Conclusions: A therapeutic exercise protocol may provide beneficial effects upon disability and pain intensity in patients with chronic non-specific back pain, including neck and low-back pain conditions In addition, It could be considered for inclusion as a back-pain-approach program in primary healthcare.Background: Back pain is highly prevalent; in Spain, it produces a very high economic cost and the scientific evidence supporting treatments shows low to moderate evidence for exercise. Therefore, the aim of this study was to assess the effectiveness of a therapeutic group exercise protocol in reducing pain intensity and disability in patients with back pain in primary health care setting. Methods: A total sample of 149 patients who suffered from chronic non-specific back pain was selected. Patients received a therapeutic exercise protocol, including auto-mobilization exercises for the neck and lumbar regions, as well as core stabilization exercises. Pain intensity and disability were evaluated before and after the therapeutic exercise protocol. Results: Statistically significant differences ( Currently, back pain presents a high lifetime prevalence from 77% to 85% and a great point prevalence from 30% to 43% ,2. Back In Spain , non-specific neck and back pain showed a 1-year prevalence of 19.5 and 19.9%, respectively, and the cost of neck pain in primary care is quite high ,5. Low-bNon-specific back pain may produce subsequent disability regarding daily living activities among patients who suffer from this musculoskeletal condition . It seemIn case of non-specific low-back pain, evidence guidelines recommend that patients should be active and receive good prognostic advice . PhysicaAccording to these recommendations, we hypothesized that a therapeutic exercise protocol would show positive effects on the disability and pain intensity of patients who suffered from chronic non-specific back pain. Thus, the main aim of this study was to determine the effects of a therapeutic exercise protocol on disability and pain intensity in patients with chronic non-specific back pain in a hospital physical therapy unit. The secondary aim was to divide the sample according to median pain intensity and disability to assess post-intervention outcomes.Single-group retrospective-descriptive study with before–after design  . The stuThis study included patients treated at the Physiotherapy Outpatient Service of the Guadarrama Hospital  between March 2015 and March 2017, as part of the program for the prevention of back pain focused on health education through the promotion of physical activity and the learning of therapeutic exercise guidelines carried out on patients referred from the Guadarrama Primary Health Center , San Carlos Primary Health Center  and El Escorial Primary Health Center ; all belong to the Public Northwest Health Area of the Community of Madrid (Spain). The inclusion criteria established in the program were: (a) patients of both genders aged 20–80 years belonging to the primary care area, (b) presenting chronic non-specific neck or low-back pain (more than 3 months of evolution). Patients with (a) an initial score of less than 15 on the Neck Disability Index (NDI), (b) an initial score equal to or less than 20 on the Oswestry Lumbar Disability Scale (OS), (c) cancer diagnosis, decompensated hypertension, ventricular dysfunction, pregnancy, or any other alteration or disease with contraindications to the practice of exercise, or (d) acute spinal pathology or other associated musculoskeletal processes requiring individualized treatment were excluded.Patients with chronic non-specific low-back pain were evaluated at the beginning and end of treatment using the Oswestry Lumbar Incapacity Scale (OS)  and the The NDI is a self-administered scale consisting of 10 Likert-type questions that assess the impact of cervical pain in the activities of daily living (ADLs) on the domains of pain intensity, self-care, load-bearing, reading, headaches, concentration, work, driving, sleep and play activities. Each question is scored from 0 (no disability) to 5 (complete disability), with a maximum score of 50. Depending on this score, the scale presents no disability (<5), mild (5–14), moderate (15–24), severe (25–34) and complete disability (>34) levels. This is a scale with a standard error of measurement (SEM) of 4.3 , with exThe OS is also an administered scale of 10 Likert-type questions that evaluate functionality in relation to low-back pain in the dimensions of pain intensity, personal care, load-support, gait, seating, standing, sleep, sexual activity, social life and repercussions when traveling. Each question is scored from 0 (no disability) to 5 (complete disability), with a score expressed as a percentage, the maximum being 100%. Depending on this percentage, the scale presents minimum (<20%), moderate (20–40%), intense (40–60%), disability (60–80%) and maximum (>80%) levels. It has a SEM of 3.54 with excellent test-retest reliability (ICC = 0.97) and internal consistency   It has aThe NPRS 10 is a 10-point interval numeric scale that assesses perceived pain from 0 (no pain) to 10 (maximum pain imaginable). Depending on the score, chronic musculoskeletal pain can be categorized as mild (<6), moderate (6–7) and severe (>7) . It has All patients were evaluated in a physiotherapy consultation at the beginning and at the end of treatment by an external evaluator who was blind to the treatments received by patients. The patients included in the program were assigned to one of the two groups, either the morning shift or the afternoon shift of the Physiotherapy Service of the Guadarrama Hospital. Each group of 8–10 patients was directed by one of the physiotherapists of the corresponding shift. Before the beginning of the program, the physiotherapists were trained in the administration of the therapeutic exercise protocol.The patients carried out 10 sessions of about 30 min duration, over the course of 2 weeks, with a protocol of exercises of automobilization of the cervical and lumbar regions based on the McKenzie concept , as wellp < 0.05. The Kolmogorov– Smirnoff test with Lillieford correction was used to determine the non-normal distribution of baseline and outcome variables. Qualitative variables were described in absolute values and frequencies and quantitative variables with mean and standard deviation (SD), or with median and interquartile range (IQR), depending on whether or not there was a normal distribution. For statistical analysis, the study used program R Ver. 3.3.3. . The level of significance was established at The Wilcoxon Signed Rank test was used on the initial and final scores of the Oswestry, NDI and NPRS 10 lumbar and cervical scales. Among the categorized outcome variables, the McNemar–Bowker test was applied with post hoc tests with Bonferroni correction. The Mann–Whitney or Kruskal–Wallis U test was applied between the result and basal variables. On the other hand, the exact Fisher test was applied between the categorized result variables and the categorical basals. On the other hand, the Mann-Whitney U test or the Kruskal-Wallis test was applied to the quantitative variables, and the Fihser exact test to the qualitative variables, between the post-treatment outcome variables and the pre-treatment variables  dichotomized based on their median.The effect size between the quantitative variables (r) was defined as <0.20 (not relevant), ≥0.20 and <0.50 , ≥0.50 and <0.80 (moderate) and ≥0.80 (large); in the qualitative variables the effect size (Cohen g) was defined as ≥0.05 and <0.15 , ≥0.15 and <0.25 (moderate) and ≥0.25 (large) and (Cramer V) as <0.212 , ≥0.212 and <0.354 (medium) and ≥0.354 (large).A total of 149 patients were treated, 32 men and 117 women with a mean age of 60  years, the median age of majority (56.4%). Almost half (46.3%) had chronic non-specific low-back pain and did not report dorsal pain (84.6%) .p > 0.001), although the presence of basal differences does not allow conclusions to be drawn.The Mann–Whitney U test  does not indicate significant differences between the initial and final outcome variables as a function of the basal variables except for the uncategorized age (p > 0.05) except in the case of NPRS 10, although the presence of baseline differences does not allow conclusions to be drawn.Fisher’s exact test of the initial and final categorized outcome variables, as a function of the categorized baseline variables, does not indicate significant differences (p < 0.001) with a difference of 8 [12 (median) 95% CI ] points and a moderate and significant effect size , (b) NPRS 10 initial lumbar vs. final  with a median difference of 2 [95% CI ] points and a moderate and significant effect size .The Wilcoxon Signed Rank test of uncategorized initial versus final outcome variables indicates significant differences: (a) initial vs final OS scale  = 9.333, p = 0.025) with a large overall effect size [Cohen’s g = 0.375 95% CI ], specifically, between the Intense and Moderate categories (p = 0.038) with a large effect size [Cohen’s g = 0.333 95% CI ], (b) in the proportion of the NPRS 10 scale categories categorized (X2(3) = 38.23, p < 0.001) with a large overall effect size [Cohen’s g = 0.411 95% CI ], among the categories (a) Slight-Moderate (p < 0.001) with a large effect size [Cohen’s g = 0.423 95%. CI ], and (b) Slight-Severe (p < 0.001) with a large effect size [Cohen’s g = 0.423 95% CI ]  in the proportion of the OS scale categories ] .p > 0.001) although the presence of basal differences does not allow conclusions to be drawn.The Mann–Whitney U test  does not indicate significant differences in the initial and final outcome variables as a function of the basal variables, except for uncategorized age (p > 0.05), except in the case of the final score in NPRS 10 as a function of the presence of dorsal pain (p = 0.028) with a medium effect size . The post hoc test fails to detect between which levels significant changes occur; however, it is evident that more than half of the patients (89.1%) presented at the end of treatment a mild level of cervical pain without being associated with the presence of dorsal pain.Fisher’s exact test of the initial and final categorized outcome variables as a function of the categorized baseline variables does not indicate significant differences (p < 0.001) with a difference of 11 [8 (median) 95% CI ] points and a large and significant effect size , (b) NPRS 10 cervical initial vs. final  with a difference of 3 [95% CI ] points and a moderate and significant effect size .Signal testing of the Wilcoxon ranges of uncategorized initial versus final outcome variables indicates significant differences : (a) ini2 (3) = 11,807, p = 0.008) with a large overall effect size [Cohen’s g = 0.293 95% CI ], specifically between the categories Moderate Disability and Complete Disability (p = 0.01) with a large and significant effect size [Cohen’s g = 0.423 95% CI ]; (b) in the proportion of the categories of the categorized NPRS 10 scale (X2(3) = 39, p < 0.001) with a large overall effect size (Cohen’s g = 0.5), between the categories (a) Mild-Moderate (p < 0.001) with a large effect size (Cohen’s g = 0.5), and (b) Mild-Severe (p < 0.001) with a large effect size (Cohen’s g = 0.5)  in the proportion of categories on the NDI scale (Xg = 0.5) .The chronic non-specific low-back and neck pain populations were split according to median (Me) pain intensity to see the post-intervention behavior of the self-reported disability variable and vice versa.p < 0.001, r = 0.37). In addition, the pre-intervention mean of OS for patients with upper disability was 42.24 ± 13.37, while the pre-intervention mean of OS for patients with lower disability was 22.48 ± 1.88. When comparing the mean values of the NPRS 10 variable between these groups at post-intervention, statistically significant between-groups differences