Conclusions: Harm-avoidance seems to be the most important dimension in personality patients with chronic pain, as previously found. We found no differences between OA groups and between sensitized groups, but there are differences between FM and OA-noCS, so harm-avoidance might be the key to describe personality in patients with CS rather than the presence of prolonged pain, as found in the literature before.Background: Personality traits are relevant for pain perception in persistent pain disorders, although they have not been studied in depth in sensitized and nonsensitized patients with knee osteoarthritis (OA). Objective: To explain and compare the personality profile of patients with OA, with and without central sensitization (CS), and fibromyalgia (FM). Setting: Participants were selected at the Rheumatology Department in two major hospitals in Spain. Participants: Case-control study where the sample consists of 15 patients with OA and CS (OA-CS), 31 OA without CS (OA-noCS), 47 FM, and 22 controls. We used a rigorous and systematic process that ensured the sample strictly fulfilled all the inclusion/exclusion criteria, so the sample is very well delimited. Primary outcome measures: Personality was assessed by the Temperament and Character Inventory of Cloninger. Results: The percentile in harm-avoidance dimension for the FM group is higher compared to OA groups and controls. The most frequent temperamental profiles in patients are cautious, methodical, and explosive. Patients with FM are more likely to report larger scores in harm-avoidance, with an increase in logistic regression adjusted odds ratio (OR It is known that personality, a person’s predispositions and patterns of thinking, feeling, and acting , plays aWe would like to focus on two pathologies where chronic pain (CP) is the main feature. The first is osteoarthritis (OA), which is already one of the ten most disabling diseases in developed countries. The worldwide estimates are that 9.6% of men and 18% of women aged over 60 years have symptomatic osteoarthritis . Even ifPsychological and personality factors should be considered an important contributor in the processing of CP, as we know that they play a role in modulating therapeutic responses and pain perception ,16. PersLittle is known in the field of personality in OA, although it is the most prevalent musculoskeletal disease; presumably, plenty of OA patients suffer CP, and there are studies that show that the patient’s personality predicts recovery after total knee arthroplasty . Çidem, The initial sample was composed of 90 patients with knee OA diagnosis and 150 with FM diagnosis at the Rheumatology Department in two major hospitals in Spain , selected by a senior rheumatologist and a senior clinical psychologist during an 18 month period. There was a control group with 35 participants.Patients with OA were divided into 2 groups: (1) presence of clinical central sensitization, defined by the presence of both spreading sensitization and temporal summation to repeated pressure pain stimulation ,31,32,33Radiological and clinical diagnosis of knee OA based on the American College of Rheumatology (ACR) criteria, affecting at least one knee with a minimum of 3 months of symptom duration prior to screening.Male or female  at least 45 years old.A minimum of 4 out of 10 on the numerical rating scale (item 5 of Brief Pain Inventory) at screening and/or a requirement for the use of an analgesic for the knee pain.The principal inclusion criteria for the OA patients were:Clinical evidence of pain or altered sensations spread beyond the knee joint by manual palpation in the baseline rheumatologist assessment.2 [At least 3 tender points in the extended version of the Arendt–Nielsen peripatellar map . A tender point is defined as a point showing a pressure pain threshold below 4 kg/cm2 .2 pressure stimulation on the anterior surface of the tibial bone.A pain score of 4 points or more in an 11-point verbal scale during a 2 s, 4 kg/cmPresence of temporal summation  on the most sensitive site of the peripatellar region [The specific inclusion criteria for the OA-CS group were:Diagnosis of FM following the ACR criteria .History of widespread nonarticular pain with insidious onset primary over 3 months.One year minimum of disease evolution.Absence of comorbid chronic fatigue syndrome.The principal inclusion criteria for FM patients were:No history of rheumatic disorder, no history of functional pain or physical widespread pain.No history of Axis I or II psychiatric illness and no history of neurological disease.Inclusion criteria for control group were:Additionally, control participants underwent a brief semistructured clinical psychopathological interview according to DSM-5 diagnostic criteria carried out by a senior member of the research team (JD) to rule out any personality disorder. A convenience sampling was carried out where the researcher selects the patients who are easily accessible in a waiting room, through a satisfaction survey of the health system.In all groups, patients with a history of psychotic disorder or substance abuse, patients with a history or diagnosis of personality disorders, and patients with a history of neuropathic pain were not included. A flow chart of the sample selected is shown in The participants signed informed consent to accept the conditions of the study. We used a methodical and strict process that allowed us to ensure the sample strictly fulfilled all the inclusion/exclusion standards; therefore, the sample was very well delimited. The final sample  was madeFirst, patients attended rheumatologic visits where they were selected, and after verifying the inclusion/exclusion criteria as well as the will to participate, they were enrolled. During the next few days, patients attended psychological assessment, performed by the same clinical psychologist, which lasted about 90 min. Patients were visited twice in case of causing too much fatigue that may have influenced answers. The research only analyzes some aspects of this broad protocol.Novelty-seeking (NS), defined as the inclination to respond impulsively to novel stimuli with active avoidance of frustration.Harm-avoidance (HA) as the tendency to inhibit responses to aversive stimuli leading to avoidance of punishment.Reward dependence (RD) as the predisposition to answer to signals of reward.Persistence (PS) as the tendency to perseverance despite frustration and fatigue.Revised Temperament and Character Inventory (TCI-R) : We admiSelf-directedness (SD), which refers to the ability to control, regulate, and adapt behavior to fit the situation.Cooperativeness (CO), which is related to acceptance of other people.Self-transcendence (ST), which is viewed as the identification with everything conceived as essential and consequential parts of a unified whole.The 3 character scales are:Exploratory excitability (NS1), impulsiveness (NS2), extravagance (NS3), and disorderliness (NS4).HA: Anticipatory worry (HA1), fear of uncertainty (HA2), shyness with strangers (HA3), and fatigability (HA4).RD: Sentimentality (RD1), openness to warm (RD2), attachment (RD3), and dependence (RD4).PS: Eagerness of effort (PS1), work-hardened (PS2), ambitious (PS3), and perfectionist (PS4).The temperament facets in NS are:Responsibility (SD1), purposefulness (SD2), resourcefulness (SD3), self-acceptance (SD4), and enlightened second nature (SD5).CO: Social acceptance (C1), empathy (C2), helpfulness (C3), compassion (C4), pure-hearted conscience (C5).ST: Self-forgetful (ST1), transpersonal identification (ST2), and spiritual acceptance (ST3).The character facets for SD are:Specifically, this inventory allows us to assess the possibility of the psychometric presence of some symptomatic personality disorders  if the scores of SD and CO are low or very low (17–33%). The lower cut-off point is situated in 35 points and the upper in 75. This questionnaire has proved to be reliable in its original version, with internal consistency alpha coefficients ranging from 0.65 for persistence to 0.89 for cooperativeness. The Spanish version also shows good estimates of internal consistency alpha coefficients, such as in our study except in the novelty-seeking scale .We performed nonparametric Kruskal–Wallis and chi-square statistical tests to analyze the differences between the four groups  in TCI-R mean percentile scores and in the distributions of the temperamental profiles and personality disorders of TCI-R, respectively. Logistic regression models were adjusted to identify the most characteristic personality pattern of these groups. For the statistical analysis we used the statistics Package SPSS 20 .Descriptive features of the final sample are shown in p < 0.001). p < 0.001) but not in the distribution of personality disorders . There are also no differences between groups in the frequency of absence/presence of personality disorder  and personality disorder  obtained depending on the temperamental profile. The contingency coefficient scored 0.589 (p < 0.05), which is high (according to the formula: Max (C) = √χ2/(χ2 + n)) and is directly proportional. After the contingency table and the chi-square test, we found a relation statistically significant between group  and temperamental profile. To obtain a descriptive profile of personality for each group, a logistic regression analysis was completed. The initial model included the following confounding factors: gender, age, academic level, and cognitive screening.The outcomes of the logistic regression between OA-CS and OA-noCS and between FM and OA-CS show no statistical significance in their profiles. We also performed logistic regression in every subdimension of each temperament, and character dimensions where we found no significant differences.The aim of this research was to describe the most frequent temperamental profile for different groups of patients, including the control group, to study whether the participants show a potential personality disorder or not, and of what type, and finally to describe the pattern of personality for different groups, focusing on the presence of CS. Many researchers found higher scores in HA and lower in SD, with some variations with the role of the other dimensions of temperament and character, for example, lower scores in NS ,20. GencRegarding the temperamental profile results of combining temperamental dimensions NS, HA, and RD, for OA-noCS patients, the most frequent profiles are cautious (19.4%) and explosive (19.4%), for OA-CS it is methodical (26.7%), for FM patients it is cautious (36.2%), and for controls it is independent (36.4%). Explosive (high scores in NS), methodical, and cautious (both low scores in NS) show high scores in the HA dimension, while independent shows high scores in RD. When SD and CO are low, the possibility of having a personality disorder exists. In our sample, most of the patients do not show a potential disorder. However, patients who do show obsessive, avoidant, and borderline disorders correspond to methodical, cautious, and explosive temperamental profile. Thus, patients with a potential personality disorder of cluster C show high scores in HA. Thus, both patients with and without personality disorder show inhibition, passive avoidance, pessimism, fear of uncertainty, cautiousness, shyness, anticipation of problems, and fatigue after stress. When the disorder is present, these traits are more exaggerated, meaning that the person is not able to control his or herself driven by the situation.After the regression analysis, we found that patients with and without CS are more likely to show RD traits, a fact that has not been found in research before. These dimensions assess the tendency to be influenced by others, be very sensitive to social signs, sentimental, and be able to understand the feelings of others. Garcia-Fontanals et al.  and GencThere are authors who state that central sensitization syndrome has been produced by the existing duration of chronic pain that begins in the early stages of life or due to innate personality traits (temperament), learned personality traits (character), or a combination of both. Our study covers an older population and, therefore, innate temperament traits are what determine the presence of SSC .The sample size is small, especially for the OA-CS group. Given the size of the sample, we were not able to carry out an analysis that differentiates between gender and age.External validity is limited by the sample size, even though the sample is very specific and restrictive, with the inclusion/exclusion criteria. For example, FM patients showed no chronic fatigue, which is a very common characteristic.The FM group was not divided into potential subgroups of patients according to severity; for example, there are few studies that show evidence in this field. Thus, it is complicated to find previous studies to compare our results with others.The effects of other symptoms of central sensitization that may be present in these patients, such as migraine, irritable bowel syndrome, or low back pain, have not been studied in OA groups due to the small sample size.This research has some limitations:Therefore, our results show that patients with CP show a diverse personality pattern compared to control subjects ,37, and Multiple differences between groups with CS and without CS have been reported in previous research; Clark et al.  found a Personality assessment with TCI-R gives us the opportunity to evaluate treatment responses. Many studies found that the pretreatment level in the SD dimension predicts the scope of improvement. When the therapy is successful, levels of SD increase, giving control across the situations ,21. TherWe changed the focus from CP to CS; however, more investigations are needed in CS syndromes to find out if this phenomenon is an important factor in the role of the HA dimension, and not the presence of CP, as is normally reported. Further research is recommended to include the controlled pain parameter that differs in personality traits.In conclusion, harm-avoidance seems to be the most important dimension in personality patients with chronic pain, as previously found. We found no differences between OA groups and between sensitized groups, but there are differences between FM and OA-noCS, so harm-avoidance might be the key to describe personality in patients with CS rather than the presence of prolonged pain, as found in the literature before.


