Explaining Hospital Length of Stay of Patients Admitted with Seasonal Influenza Infection

The annual occurrence of seasonal influenza virus poses a significant health burden. Certain populations are at higher risk for influenza infection, such as cigarette smokers, the elderly, and patients with cardiopulmonary disorders. Monitoring the length of time that patients are hospitalized with influenza is of clinical importance. The objectives of this study were to identify characteristics of patients hospitalized with influenza and to determine whether smoking correlates to extended LOS (length of stay in hospital). It was hypothesized that smoking and COPD (Chronic Obstructive Pulmonary Disease) would most significantly explain prolonged LOS. Information was collected from a cohort of adult patients admitted to hospital with influenza during the 2012- 2013 season. Both univariate and multivariate analyses were performed to compare variables with LOS as an outcome. Among 54 patients, the median age was 73.5 and the median Body Mass Index was 26.1 kg/m2. Exactly two-thirds were smokers and just under one-third was diagnosed with COPD. Univariate statistical analyses determined that patients with COPD, diabetes, and more than one comorbid condition had significantly increased LOS (p = 0.0129*, 0.0191*, 0.0046*; respectively). A generalized linear model was generated (n = 50), revealing that patients with COPD and more than one comorbid condition significantly correlated to prolonged LOS (p = 0.0266* and 0.0079*, respectively). Smoking status was not a significan indicator for lengthier LOS in either set of analyses. Promoting the use of vaccination for individuals with COPD and extensive comorbid conditions is imperative

Simulating the impact of non-pharmaceutical interventions limiting transmission in COVID-19 epidemics using a membrane computing model

[EN] Epidemics caused by microbial organisms are part of the natural phenomena of increasing biological complexity. The heterogeneity and constant variability of hosts, in terms of age, immunological status, family structure, lifestyle, work activities, social and leisure habits, daily division of time and other demographic characteristics make it extremely difficult to predict the evolution of epidemics. Such prediction is, however, critical for implementing intervention measures in due time and with appropriate intensity. General conclusions should be precluded, given that local parameters dominate the flow of local epidemics. Membrane computing models allows us to reproduce the objects (viruses and hosts) and their interactions (stochastic but also with defined probabilities) with an unprecedented level of detail. Our LOIMOS model helps reproduce the demographics and social aspects of a hypothetical town of 10 320 inhabitants in an average European country where COVID-19 is imported from the outside. The above-mentioned characteristics of hosts and their lifestyle are minutely considered. For the data in the Hospital and the ICU we took advantage of the observations at the Nursery Intensive Care Unit of the Consortium University General Hospital, Valencia, Spain (included as author). The dynamics of the epidemics are reproduced and include the effects on viral transmission of innate and acquired immunity at various ages. The model predicts the consequences of delaying the adoption of non-pharmaceutical interventions (between 15 and 45 days after the first reported cases) and the effect of those interventions on infection and mortality rates (reducing transmission by 20, 50 and 80%) in immunological response groups. The lockdown for the elderly population as a single intervention appears to be effective. This modeling exercise exemplifies the application of membrane computing for designing appropriate multilateral interventions in epidemic situations.MC and FB were sponsored by the Projects COV20 00067 of the Program SARS-COV-2 and COVID-19 infection of the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion of Spain, CB06/02/0053 of the Centro de Investigacion Biom edica en Red de Epidemiolog¿a y Salud Publica (CIBERESP), and the Regional Government of Madrid (InGeMICS-B2017/BMD-3691). For JCG, this study was partially founded by the Autonomous Community of Madrid, Spain (COVID-19 Grant, 2020) and the Ramon y Cajal Institute for Health Research (IRYCIS), Madrid, Spain. For AM, this study was supported by grants from the Spanish Ministry of Science and Innovation (PID2019-105969GB-I00), the government of Valencia (project Prometeo/2018/A/133) and cofinanced by the European Regional Development Fund (ERDF).Campos Frances, M.; Sempere Luna, JM.; Galán, JC.; Moya, A.; Llorens, C.; De-Los-Angeles, C.; Baquero-Artigao, F.... (2021). Simulating the impact of non-pharmaceutical interventions limiting transmission in COVID-19 epidemics using a membrane computing model. microLife. 2:1-14. https://doi.org/10.1093/femsml/uqab011S114

Emerging Challenges and Opportunities in Infectious Disease Epidemiology.

