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Copyright of Notfall & Rettungsmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Establishment of dedicated Stroke Centers has shown to be effective on the outcome of patients with acute ischemic stroke, as well as mechanical thrombectomy (MTE) in acute large vessel occlusion. The cost-effectiveness of this treatment has also been proven in several countries, but so far not in Switzerland. We compare the pathways and economic impact of patients with acute large vessel occlusions causing acute ischemic stroke before the establishment of the stroke center and MTE in 2016 with the time afterwards in the years 2016–2020. Local data from the Swiss Stroke Registry and hospital accounting as well as economic data from a healthcare insurance company was used for evaluation in an economic model. Both payer and societal perspectives were considered, and probabilistic sensitivity analysis was undertaken to explore uncertainty. Establishment of a new Stroke Center in Central Switzerland increased the absolute number of thrombectomies from 0 in 2015 to 55 in 2016 to 83 in 2020, as well as the percentage of MTE in large vessel occlusions (LVO) from 50.9% in 2016 to 58.2% in 2020. Over a 15-year horizon, predicted average additional costs of CHF 7,978 were associated with the establishment of a new stroke center, as well as 0.60 quality-adjusted life-years (QALY) per patient and an additional survival of 0.59 years per patient. The calculated incremental cost-effectiveness ratio was therefore CHF 13,297 per QALY gained. When societal costs were included, the new stroke care model was predicted to dominate the old care model. Robustness of model results was confirmed via probabilistic sensitivity analysis. The results rely on data from a single stroke center and, therefore, cannot be generalized. Establishment of a new Stroke Center can be cost-effective and provide better outcomes in terms of functional independence as well as quality-adjusted life-years. [ABSTRACT FROM AUTHOR]

Copyright of Notfall & Rettungsmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Notfall & Rettungsmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: This phase 2 study evaluated the efficacy and safety of transitioning to zoledronate following romosozumab treatment in postmenopausal women with low bone mass. A single dose of 5 mg zoledronate generally maintained the robust BMD gains accrued with romosozumab treatment and was well tolerated. Introduction: Follow-on therapy with an antiresorptive agent is necessary to maintain the skeletal benefits of romosozumab therapy. We evaluated the use of zoledronate following romosozumab treatment. Methods: This phase 2, dose-finding study enrolled postmenopausal women with low bone mineral density (BMD). Subjects who received various romosozumab doses or placebo from months 0–24 were rerandomized to denosumab (60 mg SC Q6M) or placebo for 12 months, followed by open-label romosozumab (210 mg QM) for 12 months. At month 48, subjects who had received active treatment for 48 months were assigned to no further active treatment and all other subjects were assigned to zoledronate 5 mg IV. Efficacy (BMD, P1NP, and β-CTX) and safety were evaluated for 24 months, up to month 72. Results: A total of 141 subjects entered the month 48–72 period, with 51 in the no further active treatment group and 90 in the zoledronate group. In subjects receiving no further active treatment, lumbar spine (LS) BMD decreased by 10.8% from months 48–72 but remained 4.2% above the original baseline. In subjects receiving zoledronate, LS BMD was maintained (percentage changes: − 0.8% from months 48–72; 12.8% from months 0–72). Similar patterns were observed for proximal femur BMD in both groups. With no further active treatment, P1NP and β-CTX decreased but remained above baseline at month 72. Following zoledronate, P1NP and β-CTX levels initially decreased but approached baseline by month 72. No new safety signals were observed. Conclusion: A zoledronate follow-on regimen can maintain robust BMD gains achieved with romosozumab treatment. [ABSTRACT FROM AUTHOR]

Summary: Managing osteoporotic patients suboptimally adherent to bisphosphonates (BPs) is difficult. Such patients who remained at higher risk for fracture (≥1 risk factor) were transitioned to denosumab or a monthly oral BP. Denosumab-treated subjects had significantly greater increases in bone mineral density and decreases in bone turnover in this 12-month study. Introduction: A clinical need exists to manage patients who are suboptimally adherent to oral BPs and remain at higher risk for fracture. Here, we compare the effects on bone mineral density (BMD) and bone turnover of transitioning such patients to denosumab or monthly oral BP (ibandronate or risedronate). Methods: In two previous multicenter, open-label studies, postmenopausal women ≥55 years previously treated with, though suboptimally adherent to, a daily or weekly BP were randomized to denosumab 60 mg subcutaneously every 6 months ( N = 852) or oral BP 150 mg monthly ( N = 851) for 12 months. In this combined post-hoc analysis, a subset of higher risk subjects was identified, and the percentage changes from baseline in BMD and serum C-telopeptide of type I collagen (sCTX-1) were assessed. Results: In the overall population, denosumab was associated with greater gains in BMD at 12 months than monthly oral BP at the total hip, femoral neck, and lumbar spine ( p < 0.0001 for all). In higher risk subjects, denosumab led to greater gains in BMD than oral BPs at the total hip (2.2 vs 0.8 %), femoral neck (1.8 vs 0.3 %), and lumbar spine (3.7 vs 1.4 %) ( p < 0.0001 for all). Denosumab also led to greater decreases in sCTX-1 in the overall population and higher risk subjects at months 1 and 6 ( p < 0.0001 for both). Adverse events and serious adverse events were generally similar between treatment groups. Conclusions: Transitioning to denosumab was well tolerated and more effective in increasing BMD and reducing bone turnover than cycling to a monthly oral BP treatment in subjects who remained at higher fracture risk despite suboptimal BP treatment. [ABSTRACT FROM AUTHOR]

