Biomedical subjects
Publications and source records attributed to J Rapoport.
We describe a 50-year-old depressive patient with severe theophylline toxicity that occurred as a result of attempted suicide. Her theophylline levels peaked at 148 mg/l. She was promptly treated with charcoal hemoperfusion, and responded well. We describe the pharmacokinetics of theophylline removal via hemoperfusion, and review the literature.
The purpose of this study was to compare the cost of a day spent in an intensive care unit and a day spent on a general nursing unit. A descriptive design was used, based on patient level data, to examine and compare unit costs per day for each of the ICU and non-ICU portions of a patient's hospital stay. Records from 386 patients who were treated in a general medical/surgical ICU were analyzed. Records for patients who received both ICU and non-ICU care during their stay were retained. Patients were categorized according to whether they had received surgical care prior to admission to the ICU (surgical group) or had no surgical care (medical group). The groups were further divided, based on whether they were discharged from hospital (survivors), or died following transfers from the ICU (non-survivors). All four groups; surgical or medical, survivors and non-survivors, were analyzed separately. The ICU direct costs per day for survivors were between six and seven times those for non-ICU care. A one day substitution of general ward for ICU care would result in a cost reduction of $1,200 per patient for survivors. The results suggest that the savings achieved by moving a patient from ICU to non-ICU care are considerable, particularly for less severe surviving patients. In making such decisions, however, clinicians must examine prospective benefits as well as costs. If the health outcomes are not influenced, the savings from substitution are considerable, and there is a strong economic argument for substitution.
OBJECTIVE: To analyze differences in intensive care unit (ICU) utilization between a Canadian province and a U.S. area. DESIGN: Retrospective data analysis of hospital discharge data and existing data from an international study of severity of illness in ICU patients. SETTING: Administrative data for the province of Alberta and the four counties of western Massachusetts for the years 1990 to 1991 were used. Detailed data on consecutive ICU admissions from two Alberta hospitals, one western Massachusetts hospital, and 24 other U.S. hospitals for 3 months in 1991 were used. MEASUREMENTS AND MAIN RESULTS: ICU use and hospital mortality rates were compared for 50,030 hospital admissions divided into 11 patient groups. ICU days per million population were two to three times as great in western Massachusetts as in Alberta. The primary reason was higher ICU incidence (percent of hospitalized patients treated in the ICU) rather than a difference in hospital admission rate or length of ICU stay. ICU incidence in western Massachusetts was significantly higher in ten of 11 patient groups--for the coronary bypass surgery group, there was no difference. The hospital mortality rate in western Massachusetts was similar to, or higher than, the mortality rate in Alberta. In Alberta, a much higher proportion of ICU patients received mechanical ventilation. For elective surgery patients, the ICU severity of illness was lower in western Massachusetts and in other U.S. hospitals than in Alberta. CONCLUSIONS: Western Massachusetts hospitalized patients are more likely to be treated in an ICU than are similar patients in Alberta. There is no evidence that the greater ICU utilization in western Massachusetts led to a lower hospital mortality rate.
Commercial peritoneal dialysis solution (CDS) is known to have a detrimental effect on the capacity of peritoneal macrophages (PM phi) to kill bacteria and produce acute phase cytokines. This cytotoxic effect is largely caused by the low pH of CDS. Because the cytoplasmic pH (pHi) is an important determinant of cellular function, the effect of CDS on the pHi of PM phi from continuous ambulatory peritoneal dialysis patients was studied. The pHi of PM phi was measured fluorometrically in N-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered salt solution (HBSS) or CDS at pH values of 5.3, 6.5, and 7.0, values that represent the pH existing in dialysate during the first 30 min of dwell time. For any given pH of the experimental medium, the pHi was always more acidic in CDS than in HBSS. When PM phi were incubated with a lactate-containing HBSS, a cellular acidification was observed that was similar to that attained by exposure to CDS at the same pH. This supports the hypothesis that the decrease in pHi was due to the influx of lactic acid from the CDS into the PM phi. In order to demonstrate a causal association between the CDS-induced cellular acidification and a defect in phagocytosis and cytokine production, these functions were studied after pHi clamping by means of K+/nigericin. It was found that clamping pHi to values below 6.5 led to a markedly reduced tumor necrosis factor-alpha production and phagocytosis. However, at values of pHi > 6.5, these functions were normal. (ABSTRACT TRUNCATED AT 250 WORDS)
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We studied the ability of human peritoneal mesothelial cells (HPMC) to produce the major pro-inflammatory cytokines interleukin-1 alpha (IL-1 alpha) and -beta when stimulated by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) or IL-1 alpha, or combinations of these three factors. Biological activity of IL-1 was measured by bioassay, and levels of IL-1 alpha and beta were determined using specific radioimmunoassays. We found that HPMC are capable of secreting IL-1 alpha and -beta in response to stimulation by these substances, but stimulation with a combination of LPS + TNF alpha, LPS + IL-1 alpha, or TNF alpha + IL-1 alpha, had a marked synergistic effect on cytokine production. A combination of all three substances together had a significantly enhanced synergistic effect. Using reverse transcription PCR, we found a peak in IL-1 alpha and beta mRNA levels three hours after stimulation. We found that LPS, TNF alpha and IL-1 alpha alone, or in combination, caused an increase in IL-1 alpha and -beta mRNA levels. Cycloheximide and actinomycin D blocked the production of IL-1 alpha and -beta protein, showing that de novo production of IL-1 or synthesis of mRNA stabilizing proteins are needed after stimulation. We thus conclude that HPMC play an important role in the amplification of the initial peritoneal inflammatory response which originates in the peritoneal macrophages, and these findings are of importance in understanding the peritoneal response to infection in continuous ambulatory peritoneal dialysis (CAPD) patients.