Virtual reality is a novel approach for distracting and alleviating anxiety, pain, and other complications during medical procedures, and it can be more effective than conventional methods. In virtual reality, the patient is completely immersed in the virtual environment, which is used to make patients feel more comfortable and can provide a positive prognosis. The data were searched by using the Boolean operator “AND” between the search phrases “Virtual reality,” and “Pediatrics” and the relevant literature was extracted. The inclusion criteria were the free full text, randomized controlled trials, studies between 2016 and 2022 and pediatric patients. This systematic review was conducted to compare randomized controlled trials of virtual reality applications in pediatric patients in different clinical settings. Of the included 15 randomized controlled trials, 12 studies were on pain and anxiety, two on brain injury and cerebral palsy, and one on awareness among asthmatic patients. This review concluded that virtual reality exposure has a beneficial effect on pediatric patients in reducing pain and anxiety, improving muscle strength and dexterity, and awareness among asthmatic patients. Pain, anxiety, and stress are generally observed during medical procedures in pediatric patients with poor prognosis, nervousness, loss of appetite, sleep disturbances, the effort to escape, and post-traumatic stress manifestations. Moreover, negligence toward health is a result of altogether pain, anxiety, and stress. Hence, new therapies are crucial to alleviate pain and anxiety in children and can be achieved by distraction during clinical procedures .Distraction methods such as the use of music, movies, and toys have been shown to have a positive impact on decreasing pain and anxiety. Virtual reality (VR) is the newest technique to provide distraction during medical procedures and has been proven to be more efficacious than other conventional methods, and is usually made up of a computer-generated environment, and three-dimensional use and orientation are feasible . The useVR is usually divided into non-immersive, fully immersive, semi-immersive, and augmented VR which is widely used in clinical practice for distraction and to keep patients calm . Hence, Research methodologyFor the purpose of performing this systematic review, the PRISMA-S statement for reporting systematic reviews was utilized . RandomiResultsOnly 15 RCTs were enrolled in this study from the PubMed database. Various variables related to VR applications were investigated and enlisted in this systematic review. Meta-analysis was not feasible due to differences in setting, inclusion criteria, and outcome characterization and assessment. However, comparisons among similar studies provide a guide for VR use in pediatric patients and relevant practices in real-life settings. Information regarding the author's name, names of journals, place of study, and year of publication were mentioned in Table Table All study designs were interventional and consistent with the inclusion criteria for this review. All studies used a randomized controlled design to demonstrate the effectiveness of VR in several parameters in pediatric patients. The majority of studies (n=12) evaluated patients' experiences with venipuncture, peripheral intravenous catheter (PIVC) installation, dental extraction, elective surgery under general anesthesia, and pain and anxiety related to those procedures. Two RCTs (n=2) assessed dexterity and muscular power in patients with cerebral palsy (CP) and one RCT (n=1) demonstrated the use of VR for creating awareness among asthmatic patients.DiscussionThis novel systematic analysis emphasizes randomized controlled research that details VR technology applications. The current medical uses of VR technology are pain distraction, anxiety relief, and rehabilitation, as revealed by data from 15 studies that were eligible for this review.Procedure-related pain that is not properly handled is extremely upsetting and can increase pain sensitivity over time, decreasing the probability that an adult would seek medical attention and even fewer possibilities in pediatric patients . VR is aThe goal of the previously conducted RCT was to identify less risky and non-pharmacological alternatives to treat pain and discomfort caused by repeated treatments when sedation is unnecessary. VRE has not, however, demonstrated any appreciable differences and patients frequently required the use of pharmaceutical treatments and analgesics (morphine), hence the use of immersive VR such as headset and audiovisual distraction led to a reduction in anxiety in the operating room before elective surgery, as the study was a pragmatic implementation, and it used established outcome scale that was validated and showed less observer bias .Another RCT reported that VR did not significantly reduce pain or anxiety in patients undergoing elective surgery. A single evaluation performed before entering the recovery room did not provide a thorough understanding of the postoperative effects of VRE. The study was discontinued in 21 children by removing the headset and was heavy and larger in size, which might have caused discomfort to the patients, as the majority of subjects were 4-5 years of age, and minor procedures were included [Chances of dentist phobia, non-cooperative conduct at the time of treatment, and the potential to avoid future dental appointments have all been linked to unpleasant prior dental experiences, including the use of local anesthetics . The HeaSimilarly, the positive influence of VR on pain, distress, needle phobia, and treatment in patients who routinely undergo PIVC procedures irrespective of their chronic status has been demonstrated . AccordiAnother RCT reported that VR using a dome screen is a practical means of diverting young children during intravenous (IV) insertion; however, its efficacy could not be validated because of the limited sample size . SimilarThere is not much research that determined the VR distraction outcome on anxiety, pain, gender, and age respectively. Similarly, another study examined the effects of audio distraction visually on anxiety in children aged four to six years compared to those aged six to eight years and discovered that it effectively reduced anxiety in the treatment groups . Hence, A major objective for pediatric patients with CP is independent walking, which was covered in this review on the use of VR in children with brain injuries and subjected to clinical and community-focused rehabilitation . This stSimilarly, VR games effectively motivate children with CP and, as a result, represent a therapeutic approach that can be utilized to speed up rehabilitation training . The exeIt is possible to use therapeutic techniques like task-directed exercise for VR rehabilitation. Thus, more engagement in daily activities, as determined by the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) in the study, may have resulted from improvements in upper limb function . AnotherThe establishment and comparison of awareness and education among asthma patients showed an efficacious impact of immersive VR content. Additionally, the asthma control status of the experimental and control groups was compared and was informative for the participants . The posIn this study, the use of VRE among pediatric patients showed a beneficial impact, and in some RCTs, it did not cause any significant difference when compared with the usual care. Gamification and VR applications can be helpful for pediatric patients. However, there is currently little empirical data and poor evidence. Future research can be conducted by including more than two databases and including more searching terms with combination and permutation for accessing and analyzing more relevant literature.


