Using plan-do-study-act (PDSA) cycles, this quality improvement (QI) project aimed to standardize an anesthetic protocol to optimize multimodal pain management for pediatric open inguinal hernia repair (OIHR).PDSA cycle 1: in December 2017, we standardized the intraoperative OIHR anesthesia protocol by replacing transversus abdominis plane (TAP) or ilioinguinal-iliohypogastric (II) blocks and fentanyl with exclusively II blocks and fentanyl. PDSA cycle 2: in January 2019, we used an opioid sparing strategy, replacing II blocks and fentanyl with II blocks and dexmedetomidine. We used statistical process control (SPC) charts to analyze data from the medical record. Outcome measures included the percent of patients requiring rescue morphine in the postanesthesia care unit (PACU), maximum PACU pain score, PACU length of stay (LOS), and anesthesia preparation duration.The team performed a total of 641 pediatric OIHRs between July 2015 and June 2021. The three groups included 203 patients in our baseline group, 127 patients in the PDSA cycle 1 group, and 311 patients in the PDSA cycle 2 group. Special cause variation (SCV) occurred for the percent of patients requiring rescue morphine, anesthesia preparation duration, and PACU LOS. The percent of patients requiring rescue morphine showed improvement. Anesthesia preparation duration improved compared to baseline. There was no SCV detected in the SPC chart for maximum PACU pain score.We implemented an opioid sparing anesthetic protocol for pediatric OIHR utilizing II blocks and dexmedetomidine without adversely affecting postoperative pain score or morphine rescue rate over 6 years. For open inguinal hernia repair (OIHR), ultrasound (U/S)-guided transversus abdominis plane (TAP) and ilioinguinal-iliohypogastric (II) blocks are both utilized for intraoperative and postoperative analgesia.4 The II block involves blockade of the ilioinguinal and iliohypogastric nerve terminations of the first lumbar nerve root of the lumbar plexus. The TAP block is a fascial plane block that targets a more extensive plexus of nerves and typically requires greater volumes of local anesthetic (LA) to obtain sufficient spread.5While the injectate of both TAP and II blocks dissects the plane between the internal oblique and transversus abdominis muscles, the intended target nerves of each are different.3 Fredrickson et al.2 randomized 41 patients undergoing OIHR to receive either TAP or II blocks. Thirty minutes to 2 hours postoperatively, pain was more frequent and ibuprofen use was higher in the TAP group; morphine consumption was similar between groups. Conversely, Sahin et al. randomized 90 children into three groups: TAP, II, and caudal.3 The total amount of perioperative analgesic consumption and pain scores at 1, 4, and 8 hours after surgery were significantly higher in the II group than the other two. The results of randomized controlled trials (RCT) in adults comparing these two blocks for OIHR are similarly mixed.6Although several studies have compared the efficacy of the two techniques in pediatrics, the results are conflicting.At Seattle Children’s Bellevue Clinic and Surgery Center (BCSC), approximately 100 OIHRs are performed annually. Before 2017, BCSC anesthesiologists administered either a TAP or II block, based on preference, for OIHR, with intraoperative IV fentanyl supplementation. In December 2017, speculation on the utility of TAP blocks for OIHR prompted BCSC anesthesiologists to standardize their practice to perform II blocks exclusively for OIHR.8 One methodology utilized dexmedetomidine, a highly selective alpha-2 agonist with both sedating and analgesic properties that binds to receptors in the spinal cord and locus coeruleus.9 In the current pediatric literature, dexmedetomidine is used for preoperative anxiety,10 procedural sedation,12 emergence delirium,15 and intensive care unit sedation.9 There are a few reports of intraoperative use for pain control.18 A quality improvement (QI) project centered on tonsillectomy and adenotonsillectomy surgeries at BCSC showed that replacing intraoperative morphine and acetaminophen with dexmedetomidine and ketorolac resulted in similar pain scores and PACU length of stay (LOS). At the same time, nausea and vomiting rescue rates improved.18 RCTs on dexmedetomidine use, specifically in pediatric OIHR, are limited to its use as an adjuvant for regional techniques.19Concurrently, a local and national shortage of IV opioid medications in 2017–2018 caused BCSC providers to explore opioid sparing pain management strategies to conserve the opioid supply.20 In January 2019, the team replaced fentanyl with dexmedetomidine in the OIHR protocol.Based upon the BCSC T&A QI project findings, the BCSC facility expanded the use of dexmedetomidine in its protocols, minimizing intraoperative opioids for multiple pediatric ambulatory surgeries in a phased manner to track effectiveness.We aimed to standardize an anesthetic protocol to optimize pain management using a multimodal approach for pediatric OIHR over 6 years. We selected maximum PACU pain score and the percent of patients requiring postoperative rescue morphine as primary outcome measures and PACU LOS and anesthesia preparation duration as balancing measures.BCSC is an ambulatory outpatient facility where clinicians incorporate evidence-based standardized anesthesia protocols into their practice to optimize delivery of patient care. Anesthesiologists and certified registered nurse anesthetists (CRNAs) can track the adoption and effectiveness of protocol changes due to the healthy patient population, low-acuity, high-volume caseload, and the informatics infrastructure built to capture electronic medical record (EMR) data, which began in 2015.In this QI project, we included American Society of Anesthesiologists class 1–2 patients 3–18 years of age undergoing OIHR at BCSC from July 1, 2015, through June 30, 2021. We chose this time frame to allow providers time to adhere to multiple protocol changes at the BCSC facility.5 All regional blocks are performed immediately following induction.Before December 1, 2017, both TAP and II blocks were performed in children aged 3-18 years, depending on the anesthesiologist’s preference. The techniques for performing TAP and II blocks at BCSC mirror those described by the New York School of Regional Anesthesia.The BCSC anesthesia team standardized their practice on December 1, 2017, to perform II blocks exclusively for patients 3–18 years of age undergoing OIHR. Adjunctive intraoperative analgesics included in the protocol during this time period included fentanyl (0.5–1 µg/kg) and ketorolac (0.5 mg/kg).This cycle began January 1, 2019, in which dexmedetomidine (0.5–1 µg/kg) replaced intraoperative fentanyl (0.5–1 µg/kg) in the OIHR protocol.Percent of patients requiring postoperative rescue morphine was one of the primary outcome measures used to assess protocol effectiveness. PACU nurses often administer oral acetaminophen for mild pain (score 1–3). Morphine is the first-line rescue analgesic for moderate (score 4–6) to severe (score 7–10) pain in our PACU.r = 0.41–0.8, reliability 69%–91%, kappa = 0.52–0.82).21 For patients 3–6 years old, the nurses favor the Faces Pain Scale-Revised .22 The nurses commonly use the numerical 0–10 visual analog scale  for patients 7 years of age and older.22 Statistical scores presented above are from references; we do not have interrater reliability scores for staff. We converted each pain assessment tool into an 11-point (0–10) score for the analyses.PACU maximum pain score was also a primary outcome measure. PACU nurses record pain scores using assessment tools at their discretion. For patients ≤3 years old, the nurses typically use the Faces, Legs, Activity, Cry, Consolability scale  software system extracts continuously updated, aggregated, and de-identified health information from the hospital’s electronic medical record. It presents the data as statistical process control (SPC) charts.25 Every X-bar chart has a paired S-chart. Control limits were set at three-sigma above and below the mean. Standard SPC chart rules were used to detect common cause and special cause variation (SCV).24This QI project used P-charts to display the percent of patients requiring postoperative rescue morphine and X-bar charts to display maximum pain score, PACU LOS, and anesthesia preparation duration.We submitted this QI project to the Seattle Children’s Institutional Review Board. The board considered this QI work and not human subjects research, so there was no further review.There were 203 patients in the baseline group, 127 in the PDSA cycle 1 protocol group, and 311 in the PDSA cycle 2 protocol group. Before December 1, 2017, TAP blocks were performed for 38% of OIHR cases (78/203), whereas II blocks were performed for 62% of OIHR cases (125/203) (baseline group). From December 1, 2017, to December 31, 2018 (PDSA 1 group), 4% of OIHR cases received a TAP block (5/127) and 96% of OIHR cases received an II block (122/127), whereas 69% of OIHR cases received intraoperative fentanyl (88/127). From January 1, 2019, to June 30, 2021 (PDSA 2 group), 96% of OIHR cases received intraoperative dexmedetomidine (298/311), whereas only 5% of OIHR cases received intraoperative fentanyl (14/311). Table Figure Figure Figure Figure This project consisted of baseline data and the implementation of two anesthesia protocols via two PDSA cycles, assessing the effectiveness of multimodal OIHR care over 6 years. There was a reduction in the percent of patients requiring rescue morphine in PACU after implementation of PDSA cycle 2, with no notable changes to PACU maximum pain score, indicating improvement with our opioid sparing II block and dexmedetomidine protocol.PACU LOS remained stable with the exception of two signals after implementation of PDSA cycle 2. The breach in December 2019 was due to extended PACU stays for several patients. One patient experienced postoperative nausea and vomiting, leading to an extended PACU stay. Three other patients had PACU stays >120 minutes, though there wasn’t any clear documentation regarding why. The May–June 2021 signal may indicate an improvement in our PACU LOS for OIHR patients, though more data need to be collected to determine if this trend continues.Anesthesia preparation duration showed several signals. The decreasing trend noted in September 2017 and shift downward starting in November 2017 may be related to increasing comfort and efficiency with II blocks, which were becoming more commonplace during this time, even though the official change from TAP to II blocks did not occur until December 2017. This improvement with the adoption of II blocks lasted over two and a half years during PDSA cycles 1 and 2, but was not sustained. Starting in September 2020, there was a shift upward from the prior mean—this increase is likely due to hiring of several new nurse anesthetists at this time. However, even with this minor shift up (mean 12.60 minutes), the anesthesia prep time remained lower than the baseline group (mean 13.37 minutes), suggesting no real change. Of note, the breach of the UCL in July 2019 was due to two cases where “Anesthesia Start Time” was charted erroneously.18 This study demonstrated similar results within a pediatric OIHR patient population. A study of 60 children undergoing OIHR randomized to receive II block ± adjunctive dexmedetomidine found prolonged duration of analgesia, lower pain scores, and less rescue analgesic requirements during the first 24 hours postoperatively in the group receiving dexmedetomidine.19 While this study