OBJECTIVE: To develop models in the Mortality Probability Model (MPM II) system to estimate the probability of hospital mortality at 48 and 72 hrs in the intensive care unit (ICU), and to test whether the 24-hr Mortality Probability Model (MPM24), developed for use at 24 hrs in the ICU, can be used on a daily basis beyond 24 hrs. DESIGN: A prospective, multicenter study to develop and validate models, using a cohort of consecutive admissions. SETTING: Six adult medical and surgical ICUs in Massachusetts and New York adjusted to reflect 137 ICUs in 12 countries. PATIENTS: Consecutive admissions (n = 6,290) to the Massachusetts/New York ICUs were studied. Of these patients, 3,023 and 2,233 patients remained in the ICU and had complete data at 48 and 72 hrs, respectively. Patients < 18 yrs of age, burn patients, coronary care patients, and cardiac surgical patients were excluded. OUTCOME MEASURE: Vital status at the time of hospital discharge. RESULTS: The models consist of five variables measured at the time of ICU admission and eight variables ascertained at 24-hr intervals. The 24-hr model demonstrated poor calibration and discrimination at 48 and 72 hrs. The newly developed 48- and 72-hr models--MPM48 and MPM72--contain the same 13 variables and coefficients as the MPM24. The models differ only in their constant terms, which increase in a manner that reflects the increasing probability of mortality with increasing length of stay in the ICU. These constant terms were adjusted by a factor determined from the relationship between the data from the six Massachusetts and New York ICUs and a more extensive data set, from which the ICU admission Mortality Probability Model (MPM0) and MPM24 were developed. This latter data set was assembled from ICUs in 12 countries. The MPM48 and MPM72 calibrated and discriminated well, based on goodness-of-fit tests and area under the receiver operating characteristic curve. CONCLUSIONS: Models developed for use among ICU patients at one time period are not transferable without modification to other time periods. The MPM48 and MPM72 calibrated well to their respective time periods, and they are intended for use at specific points in time. The increasing constant terms and associated increase in the probability of hospital mortality exemplify a common clinical adage that if a patient's clinical profile stays the same, he or she is actually getting worse.
OBJECTIVES: To present an approach for assessing intensive care unit (ICU) performance which takes into account both economic and clinical performance while adjusting for severity of illness. To present a graphic display which permits comparisons among a group of hospitals. DESIGN: A multicenter, inception cohort study. SETTING: Twenty-five ICUs in U.S. hospitals that participated in the European and North American Study of Severity Systems for ICU Patients. PATIENTS: Consecutive patients (n = 3,397) admitted to ICUs in participating hospitals between September 30, 1991 and December 27, 1991. Excluded were coronary care patients, burn patients, cardiac surgery patients and patients aged < 18 yrs. MEASUREMENTS AND MAIN RESULTS: The clinical performance index is the difference between observed hospital survival rate and survival rate predicted by the Mortality Probability Model measuring severity of illness at ICU admission. The economic performance (resource use) measure is a length of stay index, Weighted Hospital Days, which weights ICU days more heavily than non-ICU days. The economic performance index is the difference between actual mean resource use and the resource use predicted by a regression including severity of illness and percent of surgical patients. Both the clinical and economic performance indices are standardized to show how far a particular hospital is from the overall mean and are graphed together. Most of the 25 hospitals lie within 1 SD of the mean on both clinical and economic performance scales. The graph makes it easy to identify those hospitals that are outside this range. There is no evidence of a trade-off between high clinical performance and high economic performance; i.e., it is possible to achieve both. CONCLUSIONS: Cross-indexing of clinical and economic ICU performance is easy to calculate. It has potential as a research and evaluation tool used by physicians, hospital administrators, payers, and others.
