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Introduction: Rare bone diseases (RBDs) are a heterogenous group of disorders that are poorly understood and challenging to treat. This creates a plethora of unmet needs for people with RBDs as well as their families and care providers, including diagnostic delays, limited access to expert care, and a lack of specialized treatments. The RBD Summit, which took place across 2 days in November 2021, was a virtual meeting of 65 RBD experts from clinical, academic, and patient communities as well as the pharmaceutical industry. The first meeting of its kind, the RBD Summit aimed to facilitate dialog and information exchange between delegates to advance knowledge and awareness of RBDs and improve patient outcomes. Methods: Key challenges were discussed, and actions for overcoming them were proposed, including how obstacles to diagnosis can be overcome by (a) improving awareness of RBDs, (b) the implementation of a person-centered care pathway, and (c) how to narrow the communication gap between patients and healthcare professionals. Results: Agreed actions were categorized as short term and long term, and priorities determined. Conclusion: In this position paper, we provide an overview of key discussions from the RBD Summit, summarize the subsequent action plan, and discuss the next steps in this continued collaboration. [ABSTRACT FROM AUTHOR]

Summary: Robust data on osteoporosis in the Asia Pacific region could improve healthcare decision-making. Osteoporosis affects 10–30% of women aged 40 + , and up to 10% of men in 7 developed economies in Asia Pacific. Fractures affect 500–1000 adults aged 50 + per 100,000 person-years. Policymakers and clinicians must address this problem. Purpose: Osteoporosis and associated fractures result in considerable morbidity, loss of productivity, early mortality, and increased healthcare expenses. Many countries in the Asia Pacific (AP) region, especially middle- and higher-income economies, are faced with aging and increasingly sedentary populations. It is critical to consolidate and analyze the available information on the prevalence and incidence of the disease in these countries. Methods: We systematically reviewed articles and gray literature for Australia, China, Hong Kong, Japan, Singapore, South Korea, and Taiwan. We searched PubMed, ScienceDirect, JSTOR, Cochrane, Google Scholar, and other databases for data published 2009–2018. We included articles with prevalence or incidence estimates for adults with osteoporosis or related fractures. Results: All locations had data available, but of widely varying quantity and quality. Most estimates for osteoporosis prevalence ranged from 10 to 30% for women ages 40 and older, and up to 10% for men. Osteoporotic fracture incidence typically ranged between 500 and 1000 per 100,000 person-years among adults aged 50 and older. Both outcomes typically increased with age and were more common among women. Conclusion: Osteoporosis and associated fractures affect significant portions of the adult population in developed economies in the AP region. Governments and healthcare systems must consider how best to prevent and diagnose osteoporosis, and manage affected individuals, to reduce healthcare costs and mortality associated with fractures. [ABSTRACT FROM AUTHOR]

Bone fragility is a serious yet under-recognised complication of diabetes mellitus (DM) that is associated with significant morbidity and mortality. Multiple complex pathophysiological mechanisms mediating bone fragility amongst DM patients have been proposed and identified. Fracture risk in both type 1 diabetes (T1D) and type 2 diabetes (T2D) continues to be understated and underestimated by conventional risk assessment tools, posing an additional challenge to the identification of at-risk patients who may benefit from earlier intervention or preventive strategies. Over the years, an increasing body of evidence has demonstrated the efficacy of osteo-pharmacological agents in managing skeletal fragility in DM. This review seeks to elaborate on the risk of bone fragility in DM, the underlying pathogenesis and skeletal alterations, the approach to fracture risk assessment in DM, management strategies and therapeutic options. [ABSTRACT FROM AUTHOR]

