Stress-related health depreciation: Using allostatic load to predict self-rated health.

Approximately one quarter of UK adults are currently diagnosed with two or more chronic conditions, often referred to as multimorbidity. Chronic stress has been implicated in the development of many diseases common to multimorbidity. Policymakers and clinicians have acknowledged the need for more preventative approaches to deal with the rise of multimorbidity and "early ageing". However divergence may occur between an individual's self-rated health and objectively measured health that may preclude preventative action. The use of biomarkers which look 'under the skin' provide crucial information on an individual's underlying health to facilitate lifestyle change or healthcare utilisation. The UK's Understanding Society dataset, was used to examine whether baseline variation in biomarkers measuring stress-related "wear and tear" - Allostatic Load (AL) - predict changes in future self-rated health (SRH) while adjusting for baseline SRH, socioeconomic and lifestyle factors, and healthcare inputs. An interaction between baseline AL and baseline SRH was included to test for differential rates of SRH change. We examined SRH using the SF6D instrument, measuring health-related-quality of life (HRQoL), as well as its physical and mental health components separately. We found that HRQoL and physical health decline faster for those with higher baseline AL (indicating greater "wear and tear") however the same pattern was not observed for mental health. These findings provide novel insights for clinicians and policymakers on the usefulness of AL in capturing health trajectories of which individual's may not be aware and its importance in targeting resilience enhancing measures earlier in the lifecourse to delay physical health decline.

The cost of systemic corticosteroid-induced morbidity in severe asthma: a health economic analysis.

BACKGROUND: Treatment of severe asthma may include high dose systemic-steroid therapy which is associated with substantial additional morbidity. This study estimates the additional healthcare costs associated with steroid-induced morbidity by comparing three patients groups: those with severe asthma, moderate asthma and no asthma. METHODS: Patients with severe asthma (n = 808, GINA step 5 treatment) were matched by age and gender with patients with mild/moderate asthma (n = 3,975, GINA step 2 and 3 treatment) and a non-asthma control cohort (with a diagnosis of rhinitis; n = 2,412) from the Optimum Patient Care Research Database (OPCRD), a nationally representative primary care database. Prescribed drugs and publicly funded healthcare activity were monetised and annual costs per patient estimated. Regression analyses were used to estimate the additional healthcare cost associated with steroid-induced morbidity. RESULTS: Average healthcare costs per person per year range from £2603 - £4533 for the severe asthma cohort, to £978 - £2072 for the mild/moderate asthma cohort, to £560 - £1324 for the non-asthma control cohort, depending on the costing scenario. Differences in induced morbidity costs were evident between patients with asthma differentiated by steroid exposure. In relation to prescription drugs used to treat steroid-induced co-morbidities, females with severe asthma and high steroid exposure cost approximately £789 more per year than a corresponding female with no asthma, while males cost approximately £744 more than their counterparts with no asthma. Estimates were extrapolated to all healthcare costs. CONCLUSIONS: This study provides the first robust estimates of the additional cost of healthcare related to steroid-induced morbidity relative to patients with no steroid exposure. The study will help inform use of steroid-sparing strategies in this patient group.

Changes in the composition of plasma lipoproteins in the chronic uremic rat.

The effect of chronic renal failure on the lipid and apolipoprotein concentrations of plasma, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) was studied in an experimental uremic rat model. Control rats were sham-operated and were divided into adlibitum-fed and pair-fed groups. The rats were studied (after an overnight fast) 32 days after the onset of uremia. The uremic rats had a 4-fold increase in plasma urea nitrogen and creatinine. The pair-fed and ad-lib-fed controls had similar levels of plasma urea nitrogen and lipid profiles. In the uremic rats, plasma triglyceride (TG) levels were increased 3.8-fold due to increased TG in the VLDL, IDL and HDL fractions. Their 2-3-fold increase in plasma free cholesterol (FC), esterified cholesterol (EC) and phospholipids (PL) were due to FC, EC and PL increases in VLDL, IDL, LDL and HDL. Their increase in plasma apo B (x 2.4) and apo E (x 1.5) were due to increases in VLDL, IDL and LDL. Their plasma apo A-I increased 2.4 fold due to increases in the LDL and HDL fractions. Uremic rats also had increases in the FC/PL molar ratio in VLDL, IDL and LDL. In their LDL, the apo B/total cholesterol (TC), apo B/PL and apo B/apo E molar ratios were decreased. In their HDL, the apo E/TC and apo E/PL molar ratios were decreased and the apo A-I/apo E molar ratio was increased. In conclusion, chronic uremia causes both quantitative changes in the levels and qualitative changes in the composition of the plasma lipoprotein particles. These results are compatible with the decreased hepatic lipase activities and impairment of remnant clearance observed in human chronic renal failure.