Rheumatoid arthritis and incident fracture in women: a case-control study

Background:
To examine fracture incidence in women with rheumatoid arthritis (RA) for an entire geographical region of south-eastern Australia.

Methods:
Women aged 35 years and older, resident in the Barwon Statistical Division (BSD) and clinically diagnosed with RA 1994–2001 were eligible for inclusion as cases (n =1,008). The control population (n = 172,422) comprised the entire female BSD population aged 35 years and older, excluding those individuals identified as cases. Incident fractures were extracted from the prospective Geelong Osteoporosis Study Fracture Grid. We calculated rate ratios (RR) and 95% confidence intervals (CI) to compare the age- adjusted rate of fracture between the RA and non-RA populations, and used a chi-square test to compare proportions of fractures between women with and without RA, and a two-sided Mann–Whitney U-test to examine age-differences.

Results:
Among 1,008 women with RA, 19 (1.9%) sustained a fracture, compared to 1,981 fractures sustained by the 172,422 women without RA (1.2%). Fracture rates showed a trend for being greater among women diagnosed with RA (age-adjusted RR 1.43, 95%CI 0.98-2.09, p= 0.08). Women with RA sustained vertebral fractures at twice the expected frequency, whereas hip fractures were underrepresented in the RA population (p< 0.001). RA status was not associated with the likelihood of sustaining a fracture at sites adjacent to joints most commonly affected by RA (p= 0.22).

Conclusion:
Given that women with RA have a greater risk of fracture compared to women without RA, these patients may be a suitable target population for anti-resorptive agents; however, larger studies are warranted.

Arsenic, mode of action at biologically plausible low doses : what are the implications for low dose cancer risk?

Arsenic is an established human carcinogen. However, there has been much controversy about the shape of the arsenic response curve, particularly at low doses. This controversy has been exacerbated by the fact that the  mechanism(s) of arsenic carcinogenesis are still unclear and because there are few satisfactory animal models for arsenic-induced carcinogenesis. Recent epidemiological studies have shown that the relative risk for cancer among populations exposed to ≤60 ppb As in their drinking water is often lower than the risk for the unexposed control population. We have found that treatment of human keratinocyte and fibroblast cells with 0.1 to 1 μM arsenite (As^III) also produces a low dose protective effect against oxidative stress and DNA damage. This response includes increased transcription, protein levels and enzyme activity of several base excision repair genes, including DNA polymerase β and DNA ligase I. At higher concentrations (> 10 μM), As induces down-regulation of DNA repair, oxidative DNA damage and apoptosis. This low dose adaptive (protective) response by a toxic agent is known as hormesis and is characteristic of many agents that induce oxidative stress. A mechanistic model for arsenic carcinogenesis based on these data would predict that the low dose risk for carcinogenesis should be sub-linear. The threshold dose where toxicity outweighs protection is hard to predict based on in vitro dose response data, but might be estimated if one could determine the form (metabolite) and concentration of arsenic responsible for changes in gene regulation in the target tissues.

The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion

Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndrome—disorders known to contribute to both arterial and venous thrombosis. In both of these conditions and RVO, platelet activation occurs. Aspirin, not warfarin, is the most effective antithrombotic agent in RVO and, taken together, these observations suggest an important role for platelets in this common ocular thrombotic condition. Platelet glycoprotein Ia/IIa (GpIa/IIa) is an adhesion molecule mediating platelet–collagen interactions and is key to the initiation of thrombosis. Recently, the cellular density of this molecule was shown to be determined by two silent, linked polymorphisms (C807T/G873A) within the GpIa/IIa gene. There is evidence that some of the resulting genotypes are associated with thrombo-embolic disease. This study therefore aimed to establish the prevalence of the GpIa/IIa polymorphisms and the three commonest hereditary thrombophilic disorders (prothrombin gene G20210A (PT) mutation, Factor V Leiden (FVL), and the thermolabile methylene tetrahydrofolate reductase C677T (MTHFR) mutation) in patients with RVO and normal controls. The GpIa/IIa polymorphisms and thrombophilic abnormalities were all identified using the polymerase chain reaction.