Summary: COVID-19 lockdowns have impacted management of chronic diseases such as osteoporosis. Adherence to the 6-monthly dosing schedule of denosumab, the parenteral anti-osteoporosis medication most often used in Singapore, was significantly reduced during the lockdown period compared to that during pre-COVID-19 times. Patients managed by endocrinologists were more likely to be adherent. Purpose: No study thus far has quantified actual adherence rates to anti-osteoporosis therapy with denosumab during COVID-19 or explored factors associated with it. We aimed to estimate the adherence rates to denosumab in Singaporean men and women during COVID-19 lockdown and to compare it with those during the pre-COVID-19 period. Method: We conducted this retrospective, electronic medical records, and pharmacy claims database study at Singapore General Hospital, the largest hospital in the country. Patients initiated on subcutaneous denosumab between August 2019 and December 2019 and were thus scheduled to receive the second dose during the COVID-19 first-wave period from February 2020 to June 2020 (lockdown group) were analyzed, as were patients initiated anytime on denosumab between September 2011 and December 2018 (pre-COVID-19 group). Data extracted from the hospital's electronic prescription platform and patients' pharmacy purchase records were matched. Adherence was defined as being punctual (with an allowable delay of up to 4 weeks) with the second dose scheduled 6 months from the 1st dose. A sensitivity analysis with an allowable delay up to 8 weeks was also performed. We compared the adherence rates between the two periods and explored factors associated with adherence. Results: A total of 768 and 1458 patients respectively during the lockdown and pre-COVID-19 periods were analyzed. The mean adherence rate during lockdown was 63.9%. The odds of being adherent during lockdown were higher if patients were managed by endocrinologists as opposed to those by other specialists [OR 2.516 (95% CI: 1.836–3.448); p < 0.001]. Adherence rates during the pre-COVID-19 period was 75.4%. Overall, the odds of being adherent to denosumab was significantly lower during lockdown than that during the pre-COVID-19 period [OR 0.525 (95% CI 0.430–0.640); p < 0.001], and odds of being adherent were higher if patients were managed by endocrinologists than if they were managed by other specialists (OR 1.765 (95% CI: 1.444–2.158; p < 0.001). Conclusion: Adherence to denosumab was significantly lower during COVID-19 lockdown than the pre-COVID-19 period. The odds of being adherent were higher in patients managed by endocrinologists. Whether healthcare providers from certain specialties spend more time counselling and educating patients about the importance of adherence to osteoporosis medications needs to be explored further. [ABSTRACT FROM AUTHOR]

Oral bisphosphonates are approved for the treatment of bone loss associated with several conditions including postmenopausal osteoporosis. Although generally well tolerated, adverse effects such as gastroesophageal reflux and oesophageal and peptic ulceration may occur. Oral mucositis and ulceration are lesser-known side effects. Proper counselling and rigorous adherence to the administration instructions are crucial. We describe a case of bisphosphonate-induced severe oral mucosal ulceration in an elderly woman that was caused by incorrect instructions and/or incorrect understanding of instructions for oral alendronate intake. [ABSTRACT FROM AUTHOR]

This paper introduces a new HEp‐2 cell classification model under two phases. In the initial phase, the input image is segmented using the morphological operations (opening and closing), and the segmented image is given for Convolutional Neural Network (CNN) classifier that gives the classified output. In the second phase, the given input is processed under (i) segmentation process (ii) Feature Extraction, and (iii) Classification. From the segmented images; the features like Gray level co‐occurrence Matrix TGLCM) and Gray level Run Length Matrix (GLRM) are extracted. After extracting the features, they are subjected to a classification process, where Neural Network (NN) is used. Finally, the mean of both classified output (first phase and second phase) is considered to be the final classified output. As the main contribution, to enhance the classification accuracy, the hidden neurons of both classifiers (CNN and NN) are optimally chosen during the classification process. To make this possible, this paper aims to propose a new Randomized Update based Grey Wolf Optimization (RP‐GWO) algorithm. Finally, the performance of the implemented approach is compared over other conventional approaches and its superiority is proven with respect to certain measures. [ABSTRACT FROM AUTHOR]

This paper introduces a new HEp-2 cell classification model under two phases. In the initial phase, the input image is segmented using the morphological operations (opening and closing), and the segmented image is given for Convolutional Neural Network (CNN) classifier that gives the classified output. In the second phase, the given input is processed under (i) segmentation process (ii) Feature Extraction, and (iii) Classification. From the segmented images; the features like Gray level co-occurrence Matrix TGLCM) and Gray level Run Length Matrix (GLRM) are extracted. After extracting the features, they are subjected to a classification process, where Neural Network (NN) is used. Finally, the mean of both classified output (first phase and second phase) is considered to be the final classified output. As the main contribution, to enhance the classification accuracy, the hidden neurons of both classifiers (CNN and NN) are optimally chosen during the classification process. To make this possible, this paper aims to propose a new Randomized Update based Grey Wolf Optimization (RP-GWO) algorithm. Finally, the performance of the implemented approach is compared over other conventional approaches and its superiority is proven with respect to certain measures. [ABSTRACT FROM AUTHOR]

