The results of this study showed a greater ability of the Comprehensive Complication Index if compared to the conventional Clavien–Dindo classification to predict hospital stay in colon cancer patients, particularly in patients with multiple postoperative complications. These results encourage the routine use of the Comprehensive Complication Index to grade postoperative complications in colonic surgery.(1) Introduction: To date, the sensitivity of the Comprehensive Complication Index (CCI) in a homogeneous cohort of colonic resections for oncologic purposes has not been reported. The present study aims to compare the CCI with the conventional Clavien–Dindo classification (CDC) in colon cancer patients. (2) Methods: The clinical data of patients submitted to an elective colectomy for adenocarcinoma were retrieved from a prospectively maintained database. Postoperative complications and length of stay were reviewed, and CDC and CCI scores were calculated for each patient. The association of the CCI and the CDC with the length of stay, prolongation of stay and readmission rate were assessed and compared. (3) Results: The overall postoperative morbidity was 26.9%. In particular, 157 (20.4%) patients had more than one complication. A strong correlation between the two scoring systems was observed . In multivariate analysis, CCI had a higher predictive ability for all endpoints. Regarding subgroup analysis, the difference between the CCI and CDC was progressively increased when evaluating outcome measures in complicated and multi-complicated patients. (4) Conclusion: Both scoring systems adequately report the overall burden of postoperative complications. The CCI showed a greater ability than the CDC to predict hospital stay, particularly in patients with multiple postoperative complications. Although the perioperative mortality rate following elective colon cancer surgery has been significantly reduced over the past few years, postoperative morbidity remains a significant issue ,2,3.Moreover, there is growing evidence that postoperative complications not only have a direct impact on short-term outcomes but also impact systemic inflammatory response, which may adversely affect the oncological outcome ,5,6.Currently, postoperative complications constitute a universally accepted marker of surgical outcomes and quality of care; however, their expression often lacks clear standardization ,8.In 2004, Clavien, Dindo and their colleagues proposed a five-grade classification  that remSince the score calculation is based on the most severe complication only, the Clavien Dindo classification (CDC) might underestimate the real burden of postoperative morbidity, especially in patients suffering multiple complications.To overcome this potential limitation, the Comprehensive Complication Index (CCI), which integrates the severity of each postoperative complication, was recently proposed . The CCIWhile this index has been validated in different or heterogeneous surgical procedures, clinical validation of the CCI in a homogeneous cohort of colon cancer patients has not been reported to date ,13,14,15Therefore, the present study aims to compare the ability of the CCI and CDC in predicting length of stay, prolongation of stay and readmission in a large cohort of patients who underwent elective surgery for colon cancer.The present study is reported according to the STROBE guidelines for the conducting and reporting of observational cohort studies .This is a retrospective analysis of a prospectively collected database including patients aged more than 18 years who underwent an elective colectomy for cancer at a tertiary referral university hospital between January 2010 and December 2018. Patients who underwent surgical procedure performed in an emergency setting were excluded.®) pathway for colorectal surgery [All patients were managed according to the Enhanced Recovery after Surgery  was evaluated from the time of the surgical procedure to the time of discharge. Prolonged LOS was defined as an inpatient hospital stay longer than the 75th percentile of postoperative LOS. Hospital readmission for any postoperative complication occurring within 30 days of discharge was recorded. The CDC and the CCI, as main outcome measures, were benchmarked and compared by evaluating their association with LOS, prolonged LOS and readmission rate.Patients’ characteristics were summarized using numbers and percentages for categorical variables and median with interquartile range for continuous variables. The distribution of CDC and CCI was described using boxplots, and the association between the two scores was evaluated using the Spearman correlation index.Using quantile regression, we estimated two univariate models for the median LOS using either CDC or CCI as independent variables. We compared the performance of the two models using a proper goodness of fit statistic . Two mulAll the analyses were performed using R (version 3.6.0).A total of 958 consecutive patients hospitalized for colonic cancer were extracted from our prospectively constructed database. Of these, 121 patients were excluded due to emergency procedures, and 52 patients dropped out due to palliative surgery without the removal of primary cancer.A total of 770 patients were included in the final analysis. The characteristics of the study population are depicted in Right colectomy was performed in 506 (65.7%) patients, while 264 (34.3%) patients underwent left colectomy.A successful laparoscopic procedure was performed in 378 (49.1%) patients, with an increasing rate over the years reaching 82% when considering the last five years of the study period.Postoperative outcomes are reported in Overall postoperative morbidity was 26.9%, while 157 (20.4%) patients had more than one complication. A major complication according to the CDC was observed in 7.4% of patients. The median postoperative length of stay was 8 days (IQR 7-11) and the 30-day readmission rate was 4.8%. The correlation between the two scoring systems was 78.8% (95%CI: 73.0–83.5%) in the subgroup of patients with at least one complication and 74.1% (95%CI: 66.1–80.4%) in the subgroup of patients with more than one complication.A similar median CCI score was observed in patients graded as 3b and 4a according to the CDC .Regarding the univariate analysis of the study population, both CDC and CCI showed a strong association with LOS, prolonged LOS and readmission; however, the CCI had a higher predictive ability for all endpoints . The mulRegarding univariate subgroup analysis, the difference in goodness of fit between the CCI and CDC progressively increased when evaluating LOS as an outcome measure in complicated  and multi-complicated patients . For the binary outcomes, prolonged LOS and readmission, an analogue increase in the difference of AUC values between CCI and CDC was observed in the two patient subgroups. Considering prolonged LOS, CCI showed a greater AUC compared to CDC in complicated patients  and patients with more than one complication .Considering readmission as the outcome, the CCI showed a greater AUC compared to the CDC in complicated  and multi-complicated patients .Once more, the aforementioned results were confirmed by the multivariate analysis.The present study validated the CCI in a monocentric homogeneous population of patients submitted to colonic surgery for cancer. Notably, the CCI had a greater ability than the CDC to predict hospital stay, particularly in patients with multiple postoperative complications.At present, the CDC is widely used for assessing and reporting postoperative morbidity. It focuses on the most severe form of complication, which is graded according to the invasiveness of the required treatment.This system has been extensively validated and gained wide application across different fields of surgery due to its ease and reproducibility.Nevertheless, the exclusive evaluation of the most severe postoperative complication constitutes an intrinsic limitation in reporting the overall morbidity burden of a surgical procedure.The CCI system considers each complication, resulting in a score ranging from 0 to 100, which represents the overall morbidity burden of a single surgical procedure.A better correlation of the CCI with a postoperative hospital stay when compared to the CDC was observed in a series of patients who underwent esophagectomy  and gastNotably, Slankamenac et al.  externalFurthermore, the CCI was identified as an independent predictor of readmission following colonic or rectal surgery in a cohort of 284 patients .To benchmark the CDC and CCI on a homogeneous population, patients undergoing rectal surgery or emergency colonic surgery were excluded from the present study. Focusing on a homogeneous study population with similar surgical complexity and overall postoperative morbidity burden is a fundamental prerequisite to clarify the role of CCI in predicting postoperative outcome indicators. As in previous studies ,13, the However, differently from other studies , reoperaOur study population has a high mean age and comorbidity rate, while laparoscopic surgery was performed in approximately half of the patients, and 40% of patients had stage III–IV colon cancer.In our experience, all of these factors might have a relevant impact on morbidity rate and severity, length of stay and readmission ,29,30. AIn the present series, 75% of eventful patients had more than one complication reflecting the complexity of both their preoperative characteristics and surgical procedures. Limiting the analysis to the subgroup of patients with more than one complication, the CCI showed a stronger association with hospital stay when compared to the CDC.The similar ability of the two scoring systems in predicting hospital readmission could be due to the small proportion of observed events. Again, CCI better predicts readmission than CDC in the subgroup of patients with more than one complication.The low proportion of patients with major complications could explain the small difference in the predictive ability of both indexes. The retrospective design is a limitation of the present study; however, the prospective data collection and a priori defined criteria to identify each postoperative complication might mitigate the possible bias in CDC and CCI score calculation. The single-center study design could potentially decrease the generalizability of our results; however, it might simultaneously result in lower discharge criteria variability. Moreover, differences in postoperative treatment of surgical complications were minimized by the monocentric design of the study.Notably, the large series of patients is a strength of the present study, mainly because it allowed selective analyses in patients with postoperative complications and the subgroup of patients with more than one complication.Especially when the rate of uneventful patients is high, limiting analysis on the overall series may translate into unreliable results.The CCI adequately reports the overall burden of postoperative complications in patients who underwent colonic resection for cancer. The CCI demonstrated a greater ability than the CDC to predict hospital stay, particularly in patients with multiple postoperative complications.


