Responsible, Safe, and Effective Use of Biologics in the Management of Low Back Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines

BACKGROUND: Regenerative medicine is a medical subspecialty that seeks to recruit and enhance the body\u27s own inherent healing armamentarium in the treatment of patient pathology. This therapy\u27s intention is to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous or allogenic biologics. This field is rising like a Phoenix from the ashes of underperforming conventional therapy midst the hopes and high expectations of patients and medical personnel alike. But, because this is a relatively new area of medicine that has yet to substantiate its outcomes, care must be taken in its public presentation and promises as well as in its use. OBJECTIVE: To provide guidance for the responsible, safe, and effective use of biologic therapy in the lumbar spine. To present a template on which to build standardized therapies using biologics. To ground potential administrators of biologics in the knowledge of the current outcome statistics and to stimulate those interested in providing biologic therapy to participate in high quality research that will ultimately promote and further advance this area of medicine. METHODS: The methodology used has included the development of objectives and key questions. A panel of experts from various medical specialties and subspecialties as well as differing regions collaborated in the formation of these guidelines and submitted (if any) their appropriate disclosures of conflicts of interest. Trustworthy standards were employed in the creation of these guidelines. The literature pertaining to regenerative medicine, its effectiveness, and adverse consequences was thoroughly reviewed using a best evidence synthesis of the available literature. The grading for recommendation was provided as described by the Agency for Healthcare Research and Quality (AHRQ). SUMMARY OF EVIDENCE: Lumbar Disc Injections: Based on the available evidence regarding the use of platelet-rich plasma (PRP), including one high-quality randomized controlled trial (RCT), multiple moderate-quality observational studies, a single-arm meta-analysis and evidence from a systematic review, the qualitative evidence has been assessed as Level III (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best-evidence synthesis. Based on the available evidence regarding the use of medicinal signaling/ mesenchymal stem cell (MSCs) with a high-quality RCT, multiple moderate-quality observational studies, a single-arm meta-analysis, and 2 systematic reviews, the qualitative evidence has been assessed as Level III (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Lumbar Epidural Injections Based on one high-quality RCT, multiple relevant moderate-quality observational studies and a single-arm meta-analysis, the qualitative evidence has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Lumbar Facet Joint Injections Based on one high-quality RCT and 2 moderate-quality observational studies, the qualitative evidence for facet joint injections with PRP has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. Sacroiliac Joint Injection Based on one high-quality RCT, one moderate-quality observational study, and one low-quality case report, the qualitative evidence has been assessed as Level IV (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis. CONCLUSION: Based on the evidence synthesis summarized above, there is Level III evidence for intradiscal injections of PRP and MSCs, whereas the evidence is considered Level IV for lumbar facet joint, lumbar epidural, and sacroiliac joint injections of PRP, (on a scale of Level I through V) using a qualitative modified approach to the grading of evidence based on best evidence synthesis.Regenerative therapy should be provided to patients following diagnostic evidence of a need for biologic therapy, following a thorough discussion of the patient\u27s needs and expectations, after properly educating the patient on the use and administration of biologics and in full light of the patient\u27s medical history. Regenerative therapy may be provided independently or in conjunction with other modalities of treatment including a structured exercise program, physical therapy, behavioral therapy, and along with the appropriate conventional medical therapy as necessary. Appropriate precautions should be taken into consideration and followed prior to performing biologic therapy. Multiple guidelines from the Food and Drug Administration (FDA), potential limitations in the use of biologic therapy and the appropriate requirements for compliance with the FDA have been detailed in these guidelines. KEY WORDS: Regenerative medicine, platelet-rich plasma, medicinal signaling cells, mesenchymal stem cells, stromal vascular fraction, bone marrow concentrate, chronic low back pain, discogenic pain, facet joint pain, Food and Drug Administration, minimal manipulation, evidence synthesis

A Review of the Incidence Diagnosis and Treatment of Spontaneous Hemorrhage in Patients Treated with Direct Oral Anticoagulants

Anticoagulation carries a tremendous therapeutic advantage in reducing morbidity and mortality with venous thromboembolism and atrial fibrillation. For over six decades, traditional anticoagulants like low molecular weight heparin and vitamin K antagonists like warfarin have been used to achieve therapeutic anticoagulation. In the past decade, multiple new direct oral anticoagulants have emerged and been approved for clinical use. Since their introduction, direct oral anticoagulants have changed the landscape of anticoagulants. With increasing indications and use in various patients, they have become the mainstay of treatment in venous thromboembolic diseases. The safety profile of direct oral anticoagulants is better or at least similar to warfarin, but several recent reports are focusing on spontaneous hemorrhages with direct oral anticoagulants. This narrative review aims to summarize the incidence of spontaneous hemorrhage in patients treated with direct oral anticoagulants and also offers practical management strategies for clinicians when patients receiving direct oral anticoagulants present with bleeding complications

Periprocedural antithrombotic management for lumbar puncture: Association of British Neurologists clinical guideline

Lumbar puncture (LP) is an important and frequently performed invasive procedure for the diagnosis and management of neurological conditions. There is little in the neurological literature on the topic of periprocedural management of antithrombotics in patients undergoing LP. Current practice is therefore largely extrapolated from guidelines produced by anaesthetic bodies on neuraxial anaesthesia, haematology groups advising on periprocedural management of antiplatelet agents and anticoagulants, and by neuroradiology on imaging-guided spinal procedures. This paper summarises the existing literature on the topic and offers recommendations to guide periprocedural antithrombotic management for LP, based on the consolidation of the best available evidence. ​. [Abstract copyright: © Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.

