Background: Chronic pain is the leading cause of disability, affecting between 20% and 50% of the global population. The key recommended treatment is physical activity, which can be measured in daily life using a pedometer. However, poor adherence to pedometer use can result in incorrect measurements. Furthermore, only a few studies have investigated a possible curvilinear association between physical activity and chronic pain. Objective: In this study, we developed the Pain-Note smartphone app to collect real-world data on step count, using the smartphone's built-in pedometer. The aims of our research are (1) to evaluate the association between daily step count and pain level among patients with chronic pain and (2) determine if the association between daily step count and pain level was curvilinear. Methods: We conducted a cross-sectional study based on step count data collected with the app and on the results of questionnaires, which measured the duration and intensity of pain, the widespread pain index, the symptom severity score, and the insomnia severity scale, including 7 questions for symptoms of depression. We analyzed the association between step count and pain level as a nonlinear relationship using a restricted cubic spline model. A prespecified subgroup analysis was also conducted based on fibromyalgia criteria. Results: Between June 1, 2018, and June 11, 2020, a total of 6138 records were identified, of which 1273 were analyzed. The mean age of the participants was 38.7 years, 81.9% (1043/1273) were female, and chronic pain was present for more than 5 years in 43.2% (550/1273) of participants. Participants in the third and fourth quartiles for step count (more than 3045 and 5668 steps a day, respectively) showed a significant positive association between higher step count and lower numerical pain rating scale (mean difference -0.43, 95% CI -0.78 to -0.08, P=.02; -0.45; 95% CI -0.8 to -0.1, P=.01, respectively) than those in the first quartile (less than or equal to 1199 steps a day). The restricted cubic spline model for the association between step count and pain scale displayed a steep decline followed by a moderate decrease as the step count increased; the inflection point was 5000 steps. However, this association was not observed among participants who met the fibromyalgia criteria (491/1273), who showed a steep positive increase below 2000 steps. Data were collected between June 1, 2018, and June 11, 2020, and were analyzed on November 18, 2021. Conclusions: Step count measured with the Pain-Note app showed a nonlinear association with pain level. Although participants with and without fibromyalgia showed a negative correlation between step count and pain level, participants who meet the criteria for fibromyalgia may present a different relationship between walking and pain perception compared to those in the general chronic pain population.

Injectable antipsychotics had been used for patients who refuse oral medications in delirium practice. The objectives were to investigate acceptability of transdermal antipsychotic patches by patients who refuse oral medications and their effectiveness in preventing recurrence of delirium. In this retrospective observational study, data were collected between October 2019 and December 2021. The sample was represented by patients hospitalized because of acute diseases or elective surgery who had delirium on the night before the consultation and had refused oral therapy after consultation. Delirium has been diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Instead, a transdermal patch of blonanserin, a second-generation antipsychotic drug, was tried. The primary outcome was the rate of patients who accepted it. The secondary outcome was recurrence rates of delirium. As much as 95.1% of patients who refused oral medications (98/103 patients) accepted to receive the transdermal patch. Of these, 24 patients developed delirium again, whereas all five patients who refused it developed delirium again [24.5% (24/98) vs. 100% (5/5); P = 0.0014]. The present findings suggest that transdermal antipsychotic patches are more likely to be accepted by patients who refuse oral medications. Prospective studies are needed.

We evaluated functional connectivity (FC) in patients with adult autism spectrum disorder (ASD) using resting-state functional MRI (rs-fMRI) and diffusion kurtosis imaging (DKI). We acquired rs-fMRI data from 33 individuals with ASD and 33 healthy controls (HC) and DKI data from 18 individuals with ASD and 17 HC. ASD showed attenuated FC between the right frontal pole (FP) and the bilateral temporal fusiform cortex (TFusC) and enhanced FC between the right thalamus and the bilateral inferior division of lateral occipital cortex, and between the cerebellar vermis and the right occipital fusiform gyrus (OFusG) and the right lingual gyrus, compared with HC. ASD demonstrated increased axial kurtosis (AK) and mean kurtosis (MK) in white matter (WM) tracts, including the right anterior corona radiata (ACR), forceps minor (FM), and right superior longitudinal fasciculus (SLF). In ASD, there was also a significant negative correlation between MK and FC between the cerebellar vermis and the right OFusG in the corpus callosum, FM, right SLF and right ACR. Increased DKI metrics might represent neuroinflammation, increased complexity, or disrupted WM tissue integrity that alters long-distance connectivity. Nonetheless, protective or compensating adaptations of inflammation might lead to more abundant glial cells and cytokine activation effectively alleviating the degeneration of neurons, resulting in increased complexity. FC abnormality in ASD observed in rs-fMRI may be attributed to microstructural alterations of the commissural and long-range association tracts in WM as indicated by DKI.