To assess the effect of low-level laser applied at 3 weeks intervals on orthodontic tooth movement (OTM) and pain using conventional brackets (CB). 2 energy was applied on 10 points  on the canine roots on the investigational side using gallium-aluminum-arsenic diode laser  in a continuous mode. Target tissues were irradiated once in three weeks for 9 weeks at a stretch . Patients were given a feedback form based on the numeric rating scale (NRS) to record the pain intensity for a week. Silicon impressions preceded the coil activation at each visit , and the casts obtained were scanned with the Planmeca CAD/CAM™  scanner.  Twenty patients with Angle's class II div 1  needing bilateral extractions of maxillary first bicuspids were recruited. Conventional brackets MBT of 0.022 in slot (McLaughlin Bennett Trevisi) prescription braces  were bonded. After alignment and levelling phase, cuspid retraction began with nitinol closed coil spring on 19 × 25 stainless steel archwire, wielding 150 gram force. 7.5 J/cmp < 0.05).  The regimen effectively accelerated (1.55 ± 0.25 mm) tooth movement with a significant reduction in distress on the investigational side as compared to the placebo side (94 ± 0.25 mm) ( This study reveals that the thrice-weekly LLLT application can accelerate OTM and reduce the associated pain. Fixed orthodontic treatment is a lengthy and time-consuming process and on average takes 12–36 months [Interventions such as a local injection of pharmacological agents, use of magnets or direct current, and invasive surgical approaches (corticotomy) trim the total treatment time by stimulating bone remodelling but at the expense of either increased patient's suffering or systemic side effects .Low-level laser therapy (LLLT) is being used to alleviate musculoskeletal pain for decades. However, its use in dentistry is gaining popularity as a noninvasive and safe modality. Moreover, its anti-inflammatory effects and potential to induce peripheral neural blockage makes it a suitable candidate for postactivation pain and healing of tissues .LLLT, when applied at correct intensity and duration, has been proven to amp up tissue healing by increasing cell proliferation , angiogenesis, and collagen synthesis . At the A handful of researchers document the effect of LLLT on OTM, but the diversity of results pertains to different laser specifications, dosages, points of application, and intervals of application results –12, therThis research was aimed at providing a single dose of LLLT application to expedite tooth movement and lessen the discomfort associated with it.This was the placebo-controlled clinical study, and the research was conducted in the Department of Orthodontics at Baqai Medical University, Pakistan. Twenty-two patients, age ranging from 12 to 30 years , with healthy medical and dental status (no missing or impacted teeth except third molars) and no history of orthodontic treatment were recruited in the trial.The inclusion criteria were patients with 1/4 or half cusp, molar class II division 1 warranting extraction of upper bicuspids on both sides. Patients who require lower premolar extraction were excluded from the study because simultaneous lower canine retraction interferes with the retraction of upper canines. Patients with TMJ problems or taking medicines that modify bone turnover or interferes with tooth retraction, e.g., NSAIDs, bisphosphonates, and corticosteroids, were disqualified.Regular diagnostic orthodontic records were collected and thoroughly examined after the approval from the ethical board of Baqai Medical University. The whole procedure was verbally explained, and assent form was signed from the patients and legal guardians of minors.Split-mouth design was chosen by flipping a coin to circumvent individual bias, randomly assigning one side as an experimental and the other placebo group.After all the necessary procedures, banding and bonding were carried out. MBT (McLaughlin Bennett Trevisi) of 0.22 inch slot prescription braces  were bonded. The first stage of levelling and alignment was commenced with 0.014 inch heat-activated nitinol (NiTi) wire and after that by 0.016 inch NiTi, 0.017 × 0.025 in NiTi, 0.019 × 0.025 inch NiTi, and 0.019 × 0.025 SS as the final working wire. The first bicuspid was then extracted at day 21, and individual canine retraction began with 6 mm close coil NiTi spring, stretched to 150 gm force, measured with the orthodontic dynamometer  and secured with a ligature tie between the power arm of canine and first molar band.LLLT irradiation was applied soon after the placement of spring on the experimental side and was held at the placebo side without turning it on . The spr2 diameter optical fibre tip in light contact with the oral mucosa.Ga-Al-As diode laser  operated at 940 nm wavelength in a continuous, uninterrupted beam of light was used. Irradiations were delivered through the 0.04 cmMesial and distal to the cervical area of the canineMesial and distal to the apical area of the canineOne point in the middle of the rootThe target area was irradiated on ten sites, five points buccally and five palatally, for 3 secs each. The areas were as follows:2 energy density. A separate room with loud music was reserved for the procedure. All the personnel wore protective shades near irradiated laser . To avoid the carryover effect, a plastic shield of the same wavelength as that of the laser was used.The power output set at 100 mW for 3 sec at each point made the cumulative of 7.5 J/cmx and y marks were drawn on 3D imageries of study cast [Y-axis was drawn a parallel to raphe line, and medial end of the prominent rugae marked the plane for the x-axis. The distance covered by canine was given by measuring the distance from x coordinate to the most distal point on canine on both the sides, and the two reading were later compared for the effectiveness.To assess the effectiveness of regimen, the comparison of right and left sides was made, i.e., experimental and placebo at T0, T1, T2, and T3. A system suggested by Gebauer was used, and udy cast . Y-axis The analgesic effect of the LLLT evaluated by a feedback form was designed based on 11 points (from 0 to 10) numeric rating scale (NRS) where zero indicates no discomfort and 10 excruciating, terrible pain.The form was given to the patient at each appointment and collected at the subsequent show-up. They were instructed to record the pain four hours after the activation and thereupon every 24-hour interval for the next 7 days. Patients were told not to take any analgesics if needed and advised to jot it down.U test was performed to compare the canine movement and Kruskal–Wallis test for pain comparison.Data were put in and interpreted on the SPSS 20.0 version. The Mann–Whitney 22 patients were recruited in the study, and two of them later were disqualified due to spring dislodgement and use of analgesics.U test shows a statistically significant acceleration in canine movement on the experimental side in comparison to the placebo group  was formulated using NRS in contrast to others who employed a visual analogue scale (VAS). NRS is more accurate and easily understood by patients of any age and educational background .In the present study, the pain rating was very low in the lased as well as the placebo group. Highest pain scores were reported on day 1 of coil activation, which agrees with the previous studies –33. ExpeApplication of LLLT at regular orthodontic visits  accelerates OTM and decreases the pain significantly. Hence, the above regimen can be implemented in fixed orthodontic treatment to avoid the risk of patient and operator burnout.


To analyze pain, functional capacity, quality of life, anxiety and depression outcomes in patients undergoing lumbar spine surgery following use of the Second Opinion Program, and to present disagreements regarding diagnoses and therapeutic indications between the first and second opinions. A prospective, observational cohort study with 100 patients enrolled in the Second Opinion Program who underwent lumbar spine surgery. Questionnaires addressing pain intensity, level of disability, quality of life, anxiety and depression were applied prior to and within 1, 3, 6 and 12 months of surgery. Descriptive and comparative statistical analyses were performed. The following clinical outcomes were analyzed: pain intensity, level of disability, quality of life, anxiety, and depression. In this sample, 88% and 12% out of 100 patients were submitted to lumbar decompression and arthrodesis, respectively. Patients reported improvements in function, pain intensity, and quality of life factors following surgery and were able to attain the minimal clinically important difference relative to the preoperative period. Agreement between the first and second opinions was observed in 44% of diagnoses, and in 27% of therapeutic indications. Patients had favorable postoperative outcomes regarding pain, disability, and quality of life. These findings and the high rates of diagnostic and therapeutic indication disagreements corroborate the need of a second opinion in cases of spine disease with surgical indications. Degenerative spine diseases affect a large proportion of the active population. The chronic nature of these conditions has negative impacts on patient quality of life and functional capacity, leading to limitation in activities of daily living, absenteeism, and high health care costs. In some cases, the condition may progress to sciatica due to involvement of nerve roots, resulting in radiating pain to the lower limbs.An estimated 80% of affected individuals report low back pain within 12 months of the first back pain episode and tend to seek treatment alternatives more frequently. particularly in cases with severe sciatica or neurologic changes. According to recent national and international clinical guidelines, conservative management consisting of physical therapy, acupuncture and other non-invasive methods should be the primary recommendation for patients with chief complaint of low back pain and sciatica pain, except in cases with red flags.Surgical management of spine diseases is being increasingly indicated,Multidisciplinary follow-up and use of validated questionnaires are vital to measure patient experience and treatment progression. Second Opinion Programs (SOP) aimed to improve patient quality of life, and reduce spine disease treatment costs are also important.Projeto Coluna (Spine Project) was developed at Hospital Israelita Albert Einstein (HIAE) to refine the approach and management of patients suffering from degenerative spine diseases. This initiative is a collaboration between HIAE and Brazilian health insurance companies and offers an alternative for patients seeking a second medical opinion.In 2011, a SOP program named The high number of surgical indications, the scarcity of studies supporting treatment effectiveness, the need of post-procedure follow-up and the rising number of second opinion visits in surgical cases justify novel studies investigating the role of SOP in the health system.This study set out to examine the clinical outcomes of patients enrolled at SOP who underwent spine surgery, and to identify the rate of disagreements regarding diagnoses and therapeutic indications between the first and second opinions in spine surgery.To analyze pain, functional capacity, quality of life, anxiety and depression outcomes in patients undergoing to lumbar spine surgery following use of the Second Opinion Program, and to present disagreements regarding diagnoses and therapeutic indications between the first and second opinions.This is a prospective, observational cohort study comprising 100 patients who agreed to the treatment proposed by the HIAE SOP. Inclusion criteria were individuals aged over 18 years with initial indication for surgical treatment due to degenerative spine conditions , no contraindications for general anesthesia or physical therapy, and good command of the Portuguese language.o, congenital deformities, tumors, confirmed or suspected pregnancy, previous spine surgery, or follow-up-related constraints (inability to read or complete questionnaires) were excluded.Patients with spinal fractures, scoliosis greater than 20The SOP of HIAE was launched in 2011 and introduced a much needed alternative prior to therapeutic decision making. For patients with indications for lumbar spine surgery according to credentialled physicians, the health insurance companies offer a second opinion visit at HIAE. These patients are then seen by a SOP rehabilitation physician or orthopedic surgeon. Visits consist of history taking, physical examination and analysis of previous test results. Each physician described the presumptive diagnoses, and ordered other tests as needed.In the SOP, conservative or surgical management may be indicated. In cases with indications for conservative