Emicizumab: Review of the literature and critical appraisal Rodriguez‐Merchan, E. Carlos; Valentino, Leonard A.
Haemophilia : the official journal of the World Federation of Hemophilia,
January 2019, 2019-Jan, 2019-01-00, 20190101, Letnik:
25, Številka:
1
Journal Article
Recenzirano
Introduction
Emicizumab‐kywh (ACE910) is a recombinant, humanized, asymmetric bispecific antibody that functions to bring activated FIX (FIXa) and zymogen FX into an appropriate steric conformation ...to medicate the activation of FX to FXa thereby mimicking the cofactor function of FVIIIa.
Aim
The objective of this manuscript was to review the development and potential role for emicizumab in the treatment of patients with haemophilia A with and without inhibitors.
Methods
A Cochrane Library and PubMed (MEDLINE) search focusing on emicizumab in haemophilia was conducted.
Results
In total, 37 citations were retrieved and serve as the database for the literature reviewed herein. Once‐weekly subcutaneous injection of emicizumab at three dose levels has been shown to be effective as prophylaxis to prevent bleeding in a majority haemophilia A patients with inhibitors to FVIII. Likewise, prevention of bleeding was also observed in more than two thirds of patients without inhibitors to FVIII. One antidrug antibody to emicizumab has been reported in over 600 treated patients, two have developed thromboembolic events and three thrombotic microangiopathy. These thrombotic complications have occurred in conjunction with FVIII‐bypassing agents, and none have been observed following recommendations from the manufacturer regarding concomitant use of bypassing agents. The median annual treated bleeding rates were decreased in patients with as well as those without an inhibitor to FVIII.
Conclusion
The principal advantage of emicizumab is subcutaneous administration and effectiveness irrespective of the presence of inhibitors. Emicizumab could conceivably represent a new epoch in the treatment of people with haemophilia A.
Background: Symptomatic knee osteoarthritis (OA) involves millions of adults around the world.
Purpose: To analyze the effectiveness and tolerability of topical therapies and their contemporary ...placement in knee OA management criteria.
Methods: A Cochrane Library and PubMed (MEDLINE) search related to the role of topical therapies in knee OA was carried out.
Results: Many types of local therapy have been reported, including nonsteroidal anti-inflammatory drugs (NSAIDs) like diclofenac and ketoprofen; capsaicin, cream containing glucosamine sulfate, chondroitin sulfate, and camphor; nimesulide; civamide cream 0.075%; menthol; drug-free gel containing ultra-deformable phospholipid vesicles (TDT 064); 4Jointz utilizing Acteev technology; herbal therapies; gel of medical leech (Hirudo medicinalis) saliva extract; and gel prepared using Lake Urmia mud. One systematic review showed that topical diclofenac and topical ketoprofen can alleviate pain. However, another systematic review found that topical diclofenac and ketoprofen had limited efficacy in knee OA at 6 to 12 weeks. Many studies with a low level of evidence have reported some pain mitigation using the rest of aforementioned topical therapies.
Conclusions: Although some controversy exists on the role of topical NSAIDs, current management guidelines advise topical NSAIDs as an option and even first-line therapy for knee OA treatment, particularly among elderly patients. Topical NSAIDs may be contemplated as similar options to oral NSAIDs and are associated with fewer gastrointestinal complications when compared with oral NSAIDs. Caution should be taken with the use of both topical and oral NSAIDs, including close adherence to dosing regimens and monitoring, especially for patients with previous complications of NSAIDs. The role of other topical therapies needs further research.