Our results show that the frequency of the GpIa/IIa polymorphisms was similar in our normal control population to previously published series. Patients with RVO, however, had only a 10% (4/40) frequency of the lowest risk subtype (CC/GG) compared to 37.5% (15/40) in the control group—P 0.0039. The incidence of the PT, FVL, and MTHFR thrombophilic mutations was not different between the two groups, but interestingly none of the 7/40 RVO cases with a PT, FVL, or MTHFR mutation had the low-risk GpIa/IIa genotype while all but one of the controls did—P<0.05. Thus, 17.5% of RVO patients harboured more than one prothrombotic abnormality. The principal difference between the RVO and control group was the very high incidence of the intermediate-risk GpIa/IIa subtype (CT/GA)—82.5 vs 50%, P<0.05.

These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.

IEF pattern classification-derived criteria for the identification of epoetin-delta in urine

Epoetin-δ (Dynepo™ Shire Pharmaceuticals, Basing stoke, UK) is a synthetic form of erythropoietin (EPO) whose resemblance with endogenous EPO makes it hard to identify using the classical identification criteria. Urine samples collected from six healthy volunteers treated with epoetin-δ injections and from a control population were immuno-purified and analyzed with the usual IEF method. On the basis of the EPO profiles integration, a linear multivariate model was computed for discriminant analysis. For each sample, a pattern classification algorithm returned a bands distribution and intensity score (bands intensity score) saying how representative this sample is of one of the two classes, positive or negative. Effort profiles were also integrated in the model. The method yielded a good sensitivity versus specificity relation and was used to determine the detection window of the molecule following multiple injections. The bands intensity score, which can be generalized to epoetin-α and epoetin-β, is proposed as an alternative criterion and a supplementary evidence for the identification of EPO abuse.

The projected impact of population and high-risk strategies for risk-factor control on coronary heart disease and stroke events

Objective: To model the impact of both population and high-risk strategies on cardiovascular disease (CVD) outcomes.

Design, setting and participants: A CVD risk-factor survey was carried out in rural south-eastern Australia from 2004 to 2006. Using a stratified random sample, data for 1116 participants aged 35–74 years were analysed. Applying the Framingham risk equations to risk-factor data, 5-year probabilities of a coronary heart disease event, stroke and cardiovascular event were calculated. The effect of different changes in risk factors were modelled to assess the extent to which cardiovascular diseases can be prevented by changing the risk factors at a population level (population strategy), among the high-risk individuals (high-risk strategy) or both.

Results: Among men, a population strategy could reduce cardiovascular events by 19.3% (193 per 1000 per 5 years), the high-risk strategy by 12.6% (126 per 1000) and a combined strategy by 24.1% (241 per 1000); and among women, by 21.9% (219 per 1000), 19.0% (190 per 1000) and 28.7% (287 per 1000), respectively.

Conclusions: For prevention of CVD in Australia, it is important both to treat high-risk individuals and to reduce the mean risk-factor levels in the population. We show how risk-factor survey data can be used to set targets for prevention and to monitor progress in line with the recommendations of the National Preventative Health Taskforce.

Low control and high demands at work as risk factors for suicide: An Australian national population-level case-control study

OBJECTIVES: Previous research suggests that psychosocial job stressors may be plausible risk factors for suicide. This study assessed the relationship between psychosocial job stressors and suicide mortality across the Australian population. METHODS: We developed a job exposure matrix to objectively measure job stressors across the working population. Suicide data came from a nationwide coronial register. Living controls were selected from a nationally representative cohort study. Incidence density sampling was used to ensure that controls were sampled at the time of death of each case. The period of observation for both cases and controls was 2001 to 2012. We used multilevel logistic regression to assess the odds of suicide in relation to 2 psychosocial job stressors (job control and job demands), after matching for age, sex, and year of death/survey and adjusting for socioeconomic status. RESULTS: Across 9,010 cases and 14,007 matched controls, our results suggest that low job control (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.26-1.44; p < .001) and high job demands (OR, 1.36; 95% CI, 1.26-1.46; p < .001) were associated with increased odds of male suicide after adjusting for socioeconomic status. High demands were associated with lower odds of female suicide (OR, 0.81; 95% CI, 0.72-0.92; p = .002). CONCLUSIONS: It seems that adverse experiences at work are a risk factor for male suicide while not being associated with an elevated risk among females. Future studies on job stressors and suicide are needed, both to further understand the biobehavioral mechanisms explaining the link between job stress and suicide, and to inform targeted prevention initiatives.

