The aim of this systematic review was to evaluate the effectiveness of laser application in temporomandibular joint disorder. R statistical software.  PubMed, SCOPUS, Science Direct, Web of Science, and Google Scholar electronic databases were searched systematically with restricting the languages to only English and year (January 2001 to March 2020), and studies were selected based on the inclusion criteria. Study quality and publication bias were assessed by using the Robvis, a software package of  This systematic review included 32 studies (1172 patients) based on the inclusion and exclusion criteria. Most of the studies reported significant reduction of pain by the use of the laser during TMD treatment. Two-thirds of the study (78.13%) found a better outcome comparing with conventional one. According to Robvis, 84.4% of the studies were high methodological studies with low risk of bias. CRD42020177562). TMD patients suffer with continuous pain for long time even after conventional treatment. Laser therapy shows a promising outcome of pain reduction for TMD patients. Therefore, laser therapy can be recommended for the TMD patients' better outcome. This trial is registered with PROSPERO ( Temporomandibular disorder (TMD) is defined as a series of clinical problems involving muscles of mastication, temporomandibular joints (TMJ), and related structures, identified by facial pain in the TMJ region and masticatory muscle, limited or deviated mandibular movement, and TMJ sounds during jaw movement and action . While tIn the last few years, laser light has been extensively used in clinical dentistry for the treatment of soft tissue disorders, hypersensitivity of dentine, bone regeneration, and musculoskeletal pain. In TMD patients, LLLT has been used by conservative treatment methods to enhance function and decrease symptoms . The maiTherefore, the aim of this systematic review was to find out the effectiveness of laser application in temporomandibular joint pain and review the evidence from previous studies with their sample size and methodology in the management of TMD. This review will provide a precise and obvious knowledge about the benefits and procedures of laser application, which have already been successfully established in TMD management.Articles were searched in five electronic databases  where thHere, the prime concern was to find out the uses of laser in temporomandibular disorder patients in terms of reduction of pain and tenderness, improvement of mouth opening and joint sounds, and improvement in the range of jaw motion. The criteria for inclusion have been established as papers using the search keywords mainly TMJ problems and laser application. At the other side, the papers that use laser in TMJ diseases along with other problems such as anatomical defects, anomalies, myofascial pain disorder syndrome (MPDS), soft and hard tissue pathology , and previous record of TMJ surgery were excluded from the study. In the context of the exclusion criteria, it also added that those studies were not conducted in human , and publications in other languages beside English were excluded. The case reports and letter to editor were also excluded from this review. Titles and abstracts of identified studies were assessed independently to judge if the studies match the inclusion criteria.Data were extracted based on the first author, year of publication, number of samples, age and gender of samples, types of TMJ problem, laser types, laser energy and application rate, and results. The data were extracted and double-checked by the authors.At the beginning, this research search strategy provided a total of 5889 papers from databases such as PubMed, Web of Science, Google Scholar, SCOPUS, and ScienceDirect. The remaining 2378 papers were further screened after eliminating 3511 papers in the detection phase . A total of 72 studies were considered worthy, but due to unusable data format, forty studies were excluded. Thus, eventually, based on the research goals and inclusion and exclusion requirements, 32 studies  were included in this study , and theThe key characteristics of the included studies are presented in R-based Robvis software package introduced by the National Institute for Health Research (NIHR) [Publication bias was assessed by using h (NIHR) . Based oTMD management is very complex and contentious due to the difficulty of determining the exact reasons of the disease and its multifactorial character. The severity varies greatly, and the procedure is varying in terms of duration and invasiveness. Nevertheless, TMD treatment is intended to minimize discomfort, enhance mobility, and delay the progression of internal derangement as accepted by the American Society of Temporomandibular Joint Surgeons guidelines . TMD hasHowever, this systematic review tried to overview the role of laser in the management of TMJ disorder patients. After completing this review, the result showed a huge role of laser in TMD management. Most of the studies used LLLT for management of TMD, where it showed a tremendous action in reducing pain, joint clicking, muscle tenderness, and jaw movements.A study was conducted by Kulekcioglu et al. in 2003 among Turkish population to investigate the effectiveness of low-level laser therapy in the treatment of TMD. Results of the study showed a significant reduction of pain and improvement in maximum mouth opening, lateral motion, and number of tenderness points. According to Kulekcioglu et al. , LLLT in treating TMD may be considered as an alternative physical modality . AnotherOn the other hand, some researchers also tried to find out the effectiveness of the laser treatment in TMD patient, and they concluded with no significant role of LLLT. In 2005, Abreu et al. conducted a study to assess the efficacy of low-intensity laser therapy (LILT) in temporomandibular joint (TMJ) pain and mandibular dysfunction patients. The study had 2 groups, placebo and experimental (LILT). They used the infrared laser  at three TMJ points. Even though the patient treated with laser had good pain reduction, the result showed no significant changes between placebo and laser groups. Therefore, the researcher did not recommend infrared LILT as a better treatment option. Though there are benefits of applying laser in TMDs management because of noninvasiveness and cost efficient, it has no reported side effects . AuthorsAlthough some authors did not notice any important differences, some studies showed better results when comparing the LLLT with a placebo control group. In 2010, Raheem et al. observed that LLLT plays a significant role in TMDs management by reducing pain and improving maximum mouth opening, lateral motion, and muscle tenderness. Raheem et al. advised LLLT as an effective therapeutic option in myofascial pain dysfunction of TMJ for its analgesic and functional improvement .Even though LLLT is a type of treatment widely applied in physiotherapy of musculoskeletal disorders, there are only some studies that discuss its use in the management of TMD. In 2012, Dostalová et al. performed a research to observe the activity of TMJ and its surrounding tissues and compared the objective results of the effect of LLLT. LLLT was beneficial in the progress of the range of TMD and facilitated a significant pain symptoms reduction . Accordi2, power of 50 mW, power density of 1.25 W/cm2, and a 20-second exposure. He did not find any significant differences after laser application [Few more studies have been performed in 2017 by several researchers to evaluate the effectiveness of laser therapy in the treatment of TMDs. Based on the sample size, population, and study design, the result showed some controversy about laser treatment. In 2017, Rezazadeh et al. examined 45 Iran patients to discover the effectiveness of transcutaneous electrical nerve stimulation (TENS) and LLLT in treatment of TMD patients who did not respond to pharmacological therapy. The result showed a significant reduction of pain and tenderness in TMD patients . Anotherlication . This malication .Though, clinically, the use of LLLT is a better procedure in managing TMJ pain. In 2018, a study completed by Buduru et al. showed a significant pain reduction and noticed that there is no disadvantage of LLLT. Thus, the author had recommended the use of LLLT for pain reduction in TMD patients . AccordiIn the present year 2020, a study was conducted by Yamaner et al. in Turkey to investigate the impact of the ozone and low-level laser (LLL) therapies on pain and function in TMDs patients with disc displacement with reduction. The results of the study support the application of ozone as an effective therapeutic tool for pain relief and LLL as a supportive therapy for temporomandibular disorders . In thisAlthough the present study went through a systematic search strategy and review of the selective articles, one of the limitations of the present study was the database searching. Due to the limited access of database, the author only searched in five specific databases. This study advised to perform another systematic review with meta-analysis by including some more databases searching to strengthen the findings.TMD patients mostly suffer with pain symptoms along with other problems. Nowadays, LLLT became very popular because of its effective role in pain reduction and no known side effects. This systematic review evaluated the effectiveness of the laser application in TMD patient by thorough investigation of the previous studies that have been conducted on laser. After this systematic review, LLLT can be recommended as a beneficial treatment approach for TMD patients.


