Financial and economic costs of healthcare-associated infections in Africa.

BACKGROUND: Healthcare-associated infections (HAIs) remain a global health challenge, and have elevated rates in Sub-Saharan Africa. HAIs impact patients and their families by causing illness, prolonged hospital stay, potential disability, excess costs and, sometimes, death. The costs of HAIs are increasing due to spreading antimicrobial resistance. A major risk factor for HAIs is lack of water, sanitation and hygiene (WASH); environmental cleaning and healthcare waste management. In Sub-Saharan Africa, these services are lacking in at least 50% of healthcare facilities. AIM: To estimate the costs associated with HAIs at national level in 14 countries in Sub-Saharan Africa. METHODS: Economic methodologies were employed to estimate the medical costs, productivity losses and value of premature death from HAIs, drawing on national statistics and published studies to populate the economic model. RESULTS: In 2022, the number of HAIs was estimated at 4.8 million, resulting in 500,000 deaths. Health-related economic losses amounted to US$13 billion per year, equivalent to 1.14% of combined gross domestic product and US$15.7 per capita. Healthcare costs were US$500 per HAI, and represented 5.6% of total health expenditure. The costs of providing basic WASH were US$0.91 per capita, which, if they reduced HAIs by 50%, would result in benefit-cost ratios of 1.6 (financial healthcare savings alone) and 8.6 (all economic benefits). CONCLUSION: HAIs have a major health and economic burden on African societies, and a significant proportion can be prevented. It is critical that health policy makers and practitioners dedicate policy space, resources and training to address HAIs.

Results of the Avonex Combination Trial (ACT) in relapsing-remitting MS.

OBJECTIVE: To assess the safety, tolerability, and efficacy of interferon beta-1a (IFNbeta-1a) combined with methotrexate (MTX), i.v. methylprednisolone (IVMP), or both in patients with relapsing-remitting multiple sclerosis (RRMS) with continued disease activity on IFNbeta-1a monotherapy. METHODS: Eligibility criteria included RRMS, Expanded Disability Status Scale score 0-5.5, and > or = 1 relapse or gadolinium-enhancing MRI lesion in the prior year on IFNbeta-1a monotherapy. Participants continued weekly IFNbeta-1a 30 microg i.m. and were randomized in a 2 x 2 factorial design to adjunctive weekly placebo or MTX 20 mg p.o., with or without bimonthly IVMP 1,000 mg/day for 3 days. The primary endpoint was new or enlarged T2 lesion number at month 12 vs baseline. The study was industry-supported, collaboratively designed, and governed by an investigator Steering Committee with independent Advisory and Data Safety Monitoring committees. Study operations, MRI analyses, and aggregated data were managed by an academic coordinating center. RESULTS: The 313 participants had clinical and MRI characteristics typical of RRMS. Combinations of IFNbeta-1a with MTX or IVMP were generally safe and well tolerated. Although trends suggesting modest benefit were seen for some outcomes for IVMP, the results did not demonstrate significant benefit for either adjunctive therapy. The data suggested IVMP reduced anti-IFNbeta neutralizing antibody titers. CONCLUSIONS: This trial did not demonstrate benefit of adding low-dose oral methotrexate or every other month IV methylprednisolone to interferon beta-1a in relapsing-remitting multiple sclerosis.

Avonex Combination Trial in relapsing--remitting MS: rationale, design and baseline data.