Population based intervention to change back pain beliefs and disability : three part evaluation

Objective To evaluate the effectiveness of a population based, state-wide public health intervention designed to alter beliefs about back pain, influence medical management, and reduce disability and costs of compensation. Design Quasi-experimental, non-randomised, non-equivalent, before and after telephone surveys of the general population and postal surveys of general practitioners with an adjacent state as control group and descriptive analysis of claims database. Setting Two states in Australia Participants 4730 members of general population before and two and two and a half years after campaign started, in a ratio of2:1:1; 2556 general practitioners before and two years after campaign onset. Main outcome measures Back beliefs questionnaire, knowledge and attitude statements about back pain, incidence of workers' financial compensation claims for back problems, rate of days compensated, and medical payments for claims related to back pain and other claims. Results In the intervention state beliefs about back pain became more positive between successive surveys (mean improvement in questionnaire score 1.9 (95% confidence interval 1.3 to 2.5), P<0.001 and 3.2 (2.6 to 3.9), P < 0.001, between baseline and the second and third survey, respectively). Beliefs about back pain also improved among doctors. There was a clear decline in number of claims for back pain, rates of days compensated, and medical payments for claims for back pain over the duration of the campaign. Conclusions A population based strategy of provision of positive messages about back pain improves population and general practitioner beliefs about back pain and seems to influence medical management and reduce disability and workers' compensation costs related to back pain.

Mortality rates, prevalence of malnutrition, and prevalence of lost pregnancies among the drought-ravaged population of Tete province Mozambique

Background: Tete Province, Mozambique has experienced chronic food insecurity and a dramatic fall in livestock numbers due to the cyclic problems characterized by the floods in 2000 and severe droughts in 2002 and 2003. The Province has been a beneficiary of emergency relief programs, which have assisted >22% of the population. However, these programs were not based on sound epidemiological data, and they have not established baseline data against which to assess the impact of the programs. Objective: The objective of this study was to document mortality rates, causes of death, the prevalence of malnutrition, and the prevalence of lost pregnancies after 2.5 years of humanitarian response to the crisis. Methods: A two-stage, 30-cluster household survey was conducted in the Cahora Bassa and Changara districts from 22 October to 08 November 2004. A total of 838 households were surveyed, with a population size of 4,688 people. Results: Anthropometric data were collected among children 6-59 months of age. In addition, crude mortality rates (CMRs), under five mortality rates (U5MRs), causes of deaths, and prevalence of lost pregnancies were determined among the sample population. The prevalence of malnutrition was 8.0% (95% confidence interval (CI)=6.2-9.8%) for acute malnutrition, 26.9% (95% CI=24.0-29.9%) for being underweight, and 37.0% (95% CI=33.8-40.2%) for chronic malnutrition. Boys were more likely to be underweight than were girls (odds ratio (OR)=1.34; 95% CI=1.00, 1.82; p<0.05) after controlling for age, household size, and food aid beneficiary status. Similarly, children 30-59 months of age were significantly less likely to suffer from acute malnutrition (OR=0.45; 95% CI=0.26, 0.79; p<0.01) and less likely to be underweight (OR=0.37; 95% CI=0.27, 0.51; p<0.01) than children 6-29 months of age, after adjusting for the other, aforementioned factors. The proportion of lost pregnancies was estimated at 7.7% (95% CI=4.5-11.0%). A total of 215 deaths were reported during the year preceding the survey. Thirty-nine (18.1%) children <5 years of age died. The CMR was 1.23/10 000/day (95% CI=1.08-1.38), and an U5MR was 1.03/10 000/day (95% CI=0.71-1.35). Diarrheal diseases, malaria, tuberculosis, and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) accounted for more than two-thirds of all deaths. Conclusions: The observed CMR in Tete Province, Mozambique is three times higher than the baseline rate for sub-Saharan Africa and 1.4 times higher than the CMR cut-off point used to define excess mortality in emergencies. The current humanitarian response in Tete Province would benefit from an improved alignment of food aid programming in conjunction with diarrheal disease control, HIV/AIDS, and malaria prevention and treatment programs. The impact of the food programs would be improved if mutually acceptable food aid programme objectives, verifiable indicators relevant to each objective, and beneficiary targets and selection criteria are developed. Periodic re-assessments and evaluations of the impact of the program and evidenced-based decision-making urgently are needed to avert a chronic dependency on food aid.

