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CCCTC-binding factor (CTCF) is an insulator protein that binds to a highly conserved DNA motif and facilitates regulation of three-dimensional (3D) nuclear architecture and transcription. CTCF binding sites (CTCF-BSs) reside in non-coding DNA and are frequently mutated in cancer. Our previous study identified a small subclass of CTCF-BSs that are resistant to CTCF knock down, termed persistent CTCF binding sites (P-CTCF-BSs). P-CTCF-BSs show high binding conservation and potentially regulate cell-type constitutive 3D chromatin architecture. Here, using ICGC sequencing data we made the striking observation that P-CTCF-BSs display a highly elevated mutation rate in breast and prostate cancer when compared to all CTCF-BSs. To address whether P-CTCF-BS mutations are also enriched in other cell-types, we developed CTCF-INSITE-a tool utilising machine learning to predict persistence based on genetic and epigenetic features of experimentally-determined P-CTCF-BSs. Notably, predicted P-CTCF-BSs also show a significantly elevated mutational burden in all 12 cancer-types tested. Enrichment was even stronger for P-CTCF-BS mutations with predicted functional impact to CTCF binding and chromatin looping. Using in vitro binding assays we validated that P-CTCF-BS cancer mutations, predicted to be disruptive, indeed reduced CTCF binding. Together this study reveals a new subclass of cancer specific CTCF-BS DNA mutations and provides insights into their importance in genome organization in a pan-cancer setting.
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Factor de Unión a CCCTC , Aprendizaje Automático , Mutación , Factor de Unión a CCCTC/metabolismo , Factor de Unión a CCCTC/genética , Humanos , Sitios de Unión/genética , Cromatina/metabolismo , Cromatina/genética , Neoplasias/genética , Neoplasias/metabolismo , Unión Proteica , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Masculino , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismoRESUMEN
Context: Osteoporosis affects more than half of older women, but many are not treated. Whether treatment differs between rural and urban areas is unknown. Objective: To examine differences in osteoporosis treatment among postmenopausal women living in urban and rural areas of Australia. Methods: Women participating in the Australian Longitudinal Study on Women's Health, a prospective longitudinal cohort study, born between 1946-1951, and with osteoporosis or fractures, were included. Surveys from 2004 to 2019 were linked to the Pharmaceutical Benefits Scheme (government-subsidized medications) to assess osteoporosis treatment and adherence, comparing geographical areas. Results: Of the 4259 women included (mean age, 55.6 years), 1703 lived in major cities, 1629 inner regional, 794 outer regional, and 133 remote areas. Over the 15-year follow-up, 1401 (32.9%) women received treatment, including 47.4% of women with osteoporosis and 29.9% with fractures. Women in outer regional and remote areas were less likely to use antiosteoporosis treatment than those in major cities on univariable analysis (outer regional odds ratio, 0.83; 95% CI, 0.72-0.95; remote, 0.65; 0.49-0.86), but this did not remain significant on multivariable analysis. Median duration of use was 10 to 36 months, adherence varied by treatment type (34%-100%) but was not related to incident fractures, and of the women who stopped denosumab, 85% did not receive another consolidating treatment. Conclusions: One-third of women with osteoporosis/fractures received treatment, and adherence was low. There was no difference in treatment use between urban and rural areas after adjusting for risk factors, although the specific treatment used, and adherence, differed.
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The number of women involved with forensic mental health systems internationally is rising, however, limited research has explored the characteristics of those assessed for criminal responsibility. We investigated the demographic, psychiatric, and criminological characteristics of women recommended as eligible or ineligible for the defence of Not Criminally Responsible (NCR) on account of mental disorder following a criminal responsibility assessment in Central Canada. Data were collected through retrospective chart reviews of court-ordered criminal responsibility assessments for 109 women referred for evaluations between 2003 and 2019. Accused were an average age of 34.55 years, predominately identified as Indigenous (37.7%) or Caucasian (20.8%), and had often been charged with assault (47.7%). Women identified in the reports as NCR-eligible were significantly more likely to be employed, experience delusions during the index offence, and have expert reports linking their mental health symptoms to NCR legal criteria. They were also significantly less likely to have a personality disorder, substance-related diagnosis, or have used substances during the index offence. Delusions during the index offence significantly predicted assessment recommendations when controlling for age at assessment order, current substance-related diagnosis, and whether the expert report linked mental health symptoms to NCR legal criteria. Findings indicate the key factors considered by forensic mental health professionals when conducting criminal responsibility assessments with women. Meaningful differences exist between women identified as NCR-eligible and ineligible, with findings illustrating who may be more likely to receive services within the Canadian forensic mental health system.
