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Biomedical subjects

T Vos

Publications and source records attributed to T Vos.

At least 19 recordsLinked to original sources

Phosphodiesterase (PDE) 7 in inflammatory cells from patients with asthma and COPD.

In inflammatory cells, the low K(m) cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase (PDE) 4 subtype is predominant in terms of expression and function, although more recently it has been suggested that PDE 7 may also play a role in regulating inflammatory cell activity. In the present study, PDE 4 and PDE 7 subtype messenger ribonucleic acid (mRNA) transcripts in CD4 and CD8 lymphocytes from healthy (n=10) and asthmatic (n=10) subjects and polymorphonuclear neutrophils (PMNs) and CD8 lymphocytes obtained from healthy (n=10) and chronic obstructive pulmonary disease (COPD) (n=7) subjects were identified and quantified. PDE 4A, PDE 4B, PDE 4D and PDE 7A mRNA were present in similar quantities in both CD4 and CD8 lymphocytes obtained from healthy and asthmatic subjects and in CD8 lymphocytes obtained from healthy and COPD subjects. Expression of PDE 4C and PDE 7B mRNA was also observed, although transcript levels were low and variable between individuals. In addition, the effects of selective PDE 7 inhibition on both phytohaemagluttinin (PHA)-induced human peripheral blood mixed mononuclear cell (HPBMNC) proliferation and fMLP-induced neutrophil elastase (NE) release were studied. HPBMNC and human neutrophils, isolated from the venous blood of healthy volunteers (n=6) were treated with either a novel selective PDE 7 inhibitor PF 0332040 alone or in combination with rolipram. Proliferation of HPBMNC was stimulated by PHA (2microgml(-1)) and assessed by [(3)H]-thymidine incorporation, while fMLP-induced (100nM) NE release was determined using a chromogenic substrate. Both rolipram (0.003-10microM) and PF 0332040 (0.003-10microM) significantly inhibited PHA-stimulated proliferation of HPBMNC ((**)P<0.01). Co-administration of rolipram (0.3-10microM) and PF 0332040 (0.003-10microM) significantly increased the degree of inhibition observed, compared to when either drug was administered alone ((**)P<0.01). PF 0332040 (0.003-10microM) had no inhibitory effect on NE release from human peripheral blood neutrophils stimulated with fMLP (100nM), while rolipram (0.003-10microM) significantly inhibited neutrophil degranulation ((**)P<0.01). These findings suggest no evidence of altered PDE 4 or PDE 7 mRNA transcript levels in inflammatory cells isolated from the peripheral venous blood of mild asymptomatic asthmatic subjects or stable COPD subjects, however, inhibition of PDE 7 may influence mononuclear cell function.

3',5'-Cyclic-AMP Phosphodiesterases↗

A new approach to assessing the health benefit from obesity interventions in children and adolescents: the assessing cost-effectiveness in obesity project.

OBJECTIVE: To report on a new modelling approach developed for the assessing cost-effectiveness in obesity (ACE-Obesity) project and the likely population health benefit and strength of evidence for 13 potential obesity prevention interventions in children and adolescents in Australia. METHODS: We used the best available evidence, including evidence from non-traditional epidemiological study designs, to determine the health benefits as body mass index (BMI) units saved and disability-adjusted life years (DALYs) saved. We developed new methods to model the impact of behaviours on BMI post-intervention where this was not measured and the impacts on DALYs over the child's lifetime (on the assumption that changes in BMI were maintained into adulthood). A working group of stakeholders provided input into decisions on the selection of interventions, the assumptions for modelling and the strength of the evidence. RESULTS: The likely health benefit varied considerably, as did the strength of the evidence from which that health benefit was calculated. The greatest health benefit is likely to be achieved by the 'Reduction of TV advertising of high fat and/or high sugar foods and drinks to children', 'Laparoscopic adjustable gastric banding' and the 'multi-faceted school-based programme with an active physical education component' interventions. CONCLUSIONS: The use of consistent methods and common health outcome measures enables valid comparison of the potential impact of interventions, but comparisons must take into account the strength of the evidence used. Other considerations, including cost-effectiveness and acceptability to stakeholders, will be presented in future ACE-Obesity papers. Information gaps identified include the need for new and more effective initiatives for the prevention of overweight and obesity and for better evaluations of public health interventions.

Adolescent↗

Measuring the impact of intimate partner violence on the health of women in Victoria, Australia.

