Simulación de iluminación natural

This systematic review had some strengths. To my knowledge this is the first systematic review to identify the fragility risk tools for potential use in care home residents and the methods used followed the analytical methods and standards established by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) group. Additionally, the methodological qualities of the studies were assessed using QUADAS.

153 The study also had limitations: although effort was made to include the totality of published literature on the subject, it is possible that some studies escaped detection particularly those that were published after the literature search was performed. All the publications were reviewed initially by only the researcher and a second opinion was sought only when there were uncertainties therefore some relevant citations may have been missed. Also a meta- analysis of the included studies was not performed due to considerable heterogeneity in the study characteristics.

2.6 Conclusion

This systematic review identified 33 existing fragility risk tools of which four may be useable in care home residents. These tools are FRAX, QFractureScores, Garvan nomogram and BMI. Apart from BMI, all the tools are web-based (FRAX has paper-based version) and express fracture risk as absolute probability. They contain varying numbers of predictors of which BMI is common. In the next project, a questionnaire will be developed using all the predictors from the tools and acceptability tested in two care homes in preparation for the observational cohort study.

2.7 Addendum

As the initial literature search on which this project is based was conducted in 2014 a further, updated, search was conducted to determine whether any new fragility fracture assessment tools have been reported and evaluated since. The period of search was from 15/04/2014 to 19/07/2019. Identical search terms, search strings and databases (section 2.3.1.2 in thesis), were used and only publications in English language were included as in the previous search. The same criteria and procedures as in the initial search (section 2.3.1.4 in thesis) were used for the screening and the selection of publications and all the decisions were independently verified by the same second reviewer, AP.

154 A total of 989 publications were identified and 550 were left after duplicates were removed. Of these 289 were rejected because their titles indicated that they were irrelevant, 40 were rejected because they were experimental studies, 28 were rejected because they were statistical models, 2 were rejected because they were case reports and 191 publications were rejected because they contained tools which I had reviewed previously. A total of 11 full journal publications were reviewed and of these 2 have informed the addendum, in addition a 5th paper was identified from the reference list of Walter and colleagues (2017). Eight papers were rejected as they did not meet the criteria. There were 3 papers that suggest microRNAs have a future potential but the biomarkers are yet to be isolated (Walter et al., 2017, Hellmeier et al., 2016, & Bedene et al., 2016). In community dwelling older adults, the FRAX remains less sensitive than suggested in the literature (Atkinson et al et al., 2015, Duncan et al., 2014 & Holloway et al., 2015).

MicroRNAs define the physiological nature of the cell and play significant roles in the diverse biological processes such as cell differentiation, proliferation, death, immunity and metabolism (Wahid et al., 2014). Aberrantly expressed miRNAs can be used as biomarkers for the diagnosis of a variety of diseases including osteoporotic fractures. A number of miRNAs have been discovered. At the cellular level, miR-21 and miR-148a are known to play specific roles in bone homeostasis. Seeliger and colleagues discovered 9 upregulated circulating miRNA (miR-21, miR-23a, miR-93, miR-100, miR-122a, miR-124a, miR-125b, and miR- 148a) that could significantly distinguish between serum samples of osteoporotic and non- osteoporotic fractured patients in a cohort (Seeliger et al.2014). Kocijan and colleagues (2016) found that a set of 19 miRNA was consistently upregulated in three subgroups of 46 premenopausal women, 52 postmenopausal women and 55 males and that these were excellent discriminators of patients with low-traumatic fractures with area under the curve of between 0.81 and 0.89. Over a lifetime, estimating miRNA could avoid 57,919 fractures compared with

155 DEXA, 31,285 fractures compared with FRAX and 133,394 fractures compared with no monitoring (Walter et al 2017).

Analyses of miRNA have the advantage that they are minimally invasive requiring only blood samples; therefore they could be useful for care home residents. But there are a number of confounding variables with their estimation and diagnostic thresholds are yet to be established. Also the cost effectiveness of miRNA profiling is not yet known (Walter et al 2017), therefore if I had identified this tool as a predictor before now, it would not have been selected as a tool for use in care home residents. However, these biomarkers could open a novel method for the diagnosis and response to treatment of fragility fractures but more research is needed.

For the identification of high risk people, many guidelines recognise that widespread screening is currently neither feasible nor desirable and therefore adopt the case-finding strategy. The National Institute for Health and Care Excellence (NICE) has recently released new guidance for fragility fractures (NICE 2016). The guidelines state that fracture risk should be considered in the following circumstances : in all women aged 65 years and over and all men aged 75 years and over, in women aged under 65 years and men aged under 75 years in the presence of risk factors such as previous fragility fracture, current use or frequent use of oral systemic glucocorticoids, history of falls, family history of hip fracture, other causes of secondary osteoporosis, low body mass index less than 18.5 kg/m², smoking and alcohol intake of more than 14 units per week for women and more than 21 units per week for men. NICE guideline recommends that fracture risk should be estimated using diagnostic tools such as FRAX or QFractureScores.

156 The Scottish Intercollegiate Guidelines Network (SIGN 2015) recommends that the assessment should be carried out preferably using QFractureScores because of the extensive validation of QFractureScores in the UK population. The National Osteoporosis Guideline Group (NOGG) recommends the fracture risk assessment should be undertaken with FRAX and vertebral fracture assessment should be considered in postmenopausal women and men age > 50 years if there is a history of ≥ 4 cm height loss, kyphosis, recent or current long-term oral glucocorticoid therapy, or a BMD T-score ≤ - 2.5 (NOGG 2018). In the United States, the National Osteoporosis Foundation (NOF 2008) recommends FRAX and uses these risk factors for case-finding: previous fragility fractures (vertebral or non-vertebral), low body weight (less than 127Ibs [58kg] for USA citizens) and a family history of fragility fractures. But in my study, I found that both FRAX and QFractureScores were ineffective in care home residents. Vertebral fracture assessment was not done in my study because it was not practicable.

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Chapter 3. Consultation Visits to Two Care Homes to Determine the