were found with a small effect size ; p = 0.008, r = 0.242).The pre-intervention mean of NPRS 10 for patients with upper pain intensity was 8.68 ± 5.30, while the pre-intervention mean of NPRS 10 for patients with lower pain intensity was 4.48 ± 1.28. When comparing the mean values of the OS variable between these groups at post-intervention, statistically significant between-groups differences were found with a small effect size ; p = 0.01, r = 0.285). However, when comparing the mean values of the NPRS 10 variable between groups with upper (45.45 ± 10.40) and lower (21.50 ± 4.65) NDI, no statistically significant differences were found between the groups ; p = 0.2).The pre-intervention mean of NPRS 10 for patients with upper pain intensity was 7.67 ± 0.86, while the pre-intervention mean of NPRS 10 for patients with lower pain intensity was 4.72 ± 1.26. When comparing the mean values of the NDI variable between these groups post-intervention, statistically significant between-groups differences were found with a small effect size ; This study aimed to evaluate the effectiveness of a therapeutic group exercise protocol for non-specific back pain. After our program, the pain intensity reduced significantly. Our results also showed that this exercise program was acceptable, and participants improved their back health status .A recent network meta-analysis  concludeHowever, there is low-quality evidence in the literature that McKenzie was not effective for pain and function in patients with chronic low-back pain, and a low quality of evidence that Pilates, stabilization/motor control, resistance and aerobic exercise were able to improve pain and function . Several studies where they applied McKenzie exercises found an improvement between 50% to 68,76% in non-specific low-back pain intensity, but short-term and not for the long term ,50,51; tThe percentage of change of improvement for disability in our study reached 30.7%; this outcome is lower than previous studies, where they reached between 50% to 77.77% from immediately to 3 months after ,51,52, bOther therapeutic exercises and activities, such as Pilates, neuromuscular balls or yoga, are often recommended for general back pain. Researchers have conducted some studies to improve the scientific evidence on core stability, as shown in recent meta- analyses that demonstrate that core stability exercises are highly recommended for improving physical function and reducing pain in chronic low-back patients in the short term ,57,58.Therapeutic exercise is the most effective intervention for the management of back pain . PhysicaHayden et al.  show howAnother study offers inconclusive evidence for the effectiveness of the non-invasive management of cervicobrachial pain, showing that a manual therapy intervention combined with exercise resulted in a better health status in patients than manual therapy . In addiIn a recent clinical trial involving 45 patients experiencing chronic neck pain , the parThis study shows that, after a two-week intervention, therapeutic exercise improved pain intensity, functional disability, and patient satisfaction, as well as the activation of transversus of abdominis and superficial fibers of multifidus muscles in subjects with chronic non-specific low-back pain .Some studies offer low–moderate quality evidence that control-stabilization exercise interventions improve pain intensity and disability in subjects with chronic non-specific low-back pain, compared to a passive control group or to other exercises .Our study shows a pain-status improvement in patients with chronic non-specific back pain who had completed a therapeutic exercise protocol. Exercise therapy by itself, related with relaxation, is a therapeutic option commonly prescribed in the treatment of patients with chronic non-specific back pain. It is considered as an interesting intervention for increasing the range of movement . ImproveThe main limitation of the present study lies in the absence of a comparator group, due to its character as a habitual clinical practice, so the results have to be interpreted with caution.In addition, patients’ expectations were not evaluated. In this context, Ballestra et al.  demonstrA recent systematic review found evidence of increased levels of the proinflammatory biomarkers CRP, IL-6 and TNF-α and decreased levels of the anti-inflammatory biomarker IL-10 in patients with acute and chronic non-specific low-back pain . TherefoA therapeutic exercise protocol may provide beneficial effects upon disability and pain intensity in patients with chronic non-specific back pain, including non-specific neck and low-back pain conditions. It could be considered for inclusion as a back-pain-approach program in primary healthcare. Further studies are necessary, including a control group, in order to compare this therapeutic exercise protocol in patients who suffer from back pain.


Background and objective: Adequate postoperative pain control is an important component to enhance recovery. Multimodal analgesia with various pain control techniques has been widely used to alleviate postoperative pain. The use of either wound infiltration or a superficial cervical plexus block has been reported to be effective for pain management after thyroid surgery. The present study evaluated the effect of multimodal analgesia using lidocaine wound infiltration combined with intravenous parecoxib for patients monitored after thyroidectomy. Materials and Methods: A total of 101 patients with a multimodal analgesia protocol being monitored after thyroidectomy were enrolled. After the induction of anesthesia, multimodal analgesia was performed through wound infiltration of 1% lidocaine and epinephrine at a ratio of 1:200,000 (5 μg/mL) combined 40 mg intravenous parecoxib before skin excision. Patients were divided into two groups for this retrospective analysis based on the injection dose of lidocaine they received. Patients in Group I  received a 5 mL injection solution, while those in Group II  received a 10 mL dosage in a time-sequential manner, in accordance with a previous clinical trial. The primary outcome was measuring postoperative pain intensity at rest, as well as during motion and coughing, which was measured at the postoperative anesthetic care unit (PACU) and on the first day after the operation (POD 1) in the ward. Pain intensity was assessed using a numerical rating scale (NRS). The secondary outcomes were postoperative adverse events including anesthetic-related side effects, as well as airway and pulmonary complications. Results: Most of the patients reported no pain or mild pain during the observation period. The patients in Group II had a lower pain intensity during motion than Group I  when measured at the postoperative anesthetic care unit. Pain intensity during coughing was also significantly lower in the study group than in the control group  when measured at the postoperative anesthetic care unit. There were no severe adverse events in either of the groups. Only one patient (1.9%) in Group I experienced temporary vocal palsy. Conclusions: The use of lidocaine with an equal volume of intravenous parecoxib provided comparable analgesia with minimal adverse events when monitoring thyroidectomy. Adequate postoperative pain control is important for enhancing recovery ,2 and reLocal or regional analgesia plays an important role in multimodal analgesia. The rationale behind locoregional analgesia is that local anesthetics can block nociception transmission peripherally at the surgical site. Both wound infiltration and superficial cervical plexus block have been reported to be effective for pain management after thyroidectomy ,7. Hoh SThe thyroid gland, which consists of two interconnected lobes, is one of the biggest endocrine glands found in humans, measuring between 20 to 30 g. The incidence of thyroid lesions in this gland is between 4% and 7%. The majority are asymptomatic and have normal thyroid hormone secretion . ThyroidThis retrospective observational research is a secondary analysis of a prior clinical trial registered with ClinicalTrials.gov NCT 04982185), which evaluated the feasibility of routinely monitoring neuromuscular blockage during when monitoring patients after thyroidectomy. The trial was conducted in a regional teaching hospital in Kaohsiung, Taiwan. The Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-E(I)-20210070) granted ethical approval. By utilizing data from the original trial, the main goal of this retrospective analysis was to investigate the analgesic effects of multimodal analgesia by combining local wound infiltration of 1% lidocaine and intravenous parecoxib in patients being monitored after thyroidectomy. Specifically, the research compared the efficacy of two concentrations that had previously been used. We gathered the medical records of patients with either benign or thyroid cancer undergoing elective thyroidectomy with intraoperative neural monitoring, aged between 20–80 years, enrolled at the American Society of Anesthesiologists 85, which,12,13.During preparation for anesthesia, each patient was placed in a supine position with neck extension, using a donut pad, for their thyroidectomy. Before the induction of anesthesia, standard physiological monitoring  and anesthesia depth monitoring  were established. Neuromuscular transmission was continuously monitored through adductor pollicis muscle stimulation considering the train-of-four (TOF) ratio. General anesthesia was induced with fentanyl (1 µg/kg), lidocaine (1 mg/kg), propofol (2 mg/kg), and rocuronium (0.6 mg/kg). Oral endotracheal tubes with an internal diameter of 7.0- or 7.5-mm were used for females and males, respectively. An experienced anesthesiologist performed tracheal intubation using a video intubating stylet  when the lowest TOF ratio was noted. The accurate position of each endotracheal tube was confirmed using both auscultation and capnography. Mechanical ventilation was set up to keep the end-tidal CO2 between 35 and 45 mmHg, while anesthesia was maintained with sevoflurane and propofol target-controlled infusion to keep bispectral index or response entropy value between 40 and 60. A bolus of 8 mg ephedrine and rapid infusion of lactated Ringer’s solution was administrated if the mean arterial pressure dropped 20% lower than baseline for longer than two minutes. All patients received preemptive multimodal analgesia before skin incision via (1) local infiltration over the incision line with 1% lidocaine mixed epinephrine at 1:200,000 (5 μg/mL), (2) intravenous parecoxib 40 mg, and (3) a bolus of fentanyl 0.5 μg/kg. To prevent the toxicity associated with the injection of lidocaine, all pharmaceutical dosages were validated to be less than 7 mg/kg, which is the upper limit of systemic toxicity after reducing the rate of absorption using vasoconstrictors such as epinephrine . Then, 5Thyroidectomies were performed by the same surgeon following the standardized intraoperative neural monitoring protocol recommended by the international guidelines. According to departmental guidelines, thyroid surgery included total thyroidectomy and total lobectomy. Subtotal thyroidectomy was not performed in everyday practice. Skin incisions were made along previous local infiltration areas on the lower neck, followed by dissection of the central neck. After the skin flap was elevated, two pairs of trans-thyroid cartilage recording electrodes were used to record the electrophysiologic electromyographic (EMG) response that was evoked ; they wePostoperative pain intensity was assessed using the numerical rating scale (NRS) at rest, as well as during motion and coughing. The pain assessment time points were taken before discharge from PACU, on the first day after the operation (POD 1) at the ward, and one week after the operation during the outpatient department (OPD) visit. If a patient suffered from