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Biomedical subjects

Paul N Lanken

Publications and source records attributed to Paul N Lanken.

12 recordsLinked to original sources
PubMed2006

Identification of immunoglobulins that recognize 3-nitrotyrosine in patients with acute lung injury after major trauma.

Tyrosine nitration is a nitric oxide-derived post-translational modification of proteins. Elevated levels of specific plasma proteins modified by tyrosine nitration have been detected during acute and chronic inflammatory conditions, including acute lung injury (ALI). In the present study we examined whether circulating immunoglobulins against nitrated proteins are present in the plasma of subjects with clinically documented ALI. Affinity chromatography using covalently linked 3-nitrotyrosine was employed to identify plasma proteins that bind to this unusual amino acid. Western blotting and liquid chromatography-tandem mass spectrometry of in-gel digested protein bands revealed that the major proteins eluted from the affinity column were IgM and IgG. An enzyme-linked immunosorbent assay (ELISA) based on competition of horseradish peroxidase-derivatized 3-nitrotyrosine binding to plasma with unlabeled 3-nitrotyrosine was developed and validated. Using this ELISA, the levels of immunoglobulins that recognize 3-nitrotyrosine were significantly higher in the plasma of subjects with ALI compared with both normal control subjects and subjects with major trauma who did not develop ALI (0.36+/- 0.14 versus 0.03 +/- 0.05, and 0.25 +/- 0.15; P < 0.001 and P = 0.006, respectively). These data indicate that tyrosine-nitrated proteins induce the production of specific immunoglobulins during acute phase response and inflammation.

Adult↗
PubMed2006

Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.

BACKGROUND: Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS. METHODS: We randomly assigned 180 patients with ARDS of at least seven days' duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications. RESULTS: At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness. CONCLUSIONS: These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, NCT00295269.).

Adult↗
PubMed2006

Underuse of lung protective ventilation: analysis of potential factors to explain physician behavior.

OBJECTIVE: To determine the frequency of use of low-tidal-volume ventilation in appropriate patients with acute lung injury (ALI) and the factors associated with the choice of tidal volume. DESIGN: Prospective observational cohort study of patients identified with ALI or acute respiratory distress syndrome from September 2000 to November 2002. SETTING: Medical and surgical intensive care unit (ICU) at an academic tertiary-care hospital. MEASUREMENTS AND MAIN RESULTS: Measurements included the proportion for whom the ventilation tidal volume (TV) was 8.5 mL/kg/PBW on day 2 of ALI, 30% on day 4, and 24% on day 7. The use of low TV was significantly associated with clinical parameters indicative of worse disease severity, including low values for Pao2 (p = .01), Pao2/Fio2 (p = .08), and static compliance of the respiratory system (p = .006). CONCLUSIONS: Ventilation with a low TV was used in a minority of patients with ALI, despite results published in 1998 and 2000 supporting this approach. This may be related to clinicians' underrecognition of less severe cases of ALI, their reserving of low-TV ventilation for more severe cases, or both.

APACHE↗
PubMed2005

Recommendations for informed consent forms for critical care clinical trials.

BACKGROUND: Many subjects enrolled in research studies have a limited understanding of the research to which they consented. OBJECTIVE: To develop recommendations to enhance comprehensiveness and understanding of informed consent forms used in critical care clinical trials. DESIGN: Consensus process. RECOMMENDATIONS: We provide recommendations regarding the U.S. federally required basic and additional elements of informed consent as applied to critical care clinical trials. We also identify issues that investigators need to address, if relevant, in the informed consent forms of critical care clinical trials. These include the description, in understandable language, of complex and detailed experimental protocols that are the focus of the clinical trial, disclosure of death as a risk factor if mortality is an outcome variable, and the identification of who can legally serve as the prospective subject's surrogate. We also offer suggestions to enhance subjects' understanding of informed consent forms. CONCLUSIONS: The literature on informed consent forms suggest that shorter informed consent forms written at a lower reading level, when read carefully, might provide better subject understanding. Prospective evaluation is needed to determine whether our recommendations enhance the informed consent process.

Clinical Trials as Topic↗
PubMed2004

Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.

BACKGROUND: Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients. METHODS: We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen. RESULTS: Mean (+/-SD) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group (P=0.50). CONCLUSIONS: These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used.

