Frailty and Constellations of Factors in Aging HIV-infected and Uninfected Women--The Women's Interagency HIV Study.

BACKGROUND: Biological similarities are noted between aging and HIV infection. Middle-aged adults with HIV infection may present as elderly due to accelerated aging or having more severe aging phenotypes occurring at younger ages. OBJECTIVES: We explored age-adjusted prevalence of frailty, a geriatric condition, among HIV+ and at risk HIV- women. DESIGN: Cross-sectional. SETTING: The Women's Interagency HIV Study (WIHS). PARTICIPANTS: 2028 middle-aged (average age 39 years) female participants (1449 HIV+; 579 HIV-). MEASUREMENTS: The Fried Frailty Index (FFI), HIV status variables, and constellations of variables representing Demographic/health behaviors and Aging-related chronic diseases. Associations between the FFI and other variables were estimated, followed by stepwise regression models. RESULTS: Overall frailty prevalence was 15.2% (HIV+, 17%; HIV-, 10%). A multivariable model suggested that HIV infection with CD4 count<200; age>40 years; current or former smoking; income ≤$12,000; moderate vs low fibrinogen-4 (FIB-4) levels; and moderate vs high estimated glomerular filtration rate (eGFR) were positively associated with frailty. Low or moderate drinking was protective. CONCLUSIONS: Frailty is a multidimensional aging phenotype observed in mid-life among women with HIV infection. Prevalence of frailty in this sample of HIV-infected women exceeds that for usual elderly populations. This highlights the need for geriatricians and gerontologists to interact with younger 'at risk' populations, and assists in the formulation of best recommendations for frailty interventions to prevent early aging, excess morbidities and early death.

IAGG workshop: health promotion program on prevention of late onset dementia.

IAGG, WHO, and SFGG organized a international workshop on Health promotion programs on prevention of late on-set dementia. Thirty world specialists coming from Europe, North America, Asia, South America, Africa and Australia, shared their experience on methods and results of large epidemiological interventions to reduce incidents of dementia or delay its on-set. Chaired by Laura FRATIGLIONI, an expert in Epidemiological studies on dementia issues, the workshop gave opportunity for discussions and controversies about the state-of-the-art. Based on different national and international trials (ADAPT, MAPT, FINGER, GUDIAGE, GEM etc) the questions remained opened for different aspects of methodology, the choice of domain or multi domain intervention, the choice and the definition of the target populations, the best age of candidates, the issues related to the discrepancy between late effects, and interventions' duration. We are please to publish in the Journal, the presentations presented to this workshop. These publications will complete previously task force published in the journal in the last two years on methodological issues for Alzheimer's trials including end point, biomarkers, and the experience of past therapeutic trials.

Pharmacokinetic modeling of doxorubicin pharmacokinetics in dogs deficient in ABCB1 drug transporters.

BACKGROUND: The identification of dogs defective in ATP-binding cassette transporter B1 (ABCB1, MDR1) activity has prompted questions regarding pharmacokinetics (PK), efficacy and toxicity of ABCB1 substrates in these dogs. HYPOTHESIS/OBJECTIVES: Dogs defective in ABCB1 activity (ABCB1(null)) have doxorubicin (DOX) PK different from that of normal dogs (ABCB1(wt)). Utilization of a physiologically based pharmacokinetic (PBPK) model allows computer simulation to study this polymorphism's impact on DOX PK. ANIMALS: None. METHODS: A virtual ABCB1(wt) dog population was generated and DOX distribution, elimination, and metabolism simulated by PBPK modeling. An in silico population of virtual dogs was generated by Monte Carlo simulation, with variability in physiologic and biochemical parameters consistent with the dog population. This population was used in the PBPK model. The ABCB1 components of the model were inactivated to generate an ABCB1(null) population and simulations repeated at multiple doses. Resulting DOX levels were used to generate PK parameters. RESULTS: DOX exposures in the ABCB1(null) population were increased in all simulated tissues including serum (24%) and gut (174%). Estimated dosages in the ABCB1(null) population to approximate exposure in the ABCB1(wt) population at a dose of 30 mg/m(2) were 24.8 +/- 3.5 mg/m(2) for serum and 10.7 +/- 5.9 mg/m(2) for gut. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that serum DOX concentrations are not indicative of tissue exposure, especially those with appreciable ABCB1 activity, and that gastrointestinal (GI) toxicosis would be dose limiting in ABCB1(null) populations. Dosage reductions necessary to prevent GI toxicosis likely result in subtherapeutic concentrations, thereby reducing DOXs efficacy in ABCB1(null) dogs.

