Biomedical subjects

R S Phillips

Publications and source records attributed to R S Phillips.

At least 37 records · Page 2Linked to original sources

PubMed2000

Outcomes and cost-effectiveness of ventilator support and aggressive care for patients with acute respiratory failure due to pneumonia or acute respiratory distress syndrome.

PURPOSE: Many patients with acute respiratory failure die despite prolonged and costly treatment. Our objective was to estimate the cost-effectiveness of providing rather than withholding mechanical ventilation and intensive care for patients with acute respiratory failure due to pneumonia or acute respiratory distress syndrome. SUBJECTS AND METHODS: We studied 1,005 patients enrolled in a five-center study of seriously ill patients (the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments [SUPPORT]) with acute respiratory failure (pneumonia or acute respiratory distress syndrome and an Acute Physiology Score > or =10) who required ventilator support. We estimated life expectancy based on long-term follow-up of SUPPORT patients. Utilities were estimated using time-tradeoff questions. Costs (in 1998 dollars) were based on hospital fiscal data and Medicare data. RESULTS: Of the 963 patients who received ventilator support, 48% survived for at least 6 months. At 6 months, survivors reported a median of 1 dependence in activities of daily living, and 72% rated their quality of life as good, very good, or excellent. Among the 42 patients in whom ventilator support was withheld, the median survival was 3 days. Among patients whose estimated probability of surviving at least 2 months from the time of ventilator support ("prognostic estimate") was 70% or more, the incremental cost per quality-adjusted life-year (QALY) saved by providing rather than withholding ventilator support and aggressive care was $29,000. For medium-risk patients (prognostic estimate 51% to 70%), the incremental cost-effectiveness was $44,000 per QALY, and for high-risk patients (prognostic estimate < or =50%), it was $110,000 per QALY. When assumptions were varied from 50% to 200% of baseline estimates, the results ranged from $19,000 to $48,000 for low-risk patients, from $29,000 to $76, 000 for medium-risk patients, and from $67,000 to $200,000 for high-risk patients. CONCLUSIONS: Ventilator support and intensive care for acute respiratory failure due to pneumonia or acute respiratory distress syndrome are relatively cost-effective for patients with >50% probability of surviving 2 months. However, for patients with an expected 2-month survival < or =50%, the cost per QALY is more than threefold greater at >$100,000.

APACHE↗

PubMed2000

The role of glutamic acid-69 in the activation of Citrobacter freundii tyrosine phenol-lyase by monovalent cations.

Tyrosine phenol-lyase (TPL) from Citrobacter freundii is activated about 30-fold by monovalent cations, the most effective being K(+), NH(4)(+), and Rb(+). Previous X-ray crystal structure analysis has demonstrated that the monovalent cation binding site is located at the interface between subunits, with ligands contributed by the carbonyl oxygens of Gly52 and Asn262 from one chain and monodentate ligation by one of the epsilon-oxygens of Glu69 from another chain [Antson, A. A., Demidkina, T. V., Gollnick, P., Dauter, Z., Von Tersch, R. L., Long, J., Berezhnoy, S. N., Phillips, R. S., Harutyunyan, E. H., and Wilson, K. S. (1993) Biochemistry 32, 4195]. We have studied the effect of mutation of Glu69 to glutamine (E69Q) and aspartate (E69D) to determine the role of Glu69 in the activation of TPL. E69Q TPL is activated by K(+), NH(4)(+), and Rb(+), with K(D) values similar to wild-type TPL, indicating that the negative charge on Glu69 is not necessary for cation binding and activation. In contrast, E69D TPL exhibits very low basal activity and only weak activation by monovalent cations, even though monovalent cations are capable of binding, indicating that the geometry of the monovalent cation binding site is critical for activation. Rapid-scanning stopped-flow kinetic studies of wild-type TPL show that the activating effect of the cation is seen in an acceleration of rates of quinonoid intermediate formation (30-50-fold) and of phenol elimination. Similar rapid-scanning stopped-flow results were obtained with E69Q TPL; however, E69D TPL shows only a 4-fold increase in the rate of quinonoid intermediate formation with K(+). Preincubation of TPL with monovalent cations is necessary to observe the rate acceleration in stopped flow kinetic experiments, suggesting that the activation of TPL by monovalent cations is a slow process. In agreement with this conclusion, a slow increase (k < 0.5 s(-)(1)) in fluorescence intensity (lambda(ex) = 420 nm, lambda(em) = 505 nm) is observed when wild-type and E69Q TPL are mixed with K(+), Rb(+), and NH(4)(+) but not Li(+) or Na(+). E69D TPL shows no change in fluorescence under these conditions. High concentrations (>100 mM) of all monovalent cations result in inhibition of wild-type TPL. This inhibition is probably due to cation binding to the ES complex to form a complex that releases pyruvate slowly.

