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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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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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Orthopedic surgery in hemophilic patients with musculoskeletal disorders: A systematic review
Badulescu OV, Sirbu PD, Ungureanu C, Pȋnzariu A, Cojocaru E, Filip N, Bararu-Bojan I, Vladeanu M, Ciocoiu M
Experimental and therapeutic medicine. 2021;22(3):995
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Abstract
Hemophilia is a hereditary coagulopathy caused by factor VIII (hemophilia type A) or by coagulation factor IX (hemophilia type B) dysfunction, characterized by an increased bleeding predisposition, which is either spontaneous or secondary to minimal trauma. Currently, hemophilia may also be considered an 'orthopedic' condition, due to the fact that it affects the musculoskeletal system of most hemophilic patients. In recent years, constant prophylaxis using coagulation factors has led to a significant improvement in the hemophilic patient's quality of life, by reducing both life-threatening hemorrhagic phenomena, as well as the occurrence of chronic complications. Nevertheless, progressive joint bleeding remains unavoidable in this category of patients, and the onset of chronic arthropathy with secondary motor deficiency remains the main complication with an invalidating character. In such cases, orthopedic management is imperative; osteoarticular complications being managed most often with the help of conservative or surgical techniques. The purpose of this review is to provide an overview of modern orthopedic practices which are useful in the management of hemophilic patients suffering from osteoarticular disorders.
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Efficacy and Safety of a 0.1% Tacrolimus Nasal Ointment as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial
Dupuis-Girod S, Fargeton AE, Grobost V, Riviere S, Beaudoin M, Decullier E, Bernard L, Breant V, Colombet B, Philouze P, et al
J Clin Med. 2020;9(5)
Abstract
Hereditary hemorrhagic telangiectasia is a rare but ubiquitous genetic disease. Epistaxis is the most frequent and life-threatening manifestation and tacrolimus, an immunosuppressive agent, appears to be an interesting new treatment option because of its anti-angiogenic properties. Our objective was to evaluate, six weeks after the end of the treatment, the efficacy on the duration of nosebleeds of tacrolimus nasal ointment, administered for six weeks to patients with hereditary hemorrhagic telangiectasia complicated by nosebleeds, and we performed a prospective, multicenter, randomized, placebo-controlled, double-blinded, ratio 1:1 phase II study. Patients were recruited from three French Hereditary Hemorrhagic Telangiectasia (HHT) centers between May 2017 and August 2018, with a six-week follow-up, and we included people aged over 18 years, diagnosed with hereditary hemorrhagic telangiectasia and epistaxis (total duration > 30 min/6 weeks prior to inclusion). Tacrolimus ointment 0.1% was self-administered by the patients twice daily. About 0.1 g of product was to be administered in each nostril with a cotton swab. A total of 50 patients was randomized and treated. Mean epistaxis duration before and after treatment in the tacrolimus group were 324.64 and 249.14 min, respectively, and in the placebo group 224.69 and 188.14 min, respectively. Epistaxis duration improved in both groups, with no significant difference in our main objective comparing epistaxis before and after treatment (p = 0.77); however, there was a significant difference in evolution when comparing epistaxis before and during treatment (p = 0.04). Toxicity was low and no severe adverse events were reported. In conclusion, tacrolimus nasal ointment, administered for six weeks, did not improve epistaxis in HHT patients after the end of the treatment. However, the good tolerance, associated with a significant improvement in epistaxis duration during treatment, encouraged us to perform a phase 3 trial on a larger patient population with a main outcome of epistaxis duration during treatment and a longer treatment time.
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Hydroxycarbamide exposure and ovarian reserve in women with sickle cell disease in the Multicenter Study of Hydroxycarbamide
Pecker LH, Hussain S, Christianson MS, Lanzkron S
Br J Haematol. 2020
Abstract
The application of modern ovarian reserve measures to women with sickle cell disease (SCD) may help answer longstanding questions about whether SCD or hydroxycarbamide (HC; also known as hydroxyurea) affect women's reproductive lifespan. Anti-Müllerian hormone (AMH), an established marker of ovarian reserve, is used to assess the ovarian follicle pool. We used a standard clinical assay to measure AMH in 285 banked samples from 93 female subjects with haemoglobin SS from the historic Multicenter Study of Hydroxyurea (MSH), which led to the United States Food and Drug Administration approval of HC for adults with SCD. No samples from the randomised portion of the MSH remain, so samples from the decade-long MSH follow-up studies were analysed. Most subjects were exposed to HC (86/93). The median AMH levels were lower in study subjects than in age- and sex-matched reference values. The median AMH levels consistent with diminished ovarian reserve, a risk factor for infertility, occurred in subjects starting at the age of 25-30 years; in healthy women, this occurs after the age of 40 years. In multivariate analysis, taking HC was independently associated with a low AMH (β = 0·001, 95% confidence interval -0·002 to 0·000; P = 0·006). These results suggest that ovarian reserve is prematurely reduced in women with haemoglobin SS and raise the possibility that HC contributes to this finding.
