Interrelations between orthostatic postural deviations and subjects' age, sex, malocclusion, and specific signs and symptoms of functional pathologies of the temporomandibular system: a preliminary correlation and regression study.

AIMS: Studies on the relationships between postural deviations and the temporomandibular system (TS) functional health are controversial and inconclusive. This study stems from the hypothesis that such inconclusiveness is due to authors considering functional pathologies of the TS (FPTS) as a whole, without taking into account subjects' specific FPTS signs and symptoms. METHODOLOGY: Based on the author and collaborators' previous studies, the present study analyzed data on body posture from a sample of 50 subjects with (30) and without (20) FPTS. Correlation analyses were applied, taking as independent variables age, sex, Helkimo anamnestic, occlusal, and dysfunction indices, as well as FPTS specific signs and symptoms. Postural assessments of the head, cervical spine, shoulders, lumbar spine, and hips were the dependent variables. Linear regression equations were built that proved to partially predict the presence and magnitude of body posture deviations by drawing on subjects' characteristics and specific FPTS symptoms. RESULTS: Determination coefficients for these equations ranged from 0.082 to 0.199 in the univariate, and from 0.121 to 0.502 in the multivariate regression analyses. CONCLUSIONS: Results show that factors intrinsic to the subjects or the TS may potentially interfere in results of studies that analyze relationships between FPTS and body posture. Furthermore, a trend to specificity was found, e.g. the degree of cervical lordosis was found to correlate to age and FPTS degree of severity, suggesting that some TS pathological features, or malocclusion, age or sex, may be more strongly correlated than others with specific posture patterns.

Surgery is associated with better long-term outcomes than pharmacological treatment for obesity: a systematic review and meta-analysis.

Obesity is a highly prevalent disease with numerous complications. Both intensive medical treatment with the use of pharmacological drugs and bariatric surgery are current options. The objective of this meta-analysis was to compare, in the long-term, intensive medical treatment and surgery based on twelve parameters related to weight loss, cardiovascular and endocrine changes. A review of the literature was conducted in accordance with the PRISMA guidelines (PROSPERO: CRD42021265637). The literature screening was done from inception to October 2023 through PubMed, EMBASE and Web of Science databases. We included randomized clinical trials that had separate groups for medical treatment and bariatric surgery as an intervention for obesity. The risk of bias was assessed through RoB2. A meta-analysis was performed with measures of heterogeneity and publication bias. Subgroup analysis for each surgery type was performed. Data is presented as forest-plots. Reviewers independently identified 6719 articles and 6 papers with a total 427 patients were included. All studies were randomized controlled trials, three had a follow up of 5 years and two had a follow up of 10 years. Both groups demonstrated statistical significance for most parameters studied. Surgery was superior for weight loss (- 22.05 kg [- 28.86; - 15.23), total cholesterol (- 0.88 [- 1.59; - 0.17]), triglycerides (- 0.70 [- 0.82; - 0.59]), HDL (0.12 [0.02; 0.23]), systolic pressure (- 4.49 [- 7.65; - 1.33]), diastolic pressure (- 2.28 [- 4.25; - 0.31]), Hb glycated (- 0.97 [- 1.31; - 0.62]), HOMA IR (- 2.94; [- 3.52; - 2.35]) and cardiovascular risk (- 0.08; [- 0.10; - 0.05]). Patient in the surgical treatment group had better long term outcomes when compared to the non-surgical group for most clinical parameters.

Effects of neuroplasticity in people with knee osteoarthritis: A systematic review of the literature.

