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Biomedical subjects

E A Wright

Publications and source records attributed to E A Wright.

At least 19 recordsLinked to original sources

Musculoskeletal and neurologic outcomes in patients with previously treated Lyme disease.

BACKGROUND: Previous follow-up studies of patients with Lyme disease suggest that disseminated infection may be associated with long-term neurologic and musculoskeletal morbidity. OBJECTIVE: To determine clinical and functional outcomes in persons who were treated for Lyme disease in the late 1980s. DESIGN: Population-based, retrospective cohort study. SETTING: Nantucket Island, Massachusetts. PARTICIPANTS: 186 persons who had a history of Lyme disease (case-patients) and 167 persons who did not (controls). MEASUREMENTS: Standardized medical history, physical examination, functional status measure (Medical Outcomes Study 36-item Short Form Health Survey [SF-36]), mood state assessment (Profile of Mood States), neurocognitive tests, and serologic examination. RESULTS: The prevalence of Lyme disease among adults on Nantucket Island was estimated to be 14.3% (95% CI, 9.3% to 19.1%). In multivariate analyses, persons with previous Lyme disease (mean time from infection to study evaluation, 6.0 years) had more joint pain (odds ratio for having joint pain in any joint, 2.1 [CI, 1.2 to 3.5]; P = 0.007), more symptoms of memory impairment (odds ratio for having any memory problem, 1.9 [CI, 1.1 to 3.5]; P = 0.003), and poorer functional status due to pain (odds ratio for 1 point on the SF-36 scale, 1.02 [CI, 1.01 to 1.03]; P < 0.001) than persons without previous Lyme disease. However, on physical examination, case-patients and controls did not differ in musculoskeletal abnormalities, neurologic abnormalities, or neurocognitive performance. Persons with previous Lyme disease who had persistent symptoms after receiving treatment (n = 67) were more likely than those who had completely recovered to have had fever, headache, photosensitivity, or neck stiffness during their acute illness (87% compared with 13%; odds ratio, 2.4 [CI, 1.0 to 5.5]; P = 0.045); however, the performance of the two groups on neurocognitive tests did not significantly differ. CONCLUSIONS: Because persons with previous Lyme disease exhibited no sequelae on physical examination and neurocognitive tests a mean of 6.0 years after infection, musculoskeletal and neurocognitive outcomes seem to be favorable. However, long-term impairment of functional status can occur.

Adult

Tissue and T cell distribution of precursor and mature IL-16.

IL-16 is a novel cytokine, which is chemoattractant for CD4+ T cells, macrophages, and eosinophils. Recently, it was reported that IL-16 is synthesized as an approximately 80-kDa precursor molecule, pro-IL-16. Since little is known about the processing and tissue distribution of IL-16 and pro-IL-16, we investigated the distribution of IL-16 mRNA and protein in human lymphoid tissue. Northern blotting identified IL-16 mRNA predominantly in normal lymphoid organs, including PBMC, spleen, and thymus. Immunohistochemistry of human lymph node localized IL-16 protein to lymphocyte cytoplasm within T cell zones and occasionally in lymphocytes in B cell zones. Flow cytometric detection of intracellular IL-16 showed that >70% of CD4+ and CD8+ T cells constitutively expressed IL-16 protein. Western blot analysis of PBMC revealed nearly all of this protein to be approximately 80-kDa pro-IL-16 in unstimulated PBMC, and upon cell activation, the amino terminus of pro-IL-16 is processed into multiple fragments. These results show that pro-IL-16 is widely and constitutively expressed and suggest that the amino terminus of the protein can be processed upon cell activation.

Adolescent

Outcomes of children treated for Lyme disease.

OBJECTIVE: To study the outcome of Lyme disease (LD) in children identified in a total population survey of an endemic island. METHODS: We conducted a population-based retrospective cohort study off the coast of Massachusetts. Twenty-five children who met the Centers for Disease Control case definition for prior LD were compared with 26 children without LD from the same community. All children with LD received antibiotics during the acute phase of their disease. All 51 children were invited for a clinical evaluation, including 12-lead electrocardiogram (EKG), and measurement of antibodies to Borrelia burgdorferi by antibody-capture ELISA and Western blot. RESULTS: At a mean of 3.2 years from the initial manifestation of LD, children with prior LD did not have a higher prevalence of musculoskeletal or neurological symptoms, examination abnormalities, abnormal EKG, or behavioral difficulties, compared to children with no history of LD. CONCLUSION: Children who receive appropriate antimicrobial therapy for LD appear to have no demonstrable longterm morbidity.

