This article evaluates the feasibility, safety, and efficacy of MRI-guided lumbar or sacral nerve root infiltration for chronic back pain. We compared the outcomes of our MRI-guided infiltrations with data from CT-guided infiltrations reported in the literature and explored the potential advantages of MRI guidance.Forty-eight MRI-guided nerve root infiltrations were performed using a 3 T MRI machine. The optimal needle path was determined using breathhold T2-weighted sequences, and the needle was advanced under interleaved guidance based on breathhold PD-weighted images. Pain levels were assessed using a numeric rating scale (NRS) before the procedure and up to 5 months after, during follow-up. Procedure success was evaluated by comparing patients’ pain levels before and after the infiltration.The MRI-guided infiltrations yielded pain reduction 1 week after the infiltration in 92% of cases, with an average NRS substantial change of 3.9 points. Pain reduction persisted after 5 months for 51% of procedures. No procedure-related complications occurred. The use of a 22G needle and reconstructed subtraction images from T2 FatSat sequences improved the workflow.Our study showed that MRI-guided nerve root infiltration is a feasible, safe, and effective treatment option for chronic back pain. Precise positioning of the needle tip and accurate distribution of the injected solution contributed to the effectiveness of MRI-guided infiltration, which appeared to be as accurate as CT-guided procedures. Further research is needed to explore the potential benefits of metal artifact reduction sequences to optimize chronic back pain management. Low back pain is a multifactorial disease, and different treatment options are continuously discussed in the medical community . The choLower back pain treatment follows a stepwise approach. The first step is to determine whether a motor deficit is present. Should this be the case, prompt surgical evaluation is indicated to precisely define its extent. In the absence of significant motor deficit, the second step usually involves patient education and adapted oral medication, including non-steroidal anti-inflammatory drugs and muscle relaxants. Other complementary second-line treatments include massages, physiotherapy, and acupuncture , 7. UnliSeveral interventional approaches have been described for performing lumbar or sacral nerve root infiltrations. The needle route, the injected drugs, and image guidance techniques can be adapted on a case-specific basis.The three main access routes in clinical practice are (1) direct epidural interlaminar access, (2) foraminal access, and (3) caudal access. If a foraminal access is chosen, the injected products may or may not diffuse medially into the intraspinal epidural space . A relatively lateral foraminal access may also be referred to as a “selective nerve block.” Effective pain relief has been shown for the foraminal approach in multiple studies –12. The For most injections in the spinal region, a combination of an anti-inflammatory corticosteroid is advocated, in combination with a local anesthetic of the amino-amide type. Apart from intra-articular injections, the corticosteroid should preferably be non-particulate .. [The foraminal infiltration technique has been largely described under CT –19 and f. . However. . Further. –25, as i. , 26, our. .Fig. 1NoThe aim of the current report was to report further updates and improvements to the technical and clinical workflows on 48 procedures, to evaluate responses to infiltration up to 5 months of follow-up, and to perform a comparison with CT-guided intervention data available in the literature.Forty-eight MRI-guided nerve root infiltrations were carried out in 40 patients between November 2017 and July 2022, on a 3 T MRI machine . As described in a former publication [Study approval was obtained from the ethics committee of the CCER from Geneva (n°2019–02301) and all methods were performed in accordance with the relevant guidelines and regulations. All patients were informed about the study before the intervention and gave their written informed consent to participate in the study.The inclusion criteria were patients with lumbar or sacral radiculopathy selected for MRI-guided lumbar or sacral nerve root infiltrations after multidisciplinary board discussion involving radiology, neurosurgery, rheumatology, orthopedic surgery, and pain relief teams. Patients were assessed clinically by a spinal surgeon and by standard musculoskeletal MRI using sagittal T1 and T2 turbo spin echo (TSE), axial T2 TSE, and sagittal T2 TSE FatSat Short-TI Inversion Recovery (STIR) sequences. Other tests such as electromyography were not routinely performed since the diagnostic value of the intervention was considered sufficiently high.The exclusion criteria included all contraindications for MRI examinations, in particular claustrophobia and presence of metallic devices. These conditions could be ruled out already at the step of the standard before the intervention MRI mentioned above.In this study, no pregnant women were recruited for infiltration. Therefore, we cannot provide specific advice regarding the use of the technique in this particular population.In the first step, the optimal needle path was determined by a radiologist using an axial breathhold T2-weighted TSE sequence, repeated a second time for confirmation after placement of a small silicone marker on the chosen skin puncture point  until the needle came to lie directly behind the exiting nerve root in the neural foramen or a sacral foramen.On May 20, 2022, a 22G needle built from identical alloy was employed as an alternative to the standard 20G needle to compare the size of artifacts. The assessment criterion focused on visual artifacts, specifically evaluating the width of the dark band that artificially increased the apparent width of the needle as described in Scheffler et al. .In case of lumbo-sacral transitional anomaly, the L5-S1 nerve root can be difficult to reach by a direct and strictly axial access. In this situation, MRI-guidance allowed for a three-dimensional planning and execution of access path , with 0 = no pain, from 1 to 3 = minor pain, from 4 to 6 = moderate pain, and from 7 to 10 = severe pain, was derived from the visual analog scale (VAS).Patients received instructions from a staff member to quantitatively evaluate their pain level on the VAS at the aforementioned sampling points. During follow-up, patients were contacted by phone calls by the same staff member monthly from the first to the fifth month after the procedure, in order to record their pain level and other procedure-related information, such as the necessity for ultimate spinal surgery.The success of the procedure was assessed by calculating the difference between the pain level experienced by the patient during the days before the procedure and the pain level experienced at each assessment by the physician during the 5 months following the procedure.. [Artifact measurements were performed on three patients who received infiltrations with a 22G needle and three patients who received infiltrations with a 20G needle. The average artifact width for the 20G needle was found to be 2.1 mm, whereas the average width for the 22G needle was 1.4 mm according to the method used in Scheffler et alComplete follow-up responses were obtained for 39 procedures in 36 patients, with a median age of 61 years (range: 25–91). The locoregional pain related to the procedure itself was assessed as very low to mild .The pain level changes assessed by the NRS at the various time points are displayed in Fig. Out of the 39 procedures, 36 procedures (92%) showed a pain reduction 1 week after the infiltration, 33 procedures (84%) 1 month later, 31 procedures (79%) 2 months later, 30 procedures (77%) 3 months later, 24 procedures (61%) 4 months later, and 20 procedures (51%) 5 months later  and another patient underwent two infiltrations (November 2018 and July 2019). Each infiltration yielded similar results in pain reduction for both patients.Chronic back pain is a significant global medical condition, which represents one of the leading reasons for seeking medical help and abstaining from work. It presents a major medical challenge for the foreseeable future. To the best of our knowledge, this study was the first to evaluate the feasibility, safety, and efficacy of 3 T MRI-guided lumbar or sacral nerve root infiltration with a 5-month follow-up.In this analysis, we were also able to show the efficacy of this procedure under MRI guidance. A large fraction of patients (77%) reported a pain reduction 3 months after the intervention, with an average NRS change of 2.7 points. Moreover, 51% of patients reported a pain reduction after 5 months, with an average NRS change of 1.4 points. In our study, we did not perform a pain relief comparison versus CT or fluoroscopy guidance, but screening of literature data showed that our results are not inferior to that of CT or fluoroscopy procedures , 29.In this study, MRI-guided infiltrations appeared to be as effective as CT-guided infiltrations, which may be due to the precise needle tip placement and the accurate distribution of saline solution, which corresponds to the drug diffusion area.The safety profile of MRI-guided nerve root infiltration was excellent, with no reported complications during the procedures. This further supports the reliability of this technique in clinical practice.Concerning workflow, we have had good experiences with utilizing a 22G needle instead of the 20G needle used in our previous study [Procedure time optimization was observed, with a median time of 38 min in this study versus 51 min in our previous study . These pA small proportion of patients (10%) reported no pain improvement 1 month after the procedure, including two patients who received infiltrations on both sides of the vertebra. The obtained results offer significant insights for physicians. In cases where the steroid fails to produce the desired effect, which can occasionally occur, the injection of a local anesthetic around the nerve root can still offer crucial diagnostic information, despite its temporarily limited effectiveness. The images of these four patients were thoroughly examined to ascertain whether the needle’s placement or the product diffusion could have caused the failure. Analysis of the needle position data revealed that, in each patient, the needle was located approximately 1.8 mm to 2.4 mm away from nerve the root, aligning with findings from the other cases investigated by Scheffler et al. .Although our technical and clinical results are encouraging, this study has some relevant limitations. First, the patient number was relatively small, which may have prevented some findings from being identified. Second, this study showed that even when the procedure is performed within a standardized setting, patients do not always respond equally to nerve root infiltrations. Some patients did not feel any improvement after the infiltration, whereas for others, pain reduction was still effective 5 months after the procedure. This can be explained by two factors: the first one being the underlying pathology , which seems to play a crucial role regarding therapeutic efficacy; the second factor concerns secondary patient care such as physiotherapy, which has positive effects on pain reduction. Therefore, further limitations of this study are that it does not consider the different pathologies of the patients and the secondary care received.In the future, the development of metal artifact reduction (MAR) sequences holds potential for further enhancing the accuracy and efficacy of MRI-guided nerve root infiltrations. By mitigating the impact of metallic artifacts resulting from implanted devices, MAR sequences enable improved visualization and precise needle placement . HoweverAnother area for future development could be to compare the immediate to mid-term effects  with the mid- to long-term effects . Infiltrations are often requested for patients who are highly likely to eventually undergo surgery. Exploring the possibility that a positive immediate effect may serve as a predictor for a favorable mid- to long-term outcome would be intriguing and valuable. Further research is warranted to explore these possibilities and optimize chronic back pain management.In this study, we evaluated the use of 3 T MRI-guided nerve root infiltration for radicular pain management, particularly in the lumbar spine. Our findings demonstrated that MRI-guided nerve root infiltration is a safe, feasible, and precise technique in well-selected patients, with a high rate of pain improvement. The absence of complications and the overall positive response rate of 61% after 4 months and 51% after months indicate that this technique holds promise as an effective treatment option for radicular pain. Our study highlighted that the use of MRI guidance allows for accurate needle placement and precise targeting of the affected nerve root, resulting in significant pain reduction for most patients. The addition of MRI-guided nerve root infiltration to the existing range of treatment options offers a valuable tool for chronic back pain reduction. Indeed, this technique can expand the therapeutic armamentarium available to clinicians and enhance patient care by providing a safe and effective alternative.In conclusion, our study highlighted the potential of MRI-guided nerve root infiltration as a valuable technique in the management of radicular pain. With its favorable safety profile, high rate of pain improvement, and precise guidance, this technique can complement existing approaches and contribute to the comprehensive treatment of chronic back pain. Further research and larger-scale studies are warranted to validate our findings and explore the long-term outcomes and potential extended applications of MRI-guided nerve root infiltration in the field of neuroradiology.


