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1.
Cost-Effectiveness of Thrombopoietin Mimetics in Patients with Thrombocytopenia: A Systematic Review
Van Remoortel H, Scheers H, Avau B, Georgsen J, Nahirniak S, Shehata N, Stanworth SJ, De Buck E, Compernolle V, Vandekerckhove P
PharmacoEconomics. 2023
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Full text
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Editor's Choice
Abstract
OBJECTIVES Thrombopoietin (TPO) mimetics are a potential alternative to platelet transfusion to minimize blood loss in patients with thrombocytopenia. This systematic review aimed to evaluate the cost-effectiveness of TPO mimetics, compared with not using TPO mimetics, in adult patients with thrombocytopenia. METHODS Eight databases and registries were searched for full economic evaluations (EEs) and randomized controlled trials (RCTs). Incremental cost-effectiveness ratios (ICERs) were synthesized as cost per quality-adjusted life year gained (QALY) or as cost per health outcome (e.g. bleeding event avoided). Included studies were critically appraised using the Philips reporting checklist. RESULTS Eighteen evaluations from nine different countries were included, evaluating the cost-effectiveness of TPO mimetics compared with no TPO, watch-and-rescue therapy, the standard of care, rituximab, splenectomy or platelet transfusion. ICERs varied from a dominant strategy (i.e. cost-saving and more effective), to an incremental cost per QALY/health outcome of EUR 25,000-50,000, EUR 75,000-750,000 and EUR > 1 million, to a dominated strategy (cost-increasing and less effective). Few evaluations (n = 2, 10%) addressed the four principal types of uncertainty (methodological, structural, heterogeneity and parameter). Parameter uncertainty was most frequently reported (80%), followed by heterogeneity (45%), structural uncertainty (43%) and methodological uncertainty (28%). CONCLUSIONS Cost-effectiveness of TPO mimetics in adult patients with thrombocytopenia ranged from a dominant strategy to a significant incremental cost per QALY/health outcome or a strategy that is clinically inferior and has increased costs. Future validation and tackling the uncertainty of these models with country-specific cost data and up-to-date efficacy and safety data are needed to increase the generalizability.
PICO Summary
Population
Adult patients with thrombocytopenia (18 full economic evaluations).
Intervention
Thrombopoietin mimetics.
Comparison
No thrombopoietin mimetics, watch-and-rescue therapy, standard of care, rituximab, splenectomy or platelet transfusion.
Outcome
Incremental cost-effectiveness ratios varied from a dominant strategy (cost-saving and more effective), to an incremental cost per quality-adjusted life year gained/health outcome of EUR 25,000-50,000, EUR 75,000-750,000 and EUR > 1 million, to a dominated strategy (cost-increasing and less effective). Few evaluations (n= 2, 10%) addressed the four principal types of uncertainty (methodological, structural, heterogeneity and parameter). Parameter uncertainty was most frequently reported (80%), followed by heterogeneity (45%), structural uncertainty (43%) and methodological uncertainty (28%).
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Prophylactic and therapeutic strategies for intraoperative bleeding in women with von Willebrand disease and heavy menstrual bleeding: A systematic review
Eising, H. P., Punt, M. C., Leemans, J. C., Bongers, M. Y.
Blood reviews. 2023;:101131
Abstract
BACKGROUND Optimal peri-operative management for women with Von Willebrand disease (VWD) and heavy menstrual bleeding (HMB) remains undetermined. AIM AND METHODS To evaluate (pre)operative management in relation to (post)operative bleeding after endometrial ablation (EA) and hysterectomy in VWD women with HMB by performing a database search between 1994 and 2023. RESULTS Eleven cohort studies and 1 case-report were included, of overall 'low' quality, describing 691 operative procedures. Prophylaxis (Desmopressin, clotting factor concentrates or tranexamic acid) to prevent bleeding was described in 100% (30/30) of EA procedures and in 4% (24/661) of hysterectomies. Bleeding complications despite prophylaxis were described in 13% (3/24) of hysterectomies vs 0% (0/30) in EA. CONCLUSION VWD women often seem to experience bleeding complications during hysterectomy and all women with VWD received preprocedural hemostatic agents during EA, indicating potential under- and overdosing of current prophylactic strategies. Prospective studies are needed to determine the optimal (pre)operative strategy for gynecological surgical procedures in women with VWD.
