Effects of Etanercept on Experimental Osteoarthritis in Rats: Role of Histone Deacetylases.

OBJECTIVE: Mounting evidence suggests that histone deacetylases (HDAC) inhibitors reduce cartilage destruction in animal models of osteoarthritis (OA). Tumor necrosis factor (TNF)-α-blocking treatment for OA may provide effective joint protection by slowing joint damage. To investigate the effects of intraperitoneal administration of etanercept (a TNF-α inhibitor) on OA development in rats and changes in the nociceptive behavior of rats and expression of HDACs, RUNX2, and MMP13 in cartilage. METHODS: Induction of OA in Wistar rats was accomplished through anterior cruciate ligament transection (ACLT). One or five milligrams (mg) of etanercept was administered intraperitoneally for 5 consecutive weeks after ACLT to the ACLT + etanercept (1 and 5 mg/kg) groups. Nociceptive behavior and changes in knee joint width were analyzed. Cartilage was evaluated histologically and immunohistochemically. RESULTS: ACLT + etanercept significantly improved mechanical allodynia and weight-bearing distribution compared to ACLT alone. In OA rats treated with etanercept, cartilage degeneration and synovitis were significantly less pronounced than those in ACLT rats. OA-affected cartilage also showed reduced expression of HDAC 6, 7, RUNX-2, and MMP-13 in response to etanercept but increased expression of HDAC4. CONCLUSION: Our study demonstrated that etanercept therapy (1) attenuated the development of OA and synovitis in rats, (2) reduced nociception, and (3) regulated chondrocyte metabolism, possibly by inhibiting cell HDAC6 and HDAC7, RUNX2, and MMP13 and increasing HDAC4 expression. Based on new evidence, etanercept may have therapeutic potential in OA.

The COX-2 inhibitor etoricoxib reduces experimental osteoarthritis and nociception in rats: The roles of TGF-ß1 and NGF expressions in chondrocytes.

BACKGROUND: Osteoarthritis (OA) is the most common joint disease, especially affecting the knee joint. Etoricoxib, a highly selective cyclooxygenase (COX)-2 inhibitor which can reduce postoperative pain after orthopaedic surgery. The aim of this study was to investigate the effects of oral etoricoxib on the development of OA and to examine concomitant changes in the nociceptive behaviour of rats. METHOD: OA was induced in wistar rats by anterior cruciate ligament transection (ACLT) of the right knee. The ACLT + etoricoxib groups received 6.7 or 33.3 mg/kg of oral etoricoxib three times a week for 12 consecutive weeks, starting at week 8 after ACLT. Nociceptive behaviours and changes in knee joint width during OA development were analyzed. Histopathological studies were then performed on the cartilage. Immunohistochemical analysis was performed to examine the effect of etoricoxib on the expression of transforming growth factor-beta (TGF-ß) and nerve growth factor (NGF) in articular cartilage chondrocytes. RESULTS: OA rats receiving etoricoxib showed a significantly lower degree of cartilage degeneration than the rats receiving placebo. Nociceptive behaviour studies showed significant improvement in the ACLT + etoricoxib groups compared to that in the ACLT group. Moreover, etoricoxib attenuated NGF expression, but increased TGF-ß expression, in OA-affected cartilage. CONCLUSIONS: Oral etoricoxib in a rat OA model (a) attenuates the development of OA, (b) concomitantly reduces nociception, and (c) modulates chondrocyte metabolism, possibly by inhibiting NGF expression and increasing TGF-ß expression. SIGNIFICANCE: Oral administration of etoricoxib can attenuate the development of OA, with an associated attenuation of nociceptive behaviour in an experimental rat OA model. Moreover, etoricoxib attenuated NGF expression, but enhanced TGF-ß expression in OA-affected chondrocytes. These findings may pave the way for further investigations of etoricoxib as a potential therapeutic target for the treatment of the inflammatory component in OA.

A cross-sectional study of the characteristics and determinants of emergency care utilization among people with intellectual disabilities in Taiwan.

AIMS: The purpose of this study was to identify health characteristics of people with intellectual disabilities (ID) and to assess the use of emergency care facilities by these people and factors affecting this utilization. METHOD: A cross-sectional study was employed. Subjects were recruited from the Taiwan National Disability Registration System. A total of 1071 people registered with ID in Taiwan were recruited for this study in 2001. Data were collected via a structured mail-out questionnaire that was completed by the main carers of people with ID. RESULTS: Most of the carers subjectively characterized the overall health status of people with ID as good-excellent. However, people with ID carry a burden of diseases greater than that of the general population. Nearly half (47.7%) of the subjects reported having an illness in the past 7 months. Most of the morbidity was associated with neurological, psychiatric, digestive, dermatological and cardiovascular diseases or disorders. One-third of subjects took medication regularly and 15% were 'Major Illness' card beneficiaries of the Taiwan National Health Insurance scheme. About two-thirds of individuals with ID were classified as having multiple disabilities and 24.5% needed to be provided with frequent rehabilitative therapies to maintain their normal daily functions. Respondents indicated that 18.4% of the subjects had used emergency care in the past 7 months. A stepwise logistic regression model highlighted that the following need factors were significantly related to the utilization of emergency care: having an illness (OR=2.1, 95% CI=1.2-3.6), taking medicine regularly (OR=1.8, 95% CI=1.1-2.9) and self-reported health status (poor health: OR=9.9, 95% CI=2.1-45.7; bad health: OR=8.2, 95% CI=1.3-49.8). CONCLUSIONS: To ensure that people with ID minimize their utilization of emergency care, it is necessary to establish in appropriate community systems to monitor individuals with ID with poor health status, diseases and who take medicine regularly.

