Real-world efficacy of a teriparatide biosimilar (RGB-10) compared with reference teriparatide on bone mineral density, trabecular bone score, and bone parameters assessed using quantitative ultrasound, 3D-SHAPER® and high-resolution peripheral computer tomography in postmenopausal women with osteoporosis and very high fracture risk.

A retrospective analysis comparing a teriparatide biosimilar (RGB-10) with reference teriparatide for osteoporosis treatment in postmenopausal women at high fracture risk found them to be therapeutically equivalent. Both provided significant improvements in lumber spine BMD, TBS, and other parameters of bone health, assessed using multiple diagnostic methods. PURPOSE: To compare the therapeutic efficacy of a teriparatide biosimilar (RGB-10) with reference teriparatide for the treatment of osteoporosis in postmenopausal women at very high fracture risk. METHODS: A retrospective analysis of 25 postmenopausal female patients treated for osteoporosis with RGB-10 for 24 months and a matched cohort of 25 patients treated with reference teriparatide. The following outcomes were assessed at baseline, 12 and 24 months: bone mineral density (BMD) at the lumbar spine, femoral neck and total hip using dual-energy x-ray absorptiometry (DXA) and integral, trabecular and cortical volumetric and surface BMD using 3D-SHAPER® imaging, trabecular bone score (TBS), quantitative ultrasound (QUS) measurements, and high-resolution peripheral quantitative computed tomography (HRpQCT) imaging of the radius and tibia. RESULTS: No significant differences were observed between treatment groups in any of the measured parameters of BMD or bone health at baseline as well as in any timepoint when assessed using these various diagnostic methods. Both compounds provided equivalent significant improvements from baseline in measures of osteoporosis and fracture risk. CONCLUSION: The results of the analysis demonstrate the therapeutic equivalence of the teriparatide biosimilar (RGB-10) to reference teriparatide for the treatment of osteoporosis in postmenopausal women at very high risk of fracture.

Human-to-Human Transmission of Andes Virus Modeled in Syrian Hamsters.

Several occurrences of human-to-human transmission of Andes virus, an etiological agent of hantavirus cardiopulmonary syndrome, are documented. Syrian hamsters consistently model human hantavirus cardiopulmonary syndrome, yet neither transmission nor shedding has been investigated. We demonstrate horizontal virus transmission and show that Andes virus is shed efficiently from both inoculated and contact-infected hamsters.

Gaps and alternative surgical and non-surgical approaches in the bone fragility management: an updated review.

Osteoporotic fractures are one of the major problems facing healthcare systems worldwide. Undoubtedly, fragility fractures of the hip represent a far greater burden in terms of morbidity, mortality, and healthcare costs than other fracture sites. However, despite the significant impact on the health and quality of life of older adults, there is a general lack of awareness of osteoporosis, which results in suboptimal care. In fact, most high-risk individuals are never identified and do not receive adequate treatment, leading to further fragility fractures and worsening health status. Furthermore, considering the substantial treatment gap and the proven cost-effectiveness of fracture prevention programs such as Fracture Liaison Services, urgent action is needed to ensure that all individuals at high risk of fragility fracture are adequately assessed and treated. Based on this evidence, the aim of our review was to (i) provide an overview and comparison of the burden and management of fragility fractures, highlighting the main gaps, and (ii) highlight the importance of using alternative approaches, both surgical and non-surgical, with the aim of implementing early prevention of osteoporotic fractures and improving the management of osteoporotic patients at imminent and/or very high risk of fracture.

Unique human immune signature of Ebola virus disease in Guinea.

Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

Novel formulations of oral bisphosphonates in the treatment of osteoporosis.

Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of evidence; however, patient adherence to oral bisphosphonates remains poor in part due to complex dosing instructions and adverse events, including upper gastrointestinal symptoms. This problem has led to the development of novel oral bisphosphonate formulations. Buffered, effervescent alendronate is dissolved in water and so seeks to reduce upper gastro-intestinal adverse events, and gastro-resistant risedronate aims to reduce the complexity of dosing procedure (e.g. fasting prior to consumption) whilst still maintaining the efficacy of fracture risk reduction. Clinical trials and real-world data have been employed to demonstrate some benefits in terms of reduced upper gastro-intestinal adverse events, adherence, persistence and health economic outcomes. This report describes the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores where oral bisphosphonates sit in current clinical practice guidelines, review their risk-benefit profile and the consequences of poor adherence before exploring novel oral bisphosphonate formulations and their potential clinical and health economic impact. Further research is required but there are signs that these novel, oral bisphosphonate formulations may lead to improved tolerance of oral bisphosphonates and thus, improved adherence and fracture outcomes.

Effect of Artesunate-Amodiaquine on Mortality Related to Ebola Virus Disease.