moderate pain (NRS > 3) at PACU, 25 μg of fentanyl was administrated as a rescue analgesic. If a patient had persistent moderate pain (NRS > 3) during their OPD visit, 25 mg of diclofenac was prescribed. Postoperative adverse events included lidocaine toxicity-related transient neurologic symptoms (TNS), PONV, dizziness, pruritus, sore throat, airway obstruction, and postoperative pulmonary complications, with postoperative observations being recorded by a registered nurse anesthetist who was blinded to the group allocation. The outcome of intraoperative neural monitoring was evaluated using vocal palsy (both temporary and permanent). http://powerandsamplesize.com, accessed on 8-11-2022) to calculate the sample size needed in order to show at least a 15% difference in pain intensity (NRS) between groups. The power analysis found that at least 50 patients per group could be used in order to obtain a power of 0.8 with an alpha error of 0.05. Therefore, we enrolled 60 patients per group. Anesthesia data were expressed as mean ± (standard deviation). All data were expressed as mean or number of patients (%). Continuous variables between groups were carried out using Student’s t-test, while categorical nominal variables were analyzed using the chi-square test or Fisher’s exact test, as applicable. All statistical tests were two-tailed, and a p-value < 0.05 was considered statistically significant. Statistical analysis was performed with R language (version 4.1.3) and RStudio software .We used an online website  completed the study . The phyp = 0.043) upon discharge from the postoperative anesthetic care unit (p = 0.049) at the same time point .No instances of permanent vocal palsy were observed in patients undergoing monitored thyroidectomy in either Group I or Group II. One patient in Group I experienced a temporary episode of vocal palsy and spontaneous recovery was noted within 6 weeks postoperatively. A comparison of the frequencies of temporary and permanent vocal palsy between Group I and Group II revealed no significant differences  rather than to validate specific techniques or agents. We found that the combination of local wound infiltration and intravenous parecoxib provided adequate pain control and was well-tolerated. In comparison with the cervical plexus block, local wound infiltration was safe and easy to perform without ultrasound guidance. Moreover, local wound infiltration could also avoid possible adverse events related to cervical plexus block, such as phrenic nerve palsy, inadvertent vessel puncture, and local anesthetic intoxication ,21. Parecoxib sodium is the only intravenous selective cyclooxygenase-2 (COX-2) inhibitor to provide analgesia and anti-inflammation effects. After administering parecoxib sodium, it is rapidly converted to valdecoxib and reduces prostaglandin synthesis . Except There were several limitations in this retrospective study. Firstly, the design was non-randomized because it aimed to review existing clinical analgesic regimens, although the patient characteristics, disease, and surgical profiles were comparable between the two groups. Secondly, there could be a selection bias due to the patients being selected and surgical procedures being performed by a single surgeon in a healthcare system. All thyroid surgeries were performed using an intraoperative neural monitoring system; in Taiwan, this is a self-payment regimen. The study only enrolled patients who could afford to be monitored after thyroidectomy; therefore, they could be of a higher socioeconomic status. Furthermore, both total thyroidectomy and subtotal thyroidectomy are major procedures for thyroid tumors. Total thyroidectomy does not increase complications, such as hematoma or recurrent laryngeal nerve, compared to subtotal thyroidectomy . The surMultimodal analgesia using a combination of 1% lidocaine local wound infiltration with 40 mg parecoxib intravenous injection provided effective postoperative pain control with low adverse events when monitoring after thyroidectomy. The higher local wound infiltration volume of 10 mL 1% lidocaine was superior to 5 mL considering pain score on the day of operation and one week after the thyroidectomy. To minimize the risk of local toxicity from anesthetics, caution should be taken when selecting the injection technique and total dose of local anesthetics. Local infiltration might be as effective as superficial cervical plexus block, with minimal local anesthetics toxicity events. Further study is needed to determine whether local anesthetics with a longer duration  are more effective than lidocaine for postoperative pain control after thyroidectomy.


The aim of this evidence-based study is to narrate and evaluate the current evidence on recommendations for practicing physicians and other healthcare providers regarding integrative approaches to managing pain in patients with cancer. This review will assess the guideline recommendations and analyze the role of integrative medicine in addressing cancer pain in patients. The literature search highlights relevant studies that will inform evidence-based recommendations for practicing physicians, highlighting their relevance and weaknesses. Acupuncture, massage, and hypnosis have intermediate-strength evidence quality and are moderately recommended for various types of cancer pain. Most of the evidence points to acupuncture being recommended for aromatase inhibitor-related joint pain, hypnosis for procedural pain, and massage for palliative care pain. Other practices with lower-quality evidence include yoga and guided imagery with progressive muscle relaxation, mostly recommended for general cancer pain or musculoskeletal pain. Additionally, music therapy is recommended for procedural or surgical pain. Low-quality or inconclusive evidence was found for other mind-body interventions or natural products. Similarly, there is insufficient evidence to provide recommendations for pediatric patients. Further research is required to enhance our understanding of the role of integrative medicine interventions in caring for cancer patients. According to the American Cancer Society (ACS), oncologic pain derived from cancer itself can vary according to a series of factors, including the type of cancer, the stage, pain tolerance of the patient, and concomitant conditions . Other fIn the same meta-analysis , the autIntegrative practices, such as acupuncture, massage, and yoga, have demonstrated positive outcomes in the management of chronic pain . HeatherThe European Pain Federation (EFIC) defines pain as an unpleasant sensory and emotional experience that may or may not be associated with tissue damage . ChronicIntegrative medicine is a patient-centered approach that allows individuals to receive a non-traditional course of treatment, facilitating the healing process. This approach combines therapeutic methods from both conventional and alternative medicine, emphasizing the importance of therapeutic relationships. Therapeutic relationships surrounding addressing the needs of the mind, body, and spiritual needs, while still coordinating care with a team of physicians . A good A cross-sectional survey conducted at a tertiary care hospital in India explored physicians' perceptions of complementary and alternative medicine. The findings revealed that 27% of physicians recommended integrative practices for chronic pain patients, with yoga and meditation being the most commonly recommended approaches . However, the study also identified significant resistance among physicians toward integrative medicine. Approximately 39% disagreed with using integrative practices even when allopathy was ineffective, and around 60% disagreed with including integrative practices in medical curricula or training doctors on it. Furthermore, 40% of physicians did not recommend complementary and alternative medicine .Integrative medicine takes into account the patient's immediate health and needs, as well as the long-term and intricate interplay between biological, behavioral, psychosocial, and environmental factors . For exaSimilarly, a retrospective study conducted in Texas showed that patients who received integrative medicine were more likely to experience reduced pain, leading to approximately a 4% decrease in hospital costs . These fOver 50% of oncology patients experience pain, regardless of cancer stage, and in more advanced cancers, pain prevalence tends to be higher . CombineHence, this review aims to describe the benefits and applications of integrative medicine in the management of oncologic chronic pain. The discussion will focus on integrative medical therapies, such as acupuncture, hypnosis, yoga, and massage therapy, highlighting their potential advantages in the field of oncology.Integrative medicine therapies in oncologic painIntegrative oncology is a patient-centered field that incorporates evidence-based interventions, including mind and body practices, natural products, and lifestyle modifications from various traditions, alongside conventional treatments, to inform cancer care .The ASCO acknowledges that scientific evidence supports the use of therapies such as acupuncture and massage therapy in improving the quality of life for cancer patients and reducing cancer-related pain .This study aims to examine the existing evidence on integrative therapies, including acupuncture, massage, hypnosis, and yoga, in the management of oncologic pain.Current guidelinesThe SIO and the ASCO collaborated to develop a new practice guideline aimed at providing evidence-based recommendations on integrative medicine approaches for managing pain in cancer patients. In total, 227 relevant studies were analyzed to support the development of these guidelines . To deveAccording to the joint panel, the benefits of the 13 recommendations outweigh the risks for patients. However, certain practices such as mind-body interventions, natural products (including omega-3 fatty acids), music therapy, and topical pure emu oil did not meet the criteria for inclusion in the guideline. Additionally, there was insufficient evidence to make recommendations for pain management in pediatric cancer patients.The guideline also acknowledges that disparities exist among patient groups, which can result in limited access to medical care. Factors such as race and ethnicity, age, socioeconomic status, sexual orientation and gender identity, geographic location, immigrant status, and insurance access can impact the extent to which patients can receive integrative medicine. It is important for researchers to continue working on these interventions in patient care to address and overcome these structural barriers.AcupunctureAcupuncture is a technique from traditional Chinese medicine that involves inserting thin steel needles at specific points on the body known as acupoints . It has According to the ASCO, acupuncture has been shown to relieve pain and reduce other cancer-related symptoms such as chemotherapy-induced nausea, vomiting, hot flashes, and dry mouth. However, more research is needed to establish a relationship between acupuncture and other symptoms like anxiety, loss of appetite, and fatigue . In a meIn a new joint practice guideline from SIO and ASCO, four recommendations  are provided for the use of acupuncture in managing cancer pain .Aromatase inhibitors are frequently used as adjunctive hormone treatment for breast cancer patients, and have arthralgia as a major side effect . RecommeRecommendation 1.3 suggests the use of acupuncture for general cancer pain or musculoskeletal pain. This recommendation is supported by a study involving 360 patients who were assigned to receive electroacupuncture, auricular acupuncture, or usual care. Electroacupuncture was found to significantly reduce pain intensity compared to auricular acupuncture .Two other recommendations (1.8 and 1.11) with low evidence quality and weak