Complexity of chronic asthma and chronic obstructive pulmonary disease: implications for risk assessment, and disease progression and control

Although assessment of asthma control is important to guide treatment, it is difficult since the temporal pattern and risk of exacerbations are often unpredictable. In this Review, we summarise the classic methods to assess control with unidimensional and multidimensional approaches. Next, we show how ideas from the science of complexity can explain the seemingly unpredictable nature of bronchial asthma and emphysema, with implications for chronic obstructive pulmonary disease. We show that fluctuation analysis, a method used in statistical physics, can be used to gain insight into asthma as a dynamic disease of the respiratory system, viewed as a set of interacting subsystems (eg, inflammatory, immunological, and mechanical). The basis of the fluctuation analysis methods is the quantification of the long-term temporal history of lung function parameters. We summarise how this analysis can be used to assess the risk of future asthma episodes, with implications for asthma severity and control both in children and adults.

High-altitude exposure in patients with cardiovascular disease: risk assessment and practical recommendations

Because of the development of modern transportation facilities, an ever rising number of individuals including many patients with preexisting diseases visit high-altitude locations (>2500 m). High-altitude exposure triggers a series of physiologic responses intended to maintain an adequate tissue oxygenation. Even in normal subjects, there is enormous interindividual variability in these responses that may be further amplified by environmental factors such as cold temperature, low humidity, exercise, and stress. These adaptive mechanisms, although generally tolerated by most healthy subjects, may induce major problems in patients with preexisting cardiovascular diseases in which the functional reserves are already limited. Preexposure assessment of patients helps to minimize risk and detect contraindications to high-altitude exposure. Moreover, the great variability and nonpredictability of the adaptive response should encourage physicians counseling such patients to adapt a cautionary approach. Here, we will briefly review how high-altitude adjustments may interfere with and aggravate/decompensate preexisting cardiovascular diseases. Moreover, we will provide practical recommendations on how to investigate and counsel patients with cardiovascular disease desiring to travel to high-altitude locations.

Effect of Alzheimer Caregiving on Circulating Levels of C-Reactive Protein and Other Biomarkers Relevant to Cardiovascular Disease Risk: A Longitudinal Study

Providing care to a spouse with Alzheimer's disease (AD) may contribute to cardiovascular disease (CVD). The acute phase reactant C-reactive protein (CRP) is a well-established biomarker of an increased CVD risk.

Ways of coping and biomarkers of an increased atherothrombotic cardiovascular disease risk in elderly individuals

Objective. To investigate the relationship between coping and atherothrombotic biomarkers of an increased cardiovascular disease (CVD) risk in the elderly. Methods. We studied 136 elderly caregiving and noncaregiving men and women who completed the Ways of Coping Checklist to assess problem-focused coping, seeking social support (SSS), blamed self, wishful thinking, and avoidance coping. They had circulating levels of 12 biomarkers measured. We also probed for potential mediator and moderator variables (chronic stress, affect, health behavior, autonomic activity) for the relation between coping and biomarkers. Results. After controlling for demographic and CVD risk factors, greater use of SSS was associated with elevated levels of serum amyloid A (P = 0.001), C-reactive protein (CRP) (P = 0.002), vascular cellular adhesion molecule (VCAM)-1 (P = 0.021), and D-dimer (P = 0.032). There were several moderator effects. For instance, greater use of SSS was associated with elevated VCAM-1 (P < 0.001) and CRP (P = 0.001) levels in subjects with low levels of perceived social support and positive affect, respectively. The other coping styles were not significantly associated with any biomarker. Conclusions. Greater use of SSS might compromise cardiovascular health through atherothrombotic mechanisms, including elevated inflammation (i.e., serum amyloid A, CRP, VCAM-1) and coagulation (i.e., D-dimer) activity. Moderating variables need to be considered in this relationship.

Analysis of postprandial lipemia as a Cardiovascular Disease risk factor using genetic and clinical information: an Artificial Neural Network perspective

Clinical studies indicate that exaggerated postprandial lipemia is linked to the progression of atherosclerosis, leading cause of Cardiovascular Diseases (CVD). CVD is a multi-factorial disease with complex etiology and according to the literature postprandial Triglycerides (TG) can be used as an independent CVD risk factor. Aim of the current study is to construct an Artificial Neural Network (ANN) based system for the identification of the most important gene-gene and/or gene-environmental interactions that contribute to a fast or slow postprandial metabolism of TG in blood and consequently to investigate the causality of postprandial TG response. The design and development of the system is based on a dataset of 213 subjects who underwent a two meals fatty prandial protocol. For each of the subjects a total of 30 input variables corresponding to genetic variations, sex, age and fasting levels of clinical measurements were known. Those variables provide input to the system, which is based on the combined use of Parameter Decreasing Method (PDM) and an ANN. The system was able to identify the ten (10) most informative variables and achieve a mean accuracy equal to 85.21%.