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Trastornos Mentales , Humanos , Femenino , Adulto , Canadá , Estudios Retrospectivos , Trastornos Mentales/psicología , Persona de Mediana Edad , Psiquiatría Forense , Competencia Mental/legislación & jurisprudencia , Competencia Mental/psicología , Criminales/psicología , Adulto Joven , Defensa por InsaniaRESUMEN
OBJECTIVES: To project how many minimal trauma fractures could be averted in Australia by expanding the number and changing the operational characteristics of fracture liaison services (FLS). STUDY DESIGN: System dynamics modelling. SETTING, PARTICIPANTS: People aged 50 years or more who present to hospitals with minimal trauma fractures, Australia, 2020-31. MAIN OUTCOME MEASURES: Numbers of all minimal trauma fractures and of hip fractures averted by increasing the FLS number (from 29 to 58 or 100), patient screening rate (from 30% to 60%), and capacity for accepting new patients (from 40 to 80 per service per month), and reducing the proportion of eligible patients who do not attend FLS (from 30% to 15%); cost per fracture averted. RESULTS: Our model projected a total of 2 441 320 minimal trauma fractures (258 680 hip fractures; 2 182 640 non-hip fractures) in people aged 50 years or older during 2020-31, including 1 211 646 second or later fractures. Increasing the FLS number to 100 averted a projected 5405 fractures (0.22%; $39 510 per fracture averted); doubling FLS capacity averted a projected 3674 fractures (0.15%; $35 835 per fracture averted). Our model projected that neither doubling the screening rate nor reducing by half the proportion of eligible patients who did not attend FLS alone would reduce the number of fractures. Increasing the FLS number to 100, the screening rate to 60%, and capacity to 80 new patients per service per month would together avert a projected 13 672 fractures (0.56%) at a cost of $42 828 per fracture averted. CONCLUSION: Our modelling indicates that increasing the number of hospital-based FLS and changing key operational characteristics would achieve only moderate reductions in the number of minimal trauma fractures among people aged 50 years or more, and the cost would be relatively high. Alternatives to specialist-led, hospital-based FLS should be explored.
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Conservadores de la Densidad Ósea , Fracturas de Cadera , Osteoporosis , Fracturas Osteoporóticas , Humanos , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/prevención & control , Australia/epidemiología , Prevención SecundariaRESUMEN
Recent research has provided compelling evidence that children experience the negative counterfactual emotion of regret, by manipulating the presence of a counterfactual action that would have led to participants receiving a better outcome. However, it remains unclear if children similarly experience regret's positive counterpart, relief. The current study examined children's negative and positive counterfactual emotions in a novel gain-or-loss context. Four- to 9-year-old children (N = 136) were presented with two opaque boxes concealing information that would lead to a gain or loss of stickers, respectively. Half of the children chose between two keys that matched each box, whereas the other half were compelled to select one box because only one of the two keys matched. After seeing inside the alternative, non-chosen box, children were significantly more likely to report a change in emotion when they could have opened that box than when they could not have. The effects were similar for children who lost stickers and won stickers, and neither effect varied with age. These findings suggest that children may become capable of experiencing regret and relief around the same time, although their expression of these counterfactual emotions may vary with actual and counterfactual gains and losses.
