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Hydroxyurea for secondary stroke prevention in children with sickle cell anaemia: a systematic review of clinical evidence and outcomes
Aderinto, N., Olatunji, G., Kokori, E., Abdulbasit, M.
Annals of medicine and surgery (2012). 2024;86(2):1042-1047
Abstract
BACKGROUND Stroke remains one of the leading complications of sickle cell anaemia (SCA) in children. Traditionally, SCA treatment focused on symptom relief. However, the high incidence of strokes in children has prompted a reevaluation of treatment, particularly hydroxyurea, for secondary stroke prevention. This study assesses hydroxyurea's effectiveness and safety in preventing secondary strokes in paediatric SCA patients. METHODS This systematic review followed a pre-defined protocol registered with PROSPERO. Comprehensive searches were conducted across PubMed, Embase, Scopus, MEDLINE, Google Scholar, and the Cochrane Library up to August 2023. Studies were included involving paediatric SCA patients at risk of secondary stroke, assessing hydroxyurea as the primary intervention. RESULTS A total of six studies meeting inclusion criteria were included. The effectiveness of hydroxyurea in preventing secondary strokes, with variable responses reported across studies. Adverse effects, including mild neutropenia, are associated with hydroxyurea treatment but with variability in reported toxicity levels. CONCLUSION Hydroxyurea holds promise in preventing recurrent strokes in children with SCA, though its efficacy and safety profiles vary among individuals. Optimal dosages and treatment durations require further investigation, necessitating vigilant monitoring of haematological parameters. Future research should refine dosing strategies, consider individual patient characteristics, assess long-term effects, and explore ancillary benefits beyond stroke prevention.
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Long-term treatment with fostamatinib in Japanese patients with primary immune thrombocytopenia: An open-label extension study following a phase 3 placebo-controlled, double-blind, parallel-group study
Kuwana, M., Ito, T., Kowata, S., Hatta, Y., Fujimaki, K., Naito, K., Kurahashi, S., Kagoo, T., Tanimoto, K., Saotome, S., et al
American journal of hematology. 2024
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3.
Desmopressin to reduce periprocedural bleeding and transfusion: a systematic review and meta-analysis
Wang, C., Lebedeva, V., Yang, J., Anih, J., Park, L. J., Paczkowski, F., Roshanov, P. S.
Perioperative medicine (London, England). 2024;13(1):5
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Editor's Choice
Abstract
We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing surgery or other invasive procedures. We included 63 randomized trials (4163 participants) published up to February 1, 2023. Seven trials were published after a 2017 Cochrane systematic review on this topic. There were 38 trials in cardiac surgery, 22 in noncardiac surgery, and 3 in non-surgical procedures. Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95, 95% confidence interval [CI] 0.86 to 1.05) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75, 95% CI 0.47 to 1.19) when compared to placebo or usual care. However, we demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units, 95% CI - 0.94 to - 0.15), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI - 0.56 to - 0.23), and the risk of bleeding events (2 trials, RR 0.45, 95% CI 0.24 to 0.84). The certainty of evidence of these findings was generally low. Desmopressin increased the risk of clinically significant hypotension that required intervention (19 trials, RR 2.15, 95% CI 1.36 to 3.41). Limited evidence suggests that tranexamic acid is more effective than desmopressin in reducing transfusion risk (3 trials, RR 2.38 favoring tranexamic acid, 95% CI 1.06 to 5.39) and total volume of blood loss (3 trials, mean difference 391.7 mL favoring tranexamic acid, 95% CI - 93.3 to 876.7 mL). No trials directly informed the safety and hemostatic efficacy of desmopressin in advanced kidney disease. In conclusion, desmopressin likely reduces periprocedural blood loss and the number of units of blood transfused in small trials with methodologic limitations. However, the risk of hypotension needs to be mitigated. Large trials should evaluate desmopressin alongside tranexamic acid and enroll patients with advanced kidney disease.
PICO Summary
Population
Children or adults without known inherited bleeding disorders undergoing surgery or other invasive procedures (63 randomised controlled trials, n= 4,163).
Intervention
Desmopressin administered intravenously or subcutaneously before, during, or immediately after a surgical or interventional procedure.
Comparison
Placebo, usual care, or antifibrinolytic agents.