The universal definition of acute myocardial infarction (MI) requires both evidence of myocardial injury and myocardial ischaemia. In MINOCA (MI with non-obstructive coronary arteries), patients must fulfil this MI criteria, but is their chest pain similar to those who have MI with obstructive CAD (MICAD)? This study compares prospectively collected chest pain features between patients with MINOCA and MICAD. Utilising the Coronary Angiogram Database of South Australia (CADOSA), consecutive MI patients were categorized as MINOCA or MICAD based on angiographic findings. Chest pain data were collected via direct patient interviews by trained staff members. Of 6811 consecutive patients fulfilling a clinical MI diagnosis, 411 (6.0%) were MINOCA, and 5948 MICAD. The MINOCA patients were younger, more often female and had less cardiovascular risk factors than those with MICAD. There were no significant differences in chest pain characteristics between the MINOCA and MICAD cohorts in relation to pain location, quality, associated symptoms, or duration. In conclusion, MINOCA patients have chest pain characteristics that are indistinguishable from MICAD patients, suggesting that their pain is ischaemic in nature. Thus, in the presence of positive myocardial injury markers, ischaemic chest pain fulfils the universal criteria for MI, despite the absence of obstructive coronary artery disease. The universal definition of acute myocardial infarction (MI) is based upon the demonstration of acute myocardial injury  in the context of myocardial ischaemia  . In contMINOCA accounts for 5–10% of acute myocardial infarct presentations . Its diaA key challenge in the diagnosis of MINOCA is interpreting the universal definition of MI, especially considering the central role of the troponin biomarker and its ‘organ-specific’ (rather than ‘disease-specific’) properties in diagnosing MI . Thus, tThe primary objective of this study is to compare chest pain features in consecutive patients fulfilling the fourth set of universal criteria for MI with (MICAD) and without (MINOCA) obstructive coronary artery disease. The secondary objective is to determine if chest pain features differ between MICAD and MINOCA in those who also have distinctive ischaemic ECG changes , as well as those with less specific ECG changes .The study population was selected from the Coronary Angiogram Database of South Australia (CADOSA) registry.® CathPCI® Registry [CADOSA is a statewide prospective registry of consecutive patients undergoing diagnostic coronary angiography in South Australian public hospitals (population 1.6 million). The registry follows data elements and definitions  , and 10%The CADOSA registry data collection was undertaken by trained professional data abstractors based at each hospital site, who (where possible) obtained the required data elements via direct patient interviews and/or case note extraction. In addition to standard cardiovascular risk factors, comorbidities, coronary angiographic findings, and discharge medications, detailed chest pain characteristics were obtained. This includes pain location , quality , precipitating factors , relieving factors , associated symptoms  and duration . Details of these characteristics are illustrated in The study cohort included consecutive acute MI patients hospitalized between January 2012 and December 2015 undergoing coronary angiography.The inclusion criteria for acute MI were based upon the fourth set of universal criteria for MI [and (2) the presence of an ischaemic marker such as (i) chest pain, (ii) ischaemic ECG changes (ST/T wave changes or new Q waves), (iii) MI perfusion imaging markers, (iv) new regional wall motion on ventricular imaging, or (v) coronary artery thrombus. ECG features were further classified as STEMI with new or presumed ST segment elevation or new left bundle branch block not resolved within 20 min, and NSTEMI with an absence of diagnostic ST elevation. Based upon angiographic findings, the MI patients were categorized into MICAD (presence of ≥50% stenosis) or MINOCA (no coronary lesions ≥50% stenosis).a for MI , with doThe exclusion criteria included (i) out-of-hospital cardiac arrest; (ii) prior coronary artery bypass grafting or a percutaneous coronary intervention (PCI) within the preceding 6 months in MINOCA cohort; and (iii) a discharge diagnosis of takotsubo cardiomyopathy, myocarditis, pulmonary embolism, or other non-ischaemic causes as per the treating cardiologist/additional investigation, such as cardiac magnetic resonance imaging or echocardiogram. To ensure non-ischaemic causes were excluded in the MINOCA patient cohort, a comprehensive medical record review of all patients with suspected MI and non-obstructive coronaries was undertaken by SP and RT, with equivocal cases independently adjudicated by JB.The study parameters were described using frequencies and percentages for categorical variables, and median and interquartile ranges (IQR) for continuous data. Comparison between groups for categorical outcomes  was undertaken using logistic or linear regression with MINOCA as the binary independent variable. Analyses were age- and gender-adjusted where appropriate, and the final odds ratios are reported with 95% confidence intervals. Statistical significance was established at an alpha level of 0.05. All statistical analyses were performed using Stata statistical software suite (STATA/MP version 17.0 for Mac (Apple Silicon) Revision 8 March 2023; StataCorp., LP, College Station, TX, USA).Within the CADOSA Registry, from January 2012 to December 2015, there were 7118 consecutive acute MI presentations who underwent coronary angiography. Of these, 307 were excluded because of out-of-hospital cardiac arrest, and 452 cases were excluded due to clinical features suggestive of causes other than MINOCA. . A totalp < 0.05). Finally, at discharge, MINOCA patients were less likely to receive secondary cardioprotective therapies or referral to a cardiac rehabilitation program  and less likely to experience those precipitated by physical activity .As detailed in p < 0.05). Similarly, in the NSTEMI subgroup, there were no significant differences in chest pain characteristics between MICAD and MINOCA patients, except for the trigger of emotional stress, which was more prevalent in MINOCA patients compared to MI-CAD patients   .Chest pain is a hallmark symptom of MI and is caused by inadequate blood supply to the myocardium. The underlying mechanisms of chest pain in MI are complex, and involve a combination of factors including inflammation, ischaemia, and nerve activation ,10,11,12There were no differences in chest pain characteristics between those with MICAD or MINOCA. The MICAD and MINOCA cohorts were indistinguishable in relation to chest pain (i) location , (ii) quality , (iii) associated symptoms , and (iv) typical duration  . FurtherThis study provides further support for the idea that MINOCA is a unique clinical ischaemic entity, with novel prospectively collected clinical data showing chest pain characteristics indistinguishable from those in patients with MICAD. Thus, concerns that patients with MINOCA are an arbitrary collection of patients with atypical chest pain with false-positive troponin are repudiated.This study is unique, considering that it is a representative sample with consecutive patient recruitment that utilises data from direct patient interviews, and it has an appropriately defined MINOCA subgroup to compare to MICAD patients. However, despite these strengths, the study has important limitations that should be considered when interpreting the findings. Firstly, out-of-hospital cardiac arrest patients were excluded from the study, despite potentially being ischaemic in nature. These patients were excluded because the troponin changes could be the result of resuscitation efforts rather than ischaemia/infarction.Secondly, exclusion of non-ischaemic causes for the suspected MI presentation was based upon the treating clinician’s diagnosis upon discharge. CMR imaging was not undertaken in all MINOCA patients; thus, the MINOCA cohort may potentially have included patients with undiagnosed myocarditis. However, routine cardiac magnetic resonance imaging in all MINOCA patients remains a challenge at most institutions due to availability, so the study does reflect routine practice. Moreover, it is noteworthy that the MINOCA patients were similar to those with MICAD with respect to chest tightness and associated symptoms.This original prospective investigation of consecutive myocardial infarct patients provides compelling evidence that individuals with MINOCA exhibit chest pain characteristics that are clinically indistinguishable from those in patients with MICAD, with the only distinguishing factor being the absence of obstructive coronary artery disease on angiography. These findings strongly support the concept that MINOCA patients have ischaemic chest pain, thereby fulfilling the universal criteria for an acute MI in the context of myocardial injury. Certainly, they should not be disregarded as “false-positive infarcts” solely due to the absence of obstructive CAD.Despite these significant findings, this study also highlights the need for further research to explore the underlying mechanisms and potentially related clinical features of MINOCA. Future studies should aim to investigate these aspects by utilising appropriate diagnostic tools and testing modalities. By doing so, a deeper understanding of the different subtypes and etiologies of MINOCA can be achieved, thereby contributing to the development of more tailored and effective therapeutic strategies for these patients.


