Radiofrequency echographic multi spectrometry (REMS) in the diagnosis and management of osteoporosis: state of the art.

Radiofrequency Echographic Multi Spectrometry (REMS) is a radiation-free, portable technology, which can be used for the assessment and monitoring of osteoporosis at the lumbar spine and femoral neck and may facilitate wider access to axial BMD measurement compared with standard dual-energy x-ray absorptiometry (DXA).There is a growing literature demonstrating a strong correlation between DXA and REMS measures of BMD and further work supporting 5-year prediction of fracture using the REMS Fragility Score, which provides a measure of bone quality (in addition to the quantitative measure of BMD).The non-ionising radiation emitted by REMS allows it to be used in previously underserved populations including pregnant women and children and may facilitate more frequent measurement of BMD.The portability of the device means that it can be deployed to measure BMD for frail patients at the bedside (avoiding the complications in transfer and positioning which can occur with DXA), in primary care, the emergency department, low-resource settings and even at home.The current evidence base supports the technology as a useful tool in the management of osteoporosis as an alternative to DXA.

The practicality of using bone impact microindentation in a population-based study of women: A Geelong-Osteoporosis Study.

Impact microindentation (IMI) is a minimally invasive technique that allows the assessment of bone material strength index (BMSi) in vivo, by measuring the depth of a micron-sized, spherical tip into cortical bone that is then indexed to the depth of the tip into a reference material. In this study, we aimed to assess the practicality of its application in 99 women aged 42-84 yr from the Geelong Osteoporosis Study. Impact microindentation was performed in the mid-shaft of the right tibia using the OsteoProbe. Immediately following measurement, each participant was requested to rate on a Visual Analogue Scale [0-10] the level of discomfort anticipated and experienced, any initial reluctance towards the measurement and whether they were willing to repeat the measurement. Of 99 potential participants who attended this assessment phase, 55 underwent IMI measurement. Reasons for non-measurement in 44 women were existing skin conditions (n = 8, 18.2 %) and excessive soft tissue around mid-tibial region (n = 32, 72.2 %). An additional four (9.1 %) participants did not provide any reasons for declining. For 55 participants who had underwent IMI, the expectation for pain when briefed about the procedure was low (2.28 ± 2.39), as was pain experienced during the measurement (0.72 ± 1.58). Participants were not reluctant to undergo the measurement (0.83 ± 1.67), and all indicated a willingness to repeat the measurement. Results of this study showed that the IMI technique is well tolerated and accepted by women participating in the Geelong Osteoporosis Study, suggesting that the technique shows promise in a research or clinical setting.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

For older individuals there is greater variance in low mean Bone Material Strength Index values obtained with the OsteoProbe.

Purpose: Bone Material Strength Index (BMSi) quantifies the resistance of bone to a specified force in vivo at the mid tibia using impact microindentation (IMI). Anecdotal evidence suggests that within-participant variance in BMSi may be associated with the individual's mean BMSi. This study aimed to investigate associations between mean and variance of IMI measures in a population-based study. Methods: Participants were men (n = 420) and women (n = 55) from the Geelong Osteoporosis Study who underwent BMSi measurement using the OsteoProbe at recent follow-up phases (men 2016-2022; women 2022-2023). Median age was 63.7 yr (IQR 53.0-71.8). BMSi standard deviation was skewed and therefore natural log transformed (referred to as ln-SD). Linear regression models were developed with ln-SD as the dependent variable and mean BMSi as the independent variable adjusting for sex, age, height and weight. Results: In unadjusted models, greater BMSi was associated with lower ln-SD (ß = -1.58, p = 0.042). This association was sustained after adjustment (p = 0.013), and an interaction between BMSi and age was observed (p = 0.004). In those aged 63.7 yr and over (median age), mean BMSi was inversely associated with ln-SD (ß = -3.22, p = 0.002). Sex was not identified as an effect modifier. In younger participants, no BMSi*ln-SD association was observed. Conclusion: In older men and women, there was greater variance in low BMSi values. This suggests that standard deviation of the BMSi measure may provide additional information in the assessment of bone health and is worthy of further investigation. Mini abstract: In older men and women, greater variance is observed when BMSi values are low, reflecting potential variation in the bone surface.

