Objective: Neuroimaging studies on neuropathic pain have discovered abnormalities in brain structure and function. However, the brain pattern changes from herpes zoster (HZ) to postherpetic neuralgia (PHN) remain unclear. The present study aimed to compare the brain activity between HZ and PHN patients and explore the potential neural mechanisms underlying cognitive impairment in neuropathic pain patients.Methods: Resting-state functional magnetic resonance imaging (MRI) was carried out among 28 right-handed HZ patients, 24 right-handed PHN patients, and 20 healthy controls (HC), using a 3T MRI system. The amplitude of low-frequency fluctuation (ALFF) was analyzed to detect the brain activity of the patients. Correlations between ALFF and clinical pain scales were assessed in two groups of patients. Differences in brain activity between groups were examined and used in a support vector machine (SVM) algorithm for the subjects' classification.Results: Spontaneous brain activity was reduced in both patient groups. Compared with HC, patients from both groups had decreased ALFF in the precuneus, posterior cingulate cortex, and middle temporal gyrus. Meanwhile, the neural activities of angular gyrus and middle frontal gyrus were lowered in HZ and PHN patients, respectively. Reduced ALFF in these regions was associated with clinical pain scales in PHN patients only. Using SVM algorithm, the decreased brain activity in these regions allowed for the classification of neuropathic pain patients (HZ and PHN) and HC. Moreover, HZ and PHN patients are also roughly classified by the same model.Conclusion: Our study indicated that mean ALFF values in these pain-related regions can be used as a functional MRI-based biomarker for the classification of subjects with different pain conditions. Altered brain activity might contribute to PHN-induced pain. Herpes zoster (HZ) is one of the leading causes of severe pain in China, with a prevalence estimated to be 7.7% of the population who seek medical care. Moreover, 29.8% of HZ patients may develop postherpetic neuralgia (PHN) that causes pain for months or even years . NeuropaAlthough previous studies have shown that neuropathic pain can change brain plasticity , the basThe vast majority of these previous neuroimaging studies were restricted to PHN patients. Only a few studies have used neuroimaging methods to explore the differences in brain activity between HZ and PHN , 16. A pAlthough previous literature confirmed that the brain function of patients with HZ and PHN was changed compared with the HC, the differences in brain activity between HZ and PHN were inconsistent across these studies, and the neural mechanism is still unclear. Based on previous literature, we hypothesized that patients with HZ and PHN exhibit significant changes in spontaneous brain activity, which can be used to classify them from healthy controls. Thus, the present study aimed to explore the effects of HZ and PHN on brain activity and detect the neural mechanism underlying cognitive impairment in neuropathic pain patients. Resting-state functional MRI data were collected from all participants, and the amplitude of low-frequency fluctuation (ALFF) was calculated. The ALFF is the most common and widely used method for characterizing the dynamic properties of the neuronal processing unit . The corFifty-two patients  and 20 HCs (right-handed) were recruited from the Pain Medicine Department of Huazhong University of Science and Technology Union Shenzhen Hospital. Before the imaging data were collected, we explained the purpose of the study, the study procedures, and the possible risks and discomfort to all participants. Then, written confirmed consent was obtained from each participant or their companion. This study was carried out following the Declaration of Helsinki and was approved by the Ethics Committee of Huazhong University of Science and Technology Union Shenzhen Hospital. The inclusion criteria were HZ within 30 days after onset of the painful rash, dermatome below C2, age older than 50 years old, and with persistent pain [visual analog scale (VAS) ≥ 5]. All patients were diagnosed as PHN based on persistent pain (VAS ≥ 5) for more than 30 days following the initial rash caused by HZ . PatientBefore MRI scanning, spontaneous pain intensity was assessed using the VAS, which measures pain intensity on a scale of 0 to 10, with 0 indicating no pain and 10 indicating the highest tolerable pain. Additionally, to identify the qualities of pain, the McGill pain questionnaire was used, including the Pain Rating Index (PRI) and the Present Pain Index (PPI). The PRI contains four subscales to evaluate the sensory, affective and evaluative, and miscellaneous aspects of pain. The PPI is a six-level pain intensity scale, including none (0), mild (1), discomforting (2), distressing (3), horrible (4), and excruciating (5) , 21. The2, matrix = 64 × 64, flip angle = 90°, slice thickness = 3.6 mm, 40 interleaved axial slices, and 180 volume. High-resolution T1-weighted 3D MPRAGE images were acquired for all subjects: repetition time/echo time = 1,900/2.12 ms, field-of-view = 256 × 256 mm2, 320 sagittal slices, 0.6 mm slice thickness, flip angle = 9°. All the participants were instructed to lie still with their eyes closed while remaining awake. After the scan, the subjects were asked whether they remained awake during the entire scan. All acquisitions were visually inspected for the presence of imaging artifacts. None of the participants were excluded on this basis.All participants underwent MRI scans using a 3T Siemens scanner  at the Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China. Foam cushions were used in the scan process to reduce head translation and rotation. The resting-state functional MRI scans were obtained using an echo-planar imaging sequence with the parameters as follows: repetition time/echo time = 2,430/30 ms, field-of-view = 240 × 240 mmhttp://www.restfmri.net)  software (mri.net) . The firmri.net) .p < 0.001, cluster size = 5). Post hoc analyses using two-sample t-tests were also conducted among the three groups. The significant results of ANOVA were selected as an output mask in the following t-tests. A p < 0.05 (a minimum cluster size of five voxels) corrected by false discovery rate (FDR) correction was considered a difference between groups. Age and gender were controlled as covariates in all the above-mentioned statistical analyses.The ALFF for each voxel was normalized, and one-way ANOVA was used to determine whether there were any statistically significant differences in the ALFF between these groups . The mean ALFF of this ROI was extracted and normalized with Fisher's z-transformed function. The associations between the transformed ALFF value and the scores of clinical pain scales were tested using Pearson's correlation. A http://www.mlnl.cs.ucl.ac.uk/pronto/). Individual resting-state functional MRI was treated as points located in a high-dimensional space defined by the ALFF values in the preprocessed images. Significant clusters of the above ALFF analyses results were extracted and considered as a mask. This mask was applied to each preprocessed functional MRI to select the normalized ALFF values as a feature in the modeling. The classifier created in the present work  is based on binary SVMs. During the cross-validation step, a “leave-one-subject-out” method was used . These results may have important implications for understanding the brain abnormalities and the clinical characteristics of this disorder. Mean ALFF values in these pain-related regions may be used for the classification of neuropathic pain patients and healthy subjects.In the present study, resting-state functional MRI and a machine learning method were combined to explore the abnormalities of spontaneous neuronal activity in patients with HZ and PHN. We demonstrated that, compared with HC, spontaneous brain activity was reduced in both patient groups. For HZ patients, reduction in neural activity was observed in the bilateral precuneus, left PCC, right MTG, and right AG. For PHN patients, the decreased activity was noted in the bilateral precuneus, left PCC, right MTG, and MFG. The mean ALFF values extracted from all these regions were significantly correlated with the clinical pain scales in the PHN group, but not in the HZ group. This result suggested that the spontaneous activity of these regions, in some respects, reflects the pain severity in PHN. In particular, machine learning classification using SVM showed that neuropathic pain patients (HZ and PHN) and healthy subjects could be classified by the decreased activity in these regions. The classifier also partially categorized patients into HZ and PHN groups . The SVM classifier performed between HZ and PHN patients had a classification accuracy of 61.54%. We did not achieve as high a classification accuracy as in previous studies , 46. It There are several limitations in our study. Firstly, our present research used a cross-sectional design in which the MRI data of the subjects were obtained at just one time-point. This method may lead to questions about whether the results are the consequence of preexisting differences between groups. Future studies should consider a longitudinal design, which can directly monitor activity changes from acute pain to chronic pain. Secondly, all patients are allowed to take the drug therapy of the pregabalin and amitriptyline which may certainly inhibit or reduce the brain function. A well-controlled group should be established in further studies.In the present study, we discovered reduced spontaneous brain activity in the precuneus/PCC, MTG, AG, and MFG of patients with neuropathic pain. The reduced ALFF in these regions was associated with the clinical pain scales of patients with PHN. The SVM classification indicated that these abnormalities might accurately discriminate between neuropathic pain patients and healthy controls at the level of the individual. A similar analysis also demonstrated that the abnormalities in ALFF values showed potentials to distinguish patients with PHN from those with HZ. These results are likely to be valuable in explaining the underlying neural mechanisms and understanding the interaction between neuropathic