Surveillance of antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae in children with pneumonia

In order to identify optimal therapy for children with bacterial pneumonia, Pakistan's ARI Program, in collaboration with the National Institute of Health (NIH), Islamabad, undertook a national surveillance of antimicrobial resistance in S. pneumoniae and H. influenzae. The project was carried out at selected urban and peripheral sites in 6 different regions of Pakistan, in 1991–92. Nasopharyngeal (NP) specimens and blood cultures were obtained from children with pneumonia diagnosed in the outpatient clinic of participating facilities. Organisms were isolated by local hospital laboratories and sent to NIH for confirmation, serotyping and antimicrobial susceptibility testing. Following were the aims of the study (i) to determine the antimicrobial resistance patterns of S. pneumoniae and H. influenzae in children aged 2–59 months; (ii) to determine the ability of selected laboratories to identify and effectively transport isolates of S. pneumoniae and H. influenzae cultured from nasopharyngeal and blood specimens; (iii) to validate the comparability of resistance patterns for nasopharyngeal and blood isolates of S. pneumoniae and H. influenzae from children with pneumonia; and (iv) to examine the effect of drug resistance and laboratory error on the cost of effectively treating children with ARI. ^ A total of 1293 children with ARI were included in the study: 969 (75%) from urban areas and 324 (25%) from rural parts of the country. Of 1293, there were 786 (61%) male and 507 (39%) female children. The resistance rate of S. pneumoniae to various antibiotics among the urban children with ARI was: TMP/SMX (62%); chloramphenicol (23%); penicillin (5%); tetracycline (16%); and ampicillin/amoxicillin (0%). The rates of resistance of H. influenzae were higher than S. pneumoniae: TMP/SMX (85%); chloramphenicol (62%); penicillin (59%); ampicillin/amoxicillin (46%); and tetracycline (100%). There were similar rates of resistance to each antimicrobial agent among isolates from the rural children. ^ Of a total 614 specimens that were tested for antimicrobial susceptibility, 432 (70.4%) were resistant to TMP/SMX and 93 (15.2%) were resistant to antimicrobial agents other than TMP/SMX viz. ampicillin/amoxicillin, chloramphenicol, penicillin, and tetracycline. ^ The sensitivity and positive predictive value of peripheral laboratories for H. influenzae were 99% and 65%, respectively. Similarly, the sensitivity and positive predictive value of peripheral laboratory tests compared to gold standard i.e. NIH laboratory, for S. pneumoniae were 99% and 54%, respectively. ^ The sensitivity and positive predictive value of nasopharyngeal specimens compared to blood cultures (gold standard), isolated by the peripheral laboratories, for H. influenzae were 88% and 11%, and for S. pneumoniae 92% and 39%, respectively. (Abstract shortened by UMI.)^

Clinical and economic outcomes of serious postoperative infections following resection of common respiratory and gastrointestinal solid tumors

Unlike infections occurring during periods of chemotherapy-induced neutropenia, postoperative infections in patients with solid malignancy remain largely understudied. The purpose of this population-based study was to evaluate the clinical and economic burden, as well as the relationship of hospital surgical volume and outcomes associated with serious postoperative infection (SPI) – i.e., bacteremia/sepsis, pneumonia, and wound infection – following resection of common solid tumors.^ From the Texas Discharge Data Research File, we identified all Texas residents who underwent resection of cancer of the lung, esophagus, stomach, pancreas, colon, or rectum between 2002 and 2006. From their billing records, we identified ICD-9 codes indicating SPI and also subsequent SPI-related readmissions occurring within 30 days of surgery. Random-effects logistic regression was used to calculate the impact of SPI on mortality, as well as the association between surgical volume and SPI, adjusting for case-mix, hospital characteristics, and clustering of multiple surgical admissions within the same patient and patients within the same hospital. Excess bed days and costs were calculated by subtracting values for patients without infections from those with infections computed using multilevel mixed-effects generalized linear model by fitting a gamma distribution to the data using log link.^ Serious postoperative infection occurred following 9.4% of the 37,582 eligible tumor resections and was independently associated with an 11-fold increase in the odds of in-hospital mortality (95% Confidence Interval [95% CI], 6.7-18.5, P < 0.001). Patients with SPI required 6.3 additional hospital days (95% CI, 6.1 - 6.5) at an incremental cost of $16,396 (95% CI, $15,927–$16,875). There was a significant trend toward lower overall rates of SPI with higher surgical volume (P=0.037). ^ Due to the substantial morbidity, mortality, and excess costs associated with SPI following solid tumor resections and given that, under current reimbursement practices, most of this heavy burden is borne by acute care providers, it is imperative for hospitals to identify more effective prophylactic measures, so that these potentially preventable infections and their associated expenditures can be averted. Additional volume-outcomes research is also needed to identify infection prevention processes that can be transferred from higher- to lower-volume providers.^