Administration, Oral

The relationship of socioeconomic status, race, and modifiable risk factors to outcomes in patients with systemic lupus erythematosus.

OBJECTIVE: To study the relationship of race, socioeconomic status (SES), clinical factors, and psychosocial factors to outcomes in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective cohort was assembled, comprising 200 patients with SLE from 5 centers. This cohort was balanced in terms of race and SES. Patients provided information on socioeconomic factors, access to health care, nutrition, self-efficacy for disease management, health locus of control, social support, compliance, knowledge about SLE, and satisfaction with medical care. Outcome measures included disease activity (measured by the Systemic Lupus Activity Measure), damage (measured by the SLICC/ACR damage index), and health status (measured by the SF-36). RESULTS: In multivariate models that were controlled for race, SES, center, psychosocial factors, and clinical factors, lower self-efficacy for disease management (P < or = 0.0001), less social support (P < 0.005), and younger age at diagnosis (P < 0.007) were associated with greater disease activity. Older age at diagnosis (P < or = 0.0001), longer duration of SLE (P < or = 0.0001), poor nutrition (P < 0.002), and higher disease activity at diagnosis (P < 0.007) were associated with more damage. Lower self-efficacy for disease management was associated with worse physical function (P < or = 0.0001) and worse mental health status (P < or = 0.0001). CONCLUSION: Disease activity and health status were most strongly associated with potentially modifiable psychosocial factors such as self-efficacy for disease management. Cumulative organ damage was most highly associated with clinical factors such as age and duration of disease. None of the outcomes measured were associated with race. These results suggest that education and counseling, coordinated with medical care, might improve outcomes in patients with SLE.

Adult

Assessment of systemic lupus erythematosus disease activity by medical record review compared with direct standardized evaluation.

OBJECTIVE: Clinical studies of systemic lupus erythematosus (SLE) often necessitate assessment of previous disease activity, which is sometimes only possible by retrospective evaluation of information from the medical record. Using the Systemic Lupus Activity Measure (SLAM), the present study compared an assessment of disease activity obtained by chart abstraction with a direct clinical assessment. METHODS: A chart SLAM was obtained using information abstracted from the clinic notes of 46 patients with SLE who were being followed up at a referral center. Chart SLAM scores were compared with SLAM scores derived from an independent assessor's direct clinical evaluation. RESULTS: Direct SLAM and chart SLAM scores were correlated (r = 0.67 by Spearman's rank correlation, P = 0.0001). Chart review scores for disease activity tended to be lower, but to an inconsistent degree, reflecting both under- and overestimation of disease activity. The overall misclassification rate on a 3-category scale (mild, moderate, or severe activity) was 59%. CONCLUSION: Although chart SLAM scores were highly correlated with direct SLAM scores, misclassification of disease activity by chart review cannot be rectified. Thus, in research, medical record review should not be used as a proxy for the direct SLAM, nor should it be considered comparable with clinical assessments in the analysis of disease activity.

Adult

Risk factors for early work disability in systemic lupus erythematosus: results from a multicenter study.

OBJECTIVE: To study the risk factors for early work disability in systemic lupus erythematosus (SLE). METHODS: A sample of 159 SLE patients who had been employed at some time since diagnosis was drawn from a multicenter study of outcome in SLE. Disease activity, organ damage, education, income, source of health insurance, and work-related factors were measured in a standardized interview. Work disability was defined by patient self-report of not working because of SLE. The outcome measure was current work status. Seven patients were excluded from the analysis because their choice not to work was unrelated to SLE. RESULTS: An average of 3.4 years after diagnosis, 40% had quit work completely, and job modification was substantial. Univariate analysis (chi-square and t-test) showed that significant predictors of early work disability included having a high school education or less, receiving Medicaid or having no health insurance, having a job which required more physical strength, having an income below poverty level, and having greater disease activity at diagnosis. In multivariate models, significant predictors were education level (P = 0.0004), higher physical demands of the job (P = 0.0028), and higher disease activity at diagnosis (P = 0.0078). Race, sex, cumulative organ damage at diagnosis, and disease duration were not significant. CONCLUSION: Early work disability in SLE is strongly associated with some sociodemographic factors that might be amenable to intervention.