Autoinflammatory diseases (AIDs) constitute a group of clinical conditions, characterized by recurrent episodes of systemic inflammation, due to dysregulation of the innate immune system, without involving autoantibodies or antigen-specific T-cells. The patients exhibit recurrent episodes of fever with potentially serious complications and may have classic rheumatologic symptoms, including joint, skin, eye and muscle inflammation. Therefore, musculoskeletal problems and impaired quality of life can be anticipated as unavoidable consequences. In this regards any approach to ease the burden of symptoms and compensate the functional deficits are the main objectives of rehabilitation approach. For patients with inflammatory arthritis, physical therapy and rehabilitation methods have an important role in reducing joint pain and stiffness, preventing deformity, reconstructing muscle tissue and improving function. In order to justify the integration of rehabilitation approach in the management of AIDs and to determine the optimal protocols to use in this group of patients, well-designed, comprehensive, longitudinal, clinical trials using physical therapy centred outcomes are greatly needed. Table 1).11Autoinflammatory diseases (AIDs) constitute a group of inherited disorders pathophysiologically characterized by unprovoked episodes of inflammation, due to dys-regulation of the innate immune system without antigen-specific T-cells and autoantibodies, in contrast to the autoimmune diseases. AIDs manifest clinically with recurrent episodes of fever, systemic inflammation in various organs which potentially are associated with serious complications and long-term disability. Additionally, the concept of autoinflammation has been extended to a number of other disorders of uncertain genetic aetiology including Behcet’s disease, Still’s disease, and Crohn’s disease  terms to capture the most relevant papers on the topics in accordance with the literature. The search was limited to articles in the English language, starting from the earliest papers to May 2017 and carried out from the scientific search guidelines published in 2011.19 we did not plan to address this issue in this article. Because the literature was scarce in AIDs, this overview contains general information and brief descriptions on some of the clinical entities of AIDs which are commonly encountered in the Physical and Rehabilitation Medicine (PRM) branch, particularly due to musculoskeletal involvement. The other issue to be addressed is physical therapy modalities and rehabilitation techniques. Therefore, the aim of our review was to highlight potential physical therapy and rehabilitation options for the most common AIDs in the context of the general principles of PRM blended with the use of inflammatory arthritis (Table 2).Since there are already published reports in the literature for inflammatory rheumatic diseases,23Familial Mediterranean Fever (FMF) is the most common of AIDs, transmitted as an autosomal recessive pattern, and is caused by mutations in the Mediterranean fever (MEFV) gene, which encodes the protein pyrin and is located on the short arm of the 16th chromosome. Although genetic transition has been found to cause FMF, environmental factors may increase susceptibility, and the exact pathogenesis of the disease remains unclear.24Clinical manifestations appear early in the life in most of the patients. Although the MEFV is not mandatory for diagnosis, it has a 75% positive predictive value. The clinical findings include recurrent attacks of peritonitis, pleuritis, pericarditis, synovitis, febrile myalgia or erysipelas-like erythema associated with fever, resulting in pain in the abdomen, chest, joints, and muscles. The most serious complication is type AA amyloidosis, mainly affecting the kidney and is the cause of chronic renal failure.25 The presence of depression and the activity of serotonergic inflammatory cascade have been speculated to trigger FMF attacks.26 The inflammation in the knee joint is resolved without sequelae; in general, only joints with fluid aspiration. However, protracted hip arthritis may demonstrate destructive features.27 The incidence of sacroiliitis is increased in FMF patients, usually without the HLA-B27 antigen, while the pathogenic mechanisms that link these two conditions remain unknown.28 Besides, a rare case was represented by Keleş et al.29 as a co-existence of two conditions, ankylosing spondylitis (AS) and FMF, in a patient with a background of JIA.Musculoskeletal involvement in FMF occurs in 70%–75% of patients as acute attacks of mono- or oligoarthritis predominantly involving the large joints of the lower extremities with spontaneous resolution within 1 to 3 days; however, it may prolong up to 1 month or rarely longer, although less than 10% of FMF patients develop protracted arthritis and joint damage leading to disability, especially in the hips or knees.24 The attacks, that are often associated with increased levels of erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and leukocytes, usually last for 1 to 3 days and resolve spontaneously; however, they may remain up to 1 month or rarely longer, and the interval between attacks is clinically relatively symptom-free.31 Colchicine is very efficacious in preventing FMF attacks and associated amyloidosis. Symptoms during attacks may be alleviated by non-steroidal anti-inflammatory drugs (NSAIDs), whereas usual dose of colchicine administration should be continued. Glucocorticoids may decrease the duration of attacks, but may also increase their frequency. Alternative biological treatments should be considered in cases that are resistant to, or intolerant of, colchicine.32 Certainly, the most significant goals should be to achieve appropriate treatment in order to prevent subclinical inflammation and the development of ‘silent’ amyloidosis, eventually to improve quality of life (QoL) in FMF as in other chronic diseases.Articular involvement is the initial symptom in one-third of patients and attacks can be precipitated by mild traumas, physical and emotional stress, exposure to cold, fat-rich meals, and infections. Patients with recurrent arthritis carry three-times higher risk for amyloidosis as compared to patients without articular involvement. Generally, attacks tend to decrease with aging.33Behçet’s disease (BD) is a chronic, inflammatory, and systemic disease affecting all types of blood vessels. Although vasculitis and perivascular inflammation are responsible for the pathology of the lesions, genetic predisposition, autoimmunity, and viral and bacterial infections are blamed for the etiology of BD; the origin of the disease still remains unclear.34 The disease usually starts in the third decade of life.BD is found worldwide, but it is more common in a specific geographic area, defined as from Eastern Asia to the Mediterranean basin, compared with Western countries. The incidence of cases per 100,000 population varies from 80–370 in Turkey.35 The arthritis of BD is generally mono- or polyarticular and usually follows an episodic and non-erosive pattern. In prospective studies, the incidence of arthritis ranges from 40 to 70%.37 The most common affected joints are knees, ankles, wrists, and elbows. However, it may infrequently masquerade as a destructive form of sacroiliitis or enthesitis, whereby differential diagnosis particularly from spondyloarthropathies may become challenging.19 BD lacks a universally reliable, specific laboratory test that projects the diagnosis and disease activity. Therefore, clinical findings become forefront for diagnosis. The symptoms demonstrate a chronic course with unpredictable pattern of exacerbation and remission.38BD is defined as a triple-symptom complex consisting of recurrent oral/genital ulcers and relapsing uveitis. In addition to the characteristic triad, common manifestations include skin lesions, articular, cardiovascular, pulmonary, neurological, and gastrointestinal systems involvement causing a variety of clinical problems which lead to functional disability.40The disease can lead to increased mortality on account of large vessels, CNS, pulmonary and gastrointestinal systems involvement, particularly due to delayed diagnosis and treatment. In most patients with BD, arthritis can be managed with colchicine. IFNα, azathioprine and TNFα blockers may be tried in rare cases with resistant, longer lasting and disabling attacks. Therefore, the main target of treatment in BD is to prevent irreversible damage that mostly occurs early and active phase of the disease, and to prevent exacerbations of mucocutaneous and joint involvement, usually not causing damage but affecting QoL.42 A distinctive feature of SJIA is its strong association with macrophage activation syndrome, characterised by an uncontrolled activation of macrophages releasing a high amount of pro inflammatory cytokines; particularly IL-1-related cytokines . The lack of any consistent association with HLA antigens or autoantibodies allow us to consider SJIA as an autoinflamma-tory disease.43 Finally, patients with SJIA, in contrast to patients with JIA, are at risk for amyloidosis, as in auto-inflammatory syndromes. The same considerations can be also made for AoSD, an uncommon clinical entity that predominantly affects young adults. In accordance with these findings is the dramatic and sustained efficacy of IL-1blockade on AoSD symptoms, even in refractory forms of the disease. Also, inhibitors of IL-6 were effective in controlling the activity of the disease.44 In order to improve clinical symptoms and QoL, to prevent long-term complications and to inhibit damage progression, the treatment of diseases should focus on controlling the inflammation. In conclusion, we can mention both SJIA and AoSD among the expanding group of AIDs.Systemic-onset juvenile idiopathic arthritis (SJIA) is characterized by the presence of symmetric polyarthritis associated with intermittent high-grade fever  persisting for a minimum of 15 days with at least one of the following manifestations: skin rash , lymphadenopathy, hepatomegaly and/or splenomegaly, serositis in children and young adolescents <16 years of age. The clinical presentation of symptoms in SJIA is similar to that seen in adult-onset Still’s disease (AoSD) when it occurs in patients over the age of 16. Therefore, SJIA and AoSD likely represent a continuum of the the same disease entity.45 Patients with CD frequently present in adolescence with the median age of 20 to 30 years. Therapeutic recommendations are determined by disease location, activity, and associated complications. The main goals of treatment are to control inflammation, to achieve clinical remission with minimal adverse effects and to permit life to be lived as normally as possible. Treatment usually consists of anti-inflammatory agents, antibiotics, immunomodulators and disease-modifying agents.46Crohn’s disease (CD) is a chronic, granulomatous inflammatory bowel disease that is believed to result from defects in both the adaptive and innate immune systems. The disease can affect the gastrointestinal tract at any point from the mouth to the rectum, but most commonly in terminal ileum, cecum, perianal area and colon. The symptoms of CD include abdominal pain, diarrhoea, fatigue, fever, gastrointestinal bleeding, and weight loss. Extraintestinal manifestations may include erythema nodosum, pyoderma gangrenosum, uveitis, spondylitis, sacroiliitis, peripheral arthropathy, hepatobiliary complications, genitourinary and renal manifestations hematological disorders, cardio-pulmonary manifestations, vasculitis, and neurological involvement.49 The manifestations of AIDs, such as chronic joint pain, stiffness and deformity as well as adverse events due to pharmacological treatment or the disease itself may lead to cardiovascular deconditioning, muscle weakness, and poor endurance. Patients are often prone to rest due to pain, impaired exercise capacity and muscle strength. Pain frequency and intensity are higher in JIA than in other rheumatic diseases.49 Similarly, arthritis in BD affects the patients’ pain levels and may lead to temporary or permanent functional disabilities.48AIDs, including FMF, BD, SJIA, AoSD, or other AIDs contribute to the difficulties