The current study evaluated the effectiveness of VR analgesia among pediatric and adolescent patients with kidney disease undergoing venipuncture. Patients at an Italian Children’s hospital  undergoing venipuncture were randomly assigned to a No VR group  vs. a Yes VR group . After the procedure, patients gave 0–10 Verbal Numeric Pain Scale ratings. Compared with patients in the No VR Group, patients in the Yes VR group reported significantly lower “Pain intensity” and the VR group also rated “Pain unpleasantness” significantly lower than the No VR group . Patients distracted with VR also reported having significantly more fun during the venipuncture procedure. No side effects emerged. In addition to reducing pain intensity, VR has the potential to make venipuncture a more fun and less unpleasant experience for children with CKD, as measured in the present study for the first time. Finally, in exploratory analyses, children aged 7–11 in the VR group reported 55% lower worst pain than control subjects in the same age range, whereas children aged 12 to 17 in the VR group only reported 35% lower worst pain than control subjects. Additional research and development using more immersive VR is recommended. Pediatric pain management in hospitals is a priority ,2. ThereWhy are most children afraid of needles when venipuncture often lasts only a few seconds or a few minutes at most? Pain intensity can be strongly influenced by psychological factors, which can amplify how much pain patients subjectively experience. Anticipation that a venipuncture is going to be painful can amplify the nociceptive signal, increasing pain-related brain activity . Fear caVirtual Reality (VR) is emerging as a promising distraction technique for children’s pain management . ImmersiFor children suffering from chronic diseases, such as chronic kidney diseases (CKD), venipuncture is an essential procedure periodically needed for checking their medical condition. Chronic kidney disease can range from mild to end-stage renal disease, requiring dialysis or transplantation because of kidney failures ,25, and The current study was conducted in the Service of Nephrology and Dialysis at a Children’s hospital in Italy. From November 2017 to April 2018, patients undergoing venipuncture for their periodic blood analysis were recruited. Patients aged 7–17 years with different kidney diseases and who were able to understand Italian language and to complete the tests were selected with the help of a nurse. According to the exclusion criteria adopted in previous VR studies, we excluded children who were unable to wear the helmet and interact with the VR environment, with a diagnosis of epilepsy, with physical or psychological impairments, and participants not accompanied by their legal caregivers [The protocol was accepted by the ethical committee of the hospital. The study was approved by doctors and nurses of the Service of Nephrology and Dialysis and conducted in collaboration with the Service of Pediatric Psychology and the Service of Pain Therapy and Palliative Care. Patients meeting the inclusion criteria and their families were approached by the psychologist researcher in the waiting room in order to determinate their interest. Interested patients and their parents  were accompanied by the psychologist researcher into the room of the procedure to complete the written informed assent/consent forms. Using computer-generated random-number sequences obtained from a statistician not involved in data collection, patients were randomly assigned to either the No VR group or the VR group. For both the No VR and the VR group, the parent/legal guardian remained in the room for the entire medical procedure. The No VR control group  consisted of non-medical conversation by the nurse who performed venipuncture with the patient. In the Yes VR group , patients interacted with VR during venipuncture. Before the beginning of the procedure, patients in the VR group received 5 min of instructions to learn how to wear the helmet and to interact with the VR environment, with the help of the psychologist researcher. The helmet and the earphones included in the VR system were worn immediately before the beginning of the venipuncture and removed immediately after the end of the blood draw. In both groups the nurse remained in the room all the time as usual.= extremely fun; Hoffman, Sharar, Coda et al., [Worst pain, the primary outcome measure, was assessed at the end of the venipuncture, using a 0–10 Verbal Numeric Rating Scale. Participants were asked to rate their worst pain during the venipuncture (0 = “No pain” to 10 = “Excruciating pain”). Verbal Numeric Rating Scales have been validated for use in children aged 6 and higher . Accordi et al., ), and th et al., , adapted et al., ); and pa et al., ).The VR equipment consisted of a VR helmet, the Personal 3D Viewer Sony: HMZ T-2, supported by a laptop, which allowed the interaction with the VR environment. The helmet had a 45° diagonal field of view, 1280 × 720 pixels per eye, and was suitable for younger patients. The VR helmet had two miniature screens, one for each of the user’s eyes, and earphones to provide acoustic isolation and increase presence in VR, the illusion of “being there” in the computer-generated world as if it is a place they are visiting. The VR software used was called SnowWorld see , one of t-tests and chi-squared analyses were used to compare demographic variables in the two groups. A t-test for independent samples was used to compare pain, fun, and nausea between the No VR group and the Yes VR group. A researcher not involved in data collection generated the random-number sequences used for random assignment to groups, and carried out data analysis using the statistical Software SPSS 25 . Results were considered significant when associated with p values less than 0.05.Descriptive statistics were used to characterize the study sample and to describe the % reduction in worst pain in children aged 7–11 vs. 12–17; Eighty-two patients  took part in the study and were randomly assigned to the control or experimental group. None of the patients had previously used a VR system, except two males in the experimental group: one had an HTC VIVE VR system at home and the other one had played a videogame with a pair of Sony VR goggles in an arcade. Sample demographics variables are reported in Worst pain”: No VR group mean 2.74, SD = 2.76 vs. Yes VR group mean 1.56, SD = 1.83; t(80) = 2.29, p < 0.05), and “Pain unpleasantness”: No VR group mean 2.41, SD = 2.9 vs. Yes VR group mean 1.17, SD = 1.80; t(80) = 2.31, p < 0.05. The predicted pattern of higher mean levels of the cognitive component of pain (“Time spent thinking about pain”) was reported by patients in the No VR group vs. Yes VR group. However, the difference was not significant (p > 0.05) for this variable. As shown in t(80) = 6.14 (p < 0.001). No significant differences emerged for nausea levels between the two groups (p > 0.05): in both groups, patients reported mean levels of nausea less than 1 .A significant difference for fun levels emerged between the two groups: No VR group mean 4.06 (SD = 3.74), vs. Yes VR group mean = 8.06 (SD = 1.85), On a scale from 0 to 10, where 10 = “I went completely into the computer generated world”, patients who interacted with VR reported a mean presence score of 7.11 (SD = 3.00). On a scale from 0 to 10 where 10 = “indistinguishable from a real object”, mean realism of VR objects was 6.05 (SD = 3.12). Seventy-one percent of patients reported presence levels higher than 5  and the 29% of the patients reported presence levels lower or equal to 5. Sixty three percent of patients also reported a score higher than 5  when asked “How real did the objects in the virtual world seem to you”.In post-hoc exploratory analyses see , patientThe current study aimed to evaluate VR as a distraction technique for pain management in children with chronic kidney disease undergoing venipuncture. As predicted, children and adolescent patients with kidney disease reported a significant reduction in pain intensity (worst pain) when they used VR compared with the No VR group. Results showed for the first time in CKD patients that in addition to reducing sensory  pain, VR distraction was also useful for managing the emotional component of pain as indicated by the significantly lower levels of pain unpleasantness and significantly more fun during venipuncture reported by patients in the Yes VR group compared with the patients in the No VR control group. Patients who used VR also reported the predicted pattern of lower “Time spent thinking about pain” levels, however the difference between the control and the experimental group was not significant for this variable.The results of our primary outcome measure (worst pain) are in line with the recent results of Piskorz and Czub’s study, where pediatric patients of a nephrology clinic undergoing venipuncture and distracted with VR reported significantly lower levels of pain and stress compared with patients in the No VR control group . The curBeginning with the first study on immersive VR analgesia ,36, a nuAlthough subjective pain ratings are considered the gold standard of pain measurement, neuroimaging studies provide converging evidence to support the claim that VR reduces pain. fMRI brain scan studies have begun to explore changes in pain-related brain activity during VR vs. no VR during brief painful thermal pain stimuli at a safe, painful but tolerable temperature. In addition to reducing participants’ subjective experience of pain during VR vs. No VR, fMRI brain scans showed significant reductions in pain-related brain activity in all five brain regions of interest,  .In the current study, the significantly higher levels of fun reported by patients who used VR during venipuncture suggest that VR distraction can promote positive emotions and can help patients cope with the painful procedure. Some researchers speculate that VR reduces pain perception not only through a cognitive modulation , but also through an emotional activation (eliciting pleasure emotions). Hoffman, Sharar, and Coda et al.,  introducThe current study has some limitations: fear was not measured, and pain was only assessed during a single venipuncture, an important limitation. As mentioned earlier, children with chronic diseases typically have numerous venipunctures during their treatments. Whether VR continues to be effective during successive venipunctures per patient is an important research question. Previous studies with pediatric burn patients during wound cleaning suggest that VR continues to be effective when used during several treatments per patient ,45,46. AAlthough the VR system used in the current study is relatively high tech compared with the earlier studies , much moThis study contributes to a small but growing literature that supports the use of immersive virtual reality (VR) distraction as a psychological technique for pain control during venipuncture in patients with chronic kidney disease. VR significantly reduced worst pain, pain unpleasantness, and significantly increased fun during venipuncture. The patients in the current study also reported a strong illusion of going inside the computer-generated world during VR . The current study also provides the first exploratory post-hoc analyses showing a 55% reduction in worst pain during VR in patients aged 7–11 vs. a 35% reduction in worst pain during VR in patients aged 12–17, inconclusively raising the question of whether VR is more effective at reducing the pain of younger children vs. teenaged children, an interesting topic for future research.Beyond distraction, future studies may explore new ways of improving well-being and health support in children affected by chronic diseases, e.g., breathing exercises, VR mindfulness coping skills ,56,57,58


