BackgroundPediatric patients often present with vague complaints involving the anterolateral foot and ankle, the medial knee, the lower back, and the hip. In our experience, closer examination of these patients reveals a constellation of symptoms that involve pathology in the ankle, knee, back, and hip. This study aimed to detail the identification and treatment of patients with the triad of flexible flat feet, tight Achilles complex, and altered gait, and their clinical course over time.MethodsAll patients of age 18 years or younger who presented to our urban academic center outpatient clinic with foot, ankle, patellar, low back, or hip pain or pathology were included. Patients with identified tarsal coalitions, accessory naviculars, malalignment syndrome, bone cysts or tumors, soft tissue tumors, arthropathy, neuropathy, infection, limb length inequality, patellar subluxation or dislocation, or spinal pathology were excluded. For each patient, demographic information, symptom description, treatment, and clinical course, including the Foot and Ankle Outcome Score (FAOS) was recorded.ResultsA total of 62 patients were included in our study. Patients mostly presented with low back pain , medial patellar pain , anterolateral ankle pain , and vague foot pain . Overall, 53.8% of patients with back pain at the initial visit, 35.0% of patients with knee pain, 44.4% of patients with ankle pain and 80.0% of patients with foot pain improved at final follow up. While patient-reported sports and recreation subscale scores demonstrated a significant improvement at the final follow-up compared to baseline scores (p=0.02), all other scores did not significantly differ compared to baseline scores. At final follow-up, 12 of 26 (46.2%) patients reported being able to return to play in their desired sport.ConclusionComplaints of back, hip, knee, ankle, or foot pain in the pediatric population can be early markers for a constellation of conditions that include low back pain, flexible flat feet, Achilles contracture, and altered gait due to increased lateral subluxation of the patella and hip flexion. Pediatric patients often present with vague multiple complaints involving the anterolateral foot and ankle, the medial knee, the lower back, and the hip. Kosashvili et al. studied 92,000 Israeli adolescent military recruits and discovered a link between flat foot severity and the prevalence of anterior knee pain and intermittent low back pain, with moderate and severe flat foot being associated with nearly double the rate of knee and low back pain . In 2010Closer examination of patients with any of the abovementioned complaints may lead to the discovery of a constellation of symptoms that involve pathology in the ankle, knee, back, and hip. This stems from a physical triad of flexible flat feet, contracture of the gastrocnemius-soleus muscle complex, and altered gait resulting in a change in kinematics manifesting as lower back pain, lateral subluxation of the patella, and hip pain. An understanding of flat foot and the pain triad may contribute to improved patient outcomes, as the presence of flat foot diminishes the quality of life and foot function . Flat foWhile the studies above have examined adults and adolescents, the literature in pediatric patients is severely lacking, especially with regards to the described triad. This study aimed to describe, define, and assess the identification and treatment of patients with the triad of flexible flat feet, tight Achilles complex, and altered gait as well as their clinical course over time. We hypothesize that with proper early diagnosis and focused treatment, patients with this triad will clinically improve over time.Approval for our observational cohort study was obtained from Children's Hospital of Philadelphia Institutional Review Board . All patients 18 years of age and younger over a two-year period who presented to our urban academic medical center outpatient clinic were eligible to be part of our study and were retrospectively reviewed. All patients who presented with foot, ankle, patellar, low back, or hip pathology pain were included. In addition, all patients who presented with diagnoses of flexible pes planus and ankle dorsiflexion of 10 degrees or less, regardless of the presence of hip or knee pathology leading to gait instability, were also included. A combination of physical examination findings (inspection and deformity correction), as well as radiographs, were utilized for making a diagnosis of flexible pes planus in all age groups [Data were analyzed using simple descriptive statistics and statistical significance tests (one-way ANOVA and Wilcoxon signed-rank tests) as appropriate to determine any significant changes at each clinic visit compared to baseline . For all analyses, p<0.05 denotes statistical significance.In total, 62 patients were included in our study. Most of our cohort was female , between the age of 12 years and 15 years , and had a BMI less than or equal to 25.0 . In total, 19 (30.6%) patients initially did not present with pain while four (6.5%) presented with pain in one location, seven (11.3%) in two locations, 19 (30.6%) in three locations, 11 (17.7%) in four locations, and two (3.2%) in five locations (Table Thirty-two 51.6%) patients complained of back pain at initial evaluation, two (3.2%) complained of hip pain, 41 (66.1%) of knee pain, 39 (62.9%) of ankle pain, 13 (21.0%) of foot pain, and two (3.2%) of pain at other sites. Patients were not asked to detail their hip pain. Patients mostly presented with lower back pain , medial patellar pain , anterolateral ankle pain , and other foot pain  . The activities of daily living (ADL) subscale score showed an overall improvement in scores over time, with a 7.64-point improvement at the final follow-up. The sports and recreation (Sport and Rec) and quality of life (QOL) subscale scores also showed a decreasing amount of improvement compared to baseline until there was a significant improvement in scores at the final follow-up (Sport and Rec=24.92 points and QOL=22.61 points)  patients reported playing sports during their initial evaluation. In total, 37 (59.7%) patients participated in gym class, 11 (17.7%) in dance, and 26 (41.9%) in team sports. Twelve (19.4%) patients played soccer, eight (12.9%) played basketball, four (6.5%) played baseball, three (4.8%) ran (cross country and track), two (3.2%) played racket sports (tennis and squash), one (1.6%) played football, one (1.6%) wrestled, one (1.6%) played volleyball, one (1.6%) played hockey, and six (9.7%) played multiple sports. Additionally, six (9.7%) patients also reported participating in other activities . At their final follow-up, 12 of 26 (46.2%) patients reported being able to return to play in their desired sport, three (11.5%) patients reported not being able to return to play, and 11 (42.3%) declined to answer. Of the patients who were able to return to sports, nine initially presented with zero locations of pain, one with two locations, and two patients with three locations of pain.While complaints of ankle pain, knee pain, and back pain are quite common in the pediatric population, these symptoms may be part of a predictable constellation of findings that include low back pain, flexible flat feet, Achilles contracture, and altered gait due to increased lateral subluxation of the patella and hip flexion. While selected reports do exist about a correlation between pes planus, knee pain, and back pain, there is still no data published on the entire above constellation of symptoms -3,10. ThMost of our patients complained of lower back pain and medial patellar knee pain at initial evaluation. However, when examined thoroughly, they were found to have the entire described constellation of findings. While not described in the pediatric literature, there is published literature about a correlation between back pain, knee pain, and flatfeet ,12. HeigPrevious studies have also detailed the lower quality of life outcome scores associated with more severe pediatric flatfoot . While aThe lack of difference in improvement based on the initial presentation is an important finding that must be highlighted. No matter how many locations of pain a patient presented with, they had similar improvement in FAOS scores over time. In fact, patients on average reported more locations of pain at follow-up visits compared to their initial examination, indicating that they did develop complaints in a predictable pattern after their diagnosis was made. This seems to indicate that while early diagnosis is important, proper treatment centered around braces, orthotics, stretching, and strengthening can improve symptoms in these patients no matter when and how they present. The increased number of locations of pain did not correlate to the improvement seen in FAOS scores. There was no qualification of severity of pain or other outcome scores that integrate different anatomic locations of symptoms used in this cohort.This retrospective study documents a series of patients who present with a previously undescribed triad of symptoms as well as their clinical progression over time. However, this study does have its weaknesses. While this series only includes 64 patients, it does provide a solid foundation for the further exploration of this triad. Not every patient followed up for the entire two-year period, leaving an unequal number of scores at each time point and possibly skewing the data. Not every patient followed up at uniform times. The decreasing number of patients presenting for follow-up also curtailed the ability to run further stratified analysis on patient groups. Further exploration of this triad should build off this report, using subjective and objective outcome measures that encompass all anatomic locations of symptoms to document clinical progression and treatment options. Evaluation of additional confounding anatomical anomalies and variations may include femoral and tibial torsion, ligament laxity, genu recurvatum, valgus and varus may be of importance in future studies.Complaints of back, hip, knee, ankle, or foot pain in the pediatric population can be early markers for a constellation of conditions that include low back pain, flexible flat feet, Achilles contracture, and altered gait due to increased lateral subluxation of the patella and hip flexion. Early diagnosis of the entire constellation of symptoms can be made using a thorough history and physical exam coupled with an awareness of this constellation. When diagnosed and treated appropriately, these patients do clinically improve over time with return to sport possible.


