Sixteen adult patients (mean age 33 years) with whiplash injury grade II were recruited at the emergency department. [11C]-D-deprenyl positron emission tomography and computed tomography, subjective pain levels, self-rated neck disability, and active cervical range of motion were recorded within 7 days after injury and again at 6-month follow-up. Imaging results showed possible tissue injuries after acute whiplash with an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints, associated with subjective pain locale and levels, as well as self-rated disability. At follow-up, some patients had recovered and some showed persistent symptoms and reductions in [11C]-D-deprenyl uptake correlated to reductions in pain levels. These findings help identify affected peripheral structures in whiplash injury and strengthen the idea that positron emission tomography and computed tomography detectable organic lesions in peripheral tissue are relevant for the development of persistent pain and disability in whiplash injury.Knowledge of etiological mechanisms underlying whiplash-associated disorders is incomplete. Localisation and quantification of peripheral musculoskeletal injury and inflammation in whiplash-associated disorders would facilitate diagnosis, strengthen patients' subjective pain reports, and aid clinical decisions, all of which could lead to improved treatment. In this longitudinal observational study, we evaluated combined [ No peripheral tissue damage can convincingly be detected with current imaging technologies.42 The development of chronic symptoms after whiplash injuries may also be influenced by psychological and social factors26 as well as with changes in the central nervous system (CNS).36 This possibility has led to a discussion of whether tissue damage is even needed to initiate or maintain a WAD.51 Difficulties to detect and diagnose biological contributors (lesions), together with the lack of an accepted concept for what causes the symptoms in WAD, represent considerable personal, societal, and economic problems. Therefore, an objective visualization and quantification of peripheral musculoskeletal injury and possible painful inflammation in WADs would facilitate diagnosis, strengthen patients' subjective report of pain, and assist clinical decisions. In addition, it may help define new treatment targets and methods.Whiplash-associated disorder (WAD) is a globally important clinical, social, and financial problem.40 Positron emission tomography technology has been used to visualize and detect inflammation in numerous clinical settings.60 Furthermore, whiplash injury is associated with elevated production of inflammatory mediators.50 In this context, [11C]-D-deprenyl PET has emerged as a novel approach to target local inflammatory processes in the musculoskeletal system and chronic WAD.34 As in ankle sprains, expected injuries in whiplash involve muscles, periosteal tissues, ligaments, and joints. In a recent study exploring patients with unilateral ankle sprains, we demonstrated that the molecular aspects of tissue lesions in patients presenting with inflammation and pain could be visualized, quantified, and followed over time using [11C]-D-deprenyl PET/computed tomography (CT).1 We have previously reported that mitochondrial monoamine oxidase (MAO) enzymes are a major candidate for the binding target of D-deprenyl32 and that D-deprenyl discriminates between low and high grades of inflammation.31 Therefore, [11C]-D-deprenyl may be valuable in the visualization and quantification of inflammation, as well as possible pain-associated processes in the peripheral tissue of WAD.Positron emission tomography (PET) is an imaging tool that captures molecular and cellular biological processes and not mere anatomy or structure.11C]-D-deprenyl PET/CT. The aim was to characterize acute alterations and the predictive ability of [11C]-D-deprenyl uptake for whiplash signs and symptoms at a 6-month follow-up. We hypothesized that [11C]-D-deprenyl uptake would be acutely elevated, localized to anatomically relevant injured tissues, colocalized to tender points, and correlated with subjective pain experience. In addition, we hypothesized that patients with persistent pain would have prolonged elevated [11C]-D-deprenyl uptake at the injury sites at the 6-month follow-up.We conducted a prospective observational PET study in adult patients with acute whiplash injury and healthy controls using -D-deprenyl PET/CT studies on the neck region of each patient. The first imaging session was scheduled acutely within 4 to 7 days (mean 4.9 [±1.4] days) from the injury, and all follow-up imaging sessions were scheduled 6 months (mean 221 [±24] days) after the injury. Before the examination sessions, all patients refrained from alcohol and caffeine for 12 hours and from analgesics for at least 24 hours.The study design consisted of two -D-deprenyl was produced at the chemistry section of the Uppsala PET Center according to a standard manufacturing procedure with previously published methods.39 All patients were investigated with a GE Discovery ST PET/CT scanner . The scanner enables the acquisition of 47 contiguous planes of data with a distance of 3.27 mm  and 3.125 mm , resulting in a total axial field of view of 15.7 cm. The patients were scanned in the supine position with their head fixed and positioned in the scanner field of view originating 2 cm above the orbitomeatal line to allow data acquisition from the base of the skull down to the shoulder region.The radioligand [11C]-D-deprenyl in the arm. Simultaneously, a dynamic emission scan (3D mode) was initiated with a predetermined set of measurements  for up to 45 minutes. Then a single 15-minute static image was collected over the lower neck area. Positron emission tomography data were reconstructed with the ordered subset expectation maximization algorithm (2 iterations and 21 subsets). A 2.57 mm wide postprocessing filter was applied to the images. Positron emission tomography data were corrected for decay, photon attenuation, scatter, random coincidences, and dead time.The PET/CT investigation was initiated with a short CT scan  for attenuation correction of the PET emission data. Each patient received an intravenous bolus of approximately 5 MBq/kg -D-deprenyl uptake above the background signal, and ROIs containing the lesion were delineated manually in multiple adjacent slices. [11C]-D-deprenyl uptake in salivary glands and the CNS was regarded as a normal finding based on previous studies of healthy subjects. The specific lesion areas were also delineated in all images of each patient and in controls in the overlapping CT images. Finally, data from the controls were used to calculate the corresponding SUVMAX and SUVRATIO as well as reference intervals (mean ±2 SD) for each ROI. Anatomical and lesion ROIs demonstrating an uptake >2 SDs in any of the patients  were considered in the statistical analysis. These anatomical regions were identified with the help of an experienced PET radiologist (J.S.). The defined anatomical regions are approximate and can contain adjacent structures because of the physical limits of spatial resolution in PET/CT.The image analysis was performed with Voyager . First, the CT image was used to delineate the anatomical ROIs in all images of each patient and control. Second, the lesions were identified visually from the PET/CT image with elevated -D-deprenyl uptake and NRS, CROM, and NDI were also explored, see supplemental methods and results (available at http://links.lww.com/PAIN/B423).The 1-tailed nonparametric Wilcoxon signed-rank test was used to compare differences between the SUVP = 0.0008). During the follow-up, median self-rated disability (NDI) changed from 23 (20.5-28) to 17 (12.5-25.5) (P = 0.0007) and the affected neck movements (CROM) diminished from 1.5 (1-4.5) to 1 (0-2) (P = 0.008). A conventional CT scan of the neck, performed acutely and at follow-up on all patients, did not reveal any pathological findings.Baseline characteristics of the patients and outcome measures are summarized in Table 11C]-D-deprenyl uptake was visually evident and quantitatively observed in multiple locations in upper neck regions in the patients as compared with the healthy controls . A SUVMAX >2 SD above the mean in the healthy controls was observed in 14/32 (44%) of the patients' scans with a median SUVMAX of 5.3 (IQR 4.4-6.0) acutely and 4.5 (IQR 3.8-6.1) at follow-up. SUVRATIOS >2 SD of the mean of the healthy controls were observed in 22/32 (81%) of the patients' scans with a median SUVRATIO of 2.0 (IQR 1.7-3.0) at acute scans and 2.0 (IQR 1.7-2.4) at follow-up. During the acute investigations, abnormal [11C]-D-deprenyl uptake (SUVRATIO) was observed in the muscle (10 of 16 patients or 63%), bone structure (12/16 or 75%), facet joint (10/16 or 63%), occipital condyle (5/16 or 31%), groove for spinal nerve (4/16 or 25%), and temporomandibular joint (3/16 or 19%) in patients. At follow-up, abnormal [11C]-D-deprenyl uptake (SUVRATIO) was observed in the muscle (6/16 or 38%), bone structure (6/16 or 38%), facet joint (7/16 or 44%), occipital condyle (5/16 or 31%), groove for spinal nerve (2/16 or 13%), and temporomandibular joint (2/16 or 13%) in patients. The areas of elevated uptake in the upper neck were colocalized to painful locations and maximum tenderness points  was significantly and positively associated with the NRS ratings  and the NDI .The number of anatomical regions with an abnormal uptake (SUVRATIO) was significantly fewer across subjects (P = 0.017), but still more prevalent than in the healthy control group (P < 0.001). Changes  in NRS ratings between the acute stage and follow-up were significantly correlated to changes  in the number of regions with an abnormal SUVRATIO uptake , Figure At follow-up, the number of regions with elevated uptake (SUVhttp://links.lww.com/PAIN/B423).Relationships between specific anatomical locations and NDI, NRS, and CROM are reported in supplemental materials  we observed them in our previous study on chronic WAD34 and (2) these structures are involved in stabilizing the head-neck complex and most of the extension, flexion and rotation of the neck occurs between the occiput, C1 and C2.3 Many of these previously described candidate lesions have been identified in animal studies, postmortem observations, and cadaveric models but have not been identified with current imaging modalities in patients with WAD.Our study demonstrates an elevated uptake of [11C]-D-deprenyl uptake was mostly observed in bone structures and especially in upper vertebral bodies and facet joints (together with surrounding soft tissues). There is growing evidence that facet joints and capsules can be injured in whiplash and that these can be the source of pain.58 The clinical relevance of other tissue injuries is less clear, but cadaveric, postmortem, and animal whiplash injury models have systematically demonstrated injuries in the upper cervical discs and outer rim of the vertebral bodies and endplates. Endplate and adjacent bone marrow changes have been observed in patients with whiplash.29 These traumatically induced changes reflect hypervascularity because of inflammation (Modic