OBJECTIVE: To review the rationale, design and baseline data of the Avonex Combination Trial (ACT), an investigator-run study of intramuscular interferon beta-1a (IM IFNbeta-1a) combined with methotrexate (MTX) and/or IV methylprednisolone (IVMP) in relapsing-remitting multiple sclerosis (RRMS) patients with continued disease activity on IM IFNbeta-1a monotherapy. METHODS: Eligibility criteria included RRMS, Expanded Disability Status Scale score 0-5.5, and >or=1 relapse or gadolinium-enhancing MRI lesion in the prior year while on IM IFNbeta-1a monotherapy. Subjects continued IFNbeta-1a 30 mcg IM weekly and were randomized in a 2 x 2 factorial design to adjunctive weekly placebo or MTX 20 mg PO, with or without IVMP 1,000 mg/day for three days every other month. ACT was industry-supported, and collaboratively designed and governed by an Investigator Steering Committee with independent Advisory and Data Safety Monitoring Committees. Study operations, MRI analysis and aggregated data were managed by the Cleveland Clinic MS Academic Coordinating Center. RESULTS: In total 313 subjects were enrolled with clinical and MRI characteristics typical of RRMS. Most subjects (86.9%) qualified with a clinical relapse, with or without an enhancing MRI lesion, in the preceding year. At baseline, 21.4% had enhancing lesions, and 5.1% had anti-IFNbeta neutralizing antibodies. ACT's management and operational structures functioned well. CONCLUSION: This study provides an innovative model for academic-industry collaborative MS research and will enhance understanding of the utility of combination therapy for RRMS patients with continued disease activity on an established first-line treatment.

Human herpesvirus-6 encephalitis following allogeneic hematopoietic stem cell transplantation.

Immunosuppressive monoclonal antibodies directed to immune system cells may reduce rejection and graft versus host disease (GvHD) after allogeneic stem cell transplantation (SCT), but can increase the risks of viral infection. Here, we report human herpes virus-6 (HHV-6) encephalitis despite antiviral prophylaxis in 5 of 43 (11.6%) patients receiving alemtuzumab supported conditioning. Encephalitis occurred at 41-103 days (median 60 days) presenting with confusion in all patients, combined with amnesia (n=3) or seizures (n=2). MRI revealed non-specific white matter changes in two and a non-enhancing medial temporal lobe lesion in three patients. Cerebrospinal fluid (CSF) PCR amplification for HHV-6 was positive in all five patients, (600-2 25 000 (median 4700) copies/ml CSF), while analysis of peripheral blood revealed 100-22 500 (median 1200) viral copies/ml plasma. CSF protein was elevated in four patients, with minimal CSF pleocytosis. Intravenous foscarnet produced neurological improvement at 8-13 (median 11) days and negative plasma PCR at 30-66 (median 50) days. Four patients had complete neurological recovery, but one patient with persistent viral DNA in the CSF succumbed to progressive encephalopathy. Given this high incidence of HHV-6 and the possibility of successful outcome with prompt treatment, a high index of suspicion of this disorder is required in recipients of monoclonal antibody supported allografts.

Cost-description of a pilot parenteral vaccination campaign against rabies in dogs in N'Djaména, Chad.

In the discussion about policies and strategies for rabies prevention in developing countries, intervention costs arise as a major issue. In a pilot mass vaccination campaign against rabies in N'Djaména, Chad, 3000 dogs were vaccinated. We assessed vaccination coverage and cost, showing the cost per dog vaccinated for the public sector and for society. An extrapolation to city level calculated the approximate cost of vaccinating all 23 600 dogs in N'Djaména. In the pilot mass campaign with 3000 dogs the average cost per dog was 1.69 euro. to the public and the full societal cost was 2.45 euro. If all 23 600 dogs in N'Djaména were vaccinated, the average cost would fall to 1.16 euro to the public and 1.93 euro to society. Private sector costs account for 31% of the cost to vaccinate 3000 dogs, and 40% of the cost to vaccinate 23 600 dogs. Mass dog vaccination could be a comparatively cheap and ethical way to both control the disease in animals and prevent human cases and exposure, especially in developing countries. The cost-effectiveness of dog vaccination compared with treating victims of dog bites for prevention of human rabies should be further assessed and documented.

Costs attributable to AIDS at household level in Chad.

This paper assesses the economic costs of AIDS at the household level in Chad, one of the poorest countries in the world. One hundred and ninety-three AIDS patients living in four different regions were found by case identification at hospital level and through community based organizations providing psycho-social relief. They were matched by age, sex, professional category and zone of residence with controls. Costs were evaluated through a standard questionnaire. Costs at household level attributable to AIDS up to death were US$836 per case. Costs related to productivity losses made up 28% of total costs. More than half of total costs (56%) were health care related expenditures and funeral costs contributed 16%. AIDS cases relied more often on borrowing and the selling of household assets than controls for treatment. Household expenditures of AIDS cases were much higher than control households mainly due to health related expenditure. The response of concerned families to HIV/AIDS implies high costs and for most households, especially in low-income settings, the consequences of AIDS are devastating. Innovative strategies on how best to assist households are thus requested and may include the strengthening of care and treatment services being offered to AIDS cases.

