Multimorbidity patterns in the elderly: a new approach of disease clustering identifies complex interrelations between chronic conditions

Objective

Multimorbidity is a common problem in the elderly that is significantly associated with higher mortality, increased disability and functional decline. Information about interactions of chronic diseases can help to facilitate diagnosis, amend prevention and enhance the patients'' quality of life. The aim of this study was to increase the knowledge of specific processes of multimorbidity in an unselected elderly population by identifying patterns of statistically significantly associated comorbidity.

Methods

Multimorbidity patterns were identified by exploratory tetrachoric factor analysis based on claims data of 63,104 males and 86,176 females in the age group 65+. Analyses were based on 46 diagnosis groups incorporating all ICD-10 diagnoses of chronic diseases with a prevalence ≥ 1%. Both genders were analyzed separately. Persons were assigned to multimorbidity patterns if they had at least three diagnosis groups with a factor loading of 0.25 on the corresponding pattern.

Results

Three multimorbidity patterns were found: 1) cardiovascular/metabolic disorders [prevalence female: 30%; male: 39%], 2) anxiety/depression/somatoform disorders and pain [34%; 22%], and 3) neuropsychiatric disorders [6%; 0.8%]. The sampling adequacy was meritorious (Kaiser-Meyer-Olkin measure: 0.85 and 0.84, respectively) and the factors explained a large part of the variance (cumulative percent: 78% and 75%, respectively). The patterns were largely age-dependent and overlapped in a sizeable part of the population. Altogether 50% of female and 48% of male persons were assigned to at least one of the three multimorbidity patterns.

Conclusion

This study shows that statistically significant co-occurrence of chronic diseases can be subsumed in three prevalent multimorbidity patterns if accounting for the fact that different multimorbidity patterns share some diagnosis groups, influence each other and overlap in a large part of the population. In recognizing the full complexity of multimorbidity we might improve our ability to predict needs and achieve possible benefits for elderly patients who suffer from multimorbidity.     

Assessment of Social Support and Its Association to Depression,Self-Perceived Health and Chronic Diseases in Elderly Individuals Residing in an Area of Poverty and Social Vulnerability in Rio de Janeiro City,Brazil

Objectives

Social support (SS) influences the elderly ability to cope with the losses of ageing process. This study was aimed at assessing SS among elderly users of a primary healthcare unit in a poor and violent area of Rio de Janeiro City, and at verifying its association with depression, self-perceived health (SPH), marital status and chronic illnesses.

Methods

A cross-sectional study was performed based on a convenience sample of 180 individuals aged 60 years or older. SS was measured with part of the Brazilian version of Medical Outcomes Study''s SS scale, and SPH and depression were assessed, respectively, through one question and the Brazilian version of the Structured Clinical Interview for DSM-IV Axis I Disorders. SS medians were calculated for the categories of SPH, depression, marital status and chronic illnesses variables, and differences were evaluated with the Kruskal-Wallis and Mann-Whitney tests. Additionally, Pearson''s chi-square test and logistic regression were employed to identify unadjusted and adjusted associations between SS and those variables.

Results

The participant’s mean age was 73 years old, and level of education was 3 years of school education on average. They were predominantly females (73.3%), and non-married (55.0%). Among them, 74.4% perceived their SS as satisfactory, 55.0% perceived their health as good, 27.8% were diagnosed with major depression and 83.3% had hypertension. Especially for those depressed and with bad SPH, the medians of SS measure were much lower than for others, reaching an unsatisfactory level. Moreover, controlling for other factors, non-depressed individuals were more likely (OR = 2.32) to have satisfactory SS.

Conclusion

in the violent and poor area explored in this research low SS is highly prevalent in the elderly. Depressed individuals are more likely to have low SS and this condition should be investigated in depressed elderly. The reduced scale is useful for low education individuals.     

