Implementer-initiated adaptation of evidence-based interventions: kids remember the blue wig.

Adaptation of evidence-based interventions by implementers is widespread. Although frequently viewed as departures from fidelity, adaptations may be positive in impact and consistent with fidelity. Research typically catalogs adaptations but rarely includes the implementers' perspectives on adaptation. We report data on individuals implementing an evidence-based teen dating violence prevention curriculum. Key informant interviews (n = 20) and an online focus group (n = 10) addressed reasons for adaptations, adaptation processes and kinds of adaptations. All implementers described making adaptations, which they considered necessary to achieving intended outcomes. Adaptations were tailored to needs of individual students or learning opportunities presented by current events, fine-tuned over repeated applications and shared with colleagues. Adaptations modified both content and delivery and included both planned and in-the-moment changes. Implementers made adaptations to increase student engagement, and to fit students' learning needs, learning style, social maturity and culture. Student engagement served as an indicator that adaptation might be needed and provided feedback about the immediate effects of the adaptation. These findings underscore the value of fidelity assessments that measure participant response, intervention-specific guidance to implementers and evaluation of the impact of adaptations on participant response and intervention outcomes.

Measuring performance in child welfare: secondary effects of success.

The Adoption and Safe Families Act of 1997 mandates the development of a system to rate the performance of state child welfare programs. The resulting system, built on broader efforts to measure outcomes for children and families who receive support and services from the child welfare system, will inform perspectives on family foster care in the next century. Drawing on findings from evaluations of recent reform initiatives in Alabama, North Carolina, and Ohio, this article suggests that performance measurement systems must be adaptable to changing circumstances, particularly when improvements in one area can affect standards and expectations in others.

Consumer perspectives on information needs for health plan choice.

The premise that competition will improve health care assumes that consumers will choose plans that best fit their needs and resources. However, many consumers are frustrated with currently available plan comparison information. We describe results from 22 focus groups in which Medicare beneficiaries, Medicaid enrollees, and privately insured consumers assessed the usefulness of indicators based on consumer survey data and Health Employer Data Information Set (HEDIS)-type measures of quality of care. Considerable education would be required before consumers could interpret report card data to inform plan choices. Policy implications for design and provision of plan information for Medicare beneficiaries and Medicaid enrollees are discussed.

Paid advertising for AIDS prevention--would the ends justify the means?

An examination by the Centers for Disease Control and the Research Triangle Institute concluded that "hard-to-reach" populations could be reached with AIDS prevention messages through the broadcast and print media and that a study should be undertaken to assess whether paid placement of these messages could have an effect on HIV-related behaviors. The recommended target population for a study of paid advertising would be sexually active 18-24-year-old black urban dwellers. Its behavioral objectives would include abstinence and safer sex practices. For any evaluation of a paid advertising campaign to be valid, there would have to be extensive audience profiling, research into the development of the message, pretesting of the message, and involvement of the community. The proposed study would include measurement of various "dosage" levels of paid advertising, use of a no-intervention comparison group, and a novel data collection technique. Although a specific target group and specific messages would be involved, the evaluation would make a substantial contribution to resolving the broader issue of whether and how mass media should be used directly or indirectly to change or reinforce health-related behaviors.

Identification of 17 independent mutations responsible for human hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency.

Complete hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency causes the Lesch-Nyhan syndrome, an X-linked, purine metabolism disorder manifested by hyperuricemia, hyperuricaciduria, and neurologic dysfunction. Partial HPRT deficiency causes hyperuricemia and gout. One requirement for understanding the molecular basis of HPRT deficiency is the determination of which amino acids in this salvage enzyme are necessary for structural or catalytic competence. In this study we have used the PCR coupled with direct sequencing to determine the nucleotide and subsequent amino acid changes in 22 subjects representing 17 unrelated kindreds from the United Kingdom. These mutations were confirmed by using either RNase mapping or Southern analyses. In addition, experiments were done to determine enzyme activity and electrophoretic mobility, and predictive paradigms were used to study the impact of these amino acid substitutions on secondary structure.

Low arylsulphatase A activity and choreoathetotic syndrome in three siblings: differentiation of pseudodeficiency from metachromatic leukodystrophy.