pain and brain abnormalities. The present results provided new insights into functional MRI as a pain biomarker to help diagnose and classify patients with neuropathic pain. Future work should combine functional information with structural imaging data to examine whether this leads to a higher diagnostic accuracy.All datasets generated for this study are included in the article/The studies involving human participants were reviewed and approved by the Ethics Committee of the Huazhong University of Science and Technology Union Shenzhen Hospital. The patients/participants provided their written informed consent to participate in this study.WS, SY, and LX designed this work. JH, XB, DL, and YL collected the data. YL and HX analyzed the data. YL, JH, and LX discussed the results. YL wrote the initial draft. YL, JH, LX, and CJ substantially revised the manuscript. LX acquired the funding. All authors agreed to be accountable for all aspects of this work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Synthetic non-resorbable mesh is almost standard in hernia surgery. However, several studies have showed negative effects of permanent implants such as chronic inflammation and complications involving different organs bordering the mesh. Such complications can raise the risk of chronic post-operative pain (CPP). Recently promising results regarding CPP have been published in patients with Lateral Inguinal Hernia (LIH) using a slowly resorbable mesh in Lichtenstein technique. For this reason the aim of the present study was to find the effect of a slowly resorbable implant on the long-term rate of hernia recurrence and chronic post-operative pain in patients with LIH repaired with TEP procedure.® Matrix Surgical Mesh in 35 primary LIH. At 3-year follow-up the Visual Analogue Scale (VAS) and the Inguinal Pain Questionnaire were employed to assess pain. Recurrence was determined by ultrasound and clinical examination.Prospective pilot study of TEP repair using TIGRAll patients completed the pain questionnaires but one patient did not attend the planned clinical examination for the 3-year follow-up. No patients had CPP, as defined in the World Guidelines for Groin Hernia Management. Almost all patients had lower VAS score in any activity 3 years following surgery in comparison to the preoperative period. Three patients (8.8%) suffered symptomatic recurrence during the 3-year follow-up.TEP repair in patients with LIH using a synthetic long-term resorbable mesh was found to be encouraging respecting chronic post-operative pain at 3-year follow-up but at the cost of an increased risk of recurrence. The use of permanent synthetic implants in hernia surgery has led to a powerful reduction in the recurrence rates –3. HowevBiological and synthetic degradable meshes have been tested in the last few years in order to reduce the risk of CPP. Some biological meshes have shown relatively good results on recurrence and pain in small studies , 11. TheSynthetic implants with longer resorption time used in open hernia surgery have been proven to be an alternative way to prevent CPP. A pilot study using such an implant, the TIGR Matrix Surgical Mesh, in the Lichtenstein technique showed good results on chronic pain and recurrences in patients with LIH at a 3-year follow-up but a high rate of recurrences in patients with MIH . Since vDuring June 2014 and February 2015 patients consulting for groin hernia and suitable for TEP operation at the department of surgery at Halland’s Hospital/Kungsbacka, Sweden, were asked to participate in this prospective study. Twenty-seven male adult patients with thirty-five primary unilateral or bilateral inguinal hernias were included in the trial. Exclusion criteria were: BMI > 35, irreducible hernias, pre-existing inguinal pain nondependent of the hernia and unwilling or unable to give informed consent. More information about enrollment and the recruitment of the patients in the study is shown in Fig. The study was approved by the Regional Ethical Review Board in Lund, Sweden. Protocol 2014/2. All the patients enrolled in the trial provided informed consent. The study does not include any animal trial.® Matrix Surgical Mesh. The description of the hernia was done according to the Classification of the European Hernia Society (EHS) and the Swedish Hernia Register (SBR). An extended description of the operation technique has been previously published [Three surgeons, with extensive experience on the TEP technique, performed the operations under general anesthesia. During the surgery patients with Femoral, Medial Inguinal or Combined Inguinal Hernias, and patients with any medial bulging were excluded from the trial and received a perdurable mesh. Patients with LIH were implanted with a 10 × 15 cm TIGRublished .Pain was reported before and after surgery using two pain questionnaires validated for hernias , 19, theRecurrences were assessed by both physical examination by a surgeon and ultrasound performed by a radiologist experienced in hernia diagnostics.® SPSS® Statistics 24.Continues data were summarized by descriptive statistics and comparisons of continuous dependent variables were analyzed using the nonparametric Wilcoxon signed ranks test. All statistical analyses were done with IBM2 (20–33). No patient was female and no patients had sliding hernias. Other Intra-operative data is shown in Table Twenty-seven male patients with a mean age of 55.7 (26–75) years were admitted in the trial. Eight patients had bilateral and nine-teen unilateral hernias, resulting in a total of thirty-five hernias. Body Mass Index mean was 26.3 kg/mAll patients completed the pain questionnaires but one patient did not attend the planned clinical examination for the 3-year follow-up. No patient had chronic post-operative pain as described in the methods at the 3-year follow-up. Almost all the patients had lower VAS score in any activity 3 years following surgery in comparison to the preoperative period Fig. . The meaThree patients (8.8%) suffered symptomatic recurrence before the 3-year follow-up. Two patients have been re-operated, one patient for a MIH and the other one for a LIH, 28 and 18 months after primary surgery, respectively. The third patient with recurrence 18 months after primary hernioplasty is not interested in surgery because of absence of bothersome symptoms. At 36-months follow-up no other patients had symptomatic or clinically verified hernias but four new hernia recurrences (11.7%) were found solely on ultrasound.In this study, only a slowly resorbable implant, without any sutures or tacks, was used to cover the incompetent internal ring of the inguinal canal. At 3-years follow-up the majority of the patients had a competent inguinal canal, without signs of recurrence even using ultrasound examination. Three years after the surgery the mesh should have been fully absorbed , 21, theSome biological meshes used in hernia surgery have shown likewise acceptable results on recurrences –24. ThosThe idea of using a synthetic slowly degradable mesh in hernia surgery is based on the hypothesis that the body just needs a matrix to stimulate the formation of a fibrous sheet to cover the hernia defect and reinforce the abdominal wall. This concept presupposes a normal function of the regenerative connective tissue including collagen , 27. TheAll the patients with palpable recurrences in this study had the first symptoms of recurrences at least 18 months after surgery. At this time the mesh should have lost the mechanical stability to contain the abdominal pressure . If an iOne of the patients with recurrence was operated primary for bilateral hernias. The patient had a MIH recurrence solely in the side with the primary bigger defect but no recurrence has been found yet on the other side. If this situation does not change in the future, it would mean that not only connective tissue deficiencies are implicated in the recurrences, but other factors, like the size of the hernia defect, can play a role for hernia recurrences.This study found an incongruence between ultrasound verified recurrences and recurrences found by palpation at 3-year follow-up. Patients with recurrences solely confirmed by ultrasound did not have any symptoms. The reliability of ultrasound in the diagnosis of symptomatic but no palpable hernias is well known ; howeverThere is an enormous variation of the rate of pain after hernioplasty in the literature (20–45%) , 41. ThiIn the current study, we have excluded patients with preexisting inguinal pain conditions unrelated to the hernia. However, 68.6% of the included patients suffered from clinically significant inguinal pain preoperatively, which is considered a risk factor for CPP , 41. DesThis was the first study using a synthetic slowly resorbable mesh in the TEP procedure in human, thus it was planned as a safety and feasibility study. Consequently the limitations of the study lie in the non-randomization and in the small number of patients. However, the assessment of pre-operative and post-operative pain using diverse validated pain questionnaires, the rigorous assessment of possible recurrence with ultrasound and physical examination and the long follow-up strengthens the results of the present study. The role of slowly resorbable meshes on CPP in LIH repair cannot be elucidated from this study but the results regarding chronic post-operative pain in these patients are so satisfactory that it could motivate larger, randomized studies in a more selected patient population in order to confirm these findings. Given that one part of the population with inguinal hernias have collagen deficiencies , 31, 33,TEP repair in patients with LIH using a synthetic long-term resorbable mesh was found to be encouraging respecting chronic post-operative pain at 3-year follow up but at the cost of an increased risk of recurrence. Longer follow-up is necessary to establish the risk of recurrence at an even longer follow-up time than 3 years. Randomized control studies with standard mesh are necessary to know the real effect of slowly degradable implants on CPP. But such studies need more selective inclusion criteria of the patients in order to increase the potential benefits on CPP without raising the risk of recurrence in those patients.