treatment, patients can choose between treatment at HIAE or going back to their primary physician. In cases with surgical indication, patients are referred for the SOP surgical team using randomization criteria.Surgical approaches are selected during group discussions with orthopedic surgeons, neurosurgeons, and members of the multidisciplinary team (Spine Board), according to HIAE protocols and guidelines. These meetings are held weekly. Spinal decompression or arthrodesis at no more than two spinal levels may be indicated by the SOP team.Following spine Board decisions, treatment indications are communicated and discussed with the patient, who will then decide whether to go forward with the proposed procedure or seek external medical services.In this study, a total of 100 surgical patients were recruited by the SOP, between February 6, 2017 and November 29, 2018, and prospectively followed for 12 months after surgery.Patients who accepted the SOP proposal were immediately invited to participate by the team’s nurse. Those who accepted to participate signed an Informed Consent Form. Data were collected using questionnaires. The following pieces of data were collected: sociodemographic profile, diagnosis and treatment indication given by external and SOP physicians, severity of lumbar pain, functional disability, quality of life, anxiety, and depression. Questionnaires assessing clinical outcomes were applied in the preoperative period and within 1, 3, 6 and 12 months of surgery. with six response alternatives rated on a zero to five scale. The final score corresponds to the summed response score multiplied by two. Final scores range from zero (no disability) to 100% (maximum disability).The Brazilian version of the Oswestry Disability Index (ODI) was used to investigate spine-related functional disability. This questionnaire comprises ten questions addressing daily living domains,,9Pain intensity was assessed using the Visual Numerical Scale (VNS). This scale ranges from zero (no pain) to ten (maximum pain) and only one whole number must be selected.Anxiety and depression were assessed using the validated Portuguese version of the Hospital Anxiety and Depression Scale (HADS). This questionnaire comprises seven questions addressing anxiety and seven questions addressing depression . Maximum scores per domain is 21 points (summed score of 7 items rated 0 to 3). Scores higher than eight are a red flag for psychological symptoms.The EuroQoL-5D-3L (EQ-5D-3L) was used to measure quality of life. This questionnaire comprises five domains  and three response alternatives . The closer to one, the better the quality of life; the closer to zero the worse the quality of life.The following strategies were applied to minimize losses to follow-up: briefing about the importance of questionnaires and adherence to the study, scheduled (date and time) follow-up questionnaire application according to participant’s preference, matching follow-up questionnaire and medical visits to minimize the need to travel to the hospital, and regular update of telephone numbers and e-mail addresses. In that study, the mean pretreatment EuroQoL score achieved by chronic patients was 0.70 . Assuming a correlation of 0.5 and a minimal clinically important difference of 0.07 between measurements made at baseline and after 3 months, a sample size of 100 patients was deemed ideal for the surgical intervention group (assuming 55% of chronic patients would use the second opinion service).This study is part of a cohort comprising 100 patients undergoing surgical treatment and 90 patients undergoing conservative treatment following use of the SOP. Initial sample size estimation was based on van der Roer et al.Calculations were made using STATA, version 10.0. Statistical power was set at 90% and the level of significance at 5%.Demographic data were expressed as mean, median and standard deviation. Outcome data were expressed as mean scores.The minimal clinically important difference (MCID) according to disability (>12%), pain (>2 points) and quality of life (>0.03 points) questionnaires was also investigated.Instituto Israelita de Ensino e Pesquisa (IIEP).Quantitative data and parameters were analyzed with the assistance of the statistics consulting services of Patients were duly informed of their rights, follow-up periods, and the possibility of withdrawing their participation at any time after signing the Informed Consent Form.Hospital Israelita Albert Einstein, opinion # 1.804.215, CAAE: 59736016.0.0000.0071.This study was approved by the Research Ethics Committee of Over the course of the experimental period, 1,937 patients were referred to the SOP by health insurance companies. Of these, 1,491 were eligible, 476 accepted the SOP proposal, and 157 were referred for surgical assessment. A total of 100 patients agreed to participate. Lumbar decompression and lumbar arthrodesis were indicated in 88% and 12% cases, respectively. Eleven patients in the lumbar decompression group had to be reoperated due to recurrent disc herniation, infection, or hematomas. Only one patient in the lumbar arthrodesis group had to be reoperated due to infection .Postoperative follow-up was carried out within 1, 3, 6 and 12 months of surgery. Some patients did not return for follow-up questionnaire application. Within 1 month of surgery, 29 cases were lost to follow-up and one patient was hospitalized. In the third and sixth months, 39 and 25 cases were lost to follow-up, respectively. Within 12 months of surgery, 8 cases were lost to follow-up, one patient died, and one patient was hospitalized.Demographic data and characteristics of patients included in the study are shown in Scores obtained over the course of postoperative follow-up are shown in Patients reported moderate pain intensity prior to surgery . Pains scores dropped significantly  within 1 month of surgery, with approximately 70% reduction in pain intensity within 12 months. Pain scores did not differ significantly across remaining follow-up assessments.EQ-5D-3L scores increased over the course of follow-up relative to baseline. EQ-5D-3L were significantly higher at 12 relative months relative to one month after surgery.Score variations across different follow-up time points are shown in The analysis revealed disagreement on diagnoses and therapeutic indications between the first and second opinions in 56% and 73% of cases, respectively. External physicians recommended high-complexity interventions (lumbar arthrodesis) in 47% of cases, with only 31% patients allocated to lumbar decompression. In contrast, less complex interventions (lumbar decompression) were indicated in most cases (88%) seen by the SOP team. According to the first opinion, ten patients would require more than one procedure. Hence, the number of procedures totaled up 110 .In this study, patients undergoing surgical treatment after enrollment in the SOP achieved better functional capacity, pain, and quality of life outcomes. This study also revealed significant disagreements regarding diagnoses and therapeutic indications between the first and second medical opinion among physicians. In this study, follow-up assessment and validated questionnaires were used to measure improvements in the functional capacity, pain intensity, and quality of life.According to Del Castillo et al., surgical patient follow-up using specific questionnaires is extremely important for appropriate case management.,16 whereas in others the condition was more prevalent among women, often due to inappropriate posture, household chores, and smaller muscle mass.-19 In this study, pain perception was not associated with sex .Low back pain is a heterogeneous condition. Therefore, affected patients are not well-characterized. Higher prevalence has been reported among men in some studies,,19 This is thought to reflect bone, ligament, and muscle changes, loss of flexibility and adoption of inappropriate postures over time, along with age-related comorbidities and degenerative diseases, such as arthritis. Patients in this sample were comparatively younger . It has been suggested that the daily routine of working age individuals living in large cities may be related to early development of chronic low back pain. This may be explained by changes in intervertebral disk pH and nutrition induced by factors, such as longer working hours, long commuting, and greater exposure to tobacco chemicals. In this population, leisure time, preventive health care, and search for quality of life, are often not prioritized.In recent studies, patients undergoing spine surgery were aged over 50 years on average.Psychosocial compromise may interfere with assessment of outcomes, such as functional capacity and quality of life. Biopsychosocial factors are thought to have significant impacts on postoperative outcomes in patients submitted to spine surgery. Pain catastrophizing may also have negative impacts on postoperative pain intensity and functional capacity levels. Hence, the significance of psychologic screening and risk factor identification in patients with persistent pain.Depression and anxiety are the most widely reported psychological factors among patients scheduled for spine surgery and are associated with poorer outcomes.Some patients who did not report pain had functional impairments and low quality of life perception. These findings suggested, even in the absence of pain, these patients faced difficulties in activities of daily living, with direct impacts on their quality of life. However, lumbar spine surgery may have positive impacts on pain intensity, functional capacity, and quality of life even in patients with moderate biopsychosocial risk.Improvements in psychosocial and quality of life outcomes in this study emphasized the relevance of appropriate follow-up and care of patients with chronic low back pain. Findings presented are congruent with the current literature regarding the value of preoperative screening via application of validated questionnaires, and identification of factors with potential impacts on patient outcomes for timely intervention. In one study, 71% of patients undergoing spine surgery reported radiating pain to lower limbs prior to surgery. Likewise, 89% of patients in this study had preoperative sciatica.Radiating pain to lower limbs in response to nerve root compression is another common clinical condition with surgical indication in patients suffering from degenerative spine diseases. In this study, similar therapeutic recommendation were given in only 27% of cases. These findings emphasize the significance of a second medical opinion for enhanced assertiveness, since therapeutic alternatives are discussed among several specialists, according to institutional guidelines.As to therapeutic indication disagreements, a prospective study with 437 patients with cervical or low back pain revealed differences between the first and second medical opinions in 41.9% of cases. In that sample, only 6% of patients were given similar therapeutic advice in the first and second visits. In this study, this indication prevailed in approximately 90% of cases seen by the SOP team and translated into clinical improvement. Reoperation rates of 6% have been reported in patients submitted to open or endoscopic lumbar decompression due to recurrent disk herniation. Similar reoperation rates (5%) have been detected in this sample.With regard to surgical interventions indicated for degenerative spine conditions, lumbar decompression is a less invasive and cheaper procedure, with shorter length of hospital stay, and lower complication rates.Lumbar arthrodesis is a more complex procedure relative to lumbar decompression, with higher complication rates in more than 12% of cases.This study has some limitations, such as poor patient adherence to follow-up questionnaires, outcome data losses due to remote follow-up after the first month, short postoperative follow-up, and lack of follow-up of patients who refused to use the SOP.Future studies investigating SOP and management of cases are warranted. Findings of such studies may be help refine follow-up strategies, contribute to clinical practice, reduce over-indication of surgical treatment, encourage multidisciplinary approaches and adjust the allocation of resources available by health insurance companies, hospital, patients and respective families.Participants enrolled in the Second Opinion Program achieved significant improvements in functional capacity, low back pain intensity, quality of life, and psychosocial factors following surgery, and were able to attain the minimum clinically important difference across all follow-up time points. Findings of this study emphasized the significance of the Second Opinion Program, given the high rates of disagreements regarding diagnoses and therapeutic indications in patients with chronic low back pain.


