Mental component of health-related quality of life is an independent predictor of incident functional disability among community-dwelling older people: a prospective cohort study

Quality of Life Research - Previous studies have reported a positive association between poor health-related quality of life (HRQOL) and disability mainly in relation to the physical component of...     

Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorates joint swelling in established monkey collagen-induced arthritis

We examined if tocilizumab, humanized anti-interleukin-6 receptor (IL-6R) antibody, can ameliorate joint swelling after the onset of arthritis in collagen-induced arthritis (CIA). CIA was induced by the immunization of bovine type II collagen in female cynomolgus monkeys. Tocilizumab (30 mg/kg) was administered weekly for 4 weeks after the onset of arthritis. Swelling of 16 proximal interphalangeal (PIP) joints of hands and feet was monitored by measuring the longitudinal and transverse axes of PIP joints and the oval area of each PIP was calculated. Serum was collected once a week after tocilizumab injection and blood chemistry, IL-6, soluble IL-6R (sIL-6R), and anti-tocilizumab antibody were measured. At the end of study, histopathological examination of joints was performed. Tocilizumab clearly reduced joint swelling in all animals without anti-tocilizumab antibody. Histopathological study showed significant decrease in the infiltration of neutrophils into inflamed joints was observed in tocilizumab-treated animals. In conclusion, tocilizumab improved established arthritis in monkey and monkey CIA model is useful for the analysis of anti-arthritic effect of tocilizumab.     

Platelet count and indoor cold exposure among elderly people: A cross-sectional analysis of the HEIJO-KYO study

Background

Excess mortality from cardiovascular disease during cold seasons is a worldwide issue. Although some physiologic studies suggests that platelet activation via cold exposure may cause an increased incidence of cardiovascular disease in winter, the influence of indoor cold exposure in real-life situations on platelet (PLT) count remains unclear.

Diagnostic and predictive performance and standardized threshold of traditional biomarkers for drug‐induced liver injury in rats

Traditional biomarkers such as alanine and aspartate aminotransferase (ALT, AST) and total bilirubin (TBIL) have been widely used for detecting drug‐induced liver injury (DILI). Although the Food and Drug Administration (FDA) proposed standardized thresholds for human as Hy's law, those for animals have not been determined, and predictability of these biomarkers for future onset of hepatic lesions remains unclear. In this study, we investigated these diagnostic and predictive performance of 10 traditional biomarkers for liver injury by receiver‐operating characteristic (ROC) curve, using a free‐access database where 142 hepatotoxic or non‐hepatotoxic compounds were administrated to male rats (n = 5253). Standardization of each biomarker value was achieved by calculating the ratio to control mean value, and the thresholds were determined under the condition of permitting 5% false positive. Of these 10 biomarkers, AST showed the best diagnostic performance. Furthermore, ALT and TBIL also showed high performance under the situation of hepatocellular necrosis and bile duct injury, respectively. Additionally, the availability of the diagnostic thresholds in difference testing facility was confirmed by the application of these thresholds to in‐house prepared dataset. Meanwhile, incorrect diagnosis by the thresholds was also observed. Regarding prediction, all 10 biomarkers showed insufficient performance for future onset of hepatic lesions. In conclusion, the standardized diagnostic thresholds enable consistent evaluation of traditional biomarkers among different facilities, whereas it was suggested that novel biomarker is required for more accurate diagnosis and prediction of DILI. Copyright © 2014 John Wiley & Sons, Ltd.     

Prediction of human pharmacokinetics of typical compounds by a physiologically based method using chimeric mice with humanized liver

1. In this study, total body clearance (CL_t), volume of distribution at steady state (V_ss) and plasma concentration–time profiles in humans of model compounds were predicted using chimeric mice with humanized livers.

2. On the basis of assumption that unbound intrinsic clearance (CL_Uint) per liver weight in chimeric mice was equal to those in humans, CL_t were predicted by substituting human liver blood flow and liver weights in well-stirred model. V_ss were predicted by Rodgers equation using scaling factors of tissue-plasma concentration ratios (SF_Kp) in chimeric mice estimated from a difference between the observed and predicted V_ss. These physiological approaches showed high prediction accuracy for CL_t and V_ss values in humans.

3. We compared the predictability of CL_t and V_ss determined by the physiologically based predictive approach using chimeric mice with those from predictive methods reported by Pharmaceutical Research Manufacturers of America. The physiological approach using chimeric mice indicated the best prediction accuracy in each predictive method.