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Palliative Radiotherapy for Haemostasis in Malignancy: a Systematic Review
Song, J., Brown, C., Dennis, K., Gaudet, M., Haddad, A.
Clinical oncology (Royal College of Radiologists (Great Britain)). 2023
Abstract
AIMS: Palliative radiotherapy is commonly used to achieve haemostasis for malignancy-induced haemorrhages. Our study aimed to examine the efficacy of palliative radiotherapy in the control of haemorrhages caused by various types of malignancy. MATERIALS AND METHODS A systematic review of the literature was conducted to determine the level of evidence for the use of palliative radiotherapy in achieving haemostasis. Searches of the Medline, Embase and Cochrane databases were completed for studies published between January 1947 and May 2017. Studies that reported either a qualitative or a quantitative effect of radiotherapy were selected for inclusion during the review process. RESULTS In total, 836 abstracts were screened; 13 prospective and 45 retrospective studies met the criteria for inclusion in the review. Selected studies were sorted based on the underlying tumour type to provide readers the opportunity to compare dose and fractionation schedules. Significant variations in reporting of outcomes and low total patient numbers did not allow for a quantitative analysis to be carried out. A higher median dose and a hypofractionated schedule seem to provide numerically higher rates of control based on the available data. CONCLUSIONS Palliative radiotherapy is useful in the management of bleeding related to advanced and incurable malignancies. Brachytherapy seems to be effective in haemostasis of certain malignancies, especially that of gynaecological origin. Treatment should be tailored to individual patient situations given the palliative goals of any such therapy. Further prospective studies could help to delineate optimal dose and fractionation schedules.
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Oxidized Regenerated Cellulose Versus Calcium Alginate in Controlling Bleeding From Malignant Wounds: A Randomized Controlled Trial
Firmino F, Villela-Castro D, Santos Vlcg
Cancer nursing. 2023
Abstract
BACKGROUND There is no consensus on the best intervention for topical management of bleeding in malignant wounds. Although surgical hemostatic dressings are recommended, the use of calcium alginate (CA) is frequent among practitioners. OBJECTIVE The aim of this study was to evaluate the hemostatic efficacy of oxidized regenerated cellulose (ORC) and CA dressing in the management of bleeding from malignant wounds resulting from breast cancer. METHODS This was a randomized open clinical trial. The outcomes measured were total time to hemostasis and the number of hemostatic products used. RESULTS Sixty-one patients were potentially eligible for the study, 1 did not consent, and 32 were assessed to be ineligible, resulting in a sample of 28 who were randomized to 2 study groups. Total time to hemostasis was 93.8 seconds in the ORC group, with an average of 30.1 seconds (95% confidence interval, 18.6-189 seconds), and 67 seconds in the CA group, with an average of 30.4 seconds (confidence interval, 21.7 seconds to imprecise upper limit). The main difference was 26.8 seconds. Kaplan-Meier log-rank test, and Cox model showed no statistical significance (P = 0.894). A total of 18 hemostatic products were used in the CA group and 34 in the ORC group. No adverse effects were identified. CONCLUSIONS Although no significant differences were identified in terms of time, more hemostatic products were used in the ORC group, highlighting the effectiveness of CA. IMPLICATIONS FOR PRACTICE Calcium alginate may be the first choice in the management of bleeding in malignant wounds, favoring nursing in the most immediate hemostatic actions.
