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R S Phillips

Publications and source records attributed to R S Phillips.

At least 109 records · Page 6Linked to original sources
PubMed1997

Antigenic variation during malaria infection--the contribution from the murine parasite Plasmodium chabaudi.

P. chabaudi AS strain in laboratory mice provides an accessible and useful model for investigating antigenic variation in malaria parasites. Evidence that P. chabaudi AS undergoes antigenic variation is summarized. A live indirect fluorescent test (IFAT) detects a variable antigen on the surface of schizont-infected erythrocytes. Five different variable antigen types (VATS) (detected using the live IFAT) are described from a cloned mosquito transmitted parent population. Even during the rising primary parasitaemia VATS switch at high and variable rates (1.2-1.6%). Work towards cloning genes coding for the variable antigen is briefly summarized. Acquired immunity to blood-stage P. chabaudi AS is initially mediated through Th1 CD4+ T cells and after the primary parasitaemia there is a switch to Th2 CD4+ T cells. Acquired immune effector mechanisms are discussed in the context of antigenic variation by the parasite.

Animals↗
PubMed1997

The effect of erythromycin on resolution of symptoms among adults with pharyngitis not caused by group A streptococcus.

OBJECTIVE: To determine the effect of treatment with erythromycin on the resolution of symptoms among adults with pharyngitis not caused by group A streptococcus (GAS). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Ambulatory setting (hospital-based general internal medicine practices, walk-in clinic, employee health service, and university health service). PATIENTS: One hundred and eighty-six adults who met eligibility criteria and whose chief complaint included sore throat. Patients with positive cultures for GAS were excluded. INTERVENTION: Ninety-three patients received erythromycin (333 mg three times daily for 10 days) and 93 control patients received placebo. MEASUREMENTS AND MAIN RESULTS: Major outcome measurements included time to improvement in sore throat, time to improvement in cough, time to improvement in activity level, and subjective sense of well-being. The average age of the patients studied was 26.6 years; 35% were men. Patients given erythromycin had more rapid resolution of sore throat symptoms (hazard ratio 1.43: 95% confidence interval [CI] 1.00, 2.03: p = .049). Cough also resolved more rapidly in patients receiving erythromycin (hazard ratio 2.22: 95% CI 1.01, 4.88: p = .05). There were no differences between the two treatment groups in improvement of activity level or how sick patients felt in general. Most of the benefit in resolution of sore throat was conferred on patients who sought medical care within 2 days of onset. CONCLUSIONS: Our results suggest that the benefit of erythromycin treatment for patients with non-GAS pharyngitis is small and of borderline statistical significance. Because of the small size of the effect and because widespread use of erythromycin could promote drug resistance, we do not recommend routine use of erythromycin in adult patients with this type of pharyngitis.

Adult↗
PubMed1997

Relationship of body mass index to subsequent mortality among seriously ill hospitalized patients. SUPPORT Investigators. The Study to Understand Prognoses and Preferences for Outcome and Risks of Treatments.

OBJECTIVE: To determine if body mass Index (BMI = weight [kg]/height [m]2), predictive of mortality in longitudinal epidemiologic studies, was also predictive of mortality in a sample of seriously ill hospitalized subjects. DESIGN: Prospective, multicenter study. SETTING: Five tertiary care medical centers in the United States. PATIENTS: Patients > or = 18 yrs of age who had one of nine illnesses of sufficient severity to anticipate a 6-month mortality rate of 50% were enrolled at five participating sites in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were asked their current height and weight as part of the demographic data. Stratifying body mass index by percentile rank (< or = 15, 15 to 85, and > or = 85th percentiles), risk ratios for mortality were calculated by Cox Proportional Hazards using the 15th to 85th percentile of body mass index as the reference group while controlling for multiple variables such as prior weight loss, albumin, and Acute Physiology Score. A body mass index in the < or = 15th percentile was associated with an excess risk of mortality (risk ratio = 1.23; p < .001) within 6 months. High body mass index (> or = 85th percentile) was not significantly related to risk of mortality. CONCLUSIONS: Body mass index, a simple anthropometric measure of nutrition employed in community epidemiologic studies, has now been demonstrated to be a predictor of mortality in an acutely ill population of adults at five different tertiary centers. Even when controlling for multiple disease states and physiologic variables and removing from the analysis all patients with significant prior weight loss, a body mass index below the 15th percentile remained a significant and independent predictor of mortality. Examination of patient vs. proxy data did not change the results. Future studies examining variables predictive of mortality should include body mass index, even in acutely ill populations with a poor probability of survival.

