The Incidence of Pulmonary Embolism in Hospitalized Non-ICU Patients with COVID-19 during the First Wave: A Multicenter Retrospective Cohort Study in the Netherlands.

INTRODUCTION: During the first COVID-19 outbreak in 2020 in the Netherlands, the incidence of pulmonary embolism (PE) appeared to be high in COVID-19 patients admitted to the intensive care unit (ICU). This study was performed to evaluate the incidence of PE during hospital stay in COVID-19 patients not admitted to the ICU. METHODS: Data were retrospectively collected from 8 hospitals in the Netherlands. Patients admitted between February 27, 2020, and July 31, 2020, were included. Data extracted comprised clinical characteristics, medication use, first onset of COVID-19-related symptoms, admission date due to COVID-19, and date of PE diagnosis. Only polymerase chain reaction (PCR)-positive patients were included. All PEs were diagnosed with computed tomography pulmonary angiography (CTPA). RESULTS: Data from 1,852 patients who were admitted to the hospital ward were collected. Forty patients (2.2%) were diagnosed with PE within 28 days following hospital admission. The median time to PE since admission was 4.5 days (IQR 0.0-9.0). In all 40 patients, PE was diagnosed within the first 2 weeks after hospital admission and for 22 (55%) patients within 2 weeks after onset of symptoms. Patient characteristics, pre-existing comorbidities, anticoagulant use, and laboratory parameters at admission were not related to the development of PE. CONCLUSION: In this retrospective multicenter cohort study of 1,852 COVID-19 patients only admitted to the non-ICU wards, the incidence of CTPA-confirmed PE was 2.2% during the first 4 weeks after onset of symptoms and occurred exclusively within 2 weeks after hospital admission.

Development and usability of a decision aid to initiate anti-osteoporosis medication treatment in patients visiting the fracture liaison service with a recent fracture.

This study describes the development of a decision aid (DA), aimed at supporting patients in their decision whether to start anti-osteoporosis medication. People with recent fractures or osteoporosis and health professionals were supportive of the DA initiative. An experimental study been started to assess (cost-)effectiveness of the DA. PURPOSE: At fracture liaison services (FLS), patients with a recent fracture ánd osteoporosis or a prevalent vertebral fracture are advised to start anti-osteoporosis medication (AOM). This study describes the development of a decision aid (DA) to support patients and healthcare providers (HCPs) in their decision about whether to start AOM. METHODS: The DA was developed according to International Patient Decision Aid Standards (IPDAS). A systematic procedure was chosen including scope, design, prototype development, and alpha testing. A previously developed DA for women with osteoporosis was used as a basis. Furthermore, input from literature searches, the Dutch guideline on management of osteoporosis, and from people with a fracture or osteoporosis was used. The updated DA was evaluated during alpha testing. RESULTS: The DA facilitates the decision of patients whether to initiate AOM treatment and provides information on fractures and osteoporosis, general risk factors that increase the likelihood of a subsequent fracture, the role of lifestyle, personalized risk considerations of a subsequent fracture with and without AOM treatment, and AOM options and their characteristics in an option grid. Alpha testing with 15 patients revealed that patient preferences and needs were adequately presented, and several suggestions for improvement (e.g. adding more specific information, simplifying terminology, improving icon use) were accounted for. Participants from the alpha testing recommended use of the DA during outpatient visits. CONCLUSION: Professionals and persons with osteoporosis were supportive of the proposed DA and its usability. The DA could help in a shared decision-making process between patients and HCPs.

The risk of fragility fractures in men with prostate cancer treated with androgen deprivation therapy.