The Burning Month Syndrome (BMS) is an oral mucosa pain - with or without inflammatory signs - without any specific lesion. It is mostly observed in women aged 40-60 years. This pain feels like a moderate/severe burning, and it occurs more frequently on the tongue, but it may also be felt at the gingiva, lips and jugal mucosa. It may worsen during the day, during stress and fatigue, when the patient speaks too much, or through eating of spicy/hot foods. The burning can be diminished with cold food, work and leisure. The goal of this review article is to consider possible BMS etiologies and join them in 4 groups to be better studied: local, systemic, emotional and idiopathic causes of pain. Knowing the different diagnoses of this syndrome, we can establish a protocol to manage these patients. Within the local pain group, we must investigate dental, allergic and infectious causes. Concerning systemic causes we need to look for connective tissue diseases, endocrine disorders, neurological diseases, nutritional deficits and salivary glands alterations that result in xerostomia. BMS etiology may be of difficult diagnosis, many times showing more than one cause for oral pain. A detailed interview, general physical examination, oral cavity and oropharynx inspection, and lab exams are essential to avoid a try and error treatment for these patients. Burning Mouth Syndrome (BMS) is characterized by pain in the mouth with or with no inflammatory signs and no specific lesions. Synonyms found in literature include glossodynia, oral dysesthesia, glossopyrosis, glossalgia, stomatopyrosis, and stomatodyniaBMS generally presents as a triad: mouth pain, alteration in taste, and altered salivation, in the absence of visible mucosal lesions in the mouthPain is a moderate to severe burning sensation, affecting mainly the lateral borders and the tip of the tongue, and may persist for years. Pain may also be present in the gums, the lips and the jugal mucosa, with no visible lesions on oral and pharyngeal examination. Pain increases as the day progresses, in states of anxiety, fatigue, excessive speaking, and when ingesting hot and seasoned food; pain subsides with cold food, work and distractionIn 1994 Lamey et al.Stinging on the lips and mouth or intense salivation are common symptoms. Alterations in salivary content have been detected such as increased content of potassium, proteins and phosphates, making saliva thicker and stickier. Another important symptom is hypogeusia or dysgeusia, in which patients complain of a persistent metallic, salty or bitter tasteThe etiology of BMS is difficult to define, and there may be more than one etiological factor. Patients seek help from a variety of medical specialists, including dentists, ENT specialists, and dermatologists, and try a range of therapies, the most common of which are: corticosteroids, analgesics, antibiotics, estrogen, retinoids and psychotropic drugsA careful clinical history, a general physical examination, a detailed examination of the mouth and oropharynx are mandatory to avoid trial and error treatment of this syndrome.The aim of this review is to provide an overview of possible etiologies of BMS, grouping them into 4 major groups for better understanding : local, Pain in the mouth may appear due to incorrect use of orthodontic appliances, ill-positioned or corroded dental fixtures, and fixtures used for a very long time, with the patient complaining of a metallic taste. Local reaction caused by contact between the mucosa and metal leads to erythema and a burning sensation. Currently local irritation may also be caused by tongue piercing.There may be local pain by mechanical trauma in patients that repeatedly bite the jugal mucosa due to dental problems or malocclusion.Having discarded orofacial pain of dental causes, which is the most common form, parafunctional habits and behaviors should be investigated, such as temporomandibular joint (TMJ)Allergy to food coloring agents, preservatives and additives has been identified in 65% of type 3 BMS patients . Substances identified as commonly causing mouth pain are: cinnamon aldehyde, ascorbic acid, tartarazine, benzoic acid, propyleneglycol and mentholAllergy to denture materials is rare, and should be considered only after confirmation by allergy tests which correlate to clinical findingsThe causal agent is Candida albicans, and it appears in the elderly, in immunodeficient patients, in prolonged use of antibiotics, immunosuppressant medication, anti-retroviral drugs or corticosteroids. Candida infection may present with or with no inflammation on the mucosa, and patients refer burning in the mouth resulting in dysphagia and sialorrheaDental fixtures also help increase the number of fungal coloniesThis is dental conservation related infection. Causative agents are the polymicrobial oral flora saprophytes including streptococci, enterococci, staphylococci, neisseria, proteus, anaerobes and fusospiral organisms. Many infections are opportunistic. There is gingival congestion and edema of interdental papillae, there may be hyperemia of the mouth mucosa and tongue, which may show indentation marks along its lateral borders. Pain and halitosis are intense in more advanced casesSalivary gland function is altered by a variety of drugs that induce xerostomia, which affects eating and the capability to resist bacterial colonization of the teeth, and which may alter the taste.Many drugs may alter salivary gland function, the most common being anticholinergic agents, anti-histamines, anti-retroviral drugs, tricyclic antidepressants, serotonin uptake inhibitors and omeprazolXerostomia depends on the drug, the dose and individual patient differences. Burning may develop days to years after exposure to the causative agentChemotherapy agents, such as adriamycin, cause mucositis 5 to 7 days after the initial dose. The patient presents intense local pain in the oral mucosa, and if chemotherapy is maintained, may develop reduced salivary flow and gland destruction. Normally the gingiva, the dorsal surface of the tongue and the hard palate are not involvedRadiotherapy (RT) may initially cause mucositis and increased salivary flow due to local inflammation. At this moment the mucosa is extremely painful. If RT is maintained there may be permanent mucosal atrophy, causing burning on the tongue, dry mouth and swallowing difficulty. Salivary gland function is compromised depending on the radiation dose; irradiation over 40Gy/dose causes irreversible gland injuryThere are many description in literature of glossitis in patients taking ACE inhibitorsSjögren's syndrome is an autoimmune disease affecting mostly women aged between 40 and 60 years, and may be associated with other connective tissue disorders such as multiple sclerosis and rheumatoid arthritis. The classical presentation of this syndrome is keratoconjunctivitis, xerostomia and connective tissues alterations.Fibromyalgia (FM) is a chronic pain syndrome usually diagnosed based on the presence of pain in at least 11 of 18 tender points lasting at least 3 months. BMS is seen in 32.8% of FM patients, where the most frequently described oral symptoms include xerostomia (70.9%), orofacial pain (32.8%), TMJ dysfunction (67.6%), dysphagia (37.3%), and dysgeusia BMS may signal undiagnosed diabetes mellitus (DM), therefore DM should be investigated particularly in patients aged over 50 years, when the incidence of type II DM is increasedThere is controversy in literature on the role of estrogens as an oral mucosa protective factor. Although mouth pain has a high incidence in post-menopausal women, studies have not found a significant relationship between mouth pain and the number of menopausal years, the use of hormone replacement therapy of the number of years of hormone replacementPain stimuli are detected by nocireceptors, receptors with capsaicinFurther evidence that BMS may have a neurogenic origin is that these patients have thermal hypersensitivity and significant electrophysiological abnormalities compared to controlsTrigeminal neuralgia is characterized by brief episodes of intense pain in bursts, usually in people aged over 50 years, mainly involving the mandibular branch territory, sometimes causing tongue hypoesthesia or paresthesia. Trigeminal neuralgia may be caused by nerve compression due to neoplasms, vascular malformation, encephalopathy, myringomyelia, herpes zoster infection, trauma or after dental extractionGlossopharyngeal neuralgia is a rare disease occurring mostly in women aged between 40 and 60 yearsPain may also be caused by undiagnosed neoplasms, infection, elongated styloid process and vascular causes such as arterial compression, elongation or looping, mostly of the posterior inferior cerebellar arteryA burning sensation on the tongue may occur in 40% of patients with vitamin B deficiency. Tongue pain is usually located on the tip of the tongue, and patients may present papillary atrophy. Patients undergoing hemodyalisis or that restrict their diet in some way , alcoholics and the elderly are prone to vitamin B deficiencyZinc deficiency may cause organic effects such as lingual papillary atrophy, resulting in dysgeusia and glossodynia. Tanaka et al.Zeller et al.This is when careful local, systemic and emotional investigation fails to reveal an etiology for BMS.After age four, the tongue may develop grooves in some people, with folds in the anterior two thirds of the tongue. A burning sensation may ensue when there is inflammation along these grooves caused by ingesting acid and/or very seasoned food. These grooves may be entry portals for infection such as herpes simplex, candida and syphilis. This may also be part of Melkerson Rosenthal's syndrome, which progresses with granulomatous glossitis, facial palsy, lingua plicata and lip edema.It is found in 30% of Down syndrome patientsGeographic tongue is characterized by areas of pink mucosa with a grayish center. These areas may converge and are interspaced with normal mucosa. This condition is a benign condition, not a disease. Patients with this lingual alteration may be prone to cancerphobia. Psychological (stress) and local  reactions are believed to cause this condition, as well as genetic factors. Usually areas of altered mucosa increase when there is some other parallel medical conditionBMS is usually multifactorial, and these patients require an organized approach to take the various etiologies into account.The history of pain should be established, including duration, intensity , site, and factors that improve or worsen the pain. Inquiries should also be made about increased salivation, dry mouth, altered taste, the diet, the use or oral antiseptics, the type of toothpaste, habits such as chewing gum, smoking, and taking alcoholic beverages. Other information includes any relation between pain and the use of dental fixtures and prostheses, parafunctional behavior , and the use of medication and its xerostomia causing potential. A psychological history is also extremely relevant, including questions about anxiety, depression and cancerphobia.A detailed general and oral physical examination should be made, to uncover the presence of erythema, glossitis, lingual papilla atrophy, sings of tongue biting, candida infection, lingua plicata, geographic tongue, lichen planus or xerostomia.Work-up should include a complete blood count, TSH, free T4, fasting blood glucose, iron, ferritin, transferrin and folic acid. Diabetics should also be tested for glycosylated hemoglobin to check if diabetes is well controlled. Rheumatologic and autoimmune tests may be required if warranted by the clinical historyPatients with psychological conditions should be referred to a psychiatrist who will assess any relation between the onset of symptoms and events in the patients’ lives such as intense stress, loss of loved relatives, fear of cancer, etc. A dental evaluation should also be done to recommend improved dental care and adequate use of dental fixtures.