Race and ethnicity are associated with disparities in pain management in children. While low English language proficiency is correlated with minority race/ethnicity in the United States, it is less frequently explored in the study of health disparities. We therefore investigated whether English language proficiency influenced pain management in the post-anesthesia care unit (PACU) in a cohort of children who underwent laparoscopic appendectomy at our pediatric hospital in San Francisco. Our primary exposure was English language proficiency, and our primary outcome was administration of any opioid medication in the PACU. Secondary outcomes included the amount of opioid administered in the PACU and whether any pain score was recorded during the patient’s recovery period. Statistical analysis included adjusting for demographic covariates including race in estimating the effect of language proficiency on these outcomes. In our cohort of 257 pediatric patients, 57 (22.2%) had low English proficiency (LEP). While LEP and English proficient (EP) patients received the same amount of opioid medication intraoperatively, in multivariable analysis, LEP patients had more than double the odds of receiving any opioid in the PACU . LEP patients received more oral morphine equivalents (OME) than EP patients , and they also had almost double the odds of having no pain score recorded during their PACU recovery period , although the precision of these estimates was limited by small sample size. Subgroup analysis showed that children over the age of 5 years, who were presumably more verbal and would therefore undergo verbal pain assessments, had over triple the odds of having no recorded pain score . In summary, English language proficiency may affect the management of children’s pain in the perioperative setting. The etiology of this language-related disparity is likely multifactorial and should be investigated further. Disparities in pediatric pain management associated with race/ethnicity are well-documented. In emergency departments nationwide, Black children receive opioids at significantly lower rates than White children when presenting with acute appendicitis . In the linguicism  language) and expressing that “language is a social practice that shapes subjectivity and establishes power relations among members of different racial and class groups” [In the United States, race and language are intricately connected, with scholars describing the practice of  groups” . English groups” ,7, is ho groups” . In addi groups” . In addi groups” .The present study is focused on further examining the role of language disparities in perioperative care. Specifically, we conducted a retrospective cohort study in order to understand whether English language proficiency influenced PACU pain management in a cohort of children who underwent laparoscopic appendectomy at an urban pediatric hospital in San Francisco, where a large proportion of residents do not speak English at home . We hypoWe used electronic medical record data from our academic pediatric hospital located in Northern California to conduct a retrospective cohort study among patients who underwent laparoscopic appendectomy between February 2015 and July 2019. Eligible patients were age 18 years or younger and were recovered in the PACU after surgery. All laparoscopic appendectomies were performed by pediatric general surgeons who used three port sites and administered local anesthetic subcutaneously at these sites during surgical closure. All anesthetics were administered by pediatric anesthesiologists who provided a balanced anesthetic with a volatile agent, a medium- to long-acting opioid , and boluses or infusion of an intravenous sedative/hypnotic (propofol). Other analgesics and sedative/hypnotics including short-acting opioids , ketamine, and dexmedetomidine were not routinely used. For each patient, follow-up extended from the four hours preceding surgery until they were discharged from the PACU.The primary exposure of interest in our analysis was English language proficiency, which we determined based on whether an interpreter was needed when the patient and their parent or guardian presented for their appendectomy or for any prior clinical encounter. Patients were categorized as having low-English-proficiency (LEP) if they indicated that an interpreter was needed and designated as English-proficient (EP) otherwise.Our primary outcome of interest was whether a patient received any opioid medication in the PACU. Opioid medications included fentanyl, morphine, hydromorphone, oxycodone, hydrocodone, methadone, and tramadol. We created an indicator variable that equaled one if the patient received any of these opioid medications in the PACU and zero otherwise. Secondary outcomes included the amount of opioid administered in the PACU, calculated in oral morphine equivalents (OME) per kilogram ,13. We aPatient demographics included in the present study were continuous age (0–18); categorical patient- or family-reported gender ; categorical patient- or family-reported ethnicity (Hispanic or Non-Hispanic); and categorical patient- or family-reported race. For race assignation, patients and their parent/guardian could decline to answer or self-identify one or more categories from the U.S. Census list of race categories  , “Other,We also compared LEP and EP patients in terms of American Society of Anesthesiologist ratings, preexisting medical conditions , use of opioids before admission, time in the operating room, presence of appendiceal perforation and/or peritonitis, opioids administered intraoperatively (in OME per kilogram), nonopioid adjunct medications administered intraoperatively (acetaminophen and/or ketorolac), and occurrence in the PACU of laryngospasm, postoperative nausea/vomiting, low respiratory rate (<10 breaths per minute), and low oxygen saturation (<90%). We did not include these variables in our subsequent statistical analyses because we hypothesized that they were related to the outcomes in the causal pathway solely as mediators, rather than as confounders.We used generalized logistic regression to estimate the association between language proficiency and PACU opioid administration. We hypothesized that demographic factors may influence how PACU nurses assessed and treated patients’ pain. This model was therefore adjusted for demographic characteristics as enumerated above. Ethnicity was not included in this model or subsequent models as only three patients self-identified as Hispanic.Next, we examined the association between language proficiency and the amount of opioid administered in the PACU in OME per kilogram. The observed distribution of OME per kilogram administered exhibited overdispersion due to a point mass at zero and right skew, which we accommodated by using negative binomial regression, adjusting for demographic characteristics as described above. We also conducted a supplementary analysis using this method to estimate the association between language proficiency and the amount of intraoperative opioid administered in OME per kilogram.Finally, we used generalized logistic regression to estimate the association between language proficiency and whether a pain score was incorporated in the PACU after adjusting for demographic characteristics. We then conducted a subgroup analysis by stratifying our cohort by age  to delineate differences in how nurses may interact with and elicit pain scores from young children versus older, school-aged, more verbal children.Statistical analyses were performed using R version 3.6.3  . This stDuring our study period, 257 pediatric patients underwent laparoscopic appendectomy and subsequently recovered in the PACU. Of these, 57 (22.2%) were identified as LEP. The most common language spoken by LEP patients was Spanish (80.7%). Characteristics of these patients are presented in For the remainder of the results, we report 95% confidence intervals but do not interpret results using null hypothesis significance testing. Rather, we attempt to determine if regression results imply an underlying relationship between exposure and outcome .In multivariable analysis, LEP patients had more than double the odds of being administered any opioid in PACU compared to EP patients  . LEP patLEP patients also had approximately double the odds of having no pain score recorded during their PACU recovery periods  . In subgOur retrospective cohort study identifies English language proficiency as a potential contributor to disparities in children’s perioperative pain management, in addition to the racial disparities that have been reported previously in the PACU ,18 and tOptimal treatment of pain requires balancing both objective and subjective assessments of pain and can prevent long-lasting complications in a post-surgical population. Overreliance on objective pain scales, without incorporation of clinicians’ and patients’ subjective assessments, can increase patient anxiety and diminish the therapeutic alliance among patients, family members, and their healthcare providers . HoweverIn our cohort, a large proportion of children underwent no objective measurement of pain during their PACU recovery period, with LEP children being more likely to have no recorded pain score and more likely to receive opioid medication in the PACU. Our data did not elucidate what types of subjective measurements clinicians may have used to assess pain before administering opioids, or whether LEP children were overtreated or oversedated. While there were almost no documented occurrences of nausea/vomiting, low respiratory rate, or low oxygen saturation in the PACU in either the LEP or EP groups, these outcomes are often transient and may not be adequately captured in our medical record. In our open-model PACU, a low oxygen saturation event may be shorter than a minute and be rapidly corrected by stimulation or administration of supplemental oxygen. Such transitory events would not automatically be entered into the patient’s medical record. Future studies should investigate the types of non-objective assessments being done in the PACU and whether these do indeed result in oversedation.The reasons behind language-related differences in care—including the likelihood not to use objective measures of pain—are likely multifactorial and related both to interpersonal and systemic factors. Interpersonal factors may include conscious or subconscious bias against those who do not speak English  ; patientThis retrospective study was based on language assessment data from inpatient and outpatient admissions personnel and may therefore be subject to selection or information bias. A bilingual child may have been denoted as LEP if their parent or guardian was LEP; thus, a nurse could potentially assess the patient’s pain in English in the PACU even if the parent or guardian may have needed interpretation for more complicated discussions. Further, our medical record does not include information on non-English languages spoken by the patient’s assigned nurse. These types of errors are common in language data collection , and in Children with generalized peritonitis and/or perforation experience more pain following laparoscopic appendectomy . While oOur data also illustrate the complexity in portraying constructs such as ethnicity. Only three of 54 Spanish-speaking patients self-identified as Hispanic, findings which are inconsistent with our city demographics . Self-idFinally, our study was conducted at a single academic pediatric hospital in San Francisco, and findings therefore may be unlikely to reflect the experiences of patients who receive care in other hospital systems due to meaningful differences in patient and staff demographics. Subsequent larger studies may provide more precise and generalizable findings regarding potential language-related biases in pediatric populations.In this retrospective cohort study of 257 pediatric patients, we found that English language proficiency may affect the management of children’s pain in the perioperative setting at our institution. Our study underscores the importance of communication in decisions surrounding pain management. Our findings motivate further investigation regarding the role that language plays in treatment decisions in pediatric patient populations, as well as efforts to identify strategies to optimize pain management for all of our patients regardless of their language.


