Estimation of reference curves for the urinary steroid metabolome in the first year of life in healthy children : Tracing the complexity of human postnatal steroidogenesis.

CONTEXT: Complex steroid disorders such as P450 oxidoreductase deficiency or apparent cortisone reductase deficiency may be recognized by steroid profiling using chromatographic mass spectrometric methods. These methods are highly specific and sensitive, and provide a complete spectrum of steroid metabolites in a single measurement of one sample which makes them superior to immunoassays. The steroid metabolome during the fetal-neonatal transition is characterized by (a) the metabolites of the fetal-placental unit at birth, (b) the fetal adrenal androgens until its involution 3-6 months postnatally, and (c) the steroid metabolites produced by the developing endocrine organs. All these developmental events change the steroid metabolome in an age- and sex-dependent manner during the first year of life. OBJECTIVE: The aim of this study was to provide normative values for the urinary steroid metabolome of healthy newborns at short time intervals in the first year of life. METHODS: We conducted a prospective, longitudinal study to measure 67 urinary steroid metabolites in 21 male and 22 female term healthy newborn infants at 13 time-points from week 1 to week 49 of life. Urine samples were collected from newborn infants before discharge from hospital and from healthy infants at home. Steroid metabolites were measured by gas chromatography-mass spectrometry (GC-MS) and steroid concentrations corrected for urinary creatinine excretion were calculated. RESULTS: 61 steroids showed age and 15 steroids sex specificity. Highest urinary steroid concentrations were found in both sexes for progesterone derivatives, in particular 20α-DH-5α-DH-progesterone, and for highly polar 6α-hydroxylated glucocorticoids. The steroids peaked at week 3 and decreased by ∼80% at week 25 in both sexes. The decline of progestins, androgens and estrogens was more pronounced than of glucocorticoids whereas the excretion of corticosterone and its metabolites and of mineralocorticoids remained constant during the first year of life. CONCLUSION: The urinary steroid profile changes dramatically during the first year of life and correlates with the physiologic developmental changes during the fetal-neonatal transition. Thus detailed normative data during this time period permit the use of steroid profiling as a powerful diagnostic tool.

Quality of life in simultaneous pancreas-kidney transplant recipients

Currently, simultaneous pancreas-kidney transplantation (SPK Tx) is the treatment of choice in selected patients with type 1 diabetes mellitus (DM1) and terminal kidney failure (TRF). A functioning SPK transplant allows dialysis and insulin therapy to be discontinued and stabilizes or improves the complications of DM1. Nevertheless, to a greater or lesser degree, these complications (physical and psychological alterations, secondary effects of immunosuppressive therapy and the need for lifelong medication and medical follow-up) can persist after SPK Tx. Health professionals have mainly investigated the clinical features of transplant recipients. However, in the last few years, interest in analyzing perceived health and health-related quality of life (QoL) has increased. This latter concept includes the features of QoL most closely associated with a particular disease, its treatment and follow-up and therefore those elements most susceptible to modification by the health system. The general aim of this study was to measure health-related QoL in our population with SPK Tx and to determine whether there are significant differences between these patients and those with DM1 and TRF who continue to receive renal replacement therapy (RRT) and insulin therapy. More specific aims were to evaluate whether there are significant differences between the study groups and the means of the Spanish reference population in the distinct dimensions of a QoL questionnaire and whether other variables such as age, sex, years" duration of DM1, length of dialysis, and time since SPK Tx significantly affect health-related QoL.

Quality of life in simultaneous pancreas-kidney transplant recipients

Currently, simultaneous pancreas-kidney transplantation (SPK Tx) is the treatment of choice in selected patients with type 1 diabetes mellitus (DM1) and terminal kidney failure (TRF). A functioning SPK transplant allows dialysis and insulin therapy to be discontinued and stabilizes or improves the complications of DM1. Nevertheless, to a greater or lesser degree, these complications (physical and psychological alterations, secondary effects of immunosuppressive therapy and the need for lifelong medication and medical follow-up) can persist after SPK Tx. Health professionals have mainly investigated the clinical features of transplant recipients. However, in the last few years, interest in analyzing perceived health and health-related quality of life (QoL) has increased. This latter concept includes the features of QoL most closely associated with a particular disease, its treatment and follow-up and therefore those elements most susceptible to modification by the health system. The general aim of this study was to measure health-related QoL in our population with SPK Tx and to determine whether there are significant differences between these patients and those with DM1 and TRF who continue to receive renal replacement therapy (RRT) and insulin therapy. More specific aims were to evaluate whether there are significant differences between the study groups and the means of the Spanish reference population in the distinct dimensions of a QoL questionnaire and whether other variables such as age, sex, years" duration of DM1, length of dialysis, and time since SPK Tx significantly affect health-related QoL.

