via computed tomography. Multivariable relative and absolute risk regression models were used to estimate adjusted prevalence ratios (PRs) and prevalence differences, respectively, for the presence of calcified plaque. Multivariable linear regression was then used to compare group differences in the extent of CAC in those with calcified plaque., Results: A minority of participants ( n = 159, 7.4%) reported a history of regular cannabis smoking. Among all participants, 36.1% ( n = 777) had detectable CAC. In models adjusted for demographics, behavioral, and clinical cardiovascular disease factors, a history of regular cannabis smoking was not associated with the prevalence of CAC in either common carotid artery (PR: 1.14, 95% CI: 0.88 to 1.49). In the subset of participants with calcified plaque, and in separate fully adjusted multivariable linear regression models, a history of regular cannabis smoking was not associated with increased calcium volume (difference = 7.7%, 95% CI: -21.8 to 48.5), calcium density (difference = 0.4%, 95% CI: -6.6 to 7.9), or Agatston score (difference = 32.1%, 95% CI: -31.8 to 155.8) in either carotid artery. Models exploring potential effect modification by age, race/ethnicity, and tobacco smoking status showed no significant association, except for higher CAC prevalence in men with a history of regular cannabis smoking., Conclusions: In a racially and ethnically diverse cohort of older adults with a moderately high prevalence of CAC, no associations were found between a history of regular cannabis smoking, duration, or recency of cannabis smoking, and the prevalence of carotid calcified plaque. These findings were consistent across age, race/ethnicity, and cigarette smoking, except for an increased prevalence in men with a history of regular cannabis smoking. Similarly, in a subgroup with CAC, no association was found between a history of regular cannabis smoking and extent of calcification as measured by volume, density, and Agatston score., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Corroon is a member of the Board of Directors of CV Sciences, Inc., a manufacturer of hemp-derived CBD products. The remaining authors have no conflicts of interest.

Background: The Agatston coronary artery calcium (CAC) score provides robust cardiovascular disease risk prediction but upweights plaque area by a density factor. Density, however, has been shown to be inversely associated with events. Using CAC volume and density separately improves risk prediction, but it is unclear how to apply this method clinically. We aimed to evaluate the association between CAC density and cardiovascular disease across the spectrum of CAC volume to better understand how to incorporate these metrics into a single score., Methods: We performed an analysis of MESA (Multi-Ethnic Study of Atherosclerosis) participants with detectable CAC to evaluate the association between CAC density and events by level of CAC volume using multivariable Cox regression models., Results: In a cohort of 3316 participants, there was a significant interaction ( P <0.001) between CAC volume and density for coronary heart disease (CHD) risk (myocardial infarction, CHD death, resuscitated cardiac arrest). Models using CAC volume and density resulted in improvement in the C -index (0.703, SE 0.012 versus 0.687, SE 0.013) and a significant net reclassification improvement (0.208 [95% CI, 0.102-0.306]) compared with the Agatston score for CHD risk prediction. Density was significantly associated with lower CHD risk at volumes ≤130 mm 3 (hazard ratio, 0.57 per unit of density [95% CI, 0.43-0.75]), but the inverse association at volumes >130 mm 3 was not significant (hazard ratio, 0.82 per unit of density [95% CI, 0.55-1.22])., Conclusions: The lower risk for CHD associated with higher CAC density varied by level of volume, and volume ≤130 mm 3 is a potentially clinically useful cut point. Further study is needed to integrate these findings into a unified CAC scoring method.