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Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A/B): a multicentre, open-label, randomised, phase 3 trial
Srivastava A, Rangarajan S, Kavakli K, Klamroth R, Kenet G, Khoo L, You CW, Xu W, Malan N, Frenzel L, et al
The Lancet. Haematology. 2023
Abstract
BACKGROUND Fitusiran, a subcutaneous investigational siRNA therapeutic, targets antithrombin with the goal of rebalancing haemostasis in people with haemophilia A or haemophilia B, regardless of inhibitor status. We aimed to evaluate the efficacy and safety of fitusiran prophylaxis in people with severe haemophilia without inhibitors. METHODS This multicentre, open-label, randomised phase 3 study was conducted at 45 sites in 17 countries. Male participants aged at least 12 years with severe haemophilia A or B without inhibitors, who had previously been treated on-demand with clotting factor concentrates, were randomly assigned in a 2:1 ratio to receive 80 mg subcutaneous fitusiran prophylaxis once per month or to continue on-demand clotting factor concentrates for a total of 9 months. Randomisation was stratified by the number of bleeding events in the 6 months before screening (≤10 bleeds and >10 bleeds) and by haemophilia type (haemophilia A or B). The primary endpoint was annualised bleeding rate, analysed in the intention-to-treat analysis set. Safety and tolerability were assessed in the safety analysis set. This trial is registered with ClinicalTrials.gov, NCT03417245, and is complete. FINDINGS Between March 1, 2018, and July 14, 2021, 177 male participants were screened for eligibility and 120 were randomly assigned to receive fitusiran prophylaxis (n=80) or on-demand clotting factor concentrates (n=40). Median follow-up was 7·8 months (IQR 7·8-7·8) in the fitusiran group and 7·8 months (7·8-7·8) in the on-demand clotting factor concentrates group. The median annualised bleeding rate was 0·0 (0·0-3·4) in the fitusiran group and 21·8 (8·4-41·0) in the on-demand clotting factor concentrates group. The estimated mean annualised bleeding rate was significantly lower in the fitusiran prophylaxis group (3·1 [95% CI 2·3-4·3]) than in the on-demand clotting factor concentrates group (31·0 [21·1-45·5]; rate ratio 0·101 [95% CI 0·064-0·159]; p<0·0001). In the fitusiran group, 40 (51%) of 79 treated participants had no treated bleeds compared with two (5%) of 40 participants in the on-demand clotting factor concentrates group. Increased alanine aminotransferase concentration (18 [23%] of 79 participants in the safety analysis set) was the most common treatment-emergent adverse event in the fitusiran group and hypertension (four (10%) of 40 participants) was the most common in the on-demand clotting factor concentrates group. Treatment-emergent serious adverse events were reported in five (6%) participants in the fitusiran group (cholelithiasis [n=2, 3%], cholecystitis [n=1, 1%], lower respiratory tract infection [n=1, 1%], and asthma [n=1, 1%]) and five (13%) participants in the on-demand clotting factor concentrates group (gastroenteritis, pneumonia, suicidal ideation, diplopia, osteoarthritis, epidural haemorrhage, humerus fracture, subdural haemorrhage, and tibia fracture [all n=1, 3%]). No treatment-related thrombosis or deaths were reported. INTERPRETATION In participants with haemophilia A or B without inhibitors, fitusiran prophylaxis resulted in significant reductions in annualised bleeding rate compared with on-demand clotting factor concentrates and no bleeding events in approximately half of participants. Fitusiran prophylaxis shows haemostatic efficacy in both haemophilia A and haemophilia B, and therefore has the potential to be transformative in the management of all people with haemophilia. FUNDING Sanofi.
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Prostate Artery Embolization in the Treatment of Massive Intractable Bleeding from Prostatic Neoplasms: A Case Report and Systematic Review
Moramarco, L., Grande, A. M., Vertemati, M., Aseni, P.
Journal of clinical medicine. 2023;13(1)
Abstract
Lower urinary tract symptoms (LUTS) and hematuria are common symptoms in men with neoplasms, mainly affecting the elderly population. Prostatic arterial embolization (PAE) is a minimally invasive procedure that has shown promising results in managing LUTS and massive intractable prostatic hematuria in patients with benign prostatic hyperplasia (BPH) and prostate cancer (PCa). A few studies, however, have provided valuable insights into the durability and efficacy of PAE focusing on the long-term effectiveness, quality of life, and cancer-specific control of hemostasis and urinary symptoms. As a result of concomitant cardiovascular conditions, these patients often take anticoagulants or antithrombotics, which can worsen their hematuria and clinical status. Transurethral resection of the prostate (TURP) is considered a very high-risk procedure, even without massive bleeding, and requires discontinuation of vitamin K antagonists and antiplatelet therapies. Such patients usually have their surgery postponed, and PAE should be considered a safe alternative treatment. We aimed to report a narrative review from 1976 to June 2023 of the current state of PAE for massive and intractable hematuria, highlighting recent developments in this technique, including prospective cohort studies, and focusing on long-term outcome, safety, and complication management of patients with prostatic neoplasms who develop significant hemorrhagic symptoms. Additionally, we present a case report and a simple algorithm for treating intractable bleeding in a 92-year-old man with PCa and massive hematuria.