The study evaluation of the effectiveness the method of electrostimulation in treatment TMJ associated with occlusion disorders with the use of a patches by the company “Aganyan’’.The study included 54 patients with temporomandibular dysfunction syndrome who had previously undergone endodontic dental treatment. In patients temporomandibular disorders (TMD) determined on the basis of Diagnostic criteria for temporomandibular disorders(DC/TMD).All patients had occlusion disorders due to errors after dental filling restoration. To diagnose the TMJ, a CT scan was used. The complex therapy also included therapy and with the use of a patches by the company “Aganyan’’. The wearable patch includes a flexible substrate, a binder an adhesive layer, with an electrode foil attached to it. Patients applied one patch behind each TMJ. The patches were applied for eight hours every third day for three months. All the patients were given full-fledged endodontic treatment and restoration of the crown part, taking into account anatomical features.The dynamics of the complex treatment of patients diagnosed with TMJ dysfunction syndrome showed that after treatment, the clinical symptoms gradually decreased and disappeared at the end of treatment. CT scan a year after treatment showed a normal ratio of TMJ elements. Сomplex treatment was effective in 87% of patients, after 3–5 months gradually decreased pain, noise in the joints, restriction of opening and closing of the mouth disappeared. Patients recovered their chewing functions, psycho-emotional state.The results of the studies revealed a positive effects for the complex treatment dysfunctions syndrome TMJ the using the patches by the company “Aganyan” through electrical stimulation with low intensity. Temporomandibular joint (TMJ) disorders are a class of degenerative diseases of the musculoskeletal system connected with morphological and functional deformations. According to epidemiological data, TMJ disorders up to 25% of the population , 2.TMJ disorders include anomalies in the intra-articular position and/or structure of the disc, as well as temporomandibular dysfunction (TMD) which is the second most common disease of the musculoskeletal system, causing pain and disability (after chronic low back pain) .Disorders of the neuromuscular system causing pain are classified as masticatory pain dysfunction syndrome (MPDS) .distortions and functional overload, comorbid conditions [Clinical observations show that numerous factors may play role in the progression of TMD and degenerative changes connected with it. Ethiology comprex factors TMD include, trauma and micro trauma, rheumatoid arthritis, osteoarthritis, parafunction, bruxism, alocclusion, tooth loss occlusion nditions –7.Psychosocial factors include , socioeconomic status, and working conditions  sleep disorders and a busy lifestyle .The influence of sleep bruxism with clinical manifestations of temporomandibular disorders (TMD) remains controver .Clinical symptoms of dysfunctions syndrome TMJ is manifested may include one or more of the following symptoms: temporomandibular joint pain, restricted jaw movement and joint noise, otalgia, headache, neck pain and trismus, limited opening or deviation of the mandible upon opening and occlusal changes due to changes in the position of the mandible,  thereforDue to the complex and unique nature of each TMJ case, diagnosis requires an individual analysis of the patient, followed by various diagnostic modalities .The purpose of the diagnostic protocol for TMD studies is to make a clinical diagnosis while simultaneously identifying other important characteristics that may influence presentation and treatment. The most widely used diagnostic protocol for TMD studies is the Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) based on the biopsychosocial model of pain , 14.Similarly, it requires individual treatment taking into account specific characteristics of each patient’s disease.Patient’s condition evaluation along with various imaging methods can help to determine the stage of disease, to diagnose and plan the treatment. The assessment of the TMJ begins with a thorough history and clinical examination. In some cases, clinical examination data is enough for the preliminary diagnosis and start conservative treatment. However, other patients will require diagnostic imaging of the TMJ to provide information that is not available on clinical examination .As a result, TMJ identification can include any combination of the following diagnostic methods: panoramic radiography, Cone beam computed tomography (CBCT), Magnetic resonance imaging (MRI), Ultrasonography (US), arthrography –18.CT scan is considered the most useful for visualizing the TMJ bones while MRI is considered the most useful for soft tissues visualization, including the disc and its articular ratio.Arthrography is an invasive intra-articular examination; its usual indication is visualization of changes in the articular disc. Due to the inherent risk of this method, it has been superseded by MRI evaluation .US examination, can be a useful option in the assessment of disc position in internal TMJ disorders. Ultrasound is indicated when MRI is contraindicated, to differentiate between TMJ and painful conditions of the major salivary glands , 21.TMJ therapy is primarily aimed at eliminating pain, clicking joints, restoring TMJ functions. Research by various authors shows the relationship between temporomandibular disorders (TMD) and malocclusion .Since in the etiology of dysfunction, a violation of occlusion is important to achieve the correct jaw relationship, it is necessary to restore the central ratio (CR). To stabilize the occlusion, occlusal splint therapy can used weth individual occlusal guards splint. The main goal of occlusal splint therapy is to separate the occlusion and relax the masticatory muscles. In this regard, occlusal correction has become a very popular method of choice for the treatment of or prevention TMJ . SplintiWhen the compensatory capabilities of the masticatory and neuromuscular systems are overstrained, dysfunction occurs, leading to clinical symptoms and manifested by pain, strong clicking or limited mobility of the lower jaw, which forces the patient to seek help.The polyethological nature of this pathology, the complexity of the clinical picture and the diagnosis and treatment connected with it, of course, should be complex: relief of emotional stress (psychotherapeutic treatment), medication, exercises of muscle groups, massage, pharmacotherapy and physiotherapy.Myofascial pain is a common symptom and occurs in 31–76% of the population; it can be alleviated with massage, which relieves pain, relieves tension headaches and muscle pain, restores balance between masticatory muscle tension and improves chewing , 26. MasMuscle training is a simple and non-invasive method of treating TMJ and should be done in moderation and the intensity should be increased over time to avoid pain and patient frustration with the proposed treatment.Pharmacotherapy is considered to be a supportive therapy that complements other therapies to release the TMJ, reduce pain and inflammation in the joints and/or muscles.Pharmacological agents are used for TMJ in the form anti-inflammatory drugs. The most commonly used drugs are muscle relaxants, nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, tricyclic antidepressants, benzodiazepines, and corticosteroids. Therefore, drugs, TMD such as NSAIDs and corticosteroids, which inhibit the release of inflammatory cytokines, are prescribed in TMD –31. GlucModern therapies use for treatments patients with dysfunctions of the TMJ a variety method, these procedures include neurotoxins, platelet-rich plasma, botulinum therapy, etc –36.Among the also non-surgical methods used to treat TMJ physiotherapy, kinesiotaping, biofeedback –41.A systematic review has shown that Low-level laser therapy (LLLT) is effective in relieving pain and improving functional outcomes in patients with TMJ , 41. PopLLLT exerts through multiple mechanisms of action, including facilitating the release of endogenous opioids, enhancing tissue repair and cellular respiration, increasing vasodilation and pain threshold, and reducing inflammation .From non-invasive other methods of treatment, electrostimulation can be used for treatment methods in patients with dysfunctions of the TMJ and can improve the efficiency of treatment , 44.Transcutaneous Electrical Nerve Stimulation (TENS) is a well-known method of pain relief for TMD. TENS is a method based on electrical stimulation of painful areas using surface electrodes and is considered safe and non-invasive. Due to the small number of studies , TENS cannot yet be considered a standard treatment for TMD, as its effectiveness has not yet been determined .Electrical stimulation methods that exclude the use of large equipment and electrical wires or power supplies are relevant for the treatment of patients with TMJ disorders.The research that we carried out was aimed at testing of the effectiveness the method of electrostimulation in treatment of dysfunctions of the TMJ with the use of a patches by the company “Aganyan”.The potential difference causes electrons to flow across the surface of the skin from one of the electrodes to the other. In this sense, one of the electrodes can be considered as the cathode and the other electrode as the anode. The electrodes are made from various metals such as zinc and copper and are not connected to any electrical device such as a voltage or current source.A potential difference can only be created when the electrodes are made of different metals. The main difference between Aganyan patches and existing methods of electrical stimulation is that these patches are not connected to any power source or batteries.These ranges of voltages and electrical currents seem to be very safe for humans and do not have any