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OBJECTIVE: To revise and update models in the Mortality Probability Model (MPM II) system to estimate the probability of hospital mortality among 19,124 intensive care unit (ICU) patients that can be used for quality assessment within and among ICUs. DESIGN AND SETTING: Models developed and validated on consecutive admissions to adult medical and surgical ICUs in 12 countries. PATIENTS: A total of 12,610 patients for model development, 6514 patients for model validation. Patients younger than 18 years and burn, coronary care, and cardiac surgery patients were excluded. OUTCOME MEASURE: Vital status at hospital discharge. RESULTS: The admission model, MPM0, contains 15 readily obtainable variables. In developmental and validation samples it calibrated well (goodness-of-fit tests: P = .623 and P = .327, respectively, where a high P value represents good fit between observed and expected values) and discriminated well (area under the receiver operating characteristic curve = 0.837 and 0.824, respectively). The 24-hour model, MPM24 (developed on 10,357 patients still in the ICU at 24 hours), contains five of the admission variables and eight additional variables easily ascertained at 24 hours. It also calibrated well (P = .764 and P = .231 in the developmental and validation samples, respectively) and discriminated well (area under the receiver operating characteristic curve = 0.844 and 0.836 in the developmental and validation samples, respectively). CONCLUSIONS: Among severity systems for intensive care patients, the MPM0 is the only model available for use at ICU admission. Both MPM0 and MPM24 are useful research tools and provide important clinical information when used alone or together.
OBJECTIVE: To study the effect of dialysis fluid on the release of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF alpha) by peritoneal macrophages (PM) and peripheral blood mononuclear cells (MNC), and the time course and factors involved in this effect. DESIGN: PM and MNC were incubated for various periods with Dianeal itself, or Dianeal of varying pH and composition. IL-1 beta was measured by radioimmunoassay and TNF alpha by cytotoxicity assay. PATIENTS: PM were obtained by centrifugation of dialysis effluent from 3 continuous ambulatory peritoneal dialysis (CAPD) patients. MNC were obtained from healthy volunteers. RESULTS: Dialysis fluid inhibited the release of both cytokines. Indomethacin had no effect on the inhibition of TNF alpha release caused by dialysis fluid. Thus prostaglandins are not involved in this inhibition. Solutions of pH 5.2 and high lactate concentration caused an identical inhibition to that caused by dialysate, whereas the presence or absence of glucose had no effect. Thus it seems that pH and lactate are the important inhibitory factors. Time course studies showed that the inhibition of TNF alpha release was substantial after only 15 minutes of incubation with dialysate, whereas the inhibition of IL-1 beta became significant only after 60 minutes of incubation. CONCLUSIONS: Even though dialysate pH rises within 15-30 minutes after instillation into the abdomen, the initial low pH present for only a short time could have a significant effect on TNF alpha release by peritoneal macrophages, and thus on their ability to mount a normal inflammatory response. Lactate also has a significant inhibitory role. It is suggested that commercial dialysis solutions should have a pH of 7.0 and that a physiological buffer other than lactate be used.
BACKGROUND: There is considerable evidence that members of managed care organizations use fewer hospital resources than patients covered by traditional health insurance. While intensive care might seem to be an unlikely setting for such differences to exist, the relationship between health coverage and use of intensive care has not been examined. METHODS: We conducted a cross-sectional analysis of consecutive intensive care unit admissions at a regional tertiary care teaching hospital. Patients in managed care plans (n = 159) and with traditional insurance (n = 389) were compared with respect to length of stay, hospital charges, charges for specific services, and use of mechanical ventilation. The analysis controlled for severity of illness, as measured by the Mortality Probability Model, case mix, and mortality. The whole sample as well as subsamples representing medical, emergency surgery, and elective surgery patients were examined. RESULTS: The managed care group, on average, had short stays (both hospital and intensive care unit), lower charges, and less use of mechanical ventilation than the traditionally insured group. Average differences of about 30% to 40% were observed. The finding held for the whole sample as well as the medical and emergency surgery subsamples. The differences were more pronounced in the patients with lowest severity of illness. CONCLUSION: Even in a setting where there would appear to be relatively little room for discretion in treatment decisions, incentives associated with type of health insurance seemed to affect resource use.
