Adverse hypersensitivity reactions to mesna as adjunctive therapy for cyclophosphamide

Mesna is widely used for the prevention of cyclophosphamide-related hemorrhagic cystitis. It has been associated with hypersensitivity-like cutaneous and systemic reactions in adult patients. We report a series of children with malignant disease, who developed such reactions following mesna administration and discuss possible mechanisms and management issues.

Undiagnosed hypertension in a rural district in Bangladesh: The Bangladesh Population-based Diabetes and Eye Study (BPDES)

Hypertension is mainly asymptomatic and remains undiagnosed until the disease progresses. The objective of the study was to determine the prevalence of and risk factors for hypertension in rural Bangladesh. Using a population-based cluster random sampling strategy, 3096 adults aged ⩾30 years were recruited from a rural district in Bangladesh. Data collected included two blood pressure (BP) measurements, fasting blood glucose, socio-demographic and anthropometric measurements. Hypertension was defined as systolic BP (SBP) ⩾140 mm Hg or diastolic BP (DBP) ⩾90 mm Hg or self-reported diagnosed hypertension. Logistic regression techniques were used for data analyses. The crude prevalence of hypertension was 40% (95% confidence interval (CI) 38-42%) of which 82% were previously undiagnosed. People from lower socio-economic status (SES) had a significantly higher percentage of undiagnosed hypertension compared with people with higher SES (P<0.001). There was no significant gender difference in severity of hypertension. Males with higher education level compared with no education had a higher prevalence of hypertension (odds ratio 2.34, 95% CI 1.49-3.69). Older age and waist circumference in both genders, and diabetes, lack of physical activity in females were found to be associated with higher prevalence of hypertension. Our research suggests the prevalence of undiagnosed hypertension was higher in the rural area in Bangladesh than that reported from the rural area in neighbouring India and China. Lower SES was associated with a higher risk of undiagnosed hypertension. Public health programs at the grass-roots level must emphasise the provision of primary care and preventive services in managing this non-communicable disease.

Text2PreventCVD: Protocol for a systematic review and individual participant data meta-analysis of text-message based interventions for the prevention of cardiovascular diseases.

Introduction Text message interventions have been shown to be effective in prevention and management of several non-communicable disease risk factors. However, the extent to which their effects might vary in different participants and settings is uncertain. We aim to conduct a systematic review and individual participant data (IPD) meta-analysis of randomised clinical trials examining text message interventions aimed to prevent cardiovascular diseases (CVD) through modification of cardiovascular risk factors (CVRFs). Methods and analysis Systematic review and IPD meta-analysis will be conducted according to Preferred Reporting Items for Systematic review and Meta-Analysis of IPD (PRISMA-IPD) guidelines. Electronic database of published studies (MEDLINE, EMBASE, PsycINFO and Cochrane Library) and international trial registries will be searched to identify relevant randomised clinical trials. Authors of studies meeting the inclusion criteria will be invited to join the IPD meta-analysis group and contribute study data to the common database. The primary outcome will be the difference between intervention and control groups in blood pressure at 6-month follow-up. Key secondary outcomes include effects on lipid parameters, body mass index, smoking levels and self-reported quality of life. If sufficient data is available, we will also analyse blood pressure and other secondary outcomes at 12 months. IPD meta-analysis will be performed using a one-step approach and modelling data simultaneously while accounting for the clustering of the participants within studies. This study will use the existing data to assess the effectiveness of text message-based interventions on CVRFs, the consistency of any effects by participant subgroups and across different healthcare settings. Ethics and dissemination Ethical approval was obtained for the individual studies by the trial investigators from relevant local ethics committees. This study will include anonymised data for secondary analysis and investigators will be asked to check that this is consistent with their existing approvals. Results will be disseminated via scientific forums including peer-reviewed publications and presentations at international conferences.

Burden of disease and injury in Aboriginal and non-Aboriginal populations in the Northern Territory

Objective:
To quantify the burden of disease and injury for the Aboriginal and non-Aboriginal populations in the Northern Territory.