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Conducta de Elección , Emociones , Niño , Humanos , PreescolarRESUMEN
This mixed methods study explores osteoporosis among adults living in a regional area of Victoria, Australia. Three major themes emerged from interviews, which reflected the findings of surveys, concerns regarding the adequacy of care in rural areas, a desire for tailored, local care, and a desire for hybrid telemedicine or in-person services. PURPOSE: Osteoporosis or osteopenia affects over half of adults aged over 50 years. People living outside major cities in Australia have higher hip fracture rates than people living in cities, along with reduced access to bone densitometry and osteoporosis specialists. This study explores osteoporosis risk factors, knowledge, experiences of and preferences for care in people living in a regional area, to inform development of osteoporosis care programs. METHODS: Adults living in a large non-metropolitan region of Australia were invited to participate in a mixed methods study: a survey (phase 1) followed by semi-structured interviews (phase 2) with triangulation of results. Data collected included osteoporosis diagnosis, risk factors, management, knowledge, preferences for care and experience using telemedicine. Surveys were analysed quantitatively, with linear and logistic regression used to assess factors related to osteoporosis knowledge or satisfaction with telemedicine. Interview transcripts were analysed using thematic analysis by two researchers, with in-depth discussion to identify themes. RESULTS: Sixty-two participants completed the survey, and 15 completed interviews. The mean (SD) age of survey participants was 62.2 (14.1) years, 57% had a screening test for osteoporosis, and 12 (19%) had a diagnosis of osteoporosis. The mean osteoporosis knowledge score was 8.4 / 19 and did not differ with age, education, or history of osteoporosis. The majority wanted access to more information about osteoporosis but preferred method differed, and the majority preferred in-person medical consultations to telemedicine. Interview participants were aged between 57 and 87 years, and included 8 with osteoporosis or osteopenia. Three major themes emerged: concerns regarding the adequacy of care in rural areas, a desire for tailored local car and a desire for hybrid telemedicine or in-person services. CONCLUSION: Gaps exist in rural osteoporosis care, including knowledge, screening and management. People have differing experiences of care, access to services and preferences for care. High-quality care, tailored to their needs, was preferred. Improving osteoporosis services for regional Australia will require a flexible, multi-faceted approach, addressing needs of the local community and providers.
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Enfermedades Óseas Metabólicas , Osteoporosis , Adulto , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Densidad Ósea , Victoria/epidemiología , Encuestas y Cuestionarios , Osteoporosis/epidemiología , Población RuralRESUMEN
The accumulation of somatic mutations in healthy human tissues has been extensively characterized, but the mutational landscape of the healthy breast is still poorly understood. Our analysis of whole-genome sequencing shows that in line with other healthy organs, the healthy breast during the reproduction years accumulates mutations with age, with the rate of accumulation in the epithelium of 15.24 ± 5 mutations/year. Both epithelial and stromal compartments contain mutations in breast-specific driver genes, indicative of subsequent positive selection. Parity- and age-associated differences are evident in the mammary epithelium, partly explaining the observed difference in breast cancer risk amongst women of different childbearing age. Parity is associated with an age-dependent increase in the clone size of mutated epithelial cells, suggesting that older first-time mothers have a higher probability of accumulating oncogenic events in the epithelium compared to younger mothers or nulliparous women. In conclusion, we describe the reference genome of the healthy female human breast during reproductive years and provide evidence of how parity affects the genomic landscape of the mammary gland.
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Neoplasias de la Mama , Mama , Embarazo , Humanos , Femenino , Adulto , Paridad , Neoplasias de la Mama/genética , Mutación , Células EpitelialesRESUMEN
Indigenous youth in Canada and the United States of America (USA) have been disproportionately affected by the COVID-19 pandemic due to the compounding of increased illness risk and legacies of colonization. This article reports the findings of a Cochrane rapid review of 23 studies that examined mental wellbeing outcomes for Indigenous youth from March 2020 to April 2023 in Canada and the USA. Reported pandemic-related mental wellbeing impacts included changes in alcohol and substance use, anxiety, depression, sleep, and suicidality. Protective factors emerged including cultural and community connection. Results suggest that mental wellbeing worsened for many Indigenous youth during COVID-19. Clinical implications are discussed alongside guidance for service provision improvements to support Indigenous youth wellbeing, from a lens of self-determination.