Adult↗
PubMed2004

Longitudinal small-group learning during the first clinical year.

BACKGROUND AND OBJECTIVES: Ethics education for medical students has included a number of relatively vague descriptions of appropriate curricular objectives, but medical schools struggle with the general teaching of ethics, as well as with presenting the ethical dilemmas posed by managed care. This paper proposes some standards and uses them to analyze the general and managed care ethics content of the Undergraduate Medical Education for the 21st Century (UME-21) curricula. METHODS: We analyzed progress and final reports from each school to define their learning objectives, content, teaching methods, and evaluation strategies in ethics. Each was evaluated using principles of adult learning and Rest's Four Component Model of Moral Development. Good examples of curricular elements from participating schools are described. RESULTS: Ethics curricula varied widely among the schools. Goals and objectives were often stated in generalities. Teaching methods were diverse and innovative, and several new combinations of learning activities were created to highlight ethics topics. Content represented managed care and non-managed care topics in varying proportions. Student surveys of attitudes toward managed care and opinions of the ethics programs were the most commonly used as evaluation tools. Some schools were able to develop more direct means of evaluating student learning. The Four Component Model was not fully addressed in the programs developed by the participating schools. CONCLUSIONS: We make recommendations about the objectives, teaching methods, content, and evaluation methods of an ideal medical school curriculum in ethics.

Attitude of Health Personnel↗
PubMed2003

Severe sepsis: variation in resource and therapeutic modality use among academic centers.

BACKGROUND: Treatment of severe sepsis is expensive, often encompassing a number of discretionary modalities. The objective of the present study was to assess intercenter variation in resource and therapeutic modality use in patients with severe sepsis. METHODS: We conducted a prospective cohort study of 1028 adult admissions with severe sepsis from a stratified random sample of patients admitted to eight academic tertiary care centers. The main outcome measures were length of stay (LOS; total LOS and LOS after onset of severe sepsis) and total hospital charges. RESULTS: The adjusted mean total hospital charges varied from 69 429 dollars to US237 898 dollars across centers, whereas the adjusted LOS after onset varied from 15.9 days to 24.2 days per admission. Treatments used frequently after the first onset of sepsis among patients with severe sepsis were pulmonary artery catheters (19.4%), ventilator support (21.8%), pressor support (45.8%) and albumin infusion (14.4%). Pulmonary artery catheter use, ventilator support and albumin infusion had moderate variation profiles, varying 3.2-fold to 4.9-fold, whereas the rate of pressor support varied only 1.92-fold across centers. Even after adjusting for age, sex, Charlson comorbidity score, discharge diagnosis-relative group weight, organ dysfunction and service at onset, the odds for using these therapeutic modalities still varied significantly across centers. Failure to start antibiotics within 24 hours was strongly correlated with a higher probability of 28-day mortality (r2 = 0.72). CONCLUSION: These data demonstrate moderate but significant variation in resource use and use of technologies in treatment of severe sepsis among academic centers. Delay in antibiotic therapy was associated with worse outcome at the center level.

Academic Medical Centers↗
PubMed2003

Resource utilization among patients with sepsis syndrome.

OBJECTIVE: To assess the resource utilization associated with sepsis syndrome in academic medical centers. DESIGN: Prospective cohort study. SETTING: Eight academic, tertiary-care centers. PATIENTS: Stratified random sample of 1,028 adult admissions with sepsis syndrome and all 248,761 other adult admissions between January 1993 and April 1994. The main outcome measures were length of stay (LOS) in total and after onset of sepsis syndrome (post-onset LOS) and total hospital charges. RESULTS: The mean LOS for patients with sepsis was 27.7 +/- 0.9 days (median, 20 days), with sepsis onset occurring after a mean of 8.1 +/- 0.4 days (median, 3 days). For all patients without sepsis, the LOS was 7.2 +/- 0.03 days (median, 4 days). In multiple linear regression models, the mean for patients with sepsis syndrome was 18.2 days, which was 11.0 days longer than the mean for all other patients (P < .0001), whereas the mean difference in total charges was $43,000 (both P < .0001). These differences were greater for patients with nosocomial as compared with community-acquired sepsis, although the groups were similar after adjusting for pre-onset LOS. Eight independent correlates of increased post-onset LOS and 12 correlates of total charges were identified. CONCLUSIONS: These data quantify the resource utilization associated with sepsis syndrome, and demonstrate that resource utilization is high in this group. Additional investigation is required to determine how much of the excess post-onset LOS and charges are attributable to sepsis syndrome rather than the underlying medical conditions.