Much of the intellectual tradition of modern epidemiology stems from efforts to understand and combat chronic diseases persisting through the 20th century epidemiologic transition of countries such as the United States and United Kingdom. After decades of relative obscurity, infectious disease epidemiology has undergone an intellectual rebirth in recent years amid increasing recognition of the threat posed by both new and familiar pathogens. Here, we review the emerging coalescence of infectious disease epidemiology around a core set of study designs and statistical methods bearing little resemblance to the chronic disease epidemiology toolkit. We offer our outlook on challenges and opportunities facing the field, including the integration of novel molecular and digital information sources into disease surveillance, the assimilation of such data into models of pathogen spread, and the increasing contribution of models to public health practice. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. These areas represent an increasingly important component of epidemiology training programs for future generations of researchers and practitioners

Asymptomatic and yet C. difficile-toxin positive? Prevalence and risk factors of carriers of toxigenic Clostridium difficile among geriatric in-patients

Abstract Background Clostridium difficile infections (CDI) are the most frequent cause of diarrhoea in hospitals. Geriatric patients are more often affected by the condition, by a relapse and complications. Therefore, a crucial question is how often colonization with toxigenic Clostridium difficile strains occurs in elderly patients without diarrhoea and whether there is a “risk pattern” of colonized patients that can be defined by geriatric assessment. Furthermore, the probability for those asymptomatic carriers to develop a symptomatic infection over time has not been sufficiently explored. Methods We performed a cohort study design to assess the association of clinical variables with Clostridium difficile colonization. The first stool sample of 262 consecutive asymptomatic patients admitted to a geriatric unit was tested for toxigenic Clostridium difficile using PCR (GeneXpert, Cepheid). A comprehensive geriatric assessment (CGA) including Barthel Index, Mini Mental State Examination (MMSE) and hand grip-strength was performed. In addition, Charlson Comorbidity Index, body mass index, number and length of previous hospital stays, previous treatment with antibiotics, institutionalization, primary diagnoses and medication were recorded and evaluated as possible risk factors of colonization by means of binary logistic regression. Secondly, we explored the association of C. difficile colonization with subsequent development of CDI during hospital stay. Results At admission, 43 (16.4%) patients tested positive for toxin B by PCR. Seven (16.3%) of these colonized patients developed clinical CDI during hospital stay, compared to one out of 219 patients with negative or invalid PCR testing (Odds ratio 12,3; Fisher’s exact test: p = 0.000). Overall, 7 out of 8 (87.5%) CDI patients had been colonized at admission. Risk factors of colonization with C. difficile were a history of CDI, previous antibiotic treatment and hospital stays. The parameters of the CGA were not significantly associated with colonization. Conclusion Colonization with toxigenic Clostridium difficile strains occurs frequently in asymptomatic patients admitted to a geriatric unit. Previous CDI, antibiotic exposure and hospital stay, but not clinical variables such as CGA, are the main factors associated with asymptomatic Clostridium difficile carriage. Colonization is a crucial risk factor for subsequent development of symptomatic CDI

Costs and effectiveness of extended vaccination strategies against pertussis and pneumococcal disease

