Development and Validation of a Natural Language Processing Tool to Identify Patients Treated for Pneumonia across VA Emergency Departments.

BACKGROUND: Identifying pneumonia using diagnosis codes alone may be insufficient for research on clinical decision making. Natural language processing (NLP) may enable the inclusion of cases missed by diagnosis codes. OBJECTIVES: This article (1) develops a NLP tool that identifies the clinical assertion of pneumonia from physician emergency department (ED) notes, and (2) compares classification methods using diagnosis codes versus NLP against a gold standard of manual chart review to identify patients initially treated for pneumonia. METHODS: Among a national population of ED visits occurring between 2006 and 2012 across the Veterans Affairs health system, we extracted 811 physician documents containing search terms for pneumonia for training, and 100 random documents for validation. Two reviewers annotated span- and document-level classifications of the clinical assertion of pneumonia. An NLP tool using a support vector machine was trained on the enriched documents. We extracted diagnosis codes assigned in the ED and upon hospital discharge and calculated performance characteristics for diagnosis codes, NLP, and NLP plus diagnosis codes against manual review in training and validation sets. RESULTS: Among the training documents, 51% contained clinical assertions of pneumonia; in the validation set, 9% were classified with pneumonia, of which 100% contained pneumonia search terms. After enriching with search terms, the NLP system alone demonstrated a recall/sensitivity of 0.72 (training) and 0.55 (validation), and a precision/positive predictive value (PPV) of 0.89 (training) and 0.71 (validation). ED-assigned diagnostic codes demonstrated lower recall/sensitivity (0.48 and 0.44) but higher precision/PPV (0.95 in training, 1.0 in validation); the NLP system identified more "possible-treated" cases than diagnostic coding. An approach combining NLP and ED-assigned diagnostic coding classification achieved the best performance (sensitivity 0.89 and PPV 0.80). CONCLUSION: System-wide application of NLP to clinical text can increase capture of initial diagnostic hypotheses, an important inclusion when studying diagnosis and clinical decision-making under uncertainty.

Constructing Ebola transmission chains from West Africa and estimating model parameters using internet sources.

During the recent Ebola crisis in West Africa, individual person-level details of disease onset, transmissions, and outcomes such as survival or death were reported in online news media. We set out to document disease transmission chains for Ebola, with the goal of generating a timely account that could be used for surveillance, mathematical modeling, and public health decision-making. By accessing public web pages only, such as locally produced newspapers and blogs, we created a transmission chain involving two Ebola clusters in West Africa that compared favorably with other published transmission chains, and derived parameters for a mathematical model of Ebola disease transmission that were not statistically different from those derived from published sources. We present a protocol for responsibly gleaning epidemiological facts, transmission model parameters, and useful details from affected communities using mostly indigenously produced sources. After comparing our transmission parameters to published parameters, we discuss additional benefits of our method, such as gaining practical information about the affected community, its infrastructure, politics, and culture. We also briefly compare our method to similar efforts that used mostly non-indigenous online sources to generate epidemiological information.

Cost-effectiveness of adding decolonization to a surveillance strategy of screening and isolation for methicillin-resistant Staphylococcus aureus carriers.

We compared the cost-effectiveness of a methicillin-resistant Staphylococcus aureus (MRSA) programme of active surveillance plus decolonization with the current Veterans Health Administration (VHA) strategy of active surveillance alone, as well as a common strategy of no surveillance. A decision-analytical model was developed for an inpatient stay time horizon, using the VHA's perspective. Model inputs were taken from published literature where available, and supplemented with expert opinion when necessary. Effectiveness outcomes were hospital-acquired MRSA infections and deaths avoided. One-way and two-way sensitivity analyses and Monte Carlo simulations were performed. In the base-case analysis, the strategy of active surveillance plus decolonization dominated (i.e. lower cost and greater effectiveness) both the comparison strategies of active surveillance and no surveillance. In addition, the active surveillance strategy dominated the strategy of no surveillance. One-way and two-way sensitivity analyses demonstrated that at low levels of direct benefit of decolonization (1-4%), the strategy of active surveillance plus decolonization would no longer be dominant. In the probabilistic sensitivity analysis, active surveillance plus decolonization dominated both the other two strategies, and the active surveillance strategy dominated no surveillance in all of 1000 Monte Carlo simulations. These results provide a strong economic argument for adding an MRSA decolonization protocol to the current VHA active surveillance strategy.

