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1.  Validation study of the prototype of a disease-specific index measure for health-related quality of life in dementia 
Index measures for health-related quality of life (HRQoL) quantify the desirability (utility) of a certain health state. The commonly used generic index measure, e.g. EuroQol: EQ-5D, may underestimate relevant areas of specific diseases, resulting in lower validity. Disease-specific index measures on the other hand combine disease-specificity and quantification of perceived quality on several health domains of a certain disease into one single figure. These instruments have been developed for several diseases, but a dementia-specific HRQoL index instrument was not yet available. Facing the increasing individual and societal burden of dementia, specific HRQoL values with metric characteristics are especially useful because they will provide vital information for health outcome research and economic evaluations.
Aims of the study
To develop and validate the prototype of a dementia-specific HRQoL index measure: Dementia Quality of life Instrument (DQI), as the first step towards valuation of the dementia health state.
For development of the DQI we created a conceptual framework based on a review of the literature, qualitative interviews with people with dementia and their carers, expert opinion and team discussion. To assess validity we undertook a survey under 241 dementia professionals. Measurements consisted of ranking (1–5) and rating (1–10) of 5 dementia-specific DQI domains (memory, orientation, independence, social activities and mood) and simultaneously rating of 9 DQI-derived health states on a visual analogue scale (VAS). We also performed a cross-sectional study in a large sample of people with very mild to moderate dementia and their caregivers (N = 145) to assess feasibility and concurrent validity. In addition, caregivers valued 10 DQI and 10 EQ-5D + C derived health states of the patient simultaneously on the same VAS. Setting: outpatient clinics, nursing homes and patient residences.
All professionals judged the selected DQI domains to be relevant. Differences in ranking and rating behaviors were small. Mood was ranked (≥3.3) and rated (≥8.2) as most, orientation as least important (rank ≤2.6, value 7.5) health domain for dementia. For the validation part of this study the completion rates for all domains were above 98% for patients and 100% for caregivers on patients. A priori hypothesized DQI versus QOL-AD correlations that were significant in both patients and caregivers were: memory/memory, orientation/memory, independence/physical health, social activities/energy and mood/mood. Patient/caregiver inter-rater agreement was low (K < 0.2) for memory/independence, fair (K 0.2-0.4) for orientation/mood, and moderate (K 0.4-0.6) for social activities. Concurrent validity of the DQI with the EQ-5D + C was moderate. The fact that most of the correlations between the domains of these two instruments were low (≤0.40) showed that both instruments measure different elements of health status. As expected, modest correlations (≥0.40) were observed between corresponding domains of the two instruments.
Professionals judged all domains as relevant. The DQI prototype proved valid and feasible for patients and caregivers and is appropriate for very mild to moderate dementia. The differences in concurrent correlations with generic health status instruments imply that the dementia-specific DQI health domains indeed provide different information. The finding that patient HRQoL measured with the DQI was lower supports this notion. The new DQI shows comparable psychometric properties to the best available dementia-specific (QOL-AD) and generic (EQ-5D + C) measures. Further research is needed to generate values in the general population for each of the possible DQI states and to derive an algorithm that converts the 5 separate DQI domain scores into one single DQI Index score. Introducing the DQI Index will advance dementia-related HRQoL measurement by overcoming the shortcomings of generic and non-index instruments. This will allow more unequivocal interpretation of subjective dementia HRQoL states in dementia research.
PMCID: PMC3503596  PMID: 23009579
Dementia; Health-related quality of life; Dementia Quality of life Instrument (DQI); Disease-specific index instrument; Cost-effectiveness
2.  Assessing health-related quality-of-life changes in informal caregivers: an evaluation in parents of children with major congenital anomalies 
Quality of Life Research  2011;21(5):849-861.
Relatively few attempts to measure the effects on the health-related quality of life (HRQoL) of informal caregivers within the context of economic evaluations have been reported. This paper is an exploratory attempt to find suitable methods to assess caregivers’ HRQoL, using a population of parents of children with major congenital anomalies.
A total of 306 parents of children born with either congenital anorectal malformations (ARM) or congenital diaphragmatic hernia were surveyed. They rated their current HRQoL on the EQ-VAS. After that, they rated their HRQoL again on the assumption that someone would take over their caregiving activities completely and free of charge. Finally, the parents classified their HRQoL on the EQ-5D. The caregivers’ scores on the EQ-VAS and the EQ-5D were compared with scores elicited in the general population.
Most parents indicated that their HRQoL would not change if someone else took on their caregiving activities. Some methodological issues may have influenced this outcome, such as difficulties in self-assessing HRQoL changes due to caregiving, process utility, protest answers, and difficulties in understanding the hypothetical question. The HRQoL of the parents was relatively low compared with population statistics, especially in the parents of children with ARM and in mothers. This can be illustrated by the difference between the mean EQ-5D score of the mothers aged 25–34 years of the children with ARM and that of the general population (0.83 vs. 0.93; P = 0.002).
Significant HRQoL differences exist between parents caring for children with congenital anomalies and the general population. It would be useful to further improve our understanding of the HRQoL impact of informal caregiving, separating ‘caregiving effects’ from ‘family effects’, and distinguishing parent–child relationships from other caregiving situations. This study underlines the importance of considering caregivers, also in the context of economic evaluations. It indicates that general HRQoL measures, as used in patients, may be able to detect HRQoL effects in caregivers, which facilitates the incorporation in common economic evaluations of HRQoL effects in carers. Analysts and policy makers should be aware that if HRQoL improvement is an important aim, they should register HRQoL changes not only in patients but also in their caregivers.
PMCID: PMC3348487  PMID: 21858419
Economic evaluation; Valuation of informal care; Methodology; Quality of life; Neonatal surgery
3.  Relation of Health-Related Quality of Life to Metabolic Syndrome, Obesity, Depression, and Comorbid Illnesses 
Metabolic syndrome has been associated with impaired health-related quality of life (HRQoL) in several studies. Many studies used only one HRQoL measure and failed to adjust for important confounding variables including obesity, depression, and comorbid conditions.
To investigate the relationship between metabolic syndrome and HRQoL using multiple measures. We also sought to determine whether increasing body mass index (BMI) or diabetes status further modified this relationship.