Adult

Splicing features in maize streak virus virion- and complementary-sense gene expression.

The single-stranded DNA geminiviruses produce transcripts from both strands (virion- and complementary-sense) of a nuclear double-stranded DNA molecule. In maize streak virus (MSV)-infected maize plants, approximately 80% of the complementary-sense transcripts produce the C1 protein, whilst the remaining 20% are spliced to remove a 92 nt intron and produce a C1:C2 fusion protein (Rep). Disruption of the complementary-sense 3' splice site abolished virus replication. The majority of the virion-sense transcripts initiated one nucleotide upstream of the V1 (movement protein) gene and a minority a further 141 nucleotides upstream. A 76 nt intron, with features typical of plant introns, was identified within the V1 gene, upstream of the coat protein gene. Spliced and unspliced forms of each virion-sense transcript were produced, but they differed in splicing efficiency. Approximately 50% of the major transcript and less than 10% of the minor transcript were processed. Mutagenesis of the consensus 5' splice site in the V1 gene resulted in the use of alternative cryptic splice sites, confirming the importance of splicing for MSV infection. Spliced virion-sense transcripts were also identified in tissue infected with the closely-related Digitaria streak virus (DSV) but not with another subgroup I geminivirus, wheat dwarf virus. Collectively, the multiple transcript initiation sites and different splicing efficiencies suggest that splicing is an important feature in the regulation of both early and late gene expression in MSV and DSV.

Amino Acid Sequence

In vitro transendothelial migration of blood T lymphocytes from HIV-infected individuals.

OBJECTIVE: We hypothesized that differential extravasation of circulating CD4+ or CD8+ T lymphocytes contributes to HIV-associated CD8+ lymphocytic alveolitis. Differences in T-cell transendothelial migration may be intrinsic or emerge at sites where vascular endothelium is activated by overexpression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. DESIGN: We used an in vitro model of lymphocyte extravasation to assess transendothelial migration of peripheral blood mononuclear cells (PBMC) from HIV-positive individuals. We assayed bronchoalveolar lavage (BAL) fluid from HIV-positive and normal individuals to determine if increased levels of TNF-alpha and IFN-gamma were present in the lungs of HIV-infected individuals. METHODS: Transendothelial migration was assessed by determining the number and flow cytometric phenotype of PBMC adherent to or migrating across unstimulated or TNF-alpha and IFN-gamma-activated endothelial cell monolayers. We measured BAL fluid cytokine concentrations using standard antigen-capture enzyme-linked immunosorbent assays for TNF-alpha and IFN-gamma. RESULTS: T cells migrating across unactivated endothelial cells were significantly enriched for CD4+ T cells. Cytokine activation of endothelial cells allowed significantly greater transendothelial migration of CD8+ T cells compared to unactivated endothelial cells. TNF-alpha was increased in BAL fluid from HIV-positive individuals relative to controls. CONCLUSIONS: These data suggest that, in HIV-positive individuals, CD4+ T cells are migration competent and blood CD8+ T cells do not have enhanced migration competence relative to CD4+ T cells. CD8+ T cell extravasation is aided by TNF-alpha and IFN-gamma-induced endothelial cells activation.

Bronchoalveolar Lavage

What makes quality assurance effective? Results from a randomized, controlled trial in 16 primary care group practices.

OBJECTIVES: The authors estimate separately contributions of each component intervention to overall effectiveness of quality assurance cycles used to improve practice performance. METHODS: In a randomized, controlled trial, experimental cycles of quality assurance were conducted for eight patient-care guidelines, with two experimental cycles assigned to each of 16 group practices. For three separate interventions per cycle, practitioners: (1) were notified of the name of the experimental guideline, (2) discussed criteria of conformance to the guideline, and (3) received feedback on performance. Actions taken in response to interventions were documented. Using medical records data for a baseline year and for 3 months after each intervention and an additional 9 months, the authors scored each practice for conformance to two experimental guidelines and to control guidelines. RESULTS: For all patient-care guidelines combined, and for four of five guidelines showing improvement, knowledge of guidelines and review criteria alone produced no change. After feedback, performance improved and improvement persisted for at least 9 months. The number of corrective actions implemented contributed significantly to effectiveness of quality assurance. CONCLUSIONS: Feedback to providers of data on their performance is a more powerful stimulus for quality improvement than is knowledge of guidelines or discussion of review criteria.