Interventions to control MRSA: high time for time-series analysis?

Time-series methods are useful in quasi-experimental study designs in which rates of antibiotic-resistant infections are ascertained before and after an intervention. However, uncertainties remain regarding the use of time-series analysis as an appropriate research methodology for analysing the effect of infection control interventions and antibiotic policies on the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). In particular, there is still a substantial gap in our understanding of what actually happens to MRSA incidence when a planned intervention is made on use of one or more antibiotic drug classes.

The epidemiology of nephrotoxicity associated with conventional amphotericin B therapy.

PURPOSE: We sought to quantify the incidence of, define risk factors for, and examine the relation between renal functional impairment and treatment with conventional amphotericin B. SUBJECTS AND METHODS: We performed a 9-year retrospective analysis of amphotericin B-associated nephrotoxicity in 494 adult inpatients who received > or = 2 doses of amphotericin B. Nephrotoxicity was classified according to two nonmutually exclusive severity categories (50% increase or doubling in the baseline creatinine level). RESULTS: The median cumulative dosage of amphotericin B was 240 mg (interquartile range, 113 to 500 mg), with the majority of patients (n = 361) receiving it for empiric treatment. Overall, 139 (28%) patients experienced renal toxicity, including 58 (12%) with moderate-to-severe nephrotoxicity. The rate of nephrotoxicity was relatively constant during amphotericin B treatment. For each 10-mg increase in the mean daily amphotericin B dose, the adjusted rate of renal toxicity increased by a factor of 1.13 (95% confidence interval: 1.02 to 1.25). We defined 5 categorical risk factors: mean daily amphotericin B dose > or = 35 mg, male sex, weight > or = 90 kg, chronic renal disease, and use of amikacin or cyclosporine. The incidence of moderate-to-severe nephrotoxicity was 4% (6 of 137) in patients with none of these risk factors, 8% (14 of 181) in those with 1 risk factor, 18% (21 of 117) in those with 2 risk factors, and 29% (17 of 59) in patients with > or = 3 risk factors. Nephrotoxicity rarely led to hemodialysis (n = 3); however, at the time of discharge or death, 70% of patients with moderate-to-severe nephrotoxicity had a serum creatinine level that was > or = 0.5 mg/dL above baseline. CONCLUSION: Amphotericin B-related nephrotoxicity is an important dose-dependent and duration-dependent toxicity that is accentuated by certain nephrotoxic drugs and patient characteristics. Patients with more than two risk factors for nephrotoxicity are potential candidates for alternative antifungal therapy.

Parallel analysis of individual and aggregated data on antibiotic exposure and resistance in gram-negative bacilli.

To evaluate the potential bias of analyzing aggregated data, we separately examined antibiotic exposure and resistance data for 35,423 patients admitted to a university hospital in Utah, from both an individual-patient perspective and group-level perspective. From 1994 through 1998, use of defined daily doses (per 1000 patient-days) of fluoroquinolones, third-generation cephalosporins, ampicillin-sulbactam, and imipenem increased by 82%, 38%, and 99%, and decreased by 38%, respectively, whereas group-level resistance rates of Enterobacteriaceae or Pseudomonas species changed only minimally. However, in individual-patient-level analyses performed by multivariable proportional hazards regression, exposure to a fluoroquinolone, third-generation cephalosporin, ampicillin-sulbactam, or imipenem was a strong risk factor for resistance to fluoroquinolones (adjusted hazard ratio [AHR], 4.0; P<.001), third-generation cephalosporins (AHR, 3.5; P<.001), ampicillin-sulbactam (AHR, 2.3; P=.008), or imipenem (AHR, 5.7; P<.001), respectively. Thus, group-level and individual-patient-level analyses of antibiotic-use-versus-susceptibility relations yielded divergent results. Multicenter studies should include individual-patient-level data to elucidate more fully the relation between antibiotic exposure and resistance.

High rates of multiple antibiotic resistance in Streptococcus pneumoniae from healthy children living in isolated rural communities: association with cephalosporin use and intrafamilial transmission.