recommendation strength are made for acupuncture. Recommendation 1.8 states that acupuncture can be used for chemotherapy-induced peripheral neuropathy based on a study involving 75 patients, where true acupuncture demonstrated a significant reduction in neuropathic pain . RecommeRegarding acupressure, there is some controversy regarding its classification. While some experts consider it a type of acupuncture, others consider it a type of massage. Acupressure involves applying pressure with hands to specific acupoints without the use of needles . For theMassageMassage therapy is a tissue manipulation technique where muscles and other soft tissues are moved, rubbed, and pressed. According to the ASCO, this type of therapy shows short-term benefits for chronic pain relief. ASCO further adds that other benefits of massage include decreasing tension and stress levels, easing anxiety and depression, and helping with sleep problems and fatigue . MassageThe findings of a meta-analysis involving 559 participants from 12 different studies indicate that massage therapy offers significant relief for cancer pain compared to no massage treatment or conventional care. This therapy has demonstrated effectiveness, particularly in addressing postoperative pain. Among the different types of massage studied, foot reflexology was found to be more effective than body or aroma massage .In the guideline published in the Journal of Clinical Oncology, massage therapy is the most recommended type of therapy, with five out of 13 recommendations specifically mentioning massage. These recommendations include a moderate strength of recommendation for the use of reflexology, acupressure, or general massage for general cancer pain or musculoskeletal pain, as well as for patients experiencing pain during palliative or hospice care. Weak recommendations are made for reflexology and acupressure in patients with chemotherapy-induced peripheral neuropathy, as well as acupressure for palliative care .Recommendation 1.13 of the guidelines suggests the use of classic massage as a therapeutic option for patients who are experiencing pain during palliative and hospice care. The quality of evidence supporting this recommendation is considered intermediate, based on 10 studies that include seven randomized controlled trials and three systematic reviews. Both types of studies, i.e., randomized controlled trials and systematic reviews, consistently conclude that massage is an effective therapy for pain management in cancer patients receiving palliative treatment .Typically, randomized controlled trials in this area involve a range of participants, from 21 to 86 individuals. However, it is worth noting one significant study that included 380 patients with various types of advanced cancers who were experiencing moderate-to-severe pain. In this particular study, massage was shown to have immediate beneficial effects on pain and mood among patients with advanced cancer. However, no long-term reduction in pain was observed .Another recommendation, i.e., recommendation 1.5, pertains to a classic massage for cancer patients experiencing chronic pain following breast cancer treatment. Despite the low quality of evidence, this recommendation is classified as moderate. It is based on a total of four studies, including two reviews and two clinical trials .A meta-analysis examining the effects of manual therapy on chronic musculoskeletal pain in the upper limbs and thorax of female breast cancer patients included five randomized controlled trials. The researchers found that manual therapy reduced the intensity of chronic musculoskeletal pain, although no significant difference was observed in quality of life compared to control groups. The study concluded that manual therapy is considered effective for treating chronic musculoskeletal pain in the upper limbs and thorax of female breast cancer survivors .In contrast, a comprehensive review that assessed the effects of massage with or without aromatherapy on pain and other cancer-associated symptoms examined a total of 19 studies (21 reports) with very low-quality evidence, involving a combined total of 1274 participants. When it comes to pain, the quality of evidence comparing the massage group to the no-massage group was deemed very low. This was primarily due to the small size of most studies and their poor reporting, which resulted in an unclear or high risk of bias. Notably, one study even found that short-term pain was greater in the massage group compared to the no-massage group. The review highlighted the insufficient clinical evidence available on the effectiveness of massage for symptom relief in individuals with cancer, emphasizing that most studies were too small to provide reliable conclusions .Despite the conflicting reviews mentioned, a randomized clinical trial involving 230 patients contributes additional evidence supporting the effectiveness of massage for cancer patients. This particular trial employed a randomized, prospective, two-period, crossover intervention design to investigate the effects of therapeutic massage and healing touch in comparison to presence alone or standard care. The results demonstrated that pain ratings were lower after therapeutic massage and healing touch, and the group receiving therapeutic massage also required less usage of nonsteroidal anti-inflammatory drugs. Based on these findings, the study concluded that therapeutic massage and healing touch are more effective than standard care in reducing pain among cancer patients undergoing chemotherapy [The meta-analysis conducted specifically on musculoskeletal pain in breast cancer patients represents the only study focusing on this aspect . This meRecommendation 1.11 proposes the utilization of acupuncture or acupressure for patients undergoing cancer surgery or other cancer-related procedures. This recommendation is supported by a total of 12 studies, with seven focusing on acupuncture alone and three investigating the effects of acupressure. The overall quality of evidence was categorized as low, primarily due to the limited sample sizes, leading to a weak recommendation . Among tReflexology is a massage technique where pressure is applied to specific reflex points on the hands and feet, corresponding to specific areas of the body. It has been reported that massaging these points can enhance blood supply to related organs and generally reduce anxiety, pain, and fatigue . The guiRecommendation 1.4 is classified as a moderate recommendation with intermediate-quality strength. It is supported by a total of seven randomized trials involving a combined sample of 1096 patients with diverse types of cancer. With the exception of one trial, all of these studies reached the conclusion that patients who underwent reflexology treatment exhibited significantly reduced pain compared to the control group [The trial that did not show significant pain reduction in patients who received reflexology focused on patients with advanced-stage breast cancer undergoing chemotherapy and/or hormonal therapy. A total of 286 women were randomized into three groups: reflexology (n = 95), lay foot manipulation (n = 95), or conventional care (n = 96). Reflexology was performed by certified reflexologists trained in the Ingham method of reflexology, either at home or in clinical settings. Although no adverse effects were reported, the only benefit experienced by the reflexology group was a statistically significant improvement in physical functioning compared to the control group. Another finding was a reduction in the severity of dyspnea in the reflexology group compared to both the control group and the lay foot manipulation group. However, no significant differences were found between the reflexology group and the other groups regarding breast cancer-specific health-related quality of life, depressive symptomatology, state anxiety, pain, or nausea .This study contradicts the findings of another large-scale trial that also investigated the effects of reflexology in breast cancer patients . The secAnother recommendation in the new cancer pain guideline, recommendation 1.9, mentions reflexology or acupressure, despite the lack of supporting studies specifically for acupressure. The only area that has sufficient evidence to support the recommendation is acupressure for procedural pain, as previously discussed in recommendation 1.11. Recommendation 1.9 is considered to have low-quality evidence, with only two supporting studies, and is classified as a weak recommendation for patients experiencing chemotherapy-induced peripheral neuropathy. Both studies randomized approximately 60 patients into two groups: a control group and a reflexology group. No adverse effects were reported in either study . The secHypnosisHypnosis is a technique in which a professional suggests that a person undergoes changes in sensations, perceptions, thoughts, or behavior. It has been recognized as a valuable medical tool, with studies suggesting its benefits for pain management and the treatment of phobias, depression, dissociative disorders, and psychotic disorders, among others. A review conducted in 2014 found that hypnotic processes can modify both internal (self-awareness) and external  brain networks. Specifically related to pain, the review indicated that hypnosis can modulate the interconnected network of cortical and subcortical regions involved in processing noxious stimuli, leading to a significant decrease in pain sensation .According to recommendation 1.10, hypnosis can be considered as an option for patients who experience pain during surgical or procedural procedures. This recommendation is supported by 10 studies and is classified as having intermediate-quality evidence, resulting in a moderate recommendation. Among the 10 studies, six specifically focused on cancer patients undergoing breast biopsies, while the remaining studies examined procedures such as transrectal ultrasound-guided prostate procedures, percutaneous tumor treatments, and bone marrow aspirates and biopsies. Out of the 10 studies, nine concentrated on adult patients, with only one study specifically investigating pediatric cancer patients . The pedThe guideline highlights two well-designed studies that included an attention control group as well as a standard-of-care group. In both of these studies, hypnosis was provided throughout the entire procedure, rather than just shortly before it. These two trials serve as the basis for the moderate recommendation regarding the use of hypnosis in managing pain during procedures .The first study  involvedThe second study  involvedYogaYoga, an ancient practice, offers numerous mental and physical benefits. There are various types of yoga, with hatha yoga being the most popular. Hatha yoga combines different styles and emphasizes physical movements rather than stillness and meditation. It focuses on breath-controlled exercises called pranayamas, followed by a series of yoga postures known as asanas, and concludes with a resting period called savasana .Yoga incorporates breathing exercises, meditation, relaxation techniques, and poses that stretch and flex different muscle groups. It has been scientifically proven to reduce stress, promote mental calmness, and foster a connection between the mind and body. Generally, yoga improves overall quality of life, mood, and physical well-being. It also enhances physical functioning, the ability to perform daily activities, and the capacity to find meaning in the experience of illness. Additional benefits of yoga include reduced sleep problems, pain, fatigue, inflammation, and nausea. Moreover, it helps boost immune function and regulate stress hormones .The first weak recommendation with low-quality evidence is recommendation 1.2, which suggests offering yoga to breast cancer patients experiencing joint pain related to aromatase inhibitors. This recommendation