Zinc supplementation may significantly reduce mortality rate and improve serum zinc in neonatal sepsis, but has no substantial influence on hospital stay and the number of expired patients.
Objective: The aim of this study was to assess the comparative effectiveness and safety of different pharmacological agents, including abaloparatide and romosozumab, for treatment of osteoporosis in postmenopausal women. Methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Google Scholar for relevant randomized controlled trials published up to July 16, 2018. After study selection according to the preplanned criteria, we performed data extraction and quality assessment. With statistical heterogeneity and inconsistency being examined, pairwise and network meta-analyses were conducted to synthesize risk ratio and 95% CI. Finally, we calculated the surface under the cumulative ranking curve to rank the interventions, and carried out three sensitivity analyses to assess the robustness of our main results. Results: Our searches yielded 2,584 records in total, of which 21 were finally included in quantitative synthesis and all of them were of high quality. Our 5 outcomes of interest involved a total of 13 interventions and 67,524 participants. For each outcome, the estimated τ 2 values all were less than or equal to 0.0747, and the P values for test of consistency varied from 0.097 to 0.941, respectively, suggesting low heterogeneity and no inconsistency. Abaloparatide and teriparatide, without statistical difference between them, had a statistically lower risk of new vertebral or nonvertebral fractures than placebo, strontium ranelate, risedronate, raloxifene, lasofoxifene (0.25 mg/d), lasofoxifene (0.5 mg/d), denosumab, and alendronate. Zoledronic acid and romosozumab, without statistical difference between them, were significantly more efficacious than placebo, risedronate, and alendronate in preventing clinical fractures. Denosumab was statistically superior to placebo in preventing new vertebral and nonvertebral fractures, and to placebo, risedronate, and alendronate in preventing clinical fractures. For the outcomes of adverse events and serious adverse events, all of treatments were not statistically different from one another, except that zoledronic acid was statistically worse than placebo in terms of adverse events. Based on surface under the cumulative ranking curves, abaloparatide and teriparatide were two of the most effective treatments in preventing new vertebral and nonvertebral fractures; zoledronic acid and romosozumab were two of the most effective treatments in preventing clinical fractures, and denosumab and romosozumab were two of the best interventions for the outcome of adverse events. Three sensitivity analyses revealed the robustness of the main results. Conclusions: Abaloparatide and teriparatide are most efficacious in preventing new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis, whereas zoledronic acid and romosozumab are in preventing clinical fractures. Meanwhile, there is no statistical difference between abaloparatide, teriparatide or romosozumab, and placebo in terms of safety. Furthermore, in terms of adverse events, zoledronic acid is statistically worse than placebo, and two of the best interventions are denosumab and romosozumab, of which denosumab also reduces the risk of different kinds of fractures.
We aimed to evaluate the comparative efficacy and safety of drugs respectively for primary prevention and secondary prevention of osteoporotic fractures in postmenopausal women (PMW), and to further identify the optimal intervention(s) respectively for the two groups when efficacy and safety both considered. We searched three databases. Bayesian network meta-analyses were conducted for two efficacy outcomes (vertebral fractures and nonvertebral fractures) and two safety outcomes (tolerability and acceptability) respectively in primary prevention group and secondary prevention group. We synthesized hazard ratios (HRs) and 95% confidence intervals (CIs) for nonvertebral fractures, and risk ratios (RRs) for three others. Factor and cluster analyses on surface under the cumulative ranking curve (SUCRA) values were conducted to identify the best intervention(s) with efficacy and safety both considered. The study protocol has been registered in PROSPERO. We included 57 randomized trials involving fifteen anti-osteoporotic interventions and 106320 PMW. For primary prevention, only zoledronate (once per 18 months) reduced both vertebral (RR 0.46, 95% CI 0.28-0.74) and nonvertebral (HR 0.66, 95% CI 0.51-0.85) fractures. For secondary prevention, abaloparatide, alendronate, denosumab, lasofoxifene, risedronate, romosozumab, teriparatide, and zoledronate (once per 12 months) reduced both vertebral (RRs: from 0.17 to 0.62) and nonvertebral (HRs: from 0.54 to 0.81) fractures. PTH (1-84) and abaloparatide increased withdrawal risk. Romosozumab, teriparatide, denosumab and risedronate, with the greatest composite scores, constituted the optimal cluster having both superior efficacy and superior safety. Zoledronate used at 5 mg per 18 months, with the