supports the use of II block + dexmedetomidine for OIHR versus II block alone, it does not include an assessment of II block + fentanyl, as was done in our QI study.We were able to minimize intraoperative opioids in PDSA cycle 2 by utilizing II blocks and dexmedetomidine in our protocol, while maintaining low rates of moderate to severe pain in our OIHR population. Dexmedetomidine has been well established as an analgesic adjunct and can reduce the need for opioids.2 At first glance, our results seem to differ, as anesthesia preparation duration time actually improved for several years when II blocks became the standard for OIHR. However, before PDSA cycle 1, most of our OIHR patients were already receiving II blocks (62%)—our reduced preparation time may thus be due to improved skill and efficiency as providers performed this block more frequently.Prior pediatric literature suggests that II blocks are more technically challenging and time consuming than TAP blocks.15 However, stability in our PACU LOS X-bar chart indicated no deterioration in this measure once dexmedetomidine was instituted in the protocol. This may be because dexmedetomidine is common in several other protocols at BCSC and our practitioners and nurses are already comfortable with the use and pharmacokinetics of this medication.Dexmedetomidine has the potential to prolong emergence and PACU LOS in the perioperative period.26 This is not ideal since pain may be assessed differently depending on who evaluates the patient’s pain level.27 However, when separating patients by age  and thus grouping patients with similar pain assessment tool use, we found no SCV within any of the age groups for maximum PACU pain score over the 6-year project. We believe this is consistent with our combined pain scale results. Third, we did not examine hemodynamic data, such as hypotension and bradycardia (common side effects of dexmedetomidine) to determine potential limitations with its use in the pediatric population. However, ephedrine, glycopyrrolate, and atropine administration can be used as proxies for treatment of hypotension and bradycardia. In our baseline group, PDSA 1 group, and PDSA 2 group, 2%, 0%, and 5% received ephedrine, whereas 1%, 2%, and 1% received glycopyrrolate, respectively. One patient received atropine in the PDSA 1 group. Last, a limitation of many QI projects is that, while validated at their home institutions, they are not necessarily generalizable. Our team has extensive experience with anesthesia protocol implementation, dexmedetomidine administration, opioid minimization, and regional blocks, and access to a software program that extracts and displays continuously updated data from the hospital’s EMR in the form of SPC charts—these factors may not be the norm at other institutions. Regardless, this study serves as an example of how readily accessible EMR data can support QI work, encourage adoption of standardized clinical protocols, and reduce variation in practice to improve the quality of clinical care.This study has several limitations. First, despite the implementation of prescribed OIHR protocols in PDSA cycles 1 and 2, we did not have complete uptake of each of the relevant protocol changes by our team (process measure), possibly leading to less clear results. Second, though there is correlation between pain scores from different pain assessment tools, we converted scores from three different pain assessment tools into an 11-point (0–10) scale in a nonvalidated manner.By leveraging PDSA cycles, real-time EMR data, and SPC charts, we optimized an anesthesia protocol for OIHR surgery utilizing II blocks and dexmedetomidine that minimized the need for intraoperative opioids while decreasing the percent of patients requiring postoperative rescue morphine. Anesthesia preparation duration improved compared to baseline data. Further research, such as a multicenter, randomized controlled trial is needed to determine if our findings are relevant for other institutions.Dr. Daniel Low is the Chief Medical Officer and founder of AdaptX, and Dr. David Liston is a shareholder in AdaptX. The other authors have no financial interest to declare in relation to the content of this article.


Ulnar-sided wrist pain has historically been equated to lower-back pain of wrist surgery. Little is known about the relationship between psychosocial profile and the manifestation of ulnar-sided wrist pathology and their treatment outcomes. This study aimed to determine the impact of pain catastrophising, psychological distress, illness perception, and patients’ outcome expectations on patient-reported pain and hand function before and one year after surgery for ulnar-sided wrist pathology.We included patients who underwent surgical treatment for ulnar-sided wrist pathology. Before surgery, patients completed the Pain Catastrophising Scale (PCS), Patient Health Questionnaire (PHQ), Brief-Illness Perception Questionnaire (B-IPQ), and Credibility/Expectancy Questionnaire (CEQ). Pain and dysfunction were assessed before (n = 423) and one year after surgery (n = 253) using the Patient Rated Wrist/Hand Evaluation (PRWHE). Hierarchical linear regression was used to assess the relationship between psychosocial factors and the preoperative PRWHE score, postoperative PRWHE score, and change in PRWHE.Psychosocial variables explained an additional 35% of the variance in preoperative PRWHE scores and 18% on postoperative scores. A more negative psychosocial profile was associated with higher (worse) preoperative PRWHE scores  and postoperative PRWHE scores  but not with the change in PRWHE after surgery. Higher treatment expectations were associated with a lower (better) postoperative PRWHE score  and a larger change in PRWHE scores .A more negative psychosocial profile was associated with higher pain levels and dysfunction preoperatively and postoperatively. However, these patients showed similar improvement as patients with a more feasible psychosocial profile. Therefore, patients should not be withheld from surgical treatment based on their preoperative psychosocial profile alone. Boosting treatment expectations might further improve treatment outcomes.III (Cohort study).The online version contains supplementary material available at 10.1186/s12891-022-05045-x. Chronic conditions of the wrist can be challenging to manage. Especially ulnar-sided wrist pain is playfully equated to the “lower back pain” or “black-box” of the wrist due to the diverse nature of chronic complaints, insidious appearance and resulting frustration as well as the anatomical complexity –4.The anatomy of the ulnar-sided wrist, the diagnosis and treatment options have recently been summarised in a comprehensive review . In shorWhile effort has been put into understanding ulnar-sided wrist pathology based on the anatomy and biomechanics , 4, 5, pThe relationship between psychosocial profile and patient-reported pain and dysfunction is becoming well recognised for common musculoskeletal pathology. For example, pain catastrophising and depression were associated with higher scores of pain and dysfunction at presentation in patients with hip , thumb , or spinNext to the potentially better understanding of patient-reported pain and dysfunction in patients with ulnar-sided wrist pathology, psychosocial factors may be determinants for the outcome of surgery. A meta-analysis on the outcome of total knee replacement reported that a more negative psychosocial profile was associated with worse outcomes . HoweverThe association between psychosocial variables and patient-reported pain and dysfunction have been scarcely investigated in patients with ulnar-sided wrist pathology. Also, their effect on the outcome of surgery is unclear. Therefore, this study aimed to determine the impact of pain catastrophising, psychological distress, illness perception, and patients’ outcome expectations on patient-reported pain and hand function both before and at one year after surgery for ulnar-sided wrist pathology.We studied prospectively gathered data on a consecutive cohort of patients that underwent surgical treatment of ulnar-sided wrist pathology between September 2017 and June 2020 at Xpert Clinics, The Netherlands. All surgeons at our institution are certified by the Federation of European Societies for Surgery of the Hand and/or fellowship trained.After their first consultation with a hand surgeon, all our patients were invited to be included in the Hand and Wrist Cohort, a routine outcome measurement system. Upon agreement, they received secure web-based questionnaires using GemsTracker . Three rWe report this study using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement . InternaWe identified adult patients in the Hand and Wrist Cohort scheduled for surgical treatment for ulnar-sided wrist pathology by the treatment codes: USO; TFCC reinsertion; pisiformectomy; u-head implant; and Adams procedure. Generally, conservative treatment was initiated by a short period of immobilisation, followed by a rigorous program of wrist exercises. After careful anamnesis, physical examination, and imaging , surgical treatment was considered if symptoms persisted for more than three months or if patients did not want further nonoperative management. Surgical treatment was directed to the type of pathological structure(s) focussing on the reconstruction of the anatomy . ExclusiAfter the first consultation with a hand surgeon, sociodemographic characteristics were routinely collected. The variables evaluated in this study were age, sex, type of work, symptom duration, and whether the dominant side was affected.The Pain Catastrophising Scale(PCS) was used to measure pain catastrophising , 21. We The Patient Health Questionnaire-4 (PHQ), a combination of the PHQ-2 and Generalised Anxiety Disorder (GAD)-2, measured psychological distress (anxiety and depression) . We evalThe Brief Illness Perception Questionnaire(B-IPQ) was used to measure how patients perceive their illness , 24. As The Patient Rated Wrist/Hand Evaluation-DLV (PRWHE) measured patient-reported pain and dysfunction before surgery and one year after surgery , 29. The2 deviation from zero with an effect size F2 of 0.10, α of 0.05, 16 predictors and a sample size of 423, we reached a power of 99,5%. For the model at follow-up with the same effect size, α, 18 predictors, and 253 patients, we reached a power of 87,9%For a fixed regression model with an RWe checked continuous data for normal distributions with histograms and quantile–quantile plots. Normally distributed data were displayed as mean values with standard deviations (SD), and skewed data were displayed as mean values with inter-quartile ranges (IQR).We performed a hierarchical multivariable linear regression to investigate the relative contribution of different variables to the explained variance in the amount of pain and dysfunction before surgery  and after surgery (model 2). For model 1, we consecutively added sociodemographics, scheduled surgical procedure, PCS + PHQ scores, and B-IPQ scores. For model 2, we also stepwise added the CEQ expectation subscale and the preoperative PRHWE score. For model 3, the outcome was the change score in PRWHE before and after surgery. Similar to other studies, PCS and PHQ scores were added simultaneously but separately from B-IPQ since pain catastrophising and psychological distress have been studied more extensively , 12, 13.2, adjusted R2, and significance of F change are reported per step. All linear regression model assumptions were checked and satisfied.Regression coefficients (B) with corresponding 95% confidence intervals and standardised coefficients (β) are reported for all variables. To illustrate the explained variance of different models, RWe calculated Pearson correlation coefficients and variance inflation factors (VIF) to investigate whether the correlation between psychosocial variables did not bias our estimates. We interpreted the Pearson correlation coefficients as suggested by Hinkle et al.  and VIF 2 tests.Because data were collected during daily clinical practice, and participation in the routine outcome measurement was voluntary, missing data were expected. We tested for significant differences in demographic characteristics and, when available, preoperative questionnaire scores between patients who completed all questionnaires (complete responders) versus patients who completed none or only some  using analysis of variance or ChiThe sample size was calculated using GPower 3.1 . All othA total of 603 patients with ulnar-sided wrist pathology were scheduled for surgical treatment during the study period. We excluded eight patients younger than 18 years, one patient with incomplete demographic data, and 12 patients who underwent a surgical procedure less prevalent than 30 times in the dataset.Of the 582 eligible patients, 423  completed all questionnaires before surgery  and were enrolled in the study. Of these patients, 253 (retention rate is 60%) also completed the follow-up assessment. This subgroup of patients was used for models 2 and 3  and psychological distress  based on treatment.Non/partial responders more often males than complete responders (P = 0.007). There were no differences between these groups in other demographics or PRWHE, PCS, PHQ, IPQ, and CEQ scores Table .