BackgroundHip fractures are the most frequently occurring serious injury in older people. They are the most common reason for people over the age of 65 to need emergency anaesthesia and surgery, and account for the most cause of death following an accident. A fascia iliaca compartment block (FICB) is the injection of anaesthetic agents into the fascia iliaca compartment with the effect of blocking the lumbar plexus via an anterior approach. FICB targets nerves that are in the fascia iliaca compartment that include the femoral nerve and the lateral femoral cutaneous nerve. A FICB is clinically safe and efficient providing consistent analgesic effects irrespective of the performing doctor's experience in managing hip fractures. Clinical audits and feedback are a veritable tool for quality improvement.MethodsData from the National Hip Fracture Database (NHFD) for all patients admitted with a hip fracture between October 2018 and May 2019 at a District hospital was interrogated and audited. Results of this audit were discussed in the department's and the Trust's mortality review meetings. In addition, teaching sessions on the safe administration of FICB using the Loss of Resistance (LOR) technique were held for junior doctors. A re-audit was carried out in May 2020 where a retrospective study of patients admitted with a hip fracture over six months from October 2019 to April 2020 was done to assess improvement in compliance rates in the administration of fascia iliaca blocks.ResultsThis study showed a statistically significant increase in the number of patients who got a fascia iliaca block on presentation with a fractured neck of the femur from after our second audit (p < 0.00001). There were no complications associated with the administration of FICB to patients with hip fractures.ConclusionsThe administration of FICB for patients with hip fractures by admitting junior doctors using the loss of resistance (LOR) technique is a safe, simple, and rapidly effective pain management method that reduces the need for excessive systemic analgesia and provides consistent simultaneous blockade of the lateral cutaneous femoral and femoral nerves. This study showed that clinical practices could be improved through audits, staff education and by enforcing the proper utilization of clinical proformas to ensure compliance. Hip fractures are the most frequently occurring serious injury in older people. They are the most common reason for older people to need emergency anaesthesia and surgery and account for the most cause of death following an accident . The incUp to 50%-70% of patients record severe to very-severe pain on pain scoring in the first 24 hours following a hip fracture. The excruciating pain associated with hip fractures and the body's neuroendocrine "stress responses" place significant limitations on patient mobility and negatively impact outcomes. In addition, compromised pulmonary and cardiac function can also occur as a sequential reaction to uncontrolled pain and further exacerbate pre-existing comorbidities .Current strategies for pain management include systemic analgesics, such as paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), narcotics, peripheral nerve blocks, epidurals, and spinal blocks. Although narcotics are used widely in elderly patients who have suffered a hip fracture, they are most effective for static pain, inadequate for controlling dynamic pain , and comIn this study, the authors hypothesized that the number of patients receiving FICB for a neck of femur fracture in a UK district hospital could be improved upon by audits, educational/teaching sessions, and employing a clinical proforma in line with the NICE guidelines. .Data from the National Hip Fracture Database (NHFD) of all patients admitted with a hip fracture between October 2018 and May 2019 was interrogated and audited. In addition, the number of patients receiving FICB, reasons for non-administration of a block, average 24-hour pain scores using the Numeric Rating Scale (NRS), and presentation time in the Emergency department were recorded. Ethical approval was gotten from the Salisbury NHS Clinical audit unit (CA_2020/21/4371).After the first audit, results were discussed in the department of Trauma & Orthopaedics' and the Trust’s mortality review meetings. A decision for all patients with hip fractures to receive a fascia iliac block on presentation in the emergency department except when contraindicated was taken. Furthermore, the following measures were put in place to improve compliance with the administration of FICB:The authors implemented small one-to-one teaching sessions on the Loss of Resistance (LOR) technique of FICB administration for Emergency Department and Trauma & Orthopaedics junior doctors.Proper filling out of the hip fracture clinical proforma was encouraged to ensure FICB were signed off by administering doctors and a reason documented when contra-indicated.The aim of these interventions was to establish a practice of routine administration of FICB using the LOR technique for patients presenting to the emergency department with a confirmed hip fracture by all junior doctors in order to reduce the over-reliance on opiates for pain control. It was also envisaged that an improvement in rates of early FICB administration would reduce the unwanted and encumbering side effects of opiates overuse and ultimately improve postoperative outcomes for patients. AnatomyThe fascia iliaca compartment has the following limits: anteriorly, the posterior surface of the fascia iliaca that covers the iliacus muscle and the whole of the psoas muscle by a medial reflection; the anterior surface of the iliacus and psoas muscles make up the posterior limit; the lower lumbar and sacral vertebrae medially and the inner lip of the iliac crest cranio-laterally; the fascia iliac compartment is continuous with the space between the quadratus lumborum muscle and fascia cranio-medially,Landmarks and procedureThe landmarks for the procedure are the anterior superior iliac spine (ASIS) and the ipsilateral pubic tubercle  scores, and fracture classification into intracapsular were recorded. Dynamic pain scores elicited by gentle logrolling of affected extremity were assessed using the NRS scale between 0 and 10: 0 representing 'no pain at all' and 10 representing 'the worst pain ever possible". Pain scores were recorded pre-FICB administration and then at 30 minutes after a block by the performing Clinician. After this, and over the next 24 hours, pain scoring and monitoring of observations were performed in the orthopaedic wards by healthcare professionals who had had appropriate education and training on how to elicit and record pain scores. A successful block was a pain score at two hours after block administration that was <50% of the pre-FICB score. All statistical analysis was performed using SPSS . The results of each audit were compared and statistically analyzed using the student's t-test to compare continuous variables and the chi-square test for dichotomous variables. A p-value of <0.05 was considered statistically significant.The first and second audits had a total of 148 and 169 patients, respectively. Table The assessment and management of pain in elderly patients with a hip fracture can pose a serious challenge due to several reasons that include: increased incidence of complications such as gastrointestinal bleeding and nephrotoxicity from the use of non-steroidal anti-inflammatory drugs (NSAIDs); respiratory depression, sedation, confusion, and constipation from excessive narcotic pain medication usage; difficulty in pain assessment due to frequently co-existing cognitive impairment. Effective pain management pre-operatively leads to shorter hospital stays and improved outcomes in elderly patients with a hip fracture. Conversely, patients who experience uncontrolled pain are at a higher risk of developing delirium, have more extended hospital stays and report persistent pain up to six months after a hip fracture -15. The A FICB is the injection of anaesthetic agents into the fascia iliaca compartment with the effect of blocking the lumbar plexus via an anterior approach . The fasIn our study, a FICB was administered to patients in the emergency department by the admitting doctor after confirmation of a hip fracture on imaging. All patients had a weight-dependent volume of 0.25% levobupivacaine as anaesthetic agent because of its long-acting duration of effect of about 8-10 hours following a single block . The autClinical audits are a form of research, the outcomes of which provide new knowledge and a better understanding of the topic being investigated . They arThere are several limitations to this study. Both audits were conducted in a retrospective manner. We did not directly compare FICB administration to other pain control modalities; the reason for this being our study focused on the use of clinical audits to effect change in clinical practice. This also meant that not a lot of emphasis was placed on the effectiveness or not of FICB as this is already well documented in previous studies -26. AddiThe administration of fascia iliaca blocks for hip fractures is a safe, simple, and rapidly effective pain management method that reduces the need for systemic analgesia. Furthermore, FICB provides consistent simultaneous blockade of the lateral cutaneous femoral and femoral nerves irrespective of the performing doctor's experience of managing hip fractures. This study showed the effectiveness of auditing clinical practice against standards, giving feedback, and modifying practice amongst healthcare professionals to improve patient care.


