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Biomedical subjects

Sean Kennedy

Publications and source records attributed to Sean Kennedy.

8 recordsLinked to original sources

Burden of illness in Parkinson's disease.

This study quantifies direct medical care costs for individual patients with Parkinson's disease (PD) and projects total national costs of PD. Anonymous, patient-level data on health care utilization and cost were obtained from Medstat's MarketScan Research Databases. Patients were selected for study if they had either two instances of a diagnosis of PD or one diagnosis and two or more prescriptions for PD-related medication. A control group of persons without PD was selected for comparison. Total annual health care utilization and costs were calculated for both PD patients and controls. A total of 20,016 patients with PD were identified and followed up for an average of 853 days. The mean age of the patients was 73.6 years, and 51.2% were women. Total annual direct costs were 23,101 US Dollars (SD 27,529) per patient with PD versus 11,247 US Dollars (SD 16,486) for controls. The regression-adjusted incremental direct cost of PD versus control was 10,349 US Dollars (95% confidence interval, 9,053, 11,645). Adding 25,326 US Dollars in indirect costs, and multiplying by 645,000 cases of PD in the United States, the total cost to the nation is projected to be 23 billion US Dollars annually. This estimate is higher than most previous studies, with important implications for health care delivery systems worldwide.

Adolescent↗

Deregulated expression in Ph+ human leukemias of AHI-1, a gene activated by insertional mutagenesis in mouse models of leukemia.

Ahi-1/AHI-1 (Abelson helper integration site-1) encodes a family of protein isoforms containing one Src homology 3 (SH3) domain and multiple tryptophan-aspartic acid 40 (WD40)-repeat domains. The function of these proteins is unknown, but involvement in leukemogenesis has been suggested by the high frequency of Ahi-1 mutations seen in certain virus-induced murine leukemias. Here we show that in both mice and humans, Ahi-1/AHI-1 expression is highest in the most primitive hematopoietic cells with specific patterns of down-regulation in different lineages. Cells from patients with chronic myeloid leukemia (CML; n = 28) show elevated AHI-1 transcripts in all disease phases and, in chronic phase, in the leukemic cells at all stages of differentiation, including quiescent (G(0)) CD34(+) cells as well as terminally differentiating cells. In the most primitive lin(-)CD34(+)CD38(-) CML cells, transcripts for the 2 shorter isoforms of AHI-1 are also increased. Although 15 of 16 human lymphoid and myeloid leukemic cell lines showed aberrant control of AHI-1 expression, this was not seen in blasts obtained directly from patients with acute Philadelphia chromosome-negative (Ph(-)) leukemia (n = 15). Taken together, our results suggest that down-regulation of AHI-1 expression is an important conserved step in primitive normal hematopoietic cell differentiation and that perturbations in AHI-1 expression may contribute to the development of specific types of human leukemia.

Adaptor Proteins, Signal Transducing↗

Low-pass sequencing for microbial comparative genomics.

BACKGROUND: We studied four extremely halophilic archaea by low-pass shotgun sequencing: (1) the metabolically versatile Haloarcula marismortui; (2) the non-pigmented Natrialba asiatica; (3) the psychrophile Halorubrum lacusprofundi and (4) the Dead Sea isolate Halobaculum gomorrense. Approximately one thousand single pass genomic sequences per genome were obtained. The data were analyzed by comparative genomic analyses using the completed Halobacterium sp. NRC-1 genome as a reference. Low-pass shotgun sequencing is a simple, inexpensive, and rapid approach that can readily be performed on any cultured microbe. RESULTS: As expected, the four archaeal halophiles analyzed exhibit both bacterial and eukaryotic characteristics as well as uniquely archaeal traits. All five halophiles exhibit greater than sixty percent GC content and low isoelectric points (pI) for their predicted proteins. Multiple insertion sequence (IS) elements, often involved in genome rearrangements, were identified in H. lacusprofundi and H. marismortui. The core biological functions that govern cellular and genetic mechanisms of H. sp. NRC-1 appear to be conserved in these four other halophiles. Multiple TATA box binding protein (TBP) and transcription factor IIB (TFB) homologs were identified from most of the four shotgunned halophiles. The reconstructed molecular tree of all five halophiles shows a large divergence between these species, but with the closest relationship being between H. sp. NRC-1 and H. lacusprofundi. CONCLUSION: Despite the diverse habitats of these species, all five halophiles share (1) high GC content and (2) low protein isoelectric points, which are characteristics associated with environmental exposure to UV radiation and hypersalinity, respectively. Identification of multiple IS elements in the genome of H. lacusprofundi and H. marismortui suggest that genome structure and dynamic genome reorganization might be similar to that previously observed in the IS-element rich genome of H. sp. NRC-1. Identification of multiple TBP and TFB homologs in these four halophiles are consistent with the hypothesis that different types of complex transcriptional regulation may occur through multiple TBP-TFB combinations in response to rapidly changing environmental conditions. Low-pass shotgun sequence analyses of genomes permit extensive and diverse analyses, and should be generally useful for comparative microbial genomics.