Androgen Deprivation Therapy (ADT) increases long-term fracture risk in prostate cancer. Our study showed a higher fracture risk within six months of ADT use, and current use was associated with a higher risk of fragility fractures. Attention is needed for the prevention of fragility fractures at the start of ADT. PURPOSE: Androgen Deprivation Therapy (ADT) is known to increase long-term fracture risk in men with prostate cancer (PCa), although the risk of fragility fractures remains unclear. This study aims to evaluate the risk of fragility and malignancy-related fractures in men with PCa treated with ADT. METHODS: We conducted a retrospective cohort study of men with PCa. Follow-up time was divided into 30-day intervals and exposure (current, past, or no-ADT use). Current ADT use was stratified by duration of ADT use (≤ 182 days, 183-730 days, and > 730 days). Cause-specific Cox proportional hazard models were used to estimate the risk of fractures. RESULTS: We included 471 patients (mean age 70.5 (± 8.3) years). The mean follow-up time was 5.0 (± 1.7) years in patients who never started ADT, 3.4 (± 2.3) years and 4.1 (± 2.0) years in patients who started ADT at baseline and during follow-up, respectively. In total, 60 patients had a fracture, 48 (80%) fragility, and 12 (20%) malignancy-related fractures. Current ADT use was associated with a higher risk of all fractures (HR 5.10, 95% CI 2.34-11.13) and fragility fractures (HR 3.61, 95% CI 1.57-8.30). The association with malignancy-related fractures could not be studied due to no events during no-ADT use. There was an increased risk of all fractures with longer duration of ADT use. CONCLUSIONS: Current ADT use was associated with a higher risk of fragility fractures than no-ADT use. A higher fracture risk was observed within the first six months of ADT use and persisted for longer durations.

Bone Microarchitecture and Strength Changes During Teriparatide and Zoledronic Acid Treatment in a Patient with Pregnancy and Lactation-Associated Osteoporosis with Multiple Vertebral Fractures.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, of which the pathogenesis and best treatment options are unclear. In this report, we describe the case of a 34-year old woman diagnosed with severe osteoporosis and multiple vertebral fractures after her first pregnancy, who was subsequently treated with teriparatide (TPTD) and zoledronic acid (ZA). We describe the clinical features, imaging examination, and genetic analysis. Substantial improvements were observed in areal and volumetric bone mineral density (BMD), microarchitecture, and strength between 7 and 40 months postpartum as assessed by dual-energy X-ray absorptiometry at the total hip and spine and by high-resolution peripheral quantitative CT at the distal radius and tibiae. At the hip, spine, and distal radius, these improvements were mainly enabled by treatment with TPTD and ZA, while at the distal tibiae, physiological recovery and postpartum physiotherapy due to leg pain after stumbling may have played a major role. Additionally, the findings show that, despite the improvements, BMD, microarchitecture, and strength remained severely impaired in comparison with healthy age- and gender-matched controls at 40 months postpartum. Genetic analysis showed no monogenic cause for osteoporosis, and it is suggested that PLO in this woman could have a polygenic origin with possible susceptibility based on familiar occurrence of osteoporosis.

Imminent fall risk after fracture.

RATIONALE: Adults with a recent fracture have a high imminent risk of a subsequent fracture. We hypothesise that, like subsequent fracture risk, fall risk is also highest immediately after a fracture. This study aims to assess if fall risk is time-dependent in subjects with a recent fracture compared to subjects without a fracture. METHODS: This retrospective matched cohort study used data from the UK Clinical Practice Research Datalink GOLD. All subjects ≥50 years with a fracture between 1993 and 2015 were identified and matched one-to-one to fracture-free controls based on year of birth, sex and practice. The cumulative incidence and relative risk (RR) of a first fall was calculated at various time intervals, with mortality as competing risk. Subsequently, analyses were stratified according to age, sex and type of index fracture. RESULTS: A total of 624,460 subjects were included; 312,230 subjects with an index fracture, matched to 312,230 fracture-free controls (71% females, mean age 70 ± 12, mean follow-up 6.5 ± 5 years). The RR of falls was highest in the first year after fracture compared to fracture-free controls; males had a 3-fold and females a 2-fold higher risk. This imminent fall risk was present in all age and fracture types and declined over time. A concurrent imminent fracture and mortality risk were confirmed. CONCLUSION/DISCUSSION: This study demonstrates an imminent fall risk in the first years after a fracture in all age and fracture types. This underlines the need for early fall risk assessment and prevention strategies in 50+ adults with a recent fracture.

What Is the Diagnostic Performance of Conventional Radiographs and Clinical Reassessment Compared With HR-pQCT Scaphoid Fracture Diagnosis?