Ambulatory Care

Leadership for quality improvement in group practices.

OBJECTIVES: The authors studied influence of physician leaders on their colleagues' performance using data from a randomized, controlled trial of quality assurance interventions in 16 primary care practices. METHODS: The authors examined whether leaders performed better than their colleagues and looked for evidence of leaders' influence on their colleagues before intervention. As behavioral indicators of each leader's influence for improvement in response to quality assurance interventions, the authors (1) change in the leader's performance score and (2) an index of leader commitment derived from the leader's participation in quality assurance interventions; these indicators were used as covariates in a comparison in experimental practice sites of leaders' and colleagues' mean case performance scores before and after intervention. RESULTS: Leaders did not outscore their colleagues or influence their colleagues' performance scores before intervention. In response to quality assurance interventions, a leader's change in performance score significantly improved colleagues' score if the leader improved. A positive leader commitment index predicted colleagues' improvement independently of the leader change score. CONCLUSIONS: As hypothesized, physician leaders, by the example of their behavior, influenced colleagues' performance. However, leaders exerted their influence only after receiving external stimulation for quality improvement.

Adult

Consistency in performance among primary care practitioners.

OBJECTIVES: The authors studied the consistency of performance of individual physicians to evaluate the identification of outlier practitioners as a strategy for improving patient care. METHODS: The authors used a data base containing information on 430 practitioners caring for 6,090 patients in 16 group practices. The authors analyzed inter- and intraphysician differences in performance on the basis of review criteria for 8 patient care guidelines. These criteria allowed for a variety of acceptable clinical strategies, incorporated decision tree logic, and included input from participating practitioners. The authors took steps to maximize validity and controlled for potentially confounding characteristics of patients and practitioners. The authors identified outliers, evaluated the significance of differences between outliers and nonoutliers, and studied variations in performance across cases and guidelines in conformance with guidelines. RESULTS: The authors identified a few statistically significant outliers. Correlations for performance across cases seen by a given physician were low. The highest positive correlation for performance between any pair of guidelines was 0.32. CONCLUSIONS: The performance of a given practitioner is highly variable from patient to patient and from guideline to guideline. Thus, strategies focusing solely on substandard outliers will miss opportunities to improve performance.

Adult

Practice characteristics and performance of primary care practitioners.

OBJECTIVES: The authors examined organizational characteristics of 16 primary care group practices to determine their influence on quality or quality improvement. METHODS: The authors used a data base compiled during a randomized, controlled trial of quality assurance interventions consisting of measures of guideline-related performance for 630 practitioners. The authors distinguished performance under practitioners' control from performance determined partly by systems of care within each practice. The authors conducted analyses for all criteria (practitioner-controlled and system-dependent criteria) before and after quality assurance interventions using analysis of variance models with adjustments in performance scores for patient and practitioner characteristics. Specifically, the authors used as covariates the full-time versus part-time status of practitioners, whether practices were in hospitals or in health centers, and for practices within health centers, the effect of size of practice in terms of the average number of practitioners on staff during a time period. RESULTS: Full-time practitioners performed similarly before interventions but improved more after interventions overall and for practitioner-controlled criteria than did part-time practitioners. Health center practitioners performed better than did those in hospitals for system-dependent criteria before intervention. For system-dependent criteria, larger health centers performed better before interventions and improved more than did smaller health centers. CONCLUSIONS: Organizational characteristics including practice size and location (hospital-based or not) and full- or part-time status of practitioners should be considered in measuring quality and planning quality improvements, particularly in relation to care that is predominantly under system versus practitioner control.

Analysis of Variance

Are differences in practitioners' acceptance of a quality assurance intervention related to their performance?

