Socioeconomic status and determinants of hemostatic function in healthy women

Hemostatic factors are reported to be associated with coronary heart disease (CHD). Socioeconomic status (SES) is 1 of the determinants of the hemostatic profile, but the factors underlying this association are not well known. Our aim was to examine determinants of the socioeconomic differences in hemostatic profile. Between 1991 and 1994, we studied 300 healthy women, aged 30 to 65 years, who were representative of women living in the greater Stockholm area. Fibrinogen, factor VII mass concentration (FVII:Ag), activated factor VII (FVIIa), von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1) were measured. Educational attainment was used as a measure of SES. Low educational level and an unfavorable hemostatic profile were both associated with older age, unhealthful life style, psychosocial stress, atherogenic biochemical factors, and hypertension. Levels of hemostatic factors increased with lower educational attainment. Independently of age, the differences between the lowest (mandatory) and highest (college/university) education in FVII:Ag levels were 41 microg/L (95% confidence interval [CI], 15 to 66 microg/L, P=0.001), 0.26 g/L (95% CI, 0.10 to 0.42 g/L, P=0.001) in fibrinogen levels, and 0.11 U/mL (95% CI, 0.09 to 0.12 U/mL, P=0.03) in levels of vWF. The corresponding differences in FVIIa and PAI-1 were not statistically significant. With further adjustment for menopausal status, family history of CHD, marital status, psychosocial stress, lifestyle patterns, biochemical factors, and hypertension, statistically significant differences between mandatory and college/university education were observed in FVII:Ag (difference=34 microg/L; 95% CI, 2 to 65 microg/L, P=0.05) but not in fibrinogen (difference=0.03 g/L; 95% CI, -0.13 to 0.19 g/L, P=0.92) or in vWF (difference=0.06 U/mL; 95% CI, -0.10 to 0.22 U/mL, P=0.45). An educational gradient was most consistent and statistically significant for FVII:Ag, fibrinogen, and vWF. Age, psychosocial stress, unhealthful life style, atherogenic biochemical factors, and hypertension mediated the association of low educational level with elevated levels of fibrinogen and vWF. Psychosocial stress and unhealthful life style were the most important contributing factors. There was an independent association between education and FVII:Ag, which could not be explained by any of these factors.     

The 100-plus Study of cognitively healthy centenarians: rationale,design and cohort description

Although the incidence of dementia increases exponentially with age, some individuals reach more than?100 years with fully retained cognitive abilities. To identify the characteristics associated with the escape or delay of cognitive decline, we initiated the 100-plus Study (www.100plus.nl). The 100-plus Study is an on-going prospective cohort study of Dutch centenarians who self-reported to be cognitively healthy, their first-degree family members and their respective partners. We collect demographics, life history, medical history, genealogy, neuropsychological data and blood samples. Centenarians are followed annually until death. PET–MRI scans and feces donation are optional. Almost 30% of the centenarians agreed to post-mortem brain donation. To date (September 2018), 332 centenarians were included in the study. We analyzed demographic statistics of the first 300 centenarians (25% males) included in the cohort. Centenarians came from higher socio-economic classes and had higher levels of education compared to their birth cohort; alcohol consumption of centenarians was similar, and most males smoked during their lifetime. At baseline, the centenarians had a median MMSE score of 25 points (IQR 22.0–27.5); most centenarians lived independently, retained hearing and vision abilities and were independently mobile. Mortality was associated with cognitive functioning: centenarians with a baseline MMSE score?≥?26 points had a mortality percentage of 17% per annual year  in the second year after baseline, while centenarians with a baseline MMSE score < 26 points had a mortality of  42% per annual year (p?=?0.003). The cohort was 2.1-fold enriched with the neuroprotective APOE-ε2 allele relative to 60–80 year-old population controls (p?=?4.8?×?10^?7), APOE-ε3 was unchanged and the APOE-ε4 allele was 2.3-fold depleted (p?=?6.3?×?10^?7). Comprehensive characterization of the 100-plus cohort of cognitively healthy centenarians might reveal protective factors that explain the physiology of long-term preserved cognitive health.     

PATIENT SATISFACTION WITH RIZATRIPTAN VERSUS OTHER TRIPTANS: DIRECT HEAD-TO-HEAD COMPARISONS

This study summarises the impact of treatment with rizatriptan 10 mg versus other 5-HT_1B/1D receptor agonists (triptans) on patient satisfaction with medication. Rizatriptan is a potent, selective 5-HT_1B/1D receptor agonist shown to be fast, effective and well tolerated in the acute treatment of migraine. We investigated patients' overall satisfaction with treatment in studies in which direct comparisons with other triptans were made. Data from five double-blind, placebo-controlled trials in which rizatriptan 10 mg was compared with another triptan were included in the analysis. Rizatriptan 10 mg was compared with sumatriptan 100 mg in one parallel study (n=916), sumatriptan 50 mg in two crossover studies (n=1599), naratriptan 2.5 mg in one parallel study (n=502), and zolmitriptan 2.5 mg in one parallel study (n=701). Satisfaction was reported by patients on a seven-point scale ranging from ‘completely satisfied, couldn't be better’ to ‘completely dissatisfied, couldn't be worse’ at 2 hours after dosing. The percent of patients in the top two ‘satisfied’ categories (completely or very satisfied) were analysed. More patients on rizatriptan 10 mg were completely or very satisfied compared with sumatriptan 100 mg (33% vs 26%, p<0.05), sumatriptan 50 mg (40% vs 35%, p<0.05), naratriptan 2.5 mg (33% vs 19%, p<0.01), and zolmitriptan 2.5 mg (38% vs 30%, p<0.05). In all five studies more patients treated with rizatriptan 10 mg or other triptans were completely or very satisfied with treatment than patients receiving placebo (p<0.001, except naratriptan vs placebo p=0.004). The results, combined with the superior efficacy profile (fast, effective, well tolerated) of rizatriptan 10 mg, should enhance the treatment of migraine headache and lead to improved therapeutic intervention in clinical practice.     

