Determining the prevalence of tuberculosis in emergency departments in the Eastern Cape region of South Africa and the utility of the World Health Organization tuberculosis screening tool.

BACKGROUND: South Africa (SA) faces a significant tuberculosis (TB) burden complicated by high rates of HIV-TB co-infection. In SA, emergency departments (EDs) play an important role in screening for TB. OBJECTIVES: To determine the prevalence of TB in the ED and the effectiveness of the World Health Organization (WHO) TB screening tool. METHODS: This was a cross-sectional observational study, conducted in the ED at Livingstone Hospital, Port Elizabeth, from 4 June to 15 July 2018. All patients aged >18 years and able to consent were administered the WHO TB screening questions and underwent a point-of-care HIV test and demographic data collection. Patients were followed up for 1 year and tracked in the National Health Laboratory Service database to determine TB status using laboratory testing. RESULTS: Over the study period, 790 patients were enrolled. Overall, 121 patients (15.3%) were TB-positive, with 46 (38.0%) diagnosed after presenting to the ED and 75 (62.0%) with a previous TB history determined by self-report or confirmed laboratory testing. A greater proportion of the TB-positive patients were HIV-positive (49.6%) compared with the TB-negative population (24.8%). TB-positive individuals were more likely to present to the ED with a chief complaint of shortness of breath (SoB) (18.2%) compared with the TB-negative population (10.5%). Overall, the WHO TB screening tool had poor sensitivity (46.5%) and specificity (62.5%) for identifying TB-positive patients in the ED. A multiple logistic regression analysis, controlled for age and sex, showed HIV status (odds ratio (OR) 2.81; p<0.001) and SoB (OR 2.19; p<0.05) to be significant predictors of TB positivity. Adding positive HIV status and a presenting complaint of SoB increased sensitivity to 78.3%. CONCLUSIONS: EDs in SA face a high burden of TB. While WHO screening guidelines identify some of these patients, including routine HIV testing in the ED could significantly affect the number of TB diagnoses made.

Impact of endemic HIV on emergency care service delivery in South Africa.

BACKGROUND: South Africa (SA) has the highest burden of HIV in the world. This study sought to evaluate the impact of high HIV prevalence on the burden of disease in an emergency department (ED). OBJECTIVES: To determine the burden of comorbidities in HIV-positive emergency care patients, their demographic profiles and severity of illness were compared with the general ED population in order to make recommendations for resource allocation and training in EDs in SA. METHODS: A prospective cross-sectional observational study was conducted from June 2017 to July 2018 in three EDs in Eastern Cape Province. All eligible patients (aged ≥18 years, fully conscious and clinically stable) presenting to the ED during the 6-week study period were approached and asked to give consent for a point-of-care HIV test and collection of demographic information. Simple descriptive statistics were used to analyse data. Log binomial and Poisson models were fitted to estimate prevalence ratios (PRs). RESULTS: Over the total study period, 8 000 patients presented to the ED for care across all sites and 3 537 patients were enrolled. The HIV status of 2 901 individuals (82.0%) was determined. Of those who were screened, 811 (28.0%) were identified as HIV-positive. Medical complaints were more common in HIV-positive patients (n=586, 72.3%) than in trauma patients (n=225, 27.7%). In comparison, HIV-negative patients reported fewer medical complaints (n=1 137, 54.4%) and more trauma (n=953, 45.6%) (p<0.001). HIV-positive patients were more likely to have a life-threatening emergency (n=192, 23.7%) (p=0.004), to be critically ill by triage score (p<0.001) and to be admitted to the hospital (p<0.001) than those who were HIV-negative. Despite high acuity overall, people living with HIV/AIDS were significantly less likely to be deemed critically ill according to vital signs (adjusted PR 0.94; p=0.046). CONCLUSIONS: While EDs in SA provide care to high volumes of patients with trauma-related injuries, in areas where HIV prevalence is highest, patients are more likely to present with acute medical emergencies. Providers of emergency care in SA need to be well versed in the management of HIV and associated complications.

