No Association Between MTHFR A1298C and MTRR A66G Polymorphisms, and MS in an Australian Cohort

Multiple sclerosis (MS) is a complex neurological disease that affects the central nervous system (CNS) resulting in debilitating neuropathology. Pathogenesis is primarily defined by CNS inflammation and demyelination of nerve axons. Methionine synthase reductase (MTRR) is an enzyme that catalyzes the remethylation of homocysteine (Hcy) to methionine via cobalamin and folate dependant reactions. Cobalamin acts as an intermediate methyl carrier between methylenetetrahydrofolate reductase (MTHFR) and Hcy. MTRR plays a critical role in maintaining cobalamin in an active form and is consequently an important determinant of total plasma Hcy (pHcy) concentrations. Elevated intracellular pHcy levels have been suggested to play a role in CNS dysfunction, neurodegenerative, and cerebrovascular diseases. Our investigation entailed the genotyping of a cohort of 140 cases and matched controls for MTRR and MTHFR, by restriction length polymorphism (RFLP) techniques. Two polymorphisms: MTRR A66G and MTHFR A1298C were investigated in an Australian age and gender matched case-control study. No significant allelic frequency difference was observed between cases and controls at the α = 0.05 level (MTRR χ^2 = 0.005, P = 0.95, MTHFR χ^2 = 1.15, P = 0.28). Our preliminary findings suggest no association between the MTRR A66G and MTHFR A1298C polymorphisms and MS.

Trends in the incidence, severity, and short-term outcome of stroke in Perth, Western Australia

Background and Purpose-This report describes trends in the key indices of cerebrovascular disease over 6 years from the end of the 1980s in a geographically defined segment of the city of Perth, Western Australia. Methods-Identical methods were used to find and assess all cases of suspected stroke in a population of approximately 134 000 residents in a triangular area of the northern suburbs of Perth. Case fatality was measured as vital status at 28 days after the onset of symptoms. Data for first-ever strokes and for all strokes for equivalent periods of 12 months in 1989-1990 and 1995-1996 were compared by age-standardized rates and proportions and Poisson regression. Results-There were 355 strokes in 328 patients and 251 first-ever strokes (71%) for 1989-1990 and 290 events in 281 patients and 213 first-ever strokes (73%) for 1995-1996. In Poisson models including age and period, overall trends in the incidence of both first-ever strokes (rate ratio = 0.75; 95% confidence limits, 0.63, 0.90) and all strokes (rate ratio = 0.73; 95% confidence limits, 0.62, 0.85) were obviously significant, but only the changes in men were independently significant. Case fatality did not change, and the balance between hemorrhagic and occlusive strokes in 1995-1996 was almost indistinguishable from that observed in 1989-1990. Conclusions-Our results, which are the only longitudinal population-based data available for Australia for key indices of stroke, suggest that it is a change in the frequency of stroke, rather than its outcome, that is chiefly responsible nationally for the fall in mortality from cerebrovascular disease.

Mortality variation across Australia: descriptive data for States and Territories, and statistical divisions

OBJECTIVE: To describe variation in all cause and selected cause-specific mortality rates across Australia. METHODS: Mortality and population data for 1997 were obtained from the Australian Bureau of Statistics. All cause and selected cause-specific mortality rates were calculated and directly standardised to the 1997 Australian population in 5-year age groups. Selected major causes of death included cancer, coronary artery disease, cerebrovascular disease, diabetes, accidents and suicide. Rates are reported by statistical division, and State and Territory. RESULTS: All cause age-standardised mortality was 6.98 per 1000 in 1997 and this varied 2-fold from a low in the statistical division of Pilbara, Western Australia (5.78, 95% confidence interval 5.06-6.56), to a high in Northern Territory-excluding Darwin (11.30, 10.67-11.98). Similar mortality variation (all p<0.0001) exists for cancer (1.01-2.23 per 1000) and coronary artery disease (0.99-2.23 per 1000), the two biggest killers. Larger variation (all p<0.0001) exists for cerebrovascular disease (0.7-11.8 per 10,000), diabetes (0.7-6.9 per 10,000), accidents (1.7-7.2 per 10,000) and suicide (0.6-3.8 per 10,000). Less marked variation was observed when analysed by State and Territory. but Northern Territory consistently has the highest age-standardised mortality rates. CONCLUSIONS: Analysed by statistical division, substantial mortality gradients exist across Australia, suggesting an inequitable distribution of the determinants of health. Further research is required to better understand this heterogeneity.