Secondary Hyperparathyroidism (SHP) seen as a frequent complication in Chronic Kidney Disease (CKD) has many pathogenetic peculiarities that are still incompletely defined and understood. During the long course of chronic renal failure, SHP can also transform sometimes into the hypercalcemic state characterized by quasi-autonomous production of Parathyroid Hormone from the parathyroid glands: a disorder that is termed Tertiary Hyperparathyroidism. The clinical consequences of SHP in CKD are protean, encompassing bone and mineral abnormalities but as recently identified, also several metabolic and cardiovascular problems, the most important of which is vascular calcification. There have been several advances in the therapeutic armamentarium available for the treatment of SHP, though clear demonstration of a benefit regarding major clinical outcomes with any of the new agents is still lacking. This narrative review summarizes the current understanding about this disorder and highlights some of the recent research on the subject. [ABSTRACT FROM AUTHOR]

Summary: Type 1 diabetes mellitus (T1DM) is associated with a disproportionately high fracture rate despite a minimal decrease in bone mineral density. Though trabecular bone score (TBS), an indirect measure of bone architecture, is lower in adults with T1DM, the modest difference is unlikely to account for the large excess risk and calls for further exploration. Introduction: Fracture rates in type 1 diabetes mellitus (T1DM) are disproportionately high compared to the modestly low bone mineral density (BMD). Distortion of bone microarchitecture compromises bone quality in T1DM and is indirectly measured by trabecular bone score (TBS). TBS could potentially be used as a screening tool for skeletal assessment; however, there are inconsistencies in the studies evaluating TBS in T1DM. We performed this meta-analysis to address this knowledge gap. Methods: An electronic literature search was conducted using PubMed, Scopus, and Web of Science resources (all-year time span) to identify studies relating to TBS in T1DM. Cross-sectional and retrospective studies in adults with T1DM were included. TBS and BMD data were extracted for pooled analysis. Fracture risk could not be analyzed as there were insufficient studies reporting it. Result: Data from six studies were included (T1DM: n = 378 and controls: n = 286). Pooled analysis showed a significantly lower TBS [standardized mean difference (SMD) = − 0.37, 95% CI − 0.52 to − 0.21; p < 0.00001] in T1DM compared to controls. There was no difference in the lumbar spine BMD (6 studies, SMD − 0.06, 95% CI − 0.22 to 0.09; p = 0.43) and total hip BMD (6 studies, SMD − 0.17, 95% CI − 0.35 to 0.01; p = 0.06) in the case and control groups. Conclusions: Adults with T1DM have a lower TBS but similar total hip and lumbar spine BMD compared to controls. The risk attributable to the significant but limited difference in TBS falls short of explaining the large excess propensity to fragility fracture in adults with T1DM. Further studies on clarification of the mechanism and whether TBS is suited to screen for fracture risk in adults with T1DM are necessary. [ABSTRACT FROM AUTHOR]

The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus. [ABSTRACT FROM AUTHOR]

Diabetes be it type 1 or type 2 is associated with an increased risk of fragility fractures. The mechanisms underlying this increased risk are just being elucidated. Anti-diabetes medications are crucial for maintaining glucose control and for preventing micro- and macrovascular complications in diabetes. However, they may modulate fracture risk in diabetes in different ways. Thiazolidinediones have demonstrated an unfavorable effect on the skeleton, while metformin and sulfonylureas may have a neutral if not beneficial effect on bone. The use of insulin has been associated with an increased risk of fragility fractures though it is not clear whether it is due to direct influence of insulin or whether it is mediated through hypoglycemia and increased falls risk. The overall effect of incretin mimetics appears to be beneficial; however, this has to be elucidated further. The bone effects of pramlintide, a synthetic analog of amylin, have not been explored fully. Finally, issues regarding bone safety of SGLT2 (sodium-dependent glucose transporter 2) inhibitors, the newest anti-diabetic medications on the market are of concern. The purpose of this review is to provide a comprehensive overview of the effect of these medications on bone metabolism and the studies exploring the risk or lack thereof of these medications on bone loss and fragility fractures. [ABSTRACT FROM AUTHOR]