The objective of the study is to investigate pain and distress experienced by a group of adolescents and children during peripheral intravenous cannulation in a paediatric emergency department. This cross-sectional study was performed between November 2019 and June 2020 at the paediatric emergency department of the Institute for Maternal and Child Health of Trieste, Italy. Eligible subjects were patients between 4 and 17 years old undergoing intravenous cannulation, split into three groups based on their age: adolescents (13–17 years), older children (8–12 years), and younger children (4–7 years). Procedural distress and pain scores were recorded through validated scales. Data on the use of topical anaesthesia, distraction techniques, and physical or verbal comfort during procedures were also collected. We recruited 136 patients: 63 adolescents, 48 older children, and 25 younger children. There was no statistically significant difference in the median self-reported procedural pain found in adolescents  versus older and younger children . Furthermore, no significant difference was observed in the rate of distress between adolescents (79.4%), older (89.6%), and younger (92.0%) children. Adolescents received significantly fewer pain relief techniques.Conclusion: This study shows that adolescents experience similar pain and pre-procedural distress as younger children during peripheral intravenous cannulation. Needle-related procedures are part of routine medical care in emergency departments (EDs) and are the most commonly performed medical procedures among children and adolescents , represeThe aim of this study is to investigate the pain and the distress experienced by a population of adolescents in a paediatric ED, compared to younger patients, and to investigate how the age of the participants involved correlates with the number of pain relief techniques employed, and with parents’ behaviour during the procedures.This was a single-centre cross-sectional study conducted between November 2019 and June 2020 at the paediatric emergency department of the tertiary level children’s hospital Institute for Maternal and Child Health of Trieste, Italy. The study received approval from the Institutional Review Board of the Institute (RC 25/2019). All of the children’s parents were provided written informed consent before participation. We enrolled patients from 4 to 17 years undergoing peripheral intravenous cannulation. Exclusion criteria included presence of cognitive impairment, decreased vigilance (GCS < 15), need for urgent treatment, need for sedation during the procedure, administration of analgesics in the previous 8 h, and insufficient understanding of the Italian language or inability of the parents to provide a written informed consent.For every enrolled patient, the following features were collected: age, site of procedure, presence of a chronic disease, number of similar procedures in the last year, previous needle-related traumatic experiences, number of procedures performed by the operator in the last month, number of operators acting on the patient during procedure, type of techniques used for pain and distress management during procedures, need for physical restraint, and lastly, parents’ behaviour during the procedure.Enrolled patients were divided into three groups according to their age: adolescents (13–17 years), older children (8–12 years), and younger children (4–7 years).The procedural pain was self-reported by patients, immediately after the first attempt of peripheral intravenous cannulation, and was measured through the Faces Pain Scale-Revised (FPS-R), which includes a numeral rating scale from zero (no pain) to 10 (maximum pain), and a series of faces with an expression changing from no pain to severe pain . Scores The procedural distress was measured immediately before the procedure according to the patients’ age. In patients from 8 to 17 years old, it was self-reported through a validated visual scale named the “distress thermometer” , which uFor every procedure, we recorded the following pain relief strategies: (1) use of topical and local anaesthesia, (2) use of distraction techniques , (3) use of physical comfort measures, and (4) verbal comfort measures adopted by caregiver or hospital staff during the procedure. Holding the patient on parents’ laps or holding their hand, touching or caressing the patient was considered physical comfort measures. On the contrary, the active intervention required to keep a resistant or agitated child still during procedures was considered as physical restraint. Talking to patients in order to comfort them was considered a verbal comfort measure.All the study-related data was collected by an external observer in a data collection form specifically developed for the study. The external observer was a senior medical student, specifically trained on the study purpose. He did not take any active part in procedures apart from recording pain and distress scores, the number of pain and distress relief employed, and the actions of operators and parents. Trying to assure an unbiased picture of procedural pain and distress management, the operators were not aware that the external observer collected data related to the techniques employed and the staff behaviour as well.The primary study outcome was the comparison of median self-reported procedural pain among the three groups of patients. Secondarily, the three groups of patients were compared in terms of presence of distress, relationship between distress and pain, and number and type of pain relief techniques employed during procedures.p < 0.05 was considered as statistically significant. Statistical analyses were performed using SAS software, Version 9.4 .Descriptive analysis of all variables was performed by reporting frequencies and percentages for categorical, median, and interquartile ranges for continuous variables. Differences in the distribution of continuous variables between the three age groups were assessed with the Kruskal Wallis test, while the association between categorial variables and age group were tested by chi-square or the exact Fisher test, as appropriate. Wilcoxon Mann Whitney test was used to evaluate association between pre-procedural distress and self-reported procedural pain by age group. A During the study period, 164 patients were considered eligible for the study. Twenty-eight patients (17%) were excluded, due to the exclusion criteria previously outlined. We prospectively enrolled 136 patients aged 4–17 years. An overview of the patients’ and procedures’ characteristics is provided in Table Table p = 0.2) found. The rate of severe pre-procedural distress was also similar among age classes (p = 0.5).Most patients reported or were observed to experience distress before the procedure: 50 adolescents (79.4%), 43 older (89.6%), and 23 younger (92%) children, with no statistically significant differences between age classes (Table p = 0.01 and p = 0.02 respectively) was observed among adolescents and older children. This association was not significant among younger children (p = 0.4).A significant association between the presence of pre-procedural distress and higher scores of self-reported procedural pain (p < 0.0001).The number of pain relief techniques employed during procedures was inversely proportional to patient’s age Table , and thip < 0.0001); distraction techniques were employed in 35 adolescents (55.6%), 30 older children (62.5%), and 18 younger children (72.0%) (p = 0.4); physical comfort was provided for 14 adolescents (22.2%), 14 older children (29.2%), and 12 younger children (48.0%) (p = 0.1); verbal comfort was reported in 46 adolescents (73.0%), 36 older children (75.0%), and 20 younger children (80.0%) (p = 0.8).In detail, topical or local anaesthesia was used in 2 adolescents (3.2%), 21 older children (43.8%), and 20 younger children (80.0%) (Figure This study shows that adolescents experienced similar pain and pre-procedural distress to younger patients during peripheral intravenous cannulation. Adolescents received fewer pain relief techniques and did not receive topical anaesthesia in most of the cases.Needle-related procedures are the most common sources of distress and pain in paediatric Eds . While tFewer pain and distress relief interventions were employed in adolescents when compared to younger children, highlighting a tendency to underestimate and under treat their pain and distress. Furthermore, adolescents generally received limited consolation by their parents, compared to older and younger children. Future studies need to address how the patients’ age may influence the behaviour of health care operators towards the use of pain and distress relief techniques in emergency settings.Evidence shows that adolescent experiences may play a role in the genesis of needle phobia , 17, 14.This study has some limitations. It is a single-centre experience with a limited sample size; therefore, the generalizability of results should be taken with caution. We were not able to find a statistically significant difference in median pain scores among adolescents and younger patients, but this could be related to the limited sample size. Remarkably, in this setting, a clinically relevant difference such as a difference perceived by the patient may be different from a statistically significant one . As a maProcedural distress was measured only before the peripheral intravenous cannulation and not during or after procedures. The data collection form was developed specifically for the study and was not validated. Furthermore, this instrument was only quantitative and we did not perform a qualitative analysis of the pain and distress relief techniques employed. Child life specialists are not available in Italy and distraction techniques and comfort measures are managed by paediatric doctors and nurses who receive a dedicated training as part of their professional role. All the procedures were recorded by a single external observer specifically instructed in the recognition of pain and distress relief techniques. The observer was present in the room during the procedures and did not take any active part in them. Nevertheless, we cannot exclude that some factors may have influenced their judgment. Moreover, we cannot exclude that staff and parents’ behaviour may have been influenced by the participation in the study or by some cultural influence causing less use of pain and distress relief techniques in adolescents in this specific ED compared to other EDs in different regions.Finally, a separate analysis of distress in patients receiving topical anaesthesia was not performed as only two patients in the adolescents group received EMLA cream.The point of strength is the use of validated and standardized scales to measure pain and distress and the fact that a categorization was applied to allow the comparison between different ages.In conclusion, this study, which was performed in a paediatric emergency setting, showed that adolescents experienced similar values of pain and distress during peripheral intravenous cannulation when compared to children, while receiving less pain relief techniques.