OBJECTIVE: Using burden of disease methodology, estimate the health risks of intimate partner violence (IPV) among women in Victoria, Australia. METHODS: We calculated population attributable fractions (from survey data on the prevalence of IPV and the relative risks of associated health problems in Australia) and determined health outcomes by applying them to disability-adjusted life year estimates for the relevant disease and injury categories for Victoria, Australia for 2001. FINDINGS: For women of all ages IPV accounted for 2.9% (95% uncertainty interval 2.4-3.4%) of the total disease and injury burden. Among women 18-44 years of age, IPV was associated with 7.9% (95% uncertainty interval 6.4-9.5%) of the overall disease burden and was a larger risk to health than risk factors traditionally included in burden of disease studies, such as raised blood pressure, tobacco use and increased body weight. Poor mental health contributed 73% and substance abuse 22% to the disease burden attributed to IPV. CONCLUSION: Our findings suggest that IPV constitutes a significant risk to women's health. Mental health policy-makers and health workers treating common mental health problems need to be aware that IPV is an important risk factor. Future research should concentrate on evaluating effective interventions to prevent women being exposed to violence, and identifying the most appropriate mental health care for victims to reduce short- and long-term disability.

Adolescent↗

Intracranial haemorrhage due to late onset vitamin K deficiency bleeding in Hanoi province, Vietnam.

BACKGROUND: In many developing countries vitamin K prophylaxis is not routinely administered at birth. There are insufficient data to assess the cost effectiveness of its implementation in such countries. OBJECTIVE: To estimate the burden of intracranial haemorrhage caused by late onset vitamin K deficiency bleeding in Hanoi, Vietnam. METHODS: Cases of intracranial haemorrhage in infants aged 1-13 weeks were identified in Hanoi province for 5 years (1995-1999), and evidence for vitamin K deficiency was sought. The data were compared with those on vitamin K deficiency bleeding in developed countries and used to obtain an approximation to the incidence of intracranial haemorrhage caused by vitamin K deficiency bleeding in Hanoi. RESULTS: The estimated incidence of late onset vitamin K deficiency bleeding in infants who received no prophylaxis was unexpectedly high (116 per 100,000 births) with 142 and 81 per 100,000 births in rural and urban areas respectively. Mortality was 9%. Of the surviving infants, 42% were neurologically abnormal at the time of hospital discharge. Identified associations were rural residence, male sex, and low birth weight. A significant reduction in the incidence was observed in urban Hanoi during 1998 and 1999, after vitamin K prophylaxis was introduced at one urban obstetric hospital. CONCLUSIONS: Vitamin K deficiency bleeding is a major public health problem in Hanoi. The results indicate that routine vitamin K prophylaxis would significantly reduce infant morbidity and mortality in Vietnam and, costing an estimated 87 US dollars (48 pounds, 72 Euro) per disability adjusted life year saved, is a highly cost effective intervention.

Age Distribution↗

Cost-effectiveness of prescribing statins according to pharmaceutical benefits scheme criteria.

OBJECTIVES: (i) To analyse how well Pharmaceutical Benefits Scheme (PBS) criteria for prescribing lipid-lowering therapy identify people most at risk of coronary heart disease (CHD); and (ii) to determine the cost-effectiveness of primary prevention therapy with pravastatin according to these criteria in Australia. DESIGN: (i) Analysis of targeting of CHD risk according to PBS criteria; (ii) cost-effectiveness analysis for pravastatin as primary preventive therapy (40 mg/day), with a 20-year projection from 1999. PARTICIPANTS: (i) Men and women aged 25-69 years from the 1989 National Heart Foundation Risk Factor Prevalence Survey; (ii) Australian men and women, aged 25-85 years, excluding those with diabetes and existing CHD. MAIN OUTCOME MEASURES: (i) Proportion eligible for lipid lowering treatment according to PBS criteria within 15-year risk of CHD mortality groups; (ii) average net cost in Australian dollars ($) per year of life saved (YOLS), with 80% uncertainty ranges (UR). RESULTS: (i) PBS criteria do not adequately identify those most at risk of CHD, as only 61% of Australians (aged 25-69 years) with a greater than 10% 15-year risk of CHD mortality were eligible for treatment; and 11% of those at low risk of CHD mortality (< 2.5% over 15 years) were eligible for treatment. (ii) Cost-effectiveness of treatment according to PBS criteria was estimated at $110,000 (80% UR, $96,000-$150,000) per YOLS for men and $87,000 (80% UR, $80,000-$130,000) per YOLS for women. As an indicator of the likely recurrent annual costs, total first-year treatment costs (excluding the costs of non-compliers) were estimated at $940 million. Assuming compliance of 50%, cost-effectiveness of treatment was markedly improved using 32.5% 15-year risk of CHD mortality as a cut-off, with ratios of $31,000 (80% UR, $27,000-$40,000) per YOLS for men and $39,000 (80% UR, $33,000-$53,000) per YOLS for women. First-year treatment costs of $940 million were the same as treating according to PBS criteria, but absolute health impact in terms of deaths averted and years of life saved was more than doubled. CONCLUSIONS: While PBS criteria do target patients at risk of CHD, there is room for improvement in identifying those most at risk of CHD, and treatment according to PBS criteria is not likely to be the most cost-effective. For optimal cost-effectiveness, targeting of therapy for primary CHD prevention needs to be based on population-specific, multivariable risk.

