Measuring pain on digital devices using classic unidimensional pain scales such as the visual analog scale (VAS), numerical rating scale (NRS), and faces pain scale (FPS) has been proven to be reliable and valid. Emoji are pictographs designed in colorful form following the Unicode standard. It could be more beneficial to use emoji as faces of FPS on digital devices because emoji can easily fit on most devices and emoji are open-source so no approval would be needed before use. With a concise and user-friendly design, the emoji faces pain scale (Emoji-FPS) might be more generalizable to a wider population and more preferred by digital device users.This study was designed to develop an Emoji-FPS as well as to evaluate its reliability, validity, and preference on mobile devices in adult patients who underwent surgery.A modified Delphi technique with 2 rounds of web-based surveys was applied to obtain panelists’ consensus on the sequence of emoji that can best represent 6 levels of pain. The initial candidate sequences of emoji for the Delphi process were constructed referring to 2 well-validated FPSs . Then, a prospective cohort of patients scheduled to receive perianal surgery was recruited and asked to complete a web-based questionnaire on a mobile device at 5 time points . The 4 well-validated pain scales  were used as reference scales.P<.001). For test-retest reliability, Emoji-FPS scores measured at T4 and T5 were highly correlated with a ρ of 0.91. The Emoji-FPS was mostly preferred, followed by the Wong-Baker FACES, FPS-R, NRS, and VAS.After 2 rounds of surveys on 40 Delphi panelists, an Emoji-FPS was finally determined to represent 6 pain levels  from “no hurt” to “hurts worst.” For validation, 300 patients were recruited and 299 were analyzed, the mean age of whom was 38.5 (SD 10.5) years, and 106 (35.5%) were women. For concurrent validity, the Emoji-FPS was highly correlated with 4 reference scales with Spearman correlation coefficient ρ ranging from 0.91 to 0.95. Excellent agreements were observed between 4 versions of Emoji-FPS , with weighted κ coefficients ranging from 0.96 to 0.97. For discriminant validity, patients’ mean preoperative Emoji-FPS score (T1) was significantly higher than their postoperative Emoji-FPS score (T4) with a difference of 1.4 (95% CI 1.3-1.6; The Emoji-FPS is reliable and valid compared with traditional pain scales in adult surgery patients. Pain is a complex and subjective experience that is usually measured by self-reported scales . CommonlWith the steady development of telemedicine and mobile health in the past two decades, the medical community as well as pain research are adapting themselves to the increasingly digital world ,7. In paAlthough means of collecting data have been greatly developed, fewer improvements were seen for the tools used for measuring pain. The upgrade from pencil-paper to finger-touchscreen interaction provides us with more possibilities including more accurate and timely data capture, and there is a need for an upgrade of the traditional pain scale so that a new pain scale can optimize the potential of smart devices without losing validity and reliability. Evidence revealed that electronically measured VAS, NRS, and FPS have the same performance as those measured by paper and pen . However, , and  [Digital device users are not unfamiliar with emoji faces such as , , and  ,16. UntiAn emoji faces pain scale (Emoji-FPS) should possess consistent reliability and validity compared with classical pain scales. Validation of its usefulness in adults without cognitive impairment first can provide evidence for its further use in other special populations. Patients who underwent perianal surgery are suitable for initial validation of the Emoji-FPS because those patients are usually characterized by mild to moderate preoperative pain and intense postoperative pain, which provides a good opportunity to test the scale’s discriminative validity . In addiThis study aimed to (1) develop a unidimensional pain scale Emoji-FPS from the emoji faces using a modified Delphi technique; (2) test reliability and validity of the Emoji-FPS in patients scheduled to receive perianal surgery; and (3) evaluate patients’ reference over the VAS, NRS, Wong-Baker FACES, FPS-R, and Emoji-FPS.A modified Delphi technique was used to obtain experts’ consensus on which emoji sequence can best represent different pain levels. Delphi is a method for structuring a group communication process so that the process is effective in allowing a group of individuals, as a whole, to deal with a complex problem ,19. The The expert panel consists of health workers with at least 1 year of working experience in the field of anesthesiology or pain medicine. Both clinicians and nurses were included. Panelists were mainly recruited from the anesthesiology department of Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine. The snowballing technique was applied when panelists’ colleagues from other institutions had interest in participating in this study. According to the rule of thumb, a sample size of 15-30 participants was generally recommended for a homogeneous survey  . To accoSince it usually takes months before the latest version of emoji is adapted to major platforms, Emoji version 13.1 (Unicode Consortium) was used in this study . As of ABoth Wong-Baker FACES and FPS-R are well-developed and validated scales over the years, so we aimed to find a sequence of emoji that also possess some properties  of these existing face scales so that this sequence of emoji could be more likely to be valid for measuring pain. After discussions of 3 experts , a total of 10 sequences were initially constructed for the first round of the survey.The surveys were conducted on the internet from July 2021 to September 2021. Each Delphi survey questionnaire consisted of mandatory instructions for panelists. The panelists were instructed to rate each candidate emoji sequence on a Likert scale from 1 (unsuitable) to 2 (slightly suitable) to 3 (moderately suitable) to 4 (suitable) to 5 (very suitable) based on their feelings about to what extent these emoji sequences can represent the pain levels from “no hurt” to “hurts most.” All panelists’ ratings were equally weighted. Since the appearance of emoji may be different on different devices and platforms, candidate sequences of Emoji-FPS were demonstrated using emoji images from iOS, Android, Microsoft, and OpenMoji versions separately in both rounds of Delphi surveys see . In bothThe link to the web-based survey was officially distributed to 40 potential participants. The panelists were allowed to select emoji beyond those used in the initial 10 sequences if they considered none of the emoji to represent certain levels of pain, and a total of 91 emoji faces are provided in In this round, invitations of surveys were sent to those who responded in round 1. The survey was in the same form as the previous round. However, fewer emoji sequences were provided, and the number of sequences was subject to the variation in ratings from the previous round. After this round, the final sequence of emoji was determined.Patients scheduled to receive perianal surgery were identified and recruited from the anorectal surgery department of Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine. Inclusion criteria were 18-65 years old and preoperative NRS ≤3. Those with a preoperative mini-mental state examination score <26 or with perianal abscess were excluded.To test consistency between types of Emoji-FPS, pairwise comparisons were made between groups. Assuming the Pearson correlation coefficient was 0.8 (0.6 under the null hypothesis), a sample size of 51 was required to achieve 0.8 power with a significance level of 0.05. Thus, a total of 255 individuals would be needed for the 5 groups. This sample size would also provide enough power for other tests in this study. Considering the dropping out of patients, a final sample size of 300 was determined.In addition to the Emoji-FPS, a total of 4 well-validated pain scales  were selected as references. The 4 versions of Emoji-FPS  were provided  at 5 time points: before surgery (T1), wake up after surgery (T2), 4 hours after surgery (T3), the second day after surgery (T4), and 15 minutes after T4 (T5). Participants’ demographics and surgery information were also collected. To attenuate the influence of the display sequence of the 5 pain scales on the rating result, a total of 5 groups  with different sequences of pain scales were designed using a Latin square matrix to ensure that an equal number of participants would rate the 5 scales with a different display sequence  at each time . Informed consent was obtained from Delphi panelists and patients in the validation step. All study data were deidentified and encrypted when transferred or preserved. Compensation was not provided for participants.t test was used to compare patients’ Emoji-FPS results before and after surgery. The weighted κ coefficient was applied to measure pairwise consistency between versions of the Emoji-FPS. The significance level was .05. SPSS 27.0 (IBM Corp) and SAS 9.4 (SAS Institute Inc) were used for data analysis.Descriptive analyses were performed. Spearman rank correlation coefficients (ρ) were calculated to measure the correlation between scales. A paired sample , , , , , and  was finally determined to represent 6 pain levels from “no hurt” to “hurts worst”  higher than the presurgery results, indicating a sound discriminant validity , followed by Wong-Baker FACES , FPS-R , NRS , and VAS . See , , , , , and ) was developed. Satisfactory validity and reliability of the Emoji-FPS were confirmed in patients who underwent perianal surgery.In this study, a 6-level Emoji-FPS ; , , , , and  to represent a 5-point scale (from strongly disagree to strongly agree), and , , , , , , and  to represent a 7-point scale (from strongly disagree to absolutely agree). However, as O’Reilly-Shah et al [) can be used to convey the feeling of “laughing so hard I’m crying,” and it is significantly different from its named intent. This is one of the reasons why we chose to use a modified Delphi technique to determine the Emoji-FPS. Our developed Emoji-FPS was reached upon collated opinions from a group of people to avoid the subjective choice of emoji. He et al [, , , , , and . A high level of agreement was observed between their Emoji-FPS and VAS after validation in 109 patients. Compared with their proposed Emoji-FPS, our proposed Emoji-FPS does not contain the smiling face  and includes a painful face . Since smiles can be reminiscent of happiness, starting with a more neutral face might be more advantageous [The potential use of emoji in medical research has been discussed previously, although its application is still limited ,7. EmojiHe et al  also devntageous . Before It is not surprising that the Emoji-FPS was preferred by patients, followed by the Wong-Baker FACES, FPS-R, NRS, and VAS. Colorful and intuitive images could be more attractive to users than monotonic and abstract images, especially on mobile devices. In addition, emoji have fewer details than Wong-Baker FACES and FPS-R. While these details can make faces of different pain levels more distinguishable, excessive details might make users think that these faces no longer look like them, for example, if patients have a different gender, age, or race. Emoji are more concisely designed and are not limited to these specific characteristics, so they have the potential to be applied regardless of age, gender, and race.Unlike typefaces and fonts of characters appearing exactly the same across platforms, emoji could have different appearances between devices and platforms, although the meanings they convey should be unified. As the Unicode Consortium states, “while the shape of the character can vary significantly, designers should maintain the same core’ shape, based on the shapes used mostly commonly in industry practice” . In thisThis study has limitations. Only health workers were invited to decide the Emoji-FPS from thousands of emoji, and opinions from patients were not considered. However, the relatively large panel size may accommodate this shortcoming. Our Emoji-FPS was only validated among adult surgery patients in a single center, and generalization of the Emoji-FPS to other populations, such as children, might be limited. Qualitative interviews with children or patients will be planned before further validation. Due to a limitation of the design of the web-based questionnaire, patients needed to select answers to the NRS from a dropdown list, so patients’ experience of using the NRS might be compromised. Their preference for NRS might change if a better interface is provided.Our developed Emoji-FPS has been proven to be reliable and valid compared with traditional pain scales on mobile devices among perioperative patients. Further studies are needed to confirm the reliability and validity of the Emoji-FPS in other settings.


