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A C Justice

Publications and source records attributed to A C Justice.

At least 37 records · Page 2Linked to original sources

Enzyme-linked immunosorbent assay spot detection of interferon-gamma and interleukin 5-producing cells as a predictive marker for renal allograft failure.

BACKGROUND: Despite improvements in the short-term survival of renal transplants, many allografts fail over the 5-10 years after transplantation. We sought to identify an immunologic assay that could identify those patients at high risk for future allograft failure. METHODS: Blood samples were obtained from 23 renal allograft recipients with acute and/or chronic graft dysfunction and from 22 controls. Isolated peripheral blood lymphocytes (PBLs) were tested for interferon (IFN)-gamma and interleukin (IL)-5 production using an enzyme-linked immunosorbent spot assay. IFN-gamma:IL-5 ratios were calculated and compared between groups. Among the 23 patients with graft dysfunction, the ratios were also compared with graft function at 6 months. RESULTS: IFN-gamma:IL-5 ratios of > or = 15 were associated with allograft rejection episodes in 8 of 12 cases, whereas 10 of 11 episodes of graft dysfunction from other causes (infection, drug toxicity, obstruction) were associated with values <15. All normal controls had values <15 (22/22). Among the graft recipients with acute renal failure, all patients with IFN-gamma:IL-5 ratios <15 exhibited improved renal function at 6-month follow-up (14/14), whereas 8 of 9 patients with IFN-gamma:IL-5 ratios > or = 15 developed allograft failure at 6 months (sensitivity 100%, specificity 93.3%). CONCLUSION: In renal transplant recipients with acute allograft dysfunction, mitogen-induced peripheral blood lymphocyte IFN-gamma:IL-5 ratios > or = 15 were highly predictive of allograft failure within 6 months of the assay. This test may be a useful prognostic marker for identification of transplant recipients with acute graft dysfunction who are at high risk for future graft loss and thus allow targeted therapeutic interventions to prolong graft survival.

Adult↗

Does masking author identity improve peer review quality? A randomized controlled trial. PEER Investigators.

CONTEXT: All authors may not be equal in the eyes of reviewers. Specifically, well-known authors may receive less objective (poorer quality) reviews. One study at a single journal found a small improvement in review quality when reviewers were masked to author identity. OBJECTIVES: To determine whether masking reviewers to author identity is generally associated with higher quality of review at biomedical journals, and to determine the success of routine masking techniques. DESIGN AND SETTING: A randomized controlled trial performed on external reviews of manuscripts submitted to Annals of Emergency Medicine, Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology. INTERVENTIONS: Two peers reviewed each manuscript. In one study arm, both peer reviewers received the manuscript according to usual masking practice. In the other arm, one reviewer was randomized to receive a manuscript with author identity masked, and the other reviewer received an unmasked manuscript. MAIN OUTCOME MEASURE: Review quality on a 5-point Likert scale as judged by manuscript author and editor. A difference of 0.5 or greater was considered important. RESULTS: A total of 118 manuscripts were randomized, 26 to usual practice and 92 to intervention. In the intervention arm, editor quality assessment was complete for 77 (84%) of 92 manuscripts. Author quality assessment was complete on 40 (54%) of 74 manuscripts. Authors and editors perceived no significant difference in quality between masked (mean difference, 0.1; 95% confidence interval [CI], -0.2 to 0.4) and unmasked (mean difference, -0.1; 95% CI, -0.5 to 0.4) reviews. We also found no difference in the degree to which the review influenced the editorial decision (mean difference, -0.1; 95% CI,-0.3 to 0.3). Masking was often unsuccessful (overall, 68% successfully masked; 95% CI, 58%-77%), although 1 journal had significantly better masking success than others (90% successfully masked; 95% CI, 73%-98%). Manuscripts by generally known authors were less likely to be successfully masked (odds ratio, 0.3; 95% CI, 0.1-0.8). When analysis was restricted to manuscripts that were successfully masked, review quality as assessed by editors and authors still did not differ. CONCLUSIONS: Masking reviewers to author identity as commonly practiced does not improve quality of reviews. Since manuscripts of well-known authors are more difficult to mask, and those manuscripts may be more likely to benefit from masking, the inability to mask reviewers to the identity of well-known authors may have contributed to the lack of effect.