type 1) and fatty replacements of the red bone marrow (Modic type 2).43The [11C]-D-deprenyl uptake and possible injury in the region of occipital condyles  indicate another, less established potential injury mechanism. Widening of the atlanto-occipital joint spaces, which indicates possible ligamentous injury followed by instability, has been described.44 We further observed an elevated [11C]-D-deprenyl uptake in the extensor muscles of the neck in most scans. Structural changes in the muscles may play a role in the development of WAD,16 and muscle tears, hematomas, strains, and perimuscular fluid have been visualized in MRI in patients with whiplash.2 A fatty infiltration, especially in suboccipital and upper segmental extensor muscles , has been previously shown.15 In our study, tracer uptake in the temporomandibular joint was present in 3 patients. This uptake was already evident at the acute investigation, which may support the hypothesis of direct trauma to the joint  and that the whiplash trauma may be an aggravating factor for the progression of temporomandibular disorders.48 Unfortunately, MRIs were not obtained in the present cohort, so we cannot directly compare the sensitivity and specificity between MRI and [11C]-D-deprenyl.The observed [11C]-D-deprenyl uptake in the injured bone and joint structures and self-reported pain, self-rated disability, and pain localization. The colocalization between tracer uptake and pain locale was visually evident in several cases. However, a direct relation between tissue injury and self-report of pain may be an oversimplification: Nociceptive signal transmission from a tissue injury is under strong peripheral modulation but also from the CNS .53 Furthermore, social, economic, psychological, and genetic factors influence all pain experiences, including WAD.26 Still, our findings support the hypothesis that the experienced pain and disability in whiplash may be driven by an ongoing peripheral nociceptive source. The present findings also support studies suggesting inflammatory processes are involved in the development and presentation of chronic WAD.50Contrary to the idea that whiplash only affects soft tissues, our study shows a positive association between -D-deprenyl uptake shows an association with NRS and NDI. This finding supports the notion that [11C]-D-deprenyl uptake is related to the extent and severity of the injury.10 Of note, the correlations between pain ratings and [11C]-D-deprenyl uptake were modest. This is expected, as multiple factors other than tissue damage will influence individual pain ratings,45 including the anchoring of the rating scale.55Initial pain intensity and neck-related disability are the most consistent prognostic factors in patients with acute WAD.11C]-D-deprenyl uptake . The strongest evidence concerns pain from the facet joints, although the facet joint injury in patients with WAD has not previously been visualized. Facet joint capsules as the “source” of pain in WADs has been validated in animal models59; in human treatment studies, diagnostic blocks and radiofrequency neurotomy can abolish neck pain from these joints.46 Chronic pain can be traced to facet joints in about 50% of patients with whiplash in these studies, which can be compared with [11C]-D-deprenyl uptake in 44% of the patients at follow-up in our study. Particularly, noteworthy is that local inflammation and not pure mechanical injury or development of osteoarthritis has been linked to generation of pain from facet joints.24 Endplate and bone marrow changes (Modic changes) have been associated with low back pain,28 and the Modic changes in neck pain patients have been described as a dynamic phenomenon without completely disappearing during follow-up.41 We did not observe an association between pain and possible muscle injury but see supplementary materials (available at http://links.lww.com/PAIN/B423) for further details on muscle and dorsal root ganglia observations.Upper facet joints and vertebral bodies show the strongest association between pain and [11C]-D-deprenyl uptake in the upper bone structures and joints and later pain and disability. A possible explanation could be a more severe initial injury or a localization in which the healing process is abnormal. New regions of tracer uptake at follow-up might be explained by ligament insufficiency and impaired cervical position sense (proprioception) that are common in cervical pain.47 These changes can alter the kinematics of the neck with altered shear load and posture and initiate novel inflammatory processes. Such adaptation-related increases in [11C]-D-deprenyl uptake have previously been observed in both feet after recovery from a one-sided ankle sprain.1 Consequently, new uptake regions could be the first signs of adaptive or degenerative changes in the neck tissues. Of note, MRI examination can reveal pronounced degenerative changes in asymptomatic patients,21 but these changes are less frequent in patients aged <40 years.We saw indications of associations between initial [11C]-D-deprenyl uptake. To reduce the effects of blood flow, a semiquantitative measurement of the radioactivity concentration in tissue with a reference region (SUVRATIO) was used. This approach minimizes (but may not eliminate) the blood flow component. A full tracer kinetic modeling with arterial blood sampling to measure radioactivity and D-deprenyl metabolites would be needed to exclude blood flow effects. According to the available data, the main binding target for D-deprenyl is MAO enzymes in the cells that are engaged in processes involved in inflammation,32 although other protein targets distinct from MAO-B, including sigma-1,25 cannot be excluded. The complex role of MAO enzymes in peripheral inflammation warrants further studies.The main limitations of the study are the limited sample size, and the exact uptake mechanism of D-deprenyl in musculoskeletal injury remains elusive. D-deprenyl is a weak lipophilic base, and a possible local increase in blood flow in neck tissues needs to be considered when interpreting [11C]-D-deprenyl uptake is associated with pain and disability at 2 time points. Participants exposed to motor-vehicle impacts of similar forces but without experiencing neck pain would be an ideal control group to account for the specificity of neck symptoms and D-deprenyl uptake and also the psychological stress of a traumatic vehicle crash. Prospective cohort studies are needed to elucidate the predictive and diagnostic value of PET/CT in whiplash injury.The small sample size, typical for PET studies, was limited because of the high costs of PET and feasibility concerns. We conclude that [This study provides further evidence that tissue injury and inflammation in whiplash injury can be objectively visualized and quantified using PET/CT, suggesting lesions in peripheral tissue are relevant for the development of persistent pain and disability in whiplash injury. Recognition of these affected structures should advance general knowledge of whiplash disorders and facilitate individualized treatment interventions.The authors have no conflicts of interest to declare.http://links.lww.com/PAIN/B423.Supplemental digital content associated with this article can be found online at


Herniated cervical intervertebral disc  with radiculopathy is known to occur in seven or eight out of 100 people worldwide. This disease causes movement limitation, loss of strength, and pain of upper extremity. The aim of this study is the effect of conventional physiotherapy agents on predetermined parameters in patients with cervical radiculopathy and to compare the results with healthy controls.A total of 102 patients with CDH with radiculopathy and 98 healthy controls were included in the study. Visual reaction time (VRT) and auditory reaction time (ART) measurements were evaluated with reaction timer, while the pain was assessed with visual analog scale (VAS) and handgrip strength (HGS) assessed with hand dynamometer, respectively. Conventional physiotherapy  agents were applied 5 days/week for 3 weeks as treatment protocol.As a result, VAS, VRT, and ART scores were significantly decreased, and HGS scores increased significantly in both female and male patients post-treatment measures (p<0.05). There was no statistically significant difference between patient group and control group measurements in post-treatment evaluations (p>0.05).This study presents the conclusion to literature that conventional physiotherapy agents have the effect of decreasing pain and regaining motor function and also a therapeutic effect on VRT and ART in the treatment of patients with CDH with radiculopathy. Chronic pain is an emotional, effective, and undesired situation which negatively influences daily life activities and quality of life. In chronic pain grading, neck aches come the second after backaches. One out of three people in the general population complains about neck pain that develops due to various reasons in some part of their lives. One of the most common reasons for neck pain is cervical disc herniation (CDH) . It was found that evidence about the effect of conventional physiotherapy agents, which are found to have positive effects on pain, motor performance, functional attainments, and daily life activities in literature frequently used in clinics, on VRT and ART in patients with CDH with radiculopathy, were very insufficient.When situations such as pain paresthesia resulting from cervical radiculopathy disappear, the individual can show his/her real performance. In this study, the pain that appeared to be reduced on post-treatment evaluations probably led to the emergence of the muscle strength of the individuals. This situation was reflected in post-treatment results as a significant increase in HGS scores. It is thought that radiculopathy with disc hernia can also influence reaction time due to its adverse effects on individuals’ muscle strength and motor performance . HGS is In their study, Egwu et al.  stated tReaction time is also influenced by pain. In terms of analyzing the effectiveness of conventional physiotherapy agents on the musculoskeletal system, the improvement in reaction time can be an important indicator . In thisWhile the association between chronic backache and the lower extremity reaction time is one of the studied subjects in the literature, the number of studies on the association between CDH patients and VRT, ART, pain, and muscle strength is very limited , 26. In These results support that despite innovative treatment alternatives, conventional physiotherapy agents continue to be used frequently and they are effective methods that should be preferred in the treatment of patients of CDH with radiculopathy in terms of causing a decrease in the pain which has a negative influence on the patients’ daily life activities, regaining motoric function and improving reaction time.Difficulty of patients coming to attend 3-week physiotherapy sessions due to their living conditions limited the work and created limitation. Although the fact that this study is the first in this area creates a limitation for the discussion section, it will form the basis of new studies in this area.