Burden and Correlates of Geriatric Depression in the Uyghur Elderly Population,Observation from Xinjiang,China

Background

With the gradual aging of the population, geriatric depression has become a major public health issue in China owing to its overall upward trend and associated negative socio-economic impact. Dearth of information regarding the burden and correlates of geriatric depression among Uyghur minority population in Xinjiang Autonomous Region, called for a comprehensive survey involving representative sample for designing efficient targeted intervention to control this disabling disease.

Methods

A cross-sectional study was conducted among 1329 consenting Uyghur elderly in 2011 in six randomly selected communities/villages in Xinjiang. Information about socio-demographics, behavior, negative life-events, satisfaction regarding income/quality of life and other chronic diseases were collected while assessment of geriatric depression was done using Geriatric Mental State Schedule (GMS).

Results

Among these participants, majority were currently married, had attended elementary school or less, had an average annual family income of less than 3000 Yuan/person, had strong religious beliefs while 10.61% (2.77% in urban and 23.60% in rural area) had geriatric depression (5.91% among male and 14.58% among females). 61.83% were suffering from other chronic diseases, 96.16% could take care of themselves and 39.28% had experienced negative events during last two years. Religious belief (AOR = 3.92, 95% CI 1.18–13.03), satisfaction regarding quality of life (AOR = 0.53, 95% CI 0.37–0.84) and income (AOR = 0.75, 95% CI 0.35–1.60), suffering from more chronic diseases (AOR = 1.70, 95% CI 1.42–2.04), experiencing three or more negative events (AOR = 1.72, 95% CI 0.92–3.22) and lack of ability to take self-care (AOR = 2.20, 95% CI 1.09–4.48) were all associated with having geriatric depression with or without adjustment for gender, education and occupation.

Conclusion

High prevalence of geriatric depression among Uyghur elderly in Xinjiang seemed to call for urgent interventions, specifically targeting rural residents, who experienced more negative life-events, were suffering from chronic diseases and were dissatisfied with their income and quality of life.     

Changes of adult population health status in China from 2003 to 2008

Objectives

The purpose of this study was to examine the change in health status of China''s adult population between the years of 2003 and 2008 due to rapid economic growth and medical system improvement.

Methods

Data from the third and fourth Chinese national health services surveys covering 141,927 residents in 2003 and 136,371 residents in 2008 who were aged >18 years were analyzed.

Results

Chinese respondents in 2008 were more likely to report disease than in 2003. Smoking slightly decreased among men and women, and regular exercise showed much improvement. Stratified analyses revealed significant subpopulation disparities in rate ratios for 2008/2003 in the presence of chronic disease, with greater increases among women, elderly, the Han nationality, unmarried and widow, illiterate, rural, and regions east of China than other groups.

Conclusions

Chinese adults in 2008 had worse health status than in 2003 in terms of presence of chronic disease. China''s reform of health care will face more complex challenges in coming years from the deteriorating health status in Chinese adults.     

Risk Factors for Late-Life Cognitive Decline and Variation with Age and Sex in the Sydney Memory and Ageing Study

Introduction

An aging population brings increasing burdens and costs to individuals and society arising from late-life cognitive decline, the causes of which are unclear. We aimed to identify factors predicting late-life cognitive decline.

Methods

Participants were 889 community-dwelling 70–90-year-olds from the Sydney Memory and Ageing Study with comprehensive neuropsychological assessments at baseline and a 2-year follow-up and initially without dementia. Cognitive decline was considered as incident mild cognitive impairment (MCI) or dementia, as well as decreases in attention/processing speed, executive function, memory, and global cognition. Associations with baseline demographic, lifestyle, health and medical factors were determined.

Results

All cognitive measures showed decline and 14% of participants developed incident MCI or dementia. Across all participants, risk factors for decline included older age and poorer smelling ability most prominently, but also more education, history of depression, being male, higher homocysteine, coronary artery disease, arthritis, low health status, and stroke. Protective factors included marriage, kidney disease, and antidepressant use. For some of these factors the association varied with age or differed between men and women. Additional risk and protective factors that were strictly age- and/or sex-dependent were also identified. We found salient population attributable risks (8.7–49.5%) for older age, being male or unmarried, poor smelling ability, coronary artery disease, arthritis, stroke, and high homocysteine.