This cross-sectional study included 390 obese participants with elevated waist circumference and at least one other criterion for metabolic syndrome. Of these 390, 269 had metabolic syndrome [i.e., met 3 out of 5 criteria specified by the National Cholesterol Education Program (NCEP)] and 121 did not. Participants were enrolled in a primary-care based weight reduction trial. HRQoL was assessed using two generic instruments, the Medical Outcomes Study Short-Form 12 (SF-12) and the EuroQol-5D (EQ-5D), as well as an obesity-specific measure, the Impact of Weight on Quality of Life (IWQoL-Lite). Differences in HRQoL were compared among participants with and without metabolic syndrome. Multivariable linear regression was used to determine how HRQoL varied according to metabolic syndrome status, and whether factors including weight, depression, and burden of comorbid disease modified this relationship.
Metabolic syndrome was not associated with HRQoL as assessed by any of the measures. In univariable analysis, depression, disease burden, and employment status were significantly associated with worse HRQoL on all instruments. In the multivariable models, only depression remained significantly associated with reduced HRQoL on all measures. Increasing obesity and diabetes status did not modify the relationship between metabolic syndrome and HRQoL.
In contrast to previous studies, metabolic syndrome was not associated with impaired HRQoL as assessed by multiple measures. This suggests that metabolic syndrome in itself is not associated with decreased HRQoL, but other factors such as obesity, depression, and greater disease burden may significantly influence quality of life in this population.
PMCID: PMC3085045  PMID: 21042326
metabolic syndrome; obesity; health-related quality of life
4.  What determines health-related quality of life among people living with HIV: an updated review of the literature 
Archives of Public Health  2014;72(1):40.
As infection with the Human Immunodeficiency Virus (HIV) has evolved to a chronic disease, perceived health-related quality of life (HRQoL) is becoming a prominent and important patient-reported outcome measure in HIV care. Literature discusses different factors influencing HRQoL in this population, however, currently no consensus exists about the main determinants. In this review a clear, up-to-date overview of the determinants influencing HRQOL among people living with HIV is provided.
All studies published before July 2013 that identified determinants of HRQoL among people living with HIV in high-income countries, were considered in this narrative review. PubMed, Web of Science and The Cochrane Library were consulted using the keywords ‘determinants’, ‘quality of life’, ‘HIV’ and ‘AIDS’. To be included, studies should have reported overall health and/or physical/mental health scores on a validated instrument and performed multivariable regression analyses to identify determinants that independently influence perceived HRQoL.
In total, 49 studies were included for further analysis and they used a variety of HRQoL instruments: Medical Outcomes Study Short Form-36 or variants, Medical Outcomes Study-HIV, HIV Cost and Services Utilization Study measure, Multidimensional Quality of Life Questionnaire, HIV targeted quality of life instrument, Functional Assessment of Human Immunodeficiency Virus Infection, HIV Overview of Problems Evaluation System, EuroQol, Fanning Quality of Life scale, Health Index and PROQOL-HIV. In this review, the discussed determinants were thematically divided into socio-demographic, clinical, psychological and behavioural factors. Employment, immunological status, presence of symptoms, depression, social support and adherence to antiretroviral therapy were most frequently and consistently reported to be associated with HRQoL among people living with HIV.
HRQoL among people living with HIV is influenced by several determinants. These determinants independently, but simultaneously impact perceived HRQoL. Most HRQoL instruments do not capture all key determinants. We recommend that the choice for an instrument should depend on the purpose of the HRQoL assessment.
Electronic supplementary material
The online version of this article (doi:10.1186/2049-3258-72-40) contains supplementary material, which is available to authorized users.
PMCID: PMC4323115  PMID: 25671112
HIV; Acquired immunodeficiency syndrome; Quality of life; Epidemiologic factors; Review
5.  Quality of life in dementia: a study on proxy bias 
Measurement of health-related quality of life (HRQoL) in dementia is difficult. At some point people with dementia become unable to meaningfully assess their own HRQoL. At such a point in time researchers need to rely on other types of information such as observation or assessments from informal caregivers (proxies). However, caregiver assessments may be biased by several mechanisms. The current study explores whether caregivers project part of their own HRQoL in their assessments of patient HRQoL.
The participants in the current study were 175 pairs, consisting of community-dwelling persons with dementia and their caregivers. The EQ-5D, the EQ-VAS and the QoL-AD were administered to collect HRQoL measurements from patients and caregivers at baseline, 6 months and 12 months. Two linear mixed models were used to investigate factors that bias proxy ratings, one with the EQ-VAS as dependent variable, and one with the EQ-5D utility as dependent variable. The independent variables were caregiver age, caregiver sex and caregiver QoL-AD items.
The linear mixed model with EQ-VAS as dependent variable indicated that 3 caregiver characteristics, namely caregiver age, money (caregiver’s financial situation) and valuation of life as a whole were significant predictors of the patient-by-proxy VAS scores. The linear mixed model with utility value as the dependent variable showed that caregiver age and valuation of the ability to do things for fun were significant predictors of the patient-by-proxy EQ-5D utility values.
The current study was a first step in identifying factors that bias patient-by-proxy HRQoL assessments. It was discovered that caregivers project part of their own HRQoL onto patients when assessing patient HRQoL. This implies that patient-by-proxy HRQoL values should be interpreted with caution and not be used as a direct substitute for patient self-assessment, even when patients are no longer able meaningfully assess themselves.
PMCID: PMC3844427  PMID: 24011428
6.  The Impact of Bronchopulmonary Dysplasia on Caregiver Health Related Quality of Life during the First Two Years of Life 
Pediatric pulmonology  2012;48(6):579-586.
Preterm children with bronchopulmonary dysplasia (BPD) frequently require complex home medical regimens and re-hospitalization during the first two years of life. The burden of caring for these medically complex children may negatively affect caregiver health related quality of life (HRQoL). The objectives of this study were to measure caregiver HRQoL of children with BPD and to identify factors that impact caregiver HRQoL during the first two years of life.
Children (n=186) were recruited from the Johns Hopkins BPD Outpatient Clinic between January 2008 and July 2011. Caregiver HRQoL was measured using The PedsQL™ Family Impact Module. Respiratory symptoms and morbidities were assessed using questionnaires.
Among caregivers of BPD children, significant improvement in physical, worry and daily domains improved longitudinally as children aged. An association was found between lower total HRQoL scores and caregivers of BPD children who reported more respiratory symptoms and acute care usage. No difference in total HRQoL scores was found between caregivers of BPD children requiring respiratory/enteral support and caregivers of children who did not. Caregiver income and educational level did not predict total HRQoL score, but Non-White race and public insurance was associated with a higher total HRQoL score at the first outpatient visit.