A new measure for end of life planning, preparation, and preferences in Huntington disease: HDQLIFE end of life planning.

BACKGROUND: Huntington disease is a fatal inherited neurodegenerative disease. Because the end result of Huntington disease is death due to Huntington disease-related causes, there is a need for better understanding and caring for individuals at their end of life. AIM: The purpose of this study was to develop a new measure to evaluate end of life planning. DESIGN: We conducted qualitative focus groups, solicited expert input, and completed a literature review to develop a 16-item measure to evaluate important aspects of end of life planning for Huntington disease. Item response theory and differential item functioning analyses were utilized to examine the psychometric properties of items; exploratory factor analysis was used to establish meaningful subscales. PARTICIPANTS: Participants included 508 individuals with pre-manifest or manifest Huntington disease. RESULTS: Item response theory supported the retention of all 16 items on the huntington disease quality of life ("HDQLIFE") end of life planning measure. Exploratory factor analysis supported a four-factor structure: legal planning, financial planning, preferences for hospice care, and preferences for conditions (locations, surroundings, etc.) at the time of death. Although a handful of items exhibited some evidence of differential item functioning, these items were retained due to their relevant clinical content. The final 16-item scale includes an overall total score and four subscale scores that reflect the different end of life planning constructs. CONCLUSIONS: The 16-item HDQLIFE end of life planning measure demonstrates adequate psychometric properties; it may be a useful tool for clinicians to clarify patients' preferences about end of life care.

HDQLIFE: development and assessment of health-related quality of life in Huntington disease (HD).

PURPOSE: Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL-Quality of Life in Neurological Disorders and PROMIS-Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS methodology to develop new, HD-specific content. METHODS: New item pools were developed using cognitive debriefing with individuals with HD, and expert, literacy, and translatability reviews. Existing item banks and new item pools were field tested in 536 individuals with prodromal, early-, or late-stage HD. RESULTS: Moderate to strong relationships between Neuro-QoL/PROMIS measures and generic self-report measures of HRQOL, and moderate relationships between Neuro-QoL/PROMIS and clinician-rated measures of similar constructs supported the validity of Neuro-QoL/PROMIS in individuals with HD. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new item banks for Chorea, Speech Difficulties, Swallowing Difficulties, and Concern with Death and Dying, with corresponding six-item short forms. A four-item short form was developed for Meaning and Purpose. CONCLUSIONS: HDQLIFE encompasses both validated Neuro-QoL/PROMIS measures, as well as five new scales in order to provide a comprehensive assessment of HRQOL in HD.

New measures to capture end of life concerns in Huntington disease: Meaning and Purpose and Concern with Death and Dying from HDQLIFE (a patient-reported outcomes measurement system).

PURPOSE: Huntington disease (HD) is an incurable terminal disease. Thus, end of life (EOL) concerns are common in these individuals. A quantitative measure of EOL concerns in HD would enable a better understanding of how these concerns impact health-related quality of life. Therefore, we developed new measures of EOL for use in HD. METHODS: An EOL item pool of 45 items was field tested in 507 individuals with prodromal or manifest HD. Exploratory and confirmatory factor analyses (EFA and CFA, respectively) were conducted to establish unidimensional item pools. Item response theory (IRT) and differential item functioning analyses were applied to the identified unidimensional item pools to select the final items. RESULTS: EFA and CFA supported two separate unidimensional sets of items: Concern with Death and Dying (16 items), and Meaning and Purpose (14 items). IRT and DIF supported the retention of 12 Concern with Death and Dying items and 4 Meaning and Purpose items. IRT data supported the development of both a computer adaptive test (CAT) and a 6-item, static short form for Concern with Death and Dying. CONCLUSION: The HDQLIFE Concern with Death and Dying CAT and corresponding 6-item short form, and the 4-item calibrated HDQLIFE Meaning and Purpose scale demonstrate excellent psychometric properties. These new measures have the potential to provide clinically meaningful information about end-of-life preferences and concerns to clinicians and researchers working with individuals with HD. In addition, these measures may also be relevant and useful for other terminal conditions.