Population-Based Randomized Controlled Trial of a Stage-Targeted Physical Activity Intervention

BACKGROUND: Intervention trials with self-selected participants have shown that mailed stage-targeted print materials can increase participation in physical activity in the short term. We examined the effects of a mailed stage-targeted print intervention designed to promote physical activity, in a random sample of adults living in a regional city.

METHOD: Participants (n = 462, 40-60 years of age) were randomly allocated to an intervention (n = 227) or control group (n = 235). Measures included validated 2-week physical activity recall and stage of motivational readiness for physical activity. The intervention consisted of a single mailing of a letter and full-color stage-targeted booklets (specific to precontemplation, contemplation, preparation, and action/maintenance) 1 week postbaseline. Follow-up interviews were conducted at 2 and 6 months postbaseline.

RESULTS: After 2 months, participants in the intervention group were significantly more likely to meet the current American College of Sports Medicine/Centers for Disease Control and Prevention recommendation for sufficient physical activity than those in the control group (adjusted odds ratio [OR] = 2.40; 95% confidence interval [CI] = 1.44-3.99). After 6 months, intervention participants who reported receiving and reading the intervention materials were significantly more likely to be meeting the sufficient physical activity criterion compared with the control group (adjusted OR = 2.03; 95% CI = 1.16-3.56).

CONCLUSIONS: The stage-targeted print intervention was effective in promoting short-term increases in physical activity and was most effective for participants who recognized and used the materials. This low-cost, generalizable intervention has demonstrated potential as a practical population-based physical activity promotion strategy. Further research is required before widespread dissemination would be justified, as additional strategies may be required to ensure sustained change.

Checks and cheques : implementing a population health and recall system to improve coverage of patients with diabetes in a rural general practice

Identification of all diabetic patients in the population is essential if diabetic care is to be effective in achieving the targets of the St Vincent Declaration.¹ The challenge therefore is to establish population based monitoring and control systems by means of state of the art technology in order to achieve quality assurance in the provision of care for patients with diabetes. ^2,3 Disease management receives extensive international support as the most appropriate approach to organising and delivering healthcare for chronic conditions like diabetes.⁴ This approach is achieved through a combination of guidelines for practice, patient education, consultations and follow up using a planned team approach and a strong focus on continuous quality improvement using information technology. ^5,6 The current software (Medical Director) could not easily meet these requirements which led us to adopt a trial of Ferret. In designing this project we used change management⁷ and the plan, do, study, act cycle⁸ illustrated in Diagram 1.