Background: mobile applications (apps) facilitate cancer pain ecological momentary assessment (EMA) and provide more reliable data than retrospective monitoring. The aims of this study are (a) to describe the status of persons with cancer pain when assessed ecologically, (b) to analyze the utility of clinical alarms integrated into the app, and (c) to test the feasibility of implementing an app for daily oncological pain monitoring. Methods: in this feasibility study, 21 patients  responded to an app-based evaluation of physical status (baseline and breakthrough cancer pain (BTcP)) and mental health variables  daily during 30 days. Results: cancer pain characterization with the app was similar to data from the literature using retrospective assessments in terms of BTcP duration and perceived medication effectiveness. However, BTcP was less frequent when evaluated ecologically. Pain, fatigue, and mood were comparable in the morning and evening. Passive coping strategies were the most employed daily. Clinical alarms appear to be useful to detect and address adverse events. App implementation was feasible and acceptable. Conclusion: apps reduce recall bias and facilitate a rapid response to adverse events in oncological care. Future efforts should be addressed to integrate EMA and ecological momentary interventions to facilitate pain self-management via apps. Breakthrough cancer pain (BTcP) is a heterogeneous construct whose definition is far from clearly established . HoweverThe prevalence of BTcP has oscillated across studies due to the heterogeneity of assessed samples and the lack of a clear definition of BTcP , but it BTcP significantly impacts the quality of life and the emotional and functional status of patients with cancer, as well as the dissatisfaction with the treatment and the costs associated with healthcare provision ,12,13,14In the last decade, several studies have explored the characterization of BTcP cross-culturally ,12,14. WThe need for EMA in persons with cancer, however, does not only apply to pain reports in general and BTcP in particular. The life expectancy in oncological patients has increased dramatically thanks to medical advances in the treatment of this disease. Therefore, outcomes associated with quality of life should be incorporated in the routine assessment of persons with cancer . This inDespite the advantages of EMA, its implementations in health settings in general and cancer management in particular have been challenging and infrequent. For example, health care services still generally rely on face-to-face interventions to manage pain conditions (even though the COVID-19 pandemic has imposed some changes in this regard) . In termThe implementation of technological solutions for EMA, such as treatment/evaluations delivered through the internet or via smartphone applications (apps), has demonstrated to be useful for clinical practice ,35 and hSeveral apps already exist to facilitate the management of numerous health conditions ,40,41, aThe aims of this study are: (i) to characterize the patient status in terms of pain  and related factors  when assessed ecologically and daily during a certain time period ; (ii) to explore the frequency and impact of clinical alarms  when detected by the app, and (iii) to test the feasibility of implementing an app-based monitoring system for EMA in patients with cancer pain . We expect (i) to replicate the findings from past research ,12,14 whThis was a feasibility clinical trial to evaluate whether the implementation of an app to monitor patients with cancer pain daily provided novel data about the characteristics of cancer breakthrough pain and the frequency of undesired clinical events during treatment for cancer thanks to the alarms in the app. In addition, we aimed to explore whether the use of this monitoring tool was viable and resulted in actions by the medical team that could potentially improve the quality of life of the participants. The study was previously registered in Clinicaltrials.org (NTC03597737).Eligibility criteria included being 18 years or older, having the physical and mental capacity to participate in the study, having cancer pain, holding a mobile phone with an Android operating system (the app was only available for Android at the time of the study for economic reasons and because of the differences in the penetration between Android and other operating systems in Spain), and signing the informed consent form.Potential participants were patients experiencing disease-related pain with an appointment at the cancer unit (blinded) during 2017 and 2018. Individuals who meet the requirements to participate in the study of age and cancer were invited to participate by the medical team of the cancer unit. In a first step, twenty-five participants were screened for eligibility criteria. Four of them did not meet inclusion criteria as they did not have a mobile phone with an Android operating system. Thus, the final sample comprised of 21 participants. The sample size was calculated according to previous recommendations for feasibility studies, which suggest a minimum of 12 participants per group .https://play.google.com/store/apps/details?id=doloronco.code, accessed on 3 May 2021), but an individual code to access the app is needed for its use (this is provided by the physician). The participants were asked to use the app daily for 30 days, a period of time that was believed to be sufficient to obtain a picture of the pain profile of the participants and the difficulties experienced with introducing this assessment tool in the daily life of individuals with cancer.A researcher that was hired to provide assistance with the project helped the participants install the app and make the first use. The app can be downloaded for free in the Play Store  to make changes to the treatment.In this study, we used the assessment protocol validated in the Pain Monitor app . A few aAs in previous research, patients were prompted twice daily, in the morning and evening, because the experience in relation to some items can change depending on the time of the day , while the assessment of some items was more sensible in the morning  or in the evening only .-Treatment adherence: Daily treatment intake was measured with a single item, “Have you taken the pain medication prescribed by your doctor today?”. Response options are: (a) “Yes, I have taken it”, (b) “No, but I will take it”, and (c) “I have not taken it and I will not take it today”.-Pain severity: This item assesses the current level of pain (“Please indicate your current level of pain”). Responses range from 0 = “No pain” at all to 10 = “Extreme pain”.-Fatigue: This item evaluates fatigue intensity (“Please indicate your current level of fatigue”). Responses range from 0 = “No fatigue at all” to 10 = “Extreme fatigue”.-Mood: Three items were employed to assess the intensity of happiness (“Please indicate your current level of happiness”), sadness (“Please indicate your current level of sadness”), and anxiety (“Please indicate your current level of anxiety”). The three items use a similar response scale ranging from 0 = “No happiness/sadness/anxiety” at all to 10 = “Extreme happiness/sadness/anxiety”.-Perceived utility of pain treatment: This item evaluates the perceived pain relief after the baseline pain medication intake (“Please indicate to what extent the baseline medication relieved your pain today”). Responses range from 0% = “No relief at all” to 100% = “Complete relief”.-Coping strategies: we explored the coping strategies implemented by patients on a given day (“Select the coping strategies that you have used today to cope with pain. You can choose more than one option”). The following list of coping strategies was presented to the patients: inactivity, relaxing, talking to somebody, physical activity, coping self-statements, distracting/ignoring the pain, or praying. This list was created after reviewing the most frequent coping strategies employed in pain research and was validated to be used with the app in a previous investigation .The ecological momentary evaluation included previously validated single items of treatment adherence, pain severity, fatigue, mood, relief of pain treatment, and use of coping strategies to deal with the pain :-TreatmeIn addition to the morning and evening assessments, which were identical to the ones in the original app Pain Monitor, the novelty of the “breakthrough pain” version of the app was the inclusion of a breakthrough pain on-demand evaluation. The algorithm used in the breakthrough pain assessment is depicted in A maximum of three loops might then occur 30 min after the same assessment and then every 30 min if the pain severity levels are still equal or greater than 5. At the beginning of each loop, the patient is asked about the severity of the current pain to check whether the breakthrough pain episode ended. If the reported pain severity is 4 or less, the loop closes. On the contrary, if the pain severity is still 5 or over on a 0–10 scale, the patients are asked to report the amount of rescue medication used or whether they plan to take medication if the pain persists. They are then told that the app will inquire them again about their pain status 30 min later. In total, three loops can be potentially shown to the patient, each questioning about pain severity and rescue medication use. The loops only close if patients report an amelioration of the pain levels (4 or less). If the pain of 5 or over persists after the third loop, the assessment ends and a clinical alarm is sent to the medical team.n = 40) found the app easy to use, and 92.7% of them found it useful [App-related outcomes were either evaluated by phone (patients) or by paper-and-pencil (clinicians). To assess the usability of the app, the 10-item System Usability Scale (SUS)  was admit useful .n = 2). The responses for questions addressing satisfaction with the app in the medical team . Whenever the medical team considered that an action was necessary for an alarm, they responded to it by calling the patient the following working day after the alarm was generated. The clinical alarms were similar to those used in previous research  but wereThe app has several layers of access security to prevent unwanted access to the system. These systems are based on the encryption of the channel through certificates and the randomization of an access key each time the connection is made.The database provided by the app is completely anonymous since the system does not store any personal information. However, the application collects the International Mobile Equipment Identity (IMEI), which is a unique reference for each mobile phone. This number was used to link the responses in the database to a participant. To guarantee confidentiality, the storage of the IMEI of the participants was external to the system and was stored locally in the computer of the cancer clinic. Only the medical team could relate the IMEIs of the patients with their personal data .All the data collected by the app comply with the guidelines established in the laws and data protection regulations in force.t-test was conducted to compare morning-to-evening pain, fatigue, and mood scores. Then, BTcP episodes were characterized in terms of frequency , time of onset, and average pain intensity.The analysis of the data included a description of the means and standard deviations of pain severity, fatigue, and mood outcomes throughout the study, as well as the frequency and characteristics of breakthrough pain episodes. First, sociodemographic and pain characteristics  were analyzed to describe the sample. Second, mean and standard deviations were calculated for daily measures of pain, fatigue, and mood . Because these variables were asked twice a day, a Student Regarding the perceived utility of baseline medication, we calculated the proportion of time that patients reported high pain relief (70–100% of perceived medication utility in pain reduction), low pain relief (between 0 and 30% of perceived medication utility), and moderate pain relief (between 40 and 60% of perceived medication utility). The same descriptive analyses were conducted to explore the frequency of use of strategies to cope with pain.The information from the clinical alarms is reported. We indicate the type of clinical alarm, as well as the response provided by the professionals. Finally, feasibility and satisfaction outcomes are