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COVID-19 , Trastornos Relacionados con Sustancias , Humanos , Adolescente , Estados Unidos , Pandemias , Salud Mental , Trastornos de AnsiedadRESUMEN
Objective:Individuals may be motivated to conceal or minimize psychological symptoms and engage in positive impression management (PIM) in order to achieve desired outcomes across high stakes contexts (e.g. fitness for duty evaluations, pre-sentencing assessments, medical procedure evaluations, civil commitment). Despite the importance of this topic, the most recent meta-analysis of the MMPI-2, a widely used instrument for detecting PIM, was conducted more than two decades ago. Method:Using a Robust Variance Estimation method, this meta-analysis synthesized the results of 27 studies that examined the MMPI-2 (k = 22) and MMPI-2-RF (k = 5) validity scales' ability to discriminate individuals who engage in PIM from genuine responders, with a particular focus on the L, K, and S scales. Results:The MMPI-2 L scale produced the largest effect size (g = 1.30), whereas the MMPI-2-RF L-r scale effect size was moderate (g = 1.16). Moderate effect sizes were also found for the K (g = 1.01) and K-r (g = 1.21) scales, and for the MMPI-2 S scale (g = 1.23). Conclusions: Effect sizes did not significantly vary between the two versions of the MMPI. Findings suggest that both versions of the MMPI have demonstrated utility in identifying PIM, but clinicians should interpret T scores conservatively to account for the modest elevations associated with defensiveness. Findings are discussed in the context of the recently released MMPI-3.
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MMPI , Simulación de Enfermedad , Humanos , Pruebas Neuropsicológicas , Reproducibilidad de los Resultados , Simulación de Enfermedad/diagnósticoRESUMEN
Several meta-analyses of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) have examined these instruments' ability to detect symptom exaggeration or feigning. However, limited research has directly compared whether the scales across these two instruments are equally effective. This study used a moderated meta-analysis to compare 109 MMPI-2 and 41 MMPI-2-RF feigning studies, 83 (56.46%) of which were not included in previous meta-analyses. Although there were differences between the two test versions, with most MMPI-2 validity scales generating larger effect sizes than the corresponding MMPI-2-RF scales, these differences were not significant after controlling for study design and type of symptoms being feigned. Additional analyses showed that the F and Fp-r scales generated the largest effect sizes in identifying feigned psychiatric symptoms, while the FBS and RBS were better at detecting exaggerated medical symptoms. The findings indicate that the MMPI-2 validity scales and their MMPI-2-RF counterparts were similarly effective in differentiating genuine responders from those exaggerating or feigning psychiatric and medical symptoms. These results provide reassurance for the use of both the MMPI-2 and MMPI-2-RF in settings where symptom exaggeration or feigning is likely. Findings are discussed in the context of the recently released MMPI-3.
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MMPI , Proyectos de Investigación , Humanos , Brote de los SíntomasRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic had a significant impact on elective surgery for benign disease. We examined the effects of COVID-19 related delays on the outcomes of patients undergoing elective laparoscopic cholecystectomy (LC) in an upper gastrointestinal surgery unit in the UK. We have analysed data retrospectively of patients undergoing elective LC between 01/03/2019 to 01/05/2019 and 01/04/2021 to 11/06/2021. Demographics, waiting time to surgery, intra-operative details and outcome data were compared between the two cohorts. Indications for surgery were grouped as inflammatory (acute cholecystitis, gallstone pancreatitis, CBD stone with cholangitis) or non-inflammatory (biliary colic, gallbladder polyps, CBD stone without cholangitis). A p value of <0.05 was used for statistical significance. Out of the 159 patients included, 106 were operated pre-pandemic and 53 during the pandemic recovery phase. Both groups had similar age, gender, ASA-grades and BMI. In the pre-pandemic group, 68 (64.2%) were operated for a non-inflammatory pathology compared to 19 (35.8%) from the recovery phase cohort (p < 0.001). The waiting time to surgery was significantly higher amongst patients operated during the recovery phase (p = 0000.1). Less patients had complete cholecystectomy during the pandemic recovery phase (p = 0.04). There were no differences in intraoperative times and patient outcomes. These results demonstrate the impact of COVID-19 related delays to our cohort, however due to the retrospective nature of this study, the current results need to be backed up by higher evidence in order for strong recommendations to be made.