Moreover, compared to G/G subjects, heterozygous or homozygous individuals for the A allele of IL-6 rs1800797 SNP had a lower risk of having a PIt0 > 4. Dose24h and Dosetot were both higher in G/G individuals for TNFα rs1800629 , while risk of having a PIt0 > 4 and a ∆VAS > 2 was higher for G/G subjects for IL-6 rs1800795 SNP compared to carriers of the C allele. No statistically significant association between genotypes and safety outcomes was found. Thus, IL-6 and TNFα SNPs could be potential markers of baseline pain intensity and opioid dose requirements in pediatric cancer patients. Moderate to severe cancer pain treatment in children is based on the use of weak and strong opioids. Pharmacogenetics play a central role in developing personalized pain therapies, as well as avoiding treatment failure and/or intolerable adverse drug reactions. This observational study aimed to investigate the association between IL-6, IL-8, and TNFα genetic single nucleotide polymorphisms (SNPs) and response to opioid therapy in a cohort of pediatric cancer patients. Pain intensity before treatment (PI In children under the age of 14, cancer incidence reaches 150 per million person-years in the populations of North America and Europe. The distribution of cancer type varies in age groups, with leukemia, central nervous system (CNS) tumors, and lymphomas as the most common types of cancers .According to 2012 World Health Organization guidelines , as for In cancer, progression of the disease, presence of metastasis, tissue infiltration, nerve damage, and the therapies themselves are all causes of pain . MoreoveIL-6, released in response to infection, trauma, and neoplasia, shows higher concentrations in various cancer types, and in particular in individuals who are carriers of both G alleles for its SNP rs1800795 . IL-6 rsParticularly in children suffering from cancer, treating pain represents a challenge for clinicians. Among opioids, morphine is the most used active principle , but forAmong genes associated with variability in response to opioid treatments, those involved in the cytokine pathway are still poorly investigated in children. Thus, the aim of this prospective observational cohort pilot study  was to iThe materials and methods of the Suitable Treatment for Oncologic Pediatric (STOP) Pain Study were described in 2018 . BrieflyDuring the study period, we enrolled a total of 87 pediatric patients, but in this paper, we present results for patients with available genetic data for IL-6 rs1800795, rs1800796, rs1800797, IL-8 rs4073, and TNF-α rs1800629 SNPs (n = 74). We administered two structured questionnaires to enrolled children or to their parents in order to collect all patients’ demographic and clinical information ), and demographic information on parents and the familial environment, respectively. We collected data regarding cancer diagnosis and the evolution of the disease from medical charts, while data concerning health conditions and parameters potentially predictive of treatment efficacy/safety were collected and considered for the analysis as confounding variables and/or effect modifiers. We recorded all data in anonymized, individual, coded case report forms (CRFs), and then we recorded all CRFs into an electronic database.DNA analyses were performed on peripheral blood or mouth swab samples collected after patients’ recruitment . Then, g24h (mg/kg), the cumulative dose of IV ME administered during the first 24 h of treatment or titration phase; (2) Dosetot (mg/kg): total dose of IV ME from Day 1 to the end of opioid treatment; (3) DoseVAS=0 (mg/kg): ME dose required to achieve total pain relief .The dose of active principles other than morphine were converted into intravenous (IV) morphine equivalents (ME) according to the following calculations : IV ME =t0, pain intensity before treatment; (2) ∆VAS, difference between the pain intensity after 24 h of treatment and PIto; (3) Timetot (hours), time needed to reach the lowest pain intensity reported by the patient.Pain intensity (PI) was registered before the beginning of the treatment, again at every change of staff shift, and whenever patients showed pain using three different pain scales, according to the child’s age. The VAS was used for children older than 6 years of age. Wong & Baker FACES pain rating scale was administered to children 4–6 years old as an alternative outcome measure. The Face Legs Activity Cry Consolability (FLACC) scale was used for children who were unable to report the presence or the intensity of pain. The following three outcomes about pain intensity were considered: (1) PiWe evaluated the occurrence of gastrointestinal (GI) side effects , central nervous system (CNS) effects , and the occurrence of any adverse effects .t-test or by one-way ANOVA where appropriate, while differences for medians were checked using the Mann–Whitney test or the Kruskal–Wallis test. Logistic regression models were fitted to estimate the risk  and 95% Confidence Intervals, (CI)) of pain control and of side effects, and they were adjusted by age class, gender, Pit0, diagnosis, and presence of metastasis. Statistical significance was considered for p < 0.05. Data management and statistical analysis were carried out using STATA 14.Categorical variables were presented as number and percentages and compared with Fisher’s exact test. Continuous variables were presented as mean and standard deviation (SD) and median and Interquartile Range (IQ Range). Means were compared with the Student’s During the study period, we enrolled 87 subjects in the STOP Pain Project, but genetic analysis of IL-6 rs1800795, IL-6 rs1800796, IL-6 rs1800797, IL-8 rs4073, and TNFα rs1800629 SNPs were available for 74 patients. p = 0.048). Overall, 54.05% of the children were males, and most of them were aged more than 3 years . The most frequently reported diagnoses were leukemia and lymphoma (41.89%), followed by sarcoma (18.92%) and osteosarcoma (17.57%). Only 21 patients reported the presence of metastasis. Half of the patients reported the oral cavity as the pain location, with a mean value of PIt0 of 4.32 points. Morphine was administered to 51 patients (68.92%), tramadol to 17 patients (22.97%), and only in three cases did we encounter the use of more than one active principle. In these three cases, patients were administered tramadol, codeine, fentanyl, and oxycodone. These medications were not administered simultaneously. Efficacy and safety parameters, overall and for subjects with missing genetic data, showed no differences.The distribution of genotype frequencies agreed with the Hardy–Weinberg equilibrium , and wast0 significantly differed according to IL-6 rs1800797 SNP, with a higher PIt0 for A/G and G/G individuals (p = 0.017).tot was higher for individuals heterozygous and homozygous for the G allele of IL-6 rs1800797 SNP (p = 0.047). Dose24h and Dosetot were both higher in G/G individuals for TNFα rs1800629 .Several pieces of evidence suggested a role of pro-inflammatory cytokines in the mediation of cancer-related symptoms, in particular pain. Pro-inflammatory cytokines released by activated glial cells cause hyperexcitability in pain transmission neurons. Consequently, presynaptic terminals release an exaggerated amount of substance-P and excitatory amino acids, producing a massive pain response . In factVAS > 2 showed that their PI after 24 h of treatment was higher than their PI at baseline. Moreover, individuals who were homozygous for the G allele of TNFα rs1800629 SNP required a higher opioid dose, both during the first 24 h of treatment and during the entire analgesic treatment.In our study, we evaluated the role of several cytokine SNPs in opioid treatment efficacy/safety in a cohort of pediatric oncologic patients. In particular, we observed that subjects who were carriers of the A allele for the IL-6 rs1800797 SNP had a lower mean value of PI before starting opioid treatments and needed a lower total amount of the considered medications, compared to carriers of the G allele. Similarly, patients homozygous for the G allele of IL-6 rs1800795 SNP had a higher PI before they were administered with opioids and a higher risk of worsening in pain evaluation. In fact, a value of ∆IL-6 gene is localized to chromosome 7p21. The IL-6 rs1800795 SNP affects transcription, altering serum levels of IL-6 with the G allele, which is associated with higher concentrations of IL-6 in plasma . As mentIL-6 and TNFα pathways suggest a strict connection between inflammation mediators, which may stimulate pre-malignant cell proliferation, angiogenesis, and metastasis, and, tumor cells, which reversely stimulate other cells to produce pro-inflammatory and pro-angiogenic factors . In our 24h and Dosetot) could be considered as a proxy of their PI. The ability to quantify pain within a pediatric population is not simple. In fact, even if all scales used referred to a 0-to-10-point range, the use of different scales for pain evaluation may have affected these results in terms of homogeneity. An additive model for TNF rs1800629 SNP was predictive of severe pain in adults with lung cancer [Our results are in line with those already published in the literature for adult cancer patients. IL-6 serum levels were positively related to the severity of a score, including, in adult patients with gastrointestinal cancer, the six most severe cancer-related symptoms  . Althougg cancer , and in g cancer , G/G lunSpecific evidence for IL-6 rs1800797 and cancer-related pain is not available in literature. A study on adult patients suffering from sciatica demonstrated that the number of days with back and leg pain and days on sick leave were significantly higher among subjects with the IL6 rs1800797, rs1800796, rs1800795, and rs13306435 haplotypes . AnotherIL-8 rs4073 SNP has been significantly associated with severe pain among adult patients with pancreatic adenocarcinoma . On the Overall, results obtained in our study could be primarily related to the well-known existing differences between adults and children: developmental pharmacokinetic , off-labThe present study has some limitations. First, we could not establish whether any concomitant non-opioid analgesics used in our sample may have affected PI evaluation. Since some agents may synergize with opioids and/or have similar genetic influences, having this information would be very important. Another limitation was represented by the mixed nature of pain in cancer patients. In fact, pediatric cancer-related pain can vary from acute, procedure-related pain to breakthrough pain, and considering these specific mechanisms, it is essential to manage pain effectively. Thus, it was difficult to evaluate the influence of type and location of the primary cancer or the presence of metastases on PI outcomes.On the contrary, our evidence underlines the significance of pharmacogenetic studies. Remarkably, this is the first study attempting to evaluate the role of cytokine pathway gene SNPs in pediatric oncology and their impact on opioid efficacy and safety. Although we did not observe any significant association between genetic factors and opioid-related ADRs, our data showed that patients’ genetic profiles could be proxies for baseline PI and related treatment requirements.In this context, only future studies with larger sample sizes could determine the prompt impact of these SNPs on opioid efficacy for cancer-related pain treatment in children.Our results underline that IL-6 and TNFα SNPs could be potential markers of baseline pain intensity and opioid dose requirements in pediatric cancer patients. Knowledge of them could therefore address opioid treatment management in pediatric oncology. Further studies evaluating new strategies to modulate interactions between cytokines and the opioid system may identify novel therapeutic approaches in this subset in clinical practice.