Quality of life in simultaneous pancreas-kidney transplant recipients

Currently, simultaneous pancreas-kidney transplantation (SPK Tx) is the treatment of choice in selected patients with type 1 diabetes mellitus (DM1) and terminal kidney failure (TRF). A functioning SPK transplant allows dialysis and insulin therapy to be discontinued and stabilizes or improves the complications of DM1. Nevertheless, to a greater or lesser degree, these complications (physical and psychological alterations, secondary effects of immunosuppressive therapy and the need for lifelong medication and medical follow-up) can persist after SPK Tx. Health professionals have mainly investigated the clinical features of transplant recipients. However, in the last few years, interest in analyzing perceived health and health-related quality of life (QoL) has increased. This latter concept includes the features of QoL most closely associated with a particular disease, its treatment and follow-up and therefore those elements most susceptible to modification by the health system. The general aim of this study was to measure health-related QoL in our population with SPK Tx and to determine whether there are significant differences between these patients and those with DM1 and TRF who continue to receive renal replacement therapy (RRT) and insulin therapy. More specific aims were to evaluate whether there are significant differences between the study groups and the means of the Spanish reference population in the distinct dimensions of a QoL questionnaire and whether other variables such as age, sex, years" duration of DM1, length of dialysis, and time since SPK Tx significantly affect health-related QoL.

Quality of Life in Swiss Paediatric Inflammatory Bowel Disease Patients: Do Patients and Their Parents Experience Disease in the Same Way?

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBDs) may impair quality of life (QoL) in paediatric patients. We aimed to evaluate in a nationwide cohort whether patients experience QoL in a different way when compared with their parents. METHODS: Sociodemographic and psychosocial characteristics were prospectively acquired from paediatric patients and their parents included in the Swiss IBD Cohort Study. Disease activity was evaluated by the Paediatric Crohn's Disease Activity Index (PCDAI) and the Paediatric Ulcerative Colitis Activity Index (PUCAI). We assessed QoL using the KIDSCREEN questionnaire. The QoL domains were analysed and compared between children and parents according to type of disease, parents' age, origin, education and marital status. RESULTS: We included 110 children and parents (59 Crohn's disease [CD], 45 ulcerative colitis [UC], 6 IBD unclassified [IBDU]). There was no significant difference in QoL between CD and UC/IBDU, whether the disease was active or in remission. Parents perceived overall QoL, as well as 'mood', 'family' and 'friends' domains, lower than the children themselves, independently of their place of birth and education. However, better concordance was found on 'school performance' and 'physical activity' domains. Marital status and age of parents significantly influenced the evaluation of QoL. Mothers and fathers being married or cohabiting perceived significantly lower mood, family and friends domains than their children, whereas mothers living alone had a lower perception of the friends domain; fathers living alone had a lower perception of family and mood subscores. CONCLUSION: Parents of Swiss paediatric IBD patients significantly underestimate overall QoL and domains of QoL of their children independently of origin and education.

Trajectory and predictors of quality of life in first episode psychotic mania.

BACKGROUND: Little is known about the trajectory of quality of life (QoL) following a first episode of psychotic mania in bipolar disorder (BD). This 18-month longitudinal study investigated the trajectory of QoL, and the influence of premorbid adjustment and symptoms on 18-month QoL in a cohort of young people experiencing a first episode of psychotic mania. METHODS: As part of an overarching clinical trial, at baseline, sixty participants presenting with a first episode of psychotic mania (BD Type 1 - DSM-IV) completed symptomatic and functional assessments in addition to the Premorbid Adjustment Scale - General Subscale. Symptom measures were repeated at 18-month follow up. QoL was rated using the Quality of Life Scale (QLS) at designated time points. RESULTS: Mean QLS scores at initial measurement (8 weeks) were 61% of the maximum possible score, increasing significantly to 70% at 12 months, and 71.2% at 18-month follow-up. Premorbid adjustment and 18-month depressive symptoms were significantly associated with QoL at 18-month follow-up. LIMITATIONS: Study limitations include the small sample size, inclusion of participants with psychotic mania only, use of measures originally designed for use with schizophrenia spectrum disorders, and lack of premorbid or baseline measurement of QoL. CONCLUSIONS: Results suggest that QoL can be maintained early in BD, and reinforce the importance of assertively treating depressive symptoms throughout the course of this disorder. The emergence of a link between premorbid adjustment and poorer QoL in this cohort highlights the importance of assessing facets of adjustment when planning psychological interventions.

