Current recommendations controversially discuss local infiltration techniques as specific treatment for refractory pain syndromes. Evidence of effectiveness remains inconclusive and local infiltration series are discussed as a therapeutic option in patients not responding to standard therapy. The aim of this study was to investigate the effectiveness of infiltration series with techniques such as sphenopalatine ganglion (SPG) block and ganglionic local opioid analgesia (GLOA) for the treatment of neuropathic pain in the head and neck area in a selected patient group.  In a retrospective clinical study, 4960 cases presenting to our university hospital outpatient pain clinic between 2009 and 2016 were screened. Altogether, 83 patients with neuropathic pain syndromes receiving local infiltration series were included. Numeric rating scale (NRS) scores before, during, and after infiltration series, comorbidity, and psychological assessment were evaluated. p < 0.001) equaling a pain reduction of 41.0% (SD 40.4%). With infiltration series, mean pain reduction of at least 30% or 50% NRS was achieved in 54.2% or 44.6% of cases, respectively. In six percent of patients, increased pain intensity was noted. Initial improvement after the first infiltration was strongly associated with overall improvement throughout the series.  Maximum NRS before infiltration series was median 9 (IQR 8–10). During infiltration series, maximum NRS was reduced by mean 3.2 points (SD 3.3,  This study suggests a beneficial effect of local infiltration series as a treatment option for refractory neuropathic pain syndromes in the context of a multimodal approach. This effect is both significant and clinically relevant and therefore highlights the need for further randomized controlled trials. The overall prevalence of chronic pain is estimated to be about 19% in Europe . WorldwiFeasible techniques in the head and neck area are infiltrations at the sphenopalatine ganglion (SPG), the superior cervical ganglion, the stellate ganglion, and single nerve blocks of the occipital nerve and branches of the trigeminal nerve , 11.Since its first description in 1908, the sphenopalatine ganglion (SPG) block has been discussed in the literature . RecentlGanglion local opioid analgesia (GLOA) was first introduced by Mays et al. , althougAlthough different indications are discussed, blockade of the stellate ganglion (SB) is mostly used for Complex Regional Pain Syndrome (CRPS) at the upper extremities  as sympaPeripheral nerve blocks can be helpful in cranial neuralgias such as TGN and glossopharyngeal and occipital neuralgias . AlthougThe reason to use an infiltration series and not a single infiltration is mostly based on historical development of clinical practice . Until nConsidering this background, this study was performed to investigate the course of pain and pain relief, the associated symptoms, and side effects during the administration of a local infiltration series in patients with refractory neuropathic pain of the head and neck region.NCT03066037. The study was approved by the Charité Ethical Committee (EA4/107/16).This retrospective study was conducted at the outpatient pain center of the Charité University Hospital, Berlin, Campus Virchow-Klinikum. The department provides clinical care for chronic pain patients and is run by a team of pain specialists, psychotherapists, and trained pain nurses. All cases treated in the department presenting from January 2009 to June 2016 were screened for eligibility. Inclusion criteria were adult patients receiving local infiltration series for treatment of refractory neuropathic pain syndromes  , 36 or pAll patients' contacts in the department were documented in the electronic and paper-based patient filing system. For patients receiving infiltrations, a specific documentation protocol was used. Protocols contain NRS at rest, under stress, before and at 1, 6, and 24 hours after infiltration on an 11-point Likert scale (0–10). A self—assessment of pain reduction and the infiltration's burden  was assessed on a 4-point Likert scale.Additional to these infiltration protocols, the daily form of the validated German Pain Questionnaire adopting the 2007 version  was usedPatients were scheduled for the local infiltration series depending on the clinical judgement of the attending pain specialists. The infiltration series were scheduled for ten consecutive infiltrations within three weeks, but the final decision for each infiltration was based on the clinical outcome.The SPG blockade is based on an injection with local anesthetic agents (2-3 ml bupivacaine 0.25%) and opioid  with or without an adjunctive corticoid close to the ganglion . The useTo perform a ganglionic local opioid analgesia (GLOA), lipophilic opioids and local anesthetic agents (5 ml 0.5% bupivacaine and 0.03 mg buprenorphine) are injected close to paravertebral and cervical ganglions . We used∗Power 3.1.9.6 (post hoc power). Descriptive data was summarized using mean and standard deviation or median and range depending on scale level and distribution. For analysis of statistical significance, NRS scores (0–10) were explored using the exact Wilcoxon signed-rank test for paired data. To analyze independent groups, the Mann–Whitney test was applied. To examine the time point of successful pain reduction, the Kaplan–Meier analysis was performed. For analysis of the correlation between the initial and the final response to infiltration, an exact Chi-square test was performed. To analyze differences in percentage of NRS reduction throughout series by subgroups, the Kruskal–Wallis test was performed. For examination of the response rate between subgroups, the Fisher exact test was performed. All statistical significance tests used a two-sided alpha level of <5% and were intended as exploratory data analysis.All statistical analyses were performed using SPSS 25 and Gf [Like previous studies, we defined nonresponders as patients with less than 30% pain reduction and responders as patients with a pain reduction of at least 30% . As addif .N = 83 patients were included into further analysis  . PsychiaN = 60, 72.3%) as the main infiltration site. GLOA infiltration was applied in N = 12 patients (14.5%) and infiltrations at the stellate ganglion in N = 6 (7.2%). Other infiltration sites were the branches of the trigeminal nerve  and the major  and minor occipital nerve .Most patients received a blockade at the sphenopalatine ganglion (N = 81 patients). A mean reduction of maximum NRS scores during the course of infiltrations was 3.2 (SD ± 3.3); the median was 3 . This equals a relative average reduction of maximum NRS scores of 40.9% (SD ± 40.4%); the median was 44.4% (IQR 0%–70%).The maximum NRS score leading to the decision to perform the local infiltration series was a median of 9 , a 50% reduction in 37 patients (44.6%). Worsening of pain was noted in five patients (6%). The mean increase of maximum NRS in these five patients throughout the series was 1.8 (SD ± 0.83). Numeric rating scale scores during the course of infiltration are presented in During the first infiltration series, patients commonly tolerated the infiltrations well. Categorized burden showed 79.2% of patients reporting little (46.2%) to very little burden (33%). Severe (16.3%) and extreme burden (4.4%) were rarely reported.For 48 patients, data from the German Pain Questionnaire was available for a follow-up time point, which was a median of two months (IQR 1–3 months) after the infiltration series.N = 76, median 8 (IQR 6–9); follow-up N = 44, median 6 (IQR 3.3–8), and p=0.05)  .p=0.023), impact of daily activities (before median 5 (IQR 4–8); after median 4 (IQR 2–7), p=0.046), and mental constitution (before median 6 (IQR 5–8); after median 5 (IQR 2.5–7.5), p=0.002).Compared with preinfiltration status, patients reported statistically significant improvements of endurance of pain (before median 3 (IQR 3-4); after median 3 (IQR 2-3), Responders were defined as patients with maximum NRS scores decreasing by at least 30% during treatment. This analysis was repeated for patients with at least a 50% response.In univariate logistic regression models, variables with potential association with clinical response were included. In the final model, identified relevant variables predicting response were age and relevant improvement in maximum NRS scores after the first two infiltrations . NotablyTo further explore clinical subgroups, patients with three dominant pain syndromes in this study population, trigeminal neuralgia, trigeminal postherpetic neuralgia, and persistent idiopathic facial pain (PIFP), were analyzed separately in n = 38), clinically relevant NRS reduction of 30% was achieved in 22 cases (51.2%) and a reduction of 50% in 19 cases (44.2%), respectively. In patients with trigeminal postherpetic neuralgia (n = 13), a reduction of at least 30% of initial maximum NRS compared to last documented maximum pain was noted in 11 patients (84.6%) and a 50% reduction in eight patients (61.5%). In the PIFP subgroup (n = 12), a reduction of 30% NRS throughout series was achieved in 5 cases (35.7%) and a reduction of 50% in 4 cases (28.6%), respectively. Differences in response rates both for 30% reduction (p=0.081) and 50% reduction (p=0.387) were not statistically significant  the local infiltration series resulted in a meaningful clinical pain reduction of 30% in notably 54% of patients (and 50% pain reduction in 45% of patients); (2) the follow-up patients reported a lasting reduction of pain NRS, along with (3) improvements in pain-related psychometrics. Finally, we were able to identify the variables age, months with preceding pain until the first visit at the outpatient pain center, and improvement in pain NRS scores after the first two infiltrations as predicting factors for clinical response of infiltration series.Although facial pain is a rare condition with an overall incidence rate of 38.7 per 100,000 patient years, it can have a considerable impact on the patients' quality of life . RefractIn patients with neuropathic pain who fail to respond adequately to pharmacological management, the consideration of nonpharmacological therapies is recommended . InvasivThere are different approaches to access the sphenopalatine ganglion. Blocks at the sphenopalatine ganglion have been both used with regional placement of local anesthetic through the nose either via soaked cotton tips , 50 or pRegarding GLOA, a previous study shows that its treatment had an adjunctive beneficial effect in carbamazepine-treated patients with trigeminal neuralgia . In a plAs there is no communication