Design and setting:
Analysis of Northern Territory data for 1 January 1994 to 30 December 1998 from multiple sources.

Main outcome measures:
Disability-adjusted life-years (DALYs), by age, sex, cause and Aboriginality.

Results:
Cardiovascular disease was the leading contributor (14.9%) to the total burden of disease and injury in the NT, followed by mental disorders (14.5%) and malignant neoplasms (11.2%). There was also a substantial contribution from unintentional injury (10.4%) and intentional injury (4.9%). Overall, the NT Aboriginal population had a rate of burden of disease 2.5 times higher than the non-Aboriginal population; in the 35-54-year age group their DALY rate was 4.1 times higher. The leading causes of disease burden were cardiovascular disease for both Aboriginal men (19.1%) and women (15.7%) and mental disorders for both non-Aboriginal men (16.7%) and women (22.3%).

Conclusions:
A comprehensive assessment of fatal and non-fatal conditions is important in describing differentials in health status of the NT population. Our study provides comparative data to identify health priorities and facilitate a more equitable distribution of health funding.

Laboratory and non-laboratory-based risk prevention models for secondary prevention of cardiovascular disease : the LIPID study

Aims : The aims of this study were to examine whether risk prediction models for recurrent cardiovascular disease (CVD) events have prognostic value, and to particularly examine the performance of those models based on non-laboratory data. We also aimed to construct a risk chart based on the risk factors that showed the strongest relationship with CVD.

Methods and results : Cox proportional hazards models were used to calculate a risk score for each recurrent event in a CVD patient who was enrolled in a very large randomized controlled clinical trial. Patients were then classified into groups according to quintiles of their risk score. These risk models were validated by calibration and discrimination analyses based on data from patients recruited in New Zealand for the same study. Non-laboratory-based risk factors, such as age, sex, body mass index, smoking status, angina grade, history of myocardial infarction, revascularization, stroke, diabetes or hypertension and treatment with pravastatin, were found to be significantly associated with the risk of developing a recurrent CVD event. Patients who were classified into the medium and high-risk groups had two-fold and four-fold the risk of developing a CVD event compared with those in the low-risk group, respectively. The risk prediction models also fitted New Zealand data well after recalibration.

Conclusion : A simpler non-laboratory-based risk prediction model performed equally as well as the more comprehensive laboratory-based risk prediction models. The risk chart based on the further simplified Score Model may provide a useful tool for clinical cardiologists to assess an individual patient's risk for recurrent CVD events.

Relationship of nutritional and metabolic factors to non-invasive indices of macrovascular disease in diabetes