side effects .Purpose of the study evaluation of the effect using patches by the company “Aganyan” for treatment dysfunctions syndrome TMJ.The study included 54 patients  with clinical features consistent with TMJ dysfunctions syndrome were enrolled who had previously undergone endodontic dental treatment. All patients presented occlusion disorders due to errors after dental filling restoration.Patients examined for pain on palpation, at rest/during movement, muscle pain, sound on jaw movement, occlusion was also assessed. In patients temporomandibular disorders (TMD) determined on the basis of Diagnostic criteria for temporomandibular disorders(DC/TMD) .patients with the following symptoms, pain around the joint, in the pre-auricular region, in the muscles of mastication and the ear, limited or abnormal range of motion, and cranial and/or muscle pain, sound in the joint area while opening and closing the mouth.Patients included in this study did not take any medications before starting treatment that could affect the results of the study.conditions after craniofacial trauma, rheumatic pathologies, surgery in the craniocervical region, neurological disease, uncontrolled systemic disease, any TMD treatment performed in the last 6 months, patients treated with corticosteroids or bisphosphonates.Based on the clinical analysis of the patients with TMJ dysfunctions, can state that almost all the patients had occlusion disorders due to errors in dental filling. When examining the fillings, much attention was paid to the marginal fit of the filling, contact points, height in relation to the antagonist teeth, and the state of the periapical tissues. Based on x-ray studies, the quality of root canal filling was determined.To diagnose the TMJ a CBCT  was used, which provided information about the condition of the tissues, the position of the axes of the joint heads Fig. . CTBT scDiagnostics of the TMJ condition was carried out by interpreting the obtained data. Normal function of the joints was characterized by noiseless movement of the head joint during rotation and progression. In this case, the disc is always on the joint head, moving with it. Contraction of the superior belly of the lateral pterygoid muscle causes an anteromedial effect on the disc, and the elastic resistance of the retrocondylar tissues causes smooth movement of the joint head and disc. Each patient’s course of treatment was worked out basing on the clinical and X-ray assessment of the disease, the causes preceding its development and occurrence. In any case, if the patient complained of pain in the TMJ area, both at rest and during the lower jaw movement, treatment began with its relief.All the patients were given full-fledged endodontic treatment and restoration of the crown part, taking into account anatomical features under the control of X-ray diagnosis.For endodontic treatment in patients used zinc oxide (ZnO), an antifungal drug  and the probiotic “Narine” , eugenol (clove oil), which was left in the root canal for 7 days, followed by filling with zinc-eugenol paste.To obtain the correct occlusal height, casts of the upper and lower jaws, diagnostic models were obtained, followed by their installation in the articulator, after the detection of supercontacts in the patient’s oral cavity, they were occlusal adjustments.All the patients were treated symptomatically. The complex therapy included analgesics, non-steroidal anti-inflammatory drug, muscle relaxants and relaxation therapies, topical analgesics gel.The complex therapy also included a patches by the company “Aganyan’’, patches includes a flexible substrate, a binder an adhesive layer, with an electrode foil attached to it Fig. .The electrodes are made of zinc and copper. The potential difference causes electrons to flow across the skin surface from one of the electrodes to the other and create electrical currents. In this sense, one of the electrodes can be considered as a cathode, while another electrode can be considered an anode. These ranges of voltages and electrical currents appear to be very safe for humans. Patients applied 1 patch behind each TMJ 8 h every third day for three months Fig. .51 patients complained of pain around the joint, pre-auricular region, muscles of mastication and the ear region, while 37 patients complained of pain on opening the mouth during mastication, 24 patients had impaired movement of the jaws, mouth opening was normal in 43 patients and reduced in 9 patients, deviation of the mandible on closing was observed in 14 patients, 32 patients complained of sounds  is a common disorder,most the leading symptoms is pain, followed by restricted mandibular movements, which can cause difficulty in eating or speaking; noises from the temporomandibular joints during jaw movement , 50.The TMJ) disease is more common in patients aged 20–40 and women are four times more likely to suffer from this disorder.e specific characteristics of the disease .The etiology of TMD is multifactorial, мalocclusion and occlusal interference are one of the factors in the development of temporomandibular disorders, so occlusal correction is included in the complex treatment of TMJ , 53.Diagnosis and treatment of TMJ remains a challenge, and there is still no consensus on many aspects, the most widely accepted and standardized tool for assessment and classification of TMD is Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) . DiagnosAn important part of the diagnosis of TMJ is the differential diagnosis from those clinically significant but unusual conditions that require urgent treatment , 55.Due to the complexity of the for many aspects etiology of TMD diagnosis, there is no consensus on treatment, depending on the type of TMJ a wide range of treatment methods are used: from conservative options to open surgical interventions, however, choosing the optimal one remains a problem.From variety of conservative treatment options it has been shown that the use of occlusal splint reduces the intensity of pain and has a positive effect reduces the intensity of pain and has a positive effect .For the treatment of patients in this category there are no uniform standards and treatment protocols, usually used, the non-surgical path is the first and main part. It consists of pharmacological therapies such as nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants and muscle relaxants and non-pharmacological treatment: biofeedback, LLLT, TENS –47.It is well known that TENS can reduce pain in patients with TMD, but requires further study .Mechanism of effect high frequency TENS is associated with a decrease in the amount of nociceptive substances released in peripheral tissues with the release of enkephalins and β-endorphins in the descending pain modulating system .Since there are reports in the literature about the effectiveness of the method of electrical nerve stimulation for the treatment of chronic musculoskeletal pain, based on analogues of this technique, Aganyan patches have been included in complex therapy patients with TMJ dysfunction syndrome.distortions. The main patient complaints included pain, difficulty or discomfort when biting or chewing, clicking, popping or grinding sound when opening or closing the mouth, ear pain, headache, decreased ability to open or close the mouth.In this article, the authors, present the results of their own studies. The study included 54 patients with TMJ dysfunction syndrome who had previously undergone endodontic dental treatment. To evaluate the effectiveness of the treatment of patients with temporomandibular joint dysfunction, along with clinical and radiological methods was used. According to the analysis of clinical data and anamnesis, the main etiological factor TMJ dysfunction syndrome in the study group of patients was occlusal It is known that the violation of occlusion can significantly complicate the course of TMJ disease, and incorrect treatment tactics lead to instability of the formed occlusion and relapse of the disease. The pain is caused by abnormal contractions of the masticatory muscles, which can stimulate the production of inflammatory substances around the joint.Complex treatment methods of the examined patients included correction of the occlusal height of filled teeth, the complex therapy also included therapy and with the use of a patches by the company “Aganyan’’,muscle relaxant, drug treatment, if indicated, orthopedic elimination of occlusal disorders.Adequate psychotherapy, elimination of traumatic factors, the use of pharmacotherapeutic agents, normalization of functioning associated with occlusive factors, electrostimulation using of a patches by the company “Aganyan’’, made it possible to rehabilitate patients with impaired TMJ function.The uniqueness of this invention is that electrical stimulation can be used for long-term stimulation TMJ with low voltage and current without the use of wires and batteries.The strengths of this study mainly relate to the use of an alternative, side-effect-free technique to treat this category of patients using, limitations in this study are the lack of a control group with placebo.It is important to note that this is the first report in the literature on the use of a patches by the company “Aganyan” in patients with TMJ and further research is needed to determine the effectiveness of the proposed technique and to make recommendations for its use.When planning therapeutic measures for TMJ dysfunctions, it is necessary to carry out a clinical and radiological assessment, orthopantomography, CT scan, as well as eliminate the causes preceding its development , which will significantly increase the possibility to diagnose and treat dysfunction of the temporomandibular joint.The results of the studies revealed a positive effects for the complex treatment dysfunctions syndrome TMJ the using the patches by the company “Aganyan” through electrical stimulation with low intensity.