Assessment of the biological and pharmacological effects of the alpha nu beta3 and alpha nu beta5 integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors.

BACKGROUND: Cilengitide, an antiangiogenic agent that inhibits the binding of integrins alpha(nu)beta(3) and alpha(nu)beta(5) to the extracellular matrix, was studied at two dose levels in cancer patients to determine the optimal biological dose. PATIENTS AND METHODS: The doses of cilengitide were 600 or 1200 mg/m(2) as a 1-h infusion twice weekly every 28 days. A novel dose escalation scheme was utilized that relied upon the biological activity rate. RESULTS: Twenty patients received 50 courses of cilengitide with no dose-limiting toxic effects. The pharmacokinetic (PK) profile revealed a short elimination half-life of 4 h, supporting twice weekly dosing. Of the six soluble angiogenic molecules assessed, only E-selectin increased significantly from baseline. Analysis of tumor microvessel density and gene expression was not informative due to intrapatient tumor heterogeneity. Although several patients with evaluable tumor biopsy pairs did reveal posttreatment increases in tumor and endothelial cell apoptosis, these results did not reach statistical significance due to the aforementioned heterogeneity. CONCLUSIONS: Cilengitide is a well-tolerated antiangiogenic agent. The biomarkers chosen in this study underscore the difficulty in assessing the biological activity of antiangiogenic agents in the absence of validated biological assays.

Differences in patient and clinic characteristics at CARE Act funded versus non-CARE Act funded HIV clinics.

The Ryan White CARE Act supports comprehensive care to persons with HIV infection. With an annual budget of over $1 billion, it is the largest federally funded programme for HIV care in the USA. We analysed data from the HIV Costs and Services Utilization Study, a nationally representative sample of HIV patients. Patient data were collected in 1996-97 and clinic data were collected in 1998-99. We examined whether CARE Act funded clinics differed from other HIV clinics in (1) the characteristics of their patients, and (2) their organization, staffing, and services. We found that patients at CARE Act clinics were younger, less educated, poorer, and more likely to be female, non-white, unemployed, uninsured, and have heterosexual contact as an HIV risk factor, compared to patients at other HIV clinics. CARE Act clinics tended to specialize in HIV care, had more infectious disease specialists, had fewer total patients, and provided more support services (e.g. mental health, nutrition, case management, child care). These results are consistent with findings of other studies that were limited by non-probability samples or restricted geographical areas.

Access to health information and support: a public highway or a private road?

Information and communication technologies may help reduce health disparities through their potential for promoting health, preventing disease, and supporting clinical care for all. Unfortunately, those who have preventable health problems and lack health insurance coverage are the least likely to have access to such technologies. Barriers to access include cost, geographic location, illiteracy, disability, and factors related to the capacity of people to use these technologies appropriately and effectively. A goal of universal access to health information and support is proposed to augment existing initiatives to improve the health of individuals and the public. Both public- and private-sector stakeholders, particularly government agencies and private corporations, will need to collaboratively reduce the gap between the health information "haves" and "have-nots." This will include supporting health information technology access in homes and public places, developing applications for the growing diversity of users, funding research on access-related issues, ensuring the quality of health information and support, enhancing literacy in health and technology, training health information intermediaries, and integrating the concept of universal access to health information and support into health planning processes.

An evidence-based approach to interactive health communication: a challenge to medicine in the information age. Science Panel on Interactive Communication and Health.

OBJECTIVE: To examine the current status of interactive health communication (IHC) and propose evidence-based approaches to improve the quality of such applications. PARTICIPANTS: The Science Panel on Interactive Communication and Health, a 14-member, nonfederal panel with expertise in clinical medicine and nursing, public health, media and instructional design, health systems engineering, decision sciences, computer and communication technologies, and health communication, convened by the Office of Disease Prevention and Health Promotion, US Department of Health and Human Services. EVIDENCE: Published studies, online resources, expert panel opinions, and opinions from outside experts in fields related to IHC. CONSENSUS PROCESS: The panel met 9 times during more than 2 years. Government agencies and private-sector experts provided review and feedback on the panel's work. CONCLUSIONS: Interactive health communication applications have great potential to improve health, but they may also cause harm. To date, few applications have been adequately evaluated. Physicians and other health professionals should promote and participate in an evidence-based approach to the development and diffusion of IHC applications and endorse efforts to rigorously evaluate the safety, quality, and utility of these resources. A standardized reporting template is proposed to help developers and evaluators of IHC applications conduct evaluations and disclose their results and to help clinicians, purchasers, and consumers judge the quality of IHC applications.