Calcitonin attenuates cartilage degeneration and nociception in an experimental rat model of osteoarthritis: role of TGF-ß in chondrocytes.

We investigated the role of the calcitonin (Miacalcin) in the progression of osteoarthritis (OA) and in nociceptive behavior in an experimental rat model of OA and osteoporosis. OA was induced by anterior cruciate ligament transection (ACLT) of the right knee and by bilateral ovariectomy (OVX) in Wistar rats. Nociceptive behaviors (secondary mechanical allodynia and weight-bearing distribution of the hind paws) were analyzed prior to surgery and every week, beginning at 12 weeks after surgery, up to 20 weeks. At 20 weeks, histopathological studies were performed on the cartilage of the knee joints. Immunohistochemical analysis was performed to examine the effect of calcitonin on transforming growth factor (TGF)-ß1 expression in articular cartilage chondrocytes. Rats subjected to ACLT + OVX surgery showed obvious OA changes in the joints. Animals subjected to ACLT + OVX and treated with calcitonin showed significantly less cartilage degeneration and improved nociceptive tests compared with animals subjected to ACLT + OVX surgeries alone. Moreover, calcitonin increased TGF-ß1 expression in chondrocytes in ACLT + OVX-affected cartilage. Subcutaneous injection of calcitonin (1) attenuated the development of OA, (2) concomitantly reduced nociception, and (3) modulated chondrocyte metabolism, possibly by increasing cellular TGF-ß1 expression.

Primary caregivers' awareness and perception of early-onset dementia conditions in adolescents and young and middle-aged adults with Down syndrome.

The present study aims to investigate the onset of dementia conditions using the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) scale and to identify the possible factors associated with DSQIID scores in people with Down syndrome (DS). The study population was recruited from the voluntary registry members of the Republic of China Foundation for Persons with Down syndrome; primary caregivers provided DSQIID information on 196 adolescents and adults with DS (aged 15-48 years) who were entered into the database and analyzed using SPSS 20.0 software. The results described the distribution of early-onset dementia conditions in 53 adolescents and adults with DS, and 2.6% of the subjects with DS had possible dementia (DSQIID score ≧ 20). Univariate analyses found that older age (p=0.001) and comorbid conditions (p=0.003) were significantly associated with DSQIID scores. Older subjects were more likely to have higher DSQIID scores than were younger age groups after ANOVA and Scheffe's tests. Lastly, a multiple linear regression analysis revealed that age (p<0.01), severe disability level (p<0.05) and comorbid condition (p<0.01) significantly explained 13% of the variation in DSQIID scores after adjusting for the factors of gender, education level and multiple disabilities in adolescents and adults with DS. The study highlights that future research should focus on the occurrence of dementia in people with DS and on identifying its influencing factors based on sound measurements, to initiate appropriate healthy aging policies for this group of people.

Evaluation of a Leadership Orientation Program in Taiwan: preceptorship and leader competencies of the new nurse manager.

The Leadership Orientation Program is designed to provide new nurse managers with the experience and support that assures them of a smooth transition from their current roles to being managers. The main objective of this study was to gain an understanding of the relationship that exists between a nursing preceptorship and a new nurse manager's competencies; it also attempted to establish a predictive model of leader competencies to improve the program. A descriptive cross-sectional research design and rigorous questionnaires were used in this study. Fifteen new nurse managers, 101 staff nurses, and 20 nurse administrators were recruited from those engaged in ongoing preceptorship. Over the course of the study statistically significant improvements in preceptorship were noted in both new manager educational background and support from staff nurses. Eighty-five percent of new nurse managers had good or excellent performance ratings (Mean=84.25%). The significant predictive factors of nurse leader competencies were the educational background of new managers and the teaching resources available with regard to preceptorship (R(2)=88.5%, F=6.86, p<0.001).

Disability and hospital care expenses among national health insurance beneficiaries: analyses of population-based data in Taiwan.

Nationwide data were collected concerning inpatient care use and medical expenditure of people with disabilities (N=937,944) among national health insurance beneficiaries in Taiwan. Data included gender, age, hospitalization frequency and expenditure, healthcare setting and service department, discharge diagnose disease according to the ICD-9-CM coding system which has been used in Taiwan NHI diagnosis system. There were 27.88% of persons with disabilities have been hospitalized for treatments during the year 2005 and it was 3.5 times of the general population (7.95%). The mean of annual inpatient care expenditure was 163,544.21 NTD, and male patients use more inpatient care cost than female patients in people with disabilities. However, the hospitalization rate in female patients is statistical higher than male patients in the study (p<0.001). Infectious and parasitic diseases, mental disorders, diseases of the respiratory system, diseases of the circulatory system, injury and poisoning were the top five reasons for hospitalization among the subjects. Our study also found that psychiatry, internal medicine, orthopedic, surgery and neurosurgery are the top five clinical divisions which the cases used more frequently than other clinical departments in hospitalizations. The present study presents the first information of hospitalization care and medical costs in people with disabilities based on a nationwide data analyzes in Taiwan. We suggest the importance of supporting people with disabilities during hospitalizations, following up rehabilitation and there is an urgent need for cost-effective intervention programs for disability prevention, which could be offset against the cost for treating the disabled in the future.