Participants and evaluator were blinded to the group assignment. Proprioception training produced a statistically significant reduction in pain post intervention, but this reduction was small (d = 0.1) at the 3-month follow-up. JPS accuracy demonstrated statistically significant differences between the groups (p = 0.001) post-intervention and at the 3-month follow-up (p < 0.003). Statistically significant differences between means were found in both the Quick-Dash and COPM post intervention , as well as at the 3-month follow-up . There was a significant time factor for the reduction of pain intensity over time but effect sizes between groups was small at the 3-month follow-up period. Proprioceptive training improves thumb JPS accuracy; however, it does not contribute to a reduction in pain intensity in the long term. The inclusion of a proprioceptive program may be beneficial for improving individuals with thumb CMC OA sensorimotor performance. The study was registered at ClinicalTrials.gov NCT04738201. No funding was provided for this study.A randomized controlled trial of forty-five females over 18 years of age with diagnosis of thumb basal osteoarthritis in their dominant hand and with a minimum pain rating of 4/10 on the Visual Analogue Scale (VAS) during activities of daily living (ADLs) were recruited from March to June 2021. The group receiving proprioception training was compared to routine conservative physiotherapy treatment. The main purpose of this clinical trial is to test the effect of proprioception training on pain intensity in subjects with thumb osteoarthritis. Primary outcome was joint position sense (JPS) for the assessment of CMC proprioception and secondary outcomes were Visual Analogue Scale (VAS) and Canadian Occupational Performance Measure (COPM) for the assessment of patient satisfaction and the Quick-DASH which assessed upper limb function. A block randomization was carried out for the control group ( Although the pathogenesis of carpometacarpal (CMC) osteoarthritis is not understood completely, altered motor patterns exhibited during the completion of activities of daily living (ADL) can increase symptoms such as thumb pain and decreased pinch strength and thumb mobility ,2. AlterProprioception and the neuromuscular control of the thumb are essential for maintaining normal joint stabilization to avoid joint deformity or injury . AlteredThe relationship between proprioception and joint disease have been previously described in the literature ,13,14,15Decreased proprioceptive function has been previously described when patients with thumb CMC OA were compared to healthy subjects ,16. AlthTo improve the understanding of the influence of conservative interventions, it is necessary to investigate the degree of contribution that each technique, described in the literature, has on the mechanisms that cause pain. The main objective of this investigation is to determine the effect a proprioceptive joint position sense training program has on pain intensity in patients with the diagnosis of thumb CMC joint OA. Secondarily, we will assess the effect of proprioception training on JPS and function.A randomized controlled single-blind clinical trial study was conducted at a local Hand Rehabilitation Center for patients diagnosed with thumb CMC joint OA referred from three different local hospitals. Informed consent was obtained from all patients and procedures were conducted according to the Declaration of Helsinki and approved by a Local Ethical Committee (62-2020-H).Patients with thumb CMC joint OA in their dominant hand were recruited from March to June 2021. Patients who agreed to participate in the study had their thumbs evaluated individually by a rheumatologist and a physiotherapist who used both clinical and radiographic methods. Inclusion criteria included females over 18 years of age, a diagnosis of grade one to three thumb CMC joint OA according to the Eaton Classification  in theirn = 22) and experimental group (n = 23).Before randomization and after the patient signed the informed consent to participate in the study, a researcher who was blinded to the study collected the baseline outcome measurements. The blinded hand therapist took measurements at baseline, immediately following the 4-week treatment period, and finally at the 3-month follow-up. Data collection, demographic information, and outcome variables were inputted into an Excel database. A number was assigned to each participant to ensure anonymity. Following baseline data collection, the blinded researcher carried out the process of randomization. In order to ensure a balance in sample size across groups over time, a block randomization was carried out for the control group  publishing guidelines .For JPS testing, the participants were seated with the arm resting on a table in a neutral position and elbow at 90 degrees. The joint angle was measured using a standard plastic goniometer. The fulcrum of the goniometer was placed over the intersection of the first and second metacarpals ,21,22. TThe visual analogue scale (VAS) was used to evaluate pain intensity during ADL. The VAS scale has been widely used in diverse adult populations, including those with rheumatic diseases . The senThe Quick-DASH questionnaire which is well studied with established validity, reliability, and responsiveness was used to measure upper extremity function . This in©, Universidad Autónoma, Barcelona, Spain). The calculations are based on detecting a mean difference of 2 cm minimal clinically important difference (MCID) on a 10 cm VAS assuming a standard deviation of 2 cm, a 2-tailed test, an alpha level of 0.05, and a desired power of 80%. The estimated desired sample size is 15 individuals per group. To accommodate for expected dropouts before study completion, a total of 22 and 23 participants for control and experimental group were included.The sample size and power calculations were performed with the ENE 3.0 software , and an intention-to-treat analysis was conducted using the last-value-forward method. The results are expressed as means, standard deviations, and/or 95% confidence intervals. A separate 2 × 3 mixed model ANOVA, with group  as the between-subjects factor and time  as the within-subjects factor, was conducted to examine the effects of the intervention on VAS, JPS, Quick-Dash, and COPM variables. Post-hoc comparisons were conducted with Bonferroni corrections. Between-group effect sizes were calculated by using Cohen’s d coefficient which considers an effect size greater than 0.8 large, 0.5 moderate, and less than 0.2 small . The staSixty-one participants were initially assessed for eligibility. Forty-five consecutive patients who met the inclusion criteria were randomized into either the experimental group (23) or control group (22). At the final data collection time point at 3-months post treatment, 34 patients (mean ± SD age: 62 ± 7 years) were analyzed. The CONSORT flow diagram was followed to structure the progression of patients through the phases of this study . Baselinp < 0.001) for the reduction of pain intensity as measured by the VAS over time. Post-hoc analysis indicated that patients with thumb CMC OA receiving the experimental treatment had a statistically significant reduction in pain in post-intervention  period, as well as at 3-month follow-up   . Betweenp < 0.001) over the length of the study. We found statistically significant differences in the experimental group (p = 0.001) post-intervention and at 3-months follow-up (p < 0.003). There was significant difference between both groups at 3-months follow-up (p < 0.001). Between-groups effect sizes were moderate (d = 0.5) after the intervention and large (d = 1.8) at the 3-month follow-up period . The post-hoc testing revealed significant decreases in the scores of the Quick-Dash and COPM in both groups at post-intervention when compared to baseline data , as well as at 3-months follow-up . There was also no significant main effect difference between the groups at post-intervention and at 3-months follow-up (p > 0.05)  .This is the first clinical trial that reports findings of the effects of proprioceptive joint sense training on outcomes for patients with a diagnosis of thumb CMC joint OA. There is no high-level evidence defining the best techniques or exercises for proprioceptive rehabilitation for thumb CMC joint OA. The thumb exercise program used in this experiment was based on a previous study .Pain is often the primary reason patients seek rehabilitative services and can be the most influential factor on the performance of daily tasks and functional activities. Therefore, investigating the effect that conservative techniques have on pain intensity is warranted. Manual therapy, orthotic intervention, and a multi-model approach have evidence to support their use to improve function and decrease pain ,36. We fThumb OA is a progressive pathology that produces chronic pain and affects all areas of one’s life. Some studies on thumb CMC OA have used intervention techniques that are not based on the chronic pain approach ,39. OA iSome studies that investigated chronic pain concluded that people with chronic pain have a proprioceptive deficit . A studyIt is important to consider intervention strategies that focus on the central origin of pain; education on ADLs, physical and psychological approaches, and force sense proprioception have not yet been studied for efficacy in thumb CMC OA. To prevent interference with the result of the joint proprioceptive intervention, in our clinical trial, we did not include ADL re-education although some studies recommend re-education in lifestyle performance in individuals with hip and knee osteoarthritis . WithoutWe did not find significant differences between groups for pain or function. We did find statistically significant differences regarding JPS testing between groups following the intervention and at the 3-month follow-up. The MCID for JPS for CMC OA has not been established. These results confirm those obtained in the pilot study carried out by Cantero-Tellez et al. . HoweverExercises and education regarding pain have been found to be beneficial for pain intensity, self-efficacy, and social function . DespiteThere is evidence to support JPS as a clinically meaningful measure of conscious sensorimotor impairment in individuals with thumb CMC OA ,35 but aOur follow-up time was 12 weeks. It would be beneficial to determine the efficacy of the intervention at a longer follow-up period of 6 months to 12 months. We also provided a multi-modal intervention, and it is difficult to determine the exact impact that proprioception training had on the outcomes. Patients with a diagnosis of thumb CMC OA made clinically significant improvements over time in pain, function, and satisfaction in both groups, but the effects on pain intensity decreased at the 3-month follow-up. The group receiving proprioception exercises achieved both clinically and statistically significant changes in JPS error scores, suggesting that the inclusion of a proprioceptive program may be beneficial for improving sensorimotor performance.