is supported by only one randomized clinical trial . In thisAnother weak recommendation for using yoga in pain management among cancer patients is recommendation 1.6, which is supported by four randomized controlled trials with low-quality evidence. This recommendation suggests that hatha yoga may be beneficial for patients experiencing pain after undergoing treatment for breast or head and neck cancer. Two of the clinical trials specifically focused on breast cancer patients, while one involved myeloproliferative neoplasm patients, and the other included head and neck cancer patients.A study examining yoga for pain management in breast cancer patients involved 42 participants who were randomly assigned to two groups. Group 1 participated in a 10-week hatha yoga exercise program, while Group 2 engaged in a 10-week follow-up program that assessed the intensity of arm and shoulder pain. The yoga group exhibited a significant improvement in pain severity, and this improvement persisted even 2.5 months after the treatment, whereas the control group did not experience any notable difference in pain levels before and after the treatment .In another study focused on the feasibility of yoga for pain management in oncology patients, specifically 63 women with metastatic breast cancer, participants were randomized into either a yoga group or a support group. However, not all participants completed the trial, and post-intervention surveys were received from 87% of the randomized participants. Among the completed surveys, 80% of participants in the yoga group and 65% in the support group reported high satisfaction with the intervention .The sole study related to head and neck cancer was a small clinical trial with two groups, consisting of 40 patients who were randomized into an eight-week hatha yoga intervention group and a wait-list control group. In terms of feasibility, five patients from the yoga group discontinued early, while none did so in the wait-list control group. Efficacy measures indicated potential statistically significant benefits in terms of shoulder range of motion, pain, and anxiety .Overall, the studies that analyzed yoga as an oncology pain management strategy are very limited and primarily focus on feasibility. This is important because yoga involves more active and strenuous participation compared to practices like massage and hypnosis. However, larger studies are still needed to gain a better understanding of the benefits of yoga for cancer patients.Guided imagery with progressive muscle relaxationGuided imagery is the practice of using mental visualization to enhance mood and physical well-being. It involves creating mental images that engage the senses, such as sight, hearing, taste, smell, touch, or feeling. Positive guided imagery has been widely employed in cancer care and has shown effectiveness in promoting relaxation, reducing stress, improving mood, boosting the immune system, alleviating pain, and minimizing nausea and vomiting .On the other hand, progressive muscle relaxation (PMR) is a nursing intervention that involves sequentially tensing and releasing different muscle groups while attending to the resulting sensations. This technique can help release muscle tension associated with anxiety and promote mental calmness. PMR has also been utilized in cancer care and has demonstrated effectiveness in addressing fatigue, pain, nausea and vomiting, and anxiety, among other symptoms .Recommendation 1.7, which has weak evidence quality, suggests that guided imagery with PMR may be offered to patients experiencing general pain resulting from cancer treatment. This recommendation is supported by four key studies . The firAnother larger clinical trial, involving 104 patients, examined the combined effect of guided imagery and PMR. The patients were randomly assigned to two groups: Group A received guided imagery and PMR, while Group B received usual care. The study found that guided imagery and PMR were effective in alleviating pain-related distress in terminally ill cancer patients .A supporting study that validates recommendation 1.7 involved 67 patients in a randomized clinical trial. The patients were assigned to three groups: one group listened to relaxation training via audio tapes, another group received live relaxation training from nurses, and the third group received no relaxation training. The patients who received relaxation training showed significant reductions in subjective pain ratings .In contrast, another small clinical trial did not yield similar favorable results. In this study, 60 patients were randomized into three groups: guided imagery group, relaxation group, and control group. Despite the positive reception from patients, with 90% of them recommending the brief psychological intervention to others, the guided imagery and relaxation groups did not show clinically relevant influences on the postoperative physiological course of elderly patients undergoing conventional resections of colorectal cancer .Overall, the studies supporting the use of guided imagery with PMR as an oncology pain management strategy have limitations, including inconsistencies in the blinding of participants, health professionals, data collectors, and data analysts. Additionally, the limited number of favorable findings contributed to the weak strength of the recommendation .Music therapyMusic therapy encompasses various experiences such as listening to music, singing, playing instruments, or composing music. It is a clinical approach that utilizes music to achieve individualized goals, such as reducing stress, improving mood, and enhancing self-expression . Music tRecommendation 1.12, which has weak evidence quality, suggests that music therapy may be offered to patients experiencing surgical pain from cancer surgery. This recommendation is supported by three studies, although the quality of evidence is considered low . All thrIn the smallest study, 30 women undergoing mastectomy for breast cancer were randomly assigned to either the music intervention group or the control group. The study found that patients in the music intervention group experienced a greater decrease in mean arterial pressure, anxiety, and pain from the preoperative period until discharge from the recovery room, compared to women in the control group .Another randomized controlled trial examined the effects of music therapy on pain reduction in patients with breast cancer after radical mastectomy. A total of 120 breast cancer patients were randomly and equally divided into a music intervention group and a control group. Music therapy was found to significantly reduce the total pain rating index score in the music intervention group compared to the control group. The researchers concluded that music therapy has both short-term and long-term positive effects in alleviating pain among breast cancer patients following radical mastectomy .A randomized parallel trial investigated the impact of postoperative intravenous sufentanil patient-controlled analgesia combined with music therapy versus sufentanil alone on hemodynamics and analgesia in patients with lung cancer. Sixty patients were randomized into a music therapy group (receiving sufentanil) and a control group (receiving only sufentanil). Both groups received intravenous patient-controlled sufentanil analgesia. The results showed that the music therapy group had significantly lower systolic and diastolic blood pressure and heart rate scores within 24 hours after surgery compared to the control group. Additionally, the music therapy group required a lower frequency of postoperative analgesia and a lower sufentanil dose compared to the control group. The study concluded that the combined effect of music therapy and sufentanil improves the effects of intravenous patient-controlled analgesia compared to sufentanil alone after lung cancer surgery .Overall, despite the limited number of studies, it can be inferred that music therapy can be an effective tool in pain management for oncology patients. Further research in this area would strengthen these claims and potentially expand on the positive results.DiscussionNone of the evidence presented in the guideline  reached Among the 13 recommendations, seven were supported by low-quality evidence, indicating a low level of confidence in the available evidence accurately representing the true magnitude and direction of the net effect. Further research has the potential to modify the magnitude and/or direction of this net effect. All recommendations based on low-quality evidence were classified as weak recommendations, except for recommendation 1.5 . DespiteA weak recommendation is established when there is limited evidence regarding the true net effect, with some consistent results but important exceptions. Concerns may arise regarding the quality of the studies and potential disagreements among panelists. Individual considerations and other factors are taken into account, providing some level of confidence that the recommendation offers the best current guidance for practice .A strong recommendation, which was not included in the guideline, would require a high level of confidence that the recommendation reflects the best practice . Given tAcupuncture had the highest number of overall studies, with a total of 36 supporting studies. However, massage therapy had the most recommendations, with five out of 13. An interesting observation is the discrepancy between recommendations 1.4 and 1.9 [Recommendation 1.9 is controversial, as acupressure is not mentioned and it only has two very small randomized clinical trials as supporting evidence. This raises questions about the effectiveness of reflexology for patients experiencing chemotherapy-induced peripheral neuropathy from cancer treatment. Therefore, more studies are needed to determine if this recommendation is justified .As demonstrated in a study conducted in a tertiary hospital in India, there is still significant resistance among physicians to recommend integrative medical practices to their patients . ConductThe current guidelines on integrative medicine therapies for managing cancer pain provide recommendations based on available evidence. Acupuncture is moderately recommended for aromatase inhibitor-related joint pain in breast cancer patients, while yoga has a weak recommendation supported by only one study. Acupuncture and reflexology have reasonable evidence for alleviating general cancer pain or musculoskeletal pain, but acupressure lacks supporting studies. Limited evidence supports the use of general massage, hatha yoga, and guided imagery with progressive muscle relaxation for general cancer pain or musculoskeletal pain. Acupuncture and reflexology are options for chemotherapy-induced peripheral neuropathy, with stronger evidence supporting acupuncture. Procedural hypnosis is the strongest recommendation for procedural or surgical pain, and acupuncture, acupressure, and music therapy are also effective strategies. Classic massage is recommended for palliative and hospice care pain. Patients experiencing chemotherapy-induced peripheral neuropathy can consider acupuncture and reflexology as options, with stronger evidence supporting the benefits of acupuncture. No evidence was provided to recommend acupressure for chemotherapy-induced peripheral neuropathy. Mind-body interventions, natural products, music therapy, and topical pure emu oil did not meet the inclusion criteria. Further research is needed to better understand the role of integrative medicine in cancer care, and physician education on its benefits is crucial. In conclusion, further research is necessary to gain a better understanding of the role of integrative medicine interventions in the care of patients with cancer. Additionally, greater efforts should be made to educate physicians about the benefits of integrative medicine for cancer patients.