Gp120/CD4 blocking antibodies are frequently elicited in ART-naïve chronically HIV-1 infected individuals

Antibodies with the ability to block the interaction of HIV-1 envelope glycoprotein (Env) gp120 with CD4, including those overlapping the CD4 binding site (CD4bs antibodies), can protect from infection by HIV-1, and their elicitation may be an interesting goal for any vaccination strategy. To identify gp120/CD4 blocking antibodies in plasma samples from HIV-1 infected individuals we have developed a competitive flow cytometry-based functional assay. In a cohort of treatment-naïve chronically infected patients, we showed that gp120/ CD4 blocking antibodies were frequently elicited (detected in 97% plasma samples) and correlated with binding to trimeric HIV-1 envelope glycoproteins. However, no correlation was observed between functional CD4 binding blockade data and titer of CD4bs antibodies determined by ELISA using resurfaced gp120 proteins. Consistently, plasma samples lacking CD4bs antibodies were able to block the interaction between gp120 and its receptor, indicating that antibodies recognizing other epitopes, such as PGT126 and PG16, can also play the same role. Antibodies blocking CD4 binding increased over time and correlated positively with the capacity of plasma samples to neutralize the laboratory-adapted NL4.3 and BaL virus isolates, suggesting their potential contribution to the neutralizing workforce of plasma in vivo. Determining whether this response can be boosted to achieve broadly neutralizing antibodies may provide valuable information for the design of new strategies aimed to improve the anti-HIV-1 humoral response and to develop a successful HIV- 1 vaccine.

Health-related quality of life in the Cambridge City over-75s Cohort (CC75C): development of a dementia-specific scale and descriptive analyses.

BACKGROUND: The assessment of Health Related Quality of Life (HRQL) is important in people with dementia as it could influence their care and support plan. Many studies on dementia do not specifically set out to measure dementia-specific HRQL but do include related items. The aim of this study is to explore the distribution of HRQL by functional and socio-demographic variables in a population-based setting. METHODS: Domains of DEMQOL's conceptual framework were mapped in the Cambridge City over 75's Cohort (CC75C) Study. HRQL was estimated in 110 participants aged 80+ years with a confirmed diagnosis of dementia with mild/moderate severity. Acceptability (missing values and normality of the total score), internal consistency (Cronbach's alpha), convergent, discriminant and known group differences validity (Spearman correlations, Wilcoxon Mann-Whitney and Kruskal-Wallis tests) were assessed. The distribution of HRQL by socio-demographic and functional descriptors was explored. RESULTS: The HRQL score ranged from 0 to 16 and showed an internal consistency Alpha of 0.74. Validity of the instrument was found to be acceptable. Men had higher HRQL than women. Marital status had a greater effect on HRQL for men than it did for women. The HRQL of those with good self-reported health was higher than those with fair/poor self-reported health. HRQL was not associated with dementia severity. CONCLUSIONS: To our knowledge this is the first study to examine the distribution of dementia-specific HRQL in a population sample of the very old. We have mapped an existing conceptual framework of dementia specific HRQL onto an existing study and demonstrated the feasibility of this approach. Findings in this study suggest that whereas there is big emphasis in dementia severity, characteristics such as gender should be taken into account when assessing and implementing programmes to improve HRQL.

Impact of multimorbidity on disability and quality of life in the spanish older population

BACKGROUND: Population aging is closely related to high prevalence of chronic conditions in developed countries. In this context, health care policies aim to increase life span cost-effectively while maintaining quality of life and functional ability. There is still, however, a need for further understanding of how chronic conditions affect these health aspects. The aim of this paper is to assess the individual and combined impact of chronic physical and mental conditions on quality of life and disability in Spain, and secondly to show gender trends. METHODS: Cross-sectional data were collected from the COURAGE study. A total of 3,625 participants over 50 years old from Spain were included. Crude and adjusted multiple linear regressions were conducted to detect associations between individual chronic conditions and disability, and between chronic conditions and quality of life. Separate models were used to assess the influence of the number of diseases on the same variables. Additional analogous regressions were performed for males and females. RESULTS: All chronic conditions except hypertension were statistically associated with poor results in quality of life and disability. Depression, anxiety and stroke were found to have the greatest impact on outcomes. The number of chronic conditions was associated with substantially lower quality of life [β for 4+ diseases: -18.10 (-20.95,-15.25)] and greater disability [β for 4+ diseases: 27.64 (24.99,30.29]. In general, women suffered from higher rates of multimorbidity and poorer results in quality of life and disability. CONCLUSIONS: Chronic conditions impact greatly on quality of life and disability in the older Spanish population, especially when co-occurring diseases are added. Multimorbidity considerations should be a priority in the development of future health policies focused on quality of life and disability. Further studies would benefit from an expanded selection of diseases. Policies should also deal with gender idiosyncrasy in certain cases.