Equating EORTC QLQ-C30 and FACT-G scores and its use in oncological research.

OBJECTIVE: To investigate the equivalence of the European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) and the Functional Assessment for Cancer Therapy-General (FACT-G) on the basis of corresponding subscales, and where appropriate to derive a scheme for converting QLQ-C30 scores into FACT-G scores and vice versa for use in oncological research. METHOD: A calibration sample of 737 cancer patients (mean age 51.4+/-7.6 (SD), 63% female, 25% with current chemotherapy) who filled in both quality of life (QOL) questionnaires was used. Both classical test theory and the Rasch measurement model were applied. RESULTS: Three of the four subscales common to both QOL instruments (physical, emotional, functional) proved suitable for equating (acceptable inter-correlations of corresponding subscales physical (r=0.77), emotional domain (r=0.60) role/functional (r=0.63) relative to their internal consistency, sufficient unidimensionality of pooled subscales, satisfactory fit to the Rasch model). Conversion tables for these subscales were generated. CONCLUSIONS: The conversion tables developed in this study (physical, emotional and functional/role domain) appear promising for the comparison between EORTC QLQ-C30 and FACT-G scores of patient samples.

Re-validation and shortening of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire.

PURPOSE: The original Functional Assessment of Anorexia/Cachexia Therapy (FAACT) was designed to measure general aspects of quality of life (QOL) as well as specific anorexia/cachexia-related concerns. Our primary purpose was to reduce the number of anorexia/cachexia subscale items in a manner that either retains or improves reliability, validity and precision. METHODS: The FAACT was administered using an interactive computer program that allowed immediate entry of the data. A total of 213 patients were recruited. RESULTS: A combined empirical and conceptual approach led to the reduction of the anorexia/cachexia subscale (A/CS) from 18 to 12 items. A 26-item trial outcome index (TOI) combining physical well-being (PWB), functional well-being (FWB), and the A/CS-12 was highly reliable and sensitive to change in performance status rating (PSR). We found that PWB, FWB, and A/CS-12 subscales performed differently. Specifically, PWB and FWB scores decreased in patients whose (PSR) worsened. However, although A/CS-12 scores were responsive to change in PSR over time, average A/CS-12 scores of all patients, even those whose PSR worsened, improved over the course of treatment. CONCLUSIONS: Elimination of six items from the anorexia/cachexia subscale of the FAACT was accomplished without loss of internal consistency or sensitivity to change in performance status. The A/CS-12 subscale provides unique, important information not captured by a generic chronic illness questionnaire.

Reliability and validity of the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) quality of life instrument.

BACKGROUND: This paper describes the development of the Functional Assessment of Cancer Therapy-Colorectal (FACT-C)--a questionnaire assessing quality of life concerns pertinent to colorectal cancer patients. This self-report instrument combines specific concerns related to colorectal cancer with concerns that are common to all cancer patients as assessed with the FACT-General (FACT-G). METHOD: Three separate and distinct validation samples were used with different ethnic and stage of disease compositions. RESULTS: Results suggest that the FACT-C is a reliable and valid measure in both its English and Spanish language versions. Specifically, the FACT-C evidenced good internal consistency reliability and concurrent validity, as well as an ability to distinguish between groups based on functional status and extent of disease. The FACT-C was also found to be sensitive to changes in functional status. Colorectal cancer-specific items form the Colorectal Cancer Subscale (CCS) which was found to have adequate convergent and divergent validity. Internal consistency was adequate in most samples. In addition, the CCS was able to distinguish among groups that differed in functional status and was sensitive to change in functional status. CONCLUSION: It is recommended that the entire FACT-C (rather than simply the CCS) be used when studying patients with colorectal cancer in order to provide a comprehensive assessment of quality of life. Recommendations are offered concerning the appropriate use of these measures in clinical research and directions for future research with colorectal cancer patients.