Cancer pain is a challenging clinical problem that is encountered in the management of cancer pain. We aimed to investigate the clinical relevance of deep learning models that predict the onset of cancer pain exacerbation in hospitalized patients. We defined cancer pain exacerbation (CPE) as the pain with a numerical rating scale (NRS) score of ≥ 4. We investigated the performance of the deep learning models using the Matthews correlation coefficient (MCC) with different input lengths and time binning. All the pain records were obtained from the electronic medical records of the hematology-oncology wards in a Samsung Medical Center between July 2016 and February 2020. The model was externally validated using the holdout method with 20% of the datasets. The most common type of cancer was lung cancer , and the median CPE per day was 1.01. The NRS pain records showed circadian patterns that correlated with NRS pain patterns of the previous days. The correlation of the NRS scores showed a positive association with the closeness of the NRS pattern of the day with forecast date and size of time binning. The long short-term memory-based model exhibited a good performance by demonstrating 9 times the best performance and 8 times the second-best performance among 21 different settings. The best performance was achieved with 120 h input and 12 h bin lengths (MCC: 0.4927). Our study demonstrated the possibility of predicting CPE using deep learning models, thereby suggesting that preemptive cancer pain management using deep learning could potentially improve patients’ daily life. Prolonged survival, followed by advancement in diagnosis and treatment of cancer, results in an increase in the number of patients experiencing persistent pain4. This trend has also been documented in hematology patients at the time of diagnosis, during therapy, and in the last month of their life6. As per the estimates of GLOBOCAN 2020, the incidences of cancer is increasing and will be more than 19 million7. Thus, cancer-related pain would be a major issue in global healthcare systems.Cancer pain is common in patients, particularly during the advanced stages of the disease, when the prevalence is estimated to be more than 40%. This contributes to poor physical and emotional state of the patients11 Some guidelines suggest that the occurrence of three to four cancer pain exacerbation (CPE) episodes per day is acceptable12. However, a less frequent CPE could also affect patients’ daily quality of life. In addition, the interval between pain onset time and drug effect time could worsen the patients’ quality of life. In particular, hospitalized patients can only avail short-acting opioids upon informing the nurse. Thereafter, the nurse must inform the doctor for a decision. The patients would likely be left in severe pain during this processing time. From this point of view, accurate prediction of CPE could alleviate the frequency and interval of CPE and improve patients’ daily life well-being.Acute exacerbation of cancer pain is a challenging clinical problem in managing cancer pain, negatively impacting the patient’s daily life14. Cancer pain may reflect the status of cancer invasiveness, exposure to cancer treatment, pharmacodynamics of the opioids, patient’s lifestyle, and the health care system of the hospital, including the management of doctors and nurses1. Therefore, we hypothesized that the exacerbation of cancer pain is repeated according to the patient’s previous patterns and could thus, be predictable. In this study, we aimed to investigate the clinical relevance of deep learning models that predict the time of breakthrough pain onset in cancer patients.Recently, the time series model based on a deep learning algorithm has gained popularity based on its remarkable performance15. Of all the patients, we excluded 2,697 patients who underwent surgery during hospitalization and 28,173 patients with less than 20 non-zero numerical rating scale (NRS) score records. The selected 3,431 patients included pain log data for 4,870 admissions, split into the 80–20% training/test  set  at the Samsung Medical center . The Samsung Medical Center IRB waived the need for informed consent because of the retrospective nature of this study. All pain records pertaining to 34,304 patients were retrospectively collected who were admitted to the department of hematology and oncology of the Samsung Medical center in Korea between July 2016 and February 2020. Clinical data were obtained from the medical records using de-identified clinical data warehouse16. The patients could also ask the nurse for management at other times in the case of sudden pain, Herein, the nurse records the additional pain scores and notifies the doctors. As there was no quantitative consensus on the definition of CPE, we defined CPE as an NRS score of 4, a commonly used indication of opioid intervention in cancer pain management guideline[Nurse rounding occurs every day at 5:00 h, 13:00 h, and 21:00 h. During nurse rounding, nurses usually record the patient’s self-reported pain scores using NRS scales with an ordinal range from 0 (no pain) to 10 (severe and unbearable pain)Originally, the pain scores were recorded according to the time in minutes. However, considering the highly sparse signal of the data, we binned the entire NRS record in arbitrary CPE could be different among patients (inter-patient) and could also be different in the specific situation of each patient (intra-patient). Intra-patient pain pattern refers to a patient's unique pain pattern depending on the patient’s medical status. Inter-patient pain pattern refers to the pattern of medical practice, including rounding time and clinician’s management. All pain records were processed in 24-h increments to reflect these characteristics. Zero padding was used to set the start and end of all pain records to 0:00 h. Recordings at time points where there were no NRS observations in the episode, the patient was considered pain-free and were imputed to zero. Accordingly, pain records for 17, long short-term memory (LSTM)18, gated recurrent unit (GRU)19, bidirectional long short-term memory (Bi-LSTM)20, hybrid of the convolutional neural network, long short-term memory (CNN-LSTM)21, and transformer22. Each prediction model of CPE was implemented according to its respective basic recipe, and the models were constructed with a non-autoregressive prediction structure followed by a dense layer after stacking three basic blocks  and area under the precision-recall curve (AUPRC).The prediction of CPE could be regarded as a binary classification of independents (0 s and 1 s) over the next 24 h . The performance was improved in the experiments with more extended input data and larger binning size, which showed the best performance in the 120 h input length and 12 h bin lengths (MCC: 0.4927). Considering this model performance was significantly better than the base model performance . Therefore, we performed ablation studies with larger intervals binning up to 12 h, which was the least clinically available, and the sparsity of CPE was improved  (Supplementary Table Pérez-Hernández et al. investigated breakthrough pain characteristics and patterns using the Alberta breakthrough pain assessment toolOur study has certain limitations. The most prominent limitation is its single center-based design, which might limit the generalizability of our data. In addition, we used NRS records divided by hours and simply defined the breakthrough pain as the time interval with the records with an NRS above 4. By following this protocol, we have excluded many other characteristics of cancer pain, that might limit the interpretation. Additionally, our study investigated univariable models with simple structures as our goal was to explore the feasibility of pain patterns. Nevertheless, our models showed adequate performance even though there were few input data types. Subsequent validation studies, including detailed data and sophisticated model structure, would make the model perform better and more applicable.In conclusion, our study showed that cancer pain could be predictive using deep learning models. Though our exploratory study has limitations, further research could improve the model performance, and verification study could make our model applicable in real-world practice.Supplementary Information 1.Supplementary Information 2.