Editorial on the Research TopicWhiplash-associated disorder—advances in pathophysiology, patient assessment and clinical management“Whiplash injury’ refers to an acceleration-deceleration mechanism of injury to the cervical spine. Neck pain arising from such an injury—termed whiplash-associated disorder (WAD)—is the most common injury sustained in a motor vehicle crash (MVC)  and a suWhiplash-associated disorder—Advances in pathophysiology, patient assessment and clinical management, we sought to bring together a series of papers that provide new insight into mechanisms underpinning WAD, considerations in clinical assessment, as well as approaches to patient management.After a whiplash injury, approximately 50% of patients develop chronic WAD, with around 16% reporting ongoing severe pain-related disability . DespiteAndersen et al. build on this prior data with a large cohort study (N = 740) exploring PTSS, pain and quantitative sensory testing  across a 12-month period following a whiplash injury. Those patients with clinical PTSS had sensory hypersensitivity across all time points as well as greater pain intensity and more widespread pain—demonstrating a clear link between PTSS, sensory hypersensitivity and clinical outcomes. These data elegantly reflect the biopsychosocial dimensions of WAD and clinical importance of PTSS, especially in the context of a recent clinical trial targeting PTSS after whiplash injury, with clinically meaningful effects on neck pain-related disability at 6 weeks, 6 months and 12 months (Post-traumatic stress symptoms (PTSS) and sensory hypersensitivity are established predictors of poor outcome after whiplash injury , 24 and 2 months .Kasch et al. revisit results from a previously published cohort study that investigated motor and sensory dysfunction after whiplash injury—employing a unique study design using patients with ankle injuries as a control group. These authors performed a comprehensive assessment of pain, disability, nociceptive sensory processing and motor function across a 12-month period post-injury. Those patients that had reduced work capacity one year after injury had early reports of higher pain and demonstrated early sensory  and motor  dysfunction compared with whiplash patients that recovered and ankle-injured controls. These data suggest an interplay between patient symptoms, nociceptive sensitisation and motor control, that is associated with long term clinical outcome, which reflects the complexity of mechanisms underlying poor outcome after a whiplash injury.Röijezon et al. investigates the discriminative validity and reliability of the cervical movement sense test, assessing the level of proprioceptive disturbance in people with WAD, idiopathic neck pain (INP), and healthy controls. Movement acuity was found to be a valuable outcome measure to assess disturbed cervical movement sense in both WAD and INP, with few differences in outcomes between the two neck pain groups. Yet, it was concluded that altered movement control strategies may exist between types of neck pain. Future investigation of such differential strategies can be used to inform management approaches tailored to WAD.Cervical sensorimotor control, and its association with patient clinical presentation, has been explored in relation to various types of neck pain. Sensorimotor deficits are arguably most relevant for WAD, considering its associated symptoms such as dizziness and unsteadiness. One of the most commonly used cervical sensorimotor control tests is the cervical movement sense test, in which a participant or patient with a laser pointer attached to the head, follows a target line as accurately as possible with controlled head movements. The study by Oostendorp et al. provide a synthesis of recent literature on quantitative measures of quality improvement in physiotherapy care. Included were more than 800 patients with WAD and a set of quality indicators used over a 16-year period. The authors conclude that physiotherapeutic care of WAD has substantially improved, and provide detailed suggestions for continued quality assurance.Alongside investigations of pain mechanisms, assessments, and the effectiveness of various treatments, there has been an increased emphasis on the clinical translation and implementation of evidence-based and high-value care approaches. As the clinical management of WAD remains to be challenging and development of physiotherapeutic care continues, a focus on quality improvement is warranted. Quality indicators can be used to standardise the assessment of such improvements, however, evidence lacks concerning their assessment, management, and patient-related outcome measures. The combined articles in this Research Topic illustrate the variety of work being undertaken to improve the understanding and clinical management of WAD. Building on the themes presented across these articles, further investigation is required to better understand the association between biopsychosocial mechanisms and the clinical presentation of patients with WAD and the symptoms they experience. Recent investigations into the  relationship between genetic factors, biological mechanisms, and chronic pain presentations , 27 are All authors contributed to manuscript preparation and decision to submit for publication. All authors approved the submitted version.


Spinal surgery is gradually moving toward minimally invasive surgery, but there is still some lack of knowledge about the Unilateral Biportal Endoscopic (UBE) technique that has been hotly debated in recent years. We performed this systematic review and meta-analysis to clarify whether UBE is superior to percutaneous endoscopic lumbar discectomy (PELD) for relieving short-term postoperative pain and promoting functional recovery.  Computer searches of PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang databases were performed to search for studies on UBE versus PELD for single-segment lumbar disc herniation (ssLDH) from the time of database construction to Mar. 2022, and two investigators independently performed literature screening and data extraction, and evaluation of the quality of the included studies was observed as operation time, complications, and visual analogue scale (VAS) at each preoperative and postoperative stage as well as Oswestry Disability Index (ODI), and meta-analysis was performed by applying the Review Manager 5.4 software. P = 0.02) and had lower VAS of back pain at 3 days postoperatively , P = 0.04) compared to the UBE. However, there was no statistical significance between the two groups in terms of complications , P = 0.33), VAS of back pain at 30 days postoperatively , P = 0.70), VAS of leg pain at 3 days postoperatively , P = 0.33), VAS of leg pain at 30 days postoperatively , P = 0.65), and ODI at 30 days postoperatively , P = 0.47).  Meta-analysis showed that PELD had shorter operation time , CRD42021287810. Current evidence suggests that both UBE and PELD are effective in relieving short-term postoperative pain and promoting functional recovery, and there is no difference in complications between them; UBE requires longer operation time, and PELD may be superior in relieving immediate postoperative pain. This trial is registered with PROSPERO ID:  Lumbar disc herniation (LDH) is a common cause of low back and leg pain . It is mUnilateral Biportal Endoscopic (UBE) technique was first reported by De Antoni  in the 1PELD and UBE are both minimally invasive procedures used to address LDH; however, no studies have been conducted to investigate the short-term postoperative pain, functional recovery, and complications of them. Is UBE, an emerging technology, superior to PELD in the treatment of LDH? Therefore, we conducted this systematic review and meta-analysis to clarify the short-term pain and functional recovery of UBE versus PELD in the treatment of single-segment lumbar disc herniation (ssLDH) and to help clinicians make a better choice.We performed a comprehensive search in the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang databases to acquire all relevant studies up to Mar. 2022. No language restrictions. The searched literatures were then screened according to the strict inclusion and exclusion criteria. Comparison between UBE and PELD on operation time, complications, visual analogue scale (VAS), and Oswestry Disability Index (ODI) score . The search terms used include as follows: “Unilateral Biportal Endoscopic,” “Unilateral biportal endoscopy,” “Unilateral Biportal Endoscopic Discectomy,” “Biportal endoscopic spine surgery,” “Unilateral biportal endoscopic spine surgery,” “UBE,” “BESS,” “lumbar disc herniation,” “lumbar disk herniation,” and “LDH.” Two researchers independently conducted the search and browsed through the titles and abstracts of relevant studies to identify studies for inclusion, and if disagreements existed, they were discussed and resolved through discussions with a third researcher.The inclusion criteria for this study were (1) study population: patients with imaging-confirmed single-segment lumbar disc herniation; (2) interventions: all surgical procedures were UBE versus PELD; and (3) outcome indicators: VAS score and ODI score.The exclusion criteria for this study were (1) patients with other diseases such as combined lumbar spinal stenosis and tumors; (2) duplicate studies, incomplete data, and inability to obtain the full text; and (3) case reports, conference proceedings, animal experiments, reviews, and meta-analysis.Data extraction and literature quality evaluation were performed independently by two investigators and included (1) basic characteristics: study ID (author + year), design, country, surgical approach, sample size, age, follow-up time, and outcome indicators; and (2) clinical outcome indicators: operation time, complications, preoperative and postoperative VAS score for back pain, preoperative and postoperative VAS score for leg pain, and preoperative and postoperative ODI score.I2 for the included studies; if I2 < 50%, a fixed-effect model was used; if I2 > 50%, a random-effect model was used. P < 0.05 was considered statistically significant.The extracted data were analyzed using the Review Manager 5.4 software. Dichotomous variables were analyzed and assessed by calculating relative risk (RR) and 95% confidence interval (CI); for continuous variables, weighted mean difference (WMD) and 95% confidence interval (CI) were used. The size of heterogeneity was judged using the chi-square test2 combined with After the initial search of the electronic databases, a total of 63 articles were identified. The articles were further screened by titles, abstracts, and full texts according to the specific inclusion and exclusion criteria. Ultimately, 59 articles were excluded, and the other 4 –19 were The included studies were evaluated for quality using the NOS scale in terms of selection of study population, comparability of components, and outcomes, and the results are shown in P = 0.02, heterogeneity: Tau2 = 939.05, χ2 = 137.66, df = 3 (P < 0.00001), I2 = 98%); PELD has a shorter operation time compared to UBE for ssLDH , I2 = 0%). As with PELD, UBE has few complications and has a similar safety profile to PELD , I2 = 0%). The difference in VAS of back pain at postoperative 3 days was statistically significant , P = 0.04, heterogeneity: Tau2 = 0.13, χ2 = 3.70, df = 1 (p = 0.05), I2 = 73%). The difference in VAS