External validation of the Hospital-patient One-year Mortality Risk (HOMR) model for predicting death within 1 year after hospital admission

BACKGROUND Predicting long-term survival after admission to hospital is helpful for clinical, administrative and research purposes. The Hospital-patient One-year Mortality Risk (HOMR) model was derived and internally validated to predict the risk of death within 1 year after admission. We conducted an external validation of the model in a large multicentre study. METHODS We used administrative data for all nonpsychiatric admissions of adult patients to hospitals in the provinces of Ontario (2003-2010) and Alberta (2011-2012), and to the Brigham and Women's Hospital in Boston (2010-2012) to calculate each patient's HOMR score at admission. The HOMR score is based on a set of parameters that captures patient demographics, health burden and severity of acute illness. We determined patient status (alive or dead) 1 year after admission using population-based registries. RESULTS The 3 validation cohorts (n = 2,862,996 in Ontario, 210 595 in Alberta and 66,683 in Boston) were distinct from each other and from the derivation cohort. The overall risk of death within 1 year after admission was 8.7% (95% confidence interval [CI] 8.7% to 8.8%). The HOMR score was strongly and significantly associated with risk of death in all populations and was highly discriminative, with a C statistic ranging from 0.89 (95% CI 0.87 to 0.91) to 0.92 (95% CI 0.91 to 0.92). Observed and expected outcome risks were similar (median absolute difference in percent dying in 1 yr 0.3%, interquartile range 0.05%-2.5%). INTERPRETATION The HOMR score, calculated using routinely collected administrative data, accurately predicted the risk of death among adult patients within 1 year after admission to hospital for nonpsychiatric indications. Similar performance was seen when the score was used in geographically and temporally diverse populations. The HOMR model can be used for risk adjustment in analyses of health administrative data to predict long-term survival among hospital patients.

Dynamics of a Tularemia Outbreak in a Closely Monitored Free-Roaming Population of Wild House Mice.

Infectious disease outbreaks can be devastating because of their sudden occurrence, as well as the complexity of monitoring and controlling them. Outbreaks in wildlife are even more challenging to observe and describe, especially when small animals or secretive species are involved. Modeling such infectious disease events is relevant to investigating their dynamics and is critical for decision makers to accomplish outbreak management. Tularemia, caused by the bacterium Francisella tularensis, is a potentially lethal zoonosis. Of the few animal outbreaks that have been reported in the literature, only those affecting zoo animals have been closely monitored. Here, we report the first estimation of the basic reproduction number R0 of an outbreak in wildlife caused by F. tularensis using quantitative modeling based on a susceptible-infected-recovered framework. We applied that model to data collected during an extensive investigation of an outbreak of tularemia caused by F. tularensis subsp. holarctica (also designated as type B) in a closely monitored, free-roaming house mouse (Mus musculus domesticus) population in Switzerland. Based on our model and assumptions, the best estimated basic reproduction number R0 of the current outbreak is 1.33. Our results suggest that tularemia can cause severe outbreaks in small rodents. We also concluded that the outbreak self-exhausted in approximately three months without administrating antibiotics.

Development of a Novel Rabies Simulation Model for Application in a Non-endemic Environment.

Domestic dog rabies is an endemic disease in large parts of the developing world and also epidemic in previously free regions. For example, it continues to spread in eastern Indonesia and currently threatens adjacent rabies-free regions with high densities of free-roaming dogs, including remote northern Australia. Mathematical and simulation disease models are useful tools to provide insights on the most effective control strategies and to inform policy decisions. Existing rabies models typically focus on long-term control programs in endemic countries. However, simulation models describing the dog rabies incursion scenario in regions where rabies is still exotic are lacking. We here describe such a stochastic, spatially explicit rabies simulation model that is based on individual dog information collected in two remote regions in northern Australia. Illustrative simulations produced plausible results with epidemic characteristics expected for rabies outbreaks in disease free regions (mean R0 1.7, epidemic peak 97 days post-incursion, vaccination as the most effective response strategy). Systematic sensitivity analysis identified that model outcomes were most sensitive to seven of the 30 model parameters tested. This model is suitable for exploring rabies spread and control before an incursion in populations of largely free-roaming dogs that live close together with their owners. It can be used for ad-hoc contingency or response planning prior to and shortly after incursion of dog rabies in previously free regions. One challenge that remains is model parameterisation, particularly how dogs' roaming and contacts and biting behaviours change following a rabies incursion in a previously rabies free population.