Factors which may account for the high frequency of macrovascular disease in diabetics are age, sex, cigarette smoking, hypertension, obesity, lack of exercise, diet, hyperglycaemia, hyperinsulinaeroia, hypercholesterolaemia, hypertriglyceridaemia, low HDL-cholesterol concentration, elevated free fatty acid concentration and enhanced platelet aggregation. Twenty seven (13 men and 14 women) non-insulin-dependent diabetics and thirty eight age, height and weight matched healthy subjects (10 men and 28 women) were studied. None of the subjects were smokers, or hypertensive. No subject had any clinical evidence of peripheral arterial disease, coronary heart disease or cerebrovascular disease. All had apparently normal peripheral pulses and normal ankle/arm blood pressure indices. Methods for determining arterial compliance in the segment between the left subclavian artery and each common femoral artery, and proximal resistance at the common femoral artery and posterior tibial artery, have been reviewed and developed. An appropriate food intake methodology for deriving food indices from food records was developed. Biochemical determinants have been made of glucose tolerance, glycosylated haemoglobin, serum total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride, plasma free fatty acid and insulin. A significant decrease in the arterial compliance, and a significant increase in the arterial proximal resistance at the common femoral artery and posterior tibial artery in non-insulin-dependent diabetics, compared with their healthy controls, have been found. Significant negative correlation between arterial compliance and proximal resistance and, a significant positive correlation between the arterial proximal resistance of common femoral artery and posterior tibial artery were found. Differences between control (healthy subjects) and non-insulin-dependent diabetic groups indicate that preclinical peripheral arterial disease can be recognised even in mild diabetics by non-invasive measurement of arterial compliance or proximal resistance. There were significant and negative correlations between arterial compliance and each of blood glucose, blood glycosylated haemoglobin (HbAlC), plasma free fatty acid and plasma insulin concentration. There were significant and positive correlations between arterial proximal resistance of common femoral artery and posterior tibial artery and each of blood glucose, glycosylated haemoglobin and plasma free fatty acid concentration. Multivariate analysis to examine each of the biochemical factors Including blood glucose, blood glycosylated haemoglobin (HbAlC), plasma free fatty acid, plasma Insulin and lipids, showed that the factor which most influenced the arterial compliance and the proximal resistance of posterior tibial artery was the glucose level in the fasting state or the glucose response after a glucose load. In addition, the factors which most influenced proximal resistance of the common femoral artery were free fatty acid -level in the fasting state or glucose response after a glucose load. The factors which most influenced arterial compliance were glucose level in men, and the insulin level in the fasting state or the plasma free fatty acid response after a glucose load in women. These findings indicate that blood glucose, plasma free fatty acid and plasma insulin are risk factors for changes in arterial wall characteristic at a stage when no clinical evidence of macrovascular disease is apparent. Arterial compliance was decreased and the proximal resistance of posterior tibial artery was increased in those with a low intake of protective foods compared with those with a high intake whether healthy subjects or non-insulin-dependent diabetics. Arterial compliance was decreased in non-fish eaters compared with the fish eaters whether healthy subjects or non-insulin-dependent diabetics. Proximal resistance of the posterior tibia! artery in non-fish eaters was increased compared with fish eaters in healthy subjects. Overall, food variety, a protective food score consumption and fish consumption emerge as importance determinants of arterial wall characteristics at a stage when no clinical evidence of macrovascular disease is apparent.

Covert dose reduction is a distinct type of medication non-adherence observed across all care settings in inflammatory bowel disease.

BACKGROUND: Non-adherence by dose omission is common and deleterious to outcomes in Inflammatory Bowel Disease (IBD), but covert dose reduction (CDR) remains unexplored. AIMS: To determine frequency and attitudinal predictors of overall medication non-adherence and of covert dose reduction as separate entities. METHODS: A cross sectional questionnaire was undertaken involving IBD patients in three different geographical regions and care settings. Demographics, medication adherence by dose omission, and rate of patient initiated dose reduction of conventional meds without practitioner knowledge (CDR) were assessed, along with attitudes toward IBD medication. RESULTS: Of 473 respondents (mean age 50.3 years, 60.2% female) frequency of non-adherence was 21.9%, and CDR 26.9% (p<0.001). By logistic regression, significant independent predictors of non-adherence were dissatisfaction with the patient-doctor relationship (p<0.001), depression (p=0.001), anxiety (p=0.047), and negative views regarding medication efficacy (p<0.001) or safety (p=0.017). Independent predictors of covert dose reduction included regular complementary medicine (CAM) use (p<0.001), experiencing more informative (p<0.001) and comfortable (p=0.006) consultations with alternative practitioners, disbelieving doctor delivered information (p=0.021) and safety concerns regarding conventional medication (p<0.001). Neither the frequency of non-adherence (p=0.569) nor CDR (p=0.914) differed between cohorts by different treatment settings. CONCLUSIONS: Covert dose reduction of IBD medication is more common than omission of medication doses, predicted by different factors to usual non-adherence, and has not been previously reported in IBD. The strongest predictor of CDR is regular CAM use.