BACKGROUND: Conventional radiographs and clinical reassessment are considered guides in managing clinically suspected scaphoid fractures. This is a unique study as it assessed the value of conventional radiographs and clinical reassessment in a cohort of patients, all of whom underwent additional imaging, regardless of the outcome of conventional radiographs and clinical reassessment. QUESTIONS/PURPOSES: (1) What is the diagnostic performance of conventional radiographs in patients with a clinically suspected scaphoid fracture compared with high-resolution peripheral quantitative CT (HR-pQCT)? (2) What is the diagnostic performance of clinical reassessment in patients with a clinically suspected scaphoid fracture compared with HR-pQCT? (3) What is the diagnostic performance of conventional radiographs and clinical reassessment combined compared with HR-pQCT? METHODS: Between December 2017 and October 2018, 162 patients with a clinically suspected scaphoid fracture presented to the emergency department (ED). Forty-six patients were excluded and another 25 were not willing or able to participate, which resulted in 91 included patients. All patients underwent conventional radiography in the ED and clinical reassessment 7 to 14 days later, together with CT and HR-pQCT. The diagnostic performance characteristics and accuracy of conventional radiographs and clinical reassessment were compared with those of HR-pQCT for the diagnosis of fractures since this was proven to be superior to CT scaphoid fracture detection. The cohort included 45 men and 46 women with a median (IQR) age of 52 years (29 to 67). Twenty-four patients with a median age of 44 years (35 to 65) were diagnosed with a scaphoid fracture on HR-pQCT. RESULTS: When compared with HR-pQCT, conventional radiographs alone had a sensitivity of 67% (95% CI 45% to 84%), specificity of 85% (95% CI 74% to 93%), positive predictive value (PPV) of 62% (95% CI 46% to 75%), negative predictive value (NPV) of 88% (95% CI 80% to 93%), and a positive and negative likelihood ratio (LR) of 4.5 (95% CI 2.4 to 8.5) and 0.4 (95% CI 0.2 to 0.7), respectively. Compared with HR-pQCT, clinical reassessment alone resulted in a sensitivity of 58% (95% CI 37% to 78%), specificity of 42% (95% CI 30% to 54%), PPV of 26% (95% CI 19% to 35%), NPV of 74% (95% CI 62% to 83%), as well as a positive and negative LR of 1.0 (95% CI 0.7 to 1.5) and 1.0 (95% CI 0.6 to 1.7), respectively. Combining clinical examination with conventional radiography produced a sensitivity of 50% (95% CI 29% to 71%), specificity of 91% (95% CI 82% to 97%), PPV of 67% (95% CI 46% to 83%), NPV of 84% (95% CI 77% to 88%), as well as a positive and negative LR of 5.6 (95% CI 2.4 to 13.2) and 0.6 (95% CI 0.4 to 0.8), respectively. CONCLUSION: The accuracy of conventional radiographs (80% compared with HR-pQCT) and clinical reassessment (46% compared with HR-pQCT) indicate that the value of clinical reassessment is limited in diagnosing scaphoid fractures and cannot be considered directive in managing scaphoid fractures. The combination of conventional radiographs and clinical reassessment does not increase the accuracy of these diagnostic tests compared with the accuracy of conventional radiographs alone and is therefore also limited in diagnosing scaphoid fractures. LEVEL OF EVIDENCE: Level II, diagnostic study.

High-Resolution Cone-Beam Computed Tomography is a Fast and Promising Technique to Quantify Bone Microstructure and Mechanics of the Distal Radius.

Obtaining high-resolution scans of bones and joints for clinical applications is challenging. HR-pQCT is considered the best technology to acquire high-resolution images of the peripheral skeleton in vivo, but a breakthrough for widespread clinical applications is still lacking. Recently, we showed on trapezia that CBCT is a promising alternative providing a larger FOV at a shorter scanning time. The goals of this study were to evaluate the accuracy of CBCT in quantifying trabecular bone microstructural and predicted mechanical parameters of the distal radius, the most often investigated skeletal site with HR-pQCT, and to compare it with HR-pQCT. Nineteen radii were scanned with four scanners: (1) HR-pQCT (XtremeCT, Scanco Medical AG, @ (voxel size) 82 µm), (2) HR-pQCT (XtremeCT-II, Scanco, @60.7 µm), (3) CBCT (NewTom 5G, Cefla, @75 µm) reconstructed and segmented using in-house developed software and (4) microCT (VivaCT40, Scanco, @19 µm-gold standard). The following parameters were evaluated: predicted stiffness, strength, bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), separation (Tb.Sp) and number (Tb.N). The overall accuracy of CBCT with in-house optimized algorithms in quantifying bone microstructural parameters was comparable (R2 = 0.79) to XtremeCT (R2 = 0.76) and slightly worse than XtremeCT-II (R2 = 0.86) which were both processed with the standard manufacturer's technique. CBCT had higher accuracy for BV/TV and Tb.Th but lower for Tb.Sp and Tb.N compared to XtremeCT. Regarding the mechanical parameters, all scanners had high accuracy (R2 [Formula: see text] 0.96). While HR-pQCT is optimized for research, the fast scanning time and good accuracy renders CBCT a promising technique for high-resolution clinical scanning.

Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands: the COVID-OLD study.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. OBJECTIVE: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. METHODS: This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. RESULTS: A total of 1,376 patients were included (median age 78 years (interquartile range 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3-3.0)) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8-4.3)). CONCLUSIONS: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.

Early detection of hospitalized patients with COVID-19 at high risk of clinical deterioration: Utility of emergency department shock index.

BACKGROUND: The COVID-19 outbreak has put an unprecedented strain on Emergency Departments (EDs) and other critical care resources. Early detection of patients that are at high risk of clinical deterioration and require intensive monitoring, is key in ED evaluation and disposition. A rapid and easy risk-stratification tool could aid clinicians in early decision making. The Shock Index (SI: heart rate/systolic blood pressure) proved useful in detecting hemodynamic instability in sepsis and myocardial infarction patients. In this study we aim to determine whether SI is discriminative for ICU admission and in-hospital mortality in COVID-19 patients. METHODS: Retrospective, observational, single-center study. All patients ≥18 years old who were hospitalized with COVID-19 (defined as: positive result on reverse transcription polymerase chain reaction (PCR) test) between March 1, 2020 and December 31, 2020 were included for analysis. Data were collected from electronic medical patient records and stored in a protected database. ED shock index was calculated and analyzed for its discriminative value on in-hospital mortality and ICU admission by a ROC curve analysis. RESULTS: In total, 411 patients were included. Of all patients 249 (61%) were male. ICU admission was observed in 92 patients (22%). Of these, 37 patients (40%) died in the ICU. Total in-hospital mortality was 28% (114 patients). For in-hospital mortality the optimal cut-off SI ≥ 0.86 was not discriminative (AUC 0.49 (95% CI: 0.43-0.56)), with a sensitivity of 12.3% and specificity of 93.6%. For ICU admission the optimal cut-off SI ≥ 0.57 was also not discriminative (AUC 0.56 (95% CI: 0.49-0.62)), with a sensitivity of 78.3% and a specificity of 34.2%. CONCLUSION: In this cohort of patients hospitalized with COVID-19, SI measured at ED presentation was not discriminative for ICU admission and was not useful for early identification of patients at risk of clinical deterioration.

Improvement of osteoporosis Care Organized by Nurses: ICON study - Protocol of a quasi-experimental study to assess the (cost)-effectiveness of combining a decision aid with motivational interviewing for improving medication persistence in patients with a recent fracture being treated at the fracture liaison service.

BACKGROUND: Given the health and economic burden of fractures related to osteoporosis, suboptimal adherence to medication and the increasing importance of shared-decision making, the Improvement of osteoporosis Care Organized by Nurses (ICON) study was designed to evaluate the effectiveness, cost-effectiveness and feasibility of a multi-component adherence intervention (MCAI) for patients with an indication for treatment with anti-osteoporosis medication, following assessment at the Fracture Liaison Service after a recent fracture. The MCAI involves two consultations at the FLS. During the first consultation, a decision aid is will be used to involve patients in the decision of whether to start anti-osteoporosis medication. During the follow-up visit, the nurse inquires about, and stimulates, medication adherence using motivational interviewing techniques. METHODS: A quasi-experimental trial to evaluate the (cost-) effectiveness and feasibility of an MCAI, consisting of a decision aid (DA) at the first visit, combined with nurse-led adherence support using motivational interviewing during the follow-up visit, in comparison with care as usual, in improving adherence to oral anti-osteoporosis medication for patients with a recent fracture two Dutch FLS. Medication persistence, defined as the proportion of patients who are persistent at one year assuming a refill gap < 30 days, is the primary outcome. Medication adherence, decision quality, subsequent fractures and mortality are the secondary outcomes. A lifetime cost-effectiveness analysis using a model-based economic evaluation and a process evaluation will also be conducted. A sample size of 248 patients is required to show an improvement in the primary outcome with 20%. Study follow-up is at 12 months, with measurements at baseline, after four months, and at 12 months. DISCUSSION: We expect that the ICON-study will show that the MCAI is a (cost-)effective intervention for improving persistence with anti-osteoporosis medication and that it is feasible for implementation at the FLS. TRIAL REGISTRATION: This trial has been registered in the Netherlands Trial Registry, part of the Dutch Cochrane Centre (Trial NL7236 (NTR7435)). Version 1.0; 26-11-2020.