BACKGROUND: Knee osteoarthritis (OA) is associated with chronic inflammation in somatic structures, which alters sensory afferents and leads to plastic changes in the nervous system. METHODS: A systematic literature review was carried out, without language restrictions, period, or status of publication. The database used were Medline, EMBASE, Cochrane Library and clinicaltrials.gov. Extra bibliographic references were extracted through the discussion with specialists, and through scientific researches in conference papers. RESULTS: The electronic search found 938 articles. When excluding duplicates and applying the inclusion/exclusion criteria, 5 studies were considered: 2 using EEG and 3 using TMS. Significant reduction of EEG activity in the cingulate medium cortex, reduction of conditioned pain modulation (CPM) in studies with EEG, as well as the occurrence of an association between pain and motor response threshold/intracortical pain facilitation in studies with TMS were observed. CONCLUSIONS: The study contributes to a better understanding of the neurophysiological changes seen in the cingulate medium cortex, decrease in CPM and motor response threshold/intracortical pain facilitation. Advances in neuroplasticity studies may aid in the screening for early diagnosis of knee OA in the future. However, more studies are necessary.

Comparing dextrose prolotherapy with other substances in knee osteoarthritis pain relief: A systematic review.

The objective of this study is to compare the effectiveness of dextrose-prolotherapy with other substances for pain relief in patients with primary knee osteoarthritis. The literature screening was done in January 2021 through Medline (PubMed), EMBASE, and Database of the National Institute of Health based on the following criteria: randomized clinical trials that subjected patients with primary knee osteoarthritis who underwent treatment with dextrose-prolotherapy and other substances for pain relief. Paired reviewers independently identified 3381 articles and included 8 trials that met the eligibility criteria. According to the findings of this review, participants that underwent dextrose-prolotherapy showed improvements between baseline and posterior assessments and when compared to saline injections, but when compared to other substances, the results were not clear. Although dextrose-prolotherapy is a useful treatment method by itself, it is still not possible to clearly affirm that it is superior or inferior to its counterparts. There is an urgent need for further studies to bring more evidence to the field.

Cirrhosis and hernia repair in a cohort of 6352 patients in a tertiary hospital: Risk assessment and survival analysis.

The prevalence of hernias in patient with cirrhosis can reach up to 40%. The pathophysiology of cirrhosis is closely linked to that of the umbilical hernia, but other types are also common in this population. The aim of this study is to evaluate factors that influence in the prognosis after hernia repair in patients with cirrhosis. A historical cohort of 6419 patients submitted to hernia repair was gathered. Clinical, epidemiological data and hernia characteristics were obtained. For patient with cirrhosis, data from exams, surgery and follow-up outcomes were also analyzed. Survival curves were constructed to assess the impact of clinical and surgical variables on survival. 342 of the 6352 herniated patients were cirrhotic. Patient with cirrhosis had a higher prevalence of umbilical hernia (67.5% × 24.2%, P < .001) and a lower prevalence of epigastric (1.8% × 9.0%, P < .001) and lumbar (0% × 0.18%, P = .022). There were no significant differences in relation to inguinal hernia (P = .609). Ascites was present in 70.1% of patient with cirrhosis and its prevalence was different in relation to the type of hernia (P < .001). The survival curve showed higher mortality for emergency surgery, MELD > 14 and ascites (HR 12.6 [3.79-41.65], 4.5 [2.00-10.34], and 6.1 [1.15-20.70], respectively, P < .05). Hernia correction surgery in patient with cirrhosis has a high mortality, especially when performed under urgent conditions associated with more severe clinical conditions of patients, such as the presence of ascites and elevated MELD.

MICRObiota on BILIOpancreatic malignant diseases [MICROBILIO]: A systematic review.

INTRODUCTION: The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA). METHODS: This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases. RESULTS: Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies' results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA. CONCLUSION: There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.

The inconclusiveness of research on functional pathologies of the temporomandibular system and body posture: Paths followed, paths ahead: A critical review.

Objective: Literature on the functional pathologies of the temporomandibular system (FPTS) in its relationships with body posture is plagued with inconclusiveness. Despite being sometimes altogether disregarded, the issue is most relevant, due to its clinical implications. This paper aims for a deeper understanding of the origins of the inconclusiveness of research on such relationships by means of a critical analysis of the scientific literature on the subject, in order that clinicians may better treat patients with FPTS.Methods: Analysis of over 100 studies, published from 1918 through March 2018 in the PubMed database, using descriptors temporomandibular joint disorders and posture.Results: The analysis of the paths followed by researchers allowed for pinning down several methodological issues that may have led to the prevailing ambiguity on the matter.Conclusion: This review then proposes certain standardization of procedures in future studies, to be conducted by a proposed consortium of researchers.

