Harnessing the potential of data-driven strategies to optimise transfusion practice.

No one doubts the significant variation in the practice of transfusion medicine. Common examples are the variability in transfusion thresholds and the use of tranexamic acid for surgery with likely high blood loss despite evidence-based standards. There is a long history of applying different strategies to address this variation, including education, clinical guidelines, audit and feedback, but the effectiveness and cost-effectiveness of these initiatives remains unclear. Advances in computerised decision support systems and the application of novel electronic capabilities offer alternative approaches to improving transfusion practice. In England, the National Institute for Health and Care Research funded a Blood and Transplant Research Unit (BTRU) programme focussing on 'A data-enabled programme of research to improve transfusion practices'. The overarching aim of the BTRU is to accelerate the development of data-driven methods to optimise the use of blood and transfusion alternatives, and to integrate them within routine practice to improve patient outcomes. One particular area of focus is implementation science to address variation in practice.

Burden of osteoarthritis in India and its states, 1990-2019: findings from the Global Burden of disease study 2019.

OBJECTIVE: To describe the burden of osteoarthritis (OA) in India from 1990 to 2019. DESIGN: Data from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used. The burden of OA -knee OA, hip OA, hand OA, and other OA- was estimated for India and its states from 1990 to 2019 through a systematic analysis of prevalence, incidence, years lived with disability (YLD), and disability-adjusted life years (DALY) using methods reported in GBD 2019 study. RESULT: Around 23.46 million individuals in India had OA in 1990; this increased to 62.35 million in 2019. The age-standardised prevalence of OA increased from 4,895 (95% uncertainty interval (UI):4,420-5,447) in 1990-5313 (95%UI:4,799-5,898) in 2019, per 100,000 persons. Similarly, DALYs due to OA increased from 0.79 million (95%UI:0.40-1.55) to 2.12 million (95%UI:1.07-4.23); while age-standardised DALYs increased from 164 (95%UI:83-325) to 180 (95%UI:91-361) per 100,000 persons from 1990 to 2019. OA was the 20th most common cause of YLDs in India in 2019, accounting for 1.48% (95%UI:0.88-2.78) of all YLDs; increasing from 23rd most common cause in 1990 (1.25%(95%UI:0.74-2.34)). Knee OA was the most common form of OA, followed by hand OA. The prevalence, incidence, and DALYs for OA and knee OA were consistently higher in females than males. CONCLUSION: The burden and impact of OA in India are substantial and is increasing. Adopting suitable control and preventive community measures to reduce modifiable risk factors (obesity, injuries, occupational stress) are needed to reduce the current and future burden of OA in India.

Carrier-Envelope Phase-Dependent Strong-Field Excitation.

We present a joint experimental-theoretical study on the effect of the carrier-envelope phase (CEP) of a few-cycle pulse on the atomic excitation process. We focus on the excitation rates of argon at intensities in the transition between the multiphoton and tunneling regimes. Through numerical simulations, we show that the resulting bound-state population is highly sensitive to both the intensity and the CEP. The experimental data clearly agree with the theoretical prediction, and the results encourage the use of precisely tailored laser fields to coherently control the strong-field excitation process. We find a markedly different behavior for the CEP-dependent bound-state population at low and high intensities with a clear boundary, which we attribute to the transition from the multiphoton to the tunneling regime.

Long-term cost-effectiveness of Dexcom G6 real-time continuous glucose monitoring system in people with type 1 diabetes in Australia.