β = 0.12), higher age , higher PCS score , higher B-IPQ Consequence score , and higher B-IPQ Identity  were independently associated with higher (worse) preoperative PRWHE total score  to 42%  and a higher preoperative PRWHE total score  were independently associated with a higher (worse) 1-year postoperative PRWHE total score. A higher CEQ Expectancy score  was independently associated with a lower (better) 1-year postoperative PRWHE total score  and B-IPQ Consequence score  were independently associated with larger improvement in PRWHE score after one year  , QuervaiThe relationship between psychosocial factors and pain and dysfunction in patients with ulnar-sided wrist pathology provides implications and recommendations for clinical practice. First, hand surgeons should be aware of the substantial relationship between patient-reported pain and dysfunction and psychosocial factors before surgery. A part of the complaints may stem from negative psychosocial factors, or the complaints may exhibit negative psychosocial factors. Second, operating patients with a more negative psychosocial profile report similar improvement than those with a more feasible psychosocial profile meaning that these should not be withheld from surgical treatment. However, considering the greater degree of complaints before surgery, patients with a more negative psychosocial profile before surgery still have worse 1-year treatment outcomes than patients with a more positive psychosocial profile. Therefore, hand surgeons should question whether patients with a more negative psychosocial profile are sufficiently treated with surgical interventions alone. For example, patients may benefit from counselling on psychosocial factors. This is encouraged by Zale et al., who concluded that patients benefit from learning resiliency skills . AnotherAdditional file 1. Additional file 2. Additional file 3. Additional file 4.


Diagnosis and treatment of non‐odontogenic pain is challenging for endodontists. The purpose of the study was to investigate the outcomes of referrals to orofacial pain specialists made for patients with suspected non‐odontogenic pain, after evaluation and/or treatment by an endodontist.A retrospective review of dental records was conducted for 60 patients referred from a postgraduate endodontic clinic to an orofacial pain clinic. Patient demographics, pain history, endodontic, and orofacial pain diagnoses were collected. Number of visits, length of treatment, and treatments prescribed were recorded. For analysis of outcomes, data pertinent to resolution/persistence of symptoms and patient compliance were analyzed.Thirty‐five patients were included in the study. The most frequent pulpal and periapical diagnoses were previously treated (62%) and symptomatic apical periodontitis (72%), respectively. The most common orofacial pain diagnosis was temporomandibular disorder. The average time spent to diagnose and treat the pain was 17 months. Pain reduction varied and was documented for 51% of patients. Indications of non‐compliance with orofacial pain appointments and treatments were documented for 66% of patients.Non‐odontogenic pain diagnosis and treatment are challenging. Patients may have an increased predilection for developing persistent pain after endodontic treatment and/or have an undiagnosed, chronic orofacial pain condition as a true source of their chief complaint. It may be helpful for endodontists to set expectations of typical treatment times/plans when referring patients for evaluation and treatment of non‐odontogenic pain. The study and our application for waiver of authorization and/or consent was approved by the Institutional Review Board of the New York University School of Medicine (study number: i18‐01448). All patients that were referred from the New York University College of Dentistry (NYUCD) Post‐Graduate (PG) Endodontic Clinic to the Orofacial Pain Clinic (OFPC) between January 2015 and August 2018 were evaluated for inclusion. The start date of January 2015 was selected because it was the date electronic records were implemented for use at NYUCD.2.1Sixty charts were reviewed. The study inclusion criteria required patients to have attended at least one visit to the OFPC, after being referred from the PG Endodontic clinic. Subjects were excluded if they had inaccessible or incomplete patient records.2.2Electronic dental records were reviewed for each subject. For included subjects, data was collected on patient demographics, medical history, endodontic and orofacial pain diagnoses, treatment times, and outcomes. Collected patient demographics and medical history included age, gender, history of reported chronic pain, and reported depression and/or anxiety. Endodontic and orofacial pain diagnoses were collected from treatment notes. Endodontic diagnoses were made in accordance with the American Association of Endodontists diagnostic guidelines. The number of visits, length of treatment (in months), medications and treatments prescribed were recorded. For analysis of treatment outcomes, data pertinent to the resolution or persistence of clinical symptoms, patient treatment trajectories and patient compliance were analyzed. Pain resolution was captured as change in pain intensity on numerical rating scale relative to the pain intensity reported at the subjects' initial visit.2.3Study data were collected and managed using REDCap electronic data capture tools hosted by New York University Langone Medical Center  were female and the mean age was 48 ± 17.4. Forty‐three percent (15/35) self‐reported a history of depression/anxiety. Sixty percent (21/35) reported a history of a pre‐existing chronic pain disorder, distinct from their chief orofacial pain complaint , were not treatment planned for endodontic therapy because their pain was suspected to be of non‐odontogenic origin. However, the remaining 22 (63%) patients were treatment planned for endodontic treatment on one or multiple teeth (Table 3.3Eighty‐three percent 29/35) of the study subjects were diagnosed with a painful condition of non‐odontogenic origin by the orofacial pain specialist. Differential diagnoses of the non‐odontogenic pain conditions are listed in Figure 9/35 of tIn 26% (9/35) of patients there was indication that pain persisted after dental intervention. In seven out of nine, pain persisted after endodontic treatment. In two of the nine, pain persisted after tooth extraction. In the reviewed dental records, varying nomenclatures, such as trigeminal neuropathic pain, were used to describe pain that persisted after dental intervention with accompanying neuropathic pain characteristics  and/or somatosensory changes . Out of these nine patients, four were diagnosed with both trigeminal neuropathic pain and TMD, showing that multiple orofacial pain conditions can occur concurrently.Further, when assessing these nine patients, there was clear evidence that for four of the patients, pain either began or changed its character after the dental intervention of either root canal treatment or tooth extraction. Therefore, in our study, according the current orofacial pain classifications, we described the diagnosis for these patients as PTTNP. For the remaining five patients, because there was not sufficient information from the charts that show dental intervention was the causative trauma, we described the diagnosis for these patients as PIDAP.Once the patient received a diagnosis from the orofacial pain specialist, different combinations of treatment modalities were prescribed Table . PhysicaComplete pain resolution was noted in the charts of only two patients 2/35, 6%), whereas some degree of pain reduction was reported in 51% of all cases (18/35)  that a dental intervention was the initiating event for the persistent pain. Most of the patients in this retrospective study reported pain prior to endodontic treatment. However, even though there were reports of pre‐operative pain, it is also possible that the root canal treatment itself may have created an injury that contributed to the persistence of pain  in this study. This compliance rate is comparably lower than previous reporting, ranging from 42% to 93% (Riley et al., Due to the retrospective nature of this study there are inherent limitations. This is exemplified by our inability to confirm the accuracy of diagnoses and difficulty evaluating pain resolution as a treatment outcome. Additionally, our patient pool was limited, as it was confined to patients treated within a single academic institution. Despite the outlined limitations, our study confirms that the differentiation of non‐odontogenic and odontogenic pain can be challenging. Furthermore, this study highlights that a definitive diagnosis is often only made following assessment from a number of specialists. The involvement of secondary and tertiary referrals makes the process protracted and potentially financially burdensome (Devine et al., 5It should be recognized that patients with known risk factors for pain chronification may have an increased predilection for developing persistent pain after endodontic treatment and/or have an undiagnosed, chronic orofacial pain condition as a true source of their chief complaint. A multidisciplinary team is essential for identifying and managing chronic orofacial pain: often a definitive diagnosis is only made following assessments from a number of specialists, involving secondary and tertiary referrals.The authors declare no conflicts of interest.Ozge Erdogan and Lorel L. Burns designed and conducted the study, performed data analysis, and wrote the manuscript. Austin Ramsey performed data collection and edited the manuscript. James M. Uyanik contributed to study design, data collection, analysis, and manuscript editing. Jennifer L. Gibbs contributed to data analysis revised the manuscript. All authors approved the final version of the manuscript.