Early warning scores to assess the probability of critical illness in patients with COVID-19.

OBJECTIVE: Validated clinical risk scores are needed to identify patients with COVID-19 at risk of severe disease and to guide triage decision-making during the COVID-19 pandemic. The objective of the current study was to evaluate the performance of early warning scores (EWS) in the ED when identifying patients with COVID-19 who will require intensive care unit (ICU) admission for high-flow-oxygen usage or mechanical ventilation. METHODS: Patients with a proven SARS-CoV-2 infection with complete resuscitate orders treated in nine hospitals between 27 February and 30 July 2020 needing hospital admission were included. Primary outcome was the performance of EWS in identifying patients needing ICU admission within 24 hours after ED presentation. RESULTS: In total, 1501 patients were included. Median age was 71 (range 19-99) years and 60.3% were male. Of all patients, 86.9% were admitted to the general ward and 13.1% to the ICU within 24 hours after ED admission. ICU patients had lower peripheral oxygen saturation (86.7% vs 93.7, p≤0.001) and had a higher body mass index (29.2 vs 27.9 p=0.043) compared with non-ICU patients. National Early Warning Score 2 (NEWS2) ≥ 6 and q-COVID Score were superior to all other studied clinical risk scores in predicting ICU admission with a fair area under the receiver operating characteristics curve of 0.740 (95% CI 0.696 to 0.783) and 0.760 (95% CI 0.712 to 0.800), respectively. NEWS2 ≥6 and q-COVID Score ≥3 discriminated patients admitted to the ICU with a sensitivity of 78.1% and 75.9%, and specificity of 56.3% and 61.8%, respectively. CONCLUSION: In this multicentre study, the best performing models to predict ICU admittance were the NEWS2 and the Quick COVID-19 Severity Index Score, with fair diagnostic performance. However, due to the moderate performance, these models cannot be clinically used to adequately predict the need for ICU admission within 24 hours in patients with SARS-CoV-2 infection presenting at the ED.

The Prevalence of Celiac Disease in a Fracture Liaison Service Population.

Celiac disease (CD) is a known risk factor for osteoporosis and fractures. The prevalence of CD in patients with a recent fracture is unknown. We therefore systematically screened patients at a fracture liaison service (FLS) to study the prevalence of CD. Patients with a recent fracture aged ≥ 50 years were invited to VieCuri Medical Center's FLS. In FLS attendees, bone mineral density (BMD) and laboratory evaluation for metabolic bone disorders and serological screening for CD was systematically evaluated. If serologic testing for CD was positive, duodenal biopsies were performed to confirm the diagnosis CD. Data were collected in 1042 consecutive FLS attendees. Median age was 66 years (Interquartile range (IQR) 15), 27.6% had a major and 6.9% a hip fracture, 26.4% had osteoporosis and 50.8% osteopenia. Prevalent vertebral fractures were found in 29.1%. CD was already diagnosed in two patients (0.19%), one still had a positive serology. Three other patients (0.29%) had a positive serology for CD (one with gastro-intestinal complaints). In two of them, CD was confirmed by duodenal histology (0.19%) and one refused further evaluation. The prevalence of biopsy-proven CD was therefore 0.38% (4/1042) of which 0.19% (2/1042) was newly diagnosed. The prevalence of CD in patients with a recent fracture at the FLS was 0.38% and within the range of reported prevalences in the Western-European population (0.33-1.5%). Newly diagnosed CD was only found in 0.19%. Therefore, standard screening for CD in FLS patients is not recommended.

The Phenotype of Patients with a Recent Fracture: A Literature Survey of the Fracture Liaison Service.