The diathermy plus exercises group had significantly better intensity of pain than the control group at the end of the three weeks (p < 0.01). The addition of diathermy by emission of radiofrequency to the therapeutic knee exercise protocol is more effective than a therapeutic exercise protocol alone in the relief of intensity of pain in patients with patellofemoral pain in the immediate post-treatment follow-up compared with baseline scores.Although consensus has been reached about the use of therapeutic exercise in patellofemoral pain syndrome, several techniques used worldwide such as radiofrequency diathermy could be useful as complementary therapy. The objective of this randomized controlled trial was to compare the effects of adding radiofrequency diathermy to therapeutic exercises in patients with patellofemoral pain syndrome. Fifty-six participants were randomly assigned either to radiofrequency diathermy plus therapeutic exercises group (n = 29) or therapeutic exercises group (n = 27). Both groups received the same therapeutic exercises, and the diathermy group additionally received monopolar dielectric diathermy for three weeks (5–3–2 weekly sessions). Data related to intensity of pain, probability of neuropathic pain, functionality, and range of movement of the knee were measured at baseline and three weeks after the intervention. Comparing pre-treatment and values obtained at the third week, significant improvements were found in intensity of pain, neuropathic pain, functionality, and range of motion in both groups ( Patellofemoral pain syndrome is a very common musculoskeletal dysfunction, characterized by pain in the anterior surface of the knee that often tends to chronicity . AlthougNon-surgery-based treatments are frequent, outshining physiotherapy as the most common approach ,11. The Monopolar dielectric diathermy by emission of radiofrequency (MDR) is an endogenous thermotherapy, which consists in the emission of high frequency electromagnetic signals via an isolated electrode that transfers energy to soft tissues containing electrolytes: muscles, vascular, or lymphatic tissues . This moAlthough other diathermy methods have documented its capacity to reduce pain in patients with numerous degenerative and inflammatory orthopedic problems, such as in low back pain or in shoulder impingement syndrome ,22, evidA prospective single-blind randomized controlled clinical trial was conducted, in which the researcher in charge of collecting the data from patients remained blind to the treatment applied to each participant. The trial was properly registered at ClinicalTrials.gov identifier NCT04538508. The investigation protocol was designed following the Helsinki Declaration and the Good Clinical Practice guidelines, according to CONSORT Standards and considering all the clinical regulations for research in humans. In this regard, all participants were appropriately informed about the study and their rights before signing the informed consent form accepting to participate. The research protocol was approved by the Ethics Committee of Virgen de la Macarena Hospital, Seville (CEI 1696-N-17).A total of 120 participants were initially recruited for the study, who were between 18 and 65 years of age, diagnosed with patellofemoral pain syndrome, and who were not currently undergoing any type of treatment. To be eligible, patients had to meet the following inclusion criteria: (1) patients between 18 and 65 years of age; (2) referred pain in the anterior surface of the knee of 30 mm or over in the Visual Analogue Scale (VAS) during the previous three months; (3) without radiological findings compatible with osteoarthritis; (4) without sensitivity to patellar tendon or iliotibial band palpation; (5) scoring below 45 in the psychological apprehension scale (PPAS) ; (6) not2 = 0.25), and a 10% drop-out at follow-up, the desired sample size was calculated to be 30 participants per group . Sample size calculation was based on the detection of (1) an improvement of 15% in self-perceived pain intensity ; (2) a dAll 60 participants provided demographic and clinical information, and also completed a number of self-report measures and underwent a physical examination, performed by an assessor blinded to the treatment allocation of the patients. Outcome measures were assessed before the first treatment session (baseline data), and immediately after treatment (at the third week) . DemograThe Visual Analogue Scale (VAS) was used to assess the patients’ current level of pain and the highest and lowest level of pain experienced in the preceding 24 h. A score of 00 would mean “no pain” and 10 “extreme and insufferable pain” . The minThe Douleur Neuropathique-4 items (DN4) questionnaire, consisting of 10 items ,35, was The patient-reported measures of lower limb functional status were the Kujala Function Score and lower extremity functionality score. The Kujala Function Score is a 13-item self-administered questionnaire that regards symptomatology in people with patellofemoral pain syndrome, with a variable ordinal response format. The total scores range from 0 to 100 . This toThe passive range of motion (ROM) in flexion and extension was measured with a conventional two-leg goniometer (angular measurement), which has shown high intratester reliability  and intertester (ICC range 0.959–0.970 for flexion and 0.85–0.898 for extension) .http://www.randomization.com; accessed on 6 September 2020) before the start of data collection by a researcher not involved in the recruitment or treatment of patients. One researcher distributed the randomized allocation of participants using opaque envelopes, with the participants being unaware of their selection. Another blinded researcher collected outcome measurements at baseline and immediately after the last treatment.After the initial evaluation, 60 participants (considering a 1:1) with patellofemoral pain syndrome were randomly assigned to receive either MDR plus therapeutic knee exercise  or therapeutic knee exercise alone (control group). Concealed allocation was performed using an external website , while therapeutic exercises for the knee were performed daily. Each session of therapeutic exercises lasted 20 min, and, in the case of the MDR group, another 12 min of diathermy were added before the exercise protocol. Both groups were treated by a physical therapist with more than 20 years of experience in the interventions. The details of the interventions are provided below.® device , in pulsed emissions of 640 kHz and 30 V in dynamic application, with a continuous rotation and translational movement on the anterior surface of the knee  and confidence intervals (IC 95%). Firstly, the normal distribution of variables was verified by the Kolgomorov–Smirnov test, after a descriptive analysis. Levene test was used to assess the homogeneity of variances. Linearity was assessed by bivariate dispersion graphics of residual values observed from the expected values. 2 tests of independence for categorical data. Separate 2 × 2 mixed model ANOVA with time (baseline and post- treatment) as the within-subjects factor, and group (MDR plus therapeutic exercise or therapeutic exercise) was used to determine the effects of the treatment. Effect size was tested using Cohen’s d. An effect size <0.2 reflects a negligible difference, between ≥0.2 and ≤0.5 a small difference, between ≥0.5 and ≤0.8 a moderate difference, and ≥0.8 a large difference. Eta squared (η2) was also used to calculate the effect size . A p-value less than 0.05 was considered to indicate a statistically significant difference. Baseline demographic and clinical variables were examined between both groups, with independent Student’s t-test for continuous data and χp > 0.05 for all). Four general practitioners  from a primary care health center of the Andalusian Health Service  recruited 120 participants between August and September 2020. After referral by a general practitioner, patients were interviewed face to face by another blinded researcher to check that they met the inclusion and exclusion criteria. A total of 60 participants with patellofemoral pain syndrome met the inclusion criteria and were recruited for the clinical trial . After tp < 0.001); only the range of movement in extension obtained a p = 0.031 (change score extension = 1.0). Although the therapeutic exercise group also experienced changes in all subscales, except for extension (p = 0.161), these differences were smaller than in the MDR plus exercise group . Within group analysis showed a significant improvement from baseline values for all subscales in the MDR plus therapeutic exercise group , and probability of neuropathic pain . Although no significant differences between groups were found for disability and range of movement, the results showed greater improvement in Lower Extremity Functionality Score in the MDR plus therapeutic exercise group (change score: 22.4) than in the therapeutic exercise group (change score: 14.2) at post-treatment follow-up. No significant differences between groups were found for Kujala Score , Lower Extremity Functionality Score , and range of movement .An ANOVA test showed statistically significant differences between groups with respect to intensity of pain  when diathermy by radiofrequency was added to therapeutic exercises. This result agrees with those referred by previous studies such as the one of Kumaran and Watson [Considering this, our hypothesis was based on the point that MDR plus therapeutic exercise for the knee could make a difference on pain and recovery time reduction. According to the results of this study, pain decreased in 48 in VAS . We believe that these differences can be explained by the relation between pain intensity and kinesiophobia . PreviouRegarding range of motion in flexion, statistically significant improvements were observed in patients of the diathermy group compared with those in the therapeutic exercise group. This could be explained in different ways; on the one hand, it is known that patients suffering from greater pain usually show higher levels of fear to movement, so the pain relief may have improved the range of motion . While, For all the above, it could be recommended to always use exercise as the first approach for patellofemoral pain syndrome since its effects are more than demonstrated in all the outcome measures. Adding MDR could also be useful, effective, and safe to obtain higher pain reductions and reduce the time of recovery, as it has been shown in various musculoskeletal medical disorders such as sports-type injuries, in low back pain, and in urology ,52,53,54The main weakness of this study is related to the lack of a placebo group of MDR. The difficulty to solve this lies in the impossibility of producing a thermal sensation similar to diathermy without heating or promoting metabolism of the tissue. Although the use of non-emission devices is accepted, participants’ distrust could easily increase with these devices due to the lack of sensation and therefore they may suspect the sham. Another limitation is the lack of a long-term follow-up, which was not viable owing to the different places of residence of most of participants and the pandemic situation. Future research should evaluate the long-term results and implement longer treatment programs. In addition, physiological responses such as vascularity, deep muscle temperature, motor unit recruitment, etc., should be assessed. On the other hand, it should also be assessed whether the results are satisfactory enough for the application of treatment to be profitable at the clinical level.In terms of clinical relevance, this randomized clinical trial has shown significant short-term improvements in pain intensity, probability of neuropathic pain, and range of motion in flexion in patients with patellofemoral pain with a three-week MDR adjunct to exercise therapeutics. The study highlights the potential benefits of radiofrequency emission monopolar dielectric diathermy in the treatment of patellofemoral pain syndrome and provides baseline data for future research in other musculoskeletal disorders.The addition of MDR to therapeutic knee exercises is more effective than only therapeutic exercises at reducing intensity of pain, probability of having neuropathic pain, and range of motion in flexion in patients with patellofemoral pain syndrome. The main finding of the present study is that the addition of MDR to therapeutic exercise produces a greater improvement in intensity of pain and probability of neuropathic pain than only supervised exercises in patients with patellofemoral pain in the immediate post-treatment follow-up compared with baseline scores.


