Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review.

Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. BACKGROUND: Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. METHODS: Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). RESULTS: Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. CONCLUSION: Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved.

Ten-year follow-up of fracture risk in a systematic population-based screening program: the risk-stratified osteoporosis strategy evaluation (ROSE) randomised trial.

Background: Osteoporotic fractures pose a growing public health concern. Osteoporosis is underdiagnosed and undertreated, highlighting the necessity of systematic screening programs. We aimed to evaluate the effectiveness of a two-step population-based osteoporotic screening program. Methods: This ten-year follow-up of the Risk-stratified Osteoporosis Strategy Evaluation (ROSE) randomized trial tested the effectiveness of a screening program utilizing the Fracture Risk Assessment Tool (FRAX) for major osteoporotic fractures (MOF) to select women for dual-energy x-ray absorptiometry (DXA) scan following standard osteoporosis treatment. Women residing in the Region of Southern Denmark, aged 65-80, were randomised (single masked) into a screening or a control group by a computer program prior to inclusion and subsequently approached with a mailed questionnaire. Based on the questionnaire data, women in the screening group with a FRAX value ≥15% were invited for DXA scanning. The primary outcome was MOF derived from nationwide registers. ClinicalTrials.gov: NCT01388244, status: Completed. Findings: All randomised women were included February 4, 2010-January 8, 2011, the same day as approached to participate. During follow-up, 7355 MOFs were observed. No differences in incidences of MOF were identified, comparing the 17,072 women in the screening group with the 17,157 controls in the intention-to-treat analysis (IRR 1.01, 0.95; 1.06). However, per-protocol, women DXA-scanned exhibited a 14% lower incidence of MOF (IRR 0.86, 0.78; 0.94) than controls with a FRAX value ≥15%. Similar trends were observed for hip fractures, all fractures, and mortality. Interpretation: While the ROSE program had no overall effect on osteoporotic fracture incidence or mortality it showed a preventive effect for women at moderate to high risk who underwent DXA scans. Hence the overall effect might have been diluted by those who were not at an intervention level threshold risk or those who did not show up for DXA. Using self-administered questionnaires as screening tools may be inefficient for systematic screening due to the low and differential screening uptake. Funding: INTERREG and the Region of Southern Denmark.

Radiology reporting of incidental osteoporotic vertebral fragility fractures present on CT studies: results of UK national re-audit.

AIM: To describe a UK-wide re-audit of the 2019 Royal College of Radiologists (RCR) audit evaluating patient-related data and organisational infrastructure in the radiological reporting of vertebral fragility fractures (VFFs) on computed tomography (CT) studies and to assess the impact of a series of RCR interventions, initiated to raise VFF awareness, on reporting practice and outcomes. MATERIALS AND METHODS: Patient specific and organisational questionnaires largely replicated those utilised in 2019. The patient questionnaire involved retrospective analysis of between 50 and 100 consecutive, non-traumatic CT studies which included the thoracolumbar spine. All RCR radiology audit leads were invited to participate. Data collection commenced from 1 April 2022. RESULTS: Data were supplied by 129/194 (67%) departments. One thousand five hundred and eighty-six of 7,316 patients (21.7%) had a VFF on auditor review. Overall improvements were demonstrated in key initial/provisional reporting results; comment on spine/bone (93.2%, 14.4% improvement, p<0.0002); fracture severity assessment (34.7%, 8.5% improvement, p=0.0007); use of recommended terminology (67.8%, 7.5% improvement, p=0.0034); recommendations for further management (11.7%, 9.1% improvement, p<0.0002). CONCLUSIONS: The 2022 national re-audit confirms improvements in diagnostic performance and practice in VFF reporting. Continuing work is required to build on this improvement and to further embed best practice.

Call to action: a five nations consensus on the use of intravenous zoledronate after hip fracture.