Postoperative pain protocols play a critical role in recovery and prognosis. Rapid recovery pathway (RRP) is a novel multimodal postoperative analgesic platform with accelerated rehabilitation.A retrospective review of 44 patients with adolescent idiopathic scoliosis who underwent posterior spinal fusion between 2014 and 2016 was conducted. Outcomes of a conventional postoperative pain pathway were compared with patients who received RRP postoperatively.P < 0.0001), duration with Foley , and fewer days for physical therapy clearance . Overall pain score for RRP patients was lower . The number of days with patient-controlled analgesia was shorter , and daily pain scores were consistently lower in RRP. Overall narcotic use was not significantly different (P = 1).RRP patients had shorter length of stay (3.3 vs 4.4 days, Implementation of a standardized RRP with multimodal pain management and early mobilization strategies resulted in reduced daily and overall pain scores, earlier clearance by physical therapy, decreased length of stay, and patient-controlled analgesia usage, but overall no difference in narcotic consumption.Level III, Retrospective Cohort Study Spinal arthrodesis or posterior spinal fusion (PSF) has become the mainstay of treatment for severe AIS to correct and prevent further progression of the spinal deformity while preserving pulmonary function.3 Postoperative pain protocols play a critical role in quicker recovery and improved prognosis and are an important area of study and improvement.45678 Rapid recovery pathway (RRP) is a novel multimodal analgesic platform with accelerated rehabilitation, which was implemented at our institution to better control pain with less narcotic use, ultimately leading to a quicker recovery.9 The risk of opioid-induced hyperalgesia, which refers to a phenomenon where opioid administration results in lowering of pain threshold, could also be reduced.11 Furthermore, a 22% decrease in postoperative hospital costs was found using an accelerated pathway.12 The goal of this study was to evaluate the outcomes of the RRP in comparison with the conventional pain pathway in adolescent patients who underwent PSF for AIS treated at our institution. We hypothesized that patients undergoing the RRP would have earlier hospital discharges, diminished pain, and less narcotic consumption.Adolescent idiopathic scoliosis (AIS) is the most common type of scoliosis in children of age 10 to 18 years.We have done a retrospective review of two cohorts of patients with the diagnosis of AIS who underwent PSF at our institution. Patients were broken up into two cohorts based on the postoperative treatment protocol received, either the conventional pain pathway or the RRP. Patients in the conventional pain pathway cohort had their surgeries done in the summer of 2014. Patients in the RRP had their surgeries done in the summer of 2016. All surgeries were done by a single surgeon without change in technique, technology, or implants. Inclusion criteria included all postoperative AIS patients treated with PSF. Exclusion criteria included those individuals with neuromuscular, congenital, or nonidiopathic scoliosis, anterior spinal fusions, or any intraoperative complication, including hemorrhage, coagulation, or loss of motor signal that required postoperative intensive care unit monitoring greater than 24 hours.This study was done with the approval of the Children's Hospital of Orange County Institutional Review Board.The conventional pain pathway had been used until RRP was implemented at our site in 2016. Patients in the conventional pain pathway had a postoperative pain protocol that included 24-hour monitoring in the pediatric intensive care unit, a 24-hour period of nothing by mouth starting after completion of the procedure, physical therapy (PT) on postoperative day 1, scheduled weight-based dosing of ibuprofen, and intravenous (IV) dilaudid through patient-controlled analgesia (PCA) with a gradual transition to oral pain medications. Patients in the RRP had a postoperative pain protocol that included a preoperative oral dose of gabapentin 600 mg, a full diet beginning on the day of surgery, 24 hours of postoperative IV acetaminophen, IV dilaudid through PCA, IV ketorolac for 48 hours beginning postoperative day 1, hydrocodone/acetaminophen 5/325 mg orally scheduled every 6 hours, oral gabapentin 300 mg three times a day for 7 days, oral diazepam 2 mg as needed three times per day, and PT to be initiated on the day of surgery. Dosing of diazepam was standardized for consistency and ease of administration instead of weight-based dosing. Other medications were administered on a weight-based scale if no dosage was specified.13 Patients' pain score and narcotic requirement were measured at each day before discharge. Thus, the differences of daily pain score and narcotic requirement were also examined as the secondary outcomes. The mean and SD were provided for all outcomes in the conventional pathway and RRP group. Multivariate linear regression was used to examine the difference in LOS, time to Foley catheter removal, the postoperative hospital day that the patient was deemed safe for discharge by PT, number of doses of benadryl and ondansetron, and number of days with PCA with adjustment for the number of spinal levels fused which reflects patients' disease severity. A mixed-effect model was conducted to compare overall pain score and narcotic requirement between groups with number of spinal levels fused and day of surgery as the fixed effect and a random effect to account for the within-subject correlation. For pain score and narcotic requirement, only the day of surgery and the next 3 days were used in the analysis for comparison because most patients were discharged from the hospital after day 4. A Bonferroni correlation was used to adjust for the multiple comparisons among primary outcomes.The primary outcomes for our study were length of stay (LOS), time to Foley catheter removal determined by ambulation status, overall pain score measured by the visual analog score, postoperative hospital day that the patient was deemed safe for discharge by PT, overall narcotic requirement in mg/kg morphine equivalent calculated through the Opiate Equianalgesic Dosing Chart from the University of North Carolina Hospitals, number of doses of benadryl and ondansetron, and number of days with PCA.P < 0.0001; Table P = 0.01). Time to clearance for safe discharge by PT was significantly shorter in the RRP. The mean (SD) number of hospital days before clearance for discharge by PT for the conventional pathway and the RRP were 3.50 (0.67) and 2.23 (0.53) days, respectively. RRP patients took 1.26 less days to be cleared for discharge by PT, adjusted for number of spinal levels fused . The overall usage of narcotics was not significantly different between the two groups (P = 1.0000), but daily usage was less in the RRP group except for day of surgery, postoperative day 1, and postoperative day 2, although statistical significance was not reached (Table P = 0.0024). Within our secondary outcome measurements, daily pain score was consistently lower in the RRP group compared with that of the conventional pathway group  were in the conventional pathway and 22 were in the RRP who had undergone PSF for AIS for the same operative indications. Median age of patients at the time of surgery was 15 years for the conventional group with a range of 11 to 19 years and 16 years for the RRP group with a range of 11 to 21 years. In the RRP, there were 3 (14%) male patients and 19 (86%) female patients. In the conventional pathway group, there were 5 (23%) male patients and 17 (77%) female patients. Within the primary outcomes measurements, the mean (SD) LOS for the conventional pathway and the RRP were 4.41 (0.73) and 3.32 (0.57) days, respectively. Patients in the RRP group were discharged 1.08 days earlier than those in the conventional pathway group after adjusting for the number of spinal levels fused to address higher estimated blood loss and longer lengths of surgery with an increasing number of spinal levels fused (14 However, further improvements in pain control, narcotic consumption, and rehabilitation are warranted to maximize patient-oriented outcomes, minimize procedure-related morbidity, and decrease costs in total perioperative care.15 It is well known that the immediate postoperative period may present with a number of innate challenges including pain control, delayed mobilization, and numerous opioid-related adverse effects such as nausea, vomiting, abdominal pain, ileus, and opioid-induced hyperalgesia.11 Pain control can be difficult in patients undergoing multiple level spinal fusions but more so in children and adolescents. Several postoperative protocols have been designed to diminish pain and enhance recovery in adolescent patients undergoing PSF with many involving a combination of IV and oral opioids, bed rest, and strict nothing by mouth. With the advent of multimodal analgesia, other surgical subspecialties, including total joint arthroplasty and colon surgery, have seen benefits in the perioperative period.15 The RRP was designed with a multidisciplinary team to accelerate rehabilitation by decreasing pain, opioid-related complications, and LOS. Ladha et al demonstrated that the United States had the highest average dose of postoperative opioid prescriptions compared with Canada and Sweden. Further scrutiny into prescribing practices of opioid pain medications is warranted.16 Although previous research has shown that RRP decreased LOS and hospital costs by 22%, our main goal was to report our success with the implementation of this new protocol and evaluate pain scores and narcotic consumption at our institution.15 We conducted a detailed, surgeon-specific comparison of patients treated with the conventional pain pathway with those treated with the newly implemented RRP. Our results indicated that the RRP group resulted in a decrease in LOS, decrease in time to PT clearance, earlier Foley catheter removal, and decrease in daily and overall pain scores. We did not find a difference in overall narcotic consumption between protocols. This may be explained by an earlier transition to oral, around the clock opioid administration. PCA was used on average of 0.89 days less compared with the conventional pain pathway. The amount of antiemetic medications used showed no statistically significant difference, although a lower trend was seen within the RRP group. It is our impression that those individuals with the multimodal analgesia protocol were more awake, alert, mobile, and comfortable as demonstrated by earlier times to PT clearance, Foley removal based on ambulation status, daily pain scores, and hospital discharge. Our transition to an accelerated protocol proved successful to our institution focusing on early ambulation, pain management, and standardized postoperative care.With the advent of PSF in patients with AIS, we have seen several advancements in postoperative recovery.This study is limited by its retrospective design and/or selection bias. Differences may be due to the hospital staff from preoperative nurses, anesthesia, postoperative, and floor nurses being aware of a newly implemented protocol. Another contributing factor may have been added emphasis on collecting pain scores by nursing and hospital administration in the RRP. In addition, a limitation of this study is that we do not have pain data after discharge. Another limitation is not having satisfaction surveys from parents and patients regarding their perception of the postoperative care. Although these would provide a baseline understanding of patient satisfaction, satisfaction surveys were not collected during the traditional protocol, and there would have been no means for comparison. Postoperative ileus and complications were not accounted for or compared from the conventional pathway with the RRP group. Return to the emergency department was also not documented for complications to be compared between groups. Despite these limitations, this study demonstrates that an accelerated protocol for PSF for the treatment of AIS can enhance recovery by earlier mobilization, earlier diet tolerance, and earlier hospital discharge.