Archaea↗

The burden of illness associated with psoriasis: cost of treatment with systemic therapy and phototherapy in the US.

OBJECTIVE: To evaluate utilization and direct healthcare expenditures among psoriasis patients treated with systemic therapy and phototherapy in the United States. DESIGN: Cohort study using retrospective administrative medical claims. PATIENTS: Psoriasis patients treated with systemic therapy and phototherapy, as well as a matched cohort of non-psoriasis patients. All patients were covered by employer-sponsored insurance between 1 April 1996 and 31 December 2000. MAIN OUTCOME MEASURES: Estimated risk of hospitalization and total annual healthcare expenditures overall and by comorbidity status were compared for persons with psoriasis using systemic therapy or phototherapy and persons without psoriasis. Annualized utilization rates for hospitalizations, and use of emergency department, outpatient physician, outpatient laboratory, and outpatient pharmaceutical services were also compared across the two cohorts. RESULTS: Seventeen percent of psoriasis patients were treated with systemic therapy or phototherapy. Patients with comorbid anemia, carcinoma, diabetes, depression, GI disorders, hepatotoxicity, hypertension, and nephrotoxicity had significantly higher expenditures than non-psoriasis patients with the same comorbidities (p < or =0.05). Elevated risk of hospitalization also contributed to higher expenditures in patients treated with systemic therapy or phototherapy. Limitations of this study include those inherent in using claims data such as dependence on diagnosis coding, the fact that psoriasis severity cannot be determined directly from claims data, confounding comorbidities, and the fact that only direct healthcare expenditures were considered in this analysis. CONCLUSION: Psoriasis patients treated with systemic therapies/phototherapies have significantly more comorbidities and higher mean total healthcare expenditures compared to non-psoriasis patients. Psoriasis patients with selected comorbidities have significantly higher mean total healthcare expenditures compared to non-psoriasis persons with the same comorbidities.

Adult↗

The cost consequences of treatment-resistant depression.

CONTEXT: Treatment-resistant depression is a significant public health problem with profound effects on general medical and mental health-related health care costs. OBJECTIVE: To describe health care costs of patients with treatment-resistant depression as their illness progresses, in terms of pharmaceutical and medical expenditures, and to identify factors associated with increasing degrees of treatment resistance. DATA SOURCES: The MEDSTAT MarketScan Private Pay Fee for Service (FFS) Database, a medical and prescription claims database covering over 3.5 million enrollees, from 1995-2000. DESIGN AND STUDY SUBJECTS: 7737 patients with depression (ICD-9) who had 2 or more unsuccessful trials of antidepressant medication at an adequate dose for at least 4 weeks from 1995-2000 were defined as treatment-resistant in this study. Demographic and clinical characteristics were assessed for these patients with treatment-resistant depression. The number of changes in depression medication treatment regimens was used as a proxy for increasing degrees of treatment resistance and its severity. MAJOR OUTCOME MEASURE: Differences in health care expenditures associated with increasing degrees of treatment-resistant depression. RESULTS: Total depression-related and general medical health care expenditures increased significantly as treatment-resistant depression increased in severity. Multivariate analyses of patient demographic characteristics were not associated with ongoing treatment resistance. Disease severity, type of antidepressant at index, comorbid mental health disorders, and membership in a managed health care plan were associated with increasing degrees of treatment resistance. CONCLUSIONS: Depression and general medical health care expenditures increase with the degree of treatment-resistant depression. Disease management interventions for treatment-resistant depression that result in sustained remission early in the course of illness are most likely to be cost effective.

Adult↗

Severity of premenstrual symptoms in a health maintenance organization population.