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Efficacy and safety of gastroscopic hemostasis in the treatment of acute gastric hemorrhage: A meta-analysis
Pan, H. Y., Wang, X. W., He, Q. X., Lu, Y. D., Zhang, W. Y., Jin, J. W., Lin, B.
World journal of gastrointestinal oncology. 2023;15(11):1988-1997
Abstract
BACKGROUND Gastric cancer (GC) is a malignant tumor with a high incidence and mortality rate worldwide for which acute bleeding is a common clinical complication. Gastroscopic hemostasis is an important method for treating acute bleeding in GC; however, its efficacy and safety remain controversial. AIM: To systematically analyze the efficacy and safety of gastroscopic hemostasis for the treatment of acute gastric hemorrhage. METHODS The PUBMED, Web of Science, Wiley Library, EMBASE, Wanfang, CNKI, and VIP databases were searched for studies related to gastroscopic hemostatic treatment for acute GC published through February 20, 2023. The literature was screened according to the inclusion and exclusion criteria, data were extracted, and literature quality was evaluated. The meta-analysis was performed using RevMan software (version 5.3), while Begg's test for publication bias was performed using Stata 13.0 software. RESULTS Six randomized controlled trials and two retrospective analyses were retrieved. Five studies had a low, two had an uncertain, and one had a high risk of bias. Compared with the control group, the hemostatic rate of gastroscopic hemostasis was increased [relative risk (RR) = 1.24; 95% confidence interval (CI): 1.08 to 1.43; P = 0.003]; the rate of rebleeding (RR = 0.27; 95%CI: 0.09 to 0.80; P = 0.02), rate of surgery transfer (RR = 0.16; 95%CI: 0.06 to 0.43; P = 0.0003), serum C-reactive protein level [mean difference (MD) = -5.16; 95%CI: -6.11 to 4.21; P < 0.00001], interleukin-6 level (MD = -6.37; 95%CI: -10.33 to -2.42; P = 0.002), and tumor necrosis factor-α level (MD = -2.29; 95%CI: -4.06 to -0.52; P = 0.01) were decreased; and the quality of life improvement rate was increased (RR = 1.95; 95%C I= 1.41-2.71; P < 0.0001). Begg's test revealed no significant publication bias. CONCLUSION The efficacy and safety of endoscopic hemostasis were higher than those of the control group, suggesting that it is an effective treatment for acute GC hemorrhage.
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TC-325 hemostatic powder in the management of upper gastrointestinal malignant bleeding: a randomized controlled trial
Martins BC, Abnader Machado A, Scomparin RC, Paulo GA, Safatle-Ribeiro A, Naschold Geiger S, Lenz L, Lima MS, Pennacchi C, Ribeiro U, et al
Endoscopy international open. 2022;10(10):E1350-e1357
Abstract
Background and study aims Upper gastrointestinal bleeding (UGIB) from malignancy is associated with high rebleeding and mortality rates. Recently, TC-325 powder has shown promising results in the treatment of UGIB, including malignant bleeding. The aim of this study was to compare the efficacy of TC-325 versus best clinical management. Patients and methods From August 2016 to February 2020, all patients with evidence of UGIB from malignancy were randomized to receive TC-325 therapy or control group, in which endoscopic treatment was not mandatory. Exclusion criteria were hemoglobin drop without overt bleeding and UGIB from non-tumor origin. The primary outcome was 30-day mortality. Secondary outcomes were 30-day rebleeding, blood transfusion and length of hospital stay. Results Sixty-two patients were randomized, three were excluded and 59 were included in the final analysis (TC-325 group = 28; control = 31). Groups were similar at baseline. Active bleeding was observed in 22 patients in the TC-325 group and 19 in the control group ( P = 0.15). Successful initial hemostasis with TC-325 was achieved in all cases. Additional therapy (radiotherapy, surgery or arterial embolization) was equally performed in both groups (42.9 % vs 58.1 %; P = 0.243). There were no differences in 30-day mortality (28.6 % vs. 19.4 %, P = 0.406) or 30-day rebleeding rates (32.1 % vs. 19.4 %, P = 0.26). Logistic regression identified no significant predictors of rebleeding. Age, Eastern Cooperative Oncology Group (ECOG) score 3 to 4 and AIMS65 score > 1 predicted greater mortality. Conclusions TC-325 was effective in achieving immediate hemostasis in malignant gastrointestinal bleeding but did not reduce 30-day mortality, 30-day rebleeding, blood transfusion or length of hospital stay. Age, ECOG 3-4, and AIMS65 > 1 were predictive factors of mortality.