Adult↗

The burden of mental disorders in Victoria, 1996.

BACKGROUND: Between 1998 and 1999, a burden of disease assessment was carried out in Victoria, Australia applying and improving on the methods of the Global Burden of Disease Study. This paper describes the methods and results of the calculations of the burden due to 22 mental disorders, adding 14 conditions not included in previous burden of disease estimates. METHODS: The National Survey of Mental Health and Wellbeing provided recent data on the occurrence of the major adult mental disorders in Australia. Data from international studies and expert advice further contributed to the construction of disease models, describing each condition in terms of incidence, average duration and level of severity, with adjustments for comorbidity with other mental disorders. Disability weights for the time spent in different states of mental ill health were borrowed mainly from a study in the Netherlands, supplemented by weights derived in a local extrapolation exercise. RESULTS: Mental disorders were the third largest group of conditions contributing to the burden of disease in Victoria, ranking behind cancers and cardiovascular diseases. Depression was the greatest cause of disability in both men and women. Eight other mental disorders in men and seven in women ranked among the top twenty causes of disability. CONCLUSIONS: Insufficient information on the natural history of many of the mental disorders, the limited information on the validity of mental disorder diagnoses in community surveys and considerable differences between ICD-10 and DSM-IV defined diagnoses were the main concerns about the accuracy of the estimates. Similar and often greater concerns have been raised in relation to the estimation of the burden from common non-fatal physical conditions such as asthma, diabetes and osteoarthritis. In comparison, psychiatric epidemiology can boast greater scientific rigour in setting standards for population surveys.

Adolescent↗

The role of economic evaluation in mental health care.

OBJECTIVE: A consequence of the integration of psychiatry into acute and public health medicine is that psychiatrists are being asked to evaluate their services. There is pressure on mental health-care systems because it is recognized that funds should be directed where they can provide the best health outcomes, and also because there are resource constraints which limit our capacity to meet all demands for health care. This pressure can be responded to by evaluation which demonstrates the effectiveness and efficiency of psychiatric treatment. This paper seeks to remind psychiatrists of the fundamental principles of economic evaluation in the hope that these will enable psychiatrists to understand the methods used in evaluation and to work comfortably with evaluators. METHOD: The paper reviews the basic principles behind economic evaluation, illustrating these with reference to case studies. It describes: (i) the cost of the burden of illness and treatment, and how these costs are measured; (ii) the measurement of treatment outcomes, both as changes in health status and as resources saved; and (iii) the various types of economic evaluation, including cost-minimization, cost-effectiveness, cost-utility and cost-benefit analysis. RESULTS: The advice in the paper provides psychiatrists with the necessary background to work closely with evaluators. A checklist of the critical questions to be addressed is provided as a guide for those undertaking economic evaluations. CONCLUSIONS: If psychiatrists are willing to learn the basic principles of economic evaluation and to apply these, they can respond to the challenges of evaluation.

Australia↗

A model for predicting the future incidence of coronary heart disease within percentiles of coronary heart disease risk.

BACKGROUND: We present a method (The CHD Prevention Model) for modelling the incidence of fatal and nonfatal coronary heart disease (CHD) within various CHD risk percentiles of an adult population. The model provides a relatively simple tool for lifetime risk prediction for subgroups within a population. It allows an estimation of the absolute primary CHD risk in different populations and will help identify subgroups of the adult population where primary CHD prevention is most appropriate and cost-effective. METHODS: The CHD risk distribution within the Australian population was modelled, based on the prevalence of CHD risk, individual estimates of integrated CHD risk, and current CHD mortality rates. Predicted incidence of first fatal and nonfatal myocardial infarction within CHD risk strata of the Australian population was determined. RESULTS: Approximately 25% of CHD deaths were predicted to occur amongst those in the top 10 percentiles of integrated CHD risk, regardless of age group or gender. It was found that while all causes survival did not differ markedly between percentiles of CHD risk before the ages of around 50-60, event-free survival began visibly to differ about 5 years earlier. CONCLUSIONS: The CHD Prevention Model provides a means of predicting future CHD incidence amongst various strata of integrated CHD risk within an adult population. It has significant application both in individual risk counselling and in the identification of subgroups of the population where drug therapy to reduce CHD risk is most cost-effective.