explored. In particular, we report the participants’ adherence with the app (number of missing reports) and the app satisfaction results (based on the SUS questionnaire described previously). The anonymous database will be made available under reasonable request.n = 16, 76.2%). Only one participant was working at the time of study recruitment. The remaining participants were either on sick leave , permanent disability , or retired . Regarding educational level, the majority of participants had elementary or no studies , four participants had completed secondary education, and four participants had tertiary education.Twenty-one patients met the inclusion criteria and were included in the study. Of these, 17 were men (81.0%) and 4 were women (19.0%). Their mean age was 56.95 years . The vast majority of participants were married or in a relationship  or anxiety disorder .Only three patients reported having a formal diagnosis of major depressive disorder (n = 9), head (n = 4), neck (n = 4), low back (n = 2), abdomen (n = 1), and thorax (n = 1). Cancer pain duration was generally short , but a significant number of patients had been experiencing pain for longer periods . The remaining patients reported experiencing pain for between 7 and 12 months (n = 3), or over 5 years (n = 2).The participants reported that their major focus of cancer-related pain occurred in the shoulders .n = 11, 52.4%), fentanyl , tramadol , or oxycodone . Routes of medication administration were either oral (n = 12), transdermal (n = 15), or intravenous (n = 1). Regarding adherence with baseline medication, 88.70% of the times that patients responded to the adherence question, they reported that they had already taken the medication. The remaining 11.30% of times, the patients responded that they had not taken it yet, but they would take it later. None of the participants ever indicated that they were not willing to take the baseline medication that day.Regarding baseline pain, 20 participants were receiving pharmacotherapy (95.2%), 3 were receiving infiltrations (14.3%), 2 were receiving physiotherapy (9.5%), and 2 were receiving psychotherapy (9.5%). None of the participants were taking natural/alternative treatment for their baseline pain. Pharmacotherapy for their baseline included morphine  and morphine . The routes of medication administration were all oral (n = 21).Regarding the breakthrough pain, all patients reported having been prescribed pharmacotherapy. This included fentanyl  and 11 were receiving radiotherapy (52.4%).t [p = 0.383, d = 0.27). Similar to pain severity, the average fatigue reported by the participants was higher in the evening  than in the morning . Again, this difference was non-significant and small in size . The clinical characteristics of the sample are reported in t  = 0.88,  size , while the remaining three patients indicated six, four, and three episodes, respectively. The duration of episodes was generally shorter than 30 min (n = 14). The remaining episodes had a duration of between 30 and 60 min (n = 4) and between 60 and 90 min (n = 1).The characteristics of breakthrough pain episodes are reported in The average severity of pain during breakthrough episodes was higher at the initial stage of the episode, that is, at onset  or to relax (35.4% of times). The remaining strategies included talking to somebody (12.16%), performing physical activity/stretching (3.78%), distracting/ignoring the pain (0.81%), using coping self-statements (0.54%), and praying (0.27%).The distribution of coping strategies used daily is graphically represented in n = 12). Alarms referred to excessive baseline pain severity (n = 8), sleepiness (n = 17), vomiting (n = 1), and nausea (n = 1). Responses to the alarms ranged from telephone contact to provide medical advice (n = 13), arrange an appointment (n = 5) to increasing the medication (n = 2), or hospitalization (n = 1). On four occasions, the attempts to contact the patient were unsuccessful.The date of the alarm, the patient ID, the type of alarm, and response to it by the healthcare team are reported in n = 5), afternoon (n = 7), and evening (n = 7).Breakthrough pain episodes were reported at all times of the day, including morning  used the app daily during the 30 days of study. The remaining participants used the app during 25 (n = 1), 24 (n = 1), 18 (n = 1), 17 (n = 1), 14 (n = 2), and 8 days (n = 2).In terms of adherence, the majority of participants .The mean score of the System Usability Scale in patients was 85.77 (SD = 12.09). The average score of this study falls within the 4th quartile, indicating very good acceptability by users and placing our application between excellent and best imaginable in the adjective rating scale .The two clinicians of the cancer unit that participated in the study completely agreed that the app improves the safety of treatments for BTcP, that the alarms of app improved the effectiveness of treatments for BTcP, that the alarms of app improved the adherence to treatments for BTcP, that the app would be useful for them as healthcare professionals, that the app was useful for patients with BTcP, that the app could be integrated into routine care, and both would like to continue using the app. One of them mostly agreed that he felt safer with the app when treating BTcP, while the other was more enthusiastic and completely agreed. One indicated that the use of alarms resulted in no burden for him, while the other indicated a certain degree of burden. They indicated that the additional daily time they required to manage app-related clinical alarms ranged from 20 to 30 min.The main objective of the present study was to use a mobile application to provide an accurate characterization of the patients’ physical and psychological status. We also aimed to explore the utility of clinical alarms, as well as to test the feasibility of using an app for EMA in cancer pain management. Overall, our results indicated that EMA provided similar pain characterizations compared to previous studies that used retrospective paper-and-pencil assessments. We also obtained a daily characterization of psychological variables and a measure of fatigue, which is relatively novel to the literature in cancer pain. In addition, we found clinical alarms to be useful for the evaluation and management of treatment side effects. Finally, the results support the idea that the implementation of the app was feasible  in our sample. A summary of the key points discussed in the following lines can be found in Consistent with the previous literature , our EMAIn addition to BTcP, a contribution of the study was that fatigue was assessed daily during the whole study period (30 days). Fatigue is one of the most prevalent and distressing effects of cancer treatment and is defined as a subjective sense of physical, emotional, and cognitive exhaustion related to cancer disease, which negatively interferes with the patient’s functioning and quality of life . Similarn = 2; 9.5%) that received psychotherapy in our study. This is also inconsistent with recent recommendations suggesting that psychological assessments should include the patient’s desire for psychological support and the moral requirements that, when mental problems are detected, treatment should be offered [In addition to the physical characterization of cancer pain, we evaluated psychological variables that were argued to be relevant in persons with cancer pain ,23,24,25 offered ,25.Another strong point of the present study was the daily assessment of coping strategies. Several international guidelines recommend the evaluation of coping strategies as a key point of cancer pain management ,24. ThusOur second objective was to assess the utility of clinical alarms. Consistent with our hypothesis, an important finding in our study was that clinical alarms, which were set in the app, are useful to detect undesirable events in the real context in which they occur. In our study, 27 alarms were detected, and 84% of them could be adequately addressed by doctors with telephone contacts, appointment re-arrangements, or medication adjustments, among others. This is especially relevant for pain management because, in the most proximal context in which patients receive care , daily assessments are not feasible. As noted in past research, when undesired effects occur , patients should not be left in charge to decide how to react in the presence of such events . Note thIn relation to the latter objective of this study, that is, to test the results of implementing an app-based EMA, our findings suggest that this system was feasible. According to different implementation outcomes, we found high coverage/penetration, fidelity (adherence rates), usability, and acceptability. First, only four participants could not be engaged in the study due to the non-compatibility of their smartphone operative system. This indicates a high coverage rate because 84% of the participants that could be eligible actually participated in the study. Because the app offered to the participants was only available for the Android operative system, this coverage data were expected, and it is consistent with recent data showing that 20% of the Spanish population use iOS systems . Second,Similar to previous studies , our samThis paper provides several contributions regarding BTcP characterization and management. However, the findings should also be interpreted in the context of some limitations. First, no comparison group was included in the study. Therefore, it is not possible to establish robust differences in the patients’ characterization based on assessment tools . Second, subjective information was collected with the app. This means that patients may have underestimated their symptoms or might not have been motivated to reported and, in consequence, the characterization would have been incomplete. For instance, it is possible that patients experienced BTcP every day but decided not to report the episodes because they are used to them or because they were not motivated to do it. Additionally, at the end of the study, participants were not asked about the presence of non-reported BTcP episodes, so we are not able to analyze whether non-detected BTcP episodes or alarms actually existed. Similarly, changes in the pharmacological treatment were not registered in the app, so it is not possible to explore whether changes in the medication resulted in better pain management . Regarding alarms, despite that some of them were detected and addressed during the study period, 14% of them could not be solved because the participants could not be contacted by phone. To address this problem, we recommend that, in addition to sending the alarm to the physician, the app-based EMA should be followed by Ecological Momentary Intervention (EMI) delivered throughout the app when alarms occur. For example, a recent study found that physical exercise could be recommended as a function of the patients’ daily reports . TherefoDuring the last decades, routine, real-time assessments have emerged as the gold standard for oncological pain management. Different international guidelines recommend including information beyond baseline pain and BTcP. This means assessing additional health-related variables, such as fatigue, mood, and coping strategies. Ecological momentary assessments, however, are rarely implemented in cancer management health settings. According to our results, the infrequent use of app-based assessments in our immediate context is not justified. Our results showed that the use of mobile applications is well accepted both by patients and clinicians. In addition, apps are promising solutions to overcome the barriers found in paper-and-pencil or telephone traditional assessments and allow to obtain valuable real-time information that can be used to adjust oncological pharmacological, and psychological management according to the patients’ daily responses in the app. Additionally, the inclusion of clinical alarms in mobile apps could help to increase treatment safety by detecting and rapidly responding to the adverse events that may occur with the treatment, which is crucial in oncological pain management. Finally, in terms of implementation, our results support the idea that the use of app-based systems is likely to be feasible in pain and oncological units and could be especially useful in clinical practice to guarantee the safety of patients undergoing oncological treatments.


