Jonathan M. Fine

Inflammatory Markers at Hospital Discharge Predict Subsequent Mortality after Pneumonia and Sepsis

RATIONALE Survivors of hospitalization for community-acquired pneumonia (CAP) are at increased risk of cardiovascular events, repeat infections, and death in the following months but the cause is unknown. OBJECTIVES To investigate whether persistent inflammation, defined as elevating circulating inflammatory markers at hospital discharge, is associated with subsequent outcomes. METHODS Prospective cohort study at 28 sites. MEASUREMENTS AND MAIN RESULTS We used standard criteria to define CAP and the National Death Index to determine all-cause and cause-specific 1-year mortality. At hospital discharge, 1,799 subjects (77.5%) were alive and vital signs had returned to normal in 1,512 (87%) subjects. The geometric means (+/-SD) for circulating IL-6 and IL-10 concentrations were 6.9 (+/-1) pg/ml and 1.2 (+/-1.1) pg/ml. At 1 year, 307 (17.1%) subjects had died. Higher IL-6 and IL-10 concentrations at hospital discharge were associated with an increased risk of death, which gradually fell over time. Using Grays survival model, the associations were independent of demographics, comorbidities, and severity of illness (for each log-unit increase, the range of adjusted hazard ratios [HRs] for IL-6 were 1.02-1.46, P < 0.0001, and for IL-10 were 1.17-1.44, P = 0.01). The ranges of HRs for each log-unit increase in IL-6 and IL-10 concentrations among subjects who did and did not develop severe sepsis were 0.95-1.27 and 1.07-1.55, respectively. High IL-6 concentrations were associated with death due to cardiovascular disease, cancer, infections, and renal failure (P = 0.008). CONCLUSIONS Despite clinical recovery, many patients with CAP leave hospital with ongoing subclinical inflammation, which is associated with an increased risk of death.

Metal Fume Fever : Characterization of Clinical and Plasma IL-6 Responses in Controlled Human Exposures to Zinc Oxide Fume at and Below the Threshold Limit Value

Results from animal and preliminary human exposure studies have called into question whether the 5 mg/m3 8-hour time-weighted average threshold limit value (TLV) for zinc oxide fume is sufficient to protect workers against metal fume fever. The objectives of this study were to determine the clinical effects of exposures to low concentrations of zinc oxide and to ascertain whether these exposures elevated circulating levels of specific cytokines, which could account for the symptoms of the metal fume fever syndrome. Thirteen resting naive subjects inhaled, on separate days, air and 2.5 and 5 mg/m3 of furnace-generated zinc oxide fume for 2 hours. Subjects recorded symptoms and temperature and had blood drawn before and after each exposure. The mean (+/- SE) maximum rise in oral temperature at 6 to 12 hours after exposure was 1.4 +/- 0.3 degrees F after 5 mg/m3, compared with 0.6 +/- 0.5 degrees F after air exposure (P < 0.05). Mean temperature was also elevated after exposure to 2.5 mg/m3 zinc oxide (1.2 +/- 0.3 degrees F). In a parallel fashion, plasma levels of interleukin 6 (IL-6), a pyrogen, were significantly elevated after exposure to 5 mg/m3 zinc oxide. Mean IL-6 values (pg/mL) at pre-exposure and at 3 and 6 hours post-exposure were 1.9 (+/- 0.6), 2.8 (+/- 0.7), and 2.9 (+/- 0.6), respectively, on the air day and 1.6 (+/- 0.6), 4.4 (+/- 1.2), and 6.4 (+/- 1.1) on the 5 mg/m3 zinc oxide day. Zinc oxide exposure did not significantly affect plasma levels of tumor necrosis factor. Total symptom scores peaked 9 hours after the 5 mg/m3 zinc oxide exposure. Myalgias, cough, and fatigue were the predominant symptoms reported. Inhalation of zinc oxide for 2 hours at the current TLV of 5 mg/m3 produces fever and symptoms along with elevation in plasma IL-6 levels.

A statewide initiative to improve the care of hospitalized pneumonia patients: The Connecticut Pneumonia Pathway Project.

