Bluetongue disease in sheep in New South Wales - April 2023.

In 2016, bluetongue virus (BTV), serotype 16 (BTV-16), was detected in New South Wales (NSW) in sentinel cattle for the first time. Over the next 6 years, BTV-16 has been detected regularly and over an increasing area of the BTV zone in NSW. In April 2023, disease was reported in sheep on two farms on the Northern Tablelands of NSW. The consistent clinical signs included reduced exercise tolerance, facial swelling, serous nasal discharges with encrustation of the nasal plane, subcutaneous oedema of the neck and brisket and variable congestion of the coronary band. Affected sheep were mainly mature ewes and rams, with an estimated morbidity of 20% over a period of 6-8 weeks. Although there were several unexpected deaths, no veterinary examination was sought. Predominantly BTV-16 RNA was detected in sick sheep, with an incidence of infection of approximately 40% in a cross section of one flock. These events represent the first confirmation of disease due to bluetongue virus in NSW. As these cases occurred in a region with a high density of sheep, if there is ongoing transmission of BTV-16 during subsequent summers, further disease might be expected.

On the front line of HIV virological monitoring: barriers and facilitators from a provider perspective in resource-limited settings.

Scale-up of viral load (VL) monitoring for HIV-infected patients on antiretroviral therapy (ART) is a priority in many resource-limited settings, and ART providers are critical to effective program implementation. We explored provider-perceived barriers and facilitators of VL monitoring. We interviewed all providers (n = 17) engaged in a public health evaluation of dried blood spots for VL monitoring at five ART clinics in Malawi. All ART clinics were housed within district hospitals. We grouped themes at patient, provider, facility, system, and policy levels. Providers emphasized their desire for improved ART monitoring strategies, and frustration in response to restrictive policies for determining which patients were eligible to receive VL monitoring. Although many providers pled for expansion of monitoring to include all persons on ART, regardless of time on ART, the most salient provider-perceived barrier to VL monitoring implementation was the pressure of work associated with monitoring activities. The work burden was exacerbated by inefficient data management systems, highlighting a critical interaction between provider-, facility-, and system-level factors. Lack of integration between laboratory and clinical systems complicated the process for alerting providers when results were available, and these communication gaps were intensified by poor facility connectivity. Centralized second-line ART distribution was also noted as a barrier: providers reported that the time and expenses required for patients to collect second-line ART frequently obstructed referral. However, provider empowerment emerged as an unexpected facilitator of VL monitoring. For many providers, this was the first time they used an objective marker of ART response to guide clinical management. Providers' knowledge of a patient's virological status increased confidence in adherence counseling and clinical decision-making. Results from our study provide unique insight into provider perceptions of VL monitoring and indicate the importance of policies responsive to individual and environmental challenges of VL monitoring program implementation. Findings may inform scale-up by helping policy-makers identify strategies to improve feasibility and sustainability of VL monitoring.

A survey to determine the prevalence of Theileria spp. in beef cattle in the northern tablelands of New South Wales.

OBJECTIVE: To estimate the within and between herd prevalences for Theileria orientalis in beef herds in the eastern section of the New England Livestock Health and Pest Authority. DESIGN: Stratified random survey. METHODS: From each of 46 randomly selected beef cattle herds, 10 cattle were randomly selected and blood sampled. Packed cell volumes (PCV) were calculated and the number of Theileria organisms in blood smears was counted. Within-herd results were grouped into zero, low, medium or high prevalence based on the number of positive smears. A questionnaire was completed by the farmer at the time of sampling and responses to variables such as farm location and management strategies were compared with the laboratory findings. RESULTS: Theileria species at varied levels on smears were found in 33 of the 46 herds sampled, which gave a herd prevalence of 72% for this study. Approximately 18% of herds were in the medium or high prevalence group. Half of the properties reported tick activity and 70% of those used tick control. CONCLUSIONS: The 72% herd prevalence of Theileria spp. found in this study shows that infection is widespread in beef herds in the northern tablelands of New South Wales. Although 82% of the sampled herds had low or zero within-herd prevalence estimates, a significant number of herds had medium or high levels of Theileria. The risk factor questionnaire has provided some associations, such as the link between tick treatment and Theileria detection, that require more targeted studies.