Acupuncture for the Treatment of Itch: Literature Review and Future Perspectives.

Background: Chronic pruritus is a prevalent, multifactorial and debilitating condition that is often underestimated. This article reviews current evidence to evaluate the efficacy of acupuncture for the treatment of itch. Results: Although many researchers have conducted observational studies, clinical trials, and systematic reviews on the subject, the lack of more-robust and well-designed studies to prove the effectiveness of acupuncture in the management of itch is evident. Many published studies are of poor quality, with no clear description of randomization methods, and an absence of control groups and measurable clinical outcomes. In addition, a lack of standardization in methods for assessing pruritus and the acupuncture treatment protocols hinders more-comprehensive and higher-quality pooled data analysis. Conclusions: Current evidence cannot fully support acupuncture for the treatment of itch yet.

The Development of Feeding and Eating Disorders after Bariatric Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients in the postoperative period following bariatric surgery are at risk of developing eating disorders. This study aims to analyze the relation between bariatric surgery and the development and recurrence of eating disorders. MATERIAL AND METHODS: A literature review was carried out on 15 November 2020. Fourteen studies that met the eligibility criteria were included for qualitative synthesis, and 7 studies for meta-analysis. RESULTS: The prevalence of eating disorders in the postoperative period was 7.83%, based on the 7 studies in the meta-analysis. Binge eating disorder alone was 3.81%, which was the most significant factor, and addressed in 6 of these studies. CONCLUSION: The investigated studies have significant methodological limitations in assessing the relation between bariatric surgery and eating disorders, since they mostly present data on prevalence. PROSPERO CRD42019135614.

The development of laparoscopic skills using virtual reality simulations: A systematic review.

BACKGROUND: Teaching based on virtual reality simulators in medicine has expanded in recent years due to the limitations of more traditional methods, especially for surgical procedures such as laparoscopy. PURPOSE OF REVIEW: To analyze the effects of using virtual reality simulations on the development of laparoscopic skills in medical students and physicians. DATA SOURCES: The literature screening was done in April 2020 through Medline (PubMed), EMBASE and Database of the National Institute of Health. ELIGIBILITY CRITERIA: Randomized clinical trials that subjected medical students and physicians to training in laparoscopic skills in virtual reality simulators. STUDY APPRAISAL: Paired reviewers independently identified 1529 articles and included 7 trials that met the eligibility criteria. FINDINGS: In all studies, participants that trained in virtual simulators showed improvements in laparoscopic skills, although the articles that also had a physical model training group did not show better performance of one model compared to the other. LIMITATIONS: No article beyond 2015 met the eligibility criteria, and the analyzed simulators have different versions and models, which might impact the results. CONCLUSION: Virtual reality simulators are useful educational tools, but do not show proven significant advantages over traditional models. The lack of standardization and a scarcity of articles makes comparative analysis between simulators difficult, requiring more research in the area, according to the model suggested in this review. SYSTEMATIC REVIEW REGISTRATION NUMBER: Registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020176479.

A randomized controlled trial of acupuncture added to usual treatment for fibromyalgia.

OBJECTIVE: To evaluate the effectiveness of acupuncture for fibromyalgia. METHODS: Fifty-eight women with fibromyalgia were allocated randomly to receive either acupuncture together with tricyclic antidepressants and exercise (n=34), or tricyclic antidepressants and exercise only (n=24). Patients rated their pain on a visual analogue scale. A blinded assessor evaluated both the mean pressure pain threshold value over all 18 fibromyalgia points and quality of life using SF-36. RESULTS: At the end of 20 sessions, patients who received acupuncture were significantly better than the control group in all measures of pain and in 5 of the SF-36 subscales. After 6 months, the acupuncture group was significantly better than the control group in numbers of tender points, mean pressure pain threshold at the 18 tender points and 3 subscales of SF-36. After one year, the acupuncture group showed significance in one subscale of the SF-36; at 2 years there were no significant differences in any outcome measures. CONCLUSION: Addition of acupuncture to usual treatments for fibromyalgia may be beneficial for pain and quality of life for 3 months after the end of treatment. Future research is needed to evaluate the specific effects of acupuncture for fibromyalgia.