The aetiology of fractures in patients aged 50 years and older is multifactorial, and includes bone- and fall-related risks. The Fracture Liaison Service (FLS) is recommended to identify patients with a recent fracture and to evaluate their subsequent fracture risk, in order to take measures to decrease the risk of subsequent fractures in patients with a high risk phenotype. A literature survey was conducted to describe components of the bone- and fall-related phenotype of patients attending the FLS. Components of the patient phenotype at the FLS have been reported in 33 studies. Patient selection varied widely in terms of patient identification, selection, and FLS attendance. Consequently, there was a high variability in FLS patient characteristics, such as mean age (64-80 years), proportion of men (13-30%), and fracture locations (2-51% hip, <1-41% vertebral, and 49-95% non-hip, non-vertebral fractures). The studies also varied in the risk evaluation performed. When reported, there was a highly variability in the percentage of patients with osteoporosis (12-54%), prevalent vertebral fractures (20-57%), newly diagnosed contributors to secondary osteoporosis and metabolic bone disorders (3-70%), and fall-related risk factors (60-84%). In FLS literature, we found a high variability in patient selection and risk evaluation, resulting in a highly variable phenotype. In order to specify the bone- and fall related phenotypes at the FLS, systematic studies on the presence and combinations of these risks are needed.

A systematic review of economic evaluations of screening programmes for cardiometabolic diseases.

Background: The early detection and adequate management of cardiometabolic diseases (CMD) is becoming a priority to prevent future health problems and related healthcare costs. Aim: This study systematically reviewed the economic evaluations of screening programmes for the early detection of persons at risk for CMD. Methods: A systematic review was conducted using MEDLINE, Web of Science, NHSEED and the CEA registry to identify relevant articles published between 1 January 2005 and 1 May 2015. Two reviewers independently selected articles, systematically extracted data and critically appraised the study quality using the Extended Consensus on Health Economic Criteria (CHEC) List. Results: From the initial 2820 studies identified, 17 were included. Six studies assessed whether screening would be cost-effective, seven aimed to determine the most efficient screening programme and four assessed the cost-effectiveness of existing programmes. There were 11 cost-utility analyses using quality-adjusted life years (QALYs) or disability-adjusted life years. Decision-analytic modelling (e.g. Markov model) was most frequently used (n = 10), followed by simulation models (n = 4), observational (n = 2) and trial-based (n = 1) studies. All studies assessing the cost per QALY gained of screening for cardiovascular diseases and diabetes mellitus (n = 8) were below a threshold of £30 000, while those assessing chronic kidney diseases (n = 2) were above the threshold. Conclusions: In view of the heterogeneity in study objectives, country setting, screening programmes, comparators, methodology and outcomes, it is not possible to make clear recommendations about the economic value of screening programmes for CMD. Developing further screening programmes and conducting thorough economic analysis, including usual care, is needed.

Cost-effectiveness of a multicomponent-adherence intervention in fracture liaison services.

BACKGROUND: This study aims to assess the lifetime cost-effectiveness of a multi-component adherence intervention (MCAI), including a patient decision aid and motivational interviewing, compared to usual care in patients with a recent fracture attending fracture liaison services (FLS) and eligible for anti-osteoporosis medication (AOM). RESEARCH DESIGN AND METHODS: Data on AOM initiation and one-year persistence were collected from a quasi-experimental study conducted between 2019 and 2023 in two Dutch FLS centers. An individual level, state-transition Markov model was used to simulate lifetime costs and quality-adjusted life years (QALYs) with a societal perspective of MCAI vs usual care. One-way and probabilistic sensitivity analyses were conducted including variation in additional FLS and MCAI costs (no MCAI cost in baseline). RESULTS: MCAI was associated with gain in QALYs (0.0012) and reduction in costs (-€16) and is therefore dominant. At the Dutch willingness-to-pay threshold of €50,000/QALY, MCAI remained cost-effective when increasing costs of the FLS visit or the yearly maintenance cost for MCAI up to +€60. Probabilistic sensitivity analysis demonstrated MCAI to be dominant in 54% of the simulations and cost-effective in 87% with a threshold of €50,000/QALY. CONCLUSIONS: A MCAI implemented in FLS centers may lead to cost-effective allocation of resources in FLS care, depending on extra costs.

The "Can Do, Do Do" Framework Applied to Assess the Association between Physical Capacity, Physical Activity and Prospective Falls, Subsequent Fractures, and Mortality in Patients Visiting the Fracture Liaison Service.