APACHE↗
PubMed1997

Advance directives for seriously ill hospitalized patients: effectiveness with the patient self-determination act and the SUPPORT intervention. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

OBJECTIVE: To assess the effectiveness of written advance directives (ADs) in the care of seriously ill, hospitalized patients. In particular, to conduct an assessment after ADs were promoted by the Patient Self-Determination Act (PSDA) and enhanced by the effort to improve decision-making in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), focusing upon the impact of ADs on decision-making about resuscitation. DESIGN: Observational cohort study conducted for 2 years before (PRE) and for 2 years after (POST) the PSDA, with a randomized, controlled trial of an additional intervention to improve decision-making after PSDA (POST+SUPPORT). SETTING: Five teaching hospitals in the United States. PATIENTS: A total of 9105 seriously ill patients treated in five teaching hospitals. INTERVENTIONS: The PSDA mandated patient education about ADs at hospital entry and documentation of ADs in the medical record. The SUPPORT intervention, in addition, provided a nurse to facilitate communication among patients, surrogates, and physicians about preferences for and outcomes of treatment alternatives and, when clinically appropriate, to encourage completion and utilization of ADs. MEASUREMENTS: Interviews were conducted with patients, surrogates, and attending physicians about awareness, completion, and impact of ADs. Medical records were reviewed for discussion about preferences concerning resuscitation, timing and writing of "Do Not Resuscitate" (DNR) orders, evidence of ADs, and the use or forgoing of resuscitation at the time of death. RESULTS: In the three cohorts, PRE, POST, and POST+SUPPORT, average age was 63. One-quarter of patients died during the initial hospitalization, one-half were dead within 6 months, and one-half were unconscious for their last 3 days. Before the PSDA (PRE), 62% were familiar with a living will, and 21% had an AD. These rates were similar for the POST and POST+SUPPORT cohorts. Just 36 (6%) of these directives were mentioned in the medical records for PRE, but a stable 35% were documented for POST, and POST+SUPPORT had an increasing rate averaging 78% (P < .001). As previously reported for PRE patients, the POST patients with and without ADs had no significant differences in the rates of medical record documentation of discussions about resuscitation (33% vs 38%, POST without AD vs POST with AD), DNR orders among those who wanted to forgo resuscitation (54% vs 58%), and attempted resuscitations at death (17% vs 9%). The POST+SUPPORT patients had similar results, with no evidence that the intervention enhanced the effect of ADs on these three measures of resuscitation decision-making. Patients with ADs more often reported that preferences about resuscitation were discussed with a physician (e.g., for POST patients, 30% for those with no AD and 43% for those with an AD, P < .05). Only 12% of patients with ADs had talked with a physician when completing the AD. Only 42% reported ever having discussed the AD with their physician. By the second study week, only one in four physicians was aware of patients' ADs. CONCLUSIONS: In these seriously ill patients, ADs did not substantially enhance physician-patient communication or decision-making about resuscitation. This lack of effect was not altered by the PSDA or by the enhanced efforts in SUPPORT, although these interventions each substantially increased documentation of existing ADs. Current practice patterns indicate that increasing the frequency of ADs is unlikely to be a substantial element in improving the care of seriously ill patients. Future work to improve decision-making should focus upon improving the current pattern of practice through better communication and more comprehensive advance care planning.