Chronic pain is a significant health problem that affects an estimated 100 million American adults (aged ≥ 18 years). Chronic pain affects more individuals than heart disease, stroke, diabetes, and cancer combined. Chronic pain sufferers cost up to $635 billion annually in medical treatment and lost productivity. Opioids are commonly used to treat chronic pain, but their metabolic interactions with concurrently prescribed medications for concomitant disease burdens can affect potency and efficacy of pain therapy. Additionally, misuse of short-acting opioids (SAOs) for chronic pain versus breakthrough pain can create gaps in pain relief. These potentially suboptimal prescribing practices may contribute to the high economic impact associated with chronic pain.To examine the prevalence of suboptimal opioid therapy and the associated health care costs resulting from these prescribing practices in real-world patients presenting for all-causes to the emergency department (ED).This retrospective observational database cohort analysis used the linked Premier-Optum database and included patients with ED visits from 2006 to 2010 having ≥60 days supply of opioids in the 75 days prior to the visit. Suboptimal prescribing practices were identified as patients with (a) drug-drug exposures (DDEs), defined as cytochrome P-450 (CYP-450)-metabolized opioids prescribed concurrently with CYP-450 inhibitors or inducers and/or (b) monotherapy with SAOs. Comorbid conditions and principal diagnoses were documented. Readmission rates to the ED and hospital within 72 hours as well as ≤ 30, ≤ 45, ≤60, and ≤ 90 days were computed. Total costs for health care were calculated, and reimbursement rates were normalized using 2011 Medicare severity diagnosis-related group (MS-DRG) and CPT-4 information. Nonparametric bootstrapping to adjust for patient comorbidities was applied to cost data.P < 0.05) was observed at every time period except ≤ 72 hours. Respective mean increases in costs were $581, $689, $773, and $1,275 at 30, 45, 60, and 90 days. Exclusive SAO use with or without DDE resulted in a significant increase (P < 0.05) in mean costs at all times: $214 at 72 hours; $836 at 30 days; $1,023 at 45 days; $1,022 at 60 days; and $1,536 at 90 days.Of the 9,214 patients identified with chronic pain, potentially suboptimal medication practices prior to the index ED visit were found for 8,539 (92.6%) patients. These appeared to be corrected in 345 (4.0%) patients before leaving the ED. Of 675 (7.3%) patients without prior DDE or exclusive use of SAOs, 345 (51.1%) patients were discharged with one of these. Of the 8,352 patients who left the ED with DDE or exclusive use of SAOs, 1,525 (18.3%) left with a DDE without exclusive SAO use; 4,812 (57.6%) left with both DDE and exclusive SAO use; and 2,015 (24.1%) left with only exclusive SAO use. Only 862 (9.3%) patients from the entire cohort left the ED without DDE or exclusive SAO use. Patients identified with suboptimal opioid use were aged 50 ± 13.5 years and were predominantly female (64.0%). Hypertension (44.0%), fluid and electrolyte disorders (32.7%), chronic pulmonary disease (22.8%), depression (19.6%), diabetes without chronic complications (16.2%), and drug abuse (15.6%) were the most prevalent comorbid conditions identified. The most prevalent principal diagnoses involved symptoms and signs of ill-defined conditions (36.5%), injury and poisoning (18.2%), and diseases of the musculoskeletal system (13.2%). The majority of revisits to the ED and hospital admissions occurred within 72 hours (73.6%) of the index visit and within 30 days (70%), respectively. When adjusted total costs were compared for all patients whose opioid use included DDE versus those without, a significantly greater cost (This study identified potentially suboptimal opioid prescribing practices in a real-world population presenting for all-causes to the ED. The observed rate of ED revisits and inpatient admissions in these patients was associated with increased health care costs. These findings suggest that the ED has the future potential to serve as an ideal setting to identify and correct such practices, thereby improving patient care and reducing resource use and beneficiary costs. What is already known about this subjectChronic pain is a significant health problem that affects more than 100 million American adults, and chronic pain sufferers are considered to be heavy users of health care services.Chronic opioid use includes patients being medically managed for chronic conditions such as end-stage chronic obstructive pulmonary disease, osteoarthritis, rheumatoid arthritis, heart failure, and stroke.Exclusive use of short-acting opioids (SAOs) may predispose the patient to gaps in analgesia and adversely affect the patient experience compared with the appropriate use of controlled-release or long-acting opioids.What this study addsApproximately one third of patients having potentially suboptimal medication practices (medications known to interfere with opioid metabolism—drug-drug exposure [DDE]—and exclusive use of SAOs) were more likely to be seen in the ED a second time and in the inpatient setting if a DDE was involved.Average adjusted total costs for patients with DDE were higher than for patients without DDE. Total costs for patients with exclusive SAOs and DDE were consistently higher.Patients with exclusive Class-II SAOs, regardless of present DDE, had significantly more ED visits within 72 hours and through time intervals up to 90 days than patients with Class-III SAOs, although odds were higher when accompanied by DDE.2 More patients suffer from chronic pain than those with heart disease, stroke, diabetes, and cancer combined.3 Chronic pain sufferers are heavy users of health care services, costing the nation up to $635 billion annually in medical treatment and lost productivity.4 The true economic impact of chronic pain management is likely underestimated due to the use, misuse, and abuse of opioid analgesics.4 State prescription monitoring programs, in addition to federal programs and policies, have been developed to attempt to address this problem . Chronic noncancer pain has been defined as pain lasting longer than 3 months or beyond the expected period of healing of tissue pathology,4 although variation in practical application of the definition may exist to varying degrees. Based on clinician input in the design of this study, use of opioids for the majority of a 75-day period through the date of the index emergency department (ED) visit presupposes that persistent chronic pain was present.Chronic pain is a significant health problem that affects more than 100 million American adults.5 Chronic opioids are commonly used for as-needed pain relief in medically managed chronic conditions such as end-stage chronic obstructive pulmonary disease, osteoarthritis, rheumatoid arthritis, heart failure, and stroke.6 Recognition of inappropriate use of opioids and the consequences of addiction and overdosing is reflected in the recent FDA labeling changes for controlled-release and long-acting (CR/LA) opioids.8Despite well-known serious adverse events of acute respiratory depression, nocturnal hypoventilation, hypogonadism, physical dependence, and abuse, prescriptions for opioids in the treatment of chronic pain syndromes continue to rise disproportionately to the increase in the size of the U.S. population.9 Exclusive use of short-acting opioids (SAOs) may predispose the patient to gaps in analgesia, poor sleep hygiene, and adverse effects  compared with the use of CR/LA opioids. In addition to having a higher risk of abuse, Schedule II opioids have practical disadvantages compared with Schedule III opioids. Short-acting formulations of Schedule II and Schedule III opioids may result in different outcomes associated with their perceived analgesic “strength” and the likelihood that chronic or long-lasting pain may not be appropriately controlled due to their short-acting nature.Patients taking opioids and medications for concomitant medical conditions  are at increased risk for simultaneous drug-drug exposures (DDEs) and for interactions that can adversely alter opioid metabolism or amplify the adverse effect profile of these analgesics.10 Often patients without continuity or plans of care rely on the ED for maintenance of their pain management and treatment in times of “flare.” This pattern of ED use, as well as the possibility of hospital admission/readmission, is associated with a staggering price tag. Capitated reimbursements are problematic for health care systems managing these high-cost patients, and the burden of illness is especially high to accountable care organizations (ACOs) and their hospitals. These high costs serve as incentives among third-party and Centers for Medicare & Medicaid Services (CMS) payers to reduce the cost of caring for patients with chronic diseases.The magnitude of the problem associated with chronic pain and its treatment is evident in EDs nationwide.11 Additionally, the American Pain Society and the American Academy of Pain Medicine jointly published clinical guidelines to assist in the safe use of chronic opioid therapy in persistent noncancer pain in 2009.9 Because of the paucity of data concerning quality and cost within integrated care/accountable care health system models for chronic pain treatment, we sought to gain insights into opioid use in real-world patients presenting for all-causes to the ED. Specifically, our objectives were to (a) describe and quantify opioid drugs and concomitant medications known to interfere with opioid metabolism, which indicate potentially suboptimal medication practice; (b) describe and quantify comorbid conditions in this patient population; (c) determine the rate of admission for any cause to either the ED or the hospital within 72 hours and up to 90 days following an index ED visit; and (d) determine costs associated with these ED and hospital admissions. We hypothesized that among patients receiving opioids on a chronic basis who present for all-causes to the ED, there is an opportunity to identify and correct potentially suboptimal medication practices via medication reconciliation, which may result in improved patient care and safety, cost, and resource use.The need to more safely and effectively treat pain is reflected in the 2010 Patient Protection and Affordable Care Act that required the Department of Health and Human Services to enlist the Institute of Medicine to examine pain as a public health problem.12 a large U.S. hospital-based, all-payer, comparative database containing information on approximately 6 million annual hospital discharges  from primarily nonprofit, nongovernmental community and teaching hospitals, and health systems. Premier data include hospitalizations from more than 600 hospitals for the period 2000 to 2014 from all regions of the United States. In addition to the service-level data recorded in most standard hospital discharge files, the Premier database provides a daily log of all billed items, including procedures, medications, and laboratory tests, as well as diagnostic and therapeutic services at the individual patient level. The Premier data also provide information on demographic characteristics, discharge diagnoses, and discharge status . The data are not identified and comply with the Health Insurance Portability and Accountability Act of 1996.This retrospective observational database cohort analysis used the Premier research database,13 to form a single combined dataset for this study. The Optum database contains administrative claims data for an employed, commercially insured population and their dependents enrolled in select health insurance plans affiliated with United Health Group. It is representative of the nonelderly, commercially insured, managed care population of the United States, although it also contains information on several hundred thousand managed Medicaid and Medicare Advantage members. The database consists of aggregated enrollment data and inpatient, outpatient, pharmacy, and laboratory test claims, which when matched to the Premier hospital database permits continuum of care analyses.The Premier database was linked to the Optum Clinformatics databaseRecords from the Premier and Optum databases relating to a common hospital discharge were linked by matching inpatient hospitals to health plan hospitals and episodes of care in the two settings, based on hospital