The "can do, do do" framework combines measures of poor and normal physical capacity (PC, measured by a 6 min walking test, can do/can't do) and physical activity (PA, measured by accelerometer, do do/don't do) into four domains and is able to categorize patient subgroups with distinct clinical characteristics, including fall and fracture risk factors. This study aims to explore the association between domain categorization and prospective fall, fracture, and mortality outcomes. This 6-year prospective study included patients visiting a Fracture Liaison Service with a recent fracture. Outcomes were first fall (at 3 years of follow-up, measured by fall diaries), first subsequent fracture, and mortality (at 6 years). Cumulative incidences of all three outcomes were calculated. The association between domain categorization and time to the three outcomes was assessed by uni- and multivariate Cox proportional hazard analysis with the "can do, do do" group as reference. The physical performance of 400 patients with a recent fracture was assessed (mean age: 64 years; 70.8% female), of whom 61.5%, 20.3%, and 4.9% sustained a first fall, sustained a subsequent fracture, or had died. Domain categorization using the "can do, do do" framework was not associated with time to first fall, subsequent fracture, or mortality in the multivariate Cox regression analysis for all groups. "Can't do, don't do" group: hazard ratio [HR] for first fall: 0.75 (95% confidence interval [CI]: 0.45-1.23), first fracture HR: 0.58 (95% CI: 0.24-1.41), and mortality HR: 1.19 (95% CI: 0.54-6.95). Categorizing patients into a two-dimensional framework seems inadequate to study complex, multifactorial outcomes. A personalized approach based on known fall and fracture risk factors might be preferable.

Accuracy of photon-counting computed tomography for the measurement of bone quality in the knee.

Visualization and quantification of bone microarchitecture in the human knee allows gaining insight into normal bone structure, and into the structural changes occurring in the onset and progression of bone diseases such as osteoporosis and osteoarthritis. However, current imaging modalities have limitations in capturing the intricacies of bone microarchitecture. Photon counting computed tomography (PCCT) is a promising imaging modality that presents high-resolution three-dimensional visualization of bone with a large field of view. However, the potential of PCCT in assessing trabecular microstructure has not been investigated yet. Therefore, this study aimed to evaluate the accuracy of PCCT in quantifying bone microstructure and bone mechanics in the knee. Five human cadaveric knees were scanned ex vivo using a PCCT scanner (Naetom alpha, Siemens, Germany) with an in-plane resolution of 146.5 µm and slice thickness of 100 µm. To assess accuracy, the specimens were also scanned with a high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT II, Scanco Medical, Switzerland) with a nominal isotropic voxel size of 60.7 µm as well as with micro-computed tomography (micro-CT; TESCAN UniTOM XL, Czech Republic) with a nominal isotropic voxel size of 25 µm which can be considered gold standards for in vivo and ex vivo scanning, respectively. The thickness and porosity of the subchondral bone and the microstructure of the underlying trabecular bone were assessed in the load bearing regions of the proximal tibia and distal femur. The apparent Young's modulus was determined by micro-finite element (µFE) analysis of subchondral trabecular bone (STB) in the load bearing regions of the proximal tibia using PCCT, HR-pQCT and micro-CT images. The correlation between PCCT measurements and micro-CT and HR-pQCT, respectively, was calculated. The coefficients of determination (R2) between PCCT and micro-CT based parameters, ranged from 0.69 to 0.87. The coefficients of determination between PCCT and HR-pQCT were slightly higher and ranged from 0.71 to 0.91. Apparent Young's modulus, assessed by µFE analysis of PCCT images, correlated well with that of micro-CT (R2 = 0.80, mean relative difference = 19 %). However, PCCT overestimated the apparent Young's modulus by 47 %, but the correlation (R2 = 0.84) remained strong when compared to HR-pQCT. The results of this study suggest that PCCT can be used to quantify bone microstructure in the knee.

Societal costs before and up to 1 year after the first fracture liaison service visit in patients requiring anti-osteoporosis treatments.

This study aimed to estimate societal and healthcare costs incurred before and 1 year after the first fracture liaison services (FLS) visit and to explore differences in fracture type. All costs after 1 year significantly decreased compared to costs preceding the first visit. Fracture type did not significantly affect costs. INTRODUCTION: Limited literature is available on resource utilization and costs of patients visiting fracture liaison services (FLS). This study aimed to estimate the societal and healthcare costs incurred by patients with a recent fracture requiring anti-osteoporosis medication before and 1 year after the first FLS visit and to explore differences according to fracture type. METHODS: Resource utilization was collected through a self-reported questionnaire with a 4-month recall on health resource utilization and productivity losses immediately following the first FLS visit, and 4 and 12 months later. Unit costs derived from the national Dutch guideline for economic evaluations were used to compute societal and healthcare costs. Linear mixed-effect models, adjusted for confounders, were used to analyze societal and healthcare costs over time as well as the effect of fracture type on societal and healthcare costs. RESULTS: A total of 126 patients from two Dutch FLS centers were included, of whom 72 sustained a major fracture (hip, vertebral, humerus, or radius). Societal costs in the 4 months prior to the first visit (€2911) were significantly higher compared to societal costs 4 months (€711, p-value = 0.009) and 12 months later (€581, p-value = 0.001). Fracture type did not have a significant effect on total societal or healthcare costs. All costs 12 months after the initial visit were numerically lower for major fractures compared to others. CONCLUSION: Societal and healthcare costs in the year following the first FLS visit significantly decreased compared to those costs preceding the first visit.

