Evolving trends in liver transplantation: an outcome and charge analysis

BACKGROUND: Due to the limited supply and increased demand for donor livers, waiting times are progressively lengthening, which may lead to transplantation at more advanced and less cost-effective stages of disease. The purpose of this study was to evaluate the outcomes and hospital charges of liver transplantation during two recent eras to identify areas for providing more cost-effective care. METHODS: A total of 144 primary liver allografts were performed from 1991 to 1996. Patient characteristics, outcome measures, and hospital charges were compared for patients receiving allografts between 1991 and 1993 (group A) versus those receiving grafts between 1994 and 1996 (group B) using unpaired Student t tests for continuous data and chi-squared tests for categorical data. RESULTS: In comparing groups A and B, no significant differences in patient demographics, relative contraindications, or indication for transplantation existed; median waiting time from date of listing until transplant increased from 88 days to 159 days; and a shift in UNOS priority status at time of transplantation occurred, as the percentage of patients requiring inpatient care increased from 58% to 75% (P=0.034). Despite this, patient hospital and 1-year survival significantly improved from 75.0% to 90.3% (P=0.016), and from 68.1% to 88.9% (P=0.002), respectively. Total hospital charges, without correction for inflation, were $174,908+/-16,388 in A and $193,525+/-14,444 in B (P=0.288). The increased charges were associated with longer inpatient length of stay (LOS) before transplant, resulting in increased pretransplant charges from $24,088+/-4134 (A) to $39,490+/-6,196 (B) (P=0.011). Room and service (54%) was the largest pretransplant contributor to charges, while blood products (23%), room and service (21%), organ acquisition (13%), and operating room charges (11%) contributed the most after transplant. CONCLUSIONS: Longer waiting times resulting in transplantation at later stages of disease have occurred, leading to longer pretransplant LOS and its associated charges. Despite more advanced disease, patient survival rates have significantly improved with fewer infection-related deaths. LOS pretransplant, blood products, and operating room services represent potential areas for providing more cost-effective care.     

Characteristics of discrepancies between self-reported visual function and measured reading speed. Salisbury Eye Evaluation Project Team

PURPOSE: Visual impairment is a risk factor for morbidity in the elderly and is often screened for by self-report. This study evaluates whether there are subsets for whom there is a discrepancy between self-reported and measured function. METHODS: The prevalence of a discrepancy between self-reported difficulty reading a newspaper and measured reading speed was determined in 2520 community-based men and women, aged 65 to 84 years, and the discrepant group characterized by polychotomous regression. RESULTS: Of subjects who reported minimal difficulty reading a newspaper, 10.8% (227/2107) read newsprint-sized text (0.21 degrees) more slowly than 80 words/min, a level previously shown to be necessary for sustained reading. Poor visual acuity, presence of psychiatric symptoms, and less satisfaction with vision were associated with being in the group that read slowly and reported difficulty with reading. Better cognition, better visual acuity, more years of education, white race, and fewer psychiatric symptoms were associated with being in the group that read more quickly and reported minimal difficulty. When reading the text size at which subjects read their fastest, only 2.6% of those with minimal difficulty remained discrepant. These individuals were more likely to have less education, be male, be African American, and have poorer cognitive status than those who did not remain discrepant. CONCLUSIONS: A subset of the elderly population have a substantial discrepancy between self-reported reading difficulty and measured reading speed. In some, this discrepancy may be based on underlying expectations and experiences, and in others it may represent a transition from no visual impairment to visual impairment.     

Effects of cataract and scotoma on visual acuity: a simulation study.

Central field loss (CFL) and cataract both decrease visual acuity. For patients with CFL, visual acuity is further reduced when the acuity target is more visually complex. We tested visual acuity for targets of varying complexity (letters alone, letters flanked by one or two x's on each side, and words) in subjects with normal vision and in the presence of a simulated cataract, simulated scotoma, and their combination (scotoma + cataract). Visual acuity was best with normal vision and worst with scotoma + cataract for all of the acuity targets. There was little difference in visual acuity between the letters alone and flanked letters, and visual acuity was best for words under all vision conditions. The cataract had a greater impact on visual acuity when the subject's central visual field was clear (normal vision) than when it was occluded by the simulated scotoma.     