WHO antenatal care randomised trial for the evaluation of a new model of routine antenatal care.

BACKGROUND: We undertook a multicentre randomised controlled trial that compared the standard model of antenatal care with a new model that emphasises actions known to be effective in improving maternal or neonatal outcomes and has fewer clinic visits. METHODS: Clinics in Argentina, Cuba, Saudi Arabia, and Thailand were randomly allocated to provide either the new model (27 clinics) or the standard model currently in use (26 clinics). All women presenting for antenatal care at these clinics over an average of 18 months were enrolled. Women enrolled in clinics offering the new model were classified on the basis of history of obstetric and clinical conditions. Those who did not require further specific assessment or treatment were offered the basic component of the new model, and those deemed at higher risk received the usual care for their conditions; however, all were included in the new-model group for the analyses, which were by intention to treat. The primary outcomes were low birthweight (<2500 g), pre-eclampsia/eclampsia, severe postpartum anaemia (<90 g/L haemoglobin), and treated urinary-tract infection. There was an assessment of quality of care and an economic evaluation. FINDINGS: Women attending clinics assigned the new model (n=12568) had a median of five visits compared with eight within the standard model (n=11958). More women in the new model than in the standard model were referred to higher levels of care (13.4% vs 7.3%), but rates of hospital admission, diagnosis, and length of stay were similar. The groups had similar rates of low birthweight (new model 7.68% vs standard model 7.14%; stratified rate difference 0.96 [95% CI -0.01 to 1.92]), postpartum anaemia (7.59% vs 8.67%; 0.32), and urinary-tract infection (5.95% vs 7.41%; -0.42 [-1.65 to 0.80]). For pre-eclampsia/eclampsia the rate was slightly higher in the new model (1.69% vs 1.38%; 0.21 [-0.25 to 0.67]). Adjustment by several confounding variables did not modify this pattern. There were negligible differences between groups for several secondary outcomes. Women and providers in both groups were, in general, satisfied with the care received, although some women assigned the new model expressed concern about the timing of visits. There was no cost increase, and in some settings the new model decreased cost. INTERPRETATIONS: Provision of routine antenatal care by the new model seems not to affect maternal and perinatal outcomes. It could be implemented without major resistance from women and providers and may reduce cost.

Methods for economic evaluation alongside a multicentre trial in developing countries: a case study from the WHO Antenatal Care Randomised Controlled Trial.

The WHO is testing a new rationalised programme of antenatal care in a multicentre randomised trial. The motivation for this trial arose from the current uncertainty about the effectiveness of different approaches to provision of routine antenatal care. Decision makers also lack information about the costs of providing routine antenatal care and the cost-effectiveness of one programme over another. Such information will be needed before the final choice of programme can be made. The WHO trial provides an ideal opportunity to estimate and compare the incremental costs and cost-effectiveness of the new programme in four countries (Argentina, Cuba, Saudi Arabia, Thailand). A separate economic component has been organised to measure the costs of antenatal care. Methods for cost identification and measurement, and methods for economic analysis in the context of an international study are based on current recommendations for the conduct of economic evaluations alongside trials. However, several aspects require further development. In particular, this includes defining standard methods for costing in different countries; measuring women's costs of access to care; and making comparisons across international settings. The economic evaluation will also inform similar multicentre international trials and investigate issues of generalisability beyond trial settings.