Discussion

Preventing or treating conditions typically associated with aging might reduce population-wide late-life cognitive decline. Interventions tailored to particular age and sex groups may offer further benefits.     

Do we protect or discriminate? Representation of senior adults in clinical trials

Aim

The analysis of barriers responsible for low recruitment of older patients in clinical trials and presentation of possible solutions are the subject of this review.

Background

Europe''s population is ageing, and the group of people who more frequently develop neoplasms increases. Oncologists are confronted with a new challenge – how to treat cancer in this group of patients, especially considering the lack of Evidence Based Medicine (EBM) guidelines for treatment of cancer in the elderly population.

Materials and methods

Medline search and analysis of studies published between 1999 and 2012, containing key words: senior adults, cancer, elderly in clinical trials.

Results

Detailed analysis of relevant studies demonstrated that senior adults are underrepresented in clinical trials. Moreover, there is a lack of trials exclusively designed for this heterogeneous group of patients. The analysis of reasons for low recruitment of older patients in clinical trials revealed barriers dependent on patient''s and physician''s attitudes as well as institutional and logistic problems.

Conclusions

It is necessary to widen the scale of trials of all phases in the group of seniors with appropriate assessment of toxicity. This will allow a proper stratification and obtaining representative groups for statistical analysis and credible trial results. Another priority is the design of trials dedicated exclusively to the elderly.     

The Trajectories and Correlation between Physical Limitation and Depression in Elderly Residents of Beijing, 1992-2009

Background

Physical limitation and psychological distress have been reported to be related, but studies describing the change of instrumental activities of daily living (IADLs) and depression syndrome over time or exploring the link pattern for their development are limited. The study was to assess distinctive patterns for the development of physical limitation and depression and to explore their correlation to form a proper prevention strategy.

Methods

Dual trajectory analysis was conducted using data from the Beijing Longitudinal Study of Aging (BLSA) 1992–2009 hosted by Xuanwu hospital for subjects with full information on depression and physical limitation for all available visits. Physical limitation was measured by the Instrumental Activities of Daily Living (IADL) scale and depression by the Center for Epidemiological Studies Depression scale (CES-D). The covariates were gender, age at baseline and number of chronic conditions.

Results

Three heterogeneous trajectories for physical limitation and two distinct groups for an increase in depression were detected. Among them, 10.13% of subjects experienced an increase in physical limitation, while 13.22% demonstrated a high, stable level of depressive mood. In all, 80.4% of the subjects enjoyed a relatively low, stable level of IADL and CES-D scores. People in the late increase group for IADL score were more likely to have depressive mood when adjusted for gender, age and number of chronic conditions (OR = 3.900, 95%CI = 1.347–11.290).

Conclusions

The development of physical limitation among the elderly may significantly increase the risk for depressive symptoms.     

Health Insurance Coverage and Its Impact on Medical Cost: Observations from the Floating Population in China

Background

China has the world''s largest floating (migrant) population, which has characteristics largely different from the rest of the population. Our goal is to study health insurance coverage and its impact on medical cost for this population.

Methods

A telephone survey was conducted in 2012. 644 subjects were surveyed. Univariate and multivariate analysis were conducted on insurance coverage and medical cost.

Results

82.2% of the surveyed subjects were covered by basic insurance at hometowns with hukou or at residences. Subjects'' characteristics including age, education, occupation, and presence of chronic diseases were associated with insurance coverage. After controlling for confounders, insurance coverage was not significantly associated with gross or out-of-pocket medical cost.

Conclusion

For the floating population, health insurance coverage needs to be improved. Policy interventions are needed so that health insurance can have a more effective protective effect on cost.     

Screening for Depression in Low-Income Elderly Patients at the Primary Care Level: Use of the Patient Health Questionnaire-2

Introduction

Depression is one of the most common mental disorders and a leading cause of disability worldwide. It constitutes a serious public health problem, particularly among elderly individuals. Most depressed elderly patients are treated by primary care (PC) physicians. The “Patient Health Questionnaire” (PHQ-2) is an instrument used for the detection of depression in PC settings.

