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Biomedical subjects

R M Wachter

Publications and source records attributed to R M Wachter.

At least 37 records · Page 2Linked to original sources

Assessment of prognosis in patients with community-acquired pneumonia who require mechanical ventilation.

STUDY OBJECTIVES: Knowing that mortality is high in patients who require mechanical ventilation patients with community-acquired pneumonia (CAP), we hypothesized that the severity of acute lung injury could be used along with nonpulmonary factors to identify patients with the highest risk of death. We formulated a prediction model to quantitate the risk of hospital mortality in this population of patients. DESIGN: Historical prospective study using data collected over the first 24 h of mechanical ventilation. We utilized a hypoxemia index-(1 - lowest [PaO(2)/PAO(2)]) x (minimum fraction of inspired oxygen to maintain PaO(2) at > 60 mm Hg) x 100], where PAO(2) is the alveolar partial pressure of oxygen-to grade the severity of acute lung injury on a scale from 0 to 100. SETTING: Tertiary care university hospital ICU. PATIENTS: One hundred forty-four adult patients mechanically ventilated for respiratory failure caused by CAP. MEASUREMENTS AND RESULTS: Hospital mortality was 46% (n = 66). Multivariate logistic regression analysis revealed five independent predictors of hospital mortality: (1) the extent of lung injury assessed by the hypoxemia index; (2) the number of nonpulmonary organs that failed; (3) immunosuppression; (4) age > 80 years; and (5) medical comorbidity with a prognosis for survival < 5 years. At a 50% mortality threshold, the prediction model correctly classified outcome in 88% of cases. All patients with > 95% predicted probability of death died in hospital. CONCLUSIONS: Based on clinical parameters measured over the first 24 h of mechanical ventilation, this model accurately identified critically ill, mechanically ventilated patients with CAP for whom prolonged intensive care may not be of benefit.

APACHE↗

A new doctor in the house: ethical issues in hospitalist systems.

The traditional patient-primary care physician (PCP) relationship provides many ethical protections for patients, including confidentiality, shared medical decision making, and respect for patient autonomy. Hospitalist models, which introduce a purposeful discontinuity of care, threaten these protections and raise certain ethical concerns. We analyze 2 cases that explore ethical issues arising in hospitalist systems and suggest ways to ensure ethical protection for patients. The first case examines how hospitalization can disrupt the patient-PCP relationship and raise ethical issues regarding confidentiality. In the second case, we discuss decision making when the patient's goals and preferences for care change as a result of hospitalization. Effective hospitalist systems provide a model for a trusting patient-physician relationship. Although the hospitalist must take responsibility for inpatient management, the PCP has a key role in addressing important issues in the hospital and providing care after discharge. As hospitalists assume control of inpatient care, they must also provide ethical protections to patients to supplement those currently vested in the patient-PCP relationship. An approach that keeps the patient's best interests foremost, defines a clear role for the PCP, and takes advantage of the expertise and availability of hospitalists will best serve patients and physicians.

Advance Directive Adherence↗

Structural and spectral response of green fluorescent protein variants to changes in pH.

The green fluorescent protein (GFP) from the jellyfish Aequorea victoria has become a useful tool in molecular and cell biology. Recently, it has been found that the fluorescence spectra of most mutants of GFP respond rapidly and reversibly to pH variations, making them useful as probes of intracellular pH. To explore the structural basis for the titration behavior of the popular GFP S65T variant, we determined high-resolution crystal structures at pH 8.0 and 4.6. The structures revealed changes in the hydrogen bond pattern with the chromophore, suggesting that the pH sensitivity derives from protonation of the chromophore phenolate. Mutations were designed in yellow fluorescent protein (S65G/V68L/S72A/T203Y) to change the solvent accessibility (H148G) and to modify polar groups (H148Q, E222Q) near the chromophore. pH titrations of these variants indicate that the chromophore pKa can be modulated over a broad range from 6 to 8, allowing for pH determination from pH 5 to pH 9. Finally, mutagenesis was used to raise the pKa from 6.0 (S65T) to 7.8 (S65T/H148D). Unlike other variants, S65T/H148D exhibits two pH-dependent excitation peaks for green fluorescence with a clean isosbestic point. This raises the interesting possibility of using fluorescence at this isosbestic point as an internal reference. Practical real time in vivo applications in cell and developmental biology are proposed.

Amino Acid Substitution↗

An introduction to the hospitalist model.