Background and Aims: We aimed to identify predictors of change in direct measures of coronary artery calcium (CAC) volume and density in South Asian participants., Methods: We used data from participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with prevalent CAC and direct measures of CAC by serial computed tomography (CT) exams (2010-2013, 2016-2018). We examined the distribution of incident CAC volume and peak density, as well as progression and identified risk factors for progression of change in volume and density in multivariable models., Results: The study cohort consisted of 102 participants with incident CAC and 285 with CAC progression. CAC volume and density were highest, and incident CAC was most common in the left anterior descending artery (LAD). The greatest progression in volume was in the right coronary artery and the greatest change in density was in the left main. In linear regression models for CAC progression adjusted for baseline density, volume, risk factors, smoking (β +190.1, p = 0.02), baseline volume (β +0.24 per mm 3 , p < 0.01), and scan interval (β +0.15 per day, p = 0.01) were associated with change in total volume whereas Lp(a) (β +0.81 per mg/dL, p = 0.03), exercise (β +0.19 per 10 MET-min/week, p = 0.01), and baseline volume (β +0.15 per mm 3 , p < 0.01) and density (β -0.55 per unit, p < 0.01) were associated with change in total density., Conclusions: In this South Asian cohort, smoking was associated with CAC volume progression, while Lp(a) and exercise were associated with progression of peak CAC density., (Published by Elsevier B.V.)

Introduction: Agricultural pesticide spray periods increase the pesticide exposure potential of children living nearby and growing evidence indicates that they may affect children's health. We examined the association of time following a heightened agricultural production period, the Mother's Day flower harvest (May), with children's blood pressure (BP)., Methods: We included cross-sectional information of 313 children ages 4-9 years in Ecuadorian agricultural communities (the ESPINA study). Examinations occurred during a period of low flower production, but within 63-100 days (mean = 81.5, SD = 10.9) following the Mother's Day harvest. BP was measured twice using a pediatric sphygmomanometer and BP percentiles appropriate for age, gender and height were calculated., Results: Participants were 51% male, 1.6% hypertensive and 7.7% had elevated BP. The mean (SD) BP percentiles were: systolic: 51.7 (23.9); diastolic: 33.3 (20.3). There was an inverse relationship between of time after the spray season with percentiles of systolic (difference [β] per 10.9 days after the harvest: -4.3 [95%CI: -6.9, -1.7]) and diastolic BP (β: -7.5 [-9.6, -5.4]) after adjusting for race, heart rate and BMI-for-age z-score. A curvilinear association with diastolic BP was observed. For every 10.9 days that a child was examined sooner after the harvest, the OR of elevated BP/hypertension doubled (OR: 2.0, 95% CI: 1.3, 3.1). Time after the harvest was positively associated with acetylcholinesterase., Conclusions: Children examined sooner after a heightened pesticide spray period had higher blood pressure and pesticide exposure markers than children examined later. Further studies with multiple exposure-outcome measures across pesticide spray periods are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs)., Methods: Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis., Findings: Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350,000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa., Interpretation: Rates of YLDs per 100,000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world., Funding: Bill & Melinda Gates Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time., Methods: We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights., Findings: Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions., Interpretation: Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results., Funding: Bill & Melinda Gates Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex., Methods: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions., Findings: In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted., Interpretation: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis., Funding: Bill & Melinda Gates Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The pathophysiology and time course of an individual converting from asymptomatic peripheral artery disease (PAD) to symptomatic claudication is unclear. The objectives of this study were: (1) to characterize the extent of atherosclerotic disease in individuals with an abnormal ankle-brachial index (ABI), but without claudication; and over 1 year of follow-up to (2) evaluate the progression of PAD using ultrasound imaging, (3) determine changes in the ABI and leg pain symptoms, and (4) correlate PAD progression with changes in the ABI and leg symptoms. We hypothesized that PAD progression would be associated with the development of claudication and changes in the ABI, 6-minute walk distance (6-MWD), and walking quality of life. Individuals with a reduced ABI but without typical intermittent claudication noted on community screening were invited to undergo baseline and 1-year follow-up assessment, including duplex ultrasound. The initial and repeat evaluations included measurement of the ABI, lower extremity duplex arterial mapping, and assessment of leg pain and functional status. Of the 50 people studied, 44 (88%) had significant atherosclerotic lesions in the lower extremity arteries, affecting 80 legs. A total of 33 of 50 individuals (66%) returned for the 1-year follow-up visit. On ultrasound examination, two of 18 normal legs developed PAD, and in 48 legs with PAD at baseline, 17 legs (35%) developed new or progressive lesions. Thirteen legs developed new claudication. Overall, there was no significant worsening in the ABI, 6-MWD, or the Walking Impairment Questionnaire (WIQ). However, legs with new lesions or lesion progression were significantly more likely to develop claudication, and the 13 legs (seven subjects) developing claudication showed a significant decline in the 6-MWD. In conclusion, these data indicate that a significant number of people with asymptomatic PAD show progression over 1 year, that such individuals are more likely to develop claudication, and that those developing claudication have a significant decrease in their 6-MWD.