BackgroundLow back pain represents 2-3% of Emergency Department (ED) visits. In this study, we aimed to identify patient and treatment-related variables that contributed to repeat visits to the ED for low back pain within a 12-month period.MethodologyWe conducted a retrospective review of adult patients presenting to the ED of one hospital over a two-year period with the primary diagnosis of low back pain. The primary outcome included return to the ED within 12 months with the same complaint, and the secondary outcome included return to the ED within 30 days or six months.ResultsA total of 793 patients met the inclusion criteria. The rate of return to the ED with the same complaint within 30 days, six months, and 12 months of the first visit was 7%, 11%, and 14%, respectively. Patients who received opioids at discharge were more likely to return within 12 months  and six months  compared to those who did not receive opioids at discharge. Undergoing an X-ray decreased the odds of a 30-day return visit by 70% (p = 0.0067), and by 59% within 12 months (p = 0.0032). Receiving opioids at discharge also doubled the odds of return within 12 months , while receiving nonsteroidal anti-inflammatory drugs (NSAIDs) reduced the odds by 60% (p = 0.0028).ConclusionsPatients who received opioids at discharge were more likely to have a return visit for low back pain within six and 12 months. Patients who underwent X-rays at the index visit and were prescribed NSAIDs at discharge were less likely to return to the ED for low back pain. Acute low back pain in the adult population is common, accounting for 2-3% of Emergency Department (ED) visits -3. IdentOne of the most common treatment methods for low back pain is the administration of opioids, which has been shown to be moderately effective in the short-term . HoweverMany centers now attempt to provide alternative treatments for low back pain in the ED. However, the long-term effectiveness of such treatments is unclear . MultidiThe goal of this study was to identify patient and treatment-related variables that contributed to repeat visits to the ED for low back pain within a 12-month period. We hypothesized that medications administered in the ED and prescribed at discharge as well as insurance status would contribute to patients returning to the ED within 12 months with the same complaints. These findings will be beneficial when modifying new protocols for adult patients presenting to the ED with low back pain.We conducted a retrospective review of adult patients who presented to the ED for back pain at one hospital over a two-year period . Patients were identified via a search in the Electronic Medical Record for a primary diagnosis of low back pain with or without sciatica. Inclusion criteria included a primary diagnosis of low back pain and age of >18 years. Institutional review board approval was obtained prior to the start of the study. Data were collected on the following variables: age, sex, body mass index (BMI), Charlson Comorbidity Index (CCI) [Data were collected by trained research associates who were blinded to the study hypothesis using a standardized data collection form which was then stored in a centralized database. Data were monitored and evaluated for accuracy at various time points throughout data collection by a second researcher.2, overweight 25-29.9 kg/m2, obese 30+ kg/m2); Length of ED stay ; Length of hospital stay .While age, CCI, BMI, and hospital length of stay were continuous variables, they were categorized for analysis due to violations of the linearity assumption  and to iDescriptive statistics were calculated for patients as well as individual visits. The number and frequency (%) were reported. Univariate logistic mixed models with random intercepts to account for the correlation between visits for the same patient were run for the primary and secondary outcomes. We constructed multivariate logistic mixed models to determine independent risk factors for 30-day and 12-month return visits. All variables in the univariate models with p-values of <0.15 were included in the multivariate models. Because age and CCI were collinear, the final model for 12-month return visits only included age, which improved model fit based on Bayesian Information Criteria. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were reported for the multivariate models. P-values of <0.05 were considered statistically significant, and the complete case approach for missing data was used. All statistical analyses were performed in SAS version 9.4 .In total, 793 patients corresponding to 928 ED visits met the inclusion criteria. Patient characteristics are listed in Table Most patients were females (58%), 32% were less than 40 years old, 43% were 40-59 years old, and 25% were 60 or above. Approximately half of the patients had a CCI score of zero, while 31% of patients had a CCI score of two or higher. The most common insurance type was private insurance (39%). Overall, 10% of patients had more than one ED visit, and the number of visits ranged from one to 16 during the two-year study period.Characteristics of the 928 patient visits are presented in Table Univariable analysesResults from the univariable analyses of characteristics associated with return visits at 30 days, six months, and 12 months are presented in Table At all three time points, receiving an X-ray at the index visit was inversely associated with an ED return visit for back pain. Patients receiving an X-ray at the index visit were less likely to return to the ER within 30 days , six months , and 12 months .Those who received opioids at discharge were more likely to visit the ED within six months of the index visit  and within 12 months .Middle-aged patients between the ages of 40 and 59 were more likely than their younger and older counterparts to return to the ED within six months (p = 0.0452) and 12 months (p = 0.0048). Receiving NSAIDs at discharge had an inverse relationship with a return visit within 12 months .Insurance through Medicaid increased return visit risk relative to private insurance (p = 0.0061), and patients with a CCI of one were more likely to return than those with a CCI of zero (p = 0.0193).Multivariable analysesMultivariable analyses were performed to further identify independent risk factors for 30-day and 12-month return visits. Based on the univariate analyses, X-ray, follow-up, NSAIDs in ED, intravenous opioids in ED, and opioids at discharge were included in the multivariate model for 30-day returns  is similar to previous studies which range from 28% to 56% ,25. The We found that oral opioids were administered at a rate of 41% in the ED. Interestingly, this rate of opioid administration is almost identical to the 42% rate reported in a similar study . OverallEvidence-based models for the treatment of low back pain are currently being studied and will hopefully reduce unnecessary tests, identify the most effective treatments, and ultimately improve patient outcomes . In addiWithin our patient population, there was no difference in returning within 30 days for patients with private insurance versus Medicaid. However, patients with Medicaid were more likely to return within six months and had a higher odds of return visits within 12 months. Future studies should more thoroughly follow patients after discharge and try to identify obstacles that may preclude prompt primary care or specialist follow-up.LimitationsThe primary limitation of this study was its retrospective nature. Prospective data were not obtained which limits the ability to determine if there is any causal relationship between any of the associations that were observed. The patients included do not reflect a truly randomized sample but include all patients presenting to a singular institution within the given timeframe. The data were dependent on patient charts, which are subject to coding errors. However, patient data were collected by multiple individuals to reduce error in chart abstraction via double data entry. Furthermore, charts were reviewed for accuracy and consistency. There was no confirmation that opioids prescribed upon discharge were filled. Data on patient race and ethnicity were not obtained for this study but may be helpful to assess any possible relationship with the studied variables.The data in this study is from 2013-2014 and should be interpreted with caution as various changes have been made since that time. For example, wisely choosing campaigns have emphasized that imaging is rarely needed for acute low back pain and should be used sparingly, resulting in improved imaging stewardship in the ED . AdditioIn summary, receiving opioids on discharge may contribute to a return to the ED within six months and 12 months for low back pain. Furthermore, patients receiving NSAIDs at discharge and an X-ray at the index visit may be less likely to return to the ED for low back pain. Insurance status may also contribute to return visits for low back pain within six and 12 months.


