Advancing Epidemiological Science Through Computational Modeling: A Review with Novel Examples

Computational models have been successfully applied to a wide variety of research areas including infectious disease epidemiology. Especially for questions that are difficult to examine in other ways, computational models have been used to extend the range of epidemiological issues that can be addressed, advance theoretical understanding of disease processes and help identify specific intervention strategies. We explore each of these contributions to epidemiology research through discussion and examples. We also describe in detail models for raccoon rabies and methicillin-resis-tant Staphylococcus aureus, drawn from our own research, to further illustrate the role of computation in epidemiological modeling

Estimating hospital costs of catheter‐associated urinary tract infection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100140/1/jhm2079.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/100140/2/jhm2079-sup-0002-suppinfo.pd

Impact of Empiric Antimicrobial Therapy on Outcomes in Patients with Escherichia coli and Klebsiella pneumoniae Bacteremia: A Cohort Study

<p>Abstract</p> <p>Background</p> <p>It is unclear whether appropriate empiric antimicrobial therapy improves outcomes in patients with bacteremia due to <it>Escherichia coli </it>or <it>Klebsiella</it>. The objective of this study is to assess the impact of appropriate empiric antimicrobial therapy on in-hospital mortality and post-infection length of stay in patients with <it>Escherichia coli </it>or <it>Klebsiella </it>bacteremia while adjusting for important confounding variables.</p> <p>Methods</p> <p>We performed a retrospective cohort study of adult patients with a positive blood culture for <it>E. coli </it>or <it>Klebsiella </it>between January 1, 2001 and June 8, 2005 and compared in-hospital mortality and post-infection length of stay between subjects who received appropriate and inappropriate empiric antimicrobial therapy. Empiric therapy was defined as the receipt of an antimicrobial agent between 8 hours before and 24 hours after the index blood culture was drawn and was considered appropriate if it included antimicrobials to which the specific isolate displayed <it>in vitro </it>susceptibility. Data were collected electronically and through chart review. Survival analysis was used to statistically assess the association between empiric antimicrobial therapy and outcome (mortality or length of stay). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Among 416 episodes of bacteremia, 305 (73.3%) patients received appropriate empiric antimicrobial therapy. Seventy-one (17%) patients died before discharge from the hospital. The receipt of appropriate antimicrobial agents was more common in hospital survivors than in those who died (p = 0.04). After controlling for confounding variables, there was no association between the receipt of appropriate empiric antimicrobial therapy and in-hospital mortality (HR, 1.03; 95% CI, 0.60 to 1.78). The median post-infection length of stay was 7 days. The receipt of appropriate antimicrobial agents was not associated with shortened post-infection length of stay, even after controlling for confounding (HR, 1.11; 95% CI 0.86 to 1.44).</p> <p>Conclusion</p> <p>Appropriate empiric antimicrobial therapy for <it>E. coli </it>and <it>Klebsiella </it>bacteremia is not associated with lower in-hospital mortality or shortened post-infection length of stay. This suggests that the choice of empiric antimicrobial agents may not improve outcomes and also provides data to support a randomized trial to test the hypothesis that use (and overuse) of broad-spectrum antibiotics prior to the availability of culture results is not warranted.</p

Enhanced Identification of Postoperative Infections among Outpatients

Claims data complement other data sources for identification of surgical site infections following breast surgery and cesarean section

Frequency of human immunodeficiency virus (HIV) testing in urban vs. rural areas of the United States: Results from a nationally-representative sample