Authorship↗

Masking author identity in peer review: what factors influence masking success? PEER Investigators.

CONTEXT: In a previous study, we found that masking success was higher at a journal that masked reviewers to author identity. We hypothesized that masking policy or other factors could be associated with masking success. OBJECTIVES: To evaluate differences in success of masking reviewers to author identity at 7 biomedical journals and to identify factors associated with these differences. DESIGN: Written questionnaire. PARTICIPANTS: Reviewers at 3 journals with a long-standing policy of masking author identity (Annals of Emergency Medicine, Epidemiology, and Journal of the American Geriatrics Society) and 4 journals without a policy of masking author identity (Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology). MAIN OUTCOME MEASURES: Masking success (percentage of reviewers successfully masked) and reviewer characteristics associated with masking. RESULTS: There was no significant difference in masking success between journals with a policy of masking (60%) and those without (58%) (P= .92). We found no association between masking success and a policy of masking when adjusted for the reviewer characteristics of age, sex, years of reviewing experience, number of articles published, number of articles reviewed, percentage of time spent in research, editorial experience, or academic rank (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.64-2.8; P=.43). In multivariable analysis of reviewer characteristics, reviewers spending a greater percentage of time in research, the only significant predictor of masking success, were less likely to be successfully masked (OR, 1.01; 95% CI, 1.00-1.02) (P=.04). CONCLUSIONS: Masking success appears unrelated to a journal policy of masking, but is associated with reviewers' research experience and could be affected by other characteristics. Using reviewers with less research and reviewing experience might increase masking success, but the effect on review quality is unknown.

Authorship↗

Free pentosidine and neopterin as markers of progression rate in diabetic nephropathy. Collaborative Study Group.

BACKGROUND: Patients with diabetic nephropathy experience a progressive and usually inexorable decline in renal function. The presence of the structurally defined advanced glycation end product (AGE) pentosidine on tissue and circulating proteins has been correlated with the severity of diabetic complications. METHODS: To delineate a role for this AGE in the progression of diabetic nephropathy, glycohemoglobin and free and protein-bound pentosidine were measured in baseline stored serum and urine from a subgroup of patients with diabetes mellitus and proteinuria originally followed by the Collaborative Study Group Trial. To delineate a potential role for an immune-activation response to AGEs, the inflammatory markers, interleukin-6 (IL-6), C-reactive protein (CRP), and the monocyte activation marker marker neopterin were also measured at baseline. The patients chosen represented 67 subjects whose creatinine levels had "doubled" over the course of the study whether or not they later were treated with captopril, and 67 paired "non-doublers." RESULTS: Baseline disease activity, as manifested by glycohemoglobin, serum creatinine and degree of proteinuria was equal in the two groups, as was protein-bound pentosidine and the immune-markers IL-6 and CRP. At baseline the "doublers" as compared to the "non-doublers" had elevated serum levels of free pentosidine and neopterin. Baseline increases in these two parameters were also associated with an increased rate of "doubling" of serum creatinine by the proportional hazards method. CONCLUSION: Differences in individual responsiveness to AGEs, as manifested by either the production of free pentosidine or its release from a protein-bound form, and by evidence of monocyte/macrophage activation, are associated with progression of diabetic nephropathy.

Adult↗

The relation between health status changes and patient satisfaction in older hospitalized medical patients.

