Reliability of anthropometric measurements in overweight and lean subjects: consequences for correlations between anthropometric and other variables

OBJECTIVE: To estimate the reliability of anthropometric measurements in overweight and lean subjects, and to examine the influence of this reliability on correlations to other variables, since low reliability leads to underestimation of correlations. DESIGN: Replicate measurements by two observers in 26 overweight and 25 lean subjects measured at two occasions. MEASUREMENTS: Sagittal abdominal diameter (SAD), waist circumference (waist), waist-to-hip ratio (W/H) and skinfold measurements. RESULTS: Intra-class correlation coefficients (ICCs) for SAD and waist were higher than for W/H (0.98 vs. 0.90, P<0.001, and 0.97 vs. 0.90, P = 0.001, respectively). For waist, the ICC was lower for overweight than for lean subjects (0.85 vs 0.95, P=0.030), but the ICC values were comparable for SAD and W/H (0.92 vs. 0.95 and 0.78 vs. 0.83, respectively). Intra-observer variations (IOV) for SAD and waist were lower than for W/H (coefficients of variation; 1.6%, 1.4% and 2.3%, respectively), as were intra-subject variations (ISV) (2.7%, 3.0% and 3.4%, respectively). ICC values ranged from 0.84 to 0.93 and were lower for overweight than for lean subjects for biceps, subscapular and umbilical skinfolds (P=0.031, P<0.001 and P=0.048, respectively). Coefficients of variations for skinfold measurements ranged between 7.3% and 16.0% for IOV and between 14.9% and 20.8% for ISV. CONCLUSIONS: The low ICC values imply that correlations can be underestimated in overweight groups. We propose that, because of their higher reliability, SAD and waist have a higher predictive capacity for cardiovascular risk than W/H. SAD is the only measurement with high reliability in both weight groups and its use is recommended.     

Low and high circulating cortisol levels predict mortality and cognitive dysfunction early after stroke

OBJECTIVE: Elevated cortisol levels are associated with confusion and poor outcome after stroke. Dehydroepiandrosterone sulphate (DS), the most abundant adrenal androgen may act as an anti-glucocorticoid. An altered regulation of these steroids may affect numerous brain functions, including neuronal survival. The purpose of this study was to investigate serum cortisol and DS levels and the cortisol/DS ratio early after stroke and relate our findings to the presence of disorientation and mortality. DESIGN: Patients with acute ischaemic stroke (n = 88, 56 men and 32 women) admitted to a stroke unit were investigated with repeated clinical assessments and scores for degree of confusion, extent of paresis and level of functioning. Serum cortisol (C) and DS were measured on day 1 and/or day 4. Data for 28-day and 1-year mortality are presented. A control group of 65 age-matched healthy individuals was used. Multivariate analyses of mortality rates in the different tertiles or sixtiles of serum cortisol were performed with logistic regression, adjusting for age, sex, diabetes and level of consciousness. RESULTS: There was no difference in serum cortisol levels on day 1 for stroke patients when compared with control group values. Initial cortisol levels were significantly higher in the patients with acute disorientation versus orientated patients (P < 0.05). Cortisol levels on day 1 were an independent predictor of 28-day mortality, and patients with low cortisol levels (<270 nmol L(-1)) and increased levels (>550 nmol L(-1)) both had an increased 1-year mortality. DS levels on day 1 were significantly elevated in stroke patients. CONCLUSION: Hypercortisolism is associated with cognitive dysfunction early after ischaemic stroke. High and low circulating cortisol levels are associated with increased mortality after stroke. DS levels were not associated with clinical outcome.     

Exposure–response for biomarkers of anticoagulant effects by the oral direct thrombin inhibitor AZD0837 in patients with atrial fibrillation

AimsAZD0837 is a novel oral anticoagulant investigated in clinical studies for stroke prevention in patients with atrial fibrillation (AF). It is bioconverted to its active form, AR‐H067637, a potent, specific and reversible thrombin inhibitor. The effects on coagulation biomarkers were correlated with the pharmacokinetic (PK) exposure of AR‐H067637 to guide selection of the effective dose regimen for a confirmatory efficacy study in AF patients.MethodsBlood samples were obtained from 601 AF patients randomized to one of four doses of AZD0837 (blinded treatment) or dose‐adjusted vitamin K antagonists (VKA, open treatment) for 3–9 months. A pharmacodynamic model was developed to describe the time course of the AR‐H067637 exposure dependent effects and the effect of VKA on fibrin D‐dimer. The thrombin generation measured ex vivo in venous plasma was also investigated.ResultsThe PK exposure of AR‐H067637 was stable with an interindividual variability of 33% and no or minor influence of patient demographics or comedications. For AZD0837, D‐dimer levels decreased with more rapid onset than for VKA. The decrease in D‐dimer levels correlated with steady‐state plasma concentrations (C _ss) of AR‐H067637, with a maximum decrease of baseline D‐dimer levels estimated to approximately 60% for both AZD0837 and VKA therapy. The effect on thrombin generation correlated closely with the plasma concentration of AR‐H067637.ConclusionsThe effects on thrombin generation and fibrin D‐dimer levels correlated with the plasma concentration of its active form and provided comparable effects to well‐controlled VKA therapy at an exposure at least corresponding to the 300 mg once daily dose of AZD0837.     

