A systematic review of biomarkers for disease progression in Parkinson's disease

This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0707-10124).BACKGROUND: Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true disease-modifying effects. A systematic review was undertaken to determine what biomarkers for disease progression in Parkinson's disease (PD) exist. METHODS: MEDLINE and EMBASE (1950-2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with idiopathic PD diagnosed by formal criteria or clearly described clinical means were included. We made no restriction on age, disease duration, drug treatment, or study design. We included studies which attempted to draw associations between any tests used to investigate disease progression and any clinical measures of disease progression. The electronic search was validated by hand-searching the two journals from which most included articles came. RESULTS: 183 studies were included: 163 (89%) cross-sectional, 20 (11%) longitudinal. The electronic search strategy had a sensitivity of 71.4% (95% CI 51.1-86.0) and a specificity of 97.1% (95% CI 96.5-97.7). In longitudinal studies median follow-up was 2.0 years (IQR 1.1-3.5). Included studies were generally poor quality--cross-sectional with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and simplistic statistical analyses. CONCLUSION: We found insufficient evidence to recommend the use of any biomarker for disease progression in PD clinical trials, which may simply reflect the poor quality of research in this area. We therefore present a provisional 'roadmap' for conducting future disease progression biomarker studies, and recommend new quality criteria by which future studies may be judged.Publisher PDFPeer reviewe

NGOs and the Promotion of the Sexual and Reproductive Rights of Girls and Young Women with Disabilities in Zimbabwe

This case study investigates strategies used by the NGO Leonard Cheshire Disability Zimbabwe (LCDZ) to promote the SRHRs of girls and young women with disabilities in Zimbabwe. The findings show that LCDZ employed a combination of six strategies. These are: (1) building practical knowledge on SRHRs; (2) increasing community awareness and sensitivity; (3) providing SRHRs-related education; (4) enhancing access to justice and related services for survivors of sexual violence; (5) delivering assistive devices; and (6) promoting the livelihoods and economic empowerment. LCDZ made use of multi-stakeholder partnerships to implement these strategies, leveraging complementary skills and experience in the promotion of SRHRs. In each of these strategies, girls and young women with disabilities are the target group, with other stakeholders brought together to support them

Physical Activity in Individuals with Autism Spectrum Disorders (ASD): A Review

Current recommendations indicate that children and youth ages 5–17 should participate in 60 min and adults in 150 min of moderate-to-vigorous physical activity daily. Research suggests that physical activity levels of individuals with autism spectrum disorder (ASD) are lower than typically developing and developed peers. Despite evidence for PA decreasing negative behaviors and promoting positive behaviors, individuals with ASD may be less motivated and less likely to participate. Individuals with ASD may be more likely to be overweight or obese than their typically developing counterparts as a result of decreased activity levels. Conflicting findings regarding PA levels in individuals with ASD have been reported. Given mixed evidence, further inquiry is warranted. The present chapter provides a review of literature pertaining to PA in individuals with ASD. Four databases were searched. Predetermined search terms and inclusion/exclusion criteria were clearly outlined to identify relevant articles which were then critically appraised. This research provides a greater understanding of the status of PA participation of individuals with ASD

Meeting report: a hard look at the state of enamel research.

The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research (NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field

Working in preventive medicine or not? Flawed perceptions decrease chance of retaining students for the profession

Background: Recruiting and retaining students in preventive medical (PM) specialties has never been easy; one main challenge is how to select appropriate students with proper motivation. Understanding how students perceive PM practice differently from practicing doctors is necessary to guide students, especially for those for whom PM is only a substitute for medicine as their first study preference, properly during their study and, later, the practice of PM. Methods: One thousand three hundred eighty-six PM students in four Vietnamese medical schools and 101 PM doctors filled out a questionnaire about the relevance of 44 characteristics of working in PM. ANOVAs were conducted to define the relationship between students' interest, year of study, willingness to work in PM, and the degree to which students had realistic perceptions of PM practice, compared to doctors' perceptions. Results: Overall, compared to doctors' perceptions, students overestimated the importance of most of the investigated PM practice's characteristics. Moreover, students' perception related to their preference and willing to pursue a career in PM after graduation. In particular, students for whom PM was their first choice had more realistic perceptions of community practice than those who chose PM as their second choice. And, second-choice students had more realistic perceptions than first-choice students in their final years of study, but expected higher work stress in PM practice. Students who were willing to pursue a career in PM rated the importance of community practice higher than those who were not. We also found that students' perception changed during training as senior students had more realistic perceptions of clinical aspects and working stress than junior students, even though they overemphasized the importance of the community aspects of PM practice. Conclusions: To increase the number of students actually entering the PM field after graduation, the flawed perceptions of students about the real working environment of PM doctors should be addressed through vocation-oriented activities in the curriculum targeted on groups of students who are most likely to have unrealistic perceptions. Our findings also have implications for other less attractive primary health care specialties that experience problems with recruiting and retaining students

Cost-Effectiveness Analysis of Screening for and Managing Identified Hypertension for Cardiovascular Disease Prevention in Vietnam

