A pharmacoeconomic comparison of antithymocyte globulin and muromonab CD3 induction therapy in renal transplant recipients

Antithymocyte globulin (ATG) and muromonab CD3 (OKT3) are currently the only antilymphocyte preparations that are commercially available for induction immunosuppressive therapy for renal allograft transplantation in the US. ATG, in the usually prescribed doses, is more expensive than muromonab CD3, but muromonab CD3 is associated with more severe adverse effects that may affect clinical outcome and overall cost. We performed a retrospective study of all adult recipients of a first cadaveric renal allograft, who underwent transplantation between January 1991 and December 1994 who received either ATG (n = 92) or muromonab CD3 (n = 91) for induction therapy at our transplant centre. The average age of recipients was older (50 vs 44 yrs; p = 0.001) and extended donors were more commonly used in the ATG group (41 vs 13%; p = 0.0001) compared with the muromonab CD3 group. Nevertheless, at 1 year post-transplant, the incidence of rejection was lower (34 vs 47%) and graft survival was better (93 vs 85%; p = 0.03) in the ATG group. Patients who received ATG were discharged earlier (9.4 vs 13.3 days; p = 0.0001) and had similar serum creatinine levels on the day of discharge (2.4 +/- 1.5 vs 2.1 +/- 1.1 mg/dl; p = 0.25). Overall, the 1-year hospitalisation costs of transplantation and readmissions were similar [$US39,937 +/- 17,014 vs $US42,850 +/- 20,923 (currency year 1994); p = 0.22]. This is the first comparison of ATG and muromonab CD3 in renal transplant recipients to consider clinical as well as economic outcomes. For renal transplant patients in whom induction therapy is used at our centre, the initial expense of ATG can be justified by improved graft survival, fewer rejection episodes, and shorter hospital stays, which are associated with similar overall transplantation costs.     

Assessing and planning home-based care for persons with AIDS

The HIV/AIDS pandemic continues to gather momentum in many developing countries, increasing the already heavy burden on health care facilities. As a result, donors, implementing partners and communities are beginning to create home-based care programmes to provide care for persons with HIV/AIDS. This paper recommends reorienting this home care provision as a service founded in, and coming from, the community rather than the health system. A methodology, in the form of an assessment matrix, is provided to facilitate the assessment of a community's capacity to provide care for people with AIDS. The focus is on rapid assessment methods using, where possible, readily available information to clearly and systematically define current circumstances. The matrix created for a specific community is then used in the development of an action plan with interventions prioritized and tailored to local needs. A case study from a hypothetical developing country, where HIV/AIDS is a significant problem, is used to illustrate the process.     

The Health Security Act and improving the quality of care: will the Clinton reforms help or hinder?

Maintaining and improving the quality of care is central to the Health Security Act, according to this in-depth analysis of the Act's intended quality reforms. The author reviews the proposal from several perspectives, including those of administrative law, hospital administration, health services research, and risk management. In the author's opinion, quality reforms involving the federal government as purchaser of medical care and as grader of the quality of its health care providers require close scrutiny. The establishment of a National Health Board and a National Quality Management Council further heightens concerns for quality standards and oversight. The article also evaluates the proposed health quality data super-highway, making several stops for contemplation and critical analysis.     

Variation in dental service provision among adult migrant public-funded patients

OBJECTIVE: To examine type of care, oral health status and service patterns by country of birth and language. METHODS: A random sample of public-funded patients (n = 6, 109) was surveyed in 1995-96. RESULTS: Emergency care was highest among overseas-born patients who spoke a non-English language at home; edentulism was highest among Australian-born/English only patients; while a higher percentage of Australian-born persons were in the periodontal health category (chi 2; p < 0.05). Differences in caries experience were generally small (ANOVA; p < 0.05). Service provision varied by country of birth/language after controlling for socio-demographic characteristics, type of care, and oral health status in six service areas (logistic regression; p < 0.05). CONCLUSIONS: Service patterns may reflect behavioural and cultural factors of patients or providers operating independently of socio-demographic and oral health status variables. IMPLICATIONS: Variation and potential inequality in service patterns related to cultural factors existed within a group of disadvantaged patients.     

Pathologic features of prognostic significance for adrenocortical carcinoma after curative resection

OBJECTIVE: To identify the pathologic features of prognostic significance in patients with resectable adrenocortical carcinomas. DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Review of the Memorial Sloan-Kettering Cancer Center prospective adrenocortical carcinoma database from 1986 through 1996 identified 46 patients who underwent curative adrenalectomy for primary disease. All cases were reviewed by a single pathologist and each primary tumor was characterized by 16 separate pathologic parameters. MAIN OUTCOME MEASURE: Overall survival rates in the patient population. RESULTS: The 5-year overall survival rate for the entire cohort was 36% (median survival rate, 28 months). Of the pathologic factors analyzed, tumor size, number of mitotic figures, and the presence of intratumoral hemorrhage were independent prognostic factors. Patients presenting with primary tumors larger than 12 cm (n = 30) had a worse outcome compared with those with smaller tumors (n = 16) (5-year survival rate: 53% vs. 22%, P<.05). Mitotic count (> or =6 per 10 high-power fields) was a negative prognostic feature (n = 15) with a 5-year survival rate of 13% vs. 51% for 0 to 6 mitotic figures per 10 highpower fields (n = 31, P<.05). Intratumoral hemorrhage (n = 23) was also a negative prognostic factor compared with no evidence of intratumoral hemorrhage (n = 23) (5-year survival rate, 53% vs. 22%, P<.05). Overall survival rates were also calculated based on the number of pathologic risk factors. Patients with no risk factors had an 83% 5-year survival rate, which decreased to 42% with 1 factor, 33% with 2 factors, and 0% with all 3 risk factors. CONCLUSIONS: Tumor size, hemorrhage, and mitotic count correlate with survival rates for patients undergoing curative resection. Based on these pathologic factors, adrenocortical carcinomas may be divided into low- and high-risk groups.     