<p>Abstract</p> <p>Background</p> <p>Studies in the United States show that rural persons with HIV are more likely than their urban counterparts to be diagnosed at a late stage of infection, suggesting missed opportunities for HIV testing in rural areas. To inform discussion of HIV testing policies in rural areas, we generated nationally representative, population-based estimates of HIV testing frequencies in urban vs. rural areas of the United States.</p> <p>Methods</p> <p>Secondary analysis of 2005 and 2009 Behavioral Risk Factor Surveillance System (BRFSS) data. Dependent variables were self-reported lifetime and past-year HIV testing. Urban vs. rural residence was determined using the metropolitan area framework and Urban Influence Codes and was categorized as 1) metropolitan, center city (the most urban); 2) metropolitan, other; 3) non-metropolitan, adjacent to metropolitan; 4) non-metropolitan, micropolitan; and 4) remote, non-metropolitan (the most rural).</p> <p>Results</p> <p>The 2005 sample included 257,895 respondents. Lifetime HIV testing frequencies ranged from 43.6% among persons residing in the most urban areas to 32.2% among persons in the most rural areas (P < 0.001). Past-year testing frequencies ranged from 13.5% to 7.3% in these groups (P < 0.001). After adjusting for demographics (age, sex, race/ethnicity, and region of residence) and self-reported HIV risk factors, persons in the most remote rural areas were substantially less likely than persons in the most urban areas to report HIV testing in the past year (odds ratio 0.65, 95% CI 0.57-0.75). Testing rates in urban and rural areas did not change substantively following the 2006 Centers for Disease Control and Prevention recommendation for routine, population-based HIV testing in healthcare settings. In metropolitan (urban) areas, 11.5% (95% CI 11.2-11.8) reported past-year HIV testing in 2005 vs. 11.4% (95% CI 11.1%-11.7%) in 2009 (P = 0.93). In non-metropolitan areas, 8.7% (95% CI 8.2%-9.2%) were tested in 2005 vs. 7.7% (95% CI 7.2%-8.2%) in 2009 (P = 0.03).</p> <p>Conclusions</p> <p>Rural persons are less likely than urban to report prior HIV testing, which may contribute to later HIV diagnosis in rural areas. There is need to consider strategies to increase HIV testing in rural areas.</p

Technology for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva IPC-Think Tank (Part 2).

Background: The high burden of healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) is partially due to excessive antimicrobial use both in human and animal medicine worldwide. How can technology help to overcome challenges in infection prevention and control (IPC) and to prevent HAI and emerging AMR? Methods: In June 2017, 42 international experts convened in Geneva, Switzerland to discuss four potential domains of technology in IPC and AMR: 1) role and potential contribution of microbiome research; 2) whole genome sequencing; 3) effectiveness and benefit of antimicrobial environmental surfaces; and 4) future research in hand hygiene. Results: Research on the microbiome could expand understanding of antimicrobial use and also the role of probiotics or even faecal transplantation for therapeutic purposes. Whole genome sequencing will provide new insights in modes of transmission of infectious diseases. Although it is a powerful tool for public health epidemiology, some challenges with interpretation and costs still need to be addressed. The effectiveness and cost-effectiveness of antimicrobially coated or treated environmental high-touch surfaces requires further research before they can be recommended for routine use. Hand hygiene implementation can be advanced, where technological enhancement of surveillance, technique and compliance are coupled with reminders for healthcare professionals. Conclusions: The four domains of technological innovation contribute to the prevention of HAI and AMR at different levels. Microbiome research may offer innovative concepts for future prevention, whole genome sequencing could detect new modes of transmission and become an additional tool for effective public health epidemiology, antimicrobial surfaces might help to decrease the environment as source of transmission but continue to raise more questions than answers, and technological innovation may have a role in improving surveillance approaches and supporting best practice in hand hygiene

Broadening the infection prevention and control network globally; 2017 Geneva IPC-think tank (part 3).

Background: Healthcare-associated infection (HAI) is a major challenge for patient safety worldwide, and is further complicated by antimicrobial resistance (AMR) due to excessive antimicrobial use in both humans and animals. Existing infection prevention and control (IPC) networks must be strengthened and adapted to better address the global challenges presented by emerging AMR. Methods: In June 2017, 42 international experts convened in Geneva, Switzerland, to discuss two key areas for strengthening the global IPC network: 1) broadening collaboration in IPC; and 2) how to bring the fields IPC and AMR control together. Results: The US Centers for Disease Prevention and Control, the European Centre for Disease Prevention and Control, and the World Health Organization (WHO) convened together with international experts to discuss collaboration and networks, demonstrating the participating organizations' commitment to close collaboration in IPC. The challenge of emerging AMR can only be addressed by strengthening this collaboration across international organisations and between public health and academia. The WHO SAVE LIVES: Clean Your Hands initiative is an example of a successful collaboration between multiple global stakeholders including academia and international public health organisations; it can be used as a model. IPC-strategies are included within the four pillars to combat AMR: surveillance, IPC, antimicrobial and diagnostic stewardship, research and development. The prevention of transmission of multidrug-resistant microorganisms is a patient safety issue, and must be strengthened in the fight against AMR. Conclusions: The working group determined that international organisations should take the lead in creating new networks, which will in turn attract academia and other stakeholders to join. At the same time, they should invest in bringing existing IPC and AMR networks under one umbrella. Transmission of multidrug-resistant microorganisms in hospitals and in the community threatens the success of antimicrobial stewardship programmes, and thus, research and development in IPC should be addressed as an enhanced global priority

