Socioeconomic effects of establishing a new stroke center in Central Switzerland.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: The results rely on data from a single stroke center and, therefore, cannot be generalized. CONCLUSIONS: 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.

Endovascular therapy outcome in isolated posterior cerebral artery occlusion strokes: A multicenter analysis of the Swiss Stroke Registry.

PURPOSE: There is little data on the safety and efficacy of endovascular treatment (EVT) in comparison with intravenous thrombolysis (IVT) in acute ischemic stroke due to isolated posterior cerebral artery occlusion (IPCAO). We aimed to investigate the functional and safety outcomes of stroke patients with acute IPCAO treated with EVT (with or without prior bridging IVT) compared to IVT alone. METHODS: We did a multicenter retrospective analysis of data from the Swiss Stroke Registry. The primary endpoint was overall functional outcome at 3 months in patients undergoing EVT alone or as part of bridging, compared with IVT alone (shift analysis). Safety endpoints were mortality and symptomatic intracranial hemorrhage. EVT and IVT patients were matched 1:1 using propensity scores. Differences in outcomes were examined using ordinal and logistic regression models. FINDINGS: Out of 17,968 patients, 268 met the inclusion criteria and 136 were matched by propensity scores. The overall functional outcome at 3 months was comparable between the two groups (EVT vs IVT as reference category: OR = 1.42 for higher mRS, 95% CI = 0.78-2.57, p = 0.254). The proportion of patients independent at 3 months was 63.2% in EVT and 72.1% in IVT (OR = 0.67, 95% CI = 0.32-1.37, p = 0.272). Symptomatic intracranial hemorrhages were overall rare and present only in the IVT group (IVT = 5.9% vs EVT = 0%). Mortality at 3 months was also similar between the two groups (IVT = 0% vs EVT = 1.5%). CONCLUSION: In this multicenter nested analysis, EVT and IVT in patients with acute ischemic stroke due to IPCAO were associated with similar overall good functional outcome and safety. Randomized studies are warranted.

A single dose of zoledronate preserves bone mineral density for up to 2 years after a second course of romosozumab.

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 ß-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 ß-CTX decreased but remained above baseline at month 72. Following zoledronate, P1NP and ß-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.

Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates.

CONTEXT: Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis. OBJECTIVE: The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover. DESIGN AND SETTING: This was an international, multicenter, randomized, double-blind trial. PARTICIPANTS: A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study. INTERVENTIONS: Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months. MAIN OUTCOME MEASURES: Changes in BMD and bone turnover markers were measured. RESULTS: BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs -0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL). CONCLUSIONS: In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL.

Denosumab significantly increases bone mineral density and reduces bone turnover compared with monthly oral ibandronate and risedronate in postmenopausal women who remained at higher risk for fracture despite previous suboptimal treatment with an oral bisphosphonate.

UNLABELLED: 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.

The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group.

UNLABELLED: 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.

Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial.

UNLABELLED: 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.

Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet.

UNLABELLED: 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.

Cinacalcet HCl reduces hypercalcemia in primary hyperparathyroidism across a wide spectrum of disease severity.

CONTEXT: Primary hyperparathyroidism (PHPT) is characterized by elevated serum calcium (Ca) and increased PTH concentrations. OBJECTIVE: The objective of the investigation was to establish the efficacy of cinacalcet in reducing serum Ca in patients with PHPT across a wide spectrum of disease severity. DESIGN AND SETTING: The study was a pooled analysis of data from three multicenter clinical trials of cinacalcet in PHPT. PATIENTS: Patients were grouped into three disease categories for analysis based on the following: 1) history of failed parathyroidectomy (n = 29); 2) meeting one or more criteria for parathyroidectomy but without prior surgery (n = 37); and 3) mild asymptomatic PHPT without meeting criteria for either above category (n = 15). INTERVENTION: The intervention in this study was treatment with cinacalcet for up to 4.5 yr. OUTCOMES: Measurements in the study included serum Ca, PTH, phosphate, and bone-specific alkaline phosphatase, and areal bone mineral density (aBMD). Vital signs, safety biochemical and hematological indices, and adverse events were monitored throughout the study period. RESULTS: The extent of cinacalcet-induced serum Ca reduction, proportion of patients achieving normal serum Ca (≤10.3 mg/dl), reduction in serum PTH, and increase in serum phosphate were similar across all three categories. Except for decreased aBMD at the total femur indicated for parathyroidectomy group at 1 yr, no significant changes in aBMD occurred. The efficacy of cinacalcet was maintained for up to 4.5 yr of follow-up. AEs were mild and similar across the three categories. CONCLUSIONS: Cinacalcet is equally effective in the medical management of PHPT patients across a broad spectrum of disease severity, and overall cinacalcet is well tolerated.

Effects of arzoxifene on bone mineral density and endometrium in postmenopausal women with normal or low bone mass.