INTRODUCTION: Real-time continuous glucose monitoring (rt-CGM) allows patients with diabetes to adjust insulin dosing, potentially improving glucose control. This study aimed to compare the long-term cost-effectiveness of the Dexcom G6 rt-CGM device versus self-monitoring of blood glucose (SMBG) and flash glucose monitoring (FGM) in Australia in people with type 1 diabetes (T1D). METHODS: Long-term costs and clinical outcomes were estimated using the CORE Diabetes Model. Clinical input data for the analysis of rt-CGM versus SMBG and FGM were sourced from the DIAMOND study and a network meta-analysis, respectively. Rt-CGM and FGM were associated with quality of life (QoL) benefits due to reduced fear of hypoglycaemia (FoH) and fingerstick testing. Analyses were performed over a lifetime time horizon from an Australian healthcare payer perspective, including direct costs from published data. Future costs and clinical outcomes were discounted at 5% per annum. RESULTS: Rt-CGM was associated with an increased quality-adjusted life expectancy of 1.199 quality-adjusted life years (QALYs), increased mean total lifetime costs of AUD 21,596 and an incremental cost-effectiveness ratio (ICER) of AUD 18,020 per QALY gained compared with SMBG. Compared with FGM, rt-CGM was associated with an increased quality-adjusted life expectancy of 0.569 QALYs, increased mean total lifetime costs of AUD 11,064 and an ICER of AUD 19,455 per QALY gained. Key drivers of outcomes included HbA1c benefits and QoL benefits associated with reduced FoH and fingerstick testing. CONCLUSIONS: Due to improved clinical outcomes and QoL gains rt-CGM is highly cost-effective compared with SMBG and FGM in people with T1D in Australia.

Development and validation of the risk engine for an Australian Health Economics Model of Osteoporosis.

The Australian Health Economics Model of Osteoporosis (AusHEMO) has shown good face, internal and cross validities, and can be used to assist healthcare decision-making in Australia. PURPOSE: This study aimed to document and validate the risk engine of the Australian Health Economics Model of Osteoporosis (AusHEMO). METHODS: AusHEMO is a state-transition microsimulation model. The fracture risks were simulated using fracture incidence rates from the Dubbo Osteoporosis Epidemiology Study. The AusHEMO was validated regarding its face, internal and cross validities. Goodness-of-fit analysis was conducted and Lin's coefficient of agreement and mean absolute difference with 95% limits of agreement were reported. RESULTS: The development of AusHEMO followed general and osteoporosis-specific health economics guidelines. AusHEMO showed good face validity regarding the model's structure, evidence, problem formulation and results. In addition, the model has been proven good internal and cross validities in goodness-of-fit test. Lin's coefficient was 0.99, 1 and 0.94 for validation against the fracture incidence rates, Australian life expectancies and residual lifetime fracture risks, respectively. CONCLUSIONS: In summary, the development of the risk engine of AusHEMO followed the best practice for osteoporosis disease modelling and the model has been shown to have good face, internal and cross validities. The AusHEMO can be confidently used to predict long-term fracture-related outcomes and health economic evaluations when costs data are included. Health policy-makers in Australia can use the AusHEMO to select which osteoporosis interventions such as medications and public health interventions represent good value for money.

Strategies to minimize intraoperative blood loss during major surgery.

BACKGROUND: Reducing operative blood loss improves patient outcomes and reduces healthcare costs. The aim of this article was to review current surgical, anaesthetic and haemostatic intraoperative blood conservation strategies. METHODS: This narrative review was based on a literature search of relevant databases up to 31 July 2019 for publications relevant to reducing blood loss in the surgical patient. RESULTS: Interventions can begin early in the preoperative phase through identification of patients at high risk of bleeding. Directly acting anticoagulants can be stopped 48 h before most surgery in the presence of normal renal function. Aspirin can be continued for most procedures. Intraoperative cell salvage is recommended when anticipated blood loss is greater than 500 ml and this can be continued after surgery in certain situations. Tranexamic acid is safe, cheap and effective, and routine administration is recommended when anticipated blood loss is high. However, the optimal dose, timing and route of administration remain unclear. The use of topical agents, tourniquet and drains remains at the discretion of the surgeon. Anaesthetic techniques include correct patient positioning, avoidance of hypothermia and regional anaesthesia. Permissive hypotension may be beneficial in selected patients. Promising haemostatic strategies include use of pharmacological agents such as desmopressin, prothrombin complex concentrate and fibrinogen concentrate, and use of viscoelastic haemostatic assays. CONCLUSION: Reducing perioperative blood loss requires a multimodal and multidisciplinary approach. Although high-quality evidence exists in certain areas, the overall evidence base for reducing intraoperative blood loss remains limited.