Abstract The concept that a regional musculoskeletal pain may occur in the absence of identifiable tissue abnormality may be puzzling. Previously these regional complaints were generally categorized as myofascial pain syndromes, or prior to the formalization of the nociplastic pain concept, as musculoskeletal pain with a neuropathic component, and treatments were anatomically focussed. Chronic primary musculoskeletal pain is now identified under the chronic primary pain stem category with the mechanistic descriptor of nociplastic pain. It is possible that many patients previously diagnosed with myofascial pain do in fact suffer from chronic primary musculoskeletal pain, requiring a paradigm shift in management towards more centrally directed treatment strategies. Many questions remain, including validation of the proposed examination techniques, prevalence, ideal treatment, and uptake and acceptance by the healthcare community. This new classification should be welcomed as an explanation for regional pain conditions that previously responded poorly to physically focussed treatments.

Nociplastic pain is the semantic term suggested by the international community of pain researchers to describe a third category of pain that is mechanistically distinct from nociceptive pain, which is caused by ongoing inflammation and damage of tissues, and neuropathic pain, which is caused by nerve damage. The mechanisms that underlie this type of pain are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles. The symptoms observed in nociplastic pain include multifocal pain that is more widespread or intense, or both, than would be expected given the amount of identifiable tissue or nerve damage, as well as other CNS-derived symptoms, such as fatigue, sleep, memory, and mood problems. This type of pain can occur in isolation, as often occurs in conditions such as fibromyalgia or tension-type headache, or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain, as might occur in chronic low back pain. It is important to recognise this type of pain, since it will respond to different therapies than nociceptive pain, with a decreased responsiveness to peripherally directed therapies such as anti-inflammatory drugs and opioids, surgery, or injections.

Nociplastic pain is the semantic term suggested by the international community of pain researchers to describe a third category of pain that is mechanistically distinct from nociceptive pain, which is caused by ongoing inflammation and damage of tissues, and neuropathic pain, which is caused by nerve damage. The mechanisms that underlie this type of pain are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles. The symptoms observed in nociplastic pain include multifocal pain that is more widespread or intense, or both, than would be expected given the amount of identifiable tissue or nerve damage, as well as other CNS-derived symptoms, such as fatigue, sleep, memory, and mood problems. This type of pain can occur in isolation, as often occurs in conditions such as fibromyalgia or tension-type headache, or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain, as might occur in chronic low back pain. It is important to recognise this type of pain, since it will respond to different therapies than nociceptive pain, with a decreased responsiveness to peripherally directed therapies such as anti-inflammatory drugs and opioids, surgery, or injections.