Responsabilidad personal con la salud en Cuba: mapeo y juego de actores para su fomento

Fundamento: para que cualquier meta de salud sea alcanzada es necesario involucrar a múltiples actores sociales cuya participación intersectorial condiciona la materialización de las políticas públicas sanitarias. Objetivo: aportar al sector salud herramientas de decisión suficientes para que ponga en práctica una política de alianzas intersectoriales para el fomento de la responsabilidad personal con la salud de la población cubana en un horizonte temporal hasta el 2030. Métodos: estudio de prospectiva estratégica desde enero 2018 a marzo 2020. Se empleó el método Matriz de Alianzas y Conflictos: tácticas, objetivos, recomendaciones, con la participación de 12 expertos. Resultados: se identificaron 25 actores que conformaron 10 grupos. El actor con mayor poder son los ciudadanos; mientras, el objetivo estratégico con mayor movilización es trascender el paradigma paternalista de la práctica salubrista en Cuba. Se demostró la posibilidad de trabajar de forma intersectorial para desarrollar alianzas duraderas entre todos los actores involucrados y que de existir contradicciones estas no tendrán carácter antagónico. Al contrario, pueden comportarse como elementos generadores de soluciones innovadoras para el desarrollo futuro. Conclusiones: el mapeo y análisis del juego de actores permitió evidenciar las posibilidades de alianzas entre los actores sociales y el alineamiento estratégico de estos con los objetivos estratégicos formulados. Se recomienda monitorear la evolución de esta situación durante el horizonte temporal previsto con el objetivo de reevaluar el sistema y reducir la incertidumbre ante un entorno cambiante.

Foundation: for any health goal to be achieved, it is necessary to involve multiple social actors whose intersectoral participation conditions the materialization of public health policies. Objective: provide the health sector with sufficient decision tools to implement a policy of intersectoral alliances to promote personal responsibility with the health of the Cuban population in a time horizon until 2030. Methods: strategic prospective study since January 2018 to March 2020. The Matrix of Alliances and Conflicts method was used: tactics, objectives, recommendations, with the participation of 12 experts. Results: 25 actors who formed 10 groups were identified. The actor with the greatest power are the citizens; Meanwhile, the strategic objective with the greatest mobilization is to transcend the paternalistic paradigm of health care practice in Cuba. The possibility of working intersectorally to develop lasting alliances between all the actors involved was demonstrated and that if there are contradictions these will not have an antagonistic nature. On the contrary, they can behave as elements that generate innovative solutions for future development. Conclusions: the mapping and analysis of the set of actors made it possible to demonstrate the possibilities of alliances between social actors and their strategic alignment with the formulated strategic objectives. It is recommended to monitor the evolution of this situation during the planned time horizon with the aim of reevaluating the system and reducing uncertainty in the face of a changing environment.

Differences of corruption types in selected Western and central-eastern health systems during the COVID-19 pandemic: a rapid review.

Objectives: To identify, describe, and classify the cases of health corruption present in selected Western [the Netherlands and the United Kingdom (UK)] and Central-Eastern European (Poland and Slovakia) countries during the COVID-19 pandemic. Methods: A rapid review of the literature was conducted, evaluating data from 11 March 2020 to 15 April 2021. Information sources included MEDLINE via WoS, IBSS via ProQuest, Scopus, and gray literature. Results: Thirteen cases were identified across the four countries. The primary type of health corruption in Western European countries was procurement corruption, while misuse of (high) level positions was the most prevalent in Central-Eastern European countries. Actors from central governments were most involved in cases. The rule of law and anti-corruption watchdogs reported most cases in the United Kingdom and the Netherlands, while the media reported cases in Poland and Slovakia. Conclusion: The differences in types of corruption in WE and CEE countries emphasize the need to contextualize the approach to tackle corruption. Thus, further research in preventing and tackling corruption is a vital and necessary undertaking despite the inherent of conducting health corruption research.

Mean Bone Material Strength Index Values for Women are Lower Than Those for Men: Data from a Single Geographical Location.