Objective

Evaluate the performance of the PHQ-2 in a low-income and uneducated elderly PC population.

Methods

A non-probabilistic population sample of 142 individuals was selected from the healthcare unit''s users ≧60 years. Criterion validity was assessed by estimating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the PHQ-2 in comparison with the structured interview using the DSM-IV. The estimates of sensitivity and specificity were obtained from varying cut-offs of the PHQ-2 score. A Receiver Operator Characteristic (ROC) curve was constructed and the area under the curve (AUC) was calculated.

Results

The group was predominantly female (73.9%), with low education level (mean 3 years of schooling). The mean age was 72.5 years old. The prevalence of depression was 26.1%. The best values of sensitivity (0.74), specificity (0.77), PPV (0.50) e NPV (0.90) were obtained with score equal to 1. The AUC was 0.77, indicating a modest performance of the test accuracy.

Conclusion

The simplicity of the PHQ-2 is an advantage for its use in PC. The high NPV indicated that 90% of those who tested negative would not need additional tests. However, the low PPV indicated that the PHQ-2 is not sufficient to screen for depression. The application of the instrument could be the first step of the screening, that would include a second step to all those with positive tests formerly.     

A Study of Remitted and Treatment-Resistant Depression Using MMPI and Including Pessimism and Optimism Scales

Background

The psychological aspects of treatment-resistant and remitted depression are not well documented.

Methods

We administered the Minnesota Multiphasic Personality Inventory (MMPI) to patients with treatment-resistant depression (n = 34), remitted depression (n = 25), acute depression (n = 21), and healthy controls (n = 64). Pessimism and optimism were also evaluated by MMPI.

Results

ANOVA and post-hoc tests demonstrated that patients with treatment-resistant and acute depression showed similarly high scores for frequent scale (F), hypochondriasis, depression, conversion hysteria, psychopathic device, paranoia, psychasthenia and schizophrenia on the MMPI compared with normal controls. Patients with treatment-resistant depression, but not acute depression registered high on the scale for cannot say answer. Using Student''s t-test, patients with remitted depression registered higher on depression and social introversion scales, compared with normal controls. For pessimism and optimism, patients with treatment-resistant depression demonstrated similar changes to acutely depressed patients. Remitted depression patients showed lower optimism than normal controls by Student''s t-test, even though these patients were deemed recovered from depression using HAM-D.

Conclusions

The patients with remitted depression and treatment-resistant depression showed subtle alterations on the MMPI, which may explain the hidden psychological features in these cohorts.     

Alterations to the Frequency and Function of Peripheral Blood Monocytes and Associations with Chronic Disease in the Advanced-Age,Frail Elderly

Background

Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.

Design

In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81–100 yrs), and compared against that of adults (19–59 yrs), and community-dwelling seniors (61–76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases.

Results

The advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX₃CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX₃CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.

Conclusions

These data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation.     

Temperament Traits and Chronic Pain: The Association of Harm Avoidance and Pain-Related Anxiety

Objective

Anxiety symptoms are common in chronic pain patients. High levels of anxiety are associated with increased pain experience and disability. Proneness to anxiety has a large interindividual variation. The aim of the study was to determine whether the anxiety-related temperament trait Harm Avoidance (HA), is associated with pain-related anxiety.

Methods

One hundred chronic pain patients in a multidisciplinary pain clinic participated in the study. The patients were assessed using the HA scale of the Temperament and Character Inventory (TCI) of Cloninger and Pain Anxiety Symptoms Scale-20 (PASS-20). Both the HA total score and the four subscales of HA were analyzed. Current pain intensity was measured using the Visual Analogue Scale (VAS). The Beck Depression Inventory (BDI) was used to control for the influence of depression on the personality measurement.

