Inexact uniformization method for computing transient distributions of Markov chains

The uniformization method (also known as randomization) is a numerically stable algorithm for computing transient distributions of a continuous time Markov chain. When the solution is needed after a long run or when the convergence is slow, the uniformization method involves a large number of matrix-vector products. Despite this, the method remains very popular due to its ease of implementation and its reliability in many practical circumstances. Because calculating the matrix-vector product is the most time-consuming part of the method, overall efficiency in solving large-scale problems can be significantly enhanced if the matrix-vector product is made more economical. In this paper, we incorporate a new relaxation strategy into the uniformization method to compute the matrix-vector products only approximately. We analyze the error introduced by these inexact matrix-vector products and discuss strategies for refining the accuracy of the relaxation while reducing the execution cost. Numerical experiments drawn from computer systems and biological systems are given to show that significant computational savings are achieved in practical applications.

Ovine Enzootic Abortion (OEA): a comparison of antibody responses in vaccinated and naturally-infected swiss sheep over a two year period

Background Prevention and control of ovine enzootic abortion (OEA) can be achieved by application of a live vaccine. In this study, five sheep flocks with different vaccination and infection status were serologically tested using a competitive enzyme-linked immunosorbent assay (cELISA) specific for Chlamydophila (Cp.) abortus over a two-year time period. Results Sheep in Flock A with recent OEA history had high antibody values after vaccination similar to Flock C with natural Cp. abortus infections. In contrast, OEA serology negative sheep (Flock E) showed individual animal-specific immunoreactions after vaccination. Antibody levels of vaccinated ewes in Flock B ranged from negative to positive two and three years after vaccination, respectively. Positive antibody values in the negative control Flock D (without OEA or vaccination) are probably due to asymptomatic intestinal infections with Cp. abortus. Excretion of the attenuated strain of Cp. abortus used in the live vaccine through the eye was not observed in vaccinated animals of Flock E. Conclusion The findings of our study indicate that, using serology, no distinction can be made between vaccinated and naturally infected sheep. As a result, confirmation of a negative OEA status in vaccinated animals by serology cannot be determined.

The Chronic Heart-Failure Assistance by Telephone (CHAT) Study: Assessment of Telephone Support for Vulnerable Patients with Chronic Disease

Aim: To determine whether telephone support using an evidence-based protocol for chronic heart failure (CHF) management will improve patient outcomes and will reduce hospital readmission rates in patients without access to hospital-based management programs. Methods: The rationale and protocol for a cluster-design randomised controlled trial (RCT) of a semi-automated telephone intervention for the management of CHF, the Chronic Heart-failure Assistance by Telephone (CHAT) Study is described. Care is coordinated by trained cardiac nurses located in Heartline, the national call center of the National Heart Foundation of Australia in partnership with patients’ general practitioners (GPs). Conclusions: The CHAT Study model represents a potentially cost-effective and accessible model for the Australian health system in caring for CHF patients in rural and remote areas. The system of care could also be readily adapted for a range of chronic diseases and health systems. Key words: chronic disease management; chronic heart failure; integrated health care systems; nursing care, rural health services; telemedicine; telenursing

Genetic and gene expression analyses of the polycystic ovary syndrome candidate gene fibrillin-3 and other fibrillin family members in human ovaries

Several studies have demonstrated an association between polycystic ovary syndrome (PCOS) and the dinucleotide repeat microsatellite marker D19S884, which is located in intron 55 of the fibrillin-3 (FBN3) gene. Fibrillins, including FBN1 and 2, interact with latent transforming growth factor (TGF)-β-binding proteins (LTBP) and thereby control the bioactivity of TGFβs. TGFβs stimulate fibroblast replication and collagen production. The PCOS ovarian phenotype includes increased stromal collagen and expansion of the ovarian cortex, features feasibly influenced by abnormal fibrillin expression. To examine a possible role of fibrillins in PCOS, particularly FBN3, we undertook tagging and functional single nucleotide polymorphism (SNP) analysis (32 SNPs including 10 that generate non-synonymous amino acid changes) using DNA from 173 PCOS patients and 194 controls. No SNP showed a significant association with PCOS and alleles of most SNPs showed almost identical population frequencies between PCOS and control subjects. No significant differences were observed for microsatellite D19S884. In human PCO stroma/cortex (n = 4) and non-PCO ovarian stroma (n = 9), follicles (n = 3) and corpora lutea (n = 3) and in human ovarian cancer cell lines (KGN, SKOV-3, OVCAR-3, OVCAR-5), FBN1 mRNA levels were approximately 100 times greater than FBN2 and 200–1000-fold greater than FBN3. Expression of LTBP-1 mRNA was 3-fold greater than LTBP-2. We conclude that FBN3 appears to have little involvement in PCOS but cannot rule out that other markers in the region of chromosome 19p13.2 are associated with PCOS or that FBN3 expression occurs in other organs and that this may be influencing the PCOS phenotype.