Introduction Osteoporosis is a condition characterized by low bone mass and micro-architectural deterioration of the bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. APCO Framework of Clinical Standards of Care: An Innovative Initiative to Improve Osteoporosis Care The Asia-Pacific Consortium on Osteoporosis (APCO) comprises 39 osteoporosis experts from 19 countries and regions spanning the entire Asia-Pacific region (www.apcobonehealth.org). [Extracted from the article]

Examines the role of adinopectin, a bioactive protein secreted by the adipocyte tissue, in diabetes. Structure of monomeric adinopectin; Model for assembly of adinopectin complexes; Mode of action; Metabolic roles.

This article provides some recommendations on managing diabetes during air travel. Overseas travel poses special problems for people with diabetes, especially those on insulin. However, the fear of dealing with medications and acute complications should not prevent people with diabetes from traveling, whether for work or recreation. A British study in 1993 clearly demonstrated that most physicians, including diabetologists, are uncertain about how to adjust insulin doses for patients who travel across several time zones. Ideally, patients who are planning overseas travel should schedule an office visit with their health care provider at least four to six weeks before departure so as to assess their patients' current level of diabetes control, to give specific advice regarding diabetes management and prevention of acute complications. Patients should obtain a travel itinerary showing departure and arrival times, durations of flights, and time differences between the points of embarkation and disembarkation. It is also helpful to find out beforehand the serving time of meals. All medications and supplies should be carried by the patient. Insulin is stable under normal conditions at airport terminals and passenger security check points and when passing through X-ray machines.

The evolution of trabecular bone score (TBS) and bone mineral density (BMD) over the first 5 years after renal transplantation was prospectively evaluated in 164 patients. Dual energy X‐ray absorptiometry (DXA) scans were performed at 0, 6, 12, 24, and 60 months. Cumulative steroid dose, serum 25(OH)D, calcium, parathyroid hormone, and total ALP levels at these time points were checked. Incident fractures were identified from X‐rays/vertebral fracture assessments. Mean (SD) age, TBS, and lumbar spine BMD at baseline were 47.11 (9.53), 1.424 (0.097), and 0.935 (0.183) gm/cm2, respectively. Baseline TBS was lower in tertiary 1.38 (0.07) vs secondary hyperparathyroidism 1.43 (0.01) vs post‐parathyroidectomy 1.46 (0.11); P = .035. Trabecular bone score and BMD significantly decreased from baseline‐>6 months, changes after that at consecutive time points were non‐significant. 11% had incident fractures during the follow‐up period, majority being metatarsal with no vertebral or hip fractures noted. This first prospective evaluation of TBS and BMD evolution at multiple time points over 5 years suggest that microarchitectural and bone density deteriorations post‐renal transplantation stabilize after 6 months. Stabilization of these parameters could partially account for the absence of major fractures noted in this Asian population. Possible genetic and ethnic differences in fracture risk between Asian and Caucasian renal transplant patients have to be explored through large population‐based studies. [ABSTRACT FROM AUTHOR]

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies. In this Evidence-Based Guideline article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. [ABSTRACT FROM AUTHOR]