By Bayesian random effects network meta-analysis stratified by prevalent vertebral fracture (PVF), we conclude that different effective drugs should be used to prevent fragility fractures according to postmenopausal women with or without PVF and that there are two drugs (i.e., parathyroid hormone (1-84) and abaloparatide) less tolerated than placebo. Introduction No studies have compared various osteoporosis drugs in postmenopausal women (PMW) either with or without prevalent vertebral fracture (PVF). We aimed to compare them in the two different subgroups. Methods We searched different databases to select relevant studies. We performed Bayesian random effects network metaanalysis to synthesize hazard ratio (HR) and 95% confidence interval (CI) for clinical fracture stratified by PVF and to synthesize risk ratio (RR) for tolerability and vertebral fracture. Results We included 33 trials involving 79,144 PMW. In the PVF ≥ 50% subgroup, teriparatide (HR 0.39, 95% CI 0.28-0.57), romosozumab (HR 0.49, 95% CI 0.29-0.75), risedronate (HR 0.62, 95% CI 0.50-0.79), zoledronate (HR 0.67, 95% CI 0.47-0.96), and alendronate (HR 0.69, 95% CI 0.47-0.97) reduced clinical fracture risk. In the other subgroup, abaloparatide (HR 0.56, 95% CI 0.33-0.92), romosozumab (HR 0.67, 95% CI 0.47-0.95), and denosumab (HR 0.68, 95% CI 0.50-0.85) reduced clinical fracture risk. Five drugs reduced vertebral fracture risk in the PVF ≥ 50% subgroup whereas seven did in the other subgroup. All drugs did not increase withdrawal risk except for parathyroid hormone (1-84) (PTH) (RR 1.9, 95% CI 1.4-2.6) and abaloparatide (RR 1.6, 95% CI 1.2-2.3). Conclusion Different effective drugs should be used to prevent fragility fractures according to PMW with or without PVF, and romosozumab is the only one which can reduce clinical and vertebral fractures in both of the two populations. PTH and abaloparatide are less tolerated than placebo whereas the eight other drugs assessed in the study have the same tolerability as placebo.
Context The evidence about benefits and harms of drugs for glucocorticoid (GC)-induced osteoporosis (GIOP) is limited, and the comparative efficacy and safety of first-line and second-line agents to prevent GC-induced (GI) fractures remains unclear. Objective To assess the comparative clinical efficacy, safety, and tolerability of first-line and second-line agents in preventing GI fractures. Data Sources We searched 3 different databases through March 5, 2019. Study Selection We included randomized controlled trials enrolling patients receiving long-term GCs and compared a first-line and second-line agent with one another and with placebo. Data Extraction Two reviewers independently extracted study and participant characteristics and outcome data. Data Synthesis We performed multivariate random-effects network meta-analyses including base, 3 subgroups, and 12 sensitivity analyses. We included 22 papers from 19 unique trials involving 4328 patients receiving GCs. Teriparatide (risk ratio [RR] 0.11, 95% confidence interval [CI] 0.03–0.47), denosumab (RR 0.21, 95% CI 0.09–0.49), and risedronate (RR 0.33, 95% CI 0.19–0.58) reduced the risk of GI vertebral fractures, and the former 2 were the most efficacious according to violin plots including the surface under the cumulative ranking curve values calculated by base and sensitivity analyses. Oral alendronate (RR 0.33, 95% CI 0.12–0.93) reduced this risk in patients receiving GCs with at least 7.5 mg/day, while intravenous ibandronate (RR 0.25, 95% CI 0.06–0.99) was efficacious for the primary prevention of GIOP. Six drugs were similar in terms of the 5 other outcomes. Conclusions In terms of clinical efficacy and safety, second-line teriparatide and denosumab pose a challenge to first-line oral bisphosphonates for prevention of GI fractures.