Currently in the UK and Ireland, after a hip fracture most patients do not receive bone protection medication to reduce the risk of refracture. Yet randomised controlled trial data specifically examining patients with hip fracture have shown that intravenous zoledronate reduces refracture risk by a third. Despite this evidence, use of intravenous zoledronate is highly variable following a hip fracture; many hospitals are providing this treatment, whilst most are currently not. A range of clinical uncertainties, doubts over the evidence base and practical concerns are cited as reasons. This paper discusses these concerns and provides guidance from expert consensus, aiming to assist orthogeriatricians, pharmacists and health services managers establish local protocols to deliver this highly clinically and cost-effective treatment to patients before they leave hospital, in order to reduce costly re-fractures in this frail population.

Current approaches to secondary prevention after hip fracture in England and Wales - an analysis of trends between 2016 and 2020 using the National Hip Fracture Database (NHFD).

Hip fractures are strong risk factors for further fractures. However, using the National Hip Fracture Database, we observed that in England and Wales, 64% of patients admitted on oral bisphosphonates were discharged on the same and injectable drug use varies from 0-67% and 0.2%-83.6% were deemed "inappropriate" for bone protection. This variability requires further investigation. INTRODUCTION: A key aim for the National Hip Fracture Database (NHFD) is to encourage secondary fracture prevention of the 75,000 patients who break their hip annually in the UK, through bone health assessment and appropriate provision of anti-osteoporosis medication (AOM). We set out to describe trends in anti-osteoporosis medication prescription and examine the types of oral and injectable AOMs being prescribed both before and after a hip fracture. METHODS: We used data freely available from the NHFD  www.nhfd.co.uk  to analyse trends in oral and injectable AOM prescription across a quarter of a million patients presenting between 2016 and 2020, and more detailed information on the individual type of AOM prescribed for 63,705 patients from 171 hospitals in England and Wales who presented in 2020. RESULTS: Most patients (88.3%) are not taking any AOM when they present with a hip fracture. Half of all patients (50.8%) were prescribed AOM treatment by the time of discharge, but the proportion deemed 'inappropriate for AOM' varied hugely (0.2-83.6%) in different hospitals. Nearly two-thirds (64.2%) of those previously taking an oral bisphosphonate were simply discharged on the same type of medication. The total number of patients discharged on oral medication fell by over a quarter in these five years. The number discharged on injectables increased by nearly three-quarters to 14.2% over the same period, but remains hugely variable across the country, with rates ranging from 0-67% across different units. CONCLUSION: A recent hip fracture is a strong risk factor for future fractures. The huge variability in approaches, and in particular the use of injectables, in different trauma units across England and Wales requires further investigation.

Development, implementation and evaluation of a multinational FLS mentorship programme in Latin America.

Realising the benefits of systematic secondary fracture prevention requires supporting local sites to get started and becoming effective. We here describe the development, implementation and impact of a regional fracture liaison service (FLS) mentorship programme in Latin America that led to 64 FLS getting started and coverage of 17,205 patients. INTRODUCTION: Despite treatments and service models to deliver effective secondary fracture prevention, most patients are left untreated after a fragility fracture. To improve the capability to get FLS started and more effective, we describe the development, implementation and evaluation of an international programme to develop national communities of FLS mentors as part of the Capture the Fracture Partnership in Latin America. METHODS: The IOF regional team and the University of Oxford developed the curriculum and associated resources for training mentors in setting up FLS, service improvement and mentorship. Mentors were selected during a preparatory meeting, trained using live online sessions followed by regular mentor-led post-training meetings. The programme was evaluated using a pre-training needs assessment and post-training evaluation based on Moore's outcomes. RESULTS: The mentorship programme was initiated in Mexico, Brazil, Colombia and Argentina. The mentors were multidisciplinary, including orthopaedic surgery, rehabilitation, rheumatology, endocrinology, geriatrics, gynaecology and internal medicine. There was 100% participation in training sessions and reported satisfaction with the training. Since the initiation of the training programme, 22 FLS have been set up in Mexico, 30 in Brazil, 3 in Colombia and 9 in Argentina, in comparison with two in Chile and none in any other LATAM countries that were not involved in the mentorship programme. This equates to approximately 17,025 additional patients identified from 2019 to 2021 after initiation of mentorship. The mentors have engaged with 58 FLS for service development. Post-training activities include two published national best practice guidelines and other country-specific resources for FLS in the local language. CONCLUSION: Despite the COVID pandemic, the mentorship pillar of the Capture the Fracture Partnership has developed a community of FLS mentors with measurable improvement in national FLS provision. The programme is a potentially scalable platform to develop communities of mentors in other countries.