Inequitable Provision of Optimal Services for Patients with Chronic Heart failure: A National Geo-Mapping Study

Objective: To compare the location and accessibility of current Australian chronic heart failure (CHF) management programs and general practice services with the probable distribution of the population with CHF. Design and setting: Data on the prevalence and distribution of the CHF population throughout Australia, and the locations of CHF management programs and general practice services from 1 January 2004 to 31 December 2005 were analysed using geographic information systems (GIS) technology. Outcome measures: Distance of populations with CHF to CHF management programs and general practice services. Results: The highest prevalence of CHF (20.3–79.8 per 1000 population) occurred in areas with high concentrations of people over 65 years of age and in areas with higher proportions of Indigenous people. Five thousand CHF patients (8%) discharged from hospital in 2004–2005 were managed in one of the 62 identified CHF management programs. There were no CHF management programs in the Northern Territory or Tasmania. Only four CHF management programs were located outside major cities, with a total case load of 80 patients (0.7%). The mean distance from any Australian population centre to the nearest CHF management program was 332 km (median, 163 km; range, 0.15–3246 km). In rural areas, where the burden of CHF management falls upon general practitioners, the mean distance to general practice services was 37 km (median, 20 km; range, 0–656 km). Conclusion: There is an inequity in the provision of CHF management programs to rural Australians.

Lessons learned from implementation of a demonstration program to reduce the burden of anemia and hookworm in women in Yen Bai Province, Viet Nam

Background Iron deficiency, anemia and hookworm disease are important public health problems for women of reproductive age living in developing countries and affect the health of newborns and infants. Iron supplementation and deworming treatment are effective in addressing these problems in both pregnant and non-pregnant women. Daily iron supplementation and deworming after the first trimester is recommended for pregnant women although these programs usually do not operate efficiently or effectively. Weekly iron-folic acid supplementation and regular deworming for non-pregnant women may be a viable approach for improving iron status and preventing anemia during the reproductive years. Addressing these diseases at a population level before women become pregnant could significantly improve women's health before and during pregnancy, as well as their infants' growth and development. Methods and Results This paper describes the major processes undertaken in a demonstration intervention of preventive weekly iron-folic acid supplementation with regular deworming for all 52,000 women aged 15–45 years in two districts of Yen Bai province, in northern Viet Nam. The intervention strategy included extensive consultation with community leaders and village, commune, district and provincial health staff, and training for village health workers. Distribution of the drugs was integrated with the existing health service infrastructure and the village health workers were the direct point of contact with women. Iron-folic acid tablets and deworming treatment were provided free of charge from May 2006. An independent Vietnamese NGO was commissioned to evaluate compliance and identify potential problems. The program resulted in effective distribution of iron-folic acid tablets and deworming treatment to all villages in the target districts, with full or partial compliance of 85%. Conclusion Training for health staff, the strong commitment of all partners and the use of appropriate educational materials led to broad support for weekly iron-folic acid supplementation and high participation in the regular deworming days. In March 2008 the program was expanded to all districts in the province, a target population of approximately 250,000 WRA, and management was handed over to provincial authorities.

Timeliness and Clinical Impact of Hospital-Initiated Medication Reviews

Background: Medication-related problems often occur in the immediate post-discharge period. To reduce medication misadventure the Commonwealth Government funds home medicines reviews (HMRs). HMRs are initiated when general practitioners refer consenting patients to their community pharmacists, who then engage accredited pharmacists to review patients' medicines in their homes. Aim: To determine if hospital-initiated medication reviews (HIMRs) can be implemented in a more timely manner than HMRs; and to assess the impact of a bespoke referral form with comorbidity-specific questions on the quality of reports. Method: Eligible medical inpatients at risk of medication misadventure were referred by the hospital liaison pharmacist to participating accredited pharmacists post-discharge from hospital. Social, demographic and laboratory data were collected from medical records and during interviews with consenting patients. Issues raised in the HIMR reports were categorised: intervention/action, information given or recommendation, and assigned a rank of clinical significance. Results: HIMRs were conducted within 11.6 6.6 days postdischarge. 36 HIMR reports were evaluated and 1442 issues identified - information given (n = 1204), recommendations made (n = 88) and actions taken (n = 150). The majority of issues raised (89%) had a minor clinical impact. The bespoke referral form prompted approximately half of the issues raised. Conclusion: HIMRs can be facilitated in a more timely manner than post-discharge HMRs. There was an associated positive clinical impact of issues raised in the HIMR reports.