Estimates of global and regional potential health gains from reducing multiple major risk factors

Background Estimates of the disease burden due to multiple risk factors can show the potential gain from combined preventive measures. But few such investigations have been attempted, and none on a global scale. Our aim was to estimate the potential health benefits from removal of multiple major risk factors. Methods We assessed the burden of disease and injury attributable to the joint effects of 20 selected leading risk factors in 14 epidemiological subregions of the world. We estimated population attributable fractions, defined as the proportional reduction in disease or mortality that would occur if exposure to a risk factor were reduced to an alternative level, from data for risk factor prevalence and hazard size. For every disease, we estimated joint population attributable fractions, for multiple risk factors, by age and sex, from the direct contributions of individual risk factors. To obtain the direct hazards, we reviewed publications and re-analysed cohort data to account for that part of hazard that is mediated through other risks. Results Globally, an estimated 47% of premature deaths and 39% of total disease burden in 2000 resulted from the joint effects of the risk factors considered. These risks caused a substantial proportion of important diseases, including diarrhoea (92%-94%), lower respiratory infections (55-62%), lung cancer (72%), chronic obstructive pulmonary disease (60%), ischaemic heart disease (83-89%), and stroke (70-76%). Removal of these risks would have increased global healthy life expectancy by 9.3 years (17%) ranging from 4.4 years (6%) in the developed countries of the western Pacific to 16.1 years (43%) in parts of sub-Saharan Africa. Interpretation Removal of major risk factors would not only increase healthy life expectancy in every region, but also reduce some of the differences between regions, The potential for disease prevention and health gain from tackling major known risks simultaneously would be substantial.

Factors associated with the wish to hasten death: a study of patients with terminal illness

Background. There is considerable debate regarding the clinical issues surrounding the wish to hasten death (WTHD) in the terminally ill. The clinical factors contributing to the WTHD need further investigation among the terminally ill in order to enhance understanding of the clinical assessment and treatment needs that underlie this problem. A more detailed understanding may assist with the development of appropriate therapeutic interventions. Method. A sample of terminally ill cancer patients (N=256) recruited from an in-patient hospice unit, home palliative care service and a general hospital palliative care consulting service from Brisbane Australia between 1998-2001 completed a questionnaire assessing psychological (depression and anxiety), social (family relationship, social support, level of burden on others) and the impact of physical symptoms. The association between these factors and the WTHD was investigated. Results. A high WTHD was reported by 14% of patients. A discriminant function analysis revealed that the following variables were associated with a high WTHD (P

Factors to consider in Micronesian food-based interventions: a case study of preventing Vitamin A deficiency

Background: Many factors need to be considered in a food-based intervention. Vitamin A deficiency and chronic diseases, such as diabetes, heart disease and cancer, have become serious problems in the Federated States of Micronesia (FSM) following the decreased production and consumption of locally grown foods. However, agricultural and social conditions are still favourable for local food production. Aim: To identify key factors to consider in a Micronesian food-based intervention focusing on increased production and consumption of four major Micronesian staple foods: banana, breadfruit, giant swamp taro and pandanus. Methods: Ethnographic methods including key informant interviews and a literature review. Results: Pacific and Micronesian values, concepts of food and disease, and food classifications differ sharply from Western concepts. There are few FSM professionals with nutrition expertise. Traditional foods and food cultivars vary in nutrient content, consumption level, cost, availability, status, convenience in growing, storing and cooking, and organoleptic factors. Conclusions: A systematic consideration of the factors that relate to a food-based intervention is critical to its success. The evaluation of which food and cultivar of that food that might be most effectively promoted is also critical. Regional differences, for example FSM inter-island differences between the staple foods and cultivars, must be considered carefully. The evaluation framework presented here may be relevant to Pacific island and other countries with similar foods where food-based interventions are being planned. An ethnographic approach was found to be essential in understanding the cultural context and in data collection and analysis.