Validation of an instrument to evaluate quality of life in the aging population: WHOQOL-AGE.

BACKGROUND: There is a need for short, specific instruments that assess quality of life (QOL) adequately in the older adult population. The aims of the present study were to obtain evidence on the validity of the inferences that could be drawn from an instrument to measure QOL in the aging population (people 50+ years old), and to test its psychometric properties. METHODS: The instrument, WHOQOL-AGE, comprised 13 positive items, assessed on a five-point rating scale, and was administered to nationally representative samples (n = 9987) from Finland, Poland, and Spain. Cronbach's alpha was employed to assess internal consistency reliability, whereas the validity of the questionnaire was assessed by means of factor analysis, graded response model, Pearson's correlation coefficient and unpaired t-test. Normative values were calculated across countries and for different age groups. RESULTS: The satisfactory goodness-of-fit indices confirmed that the factorial structure of WHOQOL-AGE comprises two first-order factors. Cronbach's alpha was 0.88 for factor 1, and 0.84 for factor 2. Evidence supporting a global score was found with a second-order factor model, according to the goodness-of-fit indices: CFI = 0.93, TLI = 0.91, RMSEA = 0.073. Convergent validity was estimated at r = 0.75 and adequate discriminant validity was also found. Significant differences were found between healthy individuals (74.19 ± 13.21) and individuals with at least one chronic condition (64.29 ± 16.29), supporting adequate known-groups validity. CONCLUSIONS: WHOQOL-AGE has shown good psychometric properties in Finland, Poland, and Spain. Therefore, considerable support is provided to using the WHOQOL-AGE to measure QOL in older adults in these countries, and to compare the QOL of older and younger adults.

Health-related quality of life in school children: validation of instrument, child self assessment, parent-proxy assessment and school nursing documentation of health check-ups

The aims of this study were to validate an international Health-Related Quality of Life (HRQL) instrument, to describe child self and parent-proxy assessed HRQL at child age 10 to 12 and to compare child self assessments with parent-proxy assessments and school nursing documentation. The study is part of the Schools on the Move –research project. In phase one, a cross-cultural translation and validation process was performed to develop a Finnish version of Pediatric Quality of Life Inventory™ 4.0 (PedsQL™ 4.0). The process included a two-way translation, cognitive interviews (children n=7, parents n=5) and a survey (children n=1097, parents n=999). In phase two, baseline and follow-up surveys (children n=986, parents n=710) were conducted to describe and compare the child self and parent-proxy assessed HRQL in school children between the ages 10 and 12. Phase three included two separate data, school nurse documented patient records (children n=270) and a survey (children n=986). The relation between child self assessed HRQL and school nursing documentation was evaluated. Validity and reliability of the Finnish version of PedsQL™ 4.0 was good (Child Self Report α=0.91, Parent-Proxy Report α=0.88). Children reported lower HRQL scores at the emotional (mean 76/80) than the physical (mean 85/89) health domains and significantly lower scores at the age of 10 than 12 (dMean=4, p=<0.001). Agreement between child self and parent-proxy assessment was fragile (r=0,4, p=<0.001) but increased as the child grew from age 10 to 12 years. At health check-ups, school nurses documented frequently children’s physical health, such as growth (97%) and posture (98/99%) but seldom emotional issues, such as mood (2/7%). The PedsQLTM 4.0 is a valid instrument to assess HRQL in Finnish school children although future research is recommended. Children’s emotional wellbeing needs future attention. HRQL scores increase during ages between childhood and adolescence. Concordance between child self and parent-proxy assessed HRQL is low. School nursing documentation, related to child health check-ups, is not in line with child self assessed HRQL and emotional issues need more attention.