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Online AI symptom checkers and diagnostic assistants (DAs) have tremendous potential to reduce misdiagnosis and cost, while increasing the quality, convenience, and availability of healthcare, but only if they can perform with high accuracy. We introduce a novel Bayesian DA designed to improve diagnostic accuracy by addressing key weaknesses of Bayesian Network implementations for clinical diagnosis. We compare the performance of our prototype DA (MidasMed) to that of physicians and six other publicly accessible DAs (Ada, Babylon, Buoy, Isabel, Symptomate, and WebMD) using a set of 30 publicly available case vignettes, and using only sparse history (no exam findings or tests). Our results demonstrate superior performance of the MidasMed DA, with the correct diagnosis being the top ranked disorder in 93% of cases, and in the top 3 in 96% of cases.
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The results of three cases with infantile-onset Pompe disease participating in a rehabilitation program with home-based vibration training will be presented. In this retrospective observational case study, the cases participated in the neuromuscular training program "Auf die Beine", which combines two blocks of intensive, goal directed training with 6 months of home-based whole body vibration (WBV). Assessments by the means of a dual-energy X-ray absorptiometry and grip strength were applied at multiple points throughout the program. Two cases showed an increase in lean mass index of +0.319 kg/m2, +0.721 kg/m2 and bone mineral content of +0.028 kg/m2, +0.031 kg/m2 over one year. Additionally physiotherapeutic therapy goals could be achieved. In the remaining child lean mass index did not change, bone mineral content decreased by -0.03 kg. The neuromuscular rehabilitation program "Auf die Beine" has shown to be safe and effective in two of three cases for muscle and bone mass gain as well as in achievement of physiotherapeutic goals. To summarize, WBV is an innovative therapy in a rehabilitation concept, which might be helpful in Pompe disease, but further studies with larger cohorts are needed.
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Enfermedad del Almacenamiento de Glucógeno Tipo II , Vibración , Absorciometría de Fotón , Niño , Humanos , Modalidades de Fisioterapia , Estudios Retrospectivos , Vibración/uso terapéuticoRESUMEN
Individuals with primary hyperparathyroidism (PHPT) have reduced bone mineral density (BMD) according to dual X-ray absorptiometry at cortical sites, with relative sparing of trabecular BMD. However, fracture risk is increased at all sites. Trabecular bone score (TBS) may more accurately describe their bone quality and fracture risk. This study compared how BMD and TBS describe bone quality in PHPT. We conducted a retrospective cross-sectional study with a longitudinal component, of adults with PHPT, admitted to a tertiary hospital in Australia over ten years. The primary outcome was the TBS at the lumbar spine, compared to BMD, to describe bone quality and predict fractures. Secondary outcomes compared changes in TBS after parathyroidectomy. Of 68 included individuals, the mean age was 65.3 years, and 79% were female. Mean ± SD T-scores were -1.51 ± 1.63 at lumbar spine and mean TBS was 1.19 ± 0.12. Only 20.6% of individuals had lumbar spine BMD indicative of osteoporosis, while 57.4% of TBS were ≤1.20, indicating degraded architecture. There was a trend towards improved fracture prediction using TBS compared to BMD which did not reach statistical significance. Comparison of 15 individuals following parathyroidectomy showed no improvement in TBS.