Advance Care Planning↗
PubMed1997

Do advance directives provide instructions that direct care? SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

OBJECTIVE: To evaluate whether the lack of effect of advance directives (ADs) on decision-making in SUPPORT might arise, in part, from the content of the actual documents. DESIGN: Advance directives placed in the medical records were abstracted for date of completion and content of additional written instructions. We examined directives with instructions to forgo life-sustaining treatment in the current state of health to determine whether care given was consistent with preferences noted in those directives. SETTINGS: Five teaching hospitals in the United States. PATIENTS: A total of 4804 patients with at least one of nine serious illnesses were admitted to five teaching hospitals in the 2 years following implementation of the Patient Self-Determination Act. Patients were part of a randomized controlled trial to improve decision-making and outcomes. RESULTS: From the medical records of 4804 patients, a total of 688 directives were collected from 569 patients. The majority of these directives (66%) were durable powers of attorney; in addition, 31% were standard living wills or other forms of written instructions (3%). Only 90 documents (13%) provided additional instructions for medical care beyond naming a proxy or stating the preferences of a standard living will. Only 36 contained specific instructions about the use of life-sustaining medical treatment, and only 22 of these directed forgoing life-sustaining treatment in the patient's current situation. For these, the treatment course was consistent with the instruction for nine patients. In two cases, patients may have changed an inconsistent directive after discussion with hospital staff. CONCLUSION: Advance directives placed in the medical records of seriously ill patients often did not guide medical decision-making beyond naming a healthcare proxy or documenting general preferences in a standard living will format. Even when specific instructions were present, care was potentially inconsistent in half of the cases.

Advance Directives↗
PubMed1997

The illusion of end-of-life resource savings with advance directives. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

OBJECTIVE: Would increasing the documentation of advance directives (ADs) lead to a reduction in resource utilization? We examined this question by conducting three secondary analyses: (1) we tested for a change in resource use among those who died in the hospital at a time before and after an intervention that increased the documentation of ADs in the medical record; (2) we replicated analyses of published studies that reported an association of chart documentation of ADs and hospital resource use; and (3) we examined whether a potential explanation of the observed association is biased documentation of ADs among patients who have completed an AD. DESIGN: Replication of analysis of previous published studies using data from a prospective cohort study and block-randomized controlled trial. SETTING: Five teaching hospitals in the United States. PATIENTS: A total of 9105 seriously ill patients were enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), including 4301 patients in the 2 years (1989-91) before the Patient Self-Determination Act (PSDA) and 4804 in the 2 years (1992-94) after the PSDA implementation, with 2652 patients receiving the intervention and 2152 serving as controls. INTERVENTIONS: The SUPPORT intervention provided a nurse to facilitate communication among patients, surrogates, and physicians about preferences for and outcomes of treatments. Documenting existing advance directives was also one of this nurse's tasks. The Patient Self-Determination Act required that health care institutions inquire about and document existing advance directives at the time of hospital admission. MEASUREMENT: Hospital resource use was derived from the Therapeutic Intensity Scoring System and hospital length of stay, converted into 1994 dollars. RESULTS: Chart documentation of existing advance directives at the time of study admission increased with both the PSDA and the SUPPORT intervention. We found that intervention patients were more likely to have pre-existing ADs documented. Despite this increase, there was no corresponding change in hospital resource use for those who died during the enrollment hospitalization. Replication of analyses from published studies using data from the block randomized controlled trial found that ADs documented by the third day of serious illness were associated with a 23% reduction in hospital resource use among control patients ($21,284 with ADs documented compared with $26,127 without, 95% CI 1-48% reduction). However, this association was not observed among intervention patients, who had more pre-existing ADs documented in the medical record. Intervention patients with early documentation of ADs showed a trend toward greater cost ($28,017 compared with $24,178 among those without AD documentation, 95% CI 0-25% increase). The rate of documentation and characteristics of those with documentation differed between control and intervention patients. Intervention patients were more likely (as reported by patient or surrogate interview) to have ADs documented in the medical record by the third day (55% vs 32%, P < .001). In contrast to intervention patients, control patients who were older, less wealthy, less educated, more likely to prefer to forgo CPR, and more likely to want life-sustaining treatment limited had their ADs documented. These associations were not found among intervention patients when comparison was made between those with and those without an AD documented in the medical record. CONCLUSION: Increasing the documentation of pre-existing ADs was not associated with a reduction in hospital resource use. ADs documented without further intervention by the third day of a serious illness were associated with decreased hospital resource use. However, we did not find this association with an intervention that increased AD documentation. One potential explanation of these findings is that classification of those with an AD was based on cha

Advance Directives↗
PubMed1997

Preferences for cardiopulmonary resuscitation.