Alanine Racemase↗

PubMed2000

The O(2) binding pocket of myohemerythrin: role of a conserved leucine.

A conserved O(2) binding pocket residue in Phascolopsis gouldii myohemerythrin (myoHr), namely, L104, was mutated to several other residues, and the effects on O(2) association and dissociation rates, O(2) affinity, and autoxidation were examined. The L104V, -F, and -Y myoHrs formed stable O(2) adducts whose UV-vis and resonance Raman spectra closely matched those of wild-type oxymyoHr. The L104V mutation produced only minimal effects on either O(2) association or dissociation, whereas the L104F and -Y mutations resulted in 100-300-fold decreases in both O(2) association and dissociation rates. These decreases are attributed to introduction of steric restrictions into the O(2) binding pocket, which are not present in either wild-type or L104V myoHrs. The failure to observe increased O(2) association or dissociation rates for L104V indicates that the side chain of leucine at position 104 does not sterically "gate" O(2) entry into or exit from the binding pocket in the rate-determining step(s). L104V myoHr autoxidized approximately 3 times faster than did wild type, whereas L104T autoxidized >10(6) times faster than did wild type. The latter large increase is attributed to increased side chain polarity, thereby increasing water occupancy in the oxymyoHr binding pocket. These results indicate that L104 contributes a hydrophobic barrier that restricts water entry into the oxymyoHr binding pocket. Thus, a leucine at position 104 in myoHr appears to have the optimal combination of size and hydrophobicity to facilitate O(2) binding while simultaneously inhibiting autoxidation.

Amino Acid Sequence↗

PubMed2000

A leucine residue "Gates" solvent but not O2 access to the binding pocket of phascolopsis gouldii hemerythrin.

A leucine residue, Leu-98, lines the O(2)-binding pocket in all known hemerythrins. Leu-98 in recombinant Phascolopsis gouldii hemerythrin, was mutated to several other residues of varying sizes (Ala, Val), polarities (Thr, Asp, Asn), and aromaticities (Phe, Tyr, Trp). UV-visible and resonance Raman spectra showed that the di-iron sites in these L98X Hrs are very similar to those in the wild type protein, and several of the L98X hemerythrins formed stable oxy adducts. Despite the apparently tight packing in the pocket, all of the L98X Hrs except for L98W, had second order O(2) association rate constants within a factor of 3 of the wild type value. Similarly, the O(2) dissociation rate constant was essentially unaffected by substitutions of larger (Phe) or smaller (Val, Thr) residues for Leu-98. L98Y Hr showed a 170-fold decrease in the O(2) dissociation rate constant and a large D(2)O effect on this rate, which are attributed to a hydrogen-bonding interaction between the Tyr-98 hydroxyl and the bound O(2). Significant increases in autoxidation rates were observed for all of the L98X Hrs other than X = Tyr. These increases in autoxidation rates are attributed to increased solvent access to the binding pocket caused by inefficient packing (Phe), smaller size (Val, Ala), or increased polarity (Thr, Asp, Asn) of the residue 98 side chain. A leucine at position 98 appears to have the optimal size, shape, and hydrophobicity for inhibition of solvent access. Thus, "gating" of small molecule access to the binding pocket of Hr by Leu-98 is not evident for O(2), but is evident for solvent.

Animals↗

PubMed2000

Screening for cervical and breast cancer: is obesity an unrecognized barrier to preventive care?

BACKGROUND: Compared with thinner women, obese women have higher mortality rates for breast and cervical cancer. In addition, obesity leads to adverse social and psychological consequences. Whether obesity limits access to screening for breast and cervical cancer is unclear. OBJECTIVE: To examine the relation between obesity and screening with Papanicolaou (Pap) smears and mammography. DESIGN: Population-based survey. SETTING: United States. PARTICIPANTS: 11 435 women who responded to the "Year 2000 Supplement" of the 1994 National Health Interview Survey. MEASUREMENTS: Screening with Pap smears and mammography was assessed by questionnaire. RESULTS: In women 18 to 75 years of age who had not previously undergone hysterectomy (n = 8394), fewer overweight women (78%) and obese women (78%) than normal-weight women (84%) had had Pap smears in the previous 3 years (P < 0.001). After adjustment for sociodemographic information, insurance and access to care, illness burden, and provider specialty, rate differences for screening with Pap smears were still seen among overweight (-3.5% [95% CI, -5.9% to -1.1%]) and obese women (-5.3% [CI, -8.0% to -2.6%]). In women 50 to 75 years of age (n = 3502), fewer overweight women (64%) and obese women (62%) than normal-weight women (68%) had had mammography in the previous 2 years (P < 0.002). After adjustment, rate differences were -2.8% (CI, -6.7% to 0.9%) for overweight women and -5.4% (CI, -10.8% to -0.1%) for obese women. CONCLUSIONS: Overweight and obese women were less likely to be screened for cervical and breast cancer with Pap smears and mammography, even after adjustment for other known barriers to care. Because overweight and obese women have higher mortality rates for cervical and breast cancer, they should be targeted for increased screening.