of life standard and its maintenance and can further reduce QoL, mainly due to physical symptoms associated with disease activity such as arthritis.52Physical therapy and rehabilitation have important effects in relieving pain and stiffness, preventing deformity, rebuilding muscle tissue, developing dexterity, and improving function. Actually, physical therapy modalities including thermotherapy, electrotherapy, and balneotherapy frequently reduces the need for pharmacologic therapies.53Patient education is of outmost importance for the individuals to manage the consequences of the diseases. Educational interventions include energy conservation/fatigue management, sleep hygiene training, pain relief strategies, relaxation training, and exercise recommendations which have significant effects on functional disability and psychological status.54 Assistive devices such as canes, crutches, walkers, ankle-foot orthoses, or knee braces may be important for the realization of highest ambulatory potential.56Despite optimum pain control and exercise therapy, full function cannot be restored. In such cases, function may be improved by the use of proper assistive devices for daily living activities and transfer. In patients with BD who have CNS involvement may end with upper motor neuron or cerebellar impairment that can interfere with functioning.57 A basic rule is that chronic pain or inflammation seems to respond better to heat and acute pain better to cold. The usual duration of application of heat or cold is 20 to 30 minutes daily, and most can be prescribed for home use.50 Contrast baths decrease inflammation, swelling, pain, and joint stiffness. While a systematic review on the effectiveness of contrast baths indicated no physiologic effect on intramuscular temperature and the lymphatic system, an increase in skin temperature and superficial blood flow down to the subcutaneous level was noted.59 Paraffin baths and infrared radiation combined with exercises can be recommended for beneficial short-term effects for arthritic hands.57 The limitations of thermal therapy include incomplete alleviation of symptoms and the inability of some patients (particularly those with circulatory or sensory deficits) to tolerate a sufficiently intense thermal stimulus. It should be used as an adjunctive method of pain control and/or in preparation for exercise therapy.50Thermotherapy includes a cold or a hot source or a contrast bath with water submersions. Local application of a cold  or a hot , and deep heat, (shortwave diathermy or ultrasound) source can raise the pain threshold and decrease joint stiffness.63 The exercises contain aerobic, resistance, and stretching activities in water, providing similar physical benefits to exercise on land but may have additional and important psychological effects.61Hydrotherapy provides a combination of buoyancy and superficial heating for the body or body parts by immersion in a pool or a Hubbard tank containing warm water. The warmth and antigravity effects of hydrotherapy can facilitate exercise and ambulation, particularly for those with severe large-joint involvement.62 The mineral water reaction includes tiredness and fatigue especially after 5–8 baths with an associated rise in the leukocyte count and erythrocyte sedimentation rate, even within the normal range.63 The aims of balneo-therapy are to relieve pain and improve joint motion and, consequently, to make the patients feel well. Yurtkuran et al.64 conducted a clinical trial comparing spa therapy to NSAIDs and a combination of both in AS patients and found that spa therapy was more effective in relieving symptoms and improving spine mobility than NSAIDs alone, with the effect lasting up to six months. Falagas et al.65 reported a review of balneotherapy in rheumatic diseases and found a possibility that balneotherapy is associated with clinical improvement in osteoarthritis, fibromyalgia, AS, rheumatoid arthritis and chronic low back pain.Balneotherapy is the medical practice of treatment by immersion in baths, filled with thermal water with a significant mineral content. Different types of mineral water such as salt or mineral baths, sulphur baths, and radon-carbon dioxide baths may be used in this therapy.Transcutaneous electrical nerve stimulation (TENS) has been widely used as a treatment modality for acute and chronic pain, and is reported to relieve pain in 20–40% of patients with chronic, non-malignant pain and 70–90% of patients with postoperative pain.66 It has occasionally been proven beneficial in chronic arthritic knee joint pain that was unresponsive to other kind of therapies. Mannheimer and associates found that high-intensity TENS reduced joint pain in patients with RA.67 The theoretical mechanism of action of TENS is thought to involve inhibition of pain impulse transmission at the level of the substantia gelatinosa of the spinal cord and alteration of pain perception more centrally. The other possible mechanism is the release of endogenous opioids.69 Initially, TENS is carried out in the PRM departments, and if it is effective then instructions are given for home use due to its simple and safe application.50Interferential current is an electrotherapeutic technique which is able to penetrate deeply within the areas of treatment, predominantly used for treatment of pain. Therefore, it could be used for managing chronic painful conditions including in patients with JIA.70Low-level laser therapy (LLLT) is another modality to relieve pain and to improve function in patients with musculoskeletal involvement. The laser emits a single wavelength of pure light, which causes a photochemical reaction within the cell. LLLT decreases pain and morning stiffness for up to four weeks in people with rheumatoid arthritis, meaning that the effect is not long-lasting.62Therapeutic ultrasound (US) provides high frequency mechanical vibrations in a continuous fashion to relieve pain by its thermal effects or with pulsed sequencing to reduce inflammation. The heating effects of continuous ultrasound can also reduce muscle spasms and stimulate blood flow to decrease inflammatory toxins. It can penetrate deeper tissues, such as collagen, to increase its elasticity. US applied to the dorsal and palmar aspects of the hand showed increased grip strength compared to the placebo.7172Therapeutic exercise commonly provokes a favourable response in terms of physical and psychological benefits in patients with arthritis. Exercise therapy on land and in water covers sports and recreational/occupational/daily-living/aerobic activities, flexibility and muscle-strengthening/core stability exercise, and balance rehabilitation for modifying health status. It consists of planned, structured and repetitive movement of parts or the whole body.50 Children and adolescents with JIA have decreased muscle strength when compared with their normal peers. Therefore, physiotherapy and occupational therapy are important components of the rehabilitation approach to patients with JIA. Exercises which do not give weight to joints, especially swimming and cycling, should be encouraged, especially in the early stages.74Arthritic involvement of a joint always causes loss of strength in the associated muscle groups; usually at a rate of 30% per week.59The prescription of an exercise program should be as attentive as a medical prescription. Therefore, in the exercise prescription, pain threshold, exercise physiology, patient’s functional limitations, and disease activity must be taken into account. During the exacerbations, the exercises should be performed in inpatient or an outpatient clinic under supervision. It is not always easy to answer the questions about how often, in what order, and when which exercises should be introduced: exercises should be performed when the patient feels best. As pain control is usually necessary before exercise, this may be needed also after exercise.59The purpose of therapeutic stretching exercises is to prevent contracture or to increase range of motion with passive, active assisted and active exercises. Passive stretching has little place in arthritis therapy. Active-assisted stretching is used when the patient can initiate an exercise in order to achieve the joint’s available range of motion. Active stretching is generally preferred in the protection of range of motion. A stretching exercise program should be designed with the least stressful movements. The purpose of therapeutic strengthening exercises is to develop strength and endurance in specific muscle groups to facilitate functionality. The two major categories of strength are isometric and isotonic. Isometric (static) strength may be defined as the maximum force that can be applied against immovable objects by a muscle group. It is an optimum treatment for weakness associated with arthritis. Isotonic (dynamic) strength is the maximum force that can be performed in moving an object.59Aerobic (dynamic) exercise programmes improve the components of health-related fitness, enhance psychological status, reduce pain and fatigue and have a positive effect on functional capacity without exacerbating disease activity or accelerating joint damage.18 While moderate evidence supports exercise interventions in improving physical function, disease activity and chest expansion compared to controls; there is low-level evidence of improved pain, stiffness, spinal mobility and cardiorespiratory function. Supervised group exercise provides more beneficial outcomes than unsupervised home exercise.19 Geneen et al.14 suggested physical activity and exercise in pain severity reduction and improved physical function for adults with chronic pain; though these were mostly of small-to-moderate effect, and were not consistent across the reviews.Specific exercises are an effective adjuvant therapy to enhance cardiopulmonary functions in patients with AS. In addition to the medical treatments, specific exercise therapy might reduce the cardiopulmonary complications related with AS.Table 2.The main limitation of this report is that it is structured a narrative review. While narrative reviews can provide experts’ intuitive and experiential perspectives on focused topics, systematic reviews are based on the findings of comprehensive and systematic literature searches in all available resources, with minimization of selection bias. Additionally, we did not specifically search non-English language databases. Thus, we may have failed to identify potentially relevant reports that have been developed in a non-English language setting. A further limitation was that evidence supporting the use of specific physical therapies in most AIDs is lacking. Thus, in this report we recommend some therapeutic options in the context of the general principles of PRM in In conclusion, patients with AIDs have a disturbed musculoskeletal system and impaired QoL. To ease the burden of symptoms and compensation of functional deficits are the main objectives of rehabilitation approach. Although rehabilitation may not always have a direct influence on the progression of a disease, it enhances personal activities and participation in social activities, thereby improving QoL. While literature review on physical therapy modalities and rehabilitation interventions demonstrates beneficial effects on different symptoms at various levels in inflammatory arthritis, evidence in AIDs is still scarce. In order to justify the integration of rehabilitation approach in the management of AIDs, well-designed, comprehensive, longitudinal, clinical trials using physical therapy centred outcomes are greatly needed.AIDs are a group of genetically different but clinically similar disorders unified by recurrent episodes of fever and systemic inflammation, with potentially serious complications.Exercise is the most studied physiotherapy modality in terms of pain, function, and QoL for inflammatory arthritis, with few studies examining other physiotherapy modalities.Future work is needed in AIDs to clearly establish the role of physical therapy modalities and to determine the optimal protocol to use in this group of patients.The authors state that no part of the text of tables was copied from elsewhere, and all ideas presented in the manuscript are those of the authors.