INTRODUCTION: Arzoxifene, a benzothiophene estrogen agonist/antagonist, is being developed for prevention and treatment of osteoporosis and for risk reduction of invasive breast cancer in postmenopausal women. METHODS: The effects of arzoxifene 20 mg/d on bone mineral density (BMD), uterine safety, and overall safety were studied in the FOUNDATION study, a 2-yr randomized, placebo-controlled trial including 331 postmenopausal women with normal to low bone mass. RESULTS: Compared to placebo, arzoxifene significantly increased lumbar spine (+2.9%) and total hip (+2.2%) BMD. Arzoxifene decreased biochemical markers of bone metabolism compared to placebo. Changes in breast density were neutral or slightly decreased in the arzoxifene vs. placebo group. There was no evidence of endometrial hyperplasia or carcinoma in the arzoxifene group as assessed by central review of baseline and follow-up endometrial biopsies. There was no significant change between the groups in endometrial thickness assessed by transvaginal ultrasound. The incidence of uterine polyps and vaginal bleeding was not significantly different between the groups. Vulvovaginal mycotic infection was the only adverse event significantly increased in the arzoxifene vs. placebo group. Hot flushes were not significantly different between the groups. CONCLUSION: In postmenopausal women with normal to low bone mass, arzoxifene 20 mg/d increased BMD at the spine and hip and had a neutral effect on the uterus and endometrium.

Prevalencia de obesidad y sobrepeso en población escolar / Prevalence of obesity and overweight in school children population

Objetivos: 1-Determinar la prevalencia de obesidad y sobrepeso en niños que cursan 5° año de la EGB en establecimientos escolares de la ciudad de Venado Tuerto. 2-Determinar si existe relación entre el estado nutricional y la actividad física en los niños. Matriales y métodos: se encuestaron 444 niños de 5to. año EGB en 23 establecimientos escolares de la ciudad de Venado Tuerto. Las encuestas realizadas constaron de 14 preguntas y un registro de las comidas que el niño realizó durante un día. Las mismas fueron entregadas en mano y se las retiró después de 1 semana. Los niños fueron previamente evaluados según su índice de masa corporal en relación de su edad. Las categorías asignadas fueron: desnutridos (D), peso normal(PN), sobrepeso (S), obesidad (O). Como punto de corte se utilizó para S (entre los percentilos 85 y 95) y para los O (> percentilo 95) según las curvas del Instituto Nacional d Estadísticas en Salud (NCHS)...

Prevalencia de obesidad y sobrepeso en población escolar / Prevalence of obesity and overweight in school children population

Objetivos: 1-Determinar la prevalencia de obesidad y sobrepeso en niños que cursan 5º año de la EGB en establecimientos escolares de la ciudad de Venado Tuerto. 2-Determinar si existe relación entre el estado nutricional y la actividad física en los niños. Matriales y métodos: se encuestaron 444 niños de 5to. año EGB en 23 establecimiento

The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal osteoporosis.

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 1,456 women were randomized and received medication; 1,209 (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.

Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate.

Treatment of osteoporosis with PTH causes a marked increase in vertebral bone mineral density (BMD). However, this effect is rapidly reversed when the treatment is stopped. The purpose of the present study was to determine whether the bisphosphonate alendronate could preserve or enhance bone density in patients previously treated with PTH. Sixty-six postmenopausal osteoporotic women were treated for 1 yr with 50, 75, or 100 microg recombinant human PTH-(1-84) or placebo, and then were given 10 mg alendronate daily for an additional year. BMD was measured in the femoral neck, lumbar spine, and whole body. Markers of bone turnover included skeletal alkaline phosphatase, osteocalcin, and N-telopeptide. During the first year, changes in BMD (mean +/- SD) in women receiving PTH (all doses combined) were 7.1 +/- 5.6% (spine), 0.3 +/- 6.2% (femoral neck), and -2.3 +/- 3.3% (total body). After switching to alendronate for 1 yr in women who previously had received PTH, mean changes in BMD were 13.4 +/- 6.4% (spine), 4.4 +/- 7.2% (femoral neck), and 2.6 +/- 3.1% (whole body). In the subgroup of patients who had received the highest dose of PTH, the mean increase in vertebral BMD was 14.6 +/- 7.9%. All markers of bone turnover increased during treatment with PTH and decreased to below baseline after 1 yr of alendronate. In conclusion, sequential treatment of osteoporosis with PTH and alendronate results in an increase in vertebral bone density that is considerably more than has been reported with alendronate or estrogens alone. This combination of drugs may be a useful approach to maximizing bone density in women with vertebral osteoporosis.

Proto-metastatic core and comet effect: new theoretical model of the mechanism of metastasis generation.

One important aspect of cancer is its capacity to generate metastasis. The mechanism by which one or several neoplastic cells escape from the primitive tumor to start the metastatic process is still a matter of discussion, hence the need to reconsider under which circumstances and conditions 'lethal escape' is produced. Thus we introduce two concepts: proto-metastatic core and comet effect. We maintain that only one group of cells (proto-metastatic core) could escape passively from the tumor focus when they enter the bloodstream together with other detritus. The proto-metastatic core disintegrates through friction with the blood (comet effect). There are two mechanism of metastasis. In the first, only one cell leaves the vessel joined to white blood cells as it moves through an inflamed area. The second, from the proto-metastatic core, could form venous thrombus. We believe that this new theoretical model of the etiopathology of cancer will contribute to future therapies.