Lachnospira), with respect topain being “not acceptable” at 24 h postoperatively.Porphyromonas was more abundant in the group reporting anacceptable pain level at 24 h. An inverse correlation was noted between abundance ofCollinsella and maximum self-reported pain score withmovement. We have demonstrated for the first time that postoperative pain isassociated with gut microbiota composition and diversity. Further work on therelationship between the gut microbiome and somatic pain may offer new therapeutictargets.Gut microbiota play a role in certain pain states. Hence,these microbiota also influence somatic pain. We aimed to determine if there was anassociation between gut microbiota (composition and diversity) and postoperativepain. Patients (n = 20) undergoing surgical fixation of distal radius fracture underaxillary brachial plexus block were studied. Gut microbiota diversity and abundancewere analysed for association with: (i) a verbal pain rating scale of < 4/10throughout the first 24 h after surgery (ii) a level of pain deemed “acceptable” bythe patient during the first 24 h following surgery (iii) a maximum self-reportedpain score during the first 24 h postoperatively and (iv) analgesic consumptionduring the first postoperative week. Analgesic consumption was inversely correlatedwith the Shannon index of alpha diversity. There were also significant differences,at the genus level (including  Disturb of mice.These f of mice.Although it has not been thoroughly investigated in humans, there ispreclinical data available to support the relationship between gut microbiota andsomatic pain . FurtherRebound pain (RP) is a quantifiable difference in pain scoresbetween that elicited when a nerve blockade is effective, and that elicited after theblockade has resolved . RP may The primary objective of this study was to determine the association(if any) between microbiota diversity  and the To determine associations (if any) between relativeabundance of microbial taxa and other characteristics of postoperative andrebound pain, and postoperative analgesic consumption.To describe (post PNB) rebound pain by quantifying itsclinical, psychological and neurophysiological characteristics in thispatient cohort.Secondary objectives were:2With Institutional Ethical approval 11/10/16; 15 November2016, Chairperson Prof M.G. Molloy] and having obtained written informed consent fromeach, 20 ASA I-II patients scheduled to undergo upper limb surgery under axillarybrachial plexus block (ABPB) were recruited. The study was conducted at theDepartment of Anaesthesia and Intensive Care Medicine, Cork University Hospital,Ireland. The trial was registered at ClinicalTrials.gov .2.1Age 18–80 years; patients undergoing fixation of distal radiusfracture (ORIF or K-wiring) under ABPB.2.2Contraindication to regional anaesthesia, uncontrolled pain ≥ 5 at rest despite adequate analgesic measures);chronic pain syndrome; history of peripheral neuropathy; pre-existing nerve damagein the operative arm; axillary surgery in the past; cognitive impairment; language barrier; depression; diabetes; obesity(BMI > 35); antibiotic therapy in the preceding 30 days; recent (<1 year)administration of probiotics.2.3Preoperative pain levels and total analgesic consumption wererecorded in a pain diary. All patients underwent ultrasound guided ABPB. Localanaesthetic mixture containing lidocaine 2% + adrenaline 1:200.000 and bupivacaine0.5%, 10 ml each, was applied to each of the four nerves. Cefuroxime 1.5 G i.v.was administered immediately preoperatively according to hospital guidelines.Patients received i.v. diclofenac 75 mg in the operating theatre; opioids anddexamethasone were not administered.2.4Block assessment: sensory and motorfunction for each of the ulnar, median, radial, musculocutaneous nerves wereassessed and recorded immediately after arrival to the recovery room.Self-report of pain  was recorded postoperativelycommencing on the patient’s arrival to the recovery room and during the firstpostoperative week. Rebound Pain Score (RPS) was defined as the difference betweenmaximum and minimum VRS (only if the block was successful). Rebound pain waspresent by definition if RPS > 3. Patient’s self-reported acceptable pain level was recorded.short form McGill Pain Questionnaire wascompleted by the patient from immediately after arrival to the recovery room andthereafter during the first 24hrs postoperatively if the patient detected asignificant change in pain intensity and/or quality.A pain diary during the first postoperativeweek.Each patient’s analgesic consumption was recorded in a2.5Paracetamol 1 g (QDS), diclofenac 75 mg (BD) and oxycodone 10 mg were administered regularly to all patients. Oxycodone5–10 mg (fast release) four hourly was administered for breakthrough pain, at thepatient’s request.2.6Bilateral electronic quantitative sensory testing (QST) wasperformed pre- and postoperatively  by a trained investigator. Sensory threshold(ST), pain perception threshold (PPT) and pain tolerance threshold (PTT) wereassessed in each patient using a Nihon Kohden Neuropack S1 EMG/EP stimulator. ST,PPT and PTT was recorded using the staircase method (1 mA ramping), and astandardized technique in the forearm/hand (C5-T1 dermatomes) of the affected andcontralateral upper limbs.2.7Participants were given collection packs anddetailed instructions on how to collect their preoperative faecal samples  and the first sample aftersurgery. The samples were refrigerated before transport and then maintained at-80°C until analysis.2.8Microbial DNA was extracted from 0.1 g stool samples using theFastDNA® Spin Kit .2.916S rRNA amplicon sequencing was conducted using the IlluminaMiSeq platform. 16S rRNA sequencing library preparation was completed followingthe 16S metagenomic sequencing library protocol (Illumina). Genomic DNA wasamplified using primers specific to the V3-V4 hypervariable region of the 16Sribosomal RNA gene .. PCR products werevisualised using gel electrophoresis  andsuccessful PCR products were cleaned using AMPure XP magnetic beads . A second PCR reaction was completed on 5 µl of the purified DNA.Two indexing primers  wereused per sample to provide a unique index and facilitate sample pooling forsequencing on a single flow cell and demultiplexing prior to analysis. Each PCRreaction contained 5 µl index 1 primer (N7xx), 5 µl index 2 primer (S5xx), 25 µl2x Kapa HiFi Hot Start Ready mix, and 10 µl PCR grade water. PCRs conditions wereas described above, with only 8 amplification cycles. PCR products were visualisedand cleaned as described above. Samples were quantified using the Qubit 3fluorometer  and samples were pooled to anequimolar mix. The samples were sequenced using a 2 × 250 cycle kit, followingstandard Illumina sequencing protocols.2.10Collected continuous data was examined for normality. Betweengroup comparisons (e.g. presence of rebound pain) of quantitative data relating topatients  were examined using unpaired Student-t testswith Bonferroni correction. Categorical data were examined using the Chi-squaredtest or Fisher’s Exact test as appropriate. Correlation between continuousvariables was examined using Pearson’s correlation coefficient. P < 0.05 wasconsidered significant.All samples had > 52,000 reads. Data were analysed as per thefollowing biological conditions (groupings): Group 1 (pain level acceptable topatient - first 24 h: Yes vs No) and Group 2 (VRS max < 4 - first 24 h: Yes vsNo).Paired-end reads were assembled using FLASH . Further3We recruited twenty patients between February and May 2017 into thisprospective, observational study. Patient characteristics are summarised inSupplementary Table 1. No patients were excluded, but data from two patients have notbeen included in the gut microbiota analysis due a breach of protocol in samplecollection and storage. An insufficient number of faecal samples (5/20) were obtainedpreoperatively to justify a separate analysis of change in microbiome composition.The patient flowchart is illustrated in 3.1On the day before surgery, the patients’ VRS for pain at rest was4.5 (2.59) [mean (SD)]. Every block was successful for the purposes of surgicalanaesthesia; no block-related adverse events occurred. Block regression startedand completed in 6.68 (2.88) and 12.21 (3.7) hours, respectively .Seventeen of the 20 patients experienced RP after resolution of ABPB. The mean(SD) RPS reported was 5.4 (3.11). No significant correlation was identifiedbetween preoperative VRS and RPS (CC = -0.27), and magnitude of RP and age(CC = 0.15). Patient self-report of pain and analgesic consumption wascharacterised by great variation and neither demonstrated significant associationwith the type of the surgery (ORIF vs K-wiring). For 8/20 patients the pain scores(VRS 0–10) over the first 24 h postoperatively were all less than their acceptablepain threshold. The pain characteristics for the first 24 h postoperatively aresummarised in There was no significant correlation between cumulative analgesicconsumption at 24 hrs postoperatively and magnitude of RPS (CC = 0.02). Theadherence to analgesia protocol was similar amongst patients with or withoutRP.Patients’ median daily pain scores for the first postoperativeweek are summarised in One month after surgery, three of the 20 patients were takingpainkillers regularly for symptoms related to their surgery and only one wasrestricted in everyday activities as a result of his pain.).The mean (SD) time between block placement and postoperative QSTmeasurements were 21.16 (3.82) hours. When comparing pre- and postsurgical QSTresults, surgical side PPT and PTT was greater postoperatively then preoperatively. No differences were observed between (i.)surgical vs control side parameters; (ii.) control side pre- vs postoperativeparameters; (iii.) pre- vs postoperative somatosensory thresholds. Pre- andpostoperative PPT and PTT were not different amongst patients with or without RP was significantly less in patients whoreported VRS < 4 during the first 24 h postoperatively.There were no significant differences in Shannon index, evenness, richness, Simpson’s diversity, and Chao1within group 1-pain level acceptable within 24 h.Howeverratively.Fig. 2aV3.2.2.Beta diversity was not statistically significantly differentbetween groups for maximum pain score with movement (first 24 h), or analgesicconsumption .Fig. 3Pr3.2.3Abundance by phylum, family and genus from the stool samplesanalysed are summarised in Supplementary Figures 2 and 3.3.2.4Porphyromonas and theEubacterium coprostanoligenes group werediscriminative bacterial genera in those who answered “YES”, whereas the generaAlistipes, Lachnospira,Incertae Sedis, Clostridium sensu stricto1, and Subdogranulum were discriminativegenera of those who answered “NO”. For Group 2,Intestinibacter and the Eubacteriumcoprostanoligenes group were discriminative bacterial genera ofthose who gave a VRS < 4. There were no differentially abundant bacterialgenera for those who gave a VRS > 4 .LEfSe analysis was used to determine the discriminativebacteria (more abundant) most likely to explain difference between the groups.For Group 1,  VRS > 4 .Fig. 4Hi3.2.5Collinsella  andCoprobacter . Analgesicconsumption was positively correlated with the genusDialister . However, theseassociations were not present after correcting for the multiple variables ofage, Groupings 1, 2, maximum pain score with movement (first 24 h), andanalgesic consumption .Maximum pain score was inversely correlated with the generast week).Fig. 5Stp = 0.0499, r2 = 0.51).. Therewere no other significant differences noted for other measures of alphadiversity.Analgesic consumption was inversely correlated with theShannon index of alpha diversity (= 0.51).. Therew4Most patients (17/20) experienced RP after resolution of ABPB. Themagnitude of the RP, pain experience during the first week postoperatively and theanalgesic consumption varied greatly between patients. Pain perception was associatedwith the abundance of certain genii, including Collinsella. We found no correlationor association between the magnitude of RP and (i) preoperative pain scores, (ii)type of the surgery, (iii) analgesic consumption, (iv) adherence to analgesicprotocol (v) demographic data and (vi) QST results.A major finding of this study is that postoperative analgesicconsumption was inversely correlated with the Shannon index of alpha diversity. It isknown that alpha diversity is decreased in certain pain conditions e.g. IBS andchronic pelvic pain syndrome . With reCollinsella and maximum VRS withmovement. Collinsella has previously been shown to influence production of thepro-inflammatory cytokine IL-17A; its role in altering gut permeability and diseaseseverity was confirmed in experimental arthritis  for future similar studies. Secondly, our sample was inhomogeneous in terms of(i) the days spent between injury and surgery, (ii) surgery type (K-wiring vs ORIF)and surgeon. Finally, we were unable to collect sufficient pre-operative stool tojustify a second analysis relating to acute changes in gut microbiome compositionWe have demonstrated here that certain characteristics of gutmicrobiome composition and diversity are associated with the patient-reportedmagnitude of postoperative pain and analgesic consumption. We suggest that thesefindings justify further work to improve our understanding of the influence of thegut microbiome on postoperative pain, and potentially to identify new analgesicmodalities in the future.D. Brenner: Conceptualization, Datacuration, Formal analysis, Investigation, Methodology, Project administration,Writing - original draft, Writing – review & editing. P.Cherry: Data curation, Formal analysis, Software, Visualization, Writing– review. T. Switzer: Investigation, Project administration,Writing - review & editing. I. Butt: Investigation, Projectadministration, Writing - review & editing. C. Stanton: Datacuration, Formal analysis, writing - review & editing. K.Murphy: Data curation, Formal analysis, Software, Visualization, Writing- review. B. McNamara: Conceptualization, Resources, Writing -review & editing. G. Iohom: Conceptualization, Supervision,Writing - review & editing. S. O'Mahony: Conceptualization,Data curation, Formal analysis, Investigation, Methodology, Resources, Supervision,Writing - original draft, Writing – review & editing. G.Shorten: Conceptualization, Data curation, Formal analysis,Investigation, Methodology, Resources, Supervision, Writing - original draft, Writing– review & editing.This research did not receive any specific grant from funding agenciesin the public, commercial, or not-for-profit sectors. George Shorten is a fundedinvestigator, Insight II SFI Research Centre.