Chronic pain and fatigue are the main symptoms of postpoliomyelitis syndrome (PPS). This study aimed to evaluate the efficacy and safety of an anthroposophic multimodal treatment for chronic pain in PPS outpatients.n = 48): groups A and B received daily active experimental transdermal gel (ETG) or placebo gel (PTG), respectively; groups C and D received weekly external therapies, art therapies, and neurofunctional reorganization, plus either daily ETG or PTG, respectively. The pain symptoms were evaluated through a visual analogue scale (VAS), the McGill questionnaire, and thermography. Quality of life and resilience were evaluated by the WHOQOL‐BREF and Antonovsky sense of coherence questionnaires applied at baseline and after the interventions.A twelve‐week, four‐arm, randomized, double‐blind, placebo‐controlled, phase 2 prospective clinical trial was designed to compare four groups  and in the ETG . However, following the week‐to‐week evolution of pain with the concomitant use of the ETG, this significant pain reduction occurred earlier from the 4th week and continued to decrease . In the group that received the complete multimodal treatment, the greatest significant benefit in increasing quality of life occurred in the physical domain and elevation in resilience with an emphasis on meaning and comprehension domains.No related adverse events occurred, and 10% of the patients reports dysphagia improvement. In the groups C and D, pain reduction was statistically significant in both the placebo group (The anthroposophic multimodal treatment group presented both safety and efficacy as an analgesic in the groups that received the nonpharmacological therapies, much earlier when associated with the ETG. The multimodal approach corresponded to the pattern of better efficacy for both pain reduction and improvement in quality of life and resilience. This study aimed to evaluate the efficacy and safety of an anthroposophic multimodal treatment for muscle and joint chronic pain in outpatients with PPS. This twelve‐week, four‐arm, parallel, randomized, double‐blind, placebo‐controlled clinical trial which were applied to evaluate pain, quality of life and resilience at baseline and after the interventions. The treatment showed increased safety and efficacy for pain and improvement of the quality of life and resilience specially in the groups that received the nonpharmacological interventions, earlier when associated to transdermal gel. Since the Global Polio Eradication Initiative was launched in 1988 by the WHO, the number of cases has fallen by over 99%; however, an endemic transmission is continuing in Afghanistan, Nigeria, and Pakistan. The prevalence of PPS among people with polio sequelae has been estimated to be between 22% and 80% Bosch, . When coPPS is characterized by new muscle weakness and/or skeletal muscle fatigue that is persistent for at least 1 year, that is unrelated to other causes, and that occurs at least 15 years after a period of functional stability following the previous acute paralytic poliomyelitis illness. The diagnosis is based on a proper clinical workup in which all other possible explanations for the newly presented symptoms are ruled out Dalakas, .Aside from new muscular fatigue, the main symptom is myalgia and joint pain, which are both progressive characteristics of the disease. Other manifestations include cold intolerance, dysphagia and sleep and respiratory disorder, dysphonia, musculoskeletal deformities, psychosocial problems, and restless legs syndrome  to sleep disorders, and single high dose of immunoglobulin to reduced proinflammatory cytokines present in the cerebrospinal fluid of the spinal cord. Although immunomodulation with intravenous immunoglobulins showed positive results, the benefit was modest and transient. In the case of hypoventilation, assisted ventilation would be required  and acupuncture may also contribute to effective treatment to strengthen weakened muscles as well as to decrease pain Gevirtz, . In a coFull‐body clinical thermography (telethermography) has recently been used to monitor painful syndromes such as fibromyalgia and chronic adrenal fatigue, associated with chronic inflammatory processes, verified systemic changes due to mechanical overload as well as inflammatory changes in nonmusculoskeletal territories as well as indirect signs of pain‐induced sleep disturbance . We recruited 48 patients who were admitted into the Neuromuscular Disease Outpatient Clinic of the Federal University of São Paulo. The participants provided written informed consent before study entry.Inclusion criteria for patients were as follows: adults resident in Brazil aged 20–59‐years‐old; with confirmed paralytic poliomyelitis; who fulfilled the definition of PPS; had muscle  and/or joint pain.Specific exclusion criteria were as follows: had other diseases that could lead to muscle weakness; neuropathic pain; the use of a wheelchair; or who received any other type of unconventional analgesic therapy. We also excluded patients who did not agree to sign the informed consent form, who failed to perform more than three intervention sessions or who were absent on the initial and/or final evaluation days.2.2A twelve‐week, four‐arm, randomized, double‐blind, placebo‐controlled, phase 2 prospective clinical trial was designed to compare the parallel intervention of four groups with pharmacological  and nonpharmacological anthroposophic clinical interventions (NPAIs).® version 9.1 (SAS® Institute), that were divided into four groups. Groups A and B received a daily experimental transdermal gel (ETG) treatment, with either active ingredients or a placebo gel (PTG), respectively; groups C and D received an NPAI weekly, plus a daily ETG or PTG treatment, respectively.The 48 PPS patients were randomized into blocks, with randomly selected block sizes (4:8:4:4) using SAS2.3Rhus toxicodendrum D4 (1.66%), Arnica montana D3 (1.66%), Apis mellifica/ Atropa belladonna D3 (0.83%/0.83%), Mandragora officinarum D3 (1.66%), Aconitum napellus D4 (1.66%), and Hypericum perforatum D3 (1.66%).The pharmacological interventions consisted of a nightly application of the ETG in groups A and C or a nightly application of PTG in groups B and D, at a dose of 1 g in the painful regions for 12 weeks. Each patient received three vials containing 30 g each, with a doser set to 1 g, and each vial was delivered every 4 weeks for use. The PTG vials contained only the inert excipient soy lecithin. The ETG vials had a final concentration of 10% of the active ingredient. The potencies and concentrations that were used followed the safety standards of the German and Brazilian homeopathic and anthroposophic pharmacopoeias, which are regulated by the National Agency of Sanitary Vigilance (ANVISA). The industrialized ETG was developed and dispensed by the Weleda Laboratory of Brazil and obeyed the blinding rules. The active ingredients of the 10% ETG were The four groups of patients continued to receive their usual medical care, such as analgesics, during their admission periods. After completing the study, participants were offered the choice of receiving the ETG.NPAIs were performed for the patients in groups C and D once a week, following a 1‐hr sequence for each therapy, which lasted over 3 hr throughout 12 sessions. All of the patients started the interventions together in a single group by receiving the anthroposophic artistic therapy (AAT), after which half of the group received the Padovan method of neurofunctional reorganization therapy (PMRN) and the other half received the anthroposophic external therapy (AET), and then, the therapies were alternated between the groups. The performance of the activities was done with respect to the functional limitations of each patient in order to avoid the patients reaching a fatigue threshold and was evaluated weekly.AAT: The technique used was watercolor painting, according to the guidelines of the Brazilian, Dutch, and Swiss Association of Art Therapists. These sensorimotor exercises were performed with the seated patients, who applied nontoxic inks on A3 paper using a No. 20 brush. The first and last two sessions were used to evaluate the condition of each participant in terms of a comparative constitutional diagnosis through the use of a free painting exercise. The therapeutic activity was directed to the color transition using two primary colors to obtain the secondary color .PMRN: The therapeutic activity was conducted by licensed speech therapists and was performed in two stages, including body and oral exercises of reflex‐vegetative functions. Each stage had its own sequence of exercises, which recapitulated the neuromotor development of infants. The first stage  lasted for 4 weeks and included a sequence of eight body exercises, and the second stage  lasted for 8 weeks and included a sequence of 14 body exercises, which were associated with the same oral exercises of the previous stage.Warmwater footbath therapy: Patients, in a sitting position, maintained their feet and calves up to 5 cm below the popliteal line in a previously sanitized bucket containing water at 40°C (104°F).A. Montana L. (flower), Betula alba (cortex), Helianthus annuus L. (sunflower seed), Vitis vinifera L. (grape seed), Rosmarinus off. (leaf), and Lavender off. (flower) that were free of dyes, flavorings, and preservatives.Rhythmic massage therapy: Patients were placed in preheated beds in the decubitus position. The slip technique was applied with massage oil and different types of circular and rhythmic pattern movements. Fabrics that came in contact with the skin were used to keep the patients warm. The massage oil had a composition of extracts including Bandaging: Once the massage was finished, each patient, in the dorsal decubitus position, was wrapped with the dry flannel and wool sheets, with the sheets covering the body from the neck down.AET: The program was applied by registered nurses. This program involved the performance of a sequence of three techniques, with a total duration of 15–20 min each. The therapy site was maintained in a quiet, airy environment with subdued lighting and a pleasant temperature. A restful state was stimulated after the program through a sequence of three procedures:2.4Primary outcome: Pain symptoms and quantitative evaluations were assessed by:1.1The unidimensional scale for measure pain intensity assessment: numerical rating scales of visual analogue scale (VAS) Gould, .The VAS of pain was applied over the 12 weeks, with completion under the supervision of a group of nurses and/or physicians from the outpatient clinic, using a straight horizontal scale with numbers, whose extremities were defined as the extreme limits of the symptom of pain oriented from the right (“no pain”—number 0) to the left (“unbearable pain”—number 10). In groups receiving therapies (C and D), the VAS was applied before the sessions and throughout the 12 weeks. In groups that did not receive therapies (A and B), the data were collected by either weekly telephone