Pre-culturing human adipose tissue mesenchymal stem cells under hypoxia increases their adipogenic and osteogenic differentiation potentials.

OBJECTIVES: Hypoxia is an important factor in many aspects of stem-cell biology including their viability, proliferation, differentiation and migration. We evaluated whether low oxygen level (2%) affected human adipose tissue mesenchymal stem-cell (hAT-MSC) phenotype, population growth, viability, apoptosis, necrosis and their adipogenic and osteogenic differentiation potential. MATERIALS AND METHODS: hAT-MSCs from four human donors were cultured in growth medium under either normoxic or hypoxic conditions for 7 days and were then transferred to normoxic conditions to study their differentiation potential. RESULTS: Hypoxia enhanced hAT-MSC expansion and viability, whereas expression of mesenchymal markers such as CD90, CD73 and endothelial progenitor cell marker CD34, remained unchanged. We also found that pre-culturing hAT-MSCs under hypoxia resulted in their enhanced ability to differentiate into adipocytes and osteocytes. CONCLUSIONS: This protocol could be useful for maximizing hAT-MSC potential to differentiate in vitro into the adipogenic and osteogenic lineages, for use in plastic and reconstructive surgery, and in tissue engineering strategies.

The first five days: field and laboratory investigations during the early stages of the equine influenza outbreak in Australia, 2007.

Until August 2007, Australia was one of only three countries internationally recognised to be free of equine influenza (EI). This report documents the diagnosis of the first cases of EI in Australian horses and summarises the investigations that took place over the next 5 days. During that time, a multifocal outbreak was identified across eastern New South Wales and south-eastern Queensland. The use of an influenza type A pan-reactive real-time reverse transcription polymerase chain reaction allowed rapid confirmation of suspect cases of EI.

Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential.

Mesenchymal stem cells (MSCs) are usually cultured under normoxic conditions (21% oxygen). However, in vivo, the physiological "niches" for MSCs have a much lower oxygen tension. Because of their plasticity, stem cells are particularly sensitive to their environments, and oxygen tension is one developmentally important stimulus in stem cell biology and plays a role in the intricate balance between cellular proliferation and commitment towards differentiation. Therefore, we investigated here the effect of hypoxia (2% oxygen) on murine adipose tissue (AT) MSC proliferation and adipogenic differentiation. AT cells were obtained from the omental fat and AT-MSCs were selected for their ability to attach to the plastic dishes, and were grown under normoxic and hypoxic conditions. Prior exposure of MSCs to hypoxia led to a significant reduction of ex vivo expansion time, with significantly increased numbers of Sca-1(+) as well as Sca-1(+)/CD44(+)double-positive cells. Under low oxygen culture conditions, the AT-MSC number markedly increased and their adipogenic differentiation potential was reduced. Notably, the hypoxia-mediated inhibition of adipogenic differentiation was reversible: AT-MSCs pre-exposed to hypoxia when switched to normoxic conditions exhibited significantly higher adipogenic differentiation capacity compared to their pre-exposed normoxic-cultured counterparts. Accordingly, the expression of adipocyte-specific genes, peroxisome proliferator activated receptor gamma (Ppargamma), lipoprotein lipase (Lpl) and fatty acid binding protein 4 (Fabp4) were significantly enhanced in hypoxia pre-exposed AT-MSCs. In conclusion, pre-culturing MSCs under hypoxic culture conditions may represent a strategy to enhance MSC production, enrichment and adipogenic differentiation.

A chiral sex pheromone system in the pea midge, Contarinia pisi.