PIP: Economic estimations at the technology assessment stage of health interventions permit early recognition of the relative efficiencies of health care interventions and allow those that are expensive and have limited health effects to be discouraged from widespread adoption. The World Health Organization (WHO) Antenatal Care Randomized Controlled Trial includes a component aimed at estimating the incremental costs and cost-effectiveness of a new rationalized program of prenatal care relative to those associated with the standard prenatal care package. 2400 pregnant women attending 53 clinics in Argentina, Cuba, Thailand, and Saudi Arabia have been enrolled. The central concern is that the new program of prenatal care does not result in higher overall costs to either the health care system or women receiving care than the currently practiced model. Resources included in the unit cost estimation are staff, drugs and medications, materials, equipment, vehicles, utilities, and buildings and land. Monthly costing data are being collected at all study sites in Cuba and Thailand over a 12-month period and a questionnaire has been developed to assess the costs borne by women. Data from these two sources will be collated to produce tables of costs at the health facility, country, and international levels. The reliability of the results should be enhanced by the association of the economic analysis with a carefully designed randomized trial intended to minimize bias in terms of differences in the quantities of services used.

Influence of orally administered epidermal growth factor on normal and damaged intestinal mucosa in rats.

The effect of orally administered epidermal growth factor (EGF) on the mucosal growth and hydrolase activity of normal and damaged small intestine was examined in rats. Adult rats fed EGF daily at 10 times the estimated daily intake of EGF from human milk showed increases in specific activity but not total activity of various brush-border hydrolases with unaffected mucosal protein content and villus-to-crypt ratios through day 9. Ingestion of EGF for 13 days resulted in significant decreases in mucosal protein content without changes in villus height or hydrolase activity. The effect of oral EGF on recovery of damaged intestine was studied in rats fed a liquid diet supplemented with EGF at 0, 1, 10, or 20 times the estimated daily intake from human milk after treatment with methotrexate (MTX) to induce acute intestinal injury. Animals treated with MTX showed significant reductions in body weight and small intestinal villus height, mucosal protein content, and hydrolase activities through day 6 posttreatment. Daily ingestion of EGF did not affect the MTX-induced reductions in mucosal protein content and hydrolase activity by day 3 but caused significant increases in mucosal disaccharidase and leucine aminopeptidase activity by day 6 at the 1- or 10-times human milk EGF levels. Similar changes were not observed in MTX-treated rats fed the 20-times human milk level of EGF. These studies suggest that oral EGF is capable of modulating mucosal protein levels and stimulating enterocyte hydrolase expression during repair of the intestinal mucosa.

Sensory/mixability preference evaluation of cholestyramine powder formulations.

This double-blind, crossover trial compared the sensory and product preparation characteristics of two cholestyramine powder preparations. The study involved 100 healthy volunteers, aged 22-65 (mean 42 years). Questran, a currently marketed product containing sucrose as a sweetener, was compared with Questran Light, a new formulation substituting aspartame for 90 percent of the sucrose. Comparisons were conducted with the two products mixed in water and orange juice. The subjects expressed a significant overall preference for the new formulation mixed in either water (77 percent) or orange juice (80 percent) (p less than 0.01 in both comparisons). Subjects expressed an overwhelming preference for the old product (99 percent) with respect to ease of preparation, although the ratings of the new product were generally neutral rather than negative. The new product is somewhat more difficult to prepare compared with the old cholestyramine preparation, but offers significantly increased patient acceptance based on sensory evaluations.

Sources and Content of Iodine in California Milk and Dairy Products 1.

In recent years, milk and milk products have been implicated as a major contributor to dietary iodine. The possible sources of iodine in milk are supplemental iodine in dairy feeds, iodophor-containing sanitizers used at the dairy farm and/or the processing plant, iodophor-containing teat dips used to control the spread of mastitis among dairy cows, and iodine-containing medications used by veterinarians. A five-year program to determine the California raw milk iodine concentration and identify the sources of adventitious iodine has resulted in the California dairy industry deciding late in 1980 to reduce iodine supplementation of dairy feeds. This resulted in a decrease in milk iodine concentration in samples received in 1981 to 256 ± 234 µg/kg compared to 1980, when the concentration was 474 ± 304 µg/kg. The industry has set up a program to monitor the raw milk iodine concentration at the producer level, thus ensuring that the concentration will continue to decline.

Fast-Fourier-transform holography: recent results.

A numerical method for the generation of high-quality synthetic holograms has been developed. The method is based on the fast-Fourier-transform (FFT) algorithm. Recent results are presented here in the form of high-quality reconstructions together with our FFT holographic equations.