Fluoroquinolones in the management of community-acquired pneumonia.

AIMS: Review of the current guidelines for the use of respiratory fluoroquinolones in the management of community-acquired pneumonia (CAP). METHODS: Data were collected from recent clinical trials on fluoroquinolone therapy in patients with CAP and from updated recommendations of antimicrobial therapy in managing CAP, with a focus on current North American guidelines. RESULTS: Randomised clinical trials of respiratory fluoroquinolones (moxifloxacin, levofloxacin and gemifloxacin) in the treatment of CAP were identified and analysed. The bacteriology of CAP, and susceptibility rates, resistance rates and pharmacokinetic and pharmacodynamic properties of fluoroquinolones against causative pathogens in CAP, and adverse event profiles of these agents were described. Respiratory fluoroquinolones have broad-spectrum antibacterial activities against common causative pathogens in CAP and provide an important treatment option as monotherapy for outpatients with comorbidities and inpatients who are not admitted to the intensive care unit (ICU), including those with risk factors of drug-resistant Streptococcus pneumoniae. For treatment of ICU patients with severe CAP, it is recommended that fluoroquinolones be used in combination with a beta-lactam. Recent studies also demonstrated a more rapid resolution of clinical symptoms with the use of highly potent respiratory fluoroquinolones. DISCUSSION: Appropriate use of fluoroquinolone agents may shorten the duration of antimicrobial therapy and the length of hospital stay and contribute to the decreased development of resistance in patients with CAP. Adverse event profiles of these agents should be considered to facilitate the selection of an appropriate fluoroquinolone for appropriate CAP patients. CONCLUSION: The fluoroquinolone class, specifically those with adequate activity against respiratory pathogens, represents an important and convenient treatment option for patients with CAP.

Applications of airway pressure release ventilation.

The purpose of this review is to cover the definition and mechanism of airway pressure release ventilation, its advantages, and applications in acute lung injury.

Infectious pleural effusions can be identified by sTREM-1 levels.

BACKGROUND AND OBJECTIVE: Conventional methods to establish pleural infection are time-consuming and sometimes inadequate. Biomarkers may aid in making rapid diagnosis of infection. In an observational study we evaluated and compared the diagnostic value of pleural fluid levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), C-reactive protein and procalcitonin in intensive care patients with pleural effusions. METHODS: Thirty-six patients with de novo pleural effusions were included and 20 patients with pleural effusions after cardiothoracic surgery and 20 patients with pleural effusions after esophagus surgery acted as controls. Levels of sTREM-1, C-reactive protein and procalcitonin were measured in pleural effusions. RESULTS: Levels of sTREM-1 were highest in empyemas, followed by infectious exudates. Levels of sTREM-1 were low in transudates and non-infectious exudates. C-reactive protein levels were highest in exudates and empyemas, while procalcitonin levels were highest in exudates. Pleural fluid with positive culture results contained higher sTREM-1 and C-reactive protein levels as compared to samples with negative culture results. A cut-off level of 50pg/mlsTREM-1 yielded a sensitivity of 93% and a specificity of 86%, while these were 87% and 67% respectively for a cut-off value of 7.5microg/ml C-reactive protein, and 60% and 64% respectively for a cut-off value of 0.15 ng/ml procalcitonin. CONCLUSION: sTREM-1 is superior to C-reactive protein and procalcitonin in detecting infection.

Noninvasive ventilation for prevention of post-extubation respiratory failure in obese patients.