contact or in person when they arrived to pick up their gel bottles once a month.1.2Questionnaire for multidimensional pain evaluation (McGill Pain Questionnaire).This self‐reporting measure of pain questionnaire allows for the communication of the sensorial, affective, and evaluative qualities of the painful phenomena Melzack, .1.3Transcutaneous thermography using the FLIR T420 High‐performance infrared camera . Full‐body thermal images were obtained under a controlled temperature , in the abbreviated version of 26 items containing the physical, psychological, social relations, and environmental domains : resilience assessment (Orientation to Life Questionnaire to measure the sense of coherence) with 29 questions. This assessment consists of questions distributed according to three components: 11 items measuring comprehensibility, 10 items measuring manageability, and eight items measuring meaningfulness  and calculated the main statistical parameters (mean and standard deviation) of the protocol. As we analyzed eight variables , we determined a power of the sample at 80% and thus calculated the nominal margin of error, considering the statistical margin of error of 5%, that is, confidence interval of 95%. The effect size was classified following Cohen parameters into five categories: very small (d < 0.2), small (d = 0.2), medium (d = 0.5), large (d = 0.8), and very large (d > 1.2)  Cohen, .3Of the 48 recruited patients, we excluded eight patients due to the excessive absence of six patients  and the lack of attendance for the final evaluation in two patients (one in the PTG + NPAI group and one in the ETG group) in two of the groups. Thus, the sample size for the statistical analyses was 40 patients.Considering the statistical analysis of these 40 patients and the sample power at 0.8, we found the value of the nominal difference margin of error for each of the nine variables . The nominal differences of QSCA domains ranged between 3.88 and 9.47 and WHOQOL domains between 5.88 and 8.9, and 1.34 in VAS value, all acceptable for statistical analysis.The assessment of adverse events was actively conducted by the nursing and medical staff during the weekly assessment as a specific issue concomitant with the assessment of VAS and at the end of the protocol in a comprehensive manner, in addition to the guidance of spontaneous adverse event reporting throughout the 12‐week intervention and after treatment. No study‐related adverse events occurred. There were no reports of cutaneous allergies induced by the application of the transdermal gel or by the application of arnica oil during external therapies.We observed reports of dysphagia improvement in four patients who received therapies (three in the ETG + NPAI group and one in the PTG + NPAI group), which represented 10% of the total sample of 40 patients. We postulated that the PMRN intervention should have contributed more directly to this improvement, as a result of the oral exercises.The thermographic examinations showed a pattern of alterations that was observed in almost all of the patients. These alterations were maintained before and after the interventions and practically characterized the thermal signature of PPS.The main findings were a pattern of thermal asymmetry between the upper and lower regions of the body, which showed significant hypothermia in the affected limb and hyperthermal signals of osteoarthritis and sacroiliitis of the hip. In addition to these mechanical components that were linked to an imbalance of the musculoskeletal structure, we found systemic signs such as hyper‐radiation in palpebral region due to venous congestion, hyper‐radiation in the abdominal area, and also in the cervicothoracic regions including interscapular area of trapezius, rhomboid, and supraclavicular muscles, which characterized the signal of mantle.These systemic findings are due to nonrepairing sleep and fatigue expressed in the periocular region, intestinal dysbiosis as a sign of gastrointestinal dysfunction, and exacerbated thermogenesis in brown fat tissue (BAT), mediated by adrenergic activity induced by cold temperatures and/or stress as signal of mantle  and in the ETG group (p = .017), according to Table The analyses showed a significant reduction in pain in the groups that employed therapies (NPAI), both in the groups accompanied with placebo (VAS p = .268) and approximately 24.8% in the PTG group (p = .317), but these reductions were not statistically significant, as shown in Table In the groups without therapies, there was a reduction in the amount of pain of approximately 20.7% in the ETG group  and in the ETG , thus demonstrating an independent analgesic effect of NPAI.In the groups receiving NPAI, as shown in Table p = .016, d = 1.369), while in the placebo group, the significant decrease occurred only at week 12 , we noticed that, with the concomitant use of the ETG, this significant pain reduction with very large effect size occurred earlier and always continued to decrease from the 4th week  and physical  domains and almost large effect size in social  domain, compared to the placebo group  with very large effect size, and secondarily in the psychological  and environmental  domains with medium effect size as shown in Table In the group that received the complete treatment (ETG + NPAI), which represented the multimodal model, the greatest significant benefit in increasing quality of life occurred in the physical domain . Nevertheless, when the gel was associated with the therapies (NPAI), there was a large effect size  as shown in Table Resilience, which was measured by QSCA, was significantly elevated with the use of the transdermal gel, showing a medium effect size  and on comprehension domains  with large effect size.However, when comparing the concomitant use of the ETG with the therapies versus the use of the gel alone, there was a higher degree of elevation in resilience in the full intervention Table , with an4We concluded that the multimodal anthroposophic treatment presented both safety and efficacy as an analgesic in the groups that received the nonpharmacological therapies as an independent intervention, but exhibited these properties much earlier when associated with the ETG compared to the placebo gel. In the groups that used ETG, especially when associated with the therapies, there was an improvement in both the quality of life and the degree of resilience. The multimodal use of this anthroposophic treatment, which combines topical pharmacological with nonpharmacological therapy, corresponded to the pattern of better efficacy in this study for both pain reduction and improvement in quality of life and resilience. Typical thermography findings show a comorbidity with other painful, sleep disturbance, and fatigue syndromes, which should be further investigated. Although this study has a small sample, the effect size of the sample allowed us to demonstrate the benefit of this complementary approach with emphasis on pain, resilience, and quality of life. Multicenter clinical studies evaluating the medium‐ and long‐term analgesic effect of this multimodal anthroposophic treatment should be encouraged.None declared.Ricardo Ghelman conceived the study, participated in its design, collected the data, planned the analysis, participated in clinical investigation, and led the drafting of the manuscript. Jorge K. Hosomi conducted the randomization and the blinding process until data analysis. Abrahão A. J. Quadros participated in the clinical investigation, especially in recruitment. Ivete Y. Akiyama participated in the clinical investigation as the leader of the physician team. Valeria Tiveron de Souza participated in the clinical investigation as the leader of the nurse team. Jussara Falcão participated in the clinical investigation as the leader of the speech therapists team. Vera Orgolini participated in the clinical investigation as the leader of the art therapist team. Acary S. B. Oliveira participated in designing the study, the clinical investigation, and the drafting of the manuscript.


The management of neuropathic pain remains complex, generally because of the psychiatric comorbidity that is often underdiagnosed. The objectives of our work were to determine the link between depression and the characteristics of NP on the one hand and quality of life on the other hand, in a sample of subjects consulting for neuropathic pain (NP) regardless of etiology.  We conducted a cross-sectional study involving 61 neuropathic pain consulting patients in whom we assessed five parameters, namely, neuropathic pain based on DN4, pain intensity using EVA, anxiety, and depression according to the HADS and quality of life. p=0.025). A significantly positive association was found between the depression score and the pain intensity . Depressed subjects had a poor quality of life according to SF-12 and BPI.  The study population mean age was 52.71 ± 14.29 years while the sex ratio (m/f) was 0.52. The neuropathic pain's most common etiologies were postherpetic pain, carpal tunnel syndrome, and diabetic neuropathy. Depression and anxiety prevailed by 65.6% and 73.7%, respectively. The quality of life was impaired with average SF-12 physical and mental scores of 33.76 ± 8.03 and 37.78 ± 11.52, respectively. The overall mean BPI score was 5.53 ± 1.76. Patients with high DN4 scores were significantly more depressed ( Given the depressive comorbidity impact on the neuropathic pain components as well as the quality of life, screening for this comorbidity should be part of the baseline ND assessment. Pain is a reason for frequent consultations in medicine . It is aSince 1994, NP has been defined by the IASP as “pain initiated or caused by primary injury or dysfunction of the nervous system.” It has been proposed more recently to define NP as “pain associated with an injury or disease affecting the somatosensory system” . This enIn this context, several research works have studied the link between NP and depressive disorders. The prevalence of depression is estimated to be around 30% for NP patients –7. HowevIn addition, pain may also interfere with the lives of NP patients by altering their quality of life (QoL), generating disabilities that may make them end up as vulnerable excluded individuals from society . AccordiIn Tunisia, pain is not sufficiently taken into account in our care environments yet. Indeed, the majority of our health professionals are neither well informed about nor sensitized to pain and its management. In fact, there is only one pain treatment center (PTC) throughout the country that was created in 1996 at the Rabta Hospital in the capital Tunis to manage chronic rebel pain.Since the studies on the QoL and depressive disorders in NP patient are disparate and data are scarce in our context, we set the objectives of determining the prevalence of depression in a sample of subjects followed up for NP, first, and then investigate the link between this psychiatric comorbidity and NP characteristics as well as the QoL in this