A national patient survey indicated higher procedural pain than anticipated, potentially impacting on screening compliance and effectiveness. We aimed to assess whether water-assisted sigmoidoscopy (WAS), as opposed to standard CO2 from five sites across England. The primary outcome measure was patient-reported moderate/severe pain, as assessed by patients on a standard Likert scale post procedure prior to discharge. The key secondary outcome was adenoma detection rate (ADR). The costs of each technique were also measured.The WASh (Water-Assisted Sigmoidoscopy) trial was a multicentre, single-blind, randomised control trial for people undergoing BSS. Participants were randomised to either receive WAS or CO2). We found no difference in patient-reported moderate/severe pain between WAS and CO2 . ADR was 15% in the CO2 arm and 11% in the WAS arm (p=0.03); however, it remained above the minimum national performance standard in both arms. There was no statistical difference in mean number of adenomas nor overall polyp detection rate. There was negligible cost difference between the two techniques.1123 participants  were randomised (561 WAS, 562 CO2 or WAS intubation technique.In the context of enema-prepared unsedated screening sigmoidoscopies performed by screening-accredited endoscopists, no difference in patient-reported pain was seen when using either a COISRCTN81466870. However, no randomised controlled trial has assessed water-assisted sigmoidoscopy (WAS).Bowel cancer is the second most common cause of cancer death in the UK. Bowel Scope Screening (BSS) comprises a one-off sigmoidoscopy at 55 years. In a BSS survey, 39% of patients reported moderate or severe pain. Studies indicate that water-assisted colonoscopy  were lower, particularly as most trial endoscopists preferred the water-assisted technique.Bowel cancer is the second most common cause of cancer death in the UK, and is estimated to cost the English National Health Service (NHS) £1.6 billion a year.Sigmoidoscopy can be painful due to bowel distension and endoscope ‘looping’. Data from a BSS survey of 43 378 patients showed that 39% of patients report moderate or severe pain.2 insufflation. Water infusion requires a lower volume (under 1 L) than CO2 (10 to 20 L), hence reducing distension and looping. Two different techniques have been described: water immersion (WI) and water exchange (WE).Water-assisted colonoscopy (WAC) involves water infusion during scope insertion, instead of traditional CO2-assisted insertion, resulting in better patient experience during BSS. Our key secondary aim was to study whether WAS affected the ADR. We also aimed to investigate the effects of WAS on ADR, other aspects of patients’ experience and technical aspects of sigmoidoscopy. Further, we aimed to assess the cost-effectiveness of the two techniques and to perform a discrete choice experiment to elicit patient preferences during sigmoidoscopy.We aimed to investigate the effects of WAS in BSS. Our primary aim was to test the hypothesis that WAS would lead to decreased procedural pain, when compared with standard COThe WASh trial was a multicentre, prospective, two-armed, randomised, single-blinded trial designed to evaluate the effectiveness of WAS in patients referred for BSS screening.Our primary outcome measure was patient-reported moderate/severe pain, using the standard BSS Likert scale recorded after their procedure. Our key secondary outcome measure was ADR.We developed the following trial success criteria—either:primary outcome achieved  and no indication of ADR being inferior (defined as WAS ADR within 3% of control ADR); orprimary outcome not achieved  but key secondary outcome achieved Patients referred for screening sigmoidoscopy through the BSS programme were invited to take part in the study. Patients who had absolute contraindications to sigmoidoscopy, lacked capacity to give informed consent, had a previous distal colonic/rectal resection or were receiving ongoing antithrombotic treatment (excluding aspirin) were ineligible for recruitment into the study.All procedures were performed by screening-accredited endoscopists trained in WAS. Training comprised a baseline questionnaire and a slide presentation (including videos). Endoscopists then attended a training day, including live demonstrations. Prior to trial commencement, endoscopists were required to have completed a training log of at least 20 WAS procedures to confirm competence.2 pump then infusing water as required to achieve adequate luminal views as the scope advanced. Suctioning of water/faecal residue and gas was performed as needed. While the technique was ideally performed without any gas insufflation, in common with other trials one or two short blasts of CO2 were permitted at the discretion of the endoscopist, but where possible, that insufflated gas was suctioned as soon as feasible, thus adhering to the principle of keeping the colon as collapsed as possible. CO2 insufflation was reinstated for extubation, which was identical in both arms, in accordance with standard BSS practice.Procedures were performed with enema preparation and without sedation, as mandated by BSS programme. The key principle of the WAS technique was to keep the lumen as collapsed as possible, thereby concertinaing the sigmoid colon, resulting in a straighter and shorter passage between the rectum and the descending colon, hence reducing the tendency for looping. The technique is described in detail in our published protocol.2 on a 1:1 ratio using a dynamic adaptive algorithm created by the North Wales Organisation for Randomised Trials in Health Clinical Trials Unit.Participants were allocated to WAS or COThe primary outcome was participant rated procedural pain on a 4-point Likert scale (dichotomised into a binary measure of none/mild versus moderate/severe). The key secondary outcome was ADR, which was calculated from the sigmoidoscopy procedure alone. Other secondary outcomes included pain rated on a validated visual analogue scale (VAS) post procedure and prior to discharge, polyp detection, mean adenomas per procedure, overall procedure time, extent of insertion, use of Entonox, use of hand pressure, patient position changes, technique conversion rates, use of second enema, quality of mucosal views, looping and other procedure-related data. A patient experience questionnaire was completed 24 hours after the procedure. Participants remained in the trial for 14 days following their procedure, for adverse events identification purposes. We also aimed to define the sigmoidoscopist learning curve of the WAS technique during the training period. A full list of outcomes can be found in the study protocol paper.A sample of 1100 patients was calculated to provide 80% power at a 5% significance level to detect a difference of 30% between the groups on the primary outcome of pain (none/mild versus moderate/severe); this included 5% attrition . We assumed an uptake rate of 20% and thus anticipated needing to invite 5500 people within 18 months.The primary analysis was performed on an intention-to-treat basis. All statistical tests performed were two-sided using a 5% significance level and 95% CI level. Results of secondary analysis were presented without adjustment for multiple comparisons. Outcomes with under 5% missing observations were conducted as complete case analysis, and if at least 5%, multiple imputation (MI) methods were adopted. The MI model included all factors that were used in the analysis models including allocation group, scope diameter, hysterectomy, history of IBS, trust and diverticulosis. A fully defined statistical analysis plan was written, with review from the independent data-monitoring and trial steering committees, prior to completion of data collection.Mixed effects regression models were run on scale outcomes and logistic regression models  for categorical outcomes. Scope diameter, hysterectomy, history of IBS and diverticulosis were entered as fixed effect factors and screening centre as a random effect. All assumptions of fitted models were checked and evaluated to hold. The distribution of mean number of adenoma data was evaluated to be highly dispersed around zero; therefore, analysis using a zero-inflated negative binomial model was conducted.2 sigmoidoscopy. We measured costs from an NHS perspective, focussing on the direct medical costs of both procedures. Only if we observed a significant difference in effectiveness in terms of the primary outcome measure (pain) were we to progress to a full cost-effectiveness analysis.We evaluated the cost-effectiveness of WAS versus CO2). Two patients withdrew from the study following randomisation, however, did not withdraw consent to use their data. No patient was lost to follow-up.Overall, 2845 patients were screened for inclusion in the trial, of whom 1130 were recruited 40%;  between Most of the same-day outcome measures had minimal missing data (below 2%) and complete case analysis was conducted on these. The next-day patient experience questionnaire outcomes had more missing data (24% to 25%); therefore, MI techniques were adopted.Patient characteristics are detailed in 2 test).When asked immediately following the procedure to reflect on procedural pain, 44% of participants reported no pain, 40% mild, 14% moderate and 2% severe pain. The mean VAS pain score reported immediately after the procedure was 21.1 . Of the 857 (76%) who responded to the next-day survey, 28% recalled no procedural pain, 46% mild pain, 23% moderate and 3% severe pain. Of 854 respondents, 57% felt that the procedure was less painful than expected, 12% felt it was more painful and 31% stated it was as expected. Those who felt the procedure was more painful than expected (12%) were significantly lower than in the national survey (25%) , with predictive marginal estimates of 14% in WAS and 15% in CO2 (The results of the logistic (binary) regression analysis  conducte% in CO2 . Other p10.1136/gutjnl-2020-321918.supp1Supplementary data2 group . The predictive marginal estimates indicate ADR to be 11% in the WAS group, as opposed to 15% in the CO2 group . Polyp detection was 143 (25 per 100) in WAS and 147 (26 per 100) in CO2 group (NS). Median and IQR for WAS and CO2 groups were identical for all polyp sizes  and maximal polyp size per patient .Of 1123 participants, 290 (26%) had at least one polyp and 113 (10%) had at least one adenoma . Most paO2 group . The meaSixty-one per cent of procedures reached at least the descending colon . Retrofl2 group . Excellent prep was more common in the WAS group, whereas inadequate prep rates were the same in both groups.Eighty per cent of procedures had good or excellent mucosal views on the Boston Bowel Preparation Scale (BBPS).2 group .The mean overall procedure time was 7.68 (SD 4.30) minutes. After adjustment, those in the WAS group have a longer insertion (4.62 min) and overall procedure time (8.83 min) compared with the CO2 (7%) than from CO2 to WAS (2%); .Overall, 5% of procedures required a technique conversion: significantly more from WAS to CO2 group (χ2All 50 adverse events (in 47 patients) were classed as ‘expected’ and not serious, comprising 21 patients (45%) in the WAS group and 26 patients (55%) in the CO2 groups. Raw data of pain, procedure-related data and patient experience are presented in the No other outcomes revealed statistically significant differences between WAS and COOf the 856 patients who responded to the question on embarrassment experienced during the procedure, 53% reported none, 39% reported mild, 8% moderate and less than 1% severe embarrassment . Of the Of those responding to the questionnaire, 66% reported no abdominal pain or cramps, 28% reported mild, 5% moderate and 1% reported severe abdominal pain or cramps. No bleeding was reported by 97%, mild by 3%, moderate by less than 1% but none reported severe bleeding. No sleep disturbance was reported by 93%, mild by 5%, moderate by 2% and severe by less than 1%. No bloating/wind was reported by 49%, mild by 42%, moderate by 8% and severe by 1%. No bottom soreness was reported by 86%, mild by 