Carotid intima-media thickness, cardiovascular risk factors and albuminuria in a remote Australian Aboriginal community

Background: Rates of cardiovascular disease and renal disease in Australian Aboriginal communities are high, as is the prevalence of some 'traditional' cardiovascular (CV) risk factors, such as diabetes and cigarette smoking. Recent work has highlighted the importance of markers of inflammation, such as C-reactive protein (CRP), homocysteine and albuminuria as predictors of cardiovascular risk in urban westernised settings. It is not clear how these factors relate to outcome in the setting of these remote communities, but very high CRP concentrations have been shown in this and other Aboriginal communities. Methods and results: In a cross-sectional survey including 237 adults in a remote Aboriginal community in the Northern Territory of Australia, we measured carotid intima-media thickness (IMT), together with blood pressure, diabetes, lipid levels, smoking and albuminuria, CRP and fibrinogen, serum homocysteine concentration, and IgG titres for Chlamydia pneumoniae, Helicobacter pylori and cytomegalovirus. Median carotid IMT was 0.63 [interquartile range 0.54-0.71] mm. As a categorical outcome, the prevalence of the highest IMT quartile ('increased IMT', greater than or equal to0.72 mm) was compared with the lower three quartiles. Increased IMT was associated in univariate analyses with greater waist circumference, systolic BP, fibrinogen and serum albumin concentrations, urine albumin/creatinine ratio and older age as continuous variables. Associations of increased IMT with some continuous variables were not linear; univariate associations were seen with the highest quartile (versus all other quartiles) of CRP and homocysteine concentration and CMV IgG titre. In a multivariate model age, smoking, waist circumference and the highest quartile of CRP concentrations (greater than or equal to14 mg/l) remained significant predictors of IMT greater than or equal to0.72 mm. Conclusions: Measurement of carotid IMT was possible in this remote setting. Increased IMT (greater than or equal to0.72 mm) was associated with increased CRP concentrations over a range that suggests infection/inflammation may be important determinants of cardiovascular risk in this setting. The associations of IMT with markers of renal disease seen in univariate analyses were explained in this analysis by confounding due to the associations of urine ACR with other risk factors. (C) 2004 Published by Elsevier Ireland Ltd.

Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors

Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk. Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk. Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47 % (95 % CI 28-55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0 % (95 % CI 0-14) to shared environmental factors, and 53 % (95 % CI 45-63) to non-shared environmental influences. Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD.

Do risk factors for lactic acidosis influence dosing of metformin?

Background: Metformin is commonly prescribed to treat type 2 diabetes mellitus, however it is associated with the potentially lethal condition of lactic acidosis. Prescribing guidelines have been developed to minimize the risk of lactic acidosis development, although some suggest they are inappropriate and have created confusion amongst prescribers. The aim of this study was to investigate whether metformin dose was influenced by the presence of risk factors for lactic acidosis. Methods: The study was prospective, and retrieved information from patients admitted to hospital who were prescribed metformin at their time of admission. Results: Eighty-three patients were included in the study, 60 of whom had a least one risk factor for lactic acidosis. Of those 60 patients, 78.3% had a dose adjustment, with renal impairment, hepatic impairment, surgery and use of radiological contrast media - the risk factors most likely to result in a dose adjustment. When dose adjustments did occur, metformin was withheld on 88.7% of occasions. Conclusion: Metformin dose was influenced by the presence of risk factors for lactic acidosis, although it was dependent upon the number and particular risk factor/s present.