Current recommendations for management of obese patients post-extubation are based on clinical experience and expert opinions. It was hypothesised that the application of noninvasive ventilation (NIV) during the first 48 h after extubation in severely obese patients would reduce post-extubation failure and avert the need for reintubation. Following protocol-driven weaning trials, 62 consecutive severely obese patients (body mass index > or =35 kg x m(-2)) were assigned to NIV via nasal mask immediately post-extubation and compared with 62 historically matched controls who were treated with conventional therapy. The primary end-point was the incidence of respiratory failure in the first 48 h post-extubation. Compared with conventional therapy, the institution of NIV resulted in 16% (95% confidence interval 2.9-29.3%) absolute risk reduction in the rate of respiratory failure. There was a significant difference in the intensive care unit and lengths of hospital stay between the two groups. Subgroup analysis of hypercapnic patients showed reduced hospital mortality in the NIV group compared with the control group. In conclusion, noninvasive ventilation may be effective in averting respiratory failure in severely obese patients when applied during the first 48 h post-extubation. In selected patients with chronic hypercarbia, early application of noninvasive ventilation may confer a survival benefit.

Allopurinol improves endothelial function in sleep apnoea: a randomised controlled study.

Increased oxidative stress in obstructive sleep apnoea is thought to contribute to endothelial dysfunction. The objective of this study was to test the hypothesis that inhibition of xanthine oxidase by allopurinol can improve endothelial function in patients with obstructive sleep apnoea. A randomised double-blind placebo-controlled crossover study was performed on 12 patients with moderate-to-severe obstructive sleep apnoea, comparing 300 mg allopurinol daily for 2 weeks with placebo. Endothelial function was assessed using hyperaemia-induced flow-mediated vasodilation (FMD) at baseline and following treatment. Plasma malondialdehyde levels were compared in order to assess significant changes in oxidative stress. Baseline FMD correlated significantly with the severity of sleep apnoea and the time spent with an arterial oxygen saturation of <90%. Allopurinol caused a significant increase in FMD compared to placebo (10.4+/-3.2 versus 7.4+/-2.8%, respectively). Plasma malondialdehyde levels were significantly reduced with allopurinol treatment (1.5+/-0.3 versus 1.2+/-0.3 micromol.L(-1)), consistent with reduced oxidative stress. Allopurinol improves endothelial dysfunction in patients with moderate-to-severe obstructive sleep apnoea. These observations suggest that xanthine oxidase contributes significantly to vasodilatory impairment.

Clinical factors associated with hyperkalemia in patients with congestive heart failure.

BACKGROUND: Patients with congestive heart failure (CHF) are at risk for hyperkalemia because of coexisting comorbidities and use of multiple medications that impair potassium (K) excretion such as angiotensin converting enzyme (ACE) inhibitors. OBJECTIVE: To identify clinical factors associated with hyperkalemia on initial presentation in patients hospitalized for CHF. DESIGN: A case-control study. SETTING: Two university-affiliated tertiary-care hospitals. SUBJECTS: Using ICD-9 code for CHF, CHF admissions with hyperkalemia on presentation (cases) were identified from a population of 938 non-dialysis-dependent CHF patients. CHF admissions with normokalemia on presentation were used as controls. Hyperkalemia was defined as serum K > or = 5.6 mmol/L, and normokalemia as serum K > or = 3.5 and < or =5.5. METHODS: Data were collected on demographic characteristics, clinical variables, comorbidity and medication use. Factors associated with hyperkalemia on initial presentation were examined. RESULTS: Mean age did not differ between cases [76 years, standard deviation (SD) = 12] and controls (75 years, SD = 12) (P = 0.824). Mean potassium levels for cases and controls were 6.2 mmol/L (range 5.6 to 8.2) and 4.3 mmol/L respectively (P < 0.001). On multivariate analysis, diabetes mellitus [odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.04-5.59], creatinine clearance <40 mL/min (OR = 8.36, CI = 2.73-25.56), use of spironolactone (OR = 4.18, CI = 1.27-13.79), and use of ACE inhibitors (OR = 2.55, CI = 1.06-6.13) were independently associated with hyperkalemia. CONCLUSIONS: In CHF patients, hyperkalemia on presentation is independently associated with diabetes, creatinine clearance <40 mL/min, use of spironolactone, and use of ACE inhibitors. Recommendations for use of spironolactone and ACE inhibitors in CHF, and the intensity of serum K monitoring need to be clarified to account for patients at higher risk for hyperkalemia.

