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Pathogenesis of chronic disease associated with persistent lymphocytic choriomeningitis viral infection. I. Relationship of antibody production to disease in neonatally infected mice.

Mice infected shortly after birth with lymphocytic choriomeningitis (LCM) virus are not immunologically tolerant, although they carry the virus throughout life. These LCM carrier mice make anti-LCM antibody, which apparently complexes with viral antigen in the circulation and these complexes accumulate in the glomeruli. LCM carrier mice of different strains vary significantly as to concentration of detectable infectious virus in their tissue, amount and time of appearance of anti-LCM antibody, and development of an associated chronic disease. The chronic disease consists primarily of glomerulonephritis, focal hepatic necrosis, and disseminated lymphoid infiltrations. LCM carriers of the SWR/J strain contain high tissue concentrations of virus, considerable anti-LCM antibody detectable in the glomeruli by 3 wk to 2 months of age and develop chronic disease within the first 2-3 months of life. In contrast, C(3)H strain LCM carriers contain 1/1000 as much infectious virus, less detectable anti-LCM antibody, and have not, over a 24 month observation period, developed any detectable disease. B10D2 old and new carrier mice with intermediate amounts of virus develop chronic disease during the latter half of the first year of life. The pathogenesis of the glomerulonephritis of chronic LCM disease is apparently related to the formation of circulating virus-antibody complexes which are trapped in the glomerular filter. There is no evidence for direct glomerular injury by the virus nor for any autoimmune response by the host.

Animals↗

Fatigue in chronic disease.

Fatigue is an extremely common complaint among patients with chronic disease. However, because of the subjective nature of fatigue, and the lack of effective therapeutics with which to treat fatigue, this symptom is often ignored by clinicians, who instead focus on hard, objective disease end-points. Recently, the symptom of fatigue has received greater attention as part of overall health-related quality of life assessments in patients with chronic disease. Furthermore, new methods are being developed to help quantify fatigue, and are being utilized more frequently in the clinical setting. Moreover, studies in patients and using animal models of disease have provided some insight into changes within the brain which appear to be linked to the genesis of central fatigue. This review focuses on fatigue in chronic disease and outlines possible mechanisms which may give rise to central fatigue in chronic disease. Moreover, methods for measuring fatigue and an approach to the fatigued patient are discussed. Hopefully, a broader understanding of this distressing symptom will lead to the development of specific therapies for treating fatigue in these patients.

Activities of Daily Living↗

Investigating the sustainability of outcomes in a chronic disease treatment programme.

This study examines trends in chronic disease outcomes from initiation of a specialised chronic disease treatment programme through to incorporation of programme activities into routine service delivery. We reviewed clinical records of 98 participants with confirmed renal disease or hypertension in a remote indigenous community health centre in Northern Australia. For each participant the review period spanned an initial three years while participating in a specialised cardiovascular and renal disease treatment programme and a subsequent three years following withdrawal of the treatment programme. Responsibility for care was incorporated into the comprehensive primary care service which had been recently redeveloped to implement best practice care plans. The time series analysis included at least six measures prior to handover of the specialised programme and six following handover. Main outcome measures were trends in blood pressure (BP) control, and systolic and diastolic BP. We found an improvement in BP control in the first 6-12 months of the programme, followed by a steady declining trend. There was no significant difference in this trend between the pre- compared to the post-programme withdrawal period. This finding was consistent for control at levels below 130/80 and 140/90, and for trends in mean systolic and diastolic BP. Investigation of the sustainability of programme outcomes presents major challenges for research design. Sustained success in the management of chronic disease through primary care services requires better understanding of the causal mechanisms related to clinical intervention, the basis upon which they can be 'institutionalised' in a given context, and the extent to which they require regular revitalisation to maintain their effect.

Australia↗

Anemia of chronic disease: a review of pathogenesis.

Although anemia of chronic disease is a common hematologic disorder, the pathogenesis of the disease is still not well understood. Various workers have demonstrated decreased red cell life span, decreased erythropoietin levels, and inappropriate response of the bone marrow to the degree of anemia. The iron metabolism in the anemia of chronic disease is abnormal in that the macrophages in the bone marrow hold onto iron and do not release it for reutilization by the erythroid precursors. More recent studies have focused attention on cytokines produced by macrophages. These are interleukin-1 and tumor necrosis factor. These cytokines appear to be involved in both red cell production and ferrokinetics. Greater understanding of the biology of the cytokines may be the key to understanding the pathogenesis of anemia of chronic disease.

Anemia↗

Volunteer, lay tutors' experiences of the Chronic Disease Self-Management Course: being valued and adding value.