Ischaemic heart disease and Australian immigrants: the influence of birthplace and language skills on treatment and use of health services

Admission rates for ischaemic heart disease (IHD), and the use of invasive cardiovascular procedures, separation mode and length of stay (LOS) were compared between Australians from non-English speaking background (NESB; n=8627) and English speaking background (ESB; n=13162) aged 20 years and over admitted to Victorian urban public hospitals. The study covered the period from 1993 to 1998. It was found that, compared with their ESB counterparts, the incidence of admission for acute myocardial infarction was significantly higher for NESB men and women before and after controlling for confounding factors. The age-adjusted ratios for NESB women compared with their ESB counterparts ranged from 1.23 to 1.89 for cardiac catheterisation, from 0.23 to 0.27 for percutaneous transluminal coronary angioplasty (PTCA), and from 1.04 to 1.80 for coronary artery bypass grafting (CABG).
Procedure rates were comparable in men for cardiac catheterisation and CABG but higher for PTA rates in NESB men (OR: 1.29, 95%CI: 1.11-1.50) than their ESB counterparts. Both NESB men (β=0.04, 95%CI: 0.01-0.07) and women (β=0.03, 95%CI: 0.02-0.08) experienced significantly longer hospital stays than their ESB counterparts. These findings indicate there may be systematic differences in patients’ treatment and service utilisation in Victorian public hospitals. The extent to which physicians’ bias and
patients’ choice could explain these differences requires further investigation.

Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease

Background and Aim: The toxic milk (tx) mouse is a non-fatal animal model for the metabolic liver disorder, Wilson's disease. The tx mouse has a mutated gene for a copper-transporting protein, causing early copper accumulation in the liver and late accumulation in other tissues. The present study investigated the efficacy of liver cell transplantation (LCT) to correct the tx mouse phenotype.

Methods: Congenic hepatocytes were isolated and intrasplenically transplanted into 3–4-month-old tx mice, which were then placed on various copper-loaded diets to examine its influence on repopulation by transplanted cells. The control animals were age-matched untransplanted tx mice. Liver repopulation was determined by comparisons of restriction fragment length polymorphism ratios (DNA and mRNA), and copper levels were measured by atomic absorption spectroscopy.

Results: Repopulation in recipient tx mice was detected in 11 of 25 animals (44%) at 4 months after LCT. Dietary copper loading (whether given before or after LCT, or both) provided no growth advantage for donor cells, with similar repopulation incidences in all copper treatment groups. Overall, liver copper levels were significantly lower in repopulated animals (538 ± 68 µg/g, n = 11) compared to non-repopulated animals (866 ± 62 µg/g, n = 14) and untreated controls (910 ± 103 µg/g, n = 6; P < 0.05). This effect was also seen in the kidney and spleen. Brain copper levels remained unchanged.

Conclusion: Transplanted liver cells can proliferate and correct a non-fatal metabolic liver disease, with some restoration of hepatic copper homeostasis after 4 months leading to reduced copper levels in the liver and extrahepatic tissues, but not in the brain.

Effects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised, double-blind, placebo controlled trial

Background: Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA), there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA.

Methods/Design: Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics.

Discussion: Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA.

Trial registration: ACTR12605000503628; NCT00415259.