Usage of Urinary Antigen Test for Legionella on diagnosed community-acquired pneumonia in San Antonio hospitals

Purpose. To evaluate the use of the Legionella Urine Antigen Test as a cost effective method for diagnosing Legionnaires’ disease in five San Antonio Hospitals from January 2007 to December 2009. ^ Methods. The data reported by five San Antonio hospitals to the San Antonio Metropolitan Health District during a 3-year retrospective study (January 2007 to December 2009) were evaluated for the frequency of non-specific pneumonia infections, the number of Legionella Urine Antigen Tests performed, and the percentage of positive cases of Legionnaires’ disease diagnosed by the Legionella Urine Antigen Test.^ Results. There were a total of 7,087 cases of non-specific pneumonias reported across the five San Antonio hospitals studied from 2007 to 2009. A total of 5,371 Legionella Urine Antigen Tests were performed from January, 2007 to December, 2009 across the five San Antonio hospitals in the study. A total of 38 positive cases of Legionnaires’ disease were identified by the use of Legionella Urinary Antigen Test from 2007-2009.^ Conclusions. In spite of the limitations of this study in obtaining sufficient relevant data to evaluate the cost effectiveness of Legionella Urinary Antigen Test in diagnosing Legionnaires’ disease, the Legionella Urinary Antigen Test is simple, accurate, faster, as results can be obtained within minutes to hours; and convenient because it can be performed in emergency room department to any patient who presents with the clinical signs or symptoms of pneumonia. Over the long run, it remains to be shown if this test may decrease mortality, lower total medical costs by decreasing the number of broad-spectrum antibiotics prescribed, shorten patient wait time/hospital stay, and decrease the need for unnecessary ancillary testing, and improve overall patient outcomes.^

Association between cerebral oxygen metabolic rate and the incidence of nosocomial pneumonia in head injury patients

The development of nosocomial pneumonia was monitored in 96 head-trauma patients requiring mechanical ventilation for up to 10 days. Pneumonia occurred in 28 patients (29.2%) or 53.9 cases per 1,000 admission days. The incidence of nosocomial pneumonia was negatively correlated with cerebral oxygen metabolic rate (CMRO$\sb2$) measured during the first five days. The relative risk of nosocomial pneumonia for patients with CMRO$\sb2$ less than 0.6 umol/gm/min is 2.08 (1.09$-$3.98) times those patients with CMRO$\sb2$ greater than 0.6 umol/gm/min. The association between cerebral oxygen metabolic rate and nosocomial pneumonia was not affected by adjustment of potential confounding factors including age, cimetidine and other infections. These findings provide evidences underlying the CNS-immune system interaction. ^

DISTRIBUTION FUNCTIONS, MEAN SQUARED ERRORS, AND CONFIDENCE LIMITS FOR RIDGE REGRESSION ESTIMATORS

A large number of ridge regression estimators have been proposed and used with little knowledge of their true distributions. Because of this lack of knowledge, these estimators cannot be used to test hypotheses or to form confidence intervals.^ This paper presents a basic technique for deriving the exact distribution functions for a class of generalized ridge estimators. The technique is applied to five prominent generalized ridge estimators. Graphs of the resulting distribution functions are presented. The actual behavior of these estimators is found to be considerably different than the behavior which is generally assumed for ridge estimators.^ This paper also uses the derived distributions to examine the mean squared error properties of the estimators. A technique for developing confidence intervals based on the generalized ridge estimators is also presented. ^