OBJECTIVE: To examine the relation between two patient outcome measures that can be used to assess the quality of hospital care: changes in health status between admission and discharge, and patient satisfaction. DESIGN: Prospective cohort study. SETTING AND PATIENTS: Subjects were 445 older medical patients (aged > or =70 years) hospitalized on the medical service of a teaching hospital. MEASUREMENTS AND MAIN RESULTS: We interviewed patients at admission and discharge to obtain two measures of health status: global health and independence in five activities of daily living (ADLs). At discharge, we also administered a 5-item patient satisfaction questionnaire. We assessed the relation between changes in health status and patient satisfaction in two sets of analyses, that controlled for either admission or discharge health status. When controlling for admission health status, changes in health status between admission and discharge were positively associated with patient satisfaction (p values ranging from .01 to .08). However, when controlling for discharge health status, changes in health status were no longer associated with patient satisfaction. For example, among patients independent in ADLs at discharge, mean satisfaction scores were similar regardless of whether patients were dependent at admission (i.e., had improved) or independent at admission (i.e., remained stable) (79.6 vs 81.2, p = .46). Among patients dependent in ADLs at discharge, mean satisfaction scores were similar regardless of whether they were dependent at admission (i.e., remained stable) or independent at admission (i.e., had worsened) (74.0 vs 75.7, p = .63). These findings were similar using the measure of global health and in multivariate analyses. CONCLUSIONS: Patients with similar discharge health status have similar satisfaction regardless of whether that discharge health status represents stable health, improvement, or a decline in health status. The previously described positive association between patient satisfaction and health status more likely represents a tendency of healthier patients to report greater satisfaction with health care, rather than a tendency of patients who improve following an interaction with the health system to report greater satisfaction. This suggests that changes in health status and patient satisfaction are measuring different domains of hospital outcomes and quality. Comprehensive efforts to measure the outcomes and quality of hospital care will need to consider both patient satisfaction and changes in health status during hospitalization.

Aged↗

Associations between the use of do-not-resuscitate orders and length of stay in patients with stroke.

OBJECTIVES: The study sought to describe the association between do-not-resuscitate (DNR) orders and length of hospital stay (LOS), and how the association varies according to in-hospital mortality, timing of the DNR order, and admission severity of illness. METHODS: The authors conducted a retrospective cohort analysis involving standardized review of patients' medical records. The study was performed at 30 acute care hospitals in a large metropolitan area. The authors studied the data of 13,337 consecutive patients with a primary diagnosis of stroke discharged in 1991 through 1994. RESULTS: Do-not-resuscitate orders were written for 22% (n = 2,898) of the sample. In all patients, mean LOS was longer in patients with DNR orders than in patients without orders (12.0 versus 9.5 days; P < 0.001). A series of Cox regression analyses were performed to adjust LOS for admission severity of illness and other covariates. In analyses of patients discharged alive (n = 12,011), LOS was similar in patients with DNR orders written on days 1 to 2 compared with patients without DNR orders. However, LOS was longer in patients with DNR orders written on days 3 to 7 (Hazard Ratio [HR], 1.59; 95% CI, 1.43-1.77) and on day 8 or later (HR, 2.72; 95% CI, 2.34-3.16). In analyses of patients who died (n = 1,326), LOS was shorter for patients with DNR orders written on days 1 and 2 (HR, 0.59; 95% CI, 0.49-0.71) than for patients without DNR orders but was longer among patients with DNR orders written on day 8 or later (HR, 2.58; 95% CI, 2.06-3.22). In analyses stratified by admission severity, the relative effect of a DNR order tended to be less in patients with higher severity. CONCLUSIONS: The relationship between DNR orders and LOS is complex and varies according to in-hospital mortality, the timing of the DNR order, and admission severity of illness. These findings highlight the importance of explicitly accounting for such factors in studies evaluating the implications of DNR orders on the costs of hospital care.

Aged↗

Measuring prognosis and case mix in hospitalized elders. The importance of functional status.

OBJECTIVE: Although physical function is believed to be an important predictor of outcomes in older people, it has seldom been used to adjust for prognosis or case mix in evaluating mortality rates or resource use. The goal of this study was to determine whether patients' activity of daily living (ADL) function on admission provided information useful in adjusting for prognosis and case mix after accounting for routine physiologic measures and comorbid diagnoses. SETTING: The general medical service of a teaching hospital. PARTICIPANTS: Medical inpatients (n = 823) over age 70 (mean age 80.7, 68% women). MEASUREMENTS: Independence in ADL function on admission was assessed by interviewing each patient's primary nurse. We determined the APACHE II Acute Physiology Score (APS) and the Charlson comorbidity score from chart review. Outcome measures were hospital and 1-year mortality, nursing home use in the 90 days following discharge, and cost of hospitalization. Patients were divided into four quartiles according to the number of ADLs in which they were dependent. MAIN RESULTS: ADL category stratified patients into groups that were at markedly different risks of mortality and higher resource use. For example, hospital mortality varied from 0.9% in patients dependent in no ADL on admission, to 17.4% in patients dependent in all ADLs. One-year mortality ranged from 17.5% to 54.9%, nursing home use from 3% to 33%, and hospital costs varied by 53%. In multivariate analyses controlling for APS. Charlson scores, and demographic characteristics, compared with patients dependent in no ADL, patients dependent in all ADLs were at greater risk of hospital mortality (odds ratio [OR] 13.7; 95% confidence interval [CI] 3.1-58.8), 1-year mortality (OR 4.4; 2.7-7.4), and 90-day nursing home use (OR 14.9; 6.0-37.0). The DRG-adjusted hospital cost was 50% higher for patients dependent in all ADLs. ADL function also improved the discrimination of hospital and 1-year mortality models that considered APS, or Charlson scores, or both. CONCLUSIONS: ADL function contains important information about prognosis and case mix beyond that provided by routine physiologic data and comorbidities in hospitalized elders. Prognostic and case-mix adjustment methods may be improved if they include measures of function, as well as routine physiologic measures and comorbidity.