Bone material strength index (BMSi) values are obtained using impact microindentation, which assesses the ability of bone to resist indentation. Differences in BMSi between men and women are unclear, and to date, BMSi sex differences have not been compared for individuals from the same population. Therefore, we compared BMSi values for men and women drawn from the same geographical location in Australia. Participants (n = 220) were from the Geelong Osteoporosis Study. BMSi was measured, following international published guidelines, using an OsteoProbe for participants at recent follow-up phases (women 2022-2023 and men 2016-2022). Women (n = 55) were age matched to men (n = 165) in a 1:3 ratio. A two-sample t test was used to determine the intergroup difference in mean BMSi. Linear regression was also performed, adjusting for weight and height. Median (IQR) ages for men and women were 67.0 (61.7-71.5) and 67.4 (62.0-71.2) years (p = 0.998). Men were heavier (81.0 ± 10.9 vs 71.0 ± 13.9 kg, p < 0.001) and taller (173.9 ± 6.4 vs 161.5 ± 7.5 cm, p < 0.001) than women. Mean (± SD) BMSi for women (75.7 ± 7.4) was lower than for men (82.8 ± 6.8) (p < 0.001). The difference persisted after adjustment for weight and height (mean ± SE: 76.5 ± 1.1 vs 82.5 ± 0.6, p < 0.001). Given the higher fracture risk observed for women, the higher mean BMSi values in men are consistent with cross sectional data suggesting this measure may be useful in fracture prediction.

Associations Between Aldosterone-Renin-Ratio and Bone Parameters Derived from Peripheral Quantitative Computed Tomography and Impact Microindentation in Men.

Components of the renin-angiotensin-aldosterone system (RAAS) are present on bone cells. One measure of RAAS activity, the aldosterone-renin-ratio (ARR), is used to screen for primary aldosteronism. Associations between ARR and bone mineral density are conflicting. This study investigated associations between ARR and peripheral quantitative computed tomography (pQCT) and impact microindentation (IMI). Male participants (n = 431) were from the Geelong Osteoporosis Study. "Likely" primary aldosteronism was defined as ARR ≥ 70 pmol/mIU. Another group, "possible" primary aldosteronism, was defined as either ARR ≥ 70 pmol/mIU or taking a medication that affects the RAAS, but not a beta blocker, and renin < 15 mU/L. Using pQCT, images at 4% and 66% of radial (n = 365) and tibial (n = 356) length were obtained. Using IMI measurements, bone material strength index (BMSi; n = 332) was determined. Associations between ARR or likely/possible primary aldosteronism and IMI or pQCT-derived bone parameters were tested using median regression. ARR and aldosterone values were not associated with any of the pQCT-derived bone variables in either unadjusted or adjusted analyses. Men with likely primary aldosteronism (n = 16), had lower adjusted total bone area (radial 66% site, - 12.5%). No associations were observed for men with possible primary aldosteronism (unadjusted or adjusted). No associations with BMSi were observed (p > 0.05). There were no associations between ARR or aldosterone and pQCT-derived bone parameters. Men with likely primary aldosteronism had lower bone area, suggesting clinically high levels of ARR may have a negative impact on bone health.

Sequential management of postmenopausal health and osteoporosis: An update.

Increased life expectancy means that women are now in a hypoestrogenic state for approximately one-third of their lives. Overall health and specifically bone health during this period evolves in accordance with aging and successive exposure to various risk factors. In this review, we provide a summary of the approaches to the sequential management of osteoporosis within an integrative model of care to offer physicians a useful tool to facilitate therapeutic decision-making. Current evidence suggests that pharmacologic agents should be selected based on the risk of fractures, which does not always correlate with age. Due to their effect on bone turnover and on other hormone-regulated phenomena, such as hot flushes or breast cancer risk, we position hormone therapy and selective estrogen receptor modulators as an early postmenopause intervention for the management of postmenopausal osteoporosis. When the use of these agents is not possible, compelling evidence supports antiresorptive agents as first-line treatment of postmenopausal osteoporosis in many clinical scenarios, with digestive conditions, kidney function, readiness for compliance, or patient preferences playing a role in choosing between bisphosphonates or denosumab during this period. For patients at high risk of osteoporotic fracture, the "anabolic first" approach reduces that risk. The effect on bone health with these bone-forming agents or with denosumab should be consolidated with the subsequent use of antiresorptive agents. Regardless of the strategy, follow-up and treatment should be maintained indefinitely to help prevent fractures.

Estimation of Reference Evapotranspiration in a Semi-Arid Region of Mexico.