Radial extracorporeal shock wave therapy for disabling pain due to severe primary knee osteoarthritis.

OBJECTIVE: To assess the efficacy and safety of radial extracorporeal shock wave therapy (rESWT) for disabling pain due to primary knee osteoarthritis. DESIGN: Randomized, placebo-controlled trial (level of evidence, 1). SUBJECTS: A total of 105 women with disabling pain due to primary knee osteoarthritis lasting for a mean of 103 months (range 3-480 months). METHODS: Patients received either rESWT (3 sessions, each one week apart, 2,000 rESWT impulses per session, positive energy flux density 0.10-0.16 mJ/mm2) or placebo treatment. Primary outcome measure was pain on movement 3 months after the final treatment session. Secondary outcomes were pain, stiffness and limitations in physical function on the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and the level of tolerance to pressure over muscles, tendons, ligaments and skin at both the treated and the untreated side at 1 week and 3 months follow-up examinations. RESULTS: Compared with placebo treatment, rESWT led to a statistically significant improvement only in mean WOMAC scores for pain and a few of the pressure measurements. CONCLUSION: rESWT, as performed in the present study, is not efficient for treating patients with disabling pain due to primary knee osteoarthritis. Published data indicate that substantially higher energy flux densities are necessary for treatment success in this condition.

Anatomical Basis of the Myofascial Trigger Points of the Gluteus Maximus Muscle.

Myofascial pain syndrome is characterized by pain and limited range of motion in joints and caused by muscular contracture related to dysfunctional motor end plates and myofascial trigger points (MTrPs). We aimed to observe the anatomical correlation between the clinically described MTrPs and the entry point of the branches of the inferior gluteal nerve into the gluteus maximus muscle. We dissected twenty gluteus maximus muscles from 10 human adult cadavers (5 males and 5 females). We measured the muscles and compiled the distribution of the nerve branches into each of the quadrants of the muscle. Statistical analysis was performed by using Student's t-test and Kruskal-Wallis tests. Although no difference was observed either for muscle measurements or for distribution of nerve branching among the subjects, the topography of MTrPs matched the anatomical location of the entry points into the muscle. Thus, anatomical substract of the MTrPs may be useful for a better understanding of the physiopathology of these disorders and provide basis for their surgical and clinical treatment.

Comparing dextrose prolotherapy with other substances in knee osteoarthritis pain relief: A systematic review

Abstract The objective of this study is to compare the effectiveness of dextrose-prolotherapy with other substances for pain relief in patients with primary knee osteoarthritis. The literature screening was done in January 2021 through Medline (PubMed), EMBASE, and Database of the National Institute of Health based on the following criteria: randomized clinical trials that subjected patients with primary knee osteoarthritis who underwent treatment with dextrose-prolotherapy and other substances for pain relief. Paired reviewers independently identified 3381 articles and included 8 trials that met the eligibility criteria. According to the findings of this review, participants that underwent dextrose-prolotherapy showed improvements between baseline and posterior assessments and when compared to saline injections, but when compared to other substances, the results were not clear. Although dextrose-prolotherapy is a useful treatment method by itself, it is still not possible to clearly affirm that it is superior or inferior to its counterparts. There is an urgent need for further studies to bring more evidence to the field. HIGHLIGHTS Dextrose injections promote deposition of collagen into injured structures through growth factors and inflammatory cells. Dextrose-prolotherapy is a useful treatment method, but it is not superior or inferior to its counterparts.