Outcome
Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95; 95% confidence interval (CI) [0.86, 1.05]) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75; 95% CI [0.47, 1.19]) when compared to placebo or usual care. However, the authors demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units; 95% CI [-0.94, -0.15]), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI [-0.56, -0.23]), and the risk of bleeding events (2 trials, RR 0.45; 95% CI [0.24, 0.84]). The certainty of evidence of these findings was generally low.
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Effect and Safety of Diluted Vasopressin Injection for Bleeding Control During Robot-assisted Laparoscopic Myomectomy in Reproductive Women With Uterine Fibroids: A Randomized Controlled Pilot Trial (VALENTINE Trial)
Park, S. J., Lee, J. W., Hwang, D. W., Lee, S., Yim, G. W., Song, G., Lee, E. J., Kim, H. S.
In vivo (Athens, Greece). 2024;38(1):431-436
Abstract
BACKGROUND/AIM: Vasopressin injected during myomectomy is known to effectively reduce bleeding but is sometimes associated with intraoperative vasoconstriction and hypertension due to systemic absorption. Although there is a growing preference for the use of diluted vasopressin, evidence of its effect and safety is still lacking. PATIENTS AND METHODS We performed a randomized controlled pilot trial to evaluate the effect and safety of vasopressin diluted in a constant volume during robot-assisted laparoscopic myomectomy (RALM), where a total of 39 women with uterine fibroids were randomly assigned into the following three groups (group 1, 0.2 IU/ml; group 2, 0.1 IU/ml; group 3, 0.05 IU/ml with a total of 100 ml of normal saline). The primary endpoint was to compare estimated blood loss (EBL), and the secondary endpoints were to compare postoperative value and drop ratio of hemoglobin, operation time, transfusion, hospitalization, and complications among the three groups. RESULTS There were no differences in the number and largest size of uterine fibroids, total weight of uterine fibroids, console time, and volumes of intravenous fluid administered during RALM among the three groups, whereas combined operation was performed more commonly in group 2 than in groups 1 and 3 (53.9% vs. 0 to 7.7%; p=0.01). The primary and secondary endpoints were also not different among the three groups. However, two patients in group 1 (15.4%) showed vasopressin-related hypertension. CONCLUSION Vasopressin diluted in a volume of 100 ml showed an effective hemostatic effect and safety during RALM (Trial No. NCT04874246 in ClinicalTrial.gov).
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The effect of injection of epinephrine 1:100,00 solution in pterygopalatine fossa on intraoperative bleeding during endoscopic sinonasal surgeries in chronic sinusitis: a blinded clinical trial
Nasirmohtaram, S., Jalali, M., Faghih Habibi, A., Akbarpour, M.
The Journal of laryngology and otology. 2024;:1-11
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Comparison of 1-day versus 3-day intravenous terlipressin in cirrhosis patients with variceal bleeding: A pilot randomised controlled trial
Vaishnav, M., Biswas, S., Shenoy, A., Pathak, P., Anand, A., Swaroop, S., Aggrawal, A., Arora, U., Elhence, A., Jagannath, S., et al
Alimentary pharmacology & therapeutics. 2024
Abstract
BACKGROUND In cirrhosis patients with acute variceal bleeding (AVB), the optimal duration of vasoconstrictor therapy after endoscopic haemostasis is unclear. AIMS We aimed to compare efficacy of 1-day versus 3-day terlipressin therapy in cirrhosis patients with AVB post-endoscopic intervention. The primary objective was to compare rebleeding at 5 days between the two arms. Secondary objectives included rebleeding and mortality rates at 6 weeks. METHODS In this open-label, randomised controlled trial, cirrhosis patients with AVB were randomised to either 1-day or 3-day terlipressin therapy. RESULTS A total of 150 cirrhosis patients with AVB were recruited to receive either 1 day (n = 75) or 3 days (n = 75) of terlipressin therapy. One patient from 1-day arm was excluded. Modified intention-to-treat analysis included 149 patients. Baseline characteristics were comparable between the two groups. Rebleeding at 5 days: 3 (4.1%; 95% confidence interval [CI]: 0.4-9.0) versus 4 (5.3%; 95% CI: 2.0-10.0), risk difference (RD) p = 0.726 and 5-day mortality rates: 1 (1.4%; 95% CI: 0-7.3) versus 1 (1.3%; 95% CI: 0.2-7.0), RD p = 0.960 were similar. Rebleeding at 42 days: 9 (12.2%; 95% CI: 7.0-20.0) versus 10 (13.3%; 95% CI: 7.0-20.0), RD p = 0.842 and mortality at 42 days: 5 (6.8%; 95% CI: 3.0-10.0) versus 4 (5.3%; 95% CI: 2.0-10.0), RD p = 0.704 were also similar. Patients in the 1-day terlipressin therapy arm experienced significantly fewer adverse effects compared with those receiving 3 days of terlipressin therapy: 28 (37.8%) versus 42 (56%), p = 0.026. CONCLUSIONS Our results suggest that 1 day of terlipressin therapy is associated with similar 5-day and 42-day rebleeding rates, 42-day mortality and an overall superior safety profile compared with 3-day of terlipressin therapy. These findings require to be validated in double-blinded, larger, multiethnic and multicentre studies across the various stages of cirrhosis (CTRI/2019/10/021771).