13%, moderate by 1% and severe by less than 1%. No soiling was reported by 94%, mild by 5%, moderate by 1% and none reported severe soiling. No nausea/vomiting was reported by 97%, mild by 3%, moderate by less than 1% and severe by less than 1%. No faintness/dizziness was reported by 94%, mild by 6%, moderate by less than 1% and severe by less than 1% .2 arm . For prior experience subgroup, the mean number of adenomas were 19 per 100 procedures in both WAS and CO2 and for those with no prior experience, the mean adenomas were 8 per 100 procedures in WAS and 14 per 100 procedures in CO2. It should be noted that the prevalence of procedures conducted by an experienced endoscopist was low and data for it was not collected a priori for analysis; hence, these results should be interpreted with caution.Subgroup analyses were conducted on history of IBS, diverticulosis, scope diameter, scope model, extent of procedure, hysterectomy/sex, endoscopist WAS competence prior to study training, study period , BBPS and polyp detection. None aided interpretation of the results with regards to the primary outcome of patient-reported pain. Regarding the key secondary outcome of ADR, the only result of interest was that endoscopists without prior WAS experience had a significantly lower ADR in the WAS arm compared with the CO2 insertion and four were neutral. All stated that they were likely to use the water-assisted technique in their ongoing endoscopy practice.After trial recruitment had finished, the 15 participating endoscopists were asked to complete a questionnaire. Self-reported lifetime experience ranged from 38 to 400 independent water-assisted procedures (median 100), with a success rate ranging from between 60% and 70% to 95% (median 90%). Positive attitude was expressed by 14/15 (93%) towards the water-assisted technique, one was neutral. Ten (67%) preferred the water-assisted technique, one preferred CO2 cost £0.03 per litre, whereas water was of slightly higher cost; hence, the difference in price between both procedures.As there was no difference in the primary outcome measure of pain experienced by patients, we assessed the costs of the two procedures rather than performing a full cost-effectivesness analysis. With Reference to NHS costs of £388 for diagnostic flexible sigmoidoscopy with biopsy on an outpatient basis, 19 years and over,This is one of the largest RCTs assessing a water-assisted endoscopic technique to be performed to date, and the first in the UK. We believe it is also the first trial to assess the technique in enema-prepared sigmoidoscopy.2 and WAS—thus, our study proved negative according to its primary outcome measure. This might be because the technique offers no advantage in patient pain, at least in the context of enema-prepared, unsedated sigmoidoscopies performed by screening-accredited endoscopists. Although this is contrary to other trials, our results are plausible as studies to date have all been for colonoscopy rather than sigmoidoscopy. Moreover, the BSS has an endoscopist accreditation process, which may mean the standard technique is higher quality than in most other services. CO2 is also mandated in the BSS, whereas in many studies, air was used rather than CO2 insufflation: CO2 causes less pain than air.2 test),We found no difference in pain between COSeveral other potential explanations were explored. First, it is possible that trial endoscopists were inadequately trained in the water-assisted technique; however, subgroup analysis failed to show any difference in outcome between the first and second half of the study, nor was the outcome different on subgroup analysis of endoscopists with prior experience of the technique. Moreover, after the trial, the majority of endoscopists expressed a preference for water-assisted intubation, implying that they felt they had mastered the technique. While the underlying principle of the water-assisted technique that we taught was to collapse the colon down as much as possible to create a concertinaed sigmoid and straighter path from the rectum to the descending colon, we did not mandate a full water-exchange technique—it is possible that either the full water-exchange technique or a ‘corkscrew hook’ rather than push technique is required to improve comfort.Second, the technique might have been hampered by inadequate cleansing from enema-preparation; however, no difference in outcome was identified on subgroup analysis limited to cases with good or excellent prep.Third, most endoscopes did not have a dedicated irrigator channel, potentially hampering the technique; however, subgroup analysis limited to endoscopes with an irrigator channel failed to show a difference.Fourth, the post-procedure assessment of pain used in our study might have been too insensitive to detect true differences; however, this validated score did reveal a difference between the overall trial pain levels compared with the prior national survey.Fifth, unlike in colonoscopy, where the endoscopist must reach a fixed landmark (the caecum), in the BSS, the endoscopist is tasked with intubating as far as is possible within the limitations of the bowel prep and patient comfort—thus, an endoscopist might opt to cease intubation early on if a patient experiences pain, potentially removing a cohort of patients who would have experienced substantial pain with ongoing intubation. We believe this is a likely explanatory factor for the lower levels of pain experienced overall in our trial compared with the earlier BSS survey, where depth of intubation was more than in our trial—it is also possible that there has been a genuine improvement in technique, hence sigmoidoscopy comfort in recent years. Nevertheless, our trial revealed no difference in depth of intubation between the two arms.2 and water-assisted techniques.Planned subgroup analyses of specific patient cohorts  failed to show any difference in pain between the CO2 arm compared with WAS. This could not be explained by any difference in bowel prep quality, nor extubation times. This finding was unexpected, as several prior trials reported higher ADR with a water-exchange intubation technique, although it should be noted that our trial was water-assisted rather than full water-exchange technique. As there was no significant difference between trial arms in the total number of adenomas detected or the polyp detection rate, it is possible that the ADR difference was a chance occurrence. However, it is feasible that the difference was genuine, either due to the technique per se , a learning curve for the technique (unfamiliarity with the underwater view or distraction by performing the new technique), or the trial protocol . Although one of our subgroup analyses revealed no difference between the first and second half of the trial, another subgroup analysis revealed that the lower ADR was limited to endoscopists without prior experience in the water technique, implying that there may be a longer learning curve for the WAS technique that we had appreciated.In our key secondary outcome measure, ADR was above the minimum BSS performance standard in both arms but was significantly higher in the COThere was negligible difference in cost between the two procedures.2 or WAS intubation technique. Most patients included in our trial were also recruited at one site (North Tees).As with most endoscopy trials, it was not possible to blind the endoscopist to intervention arms, hence there might have been deliberate or inadvertent bias for either CO2-assisted) technique during unsedated, enema-prepared screening sigmoidoscopy performed by screening-accredited endoscopists. Patients can be reassured that irrespective of insertion technique, pain in our study was much lower than previously reported. There is no need for screening sigmoidoscopists to switch to a WAS technique, nor should the BSS programme amend national policy. Caution should be given to monitoring ADR if WAS is used in enema-prepared sigmoidoscopies. Further research is required to explain why no difference was seen in pain, and why ADRs  were lower, particularly as most trial endoscopists preferred the water-assisted technique and previous colonoscopy trials have suggested water-assisted techniques were superior.In conclusion, our trial did not show reduced patient pain using a water-assisted (cf. standard CO


We present a 76-year-old man with chronic back pain refractory to treatment secondary to spinal trauma from a motor vehicle accident 34 years ago. After trauma, multiple interventions were performed due to spinal instability. The patient was diagnosed with the postlaminectomy syndrome. Multimodal analgesia management failed to control our patient’s pain, severely affecting our patient and his family’s quality of life. For these reasons, a spinal cord stimulator was implanted despite our patient age. After four months, our patient presented with significant improvement in his life quality. Low back pain is a public health problem that increases spinal surgeries . PostlamWe present a 76-year-old man who suffered spinal trauma after a motor vehicle accident 34 years ago. After trauma, medical evaluation immediately showed grade 2 spondylolisthesis with signs of instability at the L5-S1 level. The patient was managed surgically with L5-S1 arthrodesis with intervertebral cage and iliac crest graft. Unfortunately, postoperative infection complicated the patient’s clinical course. For this reason, surgical cleanings were performed for almost six months until infection resolution  of buprenorphine with confusion and lethargy reported during the first days of treatment. The initial therapy failed to manage the pain, severely limiting his daily activities. Gabapentin 1200mg and buprenorphine ½ patch (5mcg) every 72 hours. The patient was treated by a psychiatrist for major depressive disorder with amitriptyline and lactulose for moderate constipation. Despite pharmacological pain management, the patient did not show improvement, so he was referred to our hospital for refractory pain management. It was decided to place a spinal cord stimulator.A spinal cord stimulator trial with percutaneous electrodes was placed through L1 and L2 until reaching the thoracic level. During the procedure, abundant fibrosis difficulted access to the thoracic spine; however, it was possible to place electrodes at the thoracic level (Figure Due to the considerable clinical improvement of more than 40% with a trial stimulator, a permanent electrode was implanted with similar improvement. Three months later, the patient reported how much the pain decreased. In addition, he reported improvement during the daytime with mild pain, returning to his hobbies, and significant improvement in sleep quality.Postlaminectomy syndrome occurs when the results of one or more lumbar spine surgeries performed to alleviate pain do not meet the expectations of the patient ,7. One oOur patient underwent eight spinal surgeries with no successful outcomes, as described in several studies. This result has been observed in up to 40% of patients . AccordiDespite being managed at maximal doses, the patient did not obtain adequate pain management. This is an outcome observed in other cases in which it was reported that pharmacological treatment was only helpful in a minority of patients . AccordiSpinal cord stimulation has proven to be the most effective treatment in patients with predominantly neuropathic pain in the lower extremities, showing a successful outcome in 62% of patients with FBS ,7. The gAn electrode is implanted in the posterior epidural space in contact with the spinal cord, with a stimulation frequency range between 20 and 120 Hz ,12. It iSpinal cord stimulation effectively treats limbs' radicular pain better than more invasive techniques such as reoperation or conservative management. Its use is strongly recommended in multiple conditions such as PLS. Although better results have been observed in patients younger than 65 years-old, SCS can be used within the overall framework of multimodal pain management in patients with severe deterioration in their quality of life.