Statins in Candidemia: clinical outcomes from a matched cohort study

<p>Abstract</p> <p>Background</p> <p>HMG CoA reductase inhibitors (statins) in patients with bacteremic sepsis have shown significant survival benefits in several studies. There is no data on the effect of statins in candidemic patients, however in-vitro models suggest that statins interfere with ergesterol formation in the wall of yeasts.</p> <p>Methods</p> <p>This retrospective matched- cohort study from 1/2003 to 12/2006 evaluated the effects of statins on patients with candidemia within intensive care units. Statin-users had candidemia as a cause of their systemic inflammatory response and were on statins throughout their antifungal therapy, while non-statin users were matched based on age +/- 5 years and co-morbid factors. Primary analysis was 30-day survival or discharge using bivariable comparisons. Multivariable comparisons were completed using conditional logistic regression. All variables with a p-value less than 0.10 in the bivariable comparisons were considered for inclusion in the conditional logistic model.</p> <p>Results</p> <p>There were 15 statin-users and 30 non-statin users that met inclusion criteria, all with similar demographics and co-morbid conditions except the statin group had more coronary artery disease (P < 0.01) and peripheral vascular disease (P = 0.03) and lower median APCAHE II scores (14.6 vs 17, p = 0.03). There were no differences in duration of candidemia, antifungal therapy or <it>Candida </it>species between the groups. Statins were associated with lower mortality on bivariable (OR 0.09, 95% CI 0.11-0.75, p = 0.03) and multivariable (OR 0.22, 95% CI 0.02-2.4, p = 0.21) analyses compared to controls; although, in the latter the protective effect lacked statistical signficance.</p> <p>Conclusion</p> <p>In our small, single-center matched-cohort study, statins may provide a survival benefit in candidemia, however further studies are warranted to validate and further explore this association.</p

Surgical site infections in Italian Hospitals: a prospective multicenter study

<p>Abstract</p> <p>Background</p> <p>Surgical site infections (SSI) remain a major clinical problem in terms of morbidity, mortality, and hospital costs. Nearly 60% of SSI diagnosis occur in the postdischarge period. However, literature provides little information on risk factors associated to in-hospital and postdischarge SSI occurrence. A national prospective multicenter study was conducted with the aim of assessing the incidence of both in-hospital and postdisharge SSI, and the associated risk factors.</p> <p>Methods</p> <p>In 2002, a one-month, prospective national multicenter surveillance study was conducted in General and Gynecological units of 48 Italian hospitals. Case ascertainment of SSI was carried out using standardized surveillance methodology. To assess potential risk factors for SSI we used a conditional logistic regression model. We also reported the odds ratios of in-hospital and postdischarge SSI.</p> <p>Results</p> <p>SSI occurred in 241 (5.2%) of 4,665 patients, of which 148 (61.4%) during in-hospital, and 93 (38.6%) during postdischarge period. Of 93 postdischarge SSI, sixty-two (66.7%) and 31 (33.3%) were detected through telephone interview and questionnaire survey, respectively. Higher SSI incidence rates were observed in colon surgery (18.9%), gastric surgery (13.6%), and appendectomy (8.6%). If considering risk factors for SSI, at multivariate analysis we found that emergency interventions, NNIS risk score, pre-operative hospital stay, and use of drains were significantly associated with SSI occurrence. Moreover, risk factors for total SSI were also associated to in-hospital SSI. Additionally, only NNIS, pre-operative hospital stay, use of drains, and antibiotic prophylaxis were associated with postdischarge SSI.</p> <p>Conclusion</p> <p>Our study provided information on risk factors for SSI in a large population in general surgery setting in Italy. Standardized postdischarge surveillance detected 38.6% of all SSI. We also compared risk factors for in-hospital and postdischarge SSI, thus providing additional information to that of the current available literature. Finally, a large amount of postdischarge SSI were detected through telephone interview. The evaluation of the cost-effectiveness of the telephone interview as a postdischarge surveillance method could be an issue for further research.</p

An Antibiotic-Responsive Mouse Model of Fulminant Ulcerative Colitis

Paul Allen and colleagues describe the development of a mouse model of fulminant ulcerative colitis with multiple genetic hits in immune regulation which can be moderated by anti-cytokine therapy and broad-spectrum antibiotics