Hemoglobin, iron metabolism and angiographic coronary artery disease (The Ludwigshafen Risk and Cardiovascular Health Study).

BACKGROUND Anemia has been shown to be a risk factor for coronary artery disease and mortality. The involvement of body iron stores in the development of CAD remains controversial. So far, studies that examined hemoglobin and parameters of iron metabolism simultaneously do not exist. METHODS AND RESULTS Hemoglobin and iron status were determined in 1480 patients with stable angiographic coronary artery disease (CAD) and in 682 individuals in whom CAD had been ruled out by angiography. The multivariate adjusted odds ratios (OR) for CAD in the lowest quartiles of hemoglobin and iron were 1.62 (95%CI: 1.22-2.16), and 2.05 (95%CI: 1.51-2.78), respectively compared to their highest gender-specific quartiles. The fully adjusted ORs for CAD in the lowest quartiles of transferrin saturation, ferritin (F) and soluble transferrin receptor (sTfR)/log10F index were 1.69 (95%CI: 1.25-2.27), 1.98 (95%CI: 1.48-2.65), and 1.64 (95%CI: 1.23-2.18), respectively compared to their highest gender-specific quartiles. When adjusting in addition for iron and ferritin the OR for CAD in the lowest quartiles of hemoglobin was still 1.40 (95%CI: 1.04-1.90) compared to the highest gender-specific quartiles. Thus, the associations between either iron status or low hemoglobin and CAD appeared independent from each other. The sTfR was only marginally associated with angiographic CAD. CONCLUSIONS Both low hemoglobin and iron depletion are independently associated with angiographic CAD.

Nephrolithiasis-associated bone disease: pathogenesis and treatment options

Nephrolithiasis remains a formidable health problem in the United States and worldwide. A very important but underaddressed area in nephrolithiasis is the accompanying bone disease. Epidemiologic studies have shown that osteoporotic fractures occur more frequently in patients with nephrolithiasis than in the general population. Decreased bone mineral density and defects in bone remodeling are commonly encountered in patients with calcium nephrolithiasis. The pathophysiologic connection of bone defects to kidney stones is unknown. Hypercalciuria and hypocitraturia are two important risk factors for stone disease, and treatments with thiazide diuretics and alkali, respectively, have been shown to be useful in preventing stone recurrence in small prospective trials. However, no studies have examined the efficacy of these agents or other therapies in preventing continued bone loss in calcium stone formers. This manuscript reviews the epidemiology, pathophysiology, and potential treatments of bone disease in patients with nephrolithiasis.

Randomized trial of a computerized coronary heart disease risk assessment tool in HIV-infected patients receiving combination antiretroviral therapy

Exposure to combination antiretroviral therapy (cART) can lead to important metabolic changes and increased risk of coronary heart disease (CHD). Computerized clinical decision support systems have been advocated to improve the management of patients at risk for CHD but it is unclear whether such systems reduce patients' risk for CHD.

Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control

Since 1987, when bovine spongiform encephalopathy (BSE) emerged as a novel disease in cattle, enormous efforts were undertaken to monitor and control the disease in ruminants worldwide. The driving force was its high economic impact, which resulted from trade restrictions and the loss of consumer confidence in beef products, the latter because BSE turned out to be a fatal zoonosis, causing variant Creutzfeldt-Jakob disease in human beings. The ban on meat and bone meal in livestock feed and the removal of specified risk materials from the food chain were the main measures to successfully prevent infection in cattle and to protect human beings from BSE exposure. However, although BSE is now under control, previously unknown, so-called atypical transmissible spongiform encephalopathies (TSEs) in cattle and small ruminants have been identified by enhanced disease surveillance. This report briefly reviews and summarizes the current level of knowledge on the spectrum of TSEs in cattle and small ruminants and addresses the question of the extent to which such atypical TSEs have an effect on disease surveillance and control strategies.