BACKGROUND Chronic pain is the leading cause of disability, affecting nearly half of the global population. One of the recommended treatments for chronic pain is physical activity, which can be measured in daily life by a pedometer. However, low adherence to the pedometer use could result in incorrect measurements. Due to the ubiquitous use of smartphones, we developed the “Pain-Note” app to collect step count and moving distance. With the use of the Pain-Note app, we obtained the real-world information with a smartphone built-in pedometer and assessed the relationship between daily life step count and pain. OBJECTIVE The aim of our research is (1) to evaluate the association between the daily step count and pain level using a pedometer developed on the iPhone smartphone among patients with chronic pain, and (2) determine if the association between the daily step count and pain levels is curvilinear. METHODS We conducted cross-sectional research with data collected from the “Pain-Note” app on step count and questionnaires, including the duration and intensity of pain, the widespread pain index (WPI) and symptom severity score (SS score), the insomnia severity scale (ISS), and 7 questions for depressive symptoms. We analyzed the association between step count and pain levels considering a non-linear relationship using a restricted cubic spline model. RESULTS Between June 1, 2018 to June 11, 2020, a total of 6,138 records were identified and a total of 1,323 were analyzed. Participants in the 4th quartile (more than 5793 steps a day) had an increased number of step count significantly associated with less pain in numeric pain scale (mean difference, -0.38; 95%CI, -0.74- -0.02; P=.037), compared to the 1st quartile and the restricted cubic splines for the association between step count and pain scale displayed a steep decline followed by a moderate decrease as the step count increased. However, this association was not observed among those who met the fibromyalgia criteria. CONCLUSIONS Step count measured by the “Pain-Note”-based pedometer showed an association with pain levels with an inflection point among individuals with chronic pain, whereas among participants who met the fibromyalgia criteria there was no association. These findings suggest that participants who meet the criteria for fibromyalgia present a different response between walking and pain perception than those in the general chronic pain population.

Objective. The aims of the present study were to examine the effects of short-term music interventions among patients with fibromyalgia (FM) and to clarify the alterations in functional connectivity and persistent pain. Design. Pilot study. Setting. All participants were evaluated at Juntendo University from November 2017 to January 2019. Subjects. We enrolled female patients who had been clinically diagnosed with FM (N =23). Methods. All participants listened to Mozart's Duo for Violin and Viola No. 1, K. 423, in a quiet room for 17 minutes. We compared the degree of pain using resting-state functional magnetic resonance imaging and the numeric rating scale before and after listening to music. Results. Pain scores were significantly reduced after listening to music. Further, we observed there was a significant difference in connectivity between the right insular cortex (IC) and posterior cingulate cortex (PCC)/ precuneus (PCu) before and after listening to music. We also found that the difference between the right IC-PCu connectivity and the difference in pain scores were significantly correlated. Conclusions. We found that a short period of music intervention reduced chronic pain and altered functional IC-default mode network connectivity. Furthermore, music potentially normalized the neural network via IC-default mode network connectivity, yielding temporary pain relief in patients with FM. Further longitudinal studies with larger sample sizes are required to confirm these results.

OBJECTIVEThe aim of this study was to examine the effectiveness of ramelteon and suvorexant for delirium prevention in real-world practice. It explored whether ramelteon and/or suvorexant would affect delirium prevention among both patients at risk for but without delirium (patients at risk) and those with delirium the night before a consultation.METHODSThis multicenter, prospective, observational study was conducted by trained psychiatrists at consultation-liaison psychiatric services from October 1, 2017, to October 7, 2018. Patients who were aged 65 years or older and hospitalized because of acute diseases or elective surgery, had risk factors for delirium, and had insomnia or delirium on the night before the consultation were prescribed ramelteon and/or suvorexant. The decision to take medication was left to the discretion of each patient. The primary outcome was incidence of delirium based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, during the first 7 days.RESULTSAmong 526 patients at risk, those taking ramelteon and/or suvorexant developed delirium significantly less frequently than those who did not, after control for the effects of risk factors on the estimate of an independent association between the effects of ramelteon and/or suvorexant and the outcome of developing delirium (15.7% vs 24.0%; odds ratio [OR] = 0.48;, 95% CI, 0.29-0.80; P = .005). Similar results were found among 422 patients with delirium (39.9% vs 66.3%; OR = 0.36; 95% CI, 0.22-0.59; P < .0001).CONCLUSIONSRamelteon and suvorexant appear to be effective for delirium prevention in real-world practice.