In The Netherlands, low back pain patients can consult physicians specialized in musculoskeletal (MSK) medicine. Previous studies have reported on the characteristics of patients consulting MSK physicians, and the treatment options used. There are no studies yet reporting on the course of Low Back Pain (LBP) after treatment by musculoskeletal (MSK) physicians in The Netherlands.In an observational cohort study MSK physicians recorded data about all low back pain patients presenting for a first consultation. At baseline they recorded age, gender, type and duration of the main complaint, and concomitant complaints. At the end of treatment they recorded the type of treatment and the number of treatment sessions. Patients were recruited to answer questionnaires at baseline, and at 6-weekly intervals during a follow-up period of six months. Patient questionnaires included information about previous medical consumption, together with PROMs measuring the level of pain and functional status. Latent Class Growth Analysis (LCGA) was used to classify patients into different groups according to their pain trajectories. Baseline variables were evaluated as predictors of a favourable trajectory using logistic regression analyses, and treatment variables were evaluated as possible confounders.A total of 1377 patients were recruited, of whom 1117 patients (81%) answered at least one follow-up measurement. LCGA identified three groups of patients with distinct pain trajectories. A first group (N = 226) with high pain levels showed no improvement, a second group (N = 578) with high pain levels showed strong improvement, and a third group (N = 313) with mild pain levels showed moderate improvement. The two groups of patients presenting with high baseline pain scores were compared, and a multivariable model was constructed with possible predictors of a favourable course. Male gender, previous specialist visit, previous pain clinic visit, having work, a shorter duration of the current episode, and a longer time since the complaints first started were predictors of a favourable course. The multivariable model showed a moderate area under the curve (0.68) and a low explained variance (0.09).In low back pain patients treated by musculoskeletal physicians in The Netherlands three different pain trajectories were identified. Baseline variables were of limited value in predicting a favourable course.The online version contains supplementary material available at 10.1186/s12998-021-00392-3. Low back pain (LBP) is a major health problem, with a point prevalence in Western countries of 12–30% , and manIn The Netherlands, among the various diagnostic and treatment possibilities, patients can consult physicians specialized in Musculoskeletal Medicine (MSK). MSK physicians are generally consulted by patients with musculoskeletal pain, and about half of the patients consult MSK physicians because of LBP . MSK phyWe conducted a prospective cohort study with a follow-up period of six months.All MSK physicians registered with the Dutch Association for Musculoskeletal Medicine were invited to participate in our study. Participating physicians were instructed to register all patients who presented for the first time in an MSK practice through a web-based registry. Patients were invited to take part in the study when making a first appointment. Inclusion criteria were LBP, age ≥ 18, and sufficient mastery of the Dutch language to answer questionnaires in Dutch. If patients gave informed consent, the treating physician entered email addresses of the recruited patients in the web-based registry. Thereafter, a specially designed computer program (Readmail) was used to automatically distribute invitations to patients by email to fill in web-based questionnaires.Both the treating physicians and the individual patients provided data via web-based registries. The treating physicians recorded data at baseline and at the end of the treatment. Study procedures were explained to participating physicians during specially organized information sessions. In addition, a research assistant visited all participating practices to explain the procedures. Practices that agreed to participate at a later stage were informed by telephone. Instructions were to ask all consecutive patients presented for a first consultation to participate in the study. Recruited patients received invitations to fill in web-based questionnaires within three weeks before the first consultation, and at six weekly intervals during the ensuing six months. When patients did not respond, a maximum of three reminders were sent within a period of two weeks. Both the invitation email and the web-based questionnaires contained links to a leaflet with information about the study.At baseline physicians registered data about age, gender, type and duration of the main complaint, and the existence of concomitant complaints. Complaints were registered according to the International Classification of Primary Care (ICPC) . At the At baseline, patients were asked to indicate whether their main complaint was low back pain, neck pain or any other complaint. This question was supported by text and manikins, explaining which area was considered to cover neck pain or low back pain. For other complaints, patients could explain these in text. Patients were asked to indicate whether their pain radiated to the legs or arms, and whether they had numbness or pins and needles in their legs or arms. Patients were also asked about the duration of the current episode, the time since the first episode, educational level, work status, previous specialist consultations, and previous treatments. The effect of previous treatments was measured on an ordinal scale, with four possible answer categories; 1.strong improvement, 2.little improvement, 3.unchanged, 4.deteriorated. Furthermore, all patients were asked to answer a set of Patient Reported Outcome Measures (PROMs), including a Numerical Rating Scale (NRS) for pain severity, the SF6D , and theOur study population consisted of all LBP patients who completed the baseline questionnaire. For the analyses of pain trajectories, patients were selected who completed the baseline questionnaire and at least one of the follow-up questionnaires. Latent Class Growth Analyses (LCGA) were used to explore whether subgroups of patients following distinct pain trajectories could be identified, using the NRS for pain scores . SeveralDescriptive analyses of baseline variables were carried out for the complete population included in the analyses, and for each group of patients with a distinct pain trajectory separately. For the patients that presented with high baseline pain scores two distinct pain trajectories were identified (see results). One trajectory identified a group of patients who did not improve (class 1), and one trajectory identified a group of patients who improved (class 2). Logistic regression analyses were conducted to study the univariate relationship between baseline variables and the dependent variable (i.e. high baseline pain and not improved (class 1) vs high baseline pain and improved (class 2)).2 [A backward selection procedure was carried out on cases with complete data on all variables to construct a multivariable model, based upon a p-value of 0.157 (Akaike criterion). Treatment variables were considered as possible confounders instead of predictors. Although not known at baseline, they could possibly influence the outcome. To evaluate the influence of treatment variables the backwards selection was therefore carried out twice, with and without including treatment variables . The relationship between continuous predictors and the outcome was tested for linearity, and non-linear variables were entered as splines. The fit of the final model was evaluated with the loglikelihood and the Hosmer Lemeshow test . Discrim2  was used2 . Descrip2 .The relationship between complete predictors and predictors with missing values (> 20%) was studied with univariate logistic regression analyses. In this analysis, significant relationships between predictors and the variable being either missing or not missing support the assumption that missing values are probably missing at random (MAR). When including all potential predictors in the model, the percentage of missing cases was around 40%, which required 40 multiple imputed datasets. Multivariable analyses were conducted in each dataset, and results were pooled according to Rubin`s rules . To evalData was collected from February 2014 until February 2016. A discrepancy was found between the number of patients classified with low back pain by the physician, and the self-classification by the patient through the web-based questionnaire. Frequently, patients classified themselves as other, but indicated complaints in text that would classify as low back pain. It was therefore decided to use the classification of the physician to select LBP patients. In the web-based registry MSK physicians recorded 2026 patients with LBP. Of these patients 1664 were recruited for our study. Our study population consisted of 1377 patients who answered the baseline questionnaire. A total of 1117 patients (81%) answered at least one of the follow up measures next to the baseline questionnaire and were included in the LCGA and prediction analyses. Of these 1117 patients, 93% answered the first follow-up questionnaire, 74% the second, 58% the third, and 43% the fourth. Although percentages missing increased over time, patients frequently missed intermediate questionnaires. Baseline characteristics of the whole sample, the patients who answered at least one follow-up questionnaire and were included in the analyses, and the patients who were lost to follow-up are presented in TableAdditional file Evaluation of loss to follow-up is presented in Table Model fit characteristics are presented in Additional file In Table 2) was 0.10. Bootstrap validation resulted in a corrected R2 of 0.06. Adding treatment variables in the backwards selection analysis resulted in a model which included the number of treatments (OR 0.91), but no other treatment variables such as the type of SMT administered or adjuvant treatment with McKenzie. The fit of this model was practically the same as the fit of the model without treatment variables .A multivariable model was constructed, and the model without treatment variables is presented in Table 2 of 0.10. Therefore one can question its usefulness in clinical practice. Apparently, with the baseline data collected in our study, it is hard to predict which patient might improve after consulting an MSK physician.Studying the clinical course of low back pain in patients consulting MSK physicians in The Netherlands with Latent Class Growth Analyses, three distinct pain trajectories were identified. More than half of all the patients (52%) presented with high baseline pain scores and showed considerable improvement during six months follow-up. A second group of patients with high baseline pain scores  showed no improvement. A third group, with moderate baseline pain scores (28%) showed slight, but clinically relevant improvement. The multivariable model presented showed a moderate discrimination, with an AUC of 6.77, and poor calibration, with an RPrevious studies almost invariably reported similar clusters of pain trajectories, generally including clusters with persistent high pain, clusters with more or less persistent moderate or low pain, clusters showing improvement, and clusters with a fluctuating pattern. The proportion of patients in each cluster, however, differed, possibly because of variations in the study designs. Patients were recruited in General Practice –8, 27, aMost trajectory studies reported variables that were associated with group membership. Although varying variables were reported, only higher pain intensity –8, 27, lOur study used pain trajectories to identify different courses of LBP after MSK treatment, rather than use a singular outcome measurement. Groups of patients with different trajectories were compared to assess whether baseline variables could predict a possible favourable course. We would consider that the different trajectories thus identified represent a more relevant estimation of whether patients have improved or not. A challenging question remains to what extent the clinical course represented the natural recovery or the consequence of the treatment administered. A multivariable model including treatment variables only included the number of treatments sessions, but not the type of SMT, or the adjuvant use of McKenzie treatment. No conclusions can be drawn from these findings because patients were not randomized, and physicians were at liberty to choose the type of treatment. The higher number of treatment sessions in the group of unimproved patients, for example, may well have been influenced by elongating the treatment in patients who reported no improvement to their treating physician.A strength of our study was the web-based data-collection, which enabled us to follow a large number of patients at a relatively low cost. In this way data could be collected from patients who consulted an MSK physician, with questionnaires that were tailored to their main complaint. A weakness was the difficulty to identify low back pain patients before consulting the physician. Our solution using web-based self-classification, aided with manikins, appeared to lead to a high proportion of miss-classification. Because we tailored the distribution of PROMs to the main complaint as reported by the patient, this miss-classification led to a high percentage of missing baseline ODI values. We therefore chose to use the physician’s diagnosis to identify patients with LBP, and we imputed the baseline ODI. Another weakness of our study set-up was the high proportion of patients that discontinued their participation. The response rate gradually diminished during the follow-up period. Out of the 1117 patients included in the baseline population 93% responded after 6 weeks, 74% after 12 weeks, 58% after 18 weeks, and 43% at six months. We found that some baseline variables were related to loss to follow-up which made the MAR assumption more plausible, supporting multiple imputation of missing values. However, loss to follow-up may have had an impact on the long-term course of the pain trajectories identified. Another limitation is the inclusion of all patients completing at least one follow-up measurement in our analyses. The fact that patients frequently missed intermediate questionnaires, however, supports the assumption that these measurements are missing at random.In patients with low back pain, three different clinical courses were identified in the six months after consulting an MSK physician in the Netherlands. A large group of patients presented with high baseline pain scores, and showed improvement. In patients with a high pain score at baseline, a multivariable prediction model showed a number of predictors of a favourable course. In this model, male gender, longer time since the complaints first started, shorter duration of the current episode of pain, previous specialist visit, previous pain clinic visit, effective treatment by a chiropractor, or no previous chiropractic treatment, and having work were predictors of a favourable course. The prediction model, however, showed a low AUC and a low amount of information. It is a continuing challenge to identify predictors of a favourable outcome in LBP patients.Additional file 1: Table S1. Handling of predictor variables, Table S2. Fit characteristics of pain trajectories.