The impact of socio-cultural and clinical factors on health-related quality of life reports among Hispanic and African-American cancer patients.

A hierarchical multiple linear regression approach (N = 761) was used to identify pertinent factors which influence health-related quality of life (HRQL) reports among Hispanic and African-American cancer patients. The independent variables include: performance status, disease site, disease stage, mode of administration, socio-economic status (SES), gender, age, living arrangement, race/ethnicity, religious affiliation, insurance status, and spiritual beliefs. The outcome measures, five subscales of HRQL (physical well-being, social well-being, satisfaction with treatment, emotional well-being, functional well-being) and overall HRQL (sum of the five subscales), were estimated using the Functional Assessment of Cancer Therapy (FACT) Scales. This study identified performance status and spiritual beliefs as consistent predictors of overall HRQL. This study also found no significant effects of SES, mode of administration, gender age, living arrangement and insurance status on the reporting of overall HRQL. Spiritual beliefs and performance status are important determinants of HRQL across a diverse group of cancer patients.

Clinical significance of syncope in the electrophysiologic study versus electrocardiographic monitoring (ESVEM) trial. The ESVEM Investigators.

BACKGROUND: Syncope may portend risk of death, but which patients with syncope are at high risk remains unclear. OBJECTIVE: The ESVEM trial, a multicenter randomized prospective trial, provided the opportunity to compare mortality rates of patients enrolled with syncope to those enrolled with spontaneous ventricular arrhythmias. METHODS: Patients enrolled in the ESVEM trial presenting with syncope alone (25 patients) or in combination with ventricular tachycardia (24 patients) were compared with patients with spontaneous ventricular tachycardia alone (332 patients) or ventricular fibrillation (105 patients). All patients had ventricular tachyarrhythmias induced at electrophysiology testing of >/=10 premature ventricular complexes per hour on Holter monitor. RESULTS: Of all patients randomly assigned, arrhythmic death and total mortality rates were the same for those with syncope alone, with ventricular tachycardia and syncope, with ventricular tachycardia alone, or with ventricular fibrillation. At 1 year, arrhythmic and total mortality rate for all patients was 21% and 24%, respectively; for patients with syncope alone, 30% and 29%, respectively (P = NS). At 4 years, arrhythmic death and total mortality rate for all patients was 33% and 42%, respectively; for patients with syncope alone, 37% and 42%, respectively (P = NS). CONCLUSION: Syncope, associated with induced ventricular tachyarrhythmias at electrophysiologic testing, indicates high risk for death, similar to that of patients with documented spontaneous ventricular tachyarrhythmias.

Missing data in quality of life research in Eastern Cooperative Oncology Group (ECOG) clinical trials: problems and solutions.

Incorporation of quality of life (QOL) investigation into Eastern Cooperative Oncology Group (ECOG) multi-centre clinical trials has led to innovative strategies for protocol design and high quality data collection. A scientific advisory committee reviews protocol design components, measurement selection, timing of assessments and compliance issues. Extensive educational programmes provide information about the scientific and clinical relevance of QOL protocols, as well as practical strategies for data collection and management. Compliance with QOL data collection standards is prospectively monitored and evaluated. Preliminary results from eight ECOG-run protocols found overall compliance to be approximately 85 per cent (94 per cent at baseline and 73 per cent during treatment). Selected patient and institutional factors were evaluated for their association with compliance.

Statistical analysis of quality of life with missing data in cancer clinical trials.

We summarize issues that arise when considering quality of life (QOL) data in cancer clinical trials, especially those related to missing data. We describe different types of missing data mechanisms, and discuss ways of assessing and testing missing data mechanisms. A section on presentation of study design and results describes how graphical displays can effectively document the extent of the missing data problem, as well as describe its impact on interpretation of results. Finally, we describe several different statistical methods used to analyse repeated measures, with an emphasis on their properties and their ability to adequately handle different types of missing data mechanisms. We make recommendations as to the most appropriate methods, and suggest important directions for future research.

