Cutting the cost of South African antiretroviral therapy using newer, safer drugs.

Antiretrovirals are a significant cost driver for HIV programmes. Current first-line regimens have performed well in real-life programmes, but have a low barrier to virological resistance and still carry toxicity that limits adherence. New drug developments may mean that we have access to safer, more robust and cheaper regimens, but only if the appropriate clinical trials are conducted. We briefly discuss these trials, and demonstrate the large cost savings to the South African HIV programme if these are successful.

Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study.

BACKGROUND: Osteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. We aimed to identify genetic loci that are associated with bone mineral density. METHODS: In this genome-wide association study, we identified the most promising of 314 075 single nucleotide polymorphisms (SNPs) in 2094 women in a UK study. We then tested these SNPs for replication in 6463 people from three other cohorts in western Europe. We also investigated allelic expression in lymphoblast cell lines. We tested the association between the replicated SNPs and osteoporotic fractures with data from two studies. FINDINGS: We identified genome-wide evidence for an association between bone mineral density and two SNPs (p<5x10(-8)). The SNPs were rs4355801, on chromosome 8, near to the TNFRSF11B (osteoprotegerin) gene, and rs3736228, on chromosome 11 in the LRP5 (lipoprotein-receptor-related protein) gene. A non-synonymous SNP in the LRP5 gene was associated with decreased bone mineral density (rs3736228, p=6.3x10(-12) for lumbar spine and p=1.9x10(-4) for femoral neck) and an increased risk of both osteoporotic fractures (odds ratio [OR] 1.3, 95% CI 1.09-1.52, p=0.002) and osteoporosis (OR 1.3, 1.08-1.63, p=0.008). Three SNPs near the TNFRSF11B gene were associated with decreased bone mineral density (top SNP, rs4355801: p=7.6x10(-10) for lumbar spine and p=3.3x10(-8) for femoral neck) and increased risk of osteoporosis (OR 1.2, 95% CI 1.01-1.42, p=0.038). For carriers of the risk allele at rs4355801, expression of TNFRSF11B in lymphoblast cell lines was halved (p=3.0x10(-6)). 1883 (22%) of 8557 people were at least heterozygous for these risk alleles, and these alleles had a cumulative association with bone mineral density (trend p=2.3x10(-17)). The presence of both risk alleles increased the risk of osteoporotic fractures (OR 1.3, 1.08-1.63, p=0.006) and this effect was independent of bone mineral density. INTERPRETATION: Two gene variants of key biological proteins increase the risk of osteoporosis and osteoporotic fracture. The combined effect of these risk alleles on fractures is similar to that of most well-replicated environmental risk factors, and they are present in more than one in five white people, suggesting a potential role in screening.

Molecular portrait of the progestagenic and estrogenic actions of tibolone: behavior of cellular networks in response to tibolone.

Tibolone is a synthetic steroid with estrogenic effects on brain, vagina, and bone without stimulating the endometrium. During tibolone treatment, it is thought that the progestagenic properties of tibolone stimulate cell differentiation, which effectively counterbalances the growth-stimulating effects of the estrogenic properties of tibolone. The objective of this study was to characterize the expression profile that reflects the endometrial responses to the separated estrogenic (growth-inducing) and progestagenic (growth-inhibiting) actions of tibolone, thus gaining insight into the counteracting effect of these properties of tibolone on the endometrium. The estrogenic action of tibolone was studied in the estrogen-responsive ECC1 cell line (expressing estrogen receptor alpha), and the progestagenic action was studied in the progesterone-responsive cell line Ishikawa PRAB-36 (expressing PRA and PRB). The data showed that the progestagenic and estrogenic effects of tibolone produce different expression profiles with a narrow overlap in genes; however, both properties modulate the same biological processes. The final genetic network analysis indicated that the estrogenic effect of tibolone is potentially counterbalanced by the progestagenic metabolite of tibolone via differential regulation of similar cellular processes. For example, both progestagenic and estrogenic properties stimulate proliferation, but they exert the opposite effect on apoptosis. The apoptosis network was stimulated by the progestagenic properties of tibolone; in contrast, the estrogenic effect of tibolone suppressed the apoptosis network. The current results indicate that this differential regulation is realized through modulation of a different group of genes and rarely via contraregulation of the same set of genes.

Carbohydrate craving by alcohol-dependent men during sobriety: relationship to nutrition and serotonergic function.