PURPOSE A statewide quality improvement initiative was conducted in Connecticut to improve process-of-care performance and to decrease length of stay for patients hospitalized with community-acquired pneumonia. SETTING AND METHODS Data were collected on 1,242 elderly (> or =65 years) pneumonia patients hospitalized at 31 of 32 acute care hospitals between January 16, 1995, and March 15, 1996, and on 1,146 patients hospitalized between January 1, 1997, and June 30, 1997. Interventions included feedback of performance data (Qualidigm, the Connecticut Peer Review Organization), dissemination of an evidence-based pneumonia critical pathway (Connecticut Thoracic Society), and sharing of pathway implementation experiences (hospitals). Process and outcome measures included early antibiotic administration, blood culture collection, oxygenation assessment, length of stay, 30-day mortality, and 30-day readmission rates. Analyses were adjusted for severity of illness and hospital-specific practice patterns. RESULTS After the statewide initiative, improvements were noted in antibiotic administration within 8 hours of hospital arrival (improvement from 83.4% to 88.8%, relative risk [RR] = 1.21; 95% confidence interval [CI]: 1.10 to 1.32), oxygenation assessment within 24 hours of hospital arrival (93.6% to 95.4%; RR = 1.23, 95% CI: 1.11 to 1.38), and length of stay (7 days to 5 days, P <0.001). There were no significant changes in blood culture collection within 24 hours of hospital arrival, blood culture collection before antibiotic administration, 30-day mortality, or 30-day readmission rates. CONCLUSIONS Statewide improvements were demonstrated in the care of hospitalized pneumonia patients concurrent with a multifaceted quality improvement intervention. Further research is needed to separate the effects of the quality improvement interventions from secular trends.

Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and rabbits

Occupational exposure to freshly formed zinc oxide (ZnO) particles (less than 1.0 micron aerodynamic diameter) produces a well-characterized response known as metal fume fever. An 8-hr threshold limit value (TLV) of 5 mg/m3 has been established to prevent adverse health effects because of exposure to ZnO fumes. Because animal toxicity studies have demonstrated pulmonary effects near the current TLV, the present study examined the time course and dose-response of the pulmonary injury produced by inhaled ZnO in guinea pigs, rats, rabbits, and human volunteers. The test animals were exposed to 0, 2.5, or 5.0 mg/m3 ZnO for up to 3 hr and their lungs lavaged. Both the lavage fluid and recovered cells were examined for evidence of inflammation or altered cell function. The lavage fluid from guinea pigs and rats exposed to 5 mg/m3 had significant increases in total cells, lactate dehydrogenase, beta-glucuronidase, and protein content. These changes were greatest 24 hr after exposure. Guinea pig alveolar macrophage function was depressed as evidenced by in vitro phagocytosis of opsonized latex beads. Significant changes in lavage fluid parameters were also observed in guinea pigs and rats exposed to 2.5 mg/m3 ZnO. In contrast, rabbits showed no increase in biochemical or cellular parameters following a 2-hr exposure to 5 mg/m3 ZnO. Differences in total lung burden of ZnO, as determined in additional animals by atomic absorption spectroscopy, appeared to account for the observed differences in species responses. Although the lungs of guinea pigs and rats retained approximately 20% and 12% of the inhaled dose, respectively, rabbits retained only 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of Multidisciplinary Rounds to Simultaneously Improve Quality Outcomes, Enhance Resident Education, and Shorten Length of Stay

BACKGROUNDHospital-based clinicians and educators face a difficult challenge trying to simultaneously improve measurable quality, educate residents in line with ACGME core competencies, while also attending to fiscal concerns such as hospital length of stay (LOS).OBJECTIVEThe purpose of this study was to determine the effect of multidisciplinary rounds (MDR) on quality core measure performance, resident education, and hospital length of stay.DESIGNPre and post observational study assessing the impact of MDR during its first year of implementation.SETTINGThe Norwalk Hospital is a 328-bed, university-affiliated community teaching hospital in an urban setting with a total of 44 Internal Medicine residents.METHODSJoint Commission on Accreditation of Healthcare Organizations (JCAHO) core measure performance was obtained on a monthly basis for selected heart failure (CHF), pneumonia, and acute myocardial infarction (AMI) measures addressed on the general medical service. Resident knowledge and attitudes about MDR were determined by an anonymous questionnaire. LOS and monthly core measure performance rates were adjusted for patient characteristics and secular trends using linear spline logistic regression modeling.RESULTSInstitution of MDR was associated with a significant improvement in quality core measure performance in targeted areas of CHF from 65% to 76% (p < .001), AMI from 89% to 96% (p = .004), pneumonia from 27% to 70% (p < .001), and all combined from 59% to 78% (p < .001). Adjusted overall monthly performance rates also improved during MDR (odds ratio [OR] 1.09, CI 1.06–1.12, p < .001). Residents reported substantial improvements in core measure knowledge, systems-based care, and communication after institution of MDR (p < .001). Residents also agreed that MDR improved efficiency, delivery of evidence-based care, and relationships with involved disciplines. Adjusted average LOS decreased 0.5 (95% CI 0.1–0.8) days for patients with a target core measure diagnosis of either CHF, pneumonia, or AMI (p < .01 ) and by 0.6 (95% CI 0.5–0.7) days for all medicine DRGs (p < .001).CONCLUSIONSResident-centered MDR is an effective process using no additional resources that simultaneously improves quality of care while enhancing resident education and is associated with shortened length of stay.