Pharmacokinetic consequences of a citalopram treatment discontinuation.

In this pilot study, the pharmacokinetics of citalopram (CIT) were examined in five hospitalized depressed patients after an abrupt discontinuation of a treatment with 40 mg/d of this selective serotonin reuptake inhibitor (SSRI). During the 8-day study period, clinical ratings were regularly carried out. Between days 5 and 8, the patients were treated with clomipramine (75 mg/d). The enantiomers of CIT and its metabolites, demethyl-CIT (DCIT) and CIT-propionic acid derivative (CIT-PROP), were measured repeatedly from day 0 to day 8 by a stereoselective high-performance liquid chromatography (HPLC) procedure. The following drug plasma half-lives were measured (means +/- SD): R-CIT: 66+/-11 h; S-CIT: 42+/-13 h; R-DCIT: 228+/-148 h; S-DCIT: 93+/-35 h; R-CIT-PROP: 82+/-31 h; S-CIT-PROP: 186+/-93 h.     

Leucovorin, 5-fluorouracil,and gemcitabine: A phase I study

Gemcitabine is a chemotherapy agent with efficacy in the treatment of lung, pancreas, bladder and breast cancer. It inhibits DNA synthesis by interfering with cytidine triphosphate production and also inhibits the activity of ribonucleotide reductase. Gemcitabine may potentiate fluorouracil's inhibition of thymidylate synthase. This inhibition would be expected to be sequence dependent, occurring only if gemcitabine were administered following fluorouracil (5FU).The combination of leucovorin, 5-FU, and gemcitabine was assessed in this phase I trial. Eligibility requirements included refractory solid tumor malignancy; adequate hematologic, renal and hepatic reserve; no prior therapy with the combination of leucovorin and 5FU, or with gemcitabine; ECOG performance status 0–2, and signed informed consent.Eleven men and nine women were eligible. The median age was 52.5 years and the median performance status was 1. All but three patients had prior chemotherapy. The starting doses were leucovorin 20 mg/m², 5FU 255 mg/m² and gemcitabine 600 mg/m². 5FU and gemcitabine were escalated in tandem to 340 mg/m² and 800 mg/m² and thereafter to 425 mg/m² and 1000 mg/m², respectively. Gemcitabine administration always followed that of 5FU by 30 minutes. The median number of cycles was 2 (range 1–32). Two patients at the starting dose had disease progression within the first cycle with one death on day 28. One patient with cholangiocarcinoma had a partial response and remained on study for 40 months. There were no other responses.The maximum tolerated dose is leucovorin 20 mg/m², 5FU 340 mg/m², and gemcitabine 800 mg/m². The impact of drug sequence remains undetermined.     

Oral condyloma acuminatum associated with human papillomavirus and p53 overexpression mimicking cyclosporine effect in a transplant patient

A case of human papillomavirus-associated condyloma acuminatum in the oral cavity, presumed to be fulminant cyclosporine-induced gingival hyperplasia, is reported in a 55-year-old cardiac transplant patient. Approximately 47 months following the transplant, the patient developed severe hyperplasia of the uvula and oral mucosa, resulting in difficulty swallowing. The histopathologic features of the lesion were typical of those of condyloma acuminatum. In situ hybridization of the paraffin-embedded material revealed infection with human papillomavirus types 6/11. This case lends further support to the putative role of long-term cellular immunosuppression in the development of human papillomavirus-associated squamous lesions. In addition, positive staining for p53 protein raises the possibility of concomitant p53 involvement in the pathogenesis of this oral lesion.     

Reliability of medical audit in quality assessment of medical care

Medical audit of hospital records has been a major component of quality of care assessment, although physician judgment is known to have low reliability. We estimated interrater agreement of quality assessment in a sample of patients with cardiac conditions admitted to an American teaching hospital. Physician-reviewers used structured review methods designed to improve quality assessment based on judgment. Chance-corrected agreement for the items considered more relevant to process and outcome of care ranged from low to moderate (0.2 to 0.6), depending on the review item and the principal diagnoses and procedures the patients underwent. Results from several studies seem to converge on this point. Comparisons among different settings should be made with caution, given the sensitivity of agreement measurements to prevalence rates. Reliability of review methods in their current stage could be improved by combining the assessment of two or more reviewers, and by emphasizing outcome-oriented events.     