between autonomic postganglionic sympathetic and parasympathetic neurons with afferent neurons under physiological conditions , the rolThe SNS is targeted in the SB as well: sympathetic nerves passing through the stellate ganglion innervate the head, neck, and upper extremities  and its The block of the greater occipital nerve (GON) is thought to be an effective treatment for acute migraine . FurtherTo compare different therapy options, a definition of successful treatment is needed. Although widely used, a definition of the success of nerve blocks is still not established. Generally, a relevant NRS reduction of 30% of initial NRS represents a clinically important difference . Elsner Subgroup analyses of the major clinical entities included trigeminal neuralgia, postherpetic neuralgia, and persistent idiopathic facial pain (PIFP). We observed a nonsignificant difference between the response rates to treatment. However, for the limited subgroup of PIFP patients, treatment benefit appeared numerically smaller. In contrast, patients with trigeminal neuralgia and trigeminal postherpetic neuralgia were comparable in terms of treatment response, which may be of relevance in planning prospective trials.Repetitive blocks are frequently used . One reaOur results show an overall improvement over the first 6 infiltrations. Together with our clinical experience, we recommend at least 6 scheduled infiltrations in a context-sensitive treatment. Notably, our results show that an improvement of NRS in the first and even stronger improvement in the first two infiltrations have a significant predictive value on clinical response. Therefore, the first two infiltrations could be used to identify patients with a higher likelihood to benefit from the treatment. This is relevant since it could prevent performing unnecessary interventions in patients who are unlikely to improve.Invasive procedures as investigated in this study have enhanced placebo effects , 73. ParNevertheless, the effect of placebo interventions on pain is very variable. Hrobjartsson and Gotzsche identified seven placebo interventions on pain trials which were divided into two subgroups: four German acupuncture trials with a pooled effect of standardized mean difference (SMD) −0.68 (−0.85 to −0.50) and three other trials with an effect of SMD −0.13 (−0.28 to 0.03), which equals an effect on pain on a 100 mm visual analogue scale of 16 mm and 3 mm, respectively. Thus, the placebo effect on reported pain ranges from clinically important to irrelevant .In our study, we could show a significant and clinically relevant reduction of NRS. This goes along with findings from a similar study about GLOA as a local infiltration technique . FurtherHowever, this study has limitations. The retrospective design limits the interpretation of the results. Furthermore, it is not possible to distinguish between the effects of blocks, the placebo effect, other treatments and the natural course of pain syndromes. In addition, there could be a selection bias regarding the follow-up group, since patients without pain are more likely not to visit our outpatient pain clinic. Moreover, the subgroup of patients with PIFP could have a lower response rate to treatment and thus estimated that the overall study response rates could be underestimated in their assessment. Additionally, there is very limited literature regarding head and neck nerve blocks and no standardization of its performance . Particup = 0.001), which does suggest a low probability of bias regarding the intraindividual variation. The latter may also be an important piece of information in designing prospective trials. Although there are potent correction methods for multiple comparisons, this study is exploratory with a nonconfirmatory design. In such studies, conservative procedures like Bonferroni's correction may further increase the risk of type 2 errors [In this investigation with repetitive data collections, we could not control for all factors, e.g., intraindividual variance of patients. For example, for plain NRS reduction of 3.2 points in pain intensity over the course of treatment, we achieved a power of 99.9% (2 errors .Local infiltration series are used in patients with refractory neuropathic pain syndromes despite lacking evidence. Our study provides data on effectiveness and the burden of local infiltration techniques in patients not responding to standard therapy. This is important, since randomized—controlled trials are ethically difficult to perform in invasive procedures. Furthermore, we have evaluated factors to predict response to therapy to guide patient—management during the infiltration series.In summary, this retrospective analysis demonstrates a beneficial effect of local infiltration techniques as a treatment option for refractory pain syndromes. The effects of the treatment with the infiltration series are significant and appear clinically relevant as therapeutic options are limited in this population , 80. Fur


Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg twice daily or placebo, each with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).This post hoc analysis used data pooled from three randomized controlled trials in csDMARD-inadequate responder (csDMARD-IR) patients . Using subgroup analysis from 2 × 2 tables, associations between PtGA and Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at month 3 were evaluated using Pearson’s Phi correlation coefficients. To support the main analysis, associations between select patient-reported outcomes (PROs) were also evaluated in csDMARD-naïve  and biologic (b)DMARD-IR  patients.Across csDMARD-IR treatment groups, low disease activity (defined as PtGA ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in PtGA were associated with mild Pain , and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in Pain; lack of Pain improvement was associated with little/no improvement in PtGA. In contrast, large proportions of csDMARD-IR patients who reported PtGA improvements did not report HAQ-DI or FACIT-F scores ≥ normative values  or changes in HAQ-DI or FACIT-F scores ≥ minimum clinically important difference . Generally, PtGA and Pain outcomes were moderately-to-strongly correlated at month 3 in csDMARD-IR patients, with weaker correlations evident between PtGA and HAQ-DI/FACIT-F outcomes. Similar findings were generally evident in csDMARD-naïve and bDMARD-IR patients.This analysis supports the role of Pain as a key driver of PtGA in RA; physical function and fatigue play lesser roles in patients’ perceptions of disease activity. These findings corroborate the importance of improved PROs and attainment of low symptom states for optimizing patient care.Clinicaltrials.gov: NCT00847613 ; NCT00853385 ; NCT00856544 ; NCT01039688 ; NCT00960440  Rheumatoid arthritis (RA) is associated with high levels of pain, impaired physical function, and diminished health-related quality of life (HRQoL) . From thOne of the most widely reported PROs in RA is the Patient Global Assessment of Disease Activity (PtGA), one of the seven ACR core set components recommended for assessment in RCTs , 9. ImpoInterestingly, discordance between patient and physician assessment of RA has been reported in over a third of RA patients, with patients with discordance typically reporting a higher level of disease activity than their physicians , 16. SucIn recent years, the Janus kinase and signal transducer and activator of transcription (JAK-STAT) pathway has been shown to play a central role in both inflammatory and neurogenic pain processes associated with RA and other autoimmune disorders , 21. As Tofacitinib is an oral JAK inhibitor for the treatment of RA. Sustained improvements in PROs, including PtGA, Pain, HAQ-DI, and fatigue , as well as HRQoL  have previously been reported in phase 2 , phase 3While improvements in PROs have been demonstrated, the associations between PtGA and Pain, between PtGA and HAQ-DI, and between PtGA and FACIT-F have not previously been investigated in RA patients treated with tofacitinib. This post hoc analysis used pooled data from three phase 3 RCTs of csDMARD-IR RA patients receiving tofacitinib in combination with csDMARDs to further examine and understand the degree to which PtGA is associated with patient-reported improvements in Pain, physical function (HAQ-DI), and fatigue (FACIT-F), and gain insights into these relationships. To support the main analysis, associations between select PROs were also evaluated in csDMARD-naïve  ) and bion = 795; NCT00856544) ) < 2.6 for over 1 year . In the A 2015 analysis of PROs in practice reported that clinicians are often reluctant to use PROs routinely due to a fear that it will add to their workload, rather than improve their efficiency and effectiveness ; therefoSome limitations remain associated with this post hoc analysis. First, as placebo-treated patients were advanced to tofacitinib treatment at month 3 (non-responders only) or month 6 , data in this post hoc analysis were only evaluated up to month 3, a relatively short period to adequately investigate the associations. In addition, interpretations of PtGA by patients will vary and depend on a range of additional factors, such as comorbidities, disease duration, and patient expectations . FurtherFor the first time, this post hoc analysis of pooled data from three phase 3 RCTs of csDMARD-IR RA patients demonstrates the associations between PtGA and pain, physical function, and fatigue in tofacitinib-treated patients, corroborating the importance of clinically meaningful improvements in PROs and attainment of LDA states for the optimization of patient care. Similar findings were generally seen in csDMARD-naïve and bDMARD-IR patients. Overall, the findings support the importance of PtGA in clinical practice, and the role of Pain, and, to a lesser extent, physical function and fatigue, in driving patients’ perceptions of disease activity. While PtGA remains one of the most widely reported PROs, RAPID-3 represents a time-efficient approach that collects three outcomes  and may be supplemented by the addition of a single fatigue measure to provide a more robust picture of patient wellbeing.Additional file 1: Supplementary Tables 1–2; Supplementary Figures 1–8. Proportions of patients who did/did not report improvements in HAQ-DI and FACIT-F scores ≥ MCID, stratified by clinically meaningful PtGA improvements; proportions of patients who reported clinically meaningful PtGA improvements or clinically meaningful Pain, HAQ-DI, or FACIT-F improvements alone; and Pearson Phi correlations between PtGA, and Pain and HAQ-DI outcomes.