The 2-year incidence of brain metastases (BrMs) in stage III non-small lung cell cancer (NSCLC) has been estimated to be around 30%. However, recent clinical trials have demonstrated considerably lower BrMs rates in this patient population. In this study, we aimed to review the real-world incidence, surveillance, and treatment patterns of BrMs in stage III NSCLC.Using a retrospective single-center study design, we identified patients with stage III NSCLC who received radiation with curative intent over a 10-year period. Outcome variables included BrMs incidence, overall survival (OS), and survival from date of BrMs. Additionally, we assessed patterns of BrMs surveillance in stage III NSCLC and treatment.p < 0.01). Similarly, a higher 2-year BrMs incidence was observed in patients who received planned surveillance brain MRI relative to those who did not, although statistical significance was not reached. Stereotactic radiosurgery (SRS) treated 29 of BrMs patients (78.4%) and was preferred over WBRT, which treated only 3 patients (8.1%).We identified a total of 279 stage III NSCLC patients, of which 160 with adequate records were included in the final analyses . The median OS for the entire cohort was 41 months , while the median time from BrMs to death was 19 months . Twenty-three patients (14.4%) received planned surveillance brain MRIs at 6, 12, and 24 months after completion of treatment. The remaining 137 patients (85.6%) received brain MRIs at systemic recurrence (restaging) or when neurologically symptomatic. A total of 37 patients (23%) developed BrMs, with a 2-year cumulative BrMs incidence of 17% . A higher incidence of BrMs was identified in patients with adenocarcinoma relative to those with squamous cell carcinoma (At our center, BrMs incidence in stage III NSCLC patients was lower than historically reported but notably higher than the incidence described in recent clinical trials. Routine BrMs surveillance potentially allows earlier detection of asymptomatic BrMs. However, asymptomatic BrMs were mostly detected on restaging MRI at the time of recurrence. Lung cancer is the leading cause of cancer death worldwide, accounting for 23% and 24% of all deaths by cancer in females and males respectiely . Non-smaWith recent advances in diagnostic imaging and rapid accessibility to brain MRI, the true incidence of BrMs in stage III NSCLC in a real-world  setting remains unclear. Given that up to one third of stage III NSCLC patients often develop BrMs over their disease course, our local practice has evolved to performing surveillance brain MRI at 6, 12, and 24 months after completion of initial treatment. Nonetheless, the support for routine asymptomatic BrMs surveillance in this patient population remains to be demonstrated.In this study, we aimed to determine the real-world incidence of BrMs in stage III NSCLC and analyze the surveillance and treatment patterns of BrMs in this patient population.th edition staging criteria). All patients whose treatment plan included radiation with curative intent were included, regardless of treatment completion. The following information was collected: age at diagnosis of stage III NSCLC, diagnostic imaging findings , pathology results, disease staging, radiation, and treatment plans [including whether prophylactic cranial irradiation (PCI) was utilized for BrMs prevention], and available follow-up visit information within the prior 6 months, or date of death. A total of 160 stage III NSCLC had complete data and were included in the final analyses of this study. Patients who completed treatment and surveillance elsewhere, did not have available follow-up data, or had a second primary cancer with high potential for brain metastatic disease , were excluded .The following time to event outcomes were assessed and analyzed for the entire cohort as well as for each NSCLC histology subtype. The time to overall survival (OS) outcome was summarized using Kaplan-Meier curves. The time to OS was defined as the time from date of diagnosis until death from any cause, and patients who were still alive at the completion of analysis were censored at the date of the last follow up. The time to BrMs outcome was analyzed using competing risk methods and summarized using cumulative incidence curves. Time to BrMs was defined as the time from date of diagnosis until date of BrMs with death as a competing event. Patients who experienced neither BrMs nor death were censored at the date of last follow up. The cumulative incidence of BrMs was calculated over a 2-year period. The OS from date of BrMs was defined as the time from date of BrMs until death from any cause, and patients who were still alive were censored at the date of the last follow up. The “number needed to scan” to detect asymptomatic BrMs was calculated as the total number of patients needed to get surveillance brain MRI to detect asymptomatic BrMs for the entire cohort and for patients with adenocarcinoma subtype (the most common histopathology subtype).Descriptive statistics were utilized to summarize the characteristics of the study cohort. Chi-square tests were applied to assess outcome differences between histology subtypes. All tests were two-sided with an alpha level of 0.05. All analyses were performed in SAS v9.4 .A total of 160 patients  with stage III NSCLC were included in the final analyses of this study, see p < 0.01; see The median OS from time of diagnosis for the entire cohort was 41  months. In patients with adenocarcinoma, the median OS was 51  months. Meanwhile, the median OS was 22  months for those with squamous cell carcinoma and 21  months for those with other histology subtypes. The higher OS in patients with adenocarcinoma relative to patients with squamous cell carcinoma was statistically significant  received PCI at an outside institution prior to establishing care at our cancer center. Neither of these two patients developed BrMs. Institutionally, we offer surveillance brain MRI at 6, 12, and 24 months after completion of treatment. Twenty-three patients (14.4%) received planned surveillance brain MRI to screen for asymptomatic BrMs. For the remaining patients n = 137, 85.6%), in accordance with current guidelines 5.6%, in , no planA total of 37 patients (23%) developed BrMs. Of those, 20 (54.1%) were asymptomatic. On initial BrMs identification, 18 patients (48.7%) had one brain metastasis. Meanwhile, 8 patients (21.6%) had 2-3 BrMs and 11 (29.7%) had >3 BrMs. The estimated 2-year cumulative incidence of BrMs was 17%  for the entire cohort, see p < 0.01), see Based on histology subtype, 29 patients with adenocarcinoma  developed BrMs. Of the 53 patients with squamous cell carcinoma, 6 (11.3%) developed BrMs. Meanwhile, in the 11 patients with other histology subtypes, BrMs was identified in 2 (18%) patients. The higher incidence of BrMs in patients with adenocarcinoma [2-year BrMs incidence was 21.5% (13.7-30.4)], compared to squamous cell carcinoma [2-year BrMs incidence was 7.9% (3.5-17.6)], was statistically significant  for all patients. No significant differences were noted in time from BrMs to death between NSCLC histology subtypes see Table 1.In patients with BrMs (n = 37), stereotactic radiosurgery (SRS) was utilized to treat 29 patients (78.4%) and whole brain radiation therapy (WBRT) was used to treat 3 patients (8.1%). The remaining 5 patients (13.5%) were treated with systemic therapies alone, without any form of radiation therapy, and were clinically monitored.Among patients who received no BrMs surveillance (n = 137), 31 developed BrMs (22.6%), 17 of whom were asymptomatic. Meanwhile, among the 23 patients who received surveillance brain MRI, 6 developed BrMs (26.1%), of whom 3 were asymptomatic see Table 2.Based on the total number of patients who did not develop BrMs (n = 123), the number of patients needed to receive surveillance brain MRI scans to detect 1 asymptomatic BrMs is 7 for all histology subtypes.Focusing on adenocarcinoma patients , 79 (82.3%) received no BrMs surveillance. Meanwhile, 17 (17.7%) patients received surveillance brain MRI according to our local practice. Among adenocarcinoma patients who received no BrMs surveillance (n = 79), 25 developed BrMs (31.6%), 13 of whom were asymptomatic. In the 17 adenocarcinoma patients who received surveillance brain MRI, 4 developed BrMs (23.5%), of whom 1 was asymptomatic Table 3.In this single-center study, we assessed the real-world incidence of BrMs in stage III NSCLC in the modern era of cancer staging and rapid access to advanced diagnostic imaging, including whole body PET/CT scans and brain MRI. The estimated 2-year incidence of BrMs in stage III NSCLC patients treated at our center was 17%. This estimated BrMs incidence is lower than historically described . Yet, itDue to increasing life expectancy of cancer patients and advances in diagnostic imaging, the incidence of BrMs in all cancer patients (in particular asymptomatic BrMs) is generally increasing . InteresAlthough our sample was likely enriched for targetable mutations (such as EGFR and ALK rearrangements), it remains a close representation of the real-world stage III NSCLC patient population treated at specialized cancer centers, with adenocarcinoma and squamous cell carcinoma histology subtypes comprising 60% and 33% of our cohort respectively. The incidence of BrMs was higher in patients with adenocarcinoma relative to other histology subtypes, with 30% of our patients with adenocarcinoma subtype developing BrMs. This is in alignment with the evidence of higher BrMs rates in adenocarcinoma subtype, especially in those harboring targetable mutations, such as EGFR and ALK rearrangements –16. LikeThe clinical practice of BrMs surveillance in stage III NSCLC remains controversial. Surveillance brain MRIs are not explicitly recommended and current stage III NSCLC guidelines, including the 2020 National Comprehensive Cancer Network (NCCN) guidelines , recommeRecently, our group reviewed the landmark trials that investigated PCI in stage III NSCLC . Despiteth edition classification system. Lastly, given that our center is a major academic center, there is a possibility that most of the patients who continued long-term follow-up represent a population of patients that are often doing clinically better than those who were lost to follow-up.This study has several limitations. Firstly, this is a retrospective single center study and thus the results are subject to bias. Compared to clinical trials settings, however, we believe this retrospective study was less limited by the strict inclusion/exclusion criteria often applied in clinical trials and thus had more potential to estimate a closer real-world incidence of BrMs. For example, patients participating in the PACIFIC trial successfully completed chemoradiation without disease progression prior to enrollment, whereas patients in this cohort were included if their treatment plan had curative intention, regardless of completion. Secondly, molecular testing (such as EGFR/ALK mutations status) was not available for all patients in our cohort and thus this relevant information was not incorporated in our analyses. Future studies are strongly encouraged to include the results of targetable mutations testing when assessing the association between stage III NSCLC BrMs predisposition and clinical outcomes. Thirdly, we considered the fact that the American Joint Committee on Cancer (AJCC) Classification of NSCLC underwent edition changes during our study period which may affect classification of stage III NSCLC patients. Although, we do not believe this had largely impacted our data as most of the study period comprised the 7In this retrospective single-center study, the 2-year incidence of BrMs in stage III NSCLC was 17%. This BrMs incidence is lower than historically reported, but higher than that reported in recent clinical trials. Although, we found surveillance brain MRI not superior to clinical monitoring in detecting asymptomatic BrMs, a trend of earlier BrMs detection was noted. Therefore, surveillance brain MRI may still be appropriate in selected subgroups of stage III NSCLC patients, such as patients with adenocarcinoma and those with high risk of recurrence. At our institution, PCI is not performed for stage III NSCLC and there is a clear preference to deliver SRS over WBRT to treat BrMs.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.SA, TL, RK, KT, BL, JN, SN: Conceptualization, methodology, writing, investigation, editing. RE, MD, SS, EP, AC, LV, HW, SP, KR: Writing, visualization, diting. All authors contributed to the article and approved the submitted version.