Cellular epigenetics: effects of passage history on competence of cells for "spontaneous" transformation.

"Spontaneous" neoplastic transformation of cells in culture has been shown to be an adaptive response to moderate physiological constraints such as contact inhibition and lowered concentrations of serum. These are the same constraints that promote normal differentiation of a variety of cell types. Because both normal and neoplastic development represent enduring changes in response to constraint, spontaneous transformation can be considered a form of epigenesis. This phenomenon permits the use of established cell lines in developing general epigenetic principles with all of the advantages of manipulation, efficient cloning, and quantification afforded by such systems. Being environmentally sensitive, however, the responsive capacity of cell lines is subject to fluctuation and long-term modification. I therefore set out to define the conditions used in maintaining cells that influence their competence to undergo transformation with the aim of controlling that competence. It proved to be sensitive to both the population density and frequency of three different repetitive passage regimens. Both the saturation density of the cells and their capacity to produce transformed foci varied initially in different ways within the same regimen in two consecutive passage series starting from the same frozen stock, but both parameters eventually settled down to values characteristic of each of the three regimens. As a result, three sublines were developed of high, intermediate, and low competence for transformation. Each of the sublines has special advantages for studying different aspects of epigenetic change. In the process of developing the sublines, a number of observations were made that reinforce the epigenetic nature of neoplastic transformation and are consistent with the concept of progressive state selection as the basis of the change. That concept can be considered a first step in the formal analysis of epigenesis.     

ASTRO plenary: interfraction interval is a major determinant of late effects, with hyperfractionated radiation therapy of carcinomas of upper respiratory and digestive tracts: results from Radiation Therapy Oncology Group protocol 8313

A prospective, randomized, multi-institutional, Phase I(LE)/II trial of HFX was conducted by the RTOG between 1983 and 1987. Patients with histologically proven, inoperable squamous cell carcinoma of the upper respiratory and digestive tracts stratified by site, nodal status, and performance status, were assigned to one of three arms, were assigned to one of three arms, 67.2 Gy, 72.0 Gy, or 76.8 Gy. Fractions of 1.2 Gy were given twice daily, 5 days per week: intervals of 4 to 8 hours were permitted between fractions. After acceptable rates of acute normal tissue effects were found, the randomization was changed to evaluate a new higher total dose, 81.6 Gy. Of 479 patients entered, 447 were analyzed, 63 on 67.2 Gy, 129 on 72.0 Gy, 117 on 76.8 Gy, and 138 on 81.6 Gy. The treatment arms were well balanced with respect to pretreatment characteristics. Acute reactions consisted almost entirely of pseudomembranous inflammation. "Severe" (Grade 3) acute reactions were reported in 33% to 41% and grade 4 reactions were found in 0 to 3% of patients, with no differences in frequencies among the four arms. Toxicities that developed or persisted beyond 90 days after the first treatment (408 patients evaluable greater than 90 days) did not differ among arms: grade 3+ reactions occurred in 10% to 14%, and grade 4+ effects (necroses) were reported in 5% at 67.2 Gy, 3% at 72.0 Gy, 7% at 76.8 Gy, and 2% at 81.6 Gy. Grade 3+ acute reactions occurred in 40% of patients when the interfraction interval was less than or equal to 4.5 hours versus 31% with greater than 4.5 hours (p = .03). Interfraction intervals less than or equal to 4.5 hours were associated with higher frequencies of grade 4+ late effects in all four arms, 8% of 197 patients with less than or equal to 4.5 hours versus 1% of 211 patients with greater than 4.5 hours. Estimates of late toxicity at 1, 2, and 3 years were 5.5%, 9.8%, and 15.4% with intervals less than or equal to 4.5 hours, versus 1.7% at all three periods for greater than 4.5 hours (p = .006). Local-regional control at 2 years was 25% for the assigned dose of 67.2 Gy compared to 43% to 45% for the three higher doses (p = .01), but a similar comparison for survival showed no significant difference (p = .35). There was no evidence for an effect of interfraction interval on either local-regional control (p = .38) or survival (p = .28).(ABSTRACT TRUNCATED AT 400 WORDS)