Adolescent↗

PubMed2000

Resource use and survival of patients hospitalized with congestive heart failure: differences in care by specialty of the attending physician. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

BACKGROUND: Previous studies suggest that specialty care is more costly but may produce improved outcomes for patients with acute cardiac illnesses. OBJECTIVE: To determine whether patients with congestive heart failure who are cared for by cardiologists experienced differences in costs, care patterns, and survival compared with patients of generalists. DESIGN: Prospective cohort study. SETTING: 5 U.S. teaching hospitals between 1989 and 1994. PATIENTS: 1298 patients hospitalized with an exacerbation of congestive heart failure. MEASUREMENTS: Hospital costs; average daily Therapeutic Intervention Scoring System (TISS) score; and survival censored at 30, 180, and 365 days and 31 December 1994. RESULTS: Compared with patients of generalists, patients of cardiologists were younger (mean age, 63.3 and 71.4 years; P < 0.001) and had lower Acute Physiology Scores at the time of admission (35.1 and 36.7; P < 0.001) but were more likely to have a history of ventricular arrhythmias (21.0% and 10.2%; P < 0.001). At 6 months, 201 (27%) patients of cardiologists and 149 (27%) patients of generalists had died. After adjustment for sociodemographic characteristics and severity of illness, patients of cardiologists incurred costs that were 42.9% (95% CI, 27.8% to 59.8%) higher and average daily TISS scores that were 2.83 points (CI, 1.96 to 3.68 points) higher than those of patients of generalists. Patients of cardiologists were more likely to undergo right-heart catheterization (adjusted odds ratio, 2.9 [CI, 1.7 to 4.9]) or cardiac catheterization (adjusted odds ratio, 3.9 [CI, 2.4 to 6.2]) and had higher odds for transfer to an intensive care unit and electrocardiographic monitoring. Adjusted survival did not differ significantly between groups at 30 days; however, there was a trend toward improved survival among patients of cardiologists at 1 year (adjusted relative hazard, 0.82 [CI, 0.65 to 1.04]) and at maximum follow-up (adjusted relative hazard, 0.80 [CI, 0.66 to 0.96]). CONCLUSIONS: In this observational study of patients hospitalized with congestive heart failure, cardiologist care was associated with greater costs and resource use and no difference in survival at 30 days of follow-up. Whether the trend toward better survival at longer follow-up represents differences in care or unadjusted illness severity is uncertain.

Adult↗

PubMed2000

Patient race and decisions to withhold or withdraw life-sustaining treatments for seriously ill hospitalized adults. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

PURPOSE: Patient race is associated with decreased resource use for seriously ill hospitalized adults. We studied whether this difference in resource use can be attributed to more frequent or earlier decisions to withhold or withdraw life-sustaining therapies. SUBJECTS AND METHODS: We studied adults with one of nine illnesses that are associated with an average 6-month mortality of 50% who were hospitalized at five geographically diverse teaching hospitals participating in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). We examined the presence and timing of decisions to withhold or withdraw ventilator support and dialysis, and decisions to withhold surgery. Analyses were adjusted for demographic characteristics, prognosis, severity of illness, function, and patients' preferences for life-extending care. RESULTS: The mean (+/- SD) age of the patients was 63 +/- 16 years; 16% were African-American, 44% were women, and 53% survived for 6 months or longer. Of the 9,076 patients, 5,349 (59%) had chart documentation that ventilator support had been considered in the event the patient's condition required such a treatment to sustain life, 2,975 charts (33%) had documentation regarding major surgery, and 1,293 (14%) had documentation of discussions about dialysis. There were no significant differences in the unadjusted rates of decisions to withhold or withdraw treatment among African-Americans compared with non-African-Americans: among African-Americans, 33% had a decision made to withhold or withdraw ventilator support compared with 35% among other patients, 14% had a decision made to withhold major surgery compared with 12% among other patients, and 25% had a decision made to withhold or withdraw dialysis compared with 30% among other patients (P >0.05 for all comparisons). After adjustment for demographic characteristics, prognosis, illness severity, function, and preferences for care, there were no differences in the timing or rate of decisions to withhold or withdraw treatments among African-Americans compared with non-African-American patients. CONCLUSION: Patient race does not appear to be associated with decisions to withhold or withdraw ventilator support or dialysis, or to withhold major surgery, in seriously ill hospitalized adults.