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Coaching individuals on test-taking strategies presents legal and ethical concerns and threatens the validity of psychological test score interpretations, which could lead to inaccuracies in clinical settings and injustices within the legal system. This meta-analysis examined the impact of coaching on the detection of symptom exaggeration or feigning on the MMPI-2. A total of 99 feigning studies (N = 19,536) comparing validity subscale scores between genuine and nongenuine (coached or non-coached) responders were analyzed. Potential moderating effects of control group, type of symptoms, publication status, financial incentive, and non-content validity screening were also examined regarding their impact on the effectiveness of coaching. Findings suggested that detection-based coaching (i.e., coaching regarding the presence of validity scales and detection avoidance strategies within the MMPI-2) improved individuals' ability to elude detection by the MMPI-2 validity scales. Nonetheless, the MMPI-2 validity scales still generated moderate to very large effect sizes in detecting symptom exaggeration or feigning even in the context of coaching (range g = .89 to 1.95). The findings provide reassurance for detection efforts, indicating that while the effectiveness of the MMPI-2 is somewhat diminished, it remains useful in detecting non-genuine responders even in the context of coaching. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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MMPI , Tutoría , Humanos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Osteoporosis affects over half of adults over 50 years worldwide. With an ageing population, osteoporosis, fractures and their associated costs are increasing. Unfortunately, despite effective therapies, many with osteoporosis remain undiagnosed and untreated. Models of care (MoC) to improve outcomes include fracture liaison services, screening, education, and exercise programs, however efficacy for these is mixed. The aim of this study is to summarise MoC in osteoporosis and describe implementation characteristics and evidence for improving outcomes. METHODS: This systematic scoping review identified articles via Ovid Medline and Embase, published in English between 01/01/2009 and 15/06/2021, describing MoC for adults aged ≥18 years with, or at risk of, osteoporosis and / or health professionals caring for this group. All included at least one of clinical, consumer or clinician outcomes, with fractures and bone mineral density (BMD) change the primary clinical outcomes. Exclusion criteria were studies assessing pharmaceuticals or procedures without other interventions, or insufficient operational details. All study designs were included, with no comparator necessary. Title and abstract were reviewed by two reviewers. Full text review and data extraction was performed by these reviewers for 20% of article and, thereafter by a single author. As the review was predominantly descriptive, no comparator statistics were used. FINDINGS: 314 articles were identified describing 289 MoC with fracture liaison services (n=89) and education programs (n=86) predominating. The population had prior fragility fracture in 77 studies, the median (IQR) patient number was 210 (87, 667) and the median (IQR) follow-up duration for outcome assessment was 12 (6, 12·5) months. Fracture reduction was reported by 65 studies, with 16 (37%) graded as high quality, and 19 / 47 studies with a comparator group found a reduction in fractures. BMD change was reported by 73 studies, with 41 finding improved BMD. Implementation characteristics including reach, fidelity and loss to follow-up were under-reported, and consumer and clinician perspectives rare. INTERPRETATION: This comprehensive review of MoC for osteoporosis demonstrated inconsistent evidence for improving outcomes despite similar types of models. Future studies should include implementation outcomes, consumer and clinician perspectives, and fracture or BMD outcomes with sufficient duration of follow-up. Authors should consider pragmatic trial designs and co-design with clinicians and consumers.
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INTRODUCTION: Bone mineral density, measured by dual X-ray absorptiometry (DXA), is the gold standard for diagnosis of osteoporosis. The utility of DXA relies on the accuracy of scan acquisition, interpretation of data, and the adequacy of reports. The International Society for Clinical Densitometry (ISCD) has published guidelines regarding minimum reporting guidelines. This study assessed whether DXA reports for patients receiving care at an academic teaching hospital adhere to these reporting standards, and determine whether differences exist depending on patient factors and the imaging service. METHODS: Patients aged ≥18 years, receiving care at specialist outpatient clinics between January 1, 2018 and December 31, 2019, with a DXA report available, were eligible for inclusion. DXA reports were manually reviewed for adherence to ISCD guidelines, with each criterion scored as one point, giving a total score of 14 for baseline DXA scans and 18 for repeat DXA scans. The score was then converted to a percentage. RESULTS: Of 459 DXA scans included, 214 were performed internally at our hospital and 245 performed at 23 external imaging services. Mean (SD) patient age was 60 (16.3) years, and 75.8% were female. The overall median (IQR) report score was 57.1% (42.9, 82.4). ISCD criteria with the lowest scores were recommendation and timing of future DXA scans (included in 1.1% of reports) and investigation for secondary causes of osteoporosis (included in 1.2% of reports). Reports performed internally had significantly higher scores than those performed externally, after adjusting for age, sex, indication, and type of scan (incidence rate ratio 1.83, 95% confidence interval 1.77, 1.89). Baseline DXA reports had slightly higher scores than repeat DXA scans, and, among external imaging services, rural services had higher scores than metropolitan services. CONCLUSION: This study, the largest comprehensive evaluation of DXA reports, highlights significant deficiencies and variation in report standards between imaging services. This has potential implications for osteoporosis diagnosis and management.