Purpose: Trabecular bone score (TBS) is a grey-level textural measurement acquired from dual-energy X-ray absorptiometry lumbar spine images and is a validated index of bone microarchitecture. In 2015, a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) published a review of the TBS literature, concluding that TBS predicts hip and major osteoporotic fracture, at least partly independent of bone mineral density (BMD) and clinical risk factors. It was also concluded that TBS is potentially amenable to change as a result of pharmacological therapy. Further evidence on the utility of TBS has since accumulated in both primary and secondary osteoporosis, and the introduction of FRAX and BMD T-score adjustment for TBS has accelerated adoption. This position paper therefore presents a review of the updated scientific literature and provides expert consensus statements and corresponding operational guidelines for the use of TBS. Methods: An Expert Working Group was convened by the ESCEO and a systematic review of the evidence undertaken, with defined search strategies for four key topics with respect to the potential use of TBS: (1) fracture prediction in men and women; (2) initiating and monitoring treatment in postmenopausal osteoporosis; (3) fracture prediction in secondary osteoporosis; and (4) treatment monitoring in secondary osteoporosis. Statements to guide the clinical use of TBS were derived from the review and graded by consensus using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Results: A total of 96 articles were reviewed and included data on the use of TBS for fracture prediction in men and women, from over 20 countries. The updated evidence shows that TBS enhances fracture risk prediction in both primary and secondary osteoporosis, and can, when taken with BMD and clinical risk factors, inform treatment initiation and the choice of antiosteoporosis treatment. Evidence also indicates that TBS provides useful adjunctive information in monitoring treatment with long-term denosumab and anabolic agents. All expert consensus statements were voted as strongly recommended. Conclusion: The addition of TBS assessment to FRAX and/or BMD enhances fracture risk prediction in primary and secondary osteoporosis, adding useful information for treatment decision-making and monitoring. The expert consensus statements provided in this paper can be used to guide the integration of TBS in clinical practice for the assessment and management of osteoporosis. An example of an operational approach is provided in the appendix. Summary: This position paper presents an up-to-date review of the evidence base, synthesised through expert consensus statements, which informs the implementation of Trabecular Bone Score in clinical practice. [ABSTRACT FROM AUTHOR]

Summary : This narrative review summarises the recommendations of a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) for the conduct and reporting of real-world evidence studies with a focus on osteoporosis research. Purpose: Vast amounts of data are routinely generated at every healthcare contact and activity, and there is increasing recognition that these real-world data can be analysed to generate scientific evidence. Real-world evidence (RWE) is increasingly used to delineate the natural history of disease, assess real-life drug effectiveness, understand adverse events and in health economic analysis. The aim of this work was to understand the benefits and limitations of this type of data and outline approaches to ensure that transparent and high-quality evidence is generated. Methods: A ESCEO Working Group was convened in December 2022 to discuss the applicability of RWE to osteoporosis research and approaches to best practice. Results: This narrative review summarises the agreed recommendations for the conduct and reporting of RWE studies with a focus on osteoporosis research. Conclusions: It is imperative that research using real-world data is conducted to the highest standards with close attention to limitations and biases of these data, and with transparency at all stages of study design, data acquisition and curation, analysis and reporting to increase the trustworthiness of RWE study findings. [ABSTRACT FROM AUTHOR]

Introduction: Whether parathyroidectomy is more beneficial to renal function when compared to medical therapy or observation in primary hyperparathyroidism (PHPT) is unclear. Neither has this premise been explored in non-Caucasian populations. The estimated glomerular filtration rate (eGFR) threshold below which parathyroid hormone (PTH) levels rise if at all in PHPT has also not been established. We determined if surgery was superior to medical therapy and observation in a multi-ethnic Asian patient population with PHPT and whether there was an eGFR threshold below which PTH levels further increased in them. Methods: Retrospective evaluation of patients with PHPT. Results: There were 68.6% Chinese, 17.4% Malays, 10.7% Indians, and 3.3% Eurasians. The median (interquartile range) follow-up was 18.0 months (4.5-46.8). At last follow-up, eGFR in the surgical (80 ± 30 ml/min) was higher than the medical (52 ± 32 ml/min) or observation groups (48 ± 33 ml/min); P < 0.01. This difference persisted after adjusting for age, gender, ethnicity, pre-intervention eGFR levels, nephrolithiasis, serum calcium, phosphate, urinary calcium, and duration of follow-up; P = 0.035. There was no definite eGFR level below which PTH values rose. Conclusion: Our study provides compelling evidence that in PHPT, surgery may be associated with a better renal outcome compared to medical management or observation. This has to be confirmed through prospective randomized controlled trials and the reasons for this finding have to be elucidated through functional and histological measures. The finding in our study of a lack of a specific eGFR threshold below which PTH levels further rose challenges the concept of a fixed renal threshold for secondary elevations of PTH in PHPT. [ABSTRACT FROM AUTHOR]

X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients' experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease. [ABSTRACT FROM AUTHOR]