Adult↗

PubMed2000

Patient characteristics associated with care by a cardiologist among adults hospitalized with severe congestive heart failure. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

OBJECTIVES: The goal of this study was to determine factors associated with receiving cardiologist care among patients with an acute exacerbation of congestive heart failure. BACKGROUND: Because cardiologist care for acute cardiovascular illness may improve care, barriers to specialty care could impact patient outcomes. METHODS: We studied 1,298 patients hospitalized with acute exacerbation of congestive heart failure who were cared for by cardiologists or generalist physicians. Using multivariable logistic models we determined factors independently associated with attending cardiologist care. RESULTS: Patients were less likely to receive care from a cardiologist if they were black (adjusted odds ratio [AOR] 0.53, 95% confidence interval [CI] 0.35, 0.80), had an income of less than $11,000 (AOR 0.65, 95% CI 0.45, 0.93) or were older than 80 years of age (AOR 0.23, 95% CI 0.12, 0.46). Patients were more likely to receive cardiologist care if they had college level education (AOR 1.89, 95% CI 1.02, 3.51), a history of myocardial infarction (AOR 1.59, 95% CI 1.17, 2.16), a serum sodium less than 133 on admission (AOR 1.96, 95% CI 1.30, 2.95) or a systolic blood pressure less than 90 on admission (AOR 1.97, 95% CI 1.20, 3.24). Patients who stated a desire for life extending care were also more likely to receive care from a cardiologist (AOR 1.40, 95% CI 1.04, 1.90). CONCLUSIONS: After adjusting for severity of illness and patient preferences for care, patient sociodemographic factors were strongly associated with receiving care from a cardiologist. Future investigations are required to determine whether these associations represent unmeasured preferences for care or inequities in our health care system.

Adult↗

PubMed2000

Protective immunity to erythrocytic Plasmodium chabaudi AS infection involves IFNgamma-mediated responses and a cellular infiltrate to the liver.

IFNgamma receptor (IFNgammaR) deficient mice and IL-4 deficient mice were infected with blood-stage Plasmodium chabaudi AS in order to analyse the role of Th1 (IFNgamma) and Th2 (IL-4)-associated cytokines in the development of protective immunity to the parasite. A high mortality rate and failure to reduce the primary parasitaemia to subpatent levels was observed in the IFNgammaR deficient mice. IL-4 deficient mice controlled a primary P. chabaudi AS infection in a similar manner to control mice and no mortality was observed. IFNyR deficient mice had a reduction in parasite-specific IgG and a significantly increased level of total IgE compared to control mice. There was no reduction in the level of parasite-specific IgG in IL-4 deficient mice. Cytological analysis of the cells present in the spleen and liver during the primary parasitaemia revealed a reduction in the numbers of lymphocytes, monocytes and polymorphonuclear (PMN) cells in the liver at the peak of parasitaemia in both IFNgammaR deficient mice and IL-4 deficient mice compared to control mice. Adoptive transfer studies demonstrated that cells isolated from the liver at day 11 post-infection could confer some protective immunity to P. chabaudi AS infection.

Animals↗

PubMed2000

The effect of nitric oxide on the growth of Plasmodium falciparum, P. chabaudi and P. berghei in vitro.

Protective immune mechanisms to the asexual erythrocytic stages of the malaria parasite Plasmodium chabaudi AS strain include antibody-independent mechanisms. Nitric oxide (NO) is produced during the infection and indirect evidence suggests that it can contribute to the antiparasitic mechanisms. We examined the effect of an NO producer, S-nitroso-acetyl-penicillamine (SNAP), on the growth and survival in vitro of P. chabaudi AS, P. berghei and P. falciparum. Growth of the parasites was monitored by the uptake of tritiated hypoxanthine and, in the case of P. falciparum, by morphological examination in stained blood smears. DL-penicillamine and sodium nitrite, as controls, had no inhibitory activity at the concentrations used. The results showed that at SNAP concentrations of approximately 182 microM and above NO was cytotoxic to P. falciparum but, at lower concentrations, there was a cytostatic effect and some parasites resumed growth and division after NO production had ceased. Rings were less susceptible to NO effects than later stages in the asexual cycle. The antimalarial activity of NO from SNAP also extended to the rodent parasites but, under the experimental conditions used, they were less sensitive than the human species. In the cultures of P. chabaudi, increasing the numbers of noninfected erythrocytes present did not diminish the antimalarial activity of SNAP, suggesting that here at least haemoglobin was not scavenging NO significantly.