Reference evapotranspiration (ET0) is the first step in calculating crop irrigation demand, and numerous methods have been proposed to estimate this parameter. FAO-56 Penman-Monteith (PM) is the only standard method for defining and calculating ET0. However, it requires radiation, air temperature, atmospheric humidity, and wind speed data, limiting its application in regions where these data are unavailable; therefore, new alternatives are required. This study compared the accuracy of ET0 calculated with the Blaney-Criddle (BC) and Hargreaves-Samani (HS) methods versus PM using information from an automated weather station (AWS) and the NASA-POWER platform (NP) for different periods. The information collected corresponds to Module XII of the Lagunera Region Irrigation District 017, a semi-arid region in the North of Mexico. The HS method underestimated the reference evapotranspiration (ET0) by 5.5% compared to the PM method considering the total ET0 of the study period (26 February to 9 August 2021) and yielded the best fit in the different evaluation periods (daily, 5-day mean, and 5-day cumulative); the latter showed the best values of inferential parameters. The information about maximum and minimum temperatures from the NP platform was suitable for estimating ET0 using the HS equation. This data source is a suitable alternative, particularly in semi-arid regions with limited climatological data from weather stations.

Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

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

Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials.

OBJECTIVE: To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors. DESIGN: Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. DATA SOURCES: Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events. RESULTS: The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; ß=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision. CONCLUSIONS: The evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019128391.

Reference Intervals for Bone Impact Microindentation in Healthy Adults: A Multi-Centre International Study.

Impact microindentation (IMI) is a novel technique for assessing bone material strength index (BMSi) in vivo, by measuring the depth of a micron-sized, spherical tip into cortical bone that is then indexed to the depth of the tip into a reference material. The aim of this study was to define the reference intervals for men and women by evaluating healthy adults from the United States of America, Europe and Australia. Participants included community-based volunteers and participants drawn from clinical and population-based studies. BMSi was measured on the tibial diaphysis using an OsteoProbe in 479 healthy adults (197 male and 282 female, ages 25 to 98 years) across seven research centres, between 2011 and 2018. Associations between BMSi, age, sex and areal bone mineral density (BMD) were examined following an a posteriori method. Unitless BMSi values ranged from 48 to 101. The mean (± standard deviation) BMSi for men was 84.4 ± 6.9 and for women, 79.0 ± 9.1. Healthy reference intervals for BMSi were identified as 71.0 to 97.9 for men and 59.8 to 95.2 for women. This study provides healthy reference data that can be used to calculate T- and Z-scores for BMSi and assist in determining the utility of BMSi in fracture prediction. These data will be useful for positioning individuals within the population and for identifying those with BMSi at the extremes of the population.

Discovery of pyrazolopyrrolidinones as potent, broad-spectrum inhibitors of Leishmania infection.

Introduction: Leishmaniasis is a parasitic disease that affects more than 1 million people worldwide annually, predominantly in resource-limited settings. The challenge in compound development is to exhibit potent activity against the intracellular stage of the parasite (the stage present in the mammalian host) without harming the infected host cells. We have identified a compound series (pyrazolopyrrolidinones) active against the intracellular parasites of Leishmania donovani and L. major; the causative agents of visceral and cutaneous leishmaniasis in the Old World, respectively. Methods: In this study, we performed medicinal chemistry on a newly discovered antileishmanial chemotype, with over 100 analogs tested. Studies included assessments of antileishmanial potency, toxicity towards host cells, and in vitro ADME screening of key drug properties. Results and discussion: Members of the series showed high potency against the deadliest form, visceral leishmaniasis (approximate EC50 ≥ 0.01 µM without harming the host macrophage up to 10.0 µM). In comparison, the most efficient monotherapy treatment for visceral leishmaniasis is amphotericin B, which presents similar activity in the same assay (EC50 = 0.2 µM) while being cytotoxic to the host cell at 5.0 µM. Continued development of this compound series with the Discovery Partnership with Academia (DPAc) program at the GlaxoSmithKline Diseases of the Developing World (GSK DDW) laboratories found that the compounds passed all of GSK's criteria to be defined as a potential lead drug series for leishmaniasis. Conclusion: Here, we describe preliminary structure-activity relationships for antileishmanial pyrazolopyrrolidinones, and our progress towards the identification of candidates for future in vivo assays in models of visceral and cutaneous leishmaniasis.