PURPOSE: To examine nurse-patient communication about preferences for cardiopulmonary resuscitation (CPR). DESIGN: Prospective cohort. Sampled were patients and nurses caring for patients enrolled in SUPPORT (1989-91), a multicenter study of seriously-ill hospitalized adults at four U.S. hospitals. METHODS: Information about patient preferences was obtained by interviews with patients and their designated surrogates. For selected patients, nurses were interviewed prospectively about their understanding of patients' preferences and whether they discussed these preferences with their patients. Nurse demographic information was obtained by questionnaire. Additional patient data were obtained by interview and chart review. Logistic regression was used to identify independent correlates of nurse-patient communication and nurses' understanding of patients' preferences. FINDINGS: For 1,763 study patients, 1,427 nurse interviews (response rate 81%) were obtained. The median age of interviewed nurses was 29 years; 96% were women, 68% had a bachelor's or master's degree, and 62% had worked for 5 years or more as a nurse. Nurses reported discussions about CPR with 13% of their patients, and these discussions were more likely if the nurse thought the patient did not want CPR (adjusted odds ratio [AOR] 2.68; 95% CI 1.84 to 3.90), if the nurse had spent more time with the patient (AOR 1.05; 95% CI 1.02 to 1.08) per 5 additional days, if the patient had metastatic cancer (AOR 3.56; 95% CI 1.86 to 6.78), or if the patient was in an intensive care unit at the time of study entry (AOR 2.08; 95% CI 1.26 to 3.42). Diagnosis and study site were also associated with nurses' reports of discussions with patients. Of 551 patients with available data, 58% (n = 317) wanted CPR and 30% (n = 164) did not. Nurses understood patients' CPR preferences correctly for 74% of the patients. Nurses were more likely to understand patients' preferences to forego CPR if the patient was 75 years of age or older (AOR 6.6; 95% CI 2.0 to 22.0) or if the nurse and patient had discussed the patient's preferences (AOR 25.3; 95% CI 6.5 to 98.6) or if the patient had cancer (AOR 10.9; 95% CI 2.3 to 50.1). Nurses' understanding of patients' preferences for CPR was no better than that of physicians or patients' surrogate decision-makers. CONCLUSIONS: In this sample of seriously ill hospitalized adults, discussions between patients and nurses about CPR were infrequent. Nurses' understanding of patients' preferences for care was similar to that of physicians and patients' surrogate decision-makers. Educational interventions should focus on increasing the frequency of nurse-patient discussions about end-of-life care and improving nurses' understanding of patients' preferences for care.

Adult↗
PubMed1996

Effects of alpha-deuteration and of aza and thia analogs of L-tryptophan on formation of intermediates in the reaction of Escherichia coli tryptophan indole-lyase.