Development of a Multidisciplinary Care Pathway for Fracture Prevention in Men with Prostate Cancer at Initiation of Androgen Deprivation Therapy.

Fracture risk is increased in men with prostate cancer (PCa) receiving Androgen Deprivation Therapy (ADT). However, routine assessment of fracture risk is often not systematically applied. We aimed to establish a comprehensive care pathway for fracture prevention in men with PCa starting ADT. Therefore, a multidisciplinary working group designed and implemented a care pathway using the 'Knowledge to Action' framework, based on current Dutch guidelines for PCa, osteoporosis and fracture prevention, and an extensive literature review of other guidelines. The pathway was developed according to a five-step clinical approach including case finding, fracture risk assessment based on risk factors, bone mineral density test, vertebral fracture assessment, differential diagnosis, treatment, and annual follow-up. Our fracture prevention care pathway for patients with PCa at the time of ADT initiation was designed to promote a patient-centered, multidisciplinary approach to facilitate the implementation of early fracture prevention measures.

A quasi-experimental study about shared decision-making and motivational interviewing on patients with a recent fracture attending Fracture Liaison Services.

Shared decision-making (SDM) aims to improve patients' experiences with care, treatment adherence, and health outcomes. However, the effectiveness of SDM in patients with a recent fracture who require anti-osteoporosis medication (AOM) is unclear. The objective of this study was to assess the effectiveness of a multicomponent adherence intervention (MCAI) including a patient decision aid (PDA) and motivational interviewing at Fracture Liaison Services (FLS) on multiple outcomes compared with usual care (UC). This pre-post superiority study included patients with a recent fracture attending FLS and with AOM treatment indication. The primary outcome was 1-year AOM persistence measured by pharmacy records. Secondary outcomes included treatment initiation, AOM adherence (measured by medication possession ratio [MPR]), decision quality (SDM process; 0-100, best), and decisional conflict (0-100, highest conflict), subsequent fractures, and mortality. Outcomes were tested in MCAI and UC groups at the first FLS visit and 4 and 12 months afterwards. Multiple imputation and uni- and multivariable analyses were performed. Post hoc analyses assessed the role of health literacy level. In total, 245 patients (MCAI: n = 136, UC: n = 109) were included. AOM persistence was 80.4% in the MCAI and 76.7% in the UC group (p=.626). SDM process scores were significantly better in MCAI (60.4 vs 55.1; p = .003). AOM initiation (97.8% vs 97.5%), MPR (90.9% vs 88.3%, p=.582), and decisional conflict (21.7 vs 23.0; p = .314) did not differ between groups. Results did not change importantly after adjustment. Stratified analyses by health literacy showed a better effect on MPR and SDM in those with adequate health literacy. This study showed no significant effect on AOM persistence; however, it demonstrated a significant positive effect of MCAI on SDM process in FLS attendees. (Netherlands Trial Registry, Trial NL7236 [NTR7435]; version 1.0; 26-11-2020 https://onderzoekmetmensen.nl/nl/trial/22858).

When patients participate in the decision-making process (called shared decision-making), we may be able to improve the way they take medication and experience care. We wanted to study how shared decision-making works in people who recently broke a bone and therefore needed anti-osteoporosis medication. We looked at 2 approaches that specialized nurses could use at the clinic. During the first visit, the nurses used a decision aid to discuss different medication options with the patient. During the second visit, nurses used "motivational interviewing" to better understand and support patients with taking their medication in the long term. We compared 109 patients who participated in this study with 126 patients who received normal care without the approaches. We found that the 2 approaches did not change the way people take their medication 1 year after the visits. However, patients who experienced the new approaches felt more involved in all phases of the decision to start and continue medication compared with patients receiving usual care. One year after the visits, people with higher health literacy were more likely to feel like they had been involved in the decision-making process, and more likely to continue to take their medication as prescribed.