The utility of neural network in the diagnosis of Cheyne-Stokes respiration.

The aim of this study was to design a diagnostic model to identify patients with Cheyne-Stokes respiration (CSR-CSA) based on indices of oximetric spectral analysis. A retrospective analysis of oximetric recordings of 213 sleep studies conducted over a one-year period at a Veterans Affairs medical facility was performed. A probabilistic neural network (PNN) was developed from salient features of the oximetric spectral analysis, desaturation events and the delta index. A fivefold cross-validation was used to assess the accuracy of the neural network in identifying CSR-CSA. When compared to overnight polysomnography, the PNN achieved a sensitivity of 100% (95% confidence interval [CI] 85%-100%) and a specificity of 99% (95% 97%-100%) with a corresponding area under the curve of 99% (95% CI 99%-100%). When combined with overnight pulse oximetry, PNN offers an accurate and easily applicable tool to detect CSR-CSA.

Etiology of severe pneumonia in the very elderly.

The etiology of severe pneumonia requiring mechanical ventilation in the very elderly has been imprecise because of lack of comprehensive studies and low yield of diagnostic approach. Overall, 104 patients 75 yr of age and older with severe pneumonia were studied prospectively at two university-affiliated hospitals. Microbial investigation included blood culture, serology, pleural fluid, and bronchoalveolar secretions. Streptococcus pneumoniae (14%), gram-negative enteric bacilli (14%), Legionella sp. (9%), Hemophilus influenzae (7%), and Staphylococcus aureus (7%) were the predominant pathogens in community-acquired pneumonia (CAP). Staphylococcus aureus (29%), gram-negative enteric bacilli (15%), Streptococcus pneumoniae (9%), and Pseudomonas aeruginosa (4%) accounted for most isolates of nursing home-acquired pneumonia (NHAP). The case fatality rate was 55% (53% for CAP and 57% for NHAP; p > 0.5). Activity of Daily Living (ADL) Index, pulmonary, endocrine and central nervous system (CNS) comorbidities were associated with distinct microbial etiology. By multivariate analysis, hospital mortality was associated independently with 24-h urine output (odds ratio [OR], 5.6; 95% confidence interval [CI], 2.5 to 7.9; p < 0.001), septic shock (OR, 4.3; 95% CI, 1.9 to 8.9; p = 0.0059), radiographic multilobar involvement (OR, 3.7; 95% CI, 1.8 to 15.6; p = 0.02), and inadequate antimicrobial therapy (OR, 2.6; 95% CI, 1.4 to 23.9; p = 0.034). Further studies should focus on identifying effective antimicrobial regimens in randomized trials.

Outcome of older patients with severe pneumonia predicted by recursive partitioning.

OBJECTIVES: To develop a prognostic model to predict outcome of older patients with severe pneumonia requiring mechanical ventilation. DESIGN: A nonconcurrent prospective study. SETTING: A 24-bed intensive care unit (ICU) within two university-affiliated tertiary care hospitals. PARTICIPANTS: All patients age 75 and older with severe pneumonia between June 1996 and September 1999 were included. Demographic data including activities of daily living (ADL) index score before admission, and clinical and laboratory data were collected in the first 24 hours of admission to the ICU. One hundred four patients (mean age +/- standard deviation (SD) 82.3 +/- 5.5 years) met the inclusion criteria. MEASUREMENTS: A classification tree was developed using binary recursive partitioning to predict hospital discharge. The model was compared with a logistic regression model using variables selected by the tree analysis and with the Acute Physiologic and Chronic Health Evaluation (APACHE) II. RESULTS: Outcome predictors for the classification tree were use of vasopressors, presence of multilobar pneumonia on chest radiograph, ratio of blood urea nitrogen to creatinine, Glasgow Coma Scale, urine output, and ADL score before admission. The tree achieved a sensitivity of 83.8% (95% confidence interval (CI) 69.2-92.4) and a specificity of 93.3% (95% CI 83-98.1). The predictive accuracy as assessed by the area under the curve (c-index +/- standard error) was significantly higher with the classification tree (0.932 +/- 0.03) than with logistic regression and APACHE II, (0.801 +/- 0.028 and 0.711 +/- 0.049, respectively (P < .05). CONCLUSIONS: The classification tree model demonstrated a superior predictive accuracy to that of logistic regression and APACHE II. If validated prospectively, the classification tree can be used as a tool to assess the outcome of older patients with severe pneumonia requiring mechanical ventilation on admission to the ICU. In addition, the classification tree can be used to assist healthcare workers in providing a concise summary of local outcome experience and prognostic information to patients and their surrogates.