Musculo-skeletal pain treatment is inadequate in many haemophilic patients. Analgesics are used only by 36% of adult patients. FVIII/FIX intravenous infusion is mainly used to lessen pain, followed ...in frequency by usage of NSAIDS (primarily COX-2 inhibitors). In about 30% of patients, pain continues after infusion of F VIII/IX. In acute haemarthroses pain treatment must continue until total disappearance (checked by ultrasonography) and include haematologic treatment, short-term rest of the involved joint, cryotherapy, joint aspiration and analgesic medication (paracetamol in mild pain, metamizole for more intense pain, and in a few precise patients, soft opioids such as codeine or tramadol). In the circumstance of intolerable pain we should use morphine hydrochloride either by continual infusion or a patient-controlled analgesia (PCA) pump, determined by the age, mental condition and grade of observance of the patient. Epidural blocks utilizing bupivacaine and fentanyl may be very efficacious as well. Three main strategies to alleviate chronic musculo-skeletal pain secondary to haemophilic arthropathy (joint degeneration) exist: pharmacologic management, physical medicine and rehabilitation, and intra-articular injections. As for pharmacologic management, NSAIDs (ibuprofen, diclofenac, celecoxib, robecoxib) are better than paracetamol. The advantages of tramadol or tramadol/paracetamol and non-tramadol opioids are scanty. With respect to physical medicine and rehabilitation, there is insufficient confirmation that a brace has supplementary favourable effect compared with isolated pharmacologic management. Land-based curative exercise and watery exercise have at the minimum a tiny short-run benefit. Curative ultrasound can be helpful (poor quality of evidence). The efficacy of transcutaneous electrostimulation (TENS) for pain mitigation has not been proved. Electrical stimulation treatment can procure notable ameliorations. With respect to intra-articular injections, viscosupplementation appears to be a useful method for pain alleviation in the short-run (months). The short-run (weeks) advantage of intra-articular corticosteroids in the treatment of joint pain has been shown.
Radiosynovectomy (RS) is a simple, effective and safe procedure for the control of haemophilic synovitis that causes repetitive haemarthrosis. It must be done after confirming clinically (hard and ...painless mass on palpation) and by ultrasonography the existence of synovitis in a joint with recurrent haemarthrosis. RS should be the first invasive option (instead of arthroscopic synovectomy) for treatment of chronic synovitis. The technique is highly cost effective in comparison to arthroscopic synovectomy. The indication for RS is the presence of repeated haemarthroses associated with synovitis (confirmed clinically and by imaging techniques) that cannot be controlled by means of haematological treatment. No increase in the risk of cancer has been published and the dose of radiation utilized in RS is minimal. In haemophilic patients with recurrent haemarthrosis, RS should be performed under factor coverage as soon as possible, once the existence of synovitis has been confirmed by ultrasonography. RS should really be considered as a useful adjunctive procedure to the primary intervention, which is intensive replacement therapy.
How blockchain technology can change medicine Roman-Belmonte, Juan M.; De la Corte-Rodriguez, Hortensia; Rodriguez-Merchan, E. Carlos
Postgraduate medicine,
05/2018, Letnik:
130, Številka:
4
Journal Article
Recenzirano
Although the best-known use of blockchain technology (BCT) is in the field of economics and cryptocurrencies in general, its usefulness is extending to other fields, including the biomedical field. ...The purpose of this article is to clarify the role that BCT can play in the field of medicine. We have performed a narrative review of the literature on BCT in general and on medicine in particular. The great advantage of BCT in the health arena is that it allows development of a stable and secure data set with which users can interact through transactions of various types. This environment allows the entry and operation of clinical data without compromising other sensitive data. Another important advantage of BCT is that the entire network is decentralized and is maintained by the users themselves; thus, there is no need to rely on organizations for storage. The Blockchain code is open source and can be used, modified and revised by its users. BCT literature is scarce so far. This article describes the basics of this technology and summarizes the various aspects in which BCT could change the paradigm of current medicine. The great potential of BCT, as well as its many applications in the field of health sciences, encompasses the fields of legal medicine, research, electronic medical records, medical data analysis (big data), teaching and the regulation of payment for medical services. If technological advances continue along these lines, it could bring about a revolution in medicine as we know it.