This study aimed to examine the psychometric performance of the Foot and Ankle Outcome Score (FAOS) used in Indonesian patients with chronic lateral ankle instability (CLAI).The FAOS was translated into Indonesian through standardized procedures. Among 224 patients with unilateral CLAI recruited from 14 physical therapy clinics during a 1-year period, reliabilities, construct validities, and responsiveness levels of the FAOS were examined. Active and passive range of motion of ankle dorsiflexion or plantiflexion, figure-of-eight, numeric pain rating scale (NPRS), and Short Form (SF)-36 were used to test the construct validities.The five subscales indicated adequate internal consistency  and interrater test-retest reliabilities . Subscales of the FAOS moderately converged with those selected measures with similar constructs (The Indonesian version of the FAOS demonstrated acceptable reliabilities and responsiveness, and fair construct validities among CLAI patients, although certain items in the pain and OSs subscales may need to be further explored and improved. Lateral ankle sprains are the most common musculoskeletal injury, and chronic lateral ankle instability (CLAI) represents a repetitive lateral ankle sprain with various persistent symptoms, such as intermittent pain, swelling, ankle instability, and a restricted range of motion (ROM) , 2. InsuTo evaluate the effectiveness and safety of a medical intervention for patients, patient-reported outcome measures, such as health-related quality of life (HRQOL), are considered to capture the patient’s perspective, thereby adding another dimension to understanding a patient’s response to treatment that cannot be extrapolated from physiologic endpoints . HRQOL mThe FAOS was initially developed in English and has been validated in several languages among patients with various foot- and ankle-related injuries –11. HoweTo validate and expand the use of the FAOS, this study examined its psychometric properties of score distributions, reliabilities, construct validities, and responsiveness in Indonesian patients with CLAI.During the year 2019, we recruited study participants from 14 physical therapy (PT) clinics, situated in 14 major provinces  in Indonesia. Eligible participants were aged ≥ 17 years who had been diagnosed with unilateral CLAI. The criteria for identifying unilateral CLAI consisted of one-sided, repetitive lateral ankle sprains that had occurred at least 6 weeks before the assessment, a positive anterior drawer test (an anterior translation more significant than 1 cm on the injured side vs. the uninjured side), a positive talar tilt test , and having experienced residual symptoms such as a subjective feeling of giving way [The study was approved by the Ethical Committee of the Institutional Review Board College of Medicine, Universitas Udayana/Central Public Hospital Sanglah Denpasar (permission no. 60/UN14.2.2.VII.14/LP/2019).The original version of the FAOS consists of 42 items across five subscales, including pain , other symptoms (OSs) , activities of daily living (ADLs) , sports and recreational function (SRF) , and foot- and ankle-related quality of life (FAQL)  . Each itAccording to standard international guidelines of cross-cultural adaptation , the EngEach participant received an initial assessment, including active ROM (AROM), passive ROM (PROM), and figure-of-eight, while also completing a set of questionnaires, including the FAOS, a numeric pain rating scale (NPRS), and Short Form-36 (SF-36). To evaluate the test-retest reliability, 56 participants (four randomly selected from each province) were re-administered the FAOS 3 days after the initial assessment. To evaluate the responsiveness, 60 patients in Bali Province who received PT treatment for CLAI two times per week for 1 month were also re-administered the FAOS after completing the intervention. All assessors, procedures of data collection, the interview process and interviewers’ attitudes, instrument administration, and physical assessments were standardized and equalized through participation in a 4-h online training course.The AROM and PROM measure how far the joint can be moved by the patient and the physical therapist, respectively . MeasureThe figure-of-eight assesses ankle swelling using retractable plastic tape that is marked in 1-cm increments. The tape was bandaged around the ankle in a figure-of-eight pattern applied at the insertion of the tibialis anterior tendon, the base of the 5th metatarsal, the navicular tuberosity, and the medial and lateral malleoli as anatomical landmarks . If the The NPRS measures pain severity, in which an individual rates his/her latest sensation of pain on an 11-point numeric scale. Numbers from 0 to 10 on the scale represent “no pain” to “the worst pain”. Each participant was asked to rate his/her ankle pain from three aspects, including current pain, worst pain, and least pain, in the past 24 h; the average of the three was used to represent ankle pain .The SF-36 is the most commonly used generic HRQOL instrument , 22, whiA high ceiling or floor effect on each subscale of the FAOS can make the FAOS difficult to distinguish patients from one another. The presence of a high ceiling or floor effect was considered when > 15 % of participants endorsed the highest or lowest possible score .The internal consistency of each subscale of the FAOS was determined using Cronbach’s alpha, which represents the extent to which the items of the subscale measure a similar construct. Cronbach’s alpha coefficients of ≥ 0.7 were considered acceptable. The interrater test-retest reliability for each of the subscales was determined using the interclass correlation coefficient (ICC) by evaluating whether the subscale was able to assess participants’ conditions consistently over a 3-day interval. ICCs of > 0.7 were considered satisfactory .Convergent validity was determined by computing Spearman’s correlation coefficients of the five FAOS subscales with the AROM, PROM, figure-of-eight, NPRS, and eight SF-36 subscales. Correlation coefficients of < 0.3, 0.3 ~ 0.6, and > 0.6 were respectively considered to indicate low, moderate, and high relationships . Based oThe Kaiser-Meyer-Olkin Measure of Sampling Adequacy and Bartlett’s Test of Sphericity were used to assess the suitability of the data for a factor analysis. A principal component analysis (PCA) as the extraction method and the Promax with Kaiser Normalization as the rotation method were conducted to examine the five-component structure of the FAOS. The number of factors was forced to be five in order to validate whether the Indonesian version of the FAOS showed the same five-component structure as the original FAOS. Those items with a factor loading of ≥ 0.35 were considered satisfactory .). The response to this item was used as an external reference to estimate the anchored-based responsiveness. According to Guyatt’s method [One month after the baseline assessment, 60 patients in Bali Province who received PT were followed-up, and the FAOS and the “change” item of the SF-36 (an attempt to measure the change in the HRQOL over 1 year) were re-administered at that time. We applied both distribution-based and anchored-based approaches to evaluate the responsiveness of the FAOS. Cohen’s effect sizes were calculated by dividing the mean change of each FAOS subscale with the estimated standard deviation (SD) before and after the intervention . The tims method , the ancs method . An effes method . All staAs shown in Table “grinding” to “friction” in an item of pre-final FAOS , because “grinding” is not a common word used in the medical community but a term in the food industry in Indonesia. In the pilot test, those 40 patients with a CLAI expressed that they comprehended the 42 questions in the pre-final FAOS with no difficulty.During the translation process, the expert committee changed the word As shown in Fig. As to internal consistencies of the five subscales of the FAOS, Cronbach’s alpha coefficients ranged 0.74 ~ 0.96 Table . For ther values ranging 0.32 ~ 0.53. Unexpectedly, there was a low correlation between the FAOS’s pain and the NPRS (rs = -0.06).As shown in Table The Kaiser-Meyer-Olkin Measure of Sampling Adequacy was 0.942 and Bartlett’s Test of Sphericity was < 0.001, indicating that the PCA was suitable for our data . Results of the PCA are shown in Table All items originally assigned to the three subscales of the ADLs, SRF, and FAQL displayed factor loadings of > 0.35. On the other hand, two items originally assigned to OSs (OS6 and OS7) and four items assigned to pain  displayed loading factors of < 0.35.Effect sizes on the responsiveness over the 1-month period for each subscale of the FAOS are shown in Table An appropriate measure such as the FAOS is essential for monitoring patient outcomes and the efficacy of treatment in CLAI patients. Results of this study demonstrated that all five subscales of the Indonesian version of the FAOS displayed nearly symmetrical score distributions, low floor and ceiling values, acceptable internal consistency and test-retest reliability, satisfactory responsiveness, and fair construct validity, although certain items in the pain and OSs subscales showed lower factor loadings.Among the five subscales of the FAOS, the ADLs and FAQL had the highest proportions of ceiling values, indicating that a substantial proportion of participants might not have experienced any restriction in their daily activities, and they may also have a satisfactory social life. Previous studies showed that young adults with CLAI maintained sufficient performance of their daily activities and an adequate quality of life , whereasr=-0.74) between FAOS’s pain and the NPRS [A low correlation unexpectedly existed between the pain subscale of the FAOS and the NPRS. A study even found a negative correlation  had a low loading on the latent pain subscale (Factor 4) but had a higher loading on the latent FAQL (Factor 5). This low loading might have been due to P1 evaluating the pain frequency, while the other items of the subscale evaluate the pain intensity for a specific ankle function. Another possible explanation for this finding is that participants may have misperceived P1, which asks about the extent to which the foot and ankle problem affects their daily life, like FAQL1, since other items of the pain subscale ask about the pain intensity in specific ADLs . Items PItems OS6 (morning stiffness) and OS7 (resting stiffness) were not moderately or highly correlated with OSs but were with ADLs. We noted that both OS6 and OS7 assess the severity of an ankle’s symptoms during a specific time, while the other items of the OSs assess the severity in a particular function. In addition, it seems that the type of rating scale anchors of OS6 and OS7 were the same as those of the FADL’s items (intensity type) but different from the other items of OSs (frequency type). Nonetheless, associations of morning stiffness with functional disability and pain were found to be stronger than the association of swelling and the erythrocyte sedimentation rate in patients with early rheumatoid arthritis given that morning stiffness is a symptom used as a measurement of rheumatoid arthritis . As suchBoth the distribution-based and anchor-based responsiveness statistics indicated that the FAOS is a responsive HRQOL measure for CLAI patients. Among the five FAOS subscales, pain was the most responsive, possibly because pain is the most common problem of CLAI patients and often is the main reason for a clinical visit , 2. MoreThere are some limitations to the study. First, the results possibly cannot be generalized to older populations with CLAI since the ages of our participants ranged 17 ~ 35 years, and they still maintained moderate to high levels of physical activity in their daily lives. It would be intriguing to further investigate whether the FAOS has age-related differential item functioning for CLAI patients. Second, examination of the construct validity was dependent on the selected measures, and some of those measures, such as the NPRS, might not be very appropriate, although the NPRS is one of the most commonly used tools to measure pain. It seems that the NPRS could not capture the complexity and idiosyncratic nature of the pain experiences of CLAI patients. Third, we did not measure intra-articular lesions of the ankle or physical functions of the hip and knee. Intra-articular lesions  were suggested to be the cause of persistent symptoms of CLAI and were associated with clinical outcomes , while hThe Indonesian version of the FAOS has reasonable score distributions, acceptable reliabilities and responsiveness, and fair construct validity among young CLAI patients, although certain items in the pain and OSs subscales may need to be further explored and improved.