Motivated by a search for improved quality and efficiency, increasing numbers of hospitals and physicians are moving from systems in which all primary care providers manage their own hospitalized patients or rotate this responsibility among themselves at infrequent intervals to voluntary or mandatory systems in which patients are "handed off" to the care of an inpatient physician, the "hospitalist." All hospitalists manage medical patients in the hospital. Other potential roles for these physicians include triage in the emergency department, transfer of "out-of-network" patients, management of patients in the intensive care unit, preoperative and postoperative management of surgical patients, and leadership in hospital quality improvement and regulatory work. Hospitalists may add value by being more available to inpatients, having more hospital experience and expertise, and having an increased commitment to hospital quality improvement compared with primary care providers. Potential disadvantages of the hospitalist model include loss of information as a result of discontinuity of care, patient dissatisfaction, loss of acute care skills by primary care physicians, and burnout among hospitalists. A variety of models of care are needed to meet the clinical, organizational, financial, and political demands of diverse health care systems. The favored model should be that which produces the best clinical outcomes and the highest patient satisfaction at the lowest cost.

Hospitalists↗

Hospitalists and the practice of inpatient medicine: results of a survey of the National Association of Inpatient Physicians.

The number of hospital-based physicians, or hospitalists, in the United States has grown rapidly, yet no published data have characterized hospitalists or their practices. A self-administered questionnaire was used to describe 1) the features of hospitalists, 2) the hospitals in which they practice, and 3) the practice of inpatient medicine. The questionnaire contained 48 questions that covered four domains: demographic information about the respondent, the clinical and nonclinical workload and responsibilities of the respondent, organizational and financial aspects of the respondent's practice, and the respondent's satisfaction and his or her perception of the reaction of other physicians and nurses to the hospitalist system. The overall response rate was 57%. Data are reported on 372 surveys. Respondents were young and most were men, and only 48% had practiced hospital-based medicine for more than 2 years. Eighty-nine percent of respondents were internists; of these, 51% were generalists and 38% were subspecialists. Most hospitalists limited their practices to the inpatient setting, but 37% practiced outpatient general internal medicine or subspecialty medicine in a limited capacity. In addition to providing care for inpatients, 90% of hospitalists were engaged in cohsultative medicine. Quality assurance and practice guideline development were the most frequently reported nonclinical activities (53% and 46%; respectively). Small group practices (31%) and staff-model health maintenance organizations (25%) were the most common practice settings, and 78% of participants were reimbursed through salary. Financial incentives were common (43%) but modest. Accurate information about hospitalists and their practices will be important to clinicians, educators, researchers, and policymakers as the hospitalist movement continues to grow.

Adult↗

The hospitalist movement: ten issues to consider.

The rapidly growing hospitalist model appears to be living up its promise to improve the efficiency and perhaps the quality of hospital care. The important issues no longer relate to its continued existence--even skeptics concede that it is here to stay. Instead, concern surrounds the myriad organizational and clinical issues that inevitably appear whenever there is a major change in the health care system.

Attitude of Health Personnel↗

The potential size of the hospitalist workforce in the United States.

PURPOSE: In the United States, there are currently 1,000 to 2,000 physicians who specialize in inpatient hospital care. The number of such hospitatists appears to be growing rapidly, but the ultimate size of the hospitalist workforce is not known. METHODS: We obtained workload data from 365 practicing hospitalists who completed a survey by the National Association of Inpatient Physicians. We then estimated the number of potential hospitalists, based on published national hospital census data. We assumed that hospitalists would care for all medical inpatients, but only at hospitals large enough to require > or = 3 hospitalists. We also made estimates based on the primary care physician referral base and international benchmarks. We estimated hospitalists' primary care referral base from telephone interviews with key informants. Official sources in England and Germany provided international workforce data. RESULTS: Hospitalists reported an average workload of 13 inpatients. To cover all adult medical inpatients in the United States, we estimate a potential workforce of 19,000 hospitalists. Sensitivity analysis yielded 10,000 to 30,000 hospitalists. Our alternative models yielded estimates within this same range. CONCLUSIONS: The future hospitalist workforce is potentially quite large. This finding highlights the need to evaluate the economic and clinical outcomes of hospitalist systems.

Bed Occupancy↗

Risk factors for early hospital readmission in patients with AIDS and pneumonia.