Abstract Aim To provide information about psychiatric emergency situations in Japan, we examined psychiatrists’ preference among parenteral medication since intramuscular (IM)‐olanzapine became available and clinical characteristics in patients given IM‐olanzapine compared to those given other parenteral medication. Methods We conducted a naturalistic study proceeding over a 1‐year period in 9 psychiatric emergency departments. Results Among 197 patients, the distribution of IM‐injections (n = 89) was as follows: IM‐olanzapine, 66 patients (74.2%), IM‐levomepromazine, 17 patients (19.1%), IM‐haloperidol, 5 patients (5.6%), and IM‐diazepam, 1 patient (1.1%). The distribution of intravenous (IV)‐injections (n = 108) was as follows: IV‐haloperidol, 78 patients (72.2%), and IV‐benzodiazepines (diazepam, flunitrazepam, or midazolam), 30 patients (27.8%). Advantages of IM‐olanzapine over other parenteral medications in efficacy were found as follows: less frequent needs of an additional injection despite no difference in duration until a patient became cooperative for oral administration, and less frequent needs of restraint after the injection. Furthermore, advantages of IM‐olanzapine over other injections in safety were found as follows: less frequent appearance of extrapyramidal symptoms, no occurrence of ECG abnormality and other serious adverse events except a fall, less frequent needs of an adjunctive anticholinergic drug, and less frequent needs of another kind of drug additionally injected. Conclusions Olanzapine has rapidly become the first choice of intramuscular medication in psychiatric emergency situations since it became available in Japan, probably due to the advantages in both efficacy and safety. This study reflecting psychiatric emergency practice in Japan may contribute to periodic international comparison of psychiatric emergency practice.

Objective: The endometriosis fertility index (EFI) is a novel index for predicting pregnancy after surgery. We investigated the utility of the EFI for predicting the ability to conceive without assisted reproductive technology (ART) treatment after laparoscopic surgery. Methods: From July 2011 through December 2012, we recruited 133 infertile patients who underwent laparoscopy, and the EFI was calculated. After surgery, 55 of 133 achieved pregnancy without ART treatment. We evaluated the factors that predicted a naturally successful pregnancy and compared them between the pregnant and non-pregnant subjects. Results: On a univariate linear regression analysis, we found that a younger age, shorter duration of infertility, and higher EFI were positively associated with a successful pregnancy without ART after laparoscopic surgery (p < 0.05). According to 50th percentile EFI, the cutoff EFI predicting a successful pregnancy without ART was 7, the pregnancy rate in the high-EFI group (EFI; 8-10) was significantly higher than that in the low-EFI group (EFI ≤7; p < 0.05), but the duration to natural conception after surgery was similar between the 2 groups. Conclusion: The EFI possesses greater predictive power for a successful pregnancy with natural intercourse or intrauterine insemination in infertile patients, regardless of endometriosis, than the Revised-American Society of Reproductive Medicine classification.

Scientific Reports 6: Article number: 36943; published online: 11 November 2016; updated: 11 May 2018 The Publisher is retracting this Article because the experimental approach does not support the objectives of the study. The study was designed to elucidate the maximum implication of human papilloma virus (HPV) vaccine (Gardasil) in the central nervous system.

Purpose: The aim of the present study was to determine the brain regions with altered metabolism in patients with treatment-na ve fibromyalgia (FM).Methods: We used [F-18] fluoro-D-glucose positron emission tomography to examine a total of 18 treatment-na ve FM patients and 18 age-and sex-matched healthy controls not suffering from pain. A voxel-by-voxel group analysis was performed using statistical parametric mapping.Results: No significant voxel (peak)-level results were detected in this study; however, some regions were detected as significant-size clusters. There were no significant differences in brain metabolism between FM patients and controls. However, the right thalamus and left lentiform nucleus were hypermetabolic areas in FM patients with poor prognosis compared to the healthy controls. In contrast, the left insula and left lentiform nucleus were hypometabolic areas in FM patients with good prognosis compared to the healthy controls. Compared to FM patients with good prognosis, FM patients with poor prognosis showed significant hypermetabolism in the left thalamus, bilateral lentiform nucleus, and right parahippocampal gyrus.Conclusion: The present findings suggest an association between the metabolism in the thalamus, lentiform nucleus, and parahippocampal gyrus and prognosis in FM patients. Further study with a larger number of patients is required to confirm this association. (C) 2017 Elsevier Inc. All rights reserved.

We aimed to determine the frequency of endometrial cancer in infertile women undergoing hysteroscopic endometrial polypectomy for endometrial polyps.