Validity of an artificial neural network in predicting discharge destination from a postacute geriatric rehabilitation unit.

OBJECTIVE: To develop an artificial neural network (ANN) designed to predict discharge destination from postacute geriatric rehabilitation units. DESIGN: Nonconcurrent prospective study. SETTING: Postacute geriatric rehabilitation units: a 20-bed unit in a nonproprietary skilled nursing facility and a 40-bed unit in a suburban private facility. PATIENTS: Consecutive sample of 661 patients admitted between January 1995 and February 1999, including a derivation group of 452 patients and a validation group of 209 patients. INTERVENTIONS: A feed-forward, back-propagation neural network to predict discharge destination. MAIN OUTCOME MEASURE: Discharge destination from postacute geriatric rehabilitation. RESULTS: An ANN was trained on clinical pattern set derived from 452 patients and validated prospectively on 209 consecutive patients admitted to postacute geriatric rehabilitation units. The neural network achieved a sensitivity of 85.7% (95% confidence interval [CI], 83.7-89.4) and specificity of 94.1% (95% CI, 84.4-99.1) in identifying discharge destination with a corresponding area under the curve of 95.7% (95% CI, 92.1-98.3). CONCLUSION: An ANN can predict discharge to the community postacute rehabilitation with a high degree of accuracy. It could have particular value to predict return to the community for older adults with multiple comorbidities after an acute hospitalization.

A comparison of severity of illness scoring systems for elderly patients with severe pneumonia.

OBJECTIVE: To evaluate the predictive ability of three severity of illness scoring systems in elderly patients with severe pneumonia requiring mechanical ventilation compared to a younger age group. DESIGN: Prospective cohort study. SETTING: Two university-affiliated tertiary care hospitals. PATIENTS AND PARTICIPANTS: One hundred four patients 75 years of age and older and 253 patients younger than 75 years of age enrolled from medical intensive care units. MEASUREMENTS AND RESULTS: Probabilities of hospital death for patients were estimated by the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Mortality Probability Model (MPM) II and the Simplified Acute Physiology Score (SAPS) II. Predicted risks of hospital death were compared with observed outcomes using three methods of assessing the overall goodness of fit. The actual mortality of the elderly group was 54.87 % (95 % confidence interval [CI]: 45.2-64.4 %) compared to 28.9 % (95 % CI, 23.3-34.4 %) in the younger age group. There was a significant difference in the predictive accuracy of the scoring systems as assessed by the c-index, which is equivalent to the area under the receiver operator characteristics (ROC) curve, between the two groups, but not within individual groups. Calibration was insufficient for APACHE II and SAPS II in the elderly cohort as in-hospital mortality was lower than the predicted mortality for both models. CONCLUSIONS: Although the three severity of illness scoring systems (APACHE II, MPM II and SAPS II) demonstrated average discrimination when applied to estimate hospital mortality in the elderly patients with severe pneumonia, MPM II had the closest fit to our database. Alternative modeling approaches might be needed to customize the model coefficients to the elderly population for more accurate probabilities or to develop specialized models targeted to the designed population.

Predicting active pulmonary tuberculosis using an artificial neural network.