Summary: Osteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture; osteopenia-associated vertebral, proximal humerus, pelvis, or some wrist fractures; or FRAX scores with ≥3 % (hip) or 20 % (major) 10-year fracture risk also confer an osteoporosis diagnosis. Introduction: Osteoporosis is a common disorder of reduced bone strength that predisposes to an increased risk for fractures in older individuals. In the USA, the standard criterion for the diagnosis of osteoporosis in postmenopausal women and older men is a T-score of ≤ −2.5 at the lumbar spine, femur neck, or total hip by bone mineral density testing. Methods: Under the direction of the National Bone Health Alliance, 17 clinicians and clinical scientists were appointed to a working group charged to determine the appropriate expansion of the criteria by which osteoporosis can be diagnosed. Results: The group recommends that postmenopausal women and men aged 50 years should be diagnosed with osteoporosis if they have a demonstrable elevated risk for future fractures. This includes having a T-score of less than or equal to −2.5 at the spine or hip as one method for diagnosis but also permits a diagnosis for individuals in this population who have experienced a hip fracture with or without bone mineral density (BMD) testing and for those who have osteopenia by BMD who sustain a vertebral, proximal humeral, pelvic, or, in some cases, distal forearm fracture. Finally, the term osteoporosis should be used to diagnose individuals with an elevated fracture risk based on the World Health Organization Fracture Risk Algorithm, FRAX. Conclusions: As new ICD-10 codes become available, it is our hope that this new understanding of what osteoporosis represents will allow for an appropriate diagnosis when older individuals are recognized as being at an elevated risk for fracture. [ABSTRACT FROM AUTHOR]

Summary: In a phase 2 study, continued denosumab treatment for up to 8 years was associated with continued gains in bone mineral density and persistent reductions in bone turnover markers. Denosumab treatment was well tolerated throughout the 8-year study. Introduction: The purpose of this study is to present the effects of 8 years of continued denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTM) from a phase 2 study. Methods: In the 4-year parent study, postmenopausal women with low BMD were randomized to receive placebo, alendronate, or denosumab. After 2 years, subjects were reallocated to continue, discontinue, or discontinue and reinitiate denosumab; discontinue alendronate; or maintain placebo for two more years. The parent study was then extended for 4 years where all subjects received denosumab. Results: Of the 262 subjects who completed the parent study, 200 enrolled in the extension, and of these, 138 completed the extension. For the subjects who received 8 years of continued denosumab treatment, BMD at the lumbar spine ( N = 88) and total hip ( N = 87) increased by 16.5 and 6.8 %, respectively, compared with their parent study baseline, and by 5.7 and 1.8 %, respectively, compared with their extension study baseline. For the 12 subjects in the original placebo group, 4 years of denosumab resulted in BMD gains comparable with those observed during the 4 years of denosumab in the parent study. Reductions in BTM were sustained over the course of continued denosumab treatment. Reductions also were observed when the placebo group transitioned to denosumab. Adverse event profile was consistent with previous reports and an aging cohort. Conclusion: Continued denosumab treatment for 8 years was associated with progressive gains in BMD, persistent reductions in BTM, and was well tolerated. [ABSTRACT FROM AUTHOR]