OBJECTIVE: Streptococcus pneumoniae is one of the most clinically significant pathogens with emerging antibiotic resistance. We performed a surveillance study in isolated rural populations of healthy children to estimate the prevalence of pneumococcal resistance and to contrast factors that predict pneumococcal carriage with those that specifically predict resistant pneumococcal carriage. METHODS: The study was conducted in 1998 in 2 rural communities in Utah. Families were recruited directly for participation through community canvassing. Surveillance nasopharyngeal cultures were obtained from children who were younger than 8 years. Antibiotic usage and information on other potential risk factors were obtained from questionnaires and local pharmacy records. Resistance was determined by testing isolates for susceptibility to penicillin, cefaclor, trimethoprim-sulfamethoxazole, erythromycin, ceftriaxone, and trovafloxacin. Selected resistant isolates were characterized further by serotyping, pulsed field gel electrophoresis, and Southern blot with DNA probes specific for the pneumococcal lytA gene and for antibiotic resistance genes. RESULTS: In April 1998, surveillance nasopharyngeal cultures were obtained from 368 children aged

Antibiotic prophylaxis and the risk of Clostridium difficile-associated diarrhoea.

To test the hypothesis that extended antibiotic prophylaxis increases the risk of Clostridium difficile -associated diarrhoea (CDAD), we conducted a retrospective cohort study of 2641 patients under-going cardiovascular surgery. Main outcome measures were the duration of prophylaxis (< 48 h vs. > 48 h) and the occurrence of CDAD. CDAD occurred in 31 patients (1.2%), who were significantly older (70 +/- 9 y vs. 66 +/- 10 y; P = 0.03), received more therapeutic antibiotics (2.2 +/- 1.9 vs. 0.4 +/- 0.9; P = 0.001) and had a longer postoperative hospital stay (26 +/- 19 d vs. 9 +/- 8 d; P < 0.001) than non-cases. After adjusting for confounding, we did not observe an association between prolonged prophylaxis and CDAD [adjusted odds ratio (AOR), 0.8; CI, 0.4-1.8]. In contrast, three independent predictors were identified: increasing length of hospital stay (AOR per one-day-increment, 1.03; CI, 1.01-1.05), and treatment with third generation cephalosporins (AOR, 5.9; CI, 2.2-16.0) or beta-lactam-beta-lactamase inhibitor combinations (AOR, 4.6; CI, 1.7-12.3). Our results did not confirm that extended prophylaxis after clean surgery increases the risk of CDAD, which remains an uncommon postoperative complication, associated even with short antibiotic exposure.

Methodological principles of case-control studies that analyzed risk factors for antibiotic resistance: a systematic review.

Case-control studies that analyze the risk factors for antibiotic-resistant organisms have varied epidemiological methodologies, which may lead to biased estimates of antibiotic risk factors. A systematic review of case-control studies that analyzed risk factors for antibiotic-resistant organisms addressed 3 methodological principles: method of control group selection, adjustment for time at risk, and adjustment for comorbid illness. A total of 406 abstracts were reviewed. Thirty-seven studies met the inclusion and exclusion criteria and were reviewed and evaluated for the 3 methodological principles. Thirteen (35%) of 37 studies chose the preferred control group. Eleven adjusted for time at risk. Twenty-seven adjusted for comorbid illness. Future studies need to consider more closely the optimization of control group selection, adjusting for confounding caused by time at risk, and adjusting for confounding caused by comorbid illness.

Benefits of negative penicillin skin test results persist during subsequent hospital admissions.

For an initial series of 38 patients with negative skin test results, we reviewed retrospectively all subsequent admissions over a 2-year period. For 38 patients with negative initial skin test results, there were 48 subsequent readmissions to our institution, of which 35 required antibiotics. beta-lactams were prescribed for 86% of admissions; a penicillin for 37%, and a cephalosporin for 51%. All infections were cured, and there were no allergic drug reactions during any of the admissions that were reviewed.

Developing a taxonomy for research in adverse drug events: potholes and signposts.

Computerized decision support and order entry shows great promise for reducing adverse drug events (ADEs). The evaluation of these solutions depends on a framework of definitions and classifications that is clear and practical. Unfortunately the literature does not always provide a clear path to defining and classifying adverse drug events. While not a systematic review, this paper uses examples from the literature to illustrate problems that investigators will confront as they develop a conceptual framework for their research. It also proposes a targeted taxonomy that can facilitate a clear and consistent approach to the research of ADEs and aid in the comparison to results of past and future studies. The taxonomy addresses the definition of ADE, types, seriousness, error, and causality.