The Capture the Fracture® Partnership: an overview of a global initiative to increase the secondary fracture prevention care for patient benefit.

The Capture the Fracture® Partnership (CTF-P) is a unique collaboration between the International Osteoporosis Foundation, academic units and industry partners to enhance the implementation of effective, efficient fracture liaison services (FLSs) with a good patient experience. CTF-P has generated valuable resources for the specific countries as well as the broader FLS community to improve the initiation, effectiveness and sustainability of FLS in a wide range of healthcare settings.

Complex organisational factors influence multidisciplinary care for patients with hip fractures: a qualitative study of barriers and facilitators to service delivery.

BACKGROUND: Hip fractures are devastating injuries, with high health and social care costs. Despite national standards and guidelines, substantial variation persists in hospital delivery of hip fracture care and patient outcomes. This qualitative study aimed to identify organisational processes that can be targeted to reduce variation in service provision and improve patient care. METHODS: Interviews were conducted with 40 staff delivering hip fracture care in four UK hospitals. Twenty-three anonymised British Orthopaedic Association reports addressing under-performing hip fracture services were analysed. Following Thematic Analysis of both data sources, themes were transposed onto domains both along and across the hip fracture care pathway. RESULTS: Effective pre-operative care required early alert of patient admission and the availability of staff in emergency departments to undertake assessments, investigations and administer analgesia. Coordinated decision-making between medical and surgical teams regarding surgery was key, with strategies to ensure flexible but efficient trauma lists. Orthogeriatric services were central to effective service delivery, with collaborative working and supervision of junior doctors, specialist nurses and therapists. Information sharing via multidisciplinary meetings was facilitated by joined up information and technology systems. Service provision was improved by embedding hip fracture pathway documents in induction and training and ensuring their consistent use by the whole team. Hospital executive leadership was important in prioritising hip fracture care and advocating service improvement. Nominated specialty leads, who jointly owned the pathway and met regularly, actively steered services and regularly monitored performance, investigating lapses and consistently feeding back to the multidisciplinary team. CONCLUSION: Findings highlight the importance of representation from all teams and departments involved in the multidisciplinary care pathway, to deliver integrated hip fracture care. Complex, potentially modifiable, barriers and facilitators to care delivery were identified, informing recommendations to improve effective hip fracture care delivery, and assist hospital services when re-designing and implementing service improvements.

Expected Benefits and Budget Impact From a Microsimulation Model Support the Prioritization and Implementation of Fracture Liaison Services.

Osteoporotic-related fractures cause significant patient disability, leading to a growing burden on health care systems. Effective secondary fracture prevention can be delivered by fracture liaison services (FLSs), but these are not available in most countries. A major barrier is insufficient policy prioritization, helped by the lack of economic assessments using national data and providing estimates of patient outcomes alongside health care resource use and cost impacts. The aim of this study was to develop an economic model to estimate the benefits and budget impact of FLSs and support their wider international implementation. Five interconnected stages were undertaken: establishment of a generic patient pathway; model design; identification of model inputs; internal validation and output generation; and scenario analyses. A generic patient pathway including FLS activities was built to underpin the economic model. A state-based microsimulation model was developed to estimate the impact of FLSs compared with current practice for men and women aged 50 years or older with a fragility fracture. The model provides estimates for health outcomes (subsequent fractures avoided and quality-adjusted life years [QALYs]), resource use, and health and social care costs, including those necessary for FLSs to operate, over 5 years. The model was run for an exemplar country the size of the United Kingdom. FLSs were estimated to lead to a reduction of 13,149 subsequent fractures and a gain of 11,709 QALYs. Hospital-bed days would be reduced by 120,989 and surgeries by 6455, while 3556 person-years of institutional social care would be avoided. Expected costs per QALY gained placed FLSs as highly cost-effective at £8258 per QALY gained over the first 5 years. Ten different scenarios were modeled using different configurations of FLSs. Further work to develop country-specific models is underway to delivery crucial national level data to inform the prioritization of FLSs by policy makers. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Pregnancy Vitamin D Supplementation and Childhood Bone Mass at Age 4 Years: Findings From the Maternal Vitamin D Osteoporosis Study (MAVIDOS) Randomized Controlled Trial.