Effectiveness and safety of mechanical thrombectomy for acute ischaemic stroke in Latin American countries: A systematic review.

OBJECTIVE: To describe the use, effectiveness, and safety outcomes of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) in Latin American countries. MATERIALS AND METHODS: Studies reporting MT outcomes for AIS in Latin America were identified in CINAHL, MEDLINE, Web of Science, SciELO, EMBASE, and LILACS databases. Synthesis was conducted according to effectiveness (recanalization rates) and safety measures (mortality and functional independence at 90 days). RESULTS: Seventeen studies were included, mainly from public and university hospitals. MT utilization varied from 2.6% to 50.1%, while successful recanalization ranged from 63% to 95%. Functional independence 90 days after stroke (a modified Rankin scale score of 0 to 2) was achieved in less than 40% across most studies. Mortality rates were below 30%; studies with posterior circulation strokes reported higher mortality rates. The randomized trial reported better health outcomes for functional independence among patients in the MT group (OR 2.28; 95% CI, 1.41 - 3.69), favoring MT over standard care. CONCLUSIONS: The included studies had great methodological heterogeneity due to differences in study design, the MT time window, and stroke location. The only randomized trial showed improved functional independence and lower mortality rates with MT than with standard care. The rest of the studies reported similar findings to available literature. Efforts to improve stroke care are reflected in improved patient outcomes in the region. Future studies should consider standard time window criteria and reduce the risk of bias by including representative samples and comparison groups.

Responsabilidad personal con la salud en Cuba: análisis estructural e identificación de variables estratégicas

Fundamento: el incremento de la responsabilidad personal con la salud en la población cubana es un resultado esperado del Plan de Desarrollo Socialista hasta el año 2030. Para lograr esta meta se necesita un ejercicio de planificación estratégica cuya primera etapa es el análisis estructural del problema. Objetivo: identificar las variables relacionadas con los niveles de responsabilidad personal con la salud en la población cubana, describir las relaciones entre ellas y determinar las que resultan estratégicas para fomentar el cambio. Métodos: se realizó un estudio de prospectiva estratégica para el análisis estructural de los niveles de responsabilidad personal con la salud en Cuba. Mediante muestreo no probabilístico de casos críticos se contactó con 24 expertos que elaboraron una lista de variables relacionadas con el problema de estudio y las relaciones entre ellas. Se utilizó el programa Matriz de impactos cruzados- multiplicación aplicada a una clasificación, para el análisis de los datos. Resultados: se identificaron 19 variables, de las cuales cinco son variables determinantes, seis variables estratégicas (acción intersectorial, normas sociales y marco jurídico, enfoque paternalista en salud, rendición de cuentas individual y del Estado-Gobierno, alfabetización en salud y apoyo al cuidado y bienestar), dos variables objetivo y tres variables resultados y autónomas respectivamente. Conclusiones: el incremento de los niveles de responsabilidad personal con la salud dependerá de la acción intersectorial, la actualización del marco jurídico y formas innovadoras para la rendición de cuenta de todos los actores sociales. Será necesario, además, alcanzar mejoras en la alfabetización en salud, mayor acompañamiento a los esfuerzos de los individuos para el autocuidado y el abandono de prácticas paternalistas que expropien a los ciudadanos de sus responsabilidades.

Background: the increase in personal responsibility for health in the Cuban population is an expected result of the Socialist Development Plan until the year 2030. To achieve this goal, a strategic planning exercise is needed. The structural analysis of the problem is the first stage of this exercise. Objective: to identify the variables related to the current and future levels of personal responsibility for health in the Cuban population, to describe the relationships between them and to determine those that, due to their levels of dependency and influence in the system, are strategic for promoting change. Methods: a strategic prospective study was carried out for the structural analysis of the levels of personal responsibility for health in Cuba. Through non-probabilistic sampling of critical cases, 24 experts were contacted who drew up a list of related variables to the study problem, assigned them and described the relationships between them. The cross-impact matrix-multiplication program applied to a classification was used for data analysis. Results: 19 variables were identified, of which five are determining variables, six challenge variables, two target variables and three result and autonomous variables, respectively. Intersectoral action, social norms and legal framework, paternalistic approach to health, individual and State-Government accountability, health literacy and support for care and well-being were considered strategic. Conclusions: the increase in the levels of personal responsibility for health will depend on intersectoral action, the updating of the legal framework and innovative forms for the accountability of all social actors. It will also be necessary to achieve improvements in health literacy, greater accompaniment to the efforts of individuals for self-care and the abandonment of paternalistic practices that expropriate citizens from their responsibilities.

