17 research outputs found
Hearing Aid Patients in Private Practice and Public Health (Veterans Affairs) Clinics: Are They Different?
Objective: In hearing aid research, it is commonplace to combine data across subjects whose hearing aids were provided in different service delivery models. There is reason to question whether these types of patients are always similar enough to justify this practice. To explore this matter, this investigation evaluated similarities and differences in self-report data obtained from hearing aid patients derived from public health (Veterans Affairs, VA) and private practice (PP) settings. Design: The study was a multisite, cross-sectional survey in which 230 hearing aid patients from VA and PP audiology clinic settings provided self-report data on a collection of questionnaires both before and after the hearing aid fitting. Subjects were all older adults with mild to moderately severe hearing loss. About half of them had previous experience wearing hearing aids. All subjects were fitted with wide-dynamic-range-compression instruments and received similar treatment protocols. Results: Numerous statistically significant differences were observed between the VA and PP subject groups. Before the fitting, VA patients reported higher expectations from the hearing aids and more severe unaided problems compared with PP patients with similar audiograms. Three wks after the fitting, VA patients reported more satisfaction with their hearing aids. On some measures VA patients reported more benefit, but different measures of benefit did not give completely consistent results. Both groups reported using the hearing aids an average of approximately 8 hrs per day. VA patients reported age-normal physical and mental health, but PP patients tended to report better than typical health for their age group. Conclusions: These data indicate that hearing aid patients seen in the VA public health hearing services are systematically different in self-report domains from those seen in private practice services. It is therefore risky to casually combine data from these two types of subjects or to generalize research results from one group to the other. Further, compared with PP patients, VA patients consistently reported more favorable hearing aid fitting outcomes. Additional study is indicated to explore the determinants of this result and its generalizability to other public health service delivery systems such as those in other countries. Moreover, efforts should be made to assess the potential for transferring positive elements from the VA system to the PP service delivery system, if possible. (Ear & Hearing 2005;26;513-528) It is arguable that audiology in the United States had its origins in the programs designed to provide rehabilitation for veterans who had sustained hearing damage as a result of military service in World War II. One of the major components of those programs was provision of amplification and counseling about its use. Since that time, the Department of Veterans Affairs (VA) has been a major supporter of research oriented toward the acquisition of scientific and clinical knowledge about provision of hearing aids for adults. A large volume of literature has accumulated describing the results of experiments that have featured hearing-impaired veterans as subjects. These patients receive services in a public health system in which public funds are used to provide services to improve or protect the health of veterans. At least two other entities have supported and produced research exploring hearing aids and fitting methods: hearing aid manufacturers and academic institutions such as universities and the National Institutes of Health. Many of the subjects serving in these studies were recruited from sources that would not be classified as public health services, such as free-standing dispensing practices or university-based dispensing clinics. In this article, patients seen in free-standing dispensing practices are classified as receiving services in a private practice (PP) system. University-based clinics might differ from freestanding dispensaries along several dimensions. a Some university-based clinics operate in a way that is similar to a private practice, whereas others do not follow this model. The VA public health service delivery setting is different in several key respects from most PP service delivery settings. The VA clinic is usually lo
Sterol 14α-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana
Amphotericin B has emerged as the therapy of choice for use against the leishmaniases. Administration of the drug in its liposomal formulation as a single injection is being promoted in a campaign to bring the leishmaniases under control. Understanding the risks and mechanisms of resistance is therefore of great importance. Here we select amphotericin B-resistant Leishmania mexicana parasites with relative ease. Metabolomic analysis demonstrated that ergosterol, the sterol known to bind the drug, is prevalent in wild-type cells, but diminished in the resistant line, where alternative sterols become prevalent. This indicates that the resistance phenotype is related to loss of drug binding. Comparing sequences of the parasites’ genomes revealed a plethora of single nucleotide polymorphisms that distinguish wild-type and resistant cells, but only one of these was found to be homozygous and associated with a gene encoding an enzyme in the sterol biosynthetic pathway, sterol 14α-demethylase (CYP51). The mutation, N176I, is found outside of the enzyme’s active site, consistent with the fact that the resistant line continues to produce the enzyme’s product. Expression of wild-type sterol 14α-demethylase in the resistant cells caused reversion to drug sensitivity and a restoration of ergosterol synthesis, showing that the mutation is indeed responsible for resistance. The amphotericin B resistant parasites become hypersensitive to pentamidine and also agents that induce oxidative stress. This work reveals the power of combining polyomics approaches, to discover the mechanism underlying drug resistance as well as offering novel insights into the selection of resistance to amphotericin B itself