Chronic pain imposes a large burden on individuals and society. A patient-centric digital chronic pain management app called Manage My Pain (MMP) can be used to enhance communication between providers and patients and promote self-management.The purpose of this study was to evaluate the real-world engagement of patients in urban and rural settings in Ontario, Canada with the MMP app alongside their standard of care and assess the impact of its usage on clinical outcomes of pain and related mental health.A total of 246 participants with chronic pain at a rural and 2 urban pain clinics were recruited into this prospective, open-label, exploratory study that compared the use of MMP, a digital health app for pain that incorporates validated questionnaires and provides patients with summarized reports of their progress in combination with standard care (app group), against data entered on paper-based questionnaires (nonapp group). Participants completed validated questionnaires on anxiety, depression, pain catastrophizing, satisfaction, and daily opioid consumption up to 4.5 months after the initial visit (short-term follow-up) and between 4.5 and 7 months after the initial visit (long-term follow-up). Engagement and clinical outcomes were compared between participants in the two groups.A total of 73.6% (181/246) of the participants agreed to use the app, with 63.4% (111/175) of them using it for at least one month. Individuals who used the app rated lower anxiety  at short-term follow-up and had a greater reduction in pain catastrophizing  at long-term follow-up relative to patients with pain who did not engage with the MMP app.The use of MMP by patients with chronic pain is associated with engagement and improvements in self-reported anxiety and pain catastrophizing. Further research is required to understand factors that impact continued engagement and clinical outcomes in patients with chronic pain.ClinicalTrials.gov NCT04762329; https://clinicaltrials.gov/ct2/show/NCT04762329 Several large population-based surveys show that over 1 in 5 people live with chronic pain  and is oTo bridge this gap, a patient-centric digital health app can be used as a method of remote monitoring to enhance communication between patients and HCPs and promote self-management of patients’ symptoms. While a number of pain apps have been created, they evaluate the biopsychosocial components of pain experiences inadequately and lack clinical involvement ,15-17. TA novel digital pain management solution, the Manage My Pain (MMP) app (ManagingLife Inc) , was useA prospective, open-label, multicenter exploratory study with active and comparator arms was conducted from January 8, 2018, to January 7, 2020, at 3 study sites. Participants were recruited from among new patients with chronic pain conditions who were referred to 2 tertiary academic pain centers in Toronto, Ontario, Canada  and a rural pain clinic in Ontario . All patients had pain of moderate-to-severe intensity that had persisted for at least three months. All patients, regardless of use of the Manage My Pain app, received the standard of care for the particular clinic, which included interventions such as medication management, psychological therapy, and physiotherapy.Manage My Pain , the appMMP is used by both patients and clinics to measure and monitor pain, function, and medication use. Patients can record their experiences by using the MMP app on their mobile device (compatible with Android and iOS devices) or accessing a web-based platform. When prompted by an in-app push notification triggered at 8 PM daily, patients record daily reflections in the app, where they indicate the meaningful activities they were able to accomplish. The daily reflection concept is based on acceptance and commitment therapy principles that have demonstrated an ability to improve clinical outcomes relevant to pain management . PatientEach section of the app can be customized by the patient so that it is representative of their situation. MMP is designed to capture both daily reflections and pain episodes in less than 60 seconds . As patiAs part of the registration process, patients were shown a consent screen asking for permission to share the information from MMP with their clinical team for clinical and research purposes, and they signed an informed consent form. Participants had to explicitly agree by entering a unique randomized 10-digit ID provided to them by the research coordinator, which allowed each clinic to match the participant with their clinical profile and ensure appropriate deidentification. After registration, participants had to activate their account by clicking on a link sent to them by email. Participants were instructed to download MMP through either the Apple App Store (for iPhone users) or the Google Play Store (for Android users) upon successful activation. For participants that did not have either device, a web link associated with their clinic was bookmarked for them to use MMP through their internet browser for easy access.At first access, the app provided a brief tutorial on how to set up the user’s profile, which included entering relevant medications and pain conditions. It then described how to complete a sample entry by using a touch slider to enter a numerical rating score as an integer from 0 to 10. Once the user’s pain level was indicated, additional questions were prompted, including pain location, other associated symptoms, pain characteristics, aggravating and alleviating factors, and the duration and environment of the pain episode. While all questions included a drop-down menu including prepopulated answers with associated infographics, participants were also given the option to add customized values. A Notes section where participants could enter free text was also provided. Upon completion, patients could save their entry for the patient and health care team to track and observe trends. Technical support was also offered to the participants in the event that they required troubleshooting for using the app, either by the designated research team or the ManagingLife technical support team. Email notifications for data entry on validated questionnaires were sent by the app 7 days prior to the due date set by the research coordinator, which was intended to coincide with the date of the clinical visit. This feature allowed HCPs to track the progress of patients who could not be seen through in-person visits.Participants at the 3 sites were selected using a homogeneous purposive sampling method  and giveParticipants were asked to complete questionnaires on the following pain-related outcomes: anxiety, depression, pain catastrophizing, pain disability, patient global impression of change, and daily opioid consumption. Daily opioid consumption was measured in oral morphine equivalents in milligrams upon entry into the study during the initial visit and as a part of the first follow-up clinical visit within 4.5 months of the initial visit (short-term follow-up) and during the second follow-up clinical visit between 4.5 and 7 months after the initial visit (long-term follow-up). Given that our objective was to validate the impact of the app in a real-world clinical environment, the date ranges of follow-up visits were more broadly defined to align with the date of the actual clinical visit. Clinicians at each participating site were encouraged to use the clinical reports, either digitally through the portal or printed, during their clinical visits with the patients.Participants who agreed to use the app but did not have in-person clinical appointments within these time frames were still remotely prompted to complete the questionnaires through the app portal by research staff. Patients in the nonapp group provided their data only by completing paper-based questionnaires during clinic visits or via a phone interview if no in-person clinical visit was scheduled during study-related follow-ups.The feasibility and successful adoption of the digital health solution was evaluated through clinical outcomes and patient engagement. During the initial visit, participants completed baseline questionnaires that were standardized across sites as well as questionnaires that were considered the standard of care at each individual clinical practice.As mood disorders are often prevalent in individuals with chronic pain and have been known to affect and intensify pain perception ,33, anxiFinally, participants’ opioid consumption was measured over time using oral morphine equivalents (OME) through conversion ratios outlined by the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain . Given tInstitutional ethics board approvals were obtained from each study site by the University Health Network Research Ethics Board for the academic sites (TGH and TWH) and Veritas Institutional Review Board for the rural site (IFFHT). The approval process involved confirmation that MMP has the administrative and technical safeguards in place to ensure compliance with privacy legislation.t tests or Wilcoxon rank sum tests as appropriate based on the distribution of the data. Chi-square tests or Fisher exact tests were used for categorical data. A random-effects model was used for all outcomes to account for correlations arising from repeated measures within the same individual.Continuous data were summarized using mean and standard deviation or median and interquartile ranges, and categorical data were summarized using frequency and percentages. Univariate tests for continuous data were conducted using 2-sample P values were provided where the model residuals violated the normality assumption.The main exposure of interest was whether someone used the app for at least 30 days, adjusted for time, age, gender, and study site. Each of the 6 outcomes  was also modeled to examine the association of the intervention (use of the app for at least 30 days) with the outcome after controlling for other relevant variables. The duration of usage (time) among the participants who entered data into the app was recorded as the difference between the most recent entry and the date of registration. An interaction term between time (short term or long term) and group (intervention or control) was examined to determine whether the intervention was associated with differences between groups over time. A likelihood ratio test was used to assess the statistical significance of the interaction term, and the term was included in the model if it remained statistically significant at the .05 significance level. For clinical utility, the primary analysis categorized time as baseline, short term, and long term. A sensitivity analysis was conducted using time as a continuous covariate of interest. The baseline value was adjusted for by including it in the outcome vector . Model cThe average age of participants in the study was 56.67 (SD 13.12) years, with 60.2% (148/246) of participants being female. A total of 246 participants were enrolled across the 3 sites , out of which 181 (73.6%) accepted the use of the app in their clinical care and the remaining 65 (26.4%) continued with paper-based data entry at their respective clinics. Of the 181 participants who agreed to use the app, 175 (96.7%) participants registered and provided consent to share their data. Of the 175 participants who registered, 111 (63.4%) participants used the app for at least 30 days and therefore were considered part of the intervention (app) group . Data frOf those who used the app for at least 30 days, the mean number of records entered was 113.4 (SD 129.7). The mean duration of usage from the date of registration to the date of the last record entered was 164.2 (SD 88.4) days.Quantitative analysis of the clinical outcomes was performed at 2 time points, short term and long term, following enrollment into the study. Of the 135 patients in the nonapp group, 36 (26.7%) provided their data at the short-term follow-up and 31 (23.0%) provided their data at the long-term follow-up. A total of 90 of the 111 participants in the app group provided their data through the app for the short-term follow-up, and 69 provided their data for both short- and long-term follow-ups . The priThe number of elapsed days from baseline for both the short-term and long-term follow-ups was not significantly different across the intervention and control groups .Unadjusted analyses did not find any significant differences between the intervention and control groups over time .A significant decline in daily OME in milligrams was observed in both the short-term  and long-term  time periods when compared with baseline. Depression (PHQ-9)  and disability (PDI) scores  decreased significantly for all participants . Pain CaParticipants in the app group had lower anxiety (GAD-7) scores at the short-term follow-up  and lower Pain Catastrophizing Scale scores at the long-term follow-up  . For theThis is the first multisite study at rural and urban pain clinics of a digital pain management solution that compared outcomes in patients with chronic pain who chose to use the app in addition to standard care versus those who received only standard care. A total of 73.6% (181/246) of the participants in the study chose to enroll for the app, 45.1% (111/246) continued to use it beyond one month following enrollment, and 28.0% (69/246) were still using it for 4.5 to 7 months. There was evidence of a decrease in anxiety and pain catastrophizing in participants who used the app versus those who did not use the app.Digital health applications can play a significant role in enhancing the connectivity between patients and their HCPs. Though some studies report men and younger age groups as more likely to engage with this kind of technology , our stuOur study found that use of the app was associated with a reduction in pain-related anxiety and pain catastrophizing scores. These reductions have clinical significance, given that the minimum clinically important difference in values for the GAD-7 and PCS . This may have resulted in biased estimates of results that differed by treatment group, confounding the present findings.This study of a novel digital pain management solution that incorporated validated measures for domains of pain in patients at urban and rural clinics found that 28.0% (69/246) of all patients continued to use the app on a long-term basis. Patients that engaged with the digital health solution had less anxiety and lower pain catastrophizing scores as measured by validated tools. Digital pain management applications and other health-related clinical applications deserve significant attention in the years ahead, given the push toward mobile health tools and telemedicine.