Background: Falls are common in frail older adults and often result in injuries and hospitalisation. The Nintendo® Wii™ is an easily available exercise modality in the community which has been shown to improve lower limb strength and balance. However, not much is known on the effectiveness of the Nintendo® Wii™ to improve fall efficacy and reduce falls in a moderately frail older adult. Fall efficacy is the measure of fear of falling in performing various daily activities. Fear contributes to avoidance of activities and functional decline.Methods: This randomised active-control trial is a comparison between the Nintendo WiiActive programme against standard gym-based rehabilitation of the older population. Eighty subjects aged above 60, fallers and non-fallers, will be recruited from the hospital outpatient clinic. The primary outcome measure is the Modified Falls Efficacy Scale and the secondary outcome measures are self-reported falls, quadriceps strength, walking agility, dynamic balance and quality of life assessments.Discussions: The study is the first randomised control trial using the Nintendo Wii as a rehabilitation modality investigating a change in fall efficacy and self-reported falls. Longitudinally, the study will investigate if the interventions can successfully reduce falls and analyse the cost-effectiveness of the programme. [ABSTRACT FROM AUTHOR]

Objective: Symptomatic long-term hypoparathyroidism following thyroid surgery requires an alternative and permanent therapy that would effectively restore parathyroid function and eliminate the need for substitution drug therapy. The aim of this study was to systematically review the literature on the efficacy and safety of parathyroid allotransplantation to treat post-operative hypoparathyroidism.Methods: MEDLINE, Embase, BIOSIS and the Cochrane Library were searched for published articles (from inception of each database to September 30, 2018). A total of 9 studies comprising 146 patients (177 allotransplantations) with post thyroidectomy hypoparathyroidism were identified.Results: Parathyroid tissues used for allotransplant were cultured parathyroid cells, cryopreserved parathyroid cells and encapsulated microspheres. Post-transplant immunosuppression was only reported in three studies, mainly with oral prednisolone for 2 weeks to 6 months. Mean graft survival following allotransplantation was 47% (95% CI 24%-71%) when patients were followed-up to 6 months and 41% (95% CI 2.3%-80%) at 12 months. There was significant unexplained heterogeneity observed between studies in both these groups (I2 > 50%). Parathyroid hormone (PTH) levels, and serum calcium levels post intervention was not reported in all studies, but available evidence suggests the levels remains higher (PTH level around 12 pg/ml; Ca level around 8 mg/dl) post-allotransplantation for up to 24 months.Conclusions: Long-term benefit and harms of allotransplantation is still unclear due to the clinical and statistical heterogeneity observed among the studies. Therefore, conduct of a well-designed controlled clinical trial in the immediate future on allotransplantation is of paramount importance. [ABSTRACT FROM AUTHOR]

X-linked hypophosphatemia (XLH) is the most prevalent form of hereditary hypophosphatemic rickets associated with phosphate wasting. However, its diagnosis is often missed, resulting in patients presenting late in the course of the disease when complications such as tertiary hyperparathyroidism and renal failure have already set in. Phosphate and calcitriol replacement, both of which have undesirable consequences of their own, have historically been the main stay of therapy. We describe the case of a 57-year-old gentleman with tertiary hyperparathyroidism, who was mislabelled as having achondroplasia for many years before we made a diagnosis of XLH in him. His XLH was found to be due to a hereto unreported deletion of entire exon 14 with partial deletions of introns 13 and 14 of the PHEX gene. Perioperative management in him was fraught with surgical and medical difficulties including an operation that was technically complicated due to his multiple anatomical deformities. Our case also highlights the critical importance of timely recognition and accurate diagnosis of XLH, as well as the long-term multidisciplinary management that is needed for this disorder. [ABSTRACT FROM AUTHOR]