An association was found between lower HRQoL scores and caregivers of BPD children with frequent respiratory symptoms and acute care usage. Screening for low HRQoL in caregivers of BPD children with frequent respiratory illnesses should be considered to identify those who may benefit from additional support and intervention.
PMCID: PMC4088258  PMID: 23129398
Prematurity; Bronchopulmonary Dysplasia; Caregivers; Health Related Quality of Life
7.  Associations between demographic, disease related, and treatment pathway related variables and health related quality of life in primary care patients with coronary heart disease 
Coronory heart disease (CHD) is a common medical problem worldwide that demands shared care of general practitioners and cardiologists for concerned patients. In order to improve the cooperation between both medical specialists and to optimize evidence-based care, a treatment pathway for patients with CHD was developed and evaluated in a feasibility study according to the recommendation for the development and evaluation of complex interventions of the British Medical Research Council (MRC). In the context of this feasibility study the objective of the present research was to investigate the contributions of different disease related (e.g. prior myocardial infarction), pathway related (e.g. basic medication) and demographic variables on patients` perceived health related quality of life (HRQoL) as a relevant and widely used outcome measure in cardiac populations.
Data assessing demographic, disease and pathway related variables of CHD patients included in the study were collected in a quasi-experimental design with three study arms (pathway developers, users, control group) via case record forms and questionnaires at baseline and after 6 and 12 (intervention groups), and 9 months (control group), respectively after the initial implementation on GP level. Additionally, at the same measuring points the CHD patients participating in the study were interviewed by phone regarding their perceived HRQoL, measured with the EuroQol EQ-5D as an index-based health questionnaire. Due to the hierarchical structure of the data, we performed cross-sectional and longitudinal linear mixed models to investigate the impact of disease related, pathway related and demographic variables on patients` perceived HRQoL.
Of 334 initially recruited patients with CHD, a total of 290 were included in our analysis. This was an average 13.2% dropout rate from baseline assessment to the 12-month follow-up. At all assessment points, patients` HRQoL was associated with a variety of sociodemographic variables (e.g. gender, employment, education) in each study group, but there was no association with pathway related variables. In both cross-sectional and longitudinal analyses highest HRQoL values in patients were reported in the physician group that had developed the pathway. In the longitudinal analyses there were no significant changes in the reported HRQoL values of the three groups over time.
The found associations between sociodemographic variables and the perceived HRQoL of patients with CHD are in line with other research. As there are no associations of HRQoL with pathway related variables like the basic medication, possible weaknesses in the study design or the choice of outcome have to be considered before planning and conducting an evaluation study according to the MRC recommendations. Additionally, as patients in the developer group reported the highest HRQoL values over time, a higher commitment of the GPs in the developer group can be assumed and should be considered in further research.
PMCID: PMC3464887  PMID: 22776102
Coronary artery disease; Quality of life; Multilevel analyses; Critical pathways
8.  The impact of biologics on health-related quality of life in patients with inflammatory bowel disease 
Inflammatory bowel disease (IBD) is characterized by a chronic relapsing inflammation of the gastrointestinal tract. Adult IBD patients suffer from a disabling disease which greatly affects health-related quality of life (HRQoL). A worse HRQoL in these patients may result in a defensive and ineffective use of medical attention and thus higher medical costs. Because of its chronic nature, IBD may also cause psychological problems in many patients which may also influence HRQoL and care-seeking behavior. An important factor reducing HRQoL is disease activity. Induction of remission and long-term remission are important goals for improving HRQoL. Furthermore, remission is associated with a decreased need for hospitalization and surgery and increased employment, which in turn improve HRQoL. Treatment strategies available for many years are corticosteroids, 5-aminosalicylates and immunnosuppressants, but these treatments did not show significant long-term improvement on HRQoL. The biologics, which induce rapid and sustained remission, may improve HRQoL.
To review and evaluate the current literature on the effect of biologics on HRQoL of IBD patients.
We performed a MEDLINE search and reviewed the effect of different biologics on HRQoL. The following subjects and synonyms of these terms were used: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, quality of life, health-related quality of life, fatigue, different anti-TNF medication, and biologicals/biologics (MESH). Studies included were limited to English-language, adult population, full-text, randomized, double-blind, placebo-controlled in which HRQoL was measured.
Out of 202 identified articles, 8 randomized controlled trials (RCT) met the inclusion criteria. Two RCTs on infliximab showed significant improvement of HRQoL compared to placebo which was sustained over the long term. One RCT on adalimumab showed a significant and sustained improvement of HRQoL compared to placebo. This study showed also significant decrease of fatigue in the adalimumab-treated patients. Three RCTs on certolizumab showed a significant improvement of HRQoL in the intervention group compared to placebo. Two RCTs of natalizumab treatment were found. One study showed significant and sustained improvement compared to placebo, and also scores of HRQoL comparable to that in the general population, but in the other no significant results were found.
The biologics infliximab, adalimumab, certolizumab, and natalizumab demonstrated significant improvement of HRQoL of IBD patients compared with placebo. However, we found differences in improvement of HRQoL between the different biologics.
PMCID: PMC3108643  PMID: 21694833
inflammatory bowel disease; health-related quality of life; health care costs; biologics
9.  Is progression-free survival associated with a better health-related quality of life in patients with lung cancer? Evidence from two randomised trials with afatinib 
BMJ Open  2014;4(10):e005762.
Progression-free survival (PFS) is frequently used as an efficacy end point in oncology clinical trials. However, there is limited evidence to support a positive association between improvement in PFS and improvement in health-related quality of life (HRQoL). The association between PFS and HRQoL was evaluated in two randomised trials.
Materials and methods
Data from two randomised controlled trials in patients with non-small cell lung cancer (NSCLC; LUX-Lung 1 and LUX-Lung 3) were used to investigate HRQoL in patients to determine whether tumour progression is accompanied by worsening HRQoL. HRQoL was assessed using the cancer-specific European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30, the EuroQol EQ-5D overall utility and EuroQol EQ visual analogue scale. In both studies, progression was evaluated by independent review using RECIST criteria (primary end point) and also by investigator assessment. The relationship between tumour progression and HRQoL was evaluated using analysis of covariance and a longitudinal model.