The effect of 6 weeks of treatment of NACVAN® was preliminary observed among 29 adult inpatients with spinal cord injury (SCI) or stroke-related CNP recruited to the experimental group. Pain intensity, neuropathic pain, and quality-of-life were measured at baseline (T0) and after 3 (T1) and 6 weeks (T2). Change in each outcome over time was assessed through a repeated measures analysis of variance or Wilcoxon matched-pairs test. Preliminary results show a significant reduction in pain intensity , neuropathic symptoms , and evoked pain . There were no significant reductions in other neuropathic pain dimensions and in quality-of-life components. No side-effects were detected. NACVAN® could have a beneficial adjuvant effect when used as an add-on to gabapentinoids in patients suffering from CNP due to SCI or stroke, with no adverse effect. Future analysis on a larger sample, compared with a placebo condition, could confirm these preliminary results.Gabapentinoids are first choice drugs for central neuropathic pain (CNP) despite limited evidence of efficacy and side effects affecting therapy outcomes. Nutraceuticals could improve their efficacy and tolerability. Our aim is to investigate the effect of NACVAN The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain (IASP) defines neuropathic pain (NP) as a type of pain caused by an injury or pathology of the somatosensory system, either peripherally or centrally . It affeWhen NP develops because of an injury or a pathology affecting the brain, brainstem, or spinal cord, it is defined central neuropathic pain (CNP) . It is oCentral neuropathic pain (CNP) following stroke or SCI is among the most complicated to manage. Pain resolution is unlikely, and clinically meaningful relief often corresponds to a two-point reduction in pain intensity on a numerical rating scale (NRS) at best. Treatment recommendations come from very few randomized controlled trials (RCTs) or algorithms created for the management of peripheral neuropathic pain, but patients with CNP are often unresponsive to pharmacological agents used to treat peripheral neuropathic pain .Gabapentinoids are the drugs that have shown greatest efficacy in the treatment of NP in RCTs . In partGabapentinoids and pregabalin are generally well-tolerated but can cause adverse effects including dizziness, drowsiness, peripheral edema, weight gain, asthenia, headache, and dry mouth . These sThere is, therefore, a need for strategies to improve the efficacy and tolerability of gabapentinoids and pregabalin.Different studies have suggested the potential role of nutraceuticals as adjuvants of pharmacotherapy in the field of NP. For example, B complex has important neuroprotective and neuroinflammatory effects, and numerous studies have shown that B1 (thiamine), B6 (pyridoxine), and B12  exercise an analgesic effect in different NP conditions, especially when taken in combination . These vCurcumin, a phenolic compound derived from Curcuma longa, has been found to have an analgesic effect in several pain conditions, including osteoarthritis, chronic post-surgical pain, and rheumatoid arthritis ,19. CurcSimilar results have been obtained for N-acetylcysteine (NAC), an endogenous molecule with high antioxidant properties that has shown efficacy in reducing NP by inhibiting matrix metalloproteinases . NAC appThe methanolic extract of Boswellia dalzielii, a tree plant prevalent in the Maghreb region, could be an additional, useful therapeutic agent for both the prevention and therapy of different pain conditions, as evidenced by a study recently conducted in animal models . The stu®—consisting of NAC (300 mg), turmeric extract (211 mg), Boswellia extract (200 mg), and vitamins B1 (10 mg), B6 (5 mg), and B12 (2.5 mcg). The use of this compound, therefore, could have potential benefits in different pain conditions, especially those with neuropathic characteristics, as an adjuvant of the standard pharmacotherapy. Indeed, convincing evidence has been already provided for the use of the combined use of gabapentinoids, with some of the substances within NACVAN® for some NP conditions . Preliminary controls for normality (Shapiro–Wilk test) were performed. Change in each outcome over time (T0–T1–T2) was assessed through a repeated measures analysis of variance (ANOVA) or Wilcoxon matched-pairs test, where appropriate. All statistical analyses were performed using SPSS v. 25.0 for Windows . All tests were two-tailed, and a ® intake period for an early discharge from the SU.During the study period, 29 patients were considered eligible based on the inclusion/exclusion criteria. Of these, 24 completed the study successfully, while 5 participants dropped out before the end of the NACVANBaseline socio-demographic and clinical characteristics of the final sample are shown in All 24 patients completed the questionnaires in full. The data distribution was normal except for pain intensity (NRS) at T0; the total score of the NPSI at T0, T1, and T2; the NPSI subscale “paroxysmal pain” at T0, T1, and T2; the NPSI subscale “burning  spontaneous pain” at T0, T1, and T2; and the PCS score of the SF-12 at T0.p = 0.021), from T0 to T2 , and from T1 to T2  , 7.25 after 3 weeks (T1), and 6.79 after 6 weeks (T2). The reduction in pain intensity was significant from T0 to T1  . Individp = 0.024) and from T0 to T2 , but not significant from T1 to T2  , 27.25 after 3 weeks (T1), and 25.77 after 6 weeks (T2). The reduction in the NPSI total score was significant from T0 to T1  . Individp = 0.048), but not significant from T0 to T1 (p = 0.376) nor from T1 to T2 (p = 0.213)  at baseline (T0), 11.56 (±7.23) after 3 weeks (T1), and 10.68 (±7.15) after 6 weeks (T2). The reduction in the NPSI subscale “evoked pain” score was significant from T0 to T2 (= 0.213) . IndividThere were no significant reductions in scores of the NPSI subscales “burning  spontaneous pain”, “pressing (deep) spontaneous pain”, “paroxysmal pain”, and “paraesthesia/dysesthesia”, and in physical (PCS) and mental component summary (MCS) scores of the SF-12.® intake. Overall, 33.3% of patients did not recognize any change after the NACVAN® intake, while 66.7% of them declared to feel somewhat better after the NACVAN® supplementation.® intake period.Participants reported no side-effects during the NACVAN® could have a beneficial adjuvant effect in these patients, with no adverse effect. Specifically, it could help in reducing the perceived intensity of pain and NP symptoms, in particular evoked pain, already after 3 weeks of intake. The aim of the present study was to evaluate the effects of a new commercially available nutraceutical, used as an add-on to gabapentinoids, on pain intensity and different dimension of NP in patients affected by CNP due to SCI or stroke. Results suggest that NACVAN® compounds. A recent systematic review and meta-analysis already highlighted how nutraceutical compounds can lead to an improvement in preclinical NP models [Our results confirm pre-clinical findings on the antinociceptive mechanisms of nutraceuticals and, specifically, of the NACVANP models . ParticuP models . In anotP models  pointed P models ,34.NAC may alleviate NP by improving the immune response and reducing oxidative stress, inflammatory responses, and the release of pro-inflammatory substances. Moreover, it may have neuroprotective effects, by modulating the activity of various neurotransmitters and receptors involved in pain transmission. NAC also influences excitatory and inhibitory pain signaling in the central nervous system, by interacting with glutamatergic and GABAergic systems and with the activity of ion channels . MoreoveCurcumin may have a specific effect on NP due to its affinity with the transient receptor potential vanilloid 1 (TRPV1), whose role in the genesis of NP has been found by several studies on animal models ,21,22. ABoswellia can alleviate NP by reducing immune and inflammatory responses . Moreove® compounds in humans. B vitamins has been found to relieve different symptoms of NP in a non-interventional study on patients (N = 411) with NP of different etiologies [Clinical trials testing the effect of nutraceuticals in humans are rare compared to the greater number of pre-clinical studies in this field, and our results appear, therefore, relevant. Only a few studies have in fact tested the effectiveness of the NACVANiologies , and to ents N = 1 with NPiologies .Our study can be relevant also because it has tested the effect of a nutraceutical compound acting as an add-on to gabapentinoids in patients suffering from CNP due to SCI or stroke, i.e., central NP conditions particularly difficult to manage. A recent preclinical study also tested the efficacy of an adjunctive nutraceutical treatment to an ineffective dose of gabapentinoids, showing that the co-administration resulted in a reduction in the NP intensity , and suggesting, therefore, an adjunctive effect of the nutraceuticals . In recent years, nutraceuticals have garnered significant interest both among patients and clinicians for various factors including: the involvement of inflammation and neuroinflammation mechanisms in the chronification of pain, the absence of adverse effects (much appreciated in patients with multimorbidity), the relative cost-effectiveness, and the possibility of combining them with common pain-related drugs to reduce their dose ,45. The ® in SCI and stroke patients, due to the small number of the stroke patients recruited, represent another study limitation. SCI and stroke are the main causes of CNP and patients with these conditions are often grouped together; however, we cannot exclude a different effect of NACVAN® in the two subgroups of patients [The reported findings must be considered with caution given the small number of the recruited patients and the lack of a control group. To further validate these initial findings, future investigations have to encompass a more substantial pool of participants and involve a placebo-controlled group. The lack of a comparison between the effect of NACVANpatients ,49,50. T® could have a beneficial adjuvant effect on pain intensity and on different dimensions of NP, with no adverse effect, among patients with CNP following SCI or stroke. These findings support continued research on the role of NACVAN® as an adjuvant to gabapentinoids in this population. Future analysis on a larger sample, compared with a placebo condition, could confirm these preliminary results that may be of particular interest given the recognized difficulties in the treatment of CNP conditions.Even taking into consideration the study limitations, our preliminary observations suggest that NACVAN