Activities of Daily Living↗

Management of incidental pituitary microadenomas: a cost-effectiveness analysis.

The objective of this study was to compare the cost-effectiveness of four management strategies for a patient with an incidentally discovered asymptomatic pituitary microadenoma. A decision analytic Markov model was used to determine the incremental cost-effectiveness of four clinical management strategies: 1) expectant management, 2) PRL screening, 3) an endocrine screening panel (PRL, insulin-like growth factor I, and 1-mg dexamethasone suppression test), and 4) magnetic resonance imaging (MRI) follow-up. The model incorporated the natural history of incidental microadenomas, test characteristics, pharmacological and surgical treatment outcomes, patient's quality of life, discounting, and the costs of hormone testing, bromocriptine, MRIs, hospitalization for surgery, and physician services. PRL screening, endocrine screening panel, and MRI follow-up all provided slightly greater quality-adjusted survival than expectant management, but the costs increased disproportionately more than the benefits. The incremental cost per quality-adjusted life year for PRL screening is $1,428, and that for the endocrine screening panel is $69,495. These results are most sensitive to patient anxiety about the microadenoma; increased anxiety shifts the recommended strategy to the endocrine screening panel. We conclude that in patients with an incidental asymptomatic pituitary microadenoma, a single PRL test may be the most cost-effective management strategy.

Adenoma↗

A cost-effectiveness analysis of anterior temporal lobectomy for intractable temporal lobe epilepsy.

Patients with medically intractable temporal lobe epilepsy are potential candidates for anterior temporal lobectomy (ATL), in which epileptogenic temporal lobe tissue is localized and surgically removed. This surgical approach can eliminate or drastically reduce seizures in the majority of patients. The authors used a decision-analysis model to examine the cost-effectiveness of a surgical evaluation and treatment protocol for medically intractable temporal lobe epilepsy. This model compared a cohort treated with the new protocol with a continuation of their immediate preoperative medical management and projected these differences over the patient's lifetime. The Markov model incorporated postoperative seizure status, patient quality of life, death from surgical and natural causes, discounting, and the direct medical costs associated with outpatient evaluation, hospitalization, surgery, antiepileptic drugs, and lifetime outpatient treatment. The intent-to-treat analysis included patients who underwent evaluation but were not eligible for ATL. Sensitivity analyses were also performed on the variables in the model. Data from the baseline model indicated that evaluation for ATL provided an average of 1.1 additional quality-adjusted life years (QALYs) compared with continued medical management, at an additional cost of $29,800. Combining the clinical and economic outcomes yielded a cost-effectiveness ratio of $27,200 per QALY. This value is comparable to other accepted medical or surgical interventions, such as total knee arthroplasty ($16,700/QALY) or coronary artery balloon angioplasty ($40,800/QALY). Sensitivity analyses demonstrate that the results are critically dependent on postoperative seizure status and improvement in quality of life. Although further work is necessary to quantify the improvement in quality of life after epilepsy surgery better, the present data indicate that ATL for treatment of intractable temporal lobe epilepsy is a cost-effective use of medical resources.

Adult↗

The role of functional status in predicting inpatient mortality with AIDS: a comparison with current predictors.