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Densidad Ósea , Osteoporosis , Absorciometría de Fotón , Adolescente , Adulto , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagenRESUMEN
BACKGROUND: For Australians living with cystic fibrosis (CF), increased longevity means greater consideration needs to be given to long-term endocrine sequelae such as CF-related bone disease. Deficits in bone mass accrual are most likely to occur during childhood and adolescence. Current guidelines in Australia suggest repeat dual-energy X-ray absorptiometry (DXA) scans every 2 years. This study aims to stratify clinical factors that determine future bone health in the Australian CF population and use this to guide a more streamlined approach to bone health screening. METHODS: This study was a retrospective audit of all patients diagnosed with CF who were treated at the Royal Children's Hospital Melbourne, Australia from 2000 to 2016 (n = 453). Two hundred and two patients had a DXA scan in the study period (191 with height-adjusted data) and 111 patients had more than one scan (108 with height-adjusted data). An investigation into the associations between bone mineral density (BMD) Z score and potential risk factors was conducted using DXA and historical data. RESULTS: The main predictor of future BMD was the previous BMD Z score (p < .001). Other factors found to be determinants of BMD included nutritional status, lung function (FEV1 ), age, history of previous fracture, oral corticosteroid use, and the number of hospital admissions. However, after adjusting for previous BMD, evidence of an association remained only with nutritional status, FEV1 , and number of hospital admissions. CONCLUSION: Second yearly scans may be unnecessary in children with an adequate DXA score on the initial scan who remain clinically stable. However, clinical deterioration in those whose BMD was previously normal, may require closer monitoring of bone health. We propose a guideline for the frequency of DXA monitoring in relation to clinical risk factors.
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Densidad Ósea , Fibrosis Quística , Absorciometría de Fotón , Adolescente , Australia/epidemiología , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico por imagen , Fibrosis Quística/epidemiología , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Physical activity benefits have been extensively studied. However, the public health guidelines seem unclear about the relationships between steps and movements with healthy biomarkers for people with (PWD) and without disabilities (PWOD), respectively. While public health guidelines illustrate types of exercise (eg, running, swimming), it is equally important to provide data-driven recommended amounts of daily steps or movements to achieve health biomarkers and further promote a physically active lifestyle. METHODS: Data from the National Health and Nutrition Examination Survey 2003-2006 were used. The authors conducted sensitivity, specificity, and receiver-operating-characteristic curve analyses regarding cut points from ActiGraph 7164 of daily steps and movements for health biomarkers (eg, body mass index, cholesterol) in PWD (2178 participants) and PWOD (4414 participants). The authors also examined the dose relationships of steps, movements, and healthy biomarkers in each group. RESULTS: The authors found significant differences in the cut points of daily steps and movement for health biomarkers in PWD and PWOD. For daily steps, cut points of PWD were ranged from 3222 to 8311 (area under the receiver-operating-characteristic curve [AUC] range = 0.52-0.93) significantly lower than PWOD's daily steps (range = 5455-14,272; AUC = 0.58-0.87). For daily movement, cut points of PWD were ranged from 115,451 to 430,324 (AUC = 0.53-0.91) significantly lower than the PWOD's daily movements (range = 215,288-282,307; AUC = 0.60-0.88). The authors found strong but different dose relationships of many biomarkers in each group. CONCLUSIONS: PWD need fewer daily steps or movement counts to achieve health biomarkers than PWOD. The authors provided data-driven, condition-specific recommendations on promoting a physically active lifestyle.