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Topical Propranolol Improves Epistaxis Control in Hereditary Hemorrhagic Telangiectasia (HHT): A Randomized Double-Blind Placebo-Controlled Trial
Mei-Zahav M, Gendler Y, Bruckheimer E, Prais D, Birk E, Watad M, Goldschmidt N, Soudry E
Journal of clinical medicine. 2020;9(10)
Abstract
Epistaxis is a common debilitating manifestation in hereditary hemorrhagic telangiectasia (HHT), due to mucocutaneous telangiectases. The epistaxis can be difficult to control despite available treatments. Dysregulated angiogenesis has been shown to be associated with telangiectases formation. Topical propranolol has demonstrated antiangiogenic properties. We performed a two-phase study, i.e., a double-blind placebo-controlled phase, followed by an open-label phase. The aim of the study was assessment of safety and efficacy of nasal propranolol gel in HHT-related epistaxis. Twenty participants with moderate-severe HHT-related epistaxis were randomized to eight weeks of propranolol gel 1.5%, or placebo 0.5 cc, applied to each nostril twice daily; and continued propranolol for eight weeks in an open-label study. For the propranolol group, the epistaxis severity score (ESS) improved significantly (-2.03 ± 1.7 as compared with -0.35 ± 0.68 for the placebo group, p = 0.009); hemoglobin levels improved significantly (10.5 ± 2.6 to 11.4 ± 2.02 g/dL, p = 0.009); and intravenous iron and blood transfusion requirement decreased. The change in nasal endoscopy findings was not significant. During the open-label period, the ESS score improved significantly in the former placebo group (-1.99 ± 1.41, p = 0.005). The most common adverse event was nasal mucosa burning sensation. No cardiovascular events were reported. Our results suggest that topical propranolol gel is safe and effective in HHT-related epistaxis.
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Efficacy of Timolol in a Novel Intranasal Thermosensitive Gel for Hereditary Hemorrhagic Telangiectasia-Associated Epistaxis: A Randomized Clinical Trial
Peterson AM, Lee JJ, Kallogjeri D, Schneider JS, Chakinala MM, Piccirillo JF
JAMA otolaryngology-- head & neck surgery. 2020
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Abstract
IMPORTANCE Other than nasal moisturizers, no standard-of-care medical therapy exists for epistaxis in hereditary hemorrhagic telangiectasia (HHT). With epistaxis as the greatest cause of morbidity in patients with HHT, there is a need to identify effective topical therapies. OBJECTIVE To determine the efficacy and safety of an intranasal timolol thermosensitive gel vs placebo thermosensitive gel in treating HHT-associated epistaxis. DESIGN, SETTING, AND PARTICIPANTS This double-blind, placebo-controlled randomized clinical trial was conducted from October 29, 2019, to May 20, 2020, at a tertiary care center. A total of 27 patients with HHT and moderate-to-severe epistaxis were recruited and included in this prespecified analysis: 14 in the timolol group and 13 in the placebo group. Inclusion criteria included (1) age 18 years or older, (2) clinical or genetic diagnosis of HHT, (3) screening Epistaxis Severity Score (ESS) of 4 or greater and 2 or more nosebleeds cumulatively lasting at least 5 minutes per week, (4) stable epistaxis pattern over the preceding 3 months, and (5) no change in epistaxis treatment or nasal hygiene regimen in the preceding month. Exclusion criteria included (1) contraindications to systemic β-blocker administration, (2) use of medications interacting with timolol, (3) use of antiangiogenic medications in the last month before recruitment, and (4) use of anticoagulants, antiplatelets, or fibrinolytic therapies within the last month. INTERVENTIONS Novel thermosensitive intranasal timolol (0.1%) gel vs placebo thermosensitive gel applied twice daily to each nostril for 8 weeks. MAIN OUTCOMES AND MEASURES The primary outcome was the median change in ESS and percentage of participants reaching the minimal clinically important difference in ESS. Secondary outcomes were changes in Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores, Nasal Outcome Score for Epistaxis in Hereditary Hemorrhagic Telangiectasia, and hemoglobin level. RESULTS Of 27 participants randomized (median [range] age, 55 [20-76] years; 14 women [52%]; 25 White [93%]), a total of 23 patients with HHT completed the primary outcome measure. Within the timolol gel and placebo gel groups, respectively, the median change (range) in ESS was 2.32 (0.22 to 5.97) vs 1.96 (-0.91 to 5.98), and 9 of 11 (82%) vs 9 of 12 (75%) participants experienced a clinically meaningful