Medication management at home: medication-related risk factors associated with poor health outcomes

Background: some patients may have medication-related risk factors only identified by home visits, but the extent to which those risk factors are associated with poor health outcomes remains unclear. Objective: to determine the association between medication-related risk factors and poor patient health outcomes from observations in the patients' homes. Design: cross-sectional study. Setting: patients' homes. Subjects: 204 general practice patients living in their own homes and at risk of medication-related poor health outcomes. Methods: medications and medication-related risk factors were identified in the patients' homes by community pharmacists and general practitioners (GPs). The medication-related risk factors were examined as determinants of patients' self-reported health related quality of life (SF-36) and their medication use, as well as physicians' impression of patient adverse drug events and health status. Results: key medication-related risk factors associated with poor health outcomes included: Lack of any medication administration routine, therapeutic duplication, hoarding, confusion between generic and trade names, multiple prescribers, discontinued medication repeats retained and multiple storage locations. Older age and female gender were associated with some poorer health outcomes. In addition, expired medication and poor adherence were also associated with poor health outcomes, however, not independently. Conclusion: the findings support the theory that polypharmacy and medication-related risk factors as a result of polypharmacy are correlated to poor health outcomes.

Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region - An overview of 26 cohorts involving 306,620 participants

Background and Purpose - The cause of subarachnoid hemorrhage ( SAH) is poorly understood and there are few large cohort studies of risk factors for SAH. We investigated the risk of SAH mortality and morbidity associated with common cardiovascular risk factors in the Asia-Pacific region and examined whether the strengths of these associations were different in Asian and Australasian ( predominantly white) populations. Methods - Cohort studies were identified from Internet electronic databases, searches of proceedings of meetings, and personal communication. Hazard ratios (HRs) for systolic blood pressure (SBP), current smoking, total serum cholesterol, body mass index (BMI), and alcohol drinking were calculated from Cox models that were stratified by sex and cohort and adjusted for age at risk. Results - Individual participant data from 26 prospective cohort studies ( total number of participants 306 620) that reported incident cases of SAH ( fatal and/or nonfatal) were available for analysis. During the median follow-up period of 8.2 years, a total of 236 incident cases of SAH were observed. Current smoking (HR, 2.4; 95% CI, 1.8 to 3.4) and SBP > 140 mm Hg ( HR, 2.0; 95% CI, 1.5 to 2.7) were significant and independent risk factors for SAH. Attributable risks of SAH associated with current smoking and elevated SBP ( similar to 140 mm Hg) were 29% and 19%, respectively. There were no significant associations between the risk of SAH and cholesterol, BMI, or drinking alcohol. The strength of the associations of the common cardiovascular risk factors with the risk of SAH did not differ much between Asian and Australasian regions. Conclusions - Cigarette smoking and SBP are the most important risk factors for SAH in the Asia-Pacific region.

Carotid artery intimal medial thickness, brachial artery flow-mediated vasodilation and cardiovascular risk factors in diabetic and non-diabetic indigenous Australians

Background: Indigenous Australians are at high risk for cardiovascular disease and type 2 diabetes. Carotid artery intimal medial thickness (CIMT) and brachial artery flow-mediated vasodilation (FMD) are ultrasound imaging based surrogate markers of cardiovascular risk. This study examines the relative contributions of traditional cardiovascular risk factors on CIMT and FMD in adult Indigenous Australians with and without type 2 diabetes mellitus. Method: One hundred and nineteen Indigenous Australians were recruited. Physical and biochemical markers of cardiovascular risk, together with CIMT and FMD were meausred for all subjects. Results: Fifty-three Indigenous Australians subjects (45%) had type 2 diabetes mellitus. There was a significantly greater mean CIMT in diabetic versus non-diabetic subjects (p = 0.049). In the non-diabetic group with non-parametric analyses, there were significant correlations between CIMT and: age (r = 0.64, p < 0.001), systolic blood pressure (r = 0.47, p < 0.001) and non-smokers (r = -0.30, p = 0.018). In the diabetic group, non-parametric analysis showed correlations between CIMT, age (r = 0.36, p = 0.009) and duration of diabetes (r = 0.30, p = 0.035) only. Adjusting forage, sex, smoking and history of cardiovascular disease, Hb(A1c) became the sole significant correlate of CIMT (r = 0.35,p = 0.01) in the diabetic group. In non-parametric analysis, age was the sole significant correlate of FMD (r = -0.31,p = 0.013), and only in non-diabetic subjects. Linear regression analysis showed significant associations between CIMT and age (t = 4.6,p < 0.001), systolic blood pressure (t = 2.6, p = 0.010) and Hb(A1c) (t = 2.6, p = 0.012), smoking (t = 2.1, p = 0.04) and fasting LDL-cholesterol (t = 2.1, p = 0.04). There were no significant associations between FMD and examined cardiovascular risk factors with linear regression analysis Conclusions: CIMT appears to be a useful surrogate marker of cardiovascular risk in this sample of Indigenous Australian subjects, correlating better than FMD with established cardiovascular risk factors. A lifestyle intervention programme may alleviate the burden of cardiovascular disease in Indigenous Australians by reducing central obesity, lowering blood pressure, correcting dyslipidaemia and improving glycaemic control. CIMT may prove to be a useful tool to assess efficacy of such an intervention programme. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Factors predictive of intravenous fluid administration errors in Australian surgical care wards