of back pain at postoperative 30 days was not statistically significant , P = 0.70, heterogeneity: Tau2 = 0.00, χ2 = 0.42, df = 2 (P = 0.81), I2 = 0%). PELD is better than UBE in the relief of back pain at postoperative 3 days, but at 30 days postoperatively, PELD and UBE have the same efficacy , I2 = 0%); the difference in VAS of leg pain at postoperative 3 days was not statistically significant , P = 0.33, heterogeneity: χ2 = 0.08, df = 1 (P = 0.77), I2 = 0%); the difference in VAS of leg pain at 30 days postoperatively was not statistically significant , P = 0.65, heterogeneity: Tau2 = 0.04, χ2 = 2.96, df = 2 (P = 0.23), I2 = 32%). UBE and PELD have comparable efficacy in relieving short-term postoperative pain in the leg pain , I2 = 0%); the difference in ODI score at 30 days postoperatively was not statistically significant , P = 0.47, heterogeneity: χ2 = 0.10, df = 2 (P = 0.95), I2 = 0%); UBE and PELD have similar efficacy in short-term functional recovery  PELD is a single channel, while UBE discectomy is a double channel, and although it is a minimally invasive surgery, UBE is more invasive compared to PELD. (2) UBE has a larger operating space and is bound to destroy more muscles, ligaments, and bone tissue and requires intraoperative stripping and resection of the ligamentum flavum and occlusion of part of the synovial joint . (3) We There are certain limitations of this study: (1) As an emerging technology, UBE has few relevant studies, and therefore, the number of included literature in this study is smalls; (2) the overall quality of included studies is average, and no randomized controlled trials were included; (3) some of the outcome indicators were significantly heterogeneous, and only random-effect models were used for the combined analysis.In summary, both UBE and PELD are effective in relieving short-term postoperative pain and promoting functional recovery in patients with ssLDH. UBE has longer operation time and is comparable in safety to PELD, but PELD is more minimally invasive and provides better relief of back pain within postoperative 3 days. UBE does not appear to be superior to PELD in the treatment of ssLDH. Due to the limitation of the number and quality of included studies, more randomized controlled studies with large samples, multicenter, and long follow-up are needed to further verify the above findings.


Cachexia is a syndrome of unintentional body weight loss and muscle wasting occurring in 30% of all cancer patients. Patients with cancers most commonly leading to brain metastases have a risk for cachexia development between 20 and 80%. Cachexia causes severe weakness and fatigue and negatively impacts quality and length of life. The negative energy balance in cachectic patients is most often caused by a combination of increased energy expenditure and decreased energy intake. Basal metabolic rate may be elevated due to tumor secreted factors and a systemic inflammatory response leading to inefficiency in energy production pathways and increased energy demand by the tumor and host tissues. A growing body of research explores physiological and molecular mechanisms of metabolic dysregulation in cachexia. However, decreased energy intake and physical functioning also remain important contributors to cachexia pathogenesis. Pain associated with metastatic malignancy is significantly associated with inflammation, thus making inflammation a common link between cancer pain and cachexia. Pain may also influence appetite and food intake and exacerbate fatigue and functional decline, potentially contributing to cachexia severity. Cancer pain and cachexia often occur simultaneously; however, causal relationships remain to be established. Appropriate assessment and treatment of pain in advanced cancer patients may positively impact nutrition status and physical functioning, slowing the progression of cachexia and improving quality and length of life for patients. Cachexia is a syndrome of progressive and unintentional weight loss and muscle atrophy that occurs in multiple inflammatory disease states such as heart failure, kidney failure, HIV/AIDS, and cancer . CachexiImportantly, cachexia diminishes both quality and length of life. Patients with cachexia experience severe weakness and fatigue with impaired physical functioning , increas2 or the presence of sarcopenia. Refractory cachexia occurs when patients are in a highly catabolic state with a life expectancy of <3 months  and peripheral tissues to alter metabolism, increasing catabolic and decreasing anabolic signaling. The involvement of inflammation in cachexia has been extensively reviewed , 13–15, via the Cori cycle and subsequently decreases energetic efficiency by the tumor cells (Resting energy expenditure (REE), measured by indirect calorimetry, was increased in two studies of treatment-naïve cancer patients both with and without weight loss, suggesting elevated REE may contribute to both cachexia development and progression , 19. Cauor cells .In addition to increased energy expenditure, many patients with cancer cachexia also have significantly reduced energy intake caused by a variety of Nutritional Impact Symptoms (NIS), any of a broad range of symptoms impeding nutrient intake  Figure . The tumNegative energy balance resulting from increased energy expenditure and decreased energy intake over time causes weight loss. In healthy individuals, intentional weight loss from reduced food intake and increased exercise favors loss of fat and preservation of muscle. In contrast, weight loss in a disease state such as cancer leads to significant loss of both fat and lean tissue, particularly skeletal muscle, due to the presence of non-inflammatory  and inflvia upregulation of two major pathways – the autophagy lysosomal system (ALS), and the ubiquitin-mediated proteolysis system (UPS) (via targeting of contractile proteins in the sarcomere (via decreased insulin and insulin-like growth factor (IGF-1) signaling  . The ALSem (UPS) . Markersem (UPS) , 43; howem (UPS) . The UPSarcomere , 49. Musarcomere , as wellignaling .The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” . Pain isvia the pain subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30) was significantly associated with C-reactive protein (CRP), a hepatic secretory protein associated with systemic inflammation  and increasing symptom burden measured with the M.D. Anderson Symptom Inventory. Both pain and fatigue were significant predictors of increasing cachexia severity . A prospSeveral studies identify a relationship between pain and decreased energy intake, a major contributor to negative energy balance in cachexia. In a multivariate logistic regression analysis of 368 treatment-naïve head and neck cancer patients, pain measured by the Head and Neck Patient Symptom Checklist (HNSC) was one of several significant predictors for decreased energy intake . Two stuPain also predicts for decreased physical activity, performance status, and fatigue, which may contribute to cachexia by exacerbating muscle atrophy. Fouladiun and colleagues found patients with advanced cancer and cachexia had increased pain (outside the 99% CI) compared to normative values, measured by the SF-36. SF-36 scores for bodily pain and physical functioning predicted for decreased physical activity measured by an accelerometer . SF-36 bA consequence of decreased energy intake and physical functioning is loss of lean mass and muscle strength, and these have also been associated with pain in cancer patients. Kilgour et al. found increased fatigue measured by the Brief Fatigue Inventory (BFI) to be related to decreased handgrip strength, quadriceps strength, and skeletal muscle mass index (SMMI) determined with DXA imaging in men with lung and gastrointestinal cancers. Interestingly, in multivariate regression analysis, pain, measured by ESAS, was a significant predictor in all three multivariate models , suggestvice versa, but there is a scarcity of literature to examine this question. Pain is considered a nutrition impact symptom (NIS)  , and mulom (NIS)  and decrom (NIS) . Howeverom (NIS) , enteralom (NIS) . The majom (NIS) . Finallyom (NIS) .This review provides an overview of cancer cachexia pathophysiology including contributors to negative energy balance, the common link of inflammation between cancer cachexia and cancer-related pain, and evidence for an association between cachexia and pain in cancer patients. Although existing literature presents significant evidence that cancer pain and cachexia often occur together, causal relationships cannot be established from these observational studies. The simultaneous presence of both cancer pain and cachexia may simply be evidence of advancing disease. However, pain may also contribute to cachexia by decreasing appetite, food intake, and the ability to be physically active. Increased awareness of the importance of cachexia management on clinical outcomes in cancer patients has led to the development of cachexia clinics with multidisciplinary care to treat nutrition impact symptoms. Pain is one factor to address in these settings. To further understand the interplay between pain and cachexia, prospective clinical studies examining how pain management in cachectic patients affects appetite, food intake, physical functioning, body weight and composition, and clinical outcomes related to cancer are needed.The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In all cases, the cause of the SIRVA was from an incorrect COVID-19 vaccine administration technique. Two patients developed shoulder pain immediately following the injection, one patient about 3 h after the injection, and the other four patients within the next few days. Two of the seven patients visited the orthopedic clinic after the persistent shoulder pain for 3 and 4 days and the other five patients 1–9 weeks following their injections. One of the seven patients was treated with combined intravenous antibiotic and oral non-steroidal anti-inflammatory drug (NSAID) because septic arthritis of the shoulder could not initially be ruled out, and recovered within 2 weeks. The other six patients had shoulder pain without acute fever, and five of them were treated with only oral prednisolone 30 mg/day for 5–10 days, following which the pain improved and they all could return to normal activities within 14 days, with no side effects from the prednisolone such as stomachache, nausea, vomiting, headache, or dizziness. Discussion and conclusion: In our series, the most common cause of SIRVA was an incorrect vaccination technique. Most patients responded well to oral NSAIDs or oral prednisolone. Clinical relevance: All SIRVAs were from an incorrect injection technique and not actually the vaccination, so our series highlights the importance of ensuring all vaccinators understand the importance of taking proper care with the injection technique. Additionally, most of our patients with SIRVA from a COVID-19 injection responded well to oral prednisolone (30 mg/day). If there are no contraindications, we suggest this as the first line treatment for COVID-19-related SIRVA.Background: A shoulder injury related to vaccine administration (SIRVA) is a vaccination complication that can affect daily life activities. To date, there have been no case series of patients diagnosed as SIRVA following a COVID-19 vaccination. We offer a series of seven SIRVA cases including clinical