Background: The more the cancer treatments progress, the more the needs increase to taper and discontinue opioids in cancer patients. Furthermore, opioid dependence of cancer survivors has become a bigger problem. However, a safe opioid tapering and discontinuation method has not yet been established in cancer patients.Objective: To suggest a safe opioid tapering and discontinuation method in cancer patients.Design: We reviewed opioid type, dose, administration route, administration duration, reason for tapering and discontinuation, and presence/absence of opioid withdrawal symptoms in cancer patients whose opioids needed to be tapered and discontinued.Setting/Subjects: We recruited cancer patients referred to the palliative care team of Kyoto University Hospital-Japan whose opioids were tapered and discontinued.Measurements: Opioid withdrawal symptoms were assessed by two physicians, one nurse, and one pharmacist of palliative care team.Results: Opioids were tapered and discontinued in 25 out of 145 cancer patients (17%). Opioid withdrawal symptoms were observed in 3 of the 25 cases (12%). In withdrawal symptom cases and nonwithdrawal symptom cases, the mean maximum oral morphine-equivalent doses of opioids were 352.0 and 55.7 mg/day, and the mean administration duration of opioid were 82.3 and 28.7 days, respectively. Withdrawal symptoms occurred in patients receiving higher-dose opioids with longer administration duration and their symptoms tended to appear at approximately 10% of the maximum dose.Conclusions: We suggest that withdrawal symptoms may be prevented by using a two-stage method rather than a monotonous tapering method in cancer patients whose higher-dose opioid with longer administration duration needed to be tapered and discontinued. It has led to an increase in cancer survivors and to more patients requiring tapering and discontinuation of opioids.5–7 Previous studies have explored the prevention of withdrawal symptoms in patients who do not have cancer.8–10 Treatment of the physical dependence-related withdrawal symptoms has been developed for patients with chronic pain without cancer or opioid use disorder.12 The treatment could be applied to cancer patients who use opioids. However, there are few evidence-based studies exploring opioid tapering and discontinuation in cancer patients. The purpose of this study is to recommend a safe opioid tapering and discontinuation method for cancer patients.Opioid withdrawal symptoms are induced by sudden discontinuation of long-term opioid use.13This is a retrospective chart review of patients referred to the palliative care team of Kyoto University Hospital between January and December 2015, whose pain included opioids that were discontinued within the two years preceding referral. Written informed consent was obtained from patients of case presentation. We investigated the opioid type, dose, administration route, duration of administration, reason for tapering and discontinuation, and presence/absence of opioid withdrawal symptoms. In cases of withdrawal symptoms, duration of opioid use was defined as the onset of opioid use to the onset of withdrawal symptoms. Opioid withdrawal symptoms were assessed by two physicians, one nurse, and one pharmacist of the palliative care team. We diagnosed symptoms related to opioid withdrawal if they occurred during opioid tapering, other causes could be ruled out, and they improved with opioid readministration. The estimated oral morphine-equivalent dose (MED) was calculated according to the opioid potency data in the Palliative Care Formulary.Of the 356 cancer patients referred to the palliative care team during the study period, 145 received opioids for pain. Opioids were tapered and discontinued in 25 cases (17%). Their characteristics are shown in We recognized three patterns among pain etiologies. Fourteen patients had pain related to cancer, including 12 for whom cancer treatment eliminated the pain  and 2 cases who self-decided to discontinue. Nine patients had pain related to cancer treatment: seven had chemotherapy-related mucosal pain, two had postoperative pain, and two had infected wounds. Two patients had pain not directly related to cancer or cancer treatment . Transdermal fentanyl was the most commonly chosen opioid medication for those who had difficulty taking it orally.Patient 1 was 576 mg/day and 18 days. For Patient 2, it was 240 mg/day and 23 days, and for Patient 3, it was 240 mg/day and 208 days.The mean MED of patients with and without withdrawal symptoms was 352.0 and 55.7 mg/day, respectively. The mean duration of opioid use was 82.3 and 28.7 days, respectively . Figure This was a 43-year-old woman with cervical carcinoma who received pelvic exenteration. Continuous intravenous infusion of oxycodone at 30 mg/day was started to relieve postoperative pain. The dose was increased in a stepwise way to 288 mg/day (MED 576 mg/day). The pain gradually subsided, and the oxycodone dose was reduced . ContinuThis was a 43-year-old man with hepatocellular carcinoma who had undergone liver transplantation from a living donor. A year later, he developed severe acute pancreatitis with severe abdominal pain. On admission to the hospital, continuous intravenous infusion of fentanyl at 1200 μg/day was started to control abdominal pain. The fentanyl dose was increased according to pain intensity, reaching 2400 μg/day (MED 240 mg/day) after 10 days in the hospital. Administration of a pancreatic enzyme inhibitor, antibiotic, and fluid alleviated the pancreatitis and abdominal pain. This was a 49-year-old woman with vulvar sarcoma who was irradiated with proton beam radiotherapy. Unfortunately, a very painful ulcer formed within the irradiation field one month after completion of treatment. Sustained-release oxycodone administration was started at 40 mg/day. The oxycodone dose was increased according to pain intensity, reaching 160 mg/day (MED 240 mg/day). The ulcer was treated with skin grafting and relieved the pain. The oxycodone dose was decreased every two days . Mild re14 Physical dependence should be considered when tapering after long-term opioid use.15 However, Heishman et al. point out that withdrawal symptoms can occur after acute opioid use.16World Health Organization (WHO) guidelines for the management of cancer pain have identified strategies for discontinuing in various clinical settings opioids used for chronic noncancer pain in various clinical settings that address chronic noncancer pain. The guidelines recommend that opioid be discontinued immediately without tapering for short-term opioid use (less than two weeks) if the cause of pain has been successfully treated.Patient 1 and Patient 2, who had a higher maximum MED (>200 mg/day), developed opioid withdrawal symptoms. They also had a longer duration of opioid use . Patient 2 and Patient 3 wanted to continue opioid use because of fear of recurrence of withdrawal symptoms. It can lead to psychological dependence.17 Experiencing opioid withdrawal symptoms can cause anxiety about opioid tapering.19 This leads to physical and psychological dependence in some patients and may increase the risk of developing opioid use disorder. Chemical coping is often associated with anxiety.20 It is important to prevent physical and psychological dependence on opioids.In our study, nine patients showed no opioid withdrawal symptoms without opioid tapering. Their MED was 15–50 mg/day, and the duration of opioid use was 3–37 days. 21 In our study, opioids were reduced by 6.25%–25% every one to two days. Berna et al. recommend reducing the dose in two stages in patients with long-term opioid use for chronic pain. In the first stage, the total dose is reduced by 10% every five to seven days until it reaches 30% of the total dose. Then the dose is reduced by 3% each week until discontinued.22 In our study, Patient 1 and Patient 2 developed withdrawal symptoms when the opioid was discontinued, and Patient 3 developed withdrawal symptoms at 12.5% of the maximum MED. Withdrawal symptoms usually occur at about 10% or less of maximum MED. For this reason, we recommend two-stage opioid tapering in cancer patients. Our method is to first reduce 10%–20% of the total dose every two to three days until we have reduced approximately 10% of the total dose, and then 2%–3% every day thereafter. In fact, none of the cancer pain patients had withdrawal symptoms after using this method. This may prevent the onset of withdrawal symptoms in patients who have been taking higher-dose opioids for a longer duration.To prevent withdrawal symptoms, it is recommended that opioids be tapered by 25% until discontinuation.24 Our interdisciplinary team  is working hard to improve this, and the number of the patients was small. Nevertheless, we supported the patients vigorously and continuously. In conclusion, we recommend the use of two-stage opioid tapering rather than linear tapering to prevent opioid withdrawal symptoms when a patient has been taking a higher opioid dose for a longer duration of opioid use at the start of tapering.Pain requires a multifaceted assessment and treatment. Palliative care should take a holistic approach to pain management and provide interdisciplinary care that balances analgesia and appropriate opioid use in the early stage of cancer treatment.