Background: Whether the sensitivity of Deep Learning (DL) models to screen chest radiographs (CXR) for CoVID-19 can approximate that of radiologists, so that they can be adopted and used if real-time review of CXRs by radiologists is not possible, has not been explored before. Objective: To evaluate the diagnostic performance of a doctor-trained DL model (Svita_DL8) to screen for COVID-19 on CXR, and to compare the performance of the DL model with that of expert radiologists. Materials and Methods: We used a pre-trained convolutional neural network to develop a publicly available online DL model to evaluate CXR examinations saved in.jpeg or.png format. The initial model was subsequently curated and trained by an internist and a radiologist using 1062 chest radiographs to classify a submitted CXR as either normal, COVID-19, or a non-COVID-19 abnormal. For validation, we collected a separate set of 430 CXR examinations from numerous publicly available datasets from 10 different countries, case presentations, and two hospital repositories. These examinations were assessed for COVID-19 by the DL model and by two independent radiologists. Diagnostic performance was compared between the model and the radiologists and the correlation coefficient calculated. Results: For detecting COVID-19 on CXR, our DL model demonstrated sensitivity of 91.5%, specificity of 55.3%, PPV 60.9%, NPV 77.9%, accuracy 70.1%, and AUC 0.73 (95% CI: 0.86, 0.95). There was a significant correlation (r = 0.617, P = 0.000) between the results of the DL model and the radiologists' interpretations. The sensitivity of the radiologists is 96% and their overall diagnostic accuracy is 90% in this study. Conclusions: The DL model demonstrated high sensitivity for detecting COVID-19 on CXR. Clinical Impact: The doctor trained DL tool Svita_DL8 can be used in resource-constrained settings to quickly triage patients with suspected COVID-19 for further in-depth review and testing. [ABSTRACT FROM AUTHOR]

Highlights: [•] We compared the functional characteristics of women with osteoporosis based on their falls history and single-leg stand (SLS) performance. [•] Fallers with good SLS time showed numerically or statistically better functional outcomes than did non-fallers with poor SLS time. [•] Fallers with good SLS time showed comparable functional outcomes with non-fallers with good SLS time. [•] The results indicate an important heterogeneity within fallers and non-fallers in women with osteoporosis. [•] Fall prevention strategies may be tailored based on the individual's standing balance, physical activity level, and falls history. [ABSTRACT FROM AUTHOR]

Objective: To assess the effects of adjunctive treatment with pramlintide, an analog of the beta-cell hormone amylin, on 24-h glucose fluctuations and postprandial glucose, glucagon, and triglyceride excursions in patients with type 1 diabetes intensively treated with continuous subcutaneous insulin infusion (CSII).Research Design and Methods: In this study, 18 patients (16 of whom could be evaluated) with type 1 diabetes (age 44 +/- 11 years, HbA(1c) 8.2 +/- 1.3% [mean +/- SD]) were given mealtime injections of 30 micro g pramlintide t.i.d. for 4 weeks in addition to their preexisting CSII regimen (16 lispro, 2 regular insulin). Mealtime insulin boluses were reduced by a minimum of 10% during the first 3 days, and re-adjusted thereafter based on clinical judgment. At weeks 0 (baseline), 4 (on treatment), and 6 (2 weeks off treatment), 24-h interstitial glucose concentrations were measured using a continuous glucose monitoring system (CGMS), and postprandial plasma glucose, glucagon, and triglyceride concentrations were measured in response to a standardized test meal.Results: At baseline, patients had excessive 24-h glucose fluctuations, with 59% of the CGMS measurements >140 mg/dl, 13% <80 mg/dl, and only 28% in the euglycemic range (80-140 mg/dl). After 4 weeks on pramlintide, measurements in the hyperglycemic range declined to 48% and measurements within the euglycemic range increased to 37%. This shift from the hyperglycemic to the euglycemic range occurred with a concomitant 17% reduction in mealtime insulin dosages and without relevant increases in measurements below the euglycemic range (15%) or any severe hypoglycemic events. After 4 weeks on pramlintide, postprandial glucose, glucagon, and triglyceride excursions were reduced by approximately 86, approximately 87, and approximately 72%, respectively (incremental areas under the curve, all P < 0.05 vs. baseline). At week 6 (off treatment), the 24-h glucose profile and postprandial glucose, glucagon, and triglyceride excursions approached pretreatment values.Conclusions: In this study, the addition of pramlintide to insulin therapy reduced excessive 24-h glucose fluctuations as well as postprandial glucose, glucagon, and triglyceride excursions in patients with type 1 diabetes intensively treated with insulin pumps. [ABSTRACT FROM AUTHOR]