In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) randomized trial, vitamin D supplementation in pregnancy did not lead to greater neonatal bone mass across the trial as a whole, but, in a prespecified secondary analysis by season of birth, led to greater neonatal bone mass among winter-born babies. Demonstrating persistence of this effect into childhood would increase confidence in a long-term benefit of this intervention. We investigated whether antenatal vitamin D supplementation increases offspring bone mineralization in early childhood in a prespecified, single-center follow-up of a double-blinded, multicenter, randomized controlled clinical trial based in the UK (MAVIDOS). A total of 1123 women in early pregnancy with a baseline 25-hydroxyvitamin D level 25-100 nmol/L from three research centers (2008-2014) were randomized to 1000 IU/d cholecalciferol or matched placebo from 14 weeks of gestation to delivery. Offspring born at the Southampton, UK research center were assessed at age 4 years (2013-2018). Anthropometry and dual-energy X-ray absorptiometry (DXA) were performed (yielding whole body less head [WBLH] bone mineral content [BMC], areal bone mineral density [aBMD], bone area [BA], and body composition). Of 723 children, 564 (78.0%) children attended the 4-year visit, 452 of whom had a useable DXA. Maternal vitamin D supplementation led to greater WBLH aBMD in the children compared with placebo (mean [95% confidence interval {CI}]: supplemented group: 0.477 (95% CI, 0.472-0.481) g/cm2; placebo group: 0.470 (95% CI, 0.466-0.475) g/cm2, p = 0.048). Associations were consistent for BMC and lean mass, and in age- and sex-adjusted models. Effects were observed across the whole cohort irrespective of season of birth. Maternal-child interactions were observed, with a greater effect size among children with low milk intake and low levels of physical activity. Child weight, height, and body mass index (BMI) were similar by maternal randomization group. These findings suggest a sustained beneficial effect of maternal vitamin D supplementation in pregnancy on offspring aBMD at age 4 years, but will require replication in other trials. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

How to initiate and develop Fracture Liaison Services (FLS). Recommendations from the IOF Capture the Fracture® FLS Mentors in Brazil.

Expected number of fragility fractures in Brazil, raising the healthcare prioritization for interventions that reduce fracture risk. An FLS is dedicated to managing patient with fragility fracture to reduce risk of another fracture. We review FLSs cost-effectiveness and describe key components to effectively set up FLS in Brazil. PURPOSE: To create a guideline to show health professionals, hospital managers, and stakeholders in Brazil the importance of secondary fracture prevention and how to implement a Fracture Liaison Service. METHODS: We review the cost-effectiveness for FLSs in Brazil. We describe the key components needed to set up an effective FLS including methods for identification, investigation, treatment indication, including bone drugs, supplementation, physical activity, fall prevention, and monitoring. The staffing of FLSs, value of regional clinical networks and quality improvement are also described as a guide for healthcare professionals and decision makers in Brazil. RESULTS: An FLS is a service dedicated to identifying, assessing, recommending treatment, and monitoring patient who present with a fragility fracture reducing the risk of another fracture. FLS has been implemented in Brazil since 2012 overcoming a large geography and a complex health system. Even the limitations, restrictions, differences, and characteristics of each region, it is possible for health institutions to initiate an FLS, adapted to own available resources and meet the stages of identification, investigation, treatment, and monitoring. CONCLUSION: The peculiarity of the Brazilian healthcare system means FLS implementation needs to be tailored to local reality. However, even with limitations, any attempt to capture patients who suffer a fracture due to bone fragility is effective and reduces the risk of further fractures.