Results

The HA total score was associated with PASS-20, but the association became non-significant after controlling for depression. The HA4 Fatigability subscale was associated with the PASS scales. Depression did not influence this association. Pain intensity was not correlated with HA or the PASS scales. However, the association between HA4 Fatigability and PASS was influenced by pain intensity. Higher pain intensity was associated with stronger association between the scales.

Conclusion

Harm Avoidance, representing temperament and trait-related anxiety, has relevance in pain-related anxiety. Assessing personality and temperament may deepen the clinician''s understanding of the pain experience and behavior in chronic pain patients.     

Prevalence of Chronic Conditions in Australia

Objectives

To estimate prevalence of chronic conditions among patients seeing a general practitioner (GP), patients attending general practice at least once in a year, and the Australian population.

Design, setting and participants

A sub-study of the BEACH (Bettering the Evaluation and Care of Health) program, a continuous national study of general practice activity conducted between July 2008 and May 2009. Each of 290 GPs provided data for about 30 consecutive patients (total 8,707) indicating diagnosed chronic conditions, using their knowledge of the patient, patient self-report, and patient''s health record.

Main outcome measures

Estimates of prevalence of chronic conditions among patients surveyed, adjusted prevalence in patients who attended general practice at least once that year, and national population prevalence.

Results

Two-thirds (66.3%) of patients surveyed had at least one chronic condition: most prevalent being hypertension (26.6%), hyperlipidaemia (18.5%), osteoarthritis (17.8%), depression (13.7%), gastro-oesophageal reflux disease (11.6%), asthma (9.5%) and Type 2 diabetes (8.3%). For patients who attended general practice at least once, we estimated 58.8% had at least one chronic condition. After further adjustment we estimated 50.8% of the Australian population had at least one chronic condition: hypertension (17.4%), hyperlipidaemia (12.7%), osteoarthritis (11.1%), depression (10.5%) and asthma (8.0%) being most prevalent.

Conclusions

This study used GPs to gather information from their knowledge, the patient, and health records, to provide prevalence estimates that overcome weaknesses of studies using patient self-report or health record audit alone. Our results facilitate examination of primary care resource use in management of chronic conditions and measurement of prevalence of multimorbidity in Australia.     

Tailored Implementation of Evidence-Based Practice for Patients with Chronic Diseases

Background

When designing interventions and policies to implement evidence based healthcare, tailoring strategies to the targeted individuals and organizations has been recommended. We aimed to gather insights into the ideas of a variety of people for implementing evidence-based practice for patients with chronic diseases, which were generated in five European countries.

Methods

A qualitative study in five countries (Germany, Netherlands, Norway, Poland, United Kingdom) was done, involving overall 115 individuals. A purposeful sample of four categories of stakeholders (healthcare professionals, quality improvement officers, healthcare purchasers and authorities, and health researchers) was involved in group interviews in each of the countries to generate items for improving healthcare in different chronic conditions per country: chronic obstructive pulmonary disease, cardiovascular disease, depression in elderly people, multi-morbidity, obesity. A disease-specific standardized list of determinants of practice in these conditions provided the starting point for these groups. The content of the suggested items was categorized in a pre-defined framework of 7 domains and specific themes in the items were identified within each domain.

Results

The 115 individuals involved in the study generated 812 items, of which 586 addressed determinants of practice. These largely mapped onto three domains: individual health professional factors, patient factors, and professional interactions. Few items addressed guideline factors, incentives and resources, capacity of organizational change, or social, political and legal factors. The relative numbers of items in the different domains were largely similar across stakeholder categories within each of the countries. The analysis identified 29 specific themes in the suggested items across countries.

Conclusion

The type of suggestions for improving healthcare practice was largely similar across different stakeholder groups, mainly addressing healthcare professionals, patient factors and professional interactions. As this study is one of the first of its kind, it is important that more research is done on tailored implementation strategies.     