Prevalence and associated risk factors of anemia in children and adolescents with intellectual disabilities.

Anemia is known to be a significant public health problem in many countries. Most of the available information is incomplete or limited to special groups such as people with intellectual disability. The present study aims to provide the information of anemia prevalence and associated risk factors of children and adolescents with intellectual disability in Taiwan. We analyzed physical examination charts of 937 children and adolescents with intellectual disability at the age of 6-18 years from three special schools. We collected information on their demographic characteristics (age and gender), disability condition (type and level), BMI (weight and height) and measured blood hemoglobin concentration (Hb). There were 11.6% of children and adolescents with intellectual disability with anemia (boy <13 g/dl, girl <12 g/dl), and the factors of gender, age, disability level and BMI are significantly correlated to anemia in bivariant analyses in the study. In the logistic regression analysis, the model revealed that the factors of gender (OR=0.63, 95% CI=0.41-0.95), and age (OR=3.21, 95% CI=1.77-5.82) were variables that could significantly predict the anemia occurrence of the participants. The study highlights the anemia prevalence in children and adolescents with ID is a mild public health problem among people with intellectual disabilities, but to prevent the problems become worst; the health authority should include providing children and adolescents with adequate nutrition and appropriate health protections during early childhood.

Extrinsic high-effort and low-reward conditions at work among institutional staff caring for people with intellectual disabilities in Taiwan.

The purposes of the present study were to determine whether extrinsic high-effort/low-reward conditions at work are associated with personal characteristics and the organizational environments. A cross-sectional survey was conducted (76.7% response rate, N=1243) by recruiting the staff caring for people with intellectual disabilities of Taiwan in 2006. Conditions at work were measured using Siegrist's Effort-Reward Imbalance (ERI) model, the questionnaire included 23 Likert scaled items and it divided into three scales: effort, reward and overcommitment. Multiple logistic regression modeling was conducted for extrinsic high-effort/low-reward status in relation to staff and working environmental factors. We found that 15.1% staff were in the low-effort/low-reward group, 35.9% was in the low-effort/high-reward group, 17.9% belonged to the high-effort/high-reward group and 31.1% was included in the high-effort/low-reward group. Controlling for many personal demographic and organizational characteristics, the factors of perceived job support (OR=0.91; 95% CI=0854-0.97), job control (OR=0.954, 95% CI=0.934-0.974), job demand (OR=1.155, 95% CI=1.109-1.203) and job stress (felt sometimes stressful compare to no stress at all, OR=2.305, 95% CI=1.161-4.575) of the staff were significantly correlated to the extrinsic high effort/low reward at work in the multiple logistic regression model. The present study highlights that the service providers need to be aware and understand the experiences that their staff encounters in the organizational, interpersonal and personal level regarding unfair working conditions such as high effort/low reward to improve the positive health of the staff.

Physical and mental health status of staff working for people with intellectual disabilities in Taiwan: measurement with the 36-Item Short-Form (SF-36) health survey.

Little explicit attention has been given to the generic health profile of staff working for people with intellectual disability in institutions. This study aimed to provide a profile of physical and mental health of staff working in disability welfare institutions, and to examine the possible demographic and organizational factors that explain an association with their health. A cross-sectional questionnaire survey was conducted to analyze 1243 staff (76% response rate) working in 24 institutions in Taiwan. The 36-Item Short-Form (SF-36) Taiwan version was used to measure their generic health status. The mean of Physical component scores (PCS) was slightly higher than Mental component scores (MCS) (50.83 vs. 45.12). With regard to each dimension among PCS, the mean score of Physical functioning (PF) was 57.14 (S.D.=5.93), Role limitations-physical (RP) was 49.88 (S.D.=9.69), Bodily pain (BP) was 52.14 (S.D.=8.09) and General medical health (GH) was 51.50 (S.D.=8.28). Among the MCS, Vitality (VT) was 46.19 (S.D.=6.71); Social functioning (SF) was 46.44 (S.D.=7.58); Role limitations-emotional (RE) was 47.30 (S.D.=11.89) and Mental health (MH) was 43.58 (S.D.=8.81). We found the generic health of staff working for people with intellectual disabilities were significantly lower in PCS and MCS than the Taiwan general population. Influences of staff's demographic and organizational characteristics on their health were also analyzed in the content. This study highlights the authorities and service providers need to continue to develop their awareness and understanding of the experiences that their staff encounters in the organizations, so that they can receive resources to support their positive health in working for people with intellectual disabilities.