Transversus abdominis plane (TAP) block is a method for postoperative pain management. Studies on children are gradually increasing. The aim of this retrospective study was to evaluate effectiveness of TAP block on pain control, its side effects, and parental satisfaction levels in children.Study included patients operated between January 2019 and December 2020 in Gazi University Faculty of Medicine. Total of 97 patients  between 5 and 18 years who had an ultrasound guided TAP block for lower abdominal or inguinal surgery were examined retrospectively. TAP block application time, hemodynamic variables, postoperative pain scores, postoperative analgesic requirement, sex, surgical history and satisfaction levels were evaluated.The average application time of TAP block was 9.48 ± 3.4 and the time between TAP block and surgical incision was 12.06 ± 6.1 min. Pain scores in postanesthesia care unit (PACU) and at the postoperative first hour decreased as the time between TAP block and surgical incision increased (p < 0.05). Girls have higher pain scores at PACU than boys (p < 0.05). Previous surgical history increased postoperative 1st hour pain scores . There was a significant negative correlation between pain scores at PACU, postoperative 1st, 2nd, 4th, 6th, 12th and satisfaction levels .Ultrasound-guided TAP blocks can be performed safely in children in lower abdominal surgeries. However, the efficacy of TAP block on late term postoperative pain scores is limited. Time interval between the TAP block and the incision, sex, and pain memory, as well as other factors that may improve the quality of TAP block should be considered. In pediatric age groups, the treatment of postoperative pain has more concerns than in adults. Opioids are used for postoperative analgesia. However, side effects hinder their utility in children . After sThe TAP block provides a local anesthetic drug diffusion between transversus abdominis and obliquus internus abdominis muscles. The block reaches the anterior rami of spinal nerves from T7 to L1 involved within the innervation of the abdominal wall . It provIn this retrospective study, we aimed to assess the impact of TAP block in terms of postoperative analgesia, side effects, and patient’s or parent’s satisfaction in 5 to 18 years old children who underwent lower abdominal or inguinal surgery.After obtaining ethical approval from Gazi University Clinical Research Ethics Committee , retrospective evaluation of the anesthesia records of patients <18 years old underwent lower abdominal or inguinal surgery, with an ultrasound-guided TAP block performed under general anesthesia within 2019 to 2020 were conducted. The data retained by the Departments of Pediatric Anesthesiology, and the Department of Pediatric Surgery medical charts of the patients were reviewed.A total of 141 patient files were accessed. Forty-four patients were not included in the study due to missing data or if they had received TAP block at the end of the surgery. This retrospective study involved 97 children of both sexes, aged 5–18 years, weighing 16–100 kg, who received general anesthesia for lower abdominal or inguinal surgery. All children were anesthetized using the standard protocol . 0.8–1.2 minimum alveolar concentration of sevoflurane in oxygen/air mixture was administered for the maintenance of anesthesia. After that, TAP block was performed under general anesthesia. The ultrasound  guided technique was used to identify fascia between the transversus abdominis and internal oblique muscles and assess the spreading of local anesthetic solution. Under aseptic technique and with the patient in the supine position, probe was placed on the abdominal wall at the level of T10 dermatome. Rectus abdominis muscle was visualized then probe was moved to iliac crest and costal margin distance. Musculofacial layers of the abdominal wall were visualized, and local anesthetic was injected to TAP after negative aspiration to avoid intravascular injection. TAP block was performed bilaterally with 0.25% concentration bupivacaine  by the same experienced pediatric anesthetist (B.I.). Total local anesthetic amount was limited to maximum of 0.2 mL/kg according to our hospital’s pediatric anesthesia unit postoperative pain treatment protocols. Besides all patients received intravenous acetaminophen  15 mg/kg at the end of the surgery. Patients were admitted to postoperative care unit (PACU) after surgery. Pain assessment was done using numeric rating scale (NRS) (0 to 10) if the child was older than 8 years old or cooperative [Demographic properties, history of previous surgery, type, and length of surgery, anesthetic agents, and doses, local anesthetic concentration, and doses for TAP block, the processing time of TAP block, time from TAP block to surgical incision were evaluated.Postoperative rescue analgesic need for analgesia and its time were assessed from medical records of patients. Based on these records mean arterial pressure (MAP) and heart rate (HR) were recorded in the following time points: preoperative, intraoperative 5th, 10th, 30th, 60th minutes, postoperative at PACU, 10th, 20th minutes, 1st, 2nd, 4th, 6th, 12th hours.Pain scales were assessed immediately after admission to PACU and then at 1st, 2nd, 4th, 6th, and 12th hours after surgery. The level of satisfaction of the patient or their parents was assessed with a 5-point Likert Scale at the 12th hour. General anesthesia or TAP block related complications were assessed.Statistical analysis was performed using the SPSS version 23  software. Categorical variables are presented as numbers and percentages, while continuous variables are presented as mean ± standard deviation (SD) and median (minimum-maximum). The compliance of continuous variables to normal distribution was evaluated using visual (histogram and probability graphs) and analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk tests). Mann-Whitney U test was used for data that did not comply with the normal distribution and independent samples t-test was used normally distributed data. The Pearson chi-square test was used to compare categorical variables between independent groups. Pearson correlation test was used for correlation analysis. Univariate logistic regression analysis was performed to identify the associations between the sex and past surgical history and postoperative pain scores. The receiver operating characteristic (ROC) analysis was used to determine a cut-off value for deciding a sufficient time interval between the TAP block and surgical incision to prevent pain scores of ≥4. Significance level was set at p < 0.05.The study includes 97 patients’ data with ASA I-II, 35 girls, and 62 boys, 5 to 18 (mean 12.87 ± 3.61) years old. Demographic and TAP block-related variables were shown in Assessment of the relationship between hemodynamic parameters and pain revealed a correlation between pain scores and MAP but not HR. First hour pain score and intraoperative 5th, 10th and postoperative 10th minutes MAP values were positively correlated . Also, a positive correlation was observed between 4th hour pain score and postoperative 10th minute MAP .Rescue analgesia requirement, satisfaction levels, and postoperative pain scores are shown in As the time between the TAP block application and the beginning of the surgery increased, the recovery and first hour pain scores decreased . A Pearson’s r data analysis revealed a moderate negative correlation, r = −0.62 and −0.26, respectively. Time interval between the TAP block and surgical incision did not affect pain scores at the 2nd, 4th, 6th, and 12th hours.ROC analysis revealed a cut-off value of 12.5 min for the duration of the interval between TAP block and surgical incision can predict pain scores higher than 4 with a sensitivity of 0.90 and a specificity of 0.73 for pain score at PACU and with a sensitivity of 0.62 and a specificity of 0.65 for 1st hour pain score. The ROC analysis for time interval between TAP block and surgical incision was presented in In terms of postoperative pain scores at PACU and 1st hour, the pain scores were higher in the girls than the boys  . The meaUnivariate logistic regression analysis revealed that previous surgical history increased postoperative 1st hour pain scores .There was no difference in terms of postoperative satisfaction levels between patients who have previously undergone surgery and those who were operated for the first time. An inverse correlation between pain scores at all time intervals and satisfaction levels was detected. Satisfaction increased as the pain scores decreased (p < 0.001). A negative correlation between pain scores at PACU, postoperative 1st, 2nd, 4th, 6th, 12th and satisfaction levels were observed .The reviewed anesthetic, surgical and follow-up forms at the ward revealed no TAP block and general anesthesia related complications.The most notable findings of this retrospective study are; (i)TAP block is more effective in boys than in girls, (ii) past surgical experience in our patient population had a negative impact on the analgesic effect of TAP block, (iii) the quality of TAP block weakens, and pain