Fatigue and quality of life in breast cancer survivors: a comparative study

PURPOSE: To assess fatigue and quality of life in disease-free breast cancer survivors in relation to a sample of age-matched women with no cancer history and to explore the relationship between fatigue and quality of life.METHODS: A cross-sectional study was conducted in a sample of 202 consecutive disease-free Brazilian breast cancer survivors, all of whom had completed treatment, treated at 2 large hospitals. The patients were compared to age-matched women with no cancer history attending a primary health care center. The Piper Fatigue Scale-Revised and the World Health Organization Quality of Life Instrument (WHOQOL-BREF) were used to measure the fatigue and quality of life, respectively. Socio-demographic and clinical variables were also obtained. The χ2 test, generalized linear model, and Spearman correlation coefficient were used for statistical purposes. The adopted level of significance was 5%.RESULTS: Breast cancer survivors experienced significantly greater total and subscale fatigue scores than comparison group (all p-values<0.05). In addition, survivors reported a poorer quality of life in physical (p=0.002), psychological (p=0.03), and social relationships (p=0.03) domains than comparison group. No difference was found for the environmental domain (p=0.08) for both groups. For survivors of breast cancer and for comparison group, the total and subscale fatigue scores were related to lower quality of life (all p-values<0.01).CONCLUSION: The findings of this study highlight the importance of assessing fatigue and quality of life in breast cancer survivors.

Relationship between disease severity and quality of life in patients with chronic obstructive pulmonary disease

Few studies have evaluated the relationship between Airways Questionnaire 20 (AQ20), a measure of the quality of life, scores and physiological outcomes or with systemic markers of disease in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the relationship of forced expiratory volume in 1 s (FEV1), body mass index, fat-free mass index, 6-min walk test (6MWT) results, dyspnea sensation and peripheral oxygen saturation (SpO2) with the quality of life of COPD patients. Ninety-nine patients with COPD (mean age: 64.2 ± 9.2 years; mean FEV1: 60.4 ± 25.2% of predicted) were evaluated using spirometry, body composition measurement and the 6MWT. The baseline dyspnea index (BDI) and the Modified Medical Research Council (MMRC) scale were used to quantify dyspnea. Quality of life was assessed using the AQ20 and the St. George's Respiratory Questionnaire (SGRQ). The Charlson index was used to determine comorbidity. The body mass index/airflow obstruction/dyspnea/exercise capacity (BODE) index was also calculated. AQ20 and SGRQ scores correlated significantly with FEV1, SpO2, 6MWT, MMRC and BDI values as did with BODE index. In the multivariate analyses, MMRC or BDI were identified as predictors of AQ20 and SGRQ scores (P < 0.001 in all cases). Thus, the relationship between AQ20 and disease severity is similar to that described for SGRQ. Therefore, the AQ20, a simple and brief instrument, can be very useful to evaluate the general impact of disease when the time allotted for measurement of the quality of life is limited.

The impact of short daily hemodialysis on anemia and the quality of life in Chinese patients

Anemia is a frequent complication in hemodialysis patients. Compared to conventional hemodialysis (CHD), short daily hemodialysis (sDHD) has been reported to be effective in many countries except China. The aim of the present study was to determine whether sDHD could improve anemia and quality of life (QOL) for Chinese outpatients with end-stage renal disease. Twenty-seven patients (16 males/11 females) were converted from CHD to sDHD. All laboratory values were measured before conversion (baseline), at 3 months after conversion (sDHD1), and at 6 months after conversion (sDHD2). The patient's QOL was evaluated at baseline and 6 months after conversion using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Hemoglobin concentration increased significantly from 107.4±7.9 g/L at baseline to 114.4±6.8 g/L (P<0.05) at sDHD1, and 118.3±8.4 g/L (P<0.001) at sDHD2 (Student paired t-test). However, the dose requirement for erythropoietin decreased from 6847.8±1057.3 U/week at baseline to 5869.6±1094.6 U/week (P<0.05) at sDHD2. Weekly stdKt/V increased significantly from 2.05±0.13 at baseline to 2.73±0.20 (P<0.001) at sDHD1, and 2.84±0.26 (P<0.001) at sDHD2. C-reactive protein decreased from baseline to sDHD1 and sDHD2, but without statistically significant differences. Physical and mental health survey scores increased in the 6 months following conversion to sDHD. sDHD may increase hemoglobin levels, decrease exogenous erythropoietin dose requirements, and improve QOL in Chinese hemodialysis patients compared to CHD. A possible mechanism for improvement of clinical outcomes may be optimized management of uremia associated with the higher efficiency of sDHD.