improvement in ESS. Twenty-two of the 23 participants (96%) reported improvement via the Clinical Global Impression-Improvement score, with 81% vs 58% of participants reporting reduced severity of epistaxis in the timolol vs placebo group, respectively. Of participants completing the Nasal Outcome Score for Epistaxis in HHT at follow-up visit, 7 of 10 (70%) in the timolol group achieved a clinically important difference vs 5 of 10 (50%) in the placebo group. There was no change in hemoglobin level between or within groups. Zero participants in the placebo group and 2 of 13 (15%) in the timolol group withdrew because of adverse events. CONCLUSIONS AND RELEVANCE Thermosensitive gel, alone or in combination with timolol, was highly effective in reducing HHT-associated epistaxis. The timolol group had greater improvement in epistaxis and quality of life than the placebo group, but effect estimates were imprecise, and no definitive conclusions on the superiority of timolol can be drawn. Physicians treating patients with HHT-associated epistaxis should consider a thermosensitive gel (with or without timolol) for their patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04139018.
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Telehealth Interventions for Improving Self-Management in Patients With Hemophilia: Scoping Review of Clinical Studies
Qian W, Lam TT, Lam HHW, Li CK, Cheung YT
Journal of Medical Internet Research. 2019;21(7):e12340
Abstract
BACKGROUND The introduction of home therapy for hemophilia has empowered patients and their families to manage the disease more independently. However, self-management of hemophilia is demanding and complex. The uses of innovative interventions delivered by telehealth routes such as social media and Web-based and mobile apps, may help monitor bleeding events and promote the appropriate use of clotting factors among patients with hemophilia. OBJECTIVE This scoping review aims to summarize the literature evaluating the effectiveness of telehealth interventions for improving health outcomes in patients with hemophilia and provides direction for future research. METHODS A search was conducted in Ovid MEDLINE, EMBASE, and PubMed databases for studies that (1) focused on patients with hemophilia A or B; (2) tested the use of remote telehealth interventions via the internet, wireless, satellite, telephone, and mobile phone media on patients and caregivers; and (3) reported on at least one of the following patient-/caregiver-focused outcomes related to empowering patients/caregivers to be active decision makers in the emotional, social, and medical management of the illness: quality of life, monitoring of bleeding episodes, joint damage or other measures of functional status, medication adherence, and patients' knowledge. Implementation outcomes (user metrics, cost saving, and accuracy of electronic records) were also evaluated. Reviews, commentaries, and case reports comprising ≤10 cases were excluded. RESULTS Sixteen articles fulfilled the inclusion criteria. The majority of the interventions (10/16, 62%) evaluated both implementation outcomes and patient-/caregiver-focused outcomes. User performance and accuracy and comprehensiveness of electronic records were also measured in most studies (4/16, 87%). The components of the interventions were rather homogenous and typically involved electronic logging and reminders for prophylactic infusions, reporting of spontaneous and traumatic bleeding events, monitoring of infusion product usage and home inventory, and real-time communication with health care professionals and hemophilia clinics. Telemedicine-supported education and information interventions seemed to be particularly effective among adolescent and young adult patients. Although the patients reported improvements in their health-related quality of life and perception of illness, telemonitoring devices did not appear to have a significant effect on quantifiable health outcomes such as joint health. Longitudinal studies seemed to suggest that the response and adherence rates to recording decreased over time. CONCLUSIONS Preliminary evidence from this review suggests that telehealth-delivered interventions could feasibly improve patients' adherence to medication use and promote independence in disease management. Given the complexity and resources involved in developing a mature and established system, support from a dedicated network of hemophilia specialists and data managers will be required to maintain the technology, improve adherence to prophylactic treatment and recording, and validate the electronic data locally.