4. Simulation of human plasma concentration–time profiles were generally successful with physiologically based pharmacokinetic (PBPK) model incorporating CL_Uint and SF_Kp obtained from chimeric mice.

5. Combined application of chimeric mice and PBPK modeling is effective for prediction of human PK in various compounds.

     

A randomized controlled trial on the efficacy of synbiotic versus probiotic or prebiotic treatment to improve the quality of life in patients with ulcerative colitis

ObjectiveStudies suggest that synbiotic therapy could prove more effective in the treatment of ulcerative colitis (UC) than therapies limited to probiotics or prebiotics. This study compared the effect of each of these therapies in the treatment of UC.MethodsOne hundred twenty outpatients with UC were randomly sorted into three groups of 40 patients each for probiotic, prebiotic, or synbiotic therapy. The probiotic group ingested one daily capsule consisting of Bifidobacterium longum 2 × 10⁹ colony-forming units and the prebiotic group ingested daily 8.0-g doses of psyllium. The synbiotic group underwent both treatments. All patients completed Inflammatory Bowel Disease Questionnaires (IBDQs) at the onset of the trial, at the 2-wk midpoint, and at the 4-wk end of the trial. Blood variables were also evaluated in a subset of 32 patients randomly selected from all groups and values were compared with IBDQ scores.ResultsThirty-one patients in the probiotic group, 31 in the prebiotic group, and 32 in the synbiotic group qualified for analyses. The remaining 26 patients had incomplete questionnaires. Total IBDQ scores improved within groups by the end of the trial (probiotics 162 to 169, NS; prebiotics 174 to 182, NS; synbiotics 168 to 176, P = 0.03). Individual scores improved as follows: probiotics, emotional function (P = 0.03); prebiotics, bowel function (P = 0.04); and synbiotics, systemic and social functions (P = 0.008 and P = 0.02). C-reactive protein decreased significantly only with synbiotic therapy (from 0.59 to 0.14 mg/dL, P = 0.04). There were no adverse events.ConclusionPatients with UC on synbiotic therapy experienced greater quality-of-life changes than patients on probiotic or prebiotic treatment. These data suggest that synbiotic therapy may have a synergistic effect in the treatment of UC.     

The Hearing Handicap Inventory for Elderly-Screening (HHIE-S) versus a single question: reliability, validity, and relations with quality of life measures in the elderly community, Japan

Purpose

Little is known about the usefulness of the Hearing Handicap Inventory for the Elderly-Screening (HHIE-S) and a single question (SQ) in assessing hearing impairment (HI) and the impact of HI on quality of life (QOL). The objective of this study was to examine the reliability, validity, and associations with QOL measures (i.e., subjective well-being, depressive symptoms, subjective loneliness, and physical functioning) of the HHIE-S and the SQ in the elderly community.

Methods

A self-report questionnaire including HHIE-S, SQ, Philadelphia Geriatric Center Morale Scale, Geriatric Depression Scale, UCLA Loneliness Scale, and the Tokyo Metropolitan Institute of Gerontology Index of Competence was administered to community elderly (781 males and 950 females). Among them, 97 males and 100 females also responded voluntarily to a request for test–retest and auditory tests. The criterion validity was tested by using pure-tone averages.

Results

Regarding the reliability of HHIE-S, Cronbach’s alpha coefficient was 0.91, Spearman–Brown coefficient was 0.90, and intra-class correlation coefficient was 0.85. Regarding the test–retest reliability of SQ, kappa coefficient was 0.65. HHIE-S had significantly lower sensitivity in identifying >25-dB HI, but significantly higher specificity for the detection of >40-dB HI than SQ. HHIE-S had stronger associations with QOL measures than did SQ.

Conclusions

HHIE-S had high reliability, while SQ had insufficient reliability. HHIE-S was more specific in detecting HI and more sensitive in assessing the impact of HI on QOL than SQ. HHIE-S is a more effective instrument for assessing HI and QOL research than SQ in the elderly community.     

Reliability and validity of Japanese versions of KIDSCREEN-27 and KIDSCREEN-10 questionnaires

Objective

This study aimed to assess the reliability and validity of Japanese versions of the KIDSCREEN-27 (J-KIDSCREEN-27) and KIDSCREEN-10 (J-KIDSCREEN-10) questionnaires, which are shorter versions of the KIDSCREEN-52 (J-KIDSCREEN-52).