Chronic disease is a public health issue that could be addressed, in part, by increasing the ability of individuals to better manage their condition and its consequences on a day-to-day basis. One intervention designed to facilitate this is the Chronic Disease Self Management Course (CDSMC) that is delivered by volunteer, lay tutors who themselves have a chronic disease. Although there is growing evidence of course effectiveness for participants, the experiences of tutors have been neglected. This study aims to address this omission. Telephone interviews were conducted with 11 (six male) tutors: all interviews were transcribed and thematically analysed. Being a volunteer lay-tutor was perceived to be an enjoyable and valuable experience despite the challenges associated with course delivery, such as organizational demands and managing the diverse needs of mixed groups of chronic disease participants that led to a tension between disease-specific needs and the generic approach of the course. Being valued and adding value to the lives of others were key benefits of being a volunteer tutor, along with increased confidence that they were doing something positive for others. Course delivery prompted the initiation and maintenance of tutors' own self-management behaviours.

Adult↗

Research strategies and the use of nutrient biomarkers in studies of diet and chronic disease.

OBJECTIVE: To provide an account of the state of diet and chronic disease research designs and methods; to discuss the role and potential of aggregate and analytical observational studies and randomised controlled intervention trials; and to propose strategies for strengthening each type of study, with particular emphasis on the use of nutrient biomarkers in cohort study settings. DESIGN: Observations from diet and disease studies conducted over the past 25 years are used to identify the strengths and weaknesses of various study designs that have been used to associate nutrient consumption with chronic disease risk. It is argued that a varied research programme, employing multiple study designs, is needed in response to the widely different biases and constraints that attend aggregate and analytical epidemiological studies and controlled intervention trials. Study design modifications are considered that may be able to enhance the reliability of aggregate and analytical nutritional epidemiological studies. Specifically, the potential of nutrient biomarker measurements that provide an objective assessment of nutrient consumption to enhance analytical study reliability is emphasised. A statistical model for combining nutrient biomarker data with self-report nutrient consumption estimates is described, and related ongoing work on odds ratio parameter estimation is outlined briefly. Finally, a recently completed nutritional biomarker study among 102 postmenopausal women in Seattle is mentioned. The statistical model will be applied to biomarker data on energy expenditure, urinary nitrogen, selected blood fatty acid measurements and various blood micronutrient concentrations, and food frequency self-report data, to identify study subject characteristics, such as body mass, age or socio-economic status, that may be associated with the measurement properties of food frequency nutrient consumption estimates. This information will be crucial for the design of a potential larger nutrient biomarker study within the cohort study component of the Women's Health Initiative. SETTING AND SUBJECTS: The methodology under study is expected to be pertinent to a wide variety of diet and chronic disease association studies in the general population. Ongoing work focuses on statistical methods developed using computer simulations motivated by studies of dietary fat in relation to breast and colon cancer among post-menopausal women, and ongoing pilot studies to be described in detail elsewhere, involving post-menopausal women living in the Seattle area. RESULTS AND CONCLUSION: A varied research programme appears to be needed to make progress in the challenging diet and chronic disease research area. Such progress may include aggregate studies of diet and chronic disease that include sample surveys in diverse population groups world-wide, analytical epidemiological studies that use nutrient biomarker data to calibrate self-report nutrient consumption estimates, and randomised controlled intervention trials that arise from an enhanced infrastructure for intervention development. New innovative designs, models and methodologies are needed for each such research setting.

Aged↗

Malaligned financial incentives of providers in the treatment of chronic diseases: the case of chronic heart failure.

Fee for activity based payment systems create a matrix of conflicting incentives. Hospitals, desiring to maximize revenues and minimize expenses, seek high patient volume with minimal direct variable expenses. The mix of patients, sought bias towards those whose disease related group (DRG), provide the largest contribution to hospitals fixed costs, are frequently characterized by the DRG with high reimbursements, coupled with both low length of stay and low utilization of expensive resources. Physicians, on the other hand, find hospital environments to be extraordinary practice sites. In the hospital, they can generate practice revenue without paying overhead for hospital resources. The incentives to rapidly discharge patients and reduce utilization of resources which are charged to the hospital's expense line are obscure. Hospital treatment of CHF frequently characterizes this conflict; hospitals are seeking rapid through put of CHF patients who neither require expensive hospital based resources nor demonstrate excessive length of stay. Physicians are not encumbered with immediate concerns about costs during the hospitalization, nor the length of hospitalization. The absence of absolute medical consensus on appropriateness of diagnostic and treatment strategies in this population has allowed significant variation on practice patterns to evolve, and consequently, variation on the contribution to hospital fiscal viability made by each physician. (c)1999 by CHF, Inc.