Erbium filtration: a cost-effective, dose-reducing filter which maintains abdominal image quality

The current study investigated the effect of erbium filtration on an anteroposterior abdominal image. The radiation dose reductions achieveable and the costeffectiveness of this filter were also evaluated. An assessment of the radiation dose delivered employing either the standard total filtration (3 mm Al equivalent) or 0.1 mm of erbium filtration added to the standard filtration was undertaken on 21 patients. Image quality was assessed using the Commission of European Communities (CEC) criteria. Significant reductions of 64.6 % in entrance surface (p = 0.0001) and 23.4 % in effective dose (p = 0.0099) were recorded with erbium filtration. Image quality was maintained and the cost per manSievert saved was ￡ 128. More widespread use of this dose reducing filter is advocated. Received: 7 August 1998; Revised: 19 February 1999; Accepted: 19 April 1999     

Isolation and characterization of the mouse homolog of the preprodynorphin (Pdyn) gene

We have isolated and sequenced the mouse preprodynorphin gene (Pdyn). The Pdyn gene can encode for six biologically active dynorphin peptides. The predicted mouse preprodynorphin has 90%, 67%, and 66% identity with the predicted rat, porcine, and human preprodynorphins, respectively. Using an RT-PCR technique, we show that the Pdyn gene starts being expressed at embryonic day 12.5, with a steep increase of expression by embryonic day 14.5; in the adult mouse it is expressed in the brain, but not in liver, heart, spleen, or kidney.     

FK506-associated thrombotic microangiopathy: report of two cases and review of the literature

BACKGROUND: FK506 is a recently developed immunosuppressant that has been useful in improving the survival of transplanted organs. Among the numerous adverse side effects of FK506, thrombotic microangiopathy (TMA) stands out as an infrequent but severe complication. METHODS: We report two cases of FK506-associated TMA and review the 19 previous reported cases. RESULTS: From these 21 cases, the reported incidence of FK506-associated TMA is between 1% and 4.7%. It is more frequent in females, and the mean age at presentation is 47 years. Eighty-one percent of the cases occurred in patients with kidney allografts, and the remaining patients had liver, heart, or bone marrow transplants. Clinically, TMA was diagnosed at an average interval of 9.3 months from the time of transplantation. Patients may be asymptomatic or may present with the full-blown picture of hemolytic uremic syndrome. All patients had an elevated serum creatinine level but did not always show signs of hemolysis. Trough levels of FK506 were not predictive for the development of TMA, but generally a reduction of drug dose correlated with kidney function improvement and disappearance of the hemolytic picture. The renal allograft biopsy provided a conclusive diagnosis in all 17 cases in which this procedure was performed. Treatment, which mainly consisted of reduction or discontinuation of FK506, anticoagulation, and/or plasmapheresis with fresh-frozen plasma exchange, resolved TMA in most patients (57%). However, in one of these patients (5%), the graft was subsequently lost due to causes unrelated to TMA, such as acute or chronic rejection. Despite treatment, one patient (5%) lost the graft due to acute rejection and persistent TMA, and three other patients (14%) who had bone marrow, heart, and liver transplants, died of multiple organ failure, probably unrelated to TMA. In the remaining four patients (19%), response to treatment was not reported. CONCLUSIONS: TMA must be considered in organ transplant patients treated with FK506 whenever kidney function deteriorates, even in the absence of microangiopathic hemolytic anemia. Although TMA usually responds to treatment, it may, in rare cases, lead to loss of kidney function or even the patient's death.     

Immunogenicity of peptides derived from a fibronectin-binding protein of S. aureus expressed on two different plant viruses

The D2 peptide derived from an S. aureus fibronectin-binding protein (FnBP) was expressed on the surface of the icosahedral cowpea mosaic virus (amino acids 1-30 of D2) or on the rod-shaped potato virus X (amino acids 1-38 of D2), termed CPMV-MAST1 and PVX-MAST8, respectively. Mice and rats were immunized subcutaneously with CPMV-MAST1 and mice with PVX-MAST8 in adjuvant and high titres of FnBP-specific antibody were obtained. The mouse IgG was predominantly of the IgG2a and IgG2b isotypes, which strongly bound complement component C1q, suggesting a TH1-bias in the peptide-specific responses. Sera from mice and rats immunized with CPMV-MAST1 and from mice immunized with PVX-MAST8 were shown to completely inhibit the binding of fibronectin to immobilised recombinant FnBP and rat sera against CPMV-MAST1 were able to block adherence of S. aureus to fibronectin. These studies demonstrate that the D2 peptide is highly immunogenic when expressed on 2 different plant viruses and highlight the potential of plant virus-based vaccines to protect against S. aureus infections.