Postoperative pain is a common problem that occurs in pediatric patients following neurosurgery which may lead to severe complications. Dexmedetomidine is a commonly used adjuvant medicine in craniotomy owing to its sedative, amnestic, analgesic, and neuroprotective properties. Besides, studies suggest that lidocaine has similar effects on sedation, analgesia, and neuroprotection. Both two adjuvants can reduce postoperative pain after neurosurgery in adults. However, it is still unknown whether dexmedetomidine or lidocaine can reduce postoperative pain in children undergoing craniotomy, and if yes, which is a better medicine choice. Therefore, we aimed to compare the effect of dexmedetomidine vs. lidocaine on postoperative pain in pediatric patients after craniotomy.We will perform a randomized (1:1:1), double-blind, placebo-controlled, single-center trial. Children aged 1–12 years scheduled for craniotomy will be eligible for inclusion. The 255 recruited participants will be stratified by age in two strata (1–6 years and 7–12 years), and then each stratum will be equally randomized to three groups: group D (infusion of dexmedetomidine [intervention group]), group L (infusion of lidocaine [intervention group]), and group C . Patients will be followed up at 1 h, 2 h, 4 h, 24 h, and 48 h after surgery. The primary outcome will be total sufentanil consumption within 24 h after surgery.In this clinical trial, we expect to clarify and compare the postoperative analgesic effect of dexmedetomidine vs. lidocaine infusion on pediatric patients undergoing craniotomy. We believe that the results of this trial will provide more choices for postoperative analgesia for the pediatric population.ChiCTR1800019411. Registered on 10 November 2018Chinese ClinicalTrials.gov  Acute postoperative pain is an unpleasant feeling and emotional experience caused by surgical trauma and is understood to influence pediatric patients’ emotions, behavior, and recovery after surgery, thereby further affecting morbidity and mortality. Therefore, proper perioperative analgesia management is of great significance to improve pediatric patients’ prognoses and attain a better therapeutic effect.Unfortunately, postoperative pain in children has been seriously neglected for long, especially after neurosurgeries, and their pain response may be enhanced due to inadequate analgesia . The likCommonly, perioperative analgesia includes opioid and non-opioid agents. Opioid administration is associated with serious risks and is a cause of concern with postoperative use in pediatric patients . VariousDexmedetomidine is a highly selective α2-adrenergic receptor agonist commonly used in neurosurgery . The advN-methyl-d-aspartate receptor to provide analgesic effects and reduce opioid consumption with lower concern for side effects [Previous studies had shown that systemic infusion of lidocaine has effects on sedation, analgesia, neuroprotection, and maintaining hemodynamic stability –28. Lido effects , 29. Con effects –33. Besi effects . HoweverDexmedetomidine and lidocaine are common adjuvant medicine anesthetics during operation for the sedative, analgesic, and neuroprotective properties. Besides, some studies have proved that both are effective in relieving postoperative pain in adults and children –38. HoweIt is very important to identify the intensity of postoperative pain; however, some very young children cannot correctly express their pain intensity. At present, there is no ideal assessment scale for all pain types in children. The Face, Legs, Activity, Crying, Consolability (FLACC) scale, Wong–Baker Faces Pain-rating Scale (FACES), and numerical rating scale (NRS) are the common scales for children’s assessment. The former two scales are visualized assessment scale obtained by the observers, which are suitable for children aged 1–12 years, while NRS can only be applied for children aged 7–12 years owing to the need to children actively report pain levels. Considering the sedative effect of dexmedetomidine, the postoperative sedation status of participants should be evaluated. The Ramsay Sedation Score has been proven to satisfactorily reflect the children’s postoperative sedation conditions .With this background, this randomized, double-blind, placebo-controlled, single-center trial has been designed to explore and compare the postoperative analgesic effects of intravenously administered dexmedetomidine, lidocaine, and normal saline on pediatric patients who are scheduled to undergo selective craniotomy.This study is a single institution, stratified randomized, double-blind clinical trial with three parallel arms. The 255 recruited participants will be stratified by age into two strata (1–6 years and 7–12 years), and each stratum will be randomized on the basis of 1:1:1 into three groups.We aim to clarify and compare the postoperative analgesic effect of dexmedetomidine vs. lidocaine on pediatric patients undergoing craniotomy. This study has been planned and designed according to the updated Consolidated Standards of Reporting Trials (CONSORT) statement . The CONAll patients in this study will be consecutively screened and recruited in Beijing Tiantan Hospital, Capital Medical University, and the target completion date is November 2021.The coordination center (CC) will comprise the principal investigator (PI), two anesthesiologists, two neurosurgeons, and an independent statistician. The responsibilities of the CC are coordinating and overseeing each stage of the trial including the recruitment, preoperative evaluation, perioperative intervention, postoperative follow-up visit, and analysis process to ensure study completion. The Trial Steering Committee (TSC) will include the PI, three anesthesiologists for pain management, two neurosurgeons, two neurosurgery nurses, and a statistician. The TSC will be responsible for training all the researchers involved in the trial and overseeing the review and approval of publications and presentations. An independent data monitoring committee (DMC) including two statisticians and a clinician will be formed to independently review the data security and accuracy of participants.Young children (1–12 years of age) undergoing elective craniotomy in Beijing Tiantan Hospital, Capital Medical University, will be screened for eligibility. The inclusion criteria and exclusion criteria are listed below.Aged between 1 and 12 years old.Patients scheduled for elective craniotomy.American Society of Anesthesiologists (ASA) physical status of I–III.Participants and their authorized surrogates can provide informed consents.The following are the inclusion criteria:History of psychological diseaseAirway abnormalities, reactive airway diseases, or other respiratory diseasesChildren with a known or suspected allergy and sensitivity or contraindications to intervention medicines (dexmedetomidine or lidocaine)Liver or kidney dysfunction Combined with atrioventricular block diseasePatients who have been included in other clinical trialsChildren who cannot be extubated after surgeryThe following are the exclusion criteria:Trained researchers will screen patients according to the eligibility criteria to participate in this study. Before enrollment, researchers need to explain the details to the participants and their authorized surrogates, including the benefits, risks, objectives, procedures, and other related issues, and ask them to sign an informed consent. Informed consent for patients aged 1–6 years will only be obtained from their authorized surrogates, while those for patients aged 7–12 years will be obtained both by the patient themselves and their authorized surrogates. Both dexmedetomidine and lidocaine are commonly used clinical medicines, and hence no potential harm, compensation, financial, or non-financial incentives are anticipated for the enrolled participants. Eligible patients will not be included until written informed consent is obtained. Baseline information about patients’ age, height, weight, ASA physical status, preoperative pain rating scores, laboratory findings, and surgical variables will be collected by study researchers.−1 and 8 mg mL−1, respectively. The group assignment will remain blinded to related anesthesiologists, patients, and outcome assessors until they complete the follow-up visit for the last enrolled participant. Furthermore, adverse events (AEs) or severe adverse events (SAEs) leading to prolonged hospital stay or death will be recorded by responsible doctors or nurses and reported to the PI, and the study groups will be revealed following consultation with the PI.Eligible participants will be stratified by age into two strata (age 1–6 years and 7–12 years) and then randomized in a 1:1:1 ratio for each group. The randomized allocation information after stratification will be determined by the computer-generated random number sequence through the Stata 15.1 software . This operation would be completed by a researcher who will not participate in the study. The allocation information will be placed in an opaque-sealed envelope with a serial number. A research assistant who will not participate in anesthesia management, data collection, or any follow-up visit will open this envelope and prepare the study medicines and label them as “study medicine” for double-blinding. The study medicines including dexmedetomidine, lidocaine, and normal saline will be made into 50-mL volumes. The concentration of dexmedetomidine and lidocaine would be 4 μg mLn = 85), lidocaine group , and normal saline group  according to the random number sequence. The intervention medicines will be administrated to patients immediately after tracheal intubation by the blinded anesthesiologist in charge. Infusion speed within the first 15 min will be calculated according to the following formula: 6 × body weight/4 mL h−1. The following infusion speed will be calculated as body weight/8 mL h−1. For each group, participants will receive intervention as follows:The 255 eligible patients will be stratified by age into two strata (age 1–6 years and age 7–12 years), and then each stratum will be randomly allocated to three groups at a 1:1:1 ratio: dexmedetomidine group , and end-tidal carbon dioxide partial pressure (PETCO2) will be started when the patients arrive in the operating room. Midazolam (0.025–0.075 mg kg−1) will be used intravenously as premedication before anesthesia induction. If participating children are too nervous, irritable, or