scores increase when the time interval between TAP block and incision is insufficient.Sex variations in perception and evaluation of pain have been widely studied. The studies do not fully cover pediatric population and the results are still conflicting . The paiPain memory is one of the key reasons why children who had undergone past surgery have higher pain scores in the course of the repetitive procedures. Hyperalgesia due to spinal and supraspinal changes caused by tissue damage in early life may lead to aforementioned phenomena , 15. ProPreemptive analgesia is the administration of an analgesic prior to noxious surgical stimulation. Metaanalyses have revealed different outcomes regarding the efficacy of preemptive analgesia on postoperative pain management , 17. We Transversus abdominis plane block has been an accepted part of multimodal analgesia and has been used in a wide variety of procedures, in the pediatric population for lower abdominal surgeries such as herniotomy, laparoscopy, appendectomy, laparotomy, and colostomy –20. WithTransversus abdominis plane block appears to have a valuable role in patients with comorbidities and give rise to hope, especially when central neuraxial blocks are contraindicated. Applying the TAP block alone in awake adult surgical patients offers a chance to detect complications at an early stage. However, in smaller children, TAP block is performed under general anesthesia. Unnoticing complications arising from the procedure or local anesthetics are the main risk. As local anesthetic pharmacokinetics differ in children compared to adults, this factor makes it difficult to determine nontoxic dose ranges . Based oIndications of TAP block and patient population in this study were similar to the literature , 19. We The entry points of the T6-L1 nerves are highly variable; therefore, some techniques cannot adequately block the related nerves . SubcostIn our research, we applied bilateral TAP block under ultrasound with a lateral approach. The block was performed with 0.25% concentration bupivacaine with a limit dose of 0.2 mL/kg. The mean dose of bupivacaine applied per kg was found to be 0.6 mg. Optimal dosage, volume, and kind of local anesthetic for TAP blocks are still undetermined according to the latest research, yet total dose of bupivacaine is also limited; to 2 mg/kg in neonates, 3 mg/kg in children, and 4 mg/kg in adolescents to avoid local anesthetic toxicity . In thisAcute pain generates an increasing sympathetic nerve activity. The initial response to nociceptive stimuli is the activation of some components of the sympathetic nervous system. Substances such as adrenocorticotrophic hormone, glucocorticoids, epinephrine and norepinephrine, etc., are released. Reaction to these mediators involves changes in cardiovascular, endocrine, somatosensory systems which maintains physiological functions against the imbalance due to surgical stress , 31. Acc34 for ethical reasons, it was not possible to evaluate the late effects of solely TAP block in these cases.The analysis of this data has number of limitations. The retrospective design restricts the study’s ability to test for confounding intraoperative factors. Since we administered morphine as a rescue analgesic when the pain scores was In accordance with preemptive analgesia principles, the surgical team involved in the treatment of these patients must treat cautiously in terms of adequate timing between the TAP block and surgical incision. Sex differences and pain memory, in addition to other factors that may improve the quality of TAP block, should be considered during postoperative pain management with TAP block. Also, it is critical to use the highest amount of local anesthetic drug possible when performing TAP block.


This narrative review aims to summarize non-pharmacological interventions for pain management in hemodialysis patients, assessing their potential benefits and limitations in enhancing patient well-being and quality of life. We reviewed the current literature on five primary non-pharmacological interventions: acupuncture, cognitive behavioral therapy, relaxation techniques, virtual reality, and alternative methods such as transcutaneous electrical nerve stimulation, music therapy, and aromatherapy. We analyzed the evidence regarding their effectiveness, feasibility, and optimal implementation strategies. The existing evidence supports the potential benefits of these interventions in managing pain and improving the well-being of hemodialysis patients. However, further high-quality research is needed to confirm their effectiveness, establish implementation best practices, and assess their long-term impact on patient outcomes. Non-pharmacological interventions hold promise for pain management in hemodialysis patients. Additional research is required to optimize these interventions and validate their effectiveness, contributing to comprehensive pain management strategies for this vulnerable patient population. Hemodialysis is a life-saving treatment for people with end-stage renal disease (ESRD) that involves the removal of toxins and excess fluids from the blood using an artificial kidney. Although hemodialysis is essential to maintain the health of ESRD patients, the process can cause significant pain and discomfort, leading to a lower quality of life ,2. Pain Inappropriate pain management can lead to nonadherence to treatment, increased healthcare costs, and reduced quality of life . FurtherThis narrative review aims to synthesize the evidence on NPIs for pain management in hemodialysis patients. The methods followed a simplified approach to ensure a comprehensive analysis of the available literature, consisting of the following steps: a strategy to locate pertinent publications was performed through digital repositories, encompassing databases such as PubMed, Scopus, Web of Science, and the Cochrane Library. The search strategy used a combination of keywords and subject headings related to NPIs, pain management, and hemodialysis patients. Keywords were combined using Boolean operators such as “AND” and “OR” to refine the search results. The search was carried out for articles published up to 2023. The study workflow is described in Acupuncture is a traditional Chinese medicine technique involving the insertion of thin needles into specific points on the body to stimulate the flow of energy (Qi) and restore balance ,12,13. TSeveral studies have investigated the efficacy of acupuncture for pain management in the hemodialysis group. A recent randomized control trial by Correia et al.  in 2022 RLS is a common complication that can negatively affect sleep quality and overall well-being. The study revealed that acupuncture treatment significantly decreased RLS symptoms but did not enhance sleep quality in patients on hemodialysis . A systeA randomized control trial conducted in 2020 on 50 patients divided into two groups of 25 each to determine how acupuncture can reduce pain and improve the quality of life in hemodialysis patients . The stuHowever, while these studies collectively suggest that acupuncture can have multifaceted benefits for hemodialysis patients, it is crucial to note that acupuncture must be performed by qualified professionals to ensure patient safety. As reiterated by Xu et al. , acupuncCognitive behavioral therapy (CBT) is a goal-oriented psychotherapy that focuses on identifying and modifying maladaptive thoughts, emotions, and behaviors . In the n = 33) or a waitlist control group (n = 26). CBT was administered chairside during dialysis treatments for three months, with evaluations performed three and six months post-randomization. The treatment-first group experienced significantly greater reductions in depression scores (both self-reported and clinician-reported) compared to the waitlist group [A pilot study found that a tech-assisted cognitive behavioral therapy procedure for ESRD undergoing hemodialysis was feasible and well accepted . While nst group . Furtherst group . CBT addst group ,32.In summary, CBT has shown potential for improving various aspects of well-being in hemodialysis patients, such as social support, quality of life, and mental health outcomes. Further research is needed, including exploring novel modalities such as Internet-based CBT, which could potentially enhance the accessibility and effectiveness of CBT interventions for this patient population. Another area to consider is establishing optimal implementation strategies and confirming CBT’s long-term benefits in hemodialysis patients.Relaxation techniques encompass a variety of non-invasive approaches designed to promote mental and physical relaxation, thus alleviating stress and fostering well-being . ExampleNumerous studies have investigated the potential benefits of employing relaxation techniques for pain management in individuals undergoing hemodialysis . A quasiIn 2023, a novel cluster-randomized controlled study was executed to gauge the efficacy of the Benson Relaxation technique in alleviating pain and perceived stress in patients undergoing hemodialysis . The intp < 0.05). No change was observed in the control