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Preventing postpartum hemorrhage: A network meta-analysis on routes of administration of uterotonics
Papadopoulou, A., Tournas, G., Georgiopoulos, G., Antsaklis, P., Daskalakis, G., Coomarasamy, A., Devall, A. J.
European journal of obstetrics, gynecology, and reproductive biology. 2024;295:172-180
Abstract
1. OBJECTIVE To perform a network meta-analysis to specify the route of administration that maximises the effectiveness of each of the available prophylactic uterotonics without increasing the risk for side effects. 2. DATA SOURCES Literature searches on 12th September 2022 included: CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. The reference lists of the retrieved study records were also searched. 3. STUDY ELIGIBILITY CRITERIA Population: Randomized controlled trials involving women in the third stage of labour after a vaginal or caesarean delivery in hospital or community settings. INTERVENTIONS Systemically administered prophylactic uterotonics of any route and dose for primary postpartum hemorrhage prevention. Comparison: Any other prophylactic uterotonic, or a different route or dose of a given uterotonic, or placebo, or no treatment. Outcomes (primary): postpartum hemorrhage ≥ 500 mL and ≥ 1000 mL. 4. STUDY APPRAISAL AND SYNTHESIS METHODS Risk of bias and trustworthiness assessments were performed, according to Cochrane's guidance. Direct, indirect and network meta-analyses were conducted, and results were summarized either as risk ratio or mean difference with 95% confidence intervals for dichotomous and continuous outcomes, respectively. The certainty of generated evidence was assessed according to the GRADE approach. Cumulative probabilities were calculated and the surface under the cumulative ranking curve was used to create a ranking of the available drugs. 5. RESULTS One hundred eighty-one studies involving 122,867 randomised women were included. Most studies were conducted in hospital settings in lower-middle income countries and involved women delivering vaginally. When compared with intramuscular oxytocin, carbetocin (RR 0.58, 95 % CI 0.40-0.84) and oxytocin (RR 0.75, 95 % CI 0.59-0.97) by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination (RR 0.71, 95 % CI 0.56-0.91) are probably more effective in preventing primary postpartum hemorrhage. Intramuscularly administered oxytocin and carbetocin by an intravenous bolus have a favourable side effects profile. 6. CONCLUSIONS Generated evidence was generally moderate and global inconsistency was low. Carbetocin and oxytocin by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination are probably the top uterotonics for primary postpartum hemorrhage prevention. Large scale studies exploring different routes of administration for available prophylactic uterotonics, and women's views should be conducted.
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Low-Dose Elagolix for the Treatment of Heavy Menstrual Bleeding in Patients With Uterine Leiomyomas: A Randomized Controlled Trial
Brown, E., Kroll, R., Li, H., Ng, J., Pinsky, B., Rodriguez, J. W., Thomas, J., Snabes, M. C.