We report on a family with a sibship of three children for whom the diagnosis of "an unusual form of metachromatic leukodystrophy (MLD)" had been suggested earlier. The patients had choreiform movements and dystonic posturing accompanied by dysarthria since childhood. The availability of the polymerase chain reaction enabled us to show that the three siblings have a pseudodeficiency genotype (ASAp/ASAp). There was no abnormal sulphatiduria, and we propose that the neurological disease and low arylsulphatase A activity are unrelated to one another in this family. A diagnosis of MLD carries very serious implications, and we recommend that gene amplification by polymerase chain reaction and hybridization with allele-specific oligonucleotide probes should be used to corroborate the diagnosis, especially when there is no abnormal sulphatiduria and when metachromatic material cannot be demonstrated in a sural nerve biopsy.

Populations at increased risk of HIV infection: current knowledge and limitations.

Research data describing the prevalence and patterns of behaviors that place persons at increased risk of HIV infection are extremely limited. The scarcity of data has constrained potential applications of surveillance data, research on specific high-risk behaviors, and epidemiological studies. This article critically reviews available research for four population groups: intravenous drug users, homosexual males, and sexually active adolescents and adults. The fallacies inherent in estimating risk group size underscore the need for population-based research that can provide detailed data on sexual and drug use behaviors.

Human B cell growth factor enhances proliferation and glial fibrillary acidic protein gene expression in rat astrocytes.

The proliferation and differentiation of astrocytes are fundamental events in the normal development and function of the central nervous system (CNS), and may also contribute to the pathogenesis of a number of neurological diseases. Products of T lymphocytes can stimulate proliferation of astrocytes, but the nature of the T lymphocyte-derived molecule(s) responsible for this response is unknown. The present study was undertaken to examine several well-characterized T lymphocyte-derived factors for their ability to stimulate cultured primary rat astrocytes. While recombinant human interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6), and rat or human recombinant interferon-gamma (IFN-gamma) have no proliferative effect on astrocytes, a human T cell-derived B cell growth factor (BCGF) does. This BCGF, termed 2B11, had previously been characterized by its ability to enhance the proliferation of anti-mu-stimulated human B cells, while not influencing B cell immunoglobulin synthesis. High performance liquid chromatography (HPLC)-purified 2B11-BCGF (MW approximately 20,000 daltons) stimulates the proliferation of astrocytes in a dose-dependent fashion. Purified 2B11-BCGF also induced morphological differentiation and increased mRNA transcripts for glial fibrillary acidic protein (GFAP) in rat astrocytes. In addition to demonstrating the absence of effect of other known lymphokines, the effect on astrocytes attributed to 2B11-BCGF was confirmed by blocking its activity with a monoclonal antibody specific for 2B11-BCGF. Absorption experiments demonstrated that when BCGF activity was absorbed out by large, activated human B cells, astrocyte-stimulatory activity was also depleted. Rat astrocytes were able to partially absorb out both BCGF and astrocyte-stimulatory activity. These results suggest that 2B11-BCGF is responsible for stimulating astrocyte proliferation, and that human B cells and rat astrocytes may share a similar receptor for BCGF. These findings indicate that the growth and differentiation of astrocytes can be influenced by a T cell-derived lymphokine, 2B11-BCGF, whose activity thus far appears to be distinct from other reported cytokines.

First-trimester diagnosis of Lesch-Nyhan syndrome.

Chorionic villi were sampled at 8-9 weeks' gestation in four women whose fetuses were at risk for Lesch-Nyhan syndrome. Radiochemical assay of hypoxanthine phosphoribosyl transferase activity and fetal sexing (in two fetuses by means of a Y chromosome specific cDNA probe) showed that three fetuses were affected. The biochemical findings were confirmed after therapeutic abortion in two cases and spontaneous abortion in the third. Chorion biopsy and ultramicroscale enzymology may be a suitable alternative to recombinant-DNA-based methods for first-trimester diagnosis in selected diseases where the abnormal gene product is an enzyme expressed in the chorion by the 8th week of pregnancy.

Studies on the composition of urinary glycosaminoglycans and oligosaccharides in patients with mucopolysaccharidoses who were receiving fibroblast transplants.

