Stigma and social barriers to medication adherence with urban youth living with HIV.

Youth adherence to highly active anti-retroviral therapy (HAART) is poor, and little research exists that identifies the reasons youth have difficulty adhering to medications. Given that complete adherence is necessary for favourable health outcomes, it is essential to examine the obstacles youth face in adhering to HAART. The present investigation sought to identify these barriers and to systematically examine the experiences and attitudes youth have towards medications. Twenty-five adolescents and young adults presenting to a public primary care facility for treatment of HIV infection were asked to participate in focus groups which explored their attitudes and experiences around medication adherence. Participants provided richly detailed descriptions of the challenges of managing HIV stigma and their efforts to hide their status from friends, family, doctors, and even themselves. Fifty percent of respondents indicated that they skipped doses because they feared family or friends would discover their status. These results suggest that HIV stigma impacts treatment for youth on several levels, from the accuracy of communication with medical providers to medication adherence, subsequent health outcomes, and the emergence of treatment resistant strains.

Mapping of the chromosome 19 q-arm glioma tumor suppressor gene using fluorescence in situ hybridization and novel microsatellite markers.

Allelic loss of chromosome arm 19q is a frequent event in human diffuse glioma, suggesting the presence of a tumor suppressor gene. Previous loss of heterozygosity (LOH) analyses have mapped this gene to a 1.4-megabase interval, between the genetic markers D19S412 and STD. Further narrowing of this interval has been limited by the resolution of mapped polymorphic markers. In the present study, we have used genomic clones mapped to 19q as fluorescence in situ hybridization (FISH) probes to map the breakpoints of 13 gliomas with 19q13.3 deletion boundaries. In addition, we have developed three new polymorphic microsatellite markers (D19S1180, D19S1181, and D19S1182) that map between D19S412 and STD and have used these new markers to identify two gliomas with small deletions between the D19S412 and STD markers. Collectively, these data suggest that the region of common deletion may be as narrow as 150 kb and should facilitate future efforts to identify the glioma 19q tumor suppressor gene.

Amplification of the platelet-derived growth factor receptor-A (PDGFRA) gene occurs in oligodendrogliomas with grade IV anaplastic features.

Activation of the platelet-derived growth factor (PDGF) signaling system has been implicated in the development and malignant progression of diffuse gliomas. Overexpression of PDGF system components, particularly the alpha subtype receptor (PDGFRA), is common in glial tumors, and PDGFRA gene amplification has been reported in glioblastomas. In order to address the incidence of PDGFRA gene amplification in a broad set of diffuse gliomas, we used Southern and fluorescence in situ hybridization (FISH) analyses to examine 167 astrocytic gliomas (20 grade III and 147 grade IV), 41 anaplastic oligodendrogliomas, and 29 anaplastic oligoastrocytomas. PDGFRA gene amplification was identified in 4 anaplastic oligodendrogliomas and in a single case of anaplastic oligoastrocytoma, but in none of the malignant astrocytomas. Each of the 5 tumors with PDGFRA amplification displayed features generally associated with grade IV malignancy in astrocytic tumors. Consequently, our data indicate that this gene alteration is restricted to tumors having oligodendroglial differentiation and highly anaplastic features.

Investigation of germline PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 alterations in familial glioma.

Epidemiological studies suggest that some familial aggregations of glioma may be due to inherited predisposition. Many genes involved in familial cancers are frequently altered in the corresponding sporadic forms. We have investigated several genes known to be altered in sporadic gliomas for their potential contribution to familial glioma. Fifteen glioma patients with a family history of brain tumors were identified through the Mayo Clinic Department of Neurology (nine diffuse astrocytomas, two oligodendrogliomas, two mixed oligoastrocytomas, one pilocytic astrocytoma, and one pineal glioma). Eleven of the propositi had one or more first degree relative with a glioma. Lymphocyte DNA was derived from each of the patients and analyzed by polymerase chain reaction (PCR) and direct sequencing of the PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 genes. In addition, fluorescence in situ hybridization (FISH) was performed on EBV-transformed lymphocytes from each affected individual to detect germline copy number of the p16(INK4A)/p14(ARF) tumor suppressor region. A p53 germline point mutation was identified in one family with some findings of Li-Fraumeni syndrome, and a hemizygous germline deletion of the p16(INK4A)/p14(ARF) tumor suppressor region was demonstrated by FISH in a family with history of both astrocytoma and melanoma. Thus, whereas germ-line mutations of PTEN, p53, p16(INK4A)/p14(ARF), and CDK4 are not common events in familial glioma, outside of familial cancer syndromes, point mutations of p53 and hemizygous deletions and other rearrangements of the p16(INK4A)/p14(ARF) tumor suppressor region may account for a subset of familial glioma cases. Collectively, these data lend genetic support to the heritable nature of some cases of glioma.