frightened to allow venous access, a dose of 0.5 mg kg−1 midazolam through the oral pathway will be administrated to relieve their anxiety.Routine monitoring of electrocardiography, non-invasive blood pressure measurement with 5-min interval, pulse oximetry saturation  set at ≥ 0.6, to a target SpO2 of 100%. The respiratory rate needs to be adjusted for the purpose of maintaining the PETCO2 between 35 and 45 mmHg. About 30 min before the end of the surgery, 0.1 μg kg−1 sufentanil will be administered intravenously. Corresponding treatments will be applied to maintain the mean arterial pressure and heart rate within 30% of the baseline values such as supplying blood volume or using vasoactive agents. The temperature of each participant will be monitored and maintained at 35–37 °C during the whole operation. There will be no other additional analgesics administered during surgery; furthermore, scalp nerve blockade and local infiltration anesthesia to the incision will not be applied. The infusion of dexmedetomidine and lidocaine will be discontinued when the sutures of the endocranium are completed, and all other anesthetics will be discontinued at the end of surgery. The children will then be transferred to the postoperative anesthesia care unit (PACU), inpatient ward, or intensive care unit (ICU), as decided by the anesthesiologists unrelated to this study.Anesthesia will be induced with 0.3–0.5 μg kg−1 sufentanil and 0.3 mg kg−1 ondansetron diluted in 100 mL of normal saline. No background medicines will be administrated. The pump will only provide a bolus dose infusion when the button of the electronic analgesia pump is pressed . Nurses in the PACU, ICU, and ward will be required for children aged 1–6 years to help them control the devices, and the button will be pressed when the FLACC score is > 4. Children aged 7–12 years will be administered analgesia with the help of the nurse until they are able to operate the button by themselves. When the FLACC pain score is > 5 and the FACES pain score is > 6, those children with insufficient analgesia will be administered acetaminophen at 15 mg kg− 1 orally, with enhanced single-bolus dose infusion of the electronic analgesia pump as a remedial procedure. The parameters of the electronic analgesia pump , and whether emergency rescue measures have been initiated (including the medicines’ dosage and frequency) will be recorded within 48 h after surgery.Further, an electronic analgesia pump  with sufentanil and ondansetron will be routinely used for postoperative pain and postoperative nausea and vomiting (PONV). The devices will be loaded with 2 μg kgThe primary outcome will be total sufentanil consumption within 24 h after surgery.The postoperative pain intensity assessed by a series of pain rating scales  at 1 h, 2 h, 4 h, 24 h, and 48 h after surgery. Besides, the NRS scale is only applicable to children aged 7–12, but the FLACC and FACES scales are suitable for children aged 1–12 years. We will also classify and record the pain level of patients according to the scoring criteria of the three scales.The postoperative sedation score (Ramsay) at 1, 2, 4, 24 and 48 h after surgery.Total sufentanil consumption within 1, 2, 4, and 48 h after surgery and emergency remedy medicine consumption at 1, 2, 4, 24, and 48 h after surgery.Total consumption of opioids and sedatives during operation.Postoperative complications including bleeding, infection, neurological impairment, PONV, and severe adverse effects (SAEs) like disability and death, etc.Length of hospitalization after surgery.The secondary outcomes include the following aspects:Before surgery, patients’ baseline conditions need to be collected carefully including (1) demographic variables such as sex, age, weight, and height; (2) ASA physical status; (3) baseline pain and sedation rating scores; (4) laboratory parameters; and (5) surgery variables such as incision site, lesion site, lesion character, and whether ventriculoperitoneal shunt was performed before craniotomy.During the anesthetic period, the following data will be collected: (1) heart rate, peripheral oxygen saturation, blood pressure, and electrocardiographic patterns; (2) administration of anesthetics such as propofol, remifentanil, and vasoactive agents, including medicine type, dose, and other information; (3) the total duration of surgery and several important time points including surgery-start time, surgery-end time, patient awake time, and extubation time; (4) quantity of liquid intake and output; and (5) transfer site .Follow-up visits will be conducted at 1 h, 2 h, 4 h, 24 h, and 48 h after surgery. The total sufentanil consumption; the pain rating scores with FLACC , FACES , and NRSThe blinded and trained researchers will follow up with the patient at 1 h, 2 h, 4 h, 24 h, and 48 h after surgery and collect the outcome data. The blinded anesthesiologists in charge will record the patients’ intraoperative data. The researchers in charge of patient screening will collect the baseline data. Each participant will be assigned a unique identifier, and no personal information will be revealed. The research data will be double entered into the database by two independent data managers and checked regularly. The data will be hidden from all the researchers involved until the study is completed and the final data submitted for statistical analysis. Any biased and defective cases will be retained, except for those that cannot complete the primary outcome assessment, owing to death or discharge within 24 h. All the participants with deviations and deficiencies will be retained except for the cases that are unable to complete the assessment of the primary outcome owing to death or discharge within 24 h. The DMC will be responsible for monitoring the data, and the CC will review the trial conduct once for every 30 patients included. The TSC and IRB will review the research conduct throughout the trial period.To protect confidentiality, the paper information will be stored in a locked cabinet inside the locked research office, and the electronic information will be kept in a password-protected electronic database. Special privilege to access the database to acquire personal information will require the consent of both the PI and DMC. All the information about the identification of participants used for data disclosure or statistical analysis will only appear as code numbers.It has been reported that the incidence of postoperative pain in adult patients undergoing elective craniotomy is about 60% –5. The iTo recruit this number of participants, a 3-year inclusion period is anticipated according to the turnover rates of our hospital.x̄ ± s) or interquartile range , and nominal factors will be presented as number . All tests will be two-tailed and conducted at a 5% level of significance. Kolmogorov–Smirnov tests will be performed to detect the normal distribution of continuous variables. The t-test or analysis of variance (ANOVA) will be used for categorical variables with normal distribution and equal variance. The non-parametric test will be used appropriately for categorical variables with non-normal distribution and unequal variance. The chi-squared and Fisher’s exact tests will be used to compare proportions. Then, ANOVA or Kruskal–Wallis tests will be conducted for the intergroup comparisons of the primary outcome and other continuous variables among the three groups; if there are differences, further comparisons will be performed between any pair of study groups. Nominal variables will be compared using the chi-squared and Fisher exact tests. p < 0.05 will be considered to indicate statistical significance. The repeated measurements for general linear models and multivariate analysis will be conducted for the pain scores obtained from the three scales. All participants in the randomization will be analyzed, except for those whose primary outcome is missing, and multiple imputation will be conducted if this unintended missing data are more than 10%.The statistical analysis will be performed using the SPSS 23.0 software . The continuous variables will be presented as mean ± standard deviation . The results will be disseminated to all participants, researchers, and healthcare providers through study summary documents, courses, presentations, and the Internet. The datasets analyzed during the current study will be available from the corresponding author upon reasonable request.Systemic administration of dexmedetomidine or lidocaine as an adjuvant to general anesthesia to relieve postoperative analgesia in adult patients undergoing elective surgeries is a reliable option as suggested by previous studies , 19, 29.There are several reasons to explain why the setting proposed in the present protocol is appropriate. First, dexmedetomidine and lidocaine are both promising anesthetic adjuvants in pediatric patients undergoing craniotomy. The normal saline group is supposed to be the placebo group. Such settings could help us understand whether the intervention medicines (dexmedetomidine and lidocaine) are effective and which is the preferred adjuvant choice to reduce postoperative pain. Second, previous studies have proved that the administration of lidocaine and dexmedetomidine in this protocol is clinically safe and common for children undergoing craniotomy , 48–50. We acknowledge that this study protocol could have potential limitations. First, we only studied the clinically common dose of the intervention medicines rather than compare the effects of different concentrations. Second, this is a single-center study which may increase the inherent potential bias. However, our sample size is as large as possible to reduce the potential bias from this aspect. Nevertheless, the potential bias influenced by the skills of surgeons might be decreased given that Beijing Tiantan Hospital is ranked first for neurosurgery in China.In the present protocol, we have tried to reduce bias as much as possible. We expect to conclusively determine the postoperative analgesic effects of intravenous infusion of dexmedetomidine and lidocaine in children undergoing craniotomy. This trial will provide more choices for the multi-model analgesia of pediatric patients undergoing neurosurgery and probably benefit prognosis.The version number of this Clinical Research Program is V1.2. The trial began on December 1, 2018, and the recruitment will be completed approximately on November 30.