Compared with open lumbar microdiscectomy, percutaneous endoscopic lumbar discectomy (PELD) has the advantages of remarkable preservation of paravertebral structures, less bleeding, shorter operation time and fewer complications, it is a common method for the treatment of lumbar disc herniation (LDH). Local anesthesia is recommended during PELD. However, intraoperative pain is sometimes difficult to control satisfactorily. The efficacy of bilateral intervertebral foramen block (IFB) for pain management in PELD remains unclear. Therefore, this regimen is utilized in a randomized controlled trial for the assessment the safety and effectiveness of bilateral IFB for PELD pain control.This is a single center and randomized controlled trial which will be implemented from September 2020 to September 2021. This research protocol is in accordance with the items of the Standard Protocol for Randomized Trials, which was authorized through the Ethics Committee of Huzhou Central Hospital & Affiliated Centre Hospital of Huzhou University (HZCH0465-0864). 100 participants who undergo PELD will be analyzed. Inclusion criteria contains1.patients diagnosed with LDH undergoing PELD;2.people between the ages of 18 and 75;3.consistent imaging evidence of herniation at a same level (CT or MRI);4.receive conservative treatment for 2 months.The exclusion criteria contains:1.patients with the history of severe renal and hepatic dysfunction;2.more than 1 responsible level3.LDH combined with other spinal diseases needing advanced surgical treatment ;4.Patients have mental illness that will prevent their willingness to participate in the study.Patients will be randomly divided into bilateral IFB group (with 50 patients) and local infiltration analgesia group (with 50 patients). Primary outcomes are pain score at different time points. The secondary outcomes are the operative time, radiation exposure time, length of hospital stay and postoperative complications. All the analysis is implemented through applying the IBM SPSS Statistics for Windows, version 20 .The clinical outcome variables between groups are illustrated in the Table 1.This investigation can offer a reliable basis for the effectiveness and safety of IFB in treating the PELD pain.This study protocol is registered in Research Registry (researchregistry5985). Compared with open lumbar microdiscectomy, percutaneous endoscopic lumbar discectomy (PELD) has the advantages of remarkable preservation of paravertebral structures, less bleeding, shorter operation time, and fewer complications, it is a common method for the treatment of LDH.,7Lumbar disc herniation (LDH) is a familiar cause of lower extremity radiation pain and low back pain and conservative treatment can improve symptoms of most cases. Although local anesthesia is recommended during PELD for avoiding nerve root injury, intraoperative pain is sometimes difficult to control satisfactorily under local anesthesia only,,10 especially during the process of foraminoplasty, working channel insertion, and nucleus pulposus removal.For patients with LDH undergoing surgery with spinal anesthesia or general anesthesia, it is hard to detect the accidental injury of the cauda equina nerve and nerve root due to sensory blockade.Severe pain during foraminoplasty and working channel insertion is considered to originate from the posterior longitudinal ligament. A local intervertebral foramen block (IFB) can block homolateral sinuvertebra nerve and spinal nerve located in the neuroforamen. Our preliminary research has indicated that IFB was associated with improved outcomes in terms of postoperative pain and opioid consumption. However, due to the small sample size and poor study design, the efficacy of bilateral IFB for pain management in PELD remains unclear. Therefore, this regimen is utilized in a randomized controlled trial for the assessment the safety and effectiveness of bilateral IFB for PELD pain control. We assume that that IFB is effective and safety in reducing postoperative pain in PELD.22.1This is a randomized controlled, single center trial which will be implemented from September 2020 to September 2021. This research protocol is in accordance with the items of the Standard Protocol for Randomized Trials, which was authorized through the Ethics Committee of Huzhou Central Hospital & Affiliated Centre Hospital of Huzhou University (HZCH0465–0864), and it has been registered in the research registry (researchregistry5985). All patients had signed consent forms before the surgery.2.2100 participants who undergo PELD will be analyzed. In the random envelope, all patients are assigned a random number via using the random number ;4.receive conservative treatment for 2 months.The exclusion criteria contains:1.patients with the history of severe renal and hepatic dysfunction;2.more than one responsible level3.LDH combined with other spinal diseases needing advanced surgical treatment ;4.Patients have mental illness that will prevent their willingness to participate in the study.2.32.3.1Patients receive the surgeries in prone position on the radiolucent Table 2.3.2In case of lateral and anteroposterior fluoroscopy, 18-gauge is inserted into contralateral monosegmental intervertebral foramen. 2.5 ml of 0.3% ropivacaine is infiltrated into the contralateral intervertebral foramen for the free anesthesia. Subsequently, patients receive the traditional local anesthesia with 0.3% ropivacaine, which is the same as those of the local anesthesia group for SAP anesthesia, trajectory and homolateral skin. Then adjust the needle the homolateral monosegmental intervertebral foramen. A total of 2.5 ml of the 0.3% ropivacaine is infiltrated into the homolateral intervertebral foramen to conduct the sensory-motor dissociation anesthesia. The following surgical procedures is the same as the procedures of conventional PELD.2.4 The secondary outcomes are the operative time, radiation exposure time, length of hospital stay, and postoperative complications. The radiation exposure time is obtained from the G-arm computer at the end of each procedure. Oswestry Disability Index (ODI) is also recorded at 7 days, 12 weeks, and 1 year postoperatively.Primary outcomes are pain score at different time point. Visual analog scale (VAS) is used to assess the pain (10: the maximum possible pain and 0: absent pain).2.52-tests and independent t tests, respectively. Intention-to-treat analysis is used for the outcome assessments. When P value <.05, it is considered to be significant in statistics.All data are recorded into the Microsoft Excel 2010, and then they are analyzed via applying the IBM SPSS Statistics for Windows, version 20 . Afterwards, all the data are expressed with appropriate characteristics such as mean, median, standard deviation as well as percentage. Continuous and categorical variables are analyzed using χ3The clinical outcome variables between groups are shown in Table 4,14 PTED has become one of the optimal clinical treatments for LDH due to the advantages of minimal invasion, less blood loss, and rapid recovery.,16 Surgery and anesthesia are associated with a stress reaction, immunosuppression, and postoperative pain, which prolong hospital stays and increase the economic burden of patients. Appropriate anesthesia is important to achieve improved clinical outcomes. The lack of a definitive “gold standard” and various programs of anesthesia method during operation indicate that there is much room for improving the perioperative pain control. Recently, IFB is popular used in PELD. However, if conducted unilateral IFB only, satisfactory and instant distribution of local anesthetic to the opposite side usually could not be obtained, due to the mass effect of herniated nucleus pulposus, spinal stenosis, intraspinal adhesion, different puncture site and other factors. Therefore, bilateral IFB is recommend for intraoperative pain management in PELD. Considering that the sample size is small. Our findings must be replicated in more research centers and in larger samples, and evaluate over longer periods of follow-up, before final conclusions can be drawn.To the best of our knowledge, this is the first randomized controlled trial to assess the safety and effectiveness of bilateral IFB for PELD pain control. LDH is a common orthopedic disease and a worldwide health problem characterized by low-back and radiating pain.5This investigation can offer a reliable basis for the effectiveness and safety of IFB in treating the PELD pain.Meng Wu designed and reviewed protocol. Hanmin Shan and Jiajun Hu performed the data collection and analysis. Xiaolan Sang finished the manuscript. All of the authors approved the submission.Conceptualization: Hanmin Shan.Funding acquisition: Meng Wu.Methodology: Jiajun Hu.Writing – original draft: Xiaolan Sang.