Summary Dosing regimens of oral bisphosphonates are inconvenient and contribute to poor compliance. The bone mineral density response to a once weekly delayed-release formulation of risedronate given before or following breakfast was non-inferior to traditional immediate-release risedronate given daily before breakfast. Delayed-release risedronate is a convenient regimen for oral bisphosphonate therapy. Introduction We report the results of a randomized, controlled, clinical study assessing the efficacy and safety of a delayed-release (DR) 35 mg weekly oral formulation of risedronate that allows patients to take their weekly risedronate dose before or immediately after breakfast. Methods Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5 mg immediate-release (IR) daily (n=307) at least 30 min before breakfast, or risedronate 35 mg DR weekly, either at least 30 min before breakfast (BB, n=308) or immediately following breakfast (FB, n=307). Bone mineral density (BMD), bone turnover markers (BTMs), fractures, and adverse events were evaluated. The primary efficacy variable was percent change from baseline in lumbar spine BMD at Endpoint. Results Two hundred fifty-seven subjects (83.7%) in the IR daily group, 252 subjects (82.1%) in the DR FB weekly group, and 258 subjects (83.8%) in the DR BB weekly group completed 1 year. Both DR weekly groups were determined to be non-inferior to the IR daily regimen. Mean percent changes in hip BMD were similar across groups. The magnitude of BTM response was similar across groups; some statistical differences were seen that were small and deemed by investigators to have no major clinical importance. The incidence of adverse events leading to withdrawal and serious adverse events were similar across treatment groups. All three regimens were well tolerated. Conclusions Risedronate 35 mg DR weekly is similar in efficacy and safety to risedronate 5 mg IR daily, and will allow patients to take their weekly risedronate dose immediately after breakfast. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Although oral bisphosphonates are effective treatments for postmenopausal women with osteoporosis, oral dosing may be unsuitable for some patients. An efficacious intravenously administered bisphosphonate could be beneficial for such patients. Ibandronate, a potent nitrogen-containing bisphosphonate, can be administered using extended dosing intervals, either orally or by rapid intravenous injection. The aim of this study was to identify the optimal intravenous dosing regimen for ibandronate in postmenopausal women with osteoporosis. METHODS: In a randomized, double-blind, double-dummy, phase III, noninferiority study, we compared 2 regimens of intermittent intravenous injections of ibandronate (2 mg every 2 months and 3 mg every 3 months) with a regimen of 2.5 mg of oral ibandronate daily, the latter of which has proven antifracture efficacy. The study group comprised 1,395 women (ages 55-80 years) who were at least 5 years postmenopausal. All patients had osteoporosis (lumbar spine [L2-L4] bone mineral density [BMD] T score less than -2.5). Participants also received daily calcium (500 mg) and vitamin D (400 IU). The primary end point was change from baseline in lumbar spine BMD at 1 year. Changes in hip BMD and in the level of serum C-telopeptide of type I collagen (CTX) were also measured, as were safety and tolerability. RESULTS: At 1 year, mean lumbar spine BMD increases were as follows: 5.1% among 353 patients receiving 2 mg of ibandronate every 2 months, 4.8% among 365 patients receiving 3 mg of ibandronate every 3 months, and 3.8% among 377 patients receiving 2.5 mg of oral ibandronate daily. Both of the intravenous regimens not only were noninferior, but also were superior (P < 0.001) to the oral regimen. Hip BMD increases (at all sites) were also greater in the groups receiving medication intravenously than in the group receiving ibandronate orally. Robust decreases in the serum CTX level were observed in all arms of the study. Both of the intravenous regimens were well tolerated and did not compromise renal function. CONCLUSION: As assessed by BMD, intravenous injections of ibandronate (2 mg every 2 months or 3 mg every 3 months) are at least as effective as the regimen of 2.5 mg orally daily, which has proven antifracture efficacy, and are well tolerated. [ABSTRACT FROM AUTHOR]

This study evaluated the efficacy and tolerability of risedronate once a week (35 mg and 50 mg) compared with risedronate 5 mg once daily in women with osteoporosis. We conducted a randomized, double-blind, active-controlled, 2-year study; the primary efficacy assessment was performed after 1 year. Subjects were women aged 50 years or older who had been postmenopausal for at least 5 years, with either a bone mineral density (BMD) T-score of ?2.5 or lower (lumbar spine or proximal femur) or a T-score lower than ?2 and at least one prevalent vertebral fracture. Subjects received risedronate 5 mg once daily, 35 mg once a week or 50 mg once a week. All subjects also received 1 g daily of elemental calcium supplementation and supplemental vitamin D if the baseline serum levels were low. The primary efficacy measure was percent change in lumbar spine BMD at 12 months. A total of 1456 women were randomized and received medication; 1209 (83%) women completed 12 months. The mean percent change (SE) in lumbar spine BMD after 12 months was 4.0% (0.2%) in the 5 mg daily group, 3.9% (0.2%) in the 35 mg group, and 4.2% (0.2%) in the 50 mg group; each once-a-week treatment was determined to be as effective as the daily treatment. Outcomes of the secondary efficacy measurements and safety assessments were also similar in all 3 groups after 12 months. Risedronate 35 mg and 50 mg once a week provide the same efficacy and safety as the daily 5 mg regimen; therefore, the lower dose, 35 mg once a week, is considered optimal for women with postmenopausal osteoporosis who desire a once-a-week regimen. [ABSTRACT FROM AUTHOR]

The article focuses on the clinical trial that investigates the effect of desonumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting therapy. It states that the women with a spine T-score of -1.8 to -3.5 were randomized to the human monoclonal antibody denosumab, to placebo, and to open-label oral alendronate every week. Details on the findings of the trial are also provided.