Comparing the effect of two different  One hundred and twenty-four patients undergoing laparoscopic cholecystectomy were randomly allocated to receive nalbuphine (group N), oxycodone (group O), and morphine (group M). The three groups were all given intravenous injection (iv.) of 0.15 mg/kg injection before incision and 0.05 mg/kg injection at the end of pneumoperitoneum. The Visual Analogue Scale (VAS) scores  and Ramsay sedation scores at 1, 2, 4, 8, 12, 16, 20, and 24 hours after surgery, the time of extubation, the incidence of postoperative adverse events, the satisfaction of pain treatment, and the duration of stay after surgery were all recorded. P < 0.05). The VAS scores of visceral pain at movement in group N decreased longer than those in group O (P < 0.05). Compared with that of group M, the postoperative time in Ramsay sedation score of group O increased longer than that of group N (P < 0.05). Compared with group N, patients had worse sleep quality in group O, longer length of stay in group M, and lower satisfaction in both groups.  Compared with group M, the VAS scores of visceral pain at rest decreased in group N and group O at 1-8 h after surgery (κ-receptor agonists, nalbuphine and oxycodone, during laparoscopic cholecystectomy can reduce postoperative visceral pain. Furthermore, the nalbuphine group had fewer adverse reactions, better analgesia, and better satisfaction. Compared with morphine, prophylactic use of the  In recent years, with the rapid development of enhanced recovery after surgery (ERAS), day surgery has emerged. Among them, enhanced recovery and adequate analgesia are an essential part of increasing the rate of day surgery . Laparos2) used for referred pain  to rate the following three pain components: incisional pain was defined as a superficial pain, wound pain, or pain located in the abdominal wall. Visceral pain was defined as pain inside the abdomen. Shoulder pain was defined as a sensation of pain in the shoulder. Follow-up evaluations were conducted at 1, 2, 4, 8, 12, 16, 20, and 24 h postoperatively by anesthesiologists blinded to grouping. The degree of incision pain and visceral pain was evaluated when resting and in motion (cough and deep breathing), respectively. And record the Ramsay sedation score  . The paiThe power calculation for the study was based on the VAS of visceral pain at rest at 1 h after surgery, which was our primary outcome. A pilot study involving 8 patients at our center found that the mean ± standard deviation (SD) of the VAS of visceral pain at rest at 1 h after surgery was 4.5 ± 1.8. In a sample size of 40 patients, a clinically significant reduction of 30% in the VAS of visceral pain at rest at 1 h after surgery at a power of 95% was observed, with a two-sided significance level of 0.05. To compensate for the possibility of dropouts, we recruited a total of 132 patients, with 44 patients per group.χ2 test. P < 0.05 was considered to be statistically significant.The SPSS 22.6 software was used for statistical analyses. Distribution of variables was assessed using the Kolmogorov-Smirnov test, while homogeneity of variance was evaluated using Levene's test. Quantitative data were expressed as the P > 0.05), and there was comparability between the three groups. . The VAS score of visceral pain at movement in group N was significantly decreased 2-20 h after surgery, and that in group O was significantly decreased 2-8 h after surgery (P < 0.05). There was no statistical significance in VAS scores of shoulder pain among the three groups (There was no significant difference in the VAS score of incision pain (at rest and movement) among the three groups. Compared with group M, the VAS score of visceral pain at rest in group N and group O decreased 1-8 h after surgery , while the differences between groups M and O were not statistically significant. In the case of using rescue analgesia within 24 h postoperatively, that in groups N, O, and M increased sequentially; however, the differences were not statistically significant. Unplanned discharges of patients were significantly reduced in the group N compared to group M. (P < 0.05)  .P < 0.05), and the difference was not statistically significant in group O compared to both group M and group N. The occurrence of other side effects was reduced in both group O and group N, in which 7 patients in group M had significantly more pruritus than the other two groups, and 18 patients in group M had significantly more dizziness than 4 patients in group N. The differences were all statistically significant (P < 0.05) (The occurrence of PONV in patients was significantly reduced in group N compared to group M ( < 0.05) .κ-receptor agonists, nalbuphine and oxycodone, in LC can significantly reduce postoperative visceral pain. The nalbuphine group has fewer complications such as postoperative dizziness, nausea, and vomiting and has better effect in reducing early postoperative pain and better patient satisfaction.This study mainly found that compared with morphine, preventive use of κ-opioid receptors.LC has the advantages of minimally invasive and quick recovery. With the deepening of ERAS concept, daytime surgery, which completes admission, discharge and corresponding surgery, and operation within one working day, arises at the historic moment. Nowadays, more and more clinicians use LC in daytime surgery. The development of daytime surgery would speed up patient turnover, reduce waiting time, reduce the risk of nosocomial infection, improve the use efficiency of medical resources, and reduce various expenses. A standardized daytime surgery system has clinical and economic win-win benefits . Howeverκ-receptor agonists may have the same analgesic effect on abdominal incision pain as morphine. The VAS scores of visceral pain (at rest and movement) in oxycodone and nalbuphine groups were significantly reduced within 2-8 hours after operation. It is suggested that the analgesic effect of oxycodone and nalbuphine on visceral pain may be better than that of morphine. This is because the two κ-receptor agonists inhibit the sensitization of peripheral pain κ-opioid receptors and the excitatory neurotransmission between the afferent nerves expressing κ-opioid receptors and the superficial neurons of the spinal cord that process pain signals. These functional κ-opioid receptors have abundant innervation not only for skin but also for visceral organs, which indicates that κ-opioid receptors are of great significance in inhibiting visceral pain [This study found that there was no significant difference in VAS scores of incision pain (at rest and movement) among the three groups of patients, which may be related to the layer-by-layer infiltration of 0.5% ropivacaine in the three groups of patients. It also indicates that the two ral pain .κ-opioid receptors [On Ramsay sedation score, the mean value of morphine group was less than 2 at 1-16 hours after operation. It may be related to the imperfect analgesia in this group, which improves the arousal level and offsets the sedation induced by morphine. In an experimental pain study on sedation, it was also found that morphine had no effect on sedation variables in electroencephalograph . Compareeceptors .κ-receptor agonists in terms of analgesic effect. Compared with that in the oxycodone group, VAS score of visceral pain at movement in the nalbuphine group was still significantly lower 12-20 h after operation. The reason may be that oxycodone is a semisynthetic opioid receptor agonist, which has double agonism of both μ-opioid receptors and κ-opioid receptors, and the half-life of oxycodone intravenous injection is 3.5 h. Nalbuphine, on the other hand, is a morphinan semisynthetic agonist-antagonist analgesic, which exerts pharmacological effects through agonist κ-opioid receptors and antagonist μ-opioid receptors with a half-life of 5 h. Although nalbuphine is an agonist antagonist, its analgesic effect is not weakened by μ-opioid receptors antagonism. This may be one of the reasons for the longer analgesic effect of nalbuphine [κ-opioid receptors are quite different among different internal organs, and their analgesic effect is mainly mediated by stimulating peripheral κ-opioid receptors. Under the condition of inflammation and pain sensitization, the peripheral analgesic effect of κ-opioid receptor agonists would be further enhanced. Oxycodone is a κ2-opioid receptor agonist with relatively low affinity to μ-opioid receptors, of which the μ-opioid receptor agonism is not strong. Nalbuphine mainly exerts analgesic effect through agonist κ-opioid receptors [κ-opioid receptors. In addition, nalbuphine can also increase the density and activity of opioid κ-opioid receptors, and then improve the analgesic effect [The study also found some differences between the two lbuphine , 20. Theeceptors , 20. Thec effect . The speμ-opioid receptors, which leads to respiratory depression, addiction, itching, nausea, and vomiting. This study also found that the incidence of postoperative adverse reactions in the morphine group was generally higher than that in the other two groups. Previous studies have inconsistent results in comparing the side effects of morphine and oxycodone. Yanagidate and Dohi found that morphine may have a higher incidence of nausea, vomiting, and skin pruritus [μ-opioid receptors can prevent or alleviate side effects such as skin pruritus, dizziness, nausea, and vomiting [μ-opioid receptors and κ-opioid receptors agonism may increase the occurrence of postoperative adverse reactions. Therefore, the nalbuphine group may be more advantageous in the prevention of adverse reactions than the other two groups.In the past clinical practice, the dose limitation of opioids is precisely due to its agonism of pruritus . Howeverpruritus , 24. Pedpruritus . The totpruritus , 11. Thivomiting , while oPain management is an important measure in Enhanced Recovery After Surgery (ERAS). There is a significant correlation between the number and severity of postoperative adverse reactions and the decline of patient-oriented results  . Previouκ-receptor agonists on inhibiting the release of inflammatory cytokines after operation. These will be further explored in subsequent studies.Postoperative release of inflammatory cytokines may lead to excessive stress, immunosuppression, pain sensitization, etc., which would aggravate postoperative pain and delay postoperative rehabilitation. This study did not measure cytokines by blood sampling and compared the effects of the different κ-receptor agonists, nalbuphine, and oxycodone in daytime LC. The nalbuphine group has fewer adverse reactions such as dizziness, nausea, and vomiting and has better effect in relieving early postoperative pain, which can improve patients' satisfaction with anesthesia and shorten length of stay. Therefore, it is more recommended to apply to daytime LC surgery.In conclusion, compared with morphine, postoperative visceral pain will be reduced significantly in prophylactic use of