ANTECEDENTES: La reducción de la pérdida hemática operatoria mejora los resultados y reduce los costes sanitarios. El objetivo de este artículo es revisar las estrategias actuales intraoperatorias quirúrgicas, anestésicas y hemostáticas de ahorro de sangre. MÉTODOS: Revisión descriptiva basada en publicaciones destacadas que analizaban la forma de reducir la pérdida de sangre en el paciente quirúrgico, seleccionadas a partir de una búsqueda bibliográfica en bases de datos relevantes hasta el 31 de julio de 2019. RESULTADOS: Las intervenciones se pueden iniciar precozmente en el período preoperatorio a través de la identificación de pacientes con elevado riesgo de hemorragia. Se pueden suspender los anticoagulantes de acción directa 48 horas antes de la mayoría de las operaciones quirúrgicas si la función renal es normal. Se puede continuar la administración de aspirina en la mayoría de las intervenciones. En el período intraoperatorio, se recomienda el uso de rescate celular cuando la pérdida de sangre prevista es superior a 500 ml y este método se puede continuar después de la operación en determinadas situaciones. La administración de ácido tranexámico es segura, barata y eficaz y se recomienda de forma rutinaria cuando la pérdida hemática prevista es alta. Sin embargo, la dosis óptima, el momento y la vía de administración no están bien establecidos. El uso de agentes tópicos, torniquetes y drenajes queda a discreción del cirujano. Las técnicas anestésicas incluyen la correcta posición del paciente, así como evitar la hipotermia y la anestesia regional. La hipotensión controlada puede ser beneficiosa en casos seleccionados. Las estrategias hemostáticas innovadoras incluyen agentes farmacológicos como la desmopresina, los concentrados del complejo de protrombina y concentrados de fibrinógeno, y el uso de hemostáticos viscoelásticos, pero se requiere disponer de evidencia sobre su beneficio. CONCLUSIÓN: La reducción de la pérdida hemática perioperatoria requiere un enfoque multimodal y multidisciplinario. Aunque existe evidencia de alta calidad en ciertas áreas, la evidencia general para reducir la pérdida hemática intraoperatoria sigue siendo limitada.

Peri-operative administration of tranexamic acid in lower limb arthroplasty: a multicentre, prospective cohort study.

In the UK, tranexamic acid is recommended for all surgical procedures where expected blood loss exceeds 500 ml. However, the optimal dose, route and timing of administration are not known. This study aimed to evaluate current practice of peri-operative tranexamic acid administration. Patients undergoing primary total hip arthroplasty, total knee arthroplasty or unicompartmental knee arthroplasty during a 2-week period were eligible for inclusion in this prospective study. The primary outcome was the proportion of patients receiving tranexamic acid in the peri-operative period. Secondary outcomes included: dose, route and timing of tranexamic acid administration; prevalence of pre- and postoperative anaemia; estimated blood loss; and red blood cell transfusion rates. In total, we recruited 1701 patients from 56 NHS hospitals. Out of these, 1523 (89.5%) patients received tranexamic acid and of those, 1052 (69.1%) received a single dose of 1000 mg intravenously either pre- or intra-operatively. Out of the 1701 patients, 571 (33.6%) and 1386 (81.5%) patients were anaemic (haemoglobin < 130 g.l-1 ) in the pre- and postoperative period, respectively. Mean (SD) estimated blood loss for all included patients was 792 (453) ml and 54 patients (3.1%) received a red blood cell transfusion postoperatively. The transfusion rate for patients with pre-operative anaemia was 6.5%, compared with 1.5% in patients without anaemia. Current standard of care in the UK is to administer 1000 mg of tranexamic intravenously either pre- or intra-operatively. Approximately one-third of patients present for surgery with anaemia, although the overall red blood cell transfusion rate is low. These data provide useful comparators when assessing the efficacy of tranexamic acid and other patient blood management interventions in future studies.

The role of intra-operative cell salvage in patient blood management for revision hip arthroplasty: a prospective cohort study.