Clinical isolation and resistance patterns of and superinfection with 10 nosocomial pathogens after treatment with ceftriaxone versus ampicillin-sulbactam.

Isolation of pathogens from clinical cultures and their resistance patterns may be altered by antecedent antibiotic treatment. The objective of this study was to assess the influence of treatment with ceftriaxone versus that with ampicillin-sulbactam on recovery and superinfections with 10 nosocomial pathogens. The study was designed as a historical cohort study, using a propensity score to adjust for confounding by indication and multivariate survival analyses to adjust for other confounding. Two thousand four hundred forty-five patients were treated with ampicillin-sulbactam, and 1, 308 were treated with ceftriaxone. The study analyzed two outcomes: (i) recovery of pathogens from clinical cultures and (ii) microbiologically documented infections. Data were obtained from administrative, pharmacy, clinical, and laboratory databases and by chart extraction. Following treatment, new isolation of at least 1 of the 10 target pathogens occurred for 244 patients. After adjustment, more infections occurred in the ampicillin-sulbactam group (hazard ratio [HR], 1.55; P = 0.009). This was observed with all gram-negative rods combined (HR, 3.6; P < 0.001) and with each genus of the family Enterobacteriaceae. No differences in isolation of gram-positive bacteria were evident (P = 0.33). Microbiologically documented superinfections occurred in 172 patients and were less frequent in the ceftriaxone group (3.8% versus 5%; HR, 1.6; P = 0. 015). All the Escherichia coli and Klebsiella spp. isolates were susceptible to ceftriaxone, but half were resistant to ampicillin-sulbactam. The prevalence of oxacillin resistance among Staphylococcus aureus isolates was higher in the ceftriaxone group (63% versus 31%; odds ratio, 3.8; P = 0.08). Differences in the rates of superinfections and the likely causative organisms following treatment with ceftriaxone or ampicillin-sulbactam were evident. This may guide clinicians in empirical choices of antibiotics to treat superinfection.

A survey on handwashing practices and opinions of healthcare workers.

Studies have consistently demonstrated rates of handwashing compliance are less than 50%. The objective of this study was to gain the following information about handwashing: self-reported compliance; attitudes towards handwashing in different patient settings; and attitudes towards interventions aimed at increasing compliance. A 74-question survey was administered to healthcare workers in two tertiary care hospitals. One hundred and ninety nine healthcare workers completed the survey and 89% reported that handwashing is an important means of preventing infection. Sixty-four percent believed that they washed their hands as often as their peers and 2% believed that they washed less often than their peers. Patients with diarrhoea, AIDS or patients on antibiotics led to increased handwashing. Relative to potential interventions, 76% reported that rewards for handwashing would have no effect, 73% reported that punishment would have no effect and 80% reported that easy access to sinks and availability of washing facilities would lead to increased compliance. This survey suggests that healthcare workers understand the importance of handwashing, but tend to overestimate their own compliance. Healthcare workers are not in favour of interventions involving rewards and punishments, but are more attracted to interventions that make handwashing easier.

The values of quantitative serum HIV-1 RNA levels and CD4 cell counts for predicting survival time among HIV-positive individuals with CD4 counts of < or = 50 x 10(6) cells/l.

OBJECTIVE: To evaluate the HIV-1 RNA level as a predictor of survival time among individuals with advanced AIDS. METHODS: The serum HIV-1 RNA level, the CD4 cell count, and other clinical variables were evaluated at baseline, as predictors of survival time, among 56 retrospectively identified HIV-1 positive individuals with < or = 50 x 10(6) CD4 cells/l who attended the Beth Israel Deaconess Medical Center, Division of Infectious Diseases, between 1 July 1989 and 30 September 1993. RESULTS: During follow-up, 55 of these 56 patients died. The median survival time was 20.5 months. In univariate Cox proportional hazard modeling neither the baseline HIV-1 RNA level nor the CD4 cell count were predictive of survival time. However, in multivariate models longer survival time was associated with the use of trimethoprim-sulphamethoxazole at entry [hazard ratio (HR), 0.42; P = 0.007], whereas shorter survival time was associated with a history of an AIDS-defining illness other than Pneumocystis carinii pneumonia (HR, 2.87; P = 0.007). Correlative analysis revealed a modest correlation of the baseline CD4 cell count with survival time (Spearman p = 0.41; P = 0.002). However, no correlation was found between HIV RNA levels and survival time (P = 0.5). CONCLUSIONS: In this population with very advanced disease, the HIV-1 RNA level was a poor discriminator of survival time, being inferior to the CD4 cell count and to specific clinical variables such as the nature of the prior AIDS-defining illness and the type of Pneumocystis carinii pneumonia prophylaxis employed. Among individuals with advanced AIDS, these data emphasize the relative importance of the CD4 cell count and of specific clinical factors, over the HIV-1 RNA level in predicting survival time.