Tryptophan indole-lyase catalyzes the hydrolytic cleavage of L-tryptophan to indole and ammonium pyruvate. After the enzyme is mixed with L-tryptophan in the rapid-scanning stopped-flow spectrophotometer, there is an absorbance increase at 505 nm in the pre-steady state attributed to formation of a quinonoid intermediate, which occurs in at least three consecutive first-order phases. Reaction with [alpha-2H]-L-tryptophan results in significant primary kinetic isotope effects on the first two phases, and there is a significant isotope effect on the amplitude of the absorbance increase in the second phase. This result suggests that proton transfer to carbon to form the indolenine intermediate is relatively slow and is probably at least partially rate-determining. Reaction of L-tryptophan in the presence of benzimidazole results in a rapid increase in absorbance in the first phase, followed by a decrease in absorbance in the second phase, with rate constants very similar to those observed without benzimidazole. We have also examined aza and thia analogs of L-tryptophan, with the benzene ring of the indole replaced by pyridine or thiophene. Both 4,5-thiatryptophan and 6,7-thiatryptophan form quinonoid intermediates in the reaction with tryptophan indole-lyase; however, 6,7-thiatryptophan is a better substrate (kcat/K(m) = 32% of L-trp) for tryptophan indole-lyase than is 4,5-thiatryptophan (kcat/K(m) = 4% of L-trp). Benzimidazole affects the pre-steady-state reaction of 6,7-thiatryptophan in a way similar to L-tryptophan, while benzimidazole does not affect the pre-steady-state reaction of 4,5-thiatryptophan. 4-Aza-, 5-aza-, 6-aza-, and 7-aza-L-tryptophan are all very slow substrates (kcat < 1% of L-trp) for Escherichia coli tryptophan indole-lyase. beta-Indazolyl-L-alanine is a relatively good substrate and exhibits a quinonoid intermediate in its reaction with tryptophan indole-lyase. 6-Aza- and 7-azatryptophan accumulate quinonoid intermediates in the reaction with tryptophan indole-lyase, whereas 4-aza- and 5-azatryptophans do not significantly accumulate quinonoid intermediates, and these latter compounds exhibit very high K(m) values. Addition of benzimidazole does not change the rapid-scanning stopped-flow spectra of 6-aza- and 7-azatryptophan. This suggests that the rate-determining step in the reaction changes depending on the position and type of heteroatom substitution. For 6-aza- and 7-azatryptophan, the very slow rates of elimination may be due to slow C-protonation of the azaindole, while for 4,5-thiatryptophan, the elimination of thienopyrrole is probably slow. Of all analogs examined, 6,7-thiatryptophan is most similar to tryptophan in its reaction with E. coli tryptophan indole-lyase.

Aza Compounds↗
PubMed1996

Factors associated with do-not-resuscitate orders: patients' preferences, prognoses, and physicians' judgments. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

BACKGROUND: Medical treatment decisions should be based on the preferences of informed patients or their proxies and on the expected outcomes of treatment. Because seriously ill patients are at risk for cardiac arrest, examination of do-not-resuscitate (DNR) practices affecting them provides useful insights into the associations between various factors and medical decision making. OBJECTIVE: To examine the association between patients' preferences for resuscitation (along with other patient and physician characteristics) and the frequency and timing of DNR orders. DESIGN: Prospective cohort study. SETTING: 5 teaching hospitals. PATIENTS: 6802 seriously ill hospitalized patients enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT) between 1989 and 1994. MEASUREMENTS: Patients and their surrogates were interviewed about patients' cardiopulmonary resuscitation preferences, medical records were reviewed to determine disease severity, and a multivariable regression model was constructed to predict the time to the first DNR order. RESULTS: The patients' preference for cardiopulmonary resuscitation was the most important predictor of the timing of DNR orders, but only 52% of patients who preferred not to be resuscitated actually had DNR orders written. The probability of surviving for 2 months was the next most important predictor of the timing of DNR orders. Although DNR orders were not linearly related to the probability of surviving for 2 months, they were written earlier and more frequently for patients with a 50% or lower probability of surviving for 2 months. Orders were written more quickly for patients older than 75 years of age, regardless of prognosis. After adjustment for these and other influential patient characteristics, the use and timing of DNR orders varied significantly among physician specialties and among hospitals. CONCLUSIONS: Patients' preferences and short-term prognoses are associated with the timing of DNR orders. However, the substantial variation seen among hospital sites and among physician specialties suggests that there is room for improvement. In this study, DNR orders were written earlier for patients older than 75 years of age, regardless of prognosis. This finding suggests that physicians may be using age in a way that is inconsistent with the reported association between age and survival. The process for making decisions about DNR orders needs to be improved if such orders are to routinely and accurately reflect patients' preferences and probable outcomes.

Aged↗
PubMed1996

DP-2, a heterodimeric partner of E2F: identification and characterization of DP-2 proteins expressed in vivo.