Cell salvage is an important component of blood management in patients undergoing revision hip arthroplasty surgery. However concerns regarding efficacy and patient selection remain. The aims of this study were to describe intra-operative blood loss, cell salvage re-infusion volumes and red blood cell transfusion rates for revision hip procedures and to identify factors associated with the ability to salvage sufficient blood intra-operatively to permit processing and re-infusion. Data were collected from a prospective cohort of 664 consecutive patients undergoing revision hip surgery at a single tertiary centre from 31 March 2015 to 1 April 2018. Indications for revision surgery were aseptic (n = 393 (59%)) fracture (n = 160 (24%)) and infection (n = 111 (17%)). Salvaged blood was processed and re-infused when blood loss exceeded 500 ml. Mean (SD) intra-operative blood loss was 1038 (778) ml across all procedures. Salvaged blood was re-infused in 505 of 664 (76%) patients. Mean (SD) re-infusion volume was 253 (169) ml. In total, 246 of 664 (37%) patients received an allogeneic red blood cell transfusion within 72 h of surgery. Patients undergoing femoral component revision only (OR (95%CI) 0.41 (0.23-0.73)) or acetabular component revision only (0.53 (0.32-0.87)) were less likely to generate sufficient blood salvage volume for re-infusion compared with revision of both components. Compared with aseptic indications, patients undergoing revision surgery for infection (1.87 (1.04-3.36)) or fracture (4.43 (2.30-8.55)) were more likely to generate sufficient blood salvage volume for re-infusion. Our data suggest that cell salvage is efficacious in this population. Cases where the indication is infection or fracture and where both femoral and acetabular components are to be revised should be prioritised.

Osteoarthritis.

Osteoarthritis is a major source of pain, disability, and socioeconomic cost worldwide. The epidemiology of the disorder is complex and multifactorial, with genetic, biological, and biomechanical components. Aetiological factors are also joint specific. Joint replacement is an effective treatment for symptomatic end-stage disease, although functional outcomes can be poor and the lifespan of prostheses is limited. Consequently, the focus is shifting to disease prevention and the treatment of early osteoarthritis. This task is challenging since conventional imaging techniques can detect only quite advanced disease and the relation between pain and structural degeneration is not close. Nevertheless, advances in both imaging and biochemical markers offer potential for diagnosis and as outcome measures for new treatments. Joint-preserving interventions under development include lifestyle modification and pharmaceutical and surgical modalities. Some show potential, but at present few have proven ability to arrest or delay disease progression.

Screening for osteoporosis in Chinese post-menopausal women: a health economic modelling study.

UNLABELLED: Screening and appropriate treatment for osteoporosis has been proven to be cost-effective in many populations; however, it is not clear in the Chinese population. Simulations using a validated health economics model suggest that screening for osteoporosis in Chinese women is cost-effective and may even be cost-saving in Chinese post-menopausal women. INTRODUCTION: This study aimed at determining the cost-effectiveness of osteoporosis screening strategies in post-menopausal Chinese women. METHODS: A validated state-transition microsimulation model with a lifetime horizon was used to evaluate the cost-effectiveness of different screening strategies with treatment of alendronate compared with current osteoporosis management in China. Osteoporosis screening strategies assessed were (1) universal screening with dual-energy X-ray absorptiometry (DXA) alone; (2) Osteoporosis Self-Assessment Tool for Asians (OSTA) + DXA; and (3) quantitative ultrasound (QUS) + DXA with rescreening at 2, 5 or 10-year intervals for patients screened negative by DXA. The study was performed from the Chinese healthcare payer's perspective. All model inputs were retrieved from publically available literature. Uncertainties were addressed by one-way and probabilistic sensitivity analysis. RESULTS: Screening strategies all improved clinical outcomes at increased costs, and each were cost-effective compared with no screening in women aged 55 years given the Chinese willingness-to-pay threshold of USD 20,000 per quality-adjusted life year (QALY) gained. Pre-screening with QUS and subsequent DXA screening if the QUS T-score ≤ -0.5 with a 2-year rescreening interval was the most cost-effective strategy with the highest probability of being cost-effective across all non-dominated strategies. Screening strategies were cost-saving if screenings were initiated from age 65 years. One-way sensitivity analyses indicated that the results were robust. CONCLUSIONS: Pre-screening with QUS with subsequent DXA screening if the QUS T-score ≤ -0.5 with a 2-year rescreening interval in the Chinese women starting at age 55 is the most cost-effective. In addition, screening and treatment strategies are cost-saving if the screening initiation age is greater than 65 years.

Australian insurance costs of jockeys injured in a race-day fall.