Blokovi perifernih živaca u bolesnika na antitromboticima - spas ili nepotreban rizik?

Bleeding complications after peripheral nerve blocks (PNBs) in patients treated with an antiplatelet agent and/or an anticoagulant drug are rare, with estimated incidence of 0.67% (0.51–0.83%). However, they can result in significant patient morbidity and may require follow-up investigations and interventions. The evidence for bleeding risks and complications after PNB is very low or nonexistent, therefore, recommendations and guidelines are based on retrospective analyses, case reports, expert opinions and expert panel consensus. In the manuscript, an expert panel consensus on classification of PNBs according to the potential risk of serious bleeding complications is presented. The risks of bleeding depend on the location (vicinity of the vessels and critical structures at risk from the mass effect of a hematoma), block depth (which influences needle visibility), associated comorbidities and anticoagulation status, body habitus, site compressibility, whether the bleeding or hematoma are easy or not to assess and how easy or not an intervention may be applied to prevent or treat bleeding. Also, technical factors are considered: type and size of the used needle, technical difficulties, multiple attempts, needle passes and bloody tap, use of catheters and type of nerve location technique (USG versus blind techniques) and operator experience. In all patients on antithrombotic drugs, benefits vs. risks should be weighted. A bleeding risk should be minimized with the optimization of patient’s coagulation: appropriate antithrombotic drug timing before PNB, dose of antithrombotic drug, indication for the drug and risk factors that may influence drug pharmacokinetics (bodyweight, age, renal and hepatic function). Superficial PNBs may be performed in the presence of antithrombotic drug. For deep PNBs, a recommendations for neuraxial procedures should be considered.Komplikacije krvarenja nakon blokada perifernih živaca (PNB) u bolesnika liječenih antiagregacijskim sredstvom i/ili antikoagulansima su rijetke, procijenjena incidencija je 0,67% (0,51 - 0,83%). Međutim, mogu dovesti do značajnog morbiditeta pacijenata i mogu zahtijevati naknadne pretrage i intervencije. Dokazi o rizicima od krvarenja i komplikacijama nakon PNB-a vrlo su mali ili ih uopće nema, stoga se preporuke i smjernice temelje na retrospektivnim analizama, izvješćima slučajeva, stručnim mišljenjima i konsenzusu stručne skupine. U rukopisu je predstavljen konsenzus stručnog povjerenstva o klasifikaciji PNB-a prema potencijalnom riziku od ozbiljnih komplikacija krvarenja. Rizici od krvarenja ovise o lokaciji (blizina krvnih žila i kritičnih struktura u opasnosti od masovnog učinka hematoma), dubini bloka (koja utječe na vidljivost igle), povezanim komorbiditetima i antikoagulacijskom statusu, tjelesnom habitusu, kompresiji mjesta, ako krvarenje ili hematom je lako ili ne procijeniti i koliko se lako ili ne može primijeniti intervencija za sprječavanje ili liječenje krvarenja. Također, razmatraju se tehnički čimbenici: vrsta i veličina upotrijebljene igle, tehničke poteškoće, višestruki pokušaji, prolasci iglom i krvavo tapkanje, uporaba katetera i vrsta tehnike lociranja živaca (USG u odnosu na ‚slijepe‘ tehnike), te iskustvo operatera. U svih bolesnika koji uzimaju antitrombotičke lijekove potrebno je odmjeriti korist i rizik. Rizik od krvarenja treba svesti na najmanju moguću mjeru uz optimizaciju koagulacije bolesnika: odgovarajuće vrijeme antitrombotičkog lijeka prije PNB, doza antitrombotičkog lijeka, indikacija za lijek i čimbenici rizika koji mogu utjecati na farmakokinetiku lijeka (tjelesna težina, dob, bubrežna i jetrena funkcija). Površinski PNB može se izvesti u prisutnosti antitrombotičkog lijeka. Za duboke PNB-ove treba razmotriti preporuke za neuraksijalne postupke

Comparison of Long-Term Oral Anticoagulation Therapies Including Newly Approved Reversal Agent for Dabigatran

Anticoagulants are a well-known class of agents essential for the prevention of blood clots, which may further develop into deep vein thrombosis, pulmonary embolism or stroke. Individuals at a high risk of clotting, such as those with atrial fibrillation, multiple risk factors or recent hip/knee surgery, are in need of long-term anticoagulation therapy. The purpose of this review is to highlight the pros and cons for each available anticoagulant as well as discuss pivotal clinical trials that evaluated the safety and efficacy of these agents. Warfarin, the oldest anticoagulant, requires the patient to attend frequent appointments with a health care professional in order to test their international normalized ratio (INR). Newer anticoagulants, including dabigatran, rivaroxaban and apixaban, do not require frequent INR testing and have a quicker onset of action than warfarin, providing convenience for the patient. However, many health care professionals prefer warfarin because the INR may indicate its efficacy, its dosages can be easily changed and it is typically more affordable. Additionally, dabigatran may be chosen because it is the only one of these drugs that has a reversal agent, which can be utilized in the case of major bleeding or emergent surgery. There are many opportunities for pharmacists to impact patient outcomes in the anticoagulation therapy setting. From clinics to the community pharmacy setting, the pharmacist\u27s role in patient counseling and education is crucial in reducing mortality. Additionally, drug development is a growing market as reversal agents are needed for many of these newer anticoagulation therapies