The Effect of Spinal Cord Injury on Beta-Amyloid Plaque Pathology in TgCRND8 Mouse Model of Alzheimer's Disease.

BACKGROUND: The accumulation and aggregation of Aß as amyloid plaques, the hallmark pathology of the Alzheimer's disease, has been found in other neurological disorders, such as traumatic brain injury. The axonal injury may contribute to the formation of Aß plaques. Studies to date have focused on the brain, with no investigations of spinal cord, although brain and cord share the same cellular components. OBJECTIVE: We utilized a spinal cord transection model to examine whether spinal cord injury acutely induced the onset or promote the progression of Aß plaque 3 days after injury in TgCRND8 transgenic model of AD. METHODS: Spinal cord transection was performed in TgCRND8 mice and its littermate control wild type mice at the age of 3 and 20 months. Immunohistochemical reactions/ELISA assay were used to determine the extent of axonal damage and occurrence/alteration of Aß plaques or levels of Aß at different ages in the spinal cord of TgCRND8 mice. RESULTS: After injury, widespread axonal pathology indicated by intra-axonal co-accumulations of APP and its product, Aß, was observed in perilesional region of the spinal cord in the TgCRND8 mice at the age of 3 and 20 months, as compared to age-matched non-TgCRND8 mice. However, no Aß plaques were found in the TgCRND8 mice at the age of 3 months. The 20-month-old TgCRND8 mice with established amyloidosis in spinal cord had a reduction rather than increase in plaque burden at the lesion site compared to the tissue adjacent to the injured area and corresponding area in sham mice following spinal cord transection. The lesion site of spinal cord area was occupied by CD68 positive macrophages/ activated microglia in injured mice compared to sham animals. These results indicate that spinal cord injury does not induce the acute onset and progression of Aß plaque deposition in the spinal cord of TgCRND8 mice. Conversely, it induces the regression of Aß plaque deposition in TgCRND8 mice. CONCLUSION: The findings underscore the dependence of traumatic axonal injury in governing acute Aß plaque formation and provide evidence that Aß plaque pathology may not play a role in secondary injury cascades following spinal cord injury.

Effectiveness of the EMPOWER-PAR Intervention in Improving Clinical Outcomes of Type 2 Diabetes Mellitus in Primary Care: A Pragmatic Cluster Randomised Controlled Trial.

BACKGROUND: The chronic care model was proven effective in improving clinical outcomes of diabetes in developed countries. However, evidence in developing countries is scarce. The objective of this study was to evaluate the effectiveness of EMPOWER-PAR intervention (based on the chronic care model) in improving clinical outcomes for type 2 diabetes mellitus using readily available resources in the Malaysian public primary care setting. METHODS: This was a pragmatic, cluster-randomised, parallel, matched pair, controlled trial using participatory action research approach, conducted in 10 public primary care clinics in Malaysia. Five clinics were randomly selected to provide the EMPOWER-PAR intervention for 1 year and another five clinics continued with usual care. Patients who fulfilled the criteria were recruited over a 2-week period by each clinic. The obligatory intervention components were designed based on four elements of the chronic care model i.e. healthcare organisation, delivery system design, self-management support and decision support. The primary outcome was the change in the proportion of patients achieving HbA1c < 6.5%. Secondary outcomes were the change in proportion of patients achieving targets for blood pressure, lipid profile, body mass index and waist circumference. Intention to treat analysis was performed for all outcome measures. A generalised estimating equation method was used to account for baseline differences and clustering effect. RESULTS: A total of 888 type 2 diabetes mellitus patients were recruited at baseline (intervention: 471 vs. CONTROL: 417). At 1-year, 96.6 and 97.8% of patients in the intervention and control groups completed the study, respectively. The baseline demographic and clinical characteristics of both groups were comparable. The change in the proportion of patients achieving HbA1c target was significantly higher in the intervention compared to the control group (intervention: 3.0% vs. CONTROL: -4.1%, P < 0.002). Patients who received the EMPOWER-PAR intervention were twice more likely to achieve HbA1c target compared to those in the control group (adjusted OR 2.16, 95% CI 1.34-3.50, P < 0.002). However, there was no significant improvement found in the secondary outcomes. CONCLUSIONS: This study demonstrates that the EMPOWER-PAR intervention was effective in improving the primary outcome for type 2 diabetes in the Malaysian public primary care setting. TRIAL REGISTRATION: Registered with: ClinicalTrials.gov.: NCT01545401 . Date of registration: 1st March 2012.