Is Pain Intensity Really That Important to Assess in Chronic Pain Patients? A Study Based on the Swedish Quality Registry for Pain Rehabilitation (SQRP)

Background

Incorporating the patient''s view on care and treatment has become increasingly important for health care. Patients describe the variety of consequences of their chronic pain conditions as significant pain intensity, depression, and anxiety. We hypothesised that intensities of common symptoms in chronic pain conditions carry important information that can be used to identify clinically relevant subgroups. This study has three aims: 1) to determine the importance of different symptoms with respect to participation and ill-health; 2) to identify subgroups based on data concerning important symptoms; and 3) to determine the secondary consequences for the identified subgroups with respect to participation and health factors.

Methods and Subjects

This study is based on a cohort of patients referred to a multidisciplinary pain centre at a university hospital (n = 4645, participation rate 88%) in Sweden. The patients answered a number of questionnaires concerning symptoms, participation, and health aspects as a part of the Swedish Quality Registry for Pain Rehabilitation (SQRP).

Results

Common symptoms (such as pain intensity, depression, and anxiety) in patients with chronic pain showed great variability across subjects and 60% of the cohort had normal values with respect to depressive and anxiety symptoms. Pain intensity more than psychological symptoms showed stronger relationships with participation and health. It was possible to identify subgroups based on pain intensity, depression, and anxiety. With respect to participation and health, high depressive symptomatology had greater negative consequences than high anxiety.

Conclusions

Common symptoms (such as pain intensity and depressive and anxiety symptoms) in chronic pain conditions carry important information that can be used to identify clinically relevant subgroups.     

Differentiating the Cognitive Profile of Schizophrenia from That of Alzheimer Disease and Depression in Late Life

Background

To compare the cognitive profile of older patients with schizophrenia to those with other neuropsychiatric disorders assessed in a hospital-based memory clinic.

Methods

Demographic, clinical, and cognitive data of all patients referred to the memory clinic at the Centre for Addiction and Mental Health between April 1, 2006 and August 15, 2008 were reviewed. We then identified four groups of older patients with: (1) late-life schizophrenia (LLS) and no dementia or depression (DEP); (2) Alzheimer''s disease (AD); (3) DEP and no dementia or LLS; (4) normal cognition (NC) and no DEP or LLS.

Results

The four groups did not differ in demographic data except that patients with AD were about 12 years older than those with LLS. However, they differed on cognitive tests even after controlling for age. Patients with LLS were impaired on most cognitive tests in comparison with patients with NC but not on recalling newly learned verbal information at a short delay. They experienced equivalent performance on learning new verbal information in comparison with patients with AD, but better performance on all other tests of memory, including the ability to recall newly learned verbal information. Finally, they were more impaired than patients with DEP in overall memory.

Conclusions

Patients with LLS have a different cognitive profile than patients with AD or DEP. Particularly, memory impairment in LLS seems to be more pronounced in learning than recall. These findings suggest that cognitive and psychosocial interventions designed to compensate for learning deficits may be beneficial in LLS.     

Systemic inflammation,depression and obstructive pulmonary function: a population-based study

Background

Levels of Interleukin-6 (IL-6) and C-creative protein (CRP) indicating systemic inflammation are known to be elevated in chronic diseases including chronic obstructive pulmonary disease (COPD) and depression. Comorbid depression is common in patients with COPD, but no studies have investigated whether proinflammatory cytokines mediate the association between pulmonary function and depressive symptoms in healthy individuals with no known history of obstructive pulmonary diseases.

Methods

In a population-based sample (n = 2077) of individuals aged 55 and above with no known history of obstructive pulmonary disease in the Singapore Longitudinal Ageing Study (SLAS), we analyzed the relationships between IL-6 and CRP, depressive symptoms (GDS-15 ≥5) and obstructive pulmonary function (FEV1% predicted and FEV1/FVC% predicted).

Results

High serum levels of IL-6 and CRP were associated with greater prevalence of depressive symptoms (p < 0.05). High IL-6, high CRP and depressive symptoms were independently associated with decreased FEV1% predicted and FEV1/FVC% predicted after adjusting for smoking status, BMI and number of chronic inflammatory diseases. Increasing grades of combination of inflammatory markers and/or depressive symptoms was associated with progressive increases in pulmonary obstruction. In hierarchical models, the significant association of depressive symptoms with pulmonary obstruction was reduced by the presence of IL-6 and CRP.