Estimation of drug receptor occupancy when non-displaceable binding differs between brain regions – extending the simplified reference tissue model

AimThe simplified reference tissue model (SRTM) is used for estimation of receptor occupancy assuming that the non-displaceable binding in the reference region is identical to the brain regions of interest. The aim of this work was to extend the SRTM to also account for inter-regional differences in non-displaceable concentrations, and to investigate if this model allowed estimation of receptor occupancy using white matter as reference. It was also investigated if an apparent higher affinity in caudate compared with other brain regions, could be better explained by a difference in the extent of non-displaceable binding.MethodsThe analysis was based on a PET study in six healthy volunteers using the 5-HT_1B receptor radioligand [¹¹C]-AZ10419369. The radioligand was given intravenously as a tracer dose alone and following different oral doses of the 5-HT_1B receptor antagonist AZD3783. Non-linear mixed effects models were developed where differences between regions in non-specific concentrations were accounted for. The properties of the models were also evaluated by means of simulation studies.ResultsThe estimate (95% CI) of Ki_PL was 10.2 ng ml⁻¹ (5.4, 15) and 10.4 ng ml⁻¹ (8.1, 13.6) based on the extended SRTM with white matter as reference and based on the SRTM using cerebellum as reference, respectively. The estimate (95% CI) of Ki_PL for caudate relative to other brain regions was 55% (48, 62%).ConclusionsThe extended SRTM allows consideration of white matter as reference region when no suitable grey matter region exists. AZD3783 affinity appears to be higher in the caudate compared with other brain regions.     

Enduring inequality: educational disparities in health among the oldest old in Sweden 1992–2011

Objectives

Although the past two decades have involved changes in the living conditions of the oldest old in Sweden, little is known about how health inequalities have developed in this group during the period. This study explores the educational disparities in a wide range of health outcomes among the oldest old in Sweden between 1992 and 2011.

Methods

The study uses the repeated cross-sectional design of the SWEOLD survey, a nationally representative survey of the oldest old in Sweden with comparable data from 1992, 2002, and 2011. The development of educational disparities in health was tracked across the three waves.

Results

The results show that although the prevalence of most health problems increased during the period, the prevalence of disability in activities of daily living decreased. Despite these changes, educational disparities in health remained largely unaffected.

Conclusions

The results of the study suggest that the association between education and health is remarkably robust. It prevailed into the oldest age groups, was consistently found for a wide range of health problems, and tended to be stable over extended periods of time.

     

Stimulatory effect on DNA synthesis of thymus and spleen extract from leukemic AKR mice

Summary A 30,000–50,000 molecular weight (MW) extract of thymus and spleen from 11 age groups of untreated AKR mice, 1–210 days old, was tested for in vitro effect on thymide incorporation into normal AKR lymph node cells, normal spleen cells, and leukemic thymocytes. Extracts from mice up to 5 months of age mostly had slightly inhibitory effect but concomitant with emergence of thymus leukemia in the 6-month-old mice, the extract acquired a strongly mitogenic effect on normal lymph node cells. Seven-month-old, non-leukemic animals again yielded extracts with inhibitory effect.Supported by the US Health Education and Welfare grant no. IROI CA 26109-01, Commission of the European Communities contract no. 251-77-1 BIO DK, and The Carlsberg Foundation     

Forty-six patients with primary sclerosing cholangitis: radiological bile duct changes in relationship to clinical course and concomitant inflammatory bowel disease

The clinical features of primary sclerosing cholangitis were studied in 46 consecutive patients. Jaundice was the most common symptom (57%), followed by pruritus (28%), pain (24%), and fever (15%). Thirty-three per cent of the patients had no symptoms, merely laboratory changes. No significant relationship was observed between a numerical score of radiological bile duct changes at diagnosis and the clinical picture, or the clinical course during follow-up. If clinical deterioration occurred, this seemed to happen within the first eight years after the clinical presentation. Patients with only intra-hepatic bile duct changes (n = 10) did not differ clinically from those with extrahepatic changes as well. Forty-three out of 44 patients examined had inflammatory bowel disease, usually ulcerative colitis, with total colitis in 84%. Radiological bile duct changes had a significantly higher score in patients who had to be treated with a combination of sulfasalazine and steroids, suggesting a weak relationship between severity of bowel disease and bile duct disease.