Obstetrics and gynecology. 2023
Abstract
OBJECTIVE To evaluate the safety and efficacy of elagolix 150 mg once-daily monotherapy in patients with heavy menstrual bleeding associated with uterine leiomyomas. METHODS A phase 4, randomized, double-blind, placebo-controlled, 6-month treatment study was conducted in premenopausal patients aged 18-51 years with heavy menstrual bleeding (defined as menstrual blood loss greater than 80 mL during one menstrual cycle) associated with uterine leiomyomas. Patients were randomized 2:1 to receive elagolix 150 mg once daily or placebo. The primary endpoint was reduction in menstrual blood loss volume to less than 80 mL at the final month and at least a 50% reduction in menstrual blood loss volume from baseline to the final month. RESULTS Of 82 randomized patients, 54 received elagolix 150 mg and 28 received placebo. With elagolix, 49.4% (95% CI 35.1-63.8%) of patients met the primary endpoint, compared with 23.3% (95% CI 7.2-39.5%) of patients who received placebo (P=.035). Statistically significant differences between elagolix and placebo in mean reduction of menstrual blood loss from baseline were seen as early as month 1 (P<.05 for months 1-3 and 5). Significantly more patients receiving elagolix experienced suppression of bleeding compared with placebo (P=.036). Greater improvements were observed in the elagolix group (vs placebo) in the proportion of patients with amenorrhea, in hemoglobin concentrations, and in health-related quality of life. No serious or severe adverse events were reported for elagolix, compared with 7.1% of participants in the placebo group having serious adverse events (coronavirus disease 2019 [COVID-19] n=1, enlarged uvula n=1). Three patients (5.6%) discontinued elagolix due to adverse events. CONCLUSION Elagolix 150 mg once-daily monotherapy significantly improved heavy menstrual bleeding associated with uterine leiomyomas compared with placebo in premenopausal patients. Treatment with elagolix 150 mg once daily was generally well-tolerated in this study, with no new safety signals. FUNDING SOURCE AbbVie Inc. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03886220.
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Hemodynamic Effects of Oxytocin and Carbetocin During Elective Cesarean Section in Preeclamptic Patients Under Spinal Anesthesia: A Randomized Double-blind Controlled Study
Bahr, M. H., Abdelaal Ahmed Mahmoud, M. Alkhatip A., Ahmed, A. G., Elgamel, A. F., Abdelkader, M., Hussein, H. A.
Anesthesiology and pain medicine. 2023;13(1):e128782
Abstract
BACKGROUND Oxytocin and carbetocin are uterotonic medications that are used to decrease postpartum hemorrhage (PPH). However, there are not enough clinical data about the hemodynamic side effects of carbetocin. OBJECTIVES This study aimed to compare carbetocin and oxytocin hemodynamic effects in preeclamptic patients undergoing elective cesarean section under spinal anesthesia. METHODS In this double-blind, randomized controlled trial, intravenous oxytocin or carbetocin was administered to 80 women (40 per group). The hemodynamic effects, such as blood pressure (BP), heart rate (HR), and oxygen (O(2)) saturation, were measured before the operation and after 1, 5, 10, and 15 minutes of the administration of both drugs. Intragroup and intergroup comparisons were conducted during statistical analysis. RESULTS Based on the intragroup comparison, there was a significant increase in HR and a reduction in BP from baseline to all intervals after the administration of both interventions. Moreover, based on the intergroup comparison, there was a significantly more increase in HR and a decline in BP and O(2) saturation in the oxytocin group than in the carbetocin group. There were three and seven cases that required another dose of carbetocin and oxytocin, respectively. Moreover, one case developed PPH in the carbetocin group; nevertheless, two cases developed PPH in the oxytocin group. CONCLUSIONS The minimal effect of carbetocin on patients' hemodynamics suggests extending the use of this drug instead of oxytocin as a uterotonic drug in patients with preeclampsia, hemorrhagic risk factors, and/or hypertension.
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10.
Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage
Adão, D., Gois, A. F., Pacheco, R. L., Pimentel, C. F., Riera, R.