Effectiveness and Acceptability of a Computerized Decision Support System Using Modified Wells Criteria for Evaluation of Suspected Pulmonary Embolism

STUDY OBJECTIVE Ready availability of computed tomography (CT) angiography for evaluation of pulmonary embolism in emergency departments (EDs) is associated with a dramatic increase in the number of CT angiography tests. The aims of this study are to determine whether a validated prediction algorithm embedded in a computerized decision support system improves the positive yield rate of CT angiography for pulmonary embolism and is acceptable to emergency physicians. METHODS This study was conducted as a prospective interventional study with a retrospective preinterventional comparison group. RESULTS The implementation of the computerized physician order entry-based computerized decision support system was associated with an overall increase in the positivity rate of from 8.3% (95% confidence interval [CI] 4.9% to 12.9%) preintervention to 12.7% (95% CI 8.6% to 17.7%) postintervention, with a difference of 4.4% (95% CI -1.4% to 10.1%). A total of 404 patients were eligible for inclusion. Physician nonadherence to the computerized decision support system occurred in 105 (26.7%) cases. Fifteen patients underwent CT angiography despite low Wells score and negative D-dimer result, all of whose results were negative for pulmonary embolism. Emergency physicians did not order CT angiography for 44 patients despite high pretest probability, with one receiving a diagnosis of pulmonary embolism on a subsequent visit and another, of DVT. When emergency physicians adhered to the computerized decision support system for the evaluation of suspected pulmonary embolism, a higher yield of CT angiography for pulmonary embolism occurred, with 28 positive results of 168 CT angiography tests (16.7%; 95% CI 11.4% to 23.2%) and a difference compared with preintervention of 8.4% (95% CI 1.7% to 15.4%). Physicians cited the time required to apply the computerized decision support system and a preference for intuitive judgment as reasons for not adhering to the computerized decision support system. CONCLUSION Use of an evidence-based computerized physician order entry-based computerized decision support system for the evaluation of suspected pulmonary embolism was associated with a higher yield of CT angiography for pulmonary embolism. The computerized decision support system, however, was poorly accepted by emergency physicians (partly because of increased computer time), leading to possibly selective use, reducing the effect on overall yield, and leading to removal of the computerized decision support system from the computer order entry. These findings emphasize the importance of facilitation of rule-based decisionmaking in the ED and attentiveness to the complex demands placed on emergency physicians.

Characterization of clinical tolerance to inhaled zinc oxide in naive subjects and sheet metal workers.

Clinical tolerance to the acute effects of zinc oxide inhalation develops in workers during periods of repeated exposure. The aims of this study were to determine whether clinical tolerance is accompanied by a reduction in the acute pulmonary inflammatory and cytokine responses to zinc oxide exposure and whether tolerance can be demonstrated in sheet metal workers who chronically inhale low levels of zinc oxide. Naive (never-exposed) subjects inhaled 5 mg/m3 zinc oxide on 1 or 3 days and underwent bronchoalveolar lavage 20 hours after the final exposure. Sheet metal workers inhaled zinc oxide on 1 day and control furnace gas on another day. Among naive subjects in whom tolerance was induced, bronchoalveolar lavage fluid percent neutrophils and interleukin-6 (IL-6) levels were significantly decreased compared with subjects who underwent only a single exposure. Sheet metal workers were much less symptomatic, but they still experienced a significant increase in plasma IL-6. The results indicate that clinical tolerance to zinc oxide is accompanied by reduced pulmonary inflammation and that chronically exposed sheet metal workers are not clinically affected by exposure to zinc oxide fume at the Occupational Safety and Health Administration Permissible Exposure Limit. The increase in IL-6 levels observed in the clinically responsive, and to a lesser extent, tolerant, states following zinc oxide inhalation is consistent with the dual role of IL-6 as a pyrogen and anti-inflammatory agent.