BACKGROUND: Malaria treatment is recommended for patients with suspected Ebola virus disease (EVD) in West Africa, whether systeomatically or based on confirmed malaria diagnosis. At the Ebola treatment center in Foya, Lofa County, Liberia, the supply of artemether-lumefantrine, a first-line antimalarial combination drug, ran out for a 12-day period in August 2014. During this time, patients received the combination drug artesunate-amodiaquine; amodiaquine is a compound with anti-Ebola virus activity in vitro. No other obvious change in the care of patients occurred during this period. METHODS: We fit unadjusted and adjusted regression models to standardized patient-level data to estimate the risk ratio for death among patients with confirmed EVD who were prescribed artesunate-amodiaquine (artesunate-amodiaquine group), as compared with those who were prescribed artemether-lumefantrine (artemether-lumefantrine group) and those who were not prescribed any antimalarial drug (no-antimalarial group). RESULTS: Between June 5 and October 24, 2014, a total of 382 patients with confirmed EVD were admitted to the Ebola treatment center in Foya. At admission, 194 patients were prescribed artemether-lumefantrine and 71 were prescribed artesunate-amodiaquine. The characteristics of the patients in the artesunate-amodiaquine group were similar to those in the artemether-lumefantrine group and those in the no-antimalarial group. A total of 125 of the 194 patients in the artemether-lumefantrine group (64.4%) died, as compared with 36 of the 71 patients in the artesunate-amodiaquine group (50.7%). In adjusted analyses, the artesunate-amodiaquine group had a 31% lower risk of death than the artemether-lumefantrine group (risk ratio, 0.69; 95% confidence interval, 0.54 to 0.89), with a stronger effect observed among patients without malaria. CONCLUSIONS: Patients who were prescribed artesunate-amodiaquine had a lower risk of death from EVD than did patients who were prescribed artemether-lumefantrine. However, our analyses cannot exclude the possibility that artemether-lumefantrine is associated with an increased risk of death or that the use of artesunate-amodiaquine was associated with unmeasured patient characteristics that directly altered the risk of death.

Radiofrequency echographic multi-spectrometry for the in-vivo assessment of bone strength: state of the art-outcomes of an expert consensus meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

PURPOSE: The purpose of this paper was to review the available approaches for bone strength assessment, osteoporosis diagnosis and fracture risk prediction, and to provide insights into radiofrequency echographic multi spectrometry (REMS), a non-ionizing axial skeleton technique. METHODS: A working group convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis met to review the current image-based methods for bone strength assessment and fracture risk estimation, and to discuss the clinical perspectives of REMS. RESULTS: Areal bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is the consolidated indicator for osteoporosis diagnosis and fracture risk assessment. A more reliable fracture risk estimation would actually require an improved assessment of bone strength, integrating also bone quality information. Several different approaches have been proposed, including additional DXA-based parameters, quantitative computed tomography, and quantitative ultrasound. Although each of them showed a somewhat improved clinical performance, none satisfied all the requirements for a widespread routine employment, which was typically hindered by unclear clinical usefulness, radiation doses, limited accessibility, or inapplicability to spine and hip, therefore leaving several clinical needs still unmet. REMS is a clinically available technology for osteoporosis diagnosis and fracture risk assessment through the estimation of BMD on the axial skeleton reference sites. Its automatic processing of unfiltered ultrasound signals provides accurate BMD values in view of fracture risk assessment. CONCLUSIONS: New approaches for improved bone strength and fracture risk estimations are needed for a better management of osteoporotic patients. In this context, REMS represents a valuable approach for osteoporosis diagnosis and fracture risk prediction.

Assessing the effects of long-term osteoporosis treatment by using conventional spine radiographs: results from a pilot study in a sub-cohort of a large randomized controlled trial.

OBJECTIVE: To evaluate the clinical applicability of a software tool developed to extract bone textural information from conventional lumbar spine radiographs, and to test it in a subset of postmenopausal women treated for osteoporosis with the fully human monoclonal antibody denosumab. METHODS: The software was developed based on the principles of a fractal model using pixel grey-level variations together with a specific machine-learning algorithm. The obtained dimensionless parameter, termed bone structure value (BSV), was then tested and compared to bone mineral density (BMD) in a sub-cohort of postmenopausal women with osteoporosis who were treated with the monoclonal antibody denosumab, within the framework of a large randomized controlled trial and its open-label extension phase. RESULTS: After 3 years and after 8 years of treatment with denosumab, mean lumbar spine BMD as well as mean lumbar BSV were significantly higher compared to study entry (one-way repeated measures ANOVA for DXA: F = 108.2, p < 0.00001; and for BSV: F = 84.3, p < 0.00001). The overall increase in DXA-derived lumbar spine BMD at year 8 was + 42% (mean ± SD; 0.725 ± 0.038 g/cm2 to 1.031 ± 0.092 g/cm2; p < 0.0001), and the overall increase of BSV was 255% (mean ± SD; 0.076 ± 0.022 to 0.270 ± 0.09, p < 0.0001). Overall, BMD and BSV were significantly correlated (R = 0.51; p < 0.0001). CONCLUSIONS: This pilot study provides evidence that lumbar spine BSV as obtained from conventional radiographs constitutes a useful means for the assessment of bone-specific treatment effects in postmenopausal women with osteoporosis.

[Four years after the Ebola crisis : Challenges, experiences, and implications in the German public health context]. / Vier Jahre nach der Ebolakrise : Herausforderungen, Erfahrungen und Schlussfolgerungen für den Öffentlichen Gesundheitsdienst in Deutschland.

The Ebola virus disease outbreak in West Africa in 2014/2015 was by far the biggest, most prolonged, and geographically most widespread outbreak of this disease since the discovery of the Ebola virus in 1976. Although no cases of Ebola virus disease were confirmed in Germany, a number of crisis management activities were initiated.Based on a combination of local, national, and international lessons learned, literature research, and a large number of discussions among German colleagues as well as German and foreign colleagues, the experiences of selected German public health actors as well as implications for health protection activities in Germany are presented.On the one hand, preparedness for managing unusual high consequence health events-caused by rare, highly pathogenic biological agents-including the provision of adequate material and personnel resources remains important in Germany. On the other hand, more German engagement in global health is necessary, because the dividing line between global health and local health is increasingly disappearing.