MICRObiota on BILIOpancreatic malignant diseases [MICROBILIO]: A systematic review

Abstract Introduction: The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA). Methods: This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases. Results: Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies' results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA. Conclusion: There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.

Telerehabilitation in Parkinson's disease: Influence of cognitive status.

BACKGROUND: The need for efficacy in voice rehabilitation in patients with Parkinson's disease is well established. Given difficulties traveling from home to treatment centers, the use of telerehabilitation may represent an invaluable tool for many patients. OBJECTIVE: To analyze the influence of cognitive performance on acceptance of telerehabilitation. METHODS: Fifty patients at stages 2-4 on the Hoehn-Yahr scale, aged 45-87 years old, with cognitive scores of19-30 on the Mini-Mental State Examination, and 4-17 years of education were enrolled. All patients were submitted to evaluation of voice intensity pre and post in-person treatment with the Lee Silverman Voice Treatment (LSVT) and were asked to fill out a questionnaire regarding their preferences between two options of treatment and evaluating basic technological competence. RESULTS: Comparisons between pre and post-treatment values showed a mean increase of 14dBSPL in vocal intensity. When asked about potential acceptance to participate in future telerehabilitation, 38 subjects agreed to take part and 12 did not. For these two groups, 26% and 17% self-reported technological competence, respectively. Agreement to engage in remote therapy was positively associated with years of education and cognitive status. CONCLUSION: Responses to the questionnaire submitted after completion of traditional in-person LSVT showed that the majority of patients (76%) were willing to participate in future telerehabilitation. Age, gender, disease stage and self-reported basic technological skills appeared to have no influence on the decision, whereas other factors such as cognitive status and higher school education were positively associated with acceptance of the new therapy approach.

EMBASAMENTO: A eficácia na reabilitação da voz em pacientes com doença de Parkinson está bem estabelecida. Tendo em vista as dificuldades de lidar com a locomoção de casa para centros de tratamento, o uso da telerreabilitação pode representar uma ferramenta inestimável para muitos pacientes. OBJETIVO: Analisar a influência do desempenho cognitivo na aceitação da telerreabilitação. MÉTODOS: Participaram cinquenta pacientes em estágios 2-4 de acordo com a escala de Hoehn-Yahr, com idade entre 45 e 87 anos, escores cognitivos de 19 a 30 no Mini-Exame do Estado Mental e escolaridade entre 4-17 anos. Todos foram submetidos à avaliação da intensidade da voz antes e depois do tratamento pelo Lee Silverman Voice Treatment (LSVT) e foram convidados a responder um questionário sobre suas preferências entre duas opções de tratamento. RESULTADOS: O tratamento resultou em aumento médio de 14dBNPS. Quando questionados sobre a possibilidade de aceitação para participar de um futuro programa de telerreabilitação, 38 indivíduos concordaram e 12 não. Em relação a estes dois grupos, a competência tecnológica foi referida em 26% e 17%, respectivamente. A aceitação à telerreabilitação foi positivamente relacionada com anos de estudo e estado cognitivo. CONCLUSÃO: As respostas ao Questionário após a conclusão do LSVT tradicional mostraram que a maioria dos pacientes (76%) concordaria em participar de uma futura telerreabilitação. Idade, sexo, estágio da doença ou competência tecnológica não pareceu influenciar na adesão à telerreabilitação enquanto que outros fatores, como estado cognitivo e anos de escolaridade foram positivamente relacionados com a aceitação da nova forma de terapia.

Voice telerehabilitation in Parkinson's disease. / Telerreabilitação vocal na doença de Parkinson.