Animals↗

PubMed2000

Citrobacter freundii tyrosine phenol-lyase: the role of asparagine 185 in modulating enzyme function through stabilization of a quinonoid intermediate.

Asn185 is an invariant residue in all known sequences of TPL and of closely related tryptophanase and it may be aligned with the Asn194 in aspartate aminotransferase. According to X-ray data, in the holoenzyme and in the Michaelis complex Asn185 does not interact with the cofactor pyridoxal 5'-phosphate, but in the external aldimine a conformational change occurs which is accompanied by formation of a hydrogen bond between Asn185 and the oxygen atom in position 3 of the cofactor. The substitution of Asn185 in TPL by alanine results in a mutant N185A TPL of moderate residual activity (2%) with respect to adequate substrates, L-tyrosine and 3-fluoro-L-tyrosine. The affinities of the mutant enzyme for various amino acid substrates and inhibitors, studied by both steady-state and rapid kinetic techniques, were lower than for the wild-type TPL. This effect mainly results from destabilization of the quinonoid intermediate, and it is therefore concluded that the hydrogen bond between Asn185 and the oxygen at the C-3 position of the cofactor is maintained in the quinonoid intermediate. The relative destabilization of the quinonoid intermediate and external aldimine leads to the formation of large amounts of gem-diamine in reactions of N185A TPL with 3-fluoro-L-tyrosine and L-phenylalanine. For the reaction with 3-fluoro-L-tyrosine it was first possible to determine kinetic parameters of gem-diamine formation by the stopped-flow method. For the reactions of N185A TPL with substrates bearing good leaving groups the observed values of k(cat) could be accounted for by taking into consideration two effects: the decrease in the quinonoid content under steady-state conditions and the increase in the quinonoid reactivity in a beta-elimination reaction. Both effects are due to destabilization of the quinonoid and they counterbalance each other. Multiple kinetic isotope effect studies on the reactions of N185A TPL with suitable substrates, L-tyrosine and 3-fluoro-L-tyrosine, show that the principal mechanism of catalysis, suggested previously for the wild-type enzyme, does not change. In the framework of this mechanism the observed considerable decrease in k(cat) values for reactions of N185A TPL with L-tyrosine and 3-fluoro-L-tyrosine may be ascribed to participation of Asn185 in additional stabilization of the keto quinonoid intermediate.

Alanine↗

PubMed2000

Use of administrative data to find substandard care: validation of the complications screening program.

OBJECTIVE: The use of administrative data to identify inpatient complications is technically feasible and inexpensive but unproven as a quality measure. Our objective was to validate whether a screening method that uses data from standard hospital discharge abstracts identifies complications of care and potential quality problems. DESIGN: This was a case-control study with structured implicit physician reviews. SETTING: Acute-care hospitals in California and Connecticut in 1994. PATIENTS: The study included 1,025 Medicare beneficiaries greater than 265 years of age. METHODS: Using administrative data, we stratified acute-care hospitals by observed-to-expected complication rates and randomly selected hospitals within each state. We randomly selected cases flagged with 1 of 17 surgical complications and 6 medical complications. We randomly selected controls from unflagged cases. MAIN OUTCOME MEASURE: Peer-review organization physicians' judgments about the presence of the flagged complication and potential quality-of-care problems. RESULTS: Physicians confirmed flagged complications in 68.4% of surgical and 27.2% of medical cases. They identified potential quality problems in 29.5% of flagged surgical and 15.7% of medical cases but in only 2.1% of surgical and medical controls. The rate of physician-identified potential quality problems among flagged cases exceeded 25% in 9 surgical screens and 1 medical screen. Reviewers noted several potentially mitigating circumstances that affected their judgments about quality, including factors related to the patients' illness, the complexity of the case, and technical difficulties that clinicians encountered. CONCLUSIONS: For some types of complications, screening administrative data may offer an efficient approach for identifying potentially problematic cases for physician review. Understanding the basis for physicians' judgments about quality requires more investigation.

Aged↗

PubMed2000

Does clinical evidence support ICD-9-CM diagnosis coding of complications?