Increased bone resorption in hemophilia Rodriguez-Merchan, E. Carlos; Valentino, Leonard A.
Blood reviews,
January 2019, 2019-Jan, 2019-01-00, 20190101, Letnik:
33
Journal Article
Recenzirano
In patients with hemophilia, osteoporosis is frequently observed for which the etiology remains unclear. The aim of this paper is to review the available experimental evidence indicating the presence ...of this disorder in patients with hemophilia, explore the potential mechanisms which may lead to reduced bone mineral density (BMD) and speculate on useful interventions to circumvent it. A narrative review of the English literature up to April 2018 was performed. The available evidence demonstrates an increased rate of bone resorption and an excess of osteoporosis among patients with hemophilia. FVIII and FIX may act through at least two pathways: promoting bone formation by a thrombin-mediated mitogenic effect on osteoblasts and by cytokine-mediated osteoclast activity. Another potential indirect mechanism mediated through the RANK-RANKL pathway has been suggested but remains controversial. The role of confounders such as lack of activity and immobility must be considered.
Abstract Haemophilia left untreated or treated on demand destroys the joints at a very young age. Primary haematological prophylaxis, currently the gold standard for the treatment of haemophilia, is ...not completely effective. Moreover, it is only available for 25–30% of patients worldwide. Advances in haematology, combined with the advances in orthopaedic surgery and other disciplines (physical medicine and rehabilitation, physiotherapy, specialised nursing, etc.), have made it possible to improve the musculo-skeletal manifestations of haemophilia in these patients through orthopaedic surgical interventions. These interventions are safe, even in the most complex cases, such as patients who develop inhibitors (antibodies to clotting factor) or are HIV + and HCV +. The risk of bleeding in surgical interventions is higher for people with haemophilia than for other patients and there is also a greater risk of infection. Both these factors increase the risk of a poor outcome. Whatever the surgical procedure, adequate surgical haemostasis must be achieved by infusion of concentrate of the deficient factor (factor VIII or factor IX), either in recombinant or plasma-derived form, at the correct doses (ideally for 10–14 days). In patients with inhibitor there are also the aPCCs (activated prothrombin complex concentrates) and rFVIIa (recombinant activated FVII). Surgical orthopaedic interventions that are commonly required by haemophilia patients include synovectomy (open or arthroscopic), osteotomy, arthroscopic joint debridement, tendon lengthening, arthrodesis of the ankle, total joint replacement, resection or percutaneous treatment of pseudotumours, fasciotomy for compartment syndrome, neurolysis of the ulnar nerve, and other orthopaedic interventions.
Planning and undertaking elective surgery in people with haemophilia (PWH) is most effective with the involvement of a specialist and experienced multidisciplinary team (MDT) at a haemophilia ...treatment centre. However, despite extensive best practice guidelines for surgery in PWH, there may exist a gap between guidelines and practical application. For this consensus review, an expert multidisciplinary panel comprising surgeons, haematologists, nurses, physiotherapists and a dental expert was assembled to develop practical approaches to implement the principles of multidisciplinary management of elective surgery for PWH. Careful preoperative planning is paramount for successful elective surgery, including dental examinations, physical assessment and prehabilitation, laboratory testing and the development of haemostasis and pain management plans. A coordinator may be appointed from the MDT to ensure that critical tasks are performed and milestones met to enable surgery to proceed. At all stages, the patient and their parent/caregiver, where appropriate, should be consulted to ensure that their expectations and functional goals are realistic and can be achieved. The planning phase should ensure that surgery proceeds without incident, but the surgical team should be ready to handle unanticipated events. Similarly, the broader MDT must be made aware of events in surgery that may require postoperative plans to be changed. Postoperative rehabilitation should begin soon after surgery, with attention paid to management of haemostasis and pain. Surgery in patients with inhibitors requires even more careful preparation and should only be undertaken by an MDT experienced in this area, at a specialized haemophilia treatment centre with a comprehensive care model.
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