To assess the independent prognostic role of functional status, as reflected by a measure of an inpatient's global requirement for nursing assistance with basic activities of daily living (Global ADL), we compared Global ADL with three validated AIDS mortality predictors: the Clinical AIDS Prognostic Staging (CAPS); the Severity Classification System for AIDS Hospitalization--version 2 (SCAH-2); and CD4 cell count. Our study sample consisted of 1392 patients with AIDS and a hospital stay of 3 or more days at one of 20 hospitals in 11 U.S. cities with high AIDS incidence. Data were collected from September 1990 through December 1991. Two percent of patients refused participation, and 26% were eliminated due to incomplete data collection, leaving an analytic sample of 1003 patients. Only 30% of patients had a CD4 count measured at any time during hospitalization. Cox regression was used to measure the hazard of inpatient mortality adjusted for length of stay. Overall mortality was 12%. Mortality rates for patients in Global ADL stages I-IV were 3%, 8%, 19%, and 51%, respectively (p < 0.0001). Global ADL more effectively discriminated mortality than CAPS (p < 0.001), SCAH-2 (p < 0.001), or CD4 count (p < 0.001). Global ADL also added independent information in analyses adjusted for both CAPS and SCAH-2: a single stage increase of Global ADL demonstrated a 1.9-fold increased hazard of death (CI: 1.6, 2.3). SCAH-2, assigned at discharge, was not strongly correlated with admission predictors (Global ADL: r = 0.17; CI: 0.11, 0.23 or CAPS: r = 0.03, CI: 0.02, 0.17). We conclude that Global ADL, alone or in tandem with other severity systems, provides an excellent severity adjustment for inpatient mortality with AIDS. Finally, CD4 cell counts were not routinely available and were not as predictive as Global ADL in the patients for whom both were available.

Acquired Immunodeficiency Syndrome↗

Do readers and peer reviewers agree on manuscript quality?

OBJECTIVE: To study readers' judgments of manuscript quality and the degree to which readers agreed with peer reviewers. DESIGN: Cross-sectional study. SETTING: Annals of Internal Medicine. SUBJECTS: One hundred thirteen consecutive manuscripts reporting original research and selected for publication. Each of two manuscript versions (one before and one after revision) was judged by two readers, randomly sampled from those who said (based on the title) that they would read the article; one peer reviewer (peer), chosen in the usual way for Annals; and one expert in clinical research methods (expert). Each judge completed an instrument that included a 10-point subjective summary grade of manuscript quality. MAIN OUTCOME MEASURES: Agreement on the 10-point summary grade of manuscript quality between reader-expert, reader-peer, and reader-reader. RESULTS: Readers and peers gave high grades (77% and 73% gave a grade of 5 or better, respectively), while experts were more critical (52% gave a grade of 5 or better; P < .0001). Agreement was relatively high among judge groups (in all cases, > 69%) but agreement beyond chance was poor (kappa < 0.04). One third of readers (33%) thought that the manuscript had little relevance to their work. CONCLUSION: Readers, like most peer reviewers, are generally satisfied with the quality of manuscripts but would like research articles to be more relevant to their clinical practice.

Cross-Sectional Studies↗

A new prognostic staging system for the acquired immunodeficiency syndrome.

An improved prognostic staging system is needed for patients with the acquired immunodeficiency syndrome (AIDS). To construct such a system, we analyzed the course of 117 consecutive adults who received a diagnosis of AIDS at Yale-New Haven Hospital from 1981 through 1987. The staging system was developed from the data on the first 76 patients, confirmed in the remaining 41 patients, and then applied to the entire cohort. The staging system, which is based on physiologic deficits rather than demographic or diagnostic features, gives one point for each of the following: severe diarrhea or serum albumin level under 2.0 g per deciliter, any neurologic deficit, arterial oxygen tension of 50 mm Hg or less, hematocrit below 30 percent, lymphocyte count below 150 per microliter, white-cell count below 2500, and platelet count below 140,000. The total score determines the presence of Stages I (0 points), II (1 point), or III (2 to 7 points). The three stages had distinctive prognostic gradients in our cohort. For patients in Stages I, II, and III, the median survival times were 11.6, 5.1, and 2.1 months, respectively, with one-year survival rates of 50, 30, and 8 percent. When the staging system was tested with a proportional-hazards model, no other descriptive or laboratory variable added any additional predictive power. Although this new staging system requires further validation in other populations, we believe it will be useful in evaluating new therapies and improving the precision of prognosis in patients with AIDS.

Acquired Immunodeficiency Syndrome↗