Effect of reproducibility of baseline arrhythmia induction on drug efficacy predictions and outcome in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial.

Spontaneous variability over time in the ease of induction of ventricular arrhythmias may mimic a drug effect and affect the predictive value of drug therapy guided by programmed stimulation. We assessed the effect of baseline reproducibility of arrhythmia induction on the incidence and accuracy of drug efficacy predictions in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial. Patients with sustained ventricular tachyarrhythmias induced twice during baseline electrophysiologic testing with the same stimulation technique, i.e., induced at the same pacing site with the same drive cycle length and number of extrastimuli, were identified from the ESVEM database. These patients with highly reproducible arrhythmia induction were compared to those with less reproducible arrhythmias. Of 473 randomized patients with reproducibility data, 313 (66%) had highly reproducible arrhythmias. In patients randomized to electrophysiologic testing, baseline arrhythmia reproducibility did not affect the incidence of drug efficacy predictions (70 of 157 [45%], drug efficacy predictions in patients with highly reproducible arrhythmias vs 34 of 79 [43%] with less reproducible arrhythmias, p = 0.890). Drug efficacy predictions obtained by electrophysiologic testing in patients with highly reproducible arrhythmias were not associated with decreases in arrhythmia recurrence (p = 0.202), all-cause mortality (p = 0.301), cardiac death (p = 0.358), or arrhythmic death (p = 0.307) compared to those with less reproducible arrhythmias. Analysis of patients with highly reproducible sustained monomorphic ventricular tachycardia led to similar results. In the ESVEM trial, most patients had highly reproducible arrhythmia induction during baseline electrophysiologic testing. Reproducibility of arrhythmia induction in the baseline state had no effect on the incidence or accuracy of drug efficacy predictions.

Predictors of arrhythmic death and cardiac arrest in the ESVEM trial. Electrophysiologic Study Versus Electromagnetic Monitoring.

BACKGROUND: The purpose of this study was to determine if the presenting ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation/cardiac arrest) predicted the type of arrhythmia recurrence in patients treated with antiarrhythmic drugs. METHODS AND RESULTS: In the previously reported Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, there were 486 patients who were randomized to antiarrhythmic drug testing guided by electrophysiological study or by ambulatory ECG monitoring. Use of a defibrillator (implantable cardioverter-defibrillator, ICD) without stored electrograms among 81 patients precluded determination of the type of arrhythmia recurrence; thus these patients were censored at the time of ICD implantation. Of the 486 patients, 381 presented with ventricular tachycardia and 105 with cardiac arrest. Over a 6-year follow-up period, 285 of the 486 patients had an arrhythmia recurrence; of these, 97 had an arrhythmic death or cardiac arrest as a first recurrence. In the current analysis, all 129 arrhythmic deaths/cardiac arrests that occurred any time during follow-up were evaluated as end points. CONCLUSIONS: Although univariate analysis suggested that there was an association between the presenting arrhythmia and outcome, multivariate analysis failed to substantiate the predictive value of the presenting arrhythmia. Left ventricular ejection fraction was the single most important predictor of arrhythmic death or cardiac arrest. This information may be an important factor in deciding whether to advise ICD therapy.

Multilingual translation of the Functional Assessment of Cancer Therapy (FACT) quality of life measurement system.

There is need for multilingual cross-culturally valid quality of life (QOL) instrumentation to assess the QOL endpoint in international oncology clinical trials. We therefore initiated a multilingual translation of the Functional Assessment of Cancer Therapy (FACT) Quality of Life Measurement System (Version 3) into the following languages: Dutch, French, German, Italian, Norwegian and Swedish. Prior to this project, the FACT Measurement System was available in English, Spanish and Canadian French. The FACT is a self-report instrument which measures multidimensional QOL. The FACT (Version 3) evaluation system uses a 29-49 item compilation of a generic core (29 Likert-type items) and numerous subscales (9-20 items each) which reflect symptoms associated with different diseases, symptom complexes and treatments. The FACT-G (general version) and eight of 18 available cancer-related subscales were translated using an iterative forward-backward translation sequence. After subsequent review by 21 bilingual health professionals, all near final language versions underwent pretesting with a total of 95 patients in the native countries. Available results indicate good overall comprehensibility among native language-speakers. Equivalent foreign language versions of the FACT will permit QOL evaluation of people from diverse cultural backgrounds.