Patient recovery expectations can predict treatment outcome. Little is known about the association of patient recovery expectations on treatment outcome in patients with neck pain consulting a manual therapist. This study evaluates the predictive value of recovery expectations in neck pain patients consulting manual therapists in the Netherlands. The primary outcome measure ‘recovery’ is defined as ‘reduction in pain and perceived improvement’. A prospective cohort study a total of 1195 neck pain patients. Patients completed the Patient Expectancies List (PEL) at baseline , functional status (NDI), the Global Perceived Effect (GPE) for recovery  post treatment and pain scores (NRS) at baseline and post treatment. The relationship between recovery expectancy and recovery (dichotomized GPE scores) was assessed by logistic regression analysis. Patients generally reported high recovery expectations on all three questions of the PEL (mean sumscores ranging from 11.3 to 11.6). When adjusted for covariates the PEL sum-score did not predict recovery . Separately, the first question of the PEL showed predictive potential  for recovery, but failed to reach statistical significance. In this study patient recovery expectations did not predict treatment outcome. Variables predicting recovery were recurrence and duration of pain. The precise relationship between patient recovery expectations and outcome is complex and still inconclusive. Research on patient expectancy would benefit from more consistent use of theoretical expectancy and outcome models. Among other factors, for medical care, personal experiences and those of family members and acquaintances develop these recovery expectations. Recovery expectations can also be influenced by the interactions that a patient has with the healthcare provider3.Patient recovery expectations are defined as patient’s perceptions that a certain outcome of medical care is likely to occur4. This theory encompasses two relevant aspects of medical treatment: the patient as a passive recipient of treatment and the patient’s volitional health-directed behavior. The first aspect refers to the expected occurrence of the individual’s non-volitional, internal responses to a certain external stimulus . The second aspect refers to the outcome expectancies of one’s own volitional health-directed behavior . Patient recovery expectations have the potential to influence treatment adherence and outcome. So far expectancy research within the realm of physical and manual therapy is limited and mainly aimed at low back pain. The results vary, with some studies failing to find predictive value for patient expectancy6, and others succeeding in doing so11.Recovery expectancies are believed to influence treatment outcome through mechanisms that are still largely unknown. One of the theoretical frameworks that can help unravel these mechanisms is the response expectancy theory12. At 1 month, patients with lower expectation on pain relief had a lower chance of recovery than those with high expectancies on pain relief . The expectation that spinal manipulation would help while not receiving it also lowered the chance of treatment success  compared to expecting spinal manipulation and actually receiving it. Similar results were found for the influence of expectation on functional status in this study12.A recent study on neck pain patients pre-treatment expectations were found to be related to patients’ ratings of recovery at 1- and 6-months post treatment (exercise and manipulation)13. Approximately one third of all adults is likely to experience neck pain during the course of 1 year14. Neck pain patients often seek help from manual therapists. Current guidelines incorporate known prognostic factors, but assessing expectancy prior to treatment is not a guideline recommendation. A deeper understanding of the influence of recovery expectancy on the treatment outcome in patients with neck pain consulting a manual therapist, could help improve guidelines, clinical decision making and patient outcome. This study aims to evaluate the predictive value of recovery expectancy of neck pain patients on outcome for manual therapy in the Netherlands.Neck pain is a common musculoskeletal disorder with an estimated point prevalence of 9–22% in the general population of the NetherlandsThis study is part of a large prospective cohort study with 12 months follow up in a Dutch manual therapy setting studying the associations between pain attitudes, treatment choices and outcome expectations of manual therapists and non-specific neck pain patients. For this study only demographic data and data on expectancy, functional status and recovery post treatment were extracted from the database.The manual therapists (n = 272) included in this study took part in a part-time 3-year course, aimed to reregister certified Dutch manual therapists with an internationally recognised Master of Science degree. All participating manual therapists were asked to include five consecutive patients of 18 years and over within a time frame of 6 months, that consulted them for their neck pain. Each new patient was immediately recorded in the database, providing insight in the inclusion flow.15. Excluded were all patients with known specific causes of neck pain  and patients who were unable to read and/or write Dutch. The patients received information on the study and signed an informed consent to be included in the study. Demographic information  was collected through the participating manual therapists at baseline, including those individuals who were screened for eligibility, qualified for the study, but refused to participate. This information was only used to check representativeness of the study group. Ethical approval for this study was obtained from the Medical Ethical Committee (MEC-2007-359) from Erasmus University Rotterdam, the Netherlands.All adult patients consulting with non-specific neck pain were eligible. Neck pain is defined as pain located in the area between occiput and the spinae scapulaeSocio-demographic and professional data were collected and comprised gender, age, occupational setting, number of hours at work, number of years of experience with the management of non-specific neck pain patients.Baseline data  were recorded and all patients completed a baseline questionnaire including the Numeric Rating Scale (NRS) for pain intensity, functional status (Neck Disability Index (NDI), and the Patient Expectations List (PEL). The PEL is based on the two aspects of the response expectancy theory and was developed by expert consensus specifically for use in a Dutch manual therapy setting. It models ‘expectancy’ as a two-component variable consisting of ‘treatment modality’ and ‘conviction’. It consists of 3 questions, each with a sub-question see Box . Each quSince the clinimetric properties of none of the separate PEL-questions  have been evaluated so far, we will analyse the separate questions as well as the PEL sum scores.17. The GPE was reassessed at 12 months.At the end of the individual treatment episodes, pain and the primary outcome ‘recovery’ were assessed with the Numeric pain rating scale (NRS) and Global Perceived Effect (GPE) respectively. On the GPE scale the patient scored on a 7-points Likert scale how much their condition improved or deteriorated since the start of the treatment, ranging from ‘complete recovery’ to ‘worse than ever’. The GPE has several qualities that make it an appealing tool for use in clinical practice and research; being a single question, it is easy and quick to administer and the results are seemingly simple to interpretWe used descriptive statistics (SPSS version 20.0) to summarize the baseline and post-treatment data. The independent variable was patient expectation. PEL scores were calculated for separate questions as well as for the total PEL and with the exception of the added dichotomous question, analysed as continuous variables. PEL scores for acute and non-acute neck pain patients were calculated separately. The outcome of interest was recovery (measured using the GPE) post treatment. The recovery data post treatment and at 12-months follow-up were dichotomized into “recovered” (scores ‘completely recovered’ and ‘much improved’) and “not recovered” (‘slightly improved’ to ‘worse than ever’). Recovery data at 12 months follow-up were compared to the post treatment data for stability of recovery with McNemar’s test.19.As possible confounders patient age, gender, functional status, baseline pain scores, duration and recurrence of neck pain, smoking, and sports participation were entered in the analyses20. A total of 10 datasets were created and analysis was performed on all datasets. Pooled estimates were calculated according to Ruben’s rules21. All candidate predictors derived from the literature were checked for multicollinearity. Association between candidate variables and recovery was checked using Chi-square tests. Correlation coefficients ≤ 0.35 were considered to represent low association, 0.36–0.67 modest correlations, and 0.68–0.89 high and ≥ 0.90 very high correlations23.Concerning missing data, first we evaluated whether there are specific patterns of missing data using Little’s MCAR test. We also compared baseline data between patients with and without missing data. In case this test was negative we performed multiple imputation to overcome a loss of power due to missing’s. Both predictor and outcome variables were included in the multiple imputationUnivariate analyses were performed on single PEL questions and PEL sum scores separately. Next the univariate analysis were adjusted for previous experiences with manual