Purpose: In this study we assessed the normal common femoral vein (CFV) dimensions and related hemodynamics in a cohort assembled to permit contrasts by means of sex, age, and ethnicity., Methods: The CFV diameter and the flow velocity were analyzed by means of duplex ultrasonography at rest and with a standardized Valsalva maneuver, with the subject in a 15% reverse Trendelenberg position. Mean levels of each of the CFV measurements were analyzed with age category, sex, and ethnicity, each adjusted for the other two. Multiple linear regression was used as a means of assessing the independent associations of age, sex, ethnicity, body mass index (BMI), and height to the CFV measurements., Results: The average CFV diameter at rest was 11.84 mm, increasing to 14.27 mm during the Valsalva maneuver. There was a significant (P <.0001) decline in both diameter measures beginning in patients 60 years old. The CFV diameter was larger in men (12.90 mm) than in women (11.22 mm; P <.0001). The average CFV diameter in Hispanics, Africian Americans, and Asians was significantly smaller (P <.001) than in the non-Hispanic whites in multivarate analysis. The independence of these associations was confirmed by means of multivariate analysis, and positive associations of CFV diameter with height and BMI were documented. The Valsalva response was higher in men than in women (2.67 mm vs 2.29 mm), but the percentage change was similar. CFV velocity at rest decreased significantly (P <.0001) in patients older than 50 years. The mean CFV velocity was 13.87 cm/s, and the values were significantly (P <.0001) higher in women (14.58 cm/s) than in men (12.67 cm/s). In multivariate analysis CFV velocity was higher in African Americans than in the other ethnic groups. We also documented an independent inverse association of CFV with BMI. The CFV velocity response (peak expiration post-Valsalva) increased significantly at all ages, from 52% to 83%. The percentage increase in women (68%) was slightly higher than that in men (58%). African American subjects had a somewhat higher percentage increase (74%) than the other three ethnic groups (63% to 64%). Because the flow rate is determined more by the diameter than the velocity, CFV flow associations were similar to those for diameter. Because an older age predicted both decreased diameter and velocity, the flow reduction with age was pronounced., Conclusion: Quantitative normative data that are age-, sex-, and ethnic group-specific are reported on CFV diameter, velocity, and total flow rate, both at rest and with the Valsalva maneuver. CFV diameter, velocity, and flow rate varied significantly as a function of age, sex, ethnicity, height, and BMI. The data also provide a baseline assessment for subsequent evaluations of changes with time in this cohort.

There is little information on the progression of peripheral arterial disease (PAD) over time. A series of 508 patients with a prior examination for PAD were contacted and brought in for follow-up to evaluate the natural history of PAD. A total of 85 patients were excluded because they had interventions in both limbs prior to their return visit. Progression was assessed in the remaining 423 patients for a total of 755 limbs, both quantitatively and qualitatively using six categories of PAD severity. There was a modest overall categorical progression of disease: 228 limbs (30.2%) displayed categorical progression, while 172 limbs (22.8%) improved over a 4.6-year average follow-up. Through analysis of quantitative change, it was determined that more quantitative progression occurred than was evident from categorical progression. Two of the three non-invasive tests employed, the ankle/brachial index (ABI) and posterior tibial peak forward flow velocity (peak PT), showed statistically significant progression during follow-up: mean ABI change = -0.019, 95% confidence interval (CI)= -0.031 to -0.007; mean peak PT change = -2.32 cm/s, 95% CI = -3.20 to -1.44. The toe/brachial index (TBI) also suggested progression: mean change= -0.013, but the 95% CI included no change. Standard scores (sum of the Z-scores for ABI, peak PT and TBI) were calculated. The standard score progressed approximately 0.34 units (standard deviations), p-value <0.001, over 4.6 years; or about 0.07 standard deviations per year. There were independent and statistically significant (p<0.05) associations between the rate of PAD progression (standard score change) and age, diabetes, classic ('Rose') intermittent claudication, moderate to severe PAD in the same limb, moderate to severe PAD in the contralateral limb and future therapeutic intervention. There were independent and suggestive associations (0.05