Protocol for a population-based study of rheumatic heart disease prevalence and cardiovascular outcomes among schoolchildren in Nepal

Rheumatic heart disease (RHD) remains a major contributor to morbidity and mortality in developing countries. The reported prevalence rates of RHD are highly variable and mainly attributable to differences in the sensitivity of either clinical screening to detect advanced heart disease or echocardiographic evaluation where disease is diagnosed earlier across a continuous spectrum. The clinical significance of diagnosis of subclinical RHD by echocardiographic screening and early implementation of secondary prevention has not been clearly established. METHODS AND ANALYSIS: The authors designed a cross-sectional survey to determine the prevalence of RHD in children from private and public schools between the age of 5 and 15 years in urban and rural areas of Eastern Nepal using both cardiac auscultation and echocardiographic evaluation. Children with RHD will be treated with secondary prevention and enrolled in a prospective cohort study. The authors will compare the prevalence rates by cardiac auscultation and echocardiography, determine risk factors associated with diagnosis and progression of RHD, investigate social and economic barriers for receiving adequate cardiac care and assess clinical outcomes with regular medical surveillance as a function of stage of disease at the time of diagnosis. Prospective clinical studies investigating the impact of secondary prevention for subclinical RHD on long-term clinical outcome will be of central relevance for future health resource utilisation in developing countries. ETHICS AND DISSEMINATION: The study was considered ethically uncritical and was given an exempt status by the ethics committee at University of Bern, Switzerland. The study has been submitted to the National Nepal Health Research Council and was registered with http://www.ClinicalTrials.gov (NCT01550068). The study findings will be reported in peer-reviewed publications. CLINICALTRIALS.GOV IDENTIFIER: NCT01550068.

Cyclin D1 (CCND1) A870G gene polymorphism modulates smoking-induced lung cancer risk and response to platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients

PURPOSE: The cyclin D1 (CCND1) A870G gene polymorphism is linked to the outcome in patients with resectable non-small cell lung cancer (NSCLC). Here, we investigated the impact of this polymorphism on smoking-induced cancer risk and clinical outcome in patients with NSCLC stages I-IV. METHODS: CCND1 A870G genotype was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) of DNA extracted from blood. The study included 244 NSCLC patients and 187 healthy control subjects. RESULTS: Patient characteristics were: 70% male, 77% smokers, 43% adenocarcinoma, and 27% squamous cell carcinoma. Eighty-one percent of the patients had stages III-IV disease. Median age at diagnosis was 60 years and median survival was 13 months. Genotype frequencies of patients and controls both conformed to the Hardy Weinberg equilibrium. The GG genotype significantly correlated with a history of heavy smoking (>or=40 py, P=0.02), and patients with this genotype had a significantly higher cigarette consumption than patients with AA/AG genotypes (P=0.007). The GG genotype also significantly correlated with tumor response or stabilization after a platinum-based first-line chemotherapy (P=0.04). Survival analysis revealed no significant differences among the genotypes. CONCLUSION: Evidence was obtained that the CCND1 A870G gene polymorphism modulates smoking-induced lung cancer risk. Further studies are required to explore the underlying molecular mechanisms and to test the value of this gene polymorphism as a predictor for platinum-sensitivity in NSCLC patients.

[Urine analyses for workup of kidney stone disease--interpretation and therapeutic consequences]

Nephrolithiasis is a disease with a high and even rising incidence. It has a high morbidity, generates high costs and has a high recurrence rate. Urinalysis is of importance especially in recurrent stone formers. It allows the identification and quantification of risk factors and the establishment of individual risk profiles. Based on these individual risk profiles, rational therapy for metaphylaxis of kidney stones lowers stone recurrence rates significantly. This review article aims to give a focussed overview of the most important risk factors for kidney stones and reasonable urine tests for evaluation of recurrent kidney stone formers.