UNLABELLED: Parkinson's disease (PD) is a neurodegenerative condition associated with motor, neuropsychological, sensorial, and vocal symptoms. It has been suggested that eventual obstacles faced by many patients to reach speech therapy rehabilitation centers could be overcome with the use of synchronous telerehabilitation (real time) approach employing communication technologies. PURPOSE: To investigate the efficacy of vocal telerehabilitation in PD patients. METHODS: Twenty patients diagnosed with PD and with vocal complaints participated in this study. Patients were evaluated by videoconference (Adobe Connect 8) before and after treatment. Evaluation method consisted of perceptual analysis of vocal quality measured by the GRBASI scale. Treatment was conducted following the extended version of Lee Silverman method (LSVT-X). At the end of treatment all patients were requested to fill a questionnaire to assess their experience with telerehabilitation. RESULTS: Analysis revealed decrease in magnitude of voice quality changes after the intervention, indicating improvement of vocal pattern. All patients reported satisfaction and preference for telerehabilitation compared to face-to-face rehabilitation, as well as positive perception of audio and video. Some technological adversities have been identified but did not prevent the approaches to assessment and treatment. CONCLUSION: Present results suggest that telerehabilitation methods can be considered as an effective treatment for speech symptoms associated with PD and can be indicated to patients presenting limited access to speech therapy centers and technological readiness.

Trigger points: an anatomical substratum.

This study aimed to bring the trapezius muscle knowledge of the locations where the accessory nerve branches enter the muscle belly to reach the motor endplates and find myofascial trigger points (MTrPs). Although anatomoclinical correlations represent a major feature of MTrP, no previous reports describing the distribution of the accessory nerve branches and their anatomical relationship with MTrP are found in the literature. Both trapezius muscles from twelve adult cadavers were carefully dissected by the authors (anatomy professors and medical graduate students) to observe the exact point where the branches of the spinal accessory nerve entered the muscle belly. Dissection was performed through stratigraphic layers to preserve the motor innervation of the trapezius muscle, which is located deep in the muscle. Seven points are described, four of which are motor points: in all cases, these locations corresponded to clinically described MTrPs. The four points were common in these twelve cadavers. This type of clinical correlation between spinal accessory nerve branching and MTrP is useful to achieve a better understanding of the anatomical correlation of MTrP and the physiopathology of these disorders and may provide a scientific basis for their treatment, rendering useful additional information to therapists to achieve better diagnoses and improve therapeutic approaches.

Anti-nerve growth factor in the treatment of low back pain and radiculopathy: a systematic review and a meta-analysis.

BACKGROUND: Low back pain with or without radiculopathy is an important cause of disability and economic expenditure. However, many patients are not meeting optimal pain control through existing treatments. Recent studies have linked nerve growth factor (NGF) and the pathophysiology of persistent pain. Anti-NGF could be an alternative drug treatment for low back pain. OBJECTIVE: Systematically review the efficacy and safety of anti-NGF in the treatment of low back pain. METHODS: A systematic review of the literature with no language, date or publication status restriction, using Medline, EMBASE, Cochrane Library, and the clinicaltrials.gov database. Additional literature was retrieved by conferring with experts in the field or reviewing bibliographies and annals of meetings and congresses. Search terms included "monoclonal antibodies," "nerve growth factor," "anti-ngf," "fulranumab," "tanezumab," "sciatica," "back pain," and "spine." STUDY DESIGN: Inclusion criteria were observational studies with safety as an outcome and randomized or nonrandomized controlled trials studying the efficacy and/or the safety of anti-NGF drugs on low back pain. Exclusion criteria included patients with autoimmune conditions or osteoporosis. Studies were assessed independently by 2 authors regarding inclusion/exclusion criteria, risk of bias, clinical relevance, and quality of evidence (GRADE approach). RESULTS: 1,168 studies were retrieved. After excluding duplicates and applying the inclusion/exclusion criteria, 4 RCTs remained (n = 2,109): 2 for tanezumab, one for REGN475, and one for fulranumab. Only the tanezumab studies showed any significant difference over placebo (n = 1,563) for both pain relief and functional improvement. CONCLUSIONS: There is very low evidence that systemically administered anti-NGF therapy has a small positive effect compared to placebo for both pain relief (standarized mean difference [SMD] = -0.29, 95% confidence interval [CI] -0.58 to 0.00) and functional improvement (SMD = -0.21, 95%CI -0.37 to -0.05 ) of low back pain. There was low evidence of adverse effects (AEs) compared to placebo and low evidence of neurological AEs than placebo (relative risk = 1.93, 95%CI 1.41 to 2.64).Tanezumab, as a specific anti-NGF treatment, showed low evidence of a small to moderate effect for pain relief of low back pain (SMD = -0.44, 95%CI -0.81 to -0.07); and low evidence of a small effect for functional improvement (SMD = -0.26, 95%CI -0.40 to -0.12) with systemic administration, although not clinically significant. Tanezumab and anti-NGFs overall had, respectively, moderate and low evidence of overall AEs and serious AEs and a higher risk of developing neurological AEs when compared with placebo. Although anti-NGF, specifically tanezumab, showed a low-to-moderate effect on pain relief and functional improvement, it cannot be recommended for low back pain treatment. Without more research on the pathophysiology of anti-NGFs and adverse effects, its use is not safe in the overall population. However, as corroborated by the US Food and Drug Administration, this meta-analysis underscores a role for greater insight into anti-NGF therapy for painful conditions that are refractory to current drugs, such as oncologic pain, chronic pancreatitis, and phantom-limb pain. Given the pathophysiology of axial pain involving inflammatory mediators and the adverse effects of systemic anti-NGF use, consideration of local therapies may warrant further exploration.