group. The study reported that PREs can improve pain, fatigue, and quality of life in patients with hemodialysis [A study by Heidari et al.  conductedialysis .p < 0.001). The study showed that NPIs, such as PMR, can effectively reduce pain in hemodialysis patients. These techniques, by promoting relaxation and reducing anxiety, can be instrumental in alleviating procedure-related pain experienced during hemodialysis [Similarly, another study included 100 patients who received PMR every day for four weeks . The resdialysis ,43,47.Relaxation techniques show promising potential in managing pain and improving the well-being of hemodialysis patients. However, more high-quality research is needed to confirm the effectiveness of these approaches and determine best practices for their implementation.n = 20) experienced the program on two separate occasions, and the results showed significant decreases in treatment and/or motion-related symptoms after VR exposure, with high levels of immersion in the VR environment reported. VR programs may be a safe platform to improve the experience of dialysis patients.Virtual reality (VR) is an immersive technology that allows users to experience a computer-generated environment using head-mounted displays and other sensory devices . In the Another study conducted in Spain by Romero et al.  investigA scoping review aimed to identify the potential of virtual reality interventions to affect the level of participation in self-care and quality of life in hemodialysis patients . The revA focus should be made on evaluating the optimal frequency and duration of VR interventions, determining the most effective VR content for pain management in hemodialysis patients, and exploring the potential long-term benefits of VR therapy to patients’ overall quality of life and psychological well-being.In addition to the previously mentioned NPIs, several alternative methods have been examined to manage pain in hemodialysis patients. These non-pharmacological approaches include transcutaneous electrical nerve stimulation (TENS), music therapy, and aromatherapy. TENS is a non-invasive method that involves delivering mild electrical currents through electrodes placed on the skin to help alleviate pain .In a randomized controlled trial (RCT) conducted by Yang et al. , it was Aromatherapy is a type of alternative medicine that employs plant-derived essential oils to promote physical and mental health. While aromatherapy is not a pain remedy, it effectively reduces pain levels and enhances overall comfort . AromathThe current study embarked on a quest to investigate numerous non-pharmacological interventions for alleviating pain in individuals undergoing hemodialysis. Five principal strategies were identified. Among these, acupuncture demonstrated considerable promise as a benign and efficacious supplementary therapy for managing pain, enhancing functional capacity and muscular strength, lessening symptoms of restless leg syndrome and uremic pruritus, and bettering the QOL of patients on hemodialysis ,19. NoneEmerging as an innovative immersive technology, virtual reality has demonstrated potential benefits in pain management for individuals undergoing hemodialysis. This includes improved exercise adherence, enhanced functional capacity, improved cardiovascular health and psychological state, and making hemodialysis sessions more tolerable ,54. VR iThe application of non-pharmacological interventions in the context of hemodialysis varies in terms of their timing. It is essential to understand when these interventions are typically administered to appreciate their efficacy and relevance to the hemodialysis process.Acupuncture: This ancient Chinese therapeutic technique is often scheduled adjacent to the hemodialysis session. Patients usually undergo acupuncture either preceding, following their hemodialysis sessions, or during the sessions to harness its full therapeutic potential, aiding in pain management and enhancing overall well-being [ll-being ,25. Cognitive behavioral therapy sessions are generally organized independently of the hemodialysis procedure. They can be conducted on days when patients are not undergoing dialysis or after a session to address any psychological distress. All the included studies in our narrative review were introduced during the hemodialysis sessions [sessions ,32,33. Relaxation techniques: Techniques such as progressive muscle relaxation, guided imagery, and deep breathing exercises can be integrated both during the hemodialysis to alleviate immediate discomfort and outside the session to promote holistic well-being [ll-being ,47.Virtual reality: Employed predominantly as an immersive distraction method, virtual reality interventions are typically introduced during the hemodialysis session [ session ,53. ThisOther alternative methods: The application timing for these methods can be similar. For instance, music therapy can be introduced during the hemodialysis session to provide a soothing ambiance; similarly, aromatherapy might be more effective when used during the session to induce a state of relaxation ,69.The studies that explored the benefits of different non-pharmacological interventions are summarized in Before implementing NPIs for pain management in hemodialysis, clinicians must evaluate each patient’s unique requirements and preferences. Monitoring for adverse side effects and promptly addressing them can contribute to the safety and efficacy of these interventions. We have summarized the more frequent side effects reported in the literature in Non-pharmacological interventions (NPIs) have gained popularity as an alternative or supplement to pharmacological treatments in recent years. While various studies have been conducted to investigate their usefulness, there are still significant gaps and deficiencies requiring further study.While this review endeavored to offer an exhaustive overview of NPIs in the context of hemodialysis patients, it does come with certain constraints. Notably, individuals undergoing peritoneal dialysis were not encompassed in our analysis, marking a significant limitation. Additionally, the distinction between inpatient and outpatient status of the patients was not considered. Recognizing that the requirements and treatment modalities for hospitalized patients can substantially diverge from those receiving outpatient care presents another limitation of our study.Much of the research has focused on the efficacy of specific NPIs; however, comparative studies that directly compare different treatments are needed to find the most effective pain management technique. The majority of NPI research focuses on short-term results. Future studies should focus on the long-term impacts to establish their viability and capacity to give long-term pain relief. Understanding the underlying processes through which NPIs relieve pain in hemodialysis patients is critical. Research should be conducted to understand better the physiological and psychological mechanisms of how NIP works to increase their efficiency . When usFinally, once the usefulness of NPIs has been shown, projects should concentrate on creating ways to incorporate them into routine clinical practice. Identifying challenges and facilitators, as well as defining criteria or protocols, can assist assure widespread acceptance and sustainability.There is a lack of studies addressing the efficacy of analgesic medicine or comparisons between non-pharmacological interventions and an analgesic regimen. The current evidence regarding the efficacy and safety of NPIs seems promising; they are recommended and should always be available to hemodialysis patients. However, owing to the complexity of pain and the associated medical co-morbidities that most hemodialysis patients have, there is an urge for a cautious approach to managing pain.In conclusion, a comprehensive review of the diverse NPIs for hemodialysis patients was performed. Preliminary data suggest the potential utility of these NPIs in mitigating pain and augmenting the QOL in this specific group of patients. However, a crucial need exists for high-quality research to validate their effectiveness, delineate optimal implementation methodologies, and investigate innovative approaches to enhance their reach and effectiveness.It is essential to address the identified gaps in current knowledge. Progression in the domain of pain management for hemodialysis patients could potentially be driven by implementing comparative studies, analyzing long-term outcomes, and gaining insight into the precise mechanisms through which NPIs exert their effects. It is also important to consider patient preferences, evaluate cost-effectiveness, individualize interventions, and develop effective strategies for implementation. In the final analysis, a holistic, patient-centered approach to pain management, incorporating a variety of these NPIs, might be instrumental in addressing the unique needs of patients undergoing hemodialysis. This comprehensive strategy could lead to enhanced patient outcomes and improvement in the overall quality of healthcare provided to this specific patient group.