BACKGROUND: Nosocomial outbreaks of tuberculosis (TB) have been attributed to unrecognized pulmonary TB. Accurate assessment in identifying index cases of active TB is essential in preventing transmission of the disease. OBJECTIVES: To develop an artificial neural network using clinical and radiographic information to predict active pulmonary TB at the time of presentation at a health-care facility that is superior to physicians' opinion. DESIGN: Nonconcurrent prospective study. SETTING: University-affiliated hospital. PARTICIPANTS: A derivation group of 563 isolation episodes and a validation group of 119 isolation episodes. INTERVENTIONS: A general regression neural network (GRNN) was used to develop the predictive model. MEASUREMENTS: Predictive accuracy of the neural network compared with clinicians' assessment. RESULTS: Predictive accuracy was assessed by the c-index, which is equivalent to the area under the receiver operating characteristic curve. The GRNN significantly outperformed the physicians' prediction, with calculated c-indices (+/- SEM) of 0.947 +/- 0.028 and 0.61 +/- 0.045, respectively (p < 0.001). When the GRNN was applied to the validation group, the corresponding c-indices were 0. 923 +/- 0.056 and 0.716 +/- 0.095, respectively. CONCLUSION: An artificial neural network can identify patients with active pulmonary TB more accurately than physicians' clinical assessment.

Validity of neural network in sleep apnea.

Clinical assessment of obstructive sleep apnea (OSA) is poor. Overnight polysomnography (OPG) is the standard reference test, but it is expensive and time-consuming. We developed an artificial neural network (ANN) using anthropomorphic measurements and clinical information to predict the apnea-hypopnea index (AHI). All patients completed a questionnaire about sleep symptoms, sleep behavior, and demographic information prior to undergoing OPG. Neck circumference, height, and weight were obtained on presentation to the sleep center. Twelve variables were used as inputs. The output was an estimate of the AHI. The network was trained with a back-propagation algorithm on 189 patients and validated prospectively on 80 additional patients. Data from the derivation group was used to calculate the 95% confidence interval of the estimated AHI. Predictive accuracy at different AHI thresholds was assessed by the c-index, which is equivalent to the area under the receiver operator characteristic curve. The c-index for predicting OSA in the validation set was 0.96 +/- 0.0191 SE, 0.951 +/- 0.0203 SE, and 0.935 +/- 0.0274 SE, using thresholds of > 10, > 15, and > 20/hour respectively. The actual AHI of the 80 patients in the validation data set fell within the 95% confidence limits of the values predicted by the ANN. This study suggests that ANN may be useful as a predictive tool for OSA.

Clinical and radiographic manifestations of uncommon pulmonary nontuberculous mycobacterial disease in AIDS patients.

STUDY OBJECTIVE: To determine the clinical and radiographic findings of nontuberculous mycobacteria (NTM) other than Mycobacterium avium complex (MAC) and Mycobacterium kansasii in AIDS compared with non-AIDS patients. DESIGN: A retrospective chart review of all patients in whom NTM other than MAC complex and M kansasii were isolated between April 1, 1989, and October 31, 1995. SETTING: University-affiliated hospital. PATIENTS: Fifty-four patients met the criteria for uncommon pulmonary NTM disease: (1) repeated isolation of atypical mycobacterium in colony counts of > or = 3 from two or more sputum specimens; or isolation of the organism from transbronchial or open lung biopsy specimen with histologic changes suggestive of mycobacterial disease in the absence of other pathogens; and (2) either an abnormal chest radiograph, the cause of which had not been attributed to an active infection other than atypical mycobacterial disease; or the presence of one or more symptoms indicative of pulmonary disease coupled with exclusion of other illnesses with similar symptoms and signs. RESULTS: Thirty-five patients were HIV positive. Fever was the only clinical symptom more commonly seen in HIV-infected patients with NTM than non-HIV-infected patients. Sixty-six percent of all patients with AIDS were infected by Mycobacterium xenopi. Chest radiographs of AIDS patients showed a tendency for predominance of interstitial infiltrate and rarity of fibronodular disease. No specific radiographic pattern was observed for any particular organism. Adenopathy was not a feature of uncommon pulmonary NTM in AIDS, and it should suggest an alternate diagnosis. In two patients, NTM isolation from respiratory specimens preceded dissemination. Six of 8 AIDS patients treated for pulmonary NTM remained alive at the end of the study compared with only 4 of 15 patients who were not treated for pulmonary NTM (p<0.05). CONCLUSIONS: Uncommon NTM isolated from respiratory specimens ought to be considered as serious pathogens in the presence of clinical and radiographic manifestations unexplained by other pathologic processes. Colonization with NTM could precede dissemination. Treatment of uncommon pulmonary NTM disease could possibly confer a survival benefit in AIDS patients.