Neuropathic-like Pain in Fibrous Dysplasia/McCune-Albright Syndrome.

CONTEXT: Pain is a major symptom in adults with fibrous dysplasia/McCune-Albright syndrome (FD/MAS) and response to current treatments, including bisphosphonates and standard analgesics (nonsteroidal anti-inflammatory drugs and opiates) is unpredictable. No studies have explored whether the type of pain is variable in this patient group. OBJECTIVE: To determine the frequency of neuropathic-like pain in patients with FD/MAS. DESIGN: Retrospective, dual registry study. SETTING: Community. PATIENTS: FD/MAS online registries: the US-based Familial Dysautonomia Foundation (FDF) and the UK-based Rare and Undiagnosed Diseases (RUDY) study. INTERVENTION: Subjects completed questionnaires to evaluate the presence of features of neuropathic-like pain (painDETECT) and the impact on sleep quality (Pittsburgh Sleep Quality Index) and mental health (Hospital Anxiety and Depression Scale). Descriptive statistics were used to characterize the prevalence and associated burden of neuropathic-like pain. MAIN OUTCOME MEASURES: Incidence of neuropathic, nociceptive, and unclear pain. RESULTS: Of 249 participants, one third experienced neuropathic-like pain. This group had statistically significantly (P < 0.001) worse mental well-being and sleep in comparison to those with predominately nociceptive pain. CONCLUSIONS: Neuropathic-like pain is common in patients with FD/MAS and associated with worse quality of life. Evaluation of pain in patients with FD/MAS should include assessment of neuropathic-like pain to guide personalized approaches to treatment and inform future research.

Management of patients at very high risk of osteoporotic fractures through sequential treatments.

Osteoporosis care has evolved markedly over the last 50 years, such that there are now an established clinical definition, validated methods of fracture risk assessment and a range of effective pharmacological agents. Currently, bone-forming (anabolic) agents, in many countries, are used in those patients who have continued to lose bone mineral density (BMD), patients with multiple subsequent fractures or those who have fractured despite treatment with antiresorptive agents. However, head-to-head data suggest that anabolic agents have greater rapidity and efficacy for fracture risk reduction than do antiresorptive therapies. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) convened an expert working group to discuss the tools available to identify patients at high risk of fracture, review the evidence for the use of anabolic agents as the initial intervention in patients at highest risk of fracture and consider the sequence of therapy following their use. This position paper sets out the findings of the group and the consequent recommendations. The key conclusion is that the current evidence base supports an "anabolic first" approach in patients found to be at very high risk of fracture, followed by maintenance therapy using an antiresorptive agent, and with the subsequent need for antiosteoporosis therapy addressed over a lifetime horizon.

Comparative risk of acute myocardial infarction for anti-osteoporosis drugs in primary care: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database.