identification, patient admission/discharge dates, gender, date of birth, and diagnosis-related group (DRG) or Medicare severity diagnosis-related group (MS-DRG) assignment. The Premier-Optum linked dataset comprises aggregated  enrollment data and inpatient, outpatient, pharmacy, and laboratory test claims from approximately 100,000 patients annually, and it covers a geographically diverse membership. Patients in the linked dataset predominantly present with the same demographic profile as the Optum dataset on its own.International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis and MS-DRG coding.14 ED and inpatient admissions following the index ED visit were identified from claims so as to not be limited to the Premier set of hospitals. Patients with missing demographics, comorbidities, and principal diagnoses were excluded.Patients aged ≥ 18 years with hospital ED visits between January 2006 and September 2010 were included; the first ED visit for an individual meeting all selection criteria was considered the index visit; and each individual was followed for 90 days thereafter. Patients also had to have filled prescriptions for a minimum 60-day supply of at least one opioid medication within 75 days immediately prior to the index ED visit to be considered a chronic user of opioids as defined by both study design and definition of chronic pain. Comorbid conditions were obtained from current and prior visits via Potentially suboptimal opioid medication practices were defined as patients either (a) having used at least one cytochrome P-450 (CYP-450)-metabolized opioid with at least one CYP-450 nonopioid medication matched for opioid substrate, which indicated CYP-450 DDE; or (b) having only SAO agents for chronic pain. The DDE group only was divided into those with long-acting opioids (LAOs) and those with exclusive use of SAO. Thus, four major groups were assessed: (a) no DDE or exclusive use of SAO, (b) DDE only with or without LAO use; (c) DDE with exclusive SAO use; (d) exclusive SAO use and comparison by class as Schedule II and III.15 CYP-450 inhibitors and inducers identified for this study were drawn from lists available publicly,16 excluding non-medication dietary items. SAOs included certain formulations of codeine, hydrocodone, hydromorphone, and opioids that are not specifically formulated to be long-acting. LAOs included oxycodone formulated as Oxycontin, morphine as MS-Contin or Kadian, methadone as Dolophine, fentanyl as Duragesic, and oxymorphone as Opana ER. Exclusively used Schedule II and III SAOs were separately compared in acknowledgment of different risk of abuse because of practical considerations in prescribing that may affect costs and outcomes, and because chronic or long-lasting pain that is not appropriately controlled due to the drugs’ short-acting nature could be associated with outcomes differently depending on the Schedule.The precedent for identifying DDEs comes from published sources.Descriptive analyses were conducted, including baseline demographics and clinical characteristics of the total population and opioid groups. For continuous variables mean, standard deviation, median values, and minimum and maximum values were examined. Analysis of variance was used to determine differences observed between groups. For categorical variables, frequency percentages were examined and chi-square tests used to determine differences between groups.Rates for all-cause readmission to the ED and hospital admission occurring within 72 hours, 30 days, and up to 90 days were computed as well as total costs. Multivariable hierarchical logistic regression models were developed to account for varying hospital costs while adjusting for 29 comorbid conditions  and printh percentile were trimmed to eliminate outliers.17Total costs for health care over a defined period following the index ED visit that were associated with return to the ED or in-hospital readmissions were calculated as the sum of costs to the payer and out of the pocket of the patient. Commercially insured patients’ reimbursement rates were normalized to the Medicare fee schedule after applying the national daily average for MS-DRG and American Medical Association Common Procedural Terminology (CPT) reimbursement rates for 2011. Estimated inpatient hospital costs were calculated by multiplying the length of stay by the average Medicare daily reimbursement rate (average reimbursement rate ÷ average length of stay = average daily reimbursement). All-cause physician office visits, ED visits, and other facility charges were assigned costs by using national Medicare CPT reimbursement rates. Inpatient medication costs from the Premier hospital database and medication copay amounts from the Optum data were used for prescription costs. Patients with total costs above the 9918 Median, 2.5%, and 97.5% estimates were used to determine the average cost and 95% CIs, respectively. Where the 95% CI of the difference between comparison group costs did not include zero (no difference), the difference was determined to be statistically significant.To account for variation in costs across hospitals, multivariable mixed regression models were developed with a hierarchical modeling structure using hospital site as a random effect. Additional covariates included the 29 comorbid conditions and the primary ICD-9-CM diagnosis code from the index ED visit. Nonparametric bootstrapping was applied using 1,000 replicates with replacement to compare arithmetic means for costs between groups while accounting for the skewness in the cost data.P ≤ 0.05.All data aggregation and statistical analysis were performed using WinSQL  and SAS version 9.3 . Statistical significance was defined as Of 379,614 patients with available data, 9,214 patients fit all inclusion criteria . PotentiPatients in the overall study population were aged 50.0 ± 13.5 (mean ± SD) years, and were predominantly female (64.0%), commercially insured (93.1%), and mostly treated in hospitals in the South and North Central United States . HyperteOf 9,214 patients, 14%  returned within 72 hours to the ED, 16.6%  within 30 days, 17.3%  within 45 days, 18.0%  within 60 days, and 19.0%  within 90 days. Inpatient admissions for the same respective time periods were 12.4% , 23.5% , 27.1% , 30.4% (2.802), and 33.6% . For the total population, the majority of revisits to the ED and the majority of hospitalizations occurred within 72 hours (73.6%) of the index visit and within 30 days (70%), respectively. A similar pattern for ED revisits at 72 hours and inpatient admissions at 30 days was observed for all opioid medication groups.P = 0.013) and at 60 days (P = 0.043). Although significance was not reached at the other time points, a trend toward more ED revisits among exclusive SAO patients than among other patients was observed (P = 0.090-0.099). The adjusted odds of a return visit within 45 days and within 90 days were about 1.4 times greater for exclusive SAO patients (P > 0.05).As shown in patients . SimilarP ≤0.001) at every time period assessed. The adjusted odds of a readmission were not significantly different for exclusive C-II SAO patients without DDEs, regardless of the time interval .As depicted in P > 0.05).As depicted in P < 0.001). The adjusted odds of returning to the ED among these patients was 1.37-1.50 times greater than for exclusive C-II SAO patients , 60 days , and 90 days . The adjusted odds of readmission varied between 0.88 and 1.29 times greater for exclusive C-II SAO patients, but were only significantly different at 60 and 90 days  was observed only after 72 hours. The mean increases in costs (95% CI) were $581 (95% CI = $193-$972), $689 , $773 , and $1,275  at 30 days, 45 days, 60 days, and 90 days. Exclusive SAO use in the absence and presence of DDE (P < 0.05) in mean costs (95% CI) at all times: $214 (95% CI = $22-$395) at 72 hours; $836  at 30 days; $1,023  at 45 days; $1,022  at 60 days; and $1,536  at 90 days. Comparisons between exclusive C-II versus C-III SAO use in the overall patient population, as well as in the absence and presence of a DDE, revealed a significant increase (P < 0.05) in costs between 30 and 90 days but not at 72 hours  of potentially suboptimal opioid prescribing practices in patients presenting to the ED. Both DDE and exclusive use of SAOs were identified in half (52%) of all patients. Almost 16% of the population had only DDEs, and 22% had only SAOs. Of patients treated exclusively with SAOs, three times as many Schedule II SAOs were prescribed as Class III SAOs. No beneficial changes to these reported potentially suboptimal prescribing practices were affected by hospital contact. Furthermore, these theorized suboptimal practices were associated with ED readmissions or inpatient admissions, and increased costs and poorer performance on resource use were observed.20 The FDA now requires information regarding a drug’s CYP-450 metabolism and its potential for inhibition or induction to be on the drug label.20 The degree to which a patient responds to a drug is determined by genetic variability of drug metabolism21 as well as demographic and medical factors.18 These interactions may result in either reduced efficacy or increased toxicity of the target analgesic in question.Risk of drug interactions with an opioid is largely determined by the metabolizing enzyme system. Opioid metabolism primarily occurs in the liver through Phase 1 oxidation reactions involving the CYP-450 enzyme system and through Phase 2 glucuronidation by uridine diphosphate glucuronosyltransferases.22 However, many clinicians use them around the clock to relieve chronic persistent pain due to ease in prescribing, perceived lower cost, or lack of comfort with managing CR/LA opioids.3 Many are available in combination with acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID), which limits the maximum daily dose due to the risk of hepatic, renal, or gastrointestinal toxicity.3 Nearly all of the SAOs used by this study population were CYP-450 substrates. The vast majority was fixed-dose combinations of SAOs with acetaminophen.Use of SAOs to treat chronic pain either alone or in combination with CYP-450 metabolized opioids contributed significantly to the identified suboptimal prescribing practices observed in this study. SAOs had the greatest association with return visits to the ED and hospital admissions. When further assessed by class, patients treated with Schedule II opioids incurred higher costs and had significantly more visits to the ED across all time periods, possibly due to their seeking drugs. In the presence of DDE, more revisits to the ED and hospital occurred at all time points except 72 hours. While clear guidelines on optimal prescribing are lacking, CR/LA opioids are frequently used in patients requiring longer treatment durations. Anecdotally, SAOs result in larger risk for analgesic gaps and a higher risk for aberrant drug-taking behaviors. While SAOs are commonly prescribed, these agents are frequently considered appropriate for acute, breakthrough, or chronic intermittent pain.25 A recent survey of clinicians revealed differences among disciplines and specialties on impediments and concerns of prescribing, perceived effectiveness, Schedule II versus Schedule III selection, professional education, and understanding of tamper-resistant opioid formulations.26Although medication reconciliation was not part of the major study objectives, 4% of patients did receive new prescriptions for opioid medication at the time of ED discharge. Lack of corrective practices underscores the need to optimize opioid dosing to eliminate the risk that is associated with inappropriate use of opioid medications. Multidisciplinary approaches have been suggested and include both patients and health care practitioners.27 In this study, results did not examine the type of CYP-450 enzyme or whether the interaction involved exposure to substrates, inhibitors, or inducers. The increased costs resulted from a higher number of office and outpatient visits as well as ED visits and inpatient hospitalizations, the subject of this report. In a study of a managed care database that assessed health care use and costs of patients on chronic opioid therapy, a one-year follow-up revealed that chronic opioid users had more ambulatory, emergency, and hospital visits and higher annual costs than their nonuser matched controls.28 Total health care costs more than quadrupled, with respective