therapy as a possible confounder to evaluate the association of expectancy and recovery.p < 0.10 in the univariate analysis24. Overall performance of the model will be expressed by Nagelkerke’s R2 and the discriminant ability using the area under the curve (AUC). An AUC of 1.0 indicates perfect discrimination, between 0.8 and 1 indicates acceptable discrimination, between 0.7 and 0.8 fair discrimination, whereas an AUC of 0.5–0.7 indicates poor discrimination above chance25. The goodness-of-fit of the model was determined with the Hosmer–Lemeshow statistic26.Lastly, we performed a multivariate analysis  to build a prognostic model. To be able to adhere to the criterion of at least 10 events per variable we selected the variables with a The majority (79%) of the manual therapists (MPTs) were male, with a mean age of 42.2 (SD 8.4) years, a work experience of 19.3 (SD 7.1) years, averaging almost 24.6 (SD 10.2) hours of work per week in a general practice, with a mean weekly number of neck pain patients of 12.2 (SD 8).Post-treatment data were available for 663 (50.5%) patients, 1 year follow-up data for 385 (29.4%). The demographic data of the patients are presented in Table Patients reported high recovery expectations. Overall 31% of the respondents stated that their recovery expectations were partly based on earlier positive experiences with manual therapy. Due to non-response, complete data on recovery post-treatment were available for 663 patients, of which 523 patients (79%) were classified as ‘recovered’ . Scores for question 1 and 2 yielded slightly higher recovery expectations (means 3.9 (SD 0.4 and 0.5 resp.), range 1–4) than recovery expectations for question 3 (mean 3.6 (SD 0.9), range 1–4). All PEL scores showed negative Skewness and Kurtosis.No differences were found in the total PEL scores, or the individual PEL items, between acute and non-acute neck pain patients.Mc Nemar’s test showed that there were no differences in recovery between the post-treatment measurement and the 12-month follow-up, suggesting that recovery was stable , 0.44 0.05–3.49) and 0.97 (0.94–1.32) for PEL-1, PEL-2 and PEL-3 respectively  of the final models was 0.9 (9%) and 0.10 for separate questions and total PEL respectively. This means that the models explain 9 to 10 percent of recovery. The ROC curve of the model for the total PEL showed a relatively poor discriminating ability for the model with a AUC of 0.675 (0.65–0.74). The models correctly predicted recovery for 80% of the patients.The explained variance . Closely followed by the belief that exercise therapy would add to treatment effects (PEL 3). These high recovery expectations seem to be in line with research done on outcome expectancy in other fields of healthcare28, are countered by studies that fail to establish predictive value of patient expectancies on recovery30.In this study we found that recovery expectations as measured by the PEL did not predict outcome in terms of recovery. These inconclusive results on the predictive value of expectancy are in line with earlier research. Studies that do find predictive value of patient expectancies on recovery31. Some studies use different terminology for overlapping qualities of expectancy32, others highlight only one or several aspects of expectancy33. Without a more uniform and detailed insight in the make-up of expectancy, comparison and integration of current findings is compromised. Based on perspectives from several human sciences, Thompson and Sunol proposed a helpful distinction between four types of expectation: ideal, predicted, normative and unformed. Their exact make-up and relation to terms such as ‘hope’ and ‘satisfaction’ are yet to be disentangled34.One of the factors that may contribute to these inconsistent findings, is the heterogeneity of the conceptualization and assessment of patients’ recovery expectations35.The effects of terminology may reach even further in expectancy research. Questions on spinal manipulation and exercise assume a uniform definition and meaning of what they consist of and what they can do. That assumption may very well be flawed. How reliably can one quantify expectancy if there is insufficient or at least varying insight in what ‘spinal manipulation’ and ‘exercise’ exactly are? It can be hypothesised that other studies in this field are influenced by the same mechanism, contributing to contrasting results. Lastly, the application of the GPE may add to inconsistent findings. The underlying assumptions of the GPE is that it measures a composite of multiple domains relative to ‘improvement’ or ‘recovery’ of one’s condition, but knowledge on the factors patients take into account when determining their GPE, is still limited. A mixed-method study on de GPE revealed five main themes patients used to construct ‘recovery’, and that chronic neck pain patients have different expectations of recovery than non-chronic neck pain patients. Not expecting to fully recover, may lead to reponse-shift. Lastly the GPE seems to be strongly affected by ‘current status’ instead of ‘stable change’ especially as the transition time lengthens35. Although pain scores in this study seem typical for the population35, the limited variance and low numbers of ‘non-recovery’ may have been the reason for lacking association. Although the majority of patients in this study reported longer existing neck pain, only 31% had earlier experience with manual therapy. The level of evidence for manual therapy is moderate for short-term effects of upper thoracic manipulation in acute neck pain, limited for long-term effects of neck manipulation, and limited for all techniques and follow-up durations in chronic neck pain37. Research on prognostic factors of neck pain has shown that a vast number of predictors provide low predictive value or inconclusive results, suggesting there is still much work to be done in this field38. We non-directionally postulated that earlier experience may influence outcome expectation by providing either ‘lived reference’ to the patient that may be a dominant factor in the make-up of their expectancy.In this study the covariates ‘initial pain intensity’ and ‘functional limitation’ did not contribute to the predictive model. Results of earlier research suggest that high baseline neck pain intensity and high functional limitation have a strong association with outcomeThis study explored the predictive value of patient recovery expectations on outcome for manual therapy in a large group of patients. It contributes to the growing insight in the associations between patient expectancy and treatment outcome in general, and incorporates manual therapy and non-specific neck pain in the scope of research in this field.A limitation of this study is number of missings in recovery scores, the high dropout rate and the limited variance (e.g. most patients reported relatively high PEL scores at baseline) in recovery expectancy, all negatively impacting the statistical possibilities to detect differences and associations. Some form of selection bias cannot be ruled out. Therapists were asked to include five consecutive patients and apart from inclusion flow and cross comparison with non-enrolled patients there was no process installed that guaranteed adherence to the inclusion process. Furthermore, measuring recovery expectancy as a nearly single factor variable seems to be an oversimplification of reality, blurring opportunities to find out more about its make-up and in- and external dynamics. For instance, it is unclear to what degree patients reported ‘ideal’ expectancy based on motivation instead of ‘predicted’ expectancy based on cognition and/or earlier experience. Since patient expectations on recovery were under-modelled and overall high in this study, and the GPE was dichotomised, the capacity to find possible associations with recovery may have been limited.Another limiting factor in this study is the developmental stage of the PEL. The PEL is a newly developed questionnaire and insight in its psychometric properties is lacking. There is limited insight into its psychometric properties.For practice. Understanding patient recovery expectations of treatment outcome is an important part of developing treatment plans and stimulating therapy adherence. Even though evidence is still sparse and inconclusive, there still may be practical reasons to measure recovery expectations . It may be a quick and reproducible route to an ‘agreement on treatment’ with your patients, since it provides possibilities to ‘synchronise’ preferences on treatment modalities and expectations of their outcome.31. Analogously, adopting a more frequent and nuanced GPE measurement that differentiates between acute and non-acute patients, would improve the capacity to detect possible associations between expectancy and outcome. It would also be relevant to focus on the dynamics and influenceability of recovery expectations during treatment, their physiological make-up and possible capability to influence favourable outcome39.For research. More collaboration is needed on adopting an integrative model of expectancy that incorporates aspects of the common sense model, process or structural recovery expectations and the valence of patients’ recovery expectationsPatient recovery expectations did not predict treatment outcome in this study. Variables predicting recovery were recurrence and duration of pain. Research on patient expectancy would benefit from more consistent use of theoretical expectancy models.All methods used in this study were carried out in accordance with relevant clinical guidelines and regulations on manual therapy for non-specific neck pain.