A comparison of severity of illness scoring systems for critically ill obstetric patients.

STUDY OBJECTIVE: To evaluate the predictive ability of three scoring systems, acute physiology and chronic health evaluation (APACHE II), simplified acute physiology score (SAPS II), and mortality probability models (MPM II) in critically ill obstetric patients compared to a control group of non-obstetric female patients of similar age group (range, 17 to 41 years). DESIGN: A retrospective medical chart review of obstetric and nonobstetric female patients between 17 and 41 years of age. SETTING: Two university hospitals. PATIENTS: Ninety-three obstetric patients and 96 nonobstetric female patients were identified from 12,740 consecutive ICU admissions. RESULTS: The actual mortality of the obstetric and the nonobstetric group was 10.8% (95% confidence interval [CI], 5.3 to 19.0%) and 12.5% (95% CI, 6.6 to 21.0%), respectively. The observed mortality was not statistically different from the mortality predicted by APACHE II, SAPS II, and MPM II (14.7%, 7.8%, and 9.1% for the obstetric group and 10.9%, 9.0%, and 9.9% for the nonobstetric group). Predictive accuracy was assessed by the c-index, which is equivalent to the area under the receiver operator characteristic (ROC) curve. There were no significant differences in the c-index for APACHE II, SAPS II, and MPM II within or between the obstetric group ([mean +/- SE], 0.93 +/- 0.02, 0.90 +/- 0.04, and 0.91 +/- 0.04, respectively) and the nonobstetric group (0.97 +/- 0.02, 0.95 +/- 0.03, and 0.96 +/- 0.02, respectively). CONCLUSIONS: We conclude that APACHE II, SAPS II, and MPM II assess the ICU outcome of critically ill obstetric patients as accurately as nonobstetric critically ill female patients of similar age group.

Outcome of AIDS patients requiring mechanical ventilation predicted by recursive partitioning.

Mechanical ventilatory support (VS) is often required for patients with AIDS. Patients, and/or their surrogates often ask the likely outcome of this intervention. To answer this question, we have developed a classification tree using clinical data from 71 patients with AIDS identified from the discharge abstracts of two hospitals between January 1990 and September 1994. These data were obtained at the time of hospital admission prior to any treatment and before VS was initiated. Survival was defined as discharge from the hospital that occurred in 13 of 72 admissions reviewed. A classification tree was developed by binary recursive partitioning. The output of the resulting tree was adjusted to produce a positive predictive value for death of 100% (95% confidence interval [95% CI], 94 to 100%) and a sensitivity and specificity of 98% (95% CI, 91 to 100%) and 100% (95% CI, 74 to 100%), respectively. The negative predictive value was 92% (95% CI, 64 to 100%). The tree predicted that patients with lactate dehydrogenase (LDH) levels less than 1,176 IU/L survived until hospital discharge, unless they had a positive blood culture, active tuberculosis prior to VS, a blood CD4 count less than 12 cells per cubic millimeter, or creatinine and hemoglobin values that were either above 2.4 mg/dL or less than 8.5 mg/dL, respectively. The remainder of the patients with an LDH level above 1,176 IU/L in this study died before hospital discharge. The classification tree requires prospective validation before it can be used as a predictive instrument. Nevertheless, this approach can be used to develop a concise summary of the local outcome experience of this circumstance in a manner that could be conveyed to patients and/or their surrogates.