The aim of this study was to evaluate the risk of acute myocardial infarction in patients taking osteoporosis medication. Patients were taken from the SIDIAP or CPRD database and were matched using propensity scores. Patients with diabetes and chronic kidney disease taking SERMs were at an increased risk. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment. INTRODUCTION: This study aims to evaluate the comparative safety of anti-osteoporosis drugs based on the observed risk of acute myocardial infarction while on treatment in a primary care setting. METHODS: This is a propensity-matched cohort study and meta-analysis. This study was conducted in two primary care record databases covering UK NHS (CPRD) and Catalan healthcare (SIDIAP) patients during 1995-2014 and 2006-2014, respectively. The outcome was acute myocardial infarction while on treatment. Users of alendronate (reference group) were compared to those of (1) other oral bisphosphonates (OBP), (2) strontium ranelate (SR), and (3) selective oestrogen receptor modulator (SERM), after matching on baseline characteristics (socio-demographics, fracture risk factors, comorbidities, and concomitant drug use) using propensity scores. Multiple imputation was used to handle missing data on confounders and competing risk modelling for the calculation of relative risk (sub-distribution hazard ratios (SHR)) according to therapy. Country-specific data were analysed individually and meta-analysed. RESULTS: A 10% increased risk of acute myocardial infarction was found in users of other bisphosphonates as compared to alendronate users within CPRD. The meta-analysis of CPRD and SIDIAP results showed a 9% increased risk in users of other bisphosphonate as compared to alendronate users. Sensitivity analysis showed SERMS users with diabetes and chronic kidney disease were at an elevated risk. CONCLUSIONS: This study provides additional data on the risk of acute myocardial infarction in patients receiving osteoporosis treatment. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment.

Physical function and physical activity in adults with X-linked hypophosphatemia.

We described physical function and activity in UK adults with X-linked hypophosphatemia (XLH). Our data indicate that low physical activity and impaired mobility are common in adults with XLH. Deficits in lower limbs muscle power and functional capacity contribute to the loss of physical function in adults with XLH. INTRODUCTION: There is a dearth of literature on physical function and physical activity in adults with X-linked hypophosphatemia (XLH). We described muscle strength and power, functional capacity, mobility and physical activity level and explored the relationships among these variables in adults with XLH. METHODS: Participants were recruited as part of a UK-based prospective cohort study, the RUDY Study. They underwent a clinical visit and physical examination, including assessment of handgrip strength, jump power (mechanography), six-minute walk test (6MWT) and short physical performance battery (SPPB), and completed the International Physical Activity Questionnaire (IPAQ). Performance data were analysed using parametric and non-parametric tests, whereas correlations were assessed by univariate analysis. RESULTS: Twenty-six adults with XLH (50% males) with a mean age of 44 ± 16.1 years were recruited. Jump power and 6MWT distances (p < 0.0001) were 54.4% and 38.6% lower respectively in individuals with XLH compared with normative values. These deficits were not associated with age or sex. Handgrip strength values were similar to expected values. Deficits in muscle power were more pronounced than those reported at 6MWT (p < 0.0001). Univariate analysis revealed only a correlation between total physical activity and muscle power (r = 0.545, p = 0.019). CONCLUSIONS: Adults with XLH have a marked deficit in lower limb muscle power and a reduced functional capacity, with a high incidence of impaired mobility and inactivity. In addition to metabolic effects of XLH, low physical activity may contribute to deficits in lower limb power. Further studies are required to develop novel treatment approaches to improve physical function and mobility.

Multiple myeloma screening within a fracture liaison service (FLS).

Multiple myeloma (MM) remains incurable. Although early diagnosis improves outcomes, it has been unclear which populations to target for screening with serum electrophoresis, serum free light chains and urine electrophoresis. Here, we assessed the value of MM screening in a Fracture Liaison Service, finding that 1 per 195 fragility fractures has undiagnosed MM, which can be expedited to Haematology Services. PURPOSE: A key role of the Fracture Liaison Service (FLS) is screening for secondary causes of osteoporosis. In 2019, the Royal Osteoporosis Society recommended that all patients attending FLS who are recommended anti-osteoporosis therapy have universal screening for myeloma based on serum electrophoresis, serum free light chains and urine electrophoresis. Here, we examined the impact of universal myeloma screening within an FLS. METHODS: We sampled all patients seen by the Oxfordshire FLS between January and April 2018. The completion rates and outcomes of screening were checked using the hospital and FLS databases. RESULTS: Of 950 patients identified by the FLS, 628 were eligible for MM screening; 473 (75%) of these were female, and the average age was 78.4 years. Overall, 584 had some form of myeloma screening, of which 577 (92%) had serum electrophoresis, 525 (84%) had serum free light chains and 407 (65%) had urine electrophoresis measured. A total of 327 (59%) patients had complete screening. Three patients (0.5%) had newly diagnosed myeloma and were urgently referred to Haematology Services. Furthermore, 46 (8%) patients had a detectable serum paraprotein with a likely diagnosis of monoclonal gammopathy of uncertain significance (MGUS) and referred for community annual surveillance according to local guidelines. CONCLUSION: Addition of universal myeloma screening to laboratory testing identified myeloma in 1 per 195 patients, and its precursor state MGUS in 1 per 13 patients, which may have otherwise been missed. Further analysis with long-term follow-up is needed to clearly define the value of diagnosing MGUS within the FLS setting and establish the benefits vs. costs and methods to improve screening completion rates.