Providing managed care options for a large population: evaluating the CHAMPUS reform initiative. Civilian Health and Medical Program of the Uniformed Services.

OBJECTIVES: To evaluate a managed care demonstration project in CHAMPUS (Civilian Health and Medical Program of the Uniformed Services), the insurance program covering physical and mental health care services for the dependents of active duty military personnel, military retirees, and the retirees' dependents. The demonstration project added a health maintenance organization (HMO) option and a preferred provider organization (PPO) option to the standard CHAMPUS coverage and allowed beneficiaries to select the coverage option they preferred. DATA SOURCES: Utilization, costs, access, and beneficiary satisfaction were measured using data from CHAMPUS claims records, the Defense Enrollment Eligibility Reporting System, the demonstration project contractor's HMO enrollment file, the contractor's list of network hospitals, and two surveys of CHAMPUS beneficiaries. STUDY DESIGN: Changes in utilization at 11 demonstration sites were compared with changes in utilization at 11 matched control sites. The effect of the demonstration project on costs was evaluated by estimating the costs for the demonstration sites both with and without the managed care options based on data from the control sites. Access to care and satisfaction were compared between the demonstration sites and control sites based on beneficiary surveys. DATA COLLECTION: All claims in both demonstration and control sites were used in estimating utilization changes. Two mailed surveys were sent to a randomly selected sample of active duty and retiree households with CHAMPUS beneficiaries; the sample was stratified by beneficiary type (active duty or retiree) and site. PRINCIPLE FINDINGS: Overall utilization in the CHAMPUS system decreased at the demonstration sites but stayed approximately the same at the control sites. Utilization among the enrollees in the HMO demonstration option, however, increased dramatically. Patient access to care and satisfaction generally remained at the same levels at both demonstration and control sites, but enrollees in the HMO option reported higher satisfaction. Costs to the government at the demonstration areas, based on regression estimates from the control sites, were about the same or slightly higher than what they would have been under the standard CHAMPUS system. CONCLUSIONS: Managed care plans for large government-sponsored insurance programs can reduce utilization and maintain patient access and satisfaction. Careful structuring of such plans is needed, however, if they are to reduce costs.

Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas.

PURPOSE: A recent report suggests that alterations of chromosome arms 1p and 19q are associated with chemotherapeutic response and overall survival in anaplastic oligodendroglioma patients treated with procarbazine, lomustine, and vincristine chemotherapy. We set out to further clarify the diagnostic and prognostic implications of these alterations in a broader set of diffuse gliomas, including astrocytic neoplasms and low-grade oligodendrogliomas. PATIENTS AND METHODS: Fluorescence in situ hybridization (FISH) signals from DNA probes mapping to 1p and 19q common deletion regions were enumerated in 162 diffuse gliomas (79 astrocytomas, 52 oligodendrogliomas, and 31 mixed oligoastrocytomas), collected as part of an ongoing prospective investigation of CNS tumors. RESULTS: The oligodendroglial phenotype was highly associated with loss of 1p (P =.0002), loss of 19q (P <.0001), and combined loss of 1p and 19q (P <.0001). Combined loss of 1p and 19q was identified as a univariate predictor of prolonged overall survival among patients with pure oligodendroglioma (log-rank, P =.03) and remained a significant predictor after adjusting for the effects of patient age and tumor grade (P <.01). This favorable association was not evident in patients with astrocytoma or mixed oligoastrocytoma. CONCLUSION: Combined loss of 1p and 19q is a statistically significant predictor of prolonged survival in patients with pure oligodendroglioma, independent of tumor grade. Given the lack of this association in patients with astrocytic neoplasms and the previously demonstrated chemosensitivity of oligodendrogliomas, a combined approach of histologic and genotypic assessment could potentially improve existing strategies for patient stratification and management.

Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype.