A numerical-experimental method to characterize the non-linear mechanical behaviour of human skin

Background/aims: Human skin is a complex tissue consisting of several distinct layers. Each layer consists of various components with a specific structure. To gain a better insight into the overall mechanical behaviour of the skin, we wish to study the mechanical properties of the different layers. A numerical-experimental method was developed to characterize the non-linear mechanical behaviour of human dermis.
Methods: Suction measurements at varying pressures were performed on the volar forearm skin of 10 subjects aged 19–24 years old. Deformation of dermis and fat during suction was measured using ultrasound. The experiment was simulated by a finite element model exhibiting extended Mooney material behaviour to account for the non-linear stress–strain relationship. An identification method is used to compare the experimental and numerical results to identify the parameters of the material model.
Results: C _{10, dermis} was found to be 9.4 ± 3.6 kPa and C _{11, dermis} to be 82 ± 60 kPa. A first rough estimate of C _{10, fat} was 0.02 kPa.
Conclusions: The resulting finite element model demonstrated its ability to describe the response of the skin to suction at various pressures. In the future, this method can be used to characterize the mechanical behaviour of different skin layers using various aperture sizes and to characterize the skin behaviour under various loading conditions.     

Harmonizing units and values of quantitative data elements in a very large nationally pooled electronic health record (EHR) dataset

ObjectiveThe goals of this study were to harmonize data from electronic health records (EHRs) into common units, and impute units that were missing.Materials and MethodsThe National COVID Cohort Collaborative (N3C) table of laboratory measurement data—over 3.1 billion patient records and over 19 000 unique measurement concepts in the Observational Medical Outcomes Partnership (OMOP) common-data-model format from 55 data partners. We grouped ontologically similar OMOP concepts together for 52 variables relevant to COVID-19 research, and developed a unit-harmonization pipeline comprised of (1) selecting a canonical unit for each measurement variable, (2) arriving at a formula for conversion, (3) obtaining clinical review of each formula, (4) applying the formula to convert data values in each unit into the target canonical unit, and (5) removing any harmonized value that fell outside of accepted value ranges for the variable. For data with missing units for all the results within a lab test for a data partner, we compared values with pooled values of all data partners, using the Kolmogorov-Smirnov test.ResultsOf the concepts without missing values, we harmonized 88.1% of the values, and imputed units for 78.2% of records where units were absent (41% of contributors’ records lacked units).DiscussionThe harmonization and inference methods developed herein can serve as a resource for initiatives aiming to extract insight from heterogeneous EHR collections. Unique properties of centralized data are harnessed to enable unit inference.ConclusionThe pipeline we developed for the pooled N3C data enables use of measurements that would otherwise be unavailable for analysis.     

Eczema Coxsackium Caused by Coxsackievirus A6

We present the first case of atypical hand, food, and mouth disease in our department with the distinct cutaneous morphology of eczema coxsackium. Clinicians should be aware of the possibility for more extensive cutaneous eruption related to coxsackievirus A6 infection and the diagnostic methods required to determine the diagnosis.     

Job stress and the occupational gradient in coronary heart disease risk in women. The Stockholm Female Coronary Risk Study

Recent studies of men have shown that job stress is important in understanding the occupational gradient in coronary heart disease (CHD), but these relationships have rarely been studied in women. With increasing numbers of women in the workforce it is important to have a more complete understanding of how CHD risk may be mediated by job stress as well as other biological and behavioural risk factors. The objective of this study was to examine the occupational gradient in CHD risk in relation to job stress and other traditional risk factors in currently employed women. We used data from the Stockholm Female Coronary Risk Study, a population based case-control study, comprising 292 women with CHD aged 65 years or younger and 292 age-matched healthy women (controls). An inversely graded association was observed between occupational class and CHD risk. Compared with the highest (executive/professional), women in the lowest occupational class (semi/unskilled) had a four-fold (95% CI 1.75-8.83) increased age-adjusted risk for CHD. Simultaneous adjustment for traditional risk factors and job stress attenuated this risk to 2.45 (95% CI 1.01-6.14). Neither job control nor the Karasek demand-control model of job stress substantially explained the increased CHD risk of women in the lowest occupational classes. It is likely that lower occupational class working women face multiple and sometimes interacting sources of work and non-work stress that are mediated by behavioural and biological factors that increase their CHD risk.