Patients increasingly receive care in outpatient observation services rather than being admitted to the hospital, and chest pain is the leading diagnosis among observed patients –4. ChestThe concept of hospital observation emerged in the 1970s as an alternative to ED and inpatient care , 9. For Despite rapid growth of observation services for chest pain , 18, it Our primary objective was to compare the rate at which patients with nonspecific chest pain return to the hospital within 7 days after index observation visits versus after index ED and inpatient visits. Although acuity likely differs across these three types of visits, no benchmarks have been established for assessing outcomes of observation care, making ED and inpatient care useful points of comparison . SecondaWe used 2013 and 2014 data from the Healthcare Cost and Utilization Project (HCUP)  State InWe included patients aged 18 years or older with an index visit for a first-listed  diagnosis of nonspecific chest pain. The unit of analysis was an index visit—ED visit, short-stay observation visit, or short-stay inpatient visit (defined below). Patients with multiple encounters contributed multiple index visits if the index visit met the following exclusion and inclusion criteria. We excluded index visits if the patient transferred into or out of the hospital, died in the hospital, or left against medical advice. We required that index visits have a clean period, defined as no hospitalization, observation visit, or ED visit for any reason in the past 30 days . To idenIndex ED visit. The patient was discharged from ED care without being placed under observation or admitted.Index observation visit. The patient was discharged from observation care within 2 nights after presentation to the hospital without being admitted.Index inpatient visit. The patient was discharged from short-stay inpatient care within 2 nights after presentation to the hospital.The primary independent variable was the type of index visit for nonspecific chest pain:Determination of type of index visit was based on status at time of discharge  and diagnosis at the revisit. For the latter, we created a categorical variable based on the following hierarchy: 1) any diagnosis of acute coronary syndromes (AMI or unstable angina), (2) any diagnosis of nonspecific chest pain and other conditions potentially associated with chest pain , and (3) unrelated conditions , urban/rural location, median household income quartile (derived using patient ZIP Code), as well as coexisting conditions at the index visit: prior AMI, any other ischemic heart disease, other comorbid conditions identified using Elixhauser Comorbidity software , designeWe estimated separate logistic regression models for the primary and secondary dependent variables including the covariates described above and hospital-level fixed effects, because care may be influenced by unknown factors that are constant across visits to a particular hospital.p-value was < 0.01 and the revisit rates differed by 10% or more.We used results from the models to derive risk-adjusted 7-day revisit rates for different types of index visits, applying a widely used approach for risk adjustment  . We repeWe included 1,005,866 index visits to 746 hospitals for nonspecific chest pain. Most index visits occurred in the ED  with about half as many index observation visits  and fewer index inpatient visits . Compared with patients with index observation visits, patients with index inpatient visits were more likely to be older, have Medicare insurance, and have more documented coexisting conditions, whereas patients with index ED visits were more likely to be younger, have private insurance, and have fewer coexisting conditions . Total unadjusted 7-day revisit rates after index visits for ED care, observation care, and inpatient care were 9.8, 6.3, and 8.6%, respectively  or inpatient (p < 0.001) visit.Adjusted revisit rates following an index visit for nonspecific chest pain involving ED care, observation care, and inpatient care were 9.7% (95% CI: 9.7–9.8), 6.5% (95% CI: 6.4–6.6), and 7.7% (95% CI: 7.5–8.0), respectively Fig. . The risp < 0.001), 3.7 (95% CI: 3.3–3.9) percentage points lower among patients with Medicaid (p < 0.001), 1.9 (95% CI: 1.7–2.1) percentage points lower among patients with private insurance (p < 0.001), and 2.6 (95% CI: 2.2–2.8) percentage points lower among patients with no insurance (p < 0.001). Relative to the risk-adjusted 7-day revisit rate following an index inpatient visit, the rate following an index observation visit was 1.1 (95% CI: 0.7–1.5) percentage points lower among patients with Medicare (p < 0.001), 0.8 (95% CI: 0.3–1.4) percentage points lower among patients with private insurance (p < 0.01), and 1.7 (95% CI: 0.9–2.5) percentage points lower among patients with no insurance (p < 0.001). Among patients with Medicaid, revisit rates were similar after index visits for observation and inpatient care.Results were similar across payers Fig. . Relativp < 0.001) and after an index inpatient visit (p < 0.001). Additionally, the risk-adjusted rate at which patients returned within 7 days with nonspecific chest pain or conditions potentially associated with chest pain were 2.5 (95% CI: 2.4–2.6) and 0.9 (95% CI: 0.6–1.1) percentage points lower, respectively, after an index observation visit than after an index ED (p < 0.001) or inpatient (p < 0.001) visit.Revisits for acute coronary syndromes were rare (0.3 to 0.5% of index visits), while revisits for nonspecific chest pain and conditions potentially associated with chest pain were common (4.7 to 7.2% of index visits), irrespective of the type of index visit , including a 7.2% (95% CI: 7.2–7.3) revisit rate for nonspecific chest pain or conditions potentially associated with chest pain . The results from Fig. The present analysis of hospital-based visits for nonspecific chest pain has two notable findings. First, nearly 1 in 10 patients discharged from the ED and 1 in 13 patients discharged following an inpatient hospitalization returned to the hospital within 7 days of the index visit. Second, compared with ED and inpatient visits, observation visits for nonspecific chest pain were associated with lower revisit rates (1 in 15).Risk stratification for acute coronary syndromes is a critical task in the evaluation of patients with chest pain. Reassuringly, very few returning patients in our analysis (< 0.5%) had acute coronary syndromes, suggesting that prevailing hospital practices effectively identify patients at low short-term risk. These results are consistent with a recent clinical trial . In thatAlthough patients rarely returned with acute coronary syndromes, we found that many came back with nonspecific chest pain or conditions associated with chest pain. The high rate of 7-day revisits for these recurrent, uncontrolled symptoms raise concerns—for reasons similar to the problems associated with high 30-day readmission rates for a variety of conditions following inpatient hospitalization. Hospital revisits represent potentially avoidable healthcare utilization, they may contribute to ED and hospital overcrowding, and, most importantly, they demonstrate that patients have unmet needs for care. The frequency of revisits raises questions about healthcare delivery factors including the quality of care at the index visit, the transition from the index visit to follow-up care, and access to outpatient care after the index visit. In addition to healthcare delivery factors, diverse patient factors may be associated with 7-day revisit rates including age, comorbidity, income, health insurance, social supports, health literacy, self-efficacy in managing symptoms, language barriers, and other social determinants of health.Another factor potentially contributing to revisit rates is that clinical standards of care for nonspecific chest pain remain poorly defined. Clinical practice guidelines emphasize ruling out acute coronary syndromes and other acute life-threatening conditions, but provide less information on how to evaluate and manage nonspecific and noncoronary causes of chest pain , 33. AftAlthough originally designed to avoid unnecessary inpatient hospitalizations, observation care may allow clinicians a greater opportunity to diagnose noncardiac causes of chest pain and to educate patients in the self-management of symptoms. We found that, relative to ED visits, 7-day revisit rates were 3.2 percentage points lower (˗33.0%) across all populations and 5.1 percentage points lower (− 41.8%) among Medicare patients following index observation visits. Given our study design, these differences could be due to selection bias in the populations placed under observation vs. discharged from the ED. However, our findings were similar with and without adjustment, across payer populations, and by diagnosis at the return visit. Moreover, observed patients were older than those discharged from the ED, suggesting that they would be expected to have higher, not lower, revisit rates.The results of our study are similar to two previous studies that examined outcomes after hospital visits for chest pain among Medicare beneficiaries  and patiOur study has several limitations. First, coding for coexisting conditions likely differs across ED, observation, and inpatient visits. For example, obesity was coded more often during inpatient and observation visits than during ED visits. We re-ran our models with and without conditions for which documentation varied across types of visits, as well as with and without the number of secondary conditions listed on the record, and results were similar. Second, risk-adjusted revisit rates may be higher for inpatient care than observation care because of differences in severity that are not observable in our dataset. For instance, claims data lack clinical information, such as positive cardiac biomarkers, which would reflect the risk of acute coronary syndromes. We were unable to identify revisits for patients who sought care in states not included in this study and we were unable to link records from patients who visited hospitals in multiple states. Finally, the fact that placing some patients under observation is associated with lower revisit rates does not imply that more patients with chest pain should be placed under observation in the future. Rather, the high revisit rates for nonspecific chest pain warrant thorough investigation, including rigorous testing of any future interventions designed to reduce revisits.In conclusion, up to 1 in 10 patients discharged with nonspecific chest pain returned to the hospital within 1 week. Compared with ED and inpatient care, observation visits were associated with lower revisit rates. The diagnoses at revisits were largely nonspecific chest pain and conditions associated with chest pain; acute coronary syndromes were very rare. The high rates of revisits demonstrate that patients may have unmet needs for care going beyond the need to rule out acute coronary syndromes. Future research is needed to refine clinical standards of care for nonspecific chest pain as well as investigate the healthcare delivery and patient factors that influence 7-day revisit rates.Additional file 1.Appendix Table S1. Risk Adjustment Method and Conditions at the Revisit by Type of Index Visit.