Tuberculosis in Cape Town: An age-structured transmission model.

BACKGROUND Tuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0-5, 20-24, and 45-49 years. There is little variation between age groups in the rates in the HIV-positive population. The drivers of this age pattern remain unknown. METHODS We developed an age-structured simulation model of Mycobacterium tuberculosis (Mtb) transmission in Cape Town, South Africa. We considered five states of TB progression: susceptible, infected (latent TB), active TB, treated TB, and treatment default. Latently infected individuals could be re-infected; a previous Mtb infection slowed progression to active disease. We further considered three states of HIV progression: HIV negative, HIV positive, on antiretroviral therapy. To parameterize the model, we analysed treatment outcomes from the Cape Town electronic TB register, social mixing patterns from a Cape Town community and used literature estimates for other parameters. To investigate the main drivers behind the age patterns, we conducted sensitivity analyses on all parameters related to the age structure. RESULTS The model replicated the age patterns in HIV-negative TB notification rates of Cape Town in 2009. Simulated TB notification rate in HIV-negative patients was 1000/100,000 person-years (pyrs) in children aged <5 years and decreased to 51/100,000 in children 5-15 years. The peak in early adulthood occurred at 25-29 years (463/100,000 pyrs). After a subsequent decline, simulated TB notification rates gradually increased from the age of 30 years. Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years. CONCLUSION The protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients are the key determinants of the age-structure of TB notification rates in Cape Town.

AUGMENTATION OF RECONSTITUTION OF GUT ASSOCIATED LYMPHOID TISSUE IN THE SYNGENEIC MURINE BONE MARROW TRANSPLANTATION MODEL

Gut was studied as a prototypical mucosal membrane in the murine BDF-1 syngeneic bone marrow transplant model. Measures of jejunal intraepithelial lymphocytes (IELs) and crypt cells were obtained by standard techniques and a method of quantifying gut lamina propria plasma cells (PCs) was developed. The degree of ablation of gut PCs and IELs after 900 rads total body irradiation with ('60)Co, and their repopulation effected by transplantation with 2.0 x 10('5) or 1.0 x 10('6) bone marrow cells demonstrated a prolonged period of profound depression in population levels of these cells which was not reflected by the extent of damage sustained to the epithelium. Differences in the depopulation and recovery of gut PCs and IELs revealed a tendency towards initial differentiation of effector cells. A positive dose response to high bone marrow cell innocula was obtained. Subsequent studies determined that gut IEL and PC repopulation was potentiated by the addition of IELs or buffy coat cells (BCs) to the bone marrow transplant. A method of isolating 1.4 - 4.0 x 10('7) viable IELs per gram of murine small bowel was devised employing intralumenal hyaluronidase digestion of the epithelial layer and centrifugation of the resulting suspension through discontinuous Percoll gradients. Irradiated mice received 2.0 x 10('5) bone marrow cells along with an equal number of IELs or BCs. The extent and duration of depression of numbers of IELs and PCs was markedly reduced by the addition of the IEL isolate to the transplantation innocula, and to a lesser degree by the addition of BCs. The augmentation of repopuation far exceeded that expected by simple lodging of cells suggesting that the additionally transplanted cells contained a subpopulation of mucosal membrane lymphoid stem cells or helper cells. Correlation analysis of PC versus IEL levels suggests a possible feedback mechanism governing the relative size of their populations. Normal ratios of IgA, IgM, and IgG bearing PCs was maintained post transplantation with all of the regimens. ^

CATCH across Texas: Building a model for the diffusion of effective school-based health promotion programs