BackgroundPreoperative anxiety is generally neglected in the evaluation of cardiac surgery patients due to various reasons including insufficient literature and lack of simple assessment tools. In addition to this, the association between anxiety and postoperative complications including pain has been scarcely studied. The present study was designed to assess preoperative anxiety levels in all patients coming for cardiac surgery and then evaluate the effect of different levels of anxiety on postoperative pain scores.MethodsThis prospective cohort study was conducted in a single university hospital from March 2018 to December 2019. One hundred consecutive cardiac surgery patients between the ages of 18-65 years were enrolled in this study. The level of preoperative anxiety (assessed by State Anxiety Inventory) and its effect on postoperative pain and morphine consumption was assessed.ResultsThe average age of the patients was 58.24±10.03 years of which 68% were male and 32% were female. Preoperative mild anxiety was observed in 64% of patients and moderate to severe anxiety in 36% of patients. Post-operative mean pain score was significantly high in the moderate to severe anxiety group as compared to the mild anxiety group [Mean pain difference =1.64 (95%CI: 1.38-1.89) p=0.0005], [Mean pain difference =0.51 (95%CI: 0.29-0.73) p=0.0005] at 12 hours and 24 hours respectively. Intraoperative and postoperative morphine consumption was significantly high in patients with moderate to severe anxiety.ConclusionsPatients with moderate to severe anxiety before cardiac surgery experienced higher pain scores at a post-operative period which is significantly different from the mild anxiety group. Intraoperative and postoperative analgesic requirements were also significantly increased. Anxiety is defined as a negative or life-threatening emotion that one feels generally in the ong-term or in a specific situation, that fluctuates over time . SurgeryHeightened anxiety before surgery is associated with hypertension, dysrhythmias, surgery refusal, exacerbation of coronary artery disease symptoms , slow woThere are few studies that showed a significant correlation between preoperative anxiety and postoperative pain -15. ApprThe State Anxiety Inventory (STAI) for Adults is an excellent tool for assessing anxiety. The reliability and validity of STAI are well reported. The STAI form (Y) is the definitive instrument for measuring anxiety in adults. The STAI Form Y-6 consists of six statements that evaluate how the patient feels “right now” at this moment.Pain is a subjective experience that is influenced by psychological, cultural, and other variables. The most common way to quantify pain is through self-reporting measures. A patient may describe pain intensity simply by indicating his pain on a scale. Most of these scales are unidirectional. These scales are simple and easy for the patients to use and understand and are relatively inexpensive.The visual analog scale (VAS) and numerical rating scale (NRS) are commonly used scales to assess pain. Studies have shown a good correlation between the VAS and other measurements of pain intensity. In addition, VAS and NRS are easy to understand and are reproducible over time. The numerical rating scale is used to determine the intensity of pain. Patients would be asked to rate their pain from “0” (no pain) to 10 (pain as intense as it could be). This scale is reliable, reproducible and easy to administer. Additionally, it is readily acceptable to the patient.Generally, there is an inadequate analysis of a patient’s psychological status pre-operatively, which hinders appropriate measures to reduce the patient’s anxiety. This issue needs to be addressed to reduce postoperative complications including pain.Preoperative anxiety is generally neglected due to various reasons including lack of knowledge, insufficient literature, and lack of simple assessment tools. The results of this project may also be beneficial to the anesthesia community and societies, by potentially heightening the awareness about preoperative anxiety and its effects where this is not typically considered. This awareness may lead to better prevention and readiness through the creation or improvement of policies, procedures, and training.The present study was designed to assess preoperative anxiety levels in all patients coming for cardiac surgery and then evaluate and compare with postoperative pain scores.A preprint of this article was published in Research square.This prospective cohort study was conducted in the preoperative area, ward & high dependency unit of Aga Khan University Hospital, Karachi. One hundred consecutive patients between the ages of 18-65 years were enrolled in this trial. All patients coming for cardiac surgery and planned for fast-track extubation were included. Emergency cardiac surgery patients and those who required reopening for bleeding were excluded from the study. Other excluded patients were patients taking any antipsychotic or anxiolytics, those suffering from Hypo- or hyperthyroidism, and neurological or psychological disorders.The study was conducted after approval from the institutional ethical review committee (ERC). The duration of the study was between March 2018 to December 2019. Informed written consent was taken the night before surgery from all the patients scheduled to undergo elective cardiac surgery. A copy of the informed consent was given to the patient. The confidentiality of the patient and data was maintained by assigning a number for each patient data. Electronic data was password protected and data on hard copies were kept in a lock and key.Non-probability consecutive sampling technique was used. Those patients who fulfilled the inclusion criteria were approached a night before surgery. Patients were assessed pre-operatively by using the State Anxiety Inventory (STAI) scale for adults. The STAI Form Y-6 consists of six statements that evaluate how the patient feels “right now” at this moment. The primary investigator asked these questions and answers were noted in a proforma and scoring was done. Individuals with an STAI score of more than 40 were considered as moderate to severe anxiety, and those having an STAI score of 40 or less were allocated mild anxiety group. These patients were approached after successful surgery and extubation. Anxiolytics were not given postoperatively. All patients received intravenous Tramadol 50 mg 8 hourly and intravenous paracetamol 1 gram 6 hourly, while 1 mg of intravenous morphine was given on PRN basis. The post-operative pain was determined by using a numeric pain scale at 12hr and 24hrs of surgery and total narcotic consumption was also noted along with the duration of surgery, amount of intraoperative and postoperative analgesia used. Pre-operative anxiety and post-operative pain assessment were done by the primary investigator on a predesigned data collection form.Sample size calculation was based on a previous study by Koivula et al. who reported the preoperative anxiety as 50% in coronary artery bypass graft surgery (CABG) . One hunData were analyzed by the statistical packages for social science version 17 . Mean and standard deviation were estimated for quantitative variables like age, weight, height, BMI and STAI scores, duration of surgery, intraoperative analgesics used, postoperative opioid consumption, and post-operative pain scores. The normality of the continuous data was tested by the Shapiro-Wilk test and by examining the quantile plot. Normally distributed continuous variables were presented as mean ± SD and compared between the mild vs moderate to severe anxiety using a two-sample Student t-test. When the distribution was not normal, the median along with the first (Q25) and third quartiles (Q75) was presented, and a Mann-Whitney U test was used. Frequencies and percentages were calculated for qualitative variables like gender, marital status, and type of surgery and analyzed by chi-square or Fisher’s exact test. The general linear model was used to observe the association of preoperative anxiety and pain score (continuous dependent variable) after controlling the effect of age, gender, type of surgery, diabetes, and hypertension. Regression coefficients were reported for each independent variable. A P-value ≤0.05 was considered significant.A total of 100 patients undergoing cardiac surgery  were included in the study. The average age of the patients was 58.24±10.03 years of which 68% were male and 32% were female. Out of 100 patients, CABG was performed in 88% and the rest were 12% . Diabetes mellitus was observed in 55% and 70% were hypertensive.Out of 100 patients, preoperative mild anxiety was observed in 64% of patients and moderate to severe anxiety in 36% of patients. Demographic characteristics, type of surgery, and duration of surgery were not statistically significant in patients with mild anxiety and the moderate to severe anxiety groups (Table The postoperative mean pain score was significantly high in the pre-operative moderate to severe anxiety group as compared to the mild anxiety group [Mean pain difference =1.64 (95%CI: 1.38-1.89) p=0.0005], [Mean pain difference =0.51 95%CI: 0.29-0.73) p=0.0005] at 12 hours and 24 hours respectively. Intraoperative and postoperative morphine consumption was significantly high in patients with moderate to severe anxiety groups . This is in line with the study by Mehdi et al. who suggested that the preoperative anxiety levels are much higher in female than male patients . Vilma eNo significant differences were found between preoperative anxiety and smoking, diabetes mellitus (DM), hypertension (HTN), and BMI. Type of surgery  also had no significant effect on anxiety. Valve surgery patients were slightly more anxious preoperatively in comparison with CABG surgery patients. This is in contrast with other studies where CABG patients showed higher anxiety scores . The reaA study by Kil et al in 2011 concluded that patients with higher STAI scores required a greater amount of induction and inhalational agent and were also significantly correlated with postoperative pain . We did In our study, using the standard analgesia protocol, postoperative pain scores were significantly higher in the moderate to severe anxiety group as compared to the mild anxiety group in the first 24 hrs. As expected, the analgesic requirements were also significantly increased in the moderate to severe anxiety group. This may be due to the fact that the average pain score was moderate in the anxiety group and mild in non-anxiety during the first 12 hrs. A highly significant association was found when postoperative pain was compared between non-anxious and anxious patients after adjusting age gender, type of surgery, and other comorbidities. Our study is in line with a study by Miguel et al. who measured preoperative anxiety and depression using the hospital anxiety and depression scale (HADS) and found a significant correlation of pre-operative anxiety with postoperative pain . AnalgesA study by Gresztat et al. in 2008 concluded that patients with higher preoperative anxiety respond poorly to analgesic medication, which may be due to increased perception of pain . It is dOcalan et al. looked at ENT surgeries and found a positive relationship between preoperative anxiety and postoperative pain, but a negative relationship between postoperative pain with depression. They also suggested early intervention to relieve preoperative anxiety . Other sGenerally, female patients have higher pain scores than men. In the present study, male patients showed slightly higher mean postoperative pain scores irrespective of groups during the first 24 hours as compared to females. However, the association between gender and postoperative pain was insignificant. The postoperative morphine requirement was higher in female patients than males but this association was insignificant.Pregabalin has been used as an anxiolytic agent before neurosurgery and we were able to demonstrate the anxiolytic effect and reduced postoperative analgesic requirements. It shows that anxiolysis does reduce postoperative analgesic needs.A significant association was also found between the type of surgery and postoperative pain at 24 hours, whereas postoperative pain was more at valvular surgery than CABG after adjusting other factors.Further studies are required to see the effect of preoperative anti-anxiety medication on postoperative pain management. These medications can be started on surgical floors the night before surgery and continued till the patient is called to the operative room. In addition, it is the responsibility of doctors and nurses to educate patients about the procedure and also take appropriate interventions in order to reduce anxiety and postoperative morbidities. Another approach is to give ICU tours to patients and families before surgery in order to improve satisfaction and reduce anxiety.The average age of the anxiety group was non-significantly lower than the non-anxiety group. However, postoperative pain was not affected by age, except in the 51 to 60 years group. There was no change in analgesic requirements for pain control in both groups despite higher pain scores in the anxiety group.Our study also found that patients of the anxiety group having a duration of surgery of more than 300 minutes had the greatest post-operative pain scores (5.00 ± 1.41) at 12 hours. which is moderate by our definition. This is significantly different for non-anxious patients who had mild pain at the same time. However, this difference resolved at 24 hrs.The main limitation of the study was that the study was performed in only one center and all factors responsible for preoperative anxiety, like waiting time and previous surgery experience, were not considered. Other outcomes like delirium, length of stay, and quality of life after surgery were also not reported.In conclusion, our study indicates that the patients undergoing cardiac surgery and those who experienced moderate to severe anxiety before surgery are more prone to develop higher pain scores in the postoperative period which is significantly different from the mild anxiety group. Intraoperative and postoperative analgesic requirements were also significantly increased in moderate to severe preoperative anxiety patients.