Background: Intravenous (IV) fluid administration is an integral component of clinical care. Errors in administration can cause detrimental patient outcomes and increase healthcare costs, although little is known about medication administration errors associated with continuous IV infusions. Objectives: ( 1) To ascertain the prevalence of medication administration errors for continuous IV infusions and identify the variables that caused them. ( 2) To quantify the probability of errors by fitting a logistic regression model to the data. Methods: A prospective study was conducted on three surgical wards at a teaching hospital in Australia. All study participants received continuous infusions of IV fluids. Parenteral nutrition and non-electrolyte containing intermittent drug infusions ( such as antibiotics) were excluded. Medication administration errors and contributing variables were documented using a direct observational approach. Results: Six hundred and eighty seven observations were made, with 124 (18.0%) having at least one medication administration error. The most common error observed was wrong administration rate. The median deviation from the prescribed rate was 247 ml/h (interquartile range 275 to + 33.8 ml/ h). Errors were more likely to occur if an IV infusion control device was not used and as the duration of the infusion increased. Conclusions: Administration errors involving continuous IV infusions occur frequently. They could be reduced by more common use of IV infusion control devices and regular checking of administration rates.

Re-admission to intensive care: Identification of risk factors

Background and Purpose. The re-admission of patients to intensive care is associated with increased morbidity, mortality, loss of morale for patients and family, and increased health costs. The aim of the present study was to identify factors which place patients at a higher risk of re-admission to intensive care. Method. A prospective study of patients who were re-admitted to a 22-bed tertiary level intensive care facility within a 12-month period. Data were kept on every patient re-admitted to intensive care, including standard demographic data, initial admission diagnosis, co-morbidities, re-admission diagnosis, mobility on discharge, secretions, airway, chest X-ray, PaCO2, PaO2, PaO2/FiO2and time of discharge. Subjects included 74 patients who had been re-admitted to intensive care in a 12-month period and a comparison group of patients who were not re-admitted to intensive care. A cross-tabs procedure was initially used to estimate maximum likelihood. Significant factors with an value of 65 years (p