BackgroundMany patients suffer from some degree of pain following the surgical procedures of dental implantation. The fear of pain may be one reason for postponing such prosthodontic treatments. Many procedures have been suggested to control post-implantation pain. This trial evaluated the effectiveness of using hyaluronic acid (HA) during dental implantation on patients’ perceived pain during the postsurgical soft-tissue healing period.MethodologyA split-mouth randomized controlled trial (RCT) was conducted. The trial sample consisted of 22 dental implants in 11 patients . Patients were selected from those attending the Department of Oral Medicine at the Faculty of Dentistry, University of Damascus between February 2021 and May 2022. The implants were performed in similar bone quality and density for each patient as the implants were inserted in the same jaw on both sides to ensure the same physiological conditions. The study sample was divided into two groups. The first group  consisted of 11 implants in which the implant site was drilled, following which HA was placed inside the implant site and on the surrounding bone before the flap was returned and sutured. The second group (the control group) comprised 11 implants following the conventional procedure without applying any material to the implant socket. The main outcome measure was pain perception which was assessed using the visual analog scale (VAS). Patients were asked to record their perceived pain on the first, third, and tenth days. Two-sample t-tests were used to detect significant differences.ResultsThere were statistically significant differences in the mean pain intensity between the experimental and control groups on the first, third, and tenth days (p < 0.05). The mean values of perceived pain in the control group were 5.68, 1.72, and 0.56 on the first, third, and tenth days, respectively. In comparison, the mean values of perceived pain in the experimental group were 4.52, 1.14, and 0.18 on the first, third, and tenth days, respectively. The maximum perceived pain in the control group was 7.5 on the first day following implantation, whereas the maximum value recorded in the experimental group was 6.5. At the third assessment time , the mean values were in the very mild category of pain intensity.ConclusionsThis study showed that applying HA in the implant cavity and on the surrounding bone effectively reduced pain after dental implant surgery in comparison with the control group. Patients had lower mean pain scores at one, three, and ten days following surgery compared to the conventional method. HA is suggested to be an adjunctive method to control postsurgical pain after dental implantation. Dental implantation is a surgical procedure in which a piece fixed to the jaw bones is placed to support a crown, bridge, or movable device . The sucThe body naturally produces HA which forms polysaccharide chains found in the extracellular space of connective tissue, synovial fluid, and other tissues . It has Studies have shown that a high concentration of low or moderate-molecular-weight HA molecules has the strongest effect in controlling germs compared to other elements . It has When reviewing the literature, some studies have evaluated the use of HA in relieving pain and inducing new bone formation. A study by Yilmaz et al. aimed to evaluate the effectiveness of applying HA topically to relieve the complications of extraction of the impacted lower third molars . BecauseFew previous studies have used HA in the implant socket, and most used HA topically after the placement of dental implants in the form of ointments and sprays ,17. In tStudy design and settingsTrials.gov (NCT05776290).The design of this study was a split-mouth randomized controlled trial. This trial was conducted between February 2021 and May 2022 at the Department of Oral Medicine, Faculty of Dentistry, University of Damascus. The Faculty of Dentistry at the University of Damascus Local Research Ethics Committee approved this study (UDDS-3255-13112021/SRC-1198). This trial was retrospectively registered at Clinical Sample sizeThe sample size was calculated using the G*power 3.1.7 program  with a significance level of 0.05 and statistical power of 80%. After applying the calculation assumptions, it was found that 22 implants were required .Patient recruitment and follow-upAfter examining 47 patients attending the Department of Oral Medicine, Faculty of Dentistry University Damascus, 15 patients (aged 27 to 60) met the requirements for inclusion. Patients were informed about the research using standardized and well-detailed information sheets. Upon accepting to participate in the trial, informed consent forms were obtained from patients. Of the 19 patients who consented to participate in the trial, 11 (five men and six women) were chosen randomly. The inclusion criteria were (1) bilateral tooth loss with sufficient amount of bone volume; (2) no general problems; (3) good oral health; and (4) age between 20 and 60 years. The exclusion criteria were (1) the use of immunosuppressive drugs and corticosteroids for long periods; (2) the existence of serious systemic disorders; (3) contraindications for local anesthesia or oral surgery; (4) pregnant women and nursing mothers; (5) patients receiving chemotherapy or radiation; and (6) alcoholics and heavy smokers.Experimental and control groupsA total of 11 patients were included in this trial, with 22 implants implanted, two implants in each patient’s mouth through a split-mouth design. The experimental group consisted of 11 implant cases. The skin around the mouth was initially cleaned using a polyvidone iodine solution, and the surgical area was isolated. Then, local infiltration anesthesia was established. A full-thickness buccal mucoperiosteal flap was lifted, and the implant socket was drilled. HA was injected into the implant socket by syringe and on the alveolar bone in the experimental group Figure . FinallyRandomization of the intervention sideEach patient was asked to pick an opaque sealed envelope from a container to allocate the intervention side. The containers included six envelopes with the letter R indicating the right-hand side and six envelopes with the letter L indicating the left-hand side.Outcome measuresThe pain was assessed using the VAS to determine post-implant pain intensity. Each patient was asked to mark their perception of pain at two o’clock in the afternoon on the first, third, and tenth day after implantation. The intensity of pain was classified according to the following categories: 0 = no pain, 1-3 = mild pain, 3-6 = moderate pain, and 6-10 = severe pain ,19.Statistical analysisAll statistical analyses were performed using SPSS version 20 . The Kolmogorov-Smirnov test was used to check the normality of the distributions. Levene’s test was used to evaluate the equality of variances. An independent t-test was used to compare the results between the two groups. The significance level was set at 0.05.Baseline sample characteristicsThe Consolidated Standards of Reporting Trials (CONSORT) flow diagram illustrates patient recruitment, assignment, follow-up, and inclusion in data analysis Figure . In totaPerception of painIn the first assessment time , the greatest VAS score was 6.5 in the HA group and 7.5 in the control group. The lowest VAS score in both study groups was 4. On the third day, the greatest VAS score for both study groups was 3, and the lowest VAS score was 0.5. On the 10th day, the highest VAS score was 0.5 in the HA group and 1 in the control group. The lowest VAS score was 0 in both study groups Table .In the control group, the mean VAS score was 4.52 on postoperative day one. On the third day, it decreased to 1.14, and after 10 days, it further decreased to 0.14. In the control group, the mean VAS score was 5.68 on postoperative day one. On the third day, it decreased to 1.72, and on the 10th day, it further decreased to 0.56. It was observed that at all assessment times, the mean VAS scores in the control group were significantly greater than those in the HA group (p < 0.05) Table .The study results showed that HA had a positive effect in relieving pain after dental implants, with statistically significant differences between the experimental and control groups at the three assessment times. This may be due to the physiological and structural properties of HA, as it has an anti-inflammatory effect in the initial stages, an antibacterial effect, and activates cell migration, proliferation, and differentiation. As a result, it helps the differentiation of the cells responsible for rebuilding the damaged tissue and accelerates the healing of the bony space at the site of the wound; by stimulating angiogenesis, it also accelerates bone repair.We found that the application of HA gel can reduce pain in the first and third days after the dental implant, which was also reported by Yıldırım et al. . Their sOur results also agreed with the study by Abdelmabood and Eid, who studied the effect of HA gel in relieving pain after applying it to patients with odontogenic cysts . The resOur study findings agreed with those of Yilmaz and colleagues, who used HA gel after extracting third molars . Their rOur study differed from the study reported by Marin et al. which included 30 patients with uncontrolled type 2 diabetes who had symmetrical extractions in the mandible . HA gel Study limitationsThere were some limitations of this study. The sample size did not allow for gender-based comparisons. In addition, discrimination between patient responses on the pain scale based on their age group was not done in this study. Therefore, future research work should consider gender- and possible age-related effects on the perception of pain following implantation. This trial evaluated the effect of HA on pain control; however, the effect on the quantity and quality of the newly formed bone around the inserted implants was not assessed. Furthermore, other materials should be compared with HA regarding pain control following dental implantation in future clinical trials.This study showed that applying HA in the implant cavity and on the surrounding bone effectively reduced pain after dental implant surgery in comparison with the control group. Patients had lower mean pain scores at one, three, and ten days following surgery compared to the conventional method. This material is suggested to be an adjunctive method to control postsurgical pain after dental implantation. More studies are required to assess the effect of this material on the quality of bone being formed in the post-healing period. Additionally, gender and age differences in pain perception should be evaluated in future research.