A coronary heart disease risk model for predicting the effect of potent antiretroviral therapy in HIV-1 infected men

BACKGROUND: Many HIV-infected patients on highly active antiretroviral therapy (HAART) experience metabolic complications including dyslipidaemia and insulin resistance, which may increase their coronary heart disease (CHD) risk. We developed a prognostic model for CHD tailored to the changes in risk factors observed in patients starting HAART. METHODS: Data from five cohort studies (British Regional Heart Study, Caerphilly and Speedwell Studies, Framingham Offspring Study, Whitehall II) on 13,100 men aged 40-70 and 114,443 years of follow up were used. CHD was defined as myocardial infarction or death from CHD. Model fit was assessed using the Akaike Information Criterion; generalizability across cohorts was examined using internal-external cross-validation. RESULTS: A parametric model based on the Gompertz distribution generalized best. Variables included in the model were systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, triglyceride, glucose, diabetes mellitus, body mass index and smoking status. Compared with patients not on HAART, the estimated CHD hazard ratio (HR) for patients on HAART was 1.46 (95% CI 1.15-1.86) for moderate and 2.48 (95% CI 1.76-3.51) for severe metabolic complications. CONCLUSIONS: The change in the risk of CHD in HIV-infected men starting HAART can be estimated based on typical changes in risk factors, assuming that HRs estimated using data from non-infected men are applicable to HIV-infected men. Based on this model the risk of CHD is likely to increase, but increases may often be modest, and could be offset by lifestyle changes.

Increased Framingham Coronary Heart Disease Risk Score in dementia caregivers relative to non-caregiving controls

BACKGROUND: Elderly individuals who provide care to a spouse suffering from dementia bear an increased risk of coronary heart disease (CHD). OBJECTIVE: To test the hypothesis that the Framingham CHD Risk Score would be higher in dementia caregivers relative to non-caregiving controls. METHODS: We investigated 64 caregivers providing in-home care for their spouse with Alzheimer's disease and 41 gender-matched non-caregiving controls. All subjects (mean age 70 +/- 8 years, 75% women, 93% Caucasian) had a negative history of CHD and cerebrovascular disease. The original Framingham CHD Risk Score was computed adding up categorical scores for age, blood lipids, blood pressure, diabetes, and smoking with adjustment made for sex. RESULTS: The average CHD risk score was higher in caregivers than in controls even when co-varying for socioeconomic status, health habits, medication, and psychological distress (8.0 +/- 2.9 vs. 6.3 +/- 3.0 points, p = 0.013). The difference showed a medium effect size (Cohen's d = 0.57). A relatively higher blood pressure in caregivers than in controls made the greatest contribution to this difference. The probability (area under the receiver operator curve) that a randomly selected caregiver had a greater CHD risk score than a randomly selected non-caregiver was 65.5%. CONCLUSIONS: Based on the Framingham CHD Risk Score, the potential to develop overt CHD in the following 10 years was predicted to be greater in dementia caregivers than in non-caregiving controls. The magnitude of the difference in the CHD risk between caregivers and controls appears to be clinically relevant. Clinicians may want to monitor caregiving status as a routine part of standard evaluation of their elderly patients' cardiovascular risk.

The relationship between pain intensity and severity and depression in older people: exploratory study

BACKGROUND: Pain and depression are known to be associated in later life, and both have a negative effect on physical performance both separately and in combination. The nature of the relationships between pain intensity and depression in elderly persons experiencing pain is less clear. The objectives of this study were to explore which factors are associated with depressed mood in older people experiencing pain, and to test the hypothesis that older people experiencing pain are at risk of depressed mood according to the severity or frequency of their pain. In addition we explored whether other potentially modifiable factors might increase the risk of depressed mood in these persons. METHODS: The study is a secondary analysis of baseline data for four hundred and six community-dwelling non-disabled people aged 65 and over registered with three group practices in suburban London who had experienced pain in the past 4 weeks. Intensity and frequency of pain was measured using 24 item Geriatric Pain Measure (GPM) and the presence of depressive symptoms using the 5 item Mental Health Inventory. Risk for social isolation was measured using the 6 item Lubben Social Network scale and instrumental activities of daily living (IADL) were also measured. RESULTS: Overall 76 (19%) had depressed mood. Pain frequency and severity were not statistically significantly associated with depressed mood in this population. In multivariate analyses, significant predictors of the presence of depressive symptoms were difficulties with basic ADLs (OR 2.8, 95% CI 1.1.7.8), risk for social isolation (OR 4.1, 95% CI 1.8-9.3), and basic education only (OR 2.2, 95% CI 1.1-4.4). CONCLUSION: Older people experiencing pain are also likely to experience depression. Among those experiencing pain, social network and functional status seem to be more important predictors of depressive symptoms than the severity of pain. Further studies should evaluate whether improvement of social network and functional status might reduce depressive symptoms in older patients.