E2F is a heterodimeric transcription factor that regulates the expression of genes at the G1/S boundary and is composed of two related but distinct families of proteins, E2F and DP. E2F/DP heterodimers form complexes with the retinoblastoma (Rb) protein, the Rb-related proteins p107 and p130, and cyclins/cdks in a cell cycle-dependent fashion in vivo. E2F is encoded by at least five closely related genes, E2F-1 through -5. Here we report studies of DP-2, the second member of the DP family of genes. Our results indicate that (i) DP-2 encodes at least five distinct mRNAs, (ii) a site of alternative splicing occurs within the 5' untranslated region of DP-2 mRNA, (iii) at least three DP-2-related proteins (of 55, 48, and 43 kDa) are expressed in vivo, (iv) each of these proteins is phosphorylated, and (v) one DP-2 protein (43 kDa) carries a truncated amino terminus. Our data also strongly suggest that the 55-kDa DP-2-related protein is a novel DP-2 isoform that results from alternative splicing. Thus, we conclude that DP-2 encodes a set of structurally, and perhaps functionally, distinct proteins in vivo.

Alternative Splicing↗
PubMed1996

Factors associated with change in resuscitation preference of seriously ill patients. The SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

BACKGROUND: During serious illness, patient preferences regarding life-sustaining treatments play an important role in medical decisions. However, little is known about life-sustaining preference stability in this population or about factors associated with preference change. METHODS: We evaluated 2-month cardiopulmonary resuscitation (CPR) preference stability in a cohort of 1590 seriously ill hospitalized patients at 5 acute care teaching hospitals. Using multiple logistic regression, we measured the association of patient demographic and health-related factors (quality of life, function, depression, prognosis, and diagnostic group) with change in CPR preference between interviews. RESULTS: Of 1590 patients analyzed, 73% of patients preferred CPR at baseline interview and 70% chose CPR at follow-up. Preference stability was 80% overall-85% in patients initially preferring CPR and 69% in those initially choosing do not resuscitate (DNR). For patients initially preferring CPR, older age, non-African American race, and greater depression at baseline were independently associated with a change to preferring DNR at follow-up. For patients initially preferring DNR, younger age, male gender, less depression at baseline, improvement in depression between interviews, and an initial admission diagnosis of acute respiratory failure or multiorgan system failure were associated with a change to preferring CPR at follow-up. For patients initially preferring DNR, patients with substantial improvements in depression score between interviews were more than 5 times as likely to change preference to CPR than were patients with substantial worsening in depression score. CONCLUSIONS: More than two thirds of seriously ill patients prefer CPR for cardiac arrest and 80% had stable preferences over 2 months. Factors associated with preference change suggest that depression may lead patients to refuse life-sustaining care. Providers should evaluate mood state when eliciting patients' preferences for life-sustaining treatments.

Cardiopulmonary Resuscitation↗
PubMed1996

Interactions of Escherichia coli tryptophanase with quasisubstrates and monovalent cations studied by the circular dichroism and fluorescence methods.

The reaction of tryptophanase and its W330F and W248F mutant forms with quasi-substrates forming an external pyridoxal phosphate aldimine or quinonoid is accompanied by the appearance of a positive circular dichroism (CD) peak at 290 nm. The peak seems to arise from a Tyr residue undergoing reorientation during the reaction. The peak does not appear upon formation of non-covalent Michaelis complexes of the enzyme with quasi-substrates such as indolepropionate, beta-phenyllactate and alpha-methylphenylalanine. The non-covalent complexes and external aldimines exhibit similar absorption spectra but can be distinguished by their CD and by the intensity of their fluorescence. Formation of the non-covalent complexes leads to an increase in positive CD at 420 nm while formation of the external aldimines leads to disappearance of the positive CD at 420 nm and its replacement by negative CD; it also leads to strong quenching of the coenzyme fluorescence at 500 nm. The quantum yield of fluorescence of the external aldimines is 6-times lower than that of the internal aldimine. Activating cations (K+, NH4+) strongly diminish the intensity of a negative protein CD band at 275 nm. From a comparison of the intensity of this band in the spectra of the wild-type holo- and apoenzyme and in the tryptophan mutants, it was deduced that the band belongs to a Tyr residue, which may be a part of the cation-binding site or located in its immediate vicinity.

Binding Sites↗
PubMed1996

Race, resource use, and survival in seriously ill hospitalized adults. The SUPPORT Investigators.