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9.
TIMolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (TIM-HHT)-A Prospective, Randomized, Double-Blind, Controlled, Cross-Over Trial
Andorfer KEC, Zeman F, Koller M, Zeller J, Fischer R, Seebauer CT, Vielsmeier V, Bohr C, Kühnel TS
Pharmaceutics. 2022;14(11)
Abstract
To date, there is no approved local therapeutic agent for the treatment of epistaxis due to hereditary hemorrhagic telangiectasia (HHT). Several case reports suggest the topical use of timolol. This monocentric, prospective, randomized, placebo-controlled, double-blinded, cross-over study investigated whether the effectiveness of the standard treatment with a pulsed diode laser can be increased by also using timolol nasal spray. The primary outcome was severity of epistaxis after three months, while the main secondary outcome was severity of epistaxis and subjective satisfaction after one month. Twenty patients were allocated and treated, of which 18 patients completed both 3-month treatment sequences. Timolol was well tolerated by all patients. Epistaxis Severity Score after three months, the primary outcome measure, showed a beneficial, but statistically nonsignificant (p = 0.084), effect of additional timolol application. Epistaxis Severity Score (p = 0.010) and patients' satisfaction with their nosebleeds after one month (p = 0.050) showed statistically significant benefits. This placebo-controlled, randomized trial provides some evidence that timolol nasal spray positively impacts epistaxis severity and subjective satisfaction in HHT patients when additively applied to standard laser therapy after one month. However, the effect of timolol was observed to diminish over time. Trials with larger sample sizes are warranted to confirm these findings.
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10.
Efficacy of topical hemostatic agents in malignancy-related gastrointestinal bleeding: a systematic review and meta-analysis
Karna R, Deliwala S, Ramgopal B, Mohan BP, Kassab L, Becq A, Dhawan M, Adler DG
Gastrointestinal endoscopy. 2022
Abstract
BACKGROUND AND AIMS Despite advances in endoscopic therapies, malignancy-related gastrointestinal (GI) bleeding remains difficult to manage with high rates of treatment failure and rebleeding. Topical hemostatic agents (THA) are easier to apply to the wide bleeding surface of tumors. We conducted this systematic review and meta-analysis to evaluate the efficacy of THAs in malignancy-related GI bleed. METHODS We conducted a comprehensive search of multiple electronic databases to identify studies reporting on the use of THAs in malignancy-related GI bleeding. The primary outcome was the achievement of hemostasis; secondary outcomes were early rebleeding (≤ 3 days), delayed rebleeding (>3 days), aggregate rebleeding, all-cause mortality, and GI bleed related mortality. A meta-analysis of proportions was done for all outcomes. RESULTS Out of 355 citations, total 16 studies with 530 patients were included. Primary hemostasis was achieved in 94.1% (95% CI: 91.5 - 96.0%). Early rebleeding was seen in 13.9% (95% CI: 9.7 - 19.4%) while delayed rebleeding was seen in 11.4% (95% CI: 5.8 - 21.1%). Aggregate rebleeding was seen in 24.2% (95% CI:18.5 - 31.0%). All-cause mortality was 33.1% (95% CI: 23.7 - 44.0%) while GI bleed related mortality occurred in 5.9% (95% CI: 2.2% - 14.8%). CONCLUSIONS THAs are highly effective for achieving primary hemostasis in malignancy-related GI bleeding. It should be considered as an alternative to traditional endotherapy methods in malignancy-related GI bleeds. Future studies should be designed to evaluate its efficacy and safety as a primary method of hemostasis as compared to traditional endotherapy measures.