BACKGROUND: Hospital discharge diagnoses, coded by use of the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), increasingly determine reimbursement and support quality monitoring. Prior studies of coding validity have investigated whether coding guidelines were met, not whether the clinical condition was actually present. OBJECTIVE: To determine whether clinical evidence in medical records confirms selected ICD-9-CM discharge diagnoses coded by hospitals. RESEARCH DESIGN AND SUBJECTS: Retrospective record review of 485 randomly sampled 1994 hospitalizations of elderly Medicare beneficiaries in Califomia and Connecticut. MAIN OUTCOME MEASURE: Proportion of patients with specified ICD-9-CM codes representing potential complications who had clinical evidence confirming the coded condition. RESULTS: Clinical evidence supported most postoperative acute myocardial infarction diagnoses, but fewer than 60% of other diagnoses had confirmatory clinical evidence by explicit clinical criteria; 30% of medical and 19% of surgical patients lacked objective confirmatory evidence in the medical record. Across 11 surgical and 2 medical complications, objective clinical criteria or physicians' notes supported the coded diagnosis in >90% of patients for 2 complications, 80% to 90% of patients for 4 complications, 70% to <80% of patients for 5 complications, and <70% for 2 complications. For some complications (postoperative pneumonia, aspiration pneumonia, and hemorrhage or hematoma), a large fraction of patients had only a physician's note reporting the complication. CONCLUSIONS: Our findings raise questions about whether the clinical conditions represented by ICD-9-CM codes used by the Complications Screening Program were in fact always present. These findings highlight concerns about the clinical validity of using ICD-9-CM codes for quality monitoring.

Aged↗

PubMed2000

Generalists and oncologists show similar care practices and outcomes for hospitalized late-stage cancer patients. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks for Treatment.

OBJECTIVE: The objective of this work was to identify similarities and differences in primary attending physicians' (generalists' versus oncologists') care practices and outcomes for seriously ill hospitalized patients with malignancy. DESIGN: This was a prospective cohort study (SUPPORT project). SETTING: Subjects were recruited from 5 US teaching hospitals; data were gathered from 1989 to 1994. SUBJECTS: Included in the study was a matched sample of 642 hospitalized patients receiving care for non-small-cell lung cancer, colon cancer metastasized to the liver, or multiorgan system failure associated with malignancy with either a generalist or an oncologist as the primary attending physician. MEASUREMENTS: Care practices and patient outcomes were determined from hospital records. Length of survival was identified with the National Death Index. Physicians' perceptions of patient's prognosis, preference for cardiopulmonary resuscitation (CPR), and length of relationship were assessed by interview. A propensity score for receiving care from an oncologist was constructed. After propensity-based matching of patients, practices and outcomes of oncologists' and generalists' patients were assessed through group comparison techniques. RESULTS: Generalist and oncologist attendings showed comparable care practices, including the number of therapeutic interventions, eg, "rescue care" and chemotherapy, and the number of care topics discussed with patients/ families. Length of stay, discharge to supportive care, readmission, total hospital costs, and survival rates were similar. For both physician groups, perception of patients' wish for CPR was associated with rescue care (P < 0.03), and such care was related to higher hospital costs (P < 0.000). Poorer prognostic estimates predicted aggressiveness-of-care discussions by both types of physicians. Length of the patient-doctor relationship was associated with oncologists' care practices. More documented discussion about aggressiveness of care was related to higher hospital costs and shorter survival for patients in both physician groups (P < 0.001). CONCLUSIONS: Generalists and oncologists showed similar care practices and outcomes for comparable hospitalized late-stage cancer patients. Physicians' perceptions about patients' preferences for CPR and prognosis influenced decision making and outcomes for patients in both physician groups. Length of relationship with patients was associated only with oncologists' care practices. Rescue care increased hospital costs but had no effect on patient survival. Future studies should compare physicians' palliative care as well as acute-care practices in both inpatient and ambulatory care settings. Patients' end-of-life quality and interchange between physician groups should also be documented and compared.

Adult↗

PubMed2000

The last six months of life for patients with congestive heart failure.