This communication reports studies on the composition of the urinary glycosaminoglycans and oligosaccharides in mucopolysaccharidosis patients who were being treated by fibroblast transplantation. The urinary glycosaminoglycans were precipitated with 9-aminoacridine, the oligosaccharides remaining in solution. Both fractions were further subfractionated by gel filtration. The glycosaminoglycan subfractions were examined for their content of iduronic acid, glucuronic acid, galactosamine and glucosamine. We found no changes in these parameters in a patient who had been treated by repeated fibroblast transplantations over the course of 4 1/2 years. The amino sugar composition of the oligosaccharide fraction was examined and shown to be unchanged. We also found no changes in the degree of sulphation of the urinary glycosaminoglycans specifically related to the transplant in four patients with Hurler disease and two with Hunter disease. We conclude that fibroblast transplantation does not produce detectable changes in the carbohydrate content or degree of sulphation of the urinary glycosaminoglycans and oligosaccharides.

Biochemical and histopathological studies on patients with mucopolysaccharidoses, two of whom had been treated by fibroblast transplantation.

Biochemical and pathological observations on tissues from two patients with Hurler disease (mucopolysaccharidosis IH; alpha-L-iduronidase deficiency) who had been treated by fibroblast transplants as a means of enzyme replacement treatment are reported. These results and those obtained in three surgical specimens [ligamentum flavum with dura mater from a case of Scheie disease (mucopolysaccharidosis IS; alpha-L-iduronidase deficiency); a fetus with Hurler disease; and tonsil from a patient with Hunter disease (mucopolysaccharidosis II; alpha-L-idurono-2-sulphate sulphatase deficiency)] illustrate the inadequacy of routine histological processing to demonstrate the abnormal glycosaminoglycan accumulation in this group of diseases. A combined approach using histochemistry and electron microscopy enables the extent of both extracellular and intracellular involvement to be assessed. The fetus (20 wk gestation) already showed evidence of Hurler disease. The pathological appearances in both of the fibroblast-transplanted patients were those which would have been expected in patients dying with unmodified Hurler disease. There was no detectable alpha-L-iduronidase activity in the brain, liver, kidney or in fibroblasts cultured from either the transplantation sites or from remote subcutaneous sites in either of the transplanted patients. These results are discussed from the viewpoint of their bearing on the pathophysiology of the mucopolysaccharidoses and proposals for their treatment by enzyme replacement.

A clinical trial of fibroblast transplantation for the treatment of mucopolysaccharidoses.

This paper reports the clinical and biochemical results in six patients with Hurler disease (Mucopolysaccharidosis IH; McKusick 25280), two patients with Hunter disease (Mucopolysaccharidosis II; McKusick 25285) and one patient with Sanfilippo B disease (Mucopolysaccharidosis IIIB; McKusick 25292) who were treated by fibroblast transplantation. Except for one patient who died for a coincidental reason, the patients have been studied for between 2.5 and 4.5 years. The clinical course of the disease was not materially altered. There was no evidence that the patients had developed immune responses against the transplanted fibroblasts. Transplantation did not produce measurable levels of either alpha-L-iduronidase (EC 3.2.1.76) in the leukocytes from patients with Hurler disease or of N-acetyl-alpha-D-glucosaminidase (EC 3.2.1.50) in the plasma of the patients with Sanfilippo B disease. Under the conditions used for the assay, leukocytes from the patients with Hunter disease had detectable levels of residual alpha-L-idurono-2-sulphate sulphatase activity which were increased after the transplants, although these changes were of inconstant size and their time course was not consistently related to the transplantations. Cytogenetic studies in cases where the donor was of the opposite sex detected only cells of the recipient's sex among the fibroblasts grown from biopsies of the transplantation sites. The technique used would have detected a donor to recipient cell ratio of 1:100. We found no consistent long-term trends in the excretion patterns of glycosaminoglycans and oligosaccharides from either a quantitative or qualitative point of view which could be specifically related to the transplantation. The combined administration of immunosuppressive doses of prednisolone and azathioprine was associated with an increased excretion of the lower molecular weight glycosaminoglycans. We conclude that fibroblast transplantation is not therapeutically useful in the diseases studied.