The level of psychological pain in patients with COVID-19 was investigated in this study by hypothesis testing, one-way ANOVA, multi factor ANOVA, and correlation analysis. The psychological pain thermometer and post-traumatic growth assessment scale were used as research tools. Many factors appear to influence the psychological state of COVID-19 patients including practical problems, communication problems, emotional problems, physical problems, and psychiatric/relative concerns. The severity of the disease, the surrounding environment, family health problems, life perceptions, interpersonal relationships, personal strength, mental changes, new possibilities, and the total post-traumatic growth score are also affected. There is a significant negative correlation between psychological pain and post-traumatic growth. There are significant differences in the degree of psychological pain across the demographic data. Practical problems, communication problems, emotional problems, physical problems, and spiritual/religious concerns show significant effects on the degree of psychological pain. On January 31, 2020, the World Health Organization (WHO) designated COVID-19 as a global public health emergency  ” , there were 112 people earning 2000-3000 CNY (309.6-464.4 USD) accounting for 22.6% of the total, 203 earning 3,000–5,000 CNY (464.4-774 USD) accounting for 40.9%, 129 earning 5,000–7,000 CNY (774-1083.6 USD) accounting for 26.0%, and 52 earning over 7,000 CNY  accounting for 10.5%. Two-hundred and ninety-six were married (59.7%) 163 were unmarried (32.9%), and 37 were widows or widowers, accounting for 7.5% of the total.Basic demographic information for the participants was obtained via questionnaire, mainly including age, gender, marital status, number of children, education level, and income. Psychological pain is an unpleasant emotional experience which interferes with patients' responses to cancer, somatic symptoms, and anti-cancer treatment  was used to evaluate PTG over five dimensions: life perception, interpersonal relationships, personal strength, mentality changes, and perception of new possibilities .As mentioned above, the staff explained the questionnaire requirements and confidentiality principles to the participants on site to encourage them to give serious, anonymous, and authentic responses. The questionnaire data was sorted and entered into an Excel worksheet for further analysis by two staff members to cross-check its correctness.Table 4 uses demographic data such as Gender, Age, Education, Occupation, Monthly income (CNY/USD), Marriage, Isolation time (days), Disease severity, Information, General health condition before COVID-19, Past medical history and Past psychiatric history Academic information as relevant factors. Through the process of hypothesis testing, we can judge whether many factors have a significant impact on the dependent variable. In the multivariate analysis of variance, there are many factors that affect the dependent variables, some of which may affect the dependent variables in addition to their own. Using multi-factor analysis of variance and psychological pain to make a comparison, so as to prove whether there are significant differences between them. In Table 5, severity of COVID-19 was used as the independent variable. The related factors like practical problems, communication problems, emotional problems, physical problems, and spiritual/religious concerns were analyzed by chi square. This can count the deviation degree between the actual observation value and the theoretical inference value, and the deviation degree between the actual observation value and the theoretical inference value determines the chi square value. This analysis can derive the correlation between these factors and the severity of COVID-19. If p < 0.05, the difference was considered statistically significant.Two staff members input and analyzed the data by first transforming it into SPSS files using EpiData 3.1 software before processing it in Statistical Product and Service Solutions (SPSS) 19.0. Statistical analysis was performed using SPSS as well . The three age groups with the highest scores were 46–55, 36–45, and 56–65 years. Pearson correlation analysis showed a significant positive correlation between age and psychological pain with a coefficient of 0.326.There is also a significant difference in psychological pain scores among the three age groups (at p < 0.01) in terms of income. Pearson correlation analysis results show a significant negative correlation between income and psychological pain at a coefficient of −0.433.There was a significant difference in the psychological pain score between two groups (p < 0.01). The psychological pain score of patients who isolated for more than 50 days was significantly higher than that of other groups. Pearson correlation analysis showed a significant positive correlation between the duration of isolation and psychological pain with a coefficient of 0.60.There was a significant difference in terms of isolation time as well (p < 0.001). The psychological pain score of patients in the dangerous case group was significantly higher than that of other groups. Pearson correlation analysis showed a significant positive correlation between disease severity and psychological pain with a correlation coefficient of 0.552.There was a significant difference in psychological pain scores in terms of disease severity as well (p < 0.01). Pearson correlation analysis showed that the degree of education was negatively correlated with the intensity of psychological pain at a coefficient of −0.29.The patients' educational background and knowledge of COVID-19 also produced significant differences in psychological pain scores (p < 0.01). COVID-19 was negatively correlated with the general health condition prior to diagnosis at a coefficient of 0.570.The patients' general health condition before COVID-19 also produced significant differences in their psychological pain levels , housing (9.4%), insurance/financial situations (36.7%), transportation (2.1%), work/school (61.5%), and the surrounding environment (51.0%).Emotional problems include depression (58.2%), fear (55.2%), loneliness (48.5%), nervousness (51.8%), sadness (12.7%), worry (52.8%), loss of interest in daily activities (46.2%), sleep issues (60.9%), and memory loss/inattention (18.3%).Physical problems include appearance/bodily form (5.0%), bathing/dressing (7.6%), breathing (57.2%), micturition changes (2.6%), physical constraints (7.8%), diarrhea (1.4%), eating issues (6.3%), tiredness (28.6%), edema (1.0%), fever (72.8%), dizzy (8.2%), indigestion (9.1%), pain existing previously to disease onset (5.4%), nausea (2.0%), dry mucous membranes (5.4%) or congestion (60.1%), pain related to the disease (19.2%), sexual dysfunction (2.0%), dry or itchy skin dry (0.8%), numbness of hands/feet (3.4%), and limited physical activity(3.0%). Spiritual/religious concerns also have noteworthy effects (2.4%).A Chi square test was used to probe whether the patients had significant psychological pain related to these items. The results are shown in Actual problems affecting the subjects included child and old adults care (18.6%), housing (9.4%), insurance/financial (36.7%), transportation (2.1%), work/school (61.5%), and the surrounding environment (51.0%).Communication with children/old adults (10.4%), partners (19.8%), friends (15.3%), and medical staff (1.4%) may also affect the psychology of COVID-19 patients.Depression (58.2%), fear (55.2%), loneliness (48.5%), nervousness (51.8%), sadness (12.7%), worry (52.8%), loss of interest in daily activities (46.2%), sleep issues (60.9%), and memory loss/inattention (18.3%) also affect the psychological pain of COVID-19 patients.Issues related to the patients' appearance/bodily form (5.0%), bathing/dressing (7.6%), breathing (57.2%), micturition changes (2.6%), physical constraints (7.8%), diarrhea (1.4%), eating issues (6.3%), tiredness (28.6%), edema (1.0%), fever (72.8%), dizzy (8.2%), independence (9.1%), oral pain (5.4%), nausea (2.0%), dry mucous membranes (5.4%) or congestion (60.1%), pain (19.2%), sexual dysfunction (2.0%), dry/itchy skin (0.8%), numbness of hands/feet (3.4%), and limited physical activity (3.0%) also affect their psychological pain levels.Spiritual/religious concerns (2.4%) also affected psychological pain in the patients sampled in this study.Through the data analysis in Through the data analysis in Through the data analysis in Through the data analysis in COVID-19 has an incubation period of 1–14 days. There is a lack of etiological evidence regarding the disease due to its novelty; treatments have been developed based on other similar diseases. Suspected or confirmed cases are subjected to long-term observation, which can have a substantial psychological impact on patients . At the significance level of p < 0.05, the correlation between the two groups was negative.The COVID-19 patients' PTG score was (53.58 ± 8.45), which suggests that the PTG level of COVID-19 patients is relatively low. Pearson's correlation analysis showed that the total PTG score, life perception, interpersonal relationships, personal strength, mental changes, and new possibility factors were negatively correlated with the psychological pain of patients with COVID-19 .Based on COVID-19 patients' baseline data, disease information, and psychological pain factors, chi square were conducted to determine the effects of illness severity, surrounding environment, family problems, life perception, interpersonal relationships, personal strength, mental changes, new possibilities, and post-traumatic outcomes. The disease itself was the main factor influencing the psychological pain of COVID-19 patients (p < 0.05). COVID-19 has clinical manifestations of varying severity which are treated differently; patients experiencing severe symptoms may be placed on ventilators to prevent hypoxia, which is psychologically distressing . Once any member of a family becomes a COVID-19 patient, their role in the family unit changes dramatically. The necessity to self-isolate during treatment can be extremely discomforting. COVID-19 patients are confronted with mortality daily as they navigate the course of the disease, which comes at a significant psychological cost and can create intense sadness.COVID-19 indeed creates psychological pain in patients . The results reveal a negative correlation between COVID-19 patients' psychological pain and PTG. COVID-19 patients must be isolated during treatment and receive medication, surgery, breathing machines, and any other necessary interventions while unable to be in physical proximity to loved ones, which seriously affects their quality of life and elevates their psychological pain. COVID-19 patients' mental health levels should be checked even after they are discharged from the hospital to guide them as they experience any PTG and as they readjust to their normal lives.COVID-19 patients reported psychological pain related to several independent risk factors in this study (The sample size of this study is relatively small due to the conditions of the disease and its spread across China. The foreign scale was also not localized. Although the work was revised based on China's national conditions, there are still limitations.This study suggests that there was a significant negative correlation between the total score of PTG and psychological pain. There was a significant negative correlation between psychological pain and posttraumatic growth. There are significant differences in the degree of psychological pain among different gender, age, education level, income, occupation and marriage. Practical problems, communication problems, emotional problems, physical problems, and spiritual/religious concerns have significant effects on the degree of psychological pain.Suspected and confirmed cases of COVID-19 continue to affect the lives of countless people around the world. The virus has caused severe psychological trauma to those patients who eventually overcome the disease after long-term isolation treatment. Even a moderate degree of psychological pain can seriously affect the physical and mental health of patients. By fully understanding the influencing factors of patients' psychological pain, health staff can analyze the psychological status of patients to help design the necessary aftercare.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was provided by the participants.NZ contributed to theory construction, writing the paper, and revising the paper. SY assisted in revising the paper. All authors contributed to the article and approved the submitted version.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.