The sex pheromone of the pea midge consists of 2-acetoxytridecane, (2S,11S)-diacetoxytridecane and (2S,12S)-diacetoxytridecane. The responses of male pea midges to the corresponding stereoisomers of (2S,11S)-diacetoxytridecane and (2S,12S)-diacetoxytridecane were tested in field trapping experiments and by electroantennographic recordings. When added at 20% of the pheromone component to the sex pheromone blend, the (2S,11R)- and (2R,11S)-stereoisomers of (2S,11S)-diacetoxytridecane, were shown to have a strong inhibitory effect on male attraction in the field. At the same dose, (2R,11R)-diacetoxytridecane, (2R,12R)-diacetoxytridecane, and meso-2,12-diacetoxytridecane, did not have a significant effect on male behavior. It was also shown that substitution of either (2S,11S)-diacetoxytridecane or (2S,12S)-diacetoxytridecane with the related stereoisomers reduced trap catches to the level of blank traps. The electroantennographic recordings showed similar dose-response curves for the pheromone components and the stereoisomers shown to have an inhibitory effect. It seems likely that male antennae have receptors for bothpheromone components and for inhibitory stereoisomers. Scanning electron microscopy and transmission electron microscopy of the antennae revealed three types of sensilla involved in chemoreception: sensilla circumfila, sensilla trichodea, and sensilla coeloconica. The sensilla circumfila and trichodea are both innervated by two sensory cells, whereas the sensilla coeloconica are innervated by four to five cells.

Comparison of the validity of periodontal probing measurements in smokers and non-smokers.

AIM: To determine whether the reduced inflammation and bleeding and increased fibrosis reported in tobacco smokers affect the validity of clinical probing measurements by altering probe tip penetration. METHOD: A constant force probe was used to measure probing depths and sound bone levels at six sites on 64 molar teeth (384 sites) in 20 smoking and 20 non-smoking patients from grooves made with a bur at the gingival margin prior to extraction. Connective tissue attachment levels were measured from the grooves with a dissecting microscope following extraction. Data were analysed using robust regression with sites clustered within subjects. RESULTS: Sites in smokers showed more calculus but less bleeding than sites in non-smokers (p<0.05). The mean clinical probing depth was not significantly different (smokers: 5.54 mm, confidence intervals=4.81 to 6.28; non-smokers: 6.05 mm, ci=5.38 to 6.72). The corresponding post-extraction pocket depth measurements (smokers: 4.95 mm, ci=4.30 to 5.61; non-smokers: 5.23 mm, ci=4.49 to 5.96) were less than clinical probing depth in sites from both smokers and non-smokers (p<0.01). However, the proportional difference was less in smokers (p<0.05), particularly in deeper pockets, indicating that clinical probe tip penetration of tissue was greater in non-smokers. Regression analysis indicated that the presence of calculus and bleeding also influenced the difference in clinical probe penetration (p<0.05). CONCLUSION: Clinical probing depth at molar sites exaggerates pocket depth, but the probe tip may be closer to the actual attachment level in smokers due to less penetration of tissue. This may be partly explained by the reduced inflammation and width of supra-bony connective tissue in smokers. These findings have clinical relevance to the successful management of periodontal patients who smoke.

Effectiveness and economic impact of screening for colorectal cancer by mass fecal occult blood testing.

OBJECTIVES: Fecal occult blood testing has been shown to reduce mortality from colorectal cancer in large randomized, controlled trials conducted in the United States, Denmark, and the United Kingdom, and mathematical simulation modeling found it to be cost-effective relative to other health care services. Before making a concerted effort to implement mass fecal occult blood testing based on this evidence alone, however, we considered it prudent to critically re-evaluate the effectiveness and economic impact of screening in the US population as a whole. METHODS: To assess the effectiveness of screening, we projected published outcomes from each of the three large randomized controlled trials of fecal occult blood testing to the US population, as if each clinical trial had been done in the population as a whole. We then determined the resource costs of detection and treatment that would be associated with the outcomes predicted from each trial. RESULTS: More than 1 million colorectal cancers could be expected to arise over 10 yr in the cohort of US residents eligible to enter a screening program in 1997, and trial outcomes indicate that > or = 60% of these cancers would be fatal. If the 60-67% compliance rate of the population-based randomized controlled trials were achieved, a fecal occult blood testing program would detect 30% of known colorectal cancers and save 100,000 lives over 10 yr. Screening would incur total costs of $3-4 billion over 10 yr, or $2,500 per life-year saved. CONCLUSIONS: Mass fecal occult blood testing is cost-effective, and, although not inexpensive, many would consider the total cost acceptable. Even with a concerted effort to achieve compliance, however, the effectiveness of fecal occult blood testing would be limited to saving the lives of < or = 15% of those who otherwise would die from their cancer in the first 10 yr after beginning mass screening. The limitations of fecal occult blood testing suggest the need to further evaluate the role of endoscopy in screening, and to develop more effective, noninvasive screening tools.