The Current Opioid Misuse Measure (COMM) is a questionnaire used to identify and monitor chronic pain patients on opioid therapy who may be misusing their prescription opioids. The aim of the present study was to adapt the questionnaire for its use in Spanish-speaking populations. A total of 171 individuals (131 women and 40 men) with nononcological chronic pain participated in this cross-sectional study. The most frequent pain diagnoses in the sample were fibromyalgia, herniated disc, and rheumatoid arthritis. Systematic sampling was used. All individuals were interviewed at their clinic between March 2018 and February 2020. The dimensionality of the COMM-SV items was evaluated using an optimal implementation of parallel analysis (PA) and an exploratory factor analysis. Internal consistency, test–retest reliability, and criterion and convergent validity were calculated. The COMM-SV comprises five factors: problematic interpersonal behaviour, searching for more medication than prescribed, medication misuse and self-injurious thoughts, emergency use, and memory and attention problems. It has good reliability and adequate test–retest stability. The results support its criterion and convergent validity. Given the increasing use and abuse of opioids, a valid and reliable instrument is needed in Spanish settings to identify patients with chronic pain who present aberrant behaviour related to the use of these medications. The COMM-SV enables Spanish clinicians to do that. Opioids are used as a potentially effective treatment for chronic pain   signs and symptoms of drug misuse, (2) emotional problems/psychiatric issues, (3) poor response to medications, (4) evidence of lying and illicit drug use, (5) inconsistent appointment patterns, and (6) medication misuse/abuse and nonadherence to medication. A total of 40 items were selected from the most relevant ones. The reliability-test–retest showed that 17 items appeared to provide an accurate measure of aberrant behaviour as demonstrated by good internal consistency  and 1-week test–retest reliability   with chronic nononcological musculoskeletal pain. The participants were outpatients referred by physicians from primary care health centres and from a pain unit of a general hospital in Spain. Participants were eligible for the study if they met the following conditions: (a) experiencing chronic noncancer pain, (b) prescription for pharmacological treatment with opioids for more than 90 days, (c) being over 18 years old, and (d) sufficient competence in the Spanish language (spoken and written). The exclusion criteria were as follows: (a) chronic oncological pain, (b) musculoskeletal and/or neuropathic lesions that require immediate surgery, and (c) individuals who were being treated for an oncological disease, a degenerative and/or terminal disease, or with a serious mental disorder .SD = 16.13; age range = 34–84), and mean pain duration was 16.13 years . The most frequent pain diagnoses among noncancer chronic pain patients were fibromyalgia (n = 65), spinal pain (n = 54), arthrosis (n = 12), and rheumatoid arthritis (n = 12). At the time of the study, 81% were married or cohabiting. Regarding their work status, 41% were retired, 19% were active workers, and 11% were unemployed. In total, 56% had completed primary education, 32% had completed high school, and 12% had a university degree.The patients’ mean age was 60.29 years (never) to 4 (very often). A total score equal to or more than nine (≥ 9) accurately identifies approximately 80% of patients who are at high risk of aberrant medication-related behaviour . It also has a sensitivity and specificity of 77% and 66%, respectively   to 10 (extremely painful) in order to obtain a composite pain index. This scale has been validated to measure pain in individuals with chronic pain. Numerical rating scales are commonly used in pain research and are known to provide valid and reliable measures of pain intensity across different populations   to 5 (strongly agree), and higher scores are indicative of lower tolerance. The confirmatory factor analysis of the Spanish DTS found four lower-order factors of tolerance, appraisal, regulation, and absorption that loaded onto a higher-order general factor. It showed good internal consistency  and adequate temporal stability (7-month test–retest) . In this study, the total scale was used .The Spanish version of the DTS   and the Regional Hospital Ethics Committee.At the end of their medical visit, all participants who fulfilled the eligibility criteria were informed by their doctor of the study aims, and their participation was requested. The inclusion and exclusion criteria were taken into account by the physicians, according to the information contained in the patients’ medical records before inviting the patients to take part in the study. The participants who accepted were contacted by telephone to make an appointment for the assessment, which was conducted by a trained psychologist  at their clinic . All participants were guaranteed confidentiality, and written informed consent was obtained in accordance with the Declaration of Helsinki.Each participant had a semi-structured interview with trained psychologists to obtain demographic, social, and medical history data Table . SubsequA total of 27 participants were randomly invited to attend a second interview 1 month later by phone to complete the COMM-SV questionnaire again. The data were collected between March 2018 and February 2020. A subsample of 43 participants who had been assessed 18 months before were contacted by telephone in December 2020, due to the restrictions imposed by the COVID-19 pandemic. These individuals were asked for information about medication and pain intensity and were administered the DAST-10.The data were analysed using the SPSS statistical program (Windows version 25.0). Parallel analysis (PA) was conducted using the FACTOR statistical program (version 10.10.02)  of the participating patients who completed the first and the second administration (1 month later). The ICC for test–retest reliability was calculated using baseline and 1-month post-assessment scores. Test–retest reliability is considered to be acceptable with scores equal to or greater than 0.65 , adequate (0.20 r < 0.35), good (0.35 r < 0.50), or excellent (r > 0.50).Criterion validity was assessed by calculating Pearson correlations between the COMM-SV and scores on pain intensity, depression and anxiety symptoms, and distress tolerance. We also assessed correlations between the SOAPP and the COMM-SV total scores. We followed the guidelines provided by Evers et al.  for inteCriterion validity was also assessed using a four-step hierarchical multiple regression. The predictor variables were pain intensity, distress tolerance, anxiety symptoms, and depression symptoms. To control for potential confounders, age and sex (coded as man = 0 and woman = 1) were entered in the first block. In order to estimate the contribution of pain intensity, distress tolerance, and anxiety and depression according to their relevance in the prediction of COMM-SV scores, we entered these variables in the second, third, and fourth block, respectively. Pain intensity was introduced first to control for its effect. Distress tolerance was entered in the second block because it is considered to be a dispositional variable. Anxiety and depression were introduced in the third block. The mediation model was used to investigate the indirect effects of distress tolerance on COMM-SV scores through anxiety symptoms. Direct and indirect effects were estimated using Preacher and Hayes’ techniques with 5000 bootstrap samples .The PA using exploratory RULS indicated a 5-factor structure. According to the goodness of fit indexes, the model showed a very good fit: χThe Kaiser–Meyer–Olkin (KMO) index was 0.70, indicating that the EFA was adequate for this sample.The EFA yielded five factors with eigenvalues > 1. This solution accounted for 53.4% of the variance  and with eigenvalues of 4.20, 1.97, 1.76, 1.60, 1.38, and 1.07 for factors 1, 2, 3, 4, and 5, respectively. All loadings were greater than 0.30 except for item 16 (factor loading 0.17), and communalities were between 0.27 (item 12) and 0.54 (item 13), except for item 16 . Factorial correlations values were between 0.15 (factor 3 and factor 4) and 0.37 (factor 1 and factor 3). Factor 1 consisted of 3 items  on problematic interpersonal behaviour; factor 2 comprised 3 items  on searching for more medication than prescribed; factor 3 consisted of 5 items  on medication misuse and self-injurious thoughts; factor 4 comprised 2 items  on emergency use; and factor 5 consisted of 4 items  on memory and attention problems. Table α = 0.80). The internal consistency for the factors ranged from α = 0.64 (factor 5) to α = 0.89 (factor 4).Cronbach’s alpha was calculated for the COMM-SV and its five subscales. The total score of the questionnaire showed suitable internal consistency  was calculated using baseline and 1-month post-assessment scores. Measurements were repeated twice for each participant. ICC test–retest reliability was high .Table β = 0.18, p = 0.022) significantly contributed to the prediction of opioid misuse. However, in step 3, when distress tolerance was included in the equation, this new variable alone , but not pain intensity , significantly contributed to the prediction of opioid misuse (∆R2 = 0.20). Finally, in step 4, anxiety symptoms alone , but not depression symptoms , made an additional significant contribution to the prediction of the criterion variable (∆R2 = 0.09). In this study, distress tolerance and anxiety symptoms explained 32% of opioid misuse variance.Table b = 0.25, SE = 0.05, p < 0.001). Distress tolerance was also associated with anxiety , and anxiety was shown to be associated with COMM-SV . Thus, anxiety symptoms had a significant mediating effect between distress tolerance and the COMM-SV. Given that the direct effect between distress tolerance and opioid misuse was not significant when the indirect effect of anxiety was included , it can be concluded that anxiety completely mediated the relationship between distress tolerance and opioid misuse.Figure r = 0.48 (p < 0.01), indicating a moderate positive association between both measures.Pearson’s bivariate correlation between the COMM and DAST-10 total scores yielded a value of The main objective of the present study was to analyse the psychometric characteristics