Prolonged antibiotic prophylaxis after cardiovascular surgery and its effect on surgical site infections and antimicrobial resistance.

BACKGROUND: Despite evidence supporting short antibiotic prophylaxis (ABP), it is still common practice to continue ABP for more than 48 hours after coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS: To compare the effect of short (<48 hours) versus prolonged (>48 hours) ABP on surgical site infections (SSIs) and acquired antimicrobial resistance, we conducted an observational 4-year cohort study at a tertiary-care center. An experienced infection control nurse performed prospective surveillance of 2641 patients undergoing CABG surgery. The main exposure was the duration of ABP, and main outcomes were the adjusted rate of SSI and the isolation of cephalosporin-resistant enterobacteriaceae and vancomycin-resistant enterococci (acquired antibiotic resistance). Adjustment for confounding was performed by multivariable modeling. A total of 231 SSIs (8.7%) occurred after a median of 16 days, including 93 chest-wound infections (3.5%) and 13 deep-organ-space infections (0. 5%). After 1502 procedures using short ABP, 131 SSIs were recorded, compared with 100 SSIs after 1139 operations with prolonged ABP (crude OR, 1.0; CI, 0.8 to 1.3). After adjustment for possible confounding, prolonged ABP was not associated with a decreased risk of SSI (adjusted OR, 1.2; CI, 0.8 to 1.6) and was correlated with an increased risk of acquired antibiotic resistance (adjusted OR, 1.6; CI, 1.1 to 2.6). CONCLUSIONS: Our findings confirm that continuing ABP beyond 48 hours after CABG surgery is still widespread; however, this practice is ineffective in reducing SSI, increases antimicrobial resistance, and should therefore be avoided.

Molecular typing of coagulase-negative staphylococci from blood cultures does not correlate with clinical criteria for true bacteremia.

PURPOSE: Determining whether a blood culture that contains coagulase-negative staphylococci represents bacteremia or contamination is a clinical dilemma. We compared molecular-typing results of coagulase-negative staphylococcal blood culture isolates with clinical criteria for true bacteremia. SUBJECTS AND METHODS: Pulsed-field gel electrophoresis and arbitrary primed polymerase chain reaction (PCR) were used to determine whether patients with two or more blood cultures with coagulase-negative staphylococcal isolates had the same strain of organism in each culture (same strain bacteremia). We evaluated three different clinical criteria for bacteremia: whether the patient received more than 4 days of antibiotics, whether there was an explicit note in the medical chart in which the physician diagnosed a true bacteremia, and the Centers for Disease Control surveillance criteria for primary bloodstream infection. Agreement between same-strain bacteremia and each definition was examined, based on the assumption that most true infections should be the result of a single strain. RESULTS: The study sample consisted of 42 patients and 106 isolates. Nineteen of the 42 bacteremias (45%) were the same strain. Classification of bacteremias as same-strain correlated poorly with all three clinical assessments (range of percent agreement, 50% to 57%; range of kappa statistic, 0.01 to 0.15). There were both false-positive and false-negative errors. Patients with three or more positive blood cultures were more likely to have same-strain bacteremia than those with only two positive cultures [11 of 15 (73%) vs 8 of 27 (30%), P = 0.006]. Pulsed-field gel electrophoresis was more discriminating than arbitrary primed PCR (percent agreement, 83%; kappa, 0.67). CONCLUSION: Molecular typing correlated poorly with clinical criteria for true bacteremia, suggesting either that true bacteremias are frequently the result of multiple strains or that the commonly used clinical criteria are not accurate for distinguishing contamination from true bacteremia. Vancomycin treatment of clinically defined coagulase-negative staphylococcal bacteremia may frequently be unnecessary.