Tuning the Schottky barrier height in a multiferroic In2Se3/Fe3GeTe2 van der Waals heterojunction.

The ferroelectric material In2Se3 is currently of significant interest due to its built-in polarisation characteristics that can significantly modulate its electronic properties. Here we employ density functional theory to determine the transport characteristics at the metal-semiconductor interface of the two-dimensional multiferroic In2Se3/Fe3GeTe2 heterojunction. We show a significant tuning of the Schottky barrier height as a result of the change in the intrinsic polarisation state of In2Se3: the switching in the electric polarisation of In2Se3 results in the switching of the nature of the Schottky barrier, from being n-type to p-type, and is accompanied by a change in the spin polarisation of the electrons. This switchable Schottky barrier structure can form an essential component in a two-dimensional field effect transistor that can be operated by switching the ferroelectric polarisation, rather than by the application of strain or electric field. The band structure and density of state calculations show that Fe3GeTe2 lends its magnetic and metallic characteristics to the In2Se3 layer, making the In2Se3/Fe3GeTe2 heterojunction a potentially viable multiferroic candidate in nanoelectronic devices like field-effect transistors. Moreover, our findings reveal a transfer of charge carriers from the In2Se3 layer to the Fe3GeTe2 layer, resulting in the formation of an in-built electric field at the metal-semiconductor interface. Our work can substantially broaden the device potential of the In2Se3/Fe3GeTe2 heterojunction in future low-energy electronic devices.

Spatial variability and delineation of management zones based on soil micronutrient status in apple orchard soils of Kashmir valley, India.

Knowledge and up-scaling of status, availability, and distribution of soil micronutrients are hugely significant for enhancing crop productivity and profitability. However, regional database entailing spatial variability of key micronutrients for a major apple-producing region like the Kashmir Himalayan Region (KHR) is missing. We investigated 588 topsoil samples between 2016 and 2017 (to 30 cm depth) to estimate spatial variability of extractable Zn, Cu, Mn, and Fe; develop spatial maps; and delineate potential management zones (MZs) in apple orchards using geo-statistical methods. Soil sampling was performed post-harvest season. Principal component analysis and fuzzy c-mean clustering were performed to develop MZs. Results exhibited wide variation, with high coefficient of variation (%) for Mn and Cu (123.9 and 114.4, respectively) and low (71.6) and medium (104) variability for Fe and Zn. Mean concentrations followed the order: Fe > Mn > Cu > Zn, with deficiencies evident towards central and northern regions of the study area. The best-fitted model was exponential. The nugget/sill ratio values were 0.41, 0.08, 0.37, and 0.38 for Zn, Cu, Mn, and Fe, respectively, indicating strong spatial dependence for Cu and moderate dependence for Fe, Zn, and Mn. Correlations between elevation, slope, and soil pH with micronutrients were negative, whereas with soil organic carbon and electrical conductivity positive relationships were identified. Three principal components accounted for 67·18% data variance. Based on the fuzzy performance index and modified partition entropy, five MZs were delineated, which exhibited variations from each other. These MZs highlighted the need for specific supplemental provisions in increasing soil fertility and apple productivity.