General practitioners (GPs) and out-of-hours (OOH) doctors are gatekeepers to acute hospital admissions in many healthcare systems. The aim of the present study was to investigate the whole range of reasons for acute referrals to somatic hospitals from GPs and OOH doctors and referral rates for the most common reasons. We wanted to explore the relationship between some common referral diagnoses and the discharge diagnosis, and associations with patient’s gender, age, and GP or OOH doctor referral.A registry-based study was performed by linking national data from primary care in the physicians’ claims database with hospital services data in the Norwegian Patient Registry (NPR). The referring GP or OOH doctor was defined as the physician who had sent a claim for the patient within 24 h prior to an acute hospital stay. The reason for referral was defined as the ICPC-2 diagnosis used in the claim; the discharge diagnoses (ICD-10) came from NPR.Of all 265,518 acute hospital referrals from GPs or OOH doctors in 2017, GPs accounted for 43% and OOH doctors 57%. The overall referral rate per contact was 0.01 from GPs and 0.11 from OOH doctors, with large variations by referral diagnosis. Abdominal pain (D01) (8%) and chest pain (A11) (5%) were the most frequent referral diagnoses. For abdominal pain and chest pain referrals the most frequent discharge diagnosis was the corresponding ICD-10 symptom diagnosis, whereas for pneumonia-, appendicitis-, acute myocardial infarction- and stroke referrals the corresponding disease diagnosis was most frequent. Women referred with chest pain were less likely to be discharged with ischemic heart disease than men.The reasons for acute referral to somatic hospitals from GPs and OOH doctors comprise a wide range of reasons, and the referral rates vary according to the severity of the condition and the different nature between GP and OOH services. Referral rates for OOH contacts were much higher than for GP contacts. Patient age, gender and referring service influence the relationship between referral and discharge diagnosis. For patients with acute conditions visiting a general practitioner (GP) or an out-of-hours (OOH) doctor, referral to acute admission to hospital is sometimes required in order to obtain adequate investigation and treatment. These acute admissions to hospitals constitute a large part of hospital activity and in the years 2015–2019, more than two thirds of all admissions in Norway were acute . Health A gatekeeping system, where the patients are obliged to see a GP or an OOH doctor before referral, may regulate the access to acute hospital care, and is implemented in many healthcare systems. Gatekeeping may reduce unplanned hospital admissions in general, and especially for the elderly , 8. In tDischarge diagnoses after acute admissions in Norway have been well described, and similar diagnoses for patients admitted to hospital after emergency ambulance transport in Denmark are published –11. HoweAbdominal pain and chest pain are known as two dominant clinical symptom groups in OOH services and acute referrals to hospital from primary care , 13. LikThe aim of the present study was therefore to investigate the whole range of reasons for acute referral to somatic hospital stay from GPs and OOH doctors in Norway, including referral rates for the most frequent ICPC-2 diagnoses. For three common clinical problems, abdominal pain, chest pain, and shortness of breath, and for the frequent or important referral diagnoses of pneumonia (R81), appendicitis (D88), AMI (K75), and stroke (K90), we also wanted to investigate the associations between the diagnosis given in referral contacts and the discharge diagnosis from hospital, and how these associations varied between GPs and OOH doctors and with patient’s gender and age.Norway has a well-established public primary healthcare system including a Regular General Practitioners scheme (RGPs) and OOH services , 10. RGPThe study is registry-based, using data from national health registries covering the whole population in Norway in 2017.All GP and OOH contacts result in a claim to the Control and Payment of Reimbursement to Health Service Providers database (KUHR), managed by The Norwegian Health Economics Administration (HELFO). A single claim contains the patient’s national identification number, time and date for the contact, and if the contact is a simple contact (e.g. telephone contact), an office consultation, or a home visit. Also, it is mandatory to include one or more diagnostic codes according to International Classification of Primary Care (ICPC-2) . This diPsychiatric hospitals were not included. We therefore use the term somatic hospital admissions in our study. All hospital stays are recorded in the Norwegian Patient Registry (NPR), which includes information on patient’s national identification number, time and date of the admission, degree of urgency, and one or more discharge diagnoses using the International Statistical Classification of Diseases and Related Health Problems version 10 (ICD-10). For the hospital discharge diagnoses we used the main diagnosis with three characters. An acute hospital admission was defined by the NPR’s data form as an admission required immediately or within 24 h and lasting for more than 24 h. These admissions were then included if they were related to a GP or OOH contact.N = 14,457,247) or OOH doctors  during 2017 were included. For GPs this represent both acute and follow up contacts.In this study we defined a GP or OOH doctor contact as a consultation or a home visit, telephone contacts were excluded. All such contacts with GPs (Statistics Norway (SSB) created a pseudo-anonymized identification number which replaced the national identification number in the KUHR and NPR databases. Thereby data from both sources could be combined without revealing the patients’ identities.A GP or OOH-doctor contact in KUHR was defined as the referral contact for a patient if it occurred within 24 h before an acute admission in NPR. By this definition we identified 265,518 referrals to hospital from a GP or an OOH doctor.A suitable grouping of ICPC-2 codes into presenting complaints in emergency departments (EDs) has been described by Malmström et al. . We applWe used the referral disease diagnoses pneumonia (R81), appendicitis (D88), acute myocardial infarction (K75), and stroke (K90) to study associations between a specific disease diagnosis given at referral and the discharge diagnoses after hospital stay.Numbers and frequencies for ICPC-2 chapters and the 30 most common ICPC-2 diagnoses that led to a referral were obtained. Referral rates were calculated by dividing GP and OOH contacts leading to a referral by all contacts with the same diagnosis.For referrals in the abdominal pain symptom group, we identified the ten most frequent discharge diagnoses. Generalized linear model (GLM) log-binomial regression were used to estimate relative risk (RR) of the patient being discharged with each of these diagnoses compared with all other discharge diagnoses after a referral with abdominal pain symptom. The patients’ ages, genders and if the patient had been referred by a GP or OOH doctor were used as explanatory variables and were adjusted for each other. RR was calculated for females with males as reference, age was divided by 10 and then used as a continuous variable giving RR with a 10-years increase, and OOH doctor referrals were compared with GP referrals as reference. The RRs were presented with 95% confidence intervals (CI). For referrals in both the chest pain symptom group and shortness of breath symptom group the ten most frequent discharge diagnoses were identified, and equivalent GLM were used for each of the ten discharge diagnoses.For the four disease-specific referral diagnoses pneumonia (R81), appendicitis (D88), AMI (K75) and stroke (K90) we conducted frequency analyses for discharge ICD-10 diagnoses representing > 3% of the patients referred with these diagnoses, respectively. GLM were used to estimate the RR for the discharge diagnoses. For the referral diagnosis pneumonia (R81) the corresponding discharge ICD-10 diagnosis pneumonia was used as comparison. For appendicitis (D88), AMI (K75) and stroke (K90) we used respectively acute appendicitis (K35), AMI (I21) and cerebral infarction (I63) as comparison in the analyses. Explanatory variables were gender, age, and referral from an OOH doctor or a GP. For three of the models the log-binomial regression did not converge, and a Poisson regression with robust variance estimates was applied to estimate RR .The analyses were performed using Stata 16.1. In 2017 GP and OOH-doctor contacts (consultations and home visits) resulted in 265,518 referrals to acute somatic hospital admission, 150,577 after OOH contacts and 114,941 after GP contacts , digestive (D) and cardiovascular (K) were the most frequent chapters used Table . OOH refThe 30 most common referral diagnoses accounted for 53% of the referrals, with abdominal pain/cramps general (D01) (8%), chest pain (A11) (5%) and pneumonia (R81) (3%) being the most frequent Table . Of all Referrals with an ICPC-2 diagnosis in the symptom groups abdominal pain , chest pain  or shortness of breath (8371 patients) accounted for 21% of all referrals  if the patient was referred from an OOH doctor compared with a referral from a GP (RR = 2.12 [95%CI: 1.84–2.45]). The opposite was found for diverticular disease (K57) with a lower relative risk of being discharged with diverticular disease if referred from OOH compared to GP (RR = 0.51 [95%CI: 0.46–0.56]). The relative risk for the discharge diagnosis of abdominal and pelvic pain (R10) was higher for women compared to men (RR = 1.38 [95%CI: 1.32–1.44]), but lower for acute appendicitis (K35) (RR = 0.59 [95%CI: 0.55–0.62]), acute pancreatitis (K85) (RR = 0.54 [95%CI: 0.47–0.61]) and calculus of kidney and ureter (N20) (RR = 0.40 [95%CI: 0.34–0.47]).The median patient age in the chest pain symptom group was 62 years, and 44% were women  was associated with higher age (RR = 2.13 [95%CI: 1.93–2.36]). Women referred with chest pain had a lower relative risk of being discharged with a diagnosis related to ischemic heart disease: AMI (I21) (RR = 0.54 [95% CI 0.50–0.59]), angina pectoris (I20) (RR = 0.70 [95%CI: 0.64–0.77]) and chronic ischemic heart disease (I25) (RR = 0.47 [95%CI 0.40–0.55]) compared with men.In the shortness of breath symptom group the median age was 70 years, and 50% were women , appendicitis (D88), AMI (K75), and stroke (K90) accounted for 16,811 admissions . 