To describe the appropriateness of two behavioral scales, the Behavioral Pain Scale and the Critical Care Pain Observation Tool, for pain assessment in orotracheally intubated patients admitted to intensive care units.Using the methodology recommended by the Cochrane Center, a systematic literature review was performed in the electronic database EBSCO Host . Two searches were conducted using the following English terms in the search field: “behavioral pain scale” AND “critical care pain observation tool” AND “behavioral pain scale” OR “critical care pain observation tool”. Two independent reviewers performed the critical evaluation and data extraction and synthesis.Fifteen studies were included that showed that the Behavioral Pain Scale and the Critical Care Pain Observation Tool are valid and reliable scales for pain assessment in orotracheally intubated patients admitted to the intensive care unit. The scales showed similar psychometric properties and good reliability.Both scales are adequate for assessing pain in orotracheally intubated patients admitted to intensive care units; however, they exhibit limitations in specific populations, such as trauma, burn and neurosurgical patients. Further studies on the subject and in specific populations are suggested. Thus, it is important to respect patients' own assessments when they are able to communicate or, alternatively, a properly qualified health care professional's assessment of noncommunicating patients who are intubated, undergoing invasive mechanical ventilation (IMV) and often under sedation. Due to the difficulty of assessing and controlling pain, it is often neglected, compromising patient recovery and well-being. The accurate assessment of pain contributes to effective care management; improved adequacy of therapeutic measures, including analgesic and sedative use; and shorter IMV durations and lengths of stay in the ICU.,5Critically ill patients admitted to the intensive care unit (ICU) are subjected to numerous painful procedures, and approximately 75% report severe pain, 30% report pain at rest, and 50% report pain during nursing procedures.,2Pain control is a patient right and a duty of health care professionals, and the negation and devaluation of pain are ethical errors and failures of excellence in professional practice.,5 such as the Behavioral Pain Scale (BPS), which assesses indicators such as facial expression, upper limb movements and compliance with ventilation , which aims to identify the appropriateness of the BPS and the CPOT for assessing pain in noncommunicating patients admitted to the ICU. and was guided by the following research question: How appropriate are two behavioral scales, BPS and CPOT, for assessing pain in orotracheally intubated patients admitted to the ICU?This SLR followed the methodology recommended by the Cochrane CenterSelection criteria were defined and applied according to the PICo method: Participants (adult inpatients older than 18 years), Point of Interest  and Context (the ICU).The following exclusion criteria were established: studies conducted with children under 18 years, those including adult inpatients in non-ICU settings, those that used other scales/other strategies to assess pain, qualitative studies, and studies that were not original.Thus, studies that directly compared the two scales or that mentioned the advantages of using each scale individually were included. was used in this SLR as a guide to meet the accepted standards for systematic reviews.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist® Complete; Nursing & Allied Health Collection: Comprehensive; Cochrane Central Register of Controlled Trials; Cochrane Database of Systematic Reviews; Cochrane Methodology Register; Library, Information Science & Technology Abstracts; MedicLatina). A search was also manually conducted in the references of published studies on the subject.The search was conducted in the EBSCO Host database  Complete; MEDLINETwo independent searches of the databases were performed. For both searches, the search terms "behavioral pain scale" and "critical care pain observation tool" were introduced. For the first search, the Boolean operator "AND" was used; for the second, the Boolean operator "OR" was used. The review was limited to studies published in Portuguese or English, and both searches were conducted without a time limit.The titles were read first, followed by the abstracts and then the full text of the articles found in the search in order to select those that answered the research question.The studies were read and their methodological quality (MQ) was evaluated by two independent researchers to ensure critical evaluation during article selection. In cases of disagreements between the researchers, a third evaluator was asked to review the article.,12The MQ of the studies was assessed using instruments from the Joanna Briggs Institute (MAStARI). would be included .After reading the abstract, 9 studies were selected, and these studies remained in the sample after the full text was read . The 9 s the Netherlands, China, Saudi Arabia, the United States,,18 Canada, and Italy.,21 They were published in 2011, 2014, 2015,,15,17 2016,19,21 and 2017.The 9 selected studies were conducted in different countries: Sweden,The second search with the Boolean operator "OR" resulted in 853 studies; 208 of them were excluded due to duplication, 601 after the title was read, 22 after the abstract was read and 12 after they were read in full. In the various elimination stages, studies were excluded because they were not in English or Portuguese, because they focused on a specific population other than the one considered in this review , because they were duplicates, because they were not original studies, or because they were studies on other topics . , and it showed good validity and reliability in the study population.The BPS was developed and tested in 2001 by Payen et al. had the lowest internal consistency ; the remaining versions had internal consistency ranging between α = 0.79 and α = 0.95. All versions showed good interrater agreement  and good criterion validity.During the validation process, the Brazilian version,22,26 and the discriminant validity for assessments performed before, during and after the procedure obtained a percentage agreement of 28%. However, in one of the studies, the discriminant validity was less supported because it increased during exposure to a nonpainful stimulus. Whereas in the original validation study, there were negative correlations between the pain score and the administered midazolam and fentanyl doses, in the validation study for Saudi Arabia, routine procedures, such as secretion aspiration, caused pain in all patients regardless of the administration of analgesia.There were differences in the correlations between assessments performed before, during and after a painful procedure, and was validated on a convenience sample of 105 intubated cardiac surgery patients (33 unconscious and 99 conscious) before and after extubation. The CPOT showed good interrater reliability (ICC: 0.52 - 0.88), adequate content validity (0.88 - 1.0) and criterion validity (patients who reported pain (1.62 - 3.65)), and discriminant validity was evidenced by higher CPOT scores during painful procedures than at rest . Spearman correlations of 0.40 - 0.59 (p < 0.001) showed that the patients' self-reported pain intensity scores were moderately correlated with the CPOT scores.The CPOT was developed in 2006 in French, in Quebéc, Canada, by Gélinas et al. for Iceland on a sample of 30 patients intubated after cardiac surgery, for Canada on a sample of 23 intubated patients, for the United States on a sample of 30 intubated patients, in Toronto on 66 trauma and neurosurgical patients (34 communicating and 32 noncommunicating), for the Netherlands on 68 patients undergoing mechanical ventilation, for Italy on a sample of 101 patients (41 conscious and 60 unconscious), for China on a sample of 117 critically ill ventilated patients, for Denmark on 70 patients undergoing IMV without sedation, and for Saudi Arabia on 47 noncommunicating critically ill patients.The review found that the CPOT had been validated/revalidated with communicating and noncommunicating patients admitted to the ICU. It was validated for the Swedish population on a sample of 40 intubated patients, - 0.95) and internal consistency  and good criterion validity. There was a significant correlation between the pain intensity scores reported by communicating patients and the CPOT scores; the scores increased significantly when patients were exposed to painful procedures rather than nonpainful procedures, indicating criterion validity.,20,23-25 Significant correlations were also found between CPOT scores and mean arterial pressure (p = 0.32 - 0.45). and general vital signs before, during and after a painful procedure; however, further studies should be conducted to explore the role of vital signs in pain.Validation of the CPOT revealed good reliability (ICC of 0.75 the participants and the results of the selected studies.The detection, quantification and treatment of pain in critically patients have long been a concern of health care professionals. Nevertheless, pain is common in critically ill patients, regardless of their clinical condition, and its accurate assessment using appropriate instruments allows for the use of more beneficial therapeutic measures.,21,23,24 and both scales should be used for pain assessment in this patient population.,21The BPS and CPOT have good psychometric properties and good reliability in intubated and nonintubated patients in the ICU who are unable to self-report their pain,The BPS is considered applicable to critically ill patients who are sedated, unconscious or have difficulty self-reporting pain, especially those undergoing IMV, given that one of its three domains pertains specifically to compliance with ventilation. In turn, the CPOT, in addition to the domain intended for patients undergoing mechanical ventilation, has a vocalization domain; thus, it can also be used with extubated patients, unlike the BPS, which is only intended for use with patients undergoing IMV. specific, reliable, valid and sensitive tool for assessing patient pain; however, the CPOT is a good alternative.,21 Other authors consider the CPOT the scale of choice because its discriminant validity is more supported because the score does not increase with a nonpainful stimulus, contrary to what has been observed with the BPS.Some authors have stated that the BPS is the more viable,,20,23-25 Both instruments are sensitive to painful procedures, with an observed increase in the various indicators that constitute both scales.-17 The main parameters with major changes are facial expression in the BPS,21 and muscle tension/stiffness, facial tension and ventilator tolerance/cough in the CPOT.,21In addition, there was an increase in the pain assessment scores of both the BPS and the CPOT when a painful procedure was evaluated.,20 Although this correlation has been observed, some authors suggest that further studies be conducted to explore the relationship between vital signs and pain.During painful procedures, there is a significant correlation between pain scores and vital signs, specifically blood pressure;, i.e., the higher the pain score, the higher the blood pressure will be. others argue that its application to patients with brain injuries,,28 cognitive deficits or burns,29 is a limitation.Although some consider the CPOT to have good validity for assessing pain in noncommunicating critically ill patients, particularly those with neurological and traumatic injuries, and in neurosurgical patients, however, other authors found significant differences during and after nursing care in conscious and unconscious patients.,28There is still no consensus regarding levels of consciousness, sedation and analgesia because some authors found no significant differences in the application of the two scales to patients with different levels of sedation or analgesia;,18-20,25 Their application contributes to an increased frequency of assessments and, consequently, to the reduced administration of analgesics and sedatives.,30 Researchers have suggested using the two scales simultaneously, as doing so may result in more accurate pain detection and assessment.In their practical application, both the BPS and CPOT are considered by health care professionals to be useful tools in the ICU setting because they are easy to use and remember.Although the use of the BPS and CPOT scales has been shown to have positive effects on pain management in patients admitted to the ICU, experimental studies are recommended.This systematic literature review found several studies validating the Behavioral Pain Scale and the Critical-Care Pain Observation Tool for use with orotracheally intubated critically ill patients from various cultures, and both instruments were found to be valid and reliable for assessing pain in intubated patients admitted to intensive care units.Both instruments were sensitive when applied during painful procedures, showing increases in various indicators: facial expression on the Behavioral Pain Scale and muscle tension/stiffness, facial tension and ventilator tolerance/cough on the Critical-Care Pain Observation Tool, and blood pressure on both scales.There is, however, no agreement regarding the administration of the scales in patients with different levels of consciousness, sedation and analgesia. However, it appears that the use of at least one of the scales helps to increase the frequency of assessments and, consequently, reduces the administration of analgesics and sedatives. In this regard, it is essential that health care professionals use at least one of the two analyzed scales for pain assessment in intubated patients, with the goal of improving the care provided.Further studies with an experimental design covering different critically ill patients populations admitted to intensive care units, namely, trauma, burn and neurosurgical patients, are suggested.