Cost-benefit analysis of sumatriptan tablets versus usual therapy for treatment of migraine.

We performed a systematic assessment of the costs and benefits of sumatriptan and usual therapy for migraine from society's perspective. A decision tree was constructed with probability estimates based on data from an open-label clinical trial assessing the economic and human impacts of sumatriptan and usual therapy on nursing personnel. Direct medical care costs including costs for drug, physician, and emergency room visits were considered. Benefits were estimated using the human capital approach based on the national average of weekly earnings and productivity loss estimated from a migraine clinical trial. The net benefits of sumatriptan and usual therapy for the treatment of a single migraine attack were estimated to be $50 and $20, respectively. The annual incremental net benefit of sumatriptan over usual therapy was estimated to be $114-540/patient. The price difference was offset by benefits of sumatriptan in reducing use of health care resources and productivity loss.

Developing clinical practice guidelines for spinal cord medicine. Lessons learned.

This article describes the process used by the Consortium for Spinal Cord Medicine to develop evidence-based clinical practice guidelines for managing and treating individuals with spinal cord injury and provides important information on lessons learned and the potential problems to avoid. Issues to consider during the guideline development process include topic selection and explication, methods for selecting the panel chair and panel members, the writing of recommendations and supporting scientific rationales, peer-reviewing guidelines, and the process for disseminating, implementing, and evaluating guidelines. The applicability, advantages, and disadvantages of available evidence and guideline recommendation grading systems and issues arising from the lack of scientific evidence supporting particular recommendations are also discussed.

Measuring the effect of clinical guidelines on patient outcomes.

OBJECTIVES: To identify and examine the methodologic issues related to evaluating the effectiveness of treatment adherence to clinical guidelines. The example of antiretroviral therapy guidelines for human immunodeficiency virus (HIV) disease is used to illustrate the points. METHODS: Regression analysis was applied to observational HIV clinic data for patients with CD4+ cell counts less than 500 per microL and greater than 50 per microL at baseline (n = 704), using Cox proportional hazards time-varying covariates models controlling for baseline risk. The results are compared with simpler models (Cox model [without time-varying covariates] and logistic regression). In addition, the effect of including a measure of exposure to antiretroviral guidelines in the model is explored. RESULTS: This study has three implications for modeling clinical guideline effectiveness. To capture events that are time-sensitive, a duration model should be used, and covariates that are time-varying should be modeled as time-varying. Thirdly, incorporating a threshold measure of exposure to reflect the minimum period of time for guideline adherence required for a measurable effect on patient outcome should be considered. CONCLUSIONS: The methods proposed in this paper are important to consider if guidelines are to evolve from being a tool for summarizing and transferring the results of research from the literature to clinicians into a practical tool that influences clinical practice patterns. However, the methodology tested in this study needs to be validated using additional data on similar patients and using data on patients with other diseases.

Modeling the use of triple combination therapy in five countries: nevirapine, Zidovudine, and Didanosine.