AIM:Fibromyalgia syndrome (FMS) is defined as chronic widespread pain that cannot be accounted for by any other medical disorder. Our aim was to explore the prevalence of thyroid autoimmunity in patients with FMS.METHODS:For determining thyroid function in 207 FMS patients, we tested for the titers of free tri-iodothyronine, free thyroxine, thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibody (TPOAb), anti-thyroglobulin antibody (TgAb) and anti-TSH receptor antibody (TRAb).RESULTS:Twenty-five patients who had either subclinical hyper- or hypothyroidism, or overt hypothyroidism were excluded. Sixty-nine FMS patients with autoimmune thyroid diseases (AITD) (37.9%, 69/182) were identified. The prevalence of positivity for TRAb, TgAb and TPOAb was 20.3% (n = 37), 16.5% (n = 30) and 13.2% (n = 24), respectively. Compared to control populations in previous studies, the prevalence of TRAb positivity was high, and titers of TRAb were low (1.0-1.5 IU/L). The prevalence of TPOAb and TgAb positivity was not significantly higher than that reported in FMS patients in previous studies. Clinical symptom profiles were identical for FMS patients with and without AITD.CONCLUSION:We found a high prevalence of AITD among 207 patients with clinically defined FMS, with TRAb being especially prominent among these patients. Further study is needed to evaluate changes in thyroid function among FMS patients with AITD.

Fibromyalgia is a common illness characterized by chronic widespread pain, sleep problems (including unrefreshing sleep), physical exhaustion and cognitive difficulties. The definition, pathogenesis and treatment are controversial, and some even contest the existence of this disorder. In 1990, the American College of Rheumatology (ACR) defined classification criteria that required multiple tender points (areas of tenderness occurring in muscles and muscle-tendon junctions) and chronic widespread pain. In 2010, the ACR preliminary diagnostic criteria excluded tender points, allowed less extensive pain and placed reliance on patient-reported somatic symptoms and cognitive difficulties. Fibromyalgia occurs in all populations worldwide, and symptom prevalence ranges between 2% and 4% in the general population. The prevalence of people who are actually diagnosed with fibromyalgia ('administrative prevalence') is much lower. A model of fibromyalgia pathogenesis has been suggested in which biological and psychosocial variables interact to influence the predisposition, triggering and aggravation of a chronic disease, but the details are unclear. Diagnosis requires the history of a typical cluster of symptoms and the exclusion of a somatic disease that sufficiently explains the symptoms by medical examination. Current evidence-based guidelines emphasize the value of multimodal treatments, which encompass both non-pharmacological and selected pharmacological treatments tailored to individual symptoms, including pain, fatigue, sleep problems and mood problems. For an illustrated summary of this Primer, visit: http://go.nature.com/LIBdDX.

AIM:Fibromyalgia syndrome (FMS) is an extremely rare complication of neurocognitive disorders (NCDs). We experienced seven such cases, and we discuss their clinical manifestation and pathomechanisms.METHODS:Seven patients with FMS as a complication of NCD were enrolled. We used the patients' medical records to identify clinical manifestations and obtain experimental data, such as pain questionnaire scores, cognitive tests, genetics and radiological imaging of the brain.RESULTS:The seven patients were clinically diagnosed with frontotemporal NCD (n = 3) or Alzheimer's disease (n = 4). No patient presented with any organic disorder that would explain their chronic pain. Through their courses, they experienced refractory widespread pain continuously despite analgesics. Brain magnetic resonance imaging revealed moderate or severe atrophic changes in the temporal lobes and hippocampus. Three-dimensional stereotactic surface projection (3D-SSP) analysis of brain single photon emission computed tomography (SPECT), indicated severe hypoperfusion on the right side of the medial temporal lobe, both sides of the anterior corpus callosum, anterior cingulate gyrus, and primary sensory area. Genetic analysis uncovered no pathogenic mutations.CONCLUSIONS:Neurodegenerative disorders are rarely complicated by FMS, which is associated with relatively severe pain. Central sensitization may be a possible risk factor of widespread pain in elderly patients with NCD.