Globally, approximately one in three of all adults suffer from multiple chronic conditions (MCCs). This review provides a comprehensive overview of the resulting epidemiological, economic and patient burden.There is no agreed taxonomy for MCCs, with several terms used interchangeably and no agreed definition, resulting in up to three-fold variation in prevalence rates: from 16% to 58% in UK studies, 26% in US studies and 9.4% in Urban South Asians.Certain conditions cluster together more frequently than expected, with associations of up to three-fold, e.g. depression associated with stroke and with Alzheimer's disease, and communicable conditions such as TB and HIV/AIDS associated with diabetes and CVD, respectively. Clusters are important as they may be highly amenable to large improvements in health and cost outcomes through relatively simple shifts in healthcare delivery.Healthcare expenditures greatly increase, sometimes exponentially, with each additional chronic condition with greater specialist physician access, emergency department presentations and hospital admissions. The patient burden includes a deterioration of quality of life, out of pocket expenses, medication adherence, inability to work, symptom control and a high toll on carers. This high burden from MCCs is further projected to increase.Recommendations for interventions include reaching consensus on the taxonomy of MCC, greater emphasis on MCCs research, primary prevention to achieve compression of morbidity, a shift of health systems and policies towards a multiple-condition framework, changes in healthcare payment mechanisms to facilitate this change and shifts in health and epidemiological databases to include MCCs.

Many common diseases are accompanied by disturbances in biochemical traits. Identifying the genetic determinants could provide novel insights into disease mechanisms and reveal avenues for developing new therapies. Here, we report a genome-wide association analysis for commonly measured serum and urine biochemical traits. As part of the WTCCC, 500,000 SNPs genome wide were genotyped in 1955 hypertensive individuals characterized for 25 serum and urine biochemical traits. For each trait, we assessed association with individual SNPs, adjusting for age, sex, and BMI. Lipid measurements were further examined in a meta-analysis of genome-wide data from a type 2 diabetes scan. The most promising associations were examined in two epidemiological cohorts. We discovered association between serum urate and SLC2A9, a glucose transporter (p = 2 x 10(-15)) and confirmed this in two independent cohorts, GRAPHIC study (p = 9 x 10(-15)) and TwinsUK (p = 8 x 10(-19)). The odds ratio for hyperuricaemia (defined as urate >0.4 mMol/l) is 1.89 (95% CI = 1.36-2.61) per copy of common allele. We also replicated many genes previously associated with serum lipids and found previously recognized association between LDL levels and SNPs close to genes encoding PSRC1 and CELSR2 (p = 1 x 10(-7)). The common allele was associated with a 6% increase in nonfasting serum LDL. This region showed increased association in the meta-analysis (p = 4 x 10(-14)). This finding provides a potential biological mechanism for the recent association of this same allele of the same SNP with increased risk of coronary disease.

Background and Purpose-The effect of pyrexia on cerebral ischemia has been extensively studied in animals. In humans, however, such studies are small and the results conflicting. We undertook a meta-analysis using all such published studies on the effect of hyperthermia on stroke outcome. Methods-Three databases were searched for all published studies that examined the relationship of raised temperature after stroke onset and eventual outcome. Combined probability values and odds ratios were obtained. A heterogeneity test was performed to ensure that the data were suitable for such an analysis. Morbidity and mortality were used as outcome measures. Results-Nine studies were identified totaling 3790 patients, providing our study with 99% power to detect a 9% increase in morbidity and 84% power to detect a 1% increase in mortality for the pyrexial group. The combined odds ratio for mortality was 1.19 (95% CI, 0.99 to 1.43). A heterogeneity test was highly nonsignificant (PϾ0.05) for mortality, suggesting that the data were sufficiently similar to be meta-analyzed. Combined probability values were highly significant for both morbidity (PϽ0.0001) and mortality (PϽ0.00000001). Conclusions-The results from this meta-analysis suggest that pyrexia after stroke onset is associated with a marked increase in morbidity and mortality. Measures should be taken to combat fever in the clinical setting to prevent stroke progression. The possible benefit of therapeutic hypothermia in the management of acute stroke should be further investigated. Key Words: fever Ⅲ meta-analysis Ⅲ outcome Ⅲ stroke S troke remains one of the leading causes of morbidity and mortality in the western world. Several factors have been implicated in influencing the extent of cerebral damage in acute stroke, such as high or low systolic blood pressure, 1 elevated blood glucose, and a high temperature. 2 Rodent models have consistently shown hyperthermia to be a reliable predictor of stroke outcome. One study found that elevation of rat body temperature to 40°C 24 hours after induced cerebral infarction resulted in a 3-fold increase in cerebral infarct volume. 3 Significant results were also obtained after experimental traumatic injury, with a 2.6-fold increase in rat mortality and a 13-fold increase of cerebral contusion volume. 3 Other studies have found significant effects on stroke outcome in rats with lesser degrees of hyperthermia. 2,4,5 Furthermore, it has been shown that induced hypothermia has a protective effect up to 1 hour after focal permanent ischemia. 6 In humans, however, the relationship between fever and stroke outcome has been far less extensively investigated, with studies incorporating small numbers of patients and, as recently emphasized, 7 providing conflicting results. There are no large-scale prospective studies assessing outcome between normothermic and hyperthermic patients.We sought to undertake a meta-analysis on all published studies to investigate the effect of body temperature on stroke outcome in humans. Combining the resul...