Aims: Chest pain is a common complaint at pediatric cardiology clinics and often leads to an extensive cardiac evaluation. In this study, we analyzed the causes of chest pain in Chinese children and developed diagnostic procedures and criteria for targeted myocardial enzyme testing.Methods and Results: We retrospectively analyzed the clinical data of patients aged below 18 years visiting our hospital for chest pain between 2005 and 2019. Based on auxiliary exams and clinical diagnosis, we developed diagnostic procedures and criteria for targeted myocardial enzyme testing in children with chest pain. A total of 7,251 children were included in this study. The chest pain was of cardiac origin in 581 patients (8.0%). The incidence of non-cardiac chest pain was significantly higher in the preschool group and the school-age group than in the adolescent group . Among children with cardiac chest pain, the most common concomitant symptom was chest tightness (67.0%). Myocardial enzyme testing was performed in 5,408 patients and was abnormal in 453 patients. We developed a diagnostic procedure and criteria for targeted myocardial enzyme testing using pertinent history, physical examination, and ECG findings or UCG finding. Applying the diagnostic procedure and criteria could lead to the reduction in myocardial enzyme testing while still capturing all cardiac diagnoses.Conclusion: In children, chest pain is mostly benign and rarely cardiac. During diagnosis, targeted myocardial enzyme testing based on medical history and physical examination can effectively reduce resource use. Chest pain is a common complaint at pediatric clinics, accounting for ~6 per 1,000 visits at pediatric emergency room , To dateCollins et al. , HarahshWe retrospectively analyzed the clinical data of children aged 18 years or below who visited Beijing Anzhen Hospital for chest pain between January 1, 2005 and December 31, 2019. The diagnosis was coded based on the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). Patients with incomplete clinical data or known history of heart disease were excluded from this study. We identified patients on the basis of ICD-10 billing codes for chest pain. Our study complies with the Declaration of Helsinki, and the institutional review board for clinical research at Beijing Anzhen Hospital approved the use of patient medical records for this retrospective review.We analyzed the demographics, history of the present illness, past medical history, family history, concomitant symptoms, clinical department for initial visit, and auxiliary exams. Based on criteria that were applied in retrospect, chest pain was divided into cardiac or non-cardiac , 15, 16 We analyzed the concomitant symptoms in cardiac and non-cardiac patients. Moreover, based on patient age at the initial visit, we divided the patients into the preschool group (3 years ≤ age ≤ 6 years), the school-age group (6 years < age ≤ 12 years), and the adolescent group (12 years < age ≤ 18 years). We analyzed the sex composition and the causes of chest pain in each group. Positive history of past illnesses included systemic lupus erythematous, juvenile rheumatoid arthritis, carnitine deficiency, and congenital adrenal insufficiency. Positive family history included sudden or unexplained death of a first-degree relative, severe familial hypercholesterolemia, pulmonary arterial hypertension, Marfan syndrome, and cardiomyopathy. Positive physical examination results included pathological heart murmur, pericardial friction rubs, abnormal second heart sounds, distant heart sounds, arrhythmia, tachycardia, bradycardia, hepatomegaly, pulsus paradoxus, edema, fever, shortness of breath, abnormal breath sounds in both lungs, and abnormal muscle strength or muscle tone.We retrieved and analyzed ECG reports from clinical medical records. ECG abnormalities included deviation of the electrical axis, pathological ST-segment or T-wave changes, pathological Q wave, ventricular hypertrophy, atrial enlargement, supraventricular tachycardia, frequent premature ventricular contractions, pre-excitation syndrome, and high-grade atrioventricular block.UCG, Holter test results, and chest X-ray were analyzed based on reports.The myocardial enzyme panel included creatine kinase, creatine kinase-myocardial band, lactate dehydrogenase, cardiac troponin I, and myoglobin, which were analyzed based on laboratory reports.We applied the criteria in retrospect to diagnose the causes of chest pain in children. The clinical diagnostic criteria of myocarditis and suspected myocarditis were listed in We developed diagnostic procedures and criteria for targeted myocardial enzyme testing in children with chest pain based on this retrospective study and the diagnostic procedures for chest pain in children from literature reports , 17–19. 2 test was performed to analyze sex distribution and the causes of chest pain. P < 0.05 was considered statistically significant.SPSS20.0 was used for statistical analysis. Measurement data are presented as mean ± standard deviation (P < 0.01).A total of 7,251 children were included in this study, including 4,293 boys (59.2%) and 2,958 girls (40.8%), aged 3–18 years (mean: 12.1 ± 4.0). Chest pain was more common in school-age children and adolescents. Most patients in the preschool group were girls (55.5%) while most patients in the school-age and adolescent groups were boys , and this difference in sex distribution was significant  or a general pediatrician  (The number of children who saw a doctor for chest pain was increasing each year from 2005 to 2019 . Specifi 30.04%) .n = 25), diastolic murmur (n = 32), accentuated P2 (n = 3), splitting of the second heart sound (n = 12), and continuous machine-like murmur (n = 3); 33 had arrhythmia; 62 had a tachycardia; 77 had a bradycardia; 198 patients had fever and bibasilar crackles in both lungs; six had fever and wheezing sounds in both lungs; 327 only had fever; 15 only had wheezing sounds in both lungs; two had hepatomegaly.None of the children had positive history of past illness. Four patients had a positive family history, including two patients whose fathers had dilated cardiomyopathy, one patient whose sibling had Marfan syndrome, and one patient whose father had died suddenly. Physical examination was positive in 795 children. Among them, 75 patients had pathological heart murmur, including systolic murmur , the most common concomitant symptom was chest tightness . Among patients with non-cardiac chest pain , most  had no concomitant symptoms  underwent ECG, 5,352 (73.8%) underwent UCG, 128 (1.8%) underwent Holter test, 1,037 (14.1%) underwent chest X-ray, and 5,408 (74.6%) underwent myocardial enzyme testing.n = 537, 93.6%), followed by frequent premature ventricular contractions , pre-excitation syndrome , supraventricular tachycardia , deviation of the electrical axis , pathological Q wave , and left atrial enlargement .ECG was abnormal in 574 of 7,251 children (7.9%). The most common abnormality was pathological ST-segment or T-wave changes , coronary artery dilation , generalized cardiomegaly with reduced left ventricular systolic function , pericardial effusion , large ventricular septal defect , severe pulmonary valve stenosis with pulmonary valve regurgitation , quadricuspid aortic valve with aortic sinus aneurysm , aortic valve stenosis , coronary-pulmonary arterial fistula , anomalous origin of the left coronary artery from the pulmonary artery , anomalous origin of the right coronary artery from the left sinus , pulmonary arterial hypertension , and left ventricular enlargement with normal left ventricular systolic function .UCG was abnormal in 331 of 5,352 children (6.2%). The abnormality was unrelated to chest pain in 221 of these patients (66.8%) and was related to chest pain in 110 of them (33.2%), including aortic sinus enlargement with aortic sinus aneurysm , followed by increased lung markings , pneumothorax , and pleural effusion .The Holter test was abnormal in only six of 128 children (4.7%), all of whom had frequent premature ventricular contractions. Chest X-ray was abnormal in 643 of 1,037 children (62.0%). The most common abnormality was patchy opacities in both lungs . In these 453 patients, 362 (80.0%) had abnormal ECG with normal UCG, 79 (17.4%) had abnormal ECG and UCG , 12 (2.6%) had abnormal UCG  with normal ECG.P < 0.05)  were diagnosed with cardiac chest pain, and 6,670 patients (92.0%) were diagnosed with non-cardiac chest pain. Some 3,842 cases (53.0%) were idiopathic, 2,109 (29.1%) were related to skeletomuscular diseases, 660 (9.1%) were related to respiratory diseases, 44 (0.6%) were related to gastrointestinal diseases, 12 (0.16%) were related to mental diseases, and 3 (0.04%) were related to other conditions . The inc < 0.05) .n = 431, 74.2%), followed by myocarditis , frequent premature ventricular contractions , pre-excitation syndrome , supraventricular tachycardia , anomalous origin of the left coronary artery , pulmonary hypertension , dilated cardiomyopathy , coronary-pulmonary arterial fistula , anomalous origin of the right coronary artery , aortic valve stenosis , Marfan syndrome , Kawasaki disease , large ventricular septal defect , pericardial effusion , severe pulmonary valve stenosis with pulmonary valve regurgitation , and quadricuspid aortic valve with aortic sinus aneurysm   .Six hundred and sixty cases of chest pain were caused by respiratory diseases , and 44 n = 1,308, 62.1%), followed by slipping rib syndrome , costochondritis , trauma , and straight-back syndrome . Among the 12 cases of chest pain due to mental diseases, the causes included anxiety (n = 5), depression (n = 4), and hysteria-like attacks (n = 3). Meanwhile, patients with mental diseases-related chest pain were all adolescents. Among the three cases of chest pain due to other disorders, the causes included breast mass (n = 1), dysmenorrhea (n = 1), and poor wound healing (n = 1).Among the 2,109 cases of chest pain due to skeletomuscular diseases, the most common cause was precordial catch syndrome . This approach would reduce resource use and the costs to the families.LC, HD, XL, ZY, MJ, KS, and MJ made substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data. LC drafted the work. HD and MJ revised the work critically for important intellectual content. All authors read and approved the final manuscript.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.