Interdisciplinary pain rehabilitation (IPR) usually employs a cognitive–behavioural therapeutic (CBT) approach. However, there is growing support for chronic pain treatments based on acceptance and commitment therapy (ACT). Most studies of ACT and CBT for chronic pain have evaluated their effects after psychological interventions, not after IPR. We compared the results of an ACT-based IPR programme with two CBT-based IPR programmes.We used a retrospective multicentre pretest–posttest design with matched patient groups at three centres. Data were collected from the Swedish Quality Registry for Pain Rehabilitation before and after IPR participation. Participants completed the EQ-5D health-related quality of life questionnaire, the Chronic Pain Acceptance Questionnaire, (CPAQ) and the Hospital Anxiety and Depression Scale (HADS). Analyses were performed to compare the effects of the different interventions.Neither EQ-5D nor HADS depression scores were affected by the psychological approach used. The score changes on both CPAQ subscales (activity engagement and pain willingness) indicated significant improvements between admission and discharge at all centres.These findings indicate the effectiveness of using psychological approaches to manage chronic pain. Both CBT and ACT had a beneficial effect on most of the assessed health-related parameters. According to a European survey of chronic pain, approximately 20% of the Swedish population experiences chronic pain of moderate to severe intensity.The often-cited definition of pain emphasizes that pain is always a subjective sensation related to emotional and psychological experiences.4 However, there are individual differences in how pain severity and complexity interact with other symptoms and thus affect each individual’s activity levels and participation in society. Individuals who find it difficult to manage the effects of pain on daily living, work and leisure require approaches that address the complexity of the different aspects of chronic pain.Chronic pain is a complex condition that substantially affects many aspects of daily life, such as quality of life, working status, psychological well-being and self-esteem. In addition to causing individual distress, chronic pain has serious negative effects on society and national expenditure.6 and the effect appears to be stable over time. IPR is based on a biopsychosocial model of chronic pain that includes somatic, psychological, environmental and personality aspects.79 The IPR approach comprises teamwork involving the participation of individuals from several professions; patients are usually also included as active team members. IPR interventions are synchronized and require structured, goal-directed plans. Most IPR programmes in Sweden use a cognitive–behavioural therapeutic (CBT) approach based on a combination of physical and psychological interventions. A 2015 Cochrane review of subacute neck pain treatments found low to moderate evidence for the effectiveness of CBT. However, there is growing support for the use of treatments based on acceptance and commitment therapy (ACT) for patients with chronic pain.Interdisciplinary pain rehabilitation (IPR) programmes have been reported to show positive long-term results. Two systematic reviews found that IPR produces better results than less extensive treatment or no treatment at all,13 One systematic review (2017) found that ACT was more effective than controls in clinical settings . However, a review and meta-analysis by Ost (2014) found only a small and non-significant effect size of 0.16 when ACT was compared with different CBT treatments. Most studies of ACT and CBT for patients with chronic pain have examined the effects after psychological interventions, not after interventions conceptualized as IPR. Therefore, a multicentre study was designed to compare CBT-based IPR programmes with ACT-based IPR programmes. Three centres located at university hospitals in different geographical regions in Sweden participated in the study.ACT aims to improve function by increasing psychological flexibility. Studies have shown positive results after ACT treatment for disability, depression, anxiety and physical functioning.The study aim was to compare the results of an ACT-based IPR programme with two CBT-based IPR programmes using data from matched individuals registered in the Swedish Quality Registry for Pain Rehabilitation (SQRP). The research questions were a) Are there improvements in quality of life, level of pain acceptance, anxiety and depression after IPR? b) Do these improvements differ according to the approach used (ACT-based versus CBT-based IPR programmes)?A retrospective multicentre pretest–posttest design with three matched patient groups was used. All patients participated in interdisciplinary rehabilitation programmes for long-term musculoskeletal pain. This study was performed in accordance with the Declaration of Helsinki, and the regional ethics review board approved the study (Dnr 2012/644-31/3). The study reporting conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.Most specialized pain rehabilitation centres in Sweden report data to the SQRP. The effects of IPR have been continuously evaluated by the SQRP since 1998. The SQRP questionnaire includes items on sociodemographic factors , pain duration, pain intensity and pain location, as described by Nyberg et al.The power estimation was based on the EuroQOL health-related quality of life questionnaire (EQ-5D) index values. For a design with two repeated measurements, an average 0.2 point increase, a standard deviation of 0.3, a p-level of 5% and two-tailed tests, 40 patients in each group were needed to obtain an 80% chance of detecting differences between the two groups. This sample size ensured a good chance of detecting small-to-medium-sized differences between the groups.i) disabling chronic pain ; (ii) aged 18 to 65 years; (iii) no further medical investigations needed; (iv) written consent for participation in the programme. Exclusion criteria were (i) ongoing major somatic or psychiatric disease; (ii) a history of major substance abuse or acute crisis.After initial assessment, all participants completed a rehabilitation programme at one of the three interdisciplinary pain centres from January 2009 to December 2011. The patients were mostly referred from primary care or occupational health care. The centres are in the south (Centre 2), middle (Centre 1) and north (Centre 3) of Sweden. Inclusion criteria at the time of data gathering were  age categories , (iii) country of birth (Sweden/Nordic countries vs. other countries), (iv) education level (primary school vs. secondary school/university level), (v) depression categories according to the Hospital Anxiety and Depression Scale (HADS)  and ratings of pain using a numeric rating scale (≤7 vs. >7). An SQRP statistician performed the matching procedure. The matching was performed by identifying suitable subjects comparable with the Centre 1 (middle region of Sweden) patients, who had participated in an IPR programme based on ACT. In contrast, the patients in Centres 2 and 3 (southern and northern regions) had participated in IPR programmes based on CBT. The SQRP database included 989 possible patients who ended their rehabilitation during the period January 2009 to December 2011. Of these, only 367 met the selection criteria; of the 367, a further 169 patients could not be matched to Centre 1 patients and were therefore excluded. This left 198 patients: 66 matched patients in each centre. Some of the patients in the 66 pairs identified had incomplete data (admission or discharge data); therefore, 44 pairs were identified who had high response rates on the SQRP questionnaire  score 95.5%–97.7%; Chronic Pain Acceptance Questionnaire (CPAQ) score 86.4%–97.7%); that is, 132 unique patients. The nearest neighbour matching procedure was used, ensuring the selection of individual patients with the smallest distance between them (i.e. high similarity). Each patient could only be used once to construct one pair .It is important to select appropriate covariates to include in the matching process. Matching variables were selected from those used in previous research on prediction of rehabilitation results and return to work. Registry data are collected before and after participation in a rehabilitation programme. Because chronic pain is a complex condition that is affected by several interacting factors, instruments included in the SQRP questionnaire were used to measure health-related quality of life, acceptance of chronic pain, depression and anxiety. In the present study, analyses were performed on data from the EQ-5D, the CPAQ and the HADS.Data were collected from the SQRP.23 The EQ-5D is widely used to assess a variety of medical conditions and treatments. It provides a simple descriptive profile and a single index value for health status. The five EQ-5D dimensions are mobility, self-care, usual activities, pain/discomfort, and anxiety or depression. Each dimension has three levels  comprising 243 possible health states. The EQ-5D index score ranges from −1.0 to 1.0; a score of 1.0 indicates optimal health. A global self-rated health value is obtained using a VAS ranging from 0  to 100 .The EQ-5D is a standardized instrument that measures health-related quality of life. The same study showed that people with neck/shoulder or low back pain had a lower EQ5D index score (0.66 to 0.70).The mean EQ-5D index score for the Swedish population aged 40 to 49 years is 0.86 (n = 2.870). Each item is rated on a scale from 0 (never true) to 6 ; higher scores reflect greater acceptance of pain. The CPAQ has repeatedly demonstrated good psychometric properties.26 The psychometric properties of the Swedish version of the CPAQ used in this study are similar to those of the original English scale.The CPAQ is a 20-item questionnaire designed to assess acceptance of chronic pain. The CPAQ contains 20 items that reflect activity engagement (doing activities in the presence of pain) and pain willingness (refraining from attempts to control or reduce pain). The items are rated on a 4-point Likert scale (0–3). Both the original English version and the translated Swedish version of the scale have demonstrated satisfactory validity and reliability.The HADS is a 14-item questionnaire used to identify symptoms of anxiety and depression  in hospital inpatients.The interdisciplinary pain team performed the interdisciplinary assessment at all centres using a biopsychosocial approach. Assessed patients were referred to the tertiary centres because of the complexity of their condition. Patients were individually interviewed and examined by each team member according to standardized protocols. The assessment day(s) led to recommendations, one of which was to undergo a rehabilitation programme at the centre.There were some differences between the centres in length of the assessment period (1–3 days), the professions involved in the assessment team  and the procedure used to discuss findings with patients .The programmes in all centres were implemented in groups consisting of 8 to 10 participants. Rehabilitation was based on interdisciplinary