OBJECTIVE: To characterize the experiences of patients with congestive heart failure (CHF) during their last 6 months of life. DESIGN: A retrospective analysis of data from a prospective cohort study. SETTING: Five geographically diverse tertiary care academic medical centers. PARTICIPANTS: A total of 1404 patients enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) with a diagnosis of an acute exacerbation of CHF, of whom 539 patients died within 1 year of their index hospitalization. METHODS: Data from interviews with patients or their surrogates were collected and chart abstractions performed at several time points in SUPPORT. To describe progression to death, we constructed four observational windows backward in time, beginning with patients' dates of death and ending with their date of entry into the SUPPORT project or 6 months before death, whichever came first. For each outcome, patients contributed information to all windows for which they had data collected. We describe frequency distributions for each outcome over time and report tests for trend. OUTCOME MEASURES: Outcomes examined over time included: percentage of days spent in a hospital; model-based prognostic estimates of 6-month survival; functional status; occurrence of severe physical and emotional symptoms, including pain, depression and anxiety; patients' preferences for care; and the financial impact of patients' illnesses on their families. RESULTS: As death approached, patients' prognoses became poorer and illnesses more severe. Median Acute Physiology Scores for hospitalized patients rose from 33 in the interval 6 months to 3 months before death, to 44 within 3 days of death. However, the median model-based estimate of 6-month survival was 54% even within 3 days of death. Number of functional impairments, median depression scores and percent of patients reporting severe pain or dyspnea increased as death approached, with 41% of patient surrogates reporting that the patient was in severe pain and 63% reporting that the patient was severely short of breath during the 3 days before death. Perceived quality of life did not change appreciably, with 29 to 58 % of patients reporting good to excellent quality of life in all intervals before death. As death approached, patients were more likely to prefer Do Not Resuscitate (DNR) status, with the percent of patients preferring DNR rising from 33% at 6 months to 3 months before death to 47% at 1 month to 3 days before death (P < .05). The frequency with which DNR orders were written for hospitalized patients also increased as death approached. The patients' illnesses had marked financial impact on their families, with 23 % of patients' families reporting the loss of most or all of family savings at the time of the patient's death. CONCLUSIONS: As death approaches during the last 6 months of life in CHF, illness becomes more severe, disability and the experience of certain symptoms more frequent, and patient preference not to be resuscitated more common. However, there is no significant decrement in quality of life as death approaches. Reflecting the unpredictable course of CHF during the last month of life, many patients have good median model-based 6-month prognoses and enjoy good to excellent quality of life.

APACHE↗

PubMed2000

Dying with cancer: patients' function, symptoms, and care preferences as death approaches.

OBJECTIVE: To characterize the dying experience of patients with cancer over the last 6 months of life. STUDY DESIGN: A retrospective analysis of the last 6 months of life among patients with colon cancer and non-small cell lung cancer enrolled in a prospective cohort study from June 1989 to June 1991 and from January 1992 to January 1994. SETTING: Five geographically diverse tertiary care academic medical centers participating in the Study to Understand Patient Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) Project. PARTICIPANTS: All patients enrolled in SUPPORT who had either colon cancer, metastatic to the liver or stage III or stage IV non-small cell lung cancer and died within 1 year of their index hospitalization. This report examines 316 of 520 patients with metastatic colon cancer and 747 of 939 patients with lung cancer enrolled in SUPPORT. METHODS: Data were collected by interview and chart abstraction at several time points in the SUPPORT Project. To describe progression to death, we constructed four observational windows backward in time beginning with patients' date of death and ending with their date of entry into the SUPPORT Project or 6 months before their death, whichever came first: (1) 3 days before death, (2) 3 days to 1 month before death, (3) 1 month to 3 months before death, and (4) 3 months to 6 months before death. For each outcome, patients contributed information to all windows during which they had data collected. We describe the frequency distributions of each outcome over time and report tests for trend. OUTCOME MEASURES: We examined several outcomes over time, including: percentage of days spent in a hospital; prognosis as measured by model-based prognostic estimates of 6-month survival; severity of illness as measured by the acute physiology score; functional status as measured by dependencies in activities of daily living (ADLs); severe physical and emotional symptoms, including pain, depression, and anxiety; patients' preferences for care; and the financial impact on patients' families. RESULTS: The death rate within 1 year of study entry was high among patients with metastatic colon cancer and advanced non-small cell lung cancer enrolled in SUPPORT (61% and 80%, respectively). As patients with cancer progress toward death, their estimated 6-month prognosis decreases significantly and the severity of their disease worsens. Patients' functional status also declines significantly as they approach death, such that most patients have four or more impairments within the 3 days before death. Patients with cancer experience significantly more pain and confusion as death approaches. Severe pain is common; more than one-quarter of patients with cancer experience serious pain 3 to 6 months before death and more than 40% were in serious pain during their last 3 days of life. However, dying patients are only modestly depressed and anxious during their last 3 days of life. As death approaches, patients favor comfort measures over life-extension, and about two-thirds want to forego resuscitation within 3 days of death. Families of patients dying with cancer incurred significant financial burdens during the last 6 months of life, and much of this burden was already experienced by 3 to 6 months before death. CONCLUSIONS: The last 6 months of life for patients with cancer is characterized by functional decline and poorly controlled severe pain and confusion. Although patients increasingly prefer comfort care as they near death, many die in severe pain. These findings highlight important opportunities to improve the quality of care at the end of life for patients dying with cancer.