Academic Medical Centers↗
PubMed2003

Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure.

OBJECTIVE: Positive end-expiratory pressure (PEEP) and recruitment maneuvers (RMs) may partially reverse atelectasis and reduce ventilation-associated lung injury. The purposes of this study were to assess a) magnitude and duration of RM effects on arterial oxygenation and on requirements for oxygenation support (Fio2/PEEP) in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) receiving ventilation with low tidal volumes and high levels of PEEP; and b) frequency of adverse respiratory and circulatory events attributable to RMs. DESIGN: Prospective, randomized, crossover study. SETTING: Thirty-four intensive care units at 19 hospitals. PATIENTS: Seventy-two patients with early ALI/ARDS. Baseline PEEP and Fio2 were 13.8 +/- 3.0 cm H2O and 0.39 +/- 0.10, respectively (mean +/- sd). INTERVENTIONS: We conducted RMs by applying continuous positive airway pressure of 35-40 cm H2O for 30 secs. We conducted sham RMs on alternate days. We monitored oxyhemoglobin saturation by pulse oximetry (SpO2), Fio2/PEEP, blood pressure, and heart rate for 8 hrs after RMs and sham RMs. We examined chest radiographs for barotrauma. MEASUREMENTS AND MAIN RESULTS: Responses to RMs were variable. Greatest increments from baseline SpO2 within 10 mins after RMs were larger than after sham RMs (1.7 +/- 0.2 vs. 0.6 +/- 0.3 %, mean +/- SEM, p < .01). Systolic blood pressure decreased more +/- 1.1 mm Hg, p < .01). Changes in Fio2/PEEP requirements were not significantly different at any time after RMs vs. sham RMs. Barotrauma was apparent on first radiographs after one RM and one sham RM. CONCLUSIONS: In ALI/ARDS patients receiving mechanical ventilation with low tidal volumes and high PEEP, short-term effects of RMs as conducted in this study are variable. Beneficial effects on gas exchange in responders appear to be of brief duration. More information is needed to determine the role of recruitment maneuvers in the management of ALI/ARDS.

Blood Pressure↗
PubMed2003

Relationship of pulmonary artery catheter use to mortality and resource utilization in patients with severe sepsis.

OBJECTIVE: To examine the relationship of pulmonary artery catheter (PAC) use to patient outcomes, including mortality rate and resource utilization, in patients with severe sepsis in eight academic medical centers. DESIGN: Case-control, nested within a prospective cohort study. SETTING: Eight academic tertiary care centers. PATIENTS: Stratified random sample of 1,010 adult admissions with severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were in-hospital mortality, total hospital charge, and length of stay (LOS) for patients with and without PAC use. The case-matched subset of patients included 141 pairs managed with and without the use of a PAC. The mortality rate was slightly but not statistically significantly lower among the PAC use group compared with those not using a PAC (41.1% vs. 46.8%, p =.34). Even this trend disappeared after we adjusted for the Charlson comorbidity score and sepsis-specific Acute Physiology and Chronic Health Evaluation (APACHE) III (adjusted odds ratio, 1.02; 95% confidence interval, 0.61-1.72). In linear regression models adjusted for the Charlson comorbidity score, sepsis-specific APACHE III, surgical status, receipt of a steroid before sepsis onset, presence of a Hickman catheter, and preonset LOS, no significant differences were found for total hospital charges (139,207 US dollars vs. 148,190, adjusted mean comparing PAC and non-PAC group, p =.57), postonset LOS (23.4 vs. 26.9 days, adjusted mean, p =.32), or total LOS in intensive care unit (18.2 vs. 18.8 days, adjusted mean, p =.82). CONCLUSIONS: Among patients with severe sepsis, PAC placement was not associated with a change in mortality rate or resource utilization, although small nonsignificant trends toward lower resource utilization were present in the PAC group.

APACHE↗