The impact of health promotion programs is related to both program effectiveness and the extent to which the program is implemented among the target population. The purpose of this dissertation was to describe the development and evaluation of a school-based program diffusion intervention designed to increase the rate of dissemination and adoption of the Child and Adolescent Trial for Cardiovascular Health, or CATCH program (recently renamed the Coordinated Approach to Child Health). ^ The first study described the process by which schools across the state of Texas spontaneously began to adopt the CATCH program after it was tested and proven effective in a multi-site randomized efficacy trial. A survey of teachers and administrator representatives of all schools on record that purchased the CATCH program, but were not involved in the efficacy trial, was used to find out who brought CATCH into the schools, how they garnered support for its adoption, why they decided to adopt the program, and what was involved in deciding to adopt. ^ The second study described how the Intervention Mapping framework guided the planning, development and implementation of a program for the diffusion of CATCH. An iterative process was used to integrate theory, literature, the experience of project staff and data from the target population into a meaningful set of program determinants and performance objectives. Proximal program objectives were specified and translated into both media and interpersonal communication strategies for program diffusion. ^ The third study assessed the effectiveness of the diffusion program in a case-comparison design. Three of the twenty Education Service Center regions in Texas were chosen, selected based on similar demographic criteria, and were followed for adoption of the CATCH curriculum. One of these regions received the full media and interpersonal channel intervention; a second received a reduced media-only intervention, and a third received no intervention. Results suggested the use of the interpersonal channels with media follow-up is an effective means to facilitate program dissemination and adoption. The media-alone condition was not effective in facilitating program adoption. ^

Quality of care for uninsured type 2 diabetic patients in a financial assistance medical home model

The medically uninsured population in the United States is 16% or 42 million people and consists of a significant number of Type 2 diabetic patients which is the predominant form of diabetes with 798,000 new cases diagnosed each year. There is limited health services research on uninsured populations concerning health system measures or specific disease conditions. ^ The purpose of this investigation was to determine the impact a newly implemented health care program had on the quality of care provided to patients with Type 2 diabetes. The primary study objective was to compare the quality of care while controlling for utilization, and health status of patients in the new program to their status during the previous financial assistance program. The research design was a retrospective matched-pairs design. The study population consisted of 225 patients who received medical care during 1996 and 1997 at the University Health System in San Antonio, Texas. ^ Six quality of care measures individually failed to demonstrate a statistically significant difference when compared between the two periods. However, an index measure reflecting the number of patients who received all six of the quality of care measures demonstrated a statistically significant increase in 1997 (p-value < 0.05). In 1996, 8 patients (2.6%) received all six medical management components. In 1997, 38 patients (16.8%) received all six medical management components. Four regression models were analyzed; two out of the four models demonstrated inconsistent results based on the program membership variable. ^ It is concluded that there has been a small effect of the Carelink program demonstrated by an increase from 8 to 38 patients receiving all quality of care components for Type 2 diabetics at the UHS. It is recommended that additional research be conducted in order to evaluate the quality of care provided to Type 2 diabetic patients. ^

Comparison of a traditional and a multilevel Cox Proportional Hazards model

Hierarchically clustered populations are often encountered in public health research, but the traditional methods used in analyzing this type of data are not always adequate. In the case of survival time data, more appropriate methods have only begun to surface in the last couple of decades. Such methods include multilevel statistical techniques which, although more complicated to implement than traditional methods, are more appropriate. ^ One population that is known to exhibit a hierarchical structure is that of patients who utilize the health care system of the Department of Veterans Affairs where patients are grouped not only by hospital, but also by geographic network (VISN). This project analyzes survival time data sets housed at the Houston Veterans Affairs Medical Center Research Department using two different Cox Proportional Hazards regression models, a traditional model and a multilevel model. VISNs that exhibit significantly higher or lower survival rates than the rest are identified separately for each model. ^ In this particular case, although there are differences in the results of the two models, it is not enough to warrant using the more complex multilevel technique. This is shown by the small estimates of variance associated with levels two and three in the multilevel Cox analysis. Much of the differences that are exhibited in identification of VISNs with high or low survival rates is attributable to computer hardware difficulties rather than to any significant improvements in the model. ^

Table to accompany Religion/Spirituality and Change in Meaning after Bereavement: Qualitative Evidence for the Meaning Making Model

This table accompanies the manuscript entitled "Religion/Spirituality and Change in Meaning after Bereavement: Qualitative Evidence for the Meaning Making Model" by Wortmann & Park (2009). The table summarizes the sample characteristics for published, qualitative studies that describe the involvement of religion/spirituality in adjustment after bereavement. Fields include author(s)'s last name, publication year, population characteristics and sample size, study design, age of the bereaved, type or cause of death, and time post-loss.