One of the three intraarticular agents was selected according to what agents were available for outpatients when each patient was enrolled in the study. The 15 enrolled patients were subdivided into 3 groups of 5 patients each. Three injections were performed under ultrasound guidance at a 1-week intervals over a total of 3 weeks. The visual analog scale (VAS) score, the Korean version of the Western Ontario and McMaster Universities Arthritis Index (K-WOMAC), the EuroQol five-dimension scale (EQ-5D) score, and the Korean version of the painDETECT Questionnaire (K-PDQ) score were evaluated before injection and at 1, 2, and 6 weeks after the start of the treatment protocol. The primary endpoint was the change in weight-bearing pain at 4 weeks after the last injection. Secondary endpoints included pain at rest and during walking and the K-WOMAC, EQ-5D, and K-PDQ scores. Weight-bearing pain decreased significantly more from pretreatment to 6 weeks after the start of the treatment protocol in the polynucleotide sodium-treated patients than in the patients who were treated with other agents . There were no significant between-group differences in the other secondary endpoints. No adverse events occurred. In conclusion, polynucleotide sodium could effectively reduce weight-bearing pain in the patients with knee osteoarthritis compared to standard hyaluronic acid viscosupplementation.Degenerative arthritis of the knee joint has become a major social problem worldwide due to population aging. There are several treatment options for knee osteoarthritis, and the intraarticular injection of sodium hyaluronate is commonly selected by many clinicians as a nonsurgical treatment. However, the efficacy of the treatment is controversial. In this pilot study, we aimed to compare polynucleotide sodium (Conjuran Osteoarthritis (OA) is a degenerative disease of the synovial joints that has a high prevalence and causes severe pain and disability, resulting in decreased quality of life . The maiSodium hyaluronate is a pharmaceutical treatment that has been commonly used for moderate OA in recent years ,7. BecauAn intraarticular injection agent that can be used as an alternative to sodium hyaluronate is crosslinked sodium hyaluronate, which has a higher molecular weight and greater stability and viscosity than unmodified sodium hyaluronate due to crosslinking. Therefore, this crosslinked agent may be expected to have a longer duration of action than hyaluronate ,16,17. A® group, n = 5) sodium hyaluronate  or cross-linked sodium hyaluronate  at a 1-week intervals. One of the three intraarticular agents was selected according to what agents were available for outpatients when each patient was enrolled in the study. This clinical trial was approved by the Institutional Review Board of Seoul St. Mary’s Hospital (KC20RISI0659), and was registered at http://www.clinicaltrials.gov/ on 29 October 2020 (2020-2733-0001). The requirement for patient consent was waived due to the retrospective nature of the study, which used only formal electronic medical records. This study was conducted in accordance with the Declaration of Helsinki.In this pilot study, we retrospectively reviewed the medical records of 15 patients who met the inclusion and exclusion criteria and whose knee joints had been treated with intraarticular knee joint injections at the pain center of Seoul St. Mary’s Hospital from June 2020 to August 2020. The 15 enrolled patients were subdivided into 3 groups of 5 patients each, and they received 3 intraarticular injections in the affected knee of polynucleotide sodium,  was colorless and viscoelastic and was provided in prefilled sterile syringes containing a solution of 2 mL of (concentration 20 mg/mL). Crosslinked sodium hyaluronate with a molecular weight >10,000 kDa  was provided in a prefilled sterile syringe containing 60 mg of crosslinked hyaluronic acid in 3 mL of a solution. Linear high molecular weight hyaluronate sodium with a mean molecular weight of 3000 kDa  was provided in a prefilled sterile syringe containing 20 mg of hyaluronic acid in 2 mL of a solution.The polynucleotide sodium used in this study , the second injection was performed one week later (T1), and the third injection was performed two weeks later (T2). Then, the patients returned for a clinical follow-up four weeks after the end of the protocol (T6). All clinical parameters were evaluated immediately before the first treatment (T0), after each subsequent injection , and at the final follow-up (T6). The protocol of the study is shown in The primary outcome of the study was the change in the VAS (100 mm) score for knee pain under weight bearing from T0 to T6. The secondary outcomes included the changes in the VAS score  for knee®, Armonk, NY, US) was used, and the two-way significance level was 0.05. A total of 15 patients were assessed, including 5 in each group. To compare the changes in each parameter from T0 to T6 among groups, one-way ANOVA was performed, and post hoc analysis was performed with Tukey’s honestly significant difference (HSD) test only when significant results were revealed by one-way ANOVA. Paired t tests were performed for intragroup comparisons.For statistical analysis, SPSS Statistics . On post hoc analysis, the VAS score for weight-bearing pain decreased more from T0 to T6 in group C than in group H .The change in the weight-bearing pain score from T0 to T6 significantly differed among the three groups . According to the post hoc analysis, the VAS pain score at rest decreased more from T0 to T6 in group C than in group H . The changes in the K-WOMAC and EQ-5D scores over time did not differ among the three groups.The change in the pain score at rest from T0 to T6 also significantly differed among groups  but also cause physiologic changes ,25. The We included evaluations of clinical aspects, including quality of life and neuropathic pain components. Contrary to our study, previous studies have evaluated only pain and function in patients with knee OA ,18,19,32The limitations of this study are as follows: (1) the follow-up period was short; (2) the number of patients per group was small; (3) blinding was absent, and (4) no restrictions were imposed on the use of analgesic medications. In the future, a double-blinded clinical trial should be conducted to overcome these limitations. In addition, crosslinked sodium hyaluronate was injected only once, and the other two drugs were injected three times for comparison with each other, so there is concern about whether the pure effects of the drugs can be compared when the same number of injections of the medication were not administered. According to Korean insurance standards, crosslinked sodium hyaluronate can be applied up to once within six months, sodium hyaluronate can be applied up to 3 times within 6 months, and polynucleotides can be applied up to 5 times within 6 months. In clinical practice, crosslinked sodium hyaluronate can be injected only once, but if polynucleotide sodium is injected once and the effect is not sufficient, another injection may be given at the next visit. The protocol of the study reflects this clinical situation, and a similar design will be used in the planned double-blinded randomized controlled study in the future.In this preliminary study, we showed that polynucleotide sodium could reduce weight-bearing pain more effectively 6 weeks after the start of treatment than sodium hyaluronate and crosslinked sodium hyaluronate in knee OA patients. To address the limitations imposed by the preliminary nature of this study, our center is conducting a randomized study with a larger sample size.


A large phase III trial (PRONOUNCE study) may define it better but, until now, an alert has been sent in patients with preexisting CVD .