OBJECTIVE: To examine the association between patient race and hospital resource use. DESIGN: Prospective cohort study. SETTING: Five geographically diverse teaching hospitals. PATIENTS: Patients were 9,105 hospitalized adults with one of nine illnesses associated with an average 6-month mortality of 50%. MEASUREMENTS AND MAIN RESULTS: Measures of resource use included: a modified version of the Therapeutic Intervention Scoring System (TISS); performance of any of five procedures (operation, dialysis, pulmonary artery catheterization, endoscopy, and bronchoscopy); and hospital charges, adjusted by the Medicare cost-to-charge ratio per cost center at each participating hospital. The median patient age was 65; 79% were white, 16% African-American, 3% Hispanic, and 2% other races; 47% died within 6 months. After adjusting for other sociodemographic factors, severity of illness, functional status, and study site, African-Americans were less likely to receive any of five procedures on study day 1 and 3 (adjusted odds ratio [OR] 0.70; 95% confidence interval [CI] 0.60, 0.81). In addition, African-Americans had lower TISS scores on study day 1 and 3 (OR -1.8; 95% CI-1.3, -2.4) and lower estimated costs of hospitalization (OR (-)$2,805; 95% CI (-)$1,672, (-)$3,883). Results were similar after adjustment for patients' preferences and physicians' prognostic estimates. Differences in resource use were less marked after adjusting for the specialty of the attending physician but remained significant. In a subset analysis, cardiologists were less likely to care for African-Americans with congestive heart failure (p < .001), and cardiologists used more resources (p < .001). After adjustment for other sociodemographic factors, severity of illness, functional status, and study site, survival was slightly better for African-American patients (hazard ratio 0.91; 95% CI 0.84, 0.98) than for white or other race patients. CONCLUSIONS: Seriously ill African-Americans received less resource-intensive care than other patients after adjustment for other sociodemographic factors and for severity of illness. Some of these differences may be due to differential use of subspecialists. The observed differences in resource use were not associated with a survival advantage for white or other race patients.

Adult↗
PubMed1996

Effect of physician gender on the prescription of estrogen replacement therapy.

OBJECTIVE: To determine if women cared for by female physicians are more likely to receive postmenopausal estrogen replacement therapy than women cared for by male physicians. DESIGN: Case-control study with follow-up telephone survey. SETTING: An outpatient practice at an urban teaching hospital in Boston, Massachusetts. PARTICIPANTS: Subjects were women begun on estrogen replacement therapy during an 18-month period; controls were matched on age and month of visit. Seventy-one cases (mean age 60 years, 41% nonwhite) and 142 controls (mean age 60 years, 48% nonwhite) were identified. Fifty-two (82%) of 64 eligible case patients and 89 (80%) of 111 eligible control patients completed a follow-up telephone interview assessing their preferences for female physicians and interest in estrogen replacement therapy. MAIN RESULTS: After adjusting for potential confounders using conditional logistic regression, patients with female physicians were more likely to begin estrogen replacement therapy than those seen by male physicians (odds ratio [OR] 5.4; 95% confidence interval [CI] 1.8, 15.3). Case patients selected their primary care physician more often than control patients and were more interested in estrogen replacement therapy. After adjusting for potential confounders including patients' preferences to select their physician and their interest in estrogen replacement therapy, patients with female physicians were still more likely to begin estrogen replacement therapy than those seen by male physicians (OR 11.4, 95% CI 1.1, 113.6). CONCLUSIONS: We conclude that female patients are more likely to be prescribed estrogen replacement therapy if they are cared for by female physicians rather than male physicians even after accounting for patient preferences. Further research is required to determine whether these differences reflect differences in physicians' knowledge or attitudes regarding estrogen replacement therapy or reflect gender differences in how physicians discuss estrogen replacement therapy with their patients.

