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.

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.

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.

Older Medicare enrolees' choices for insured services.

OBJECTIVES: The Medicare Trust Fund is expected to be bankrupt in the next decade, thus threatening the viability of the Medicare Program. We have ascertained what Medicare enrollees' priorities for insured services would be, and why, if it were fiscally necessary to limit Medicare benefits to maintain the viability of the Program. DESIGN: A cross-sectional survey using anonymous, inperson interviews and an innovative instrument to elicit choices. SETTING: General Internal Medicine outpatient clinic at a university teaching hospital. PARTICIPANTS: One hundred five adults, 65 years of age and older, who had primary care physician visits between July and September 1995. MEASUREMENTS: Desire to personally select insurance benefits, insurance benefit choices, and the reasons for selection or rejection of benefits. RESULTS: Subjects of various educational and economic backgrounds were able to carry out the selection process with relative case, and four-fifths of respondents preferred to make their own choices about insured services. The most frequently selected services were hospitalization, outpatient care, prescription drugs, eye care, and home care, in descending order. Subjects selected 52 different combinations of services. Only 2% of respondents picked the current Medicare service package. The reasons given for selection varied by service; cost and current or anticipated need for a service were the most frequently cited forces driving the choices made. CONCLUSION: These data suggest that Medicare enrollees prefer some element of choice about their health insurance coverage. Their choices vary widely and differ from the current Medicare package.

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.

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.

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.

Cost-benefit analysis of safety belts in Texas school buses.

Although safety belts have been shown to reduce the risk of serious injury or death in automobile crashes, evidence of their effectiveness in school buses is uncertain. In this paper, the potential costs and benefits of mandatory safety belts in Texas school buses are estimated, based on the assumption that their effectiveness is less than or equal to rear seatbelt effectiveness in autos. Costs are based on both retrofitting old buses with belts and installing them in new buses. Benefits include the direct and indirect (forgone earnings) cost-savings from preventable injuries and fatalities. Results indicate that a law mandating safety belts in Texas school buses would not be cost-beneficial. Annual benefits would exceed the annual costs of installing belts in new school buses. However, the benefits would not be large enough to compensate for the five-year costs associated with retrofitting old buses.

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.

Sex differences in the comprehension of spatial orientation.

This research examined effects of instruction upon acquisition of Piaget's concept of horizontality and determined sex differences related to this acquisition. Hypotheses tested were that there are no significant differences (a) in performance on perception and prediction tasks, (b) by sex in the ability to comprehend horizontality, (c) by sex in the stage of development after instruction, and (d) by sex after instruction on the number of correct responses on horizontal tasks. Subjects were 18 male and 17 female rural, public school pupils ranging in age from 8 years, 0 months to 9 years, 11 months. Test instruments were a cylindrical bottle half-filled with colored water and eight pictures of bottles positioned at angles from 0 to 315 degrees at increments of 45 degrees. Chi square tests indicated that males performed significantly better than females on perception and prediction, and that instruction significantly improved male performance on prediction and female performance on prediction and perception. It was concluded that females, if given instruction, could more closely approximate the performance of males on the horizontal water level task.

Efficacy of psychoeducational interventions on pain, depression, and disability in people with arthritis: a meta-analysis.

Meta-analysis is a technique which combines data from several properly and similarly designed controlled studies so as to increase the power of the relevant statistical analysis. Fifteen studies on the effects of psychoeducational interventions on disability, pain and depression in individuals with chronic rheumatoid arthritis or osteoarthritis were analyzed by this method. The results indicate that patient education can indeed contribute to improving the health status of such patients.

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.

Changes in follow-up care for Medicare surgical patients under the prospective payment system.

In this study, changes in the number, site, and source of follow-up visits and allowed charges were examined for follow-up visits provided to Medicare surgical patients between 1984 and 1986. Among the 21 surgical procedures studied, follow-up visits decreased by 5.2%, after adjusting for case mix. Despite the physician fee freeze during the most of the study period, total allowed charges increased by 8.1%, indicating that the average intensity of visits increased by 14.0%. Inpatient visits decreased 6.7%, while outpatient visits increased 3.9%. Thus, while some substitution of outpatient for inpatient visits occurred, prospective payment system-related reductions in inpatient length of stay were associated with reductions in both the total visits and total allowed charges. Holding other factors constant, the 9.5% overall reduction in length of stay produced a 6.4% reduction in total allowed charges. The authors concluded, then, that prospective payment system had a significant effect in reducing the growth of Medicare expenditures for physician visits. The reduction in submitted claims for inpatient follow-up visits and the absence of a strong substitution effect suggest that some inpatient visits may not have been necessary. These results also raise several issues concerning Medicare's global fee for surgical procedures, and provide additional evidence in support of a uniform global fee policy under the new Medicare fee schedule.

A model for estimating the impact of changes in children's vaccines.

OBJECTIVES: To assist in strategic planning for the improvement of vaccines and vaccine programs, an economic model was developed and tested that estimates the potential impact of vaccine innovations on health outcomes and costs associated with vaccination and illness. METHODS: A multistep, iterative process of data extraction/integration was used to develop the model and the scenarios. Parameter replication, sensitivity analysis, and expert review were used to validate the model. RESULTS: The greatest impact on the improvement of health is expected to result from the production of less reactogenic vaccines that require fewer inoculations for immunity. The greatest economic impact is predicted from improvements that decrease the number of inoculations required. CONCLUSIONS: Scenario analysis may be useful for integrating health outcomes and economic data into decision making. For childhood infections, this analysis indicates that large cost savings can be achieved in the future if we can improve vaccine efficacy so that the number of required inoculations is reduced. Such an improvement represents a large potential "payback" for the United States and might benefit other countries.