presentations, investigations and treatment outcomes. Methods: A retrospective chart review was performed for seven patients who developed SIRVA following a COVID-19 vaccination between April 2021 and October 2021. All patients had no prior shoulder pain before their vaccination and then developed shoulder pain within a few days following the vaccination, which did not spontaneously improve within 1 week. Results: Four of the seven patients were male, and the average age was 62.29 ± 7.76 years. The average body mass index was 25.1 ± 2.2 kg/m The COVID-19 pandemic has had a great effect on normal life activities worldwide. To aid the return to normal life activities, one of the important key factors has been the COVID-19 vaccines, which have been widely applied for immunization since early 2021. However, there have been some adverse effects after the COVID-19 vaccinations, which can be divided into local and systemic adverse effects. Most of these effects usually spontaneously resolve within a few days after the vaccination. If the clinical symptoms persist for more than two days, the doctor should be concerned about more serious complications. A shoulder injury related to vaccine administration (SIRVA) is one complication that begins within 48 h following a vaccination, with the main symptoms of shoulder pain with limited range of motion. The pathogenesis of SIRVA is still uncertain, but a widely accepted theory is that injecting the vaccine into the subdeltoid bursa produces a prolonged inflammatory response . This coTo date, there have been no case series published in the literature on patients diagnosed as SIRVA following a COVID-19 vaccination. In this case series, we present seven cases of SIRVA including clinical presentations, physical examinations, investigations, medications, and treatment outcomes after treatment with some combination of oral prednisolone, oral non-steroidal anti-inflammatory drugs (NSAIDs), intraarticular steroid injection, and/or intravenous antibiotic.In our institution we had seven patients between April 2021 and October 2021 who were diagnosed as SIRVA according to the definition of the National Vaccine Injury Compensation Program (VICP) by one of two sports medicine orthopedists. The VICP definition is “shoulder pain with limited range of motion within 48 h after vaccination with no prior history of pain, inflammation, or dysfunction of the affected shoulder before vaccine administration” [2. In all cases, our investigations found that the cause of the SIRVA was from an incorrect COVID-19 vaccine administration technique. The cause of the SIRVA in three of the seven patients was use of an incorrect landmark (thus resulting in the injection being given too high on the arm) for the injection, and the cause in the other four cases was from an incorrect direction of the needle causing the vaccine to be injected into the bursa rather than the deltoid muscle. Two patients developed their shoulder pain immediately following the injection, one patient about 3 h after the vaccination, and the other four patients within the next few days. Two of the seven patients visited the orthopedic clinic after persistent shoulder pain for 3 and 4 days and the other five patients 1–9 weeks after their injections. One of the seven patients was treated with combined intravenous antibiotic and oral NSAID because septic arthritis of the shoulder could not initially be ruled out and recovered within 2 weeks. The other six patients had shoulder pain without acute fever, and five of them were treated with only oral prednisolone 30 mg/day for 5–10 days following which the pain improved and they all could return to normal activities within 14 days, with no side effects from the prednisolone such as stomachache, nausea, vomiting, headache, or dizziness. The 7th patient received combined oral prednisolone and an intraarticular steroid injection and recovered in 7 days.During the study period, seven patients visiting the orthopedic clinic of our hospital with clinical symptoms of shoulder pain were diagnosed as SIRVA, as they had had no prior shoulder pain before their vaccination and the shoulder pain developed quickly or within a few days after the vaccination and did not spontaneously improve within 1 week. The patients’ characteristics are shown in 3, monocytes 1%, polymorphonuclear neutrophils 99%, red blood cell count 23,400 cells/mm3, and no crystals or organisms. The fluid was sent for culture which showed no organisms. These findings were indeterminate, so he was admitted and treated with combined intravenous cefazolin 1 gm every 6 h for 3 days and oral celecoxib (400 md/day) for 7 days, when the intravenous cefazolin was changed to oral cephalexin (1000 mg/day) for a further 7 days. One day after admission for the intravenous antibiotic, his fever resolved, and he was discharged on day 4 after switching to an oral antibiotic. Over the next few days his symptoms gradually improved, and he could move his shoulder with a full range of motion in all directions 2 weeks after the initial diagnosis and treatment.The first case was a 52-year-old Thai male without prior shoulder pain who developed right shoulder pain on day 2 after his Sinovac vaccination. In this case, the injecting nurse used a 1.5-inch 27-gauge needle, with an injection site 3 fingerbreadths below the mid-lateral edge of the acromial process. The direction of the needle was oblique to the skin cephalad A. He begThe second case was a 51-year-old Thai female with no history of shoulder pain. She received an Oxford-AstraZeneca COVID-19 vaccine with a 1.5-inch 25-gauge needle, based on the landmark of 1 fingerbreadth below the midlateral edge of the acromial process B. The diThe third case was a 66-year-old Thai male who began to have right shoulder pain immediately after a second dose of AstraZeneca. The injection was given with a 1.5-inch 25-gauge needle. The injection landmark was 3 fingerbreadths below the mid-lateral edge of the acromial process. The direction of the needle was 30◦ cephalad to the skin A. The paThe fourth case was a 71-year-old Austrian male who began to feel left shoulder pain one day after a second dose of AstraZeneca vaccine. The injection was given with a 1.5-inch 25-gauge needle and the landmark was 1 fingerbreadth below the mid-lateral edge of the acromial process B. The neThe fifth case was a 68-year-old Thai female who began to feel right shoulder pain with limited range of motion 24 h after a second dose of AstraZeneca vaccine. She had had no shoulder pain before the vaccination. The vaccination landmark was 3 fingerbreadths below the acromial process and the needle direction was 45 degrees cephalad to the skin. Her symptoms had persisted for 14 days without improving. They were worse at night, and she could not lay on her right shoulder. She decided to see an orthopedist and the clinical examination showed tenderness at the deltoid muscle. She had a full range of shoulder motion, but with pain at some points. She was sent for ultrasonography which showed a thin layer of subdeltoid bursal fluid and a partial thickness tear of the subscapularis tendon A,B. She The sixth case was a 64-year-old Thai male who had received his first dose of AstraZeneca vaccine. The vaccination landmark was 3 fingerbreadths below the acromial process with a needle direction of 30 degrees cephalad to the skin. He had developed right shoulder pain with limited range of motion in all directions within 48 h of receiving the vaccine. He did not take any medications, and when the symptoms had not improved in a month he decided to see an orthopedist. A physical examination showed tenderness at the deltoid muscle with limited range of motion in all directions. An ultrasonography showed tenosynovitis at the long head of the biceps and a low-grade partial tear of the subscapularis tendon A,B. He wThe seventh case was a 64-year-old Thai female who presented with right shoulder pain 9 weeks after a first dose of the AstraZeneca vaccine. The symptoms had begun immediately after the vaccination and gradually gotten worse, to the point that it was painful to complete daily activities and she could not sleep on her right side. In her case, the injection landmark was 1 fingerbreadth below the mid-lateral edge of the acromial process. At the OPD, the physical examination showed limited range of right shoulder motion and pain on the forward motion elevation resistance test and external rotation. Ultrasonography showed calcific tendinopathy of the supraspinatous tendon without bursitis A,B. She We report a series of seven patients who developed a SIRVA after a COVID-19 vaccination, all of which were the result of an incorrect COVID-19 vaccination technique. Following their examinations, four of the five patients who received only oral prednisolone had rapid improvement, and one patient who received combined oral prednisolone and TA injection also had rapid improvement. One patient received an antibiotic and NSAID due to fever with the shoulder pain, following which he gradually improved over the next 14 days and the 7th patient, who received only oral prednisolone also improved over 14 days. In cases of SIRVA, if the patient has no contraindications such as fever, we recommend giving oral prednisolone (30 mg/day) for at least 5 days.2. The other factor which has been reported as associated with SIRVA is sex. Two large series reported that SIRVA was predominant in females with incidences of 82.6% and 82.8% [SIRVA is a rare complication that can occur following a vaccination. The risk factors for this complication are BMI, sex, age and type of vaccine. One study reported that overweight patients had an increased risk of SIRVA , while ond 82.8% ,6. In ound 82.8%  and AtanHowever, the most common cause of SIRVA, as with most other vaccines, remains an incorrect injection technique. The recommended vaccine injection technique for the COVID-19 vaccines involves three things. First, the landmark should be 2 or 3 fingerbreadths, depending on the size of the patient, below the acromial process C. If theThe main symptom of SIRVA is shoulder pain beginning a few minutes to a few days after the vaccination which does not resolve by a week or so. This is different from the quite common local effect of a vaccination which is usually not severe and clears up in 2–3 days. The key factor in considering SIRVA is the absence of prior shoulder pain before the vaccination. All patients in our study met these conditions, and all complained of difficulty in performing their normal daily activities. There have been reports of neurological symptoms such as weakness or numbness, but these were not found in our study [The most common physical examination finding of SIRVA is pain while moving the shoulder with incidences of 55.9% and 85% in reported studies ,3. The dNot all patients with a SIRVA are sent for further investigations such as radiography, ultrasonography and/or MRI. Atanasoff et al.  reportedThere have been several modalities for treating SIRVA reported in case series, including nonsteroidal anti-inflammatory drugs, lidocaine patches, opioid medications, intra-articular steroid injections, oral steroids, acupuncture and even surgery ,3,6. A SAll SIRVAs following a COVID-19 vaccination in this series were the result of an incorrect COVID-19 vaccination technique. Most patients responded well to a short course of oral prednisolone.