BACKGROUND: The risk of falls and injuries in horseracing varies with sex and experience of the jockey. AIMS: To determine whether the incidence and costs of insurance claims also differ by such factors. METHODS: A retrospective analysis of compensation claims by flat racing and jumps jockeys injured in a race-day fall in Australia between 2002 and 2009. Claim incidence, costs, absentee days and location, cause and type of injury sustained were described, stratified by jockey sex, age and experience. RESULTS: The incidence of claims by flat and jumps racing was 0.6 and 6.5 per 1000 rides, respectively. The mean cost of a claim was 43374 Australian dollars (AUD) (SD 249612) in flat racing and AUD 52589 (SD 157808) in jumps racing. The incidence of claims was greater for experienced flat racing jockeys than apprentices but mean costs were higher for apprentices. After adjustment for experience, there were no sex differences in the average cost or incidence of flat racing jockeys' claims. In general, the fall incidence declined, but the claim incidence and median cost of a claim increased, with age. On average, jockeys were absent from work for 9 weeks following a substantive injury. Limb fractures (33%), muscular or soft tissue injuries (28%) and contusions (17%) were the most commonly reported injuries. CONCLUSIONS: The economic costs of jockey injuries sustained in race-day falls are considerable. Identification of differences in incidence and costs of insurance claims between jockey characteristics will assist decision makers in the development and assessment of targeted safety strategies.

Screening for and treatment of osteoporosis: construction and validation of a state-transition microsimulation cost-effectiveness model.

UNLABELLED: This study aimed to document and validate a new cost-effectiveness model of osteoporosis screening and treatment strategies. The state-transition microsimulation model demonstrates strong internal and external validity. It is an important tool for researchers and policy makers to test the cost-effectiveness of osteoporosis screening and treatment strategies. INTRODUCTION: The objective of this study was to document and validate a new cost-effectiveness model of screening for and treatment of osteoporosis. METHODS: A state-transition microsimulation model using a lifetime horizon was constructed with seven Markov states (no history of fractures, hip fracture, vertebral fracture, wrist fracture, other fracture, postfracture state, and death) describing the most important clinical outcomes of osteoporotic fractures. Tracker variables were used to record patients' history, such as fracture events, duration of treatment, and time since last screening. The model was validated for Chinese postmenopausal women receiving screening and treatment versus no screening. Goodness-of-fit analyses were performed for internal and external validation. External validity was tested by comparing life expectancy, osteoporosis prevalence rate, and lifetime and 10-year fracture risks with published data not used in the model. RESULTS: The model represents major clinical facets of osteoporosis-related conditions. Age-specific hip, vertebral, and wrist fracture incidence rates were accurately reproduced (the regression line slope was 0.996, R(2) = 0.99). The changes in costs, effectiveness, and cost-effectiveness were consistent with changes in both one-way and probabilistic sensitivity analysis. The model predicted life expectancy and 10-year any major osteoporotic fracture risk at the age of 65 of 19.01 years and 13.7%, respectively. The lifetime hip, clinical vertebral, and wrist fracture risks at age 50 were 7.9, 29.8, and 18.7% respectively, all consistent with reported data. CONCLUSIONS: Our model demonstrated good internal and external validity, ensuring it can be confidently applied in economic evaluations of osteoporosis screening and treatment strategies.

Projection of osteoporosis-related fractures and costs in China: 2010-2050.

UNLABELLED: A state-transition microsimulation model was used to project the substantial economic burden to the Chinese healthcare system of osteoporosis-related fractures. Annual number and costs of osteoporosis-related fractures were estimated to double by 2035 and will increase to 5.99 (95 % CI 5.44, 6.55) million fractures costing $25.43 (95 % CI 23.92, 26.95) billion by 2050. Consequently, cost-effective intervention policies must urgently be identified in an attempt to minimize the impact of fractures. INTRODUCTION: The aim of the study was to project the osteoporosis-related fractures and costs for the Chinese population aged ≥50 years from 2010 to 2050. METHODS: A state-transition microsimulation model was used to simulate the annual incident fractures and costs. The simulation was performed with a 1-year cycle length and from the Chinese healthcare system perspective. Incident fractures and annual costs were estimated from 100 unique patient populations for year 2010, by multiplying the age- and sex-specific annual fracture risks and costs of fracture by the corresponding population totals in each of the 100 categories. Projections for 2011-2050 were performed by multiplying the 2010 risks and costs of fracture by the respective annual population estimates. Costs were presented in 2013 US dollars. RESULTS: Approximately 2.33 (95 % CI 2.08, 2.58) million osteoporotic fractures were estimated to occur in 2010, costing $9.45 (95 % CI 8.78, 10.11) billion. Females sustained approximately three times more fractures than males, accounting for 76 % of the total costs from 1.85 (95 % CI 1.68, 2.01) million fractures. The annual number and costs of osteoporosis-related fractures were estimated to double by 2035 and will increase to 5.99 (95 % CI 5.44, 6.55) million fractures costing $25.43 (95 % CI 23.92, 26.95) billion by 2050. CONCLUSIONS: Our study demonstrated that osteoporosis-related fractures cause a substantial economic burden which will markedly increase over the coming decades. Consequently, healthcare resource planning must consider these increasing costs, and cost-effective screening and intervention policies must urgently be identified in an attempt to minimize the impact of fractures on the health of the burgeoning population as well as the healthcare budget.