medical and pharmacy costs noted to be about 5 and 3.5 times greater. Moreover, patients exhibiting nonadherence with chronic opioids identified by urine drug monitoring had more hospital days and were 14% more expensive compared with adherent patients. Unlike our study, this analysis did not specifically relate health care burden to suboptimal opioid prescribing practices.It is well documented that patients requiring chronic opioid analgesia with CYP-450 DDEs/interactions impact adversely on health care costs and resource use. During a six-month observational period, patients at risk for developing a pharmacokinetic drug-drug interaction had higher medical and pharmacy costs than their matched controls without DDE.29 This study considered costs at several intervals up to 90 days to ensure that variation in patients’ access to primary care physicians and clinics, to local and mail-order prescription refills, and to other unexpected resource use would be captured.Readmission rates were assessed at ≤72 hours and from 30 to 90 days. Readmissions prior to 72 hours may not bring additional reimbursement to the health care provider, so this is important from the hospital finance perspective. Medicare has previously proposed calculating the costs by combining a patient’s hospital expenses with fees incurred up to 90 days after discharge, and previous studies have also used 90 days as a cut-off point.30 interpretation of this data and identification of shortfalls of optimal therapy may be beyond traditional medication reconciliation.32 This role would be ideally suited for clinically trained pharmacists within either the ACO environment or via third-party payer drug utilization review.32 These pharmacists often serve on pain management teams, are familiar with computerized surveillance systems, and are experienced in the development of disease management optimization programs.33 The financial barriers associated with dedicating a clinical pharmacy specialist to providing medication therapy management recommendations real-time during the medication reconciliation process may be insurmountable, but they are potentially overcome by the cost data presented here.34ACOs provide an opportunity to promote responsible pain management and reduce costs in chronic pain sufferers. The Joint Commission recently released several Sentinel Event Alerts specifically noting the importance of both medication reconciliation and the safe use of opioids in hospitals. While medication reconciliation is defined by the CMS as “the process of identifying the most accurate list of all medications that the patient is taking, including name, dosage, frequency, and route, by comparing the medical record to an external list of medications obtained from a patient, hospital or other provider,”This study represents a real-world population providing data from all geographical areas of the United States with significant representation from South and North Central regions. Four groups of opioid medication prescribing patterns were identified and highlight ongoing multiple suboptimal prescribing practices by providers. These statistical analyses include generalized linear models for cost analysis, which help account for differences in patient and hospital characteristics between comparison groups, and the use of bootstrap analysis for comparing arithmetic mean costs.Use of the Optum database represents only commercially insured patients and their dependents aged 18-64 years. Medicare Advantage patient data were not available for this study. In addition, the lack of uninsured or state Medicaid-covered patients likely skews the presented data more favorably than is actually realized in the real-world health system setting. Given the nature of medical claims data, it is unclear whether observed changes to potentially suboptimal opioid practices were physician directed or the result of patient nonadherence. Potential for miscoded or missing data and the inability to control for uncaptured elements such as outpatient over-the-counter analgesics  may influence outcomes. Associations with DDEs and/or exclusive SAOs are evaluated at the population level rather than on an individual patient level, so extrapolation to any individual patient prospectively might be problematic.Costs were estimated using average 2011 MS-DRG payment amounts, so because amounts in prior years might have been less, the use of the 2011 amounts potentially produces values higher than were necessarily true. Readmissions from all-causes are not necessarily due to opioid medication, but this is indicative of the population-level view taken by the analysis. Reliance on pharmacy claims data assumes that patients are adherent with their medications for the full course of their prescriptions, although their actual duration of treatment and levels of day-to-day adherence are unknown. This limitation is offset by evidence that outpatient pharmaceutical claims data provide a more precise measure of patient medication use than self-reported medication use. Finally, this study presents statistical associations, not “cause and effect.”35 Its reclassification highlights the problem of drug abuse and dependence and the need for more restrictive prescribing practices. While our study includes hydrocodone combination medications as Schedule III, the health care outcomes and associated costs of C-II SAOs to treat chronic pain are significant and remain relevant and pertinent to opioid use practices.Since the design and completion of this study, the DEA has rescheduled hydrocodone combination medications from C-III to C-II. Although dosage of hydrocodone in these combination products is lower, its mechanism of action is identical to oxycodone and morphine.This study represents a retrospective observational analysis of the occurrence and prevalence of potentially suboptimal opioid medication prescribing and the cost implications associated with these practices. The in-depth opioid drug review demonstrates the magnitude of the problem and the need for targeted medication reconciliation and education. EDs provide an ideal setting to uncover these practices and initiate action that could include medication reconciliation and therapy recommendations by clinical pharmacy specialists. This resultant practice should reduce medication errors and admissions, improve patient outcomes, and be cost-effective for ACOs and other health care payers.


What is the association of different dosages of pregabalin and gabapentinoids with pain control and adverse outcomes in patients undergoing spine surgery?In this systematic review and network meta-analysis of 27 randomized clinical trials with 1861 patients, gabapentin 900 mg per day was associated with the lowest Visual Analog Scale pain score and was found to be the best in terms of reducing opioid consumption, followed by gabapentin 1200 mg per day, gabapentin 600 mg per day, gabapentin 300 mg per day, pregabalin 300 mg per day, pregabalin 150 mg per day, and pregabalin 75 mg per day. No statistically significant difference in adverse events  was noted among all treatments.These findings may guide clinicians and surgeons in determining the appropriate dosage of pregabalin and gabapentinoids in patients undergoing spine surgery. This systematic review and network meta-analysis evaluates the associations of pain, opioid consumption, and adverse events with different dosages of pregabalin and gabapentin in patients undergoing spine surgery. Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not been well established.To evaluate the associations of pain, opioid consumption, and adverse events with different dosages of pregabalin and gabapentin in patients undergoing spine surgery.PubMed/MEDLINE, Embase, Web of Science, Cochrane library, and Scopus databases were searched for articles until August 7, 2021.Randomized clinical trials conducted among patients who received pregabalin or gabapentin while undergoing spine surgery were included.Two investigators independently performed data extraction following the PRISMA  reporting guideline. The network meta-analysis was conducted from August 2022 to February 2023 using a random-effects model.The primary outcome was pain intensity measured using the Visual Analog Scale (VAS), and secondary outcomes included opioid consumption and adverse events.Twenty-seven randomized clinical trials with 1861 patients  were included in the systematic review and network meta-analysis. Compared with placebo, the VAS pain score was lowest with gabapentin 900 mg per day, followed by gabapentin 1200 mg per day, gabapentin 600 mg per day, gabapentin 300 mg per day, pregabalin 300 mg per day, pregabalin 150 mg per day, and pregabalin 75 mg per day. Additionally, gabapentin 900 mg per day was found to be associated with the lowest opioid consumption among all dosages of gabapentin and pregabalin, with a mean difference of −22.07%  for the surface under the cumulative ranking curve compared with placebo. There was no statistically significant difference in adverse events  among all treatments. No substantial inconsistency between direct and indirect evidence was detected for all outcomes.These findings suggest that gabapentin 900 mg per day before spine surgery is associated with the lowest VAS pain score among all dosages. In addition, no differences in adverse events were noted among all treatments. Adequate postoperative pain control has been linked to better outcomes, lower opioid consumption, shorter hospital stays, and reduced costs.5 In recent years, high-quality evidence has demonstrated the effectiveness and safety of using gabapentinoids to treat neuropathic pain following spinal cord injury.7 A previous meta-analysis8 with limited sample size and no head-to-head comparisons found that both gabapentin and pregabalin were effective in reducing postoperative pain and opioid consumption following spine surgery compared with placebo. However, new trials with direct comparisons have been published, and the results are conflicting. The aim of this study is to conduct a systematic review and meta-analysis to compare the effectiveness and safety of gabapentin and pregabalin for spine surgery in the perioperative period.Gabapentinoids, such as gabapentin and pregabalin, can inhibit central nervous sensitization. Although these 2 drugs have similar mechanisms of action and chemical structures, pregabalin is more potent and takes effect more quickly than gabapentin.PRISMA) reporting guideline and registered the study in PROSPERO (CRD42020188512). This study is a systematic review and meta-analysis conducted in accordance with the guidelines outlined by the Common Rule, which exempts this research from the requirement of institutional review board approval.We followed the PICO  search protocol framework to investigate the use of gabapentin and pregabalin in patients undergoing spinal surgery. The primary outcome of our study was pain intensity measured using the Visual Analog Scale (VAS), with secondary outcomes including adverse events  and opioid consumption. We adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses  extracted data onto a preplanned Excel  spreadsheet, including study characteristics, patient demographics, outcomes, and funding sources. Pain intensity was standardized using VAS scores ranging from 0 to 10 (with higher scores indicating worse pain), and opioid consumption was measured in milligrams and all data were converted into morphine milligram equivalents. We considered the concept of minimum clinically important differences (MCIDs) and assessed the quality of included studies using the Cochrane risk-of-bias tool.2 and I2 values. We used the surface under the cumulative ranking curve (SUCRA) to assess treatment performance.15 The SUCRA value closer to 100% indicates a higher probability of a treatment being among the top-ranked treatments or the best option overall.16 Inconsistency between direct and indirect comparisons was evaluated using the design-by-treatment interaction model.17 Also, Egger test and a funnel plot were performed for small-study bias.20 In our study, we used a meta-regression analysis to explore associations between study-level characteristics and treatment effects. Meta-regression analysis is a statistical method commonly used to investigate the associations of various factors with treatment effects across multiple studies. By considering study-level characteristics as covariates, we aimed to