population.A multicenter cross-sectional study was conducted at the Rabta PTC in Tunis and the functional exploration department at Hbib Bourguiba Hospital in Sfax, over a four-month period extending from March to June 2015.We included patients treated for NP, aged between 18 and 80 years. They all have a Neuropathic Pain (NP4) questionnaire score that is equal to or greater than four.A group of patients was excluded; it involved pregnant women, patients with a personal psychiatric record, and those who experienced traumatic events during the last three months /professional (such as harassment or conflict), rape, road accident, and major financial difficulties) as well as those who were under tricyclic antidepressants treatment, the dose of which is ≥75 mg/day.Nonconsenting patients and those suffering from cognitive impairment were not included, either.We developed a semistructured questionnaire to collect the participants' sociodemographic data and records.We used a four-question Neuropathic Pain (NP4) questionnaire for the diagnosis. This is a recent, simple, and quick tool to go through the diagnosis. It consists of seven items on the pain clinical description and another three-item part for the physical examination. A threshold value of an overall score greater than or equal to 4/10 establishes the NP diagnosis. In this study, we used the validated Arabic version .In order to evaluate the pain severity, we used the Visual Analogic Scale (VAS) . The VASThe patient has to position the cursor along this line to better indicate his pain intensity. The doctor can see the other side that consists of graduations, too. The positioning of the cursor by the patient allows the doctor to read the pain intensity.  0: absence of pain  1–4: low-intensity pain  5–7: moderate-intensity pain  >7: severe-intensity painReading the VAS allows the classification of the intensity according to the following interpretation:For the depression screening, we used the Arabic version of the Hospital Anxiety and Depression Scale (HADS) . This isThe patients' quality of life was assessed through two scales: the Short Form 12-item survey (SF-12) and the Brief Pain Inventory (BPI) in their Arabic versions .SF-12 is a shortened version of the SF-36 questionnaire containing its main items only in order to have a faster evaluation by reducing the number of questions to the third. It calculates two scores: a physical quality of life score and a mental quality of life score.While the physical domain explores the functional capacity related to pain, the psychological field investigates the NP influence on the patient's morale, mood, and well-being.We considered a threshold based on the averages of the physical and mental scores of the Tunisian general population . Thus, aThe Brief Pain Inventory (BPI), a concise pain self-administered questionnaire originally designed to assess cancer pain , is currThe study was approved of by the Sfax Faculty of Medicine Committee. The participating patients were informed of the study purpose and we obtained their oral consent. All the subjects diagnosed with psychiatric disorders were advised to consult a specialist.rd version). The continuous variables distribution was compared to a normal distribution using the Shapiro–Wilk's test.The collected data were entered and analyzed using the Statistical Package for Social Sciences (SPSS) computer software  for the qualitative variables. We also estimated the means, medians, and standard deviations and determined the extreme values for the quantitative variables.r,” the linear adjustment curves, the Student t-test, and the coefficient of determination “R2.” The comparison of the several averages was performed by the “ANOVA” test. The significance threshold was fixed to p < 0.05.The study of the relationship between the qualitative variables was achieved by Pearson's chi-square test and Fisher's exact test. The study of the relationship between the quantitative variables was done by the Pearson correlation test “A total of 61 patients were included in our study among whom forty-three were recruited from the PTC and 18 were recruited from the Functional Exploration Service. The population consisted of 40 women and 21 men, with a sex ratio of 0.52. The group average age was 52.71 ± 14.29 years. 72.1% of the study population were married, and 75.6% had some type of education. In fact, 42% of the cases attended secondary education; 19%, the primary schools; and only 14%, the higher institutions. Twenty-four patients (39.3%) were active at the time of the study. In addition, forty-one of the patients (67.2%) were urban dwellers and twenty subjects were of rural origin. The socioeconomic level was average in 72% of the population, low in 25%, and high in 5% of the cases.In terms of clinical characteristics, 67.21% of the patients had a medical record: 34% had high blood pressure and 34% suffered from diabetes. The psychiatric family record of depression was revealed in seven patients, which represented 11.5% of the population.The NP characteristics of the study population are summarized in p=0, r = 0.5).The study population mean depression score was 9.67 ± 5.2. Forty patients (65.57%) had depressive symptomatology with a mean score of 12.9 ± 3.79 according to the HADS. Depression was severe in 10 patients (25%), was of mild intensity in 16 subjects (40%), and was of light intensity in 14 patients (35%). In addition, the prevalence of anxiety was estimated at 73.77% of the cases, with an average score of 11.3 ± 4.48. We also found out that depression was positively correlated with anxiety , the mean physical and mental scores were 33.76 ± 8.03 and 37.78 ± 11.52, respectively. The Brief Pain Inventory (BPI) scores had an average of 5.53 ± 1.76. The scores of the different dimensions are summarized in p=0).Relying on a dimensional approach, our study showed that depression is linked to etiology, intensity, and NP history . In factr = −0.46, p=0) and physically .According to SF-12, most of the depressed subjects were found to have a significantly affected quality of life both mentally  and illiteracy (p=0.003). In addition, it reached no statistically significant correlations between depressive symptomatology and other sociodemographic features.Our study also revealed a relationship between depression and a low socioeconomic level . However, this difference is not that significant. In a review by Bair et al., the presence of chronic pain was associated with the presence and severity of depressive symptomatology . On the p=0.013, r = 0.31). The longer the duration of the treatment was, the more the patients were inclined to reveal depressive symptoms. Several explanations could be suggested to support this link. A long-term drug intake may have a heavy impact on the patient and become a source of psychological distress. In addition, the NP generally exhibits a partial response to analgesics, requiring the resort to therapeutic combinations, and therefore may expose the patient to a greater risk of adverse effects [However, we found a statistically significant positive correlation between treatment duration and the depression mean score . In case the NP affects the lower limbs, it may result in a handicap for walking, which is added to the depressive symptomatology. Indeed, depression is characterized by motor functions slowdown and asthenia as well as somatic complaints. A clinical cross is therefore revealed between these two entities. This depression/NP crossover is also found for other BPI items in our study. Thus, NP patients with a severe intensity depression have high averages of pain interference in their “relationship with others” (p=0) and hence could be an important factor [Another finding of our study is the significant link between depression and QoL of our pain-suffering patients according to the SF-12 scales. Our results, as well as those of the literature, have agreed on the deleterious effect of depression on the QoL dimensions and symptoms –38. The t factor . In addiIn addition, several authors have argued that the pain intensity would depend on the interaction between the cognitive, emotional, sociocultural, and physical factors  and woulThis correlation, however, is to be taken with caution since the change in the relationship with the environment is at the heart of depression. The depressive symptomatology acts on the mood and is at the origin of an isolation of the suffering person.In summary, our results emphasized the close relationship between NP, depression, and QoL of the pain sufferer. This relationship is to be taken into consideration when dealing with such patients. Indeed, several particularly NP promising psychosocial treatments including both cognitive restructuring , 42 and Our research study may suffer some limitations. It might be criticised for involving NP patients who were admitted to the PTC and the Functional Investigation Service. Actually we chose these centers because of the varied population, compared to a population of a specific hospital service. Nevertheless, we have tried to limit the methodological bias throughout the study by recruiting patients whose NP is the main reason for consultation.The second possible limitation is the reduced number of the involved patients in the study. This is a real weakness that limits the significance of some results and the scope of our interpretations. Therefore, our conclusions need to be confirmed by subsequent studies with a larger sample.Third, it is important to point out that two-thirds of the patients were taking medication during the study. This means that drug effects on pain assessment and scaling results are possible. As a matter of fact, we considered it unethical to stop the drugs course for the exploratory purposes of our study.Ultimately, the HADS we chose to evaluate the depressive symptomatology is a screening and not a diagnosis scale. An overestimation of this disorder is then possible in the absence of an associated psychiatric interview. However, this tool has been specially developed to avoid confusion related to the symptoms revealed in both depression and somatic disease cases. We also opted to this tool as we were motivated by its rapidity and ease of use.Our results highlighted a high prevalence of depression among NP patients and its intricacy with the different NP components as well as its negative impact on QoL. In clinical practice, when we notice a significant alteration of an NP patient QoL, we should not be satisfied to attribute it to his pain or causal pathology. We should rather look for depression that could have aggravated this deterioration. Consequently, screening for depressive comorbidity should be an integral part of the baseline NP assessment. In this context, the HADS is an easy-to-use screening tool. Sensetizing the intervening parts on NP patients about the value of using this tool is also essential. In fact, the QoL assessment should also be part of the management of any pain sufferer as soon as the NP diagnosis is performed.