Conclusions

This study found for the first time an association of depressive symptoms and pulmonary function in older adults which appeared to be partly mediated by proinflammatory cytokines. Further studies should be conducted to investigate proinflammatory immune markers and depressive symptoms as potential phenotypic indicators for chronic obstructive airway disorders in older adults.     

Chronic delivery of antibody fragments using immunoisolated cell implants as a passive vaccination tool

Background

Monoclonal antibodies and antibody fragments are powerful biotherapeutics for various debilitating diseases. However, high production costs, functional limitations such as inadequate pharmacokinetics and tissue accessibility are the current principal disadvantages for broadening their use in clinic.

Methodology and Principal Findings

We report a novel method for the long-term delivery of antibody fragments. We designed an allogenous immunoisolated implant consisting of polymer encapsulated myoblasts engineered to chronically release scFv antibodies targeted against the N-terminus of the Aβ peptide. Following a 6-month intracerebral therapy we observed a significant reduction of the production and aggregation of the Aβ peptide in the APP23 transgenic mouse model of Alzheimer''s disease. In addition, functional assessment showed prevention of behavioral deficits related to anxiety and memory traits.

Conclusions and Significance

The chronic local release of antibodies using immunoisolated polymer cell implants represents an alternative passive vaccination strategy in Alzheimer''s disease. This novel technique could potentially benefit other diseases presently treated by local and systemic antibody administration.     

Cysteamine attenuates the decreases in TrkB protein levels and the anxiety/depression-like behaviors in mice induced by corticosterone treatment

Objective

Stress and glucocorticoid hormones, which are released into the circulation following stressful experiences, have been shown to contribute significantly to the manifestation of anxiety-like behaviors observed in many neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays an important role in stress-mediated changes in structural as well as functional neuroplasticity. Studies designed to elucidate the mechanisms whereby TrkB signaling is regulated in chronic stress might provide valuable information for the development of new therapeutic strategies for several stress-related psychiatric disorders.

Materials and Methods

We examined the potential of cysteamine, a neuroprotective compound to attenuate anxiety and depression like behaviors in a mouse model of anxiety/depression induced by chronic corticosterone exposure.

Results

Cysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus. Furthermore, cysteamine treatment reversed the anxiety and depression like behavioral abnormalities induced by chronic corticosterone treatment. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine.

Conclusions

The animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders.     

Reproducibility and Respiratory Function Correlates of Exhaled Breath Fingerprint in Chronic Obstructive Pulmonary Disease

Background

The electronic nose (e nose) provides distinctive breath fingerprints for selected respiratory diseases. Both reproducibility and respiratory function correlates of breath fingerprint are poorly known.

Objectives

To measure reproducibility of breath fingerprints and to assess their correlates among respiratory function indexes in elderly healthy and COPD subjects.

Method

25 subjects (5 COPD patients for each GOLD stage and 5 healthy controls) over 65 years underwent e-nose study through a seven sensor system and respiratory function tests at times 0, 7, and 15 days. Reproducibility of the e nose pattern was computed. The correlation between volatile organic compound (VOC) pattern and respiratory function/clinical parameters was assessed by the Spearman''s rho.

Measurements and Main Results

VOC patterns were highly reproducible within healthy and GOLD 4 COPD subjects, less among GOLD 1–3 patients.VOC patterns significantly correlated with expiratory flows (Spearman''s rho ranging from 0.36 for MEF25% and sensor Co-Buti-TPP, to 0.81 for FEV1% and sensor Cu-Buti-TPP p<0.001)), but not with residual volume and total lung capacity.

Conclusions

VOC patterns strictly correlated with expiratory flows. Thus, e nose might conveniently be used to assess COPD severity and, likely, to study phenotypic variability. However, the suboptimal reproducibility within GOLD 1–3 patients should stimulate further research to identify more reproducible breath print patterns.