of the Spanish version of the COMM, which is a questionnaire that identifies chronic noncancer pain patients who misuse opioid prescriptions. This instrument detects aberrant behaviour related to prescribed opioids and serves as a tool for monitoring medical treatment. To our knowledge, the present study is the first to analyse the structural validity of the COMM using data from a sample of Spanish patients with chronic pain.As indicated by the factor analysis of the COMM-SV, the 17 items are grouped into five factors. This factor structure is different from the ones found in previous studies. According to Rogers et al. , the oriRegarding convergent validity, an expected significant association was found between the total scores on the COMM-SV total score and the DAST-10 scale (Sandin et al., We assessed the criterion validity of the COMM-SV by investigating correlations between the risk of misuse as measured with the SOAPP (Butler et al., This study has some limitations that should be considered. Firstly, the size of the clinical sample was relatively small. Secondly, women were overrepresented in the sample, which may have biased the findings. Future research should replicate these results using a larger sample with more male participants. Thirdly, only self-report measures were used, and so the results may be biased due to shared method variance. Fourthly, the cross-sectional and correlational design employed cannot be used to make causal statements.Despite these limitations, this study represents the first attempt to validate the COMM-SV. The findings suggest that the Spanish version of the COMM provides a reliable measure that can help clinicians evaluate and identify patients with aberrant behaviour related to the use of opioid medication. Given the growing concern in Spain on the use and abuse of opioid analgesics (Santana Pineda et al.,


Aim: To measure the extent of polypharmacy, multimorbidity and potential medication-related problems in elderly patients with chronic pain receiving home care.Methods: Data of 355 patients aged ≥65 years affected by chronic pain in home care who were enrolled in the ACHE study in Berlin, Germany, were analyzed. History of chronic diseases, diagnoses, medications including self-medication were collected for all patients. Multimorbidity was defined as the presence of ≥2 chronic conditions and levels were classified by the Charlson-Comorbidity-Index. Polypharmacy was defined as the concomitant intake of ≥5 medications. Potentially clinically relevant drug interactions were identified and evaluated; underuse of potentially useful medications as well as overprescription were also assessed.Results: More than half of the patients (55.4%) had moderate to severe comorbidity levels. The median number of prescribed drugs was 9 (range 0–25) and polypharmacy was detected in 89.5% of the patients. Almost half of them (49.3%) were affected by excessive polypharmacy (≥10 prescribed drugs). Polypharmacy and excessive polypharmacy occurred at all levels of comorbidity. We detected 184 potentially relevant drug interactions in 120/353 (34.0%) patients and rated 57 (31.0%) of them as severe. Underprescription of oral anticoagulants was detected in 32.3% of patients with atrial fibrillation whereas potential overprescription of loop diuretics was observed in 15.5% of patients.Conclusion: Multimorbidity and polypharmacy are highly prevalent in elderly outpatients with chronic pain receiving home care. Medication-related problems that could impair safety of drug treatment in this population are resulting from potentially relevant drug interactions, overprescribing as well as underuse. Over the last few decades, the population of older adult has grown worldwide especially in the developed countries . BetweenPolypharmacy is a common clinical consequence of multimorbidity in older adults encompassing not only prescribed but also over-the-counter medications including among others herbal supplements . CommonlACHE study (“Development of a Model for PAin Management in Older Adults ReCeiving Home CarE”) in Germany. Briefly, ACHE was an observational cross-sectional analysis of a population-based cohort of older adults which focused on pain management in home care and has been described previously in detail . As cognitively impaired older adults are also at increased risk of multimorbidity and the negative consequences of polypharmacy, patients with cognitive impairment were also eligible for inclusion in ACHE. Hence, patients were enrolled independently from their cognitive status as determined by the Mini Mental Status Examination (MMSE) (Home-dwelling elderly with chronic pain recruited between 09/2017 and 10/2018 in the framework of n (MMSE) .Five trained investigators interviewed the participants, collected demographic data, the level of care as well as the education level  and documented the concurrent medications used regularly or as needed based on drug packages and medication plans available at participants’ homes. According to the Pharmaceutical Care Network Europe (PCNE) classification , we perfFor the assessment of comorbidities, history of chronic diseases was obtained by thoroughly reviewing the participants’ medical records, physician reports, nursing records as well as self-reported diagnoses. Polypharmacy was defined as the concomitant intake of ≥5 medications whereas excessive polypharmacy as ≥10 medications, taken regularly or on-demand . Our anaThe individuals’ burden of current diseases in chronic pain patients was assessed by the original Charlson-Comorbidity-Index (CCI)  which is2DS2-VASc  score for patients with AF to evaluate their risk of thromboembolism . We used Mann-Whitney U test to check the association of the CCI score (continuous) with sex , prevalence of polypharmacy  and excessive polypharmacy . Chi-squared test was used to examine the association between sex and both polypharmacy and excessive polypharmacy as well as the association of comorbidity levels  with level of care  and education level [highest school education  and highest professional education ]. Spearman’s correlation was used to test the correlation between the CCI score and the number of prescribed medications (continuous), age (continuous) and MMSE score (continuous). Kruskal-Wallis H test was used for associations between number of prescribed medications (continuous) and levels of comorbidity . The post-hoc Dunn-Bonferroni test was applied for pairwise comparison between the groups. In addition, we used the Jonckheere-Terpstra test to check for an overall trend between the groups and calculated the corresponding Kendall’s tau-b (τ) correlation coefficient. Data were analyzed using IBM SPSS Statistics, version 25 . Two-tailed statistical significance was assessed at level 0.05.ACHE study and data were analyzed as two cohorts: the medication-analysis cohort and the multimorbidity cohort , congestive heart failure (CHF) (41.3%), diabetes with/without organ damage (32.1%), dementia (27.2%), coronary heart diseases (26.9%) and chronic pulmonary diseases (25.1%) . Overalls = 0.345, p < 0.001). The prevalence of polypharmacy (≥5 prescribed drugs) was 89.5% (n = 316) and almost half of the patients  were affected by excessive polypharmacy (≥10 prescribed drugs) . Patients affected by prescribed polypharmacy had significantly higher CCI scores  than patients without polypharmacy . Similarly, excessive polypharmacy was also associated with higher CCI scores . Moreover, significant associations were found between the number of prescribed medications and different levels of comorbidity . The adjusted p-values of the post-hoc analysis are shown in p < 0.001). Polypharmacy and excessive polypharmacy were detected in all levels of comorbidity.Among the medication-analysis cohort, 3,703 medication products were screened during data collection yielding 3,612 (97.5%) medication products for analysis after screening for data quality as per our preset criteria . Of thosd drugs) . There wIn total, 184 clinically relevant potential DDI from which 57 (31.0%) evaluated as severe were detected in more than a third (34.0%) of patients in the medication-analysis cohort  patients  but only 44 (67.7%) patients were anticoagulated with direct oral anticoagulants (DOAC) or vitamin-K-antagonist (VKA), while 21 (32.3%) received no oral anticoagulants; of these, 19 patients were ≥75 years old. The three most prescribed anticoagulants were apixaban (36.4%), phenprocoumon (29.5%) and rivaroxaban (20.5%).In our multimorbidity cohort, 65/334 (19.5%) patients (mean age 82.8 ± 7.4 years) had AF . All of Among the diuretics, all diuretic agents including potassium-sparing diuretics were included in DDI evaluation amounting to 281 diuretic prescriptions in 224 patients. We found 131 potential DDI, 36 (27.5%) of them were evaluated as severe  patients were treated with diuretics. By far, the most commonly prescribed diuretic was torasemide, prescribed in 160 (82.1%) patients. Loop diuretics were combined with thiazide/thiazide-like diuretics in 11/195 (5.6%) patients. In one patient, torasemide and furosemide were even co-prescribed. Among 174 (89.2%) patients receiving loop diuretics, 27 (15.5%) patients had no documented indication for CHF, advanced chronic kidney disease or edema.Overall, 85/353 (24.1%) patients took simvastatin once daily in an average dose of 29.9 ± 14.5 mg. We found 17 potential DDI between simvastatin and other drugs . Of these, 11 interactions were rated as severe  for whom we checked the whole DDI profile appears of interest . The pate severe .The present study revealed that multimorbidity and polypharmacy along with the consequences of polypharmacy  were highly prevalent in our cohort of older adults with chronic pain receiving home care that also included patients with severe cognitive impairment. To the best of our knowledge, this is the first cross-sectional prospective study in Germany to examine the burden of multimorbidity and polypharmacy in this setting involving chronic pain patients. Chronic pain has been reported to be associated with high burden of comorbid diseases and high risk of polypharmacy . In one We found a median CCI score of 3 (IQR: 2–4) in both men and women and an overall range of 0–13. More than half of the patients (55.4%) had moderate (35.6%) to severe (19.8%) comorbidity levels . HoweverThe median number of prescribed drugs was 9 (range 0–25) and 10 (range 0–25) when self-medication was included. In