IntroductionIn the United States (US), appendicitis is the most common acute abdominal emergency requiring surgery. Patients with appendicitis continue to display a complex and atypical range of clinical manifestations, providing a subsequent high risk for emergency physicians to miss acute abdominal pathology on a patient’s initial visits. Due to the risk of potential perforation, the proper and timely clinical identification of acute appendicitis is vital. The current study aims to identify clinical characteristics that could be useful in identifying patients at risk for having acute appendicitis that was misdiagnosed on their initial visits.MethodsMedical charts consisting of patients between the ages of 19 and 55 years on their second visit were flagged and reviewed by the emergency department quality assurance (EDQA) committee. The retrospective chart review included patients who presented to the emergency department (ED) with the chief complaint of an abdominal-related complaint, were discharged, returned within 72 hours, and were diagnosed with a pathologically confirmed appendicitis. All patients were managed operatively, with pathology results reviewed for evidence of acute appendicitis. Those with confirmed pathologic appendicitis upon return were considered to have a “misdiagnosis.” Any patients managed nonoperatively and those with negative pathology were excluded from the study and considered not to have appendicitis.ResultsFifty-five patients were identified through the EDQA committee from May 2011 to January 2014. After exclusion criteria were applied, 18 patients met the inclusion criteria for this study . The mean age was 36.2 (range: 19-55). The most common presenting complaint on the initial visit was pain in the epigastric region of the abdomen . Twenty-two percent (n = 4) of patients had pain in the right lower quadrant documented in the physician’s note on the initial visit and 83% (n = 15) had right lower quadrant pain documented on the second visit. Two patients (11%) did not have right lower quadrant tenderness on either visit. The most common discharge diagnosis on the initial visit was undifferentiated abdominal pain (50%), followed by gastritis (28%). Opioid pain medication was administered or prescribed to 39% (n = 7) of the patients. The average return time was 23.9 hours.ConclusionThe administration of opioid pain medication is associated with many of the return visits to the emergency department for missed appendicitis. Finally, discharge diagnosis and planning are imperative, as detailed early appendicitis instructions or extended ED observation can include more cases and decrease litigation risk. Up to 300,000 appendectomies are performed each year in the US. With an average lifetime risk of up to 25%, it is the most common abdominal surgical emergency . Most ofClassically, the presentation of acute appendicitis is described as periumbilical or upper abdominal pain that gradually transitions or radiates to the right lower quadrant . HoweverThe initial exam also remains variable, ranging from a benign soft abdomen to peritoneal signs. The classic exam signs of McBurney’s point tenderness, Rovsing’s sign, and Psoas sign remain notoriously nonspecific and do not offer a significant increase to the post-test probability . MultiplUnfortunately, the clinical decision rule suffered from poor sensitivities and did not provide an adequate “rule out” strength for routine use in the emergency department . More reOur study was a qualitative, retrospective analysis of the collected data on all patients who returned to our emergency department within 72 hours following an initial visit for abdominal pain. They were discharged home on the initial visit with a diagnosis other than acute appendicitis and were ultimately diagnosed with pathology proven acute appendicitis on the second visit. Data collection was over three years from May 2011 to January 2014. The study was performed in Paterson, NJ, at St. Joseph’s Regional Medical Center located in the tri-state area of New York City, with a busy urban emergency department with an annual volume of 170,000 visits per year.Patients were seen in the emergency department by residents of emergency medicine, internal medicine, general surgery, family medicine, and board-certified emergency medicine attendees. The hospital institutional review board (IRB) approved this study before the initiation of data collection. Patients were identified by an EDQA committee and reviewed for clinical appropriateness. All patient data, including age, sex, appendix pathology results (including perforation), time of return visit and opioid medication administration on the initial visit, presenting chief complaint, abdominal exam on all visits, and initial discharge diagnosis were obtained through the emergency department and hospital computerized record system, respectively, MEDHOST 2013  and Soarian Clinicals 2014 .Data collected were entered into an Excel spreadsheet . All patients’ identifying data were stored on a secure password-protected computer. Patient data were de-identified with an alphanumeric code and, subsequently, password protected again. All patients underwent either conventional or laparoscopic appendectomy. Patients who had normal pathology of the appendix were excluded. Data were analyzed using Microsoft Excel 2010. Descriptive statistics were provided as a proportion . Variables with significant variations were presented as median with interquartile range. Standard calculations were completed using basic statistical methods.Between May 2011 and January 2014, 55 patients were identified through the EDQA committee for review. After exclusion criteria were applied, 18 patients were included in this study. Of those 18 patients, seven (38%) were male and 11 (62%) were female (Tables The mean age was 36.2 (range: 19-55). The most common presenting complaint on the initial visit was a pain in the epigastric region of the abdomen . Twenty-two percent (n = 4) of patients had pain in the right lower quadrant documented in the physician’s note on the initial visit and 83% (n = 15) had right lower quadrant pain documented in the second visit. Two patients (11%) did not have right lower quadrant tenderness on either visit. , followed by gastritis (28%). Opioid pain medication was administered or prescribed to 39% (n = 7) of the patients. The average return time was 23.9 hours. The total number of patients who had histologic evidence of perforation was six (33%) (Table The diagnosis of acute appendicitis remains a difficult diagnosis to make secondary to multiple factors, including the inherent progression of the disease process and the substantial heterogeneity in the patient population . Most ofThis study has shown that this is indeed the case with the main presenting chief complaint as epigastric pain with a right lower quadrant that is nominally tender in 22% of patients on the initial visit, followed by a sharp increase to 83% of patients having right lower quadrant tenderness on the second visit exam Figure . This ilOf note, two patients in this study did not have right lower quadrant tenderness on either visit. Multiple case studies have reported that tenderness on the exam may correlate to the degree of inflammation of the appendix and surrounding tissue and the location of the appendix -12. RetrAdditionally, the perforation of the appendix has historically led to increased morbidity and mortality, with a mortality rise from 1% to 3% if perforation occurs . PapandrAlso, historically, the diagnosis of appendicitis in females is more difficult due to gynecologic considerations of urinary tract infection, pelvic inflammatory disease, ovarian cysts, and torsion, making them more likely to have a perforation when the diagnosis of acute appendicitis is made . InteresMoreover, the discharge diagnosis and planning for any patient in the emergency department is crucially vital for patient safety and the continuance of care. This study has shown that of the patients that were discharged home on their initial encounter, the most common diagnosis was abdominal pain followed by gastritis. Rusnak et al. reported in 1994 that the most common diagnoses of missed appendicitis that went to litigation were gastroenteritis, abdominal pain, peptic ulcer disease, and urinary tract infection . This leFurthermore, Rusnak et al. report on the use of narcotic pain medication use in cases that have gone to litigation. From his retrospective review of malpractice claims, narcotic pain medication administration was administered before discharge in 56% of the cases . They adTo our knowledge, no other study published in the medical literature has been able to compare initial and subsequent visits of patients with pathology-proven appendicitis. Besides, we were able to provide a time estimate for a return visit that ultimately led to the diagnosis of acute appendicitis. Migration of pain from the epigastric/periumbilical area to the right lower quadrant, although considered classic, is only seen in up to 50% of patients presenting with acute appendicitis. Opioid pain medication is associated with many of the return visits to the emergency department for missed appendicitis. Finally, discharge diagnosis and planning is imperative, as detailed early appendicitis instructions or extended ED observation can include more cases and decrease litigation risk.


Inadvertent intravascular injection has been suggested as the most probable mechanism behind serious neurological complications during transforaminal epidural steroid injections. Authors believe a smaller gauge needle may lead to less intravascular uptake and less pain. Theoretically, there is less chance for a smaller gauge needle to encounter a blood vessel during an injection compared to a larger gauge needle. Studies have also shown smaller gauge needle to cause less pain. The aim of the study was to quantify the difference between a 22-gauge needle and 25-gauge needle during lumbosacral transforaminal epidural steroid injection in regards to intravascular uptake and pain perception.This was a prospective single blind randomized clinical trial performed at outpatient spine practice locations of two academic institutions. One hundred sixty-two consecutive patients undergoing lumbosacral transforaminal epidural injections from February 2018 to June 2019 were recruited and randomized to each arm of the study – 84 patients were randomized to the 22-gauge needle arm and 78 patients to 25-gauge arm. Each transforaminal injection level was considered a separate incidence, hence total number of incidence was 249 (136 in 22-gauge arm and 113 in 25-gauge arm). The primary outcome measure was intravascular uptake during live fluoroscopy and/or blood aspiration. The secondary outcome measure was patient reported pain during the procedure on the numerical rating scale.p = 0.701]. Average numerical rating scale scores during the initial needle entry for 22-gauge and 25-gauge needle was 3.46  and 3.13  respectively [p = 0.375].Fisher exact test was used to detect differences between 2 groups in regards to intravascular uptake and paired t-tests were used to detect differences in pain scores. The incidence of intravascular uptake for a 22-gauge needle was 5.9%  and for a 25-gauge needle, 7.1%  [The study showed no statistically significant difference in intravascular uptake or pain perception between a 22-gauge needle and 25-gauge needle during lumbosacral transforaminal epidural steroid injections.ClinicalTrials.gov NCT04350307. Registered 4/17/2020. (Retrospectively registered). Over 40 million epidural injections are administered every year in the United States as per data obtained from Centers for Medicare & Medicaid Services . AlthougInadvertent intravascular injection has been suggested as the most probable mechanism behind serious neurological complications during TFESI –6. The iAlthough several needle types have been studied in the past, needle gauge has never been assessed with respect to intravascular uptake. It can be beneficial to know whether needle size plays a factor in intravascular uptake during TFESI. This study aims to look at two needle sizes – 22-gauge and 25-gauge needle. It can be hypothesized that 25-gauge needle due to its smaller diameter can potentially lead to less intravascular uptake. Theoretically, when taken into account the surface area covered by a needle while it