Compliance with HRQoL questionnaire completion was high. In both studies, patients with progression consistently experienced numerically poorer HRQoL at the time of progression than patients without progression. Differences in mean scores were statistically significant (p<0.05) between patients with and without progression at week 4 in all analyses in LUX-Lung 1 and at multiple time points in LUX-Lung 3. Results from the longitudinal analysis showed that progression (by independent review and investigator assessment) appears to have consistent negative impact on all three HRQoL measures (all p<0.0001).
Tumour progression in patients with NSCLC was associated with statistically significant worsening in HRQoL. These findings confirm the value of PFS as a patient-relevant end point.
PMCID: PMC4216861  PMID: 25361836
10.  Physical activity and health related quality of life 
BMC Public Health  2012;12:624.
Research on the relationship between Health Related Quality of Life (HRQoL) and physical activity (PA), to date, have rarely investigated how this relationship differ across objective and subjective measures of PA. The aim of this paper is to explore the relationship between HRQoL and PA, and examine how this relationship differs across objective and subjective measures of PA, within the context of a large representative national survey from England.
Using a sample of 5,537 adults (40–60 years) from a representative national survey in England (Health Survey for England 2008), Tobit regressions with upper censoring was employed to model the association between HRQoL and objective, and subjective measures of PA controlling for potential confounders. We tested the robustness of this relationship across specific types of PA. HRQoL was assessed using the summary measure of health state utility value derived from the EuroQol-5 Dimensions (EQ-5D) whilst PA was assessed via subjective measure (questionnaire) and objective measure (accelerometer- actigraph model GT1M). The actigraph was worn (at the waist) for 7 days (during waking hours) by a randomly selected sub-sample of the HSE 2008 respondents (4,507 adults – 16 plus years), with a valid day constituting 10 hours. Analysis was conducted in 2010.
Findings suggest that higher levels of PA are associated with better HRQoL (regression coefficient: 0.026 to 0.072). This relationship is consistent across different measures and types of PA although differences in the magnitude of HRQoL benefit associated with objective and subjective (regression coefficient: 0.047) measures of PA are noticeable, with the former measure being associated with a relatively better HRQoL (regression coefficient: 0.072).
Higher levels of PA are associated with better HRQoL. Using an objective measure of PA compared with subjective shows a relatively better HRQoL.
PMCID: PMC3490805  PMID: 22871153
Health related Quality of Life; Objective measure; Self reports; Physical activity; EQ-5D
11.  Underlying Dimensions of the Five Health-Related Quality-of-Life Measures Used in Utility Assessment 
Medical care  2010;48(8):718-725.
Preference-weighted health-related quality-of-life (HRQoL) indexes produce a summary score from discrete health states determined by questions falling into several attributes, such as pain and mobility. Values of HRQoL are used alongside other health outcomes to monitor the health of populations.
The purpose of this study was to examine among US adults, the underlying factor structure of HRQoL attribute scores across 5 indexes of HRQoL: EuroQol-5 Dimension, Health Utilities Index Mark 2, Health Utilities Index Mark 3, Short Form-6 Dimension, and Quality of Well-Being Scale Self-Administered form.
The National Health Measurement Study surveyed a nationally representative sample of 3844 noninstitutionalized adults aged 35 to 89 years residing in the continental US. Simultaneous data on all 5 indexes were collected cross-sectionally from June 2005 to August 2006. Exploration of underlying dimensions of HRQoL was done by categorical exploratory factor analysis of HRQoL indexes' attribute scores. Item response theory was applied to explore the amount of information HRQoL attributes contribute to the underlying latent dimensions.
Three main dimensions of HRQoL emerged: physical, psychosocial, and pain. Most HRQoL index attributes contributed to the physical or psychosocial dimension. The 3 dimensions were correlated: 0.47 (physical and psychosocial), 0.57 (physical and pain), 0.46 (psychosocial and pain). Some HRQoL index attributes displayed relatively more unique variance: HUI3 hearing, speech, and vision, and some contributed to more than 1 dimension The identified factor structure fit the HRQoL data well (Comparative Fit Index = 0.98, Tucker-Lewis Index = 0.98, and Root Mean Square Error of Approximation = 0.042).
The attributes of 5 commonly used HRQoL indexes share 3 underlying latent dimensions of HRQoL, physical, psychosocial, and pain.
PMCID: PMC3635481  PMID: 20613664
health-related quality-of-life; patient reported outcomes; factor analysis; item response theory; health dimensions; EQ-5D; HUI2; HUI3; SF-6D; QWB-SA
12.  Exploring health-related quality of life in eating disorders by a cross-sectional study and a comprehensive review 
BMC Psychiatry  2014;14:165.
People with eating disorders (ED) often report poor health-related quality of life (HRQoL), which is explicitly correlated to illness’ severity and its effects on cognitive performance. We aimed to analyze health-related quality of life (HRQoL) in subgroups of eating disorder (ED) patients by using the brief version of WHOQoL questionnaire (WHOQoL-BREF) before treatment administration. Moreover, in order to compare our findings with other published data, we carried out a comprehensive review of the literature on HRQoL in ED patients.
Our review was carried out by means of an accurate data mining of PsychInfo and Medline databases and other available sources. In our cross-sectional study, eighty female ED patients (26 with bulimia nervosa, 33 with anorexia nervosa, 7 with binge eating disorder and 14 with ED not otherwise specified) completed the WHOQoL-BREF. HRQoL scores were compared among ED subgroups and clinical information (presence of previous contacts, length of illness, psychiatric comorbidity) was considered in the analysis.
Our review shows that with few exceptions ED patients have a poorer HRQoL than the healthy population of control and sometimes the mental component of HRQoL is the most involved dimension. Moreover, there are no differences in the HRQoL among ED groups, even if AN patients in some studies have a lower HRQoL scores. Furthermore, BED patients have a poorer HRQoL than obese patients who do not have binge episodes. Finally, all treatments were positively correlated with an improvement on general and specific QoL dimensions. In our sample, ED subgroups differed only for Psychological Health HRQoL scores (F = 4.072, df = 3; p = 0.01). No differences were found between inpatients and outpatients, treatment naïve and previously treated patients and patients with or without psychiatric comorbidity. Moreover, HRQoL scores were not correlated to length of illness within each ED subgroup.
The analysis of the literature adds some relevant information on HRQoL in ED and may address the future research toward the exploration of specific questions. One of these may be the prominent role of Psychological Health domain in HRQoL, since our study confirms that this component is able to differentiate eating disorders.