Journal Article↗

Representativeness of a roster of volunteer North American twins with chronic disease.

To identify large numbers of twins affected by chronic disease as potential subjects for studies of environmental and genetic chronic disease determinants, we advertised for affected twins over the period 1980-91 in newspapers across North America. Responses were received from 17 245 twin pairs in which cases of cancer or other chronic disease had occurred. To assess the representativeness of affected twins identified by advertising, we evaluated the pattern of reporting, compared the cases identified to the number of cases estimated to be prevalent among all North American twins, compared the cases to population-based singleton case series, compared the healthy co-twins to population-based samples of healthy persons, assessed the impact on ascertainment of opinions about disease causation, compared the pattern of prospective to retrospective ascertainment of disease in the originally unaffected co-twins of cases, and compared the results of the prospective ascertainment of disease in co-twins to comparable published estimates. Youth, gender, zygosity, education, and disease concordance were found to be overall determinants of ascertainment. Disease-discordant DZ twins appeared to be modestly underascertained. While somewhat better educated, both concordant and discordant pairs were judged to be reasonably representative of affected non-Hispanic white North American twin pairs of comparable status, ie of comparable age, sex, race, and zygosity. If interpreted with caution, the concordance patterns of such twins can be used to generate genetic hypotheses, but should not be the basis of definitive heritability analyses. We conclude that advertising offers a method of identifying pairs of twins that can serve as subjects for studies designed to identify disease determinants.

Adult↗

Evaluation of bone marrow iron stores in anemia associated with chronic disease: a comparative study of serum and red cell ferritin.

The serum ferritin (SERFER) may be elevated and misleading in the setting of chronic disease (chronic inflammation, liver disease, and neoplasm). The red cell ferritin (RBCFER) may be more stable in clinical situations that affect the SERFER. We compared the ability of SERFER and RBCFER to assess iron stores in these settings. Iron stores were defined by bone marrow aspirate staining. We studied 120 anemic (Hb < 14 g/dl) male patients. Twenty-eight (23%) were iron deficient based on the absence of marrow iron. The SERFER correlation with marrow iron stores (r = 0.58; P < 0.001) was better than the RBCFER (r = 0.36; P < 0.001). Cutoff values for the diagnosis of iron deficiency were determined by chi-square analysis (SERFER < 70 ng/ml; RBCFER < or = 4 ag/RBC). The sensitivity for detecting iron deficiency with SERFER (0.60) was less than RBCFER (0.82). The specificity of SERFER (0.90) was slightly better than RBCFER (0.83). Neither difference reached statistical significance (P > 0.05). The positive predictive value between the two assays was the same (SERFER 0.65 vs. RBCFER 0.59). The combination of SERFER < 70 ng/ml with RBCFER < or = 4 ag/RBC was more specific (0.97) when compared with the SERFER alone (0.90) (P = 0.04). In addition, the potential of this combination to predict iron deficiency (0.82) was higher than that seen with either SERFER (0.65) or the RBCFER (0.59). Our findings show that the RBCFER as a single assay is not anymore accurate than the SERFER. However, we find that the RBCFER can effectively complement the SERFER to either predict iron depletion or confirm the presence of bone marrow iron.

Anemia↗

Revisions to chronic disease surveillance indicators, United States, 2004.

To allow public health officials to uniformly define, collect, and report chronic disease data, Indicators for Chronic Disease Surveillance was released by the Council of State and Territorial Epidemiologists in 1999. This publication provided standard definitions for 73 indicators developed by epidemiologists and chronic disease program directors at the state and federal levels. The indicators were selected because of their importance to public health and the availability of state-level data. This report describes the latest revisions to the chronic disease indicators published in 2004. The revised set of 92 indicators includes 24 for cancer; 15 for cardiovascular disease; 11 for diabetes; 7 for alcohol; 5 each for nutrition and tobacco; 3 each for oral health, physical activity, and renal disease; and 2 each for asthma, osteoporosis, and immunizations. The remaining 10 indicators cover such overarching conditions as poverty, education, and life expectancy. Although multiple states have used the indicators, wider adoption depends on increased epidemiology capacity at the state level and improved access to surveillance data.

Chronic Disease↗

A public health framework for chronic disease prevention and control.