OBJECTIVE: To describe severity of emotional and physical symptoms in a large diverse sample; to examine demographic, health status, and behavioral correlates of symptom severity; and to describe use of medications and alternative remedies for premenstrual symptoms. METHODS: A total of 1194 women, ages 21-45, selected from members of a large northern California health maintenance organization, completed daily ratings of symptom severity for two menstrual cycles. An empirically derived algorithm defined symptom severity groups as minimal (n = 186), moderate (n = 801), severe (n = 151), or premenstrual dysphoric disorder (n = 56). Symptom severity as a continuous variable was defined by the two-cycle mean symptom ratings in the luteal phase. Demographic, health status, and behavioral factors and use of treatments for premenstrual symptoms were assessed by self-report. RESULTS: Luteal phase symptom-specific ratings were generally significantly greater in the premenstrual dysphoric disorder group than in the other groups (P <.001). Symptom severity score increased with each comorbidity and decreased with each year of age. Symptom severity was also inversely associated with oral contraceptive use (emotional symptoms) and better perceived health (physical symptoms). Hispanics reported greater severity of symptoms, and Asians less, relative to whites. Use of herbal and nutritional supplements for premenstrual symptoms steadily increased from 10.8% in the minimal group to 30.4% in the premenstrual dysphoric disorder group (P <.01). CONCLUSION: The degree of premenstrual symptom severity varies in the population, is relatively constant within each woman over two consecutive cycles, particularly for emotional symptoms, and is influenced by age, race/ethnicity, and health status.

Adult↗

Premenstrual dysphoric disorder: is there an economic burden of illness?

OBJECTIVE: To quantify the economic burden associated with premenstrual dysphoric disorder (PMDD) by assessing health care service use and related expenditures, work loss, role limitation, and productivity. METHODS: Women ages 21 to 45, randomly selected from membership of a northern California HMO (n = 1,194), provided prospective daily symptom ratings and survey data on health care use and productivity for two menstrual cycles. Summary measures of 12-month utilization and expenditures based on HMO encounter data also were constructed. Based on daily symptom ratings, we classified women as having minimal (n = 186), moderate (n = 801), and severe (n = 151) premenstrual symptoms, or PMDD (n = 56) and compared health care use and expenditures, predicted values of productivity and work loss, and marginal effects of symptom severity on outcome measures. RESULTS: Women with PMDD had higher degrees of luteal phase (premenstrual) productivity impairment than those with minimal symptoms. Compared with the minimal and moderate symptom groups, women with PMDD continued to report lower productivity (P <0.01) in the 5 to 10 days after onset of menses (follicular phase). We found little evidence that women spent more time in bed, reduced time at work, or decreased activities at home or school as a result of premenstrual symptoms. As symptom severity increased, the likelihood of health care service use increased only for an emergency department, obstetrician/gynecologist, or alternative medicine provider visit. There were no significant differences in health care expenditures across the symptom groups. CONCLUSION: The economic burden associated with PMDD manifests itself primarily in reported productivity decrements rather than health care utilization or costs associated with time away from work.

Adult↗

Physician-to-physician consultation via electronic mail: the Walter Reed Army Medical Center Ask a Doc system.

INTRODUCTION: Physician-to-physician consultation and discussion have traditionally been conducted by telephone, paper, and "curbside" (face to face meetings). The implementation and use of physician-to-physician consultation via electronic mail in a military health care system has not been reported previously. METHODS: The group mail function of the Composite Health Care System, the main outpatient medical automation system for the Department of Defense, was modified to create mailgroups for every specialty of the Walter Reed Army Medical Center to facilitate ease of physician-to-physician consultation. This modification was called the "Ask a Doc" system. The system was deployed to a 21-state health care network among triservice participants. RESULTS: There were 3,121 consultations logged from April 22, 1998, to December 31, 2000. Growth in use expanded initially and was sustained during a 3-year period. Average response time to consultations was less than 1 day (11.93 hours). Additional training and maintenance requirements were minimal. In general, the use of electronic consultation mirrored that of clinical practice. Most specialty consultations involved the disciplines of internal medicine. CONCLUSIONS: Use of the Ask a Doc system was representative of total clinical workload and increased access to specialty medical care over a wide geographic area. The distribution of use indicated that user statistics were legitimate, and quality improvement programs could easily troubleshoot the system. Ask a Doc was inserted into a regional health care network with minimal cost to support and implement and was sustained with very little effort for 3 years. Barriers to even wider use currently include lack of secure communications and the difficulty in assigning workload credit for electronic consultations.

Computer Communication Networks↗