PMCID: PMC4058000  PMID: 24898768
Eating disorders; Anorexia nervosa; Bulimia nervosa; Binge eating; HRQoL; Quality of life; WHOQoL-BREF; SF-36; Review
13.  Double disadvantage: a case control study on health-related quality of life in children with sickle cell disease 
Low health-related quality of life (HRQoL) of children with sickle cell disease (SCD) may be associated with consequences of the disease, or with the low socio-economic status (SES) of this patient population. The aim of this study was to investigate the HRQoL of children with SCD, controlling for SES by comparing them to healthy siblings (matched for age and gender), and to a Dutch norm population.
The HRQoL of 40 children with homozygous SCD and 36 healthy siblings was evaluated by the KIDSCREEN-52. This self-report questionnaire assesses ten domains of HRQoL. Differences between children with SCD and healthy siblings were analyzed using linear mixed models. One-sample t-tests were used to analyze differences with the Dutch norm population. Furthermore, the proportion of children with SCD with impaired HRQoL was evaluated.
In general, the HRQoL of children with SCD appeared comparable to the HRQoL of healthy siblings, while children with SCD had worse HRQoL than the Dutch norm population on five domains (Physical Well-being, Moods & Emotions, Autonomy, Parent Relation, and Financial Resources). Healthy siblings had worse HRQoL than the Dutch norm population on three domains (Moods & Emotions, Parent Relation, and Financial Resources). More than one in three children with SCD and healthy siblings had impaired HRQoL on several domains.
These findings imply that reduced HRQoL in children with SCD is mainly related to the low SES of this patient population, with the exception of disease specific effects on the physical and autonomy domain. We conclude that children with SCD are especially vulnerable compared to other patient populations, and have special health care needs.
PMCID: PMC2988059  PMID: 20977722
14.  Respiratory symptoms in adults are related to impaired quality of life, regardless of asthma and COPD: results from the European community respiratory health survey 
Respiratory symptoms are common in the general population, and their presence is related to Health-related quality of life (HRQoL). The objective was to describe the association of respiratory symptoms with HRQoL in subjects with and without asthma or COPD and to investigate the role of atopy, bronchial hyperresponsiveness (BHR), and lung function in HRQoL.
The European Community Respiratory Health Survey (ECRHS) I and II provided data on HRQoL, lung function, respiratory symptoms, asthma, atopy, and BHR from 6009 subjects. Generic HRQoL was assessed through the physical component summary (PCS) score and the mental component summary (MCS) score of the SF-36.
Factor analyses and linear regressions adjusted for age, gender, smoking, occupation, BMI, comorbidity, and study centre were conducted.
Having breathlessness at rest in ECRHS II was associated with mean score (95% CI) impairment in PCS of -8.05 (-11.18, -4.93). Impairment in MCS score in subjects waking up with chest tightness was -4.02 (-5.51, -2.52). The magnitude of HRQoL impairment associated with respiratory symptoms was similar for subjects with and without asthma/COPD. Adjustments for atopy, BHR, and lung function did not explain the association of respiratory symptoms and HRQoL in subjects without asthma and/or COPD.
Subjects with respiratory symptoms had poorer HRQoL; including subjects without a diagnosis of asthma or COPD. These findings suggest that respiratory symptoms in the absence of a medical diagnosis of asthma or COPD are by no means trivial, and that clarifying the nature and natural history of respiratory symptoms is a relevant challenge.
Several community studies have estimated the prevalence of common respiratory symptoms like cough, dyspnoea, and wheeze in adults [1-3]. Although the prevalence varies to a large degree between studies and geographical areas, respiratory symptoms are quite common. The prevalences of respiratory symptoms in the European Community Respiratory Health Study (ECRHS) varied from one percent to 35% [1]. In fact, two studies have reported that more than half of the adult population suffers from one or more respiratory symptoms [4,5].
Respiratory symptoms are important markers of the risk of having or developing disease. Respiratory symptoms have been shown to be predictors for lung function decline [6-8], asthma [9,10], and even all-cause mortality in a general population study [11]. In patients with a known diagnosis of asthma or chronic obstructive pulmonary disease (COPD), respiratory symptoms are important determinants of reduced health related quality of life (HRQoL) [12-15]. The prevalence of respiratory symptoms exceeds the combined prevalences of asthma and COPD, and both asthma and COPD are frequently undiagnosed diseases [16-18]. Thus, the high prevalence of respipratory symptoms may mirror undiagnosed and untreated disease.
The common occurrence of respiratory symptoms calls for attention to how these symptoms affect health also in subjects with no diagnosis of obstructive airways disease. Impaired HRQoL in the presence of respiratory symptoms have been found in two population-based studies [6,19], but no study of respiratory sypmtoms and HRQoL have separate analyses for subjects with and without asthma and COPD, and no study provide information about extensive objective measurements of respiratory health.
The ECRHS is a randomly sampled, multi-cultural, population based cohort study. The ECRHS included measurements of atopy, bronchial hyperresponsiveness (BHR), and lung function, and offers a unique opportunity to investigate how respiratory symptoms affect HRQoL among subjects both with and without obstructive lung disease.
In the present paper we aimed to: 1) Describe the relationship between respiratory symptoms and HRQoL in an international adult general population and: 2) To assess whether this relationship varied with presence of asthma and/or COPD, or presence of objective functional markers like atopy and BHR.
PMCID: PMC2954977  PMID: 20875099
15.  Secondary Prevention in Patients with Coronary Heart Diseases: What Factors Are Associated with Health Status in Usual Primary Care? 
PLoS ONE  2012;7(12):e51726.
For patients with coronary heart diseases a substantial part of secondary prevention is delivered in primary care. Along with the growing importance of prevention, health-related quality of life (HRQoL) is an indicator of patient-centered care that has gained increased attention. Different approaches for reorganization in primary care have been associated with improvements in HRQoL. However, these are often results of complex interventions. Evidence on aspects concerning usual primary care that actually have an impact on HRQoL remains scarce. Therefore, this observational study aimed to identify factors which are associated with HRQoL in usual primary care at practice and patient-level.
This observational study was conducted in eight European countries. We were able to match data from survey instruments for 3505 patients with coronary heart disease (CHD) in 228 practices. A multilevel analysis was performed to identify associations of EQ-5D scores at patient and practice-level.