Guideline for the non-surgical management of hip and knee osteoarthritis

Introduction: Chronic disease is a major public health burden on Australian society. An increasing proportion of the population has risk factors for, or at least one, chronic disease, leading to increasing public health costs. Health service policy and delivery must not only address acute conditions, it must also effectively respond to the wide range of health and public service requirements of people with chronic illness.^1,2 Strong primary health care policy is an important foundation for a successful national health delivery system and long term management of public health, and is linked to practical outcomes including lower mortality, decreased hospitalisation and improved health outcomes.¹ National strategic health policy has recently given increased recognition to the importance of chronic disease management, with the Australian Federal Government endorsement of a number of initiatives for the prevention (or delay in onset), early detection and evidence based management of chronic disease, including osteoarthritis.^1,3
Chronic musculoskeletal conditions, including arthritis, account for over 4% of the national disease burden in terms of disability adjusted life years. Over 6 million Australians (almost one-third of the population) are estimated to have a chronic musculoskeletal disease; chronic musculoskeletal disease represents the main cause of long term pain and physical disability. In Australia, osteoarthritis is self reported by more than 1.4 million people (7.3% of the population4) and is the tenth most commonly managed problem in general practice.5 This number is set to rise as the elderly population grows. Osteoarthritis exerts a significant burden on the individual and the community through reduction in quality of life, diminished employment capacity and an increase in health care costs. For further details, refer to the Evidence to support the National Action Plan for Osteoarthritis, Rheumatoid Arthritis and Osteoporosis: Opportunities to improve health-related quality of life and reduce the burden of disease and disability (2004).⁶
As such, federal government health policy has identified arthritis as a National Health Priority Area and adopted a number of initiatives aimed at decreasing the burden of chronic disease and disability; raising awareness of preventive disease factors; providing access to evidence based knowledge; and improving the overall management of arthritis within the community.4 In 2002, all Australian health ministers designated arthritis and musculoskeletal conditions as Australia’s seventh National Health Priority Area. In response, a National Action Plan was developed in 2004 by the National Arthritis and Musculoskeletal Conditions Advisory Group (NAMSCAG).6 The aim of this document was to provide a blueprint for national initiatives to improve the health related quality of life of people living with osteoarthritis, rheumatoid arthritis and osteoporosis; reduce the cost and prevalence of these conditions; and reduce the impact on individuals, their carers and their communities within Australia. The National Action Plan was developed to complement both the National Chronic Disease Strategy – which is broader – and the National Service Improvement Framework for Osteoarthritis, Rheumatoid Arthritis and Osteoporosis, in addition to other national and state/ territory structures.

Use of high resolution digital multi-spectral imagery to assess the distribution of disease caused by Phytophthora cinnamomi on heathland at Anglesea, Victoria

Disease caused by the soilborne plant pathogen Phytophthora cinnamomi causes long-term floristic and structural changes in native vegetation communities in Australia. Key components of the management of this disease are to know where it occurs and the rate at which it spreads. The distribution of P. cinnamomi has generally been assessed as locality points of infestation and mapping the extent of diseased vegetation in any area is difficult and costly. This study was undertaken in P. cinnamomi-infested heathland communities in southern Victoria, Australia, where the symptoms of P. cinnamomi arise as a mosaic within healthy vegetation. We investigated the potential to improve the efficiency and effectiveness of mapping and monitoring vegetation affected by P. cinnamomi using digital multi-spectral imaging. This technique was developed for the purposes of monitoring vegetation and provides a single, seamless ortho-rectified digital image over the total area of interest. It is used to spatially quantify small differences in the characteristics of vegetation. In this study, the symptoms of disease caused by P. cinnamomi infestation were related to differences in the imagery and were used to map areas of infestation. Comparison of the digital multi-spectral imaging indications with on-ground observations gave moderate accuracy between the datasets (κ = 0.49) for disease and healthy indications. This study demonstrates the ability of the technique to determine disease extent over broad areas in native vegetation and provides a non-invasive, cost effective tool for management.

Pituitary disease - perspectives of patients and partners

Aim. To explore experiences of pituitary disease of people with pituitary disease (PD) and their partners (PT).

Background. Pituitary disease encompasses a range of hormonal abnormalities that produce a variety of signs and symptoms depending on the underlying cause.

Design. A triangulated exploratory study.

Methods. The study was conducted in three phases: (a) non-participant monitoring of an Internet pituitary chat room over four months; (b) in-depth structured interviews with PD attending a pituitary outpatient clinic (n = 8) and PT (n = 6), (c) focus groups (n = 12). Data were collected in 2005.

Results. Four themes emerged from the discussion in each phase: 'need to be normal', 'emotional merry-go-round', 'damage to the self', and 'doctor ignorance'. Symptoms of pituitary disease were often mistaken for sinusitis, 'getting old before my time', hypochondria, stress, and 'something sinister changing the way I look'. Time to diagnosis varied from four weeks to 15 years. PD felt included in decision-making but partners relied on PD for information. Body image changes were significant making PD feel like a 'freak show for medical students' and the emotional distress persisted after treatment and 'cure'. The word 'tumour' caused significant stress and anxiety and depression was common. PD and PT felt general practitioners (GP) lacked information about pituitary disease.