Pain is an early symptom of Fabry disease (FD) and is characterized by a unique phenotype with mainly episodic acral and triggerable burning pain. Recently, we designed and validated the first pain questionnaire for adult FD patients in an interview and a self-administered version in German: the Würzburg Fabry Pain Questionnaire (FPQ). We now report the validation of the English version of the self-administered FPQ (enFPQ).After two forward–backward translations of the FPQ by native German and native English speakers, the enFPQ was applied at The Mark Holland Metabolic Unit, Manchester, UK for validation. Consecutive patients with genetically ascertained FD and current or previous FD pain underwent a face-to-face interview using the enFPQ. Two weeks later, patients filled in the self-administered enFPQ at home. The agreement between entries collected by supervised administration and self-administration of the enFPQ was assessed via Gwet’s AC1-statistics (AC1) for nominal-scaled scores and intraclass correlation coefficient (ICC) for interval-scaled elements.Eighty-three FD patients underwent the face-to-face interview and 54 patients sent back a completed self-administered version of the enFPQ 2 weeks later. We found high agreement with a mean AC1-statistics of 0.725 for 55 items, and very high agreement with a mean ICC of 0.811 for 9 items.We provide the validated English version of the FPQ for self-administration in adult FD patients. The enFPQ collects detailed information on the individual FD pain phenotype and thus builds a solid basis for better pain classification and treatment in patients with FD. Fabry disease (FD) is an X-linked lysosomal storage disorder based on mutations in the gene encoding α-galactosidase A (α-GAL). Deficiency in enzyme activity leads to cellular deposition of globotriaosylceramide Gb3) with consecutive multiorgan disease . Treatme with conFollowing a standard procedure , the GerThe datasets analyzed during the current study are available from the corresponding author on reasonable request.Between March 2018 and February 2020, consecutive FD patients underwent a face-to-face interview with the enFPQ during their regular visit at The Mark Holland Adult Inherited Metabolic Unit, Manchester, UK. Each question was read out to the patient and the reply was documented by the interviewer. Study participants were asked to fill in the enFPQ again on their own after 2 weeks and to send in their responses back by postal mail.Male and female native English-speaking patients ≥ 18 years were enrolled in our study, if FD was genetically ascertained and if patients had a current or past pain history. All patients were recruited at The Mark Holland Metabolic Unit, the NHS England national Lysosomal Storage Disorders referral center the North of England in Manchester, UK. We provide the individual genotype in the supplement section  and R version 3.6.3 . The sample size was estimated in analogy to our previous study and to other studies , 14. SinTable All FPQ items were completed by 30/39 (77%) study participants, while 6/39 (15%) patients left question 13 unanswered (number of working days lost due to pain in the last year), either only in the self-administered FPQ session (n = 3) or in both sessions (n = 3). The remaining 3/39 (8%) patients did not answer the following questions: 7c (pain development during life), 7c and 13 (number of working days lost due to pain in the last year), and sub-questions about pain in childhood for questions 1–4. The overall acceptance by the patients was good and patients gave a positive feedback about the content and the format of the questions.There was high agreement when comparing the face-to-face interview version with the self-administered version of the enFPQ for nominal scaled items with a mean of all AC1-statistics of 0.725 (range 0.286–1.000). All items of the questions 1–5 (the four major pain phenotypes and sensitivity impairment), except for question 4b (pain evoked by cold objects), showed at least good agreement with AC1-statistics ≥ 0.600 Table . QuestioRegarding the scored interval-scaled items of the questionnaire, agreement was very high with a mean of all ICC-statistics of 0.811, and with each item showing at least high agreement , the first pain questionnaire for adult patients and self-administration. This questionnaire is based on its German FPQ version for face-to-face interview  and selfPain in FD is distinct in its phenotype and not reflected by standardized pain questionnaires , 15, 16.The number of patients who entered final statistical analysis was relatively low which may be a potential source of bias due to selection, however, statistical analysis gave good to very good test–retest-reliability results for the majority of the enFPQ questions.As observed also in our previous work validating the German versions of the FPQ, some patients gave inconsistent answers at the two sessions when asked the same question. This may be the case in patients with low frequency of pain episodes who then have difficulties in remembering the intensity or duration of a distinct pain phase. Judging if changes in pain are due to medication or the natural course of the disease may also be challenging for patients. Cognitive impairment as known in FD may be another reason contributing to inconsistency in answering repetitively asked questions  and whicPain in FD has a distinct phenotype and therefore requires appropriate tools for standardized assessment in clinical practice, research, and clinical trials. The enFPQ is a useful tool to assess Fabry associated pain and may improve pain management in FD patients, and whilst pain is often a common first symptom in childhood it remains a significant problem in adults.Additional file 1: English version of the Würzburg Fabry Pain Questionnaire (enFPQ).Additional file 2: Individual genotype of study cohort.Additional file 3: Supplementary methods.


Compared with the control group, the ESPB group also showed significantly lower pain scores and incidence of PONV. A separate analysis of RCTs comparing ESPB with oblique subcostal transversus abdominis plane (OSTAP) block showed that the analgesic efficacy of ESPB was similar to that of OSTAP block. The results of this meta-analysis demonstrated that ESPB may provide effective postoperative analgesia in patients undergoing LC.Ultrasound-guided erector spinae plane block (ESPB), a recent regional analgesic technique, has been used to manage acute pain after surgery. The aim of this meta-analysis is to identify the benefits of ESPB in patients undergoing laparoscopic cholecystectomy (LC). The authors searched PubMed, EMBASE, CENTRAL, CINAHL, and Web of Science to identify all randomized controlled trials (RCTs) evaluating the effects of ESPB on postoperative pain after LC. Primary outcome was defined as 24 h cumulative opioid consumption. Secondary outcomes were pain scores and the incidence of postoperative nausea and vomiting (PONV). We estimated mean differences (MD) and odds ratio (OR) using a random-effects model. A total of 8 RCTs, including 442 patients, were included in the final analysis. Postoperative opioid consumption was significantly lower in the ESPB group than in the control group (MD −4.72, 95% CI −6.00 to −3.44,  Laparoscopic cholecystectomy (LC) is commonly performed with more than 500,000 cases per year to treat gallbladder disease . LC prodIn recent years, the advent of ultrasound-guided interfascial plane blocks has been reported in the area of regional anesthesia and pain management. One of the novel techniques introduced in the literature is the erector spinae plane block (ESPB). It was first described in 2016 for the management of thoracic neuropathic pain, and has subsequently been used for acute pain control after surgery . In thisIn the past year, publications referring to ESPB have increased significantly. Subsequently, meta-analyses have been published, supporting the analgesic efficacy of ESPB ,7. HowevThe authors performed the systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline . The preAll RCTs evaluating the effects of ESPB compared with no block or other regional blocks on postoperative pain after LC were included. There were no restrictions on publication year, language, and region. The authors excluded nonrandomized studies of intervention, case reports, letters to editors, review articles, and animal studies. The primary outcome was defined as cumulative opioid consumption at 24 hour postoperatively. The secondary outcomes included pain scores at 12 h and 24 h after surgery and the incidence of postoperative nausea and vomiting (PONV).Two authors (C.H.K. and J.Y.H.) independently conducted a literature search  to identify all RCTs evaluating the analgesic efficacy of ESPB in patients undergoing LC. The search terms consisted of Medical Subject Headings terms and keywords, including “erector spinae plane”, “erector spinae plane block”, “ESB”, “ESP”, and “ESPB”. Each result was combined by the Boolean operator “AND” or “OR”. Detailed search terms for each database are shown in http://www.getdata-graph-digitizer.com) was used to digitize and extract the data from the graph. Any discrepancy was settled by discussion with the corresponding authors (H.J.S. and J.H.R.).Two authors (C.H.K. and J.Y.H.) independently read the titles and abstracts of the articles to remove obviously irrelevant studies. Subsequently, the full texts of the articles were retrieved and reviewed to include studies that met the aim of this study. Data from the final included articles were extracted and summarized in a spreadsheet by two independent authors (C.H.K. and J.Y.H.). The extracted data included first author, publication year, sample size, local anesthetics, target spine level, patient-controlled analgesia (PCA) consumption, pain scores, and the incidence of PONV. In addition, GetData Graph Digitizer 2.26 (Two independent authors (C.H.K. and J.Y.H.) assessed the quality of the final included articles using the Cochrane Collaboration’s tool for assessing risk of bias for RCT , which c2 statistic estimated the degree of heterogeneity among the final included articles. It was interpreted as no (0–25%), low (25–50%), moderate (50–75%), or high (75–100%).This meta-analysis was conducted using R version 3.6.1   with “meA total of 1946 articles were retrieved from the literature search, and 454 duplicate articles were removed. Subsequently, 1482 irrelevant articles were excluded after screening the titles (n = 1445) and abstracts (n = 37). Ten full-text articles were obtained and assessed, and 2 articles were excluded from the final analysis. The reason for the exclusion was as shown below: case report (n = 1), conference abstract (n = 1). Therefore, a total of 8 RCTs with 442 patients were included in the final analysis  16,17,1,21,22,23The risk of bias is summarized in p < 0.001) . Postoperative cumulative opioid consumption was reported in 7 RCTs, including 333 patients ,21,22,23< 0.001) . A moderp = 0.031) (p = 0.194)  a, wherea= 0.194) b. A low p = 0.005) .The incidence of PONV was reported in 6 RCTs, including 252 patients ,20,22,23= 0.005) . A low lp = 0.282) .Three RCTs ,19,23, i= 0.282) . A high p = 0.090) (p = 0.051) (2 = 0%).Three RCTs ,19,23, c= 0.090) a and pos= 0.051) b. A low p = 0.336) .Three RCTs also reported the incidence of PONV ,19,23. T= 0.336) . A low lThe results of this meta-analysis showed that ESPB reduced postoperative opioid consumption, pain scores, and the incidence of PONV. This is the first meta-analysis to demonstrate the analgesic efficacy of ESPB in patients undergoing LC. However, ESPB could not provide better analgesia compared to OSTAP block in patients undergoing LC.The important finding of the current report is that ESPB reduced postoperative opioid consumption. This concurs well with the results of previous meta-analyses ,7,26. OpThe present analysis also showed that ESPB is associated with a reduction of pain scores until postoperative 12 h. Appropriate pain management is obviously an important aspect of perioperative anesthetic and surgical care. Additionally, acute surgical pain is a significant risk factor for the development of chronic pain and thereby a key target for intervention in reducing the risk of chronic postsurgical pain (CPSP) . FurtherPONV is one of the most common and distressing complications after anesthesia and surgery. The general incidence of PONV can be as high as 80% in a subset of high-risk patients . PeriopeContrarily, this meta-analysis found no significant differences in postoperative opioid consumption, pain scores, and the incidence of PONV between the ESPB group and the OSTAP group. Given that these findings are based on a limited number of RCTs, the results from such analyses should consequently be treated with caution. Further studies on the comparison between ESPB and OSTAP block are therefore suggested in order to establish appropriate regional analgesia for patients undergoing LC. The result of this study showed low to moderate level of heterogeneity except for postoperative opioid consumption between the ESPB group and the OSTAP group. Although positive aspects of ESPB in terms of postoperative analgesia were described in the present study, heterogeneity remained to be answered since a moderate to high level of heterogeneity was found in postoperative opioid consumption. This could be explained by several factors, including different types of local anesthetics , various concentrations of local anesthetics (0.25–0.5%), and different targets of the spinous process . An amount of 20 mL of 0.25% bupivacaine was used in most studies ,18,19,21This study has a few limitations. First, dermatomal sensory testing of the block was not performed in all RCTs. Thus, the success or failure rate of ESPB remains unknown, and this might have influenced the results of our analyses. Second, although we converted the doses of various types of opioid to morphine-equivalent doses, we cannot completely rule out the effect of different types of opioid on our results. Third, the result of this study showed that the analgesic effect of ESPB is limited to 12 h postoperatively (acute postoperative pain). However, a more prolonged analgesic effect of ESPB should be obtained to prove its impact on the prevention of chronic postsurgical pain. Further studies with more prolonged follow-up are needed to establish the effect of ESPB on chronic postoperative pain or postoperative clinical syndrome. In conclusion, the present study showed that ESPB reduced postoperative opioid consumption, pain scores, and the incidence of PONV in patients undergoing LC. Further investigations are needed for ESPB to be routinely implemented as appropriate regional analgesia for patients undergoing LC.