Methods

The present analyses are based on a pre-existing dataset of the J-KIDSCREEN-52 validation study, including 1564 children and adolescents aged 8–18 years and their 1326 parents. All were asked to complete the J-KIDSCREEN and Pediatric Quality of Life Inventory (PedsQL) questionnaires. Test–retest reliability was assessed with Intraclass Correlation Coefficients (ICCs) in a one-way random effects model, and internal consistency reliability was measured using Cronbach’s alpha coefficients. Agreement between child and parent scores was evaluated using ICCs in a two-way mixed effects model. To assess concurrent validity, a sub-sample of 535 parents evaluated their child’s mental health status using the Strengths and Difficulties Questionnaire (SDQ).

Results

For children, test–retest ICCs were ≥0.60 and Cronbach’s alpha ≥0.70 for every dimension of both instruments. Correlations of corresponding dimensions between the J-KIDSCREEN-27 or -10 and the PedsQL were acceptable. For parents, test–retest ICCs were ≥0.60, Cronbach’s alpha ≥0.70, and ICCs between child and parent scores ≥0.41 in every dimension of both instruments. In multivariate logistic regression models, after adjusting for confounders, lower health-related QOL in every dimension of both instruments, except Physical Well-being, was significantly associated with higher odds ratios for borderline and clinical ranges of the SDQ.

Conclusion

The child/adolescent and parent/proxy versions of the J-KIDSCREEN-27 and J-KIDSCREEN-10 demonstrated acceptable levels of reliability and validity.

     

Soy product intake is inversely associated with serum homocysteine level in premenopausal Japanese women

Soybeans, which are an excellent source of folate, vitamin B-6 and minerals, may reduce serum homocysteine level. However, there is a possibility that dietary soy raises the serum homocysteine level because isoflavones, which are weak estrogens contained in soybeans, may exert antiestrogenic effects in a high estrogen environment, such as in premenopausal women. The present study examined a cross-sectional relationship between soy product intake and serum homocysteine level in 201 premenopausal Japanese women. Intakes of soy products, folate, methionine and vitamins B-6 and B-12 were estimated by a semiquantitative food frequency questionnaire. Folate status was also assessed by measuring serum folate. Soy product intake in terms of soy protein as well as soy isoflavone intake was modestly but significantly inversely associated with serum homocysteine level (r = -0.15, P = 0.04) after controlling for covariates. Soy product intake was also significantly positively correlated with serum folate (r = 0.15, P = 0.04). Although it is unclear the extent to which each component of soy, such as folate and isoflavones, is associated with the serum homocysteine concentration, this biochemical complex appears to have a favorable effect on homocysteine metabolism in premenopausal women.     

Antitumor effect of monoclonal antibody-carboplatin conjugates in nude mice bearing human ovarian cancer cells

Background. The antitumor effect and toxicity of immunoconjugates were studied in nude mice bearing a human ovarian cancer cell line, OVA-1. Methods. We studied the tissue distribution of an anti-cytokeratin-8 monoclonal antibody (6D7) in OVA-1-bearing nude mice by giving 6D7 labelled with ¹²⁵I. The immuno conjugate consisted of 6D7 and carboplatin (6D7-conjugate), coupled via carboxymethyl dextran, and this was intraperitoneally administered to OVA-1 bearing nude mice. The tumor volume and the body weight were measured for 5 weeks. Tissue platinum concentrations in the OVA-1 tumor, blood, liver, kidney, and spleen, were measured from 3 to 120 min after administration of the conjugate. The results were compared with those in nude mice treated with nonspecific mouse IgG coupled with carboplatin (IgG-conjugate) or carboplatin alone. Results. The coupling rate of the drug to 6D7 was approximately 80%, and was stable over several measurements at various times. In-vivo accumulation of 6D7 labelled with ¹²⁵I in the OVA-1 tumors was significantly higher than that in mice that received nonspecific mouse- IgG-¹²⁵I, with tumor/ blood radioactivity ratios of 14.0 and 1.28, respectively. The tumor growth rate in mice that were administered 6D7-conjugate was (at a maximum) 40% lower than the tumor growth rate in mice administered carboplatin. The body weight of the mice that received 6D7-conjugate did not decrease during the 5-week observation period, while the body weight of the mice that received carboplatin decreased by a maximum of 10%. In addition, upon administration of 6D7-conjugate, the platinum concentration in the tumor was maintained for a longer period than after the administration of carboplatin alone. Conclusions. The tumor growth suppression effect was significantly higher in the mice bearing the OVA-1 tumor that received 6D7-conjugate than in the animals that received carboplatin alone. This difference could be caused by differences in the platinum concentrations in the tumor between the two groups. Received: November 9, 1998 / Accepted: March 23, 1999