A Model of Rights

In this paper, we develop a simple model of the rights a government provides its citizenry. Rights are treated as public goods and taken as primitives in agents utility functions; each agent has preferences over the entire policy vector. We model the interaction among citi-zens and the government as a game in which an exogenous lobbying set makes contributions to the government to in uence policy formu-lation in the matter of rights. When examining contribution schedules comprising truthful Nash strategies, we find that members of the lob-bying set obtain rights closer to their most-preferred bundle, while the rights of non-lobbyers further diverge from their most-preferred bun-dle. Further, if the lobbying set comprises the entire population, the government s allocation of rights does not differ from the allocation achieved in the absence of contributions.

Colorectal cancer screening: Racial/ethnic and gender disparities in a population-based cross-sectional analysis of the United States

Gender and racial/ethnic disparities in colorectal cancer screening (CRC) has been observed and associated with income status, education level, treatment and late diagnosis. According to the American Cancer Society, among both males and females, CRC is the third most frequently diagnosed type of cancer and accounts for 10% of cancer deaths in the United States. Differences in CRC test use have been documented and limited to access to health care, demographics and health behaviors, but few studies have examined the correlates of CRC screening test use by gender. This present study examined the prevalence of CRC screening test use and assessed whether disparities are explained by gender and racial/ethnic differences. To assess these associations, the study utilized a cross-sectional design and examined the distribution of the covariates for gender and racial/ethnic group differences using the chi square statistic. Logistic regression was used to estimate the prevalence odds ratio and to adjust for the confounding effects of the covariates. ^ Results indicated there are disparities in the use of CRC screening test use and there were statistically significant difference in the prevalence for both FOBT and endoscopy screening between gender, χ2, p≤0.003. Females had a lower prevalence of endoscopy colorectal cancer screening than males when adjusting for age and education (OR 0.88, 95% CI 0.82–0.95). However, no statistically significant difference was reported between racial/ethnic groups, χ 2 p≤0.179 after adjusting for age, education and gender. For both FOBT and endoscopy screening Non-Hispanic Blacks and Hispanics had a lower prevalence of screening compared with Non-Hispanic Whites. In the multivariable regression model, the gender disparities could largely be explained by age, income status, education level, and marital status. Overall, individuals between the age "70–79" years old, were married, with some college education and income greater than $20,000 were associated with a higher prevalence of colorectal cancer screening test use within gender and racial/ethnic groups. ^

Federally regulated institutional review boards: The aspects of a "model" IRB---Is the current system in need of a tune up or complete overhaul?

Institutional Review Boards (IRBs) are the primary gatekeepers for the protection of ethical standards of federally regulated research on human subjects in this country. This paper focuses on what general, broad measures that may be instituted or enhanced to exemplify a "model IRB". This is done by examining the current regulatory standards of federally regulated IRBs, not private or commercial boards, and how many of those standards have been found either inadequate or not generally understood or followed. The analysis includes suggestions on how to bring about changes in order to make the IRB process more efficient, less subject to litigation, and create standardized educational protocols for members. The paper also considers how to include better oversight for multi-center research, increased centralization of IRBs, utilization of Data Safety Monitoring Boards when necessary, payment for research protocol review, voluntary accreditation, and the institution of evaluation/quality assurance programs. ^ This is a policy study utilizing secondary analysis of publicly available data. Therefore, the research for this paper focuses on scholarly medical/legal journals, web information from the Department of Health and Human Services, Federal Drug Administration, and the Office of the Inspector General, Accreditation Programs, law review articles, and current regulations applicable to the relevant portions of the paper. ^ Two issues are found to be consistently cited by the literature as major concerns. One is a need for basic, standardized educational requirements across all IRBs and its members, and secondly, much stricter and more informed management of continuing research. There is no federally regulated formal education system currently in place for IRB members, except for certain NIH-based trials. Also, IRBs are not keeping up with research once a study has begun, and although regulated to do so, it does not appear to be a great priority. This is the area most in danger of increased litigation. Other issues such as voluntary accreditation and outcomes evaluation are slowing gaining steam as the processes are becoming more available and more sought after, such as JCAHO accrediting of hospitals. ^ Adopting the principles discussed in this paper should promote better use of a local IRBs time, money, and expertise for protecting the vulnerable population in their care. Without further improvements to the system, there is concern that private and commercial IRBs will attempt to create a monopoly on much of the clinical research in the future as they are not as heavily regulated and can therefore offer companies quicker and more convenient reviews. IRBs need to consider the advantages of charging for their unique and important services as a cost of doing business. More importantly, there must be a minimum standard of education for all IRB members in the area of the ethical standards of human research and a greater emphasis placed on the follow-up of ongoing research as this is the most critical time for study participants and may soon lead to the largest area for litigation. Additionally, there should be a centralized IRB for multi-site trials or a study website with important information affecting the trial in real time. There needs to be development of standards and metrics to assess the performance of the IRBs for quality assurance and outcome evaluations. The boards should not be content to run the business of human subjects' research without determining how well that function is actually being carried out. It is important that federally regulated IRBs provide excellence in human research and promote those values most important to the public at large.^