BackgroundSpinal stenosis is a degenerative narrowing of the spinal canal with encroachment on the neural structures by surrounding bone and soft tissue. This chronic low back condition can cause restrictions in mobility, impairment of daily activities, opioid dependence, anxiety, depression, and reduced quality of life. Spinal stenosis can be treated through surgical and nonsurgical methods, but neither has proven consistently reliable. Cannabidiol (CBD) has also been observed to have anxiolytic, anti-inflammatory, antiemetic, and antipsychotic behaviors. CBD may provide greater nonsurgical treatment options for the pain associated with spinal stenosis while minimizing the need for opioids. An observational study was undertaken to assess the effects of CBD on patients suffering from chronic spinal stenosis.MethodologyThis observational study was investigator-initiated and designed to determine the effect of hemp-derived CBD gel caps for patients with spinal stenosis related to low back pain and leg pain relative to patient outcomes, medication utilization, and quality of life outcome measures. A total of six physician visits would be required where a set of surveys would be filled out each four weeks apart.ResultsThe study population consisted of 48 patients. The patient population’s age ranged from 63 to 95 years and was normally distributed, with a mean age of 75 ± 7.13 years. The sex distribution was 33% male and 67% female patients. The pain was broken down between the six visits for each of the following four questions: pain right now, usual pain level during the week, best pain level during the week, and worst pain level during the week. Usual pain levels (p < 0.001) and worst pain levels (p < 0.005) demonstrated statistically significant improvement over time, while pain right now (p > 0.05) and best pain level (p > 0.05) stayed consistent throughout without statistical significance.ConclusionsThis open-label, prospective, observational study found that treatment with hemp-derived CBD gel caps was associated with significant improvements in pain scores and several quality-of-life measures for patients with lumbar spinal stenosis. Low back pain is the leading cause of disability in 160 countries and is one of the most common health problems among individuals seeking medical care . The burCannabidiol (CBD) is the second most prevalent component of cannabis (marijuana). The most prevalent psychoactive component of cannabis is Δ9‐tetrahydrocannabinol (THC) . THC exhLower back pain has a litany of causes including intervertebral disk degeneration or extrusion, Modic changes, coronavirus disease, and spondylolysis ,9. SpinaStudy designThis observational study was investigator-initiated and designed to determine the effect of hemp-derived CBD gel caps for patients with spinal stenosis-related low back pain and leg pain relative to patient outcomes, medication utilization, and quality of life outcome measures. The Institutional Review Board at Thomas Jefferson University approved a standardized protocol.Patient populationInclusion criteria included proficiency in the English language, age greater than or equal to 60, a history of neurogenic claudication or radicular leg symptoms for greater than three months, and confirmatory radiographic imaging showing lumbar spinal stenosis at one or more levels. Patients with unstable degenerative spondylolisthesis were excluded from this study. Patients were also excluded if they had undergone any prior lumbar spinal surgeries. Patients were not excluded for any pulmonary, cardiovascular, or neurological diseases. Eligible patients were referred to a Research Assistant who would go over the informed consent highlighting both the benefits and risks. The Research Assistant would then offer the patients who enrolled compensation of $25 upon completing the first survey and a coupon for a bottle of hemp-derived CBD gel caps for the following five visits.Study interventionsA total of six physician visits would be required where a set of surveys would be filled out each four weeks apart. The first survey would be compensated $25, and each following visit would be compensated with a coupon for a free bottle of “CBD-rich” gel caps . The gel caps used specifically were the 15 mg “Full Spectrum Hemp Extract Soft Gels,” containing 0.3% THC, with the packaging recommending its use as one capsule twice daily.Study measuresSeven surveys used at each visit: Pain Numeric Rating Scale, The Roland-Morris Low Back Pain and Disability Questionnaire, The Inventory of Depression and Anxiety Symptoms Second Version (IDAS-II), Brief Inventory of Psychosocial Functioning (B-IPF), Pittsburgh Sleep Quality Index (PSQI), The Daily sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU), and a Medical and Psychiatric Treatment Receipt.Statistical analysisDescriptive statistics were used to summarize the data collected over each of the six visits. The data were analyzed both by patient visit intervals as well as continuous data, presented as mean (standard deviation), and categorical data are presented as cell count . Analysis of variance (ANOVA) testing was performed to calculate the p-values for continuous data and chi-square testing was used for categorical data. Following the descriptive tables, a set of regressions are also presented. Each regression focused on the four different pain scores as the main dependent outcome. Significance was determined at a p-value of <0.05. All statistical analyses were done using R Studio .During this study, a total of 111 patients provided informed consent and completed baseline questionnaires. However, participants dropped out after each visit. Only patients who completed all six visits were included in the final study sample, which resulted in a final study population of 48 patients   on cell membranes . These cGeneralizability of resultsAs previously indicated, each visit had fewer patients following up. This could have been from the observational study design and not directly handing patients the CBD gel caps. The dropout rate could have contributed to bias and limited the generalizability of results. Significant improvements were observed in the patient’s usual pain scores as well as their worst pain scores. These results serve as a stepping stone in the evidence showing a positive trend, suggesting the generalizability of the results.Study limitationsThere were several limitations associated with this study. This study was an open-label study, and there was no control group. Another limitation of the study was that each study visit saw people drop out of the study, which could have impacted our results. These participants dropping out may have been exacerbated by the lack of financial incentives to complete the surveys. The surveys themselves were a limitation of this study for two reasons, the first being that they were exceedingly long, leading to survey fatigue taking 30-45 minutes to complete. Second, because the surveys were long, it could have deterred patients from returning for future visits. Another limitation is selection/volunteer bias. Cannabis has a sizeable negative stigma surrounding it, and the patients open to trying CBD may have been more open to positive changes. The one major limitation of this study is that patients could receive other medical interventions such as physical therapy, injections, or other medications during the study, and it is not clear if the benefits seen in the outcome measures were due to CBD or other interventions. The hemp gel caps used in our study contained 15 mg of CBD, and the product label states that patients should use one capsule twice a day; two limitations surrounding these capsules are it is not known if 30 mg/day is the right dose for pain, and this study did not ask patients if they took the gel caps or how many a day. The last limitation is expectancy bias; the data were collected through self-reported surveys.This open-label, prospective, observational study found that treatment with hemp-derived CBD gel caps was associated with significant improvements in pain scores and several quality-of-life measures. Improvements in pain scores ultimately led to improvements in patients’ quality of life. This study did see fewer increases in quality-of-life measures than previous research involving both THC and CBD. However, the CBD gel caps were not associated with any adverse effects. Using CBD to help alleviate pain in spinal stenosis is supported by the evidence in this study. While first of its kind, this study supports the evidence that cannabis products can be a safe and effective treatment option for managing chronic pain.