The relationship between meeting patients' information needs and their satisfaction with hospital care and general health status outcomes.

OBJECTIVE: The objective of this study was to determine if there is an association between meeting patients' information needs and their overall satisfaction with care and their general health status outcomes. STUDY DESIGN: This non-experimental study used data from hospital medical records as well as patient-completed surveys conducted two and eight weeks post discharge. The setting involved three community hospitals in the southeastern section of the US that provided care to a series of 167 acute myocardial infarction (Acute MI) patients. MEASURES: The independent variable was an index measuring how well patients' information needs were met. The dependent variables were patient satisfaction (ratings of satisfaction with care process, global satisfaction, and health benefit) and general health status outcomes (physical function, psychosocial function and quality of life). Covariates used as control variables to hold patient characteristics constant, included demographics (age, gender) and clinical measures of acute MI severity, comorbidity, angina (at eight weeks), and dyspnea (at eight weeks). ANALYSIS: Univariate analyses were employed to: (1) describe patients' characteristics; (2) determine the relative importance of meeting different types of information needs; and (3) identify information need areas most likely not to be met. Multivariate linear regression and logistic regression was used to evaluate the association between patients' ratings of meeting information needs with satisfaction and health outcomes, respectively, after controlling for covariates. RESULTS: The multivariate regression results show that meeting information needs are positively and significantly associated with both patient satisfaction measures (i.e., Ratings of Care Processes, p < 0.01; Global Satisfaction, p < 0.05, Perceived Health Benefit, p < 0.01) and one general health status measure (i.e. Quality of Life, p < 0.01). CONCLUSION: The results suggest that providers of care should ensure that they meet the information needs of patients with specific conditions because patients' perceptions of both quality of care and quality of life are associated with the clinicians' ability to transfer key information to their patients.

Incentives to promote quality improvement in long-term care.

Long-term care acute care providers are using innovative, data-based approaches and information systems solutions to position themselves for the future. These approaches will significantly improve the ability of these providers to treat patients, justify their continued existence, and compete in the marketplace.

The total costs of illness: a metric for health care reform.

Systems thinking is a fundamental element of quality management and should be a fundamental element of health care reform. An implication of systems thinking is that one aim of health care should be to minimize the total costs of illness, not simply the direct medical expenditures. If we are to continue to improve health care over time, we should measure its impact on the total costs of illness to the patient, family, employer, and society. Thus a system of measurement is needed that quantifies total costs of illness and also suggests how these constituencies can collaborate to improve processes and reduce total costs. This article introduces the total costs of illness concept, contrasts it with societal costs of illness, describes a measurement system we developed to quantify it, and describes a case study examining the total costs of back injury illness to employers. We found that medical expenditures accounted for less than half of the total costs of illness, the average total costs of illness varied by over 350 percent among employers, and a simple metric (days off work) explained 62.5 percent of the variance in total costs of illness.

Removing the assumption of conditional independence from Bayesian decision models by using artificial neural networks: some practical techniques and a case study.

The article describes how artificial neural networks with special designs can be applied to approximate a subjective Bayesian decision model without the assumption of conditional independence. New techniques are proposed to resolve some of the practical difficulties during the processes of problem structuring, knowledge elicitation, quantitative modeling, and model interpretation. A Bayesian model considering the conditional dependencies to predict a teenager's marijuana use was constructed by experts using these techniques, and compared to another conventional Bayesian model which assumed conditional independence. The new approach without the assumption of conditional independence had predictive power (r = 0.7) in the test of linearity compared to the conventional approach (r = 0.58) on a data set (n = 129). Its receiver operating characteristic curve dominated the alternative approach within the range (true positive fraction > 0.7) that we were interested in. The interpretations of the possible conditional dependencies provided by the artificial neural network after the training process were consistent with the expert's descriptions.

Assessing the needs of breast cancer patients and their families.

Patient needs have long been elicited only through the use of customer satisfaction surveys, which unfortunately are not designed to obtain the in-depth information needed to guide the improvement of health care services. Through the use of the integrative group process and the help of many patients and hospital staffs, we developed a needs assessment survey for women with breast cancer. This article outlines this process and the results and discusses how we used these results to create a computer program designed to help women with breast cancer and their families.

Focus on sustainability.