The active metabolite of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), is produced mainly by the kidney, but there is evidence for extrarenal production in certain circumstances. We studied whether peritoneal macrophages (PM) from CAPD patients were capable of metabolizing 25-OH-D3 to 1,25(OH)2D3. We found that PM were able to metabolize 25-OH-D3 in vitro; the main product following 16 hours of incubation was 19-nor, 10-oxo, 25-OH-D3 with smaller amounts of 1,25(OH)2D3. However, after shorter incubations of three and five hours a larger portion of 1,25(OH)2D3 was produced. The metabolism of 25-OH-D3 was greatly enhanced in PM harvested during episodes of peritonitis. This property was specific for PM of CAPD patients, and was not found in PM from normal subjects. However, incubation of control PM with peritoneal effluent from CAPD patients resulted in induction of the ability of these cells to metabolize 25-OH-D3. This induction was enhanced by preincubation with peritoneal effluent from CAPD patients suffering from peritonitis. Prostaglandin E2 was found to be involved in this synthesis: addition of PGE2 to normal PM induced metabolism of 25-OH-D3, and incubation of PM from CAPD patients with indomethacin decreased the metabolism of 25-OH-D3. The vitamin D metabolites produced by PM from CAPD patients could have a role in immunological resistance to peritoneal infections.
We measured the serum parathyroid hormone (PTH) levels in 20 patients treated with continuous ambulatory peritoneal dialysis before and after oral treatment with 24,25-dihydroxyvitamin D3- 24,25(OH)2D3. This metabolite was given in addition to existing treatment with 1 alpha-OH-D3 and calcium carbonate. Administration of 24,25(OH)2D3 led to a significant decrease in PTH levels (intact molecule) from 382 +/- (SE) 65 to 245 +/- 54 pg/ml in 9 patients whose initial levels were extremely high (p = 0.01). No side effects were observed. On the average, calcium values were unchanged and within the normal range throughout the study period; however, a few episodes of mild asymptomatic hypercalcemia occurred which responded quickly to reduction of the calcium carbonate dosage. The present study suggests that oral administration of 24,25(OH)2D3 combined with 1 alpha-OH-D3 is safe and capable of suppressing the raised serum PTH levels of end-stage renal disease patients without the danger of significant hypercalcemia.
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This study assessed the relationship between admission time (from hospital admission to ICU admission) and mortality predicted by the Mortality Prediction Model (MPM), actual mortality, and resource use. All admissions, except elective surgery patients, to the general medical/surgical ICU of a tertiary care hospital during a 24-month period were studied (n = 1,889). Patients admitted to the ICU within 1 day of hospital admission had lower predicted and actual mortality, and used fewer resources than patients admitted later. Predicted mortality was higher than actual mortality for patients admitted to the ICU early and was lower than actual mortality for later ICU admissions. Transfers had higher predicted and actual mortality, and used more resources than nontransfer patients. Time from hospital admission to ICU admission can be a potentially useful variable in models of ICU outcome.
Factors related to hospital resource use by intensive care unit (ICU) patients, including severity of illness at admission and intensity of therapy during the first 24 ICU hours were explored in this study. Analysis was based on 2,749 patients admitted to the general medical-surgical ICU at Baystate Medical Center, Springfield, Massachusetts, between February 1, 1983 and January 10, 1985. Resource use was indexed by hospital length of stay (LOS) adjusted for differences between ICU and other hospital days. Severity of illness was measured by the Mortality Prediction Model (MPM0), a validated predictor of outcome but not previously used to analyze resource consumption. Intensity of therapy was measured using the Therapeutic Intervention Scoring System (TISS). The 10% of patients with longest ICU stays were significantly different from the other 90% with respect to previous ICU use, MPM probability, and TISS score. Variability in resource use was analyzed using four diagnosis-related groups (DRGs) accounting for large numbers of ICU patients. The relationship between severity of illness and resource was nonlinear: as severity increased from low levels, resource use increased at a decreasing rate, reached a plateau, and eventually declined. Within each DRG, MPM0 explained a statistically significant percentage of the variability in resource use.
This study compares the length of hospital stay of a group of patients treated in a community hospital during a period of five-day-a-week physical therapy coverage with the length of stay of a similar patient group treated during a period of seven-day-a-week physical therapy coverage. Comparisons of length of stay were made between the two groups and between subgroups based on diagnosis (stroke or orthopedic disorder) and surgical versus nonsurgical status. Multiple regression analysis was used to control for other factors influencing length of hospital stay. The mean length of stay was shorter for the seven-day-a-week group, and in a few subgroups the difference in length of stay was statistically significant. The results of this study suggest that weekend physical therapy may help reduce length of hospital stay. This finding should interest individuals concerned with the cost-effective use of physical therapy, especially under hospital reimbursement systems such as the Medicare diagnosis-related group.