OBJECTIVE: To determine risk factors for early readmission to the hospital in patients with AIDS and pneumonia. DESIGN: Case-control analysis. SETTING: A municipal teaching hospital serving an indigent population. PATIENTS: Case patients were all AIDS patients hospitalized with Pneumocystis carinii pneumonia or bacterial pneumonia between January 1992 and March 1995 who were readmitted for any nonelective reason within 2 weeks of discharge (n = 90). Control patients were randomly selected AIDS patients admitted during the study period who were not early readmissions (n = 87), matched by proportion of Pneumocystis carinii to bacterial pneumonia. MEASUREMENTS AND MAIN RESULTS: Demographics, social support, health-related behaviors, clinical aspects of the acute hospitalization, and general medical status were the main predictors measured. RESULTS: Patients were at significantly increased risk of early readmission if they left the hospital unaccompanied by family or friend (odds ratio [OR] 4.76; 95% confidence interval [CI] 2.06, 11.0; p =.0003), used crack cocaine (OR 3.40; 95% CI 1.02, 11.3; p =. 046), had one or more coincident AIDS diagnoses (OR 3.65; 95% CI 1. 44, 9.26; p =.0065), or had been admitted in the preceding 6 months (OR 2.82; 95% CI 1.21, 6.57; p =.016). Demographic characteristics, alcoholism, intravenous drug use, illness severity on admission, and length of hospitalization did not predict early readmission. CONCLUSIONS: Absence of companion at discharge and crack use were important risk factors for early readmission in patients with AIDS and pneumonia. Additional AIDS comorbidity and recent antecedent hospitalization were also risk factors; however, demographics and measures of acute illness during index hospitalization did not predict early readmission.

AIDS-Related Opportunistic Infections↗

Financial implications of implementing a hospitalist program.

The use of hospitalists, who are physicians specializing in providing hospital inpatient care, has become increasingly popular. Preliminary data suggest that hospitalists can shorten inpatient lengths of stay and lower costs without compromising clinical outcomes or patient satisfaction. The role of hospitalists, their position in the organizational framework, and their contractual and financial relationships are influenced by the structure of the healthcare organization in which they work. Although hospitalist programs can benefit hospitals and medical groups financially, they rarely become self-supporting through professional fees alone. The long-term viability of hospitalist programs frequently will depend on the support the programs receive from whichever entity benefits from hospitalist-generated efficiencies.

California↗

Structural basis of spectral shifts in the yellow-emission variants of green fluorescent protein.

BACKGROUND: Because of its ability to spontaneously generate its own fluorophore, the green fluorescent protein (GFP) from the jellyfish Aequorea victoria is used extensively as a fluorescent marker in molecular and cell biology. The yellow fluorescent proteins (YFPs) have the longest wavelength emissions of all GFP variants examined to date. This shift in the spectrum is the result of a T203Y substitution (single-letter amino acid code), a mutation rationally designed on the basis of the X-ray structure of GFP S65T. RESULTS: We have determined the crystal structures of YFP T203Y/S65G/V68L/S72A and YFP H148G to 2.5 and 2.6 A resolution, respectively. Both structures show clear electron density for nearly coplanar pi-pi stacking between Tyr203 and the chromophore. The chromophore has been displaced by nearly 1 A in comparison to other available structures. Although the H148G mutation results in the generation of a solvent channel to the chromophore cavity, intense fluorescence is maintained. The chromophore in the intact protein can be titrated, and the two variants have pKa values of 7.0 (YFP) and 8.0 (YFP H148G). CONCLUSIONS: The observed red shift of the T203Y YFP variant is proposed to be mainly due to the additional polarizability of the pi-stacked Tyr203. The altered location of the chromophore suggests that the exact positions of nearby residues are not crucial for the chemistry of chromophore formation. The YFPs significantly extend the pH range over which GFPs may be employed as pH indicators in live cells.

Amino Acid Sequence↗

Reorganizing an academic medical service: impact on cost, quality, patient satisfaction, and education.