After dropping patients with missing information, our cohort consisted of 2656 patients. In this sample, 30.5% were female and the mean age was 67.5 years (SD 10.1). The final model included a total set of 14 potential explanatory variables. At practice-level no variable was associated with EQ-5D. At patient-level, lower education (r = −0.0381, p<0.0001), female gender (r = −0.0543, p<0.0001) and a higher number of other conditions (r = −0.0340, p<0.0001), had a strong negative effect on HRQoL. Strong positive associations with HRQoL were found for a good medication adherence (Morisky) (r = 0.0195, p<0.0001) and more positive evaluations of physicians' clinical behavior (r = 0.0282, p = 0.002). In terms of HRQoL no differences between single-handed and group practices exist.
The results of our study suggest that a better patient-physician relationship rather than organization of CHD care is associated with higher HRQOL in the primary care setting. The results may imply that interventions to improve HRQoL require a strong patient-centered approach.
PMCID: PMC3530503  PMID: 23300560
16.  Health-related quality-of-life of coal-based sponge iron plant workers in Barjora, India: a cross-sectional study 
BMJ Open  2014;4(9):e006047.
During the last decade, coal-based sponge iron plants, a highly polluted industry, have grown rapidly in Barjora, India. Understanding their workers’ perception of health is essential in people-centered healthcare. The aim of the study was to assess their health-related quality-of-life (HRQoL), and to determine factors that independently predict their HRQoL.
Cross-sectional study.
Coal-based sponge iron plants in Barjora, India.
258 coal-based sponge iron plant workers.
Primary outcome measure
HRQoL was measured using the EuroQol-5D-5L.
The response rate was 100%. Participants with problems in mobility, self-care, usual activities, pain/discomfort and anxiety/depression were 23.3%, 5.1%, 10.9%, 39.5% and 45.5%, respectively. 36.8% of participants reported health state 11111 (no problem in any EQ-5D dimension). The mean visual analogue scale (EQ-VAS) was 69.8 (18.5 SD). The odds of mobility problems decreased with age (OR 0.95, 95% CI 0.91 to 0.99, p=0.016), were lower in participants with presence/history of any respiratory disease (0.27, 0.13 to 0.55, p<0.001), scheduled caste/scheduled tribe/other backward class workers (0.44, 0.22 to 0.89, p=0.021), manual workers (0.40, 0.16 to 0.99, p=0.047) and non-smokers (2.63, 1.27 to 5.46, p=0.009). The odds of pain/discomfort and anxiety/depression were lower in participants with any respiratory disease (0.44, 0.24 to 0.79, p=0.006; and 0.52, 0.29 to 0.92, p=0.026, respectively). The EQ-VAS was worse in manual participants (coefficient −6.91, 95% CI −12.40 to −1.41, p=0.014), with any respiratory disease (−8.13, −13.12 to −3.13, p=0.002), alcohol drinkers (−4.81, −9.47 to −0.15, p=0.043), literates (7.70, 0.97 to 14.43, p=0.025) and Hindus (13.41, 2.62 to 24.20, p=0.015).
Many coal-based sponge iron plant workers in Barjora have problems in their HRQoL, and the predictors of different aspects of HRQoL were identified. The study findings could be taken into consideration in future interventional studies aimed at improving the HRQoL of these workers.
PMCID: PMC4158191  PMID: 25190619
17.  Health-related quality of life assessment in people with multiple sclerosis and their family caregivers. A multicenter study in Catalonia (Southern Europe) 
To measure the health-related quality of life (HRQoL) of multiple sclerosis (MS) patients and their caregivers, and to assess which factors can best describe HRQoL.
A cross-sectional multicenter study of nine hospitals enrolled MS patients and their caregivers who attended outpatient clinics consecutively. The instruments used were the SF-36 for patients and the SF-12 and GHQ-12 for caregivers. Classification and regression tree analysis was used to analyze the explanatory factors of HRQoL.
A total of 705 patients (mean age 40.4 years, median Expanded Disability Status Scale 2.5, 77.8% with relapsing-remitting MS) and 551 caregivers (mean age 45.4 years) participated in the study. MS patients had significantly lower HRQoL than in the general population (physical SF-36: 39.9; 95% confidence interval [CI]: 39.1–40.6; mental SF-36: 44.4; 95% CI: 43.5–45.3). Caregivers also presented lower HRQoL than general population, especially in its mental domain (mental SF-12: 46.4; 95% CI: 45.5–47.3). Moreover, according to GHQ-12, 27% of caregivers presented probable psychological distress. Disability and co-morbidity in patients, and co-morbidity and employment status in caregivers, were the most important explanatory factors of their HRQoL.
Not only the HRQoL of patients with MS, but also that of their caregivers, is indeed notably affected. Caregivers’ HRQoL is close to population of chronic illness even that the patients sample has a mild clinical severity and that caregiving role is a usual task in the study context.
PMCID: PMC2778410  PMID: 19936174
health-related quality of life; multiple sclerosis; caregivers
18.  Highly active antiretroviral treatment and health related quality of life in South African adults with human immunodeficiency virus infection: A cross-sectional analytical study 
BMC Public Health  2007;7:244.
Health Related Quality of Life (HRQoL) is an important outcome in times of Highly Active Antiretroviral Treatment (HAART). We compared the HRQoL of HIV positive patients receiving HAART with those awaiting treatment in public sector facilities in the Free State province in South Africa.
A stratified random sample of 371 patients receiving or awaiting HAART were interviewed and the EuroQol-profile, EuroQol-index and Visual Analogue Scale (VAS) were compared. Independent associations between these outcomes and HAART, socio-demographic, clinical and health service variables were estimated using linear and ordinal logistic regression, adjusted for intra-clinic clustering of outcomes.
Patients receiving HAART reported better HRQoL for 3 of the 5 EuroQol-dimensions, for the VAS score and for the EuroQol index in bivariable analysis. They had a higher mean EuroQol index (0.11 difference, 95% confidence interval [CI] 0.04; 0.23), and were more likely to have a higher index (odds ratio 1.9, 95% CI 1.1; 1.3), compared to those awaiting HAART, in multivariate analysis. Higher mean VAS scores were reported for patients who were receiving HAART (6.5 difference, 95% CI 1.3; 11.7), were employed (9.1, 95% CI 4.3; 13.7) or were female (4.7, 95% CI 0.79; 8.5).