Actuarial Analysis↗

The burden of mental disorders: a comparison of methods between the Australian burden of disease studies and the Global Burden of Disease study.

The national and Victorian burden of disease studies in Australia set out to examine critically the methods used in the Global Burden of Disease study to estimate the burden of mental disorders. The main differences include the use of a different set of disability weights allowing estimates in greater detail by level of severity, adjustments for comorbidity between mental disorders, a greater number of mental disorders measured, and modelling of substance use disorders, anxiety disorders and bipolar disorder as chronic conditions. Uniform age-weighting in the Australian studies produces considerably lower estimates of the burden due to mental disorders in comparison with age-weighted disability-adjusted life years. A lack of follow-up data on people with mental disorders who are identified in cross-sectional surveys poses the greatest challenge in determining the burden of mental disorders more accurately.

Australia↗

Cost-effectiveness analysis of humanitarian relief interventions: visceral leishmaniasis treatment in the Sudan.

Spending by aid agencies on emergencies has quadrupled over the last decade, to over US$6 billion. To date, cost-effectiveness has seldom been considered in the prioritization and evaluation of emergency interventions. The sheer volume of resources spent on humanitarian aid and the chronicity of many humanitarian interventions call for more attention to be paid to the issue of 'value for money'. In this paper we present data from a major humanitarian crisis, an epidemic of visceral leishmaniasis (VL) in war-torn Sudan. The special circumstances provided us, in retrospect, with unusually accurate data on excess mortality, costs of the intervention and its effects, thus allowing us to express cost-effectiveness as the cost per Disability Adjusted Life Year (DALY) averted. The cost-effectiveness ratio, of US$18.40 per DALY (uncertainty range between US$13.53 and US$27.63), places the treatment of VL in Sudan among health interventions considered 'very good value for money' (interventions of less than US$25 per DALY). We discuss the usefulness of this analysis to the internal management of the VL programme, the procurement of funds for the programme, and more generally, to priority setting in humanitarian relief interventions. We feel that in evaluations of emergency interventions attempts could be made more often to perform cost-effectiveness analyses, including the use of DALYs, provided that the outcomes of these analyses are seen in the broad context of the emergency situation and its consequences on the affected population. This paper provides a first contribution to what is hoped to become an international database of cost-effectiveness studies of health interventions during relief operations, which use a comparable measure of health outcome such as the DALY.

Altruism↗

Injuries and noncommunicable diseases: emerging health problems of children in developing countries.

The present article identifies, for children living in developing countries, the major causes of ill-health that are inadequately covered by established health programmes. Injuries and noncommunicable diseases, notably asthma, epilepsy, dental caries, diabetes mellitus and rheumatic heart disease, are growing in significance. In countries where resources are scarce it is to be expected that increasing importance will be attached to the development and implementation of measures against these problems. Their control may benefit from the application of elements of programmes directed against infectious, nutritional and perinatal disorders, which continue to predominate.

Adolescent↗

Extended preservation and effect of nitric oxide production in liver transplantation.

Liver transplantation (Ltx) has become a routine procedure for patients with end-stage liver disease. Despite ongoing progress on short- and long-term graft survival, primary dysfunction (PDF) remains a major problem. PDF is significantly associated with the duration of cold ischemia- and, possibly, with reperfusion-related injury. Nitric oxide (NO) has many physiological functions and plays an important role in modulating tissue injury. However, the mechanism of NO action in ischemia/reperfusion injury after Ltx is thus far unknown. In this study we investigated the role of inducable NO synthase (iNOS) in the liver after preservation with UW solution using the orthotopic Ltx model in the rat. Male Brown Norway rats were used for the Ltx procedure. After donor hepatectomy, livers were stored on ice-cold UW solution for 24 or 40 h and subsequently transplanted. A control group consisted of rats with Ltx after less than 1 h storage. Post-transplant blood samples were taken at 48 h to determine standard parameters for liver injury (aspartate transaminase, lactate dehydrogenase). Liver biopsies were obtained for detection of expression of iNOS (western blot) 24 and 48 h post-transplant. We observed that a preservation time of 24 h in UW solution presents no problem for graft survival after Ltx in rats with some brain function and in healthy animals. After 40 h preservation, liver damage is obvious and graft survival reduced, indicating the limits of cold storage may be within reach. With longer preservation times, more NOs was detected in liver tissue. This finding suggests that NO has a role in ischemia/reperfusion-related injury. Current intervention with NOS inhibitors will reveal whether NO has a negative or a positive effect on graft survival after Ltx.