Potential role of statins as immunomodulators in pneumococcal pneumonia

Background: Mortality in pneumococcal pneumonia remains as high as 20%, and most deaths occur within the first two weeks of hospitalization despite eradication of the causative organisms by antimicrobials in the first 24 hours. An inflammatory response rather than active infection could be responsible for this early mortality. Statins have been shown to have potent immunomodulatory activity in vitro. We investigated whether there was decreased severity or improved outcome in patients who were receiving statins at the time they were admitted for pneumococcal pneumonia. ^ Methods: Patients seen at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas from January, 2000 to June, 2010 with a diagnosis of pneumococcal pneumonia were included in this retrospective cohort study. Electronic medical records were reviewed to record demographic characteristics, comorbidities, laboratory values and statin use at the time of admission. Severity of pneumonia was determined using the Pneumonia Outcomes Research Team (PORT) classification. Uni- and multivariate Cox regression was used to evaluate survival. We adjusted for all variables in the multivariate model if they were significant in the univariate model at p<0.05. ^ Results: Of 347 patients admitted for pneumococcal pneumonia, 90 (25.9%) were taking statins at the time of presentation. Patients in the statin group were older (age: 68.0±9.7 vs. 62.5±12.3 years, p<0.001) and had higher prevalence of diabetes, coronary artery disease and kidney disease (p<0.05 for each comparison). Liver disease and alcohol consumption were less prevalent among statin users (p<0.05). The PORT scores were normally distributed in both groups with statin users having higher mean scores at admission as compared to patients not on statins (108±32 vs. 96±32, p = 0.002). The Cox proportional hazard analyses, adjusted for age, comorbidities, length of stay and PORT scores, showed a significantly reduced risk of mortality among statin users at 14 days (HR: 0.39; 0.15-0.98, p=0.045), 20 days (0.35; 0.14- 0.88, p=0.03) and 30 days(0.41; 0.17-0.95, p=0.01) after presentation. ^ Conclusion: Statin use is associated with improved clinical outcomes in patients with pneumococcal pneumonia.^

The incidence of necrotizing changes in adults with pneumococcal pneumonia

Background. Necrotizing pneumonia is generally considered a rare complication of pneumococcal pneumonia in adults. We systematically studied the incidence of necrotizing changes in adult patients with pneumococcal pneumonia, and examined the severity of infection, the role of causative serotype and the association with bacteremia. ^ Methods. We used a data base of all pneumococcal infections identified at our medical center between 2000 and 2010. Original readings of chest X-rays (CXR) and computerized tomography (CT) were noted. All images were then reread independently by 2 radiologists. The severity of disease was assessed using the SMART-COP scoring system. ^ Results. There were 351 cases of pneumococcal pneumonia. Necrosis was reported in no original CXR readings and 6 of 136 (4.4%) CTs. With re-reading, 8 of 351 (2.3%) CXR and 15 of 136 (11.0%) CT had necrotizing changes. Overall, these changes were found in 23 of 351 (6.6%, 95% CI 4.0 - 9.1) patients. The incidence of bacteremia and the admitting SMART-COP scores were similar in patients with and without necrosis (P=1.00 and P=0.32, respectively). Type 3 pneumococcus was more commonly isolated from patients with than from patients without necrotizing pneumonia (P=0.05), but a total of 10 serotypes were identified among 16 cases in which the organism was available for typing. ^ Conclusions. Necrotizing changes in the lungs were seen in 6.6% (95% CI 4.0 - 9.1) of a large series of adults with pneumococcal pneumonia. Patients with necrosis were not more likely to have bacteremia or more severe disease. Type 3 pneumococcus was commonly implicated, but 9 other serotypes were also identified.^

Risk factors of pneumonia in traumatic spinal-cord-injured patients

Pneumonia is a well-documented and common respiratory infection in patients with acute traumatic spinal cord injuries, and may recur during the course of acute care. Using data from the North American Clinical Trials Network (NACTN) for Spinal Cord Injury, the incidence, timing, and recurrence of pneumonia were analyzed. The two main objectives were (1) to investigate the time and potential risk factors for the first occurrence of pneumonia using the Cox Proportional Hazards model, and (2) to investigate pneumonia recurrence and its risk factors using a Counting Process model that is a generalization of the Cox Proportional Hazards model. The results from survival analysis suggested that surgery, intubation, American Spinal Injury Association (ASIA) grade, direct admission to a NACTN site and age (older than 65 or not) were significant risks for first event of pneumonia and multiple events of pneumonia. The significance of this research is that it has the potential to identify patients at the time of admission who are at high risk for the incidence and recurrence of pneumonia. Knowledge and the time of occurrence of pneumonias are important factors for the development of prevention strategies and may also provide some insights into the selection of emerging therapies that compromise the immune system. ^

Epidemiology of Acute Lung Injury and Acute Respiratory Distress Syndrome in children in Vietnam

Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) are life- threatening disorders that can result from many severe conditions and diseases. Since the American European Consensus Conference established the internationally accepted definition of ALI and ARDS, the epidemiology of pediatric ALI/ARDS has been described in some developed countries. In the developing world, however, there are very few data available regarding the burden, etiologies, management, outcome, and factors associated with outcomes of ALI/ARDS in children. ^ Therefore, we conducted this observational, clinical study to estimate the prevalence and case mortality rate of ALI/ARDS among a cohort of patients admitted to the pediatric intensive care unit (PICU) of the National Hospital of Pediatrics in Hanoi, the largest children's hospital in Vietnam. Etiologies and predisposing factors, and management strategies for pediatric ALI/ARDS were described. In addition, we determined the prevalence of HIV infection among children with ALI/ARDS in Vietnam. We also identified the causes of mortality and predictors of mortality and prolonged mechanical ventilation of children with ALI/ARDS. ^ A total of 1,051 patients consecutively admitted to the pediatric intensive care unit from January 2011 to January 2012 were screened daily for development of ALI/ARDS using the American-European Consensus Conference Guidelines. All identified patients with ALI/ARDS were followed until hospital discharge or death in the hospital. Patients' demographic and clinical data were collected. Multivariable logistic regression models were developed to identify independent predictors of mortality and other adverse outcome of ALI/ARDS. ^ Prevalence of ALI and ARDS was 9.6% (95% confidence interval, 7.8% to 11.4%) and 8.8% (95% confidence interval, 7.0% to 10.5%) of total PICU admissions, respectively. Infectious pneumonia and sepsis were the most common causes of ALI/ARDS accounting for 60.4% and 26.7% of cases, respectively. Prevalence of HIV infection among children with ALI/ARDS was 3.0%. The case fatality rate of ALI/ARDS was 63.4% (95% confidence interval, 53.8% to 72.9%). Multiple organ failure and refractory hypoxemia were the main causes of death. Independent predictors of mortality and prolonged mechanical ventilation were male gender, duration of intensive care stay prior to ALI/ARDS diagnosis, level of oxygenation defect measured by PaO2/FiO2 ratio at ALI/ARDS diagnosis, presence of non-pulmonary organ dysfunction at day one and day three after ALI/ARDS diagnosis, and presence of hospital acquired infection. ^ The results of this study demonstrated that ALI/ARDS was a common and severe condition in children in Vietnam. The level of both pulmonary and non-pulmonary organ damage influenced survival of patients with ALI/ARDS. Strategies for preventing ALI/ARDS and for clinical management of the disease are necessary to reduce the associated risks.^

Robust effect sizes and their confidence intervals for group difference between trajectories in hierarchical linear growth model

Hierarchical linear growth model (HLGM), as a flexible and powerful analytic method, has played an increased important role in psychology, public health and medical sciences in recent decades. Mostly, researchers who conduct HLGM are interested in the treatment effect on individual trajectories, which can be indicated by the cross-level interaction effects. However, the statistical hypothesis test for the effect of cross-level interaction in HLGM only show us whether there is a significant group difference in the average rate of change, rate of acceleration or higher polynomial effect; it fails to convey information about the magnitude of the difference between the group trajectories at specific time point. Thus, reporting and interpreting effect sizes have been increased emphases in HLGM in recent years, due to the limitations and increased criticisms for statistical hypothesis testing. However, most researchers fail to report these model-implied effect sizes for group trajectories comparison and their corresponding confidence intervals in HLGM analysis, since lack of appropriate and standard functions to estimate effect sizes associated with the model-implied difference between grouping trajectories in HLGM, and also lack of computing packages in the popular statistical software to automatically calculate them. ^ The present project is the first to establish the appropriate computing functions to assess the standard difference between grouping trajectories in HLGM. We proposed the two functions to estimate effect sizes on model-based grouping trajectories difference at specific time, we also suggested the robust effect sizes to reduce the bias of estimated effect sizes. Then, we applied the proposed functions to estimate the population effect sizes (d ) and robust effect sizes (du) on the cross-level interaction in HLGM by using the three simulated datasets, and also we compared the three methods of constructing confidence intervals around d and du recommended the best one for application. At the end, we constructed 95% confidence intervals with the suitable method for the effect sizes what we obtained with the three simulated datasets. ^ The effect sizes between grouping trajectories for the three simulated longitudinal datasets indicated that even though the statistical hypothesis test shows no significant difference between grouping trajectories, effect sizes between these grouping trajectories can still be large at some time points. Therefore, effect sizes between grouping trajectories in HLGM analysis provide us additional and meaningful information to assess group effect on individual trajectories. In addition, we also compared the three methods to construct 95% confident intervals around corresponding effect sizes in this project, which handled with the uncertainty of effect sizes to population parameter. We suggested the noncentral t-distribution based method when the assumptions held, and the bootstrap bias-corrected and accelerated method when the assumptions are not met.^