PIP: In recent years, sustainability has become one of the most critical concepts in international development and is having a dramatic impact on the way development is conceptualized and carried out. The US Agency for International Development (USAID) is incorporating this concept into its programs and projects. Factors encouraging sustainability of projects and programs include host government policies that support or constrain program objectives, national and/or local commitment to project goals, managerial leadership that helps shape improved policies, collaboration at all staff levels in program management, financial resources that cover program operational costs, appropriate program technology, integration of the program with the social and cultural setting of the country, community involvement in the program, sound environmental management, technical assistance oriented to transferring skills and increasing institutional capacity, perception by the host country that the project is "effective," training provided by the project to transfer skill needed for capacity-building, integration of the program into existing institutional framework, and external political, economic and environmental factors. Impediments to sustainability are often inherent in the donor agency's programming process. This includes the implicit assumption that program objectives can be accomplished in a relatively short time frame, when in fact capacity-building requires a lengthy commitment. USAID professionals are pressured to show near-term results which emphasize outputs rather than purpose and goal-level accomplishments achievable only after extensive effort. The emphasis on obligating money and on the project paper as a sales document leads project designers to talk with a great deal more certainty about project results than is warranted by the complex development situation. Uncertainty and flexibility should be designed into projects so activities and objects can change as more information and on-site experience is gained. Instead of outputs, success should be measured in processes that will continue to produce long-term results. Emphasis should be placed on establishing policymaking processes and decision making procedures in the recipient country that will lead to sound economic policymaking on a continuing basis. Sustainable efforts in agriculture, health, rural development and their evaluation are examined for several USAID projects.^ieng

The Quality Assessment Index (QAI) for measuring nursing home quality.

There have been few detailed evaluations of measures of quality of care in nursing homes. This is unfortunate because it has meant that much research on factors affecting nursing home quality has used measures of questionable reliability and validity. Moreover, some measures currently in use have been developed using methodologies not based on solid conceptual grounds, offering little reason to expect them to have much internal or external validity. In this article we suggest characteristics that should be present in measures of nursing home quality, propose a methodology for the development of such measures, propose a specific nursing home quality measure (the Quality Assessment Index or QAI), and report the results of several tests of its validity and reliability.

Quality assurance for psychiatric emergencies. An analysis of assessment and feedback methodologies.

Improvement in the quality of evaluation and treatment of behavioral emergencies presenting to hospital emergency rooms requires a multicomponent assessment of resources, clinician performance, and outcome. The authors present a summary of data and conclusions derived from index-based assessment of quality of care in over 2000 psychiatric emergencies. The study revealed that emergency room physicians rendered high-quality medical care, but were deficient in crucial aspects of psychiatric evaluation and treatment including evaluation of dangerousness and substance abuse and provision of appropriate follow-up care. A positive association was observed between quality of care and compliance with referral. Subsequent review with the staff pointed to issues such as staffing, emergency room and community resources, and adequacy of documentation as significant influences on quality of care, as assessed by the chart-audit, index approach. A pilot study demonstrated uniform improvement of quality scores in a small group of physicians receiving written and oral feedback about their performance. The use of focused quality assessment studies that examine both structural and process factors, and their correlation with outcome, is discussed in light of the information obtained from the previously described study. A feedback methodology that emphasizes an interactive process to identify deficiencies in care and to explore their causes and remedies is presented.

How to construct a subjective index.

We present a method of constructing quantitative indices, which is based on the subjective opinions of a panel of experts, and discuss how a Bayesian probability model and panel opinions can be used together to produce an index. Among the advantages of the method are its face validity and ease of construction. Research shows that when expert opinions are solicited according to certain guidelines, subjective methods may be as accurate as the more objective ones. Guidelines along with a brief report of a recent application are also discussed.

A decision theoretic methodology for severity index development.

Severity indices are a key element in evaluation of health programs. But the methodologies used in development of such indices are rarely clearly defined. Moreover, there have been no tests of transportability of the index development methodologies that do exist, so there is no guarantee that panels of physicians convened by different facilitators would produce indices with similar performance characteristics. This paper describes a replicable index development strategy, a heart disease severity index developed by using that methodology, and a test of that methodology's transportability.

Assessment of level of care: implications of interrater reliability on health policy.

In Wisconsin, level-of-care assessments are used to set Medicaid reimbursement and determine nursing home eligibility. This study examined three methods of assessing level of care: 1) the Wisconsin quality assurance project (QAP) method, based on observations of patients, patient records, and staff interviews; 2) the Wisconsin standard (STD) method, based primarily on a clinical record review; and, 3) an adaptation of New York's "DMS-I," a checklist with numerical weights used to set level of care. Results address interrater reliability, the agreement between assessments by research teams and actual levels of care set by the State, and the implications that agreement has for reimbursement.