A cytolytic function for a sialic acid-binding lectin that is a member of the pentraxin family of proteins.

A variety of invertebrates possess plasma lectins with sialic acid recognition capabilities. One of the best studied of these lectins is limulin, which is a member of the pentraxin family of proteins and is found in the plasma of the American horseshoe crab, Limulus polyphemus. We find that limulin is one of several sialic acid-binding lectins of Limulus plasma and is present at a much lower abundance than Limulus C-reactive protein, the other plasma pentraxin. Limulin was purified by sequential affinity chromatography on phosphorylethanolamine-agarose, which isolates the pentraxins and separates limulin from the other sialic acid-binding lectins of the plasma, followed by fetuin-Sepharose, which binds limulin and separates it from Limulus C-reactive protein, the most abundant pentraxin of the plasma. We show here that limulin is the mediator of the Ca+2-dependent hemolytic activity found in the plasma of Limulus. Plasma that was depleted in the pentraxins by passage over phosphorylethanolamine-agarose or was depleted in the sialic acid-binding lectins by passage over fetuin-Sepharose lacked hemolytic activity. Purified limulin was hemolytic at concentrations of 3-5 nM. The other sialic acid-binding lectins of Limulus plasma and Limulus C-reactive protein were nonhemolytic. Foreign cell cytolysis by limulin represents a novel function for a plasma lectin and is the first documented function for limulin.

Design and analysis of the ESVEM Trial.

Inadequate understanding of the design and statistical approach of a clinical trial and the failure to recognize subjective aspects of the analysis often result in misinterpretation of trial results. This is exacerbated by the push to shorten publications and the wish for a simple message that summarizes the outcome of the trial. The purpose of this review is to critically review the design and statistical analyses of the results, to evaluate the assumptions underlying the statistical tests, and to examine the results of exploratory analysis on the interpretation of major findings of the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial. The trial was unusual because its primary objective was to compare testing methods instead of treatments. This necessitated using a subset of the original randomized groups for sensible analysis of the clinical question. Nevertheless, the two groups appeared to be well balanced. The absence of a difference in outcome could be verified by several analyses. In addition, confidence intervals were narrow, indicating the high precision and reliability of the findings. However, the comparison of antiarrhythmic drugs is problematic because the trial was not designed to address this issue. There were differences in the distribution of clinical characteristics between the groups who received different antiarrhythmic drugs. Nevertheless, using both univariate analyses and a variety of adjustments for important prognostic variables, treatment with sotalol appeared to be a significant predictor of reduced arrhythmia recurrence, and sotalol was consistently associated with a trend for nearly a 50% reduction in sudden death and all-cause mortality as compared with the other drugs administered in the trial. In conclusion, the ESVEM trial raises a number of interesting and instructive issues about clinical trial design and analysis.

The Myocarditis Treatment Trial: design, methods and patients enrollment.

The Myocarditis Treatment Trial was a multicentre clinical trial conducted to determine the efficacy of immunosuppressive therapy for treatment of biopsy-documented myocarditis, and to improve understanding of the immunological mechanisms in the development of myocarditis. Thirty-one centres screened 2305 patients with unexplained heart failure, and 2233 patients underwent an endomyocardial biopsy which provided adequate tissue for diagnosis. Those with a positive biopsy and a left ventricular ejection fraction (LVEF) less than 45% were randomly assigned to receive immunosuppressive therapy plus conventional drug therapy for congestive heart failure (66 patients) or conventional therapy only (45 patients) for 24 weeks. For 28 additional weeks all patients received conventional therapy only. In addition to diagnostic and clinical data, serum and myocardial tissue for immunological marker analysis and histopathologic evaluation were collected at baseline and at 12, 28 and 52 weeks after randomization. The primary analysis of efficacy was designed as a comparison of the mean increase in LVEF at week 28 between treatment limbs. Secondary objectives were to evaluate survival differences, and changes in the histopathology of the disease and immunological markers. Randomized patients were relatively young (mean age, 42.0 years +/- 13.8 standard deviation (sd) and entered the Trial with a mean LVEF percent of 24.3 +/- 10.1 sd) and mean exercise treadmill duration of 9.4 (+/- 5.3 sd) minutes. The incidence of biopsy-documented myocarditis was low (9.6%). The analyses of outcome and immunological data are reported elsewhere.