Subclinical deformities of the hip are significant predictors of radiographic osteoarthritis and joint replacement in women. A 20 year longitudinal cohort study.

OBJECTIVE: Femoroacetabular Impingement (FAI) and Acetabular Dysplasia are common deformities, which have been implicated as a major cause of hip osteoarthritis (OA). We examined whether these subtle deformities of the hip are associated with the development of radiographic OA and total hip replacement (THR) in women. DESIGN: A population-based, longitudinal cohort of 1003 women underwent pelvis radiographs at years 2 and 20. Alpha Angle, Triangular Index Height, Lateral Centre Edge (LCE) angle and Extrusion Index were measured. An alpha angle of greater than 65° was defined as Cam-type FAI. Radiographic OA and the presence of a THR were then determined at 20 years. RESULTS: Cam-type FAI was significantly associated with the development of radiographic OA. Each degree increase in alpha angle above 65° was associated with an increase in risk of 5% (Odds Ratio (OR) 1.05 [95% confidence interval (CI) 1.01-1.09]) for radiographic OA and 4% (OR 1.04 [95% CI 1.00-1.08]) for THR. For Acetabular Dysplasia, each degree reduction in LCE angle below 28° was associated with an increase in risk of 13.0% (OR 0.87 [95% CI 0.78-0.96]) for radiographic OA and 18% (OR 0.82 [95% CI 0.75-0.89]) for THR. CONCLUSIONS: This study demonstrates that Cam-type FAI and mild Acetabular Dysplasia are predictive of subsequent OA and THR in a large female population cohort. These are independent of age, BMI and joint space and significantly improve current predictive models of hip OA development.

A systematic review of models used in cost-effectiveness analyses of preventing osteoporotic fractures.

This review was aimed at the evolution of health economic models used in evaluations of clinical approaches aimed at preventing osteoporotic fractures. Models have improved, with medical continuance becoming increasingly recognized as a contributor to health and economic outcomes, as well as advancements in epidemiological data. Model-based health economic evaluation studies are increasingly used to investigate the cost-effectiveness of osteoporotic fracture preventions and treatments. The objective of this study was to carry out a systematic review of the evolution of health economic models used in the evaluation of osteoporotic fracture preventions. Electronic searches within MEDLINE and EMBASE were carried out using a predefined search strategy. Inclusion and exclusion criteria were used to select relevant studies. References listed of included studies were searched to identify any potential study that was not captured in our electronic search. Data on country, interventions, type of fracture prevention, evaluation perspective, type of model, time horizon, fracture sites, expressed costs, types of costs included, and effectiveness measurement were extracted. Seventy-four models were described in 104 publications, of which 69% were European. Earlier models focused mainly on hip, vertebral, and wrist fracture, but later models included multiple fracture sites (humerus, pelvis, tibia, and other fractures). Modeling techniques have evolved from simple decision trees, through deterministic Markov processes to individual patient simulation models accounting for uncertainty in multiple parameters. Treatment continuance has been increasingly taken into account in the models in the last decade. Models have evolved in their complexity and emphasis, with medical continuance becoming increasingly recognized as a contributor to health and economic outcomes. This evolution may be driven in part by the desire to capture all the important differentiating characteristics of medications under scrutiny, as well as the advancement in epidemiological data relevant to osteoporosis fractures.

A systematic review and meta-analysis of utility-based quality of life for osteoporosis-related conditions.