OBJECTIVE: In this study, we modify previously published models to estimate the short- and long-term consequences of nevirapine triple combination therapy use in five developed countries. Current pharmacoeconomic practice requires the de novo model development for each new therapy comparison. This approach is lengthy and costly, and it may yield models with very different structures. Standardized, detailed disclosure of model assumptions and parameters makes it possible to recycle published models with minor structural modifications to examine the efficiency of therapies based on new trial data. METHODS: Two well-publicized models of HIV therapy are modified to fit new trial data comparing double and triple combination therapy with nevirapine; model parameters are adjusted to represent clinical practice and cost structure in five countries. A short-term model uses trial data from advanced-stage patients to estimate first-year costs and consequences. A long-term model uses data from antiretroviral-naïve patients to estimate long-term cost-effectiveness. RESULTS: During the first year, for each 100 individuals treated with nevirapine triple combination therapy, 2.7 deaths and 30.8-31.4 opportunistic disease events would be averted compared to employing dual therapy. Additionally, 61% to 142% of the first-year costs of nevirapine therapy would be offset by other medical care costs savings [FF19,749, DM3,778, 3334 (x1000) lire, 293 (x1000) ptas, and US $3,569]. Compared to dual combination therapy, nevirapine triple combination therapy is predicted to yield incremental cost-effectiveness ratios (discounted at 3%) of FF101,057, DM30,709, 28,066 (x1000) lire, 1294 (x1000) ptas, and US $14,338. CONCLUSION: Published, well-constructed, and documented cost-effectiveness models can be reused to estimate the economic impact of therapies for HIV disease. Such models can also be used to provide insight into the factors that affect efficiency across countries. Our use of clinical trial data on nevirapine, together with published HIV economic models, provides support for the hypothesis that nevirapine is cost-effective under the cost structures of five developed countries.

Costs of developing childhood immunization registries: case studies from four All Kids Count projects.

We conducted case studies using structured interviews at four sites to understand the financial resources needed to implement childhood immunization registries. The total cost of planning and implementing a central registry ranged from $2.4 million to almost $7 million over the first five years. In addition, substantial investment by individual or group providers often was required. Registries are large information systems that require considerable investment of developmental resources, regardless of the number of children eventually entered into the system. Given the substantial investment that a registry represents, the realistic anticipation of such resource needs is important to successful planning and implementation.

Cost-effectiveness of transesophageal echocardiography to determine the duration of therapy for intravascular catheter-associated Staphylococcus aureus bacteremia.

BACKGROUND: The appropriate duration of therapy for catheter-associated Staphylococcus aureus bacteremia is controversial. Conventional practice dictates that all patients receive prolonged courses of intravenous antibiotics. Some clinicians recommend abbreviated therapeutic courses, but an alternate approach involves prospectively identifying patients for whom abbreviated therapy is appropriate. OBJECTIVE: To determine the cost-effectiveness of transesophageal echocardiography (TEE) in establishing duration of therapy for catheter-associated S. aureus bacteremia. DESIGN: Cost-effectiveness analysis. DATA SOURCES: MEDLINE search of literature; clinical data from patients with S. aureus bacteremia (n = 196) and patients with endocarditis (n = 60); and costs obtained from the study institution, regional home health agency, and national estimates of professional and technical fees. TARGET POPULATION: Patients with catheter-associated S. aureus bacteremia on native heart valves without intravenous drug use or clinically apparent metastatic infection, immunosuppression, or indwelling prosthetic devices. TIME HORIZON: Patient lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Antibiotic treatment based on TEE results compared with 2- or 4-week empirical therapy. OUTCOME MEASURES: Quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: Compared with empirical short-course therapy, the TEE strategy cost $4938 per quality-adjusted life-year (QALY) gained. The effectiveness of the TEE strategy and the effectiveness of the long-course strategy were sufficiently similar that the additional cost of empirical long-course therapy ($1,667,971 per QALY) was higher than that which society usually considers cost-effective. RESULTS OF SENSITIVITY ANALYSES: In a four-way sensitivity analysis (endocarditis prevalence, TEE cost, short-course relapse rate, and TEE specificity), compared with empirical short-course therapy, the TEE strategy results ranged from cost savings to $155,624 per QALY. CONCLUSION: Within the limitations of existing empirical data, this study suggests that for patients with clinically uncomplicated catheter-associated S. aureus bacteremia, the use of TEE to determine therapy duration is a cost-effective alternative to 2- or 4-week empirical therapy.

Decision-analysis of transjugular intrahepatic portosystemic shunt versus distal splenorenal shunt for portal hypertension.