Allelic alterations of chromosomes 1 and 19 are frequent events in human diffuse gliomas and have recently proven to be strong predictors of chemotherapeutic response and prolonged survival in oligodendrogliomas (Cairncross et al., 1998; Smith et al., submitted). Using 115 human diffuse gliomas, we localized regions of common allelic loss on chromosomes 1 and 19 and assessed the association of these deletion intervals with glioma histological subtypes. Further, we evaluated the capacity of multiple modalities to detect these alterations, including loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH). The correlation coefficients for detection of 1p and 19q alterations, respectively, between modalities were: 0.98 and 0.87 for LOH and FISH, 0.79 and 0.60 for LOH and CGH, and 0.79 and 0.53 for FISH and CGH. Minimal deletion regions were defined on 19q13.3 (D19S412-D19S596) and 1p (D1S468-D1S1612). Loss of the 1p36 region was found in 18% of astrocytomas (10/55) and in 73% (24/33) of oligodendrogliomas (P < 0.0001), and loss of the 19q13.3 region was found in 38% (21/55) of astrocytomas and 73% (24/33) of oligodendrogliomas (P = 0.0017). Loss of both regions was found in 11% (6/55) of astrocytomas and in 64% (21/33) of oligodendrogliomas (P < 0.0001). All gliomas with LOH on either 1p or 19q demonstrated loss of the corresponding FISH probe, 1p36 or 19q13.3, suggesting not only locations of putative tumor suppressor genes, but also a simple assay for assessment of 1p and 19q alterations as diagnostic and prognostic markers.

Effect of a large managed care program on emergency department use: results from the CHAMPUS reform initiative evaluation.

STUDY OBJECTIVE: To determine the effect of the CHAMPUS Reform Initiative (CRI) on emergency department use and charges, and to ascertain whether any reductions were concentrated among repeat users of the ED, those with less serious ED diagnoses, or those with selected chronic medical conditions. METHODS: Participants were approximately 1.2 million beneficiaries of the Civilian Health and Medical Program of Uniformed Services (CHAMPUS) residing within either 11 military hospital catchment areas in California and Hawaii ("demonstration areas") or 11 matched control areas in other parts of the United States. Under CRI, participants were offered a choice of the standard CHAMPUS indemnity plan, a Preferred Provider Organization-type plan, or a network-model Health Maintenance Organization plan. Beneficiaries were encouraged to use alternatives to the ED for nonemergency conditions. Visits to civilian EDs during two 12-month periods, before and after institution of CRI, were compared. RESULTS: Under CRI, the number of CHAMPUS ED visits decreased by approximately 40% relative to the control, and allowed charges fell by almost 50%. Relative reductions in ED use under CRI were seen among both frequent and infrequent users of the ED. ED case-mix severity increased modestly relative to control (+3.5% versus +.9%). ED use among patients with diabetes, hypertension, and asthma fell sharply in the demonstration areas (by 14% to 41%) but rose in control areas (by 4% to 9%). CONCLUSION: In one of the largest managed care demonstrations ever conducted, a nonintrusive use management program and improved access to outpatient care appeared to reduce ED use, allowed charges, and costs to the government. Reductions in ED use were concentrated to some extent among repeat users and patients with less severe illnesses and were effected without capitation of provider groups or strict gatekeeping requirements.

The effects of benefit design and managed care on health care costs.

Recently, the Department of Defense replaced its traditional fee-for-service insurance plan for military health care beneficiaries with an HMO/PPO hybrid. Using survey and claims data, we compare changes in costs over two years at sites that implemented this initiative (CRI) with changes at matched control sites. The results indicate that CRI substantially raised per beneficiary government costs for providing benefits (as compared to predicted costs in the absence of CRI). We attribute this difference to the higher overhead of managed care and the increased expenditures by HMO participants.

Satisfaction and dissatisfaction in institutional practice: results from a survey of U.S. military physicians.

Because of recent concerns about the professional satisfaction of physicians in general and of military physicians in particular, the authors surveyed a national sample of 1,392 military physicians; 88% responded. Two-thirds of physicians were at least somewhat satisfied with the professional abilities of their peers and with the quality of care they were able to provide, but only 19% were satisfied with salary and 27% with practice efficiency. Characteristics of physicians that were independently related to overall satisfaction included age, recruitment pathway, workload, specialty, and perceived availability of key resources. Indicator variables for the individual medical facilities were also significantly related to global satisfaction, suggesting a separate "hospital effect" that bears additional investigation. Efforts to improve satisfaction may enhance recruitment and retention of military physicians.