team collaboration, and the patient was considered an active team member. Several core sessions were conducted in group settings in all centres. The patients were also given individual activities and contacts according to their individual goals. Based on each patient’s needs and with the patient’s agreement, at the end of the programme contacts were made with external collaborating partners such as workplaces, the Swedish Social Insurance Agency and the patient’s general practitioner. we determined that all centres provided a high-intensity IPR with more than 100 hours of rehabilitation. In a 2020 study, Rivano-Fischer et al. investigated differences in the severity of patients’ problems between university hospital units and other units in all regions in Sweden. They found that patients in university hospital centres had significantly lower EQ5D index scores than those in medium units (p = 0.004)  and lower EQ-VAS  scores than those in large units (p < 0.001) . The three centres used in the present study are all at the university hospital level.The three centres were compared on variation in the number of days of rehabilitation, number of days per week and number of hours per day. Using previously proposed intensity categories, and a manual was used as a framework for the interventions. The focus was on building up a behavioural repertoire in valued life directions, rather than emphasizing reductions in pain and distress. Weekly, the rehabilitation team emphasized one of the dimensions according to the manual . Typically, two team members (e.g. a psychologist and a physiotherapist) worked together. This model has been successfully used in team-based pain rehabilitation.3436 The team received ongoing tutoring from the ACT manual during the first 2 years. The 8-week rehabilitation programme was considered high-intensity IPR (>100 hours) and was mostly group-based, with the potential for individual adaptations during specific sessions and individual sessions if needed. The programme included physical training, body awareness training, exposure training, activity-based exposure and training, activity balance training, creativity groups and group therapy. The programme was provided on 3 days/week for 6 hours/day.The rehabilitation programme was standardized according to ACT principles The programmes were provided 5 days/week, 6 to 7 hours/day, and were considered high-intensity IPR programmes (>100 hours).The outpatient rehabilitation programmes at Centres 2 (4 weeks) and 3 (5 weeks) were based on cognitive–behavioural principles and focused on pain management, education about pain and its consequences, and bodily and psychological reactions to pain. The programmes included physical and occupational therapy, information and training on coping strategies, information about bodily and psychological reactions to chronic pain, relaxation and body awareness training. Other sessions included in the programme addressed ergonomics and education about pain mechanisms and their consequences. Except for the programme duration and number of participants, the only differences between the IPR structure in Centres 2 and 3 were that Centre 2 exhibited a stronger tendency toward group-based interventions than Centre 3 and that contacts with other stakeholders in Centre 2 were made based on individual needs.Data were analysed using SPSS Statistics for Windows, Version 17.0. . Non-parametric statistical methods were used because all data were measured using ordinal scales and the sample was small. Basic descriptive statistics were also calculated to determine whether there was a significant difference between the three rehabilitation settings (Friedman test). Any significant differences found were examined using Wilcoxon’s signed rank test to test for differences between Centre 1 and Centre 2 and between Centre 1 and Centre 3. Changes within each centre’s pre- and post-rehabilitation programme were investigated using the Wilcoxon signed rank test.Demographic information  for patients in all centres is shown in There were significant differences at baseline between Centres 1, 2 and 3 on EQ index score; subjects in Centre 1 tended to score lower than subjects in Centres 2 and 3 . There were also significant differences at baseline between Centres 1 and 2 on HADS depression score ; subjects in Centre 1 scored lower than subjects in Centre 2. There were significant differences between Centres 1 and 3 on CPAQ pain willingness  and HADS anxiety score (Wilcoxon signed rank test: n = 39 p = 0.004); subjects in Centre 1 tended to score lower than subjects in Centre 3 (p = 0.053) .The Centre 1 participants had improved significantly at discharge on all assessments; that is, they experienced greater acceptance of pain (doing activities despite the presence of pain [p < 0.001] and refraining from attempts to control or reduce pain [p < 0.001]), better reported health status (p = 0.039), better quality of life (p = 0.034) and less anxiety (p < 0.001) and depression (p < 0.001). Almost the same improvements were reported for Centre 2, except for EQ-5D index score, which did not significantly improve. Improvements were also noted in Centre 3, whose patients increased their activity engagement (p = 0.001) and had lower depression at discharge (p < 0.001) .Health-related quality of life and depression level were not affected by the type of rehabilitation programme. However, there was a significant difference in anxiety score changes between admission and discharge between Centres 1 and 3 (p = 0.039) . There wThe present study, which used matched comparison groups, showed that IPR with both ACT and CBT interventions improved important health-related parameters in patients with chronic pain. The main difference between the psychological approaches used as a basis for IPR was in the scores on the CPAQ subscales activity engagement and pain willingness. Only patients from Centre 1, who received the ACT-based IPR, reported improvements on both subscales, suggesting that IPR based on ACT methodology increases pain acceptance more than CBT-based IPR.The baseline data suggested that patients in Centre 1 were admitted to IPR with poorer health-related quality of life and experienced greater depression and anxiety than patients in Centres 2 and 3. However, patients in Centres 1 and 2 improved on almost all the included variables, and patients from Centre 3 showed improvements on two variables. These results suggest that IPR based on both the ACT and CBT methodologies produces substantial improvements on several important health-related areas, although some differences may exist. Even though CBT has been the leading psychological treatment for patients with chronic pain, only small to medium effect sizes have been found for CBT interventions compared with controls. Wetherell et al. (2011) found few differences between ACT and CBT, although a few measures showed small effects in favour of CBT.A recent meta-analytic review of acceptance and mindfulness-based interventions found small effects for pain intensity, depression, disability and quality of life. However, a moderate effect was found for anxiety and pain interference.The present findings demonstrated that different psychological-based IPR programmes had a positive effect on several important areas of health. Targeted areas such as pain acceptance showed greater improvement after the ACT-based programmes.Centre 1 used a protocol-driven ACT intervention at the time of observation, whereas Centres 2 and 3 followed the CBT chronic pain model. However, because research in ACT methodology is developing progressively, the possibility cannot be ruled out that Centres 2 and 3 incorporated some ACT-related principles into their interventions, at varying degrees, at the time of data collection; Centres 2 and 3 did not use any ACT manual, training or supervision at the time of this study.An important aspect of using matching methods is to determine the quality of the resulting matched samples. All matching should be followed by an assessment of the covariate balance in the matched groups, where balance is defined as the similarity of the empirical distributions of the covariates in the matched groups. In the present study, the three matched groups were considered to be balanced. However, the matching procedure was fraught with difficulties. For example, more patients in Centre 3 were of higher education level, and fewer were immigrants, than patients in Centres 1 and 2. The matching procedure started with a large number (989) of patient participants in the IPR programmes and resulted in 132 suitable patients (44 pairs), which indicates a problem with the design used. This may be because the patients participating in the ACT programme served as a basis for identifying eligible pairs; we searched for complete patient data and used several inclusion criteria. We reduced bias by not using multiple controls for each patient at Centre 1.To summarize, this study demonstrates the effectiveness of psychological approaches for the management of chronic pain. Both CBT and ACT are effective in improving important health-related parameters in patients with chronic pain. However (and not unexpectedly), ACT seems more effective in increasing acceptance of chronic pain, a concept that is foundational to ACT but not to CBT.To compare ACT-based versus CBT-based IPR, patients at three centres were matched on five key variables that are confounding factors for pain rehabilitation outcomes. These variables were age, education level, country of birth, level of depression/anxiety and perceived pain intensity levels. However, although the matching procedure was carefully conducted, an important confounding variable may have been missed and some variability may not have been controlled for. Additionally, the lack of randomization may have reduced the internal validity (making it more difficult to differentiate the rehabilitation programmes in terms of their effectiveness).After matching, the sample size was rather small, which may have affected the reliability of the cause-and-effect relationship found. Non-parametric statistical methods were used because of the small sample size. were university clinics and followed the SQRP regulations on pain rehabilitation. The study was conducted in centres in the southern, central and northern parts of Sweden, which helped to avoid sociogeographical biases. However, we cannot rule out the possibility that some regional differences affected the results.Furthermore, the three centres did not follow one unified protocol (except for choosing between ACT and CBT); thus, other variables may have affected the results. However, although the treatment duration varied between the three centres, they shared important characteristics that ensured that the IPR delivery was generally similar: all provided high-intensity IPR programmes (>100 hours), were accredited by the Commission of Accreditation of Rehabilitation Facilities,This study demonstrated the effectiveness of psychological approaches in the management of chronic pain and their effect on important health-related parameters. Both CBT and ACT had a beneficial effect on most of the parameters measured.