Transjugular intrahepatic portosystemic shunt (TIPS) and surgical distal splenorenal shunt (DSRS) are treatments for complications of portal hypertension. TIPS is widely used because it is relatively easy to place. Because TIPS may malfunction over time, it is unclear whether TIPS is superior to DSRS in patients with Child's class A cirrhosis who enjoy a longer survival. This study compared the cost-effectiveness of TIPS to DSRS for portal hypertension in Child's class A cirrhosis. A decision analysis model was used to evaluate the number of procedures, life expectancy, and costs over the first 2 years in patients with Child's class A cirrhosis who underwent a TIPS or DSRS. Patients who received TIPS survived 1.96 years, required 1.7 procedures, and incurred $41,685 in costs. Patients who underwent a DSRS survived 1.86 years, required 1.0 procedure, and incurred $26,951 in costs. The cost-effectiveness of TIPS compared with DSRS was $147,340 per life-year saved. Adjusting the rate of TIPS dysfunction, 1-year survival, or the number of ultrasounds to detect TIPS dysfunction did not change the results. In patients with Child's class A cirrhosis, DSRS is a more cost-effective treatment than TIPS. Until the results of a randomized controlled trial comparing TIPS with DSRS are available, TIPS should be regarded as experimental and prohibitively expensive in Child's class A cirrhosis.

The health insurance puzzle: a new approach to assessing patient coverage preferences.

Previous studies of preferences for health insurance benefits have required individuals to make a series of complex and repetitive decisions, and have assumed that all insured benefits are desirable. This study reports the development and testing of a simple, innovative instrument to measure preferences for health insurance benefits. The newly developed instrument (Puzzle) is designed to allow subjects to select health benefits in a way that underscores the trade-offs dictated by budgets and costs. A "puzzle-like" frame representing budget constraints and "puzzle piece" benefit cards proportionately sized to represent the premium price of a single year's coverage comprise the instrument. In a comparison procedure (Money Game), participants "purchase" individual benefits by exchanging "play" money for benefit tokens. The Puzzle's utility was assessed by examining the convergence of results from both instruments and the subject's ratings of and preference for the instruments. One hundred five elderly Medicare enrollees seen in the general Internal Medicine outpatient clinic of a major southeastern teaching hospital were interviewed. Subjects answered interviewer-administered questionnaires and completed both the Puzzle and the Money Game. Both McNemar's test and Kendall's tau-b indicated a high degree of concordance between benefit choices made using the two instruments. Descriptive statistics demonstrated that the Puzzle was clear, easy to use, understandable, and preferred to the Money Game. The results suggest that the Puzzle is a promising tool for assessing health insurance coverage preferences under circumstances of limited expenditures, which can be modified for use with various populations who face limited insurance benefits.

Impact of a new universal purchase vaccine program in North Carolina.

OBJECTIVE: To explore the effects of state universal purchase (UP) of vaccines for all children, regardless of income or insurance status, on North Carolina physicians and families. DESIGN: Cross-sectional survey. PARTICIPANTS: Pediatricians and family physicians (N = 2163) were surveyed in 1995 to compare immunization charges in North Carolina (new UP) with those of Massachusetts (UP) and Texas (free market). MAIN OUTCOME MEASURES: Patient charges for immunizations and well-child visits and physician perceptions of the effects of state immunization programs. Models were devised to simulate the net effect of the North Carolina UP program on immunization revenue for physicians and on families' out-of-pocket costs for well-child care. RESULTS: Physician participation rates in the 2 UP programs were very high. North Carolina physicians reported substantial decreases in immunization charges and reduced referrals to public clinics, but thought that UP increased their administrative burden. Sixty percent of North Carolina physicians increased charges for well-child visits, nearly twice that in the 2 control states. Families who previously had received immunizations from public clinics but chose to remain in the private-sector "medical home" for immunizations after implementation of UP had increased out-of-pocket expenses that varied by their insurance status. CONCLUSIONS: The North Carolina UP program is effective in decreasing patient immunization charges and reducing referrals to public clinics. However, UP does not eliminate cost as a barrier to immunization, nor does it enable all children to remain in their medical homes. Underinsured children still may face considerable financial barriers to immunization in a UP system.