The Cochrane Database of Systematic Reviews. 2023;2(2):Cd013176
Abstract
BACKGROUND Upper endoscopy is the definitive treatment for upper gastrointestinal haemorrhage (UGIH). However, up to 13% of people who undergo upper endoscopy will have incomplete visualisation of the gastric mucosa at presentation. Erythromycin acts as a motilin receptor agonist in the upper gastrointestinal (GI) tract and increases gastric emptying, which may lead to better quality of visualisation and improved treatment effectiveness. However, there is uncertainty about the benefits and harms of erythromycin in UGIH. OBJECTIVES To evaluate the benefits and harms of erythromycin before endoscopy in adults with acute upper gastrointestinal haemorrhage, compared with any other treatment or no treatment/placebo. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search date was 15 October 2021. SELECTION CRITERIA We included randomised controlled trials (RCTs) that investigated erythromycin before endoscopy compared to any other treatment or no treatment/placebo before endoscopy in adults with acute UGIH. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were 1. UGIH-related mortality and 2. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. visualisation of gastric mucosa, 3. non-serious adverse events, 4. rebleeding, 5. blood transfusion, and 5. rescue invasive intervention. We used GRADE criteria to assess the certainty of the evidence for each outcome. MAIN RESULTS We included 11 RCTs with 878 participants. The mean age ranged from 53.13 years to 64.5 years, and most participants were men (72.3%). One RCT included only non-variceal haemorrhage, one included only variceal haemorrhage, and eight included both aetiologies. We defined short-term outcomes as those occurring within one week of initial endoscopy. Erythromycin versus placebo Three RCTs (255 participants) compared erythromycin with placebo. There were no UGIH-related deaths. The evidence is very uncertain about the short-term effects of erythromycin compared with placebo on serious adverse events (risk difference (RD) -0.01, 95% confidence interval (CI) -0.04 to 0.02; 3 studies, 255 participants; very low certainty), all-cause mortality (RD 0.00, 95% CI -0.03 to 0.03; 3 studies, 255 participants; very low certainty), non-serious adverse events (RD 0.01, 95% CI -0.03 to 0.05; 3 studies, 255 participants; very low certainty), and rebleeding (risk ratio (RR) 0.63, 95% CI 0.13 to 2.90; 2 studies, 195 participants; very low certainty). Erythromycin may improve gastric mucosa visualisation (mean difference (MD) 3.63 points on 16-point ordinal scale, 95% CI 2.20 to 5.05; higher MD means better visualisation; 2 studies, 195 participants; low certainty). Erythromycin may also result in a slight reduction in blood transfusion (MD -0.44 standard units of blood, 95% CI -0.86 to -0.01; 3 studies, 255 participants; low certainty). Erythromycin plus nasogastric tube lavage versus no intervention/placebo plus nasogastric tube lavage Six RCTs (408 participants) compared erythromycin plus nasogastric tube lavage with no intervention/placebo plus nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin plus nasogastric tube lavage compared with no intervention/placebo plus nasogastric tube lavage on all-cause mortality (RD -0.02, 95% CI -0.08 to 0.03; 3 studies, 238 participants; very low certainty), visualisation of the gastric mucosa (standardised mean difference (SMD) 0.48 points on 10-point ordinal scale, 95% CI 0.10 to 0.85; higher SMD means better visualisation; 3 studies, 170 participants; very low certainty), non-serious adverse events (RD 0.00, 95% CI -0.05 to 0.05; 6 studies, 408 participants; very low certainty), rebleeding (RR 1.13, 95% CI 0.63 to 2.02; 1 study, 169 participants; very low certainty), and blood transfusion (MD -1.85 standard units of blood, 95% CI -4.34 to 0.64; 3 studies, 180 participants; very low certainty). Erythromycin versus nasogastric tube lavage Four RCTs (287 participants) compared erythromycin with nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin compared with nasogastric tube lavage on all-cause mortality (RD 0.02, 95% CI -0.05 to 0.08; 3 studies, 213 participants; very low certainty), visualisation of the gastric mucosa (RR 1.19, 95% CI 0.79 to 1.79; 2 studies, 198 participants; very low certainty), non-serious adverse events (RD -0.10, 95% CI -0.34 to 0.13; 3 studies, 213 participants; very low certainty), rebleeding (RR 0.77, 95% CI 0.40 to 1.49; 1 study, 169 participants; very low certainty), and blood transfusion (median 2 standard units of blood, interquartile range 0 to 4 in both groups; 1 study, 169 participants; very low certainty). Erythromycin plus nasogastric tube lavage versus metoclopramide plus nasogastric tube lavage One RCT (30 participants) compared erythromycin plus nasogastric tube lavage with metoclopramide plus nasogastric tube lavage. The evidence is very uncertain about the effects of erythromycin plus nasogastric tube lavage on all the reported outcomes (serious adverse events, visualisation of gastric mucosa, non-serious adverse events, and blood transfusion). AUTHORS' CONCLUSIONS We are unsure if erythromycin before endoscopy in people with UGIH has any clinical benefits or harms. However, erythromycin compared with placebo may improve gastric mucosa visualisation and result in a slight reduction in blood transfusion.