This quality improvement project (QI) focused on reducing procedural pain. Phase I of this project demonstrated a need to improve our patients' and nurses’ satisfaction with pain control management during hydrotherapy. In this phase (Phase II), we educated the nursing staff on 1) appropriate dosing and timing of opioid administration  and 2) need for more frequent midazolam administration before hydrotherapy. We also assessed the safety and potential benefits of ketamine for procedural pain control.Patients undergoing wound cleaning procedures were surveyed for up to three hydrotherapy encounters. Nurses were educated on procedural pain control prior to this current phase. A convenience sample of patients underwent ketamine administration. Ketamine was administered per protocol starting at 0.3 or 0.4 mg/kg with intermittent boluses of 0.25 mg/kg as needed. Demographics, opioid , midazolam, and ketamine doses and time of administration, and adverse events were collected. Patient pain scores (1-10) before and after hydrotherapy and patient and nurse satisfaction scores (1-10) after hydrotherapy were collected. Paired t-tests and one-way ANOVA were performed. P < 0.05 was considered significant.During Phase II, 9 patients and 19 encounters were analyzed; of which ketamine was administered for 10 events. Compared to Phase I (28 Patients and 50 encounters), education of the nursing staff resulted in a significant improvement in giving midazolam prior to hydrotherapy  and opioid administration . Timing of opioid administration did not improve when compared to Phase I . Both patient  and nurse  satisfaction scores regarding pain control improved. None of the patients who received ketamine experienced adverse effects. Notably, the use of ketamine improved nurse satisfaction scores with patient pain control . While patients on ketamine were more satisfied with pain control, significance was not reached .Our data demonstrate that nurse education regarding medication administration was effective, but further education is needed to improve the timing of opioid administration. Ketamine offers additional benefits that deserve additional study.


The treatment tolerance was also evaluated. Eighteen patients  were analyzed. At baseline, hand pain VAS was 60 mm  and FIHOA 15 . After 4 weeks, taVNS significantly reduced hand pain VAS, with a median decrease of 23.5 mm  (p = 0.001), as well as FIHOA, with a median decrease of 2 points  (p = 0.01). No serious adverse events were reported. One patient stopped taVNS because of auricular discomfort. This first proof-of-concept trial indicated that taVNS is feasible and may decrease joint inflammation and clinical symptoms in EHOA, arguing for a randomized controlled study versus sham stimulation.Beyond its effect on vegetative functions, the activation of the vagus nerve inhibits inflammation and reduces pain signaling. The aim of this open-label pilot study was to determine the efficacy and tolerance of transcutaneous auricular VNS (taVNS) on erosive hand osteoarthritis (EHOA) symptoms. Symptomatic EHOA patients with hand pain VAS ≥ 40/100 mm and ≥1 interphalangeal swollen joint(s) were included. The taVNS was performed for 4 weeks using an auricular electrode applied one hour per day and connected to a TENS device with pre-established settings. Clinical efficacy was evaluated by changes between baseline and at 4 weeks with hand pain VAS and the functional index FIHOA score, using a Wilcoxon  Erosive hand osteoarthritis (EHOA) represents around 10% of symptomatic HOA patients, and is more frequently observed in tertiary specialized centers i.e., 25–55%) [5–55% [2]The vagus nerve (VN) is the main nerve of the parasympathetic system. In the 2000s, Tracey and colleagues deciphered the “cholinergic anti-inflammatory pathway” in which vagal afferent fibers activate vagal efferent fibers that thereby decrease systemic inflammation. This effect is mediated through the release of acetylcholine binding with one of its receptors, the α-7 nicotinic acetylcholine receptor, expressed on macrophages, and whose activation inhibits cytokine production . AfferenConsidering taVNS’s efficacy on pain and inflammation as well as its safety profile, we hypothesized that taVNS using a transcutaneous electrical nerve stimulation (TENS) device could be a new treatment for symptomatic EHOA, a subtype of painful and inflammatory arthritis . This fiThis was a monocentric open-label study evaluating the efficacy and the safety of taVNS in symptomatic inflammatory EHOA (NCT03919279).Patients aged ≥18 years, with hand OA defined according to the American College of Rheumatology criteria , with ≥1Exclusion criteria were isolated thumb base OA, other rheumatic diseases, local auricular diseases, ECG abnormalities, symptomatic orthostatic hypotension, or history of recurrent vagal syncope. Patients who were using NSAIDs were told to stop using them at least 48 h before inclusion. The complete list of exclusion criteria is provided in the online Since this study is the first one assessing VNS in OA (including EHOA), it was not possible to calculate a sample size. Moreover, due to the pilot design of the trial, we arbitrarily determined the number of patients to be included.The procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Comité de Protection des Personnes OUEST 1 number 2019T2-09) and with the Helsinki Declaration of 1975, as revised in 2000. All patients gave their written informed consent.Before inclusion, patients were given explanations regarding vagus nerve innervation of the ear and the goal of this study. At inclusion, radiographic erosive status was documented by hand radiographs performed within the two years before inclusion and was confirmed by a rheumatologist expert in HOA. ECG and research of orthostatic hypotension were performed before taVNS. TaVNS was performed by the application of an auricular electrode  placed at the cymba concha of the left ear. The auricular electrode containing the anode was applied with a conductive gel without prior disinfection  and was connected to a TENSeco2 device  . All patThe primary endpoint was 0–100 mm hand pain VAS at 4 weeks. Each patient was asked, ”How much pain in your hand did you experience during the last 48 h?” as recommended by the OARSI . Secondat-test. The comparison also included FIHOA, the number of painful and swollen joints, the cardiac frequency, and blood pressure. Side effects were reported by frequency and percentage. Proportions  of patients reaching the PASS and MCII were calculated. All tests were two-sided and a p-value < 0.05 indicated statistical significance. Statistical analysis was performed using GraphPad Prism 8.2.1, San Diego, CA, USA.Continuous variables are presented as median and interquartile range. Qualitative variables are presented as frequency and percentage. Comparison for hand pain VAS between baseline and 4 weeks was performed using the paired Wilcoxon Twenty patients were included between May and October 2019. Two patients were lost to follow-up after the first session at hospital (not for safety issues). Thus, 18 patients (83% women) were analyzed.p = 0.19).Baseline hand pain VAS was 60 mm  . As shown = 3) or local transient pain (n = 3). The other adverse events are reported in n = 10) or mild (n = 3), and transient (n = 8). Three adverse events were not considered related to the device or the stimulation . One of the 18 patients stopped taVNS 5 days after the inclusion because of local discomfort. No patient developed orthostatic hypotension.Eight patients reported 13 adverse events . There wThis is the first proof-of-concept study evaluating the feasibility of VNS in OA. We observed a symptomatic efficacy of taVNS in EHOA. After 4 weeks of stimulation, patients had a significant reduction of pain, painful and swollen joints and of their functional impairment. However, we cannot rule out a placebo effect since there was no control group. Treatment tolerance was good without any serious adverse events, which encourages a randomized and sham-controlled trial.Since pain and inflammation are typical features of EHOA, we hypothesized that taVNS could be a valuable therapeutic strategy for this OA subtype. After 4 weeks of taVNS, 55% of patients reached the PASS and 72% the MCII for pain, suggesting a symptomatic effect in EHOA. Eight patients reported side effects, but most of them were transient and considered minor. The most frequent adverse event was a local auricular discomfort such as tingling or a local transient pain, which led to only one discontinuation . Such a Previous taVNS studies have demonstrated a clinically relevant efficacy in RA, Sjogren syndrome or lupus ,34,35,36Transcutaneous VNS is a new field of research and can be done at the ear or at the cervical branch ,38. SincHowever, this pilot study has limitations. First, it was an open-label trial and therefore a placebo effect cannot be ruled out—especially with a device such as TENS, which could have the same or a higher placebo effect than oral placebos . RegressThis pioneering proof-of-concept study suggests that 4 weeks of taVNS treatment is feasible, safe and capable of alleviating symptoms and clinical inflammation in subjects with symptomatic EHOA. A randomized controlled trial versus sham stimulation is necessary to confirm these encouraging results for this neglected disease.