Long-term recovery of patients undergone cervical spine surgery is of paramount importance to improve their quality of life. In this study we aimed to evaluate the effects of foot massage on relieving pain and anxiety of patients with anterior cervical discectomy and fusion (ACDF).Enrolled patients undergone ACDF and diagnosed with anxiety disorder at least six months before surgery were treated with 10-min foot massage on a daily basis for four weeks using sweet almond oil. Patients were assessed by neck pain visual analog pain scale (NP-VAS), neck disability index (NDI) and self-rating anxiety scale.p = 0.021) compared to the control group and more reduction compared to baseline (p = 0.046). In terms of quality of life, while both groups demonstrated improvement in pain relief (p = 0.015 for the intervention group and p = 0.037 for the control group), only the intervention group showed improved mental function (p = 0.031).More significant relief in NP-VAS was observed in patients who received foot massage treatment. No significant difference in NDI reduction was seen in patients with or without the treatment. Intervention group demonstrated less anxiety during follow-up (This study found that foot massage was effective in alleviating pain and anxiety, while improving quality of life in patients undergone ACDF, indicating that this intervention should be considered in the clinical management of these patients. Anterior cervical discectomy and fusion (ACDF) represents one of the most frequently conducted spinal procedures. ACDF is a widely-used procedure to treat several cervical spine pathologies, such as prolapsed intervertebral disc spondylosis, degenerative disc disease and trauma . ACDF isMassage therapy has increasingly been used as a technique to promote the mobilization of structures such as muscles and subcutaneous tissues, through the appliance of mechanical force to tissues . MassageComplementary intervention following surgery is increasingly considered effective and acceptable alternative management of pain. Massage therapy is a complementary intervention, which has been shown to relax patients and improve quality of life of patient undergone thoracic surgery or cardiac surgery , 10. AccCompared with massage on other body parts, foot message is a form of complementary intervention suitable for patients with ACDF as potential harm imposed by the message on the spine is avoided. To date, limited studies have been reported regarding the effects of foot massage in alleviating anxiety and pain in patients with ACDF. There is a lack of clear evidence on the effectiveness of foot massage, which precludes recommending this routine in the postoperative care of patients undergone ACDF. To clarify the benefit of foot massage in clinical practice, herein we aimed to conduct a randomized clinical trial to evaluate whether patients who received a four-week foot massage experienced less pain and anxiety and improved quality of life. Our results could provide valuable information to guide the clinical management of patients undergone ACDF.The study was approved by the Ethics Committee of Liaocheng people’s Hospital. Consent forms were acquired from all patients. A total of 118 patients undergone ACDF during the period of 2016–2018 in Liaocheng People’s Hospital were assessed for eligibility. The inclusion criteria were as follows: (1) age over 18 years, (2) administration for over 1 day after surgery, (3) received an open reduction and internal fixation surgery. Since long-term diabetes is thought to have significant negative impact on spinal surgery [Randomization was performed using block randomization by a research scientist blind to the study. Equal numbers (n = 43 each group) of patients were assigned to either intervention group or control group. In the intervention group, massage treatment lasted four weeks. The treatment time we chose was mainly based on the time in hospital of the patients. In our hospital, the patients with anterior cervical discectomy and fusion are usually discharged one months after operation.On the second day after surgery, patients in the intervention group were guided to lay in a supine position and given a whole-body relaxation procedure, which lasted for five minutes. Then each foot was given 5–10 min of massage using sweet almond oil, which is the most commonly used lubricant in massage. During the massage, the subjects’ feet were elevated using a pillow. The massage procedure was performed on both sides of the foot , such that the fingers were placed on the dorsal side of the foot and the thumbs on the plantar side. Then, the plantar region of the foot was pressed with one thumb, stroking upward using less pressure. This was done first on the heel and was later continued on the toes, with the plantar side of the foot held facing the therapist so that the fingers of the therapist were placed on the dorsal side of the toe. This procedure was repeated 5–10 times in a single massage session. An experienced therapist performed massage for all patients to ensure consistent therapy. Routine care was also given to both groups of patients. The patients did not receive massage on other parts of the body. The massage was conducted every other day from 4 weeks.The questionnaires for evaluating pain, anxiety and quality of life were filled out by patients both before the intervention and after the 4-week intervention. Patients were guided to report neck pain assessed by neck pain visual analog scale (NP-VAS), in which patients were guided to indicate the pain intensity on a straight horizontal line of fixed length with the ends being defined as the extreme limits of pain intensities , 13. TheSelf-rating anxiety scale (SAS) was alsoAssessment of quality of life was conducted using the QUALEFFO-41 subscales as the QUALEFFO‐41 subscales have been well validated to assess quality of life regarded to the orthopedic patients –17. The p values were derived from Chi-square test or Fisher’s exact test. Effect size was calculated using Phi, which can be computed by finding the square root of the chi-squared statistic divided by the sample size. Clinical relevant differences were set at effect size ≥ 0.4.Parametric data were presented as mean ± standard deviation (SD) and compared via the Student’s t-test or Wilcoxon signed rank test as appropriate. Non-parametric data were presented as mean and A total of 118 patients were enrolled in this study and 86 patients were assigned randomly to the intervention group (n = 43) and the control group (n = 43)  . However, the intervention group showed lower NP-VAS in the follow-up period compared to the control group (p < 0.05).We first evaluated the effects of foot massage in alleviating neck pain and neck disability after ACDF. As shown in Fig. up) Fig. a and NDIup) Fig. b (p < 0.p = 0.046), and the post-intervention score was remarkably lower in the intervention group compared to the control group (p = 0.021).Since we enrolled patients with short-term anxiety because of injury and surgery, it is important to evaluate whether foot massage could reduce anxiety among the patients. Patients were asked to give a SAS score, which was based on a scoring system consisted of 20 items. As reported in Table p = 0.041). In addition, only the intervention group showed a significant reduction in mental function compared to baseline. The total scores of the two groups were not significantly different.In terms of quality of life, we assessed patients in terms of general physical function, pain, social function, mental function and general health perception using the QUALEFFO-41 scores Table . We founIn the search for a more effective postoperative management of ACDF, psychological factors in addition to pain, such as anxiety should be considered. Postoperative anxiety has been associated with longer hospital stay, higher re-admission rates and dissatisfaction with the received care . HoweverHere we showed that patient who received foot massage demonstrated markedly alleviated anxiety. Emerging studies have suggested that relaxation, which can be induced in a variety of ways, affects pain. Foot massage is gaining popularity as an approach for pain management. In the present study, we showed that foot massage was associated with decreased neck pain and disability in patients undergone ACDF. Consistent with our study, Eghbali et al. demonstrated that after arthroscopic knee surgery, massage on the healthy foot, hands, and upper shoulder relieved pain . AnotherIn contrast to a study by Adogwa et al. on preoperative treatment of anxiety in ACDF management, which showed that preoperative treatment of anxiety did not improve NDI, thereby exerting no functional benefit , we showOur evaluation was based on questionnaires to provide numeric values in the assessment of pain, anxiety, disability and general health state, which nonetheless lacks clinically significant meaning. Thus, in the study by Parker et al. on ACDF, the minimal clinical important difference (MCID) has been introduced to measure the critical threshold of achieving treatment effectiveness . Here weHere we have demonstrated that postoperative foot massage for four weeks is associated with effectively reduced neck pain and neck disability, relieved anxiety and improved quality of life in patients. These findings suggest that foot massage is worth being used as a complementary care for patients undergone ACDF.