Animals↗

Dental caries, fluoride levels and oral hygiene practices of school children in Matebeleland South, Zimbabwe.

1386, 5-6-yr-old and 1326, 12-yr-old schoolchildren in the mainly rural province of Matebeleland South, in Zimbabwe, were examined for dental caries and interviewed about their oral hygiene practices. Fluoride contents of the drinking water source of the schools were determined and were found to be in the range 0.05-2.5 ppm. Among 5-6-yr-old children, 25.2% were affected with caries and the mean dmft score was 0.6 whereas 19.8% of the 12-yr-old children had caries, and the mean dmft score was 0.3. In both age groups low fluoride levels in drinking water (<0.8 ppm) were associated with higher prevalence of caries (5-6-yr-olds: OR 2.47; 12-yr-olds: OR 2.09). Chewing sticks were the most commonly applied oral hygiene practice. Children who reported using chewing sticks had fewer carious lesions than children who reported the use of toothbrush and toothpaste.

Child↗

Child sexual abuse in Matabeleland, Zimbabwe.

The extent, nature, causes and consequences of child sexual abuse in Matabeleland. Zimbabwe, are explored by an intersectoral working group consisting of health, legal and AIDS prevention workers who were struck in the course of their work by the regularity with which they saw sexually abused children infected with HIV and STDs. Methods used in this study are record review, focus group discussions, structured and in-depth interviews. Child sexual abuse cases form between 40-60% of the rape cases brought to the attention of hospitals, police and court and many more are believed to remain unreported. Half of the sexual abuse in children is detected through STDs and some have HIV. The majority of offenders are mature men known to the child. Factors influencing child sexual abuse are male dominance in society, men's professed inability to control sexual desire, and magic beliefs. Victims are traumatized by the abuse itself as well as by subsequent problems in family, health and in court. Since child sexual abuse may endanger the life and well-being of the child, it is a serious problem that requires urgent action.

Acquired Immunodeficiency Syndrome↗

Comparative bioavailability study of two haloperidol decanoate containing products.

In our hospital pharmacy an injectable solution of haloperidol decanoate 141 mg/ml (equivalent to haloperidol 100 mg/ml) in sesame oil was prepared. The aim of this study was to prove bioequivalence of this formulation with the reference product, Haldol Decanoas. 15 schizophrenic patients, already stabilized with Haldol Decanoas, were enrolled. Intramuscular injections were given every three weeks in the following doses: 100 mg (1 x), 200 mg (7 x) and 300 mg (7 x). In this open, randomized, cross-over study all patients received four injections of the reference product, and four injections of the test product. Only after the fourth injection of each product (when steady-state levels were reached) a concentration-time profile of haloperidol was established during the dose interval of 21 days. The pharmacokinetic parameters AUC0-21 and Cmax were statistically evaluated. Based on these parameters the conclusion was drawn that both products were bioequivalent. The preparation of this injectable haloperidol decanoate solution in our hospital pharmacy amounts to an annual saving of approximately $39,000.

Adult↗

Attitudes to sex and sexual behaviour in rural Matabeleland, Zimbabwe.

Though HIV prevention campaigns in Zimbabwe have increased public awareness of HIV, they have not meaningfully changed sexual behaviour. Possibly these campaigns are based on wrong assumptions about sexual behaviour. By means of 111 structured interviews with hospital patients, secondary school students and teachers, and 11 focus group discussions with traditional healers, midwives, village community workers, secondary school students and teachers, and commercial sex workers in a rural district of Matabeleland in Zimbabwe, this low-budget study explores attitudes towards sex and sexual behaviour in order to define more appropriate health education messages. Results indicate that traditional sex education no longer takes place and that communication between sexual partners is limited. The almost ubiquitous expectation of women to get rewards for sex outside marriage motivates mostly single women out of economic necessity to meet the male demand for sexual partners, which is created by large scale migrant labour and men's professed 'biological' need for multiple partners. Types of sexual behaviour other than penetrative vaginal sex are uncommon and considered deviant. Safe sex messages from the West therefore are inappropriate in the Zimbabwean context. Recommendations are given to restore traditional communication about sexual matters across generations and to urge sexual partners to discuss sex. Women who, for economic reasons, engage in casual sex should at least learn to negotiate the use of condoms. Men seriously need to reconsider their attitudes to sex and sexual practices in view of the high HIV sero-prevalence. Faithfulness, rather than multiple sexual contacts, should become a reason to boast.

Adolescent↗