Development and external validation of a 1- and 5-year fracture prediction tool based on electronic medical records data: The EPIC risk algorithm.

OBJECTIVES: We aimed to develop and validate a fracture risk algorithm for the automatic identification of subjects at high risk of imminent and long-term fracture risk. RESEARCH, DESIGN, AND METHODS: A cohort of subjects aged 50-85, between 2007 and 2017, was extracted from the Catalan information system for the development of research in primary care database (SIDIAP). Participants were followed until the earliest of death, transfer out, fracture, or 12/31/2017. Potential risk factors were obtained based on the existing literature. Cox regression was used to model 1 and 5-year risk of hip and major fracture. The original cohort was randomly split in 80:20 for development and internal validation purposes respectively. External validation was explored in a cohort extracted from the Spanish database for pharmaco-epidemiological research in primary care. RESULTS: A total of 1.76 million people were included from SIDIAP (50.7 % women with mean age of 65.4 years). Hip and major fracture incidence rates were 3.57 [95%CI 3.53 to 3.60] and 11.61 [95%CI 11.54 to 11.68] per 1000 person-years, respectively. The derived model included 19 risk factors. Internal validity showed good results on calibration and discrimination. The 1-year C-statistic for hip and major fracture were 0.851 (95%CI 0.853 to 0.864), and 0.717 (95%CI 0.742 to 0.749) respectively. The 5-year C-statistic for hip and major fracture were 0.849 (95%CI 0.847 to 0.852) and 0.724 (95%CI 0.721 to 0.727) respectively. External validation showed good performance for hip and major fracture risk prediction. CONCLUSIONS: We have developed and validated a clinical prediction tool for 1- and 5-year hip and major osteoporotic fracture risks using electronic primary care data. The proposed algorithm can be automatically estimated at the population level using the available primary care records. Future work is needed on the cost-effectiveness of its use for population-based screening and targeted prevention of osteoporotic fractures.

The repurposing of Tebipenem pivoxil as alternative therapy for severe gastrointestinal infections caused by extensively drug-resistant Shigella spp.

Background: Diarrhoea remains one of the leading causes of childhood mortality globally. Recent epidemiological studies conducted in low-middle income countries (LMICs) identified Shigella spp. as the first and second most predominant agent of dysentery and moderate diarrhoea, respectively. Antimicrobial therapy is often necessary for Shigella infections; however, we are reaching a crisis point with efficacious antimicrobials. The rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. Methods: Aiming to identify alternative antimicrobial chemicals with activity against antimicrobial resistant Shigella, we initiated a collaborative academia-industry drug discovery project, applying high-throughput phenotypic screening across broad chemical diversity and followed a lead compound through in vitro and in vivo characterisation. Results: We identified several known antimicrobial compound classes with antibacterial activity against Shigella. These compounds included the oral carbapenem Tebipenem, which was found to be highly potent against broadly susceptible Shigella and contemporary MDR variants for which we perform detailed pre-clinical testing. Additional in vitro screening demonstrated that Tebipenem had activity against a wide range of other non-Shigella enteric bacteria. Cognisant of the risk for the development of resistance against monotherapy, we identified synergistic behaviour of two different drug combinations incorporating Tebipenem. We found the orally bioavailable prodrug (Tebipenem pivoxil) had ideal pharmacokinetic properties for treating enteric pathogens and was effective in clearing the gut of infecting organisms when administered to Shigella-infected mice and gnotobiotic piglets. Conclusions: Our data highlight the emerging antimicrobial resistance crisis and shows that Tebipenem pivoxil (licenced for paediatric respiratory tract infections in Japan) should be accelerated into human trials and could be repurposed as an effective treatment for severe diarrhoea caused by MDR Shigella and other enteric pathogens in LMICs. Funding: Tres Cantos Open Lab Foundation (projects TC239 and TC246), the Bill and Melinda Gates Foundation (grant OPP1172483) and Wellcome (215515/Z/19/Z).