Cost of initial therapy in the Electrophysiological Study Versus ECG Monitoring trial (ESVEM).

BACKGROUND: Patients randomized to either serial electrophysiological testing (EPS) or serial Holter monitoring (HM) to guide antiarrhythmic therapy for life-threatening ventricular arrhythmias had equivalent rates of mortality and arrhythmia recurrence in the ESVEM study. This report analyzes the effects of EPS, HM, and clinical factors on the charges for initial evaluation and management of patients with life-threatening ventricular arrhythmias. METHODS AND RESULTS: Ten of 14 clinical centers participating in ESVEM provided bills from the initial hospitalization for randomized patients. Predictors of charges (1991 dollars) were analyzed by linear regression after logarithmic transformation. Initial hospital charge data were obtained for 286 patients randomized in ESVEM (88% of patients eligible for this substudy, 59% of all ESVEM patients). Patients with charge data were somewhat more likely to be older, to be female, and to have failed previous antiarrhythmic drug therapy at study entry and were less likely to have a drug predicted effective after randomization. Mean overall hospital charges were $35,986 (SD, $32,628) with a median of $24,532 (interquartile range, $16,126 to $43,593). Prerandomization patient characteristics generally had insignificant effects on charges, with the exception of presentation with resuscitated sudden death (28% increase in charges, P = .01) and heart failure (26% increase in charges, P = .02). Patients randomized to EPS had higher mean charges for evaluation ($42,002 versus $29,970, P = .0015) as well as more drug trials (3.0 versus 2.1, P = .0001) and a longer hospital stay (19.6 versus 13.9 days, P = .0007). In a multivariate regression model, failure to find an effective drug (P = .0001), the number of drug trials (P = .0001), and resuscitated sudden death as the presenting arrhythmia (P = .0001) were the only independent predictors of higher initial charges. CONCLUSIONS: (1) Initial hospital charges are significantly higher for EPS-guided than HM-guided therapy. (2) The higher charges for EPS-guided therapy were due to a greater number of drug trials and a lower probability of finding an effective drug. (3) Failure to find an effective drug, a larger number of drug trials, and a history of resuscitated sudden death independently predict higher charges.

Diagnostic and prognostic importance of chromosomal aberrations identified in 61 dogs with lymphosarcoma.

To determine the diagnostic and/or prognostic importance of chromosomal aberrations identified in dogs with malignant (non-Hodgkin's) lymphoma, clinical stages for 61 dogs with lymphosarcoma were determined, the lymph node(s) were histopathologically graded, and the malignant tissue lymphocytes were karyotyped. The results from life table survival curve analysis demonstrated that first remission length and survival time were significantly longer in 15 of 61 (25%) dogs that had a trisomy of chromosome 13 as the primary chromosomal aberration than in those dogs (46/61, 75%) with other primary chromosomal aberrations (P < 0.05). Sex, age, weight, histopathologic subtype and grade, World Health Organization (WHO) clinical stage, WHO and modified Karnofsky performance status, chromosomal modal number, and treatment protocol were of no prognostic importance in predicting first remission length or survival time (P > 0.05). Multivariate analysis did not identify a significant correlation between the prognostic groups or within the various prognostic subsets (P > 0.05). The pathogenesis of canine and human non-Hodgkin's lymphoma, as observed cytogenetically, differs.