nursing homes in Germany, an average of 5.9 ± 3 (range 0–16) drugs prescribed concomitantly per resident was reported , while iDDI involving simvastatin, a well-known substrate of cytochrome P450 (CYP) 3A4  predispoAs a case study, we demonstrated the overall DDI profile of a multimorbid female patient affected by excessive polypharmacy and experiencing a complex drug regimen. For this patient, we detected several DDI involving anticoagulants and diuretics. This case also illustrates an increased number of prescribed drugs proportional to a high CCI, with a comorbidity score of 5. Notably, guideline-based treatments for several diseases facilitate polypharmacy as illustrated in this patient treated for CHF, hypertension and AF and was therefore included in the AF subgroup analysis.2DS2-VASc score ≥2 should be anticoagulated with DOAC or VKA due to risk of stroke (2DS2-VASc score of 5 (range 3–8). However, about a third (32.3%) of them did not receive anticoagulant therapy with either DOAC or VKA suggesting a state of underprescription of potentially useful medications. Though current AF management guidelines recommend oral anticoagulant treatment at age ≥75 years regardless of additional risk factors for stroke (Patients with AF and a CHAf stroke . In our r stroke , underusr stroke .Diuretics, commonly prescribed in the elderly, often cause hypovolemia and hyponatremia which increase the risk of falling that was associated with higher morbidity and mortality in older adults . ElderlySuboptimal prescribing in elderly includes, besides unnecessary prescribing or overprescribing, underuse or underprescribing of indicated medications . The latACHE. However, the following limitations are acknowledged:This study is the first to examine the burden of multimorbidity and polypharmacy in older adults with chronic pain receiving home care. The strengths of our study lie in the rigorous evaluation of the drug profile including self-medication and drugs prescribed regularly or on-demand as well as including patients with severe cognitive impairment. In contrast to previous studies that excluded patients with cognitive impairment , patientFirst, this is a cross-sectional cohort study. As such, patients were interviewed once; follow-up data of patients were not available. In addition, contacts with the treating physician were not implemented in the study design. Hence, it was not possible to assess the persistence of polypharmacy or notify the physician in case of suspected DDI or trace the outcome of the potential DDI whether a corrective action was taken by the physician or a follow-up for clinical condition was undertaken. Second, our sample size was small, and the study reflects local data to the city of Berlin regarding patients with chronic pain in the home care setting which may limit the generalizability of our findings concerning prevalence rates of multimorbidity and polypharmacy and its consequences. Nevertheless, we preferred to analyze qualitatively the prescribed medications rather than to systematically report the prevalence of medication errors, DDI and inappropriate medication use to get an insight into the consequences of polypharmacy in multimorbid chronic pain patients. This highlights also how significant DDI could be regardless of their actual prevalence and helps instigate awareness on the harmful effects of DDI in this group.Multimorbidity and polypharmacy are highly prevalent in elderly outpatients with chronic pain receiving home care. Regular monitoring and evaluation of medications in this population appears thus important together with strategies aiming to optimize therapy by addressing differential aspects of medication-related problems including drug interactions, overprescribing as well as underuse.


Introduction: Neuropathic pain is a painful condition that arises after a lesion or an insult to the somatosensory nervous system, either in a central or peripheral location. The most common cause of neuropathic pain is diabetes. Controlled trials have been conducted on recent advancements in medicine to investigate the effect of vitamin C in the treatment of neuropathic pain. In this study, we aim to investigate the role of vitamin C in reducing pain associated with diabetic neuropathy.Methods: This open-label, parallel-arm, interventional study was conducted in a public tertiary care hospital in Pakistan from April 2019 to March 2021. A total of 300 type II diabetic patients with newly diagnosed painful peripheral diabetic neuropathy, of either gender, were enrolled in the study. The intervention group received 60 mg duloxetine along with 200 mg oral vitamin C. The control group received 60 mg duloxetine without any additional intervention. Patients were asked to return for follow-up after 12 weeks.Results: The mean visual analog score (VAS) was significantly lower in both, the intervention  and the control group , at week 12 compared to day 0. However, in comparison, VAS score in intervention at week 12 was significantly lower as compared to the control group .Conclusion: The use of vitamin C could be cost-effective and would be a safe and useful adjunctive therapy for pain associated with diabetic peripheral neuropathy. Neuropathic pain is a painful condition that arises after a lesion or an insult to the somatosensory nervous system, either in the central or peripheral location . It affePharmacological therapy is worldwide used as the first line of management of neuropathic pain, followed by interventional strategies, such as nerve blocks and neuromodulators. Antidepressants and antiepileptics have been the most studied drugs in neuropathic pain, including those with confirmed efficacy, like amitriptyline and serotonin-noradrenaline reuptake inhibitors . VariousControlled trials have been conducted on recent advancements in medicine to investigate the effect of vitamin C in the treatment of neuropathic pain, especially post-herpetic neuralgia and cancer-related neuropathy ,7. The aHowever, limited data are available on the effectiveness of vitamin C in the long-term control of different types of neuropathic pain, and whether it could reduce the requirement of interventional pain strategies. In this study, we aim to investigate the role of vitamin C in reducing diabetic neuropathic pain.This open-label, parallel-arm, interventional study was conducted in a public tertiary care hospital in Pakistan from April 2019 to March 2021. We enrolled 300 type II diabetic patients with newly confirmed painful peripheral diabetic neuropathy, of either gender, via consecutive convenient non-probability sampling. The study was conducted after approval from the institutional review board. Informed consent was attained from all participants. Biothesiometry was done for all the patients to diagnose and confirm peripheral diabetic neuropathy after clinical and physical examination. Biothesiometry score of 16 volts or above was diagnostic for painful diabetic peripheral neuropathy (PDPN).https://www.randomizer.org/). The intervention group received 60 mg duloxetine along with 200 mg oral vitamin C. The control group received 60 mg duloxetine without any additional intervention. Patients with diabetic foot, retinopathy, and nephropathy were excluded from the study.After enrollment, participants were randomized into two groups by a 1:1 ratio using an online software research randomizer . VAS has a range of 0 to 10, with a higher number indicating greater severity of pain. Patients were asked to return for follow-up after 12 weeks. During follow-up, the pain was recorded again on the VAS scale. The occurrence of adverse events was recorded. Upon follow-up, one patient had stopped taking the medication in the intervention group due to adverse events, while 11 and 13 patients were lost to follow-up in the experiment and placebo group, respectively.Data were processed through and analyzed using the Statistical Packages for Social Sciences version. 23.0 . Mean and standard deviation (SD) was calculated for continuous variables; frequencies and percentages were calculated for categorical variables. The mean pain score was compared using the t-test. Adverse events in both groups were compared using chi-square. A p-value of less than 0.05 meant that there is a difference between the two groups and the null hypothesis was void.In the control group, participants were significantly younger, compared to the interventional group . However, there was no difference in gender distribution and duration of diabetes  was significantly lower in both, the intervention  and the control group , at week 12 compared to day 0. However, in comparison, VAS score in intervention at week 12 was significantly lower as compared to the control group  (Table The most common adverse event in both groups was constipation, followed by orthostatic hypotension. There was no significant difference in adverse events between both groups Table .The results of our study compared the VAS score between the control and intervention groups. It demonstrated that the VAS score was significantly lower in both groups at week 12 as compared to day 0. However, the reduction was more in the vitamin C group at week 12 as compared to the control group. Moreover, constipation was the most common adverse event in both groups, followed by orthostatic hypotension. Consistent with other studies, the results of our study support the evidence that vitamin C plays a considerable role in reducing pain. In randomized control trials, vitamin c supplementation showed a decline in the incidence of complex regional pain syndrome ,11. SimiVitamin C tends to protect cells and tissues from oxidative damage. It is considered to be a potent antioxidant and can eradicate a wide range of reactive oxygen species. It is assumed to act in oxidative stress conditions because of its well-known oxidative stress properties . It alsoThe study has its limitation. First, since the study was conducted in a single institute, the sample size was less diverse. Second, participants’ compliance with medication was not monitored, which might have impacted the result.Vitamin C plays a synergistic role in reducing pain in patients with diabetic neuropathy. It improves QOL due to its analgesic properties. Moreover, it is cost-effective and appears to be a safe and adjuvant therapy for specific pain relief. Patients should be encouraged to take vitamin C along with pharmacological management to get maximum relief from pain.