The effects of preferred provider options in fee-for-service plans on use of outpatient mental health services by three employee groups.

Descriptions of how preferred provider organizations (PPOs), offered as options to employees enrolled in fee-for-service plans, affected use of outpatient mental health services are provided. Data are from the RAND Preferred Provider Organization Study, which has a sample of employees who enrolled in fee-for-service plans 1 year before and 2 years after a PPO option was offered by three employers in two U.S. sites. To study effects of the optional PPOs on access to mental health care, usage patterns among those who initially stated that they did or did not intend to use PPO providers were examined. By the end of the second post-PPO year, employees had a similar annual probability of having an outpatient mental health visit whether or not they initially intended to use PPO providers. However, during the first post-PPO year, there was a decrease in the probability of use for those initially intending to use PPO providers, relative to those who did not intend to do so, among employees who had no regular medical provider. To study effects of the PPO option on usage levels of mental health care services, users of mental health services who primarily visited PPO were compared with those who primarily visited non-PPO providers. Users who visited PPO providers had significantly lower levels of use, controlling for other factors, than those who primarily visited non-PPO providers. Therefore, despite lower cost sharing for services received from PPO providers, the PPO option appeared to lower outpatient mental health care costs while having no more than a transient effect on access. This study did not evaluate mental health outcomes.

Mental health and selection of preferred providers. Experience in three employee groups.

While Preferred Provider Organizations (PPOs) are designed to contain the costs of health care, they may not be able to do so if sicker individuals opt not to use PPO providers. This study examined how level of mental health status and prior use of mental health services affected the decision to use or not use PPO providers for mental health care for employees enrolled in fee-for-service plans with a PPO option. Data were obtained from an employee survey and claims data on three large employee groups. It was not possible to examine effects of sickliness on the intent to select PPO providers for mental health care directly because about one half of employees could not identify who they would visit for mental health care or even how they would select a provider for such care. The intent to use PPO or non-PPO providers for general medical care, however, was not significantly associated with mental health status when other factors were controlled. Furthermore, among persons who used mental health services after implementation of the PPO option, those who had previously visited providers who were to become part of the PPO panel tended to stay with PPO providers, while those who previously visited providers who were not to enter the PPO panel subsequently selected away from PPO providers for mental health care. This pattern of results suggests that established individual patient-provider relationships, rather than sickliness, determined the selection of PPO versus non-PPO providers for mental health care for employees enrolled in these optional PPO fee-for-service plans.

Using DRGs to pay for inpatient substance abuse services: an assessment of the CHAMPUS reimbursement system.

In October 1988, the Civilian Health and Medical Program of the Uniformed Services (CHAMPUS) introduced a prospective payment system based on diagnostic-related groups (DRGs) to pay for substance abuse services. These services were initially excluded from the new payment system because of concerns that a DRG-based system may have a large and poorly understood financial impact on individual hospitals. This report assesses the performance of a DRG system in explaining variation in costs at the individual patient level and evaluates how well this payment system predicts resource use across hospitals. Overall, the substance abuse DRGs explained only 4.2% of the total variance in charges. It was found that the Medicare DRG-based system had to be modified to reflect the characteristics of the younger CHAMPUS population by splitting DRG 435 to account for the increased costliness of beneficiaries younger than 21 years. In addition, the study revealed substantial variation in the impact of the DRG system on hospital revenue. These differences largely reflected significant differences between general and specialty hospitals.

Physician's extenders' performance in Air Force clinics.

We evaluated the quality of care of physician's extenders (PEs: 23 physician's assistants, 7 primary care nurse practitioners) in Air Force primary medicine clinics, as part of an evaluation of PEs' assuming a considerable portion of the care, formerly provided by physicians in the military medical system. Physician's assistants performed at least as well as physicians on 25 out of 28 nonredundant process-of-care criteria; nurse practitioners met the physicians' standard on 14 of 19 criteria. In a comparison of physician's assistants with nurse practitioners, the two groups' performance was not significantly different. No major differences were found in PEs' and physicians' use of ancillary services (laboratory, x-ray, physical therapy) or orders for further care. As expected, PEs consulted physicians infrequently, but more often for serious complaints and at rates similar to those found in a civilian HMO setting. We conclude that the Air Force can deliver the same quality of care when PEs treat a sizable proportion of patients formerly treated by physicians.