59% of the patients referred with the diagnose pneumonia (R81) were discharged with a corresponding ICD-10 pneumonia-diagnosis (J12–18) (Table Of patients referred with appendicitis (D88) 51% were discharged with the corresponding ICD-10 diagnosis acute appendicitis (K35), and 24% with the symptom describing diagnosis abdominal and pelvic pain (R10) Table .Table 7DFor patients referred with the diagnosis AMI (K75), 43% were discharged with the corresponding ICD-10 diagnosis AMI (I21), 12% with pain in throat and chest (R07), and 7% with angina pectoris (I29) Table . The disAfter referral with the diagnosis stroke K90), 30% of the patients were discharged with the ICD-10 diagnosis cerebral infarction (I63), 10% with transient cerebral ischemic attack (TIA) (G45) and 4% with intracerebral haemorrhage (I61), whereas 56% had other diagnoses  or the disease diagnose appendicitis (D88). Probably, in some cases a more precise or severe diagnosis than the right one according to diagnosis criteria may be used to prepare the hospital receiving the patient. Distinction between symptom and disease diagnosis in referrals must be interpreted with caution. In a prehospital setting in helicopter medical services in Finland, ICPC-2 coding was tested for inter-rater reliability for six written fictional cases [Diagnosis coding may vary between doctors, both in general practice and in OOH services. In a clinical situation with abdominal pain when appendicitis is suspected, the physician may apply either a symptom diagnosis al cases . The resal cases . This suThe linkage between the GP and OOH doctor contacts in KUHR and hospital admission in NPR has some uncertainties. The primary care contact prior to admission might be random, and not related to the admission. In a previous study we found a distinct accumulation of GP and OOH contacts within 24 h before acute hospital admission , 10. ThiOur overall OOH referral rate (11%) is higher than the rate described in studies from England (7 and 10%) , 26, andDiagnoses from the ICPC-2 chapter general and unspecified conditions (A) was most frequent for referrals from OOH doctors, similar to findings from other studies , 27. TheAbdominal pain is a common symptom in general practice, and the second most frequent reason for contacting OOH services , 21, 28.We found that the referral rates for chest pain and heart pain from OOH doctors were 0.37 and 0.66, respectively. In a prospective study from Norwegian OOH services 50 out of 100 patients presenting at the casualty clinic with chest pain as the main symptom were referred to hospital . HoweverFor referrals with abdominal and chest pain symptoms, the most frequent ICD-10 discharge diagnoses were the corresponding symptom-based diagnoses abdominal and pelvic pain (R10) and pain in throat and chest (R07). Our previous study showed that these discharge diagnoses were the overall second and third most frequent discharge diagnoses after acute admissions to hospital, irrespective of referral agent , 10. SucOnly 1% of patients referred with chest pain were discharged with gastro-oesophageal reflux disease (K01). This could be due to effective gatekeeping treating these patients in primary care and is in line with previous research from Norway where 5 out of 100 patients attending OOH services with chest pain were diagnosed with dyspepsia by OOH doctor, and none were referred to hospital .Chest pain is a core presenting symptom for AMI for both women and men, although atypical symptom presentations in women have received increased attention , 29, 30.GPs accounted for a somewhat larger share of the disease-specific referral diagnoses pneumonia (R81), appendicitis (D88), AMI (K75), and stroke (K90) than the symptom groups abdominal pain, chest pain, and shortness of breath, suggesting that GPs are more likely than OOH doctors to use specific disease diagnoses. This could be due to better knowledge of the patient’s history or better diagnostic facilities.For referrals with diagnoses pneumonia, appendicitis and AMI the most frequent discharge diagnoses were the corresponding disease diagnosis. Correspondingly, referrals with the diagnosis stroke were often discharged with a diagnosis of cerebral infarction, TIA, or intracerebral haemorrhage. This indicates that when the referral diagnosis is a disease-specific diagnosis, the primary care doctor is more certain of a specific disease compared with cases where a symptom diagnosis is used. Hospital doctors could take this into consideration when receiving patients referred acutely from primary care with a disease-specific diagnosis.Patients from OOH services with the referral diagnosis AMI are less likely to be discharged with the diagnosis angina pectoris or chronic ischemic heart disease than patients from general practice. Angina pectoris and chronic ischemic heart disease typically have a less acute presentation, leading to contact with the GP rather than the OOH services, again illustrating that GPs treat cases with a lower degree of urgency.An adequate gatekeeper role for acute hospital admissions must balance the task to discover all patients with serious conditions with the risk of unnecessary admissions , 31. TheOur study reveals that one third of patients referred with chest pain and one quarter of patients referred with abdominal pain were discharged with a symptom diagnosis, hence no severe condition was revealed at hospital. Likewise, 24% of patients referred with appendicitis, and 12% referred with AMI were discharged with a symptom describing discharge diagnosis. We believe this to be a reasonable level of accuracy, but attention to this topic should be high and an objective for further research. The topic of referral practice should be emphasized in medical education, and policy makers should be aware of the issue over- and underdiagnosis.Referrals to hospital are always a matter of clinical medical assessment. In a gatekeeping system this also applies for emergencies. Both GPs and OOH doctors seem to perform gatekeeping for acute hospital admissions based on their setting and the different patient populations. Our findings suggest that there should be an accept of more symptom-based referrals from OOH services. The GP’s knowledge of the patient’s medical history is valuable also when performing gatekeeping for acute referrals to hospital. The large variation of referral diagnoses implies that a broad medical competence is necessary when assessing emergencies.Referral rates for OOH contacts were much higher than for GPs’ contacts, and showed considerable variation by different diagnoses, thus reflecting the severity of the conditions and the nature of the services. Abdominal pain and chest pain were two major reasons for referral, and the most frequent discharge diagnosis for both was the corresponding ICD-10 symptom describing diagnosis. Women referred with chest pain were less likely to be discharged with a diagnosis reflecting ischemic heart disease, whereas women referred with AMI were more often discharged with the diagnosis pain in throat and chest.


Self-management of ambulatory cancer pain is full of challenges. Motivated by the need for better pain management, we developed a WeChat-supported platform, Medication Housekeeper (MediHK), to enhance communication, optimize outcomes, and promote self-management in the home setting.We conducted a randomized controlled trial to assess whether the joint physician-pharmacist team through MediHK would provide better self-management of ambulatory patients with cancer pain.Patients were randomly assigned to either an intervention group or control group. During the 4-week study period, the pharmacist would send 24-hour pain diaries daily, adverse drug reaction (ADR) forms every 3 days, and the Brief Pain Inventory form every 15 days to patients in the intervention group via MediHK. If a patient needed a change in drug/dosage or treatment of an ADR after the comprehensive review, the pharmacist would propose pharmacological interventions to the attending physician, who was then responsible for prescribing or adjusting pain medications. If no adjustments were needed, the pharmacist provided appropriate targeted education based on knowledge deficits. Patients in the control group received conventional care and did not receive reminders to fill out the forms. However, if the control group patients filled out a form via MediHK, the pain management team would review and respond in the same way as for the intervention group. The primary outcomes included pain intensity and pain interference in daily life. Secondary outcomes included patient-reported outcome measures, medication adherence, ADRs, and rehospitalization rates.P=.001), 1 (IQR 0-2) vs 2 , and 2 (IQR 2-4) vs 4 , respectively, at the end of the study. The pain interference on patients' general activity, mood, relationships with others, and interests was reduced, but the difference was not statistically significant compared with the control group (Ps=.10-.76). The medication adherence rate increased from 43% to 63% in the intervention group, compared with an increase of 33% to 51% in the control group (P<.001). The overall number of ADRs increased at 4 weeks, and more ADRs were monitored in the intervention group (P=.003). Rehospitalization rates were similar between the 2 groups.A total of 100 patients were included, with 51 (51%) in the intervention group and 49 (49%) in the control group. The worst pain scores, least pain scores, and average pain scores in the intervention group and the control group were statistically different, with median values of 4 (IQR 3-7) vs 7 (IQR 6-8; The joint physician-pharmacist team operating through MediHK improved pain management. This study supports the feasibility of integrating the internet into the self-management of cancer pain.Chinese Clinical Trial Registry ChiCTR1900023075; https://www.chictr.org.cn/showproj.aspx?proj=36901 Pain is a common and challenging issue for cancer patients, affecting most at some stage of their disease . A meta-Both the World Health Organization and the European Society for Medical Oncology recommended that cancer pain patients should be active in their self-management of their pain. Patient-reported outcomes are increasingly used in routine ambulatory cancer care to guide clinical decisions, enhance communication, and improve symptom management . ElectroThis study established a physician-pharmacist collaboration team that participated in the self-management of ambulatory patients with cancer pain through a WeChat-supported platform: Medication Housekeeper (MediHK). We aimed to assess whether the joint physician-pharmacist team operating through MediHK would provide better self-management of ambulatory patients with cancer pain and optimize therapeutic outcomes.Patients were managed by MediHK, a WeChat-supported platform designed by the research team. An engineer from Hunan Normal University’s College of Information Science and Engineering provided technology support for building MediHK. MediHK has been patented by the National Intellectual Property Administration, People’s Republic of China (ZL 2015 1 0648320.2). MediHK contains 2 opening screens: (1) the patient interface  and (2) We conducted 3 rounds of consensus-building using Delphi methods  to deterWhen the patient’s expression was not clear, there was no guarantee that the same physician or pharmacist would communicate back. However, since the previously submitted forms and consultation questions were available through MediHK, the new physician or pharmacist would review the patient’s history in all aspects. Patient information was protected by encryption. Note that all screenshots of the app include translations that have been added for clarity for this paper.This study used the Brief Pain Inventory  to assess cancer pain, and it has been widely used for its good construct and concurrent validity . It provWe designed a list to record the medication history of ambulatory patients with cancer pain . The MorMany patients treated with opioids may experience adverse events. To comprehensively capture ADRs of patients outside of the hospital, we designed a form  with WorWe designed a pain diary to capture patients’ daily pain in the home setting over time. The pain diary included 5 modules : (1) a pThis was a 2-arm, randomized controlled clinical trial, and the study has been registered at Chictr.org ChiCTR1900023075; https://www.chictr.org.cn/showproj.aspx?proj=36901. Ambulatory patients with cancer pain in a tertiary hospital were included and assigned to either a control group  or an intervention group , with an allocation ratio of 1:1 using a random number table. Our pre-experiment included 72 patients who met the criteria for inclusion. The preliminary results showed that the average NRS of patients in the control group was 5.85 (SD 2.442). The average score of patients in the intervention group was expected to be <4. Assuming a type I error of 5%, a type II error of 20%, and considering the design of similar sample content, the sample size required for each group was calculated to be 37 patients. Allowing for 20% attrition, 100 patients (50 participants per group) were planned to be enrolled. The study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of Xiangya Hospital of Central South University . All participants signed an informed consent form before participation.The pharmacist would send daily 24-hour pain diaries, ADR forms every 3 days, and the BPI form every 15 days via MediHK. The pharmacist would first review patient demographic information, check the form regarding pain intensity and interference in daily life, conduct medication therapy reviews, and review ADRs and medication adherence. If the patient needed a change in drug/dosage or treatment of an ADR after the comprehensive review, the pharmacist would propose pharmacological interventions to the attending physician. The physician was responsible for prescribing or adjusting pain medications. If no changes were needed, the pharmacist provided appropriate targeted education based on patient knowledge deficits.Patients in the control group received conventional care. Before the patient was discharged from the hospital, the pharmacist conducted detailed medication education. However, the control group patients did not receive a reminder to fill out the forms. If they filled out the form via MediHK, the pain management team would also review and respond the same way as for the intervention group.The inclusion criteria of participants included: (1) age ≥18 years; (2) diagnosis of malignant tumors by a pathological or cytological method; (3) pain that met the cancer pain diagnostic criteria according to National Comprehensive Cancer Network Guidelines and was moderate to severe (NRS ≥4); (4) ability of patients or their families to read Chinese and use WeChat; (5) a normal verbal ability and performance status; and (6) agreement to participate in the study and sign the informed consent form.Exclusion criteria of participants were: (1) nonmalignant pain; (2) hepatic dysfunction  or renal dysfunction (serum creatinine ≥2.5×ULN); (3) participation in other clinical trials; and (4) hospitalization during the 4-week trial period.At the patients’ first visit to the ambulatory clinic, the physician provided a detailed consultation and, then, determined a treatment plan after discussion with the pharmacist; an account was created for eligible patients. After registration, the pharmacist demonstrated the use of each MediHK module to patients, including what information was collected in each form and how to fill it out and how to switch the interface to send a form or question. Even though the operation of MediHK was simple enough, the training process was approximately 10 minutes. The specific time depended on patient understanding, ability, and proficiency in WeChat. After training, patients were assigned to a pain management team and were required to complete PROMs and forms. Patients at home could contact their pain management team at any time through MediHK if they had any trouble with pain. The pain management team was required to complete standardized clinical pain management training and had at least 10 years of hospital work experience for clinical pharmaceuticals for cancer pain before performing pain-management work.Patients were observed for 4 weeks. At week 4, the patients were required to complete and submit the PROMs through MediHK or report through phone calls within 1 day. Patients could continue to use MediHK after the completion of the study.The primary outcomes included pain intensity and pain interference in daily life. Secondary outcomes included PROMs, medication adherence, ADRs, and rehospitalization rates.t tests. If not normally distributed, the data were expressed as the median (IQR), and the comparison between groups underwent a Mann-Whitney U test. Counting data were expressed as a frequency and percentage. A chi-square (c2) test or Fisher exact test was used for comparison between groups. We screened for factors affecting the pain intensity of outpatients with cancer pain by multivariate linear regression analysis . We defined P<.05  as statistically significant.All data were analyzed using SPSS software , and all charts were made by the graphing software GraphPad (version 8.0.2 (263); GraphPad Prism). For measurement data, the normality test adopted the Kolmogorov-Smirnov method. If normally distributed, the data were expressed as mean (SD), and the comparison between the 2 groups used 2 independent sample Ps>.05; A total of 100 patients joined and completed this study, with 51 (51%) in the intervention group and 49 (49%) in the control group. Demographic information  and clinical information  of the 2 groups were not statistically different, nor was the intensity, pain interference, and adherence to pain medications at baseline Ps>.05; .P=.001), 1 (IQR 0-2) vs 2 , and 2 (IQR 2-4) vs 4 , respectively, favoring the intervention group. The difference in the present pain score of the 2 groups was not statistically significant (P=.23). However, the score of the intervention group was numerically lower than that of the control group  vs 7 , with an average of 4.64 forms per person per day vs 0.06 forms per person per day, respectively. The most common forms submitted by the control group were the BPI , pain diary , and medication list  to 63% (32/51), while that of the control group increased from 33% (16/49) to 51% . In addition, 3 cases of intestinal obstruction and 2 cases of delirium were observed in the intervention group. The overall incidence of ADRs was 36% (36/100) across the 2 groups at baseline and increased to 56% (56/100) at week 4. ADR incidence in the intervention group was significantly higher than in the control group .The 2 groups had a similar rehospitalization rates within the 4-week trial. There was no significant difference between the 2 groups within 4 weeks  and average pain  [Yang et al  develope; P<.01) . However; P<.01) . CompareP<.01). These findings support our vision of making full use of prescient and promising internet platforms to manage cancer pain. In another study with an internet application consisting of a pain diary and a pain education and consultation module, the present pain intensity and the worst pain intensity of patients in the intervention group were significantly reduced within 6 weeks [Furthermore, we received more positive results because of our 4-week observation time. One study evaluated the effectiveness of pain management of a mobile phone app. Results showed that the pain relief rate was significantly different between the trial and the control groups  . SimilarRegrettably, we did not record the impact of education status and age in keeping medical records. Patients who had never received education may take longer to keep records. However, since the included patients or their families were all able to use WeChat proficiently, we believed that MediHK was feasible; for patients who were too old or unable to record, family members or caregivers would help to send the form. In total, we accounted for the universal applicability of MediHK when we developed it to ensure easy operation. The only complicated step was the switch between the interface. However, this was emphasized when training in the outpatient clinic.Knowledge deficits, inadequate pain assessment, misconceptions of pain, complex environments, and infrequent communication with health care providers are barriers in pain management. A joint physician-pharmacist team operating through a digital health platform can improve it. The cancer patient pain assessment was complicated. It is necessary to select quantification tools and assess the cause, location, quality, and relieving or aggravating factors of the pain comprehensively. The time that physicians spend on each patient is limited, and it is difficult to provide long-term and continuous monitoring. The digital platform can better solve these problems. The platform trains patients to record their pain conditions in a more standardized and targeted manner. During clinical encounters, clinicians can spend more time addressing patients’ concerns in a meaningful way, rather than running through checklists of questions . In addiIt is essential to consider the clinical workflow, security and liability, and the time-cost. We conducted a preliminary investigation and consideration in the early stage and carried out several rounds of related process optimizations and software improvements. In addition, when patients first visited the clinic, we would state that their physicians and pharmacists would provide the home services via the platform, and patients trusted this service. Finally, patients signed an exemption agreement and informed consent to ensure medical safety before using the platform. The satisfaction of patients and medical workers on such digital health platforms matters. One study designed a module in a mobile app to survey overall satisfaction, and the questionnaire was completed by participants at the end of the study . AnotherThere were some strengths of this study. First, this study was a real-world randomized controlled trial conducted in a large ambulatory clinic of a tertiary hospital. All patients were clinically recruited and randomly assigned. The integration of PROMs has not been a feature of other eHealth and (web) application–related studies, allowing this digital health study to help advance this field. In addition, real‐time reporting can facilitate just‐in‐time interventions based on an individual's current circumstance or environment. This study achieved real-time communication between ambulatory patients with cancer pain and health care providers through MediHK, extending medical services to ambulatory patients as a pathway for the self-management in home settings.The study had the several limitations. First, this study had abnormally high participation, which will not necessarily reflect what would happen when patients use the platform independently, because pharmacists would send daily notifications. Second, it was prospectively powered and conducted in a randomized manner, but inevitable confounding factors can exist in the real world. Multivariate linear regression can only explain a small part of the influence of different pain intensity types. Third, since the study was conducted in a single tertiary hospital, applying this approach in other clinical settings may require some individualization to meet specific needs. Fourth, the observation time of only 4 weeks limited the long-term application of the results. Fifth, this study lacked further assessment about buy-in from both patients and the pain management team.The joint physician-pharmacist team operating through MediHK enhanced communication, optimized outcomes, and promoted self-management of patients in home settings. This study supports the feasibility of integrating the internet into patient self-management of cancer pain. In the future, it will be necessary to enlarge the sample size to further explore the long-term effects of this method on the self-management of ambulatory patients with cancer pain.