Responding to racial and ethnic disparities in use of HIV drugs: analysis of state policies

OBJECTIVES: The objectives of this study were to assess racial/ethnic trends in surveillance data in four states--California, New York, Florida and Texas, identify structural barriers to and facilitators of access to HIV pharmaceuticals by individuals in Medicaid and the AIDS Drug Assistance Program (ADAP), and identify treatment education and outreach efforts responding to the needs of ethnic minority HIV patients. METHODS: State surveillance and claims data were used to assess trends by race/ethnicity in AIDS cases and mortality as well as participation rates in Medicaid and ADAP. Key informant interviews with state program administrators and local clinic-based benefit eligibility workers were used to identify social and policy barriers to and facilitators of access to HIV drugs and state strategies for overcoming racial/ethnic disparities. RESULTS: Racial/ethnic disparities in the reduction of AIDS-related mortality were identified in three of the four states studied. Policy barriers included Medicaid requirements for legal immigration status and residency, limits on Medicaid eligibility based on disability requirements, and state-imposed income and benefit limits on ADAP. Social barriers to accessing AIDS medications included lack of information, distrust of government, and HIV-related stigma. State strategies for overcoming disparities included contracting with community-based organizations for treatment education and outreach, the use of regional minority coordinators, and public information campaigns. CONCLUSIONS: State policies play a significant role in determining access to HIV drugs, and state policies can be used to reduce racial/ethnic disparities in pharmaceutical access. Overall, eliminating racial/ethnic disparities in access to HIV pharmaceuticals appears to be an achievable goal.     

Phase III trial of cyclophosphamide, epirubicin, fluorouracil (CEF) versus cyclophosphamide, mitoxantrone, fluorouracil (CNF) in women with metastatic breast cancer

Background: The mitoxantrone combination CNF and the epirubicin combination CEF have shown similar activity and less toxicity than the standard CAF combination in metastatic breast cancer (MBC). A prospective randomised study was started to compare safety and activity between CEF and CNF administered using a classical chemotherapeutic schedule in MBC.Patients and methods: From December 1987 to June 1993, 151 patients were randomised to receive cyclophosphamide (C) 100mgm^–2 p.o. days 1–14, fluorouracil (F) 500mgm^–2 i.v. days 1 and 8, and epirubicin (E) 30mgm^–2 i.v. days 1 and 8, or mitoxantrone (N) 6 mgm^–2 i.v. days 1 and 8, every 4 weeks. Seventythree patients were eligible for CEF and 72 for CNF.Results: Objective responses were observed in 61.6 of the CEF group and 44.4 in CNF group (p=0.004). The median duration of response was 64 weeks in CEF and 50 weeks in CNF group (p=0.02) and median time to progression was 51 and 33 weeks, respectively (p=0.0004). At the time of analysis, all except six patients (one in CNF and five in CEF) had died and the median survival time in the CEF group was longer than in CNF (74.4 weeks vs 51.4 weeks; log-rank ² test p=0.015). CNF produced more hematologic toxicity than CEF (WHO scale; grades 2–4): leucopenia 84% vs 68% (p=0.03) and trombocytopenia 17% vs 4.5% (p=0.01); CEF caused more grade 2 and 3 alopecia: 93% vs 70% (p=0.00 1).Conclusion: The combination CEF using this schedule and dosage in metastatic breast cancer is more effective with less toxicity than CNF, except for alopecia, and was associated with longer survival.     

Antibiotic resistance in Streptococcus pneumoniae in six Latin American countries: 1993-1999 surveillance

The impact of invasive pneumococcal invasive disease is increased by the emergence of antibiotic resistance. We report regional and temporal variations in antibiotic resistance for 4,105 invasive Streptococcus pneumoniae isolates collected from Latin American children <5 years, between 1993 and 1999. Reduced susceptibility to penicillin was detected in 1,182 isolates (28.8%); 36% of these were resistant (> or = 2 microg/ml), including 12.6% with MIC > or = 4 microg/ml, occurring primarily in serotypes 14 and 23F. Reduced susceptibility to third-generation cephalosporins was detected in 12.1% of the collection. Mexico had the highest proportion of reduced susceptibility to penicillin (51.6%) and to third-generation cephalosporins (22%), whereas Brazil had the lowest at 20.9% and 0.7%, respectively. Isolates cultured from patients with pneumonia were more likely to have reduced susceptibility to third-generation cephalosporins than isolates from patients with meningitis (p < 0.0001). Susceptibility to trimethoprim-sulfamethoxazole, chloramphenicol, erythromycin, and vancomycin was tested by disk diffusion for 2.899 isolates. Reduced susceptibility was observed for 45.6%, 11.5%, 6.9%, and 0%, respectively. Thirty-one percent of the strains were resistant to > or = 2 drugs. High levels of antibiotic resistance in Latin America emphasize the need for the development of and adherence to rational antibiotic use guidelines. On-going surveillance will monitor the impact of these programs.     