Radium-223 (Ra-223), an alpha-emitting radiopharmaceutical, established an improved overall survival and health-related quality of life (HRQoL) in symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients. However, effects on pain were not specifically evaluated. Here we assess integrated HRQoL, pain, and opioid use in a contemporary, more extensively pretreated, symptomatic and asymptomatic mCRPC population.mCRPC patients scheduled for Ra-223 treatment were included and analyzed for HRQoL, pain, and opioid use, using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory-Short Form (BPI-SF) questionnaires and recording of opioid use and dosage, respectively. Primary outcome measure was the percentage of patients experiencing a complete pain response . A complete or partial pain response (better BPI-SF score and decrease in opioid use) and a better or no change in HRQoL was evaluated as an integrated overall clinical response (IOCR). Secondary endpoints included the time to pain progression (TPP) and Total FACT-P deterioration (TTFD), defined as time from first Ra-223 treatment to clinical meaningful increase in BPI-SF Worst pain item score and Total FACT-P score, respectively.This registry included 300 patients, of whom 105 (35%) were evaluable for FACT-P and BPI-SF during Ra-223 treatment. Forty-five (43%) patients had pain at baseline (PAB) (BPI-SF Worst pain score 5–10 points) and 60 (57%) had no pain at baseline (no-PAB) (BPI-SF Worst pain score 0–4 points). Complete pain response was achieved in 31.4% of the patients, while 58% had an IOCR. The median TTP and TTFD were 5.6 and 5.7 months, respectively, while the difference between PAB and no-PAB patients was not significant.In contemporary, extensively pretreated mCRPC patients, Ra-223 treatment induced complete pain responses while integrated analysis of HRQoL, pain response, and opioid use demonstrated that the majority of patients derive clinical benefit. Each year, over 1.2 million men are diagnosed with prostate cancer worldwide and approximately 350,000 patients succumb to the consequences of this disease, rendering it the most common non-cutaneous cancer in males and the second largest cause of cancer-related death in men .In the ALSYMPCA study, the alpha-emitter Radium-223 dichloride (Ra-223) showed a 3.6 month overall survival (OS) benefit and favorable HRQoL in symptomatic mCRPC patients . HoweverThe primary objective of this prospective observational study was to evaluate the efficacy of Ra-223 on patient-reported pain and analgesics use. Secondly, we performed an integrated analysis of the effect of Ra-223 on patient-reported pain, analgesic use, and HRQoL in a contemporary real-life cohort. Since in daily practice, both patients with pain at baseline (PAB) and no-pain at baseline (no-PAB) are treated with Ra-223, these subgroups were assessed separately .A non-interventional, multicenter, prospective observational registry was initiated to evaluate clinical outcomes, HRQoL, pain, and analgesic use in a real-life mCRPC population treated with Ra-223. The study design is fully described elsewhere . In shorPatients were treated with Ra-223 at 4-week intervals. Dosing was according to the manufacturers’ guidelines, which was a dose of 50 kBq per kilogram of body-weight intravenously and from April 2016 on, 55 kBq per kilogram of body-weight intravenously. Number of treatments was at the physician’s discretion, who provided the motivation for discontinuation. Patients were evaluated at the outpatient clinic prior to each treatment, where performance scores and clinical lab assessments were documented. Radiological evaluation during and after Ra-223 treatment and frequency of follow-up visits were at the physician’s discretion. Patients’ baseline characteristics within 14 days prior to the first Ra-223 treatment were recorded. Baseline characteristics, efficacy assessments, and patient-reported outcome measures (PROMs) were stored in an electronic case-report form. Follow-up was continued until start of subsequent treatment or death. Data collection was performed on-site at the end of follow-up.HRQoL and pain were assessed using the validated PROMs, Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory-Short Form (BPI-SF), respectively –12. FurtThe BPI-SF contains 4 items on pain severity  and 7 items on pain interference  . Every qThe FACT-P is a validated 39-item questionnaire, including the FACT-General subscales: Physical well-being (PWB), Social/Family well-being (SWB), Emotional well-being (EWB), Functional well-being (FWB), and a prostate cancer subscale (PCS) . Items aPatients were asked to fill out a list of all analgesics, dosages, and frequencies used in the past 4 weeks , a complete pain response was defined as a score of 0 on the BPI-SF Worst pain item and no increase in daily use of analgesics; a partial response was defined as a pain reduction of at least 2 points on the BPI-SF Worst pain item or a reduction of at least 25% of daily use of analgesics; pain progression was defined as an increase in pain of at least 2 points on the BPI-SF Worst pain item or an increase of at least 25% of daily analgesic use. Indeterminate response was defined as all pain decreases, not captured by complete response or partial response . PatientSecondary endpoints included the percentage of patients experiencing a partial and an indeterminate pain response. Moreover, patients were categorized by their Total FACT-P response, which was “improved HRQoL” (better score meeting CMC-FACT), “no change in HRQoL” (no change or changes not meeting CMC-FACT), or “worse HRQoL” (deteriorated score meeting CMC-FACT). A complete or partial pain response and an improved HRQoL or no change in HRQoL were evaluated as an integrated overall clinical response (IOCR).Moreover, secondary outcomes included time to Total FACT-P deterioration (TTFD), time to pain progression (TPP), progression-free survival (PFS), and OS. Definitions of the secondary endpoints are listed in Supplementary Table The rationale for sample size calculation is detailed in Supplementary Text www.graphpad.com.TENALEA, an online service, was used to collect data. IBM SPSS statistics for iOS, version 25  and Statistical Analysis System (SAS) statistical software were used for statistical analysis and for constructing graphs. Additional graphs and analyses were made and performed using GraphPad Prism for iOS version 8.00, GraphPad Software, La Jolla, CA, USA, Between April 2015 and March 2018, 305 mCRPC patients from 20 Dutch hospitals scheduled for Ra-223 treatment were included. Five patients were excluded because written approval to use identifiers  could not be retrieved or was not stored according to guidelines .The registry sample and the evaluable sample were comparable on most baseline characteristics, survival characteristics, and treatment outcomes Table . Howeverp < 0,001). After a median follow-up of the evaluable sample of 13.2 months, PAB patients had a significantly shorter OS than no-PAB patients  . The percentage of patients experiencing a complete pain response for the duration of Ra-233 treatment was 31.4% , suggesting a worse HRQoL.FACT-P baseline values are reported in Supplementary Table During treatment, 31.4% of the evaluable sample had a clinically meaningful improvement of Total FACT-P, with no significant difference between PAB and no-PAB patients Table . ChangesUse of analgesics in the evaluable sample decreased during Ra-223 treatment and remained low during follow-up Fig. . The scoIn the ALSYMPCA, pain was evaluated using the non-pain-specific questionnaires FACT-P and EQ-5D , 5. The In this study, outcomes of the different PROMs were integrated into an IOCR, which was established in 58% of patients. Cancer-related pain and HRQoL are not mutually exclusive, as was reported previously , 22. HowThe strength of this study lies in the inclusion of a contemporary real-world population, pretreated with multiple mCRPC treatment options. Moreover, both symptomatic and asymptomatic patients were included, as this inclusion criterion of the ALSYMPCA is generally not considered in daily practice. This makes the results of this study directly applicable to current prostate cancer patients’ treatment. There is a growing interest in real-life data, however, PROMs are rarely reported. In line with the increased interest in PROMs outcomes from randomized trials, we would argue in favor of including these outcomes in real-life cohorts.Limitations of this study include its non-randomized nature and the likelihood of survival and selection bias. Another limitation is the lower than expected questionnaire completion rates. The percentage of patients evaluable was within the previously reported 10–70% range of response rates in studies on self-reported outcome measures in real-life populations –27, but In conclusion, our study shows that a significant proportion of Ra-223-treated symptomatic and asymptomatic, extensively pretreated mCRPC patients experience an improved HRQoL and pain response. These results suggest that the majority of contemporary mCRPC patients derive clinical benefit from Ra-223 treatment.Supplementary Table 1Supplementary Table 2Supplementary Table 3Supplementary Table 4Supplementary Table 5Supplementary Table 6Supplementary Text 1Supplementary figure legendsSupplementary Figure 1Supplementary Figure 2Supplementary Figure 3Supplementary Figure 4Change in Brief Pain Inventory Short Form (BPI-SF) subscale scores over time in the evaluable sample (black line), patients with pain at baseline (red line), and patients without pain at baseline (green line).Supplementary Figure 6.Supplementary Figure 7