traverses through tissue planes, there is less chance for a smaller diameter needle to encounter/puncture a blood vessel during an injection compared to a larger diameter needle. Studies have also shown smaller diameter needle to cause less pain [There are multiple ways to assess intravascular uptake during TFESI. Traditionally, blood aspiration, local anesthetic test dose and/or live fluoroscopy have been used to detect intravascular uptake during spinal procedures, but none of these methods have shown to be particularly sensitive. Digital subtraction angiography (DSA) has gained traction over the last decade and it has shown to be much more sensitive than other methods in detecting intravascular uptake , 26–28. Institutional Review Board approval was obtained prior to the initiation of this study. There was no funding source involved in this study. Data is presented in accordance with the Consolidated Standards of Reporting Trials (CONSORT) statement and is available as Inclusion criteria included 1) patients with low back pain and/or radicular pain, 2) patients scheduled for lumbosacral TFESI. Exclusion criteria included 1) patients with contrast/local anesthetic allergy, 2) patients with pregnancy, coagulopathy, systemic infection, and inability to provide informed consent, 3) vulnerable patient population including prisoners, 4) patients with severe anxiety, 5) patients with prior lumbar surgery, 6) age < 18 years old, and 7) Body Mass Index (BMI) > 40.One hundred sixty-two consecutive patients were recruited and randomized to each arm of the study – 22-gauge vs 25-gauge . Eighty-four patients were randomized to 22-gauge arm and 78 patients to 25-gauge arm Fig. . InitialAll injections were administered by Physical Medicine and Rehabilitation (physiatry) specialists who had completed a fellowship in interventional spine procedures and had at least 1 year of experience in interventional spine care. All practitioners used a similar approach for lumbosacral TFESI – subpedicular/supraneural approach. The target for L1-L5 TFESI was at the superior and posterior aspect (six o’clock position of the pedicle in the AP projection) of the lumbar neuroforamen. The target for S1 TFESI was at the superolateral aspect of dorsal S1 foramen. Providers were allowed to switch the TFESI approach to infraneural ‘Kambin’s’ triangle or interlaminar/caudal approach if the planned injection could not be administered with the initial approach.The primary outcome measure was intravascular uptake during live fluoroscopy and/or blood aspiration. DSA was not available at all study locations and was therefore not utilized. The secondary outcome measure was patient reported pain during the procedure from 1 to 10 on the numerical rating scale (NRS).After obtaining informed consent, patients were asked to record pre-procedure pain level on the NRS. Study coordinator explained the study design to the patients and specifically asked patients to pay attention to pain scores during 2 occasions – first one, during the initial needle entry after they feel the burn of the numbing agent and the second, during the administration of the steroids towards the end of the procedure. Interventionalists would also remind the patients to assess their pain during these 2 phases of the procedure. Patients were then brought to the fluoroscopy suite and placed in prone position on the fluoroscopy table. A procedural time-out was then conducted as per facility guidelines. The patients were prepped and draped in a standard sterile fashion in the prone position and the C-arm was positioned so that an oblique view of the neuroforamen was visualized and target marked. The soft tissues overlying this structure were infiltrated with 1–5 mL of 1% lidocaine (10 mg/mL) without epinephrine using a 27-gauge 1.5 in. needle. Lidocaine was injected at the skin (without creating a significant skin wheel) and through the subcutaneous tissue to 1 to 1.5 in. depth (maximum of 2 passes through the subcutaneous tissue). Then, a 22-gauge or 25-gauge (as per randomization) Quincke needle was inserted toward the target using an ipsilateral oblique trajectory view. Patients were blinded to the gauge of the needle. The needle was advanced under an oblique, AP and lateral visualization, to confirm correct needle tip placement. Aspiration was confirmed to be negative for cerebrospinal fluid and/or blood. Then a 1–2 mL volume of contrast dye (Omnipaque-240/Iohexol 240 mg/mL) was injected under live fluoroscopy to look for intravascular uptake. Needle tip was repositioned until an epidural only contrast pattern was observed prior to injecting the steroid. After obtaining satisfactory contrast flow pattern and negative blood aspiration, the injectate  was administered at each level along the nerve root and into the epidural space very slowly based on patient tolerance. Patients were reminded by interventionalists to assess their pain during this time. For the purposes of this study, only the initial contrast pattern was utilized. If an epidural only contrast flow was not obtained or persistent intravascular uptake was noted despite multiple needle redirections, the procedure was either abandoned or another approach was utilized  as per patient and provider discretion. Live fluoroscopy and blood aspiration were utilized to confirm intravascular uptake at every injection level. Intravascular injection noted by either method was reported as ‘present’ for each level. Digital subtraction angiography or lidocaine test dose method was not used to confirm intravascular spread. At the conclusion of the procedure, all needle(s) were re-styletted, withdrawn and sterile dressings were placed. Patients were then brought to the recovery area and study coordinator or nurse  presented patients with written post-procedural questionnaire (paper form). Patients were specifically asked to rate the pain during the initial needle entry and also during the administration of injectate (steroid mixture). Overall tolerability of the procedure was also measured on an ordinal scale (‘well tolerated’ at 1 and ‘poorly tolerated’ at 4).Each needle entry at any given lumbosacral level was considered a separate incidence. For instance, a bilateral L5 TFESI was considered 2 separate incidences. Fisher exact test was used to detect differences between 2 groups in regards to intravascular uptake and paired t-tests were used to detect differences in pain scores. Both primary and secondary outcome measures were analyzed based on intent-to-treat principle.A total of 249 TFESI injections were completed on 162 subjects. No serious complications were reported in any patients. Baseline demographics for both study groups are listed in Table Eighty-seven patients received 2 level injections and the remaining 75 patients received 1 level injections. Each level was considered a separate incidence, hence total number of incidence was 249. Patients enrolled had TFESI at L2 to S1 levels. The most common level of injection was L5 neuroforamen for both groups. In four patients, the target could not be obtained  due to technical difficulties (osteophytes/difficult anatomy) hence reassigned to 22-gauge needle arm and was completed successfully. Two other patients in 22-gauge group (both at S1 neuroforamen) were reassigned to interlaminar or caudal approach due to persistent intravascular uptake. All other patients had successful completion of the injection according to their assignments.p = 0.701, Fig. The overall incidence of intravascular uptake for both the 22-gauge and 25-gauge group was 6.4% (16 out of 249) in this study. The incidence of intravascular uptake for 22-gauge group was 5.9% . The incidence of intravascular uptake for 25-gauge group was 7.1% . There was no statistically significant difference between both groups in regards to intravascular uptake . Again, both groups showed no statistically significant difference in overall tolerability.Pain scores (NRS) for 22-gauge and 25-gauge groups are listed in Table The results of this study showed no statistically significant difference between the use of a 22-gauge and 25-gauge needle in regards to intravascular uptake or pain scores. One would expect the smaller gauge needle to reduce incidence of intravascular uptake but this study did not demonstrate any benefit in using a smaller bore 25-gauge needle as opposed to a larger bore 22-gauge needle. On the contrary, there seemed to be some disadvantage in using the 25-gauge needle as it can be hard to penetrate firm ligaments/skin and navigate around osteophytes, hence harder to steer and reach the target. Even though this study excluded patients with BMI > 40, all interventionalists found it less desirable to use 25-gauge needle as it took longer and required more fluoroscopic images to complete the procedure. In addition, it is to be noted that there were 6 cases in this study which switched assignment after randomization, and 4 of them were in 25-gauge arm . The other 2 assignment changes were due to persistent intravascular uptake, hence reassigned to interlaminar approach. Although not quantified in this study, 25-gauge needle can be difficult to steer through deeper tissue planes limiting its potential use in clinical practice. In this study, there was no outcome measure to gauge the difficulty level associated with completing a lumbosacral TFESI using 25-gauge needle. Authors recommend future studies looking at procedure time/exposure to further quantify this phenomenon in a more objective manner.Although patients with lumbar surgery were excluded from the study, low thoracic and sacral surgeries can also result in increased vascularity in lumbar region due to post-surgical changes. On post-hoc analysis, none of the patients had documented low thoracic or sacral surgeries prior to enrolling in the study.The study may also suggest that a smaller gauge needle may not lead to less pain. Although the study was not well designed to detect the differences in pain perception, the results suggest no difference in pain scores or tolerability between the 2 groups. Patients were specifically asked to rate the pain during the initial needle entry and also during the administration of injectate (steroid mixture) hoping to differentiate pain experienced at various stages of the procedure, but no statistically significant differences were observed.Similar to prior studies on intravascular uptake, one of the limitations of this study was also the relatively small sample size. A sample size of 249 was not enough to detect small changes that may exist between the 2 groups especially given the low overall incidence of intravascular uptake during TFESI. Also true randomization at injection event level was not possible as one patient could have had multiple events. Although initial goal was to recruit around 250 patients, study was terminated early at 162 patients, hence an ‘event’ was changed from patients to level of injections for statistical analysis possibly implying cluster randomization.Authors did not use digital subtraction angiography to detect intravascular uptake as it was not available at all study locations. Instead, standard live fluoroscopy and/or vascular aspiration were used. Studies have shown DSA to increase the sensitivity of detecting intravascular uptake , 26–28.Pain scores were obtained after the procedure when patients were in the recovery room which could have led to recall bias. When patients were asked to rate pain during the initial needle entry, they could in fact be assessing the needle used for local anesthetic infiltration. More accurate pain scores could have been obtained if asked during the procedure immediately after placement of the needle and administration of steroids. Although the procedure was standardized in the research protocol, there may still be differences in how the injection was performed between various interventionalists (five in this study) which can affect patients’ pain perception. Sensitivity analysis  appeared to affect pain scores but had limited impact on the rate of intravascular uptake.One would expect the smaller 25-gauge needle to reduce incidence of intravascular uptake and be less painful during TFESI, but the study finds no conclusive evidence. In conclusion, the study showed no statistically significant difference in intravascular uptake or pain perception between a 22-gauge needle and 25-gauge needle during lumbosacral TFESI.Additional file 1.