Boric acid susceptibility testing of non-C. albicans Candida and Saccharomyces cerevisiae: comparison of three methods.

To establish the best method for boric acid susceptibility testing, we compared two agar dilution methods (high and low inoculum) and a standard broth microdilution method (from the National Commitee for Clinical Laboratory Standards document NCCLS M-27A). Saccharomyces cerevisiae (37) and non-C. albicans Candida (39) isolates, as well as one isolate of Trichosporon sp., were included. All were isolated from female workers with vulvovaginitis. Good agreement within a fourfold dilution range was found between the three methods, and only the broth microdilution method versus the agar dilution method with high inoculum showed significant discrepancies. Reading results was easier with the broth microdilution method than with the agar dilution methods because of partial growth inhibition in the latter. In conclusion, broth microdilution is a suitable method for testing yeast susceptibility to boric acid.     

Comparison of the susceptibilities of Candida spp. to fluconazole and voriconazole in a 4-year global evaluation using disk diffusion

From June 1997 to December 2001, results of in vitro susceptibility tests of yeast isolates from 35 countries were collected. For 2001 alone, fluconazole results were reported for 22,111 yeast isolates from 77 institutions in 30 countries. Of these isolates, 18,569 were also tested for susceptibility to voriconazole. All study sites tested clinical yeast isolates by recently endorsed NCCLS disk diffusion method M44-P. Disk test plates were automatically read and results were recorded with the BIOMIC Image Analysis System. Species, drug, zone diameter, susceptibility category, MIC, and quality control results were electronically submitted by e-mail quarterly for analysis. Duplicate test results (same patient and same species with same sensitivity-resistance profile and biotype results during any 7-day period) and uncontrolled test results were eliminated from this analysis. The proportion of Candida albicans isolates decreased from 69.7% in 1997 to 1998 to 63.0% in 2001, and this decrease was accompanied by a concomitant increase in C. tropicalis and C. parapsilosis. The susceptibility (susceptible [S]or susceptible-dose dependent [S-DD]) of C. albicans isolates to fluconazole was virtually unchanged, from 99.2% in 1997 to 99% in 2001; the C. glabrata response to fluconazole was unchanged, from 81.5% S or S-DD in 1997 to 81.7% in 2001, although the percentage of resistant isolates from blood and upper respiratory tract samples appeared to increase over the study period; the percentage of S C. parapsilosis isolates decreased slightly, from 98% S or S-DD in 1997 to 96% in 2001; and the percentage of S isolates of C. tropicalis increased slightly, from 95.7% in 1997 to 96.9% in 2001. The highest rate of resistance to fluconazole among C. albicans isolates was noted in Ecuador (7.6%, n = 250). Results from this investigation indicate that the susceptibility of yeast isolates to fluconazole has changed minimally worldwide over the 4.5-year study period and that voriconazole demonstrated 10- to 100-fold greater in vitro activity than fluconazole against most yeast species.     

Effect of MALP-2, a lipopeptide from Mycoplasma fermentans, on bone resorption in vitro

Mycoplasmas may be associated with rheumatoid arthritis in various animal hosts. In humans, mycoplasma arthritis has been recorded in association with hypogammaglobulinemia. Mycoplasma fermentans is one mycoplasma species considered to be involved in causing arthritis. To clarify which mycoplasmal compounds contribute to the inflammatory, bone-destructive processes in arthritis, we used a well-defined lipopeptide, 2-kDa macrophage-activating lipopeptide (MALP-2) from M. fermentans, as an example of a class of macrophage-activating compounds ubiquitous in mycoplasmas, to study its effects on bone resorption. MALP-2 stimulated osteoclast-mediated bone resorption in murine calvaria cultures, with a maximal effect at around 2 nM. Anti-inflammatory drugs inhibited MALP-2-mediated bone resorption by about 30%. This finding suggests that MALP-2 stimulates bone resorption partially by stimulating the formation of prostaglandins. Since interleukin-6 (IL-6) stimulates bone resorption, we investigated IL-6 production in cultured calvaria. MALP-2 stimulated the liberation of IL-6, while no tumor necrosis factor was detectable. Additionally, MALP-2 stimulated low levels of NO in calvaria cultures, an effect which was strongly increased in the presence of gamma interferon, causing an inhibition of bone resorption. MALP-2 stimulated the bone-resorbing activity of osteoclasts isolated from long bones of newborn rats and cultured on dentine slices without affecting their number. In bone marrow cultures, MALP-2 inhibited the formation of osteoclasts. It appears that MALP-2 has two opposing effects: it increases the bone resorption in bone tissue by stimulation of mature osteoclasts but inhibits the formation of new ones.     