Data from the Framingham Study and other population studies indicate that intermittent claudication (IC) sharply increases in late middle age and is somewhat higher among men than women. Noninvasive testing in populations indicates that the true prevalence of peripheral arterial disease (PAD) is at least five times higher than would be expected based on the reported prevalence of IC. Peripheral arterial disease correlates most strongly with cigarette smoking and either diabetes or impaired glucose tolerance. Other risk factors for PAD include hypertension; low levels of high-density lipoprotein cholesterol; and high levels of triglycerides, apolipoprotein B, lipoprotein(a), homocysteine, fibrinogen and blood viscosity. Individuals with PAD are more likely to have coronary heart disease and cerebrovascular disease than those without PAD. Because of the high risk of both nonfatal and fatal cardiovascular disease (CVD) events in PAD patients, individuals with evidence of PAD should undergo both a careful examination of the entire cardiovascular system and aggressive modification of CVD risk factors.

The WHO/Rose questionnaire has served as the epidemiologic and clinical standard in the assessment of leg pain in patients with peripheral arterial disease (PAD) for over three decades. However, the structure of this questionnaire does not allow assessment of leg-specific (i.e. right versus left) symptoms. We studied 508 patients aged 39-95 years (mean 68 years), initially referred for PAD non-invasive testing. A revised questionnaire, the San Diego Claudication Questionnaire, was administered which allowed determination of leg-specific symptoms and evaluated thigh and buttock as well as calf pain. Leg-specific symptoms were categorized into no pain, pain at rest, non-calf claudication, non-Rose calf claudication, and Rose claudication. At the same visit, the ankle brachial index, the toe brachial index, and peak posterior tibial flow velocity were measured by Doppler ultrasound and five categories of non-invasive results by type and severity of PAD were defined. Legs with previous intervention (Rx), surgery or angioplasty, were evaluated separately. Claudication was reported in 42% of no Rx legs and 50% of Rx legs; 40% of claudication was atypical (not Rose); 64% of no Rx and 81% of Rx legs had PAD by non-invasive testing, and 27% of affected legs had severe PAD. The correlation between the severity of symptoms and the severity of ipsilateral PAD in no Rx legs was r = -0.40, p < 0.001. In Rx legs, this correlation was somewhat less (r = 0.27, p < 0.001) due to more symptomatology at lesser degrees of PAD, suggesting reporting bias and/or more residual disease than evident from non-invasive testing. To our knowledge, these results provide the first comparison between a standardized assessment of leg pain and the severity of ipsilateral PAD by non-invasive testing.

In infancy, rats were provided handling stimulation and compared at 110 and 215 days of age with non-handled controls. Measurements were made of corpus callosum area, perimeter and length; and width measures were taken at 7 points along the longitudinal axis of the callosum. Callosal size was larger in males than in females, even when adjusted for the larger brain weight of the male. At 110 days handling stimulation increased callosal parameters and resulted in a more regular callosum in males, but this effect was no longer apparent by 215 days. Within the callosum, region-specific effects were found, suggesting that certain callosal fiber populations were involved. Handled males have previously been shown to be more lateralized than non-handled males; thus at least in this experimental system, increased callosal size and regularity is associated with greater hemispheric specialization.