Omdat het Nederlandse Rijksvaccinatieprogramma al intensief is en de gezondheidszorg kampt met gelimiteerde budgetten, zijn de mogelijkheden voor opname van nieuwe vaccins in het Rijksvaccinatieprogramma beperkt. Naast vele andere factoren, hebben doelmatigheidsuitkomsten een groot effect op de beslissing om een vaccin op te nemen in het Rijksvaccinatieprogramma.In het eerste gedeelte van dit proefschrift ligt de focus op de (kosten-) effectiviteit van pneumokokkenvaccinatie.Het blijkt dat er grote verschillen zijn in de geobserveerde epidemiologie na de introductie van het vaccin in Amerika en Europa. In Europa werden er minder pneumokokken gevallen voorkomen in ongevaccineerde individuen (‘herd immunity’) terwijl er meer ziekte werd waargenomen veroorzaakt door serotypen waartegen het vaccin geen bescherming biedt (serotypevervanging). Dit had tot gevolg dat de kosteneffectiviteit van het destijds gebruikte 7-valente pneumokokkenvaccin minder gunstig was dan eerder voorspeld. Meer valente pneumokokkenvaccins hebben een grotere kans om te worden beschouwd als kosteneffectief omdat deze waarschijnlijk meer directe en herd immunity effecten bieden terwijl de kans op serotypevervanging kleiner is. Als gevolg van deze potentiele herd immunity zal het vaccineren van andere (risico-) groepen potentieel minder gunstig worden. Zo blijkt uit een economisch model dat het vaccineren van risicogroepen in Engeland waarschijnlijk niet als kosteneffectief kan worden beschouwd tenzij het vaccin ook bescherming biedt tegen niet-invasieve pneumonie. Dit laatste wordt momenteel onderzocht in een grote Nederlandse klinische trial.Het tweede gedeelte van dit proefschrift verkent de impact van de uitbreiding van het huidige pertussis vaccinatie programma naar adolescenten en volwassenen. Gegeven de complexiteit van de pertussis transmissie, was het nodig een dynamisch transmissie model te ontwikkelen. Dit model suggereert dat de meest kosteneffectieve leeftijd om een extra booster te introduceren rond de 12 jaar is. Het beoogde beschermende effect voor (gedeeltelijk) ongevaccineerde zuigelingen bleek echter minimaal te zijn.Gezien de dynamiek van infectieziekten zijn soms complexe methoden nodig om de impact van nieuwe vaccinatieprogramma’s te voorspellen. Het uitbreiden van het huidige pneumokokken–en pertussis vaccinatieprogramma biedt de mogelijkheid om de morbiditeit en mortaliteit te verminderen en de ziektegerelateerde kosten te verlagen.A crowded vaccination schedule and restrained health–care budgets limit the uptake of new vaccines into the Dutch national immunization programs (NIP). Next to many other factors, costeffectiveness considerations highly influence the decision whether to introduce vaccines into Dutch NIP.The first part of this thesis focuses on the (cost-) effectiveness of pneumococcal vaccination. It is shown that there are large differences in the observed disease epidemiology after implementation of paediatric pneumococcal immunization programs between the USA and Europe. In Europe, less cases of pneumococcal disease were avoided in unvaccinated individuals (herd effects) than in theUSA, while significant replacement was observed in Europe with strains not included in the vaccine.As a consequence, the 7-valent pneumococcal vaccine, which was previously used in the Dutch NIP, was less cost-effective as predicted beforehand. More valent pneumococcal vaccines are more likely to be considered cost-effective as more direct and herd effects and less serotype replacement effects are expected. These potential herd effects reduce the cost-effectiveness of elderly and adult (risk) groups vaccination in time. In particular, a modelling study showed that vaccinating risk groups in England was unlikely to be considered cost-effective in the base-case analysis unless the vaccine would also offer protection against non–bacteraemic pneumonia. Evidence on whether the latter occurs is awaited from a large Dutch clinical trial.The second part of the thesis explores the impact of extending the childhood pertussis vaccination programme to adolescents and adults. Given the nature of the problem, the development of a complex population dynamical model was required. The developed dynamic model showed that the most (cost-) effective age for the introduction of an additional booster is around 12 years. Nevertheless, this strategy only offered limited indirect protection to the (partly)unvaccinated infants with potentially most serious disease which might be considered the primary aim of extended pertussis vaccination.In conclusion, the dynamics of infectious diseases makes it challenging to predict the impact of new vaccination programs. Extending the vaccination programs against pneumococcal disease and pertussis offers the possibility to prevent morbidity and mortality and decrease the economic burden of disease for society

Cost of care for hospitalized patients with pulmonary mycobacterial diseases in the United States.

Background: Pulmonary mycobacterial diseases describe both tuberculosis (TB) and nontuberculous mycobacteria (NTM). Few data are available measuring the cost burden of mycobacterial diseases on the national level. The purpose of this study was to evaluate the cost burden and measure emerging trends in hospitalization of pulmonary TB and NTM in the US from 2001 through 2012. Methods: This study was a retrospective community based cost analysis of hospitalized patients with a principal diagnosis of pulmonary mycobacterial diseases from 2001 through 2012. Data for pulmonary TB and NTM were retrieved from the Healthcare Cost and Utilization Project (HCUP), US Department of Health and Human Services. The statistical significance of observed trends of NTM and TB national hospital costs was calculated using Poisson log-linear regression. Results: A total of 20,049 hospital admissions were reported for pulmonary NTM and 69,257 for pulmonary TB in the US from 2001 through 2012. The total associated cost of these admissions was $903,767,292 for pulmonary NTM and$2,078,113,317 for pulmonary TB. During the study period, the national hospital costs of pulmonary NTM increased at a statistically significant rate in the US over each year (P=0.001). However, no such increase was found for national hospital costs of pulmonary TB. Conclusion: The national hospital cost of NTM management is increasing. These results emphasize the importance of continued research in pulmonary NTM in order to improve current guidelines in prevention and treatment strategies

Future research directions in pneumonia

Copyright © 2018 by the American Thoracic Society. Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group’s specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia

Addressing the Health Needs of an Aging America: New Opportunities for Evidence-Based Policy Solutions

This report systematically maps research findings to policy proposals intended to improve the health of the elderly. The study identified promising evidence-based policies, like those supporting prevention and care coordination, as well as areas where the research evidence is strong but policy activity is low, such as patient self-management and palliative care. Future work of the Stern Center will focus on these topics as well as long-term care financing, the health care workforce, and the role of family caregivers