Anti-tumor necrosis factor antagonists in the treatment of low back pain and radiculopathy: a systematic review and meta-analysis.

BACKGROUND: Low back pain, with or without radiculopathy, is an important cause of disability and economic expenditure. However, many patients are not achieving optimal pain control with existing medications. Tumor necrosis factor antagonists (anti-TNFα) could be an alternative drug treatment. OBJECTIVES: Systematic review the efficacy and safety of anti-TNFα in the treatment of low back pain with or without radiculopathy. STUDY DESIGN: Inclusion criteria were observational studies with safety as an outcome, and randomized or nonrandomized controlled trial (RCT) studies on efficacy and/or safety of anti-TNFα drugs on low back pain. Exclusion criteria included patients with auto-immune conditions or osteoporosis. RESULTS: Studies were assessed independently by 2 authors regarding inclusion/exclusion criteria, risk of bias, clinical relevance, quality, and strength of evidence (GRADE approach). Of the 1,179 studies retrieved, all duplicates were excluded and then the inclusion/exclusion criteria was applied. One observational study (n = 143) and 11 RCTs remained (n = 539): 8 for etanercept (n = 304), one for adalimumab (n = 61), one for adalimumab and etanercept (n = 60), one for infliximab (n = 40) and one for REN-1654 (n = 74). Only 3 etanercept and 2 adalimumab studies showed statistically significant pain relief when compared to placebo. There was no difference in the overall incidence of adverse effects when comparing anti-TNF-α and placebo. LIMITATIONS: Despite the statistically significant effect, this meta-analysis has important limitations, such as high heterogeneity and high use of outcome imputation. CONCLUSIONS: There is low evidence that epidural etanercept has a low-to-moderate effect size when compared to placebo for pain due to discogenic lumbar radiculopathy (5 studies, n=185), with a standardized mean difference = -0.43 (95% confidence interval [CI] -0.84 to -0.02).There is moderate evidence that epidural etanercept does not have a higher adverse effects incidence rate when compared to placebo for discogenic lumbar radiculopathy (5 studies, n = 185) with a relative risk (RR) = 0.84 (95% CI 0.53 to 1.34).There is moderate evidence that anti-TNFα does not have a higher adverse effects incidence rate when compared to placebo for low back pain (10 studies, n= 343) with an RR = 0.93 (95% CI 0.56 to 1.55).We strongly suggest that anti-TNFα continue to be studied in experimental settings for the treatment of low back pain. We cannot currently recommend this therapy in clinical practice. New research could shed some light on the efficacy of anti-TNFα and change this recommendation in the future.