HAART was associated with improved HRQoL in patients enrolled in a public sector treatment program in South Africa. Our finding that the EuroQol instrument was sensitive to HAART supports its use in future evaluation of HIV/AIDS care in South Africa. Longitudinal studies are needed to evaluate changes in individuals' HRQoL.
PMCID: PMC2194770  PMID: 17854510
19.  Health-Related Quality of Life in Parkinson disease: Correlation between Health Utilities Index III and Unified Parkinson's Disease Rating Scale (UPDRS) in U.S. male veterans 
To apply a scaled, preference-based measure to the evaluation of health-related quality of life (HRQoL) in Parkinson's disease (PD); to evaluate the relationship between disease-specific rating scales and estimated HRQoL; and to identify predictors of diminished HRQoL.
Scaled, preference-based measures of HRQoL ("utilities") serve as indices of impact of disease, and can be used to generate quality-adjusted estimates of survival for health-economic evaluations. Evaluation of utilities for PD and their correlation with standard rating scales have been limited.
Utilities were generated using the Health Utilities Index Mark III (HUI-III) on consecutive patients attending a PD Clinic between October 2003 and June 2006. Disease severity, medical, surgical (subthalamic nucleus deep brain stimulation (STN-DBS)), and demographic information were used as model covariates. Predictors of HUI-III utility scores were evaluated using the Wilxocon rank-sum test and linear regression models.
68 men with a diagnosis of PD and a mean age of 74.0 (SD 7.4) were included in the data analysis. Mean HUI-III utility at first visit was 0.45 (SD 0.33). In multivariable models, UPDRS-II score (r2 = 0.56, P < 0.001) was highly predictive of HRQoL. UPDRS-III was a weaker, but still significant, predictor of utility scores, even after adjustment for UPDRS-II (P = 0.01).
Poor self-care in PD reflected by worsening UPDRS-II scores is strongly correlated with low generic HRQoL. HUI-III-based health utilities display convergent validity with the UPDRS-II. These findings highlight the importance of measures of independence as determinants of HRQoL in PD, and will facilitate the utilization of existing UPDRS data into economic analyses of PD therapies.
PMCID: PMC2939643  PMID: 20799993
20.  Health-related quality of life and long-term care needs among elderly individuals living alone: a cross-sectional study in rural areas of Shaanxi Province, China 
BMC Public Health  2013;13:313.
The number of elderly individuals living alone is rising, especially in rural areas of China, and their health-related quality of life (HRQoL) is an increasing public health concern. However, little is known about factors that influence HRQoL and the need for long-term care services. The aim of the study was to identify these factors and the long-term care requirements of persons aged 60 and older living alone in rural areas of Shaanxi Province, China.
The study included 424 older subjects, selected by stratified random sampling. Logistic regression adjusted for age was conducted to analyze factors influencing HRQoL and the need for long-term care services. Pearson correlative analysis was conducted to assess the correlation between HRQoL score and long-term care needs.
HRQoL among elderly subjects living alone declined with age in both males and females. The main diseases influencing HRQoL among the elderly were hypertension, cardiac disease, chronic bronchitis, neurological disease and cancer. Cataract disease was the most important factor related to HRQoL. This was followed by long-term care needs, living conditions, economic status, Cardiovascular disease, osteoporosis and age. Factors affecting long-term care needs were economic status, education level, alcohol intake, living conditions, general health and age. HRQoL and long-term care needs among this elderly population were significantly correlated (r=−0.204, p<0.01).
For elderly persons living alone, factors such as chronic disease, lower income level and living in a rural area may limit their ability to form social relationships. Reducing the level of loneliness, with better care and support, may be helpful in improving their HRQoL. There is a need for an overall improvement in the planning, provision and financing of long-term care and psychogeriatric services for elderly individuals living alone in China.
PMCID: PMC3642010  PMID: 23566211
Health-related quality of life; SF-36; Long-term care; Elderly subjects living alone
21.  Comparing Health-Related Quality of Life of Cancer Patients under Chemotherapy and of Their Caregivers 
The Scientific World Journal  2012;2012:135283.
Introduction. Cancer is a major disorder physically and psychologically affecting both patients and their caregivers. In this study, health-related quality of life (HRQoL) of patient-caregiver dyads during the period of chemotherapy was assessed. Material and Methods. Two hundred twenty-two cancer patient-caregiver dyads were enrolled in the study, which was conducted from October 2008 to March 2009. HRQoL was evaluated with EQ-5D. Results. The mean age of the sample was 57.4 and 48.9 for patients and caregivers, respectively. The EQ-5D descriptive system indicates that female patients more frequently experience anxiety and depression than male patients. Male and higher-education caregivers had higher VAS scores, while demographic factors did not seem to influence patients' HRQoL. Anxiety and depression of caregivers were correlated with patients' problems in self-care and usual activities. Conclusions. Quality of life is highly influenced during the period of chemotherapy for both patients and caregivers and is often under reported. Interventions that can improve HRQoL, especially in the domain of mental health for both cancer patients and their caregivers, need to be implemented.
PMCID: PMC3348659  PMID: 22619584
22.  The effects of fatigue, pain, and depression on quality of life in ischemic stroke patients: The Bergen Stroke Study 
Many patients with cerebral infarction suffer from symptoms such as pain, fatigue, and depression. The aim of this study was to evaluate these symptoms in relation to health-related quality of life (HRQoL) on long-term follow-up.
Materials and methods
All surviving stroke patients admitted to the Stroke Unit, Haukeland University Hospital, Norway between February 2006 and November 2008 were sent a questionnaire, including a visual analog pain scale, Fatigue Severity Scale, Depression Subscale of Hospital Anxiety and Depression Scale, Barthel Index, and three measures of HRQoL – 15D, EuroQol, and EuroQol Visual Analogue Scale – at least 6 months after stroke onset. Cox regression survival analysis, including EQ-5D, was performed by November 2009.
The questionnaire was returned by 328 patients. All three symptoms were reported by 10.1% of the patients, and 26% reported two symptoms. There was a significant association between worse HRQoL scores and an increasing number of cooccurring symptoms for all three HRQoL scores. Fatigue, depression, pain, functional state, and sleeping disorder on follow-up accounted for 58%–83% of the variability in HRQoL, depending on which HRQoL scale was used. Cox regression analysis showed that mortality was associated with a low EuroQol score (P = 0.016).
Pain, fatigue, and depression were common symptoms among these stroke patients and, to a large extent, they determined the patients’ HRQoL. Low HRQoL was associated with increased mortality.