Activities of Daily Living↗

PubMed2000

Dying with lung cancer or chronic obstructive pulmonary disease: insights from SUPPORT. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

CONTEXT: Many are calling for patients with advanced chronic obstructive pulmonary disease (COPD) to receive hospice care, but the traditional hospice model may be insufficient. OBJECTIVE: To compare the course of illness and patterns of care for patients with non-small cell lung cancer and severe COPD. DESIGN: Prospective cohort study of seriously ill, hospitalized adults. SETTING: Five teaching hospitals in the United States. PATIENTS: Patients with Stage III or IV non-small cell lung cancer (n = 939) or acute exacerbation of severe COPD (n = 1008). MAIN OUTCOME MEASURES: Patients' preferences for pattern of care and for ventilator use; symptoms; life-sustaining interventions; and survival prognoses. RESULTS: Sixty percent in each group wanted comfort-focused care; 81% with lung cancer and 78% with COPD were extremely unwilling to have mechanical ventilation indefinitely. Severe dyspnea occurred in 32% of patients with lung cancer and 56% of patients with COPD and severe pain in 28 % of patients with lung cancer and 21% of patients with COPD. Patients with COPD who died during index hospitalization were more likely than patients with lung cancer to receive mechanical ventilation (70.4% vs 19.8%), tube feeding (38.7% vs 18.5%), and cardiopulmonary resuscitation (25.2% vs 7.8%). Mechanical ventilation had greater short term effectiveness in patients with COPD, based on survival to hospital discharge (76% vs 38%). Patients with COPD maintained higher median 2-month and 6-month survival prognoses, even days before death. CONCLUSIONS: Hospitalized patients with lung cancer or COPD preferred comfort-focused care, yet dyspnea and pain were problematic in both groups. Patients with COPD were more often treated with life-sustaining interventions, and short-term effectiveness was comparatively better than in patients with lung cancer. In caring for patients with severe COPD, consideration should be given to implementing palliative treatments more aggressively, even while remaining open to provision of life-sustaining interventions.

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PubMed2000

Prediction of survival for older hospitalized patients: the HELP survival model. Hospitalized Elderly Longitudinal Project.

OBJECTIVE: To develop and validate a model estimating the survival time of hospitalized persons aged 80 years and older. DESIGN: A prospective cohort study with mortality follow-up using the National Death Index. SETTING: Four teaching hospitals in the US. PARTICIPANTS: Hospitalized patients enrolled between January 1993 and November 1994 in the Hospitalized Elderly Longitudinal Project (HELP). Patients were excluded if their length of hospital stay was 48 hours or less or if admitted electively for planned surgery. MEASUREMENTS: A log-normal model of survival time up to 711 days was developed with the following variables: patient demographics, disease category, nursing home residence, severity of physiologic imbalance, chart documentation of weight loss, current quality of life, exercise capacity, and functional status. We assessed whether model accuracy could be improved by including symptoms of depression or history of recent fall, serum albumin, physician's subjective estimate of prognosis, and physician and patient preferences for general approach to care. RESULTS: A total of 1266 patients were enrolled over a 10-month period, (median age 84.9, 61% female, 68% with one or more dependency), and 505 (40%) died during an average follow-up of more than 2 years. Important prognostic factors included the Acute Physiology Score of APACHE III collected on the third hospital day, modified Glasgow coma score, major diagnosis (ICU categories together, congestive heart failure, cancer, orthopedic, and all other), age, activities of daily living, exercise capacity, chart documentation of weight loss, and global quality of life. The Somers' Dxy for a model including these factors was 0.48 (equivalent to a receiver-operator curve (ROC) area of 0.74, suggesting good discrimination). Bootstrap estimation indicated good model validation (corrected Dxy of 0.46, ROC of 0.73). A nomogram based on this log-normal model is presented to facilitate calculation of median survival time and 10th and 90th percentile of survival time. A count of geriatric syndromes or comorbidities did not add explanatory power to the model, nor did the hospital of patient recruitment, depression, or the patient preferences for general approach to care. The physician's perception of the patient's preferences and the physician's subjective estimate of the patient's prognosis improved the estimate of survival time significantly. CONCLUSIONS: Accurate estimation of length of life for older hospitalized persons may be calculated using a limited amount of clinical information available from the medical chart plus a brief interview with the patient or surrogate. The accuracy of this model can be improved by including measures of the physician's perception of the patient's preferences for care and the physician's subjective estimate of prognosis.

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