This study aimed to statistically combine multiple health state utility values (HSUVs) reported in the literature for patients with osteoporosis and osteoporotic fractures. Fracture events were associated with decrements in HSUVs which differed between fracture sites. We have provided summary values for use in future health economics analyses in osteoporosis. Osteoporotic fractures have high financial and health burden. Economic evaluations on osteoporotic fracture prevention have been frequently performed in past decades. One of the challenges in the economic evaluations was to identify consistent health state utility values (HSUVs) to use for osteoporotic fracture-related conditions. The objective of this study was to determine summary measures of multiple HSUVs reported in the literature for patients with osteoporosis and osteoporotic fractures. We performed a systematic review, meta-analysis and meta-regression of published literature that reported HSUVs for osteoporotic fracture-related conditions. There were 62 studies representing 142,477 patients included. In total, 362 HSUVs were identified: 106 for pre-fracture; 89 for post-hip fracture; 130 for post-vertebral fracture and 37 for post-wrist fracture. The pooled HSUVs, using a random-effects model were 0.76 (95% CI 0.75, 0.77, I (2) = 0.99) for pre-fracture; 0.57 (95% CI 0.52, 0.63, I (2) =1) for post-hip fracture; 0.59 (95% CI 0.55, 0.62, I (2) = 0.99) for post-vertebral facture and 0.72 (95% CI 0.67, 0.78, I (2) = 1) for post-wrist fracture. Heterogeneities were addressed through meta-regression. HSUVs immediately following hip, vertebral and wrist fractures were 0.31, 0.44 and 0.61, respectively. Patients' HSUVs improved over time following fracture events: HSUVs for the first year after hip, vertebral and wrist fractures were 0.59, 0.55 and 0.78, respectively; and 0.66, 0.66 and 0.81 for subsequent years. Fractures were associated with significant decrements in HSUVs. This study provides a standard set of HSUVs that can be used in health economic assessments in osteoporosis.

Cost-effectiveness of the Concord Minimal Trauma Fracture Liaison service, a prospective, controlled fracture prevention study.

UNLABELLED: We evaluated the cost-effectiveness of a fracture liaison service prospectively designed to have a parallel control group treated by standard care. The clinical effectiveness of this service was associated with an incremental cost-effectiveness ratio versus standard care of Australian dollars (AUD) 17,291 per quality-adjusted life year (QALY) gained. INTRODUCTION: Osteoporotic fractures are a major burden for national health services. The risk of re-fracture following an osteoporotic fracture is particularly high. In a study unique in prospectively having a control group treated by standard care, we recently demonstrated that a Minimal Trauma Fracture Liaison (MTFL) service significantly reduces the risk of re-fracture by 80%. Since the service involves greater use of resources, we have now evaluated whether it is cost-effective. METHODS: A Markov model was developed that incorporated fracture probabilities and resource utilization data (expressed in AUD) obtained directly from the 4-year MTFL service clinical study. Resource utilization, local cost and mortality data and fracture-related health utility data were used to calculate QALYs with the MTFL service and standard care. Main outcome measures were: additional costs of the MTFL service over standard care, the financial savings achieved through reduced fractures and changes in QALYs associated with reduced fractures calculated over a 10-year simulation period. Costs and QALYs were discounted at 5% annually. Sensitivity analyses quantified the effects of different assumptions of effectiveness and resource utilization associated with the MTFL service. RESULTS: The MTFL service improved QALYs by 0.089 years and led to increased costs of AUD 1,486 per patient versus standard care over the 10-year simulation period. The incremental cost-effectiveness ratio versus standard care was AUD 17,291 per QALY gained. Results were robust under all plausible assumptions. CONCLUSIONS: The MTFL service is a cost-effective intervention to reduce recurrent osteoporotic fractures.

Extreme ultraviolet interferometer using high-order harmonic generation from successive sources.

We present a new interferometer technique whereby multiple extreme ultraviolet light pulses are generated at different positions within a single laser focus (i.e., from successive sources) with a highly controllable time delay. The interferometer technique is tested with two generating media to create two extreme ultraviolet light pulses with a time delay between them. The delay is found to be a consequence of the Gouy phase shift. Ultimately the apparatus is capable of accessing unprecedented time scales by allowing stable and repeatable delays as small as 100 zs.