BACKGROUND: Several studies report reduced serotonin (5HT) in alcohol-dependent subjects. Furthermore, alcohol increases 5HT in animals. Thus, alcohol dependence may be an attempt to self-medicate reduced 5HT. Relevant to this, reducing 5HT increases carbohydrate intake, and several studies report increased carbohydrate intake in alcohol-dependent subjects. Like alcohol, carbohydrate increases 5HT. We hypothesized that a subgroup of the alcohol-dependent population self-medicates reduced 5HT with alcohol and alternatively with carbohydrate when not drinking. METHODS: Three groups were recruited: a high carbohydrate craving alcohol-dependent group (n = 10), a low carbohydrate craving alcohol-dependent group (n = 11), and a nonaddicted control group (n = 12). All groups were placed on a high-carbohydrate, low-protein diet for 2 days and then a high-protein, low-carbohydrate diet for 2 days. The effects of diet on mood, alcohol craving, stress, and 5HT were measured. RESULTS: Although both alcohol-dependent groups had similar alcohol cravings at baseline, only the carbohydrate-craving alcohol-dependent group craved alcohol significantly more when under the stress of the research protocol. The carbohydrate-craving alcohol-dependent subjects presented with distinct personality disorders and were uniquely sensitive to the adverse effects of carbohydrate on mood. Diet had a unique effect on 5HT in the high carbohydrate craving alcohol-dependent group. The results of platelet 5HT uptake demonstrated that the high-protein, low-carbohydrate diet significantly increased Km values of high carbohydrate craving alcohol-dependent subjects, whereas it reduced the Km values of both non-carbohydrate-craving alcohol-dependent subjects and nonaddicted controls. CONCLUSION: Carbohydrate-craving alcohol-dependent subjects are a distinct subgroup of the alcohol-dependent population.

Reusable biopsy forceps: a cost-effective measure for the endoscopy suite.

Some healthcare practitioners have recommended the use of disposable medical accessories as standard practice. Advantages of using disposable medical equipment include the potential for infection prevention, convenience, and decreased reprocessing and storage costs. Disadvantages of reusable accessories include the initial cost, "down time" required for repair and, most importantly, the potential for spreading infection. In this study, the investigators provide a cost analysis of reusable biopsy forceps for a 12-month period from April 1993 through March 1994. This prospective, descriptive study evaluated purchase price, number of uses, repair history, and cleaning costs for reusable biopsy forceps used in the endoscopy unit of a large multi-specialty clinic. Results of the study revealed that the reusable biopsy forceps became cost-effective after seven uses.

The impact of OSHA regulations on nursing care cost and compliance.

The Occupational Safety and Health Administration (OSHA) requires health care facilities to protect employees from bloodborne pathogens. One of the mandates is to provide personal protective equipment (PPE) to employees at no cost to the employee. In this article, the authors explore the cost and compliance of implementing the new OSHA regulations for nursing staff assisting with colonoscopies over a 6-month period. The data were collected on a total of 461 procedures. The cost of implementing PPE for the nursing staff was $2.98 per procedure. The PPE available for the nursing staff included goggles, splash-proof gown, face mask, shoe covers, and latex gloves. The total cost of implementing the new regulations for the nursing staff assisting with colonoscopies was $2,747.56 and was projected to cost approximately $50,000 yearly if implemented for all GI procedures in the institution. Staff compliance rates for the five pieces of PPE ranged from 6.5 to 97.8%.

The impact of disposable equipment on room fee reimbursement for endoscopic retrograde cholangiopancreatography.

Disposable equipment is widely used in many gastroenterologic procedures. Such equipment decreases risks of cross contamination, is convenient, and decreases the processing, storage, and cost of reusable equipment. However, disposable equipment has a far-reaching environmental impact. Most disposable equipment must be handled as infectious waste. Moreover, cumulative costs associated with disposable equipment may be quite high. In this study, the authors attempted to delineate the percentage of room fee reimbursement spent on disposable equipment. The procedure selected for the study was Endoscopic Retrograde Cholangiopancreatography (ERCP). Two hundred forty-eight procedures were surveyed over a 6-month period between September 1992 and February 1993, and the total cost of each procedure was calculated. Reimbursement figures for diagnostic and therapeutic ERCPs were obtained for Medicare, contracted providers, and private payors. The percentage of room fee reimbursement monies used for disposable equipment for diagnostic ERCPs ranged from 5.8 to 12.8%. For disposable equipment in therapeutic ERCPs the percentage of room fee reimbursement monies ranged from 40.5 to 59.7%. Combining both diagnostic and therapeutic ERCPs, the percentage of room fee reimbursement to defray the cost of disposable equipment was 42.4%. Disposable equipment costs are a large portion of the room fee reimbursement. leaving potentially inadequate revenues for salaries, general upkeep of equipment, and capital to buy new or replace aging equipment.