Chronic noncommunicable diseases are leading causes of death and disability in many developing countries. Several low-income countries lack mortality and morbidity data and do not yet know their burden of noncommunicable diseases. Cost studies are scarce, but in middle-income countries such as those of Latin America and the Caribbean, the cost of illness not only represents much of the direct costs of medical care, but also has an impact on family disposable income. Studies have reported that in low-resource settings, given incomplete health coverage and partial insurance, out-of-pocket expenses are high. Persons with chronic conditions, in many instances, have to forego care because of their inability to pay. Poverty and chronic noncommunicable diseases have a two-way interaction. These conditions warrant attention from poverty-reduction programs. Evidence shows that to have an impact on the burden of chronic diseases, action must occur at three levels: population-wide policies, community activities, and health services. The latter includes both preventive services and appropriate care for persons with chronic conditions. A public health approach embodies a systems perspective, containing the continuum of prevention and control, from determinants to care. In this framework it is critical to identify and address interactions and interventions that connect between and among the three levels of action.

Caribbean Region↗

Long-term trends in Indigenous deaths from chronic diseases in the Northern Territory: a foot on the brake, a foot on the accelerator.

OBJECTIVE: To examine trends in Northern Territory Indigenous mortality from chronic diseases other than cancer. DESIGN: A comparison of trends in rates of mortality from six chronic diseases (ischaemic heart disease [IHD], chronic obstructive pulmonary disease [COPD], cerebrovascular disease [CVD], diabetes mellitus [DM], renal failure [RF] and rheumatic heart disease [RHD]) in the NT Indigenous population with those of the total Australian population. PARTICIPANTS: NT Indigenous and total Australian populations, 1977-2001. MAIN OUTCOME MEASURES: Estimated average annual change in chronic disease mortality rates and in mortality rate ratios. RESULTS: Death rates from IHD and DM among NT Indigenous peoples increased between 1977 and 2001, but this increase slowed after 1990. Death rates from COPD rose before 1990, but fell thereafter. There were non-significant declines in death rates from CVD and RHD. Mortality rates from RF rose in those aged > or = 50 years. The ratios of mortality rates for NT Indigenous to total Australian populations from these chronic diseases increased throughout the period. CONCLUSIONS: Mortality rates from IHD and DM in the NT Indigenous population have been increasing since 1977, but there is evidence of a slower rise (or even a fall) in death rates in the 1990s. These early small changes give reason to hope that some improvements (possibly in medical care) have been putting the brakes on chronic disease mortality among Aboriginal and Torres Strait Islander peoples.

Cardiovascular Diseases↗

A population-based analysis of health behaviours, chronic diseases and associated costs.

Health behaviours influence the future incidence of certain common chronic diseases and thus have an impact on health status and utilization of health care services and costs. We analyzed person-level data of the Albertan adult population from the Canadian Community Health Survey, Cycle 1.1 (2000) to determine health care costs associated with specific health behaviours (smoking, sub-optimal diet, physical inactivity) and chronic disease states (heart disease, diabetes, COPD). We found that 74.7 percent of the population exhibited one or more risk behaviours, while 10.5 percent had one or more of the chronic diseases of interest. Greater health care utilization and costs were noted in groups exhibiting risk behaviour and chronic disease states. Approximately 31 percent of health care costs in Alberta were attributable to people having one or more of the three chronic diseases. Our findings of higher health care costs incurred by those exhibiting unhealthy behaviour prior to development of disease, as well as by those with multiple co-existent diseases, are important indicators to guide future prevention and treatment strategies of chronic illness.

Adult↗

Can the relation between tooth loss and chronic disease be explained by socio-economic status? A 24-year follow-up from the population study of women in Gothenburg, Sweden.

The objective of this study was to evaluate the association between number of missing teeth and all cause, cardiovascular, and cancer mortality as well as morbidity and to explore whether socio-economic factors mediate this association. An ongoing prospective cohort study of 1462 Swedish women included a dental survey in 1968/69 with follow-up until 1992/93. The dental examination included a panoramic radiographic survey and a questionnaire. Number of missing teeth at baseline was analysed in a Cox proportional hazards model to estimate time to mortality and morbidity. Number of missing teeth, independently of socio-economic status variables (the husband's occupational category, combined income, and education) was associated with increased all cause mortality and cardiovascular disease mortality respectively (relative risk (RR): 1.36; 95% confidence interval (95% CI): 1.18-1.58) and (RR: 1.46; 95% CI: 1.15-1.85 per 10 missing teeth), but no associations were found for cancer mortality (RR: 1.18; 95% CI: 0.91-1.52). The relation between poor oral health and future cardiovascular disease could not be explained by measures of socio-economic status in this study.

Adult↗