Background: Surgery is a frequent cause of persistent pain, defined chronic post-surgical pain (CPSP). The capsaicin 8% patch (Qutenza®) is approved for the treatment of postherpetic neuralgia (PHN) and for diabetic peripheral neuropathy (DPN) of the feet. We propose a review of the literature on use of the capsaicin 8% patch to treat neuropathic pain associated with surgery; (2) Methods: We identified the articles by searching electronic databases using a combination of such terms as “capsaicin 8% patch”, “®Qutenza”, and “chronic postsurgical pain”; (3) Results: We identified 14 selected studies reporting on a total of 632 CPSP cases treated with capsaicin 8% patch. Treatment with the capsaicin 8% patch significantly reduced the average pain intensity. Only 5 studies reported adverse events (AEs) after the patch application. The most common AEs were erythema, burning sensation and pain; (4) Conclusions: Our review indicate that capsaicin 8% patch treatment for CPSP is effective, safe and well tolerated, but randomized controlled trials on efficacy, safety and tolerability should be conducted.(1)  In 2014, Werner and Kongsgaard proposed an updated definition ; knee surgery, 12.9% [n = 48]; parietal surgery, 11.3% [n = 42]; mastectomy, 4.0% [n = 15]; back surgery, 1.6% [n = 6]; traumatic surgery, 1.3% [n = 5]; abdominal surgery, 1.1% [n = 4]; head surgery, 0.5% [n = 2]; and not specified, 52.2% [n = 194]) occurred in all cases.CPSP of various aetiology , chest , back , abdomen , upper limbs  and lower limbs . Other or non-specified body regions were treated in 46.8% of patients (n = 192). Mankowski C et al. and Pinto TJ et al. did not specified painful body regions.As shown in Pain intensity. In all studies, pain was of at least moderate severity and was frequently unresponsive to, or poorly controlled by, conventional therapy. Treatment with the capsaicin 8% cutaneous patch significantly reduced the average pain intensity. The NRS baseline score of 6.9 decreased to all subsequent visits.The duration of application of capsaicin 8% patch varied between 30 and 65 min, with most patients treated for 60 min. Each patch was applied for 30 min to the feet and for 60 min to other areas of the body, as recommended . RobertsIn 7 studies more than one application was required ,26,29,30Baseline pain intensity is reported in Adverse Events. Only 5 studies reported adverse events (AEs) after the capsaicin 8% cutaneous patch application [lication ,21,29,30n = 91), burning sensation (n = 78) and pain (n = 35).The most common AEs were application site reactions. The main AEs were erythema (®). Subsequent cooling was carried out in 4 studies [A local anaesthetic pre-treatment was reported in 8 studies ,23,27,29 studies ,18,19,21No systemic AEs were reported.Treatment discontinuation was reported by Bischoff et al. A patient experienced severe pain at the application site, which necessitated patch removal, and was withdrawn from the study.Between 20 and 56% of patients undergoing surgery develop chronic pain. Patients may develop CPSP after “common surgical procedures”. The majority of included patients in our review were post-thoracotomy (15.1%). Thoracotomy is reported as one of the most common causes of CPSP with an incidence of 20–40% . Other cTricyclic antidepressants and anticonvulsivants are recommended as first-line therapy, but systemic adverse effects may limit their use particularly in elderly patients . In 2015Capsaicin 8% patch is indicated in adults for the treatment of neuropathic pain associated with postherpetic neuralgia (PHN) and for neuropathic pain associated with diabetic peripheral neuropathy (DPN) of the feet . Most ofThe efficacy of 8% capsaicin patch for the treatment of peripheral neuropathic pain has been investigated in several trials in patients with CPSP. The efficacy of single and multiple applications of the capsaicin 8% patch in patients with CPSP was assessed in this review. Off label use of the capsaicin 8% patch in relieving CPSP proved temporarily effective.It should be noted that the capsaicin 8% patch has been shown to be also effective in patients with CPSP localized to the face, although current recommendations restrict the application of the patch to this region . Gaul C Only in a study included in this review no significant difference in pain reduction was demonstrated comparing the pain relief of a capsaicin 8% patch with an inactive placebo patch. Bischoff JM et al. considered patients with CPSP due to inguinal herniorrhaphy. The authors suppose that the interruption of cutaneous nerve transmission alone may be insufficient to relieve postherniorrhaphy pain and seem to indicate that nerve injury, as well as deep tissue inflammation, may contribute to the development and maintenance of persistent postherniorrhaphy pain.In our review, the capsaicin 8% patch was generally well tolerated in patients with CPSP. Of the 632 patients receiving the capsaicin 8% patch in the studies included in this review, 32.3% reported treatment-related AEs. Most AEs were self-limiting and mild or moderate in severity. No AEs led to discontinuation in patients treated with the capsaicin 8% patch. The most frequently reported AEs were transient application-site reactions. Only burning sensations, erythema and local pain were reported as side effects, the treatment of which was easily manageable. Other frequently reported AEs (<5% of patients) such as nausea, nasopharyngitis, bronchitis, sinusitis, vomiting, pruritus or hypertension were not reported .Use of local anaesthetic before application, local cooling, and availability of short-acting opioids for pain relief in the first few days following treatment all help to increase tolerability of the treatment.Capsaicin has the advantage of site-specific delivery with lower total systemic dose and avoidance of first-pass metabolism, reducing the risk of drug interactions and adverse effects. In fact, capsaicin 8% patch was well tolerated with only minor application site events by our patients.Limitations. Recommendations on the effectiveness of capsaicin patch could not be drawn due to the studies design included in our review. This study was based on observational studies, the majority of which were case series or case reports. Due to the greater potential for bias, they are often excluded from systematic reviews of treatments. We consider case series and observational studies essential to contribute to the available evidence base, and their results supplement the limited evidence available from other studies. We did not perform a meta-analysis due to the design of most of the studies  and the lack of a comparator.Persistent postoperative pain affects millions of patients every year; it is a potential burden for the healthcare systems that until recently has been an unrecognized complication of surgery. What we can do to prevent patients from developing chronic pain postsurgery is now considered one of the most important research priorities in anesthesia and perioperative medicine.To date and to our knowledge, however, only very little data is available on the efficacy of high-dose capsaicin therapy in patients with CPSP, although the treatment of neuropathic pain in these patients is a particular challenge due to the complexity and diversity of symptoms. CPSP is challenging to manage because patients are often non-compliant or unable to tolerate recommended existing systemic treatments. Our review indicate that 8% capsaicin patch treatment for CPSP is effective, safe and well tolerated, but randomized controlled trials on efficacy, safety and tolerability should be conducted.