Factors Associated with the Hospitalization of Low-risk Patients with Community-acquired Pneumonia in a Cluster-Randomized Trial

AbstractBACKGROUND: Many low-risk patients with pneumonia are hospitalized despite recommendations to treat such patients in the outpatient setting. OBJECTIVE: To identify the factors associated with the hospitalization of low-risk patients with pneumonia. METHODS: We analyzed data collected by retrospective chart review for 1,889 low-risk patients (Pneumonia Severity Index [PSI] risk classes I to III without evidence of arterial oxygen desaturation) enrolled in a cluster-randomized trial conducted in 32 emergency departments. RESULTS: Overall, 845 (44.7%) of all low-risk patients were treated as inpatients. Factors independently associated with an increased odds of hospitalization included PSI risk classes II and III, the presence of medical or psychosocial contraindications to outpatient treatment, comorbid conditions that were not contained in the PSI (cognitive impairment, history of coronary artery disease, diabetes mellitus, or pulmonary disease), multilobar radiographic infiltrates, and home therapy with oxygen, corticosteroids, or antibiotics before presentation. While 32.8% of low-risk inpatients had a contraindication to out-patient treatment and 47.1% had one or more preexisting treatments, comorbid conditions, or radiographic abnormalities not contained in the PSI, 20.1% had no identifiable risk factors for hospitalization other than PSI risk class II or III. CONCLUSIONS: Hospital admission appears justified for one-third of low-risk inpatients based upon the presence of one or more contra-indications to outpatient treatment. At least one-fifth of low-risk inpatients did not have a contraindication to outpatient treatment or an identifiable risk factor for hospitalization, suggesting that treatment of a larger proportion of such low-risk patients in the outpatient setting could be achieved without adversely affecting patient outcomes.

Airway oedema and obstruction in guinea pigs exposed to inhaled endotoxin.

Protein extravasation and airway conductance (SGaw) were examined in awake guinea pigs exposed to inhaled endotoxin or saline for three hours. A significant increase in protein extravasation (as estimated by the leakage of protein bound Evans blue dye) was seen in the conducting airways of endotoxin exposed animals compared with saline exposed animals. Mean dye extravasation was significantly increased by one to threefold in the mainstem and hilar bronchi of endotoxin exposed animals. These changes in extravasation were accompanied by decrements in pulmonary function and by an influx of polymorphonuclear leucocytes into the airway wall. The SGaw decreased significantly by 60-90 minutes into exposure to endotoxin and had decreased by 22% and 34% at the end of exposure in the low and high dose endotoxin groups, respectively. Similar findings were obtained in animals exposed to cotton dust. Contrary to studies suggesting that platelet activating factor (PAF) is involved in the systemic and peripheral lung effects of endotoxin, pretreatment with the PAF antagonist WEB2086 did not prevent the conducting airway injury produced by inhaled endotoxin.

Conscious or unconscious: The impact of sedation choice on colon adenoma detection

AIM To determine if anesthesiologist-monitored use of propofol results in improved detection of adenomas when compared with routine conscious sedation. METHODS This retrospective study was conducted at two separate hospital-based endoscopy units where approximately 12,000 endoscopic procedures are performed annually, with one endoscopy unit exclusively using anesthesiologist-monitored propofol. Three thousand two hundred and fifty-two patients underwent initial screening or surveillance colonoscopies. Our primary end point was the adenoma detection rate, defined as the number of patients in whom at least one adenoma was found, associated with the type of sedation. RESULTS Three thousand two hundred and fifty-two outpatient colonoscopies were performed by five selected endoscopists. At least one adenoma was detected in 27.6% of patients (95% CI = 26.0-29.1) with no difference in the detection rate between the anesthesiologist-propofol and group and the gastroenterologist-midazolam/fentanyl group (28.1% vs 27.1%, P = 0.53). CONCLUSION The type of sedation used during colonoscopy does not affect the number of patients in whom adenomatous polyps are detected.