PMCID: PMC3402053  PMID: 22910531
cerebral infarction; symptoms; mortality
23.  An observational study of patient versus parental perceptions of health-related quality of life in children and adolescents with a chronic pain condition: who should the clinician believe? 
Previous pediatric studies have observed a cross-informant variance in patient self-reported health-related quality of life (HRQoL) versus parent proxy-reported HRQoL. This study assessed in older children and adolescents with a variety of chronic pain conditions: 1) the consistency and agreement between pediatric patients’ self-report and their parents’ proxy-report of their child’s HRQoL; 2) whether this patient-parent agreement is dependent on additional demographic and clinical factors; and 3) the relationship between pediatric patient HRQoL and parental reported HRQoL.
The 99 enrolled patients (mean age 13.2 years, 71% female, 81% Caucasian) and an accompanying parent completed the PedsQLTM 4.0 and 36-Item Short-Form Health Survey Version 2 (SF-36v2) at the time of their initial appointment in a pediatric chronic pain medicine clinic. Patients’ and parents’ total, physical, and psychosocial HRQoL scores were analyzed via an intra-class correlation coefficient, Spearman’s correlation coefficient, Wilcoxon signed rank test, and Bland-Altman plot. A multivariable linear regression model was used to evaluate the association between clinical and demographic variables and the difference in patient and proxy scores for the Total Scale Score on the PedsQL™.
With the exception of the psychosocial health domain, there were no statistically significant differences between pediatric patients’ self-report and their parents’ proxy-report of their child’s HRQoL. However, clinically significant patient-parent variation in pediatric HRQoL was observed. Differences in patient-parent proxy PedsQL™ Total Scale Score Scores were not significantly associated with patient age, gender, race, intensity and duration of patient’s pain, household income, parental marital status, and the parent’s own HRQoL on the SF-36v2. No significant relationship existed among patients’ self-reported HRQoL (PedsQL™), parental proxy-reports of the child’s HRQoL, and parents’ own self-reported HRQoL on the SF-36v2.
We observed clinically significant variation between pediatric chronic pain patients’ self-reports and their parents’ proxy-reports of their child’s HRQoL. While whenever possible the pediatric chronic pain patient’s own perspective should be directly solicited, equal attention and merit should be given to the parent’s proxy-report of HRQoL. To do otherwise will obviate the opportunity to use any discordance as the basis for a therapeutic discussion about the contributing dynamic with in parent-child dyad.
PMCID: PMC3478968  PMID: 22824550
Health-related quality of life; Chronic pain; Pediatric; Children; Adolescents; Proxy-report; Child-parent agreement
24.  Factors associated with health-related quality of life among Chinese caregivers of the older adults living in the community: a cross-sectional study 
Under the culture of filial piety and due to the Confucianism spirit in China, family caregivers usually undertake the responsibilities of caring for the older adults. They usually suffer from a heavy burden which is believed to impair their mental and physical health. Thus this study aims to describe the health-related quality of life (HRQOL) among Chinese caregivers of the older adults living in the community and explore the predictors of caregivers’ HRQOL.
A cross-sectional study was conducted through convenience sampling. The study population was composed of 1,144 caregivers of older adults who suffered from one or more types of chronic diseases in 15 communities in 3 eastern cities of China. Family caregivers were interviewed face-to-face using the 36-item Short-Form Health Survey (SF-36) and the ZARIT Caregiver Burden interview (ZBI) scales. The Antonovsky's Sense of coherence (SOC) scale was also used to measure personal coping capability of the caregivers. Hierarchical multiple regression analysis (HMR) was performed to explore the predictors of caregivers’ HRQOL.
The majority of the caregivers were females (60.0%) or adult children (66.5%). Mental QOL was significantly lower than physical QOL. Hierarchical multiple regression analysis showed that Demographic Characteristics of Caregivers, Patients’ Characteristics, and Subjective Caregiver Burden explained most of the total variance of all aspects of HRQOL. While, Objective Caregiving Tasks was only associated with physical QOL. Subjective Caregiver Burden was the strongest predictor of both physical and mental QOL. SOC was also a strong predictor of physical and mental QOL.
The mental QOL of the caregivers of older adults was disrupted more seriously than physical QOL. Additionally, Subjective Caregiver Burden might decrease caregiver’ health. A decrease in caregiver burden could promote better management of caregiving tasks, and improve HRQOL. Also, coping capabilities, like SOC, are needed to decrease the impact of caregiving on HRQOL of Chinese caregivers of the older adults.
PMCID: PMC3541082  PMID: 23186128
Older adults; Subjective caregiver burden; Sense of coherence; HRQOL
25.  Patients with Asthma and Comorbid Allergic Rhinitis: Is Optimal Quality of Life Achievable in Real Life? 
PLoS ONE  2012;7(2):e31178.
Asthma trials suggest that patients reaching total disease control have an optimal Health Related Quality of Life (HRQoL). Moreover, rhinitis is present in almost 80% of asthmatics and impacts asthma control and patient HRQoL. We explored whether optimal HRQoL was reachable in a real-life setting, and evaluated the disease and patient related patterns associated to optimal HRQoL achievement.
Methods and Findings
Asthma and rhinitis HRQoL, illness perception, mood profiles, rhinitis symptoms and asthma control were assessed by means of validated tools in patients classified according to GINA and ARIA guidelines. Optimal HRQoL, identified by a Rhinasthma Global Summary (GS) score ≤20 (score ranging from 0 to 100, where 100 represents the worst possible HRQoL), was reached by 78/209 (37.32%). With the exception of age, no associations were found between clinical and demographic characteristics and optimal HRQoL achievement. Patients reaching an optimal HRQoL differed in disease perception and mood compared to those not reaching an optimal HRQoL. Asthma control was significantly associated with optimal HRQoL (χ2 = 49.599; p<0.001) and well-controlled and totally controlled patients significantly differed in achieving optimal HRQoL (χ2 = 7.617; p<0.006).
Approximately one third of the patients in our survey were found to have an optimal HRQoL. While unsatisfactory disease control was the primary reason why the remainder failed to attain optimal HRQoL, it is clear that illness perception and mood also played parts. Therefore, therapeutic plans should be directed not only toward achieving the best possible clinical control of asthma and comorbid rhinitis, but also to incorporating individualized elements according to patient-related characteristics.
PMCID: PMC3281945  PMID: 22363573

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