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Laser-Assisted Control of Epistaxis in Hereditary Hemorrhagic Telangiectasia: A Systematic Review
Abiri A, Goshtasbi K, Maducdoc M, Sahyouni R, Wang MB, Kuan EC
Lasers in surgery and medicine. 2019
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Abstract
BACKGROUND AND OBJECTIVES Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, causes recurrent mucous membrane hemorrhage, especially epistaxis. In this systematic review, we discuss the efficacies of the three most common laser photocoagulation treatments for HHT-related epistaxis. STUDY DESIGN/MATERIALS AND METHODS A systematic literature search was conducted in PubMed and MEDLINE from database inception to March 2019. Studies reporting epistaxis outcomes following argon, neodymium-doped yttrium aluminum garnet (Nd:YAG), and diode laser photocoagulation for HHT were included. chi(2) and Barnard's exact tests were utilized to detect differences in reduced epistaxis frequency and intensity rates. RESULTS Fifteen out of 157 published studies met our eligibility criteria, spanning a collective 362 patients. Argon, Nd:YAG, and diode laser therapy reduced epistaxis frequency in 90.4%, 88.9%, and 71.1% of patients, respectively, and reduced epistaxis intensity in 87.8%, 87.2%, and 71.1% of patients, respectively. Diode laser photocoagulation significantly underperformed in both outcome measurements when compared with argon (frequency: P = 0.005; intensity: P = 0.034) and Nd:YAG (frequency: P = 0.012; intensity: P = 0.041). There was no significant difference between argon and Nd:YAG in reducing HHT epistaxis frequency (P = 0.434) or intensity (P = 0.969). Categorizing HHT patients by clinical severity demonstrated a higher rate of improvement in the mild-moderate group compared with the severe group in both argon (P < 0.001) and Nd:YAG (P < 0.001) therapeutic methods. While no significant differences were found in rates of improved epistaxis outcomes between argon and Nd:YAG in mild-moderate HHT patients (frequency: P = 0.061; intensity: P = 0.061), Nd:YAG demonstrated greater rates of reduction in epistaxis frequency (P = 0.040) and intensity (P = 0.028) than argon among severe HHT patients. CONCLUSIONS HHT is a lifelong disease, plaguing patients with debilitating epistaxis. Intranasal laser photocoagulation of telangiectasias using argon or Nd:YAG laser therapy can yield improved epistaxis outcomes compared with diode laser photocoagulation. In severe cases of HHT, Nd:YAG laser therapy provides greater improvements in epistaxis outcomes than argon photocoagulation. Lasers Surg. Med. (c) 2019 Wiley Periodicals, Inc.
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Surgical Risk on Patients with Coagulopathies: Guidelines on Hemophiliac Patients for Oro-Maxillofacial Surgery
Laino L, Cicciu M, Fiorillo L, Crimi S, Bianchi A, Amoroso G, Monte IP, Herford AS, Cervino G
International journal of environmental research and public health. 2019;16(8)
Abstract
BACKGROUND Haemophilia is a disease of genetic origin, which causes a defect in blood coagulation. Under normal conditions, in the case of leakage from the blood vessels, the blood forms a clot that reduces or blocks the bleeding. This process involves the activation of several plasma proteins in a cascade-like species. Two of these proteins, produced in the liver, factor VIII and factor IX, are deficient or present a functional defect in people with haemophilia. Because of this deficit, the haemophiliacs easily suffer external and internal bleeding. Surgical treatment of these patients is to be observed, and often their treatment is delayed due to unclear guidelines and risks in treating these patients. The aim is to provide clear guidelines in the case of surgical treatment of these patients. METHODS In this study, we have considered all the guidelines that refer to the gold-maxillofacial surgery, focusing on the literature of the last 10 years. RESULTS Surely, this collection of guidelines will favor the choice of the clinician towards safer and predictable protocols. This study does not want to create a guideline but evaluates the literature of the last 10 years, and highlights the latest for the treatment of these patients., with the aim of informing the pathology and at the same time making the surgical maneuvers safer. CONCLUSIONS Despite the research of literature has produced few results, it was nevertheless possible to draw up a guideline thanks to additional information extrapolated from textbooks and other scientific articles. According to the guidelines, it is possible to proceed to the treatment of these patients, if with appropriate therapy in a safe and risk-free manner.