Adult↗
PubMed1996

Choices of seriously ill patients about cardiopulmonary resuscitation: correlates and outcomes. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

PURPOSE: For patients hospitalized with serious illnesses, we identified factors associated with a stated preference to forgo cardiopulmonary resuscitation (CPR), examined physician-patient communication about these issues, and determined the relationship of patients' preferences to intensity of care and survival. PATIENTS AND METHODS: The study was a cross-sectional evaluation of patient preferences. The setting was five geographically diverse academic acute-care medical centers participating in the SUPPORT (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments) project. Study participants were hospitalized patients > or = 18 years of age with 1 of 9 serious illnesses who were interviewed between days 3 and 6 after qualifying for the study. Using standardized interviews, patients provided information on demographics, preferences for CPR and other treatments, quality of life, functional status, perceptions of prognosis, and whether the patient had discussed CPR preferences with his or her physician. Data abstracted from the medical record included physiologic measures, therapeutic intensity, whether CPR was provided, and whether there was a do-not-resuscitate order. RESULTS: Of 1,995 eligible patients, 84% were interviewed (mean age 62 years, 58% men, inhospital mortality 7%, 6-month mortality 33%). Of the respondents, 28% did not want CPR. Factors associated independently with not wanting CPR included: hospital site; diagnosis; being older; being more functionally impaired; and patient perception of a worse prognosis. Only 29% of patients had discussed their preferences with their physician; 48% of those who did not want CPR reported such discussions. After adjusting for illness severity and factors associated with CPR preferences, patients not wanting CPR had lower intensity of care; similar inhospital mortality; and higher mortality at 2 and 6 months following study entry. CONCLUSIONS: The diagnosis, patients' perception of the prognosis, and hospital site were significantly associated with patients' resuscitation preferences after adjusting for patient demographics, severity of illness, and functional status. The rate of discussing CPR was low even for patients who did not want CPR. Patient preferences not to receive CPR were associated with a small decrease in intensity of care but no difference in hospital survival.

Aged↗
PubMed1996

Kinetics of nitric oxide production during infection and reinfection of mice with Plasmodium chabaudi.

We have shown previously that at the time of peak primary parasitaemia of P. chabaudi infection in NIH mice, significant levels of nitric oxide are produced, detectable as nitrate in the serum, and that these contribute to the protective immune response to infection. Here, we demonstrate that following reinfection, mice show a markedly diminished ability to produce nitrate. However, if mice are treated with L-NG-monomethyl arginine specifically to block nitric oxide metabolism during the primary infection, and are then reinfected, production of nitrate is restored to levels approaching those attained at peak primary parasitaemia. These experiments, together with others we have reported, indicate that whereas nitric oxide appears to play a significant role in control of the primary parasitaemia of P. chabaudi infection, it performs no such function during subsequent patent parasitaemias. Furthermore, they suggest that factors as yet unknown may regulate nitric oxide activity during malaria infection, such that under normal circumstances its production comes under strict control. This is exemplified by the observation that after the burst of nitric oxide activity that coincides with peak primary parasitaemia, there follows a prolonged period of immunological tolerance during which nitrate levels remain low even at secondary challenge infection. This tolerized state is lifted only several months after initial infection, when the nitric oxide activity at reinfection appears to correlate with the size of the parasite challenge and the presence of a patent parasitaemia. The implications of these findings for protective immunity to malaria, malarial immunosuppression, and immunoregulation in general, are discussed.

Animals↗
PubMed1996

Amylase gene structures in primates: retroposon insertions and promoter evolution.

Amylase transcription in the human salivary gland results from the evolutionary juxtaposition of two inserted elements, a gamma-actin pseudogene and an endogenous retrovirus, to create an unusual salivary-specific promoter. We utilized these structures as molecular tags to characterize the amylase genes in extant primates by polymerase chain reaction amplification of promoter fragments from genomic DNA. Six distinct amylase promoter structures were identified, which allowed us to infer the structures of common ancestors and trace the evolution of the modern human amylase promoters. Our data show that integration of the pseudogene and retrovirus were evolutionarily recent events. The gamma-actin pseudogene integrated after the divergence of the New World monkeys from the primate ancestral tree, and the retrovirus integrated later, after the divergence of the Old World monkeys. The New World monkey amylase promoter represents the mammalian amylase precursor structure before integration of the two retroposons. Two distinct amylase genes were identified in the Old World monkeys, one with a complete gamma-actin pseudogene insert and another novel structure with a truncation of the gamma-actin sequences. We demonstrated abundant amylase expression in the saliva of an Old World monkey, indicating that the endogenous retrovirus is not required for amylase transcription in the primate salivary gland.

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