Phytophthora cinnamomi and Australia’s biodiversity : impacts, predictions and progress towards control

Phytophthora cinnamomi continues to cause devastating disease in Australian native vegetation and consequently the disease is listed by the Federal Government as a process that is threatening Australia’s biodiversity. Although several advances have been made in our understanding of how this soil-borne pathogen interacts with plants and of how we may tackle it in natural systems, our ability to control the disease is limited. The pathogen occurs widely across Australia but the severity of its impact is most evident within ecological communities of the south-west and south-east of the country. A regional impact summary for all states and territories shows the pathogen to be the cause of serious disease in numerous species, a significant number of which are rare and threatened. Many genera of endemic taxa have a high proportion of susceptible species including the iconic genera Banksia, Epacris and Xanthorrhoea. Long-term studies in Victoria have shown limited but probably unsustainable recovery of susceptible vegetation, given current management practices. Management of the disease in conservation reserves is reliant on hygiene, the use of chemicals and restriction of access, and has had only limited effectiveness and not provided complete control. The deleterious impacts of the disease on faunal habitat are reasonably well documented and demonstrate loss of individual animal species and changes in population structure and species abundance. Few plant species are known to be resistant to P. cinnamomi; however, investigations over several years have discovered the mechanisms by which some plants are able to survive infection, including the activation of defence-related genes and signalling pathways, the reinforcement of cell walls and accumulation of toxic metabolites. Manipulation of resistance and resistance-related mechanisms may provide avenues for protection against disease in otherwise susceptible species. Despite the advances made in Phytophthora research in Australia during the past 40 years, there is still much to be done to give land managers the resources to combat this disease. Recent State and Federal initiatives offer the prospect of a growing and broader awareness of the disease and its associated impacts. However, awareness must be translated into action as time is running out for the large number of susceptible, and potentially susceptible, species within vulnerable Australian ecological communities.

Prevalence, detection and drug treatment of hypertension in a rural Australian population : the Greater Green Triangle Risk Factor Study 2004

Background: Hypertension is an important risk factor for cardiovascular disease; however, limited findings are available on its detection and management in rural Australia.

Aim: To assess the prevalence, awareness and treatment of hypertension in a rural South-East Australian population.

Methods: Three cross-sectional surveys in Limestone Coast, Corangamite Shire and Wimmera regions during 2004–2006 using a random population sample (n = 3320, participation rate 49%) aged 25–74 years. Blood pressure was measured by trained nurses. Information on history of hypertension and medication was obtained by questionnaires. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg and/or on antihypertensive drug treatment.

Results: Overall, one-third of participants had hypertension; of these, two-thirds, 54% (95% confidence interval (CI) 47–60) of men and 71% (95% CI 65–77) of women, were aware of their condition. Half of the participants with hypertension were treated and nearly half of these were controlled. Both treatment and control were more common in women (60%, 95% CI 54–67 and 55%, 95% CI 47–64) compared with men (42%, 95% CI 36–49 and 35%, 95% CI 26–44). Monotherapy was used by 55% (95% CI 48–61) of treated hypertensives. Angiotensin-converting enzyme inhibitors were the most frequently used class of antihypertensive drugs in men, whereas angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists and diuretics were all widely used among women.

Conclusion: This study emphasizes suboptimal detection and treatment of hypertension, especially in men, in rural Australia.

A tangled tale of two teal : population history of the grey Anas gracilis and chestnut teal A. castanea of Australia

Two Australian species of teal (Anseriformes: Anatidae: Anas), the grey teal Anas gracilis and the chestnut teal A. castanea, are remarkable for the zero or near-zero divergence recorded between them in earlier surveys of mitochondrial DNA (mtDNA) diversity. We confirmed this result through wider geographical and population sampling as well as nucleotide sampling in the more rapidly evolving mtDNA control region. Any data set where two species share polymorphism as is the case here can be explained by a model of gene flow through hybridization on one hand or by incomplete lineage sorting on the other hand. Ideally, analysis of such shared polymorphism would simultaneously estimate the likelihood of both phenomena. To do this, we used the underlying principle of the IMa package to explore ramifications to understanding population histories of A. gracilis and A. castanea. We cannot reject that hybridization occurs between the two species but an equally or more plausible finding for their nearly zero divergence is incomplete sorting following very recent divergence between the two, probably in the mid-late Pleistocene. Our data add to studies that explore intermediate stages in the evolution of reciprocal monophyly and paraphyletic or polyphyletic relationships in mtDNA diversity among widespread Australian birds.