Long-term disability after first-ever stroke and related prognostic factors in the Perth Community Stroke Study, 1989-1990

Background and Purpose-Few reliable estimates of the long-term functional outcome after stroke are available. This population-based study aimed to describe disability, dependency, and related independent prognostic factors at 5 years after,a first-ever stroke in patients in Perth, Western Australia. Methods-All individuals with a suspected acute stroke who were resident in a geographically defined region (population, 138 708) of Perth, Western Australia, were registered prospectively and assessed according to standardized diagnostic criteria over a period of 18 months in 1989 to 1990. Patients were followed up prospectively at 4 and 12 months and 5 years after the index event. Results-There were 370 cases of first-ever stroke, and 277 patients survived to 30 days. Of these early survivors, 152 (55%) were alive at 5 years, and among those who were neither institutionalized (n=146) nor disabled (n=129) at the time of their stroke, 21 (14%) were institutionalized in a nursing home, and 47 (36%) were disabled. The most important predictors of death or disability at 5 years were increasing age, baseline disability defined by a Barthel Index score of <20/20 (odds ratio [OR], 6.3; 95% confidence interval [CI], 2.7 to 14), moderate hemiparesis (OR, 2.7. 95% CI, 1.1 to 6.2), severe hemiparesis (OR, 4.5; 95% CI, 1.1 to 19), and recurrent stroke (OR, 9.4; 95% CI, 3.0 to 30). A low level of activity before the stroke was a significant predictor of institutionalization, and subsequent recurrent stroke was a consistent, independent predictor of institutionalization, disability, and death or institutionalization, increasing the odds of each of these 3 adverse outcomes by 5- to 15-fold. Conclusions-Among 30-day survivors of first-ever stroke, about half survive 5 years; of survivors, one third remain disabled, and I in 7 are in permanent institutional care. The major modifiable predictors of poor long-term outcome are a low level of activity before the stroke and subsequent recurrent stroke. Efforts to increase physical activity among the elderly and to prevent recurrent stroke in survivors of a first stroke are likely to reduce the long-term burden of cerebrovascular disease.

Ten-year risk of first recurrent stroke and disability after first-ever stroke in the Perth Community Stroke Study

Background and Purpose-Limited information exists on the long-term prognosis after first-ever stroke. We aimed to determine the absolute frequency of first recurrent stroke and disability and the relative frequency of recurrent stroke over 10 years after first-ever stroke in Perth, Western Australia. Methods-For a 12-month period beginning February 1989, all individuals with suspected acute stroke or transient ischemic attack who lived in a geographically defined and representative region of Perth were registered prospectively. Patients with a definite first-ever stroke were followed up 10 years after the index event. Results-Over 10 years of follow-up, the cumulative risk of a first recurrent stroke was 43% (95% confidence interval [CI], 34 to 51). After the first year after first-ever stroke, the average annual risk of recurrent stroke was approximate to4%. Case fatality at 30 days after first recurrent stroke was 41%, which was significantly greater than the case fatality at 30 days after first-ever stroke (22%) (P=0.003). For 30-day survivors of first-ever stroke, the 10-year cumulative risk of death or new institutionalization was 79% (95% CI, 73 to 85) and of death or new disability was 87% (95% CI, 81 to 92). Conclusions-Over 10 years of follow-up, the risk of first recurrent stroke is 6 times greater than the risk of first-ever stroke in the general population of the same age and sex, almost one half of survivors remain disabled, and one seventh require institutional care. Effective strategies for prevention of stroke need to be implemented early, monitored frequently, and maintained long term after first-ever stroke.

Role of smoking in global and regional cardiovascular mortality

Background - Smoking is a major cause of cardiovascular disease mortality. There is little information on how it contributes to global and regional cause-specific mortality from cardiovascular diseases for which background risk varies because of other risks. Method and Results - We used data from the American Cancer Society's Cancer Prevention Study II (CPS II) and the World Health Organization Global Burden of Disease mortality database to estimate smoking-attributable deaths from ischemic heart disease, cerebrovascular disease, and a cluster of other cardiovascular diseases for 14 epidemiological subregions of the world by age and sex. We used lung cancer mortality as an indirect marker for accumulated smoking hazard. CPS-II hazards were adjusted for important covariates. In the year 2000, an estimated 1.62 (95% CI, 1.27 to 2.04) million cardiovascular deaths in the world, 11% of total global cardiovascular deaths, were due to smoking. Of these, 1.17 million deaths were among men and 450 000 among women. There were 670 000 (95% CI, 440 000 to 920 000) smoking-attributable cardiovascular deaths in the developing world and 960 000 (95% CI, 770 000 to 1 200 000) in industrialized regions. Ischemic heart disease accounted for 54% of smoking-attributable cardiovascular mortality, followed by cerebrovascular disease (25%). There was variability across regions in the role of smoking as a cause of various cardiovascular diseases. Conclusions - More than 1 in every 10 cardiovascular deaths in the world in the year 2000 were attributable to smoking, demonstrating that it is an important preventable cause of cardiovascular mortality.

Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data

Background Our aim was to calculate the global burden of disease and risk factors for 2001, to examine regional trends from 1990 to 2001, and to provide a starting point for the analysis of the Disease Control Priorities Project (DCPP). Methods We calculated mortality, incidence, prevalence, and disability adjusted life years (DALYs) for 136 diseases and injuries, for seven income/geographic country groups. To assess trends, we re-estimated all-cause mortality for 1990 with the same methods as for 2001. We estimated mortality and disease burden attributable to 19 risk factors. Findings About 56 million people died in 2001. Of these, 10.6 million were children, 99% of whom lived in low-and-middle-income countries. More than half of child deaths in 2001 were attributable to acute respiratory infections, measles, diarrhoea, malaria, and HIV/AIDS. The ten leading diseases for global disease burden were perinatal conditions, lower respiratory infections, ischaemic heart disease, cerebrovascular disease, HIV/AIDS, diarrhoeal diseases, unipolar major depression, malaria, chronic obstructive pulmonary disease, and tuberculosis. There was a 20% reduction in global disease burden per head due to communicable, maternal, perinatal, and nutritional conditions between 1990 and 2001. Almost half the disease burden in low-and-middle-income countries is now from non-communicable diseases (disease burden per head in Sub-Saharan Africa and the low-and-middle-income countries of Europe and Central Asia increased between 1990 and 2001). Undernutrition remains the leading risk factor for health loss. An estimated 45% of global mortality and 36% of global disease burden are attributable to the joint hazardous effects of the 19 risk factors studied. Uncertainty in all-cause mortality estimates ranged from around 1% in high-income countries to 15-20% in Sub-Saharan Africa. Uncertainty was larger for mortality from specific diseases, and for incidence and prevalence of non-fatal outcomes. Interpretation Despite uncertainties about mortality and burden of disease estimates, our findings suggest that substantial gains in health have been achieved in most populations, countered by the HIV/AIDS epidemic in Sub-Saharan Africa and setbacks in adult mortality in countries of the former Soviet Union. our results on major disease, injury, and risk factor causes of loss of health, together with information on the cost-effectiveness of interventions, can assist in accelerating progress towards better health and reducing the persistent differentials in health between poor and rich countries.

Validation of the Action Research Arm Test using item response theory in patients after stroke

Objective: To validate the unidimensionality of the Action Research Arm Test (ARAT) using Mokken analysis and to examine whether scores of the ARAT can be transformed into interval scores using Rasch analysis. Subjects and methods: A total of 351 patients with stroke were recruited from 5 rehabilitation departments located in 4 regions of Taiwan. The 19-item ARAT was administered to all the subjects by a physical therapist. The data were analysed using item response theory by non-parametric Mokken analysis followed by Rasch analysis. Results: The results supported a unidimensional scale of the 19-item ARAT by Mokken analysis, with the scalability coefficient H = 0.95. Except for the item pinch ball bearing 3rd finger and thumb'', the remaining 18 items have a consistently hierarchical order along the upper extremity function's continuum. In contrast, the Rasch analysis, with a stepwise deletion of misfit items, showed that only 4 items (grasp ball'', grasp block 5 cm(3)'', grasp block 2.5 cm(3)'', and grip tube 1 cm(3)'') fit the Rasch rating scale model's expectations. Conclusion: Our findings indicated that the 19-item ARAT constituted a unidimensional construct measuring upper extremity function in stroke patients. However, the results did not support the premise that the raw sum scores of the ARAT can be transformed into interval Rasch scores. Thus, the raw sum scores of the ARAT can provide information only about order of patients on their upper extremity functional abilities, but not represent each patient's exact functioning.

Validity of verbal autopsy procedures for determining cause of death in Tanzania

Objectives: To validate verbal autopsy (VA) procedures for use in sample vital registration. Verbal autopsy is an important method for deriving cause-specific mortality estimates where disease burdens are greatest and routine cause-specific mortality data do not exist. Methods: Verbal autopsies and medical records (MR) were collected for 3123 deaths in the perinatal/neonatal period, post-neonatal < 5 age group, and for ages of 5 years and over in Tanzania. Causes of death were assigned by physician panels using the International Classification of Disease, revision 10. Validity was measured by: cause-specific mortality fractions (CSMF); sensitivity; specificity and positive predictive value. Medical record diagnoses were scored for degree of uncertainty, and sensitivity and specificity adjusted. Criteria for evaluating VA performance in generating true proportional mortality were applied. Results: Verbal autopsy produced accurate CSMFs for nine causes in different age groups: birth asphyxia; intrauterine complications; pneumonia; HIV/AIDS; malaria (adults); tuberculosis; cerebrovascular diseases; injuries and direct maternal causes. Results for 20 other causes approached the threshold for good performance. Conclusions: Verbal autopsy reliably estimated CSMFs for diseases of public health importance in all age groups. Further validation is needed to assess reasons for lack of positive results for some conditions.

Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: The health, aging, and body composition study

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68-80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index < 0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [ORintegral] = 1.34, 95% confidence interval [CI] 1.10-1.63; ORtrabecular = 1.25, 95% CI 1.02-1.53; ORcortical = 1.36, 95% CI 1.11-1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03-1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-alpha). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.

Circadian blood pressure variation after acute stroke

We aimed to characterise the patterns of circadian blood pressure (BP) variation after acute stroke and determine whether any relationship exists between these patterns and stroke outcome. BP was recorded manually every 4 h for 48 h following acute stroke. Patients were classified according to the percentage fall in mean systolic BP (SBP) at night compared to during the day as: dippers (fall >= 10-= 20%); non-dippers (>= 0-