Conclusions. Pituitary disease has a major impact on psychological well-being. PD but not PT felt involved in decisions about their management. GPs may need more education about pituitary disease. The study adds important information about the emotional effects of pituitary disease and its treatment.

Relevance to clinical practice. Pituitary disease is a generic term encompassing a range of underlying disease processes that often produce vague symptoms, often attributed to other causes, which delays diagnosis and treatment. Pituitary disease has a significant under recognised impact on people's mental and physical wellbeing and self-concept. Although the underlying hormonal imbalances associated with pituitary disease are largely reversible (cured), emotional distress persists. Regular monitoring of emotional wellbeing as well as medical and hormone status is warranted.

HOMA insulin sensitivity index and the risk of all-cause mortality and cardiovascular disease events in the general population : the Australian diabetes, obesity and lifestyle study (AusDiab) study

Aims/hypothesis We assessed whether the relationships between insulin sensitivity and all-cause mortality as well as fatal or non-fatal cardiovascular disease (CVD) events are independent of elevated blood glucose, high blood pressure, dyslipidaemia and body composition in individuals without diagnosed diabetes.
Methods Between 1999 and 2000, baseline fasting insulin, glucose and lipids, 2 h plasma glucose, HbA1c, anthropometrics, blood pressure, medication use, smoking and history of CVD were collected from 8,533 adults aged >35 years from the population-based Australian Diabetes, Obesity and Lifestyle study. Insulin sensitivity was estimated by HOMA of insulin sensitivity (HOMA-%S). Deaths and fatal or non-fatal CVD events were ascertained through linkage to the National Death Index and medical records adjudication.
Results After a median of 5.0 years there were 277 deaths and 225 CVD events. HOMA-%S was not associated with all-cause mortality. Compared with the most insulin-sensitive quintile, the combined fatal or non-fatal CVD HR (95% CI) for quintiles of decreasing HOMA-%S were 1.1 (0.6–1.9), 1.4 (0.9–2.3), 1.6 (1.0–2.5) and 2.0 (1.3–3.1), adjusting for age and sex. Smoking, CVD history, hypertension, lipid-lowering medication, total cholesterol and waist-to-hip ratio moderately attenuated this relationship. However, the association was rendered non-significant by adding HDL. Fasting plasma glucose, but not HOMA-%S significantly improved the prediction of CVD, beyond that seen with other risk factors.
Conclusions/interpretation In this cohort, HOMA-%S showed no association with all-cause mortality and only a modest association with CVD events, largely explained by its association with HDL. Fasting plasma glucose was a better predictor of CVD than HOMA-%S.

Bacille Calmette-Guérin vaccine-related disease in HIV-infected children: a systematic review

Objective: To describe the characteristics and risk of bacille Calmette-Guérin (BCG) vaccine related disease in human immunodeficiency virus (HIV) infected infants.
Methods: Systematic literature review of articles published from 1950 to April 2009 in the English language. We identified all microbiologically confirmed cases of disseminated BCG disease in vertically HIV-infected children reported in the literature.
Results: Sixteen observational studies and 11 case reports/series were included. Observational studies suffered from high rates of loss to follow-up and death. Loco-regional BCG disease was reported in both HIV-infected and non-infected children. Disseminated BCG disease was reported only in children with immunodeficiency and only in studies employing sophisticated laboratory techniques. Sixty-nine cases of disseminated BCG were identified in the literature: 47 cases were reported in six observational studies, the majority (41/47) from the Western Cape of South Africa. A Brazilian cohort study reported no cases of disseminated BCG amongst 66 HIV-infected children observed over a 7-year period. A recent South African surveillance study reported 32 cases of disseminated BCG over a 3-year period, estimating the risk of disseminated BCG to be 992 per 100 000 vaccinations in HIV-infected children. Few cases of severe disseminated TB were reported in the cohort studies among HIV-infected children vaccinated with BCG.
Conclusion: Data on the risk of BCG vaccination in HIV-infected children are limited. Targeted surveillance for BCG complications employing sophisticated diagnostic techniques is required to inform vaccination policy.