explore how these factors may be associated with treatment effects.22 A network meta-regression analysis extends these concepts by incorporating both treatment comparisons and covariates simultaneously. It allows for the examination of how treatment effects may be influenced by various factors, such as patient characteristics, study characteristics, or treatment characteristics. By considering these effect modifiers, network meta-regression can provide additional insights into the factors that may impact treatment effects and help explain the heterogeneity observed across studies. Levels of evidence are defined according to Halperin et al.23 Last, we used a semiautomated web application, Confidence in Network Meta-analysis (CINeMA),24 for the certainty of evidence for each outcome.We performed network meta-analysis using Stata statistical software version 17 (StataCorp) to estimate treatment effects. Forest plots were used to compare treatments with placebo as the reference group. Heterogeneity was assessed using τA total of 485 articles were identified through the database search. After the removal of duplicates, 478 articles remained. Next, 418 articles were excluded by checking the titles and abstracts. After checking the full text of the remaining studies, 33 articles were excluded according to exclusion criteria and mismatching of inclusion criteria, with details listed in eTable 2 in 51 The network graphs are presented in 50 the US ,43 and Europe .47 eTable 3 in 50 had funding from pharmaceutical companies, research centers from universities, and relevant departments from hospitals and foundations  including 777 patients who used placebo, included in the analysis.ndations .This outcome included 20 trials with 1427 patients. According to the head-to-head comparisons  among all treatments. These results suggest that gabapentin 900 mg per day before spine surgery may be an effective and safe option for reducing pain and opioid consumption in these patients.52 conducted a systematic review and meta-analysis that evaluated the effectiveness, adverse events, and withdrawal rates of various pharmacological interventions for managing chronic spinal cord injury pain. They found that tricyclic antidepressants, gabapentinoids, and opioids were the most effective in reducing pain, with the lowest withdrawal rates. They also found that these interventions had common adverse events, but they were generally mild to moderate. Tong et al6 conducted a network meta-analysis with 7 trials and found that pregabalin was the most effective for relieving pain and gabapentin performed better in aspects associated with drug therapy–related safety for patients with spinal cord injury. A Cochrane review conducted by Wiffen et al53 examined the existing research on the use of gabapentin for managing chronic neuropathic pain in adults. The study found that gabapentin at doses of 1200 mg or more daily can provide good levels of pain relief for some people with postherpetic neuralgia and painful diabetic neuropathy. The study also found that adverse events withdrawals were more common with gabapentin than with placebo and that individual adverse events occurred significantly more often with gabapentin, such as dizziness, somnolence, peripheral edema, and gait disturbance. Although those studies focused on neurogenic pain, our study targeted a different subset of population. Our study specifically focuses on pregabalin and gabapentin in patients undergoing spine surgery, whereas Tong et al6 and Canavan et al52 evaluated a wide range of pharmacological interventions for chronic spinal cord injury pain, and Wiffen et al53 focused on postherpetic neuralgia and painful diabetic neuropathy.Canavan et al54 evaluated the effectiveness of perioperative pregabalin administration in preventing chronic postoperative pain across different surgical procedures. They found that perioperative pregabalin administration does not prevent chronic postoperative pain, whereas our study found that pregabalin may have benefits in reducing pain in spine surgery. Verret et al55 conducted a large meta-analysis of 281 trials and assessed the effectiveness and safety of gabapentinoids in reducing postoperative pain and reducing opioid consumption after surgery. They concluded that there is no clinically significant analgesic effect for the perioperative use of gabapentinoids and also no effect on the prevention of postoperative chronic pain, with more risk of adverse events. Our study focused on patients undergoing spine surgery and found that gabapentin 900 mg per day before spine surgery was associated with the lowest VAS pain score among all dosages, and no differences in adverse events were noted among all treatments.Martinez et al56 and Waelkens et al.57 These studies underscore the significance of adopting a comprehensive strategy that combines various interventions to effectively manage pain and enhance patient outcomes. Peene et al56 noted that although gabapentinoids have proven efficacy in managing pain in the patient population undergoing lumbar laminectomy, they are not recommended as the first line of treatment because of the substantial risk of important adverse effects, including sedation, dizziness, and visual blurring. It is important to consider the risk-benefit profile of gabapentinoids and exercise caution when prescribing them. Our study further contributes to this understanding by specifically examining the comparative effectiveness of different dosages of gabapentinoids in the context of spine surgery, providing additional insights into their use and helping clinicians make informed decisions regarding pain management strategies in this population. In contrast to the study by Waelkens et al,57 which concluded that gabapentinoids are not recommended as part of a multimodal analgesic regimen in complex spine surgery because of limited evidence and concerns regarding adverse effects. Our study found no significant difference in the occurrence of adverse effects when comparing different dosages of gabapentinoids in patients undergoing spine surgery. This suggests that, within the dosages evaluated, the use of gabapentinoids does not pose a greater risk of adverse effects compared with other pain medications. However, it is important to note that the potential for adverse effects, such as sedation and respiratory depression, is still a concern with gabapentinoid use, as highlighted in the studies by Peene et al56 and Waelkens et al.57 Therefore, clinicians should carefully consider the risk-benefit profile of gabapentinoids and monitor patients closely for any adverse reactions when using these medications in the perioperative period. Our study adds to the existing literature by providing specific insights into the comparative effectiveness and safety of gabapentinoids in pain management during spine surgery, helping clinicians make informed decisions regarding their use in this context.Optimal pain control for spine surgery necessitates a multimodal approach, as emphasized by the guideline recommendations put forth by Peene et alThe use of gabapentinoids, such as gabapentin, to reduce opioid consumption in perioperative pain management has important implications. By minimizing opioid use, we can improve patient outcomes, mitigate risks and complications, and contribute to efforts to address the opioid crisis. Our study adds to the growing evidence supporting multimodal analgesic approaches that combine nonopioid medications and techniques for optimal pain control while minimizing opioid requirements. Reducing opioid consumption should be a primary goal in perioperative pain management, and our study highlights the potential of gabapentinoids, specifically gabapentin, in achieving this goal.27 it is important to discuss the differences observed between gabapentin 900 mg and 600 mg. The study by Pandey et al27 did not find gabapentin 900 mg to be superior to 600 mg in terms of pain control, which contrasts with our network meta-analysis results where gabapentin 900 mg demonstrated a lower VAS score compared with placebo and compared with gabapentin 600 mg. Several factors may explain these divergent findings. Variations in patient characteristics, surgical procedures, or study methods between the Pandey study27 and the trials included in our meta-analysis could contribute to the disparate outcomes. It is important to note that network meta-analysis offers a more comprehensive synthesis of evidence by incorporating both direct and indirect treatment comparisons. This approach allows for a more reliable estimation of treatment effects, particularly when there is a lack of head-to-head trials comparing specific dosages. However, despite the favorable findings for gabapentin 900 mg in our network meta-analysis, the presence of large overlap in the confidence intervals for the VAS estimates between gabapentin 900 mg and 600 mg suggests some uncertainty in the precise magnitude of the difference. In our study, we aimed to investigate the potential confounding effect of perioperative comedication and pharmaceutical funding on the primary outcomes of pain intensity, secondary outcomes of opioid consumption, and adverse effects. To address this, we performed a meta-regression analysis that allowed us to examine the influence of comedication use and funding source on the study outcomes. Specifically, we analyzed the impact of commonly used painkillers such as acetaminophen, celecoxib, and ketorolac, as well as the presence of funding from pharmaceutical companies or other foundations. Interestingly, our analysis revealed that neither the use of comedication nor the funding source had a significant association with the reported pain intensity, opioid consumption, or occurrence of adverse effects in our study population. These findings indicate that the inclusion of additional pain medications during the perioperative period and the funding source of the studies did not have a substantial impact on the observed outcomes. By conducting this meta-regression analysis, we provided more robust and reliable findings. It is important to consider these results when interpreting the overall findings of our study and when designing future research studies in the field of perioperative pain management.In the context of our study and the findings from the 2005 study by Pandey et al,Although, to our knowledge, this study is the first network meta-analysis on this topic, it has several limitations. The included studies exhibited heterogeneity in methods and patient populations, which may impact the overall conclusions. The limited number of subjects receiving gabapentin 900 mg per day reduced the precision of our estimates for this dosage. The heterogeneity in the duration of perioperative administration of gabapentinoids could introduce variability in treatment effects. Our study primarily focused on short-term outcomes and may not capture long-term effectiveness and safety data. Adverse events not included in the study may exist owing to the lack of comprehensive data. The generalizability of our findings to all patients undergoing spine surgery may be limited because of differences in surgical procedures and patient populations among the included trials. The determination of MCID for postoperative pain, particularly in the context of spine surgery, is not straightforward and can vary depending on multiple factors such as the patient population, the surgical procedure, and the measurement instrument used. This limitation restricts the accuracy and interpretation of the SUCRA values, which should be interpreted cautiously. Future research with larger sample sizes, robust methods, standardized outcome measures, and longer follow-up durations is needed to address these limitations and provide more conclusive evidence on the optimal dosages and safety of gabapentinoids in the perioperative setting.In conclusion, our study findings suggest that the preoperative administration of gabapentin and pregabalin may effectively alleviate postoperative pain and reduce opioid consumption in patients undergoing spine surgery. However, it is important to note that increasing the dosage of gabapentin above 900 mg was not found to be associated with further pain reduction. It is crucial for future research to encompass larger, well-designed RCTs to validate our findings and ascertain the optimal dosage and long-term safety of these medications for patients undergoing spine surgery.