CONTEXT: Academic medical centers are under enormous pressure to improve quality and cut costs while preserving education. OBJECTIVE: To determine whether a reorganized academic medical service, led by faculty members who attended more often and became involved earlier and more intensively in care, would lower costs without compromising quality and education. DESIGN: Alternate-day controlled trial. SETTING: Inpatient academic general medical service. PATIENTS: The 1623 patients discharged from the Moffitt-Long medical service between July 1, 1995, and June 30, 1996. INTERVENTIONS: We divided our 4-team inpatient general medical service into 2 managed care service (MCS) teams and 2 traditional service (TS) teams. The MCS faculty served as attending physicians more often and were required to provide early input into clinical decisions. Patients were assigned to teams based on alternate days of admission. MAIN OUTCOME MEASURES: Outcome measures included resource use and outcomes for MCS vs TS patients, and for MCS patients vs patients seen the previous year, adjusted for demographic characteristics and case mix. Satisfaction of patients, house staff, and faculty was also assessed, as was educational emphasis. RESULTS: A total of 806 patients were admitted to the MCS and 817 to the TS. Demographic characteristics and case mix were similar. Clinical outcomes, including mortality and readmission rates, were also similar, as was patient satisfaction. Resident and faculty satisfaction were high on both services. The average adjusted length of stay of patients on the MCS was 4.3 days vs 4.9 days on the TS and 5 days in 1994-1995 (adjusted P=.01 for MCS vs TS; MCS vs 1994-1995, P<.001). Average adjusted hospital costs were $7007 on the MCS vs $7777 on the TS and $8078 in 1994-1995 (adjusted P=.05 for MCS vs TS; MCS vs 1994-1995, P=.002). CONCLUSIONS: A reorganized academic medical service, led by faculty members who attended more often and became involved earlier and more intensively, resulted in significant resource savings with no changes in clinical outcomes or patient, faculty, and house staff satisfaction.

Academic Medical Centers↗

Construction and analysis of a semi-quantitative energy profile for the reaction catalyzed by the radical enzyme galactose oxidase.

Galactose oxidase (GOase) is a mononuclear type 2 copper enzyme which oxidizes primary alcohols to aldehydes using molecular oxygen (RCH2OH + O2 = RCHO + H2O2). An unusual crosslink between tyrosine 272 and cysteine 228 provides a modified tyrosine radical site which acts as a ligand for the active site copper and is believed to act as a one-electron redox center. The single active site copper is believed to act as a second one-electron redox center. The use of the tyrosine one-electron redox center and the copper one-electron redox center allows removal of two electrons from alcohol substrate for subsequent transfer to molecular oxygen. Previously, we and others have proposed a detailed step-by-step radical mechanism for the reaction catalyzed by galactose oxidase. The catalytic cycle can be divided into two half reactions. The first half reaction entails transfer of two electrons and two protons from the alcohol substrate to the enzyme to form aldehyde product and two-electron-reduced enzyme (one electron at the tyrosine center and one at the copper center). The second half reaction entails transfer of two electrons and two protons from the two-electron-reduced enzyme to O2 to form H2O2 product and regenerate fully oxidized catalytically active enzyme ready for another catalytic cycle. In this paper, we describe the construction of a semi-quantitative energy profile for this radical mechanism. Several significant points emerge from this analysis. One point is the prediction that galactose oxidase should have an unusually low redox potential for copper, to our knowledge lower than any other redox active copper protein. Another point is that the distorted or entatic copper site causes the unusually low redox potential. A final point is that crosslinking of tyrosine 272 and cysteine 228 alters the redox properties of the tyrosine center to enhance catalysis compared to what would be expected for a normal tyrosine.

Energy Transfer↗

Effect of evaluator and resident gender on the American Board of Internal Medicine evaluation scores.

OBJECTIVE: To examine the effects of resident and attending physician gender on the evaluation of residents in an internal medicine training program. DESIGN: Cross-sectional study. SETTING: Large urban academic internal medicine residency program. PARTICIPANTS: During their first 2 years of training, 132 residents (85 men, 47 women) received a total of 974 evaluations from 255 attending physicians (203 men, 52 women) from 1989 to 1995. MEASUREMENTS: The primary measurements were the numerical portions of the American Board of Internal Medicine evaluation form. Separate analyses were performed for each of the nine evaluation dimensions graded on a scale of 1 to 9. The primary outcome was the difference in the average scores received by each resident from male versus female attending physicians. RESULTS: Compared with female trainees, male residents received significantly higher scores from male attending physicians than from female attending physicians in six of the nine dimensions: clinical judgment, history, procedures, relationships, medical care, and overall. Similar trends, not reaching conventional levels of statistical significance, were observed in the other three categories: medical knowledge, physical exam, and attitude. These differences ranged from 0.24 to 0.60 points, and were primarily due to higher grading of male residents by male attending physicians than by female attending physicians. CONCLUSIONS: In one academic training program, we found a significant interaction in the grading process between the gender of internal medicine residents and the gender of their attending evaluators. This study raises the possibility that subtle aspects of gender bias may exist in medical training programs.

Bias↗