Purpose: The goal of this study was to compare our institution’s recently implemented enhanced recovery after surgery (ERAS) protocol to previous post-operative management for adolescent idiopathic scoliosis patients undergoing posterior spinal fusion, specifically assessing length of stay, opioid consumption, and pain scores.Methods: This is a retrospective analysis that compares the length of stay, opioid consumption, and pain scores of patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis. Patients were analyzed prior to the implementation of our ERAS protocol, deemed the traditional pain pathway (TPP), to those who underwent the ERAS pathway. All patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis were included. Patients were excluded if they weighed less than 40kg, had significant comorbidities, or had non-idiopathic causes of scoliosis.Results: We examined 22 patients in the TPP cohort and 20 in the ERAS cohort. Length of stay in the ERAS cohort was significantly reduced compared to the TPP by 1.7 days (P<0.01). Overall opioid consumption was also significantly reduced in the ERAS with 1.4 ± 0.7 morphine equivalents (ME)/kg compared to the TPP 2.4 ± 1.1 ME/kg (P < 0.01). We found no difference in pain scores between the two groups.Conclusion: Implementation of an ERAS pathway at our institution significantly reduced length of stay and opioid consumption in adolescent idiopathic scoliosis patients undergoing posterior spinal fusion. These outcomes reduce morbidity and costs associated with posterior spinal fusion and provide an overall improvement in the quality of care for our patients. The postoperative period for adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion (PSF) is fraught with challenges, including adequate postoperative pain control and prolonged hospitalization. Inadequate postoperative pain control can contribute to prolonged hospital stays and even intensive care unit (ICU) admissions. While intravenous opioid medications are the mainstay of postoperative pain management for PSF patients, other techniques include epidural analgesics, intrathecal opioids, systemic ketamine, and gabapentinoids . DespiteEnhanced recovery after surgery (ERAS) protocols were originally developed to improve overall outcomes in surgical patients . In the Studies examining ERAS outcomes in AIS patients undergoing PSF are few -13. The In this study, we assessed the efficacy of a newly implemented ERAS protocol for patients with AIS undergoing PSF. Primary outcomes included LOS, opioid usage, and pain scores. All patients included in this study had a PSF performed by one of two orthopedic surgeons from December 2013 to April 2018. All patients who underwent PSF for AIS were included in the study. Patients were excluded if they weighed less than 40 kg, had significant comorbidities, or had non-idiopathic causes of scoliosis. The traditional pain pathway (TPP) cohort included patients who had their operations between December 2013 and April 2017. The ERAS cohort included all patients from May 2017 to April 2018, after the implementation of the ERAS protocol. This change served as a surrogate for intervention in our study allowing us to analyze the differences between these two groups. We collected all data retrospectively from our institution’s electronic medical records and recorded the LOS from the date of surgery until discharged from the hospital. Postoperative opioid usage was recorded and all medications were converted to morphine-equivalents (ME). ME per kg (ME/kg) was then calculated. Nurse charting of pain levels using the visual analog scale (VAS) was reviewed and the daily average and highest pain score was recorded for each patient. We also reviewed each group for any potential complications including urinary retention, neurologic deficits, local wound pathology, prolonged ventilation, or return to trip to the operating room within three months. Our institutional review board reviewed and approved this study.Traditional pain pathway (TPP)The TPP included surgeon-administered intraoperative intrathecal morphine, a first postoperative night stay in the pediatric intensive care unit (PICU), and highly variable postoperative pain medication administration. Without a standardized protocol, much of the post-operative pain management was left to the discretion of different medical teams. Teams that managed postoperative pain during the TTP varied between the pediatric medicine team and the primary surgical team without consistency. Furthermore, members of these teams frequently changed personnel which resulted in a wide variety of opioid and non-opioid medications utilized. These included morphine, oxycodone, and hydromorphone. Providers proved a range of frequency and dosages of pain medication administration ranging from patient-controlled to PRN.ERAS pathwayOur ERAS protocol emphasized multimodal pain control. The acute pain service (APS) managed all postoperative pain medications in order to decrease variability in treatment. Preoperatively patients received gabapentin, celecoxib, and midazolam. Intraoperatively, they received total intravenous anesthetic of propofol, remifentanil, and ketamine, while receiving methadone, dexamethasone, ondansetron, acetaminophen, and methocarbamol for pain control. Since the use of intrathecal morphine was abandoned, patients no longer required monitoring in the PICU on the first night postoperatively. They went from the post-anesthesia care unit (PACU) to the general post-surgical floor. On postoperative day 0 (POD0), patients were placed on hydromorphone, methadone, acetaminophen, ketorolac, methocarbamol, ondansetron, diazepam, and a bowel regimen. On POD1, gabapentin and oxycodone were added. Ketorolac and diazepam were discontinued and ibuprofen was started on POD2. On the morning of POD3, hydromorphone was discontinued and patients remained on an oral pain regimen for the remainder of their stay comprising oxycodone, acetaminophen, ibuprofen, methocarbamol, ondansetron, gabapentin, and a bowel regimen. See Appendix - Figure Patient selectionWe identified all patients undergoing PSF performed by two different surgeons from December 2013 to April 2018 (n = 75). Of the cases reviewed, we excluded 33 patients due to non-idiopathic causes of scoliosis as shown in Figure Additionally, we excluded patients who weighed less than 40kg (n = 2) and a patient with pre-operative prolonged QTc because the medications included in the ERAS pathway were contraindicated. Of the remaining patients (n = 42), the TPP group included all surgeries prior to May 2017 (n = 22) and the ERAS group included those after the implementation of the new protocol (n = 20).Statistical analysisAll statistical analysis was performed in Statistical Analysis Software (SAS) 9.4 , with significance set to α=0.05. Baseline preoperative characteristics of the two groups were compared using Wilcoxon-Mann-Whitney tests for interval data, and Fisher’s exact test for nominal frequency data. Postoperative differences in LOS, total postoperative opioid consumption, opioid consumption by POD0-3, and average pain from POD0-3 were compared between groups using Wilcoxon-Mann-Whitney tests. Effect sizes  for these comparisons were also computed. Differences between groups in changes in opioid dose and pain from POD0 through POD3 were analyzed using repeated measures linear mixed models. The focus of those analyses was on the group by POD interaction effect, which tests for differences between groups in the magnitude of changes in opioid dosage or pain over the postoperative study period. Where those interactions were non-significant, we removed them from the models and tested for the main effects of group and day. The sample analyzed is a convenience sample of all available eligible procedures during the designated study period. No prior power analysis was performed.We examined 22 patients in the TPP cohort and 20 patients in the ERAS cohort. Patient characteristics for each group are shown in Table Both cohorts had similar age and sex distributions and were of similar height and weight. The median number of levels operated on was nearly identical between cohorts , and surgical times were similar .Patients managed with the ERAS pathway experienced a significantly shorter length of hospitalization than the TPP patients. LOS in the ERAS cohort was 1.7 days shorter than in the TPP cohort , as shown in Figure When comparing overall opioid consumption between the two groups, we found that ERAS patients required significantly fewer opioids postoperatively. Corrected for weight, total opioid consumption in the ERAS cohort was 1.4 ± 0.7 ME/kg compared to the TPP 2.4 ± 1.1 ME/kg . Though not statistically significant, the ERAS group trended towards using fewer opioids when comparing ME/kg on POD 1, 2, and 3 .Regarding complications, we found that neither group had difficulty with urinary retention or prolonged ventilation. However, the TTP group did have two patients that required a return to surgery. The first developed wound dehiscence and leg weakness that required a repeat trip to surgery and hospitalization for IV antibiotics. The other had a large subfascial hematoma causing sensory changes in their leg, which required a return to surgery for evacuation. Both patients' neurologic deficits returned fully by their first post-operative visit and neither had further wound complications.The goal of any ERAS pathway is to improve overall patient outcomes using a multimodal, evidenced-based approach . The useIncreased LOS is correlated with morbidity and serves as the surrogate of postoperative milestones. In adolescent scoliosis patients undergoing surgical fixation, prolonged LOS is directly related to increased risk for surgical site infections, sepsis, and readmission -17. In pIn addition to enhanced outcomes, ERAS protocols also provide cost savings for patients, their families, and the healthcare system overall ,20. PSF While opioids are frequently prescribed postoperatively, it is not without the potential for significant risk to patients’ health. Short-term complications include acute respiratory depression, constipation, and altered sensorium, while long-term complications include risk for opioid use disorders ,23. The Given the accelerated nature of the ERAS pathway with an emphasis on early ambulation, one might anticipate an increase in daily opioid analgesic requirements. We found that the TPP patients used slightly fewer opioids on POD0, but that trend quickly changed to the ERAS group requiring less on POD 1, 2, and 3, as shown in Table We attribute the lower opioid consumption on POD0 in the TPP group to the use of intra-operatively administered intrathecal morphine, which was not included in the postoperative opioid utilization calculations. Conversely, the ERAS cohort did not receive intrathecal morphine and instead received postoperative methadone, which was calculated in opioid consumption totals. By removing intrathecal morphine and administering methadone, patients were judged to be at a lower risk for postoperative respiratory depression and therefore able to avoid an overnight stay in the PICU for monitoring.We must consider the limitations of this study. First, our sample size is relatively small, which is likely due to stringent exclusion criteria. We placed an emphasis on only including healthy patients with adolescent idiopathic scoliosis in order to limit confounding variables. Secondly, the numeric pain scale is fairly subjective and highly variable between patients, and therefore may not be the best way to measure pain. Lastly, since this was an unblinded retrospective study, surgeons were aware of the ERAS pathway implementation and may have introduced bias when discussing expectations with families prior to surgery. Overall, while additional patients would increase the power of the study, we are satisfied that our new ERAS pathway provided significant results.The ERAS pathway at our institution significantly reduced LOS and opioid consumption in AIS patients undergoing PSF. We hope this pathway can serve as a model to reduce the overall utilization of opioids for AIS patients, thus reducing the associated risks. Additionally, we feel that this ERAS pathway better controls patients’ post-operative pain allowing for earlier rehabilitation resulting in reduced LOS. While this study only focuses on immediate post-operative care in the hospital setting, further studies would be necessary to assess the effect of the ERAS pathway on recovery as a whole. This could include long-term follow-up with patient-reported outcomes after PSF surgery. Overall, we feel this ERAS pathway has improved recovery after PSF surgery for AIS and continues to be utilized at our institution.