Simulation study of joint transition and Weibull survival model with shared parameters

This study investigates a theoretical model where a longitudinal process, that is a stationary Markov-Chain, and a Weibull survival process share a bivariate random effect. Furthermore, a Quality-of-Life adjusted survival is calculated as the weighted sum of survival time. Theoretical values of population mean adjusted survival of the described model are computed numerically. The parameters of the bivariate random effect do significantly affect theoretical values of population mean. Maximum-Likelihood and Bayesian methods are applied on simulated data to estimate the model parameters. Based on the parameter estimates, predicated population mean adjusted survival can then be calculated numerically and compared with the theoretical values. Bayesian method and Maximum-Likelihood method provide parameter estimations and population mean prediction with comparable accuracy; however Bayesian method suffers from poor convergence due to autocorrelation and inter-variable correlation. ^

A cross sectional examination of risky sexual behaviors among a population of drug users

This study is a secondary data analysis that assesses the relationship between risky sexual behaviors and sexually transmitted infections (STIs) among drug users. This study analyzes data collected from drug users in the Houston Metropolitan area during 2004 and through August 2005, by researchers with the DASH (Drugs, AIDS, STDs and Hepatitis) project at The University of Texas at Houston School of Public Health. Specifically, the sexually transmitted infections that will be of interest in this proposed study are Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV). Risky sexual behaviors that will be examined include lack of condom use, sexual orientation, trading sex for drugs, trading sex for money, and number of male and female sexual partners in the last 4 weeks. ^ Unadjusted, gender, sexual orientation, number of recent male and female sex partners, and a history of injection drug use were all found to be significant independent variables that increased the odds of STI status. When included in an overall model, these variables significantly increased the odds of STI status, including HBV infection, HIV infection, and HBV/HIV co-infection. History of injection drug use was significant for both HBV and HBV/HIV co-infection, whereas a gay sexual orientation was significant for both HIV and HBV/HIV co-infection. Additionally, having excessive female sex partners was significant for HIV infection. This significant association increases the need for implementation of stronger intervention programs tailored to suit this population's needs such as a combination of drug and sexually transmitted disease (STD) treatment. ^ The importance of these findings is that they establish the strength of associations between the previously mentioned risky sexual behaviors and STI status among drug users. This is crucial for assessing future risk of infection as well as for serving as a necessary component in intervention and treatment programs both for drug use and STIs. ^

Effect of a lifestyle physical activity intervention on transtheoretical model variables

Purpose. To determine the effect a stage-based, lifestyle physical activity intervention has on Transtheoretical Model variables in a population of breast cancer survivors. ^ Methods. Sedentary breast cancer survivors (N=60) were randomized to either a standard care study condition or to a 6-month, 21-session intervention. The Transtheoretical Model variables stage of change, self-efficacy, decisional balance (pros and cons to exercise), and processes of change were measured at baseline, 3 months, and 6 months. ^ Results. Women in the lifestyle group had significantly higher self-efficacy than women in the standard care group (F=9.55, p=0.003). Although there was not a significant difference between the two groups for perceived pros of exercise, there was a significant difference between the groups for perceived cons of exercise. Women in the lifestyle group perceived significantly fewer cons of exercise at both 3 and 6 months compared with women in the standard care condition (F=5.416, p=0.025). Between baseline and the 6 month assessment, the intervention also had an effect on three of the processes of change, while seven of the processes were not significantly affected by the intervention. ^ Conclusions. Data from the pilot study suggest that a stage-based, lifestyle physical activity intervention has an effect on Transtheoretical Model variables, which have been shown to facilitate exercise adoption, and should be tested in a larger trial. ^