OBJECTIVES: The authors assessed whether practitioners' attitudes toward quality assurance after the intervention are related to their performance before and after the intervention. METHODS: A data base was compiled including a survey of practitioners participating in a randomized, controlled trial of externally coordinated quality assurance in 16 practices. The survey evaluated whether practitioners noticed changes in their performance or improvements in care as a result of the external review and whether they preferred internal review or external review that promoted practitioner input and a collegial atmosphere. RESULTS: Practitioners' differences in accepting quality interventions related to quality improvement. A minority of practitioners believed that they had changed their practice or that care had improved in response to quality assurance; these options were not associated with actual performance. Many practitioners approved of internal quality assurance; however, most preferred external review. A few totally disagreed with quality assurance. Greater approval of externally coordinated review was marginally associated with worse baseline performance and significantly associated with better postintervention performance. This relationship was reversed for internal review. CONCLUSIONS: It is commonly perceived that practitioners resent external quality assurance. Our results show the opposite. These findings predict practitioner acceptance for a mode of quality assurance now widely used.

Ambulatory Care

Issues of variability and bias affecting multisite measurement of quality of care.

OBJECTIVES: Using data from a randomized trial to improve the quality of ambulatory care, the authors quantify the various sources of variability and bias that affect measures of quality of care and suggest experimental designs and analyses that reduce both bias and variability. METHODS: There is a growing desire among health care researchers and government agencies to profile and compare practitioner performance. Such efforts are complicated by extreme inherent variability in most measures of quality of care, as well as potential biases introduced by "experiments," where patients cannot act as the unit of randomization. When the authors measured practitioner performance for eight patient-care guidelines, they found little association of level of performance across guidelines. Thus, the authors considered performance for each guideline separately, also taking into account variability between patients, practitioners, and practice conditions. RESULTS: Randomization can reduce bias in large studies but should be supplemented by multivariate models. A preintervention and postintervention design can reduce variability, but much of the variability that remains is because of unmeasured patient/error variance. CONCLUSIONS: Incorporation of these concepts into future studies using quality measurements will help researchers design smaller and more sensitive trials to draw more accurate and precise conclusions.

Adult

The independence and stability of socioeconomic predictors of morbidity in systemic lupus erythematosus.

OBJECTIVE: We studied the relationship between systemic lupus erythematosus (SLE) morbidity and socioeconomic status (SES) at 5 centers. METHODS: Ninety-nine patients who met American College of Rheumatology criteria for SLE were randomly sampled at each center, balancing by race and insurance status. Subjects were interviewed for current and past SES factors, such as insurance, occupation, employment, education, and income. SLE disease activity was measured by the SLE Activity Measure (SLAM). RESULT: Higher education, private insurance/Medicare, and higher income were associated with less disease activity at diagnosis. Controlling for SES, race, and center, the best predictors of less active disease at diagnosis were private insurance/Medicare (P = 0.002) and higher education (P = 0.007). From the time of diagnosis to the study visit (mean 3.5 years), insurance, income, and employment status changed for a significant number of subjects (37%, 16%, and 21%, respectively). CONCLUSION: Private insurance or Medicare and higher education are associated with less active disease at diagnosis of SLE. Health insurance, income, and employment status are unstable measures of socioeconomic status and may explain the variability in conclusions of previous studies on the role of SES in SLE.

Adult

Predictors of blood loss during total hip replacement surgery.

OBJECTIVE: To determine total blood loss and transfusion requirements during primary total hip replacement (THR) surgery; and, to identify predictors of increased blood loss. METHODS: This was a prospective cohort study of 295 consecutive patients undergoing primary THR at a 700-bed teaching hospital in Boston, Massachusetts. The main outcome measures were the total blood loss, which was defined (in units) as the initial hematocrit minus final hematocrit divided by 3 plus the number of units transfused, and the number of autologous and homologous units of blood transfused. RESULTS: The mean total blood loss was 3.6 units, and the mean total units transfused was 2.1. Univariate predictors of greater total blood loss (at P < 0.05) included being male, receiving general anesthesia, and higher American Society of Anesthesiologists (ASA) class. In multiple linear regression models which controlled for demographic and clinical variables (age, race, marital status, education, smoking history, obesity, underlying disease, payor status, cemented prosthesis, comorbidity, and season of operation), being male, receiving general anesthesia, and having an ASA score of 3 predicted greater total blood loss. CONCLUSION: Preoperative characteristics can help determine which patients should donate either more or less than the customary 2 units of blood.

Aged