We performed a meta-analysis to evaluate the effect of prophylactic negative pressure treatment for post-surgery groin wounds management in vascular surgery. A systematic literature search up to April 2022 was performed and 1537 total number of groin vascular surgery incisions at the baseline of the studies; 729 of them were using the prophylactic negative pressure treatment, and 808 were using control. Odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of prophylactic negative pressure treatment for post-surgery groin wounds management in vascular surgery using the dichotomous, and contentious methods with a random or fixed-effect model. The prophylactic negative pressure treatment subjects had a significantly lower surgical site wound infection (OR, 0.26; 95% CI, 0.16-0.42, P < .001) in subjects after vascular surgery compared with control. However, prophylactic negative pressure treatment did not show any significant difference in revision surgery (OR, 0.73; 95% CI, 0.52-1.00, P = .05), readmission (OR, 0.93; 95% CI, 0.66-1.32, P = .69), mortality in hospital (OR, 0.54; 95% CI, 0.29-1.01, P = .05), and length of hospital stay (MD, À0.24; 95% CI, À0.91-0.44, P = .49) compared with control in subjects after vascular surgery. The prophylactic negative pressure treatment subjects had a significantly lower surgical site wound infection and no significant difference in revision surgery, readmission, mortality in hospital, and length of hospital stay compared with control in subjects after vascular surgery. The analysis of outcomes should be with caution because of the low sample size of 2 out of 10 studies in the meta-analysis and a low number of studies in certain comparisons.
Purpose Astragaloside IV (AS-IV) is a natural saponin substance extracted from the plant Radix Astragali with anti-inflammatory, antioxidant, anti-apoptotic, and liver-protecting effects. This study was to evaluate the liver protection effect of AS-IV on mice after acute alcohol stimulation. Materials and Methods Mice were orally administrated with AS-IV (50, 150, and 500 mg/kg, respectively), and sodium carboxymethyl cellulose (CMC, 50 mg/kg) daily for 7 days, before giving five alcohol-intragastric injections. Results Results suggested that the levels of serum ALT and AST, liver SOD, GSH-PX, 4-HNE, and MDA, serum and liver TNF-α, IL-1β, and IL-6, serum lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP), diamine oxidase (DAO) and Myeloperoxidase (MPO), the mRNA and protein expression of hepatic NLRP3, Caspase-1, IL-1β, and IL-18 were significantly decreased in AS-IV-treated mice compared with the model group. Moreover, the effect of AS-IV on histopathology of liver tissue confirmed its protective function. Furthermore, AS-IV ameliorated the gut microbiota imbalance and adjusted the abundance of the following dysfunctional bacteria closer to the control group: Butyricicoccus , Turicibacter , Akkermansia , Anaerotruncus , and Mucispirillum . A strong correlation between intestinal bacteria and potential biomarkers was found. Conclusion Together, our findings indicated that AS-IV exert the hepatoprotective effect by modulating the gut microbiota imbalance and regulating NLRP3/Caspase-1 signaling pathway.
Purpose: The aim of this study was to investigate the risk of cardiovascular mortality (CVM) in patients with breast cancer (BC). Methods: Patients diagnosed with primary BC between 2010 and 2018 were identified through the Surveillance, Epidemiology and End Results (SEER) database. Standardized mortality rate (SMRs) for cardiovascular disease (CVD) were calculated to compare the CVM of BC patients with that of the general population. Multivariate competing risk models were performed to identify predictors of CVM in BC patients. Results: Overall, 399,014 BC patients were included from the SEER database, of whom 7023 (1.8%) suffered death from CVD. The significantly higher overall SMR of CVM was observed in BC patients (SMR = 4.84, 95% CI: 4.72–4.95). Multivariate competing risk regression analysis revealed age, sex, race, American Joint Committee on Cancer stage, year of diagnosis, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, BC subtype, surgery, and median household income as independent predictors of CVM in BC patients. Conclusions: Compared to the general population, BC patients have a higher risk of experiencing CVM during the follow-up period after diagnosis. Early detection and intervention of cardiovascular risk factors will improve overall survival of BC patients.
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