Study protocol of EMPOWER participatory action research (EMPOWER-PAR): a pragmatic cluster randomised controlled trial of multifaceted chronic disease management strategies to improve diabetes and hypertension outcomes in primary care.

BACKGROUND: Chronic disease management presents enormous challenges to the primary care workforce because of the rising epidemic of cardiovascular risk factors. The chronic care model was proven effective in improving chronic disease outcomes in developed countries, but there is little evidence of its effectiveness in developing countries. The aim of this study was to evaluate the effectiveness of the EMPOWER-PAR intervention (multifaceted chronic disease management strategies based on the chronic care model) in improving outcomes for type 2 diabetes mellitus and hypertension using readily available resources in the Malaysian public primary care setting. This paper presents the study protocol. METHODS/DESIGN: A pragmatic cluster randomised controlled trial using participatory action research is underway in 10 public primary care clinics in Selangor and Kuala Lumpur, Malaysia. Five clinics were randomly selected to provide the EMPOWER-PAR intervention for 1 year and another five clinics continued with usual care. Each clinic consecutively recruits type 2 diabetes mellitus and hypertension patients fulfilling the inclusion and exclusion criteria over a 2-week period. The EMPOWER-PAR intervention consists of creating/strengthening a multidisciplinary chronic disease management team, training the team to use the Global Cardiovascular Risks Self-Management Booklet to support patient care and reinforcing the use of relevant clinical practice guidelines for management and prescribing. For type 2 diabetes mellitus, the primary outcome is the change in the proportion of patients achieving HbA1c < 6.5%. For hypertension without type 2 diabetes mellitus, the primary outcome is the change in the proportion of patients achieving blood pressure < 140/90 mmHg. Secondary outcomes include the proportion of patients achieving targets for serum lipid profile, body mass index and waist circumference. Other outcome measures include medication adherence levels, process of care and prescribing patterns. Patients' assessment of their chronic disease care and providers' perceptions, attitudes and perceived barriers in care delivery and cost-effectiveness of the intervention are also evaluated. DISCUSSION: Results from this study will provide objective evidence of the effectiveness and cost-effectiveness of a multifaceted intervention based on the chronic care model in resource-constrained public primary care settings. The evidence should instigate crucial primary care system change in Malaysia. TRIAL REGISTRATION: ClinicalTrials.gov NCT01545401.

Role of video games in improving health-related outcomes: a systematic review.

CONTEXT: Video games represent a multibillion-dollar industry in the U.S. Although video gaming has been associated with many negative health consequences, it also may be useful for therapeutic purposes. The goal of this study was to determine whether video games may be useful in improving health outcomes. EVIDENCE ACQUISITION: Literature searches were performed in February 2010 in six databases: the Center on Media and Child Health Database of Research, MEDLINE, CINAHL, PsycINFO, EMBASE, and the Cochrane Central Register of Controlled Trials. Reference lists were hand-searched to identify additional studies. Only RCTs that tested the effect of video games on a positive, clinically relevant health consequence were included. Study selection criteria were strictly defined and applied by two researchers working independently. Study background information (e.g., location, funding source); sample data (e.g., number of study participants, demographics); intervention and control details; outcomes data; and quality measures were abstracted independently by two researchers. EVIDENCE SYNTHESIS: Of 1452 articles retrieved using the current search strategy, 38 met all criteria for inclusion. Eligible studies used video games to provide physical therapy, psychological therapy, improved disease self-management, health education, distraction from discomfort, increased physical activity, and skills training for clinicians. Among the 38 studies, a total of 195 health outcomes were examined. Video games improved 69% of psychological therapy outcomes, 59% of physical therapy outcomes, 50% of physical activity outcomes, 46% of clinician skills outcomes, 42% of health education outcomes, 42% of pain distraction outcomes, and 37% of disease self-management outcomes. Study quality was generally poor; for example, two thirds (66%) of studies had follow-up periods of <12 weeks, and only 11% of studies blinded researchers. CONCLUSIONS: There is potential promise for video games to improve health outcomes, particularly in the areas of psychological therapy and physical therapy. RCTs with appropriate rigor will help build evidence in this emerging area.