Currently, there are new trends in orthodontics that are increasingly being used in clinical practice, such as aligners. It is important to know the influence of pain perception in orthodontic patients in order to be able to apply less painful and more comfortable techniques for patients. The advancement of different fixed and removable appliances, using precision digital fabrication methods, is increasingly harnessed in the daily life of our society. Negative experiences such as periodontal pain can cause the rejection of orthodontic treatment. Therefore, the study of the location, intensity and type of pain according to the different techniques is beneficial for improving the quality and success of orthodontic treatment. The objective of this prospective clinical study was to analyze the pain  that patients presented after the placement of different types of orthodontic appliances: conventional, low friction, lingual and aligners. The sample consisted of 120 patients divided into four groups: conventional (CON), low friction (LF), lingual (LO) and aligners (INV). The participants were given the Short-Form McGill Pain Questionnaire (Ortho-SF-MPQ), where they had to record the pain intensity  and the periodontal location at different time points, from the first 4 h to 7 days after the start of treatment. In all the study groups, the most frequent location was both anterior arches, with maximum values between 56.7% (CON group at 24 h) and 30% (LO group at 4 h). The “whole mouth” and “complete lower arch” locations were indicated only by the patients in the lingual group. Regarding pain intensity, the patients reported a higher percentage of mild–moderate pain during the first 3 days of treatment ; later, the reported pain decreased to no pain/mild pain, especially in the lingual group, until reaching values close to zero at 7 days post-treatment. The most frequent type of pain was acute in the low friction and lingual groups . On the contrary, in the conventional (36.7% at 4 h) and Invisalign (40% at 24 h) groups, the sensitive type was the most frequent. There are differences regarding periodontal pain in its intensity, location and type according to the use of different orthodontic techniques. There are new orthodontic techniques, such as aligners, that should be compared with conventional techniques. According to patients, dental treatments are associated with suffering a certain degree of pain. We found that 77% of patients suffered pain during visits to orthodontists  and 6% oPatients describe the sensation of pain and discomfort as pressure, tension, pain in the teeth and general pain . If we aMost of the authors consulted consider that the pain experienced by patients and the discomfort associated with orthodontic treatment will have a negative influence on the quality of their oral life ,27,28,29In the literature, we find that most of the studies that analyze the location of pain with the different techniques do so by comparing pain in the mucosa, lips and tongue. The results show that there would be greater lingual pain in lingual orthodontics and greater labial and vestibular pain in conventional vestibular orthodontics ,31. Wu eFor measuring pain, the McGill Pain Questionnaire (MPQ) can be used, since it measures the three dimensions of pain according to Melzack: sensory, affective and evaluative . Our stuThe importance of this study lies in the possibility of comparatively assessing the characteristics of pain that our patients present after the placement of orthodontic appliances at the level of periodontal pain. Knowing if there are differences in intensity and type of pain would allow us to gain another point of consideration when choosing the type of appliance to be placed. The increased demand for aligners in recent decades has led to their comparison with the latest vestibular and lingual bracket systems, together with the use of high-precision digital tools. Therefore, they were analyzed in the present clinical study in reference to perception of periodontal pain.The null hypothesis of our study is that there are no differences in periodontal pain in terms of location, intensity and type in patients with different orthodontic techniques.A clinical study was carried out to analyze pain perception in patients with fixed and removable orthodontics. All the participants were informed about the protocols and agreed to participate voluntarily. The participants chose and knew the type of equipment with which they were going to be treated. In total, there were 120 participants, of which 55% were women (66) and 45% men (44). None of the participants who consented to the study withdrew during its development. This work followed the guidelines established by the Declaration of Helsinki for human research; the project was approved by the bioethics committee of the University of Salamanca (USAL_16/060) and was carried out during the first semester of 2020.This prospective clinical study was carried out on 120 patients, a sample size similar to other published studies ,15. To dThe sample was divided into four study groups of 30 people each.®, 3M, Rogers, AK, USA).Group 1: Vestibular conventional brackets—CON .Group 2: Vestibular low friction brackets—LF .Group 3: Lingual brackets—LO .Group 4: Aligners—INV ; with a negative tooth size–arch length discrepancy (TSALD) between −6 and −2 mm ; those wAfter the placement of the appliances, the patients received a Short-Form McGill Pain Questionnaire (Ortho-SF-MPQ), consisting of a drawing of the two dental arches where they had to highlight the location of the pain suffered and a questionnaire where they were to fill in the intensity  and the type of pain . For a better understanding of the results regarding the type of pain, those with a percentage higher than 15% were considered . The remaining types of pain, due to their low individual incidence, were considered as a single group labeled “other types of pain” ,38. Both questionnaires were clearly explained to the participants before starting the treatment to ensure they completely understood them, and they were asked to fill them in at different times after the placement of the appliance: 4 h (T4h), 8 h (T8h), 24 h (T1), 2 days (T2), 3 days (T3), 4 days (T4), 5 days (T5), 6 days (T6) and 7 days (T7) ,39. For analysis of the location, according to the areas marked by the patients  and to delineate them better it was decided to divide them into upper arch (anterior and/or posterior), lower arch (anterior and/or posterior), pain in both arches (anterior and/or posterior), pain in the entire mouth and pain in the entire lower arch. p < 0.05, as statistically significant and p < 0.01 as highly significant.To analyze the data, we used the SPSS v. 20 software . Mean and standard deviation were used to describe the distribution of the quantitative variables of the studied population. For the nominal and ordinal data, the sample distribution (the number of patients and the corresponding percentage) was determined. To compare two or more nominal or ordinal distributions, the Chi-square test was performed. Two statistical significance levels were established After analysis of the 120 participants, it was found that the sample’s mean age was 30.0 ± 7.5 years. The degree of crowding presented by the patients was also analyzed prior to treatment, finding no statistically significant differences between the groups .p < 0.05), and at 4 h, 24 h, 2 days, 3 days, 5 days, 6 days and 7 days (p < 0.01)  .The most frequent location reported by all the patients was “both anterior arches”. The maximum value was found at 4 h in the LO (30%) and INV (53.3%) groups and at 24 h in CON (56.7%) and LF (50%). The next most frequent locations of pain were “maxillary anterior” and “mandibular anterior” .We found that the types of pain “whole mouth” and “complete lower arch” were only referenced by lingual orthodontic patients with a maxima of 13.3% at 24 h and 16.7% at 8 h, respectively.In As in the previous case, we found that, at the level of the anterior maxilla, the LO group presented a lower percentage of patients with pain in this location than the other three groups, although with less difference. The LF group suffered a decrease at 24 h and an increase at 7 days in contrast to the CON and INV groups, where the number of patients with pain increased in this location at 24 h and decreased after 7 days of treatment .In p < 0.05) and between T3 and T7 (p < 0.01). However, we did not find statistically significant differences at 8 h and 2 days after the placement of the appliances  rated their pain as mild (46.7%) and moderate (40.0%), compared to a mild intensity in the other three study groups (60.0% in LF and LO and 66.7% in INV). The level of pain increased in all groups to mild/moderate up to the fourth day of analysis. After 5 days of analysis, the percentage of patients without pain in the lingual orthodontic group was significantly higher than that in the other three treatment groups . p < 0.01. In the first 24 h of analysis, “acute pain” was the most frequent type of pain in the low friction groups and in lingual orthodontics, followed by “sensitive pain”. In contrast, in the conventional and Invisalign groups, the most frequent type of pain referred to by patients was “sensitive pain”. Subsequently, these groups reported a more “stabbing and throbbing” pain in the case of the conventional group, and a type of “acute pain” in the Invisalign group  behaved similarly to the rest of the techniques in terms of location and degree of pain.