Conclusion: Distraction through an anti-stress ball reduces the perception of pain experienced by the chronic renal patients undergoing haemodialysis. However, the trial’s retrospective registration may introduce a risk of selective-outcome reporting. Further research with prospectively registered trials is recommended to validate the findings. Background: Pain in patients under haemodialysis affects the quality of life of chronic renal patients. Distraction has been effective in controlling pain induced by the insertion of needles. Once applied adequately, distraction promotes endorphin release, with efficacy in acute pain management. This study evaluates pain perception while puncturing the haemodialysis device, using an anti-stress ball as a distraction strategy. Methods: This study is a retrospectively registered pilot randomised controlled trial of 47 chronic renal patients undergoing regular haemodialysis programs in a dialysis unit, in the central region of Portugal. Patients were randomly allocated into control and intervention groups. The intervention group received an anti-stress ball on the opposite limb of the vascular access, while the control group underwent pain evaluation without any intervention. Pain was monitored using a numeric pain scale. The study aimed to evaluate pain during vascular access cannulation and explore the potential benefits of using an anti-stress ball to reduce this pain. Results: Patients in the intervention group experienced significantly lower pain scores (−1.23;  Kidneys maintain fluid, electrolyte, and metabolic-acid balance . Kidney Raghibi et al. (2018) showed that distraction effectively controls pain resulting from needle insertion. Distraction aims to divert concentration away from the painful stimulus and can reduce anxiety, fear, and pain intensity itself. When properly performed, distraction promotes endorphin release, which is effective in acute pain management .®) as ones that had the most effective results in reducing pain [Three strategies have been identified in reducing pain during cannulation of the arteriovenous fistula for haemodialysis: (1) puncture technique, indicating the buttonhole technique as the one that translates a lower level of pain during cannulation; (2) use of non-pharmacological therapies, such as transcutaneous electrical stimulation, placing the users’ feet in hot water ten minutes before puncture, cryotherapy at the puncture site, acupuncture, audio-visual distraction techniques, and aromatherapy with lavender essence, or thermotherapy of the vascular access ; and (3) application of local anaesthetic before puncturing the venous access, identifying creams based on lidocaine and prilocaine , using the numeric pain scale for all patients. This initial pain assessment was conducted without any intervention, as pain was not previously evaluated.n = 47).The required sample size was calculated based on a 95% confidence level, a margin of error of 5%, a 1.2% proportion of the condition, and a population size of 10,000,000 people. The calculated sample size was 35 participants. However, the study used a convenience sample, which included all eligible participants , using the numeric pain scale for all patients. This initial pain assessment was conducted without any intervention. Overall, the study aimed to evaluate pain during vascular access cannulation and explore the potential benefits of using an anti-stress ball to reduce this pain.When starting the intervention, the control group continued pain assessment without any intervention, while the intervention group received the distraction technique in addition to pain assessment by scale. The study was divided into two parts, with four weeks designated for its application . EnrolmeNo adverse events or harms were reported by the participants during the study. The use of an anti-stress ball was a non-invasive intervention, and no negative effects were observed. The potential for harm in the future full-scale trial will be carefully monitored and reported.Data were collected using a form divided into three parts: sociodemographic characterisation, clinical characterisation, and assessment of pain perception using a numerical 0–10 scale. t-test to compare differences in pain scores between the intervention and control groups. Paired t-tests were employed to compare pain scores within each group before and after the intervention. The level of significance was set at p < 0.05. The IBM Statistical Package for the Social Science (SPSS®) v.27 software was used for data analysis.Data were analysed using intention-to-treat principles. Descriptive statistics were used to summarize demographic and clinical characteristics. The primary outcome of the pain level was analysed using an independent samples Ethical considerations were carefully addressed throughout the pilot study (DIAV-105 on 6 June 2022). All participants provided written informed consent before participating in the study, and their confidentiality was maintained by anonymizing data and ensuring that no personally identifiable information was disclosed. The study protocol was approved by the relevant institutional review board, and all research activities were conducted in accordance with the principles of the Declaration of Helsinki and local ethical guidelines.The pilot trial was registered with the RCT—NCT05729113, and the study protocol is available upon request. No significant changes were made to the protocol during the study. Any minor deviations from the protocol were documented and will be considered when designing the future full-scale trial.According to the results obtained in In the control group, 52.5% lived in a village, 26.1% lived in a town, and 21.7% lived in a city. For the intervention group, 37.5% lived in a village, 29.2% lived in a town, and 33.3% lived in a city. Most of the sample had completed primary education (56.5% in the control group and 50.0% in the intervention group), and the meantime on dialysis was 65.96 (SD = 73.12) months in the control group and 79.21 (SD = 85.84) months in the intervention group. Regarding the type of vascular access, 95.7% of the control group used arteriovenous fistula (AVF) and 4.3% of prosthetic haemodialysis access (PHE). The time of use of vascular access, as shown in The vascular accesses were located in the wrist (13%), forearm (13%), elbow (39.1%), and arm (8%) in the control group. In the intervention group, 20.8% of the access was in the wrist, 20.8% in the forearm, 25% in the elbow, and 8% in the arm. As for the mean pain level , we fount-test showed statistically significant differences between the two groups concerning the reduction in mean pain levels before and after the intervention (p < 0.05). Statistically significant differences were observed between both groups concerning the mean pain before the intervention (p < 0.05).A Student’s Pain at the time of cannulation for vascular access during haemodialysis is a common concern for chronic renal patients who undergo this procedure three times a week. This procedure involves the insertion of needles into the patient’s arteriovenous fistula or graft, which can cause discomfort and pain. Patients may also experience anxiety and fear of the procedure, which can exacerbate their pain perception. Therefore, minimizing pain during this procedure is crucial to improving patients’ quality of life and promoting compliance with the treatment regimen ,13.The study’s results showed that the mean age of patients in both the control and intervention groups was consistent with the records of the Portuguese Nephrology Society, which indicated that the majority of patients undergoing renal function replacement treatment in Portugal are elderly, with a mean age of 67.5 years . In the Furthermore, the study found that the gender distribution of the patients was consistent with the SPN data, with males comprising the majority of patients in both the control and intervention groups. Specifically, the control group had 57% males and 44% females, while the intervention group had 58% males and 42% females. The study did not reveal any statistically significant differences related to gender or time under haemodialysis treatment, which is consistent with the findings of previous studies .Pain associated with cannulation is a common and significant problem in haemodialysis patients. Cannulation is the process of accessing the patient’s bloodstream through a vascular access point to remove blood and filter it through the dialysis machine. The most common types of vascular access points are arteriovenous fistula (AVF), arteriovenous graft (AVG), and central venous catheter (CVC). However, the cannulation process can be painful and uncomfortable, and patients often report anxiety and fear of pain associated with the procedure. Therefore, it is essential to manage pain during the cannulation process to improve the patient’s experience and adherence to the treatment. Different pain management strategies can be used, including topical anaesthetics, distraction techniques, and psychological support. Furthermore, healthcare providers should regularly assess and monitor pain levels in haemodialysis patients to ensure optimal pain management.These findings suggest that pain associated with vascular access cannulation is a common concern for patients undergoing haemodialysis. However, the severity of pain reported can vary across studies ,13,14,15p = 0.690), type of vascular access (p = 0.563), and duration of vascular access (p = 0.806) in relation to pain perception during vascular access cannulation, which is consistent with our findings [p < 0.05). In our study, we observed a reduction in the mean difference in pain before and after the intervention in both groups (p < 0.05). However, we did not observe any significant differences in pain perception between the different puncture sites (p > 0.05). Variables such as time on dialysis, type of vascular access, and duration of vascular access, also showed no statistical significance in reducing pain during vascular access cannulation for haemodialysis in either group (p > 0.01).Kaza et al. (2014) obtained statistically insignificant results for time on dialysis (findings . Howeverp < 0.002) [p < 0.05). A study by Nasirzadeh and collaborators, in 2019, compared two distraction techniques  as non-pharmacological strategies. Both techniques positively affected decreasing the mean pain level during arteriovenous fistula cannulation. The group that tested the effect of virtual reality had a significantly lower mean pain level compared to the guided visualisation group (p < 0.001) [p < 0.05) [Regarding the distraction effect on decreasing pain intensity at the time of needle insertion in the arteriovenous fistula for haemodialysis, Raghibi et al. 2018) concluded that distraction reduced the intensity of pain during needle insertion for haemodialysis (< 0.002) , which i< 0.001) . These r concludeThis study assessed the effectiveness of using an anti-stress ball as a distraction technique to reduce pain perception during vascular access cannulation for haemodialysis. Both control and intervention groups showed decreased pain perception between the first and second part of the study. However, the intervention group showed a greater difference in pain perception than the control group, with statistically significant differences. Participants in the intervention group reported the effectiveness of the distraction technique.Although the study findings provide valuable insights into the effectiveness of using an anti-stress ball as a distraction technique in reducing pain perception during vascular access cannulation for haemodialysis patients, there are several limitations to consider. First, the study had a small sample size, which limits the generalizability of the results. Second, the study was conducted in a single centre, which may not represent the broader population of haemodialysis patients in Portugal. Third, the study did not account for other factors that may contribute to pain perception, such as anxiety levels, individual pain tolerance, and the presence of comorbidities. Fourth, the study did not assess the long-term effects of the intervention, and it is unclear whether the intervention can sustainably reduce pain perception during vascular access cannulation over time. Lastly, the retrospective registration of the trial may introduce a risk of selective-outcome reporting.Further research is needed to explore the effectiveness of other non-pharmacological strategies in reducing pain perception during vascular access cannulation for haemodialysis. The lack of studies reporting on this issue highlights the need for more research in this field, including prospectively registered trials with rigorous randomisation methods.The study suggests that the anti-stress ball technique can be a useful intervention for pain reduction during vascular access cannulation for haemodialysis. The low cost of the anti-stress ball technique makes it a recommended intervention for healthcare professionals to consider when caring for haemodialysis patients. However, the trial’s retrospective registration may introduce a risk of selective-outcome reporting.Further research is needed to explore the effectiveness of other non-pharmacological strategies in reducing pain perception during vascular access cannulation for haemodialysis, with larger sample sizes and longer data collection periods, and multiple centres. Additionally, exploring other non-pharmacological strategies for pain reduction in haemodialysis patients could provide valuable insights and potentially improve patient outcomes. Prospective trials with rigorous randomisation methods are recommended to validate the findings of this study and advance the understanding of pain management in this patient population.