Cardiovascular disease and PPARdelta: Targeting the risk factors

Metabolism, in part, is regulated by the peroxisome proliferator-activated receptors (PPARs). The PPARs act as nutritional lipid sensors and three mammalian PPAR subtypes designated PPARalpha (NR1C1), PPARgamma (NR1C3) and PPARdelta (NR1C2) have been identified. This subgroup of nuclear hormone receptors binds DNA and controls gene expression at the nexus of pathways that regulate lipid and glucose homeostasis, energy storage and expenditure in an organ-specific manner. Recent evidence has demonstrated activation of PPARdelta in the major mass peripheral tissue (ie, adipose and skeletal muscle). It enhances glucose tolerance, insulin-stimulated glucose disposal, lipid catabolism, energy expenditure, cholesterol efflux and oxygen consumption. These effects positively influence the blood-lipid profile. Furthermore, PPARdelta activation produces a predominant type I/slow twitch/oxidative muscle fiber phenotype that leads to increased endurance, insulin sensitivity and resistance to obesity. PPARdelta has rapidly emerged as a potential target in the battle against dyslipidemia, insulin insensitivity, type II diabetes and obesity, with therapeutic efficacy in the treatment of cardiovascular disease risk factors. GW-501516 is currently undergoing phase II safety and efficacy trials in human volunteers for the treatment of dyslipidemia. The outcome of these clinical trials are eagerly awaited against a background of conflicting reports about cancer risks in genetically predisposed animal models. This review focuses on the potential pharmacological utility of selective PPARdelta agonists in the context of risk factors associated with metabolic and cardiovascular disease.

Environmental factors that influence the community participation of adults with aphasia: The perspective of service industry workers

Background: The loss of language and the inability to communicate effectively as a result of aphasia often affects community participation. Within the World Health Organisation International Classification of Functioning, Disability and Health, disability is recognised as a dynamic interaction between the individual's health condition, such as aphasia, and his or her personal and environmental factors. There has been little research identifying the environmental facilitators and barriers to participation for people with aphasia in the community, and no research focusing on the perspective of service industry workers. Aims: This study aimed to identify barriers and facilitators to community participation for adults with aphasia from the perspective of service industry workers. Methods & Procedures: Eight focus groups were conducted with 24 service industry employees. Transcripts of the focus group discussions were analysed using qualitative content analysis procedures, and barriers to and facilitators for participation of people with aphasia were identified. Outcomes & Results: Results revealed that the participation of people with aphasia in the community can be affected by many environmental factors within three broad categories: (1) people environmental factors, (2) physical environmental factors, and (3) business or organisational environmental factors. Conclusions: Service industry employees were able to identify a range of factors that would act as barriers and facilitators for people with aphasia. Some of the more significant findings include the lack of other people's awareness about aphasia, the willingness of service industry workers at the individual level to accommodate people with aphasia, and the difficulty in making the necessary system, policy, and procedural changes at the organisational level. Speech pathologists are encouraged to assist service industry providers to be more aphasia-friendly through education and training, in addition to assisting people with aphasia to become self-advocates.

Genes for the majority of group A streptococcal virulence factors and extracellular surface proteins do not confer an increased propensity to cause invasive disease

Background. The factors behind the reemergence of severe, invasive group A streptococcal (GAS) diseases are unclear, but it could be caused by altered genetic endowment in these organisms. However, data from previous studies assessing the association between single genetic factors and invasive disease are often conflicting, suggesting that other, as-yet unidentified factors are necessary for the development of this class of disease. Methods. In this study, we used a targeted GAS virulence microarray containing 226 GAS genes to determine the virulence gene repertoires of 68 GAS isolates (42 associated with invasive disease and 28 associated with noninvasive disease) collected in a defined geographic location during a contiguous time period. We then employed 3 advanced machine learning methods (genetic algorithm neural network, support vector machines, and classification trees) to identify genes with an increased association with invasive disease. Results. Virulence gene profiles of individual GAS isolates varied extensively among these geographically and temporally related strains. Using genetic algorithm neural network analysis, we identified 3 genes with a marginal overrepresentation in invasive disease isolates. Significantly, 2 of these genes, ssa and mf4, encoded superantigens but were only present in a restricted set of GAS M-types. The third gene, spa, was found in variable distributions in all M-types in the study. Conclusions. Our comprehensive analysis of GAS virulence profiles provides strong evidence for the incongruent relationships among any of the 226 genes represented on the array and the overall propensity of GAS to cause invasive disease, underscoring the pathogenic complexity of these diseases, as well as the importance of multiple bacteria and/ or host factors.

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.