OBJECTIVE:To inform development of guidelines for hypertension management in Vietnam, we evaluated the cost-effectiveness of different strategies on screening for hypertension in preventing cardiovascular disease (CVD). METHODS:A decision tree was combined with a Markov model to measure incremental cost-effectiveness of different approaches to hypertension screening. Values used as input parameters for the model were taken from different sources. Various screening intervals (one-off, annually, biannually) and starting ages to screen (35, 45 or 55 years) and coverage of treatment were analysed. We ran both a ten-year and a lifetime horizon. Input parameters for the models were extracted from local and regional data. Probabilistic sensitivity analysis was used to evaluate parameter uncertainty. A threshold of three times GDP per capita was applied. RESULTS:Cost per quality adjusted life year (QALY) gained varied in different screening scenarios. In a ten-year horizon, the cost-effectiveness of screening for hypertension ranged from cost saving to Int$758,695 per QALY gained. For screening of men starting at 55 years, all screening scenarios gave a high probability of being cost-effective. For screening of females starting at 55 years, the probability of favourable cost-effectiveness was 90$ 15,883 in all screening scenarios among males. Similar results were found in females when starting screening at 55 years. Starting screening in females at 45 years had a high probability of being cost-effective if screening biannually was combined with increasing coverage of treatment by 20% or even if sole biannual screening was considered. CONCLUSION:From a health economic perspective, integrating screening for hypertension into routine medical examination and related coverage by health insurance could be recommended. Screening for hypertension has a high probability of being cost-effective in preventing CVD. An adequate screening strategy can best be selected based on age, sex and screening interval

Why do graduates choose to work in a less attractive specialty? A cross-sectional study on the role of personal values and expectations

Background: Primary health care (PHC), of which preventive medicine (PM) is a subspecialty, will have to cope with a deficiency of staff in the future, which makes the retention of graduates urgent. This study was conducted in Vietnam, where PM is an undergraduate degree in parallel to medical training. It aims to identify facilitating and hindering factors that impact recruitment and retention of PM graduates in the specialty. Methods: A cross-sectional study enrolled 167 graduates who qualified as PM doctors from a Vietnamese medical school, between 2012 and 2018. Data were collected via an online questionnaire that asked participants about their motivation and continuation in PM, the major life roles that they were playing, and their satisfaction with their job. Multiple regression analyses were used to identify which life roles and motivational factors were related to the decision to take a PM position and to stay in the specialty, as well as how these factors held for subgroups of graduates (men, women, graduates who studied PM as their first or second study choice). Results: Half of the PM graduates actually worked in PM, and only one fourth of them expressed the intention to stay in the field. Three years after qualification, many graduates had not yet decided whether to pursue a career in PM. Satisfaction with opportunities for continuous education was rated as highly motivating for graduates to choose and to stay in PM. Responsibility for taking care of parents motivated male graduates to choose PM, while good citizenship and serving the community was associated with the retention of graduates for whom PM was their first choice. Conclusions: The findings demonstrate the importance of social context and personal factors in developing primary care workforce policy. Providing opportunities for continued education and enhancing the attractiveness of PM as an appropriate specialty to doctors who are more attached to family and the community could be solutions to maintaining the workforce in PM. The implications could be useful for other less popular specialties that also struggle with recruiting and retaining staff

Practicing doctors' perceptions on new learning objectives for Vietnamese medical schools

<p>Abstract</p> <p>Background</p> <p>As part of the process to develop more community-oriented medical teaching in Vietnam, eight medical schools prepared a set of standard learning objectives with attention to the needs of a doctor working with the community. Because they were prepared based on government documents and the opinions of the teachers, it was necessary to check them with doctors who had already graduated and were working at different sites in the community.</p> <p>Methods</p> <p>Each of the eight medical faculties asked 100 practising recent graduates to complete a questionnaire to check the relevance of the skills that the teachers considered most important. We used mean and standard deviation to summarize the scores rated by the respondents for each skill and percentile at four points: p50, p25, p10 and p5 to describe the variation of scores among the respondents. Correlation coefficient was used to measure the relationship between skill levels set by the teachers and the perception of practicing doctors regarding frequency of using skills and priority for each skill. Additional information was taken from the records of focus group discussions to clarify, explain or expand on the results from the quantitative data.</p> <p>Results</p> <p>In many cases the skills considered important by teachers were also rated as highly necessary and/or frequently used by the respondents. There were, however, discrepancies: some skills important to teachers were seldom used and not considered important by the doctors. In focus group discussions the doctors also identified skills that are not taught at all in the medical schools but would be needed by practising doctors. </p> <p>Conclusion</p> <p>Although most of the skills and skill levels included in the learning objectives by the teachers were consistent with the opinions of their graduates, the match was not perfect. The experience of the graduates and their additional comments should be included as inputs to the definition of learning objectives for medical students.</p

The liver X receptor pathway is highly upregulated in rheumatoid arthritis synovial macrophages and potentiates TLR-driven cytokine release

&lt;p&gt;Objectives: Macrophages are central to the inflammatory processes driving rheumatoid arthritis (RA) synovitis. The molecular pathways that are induced in synovial macrophages and thereby promote RA disease pathology remain poorly understood.&lt;/p&gt; &lt;p&gt;Methods: We used microarray to characterise the transcriptome of synovial fluid (SF) macrophages compared with matched peripheral blood monocytes from patients with RA (n=8).&lt;/p&gt; &lt;p&gt;Results: Using in silico pathway mapping, we found that pathways downstream of the cholesterol activated liver X receptors (LXRs) and those associated with Toll-like receptor (TLR) signalling were upregulated in SF macrophages. Macrophage differentiation and tumour necrosis factor α promoted the expression of LXRα. Furthermore, in functional studies we demonstrated that activation of LXRs significantly augmented TLR-driven cytokine and chemokine secretion.&lt;/p&gt; &lt;p&gt;Conclusions: The LXR pathway is the most upregulated pathway in RA synovial macrophages and activation of LXRs by ligands present within SF augments TLR-driven cytokine secretion. Since the natural agonists of LXRs arise from cholesterol metabolism, this provides a novel mechanism that can promote RA synovitis.&lt;/p&gt