Spectrum of Mutations in the CFTR Gene in Cystic Fibrosis Patients of Spanish Ancestry

We analyzed 1,954 Spanish cystic fibrosis (CF) alleles in order to define the molecular spectrum of mutations in the CFTR gene in Spanish CF patients. Commercial panels showed a limited detection power, leading to the identification of only 76% of alleles. Two scanning techniques, denaturing gradient gel electrophoresis (DGGE) and single strand conformation polymorphism/hetroduplex (SSCP/HD), were carried out to detect CFTR sequence changes. In addition, intragenic markers IVS8CA, IVS8-6(T)n and IVS17bTA were also analyzed. Twelve mutations showed frequencies above 1%, p.F508del being the most frequent mutation (51%). We found that eighteen mutations need to be studied to achieve a detection level of 80%. Fifty-one mutations (42%) were observed once. In total, 121 disease-causing mutations were identified, accounting for 96% (1,877 out of 1,954) of CF alleles. Specific geographic distributions for the most common mutations, p.F508del, p.G542X, c.1811 + 1.6kbA > G and c.1609delCA, were confirmed. Furthermore, two other relatively common mutations (p.V232D and c.2789 + 5G > A) showed uneven geographic distributions. This updated information on the spectrum of CF mutations in Spain will be useful for improving genetic testing, as well as to facilitate counselling in people of Spanish ancestry. In addition, this study contributes to defining the molecular spectrum of CF in Europe, and corroborates the high molecular mutation heterogeneity of Mediterranean populations.     

Are routine cranial ultrasounds necessary in premature infants greater than 30 weeks gestation?

The purpose of this study was to validate the recommendation of the American Academy of Neurology and the Child Neurology Society that screening cranial ultrasonography be performed routinely on all infants of less than 30 weeks gestation at 7 to 14 days of age and again between 36 and 40 weeks postmenstrual age, and, by using this practice parameter, to determine the number of babies with a clinically significant abnormal screening cranial ultrasound (US) who would otherwise have been missed. A retrospective study of 486 infants of 30 to 33 weeks gestation born January 1, 1999 to June 30, 2004 was done. All had screening cranial ultrasounds. Grade III and/or grade IV intraventricular hemorrhage (IVH) occurred in 4 (0.8%) infants of 30 to 31 weeks gestation. Infants with significant IVH had either risk factors for brain injury or symptoms that would eventually warrant US during their hospitalization. Seven (1.4%) infants had periventricular leukomalacia (PVL). All infants with a final diagnosis of PVL had pre- and/or perinatal risk factors associated with PVL. There was a significant trend toward fewer abnormal cranial ultrasounds from 30 to 33 weeks gestation (p=0.04). Our study supports the recommendation by the American Academy of Neurology and the Child Neurology Society that screening US can be limited but suggests that the gestational age cut off should be 30 weeks or less.     

Lipid abnormalities in stable liver transplant recipients – effects of cyclosporin, tacrolimus, and steroids

Dyslipidemia is common after liver transplantation, but the underlying mechanisms are largely unknown. We studied the lipid profile of 27 liver transplant recipients randomized to receive either cyclosporin (CyA, n = 14) or tacrolimus (n = 13) and compared them with 20 healthy, matched controls. Before transplantation, patients presented low total and low-density lipoprotein (LDL) cholesterol (as compared to controls) that increased shortly, i. e., 3 months, after transplantation. Eighteen months post-transplantation, total and LDL cholesterol levels decreased to pretransplant values but tended to remain higher in CyA-treated patients. However, at that time, prednisone treatment was more prevalent among CyA-treated than tacrolimus-treated patients and fully accounted for the difference in cholesterol levels. Indeed, regardless of therapy, patients not receiving prednisone exhibited lower cholesterol levels than prednisone-treated patients and controls. We conclude that prednisone therapy, rather than CyA or tacrolimus immunosuppression, seems to be the major determinant of increased cholesterol levels. Received: 19 June 1997 Received after revision: 24 October 1997 Accepted: 10 November 1997