Hypertonic saline solution has been frequently utilized in clinical practice. However, due to the nonphysiological osmolality, hypertonic saline infusion usually induces local vascular pain. We conducted this study to evaluate the effect of lidocaine coinfusion for alleviating vascular pain induced by hypertonic saline.One hundred and six patients undergoing hypertonic saline volume preloading prior to spinal anesthesia were randomly allocated to two groups of 53 each. Group L received a 1 mg/kg lidocaine bolus followed by infusion of 2 mg/kg/h through the same IV line during hypertonic saline infusion; Group C received a bolus and infusion of normal saline of equivalent volume. Visual analogue scale (VAS) scores of vascular pain were recorded every 4 min.P < 0.05). The overall incidence of vascular pain during hypertonic saline infusion in Group L was 48.0%, which was significantly lower than the incidence (79.6%) in Group C (P < 0.05).The vascular pain severity in Group L was significantly lower than that in Group C for each time slot (Lidocaine coinfusion could effectively alleviate vascular pain induced by hypertonic saline infusion.ChiCTR1900023753. Registered on 10 June 2019.Chinese Clinical Trial Registry, number:  Hypertonic saline solution has been frequently utilized for fluid resuscitation, management of hyponatremia, and reducing intracranial pressure, among other procedures. In anesthetic practice, hypertonic saline is one alternative for volume preloading before spinal anesthesia. In some institutions in China, hypertonic saline with a concentration not exceeding 3% is allowed to be infused via peripheral veins. However, due to the nonphysiological osmolality, hypertonic saline infusion usually induces local vascular pain. Patients may experience the sensation of stinging and compression around the site of venous cannulation, which reduces patient satisfaction.Lidocaine is a widely used local anesthetic agent. It can reduce propofol injection pain when administered in the same vein, and it can also decrease pain when hypertonic saline is injected for sclerotherapy, implying its local anesthetic effect on local vein , 2. Lidowww.chictr.org.cn (Number: ChiCTR1900023753) prior to patient enrollment. The study was conducted in accordance with CONSORT guidelines. No changes were made to the protocols or analyses after the trial commenced. After obtaining written informed consent from all patients, we conducted this prospective, double-blinded, randomized, controlled trial in the First Affiliated Hospital of Nanchang University from October 2019 to March 2021. Inclusion criteria: aged 18–65, American Society of Anesthesiologist (ASA) classes I and II, scheduled for elective surgery requiring spinal anesthesia. Patients with chronic pain, abnormal sensation, neurologic deficits, and allergy to lidocaine were excluded.This clinical trial was approved by the China Ethics Committee of Registering Clinical Trials (ChiECRCT20190219) and was registered in the Chinese Clinical Trial Registry, An attending anesthesiologist from the First Affiliated Hospital of Nanchang University, who was independent of patient management and data collection, generated random numbers (in a 1:1 ratio) using SAS 9.2 software . The results of randomized allocation were sealed in sequentially numbered opaque envelopes. A total of 106 patients were randomly allocated into two equal groups: a lidocaine group (Group L) and a placebo control group (Group C). All the subjects received 200 ml of 3% hypertonic saline via peripheral vein for volume preloading before spinal anesthesia. Patients in Group L received a bolus of 1 mg/kg lidocaine at the initiation of hypertonic saline infusion, followed by continuous infusion of lidocaine at the speed of 2 mg/kg/h. In Group C, normal saline was used as placebo; patients in Group C received a bolus of normal saline at the initiation of hypertonic saline infusion, followed by continuous infusion of normal saline, and the volume of normal saline was equal to the volume of lidocaine in Group L.2) was performed for all patients on their arrival at the anesthesia preparation room. A nurse who was in charge of drug preparation, opened an opaque envelope, delivered a preprepared syringe  into the room, and then left. Therefore, the medical staff and patients in the anesthesia preparation room were blinded to the allocation. A 22-gauge i.v. cannula was inserted into the vein on the dorsum of the hand. To maintain hemodynamic stability, 200 ml of 3% hypertonic saline was administered for volume preloading prior to spinal anesthesia. Hypertonic saline was infused at the speed of 10 ml/min controlled by an electronic infusion pump. Meanwhile, in Group L, lidocaine was simultaneously infused into the same venous line through a 3-way stopcock and an infusion extension line. The dosage of lidocaine was a bolus of 1 mg/kg (0.1 ml/kg) followed by continuous infusion of 2 mg/kg/h (0.2 ml/kg/h), which was administered by a microinfusion syringe pump. Lidocaine coinfusion was stopped when the 200 ml of hypertonic saline preloading was accomplished. In Group C, an equivalent volume of normal saline was coinfused. Spinal anesthesia was performed after volume preloading, followed by surgical operation.Patients were fasted for 6 h before anesthesia and given no preoperative sedatives. Monitoring of ECG, noninvasive blood pressure (BP) and pulse oximetry  by using a visual analogue scale (VAS) score, which varied from 0 (no pain) to 10 (the worst imaginable pain). Major adverse effects, such as tinnitus, dizziness, and extravasation, phlebitis, and venous thrombosis on the cannulation site were also observed and recorded in this study. No changes were made regarding trial outcomes after the trial commenced.The incidence of vascular pain was the primary outcome of this study. During the hypertonic saline infusion, vascular pain was assessed and recorded every 4 min . Data were expressed as the mean ± SD, or number of patients (% frequency), or median (range), as appropriate. Numerical data were compared using t-test if normally distributed, or using Mann–Whitney U test if not normally distributed. Categorical data were compared using a Chi-square test or Fisher’s exact test. P > 0.05) observed between the two groups with respect to age, weight, height, gender, and ASA classification . There were 26 (52.0%) patients out of 50 in Group L who did not experience any pain during the 20-min infusion, while there were only 10 (20.4%) patients in Group C who did not complain of any pain. The overall incidence of vascular pain in Group L was 48.0%, which is significantly lower than the incidence (79.6%) of vascular pain in Group C  out of 50 in Group L experienced transient tinnitus or/and dizziness during the infusion. No other complications were observed in this study.Hypertonic sodium chloride solution is one of the fluids commonly used in clinical practice. It is frequently utilized for management of hyponatremia, reducing intracranial pressure, and alleviating cerebral edema associated with neurological injuries , 6. FurtIn some institutions, it is common practice to allow only central venous line infusion of hypertonic saline due to the safety concerns associated with peripheral venous infusion such as extravasation, tissue ischemia, phlebitis, and venous thrombosis. Nevertheless, growing evidence has demonstrated that the incidence of local tissue damage was very low and the degree of injury was mild, when 3% sodium chloride solution was infused peripherally for a prolonged duration , 12, 13.Due to the nonphysiological osmolality, infusion of hypertonic solution via a peripheral vein usually induces local vascular pain. The mechanisms of vascular pain evoked by hypertonic saline have not yet been fully elucidated. It is believed that the osmolality-associated pain is mediated by nociceptors in the vessel wall , 16. In Vascular pain usually reduces patients’ satisfaction, and alleviating vascular pain is an important issue , 19. LidIn the present study, lidocaine was simultaneously and continuously infused into the same vein into which hypertonic saline was infused. Therefore, lidocaine could work through the combination of both a local anesthetic effect and a central analgesic effect. The results of our study suggested that lidocaine coinfusion was effectual in relieving vascular pain associated with persistent hypertonic saline infusion. The overall incidence of pain during the 20-min infusion was 48.0% in Group L, a reduction of 32% compared with placebo group; and the median pain scores with lidocaine coinfusion were significantly lower than those in Group C in each time slot. The adverse events associated with lidocaine were mild; only 8% of the patients in lidocaine group complained of transient tinnitus or dizziness and did not require any intervention, which indicated the safety of lidocaine coinfusion. Since lidocaine is a worldwide commonly used drug and inexpensive ($0.5/100 mg in China), lidocaine coinfusion deserves further studies in reducing vascular pain associated with hyperosmolar fluid infusion.There were some limitations in this study. First, we did not monitor the blood levels of lidocaine. The dose of lidocaine used in the current trial was based on previous studies , 30. ThiIn conclusion, this study showed that 3% hypertonic saline infusion through the peripheral vein did not cause obvious local tissue injuries but induced vascular pain. Lidocaine coinfusion could effectively mitigate vascular pain during hypertonic saline infusion.


However, it is unclear if the Foundation Medicine test would result in a better outcome than the standard on-site molecular testing. In this retrospective chart review, we identified the FM cases from an academic Canadian hospital and determined whether these test results improved treatment options for those patients.The use of Next-Generation Sequencing (NGS) has recently allowed significant improvements in cancer treatment. Foundation Medicine® Software.A retrospective analysis was performed on patients with solid tumors who had FM testing between May 1, 2014 and May 1, 2018. Clinical factors and outcomes were measured using descriptive statistics using Microsoft ExcelOut of 66 FM tests, eight patients (= 12%) had a direct change in therapy based on the FM tests. Identified were 285 oncogenic mutations ; where TP53 , CDKN2A , KRAS  and APC  were the most common FM mutations identified.A small proportion of FM reports identified actionable mutations and led to direct treatment change. FM testing is expensive and a few of the identified mutations are now part of routine on-site testing. NGS testing is likely to become more widespread, but this research suggests that its true clinical impact may be restricted to a minority of patients. Precision medicine, also known as targeted medicine/genomic medicine or personalized medicine, is increasingly important in the management of cancers . Some caSome of the significant challenges in the implementation of precision medicine pertain to molecular testing and drug access. With regards to detecting molecular alterations, these can be performed for a few specific oncogenic driver mutations that have an approved and available therapy. However, each test utilizes precious pathological specimen, and with an increasing number of mutations to look for this brings obvious challenges. Furthermore, more clinical trials are selecting patients based on new biomarkers as they have a higher likelihood of success . Alterna® . Foundation Medicine® testing has been broadly used especially in the USA with FDA approval and in research development to aid with emerging and potential targeted therapies . The data was analyzed using descriptive statistics. All statistical analyses were completed using Microsoft Excel software.The primary endpoint for data analysis was the proportion of patients whose Foundation Medicine® testing performed in the period under study. Of the 76 tests, 10 were excluded due to sample testing failure, leading to 66 or 87% valid patient tests. The reason given by Foundation Medicine® for sample failure were as follows: two were because DNA yield was too low, two were because gross sample blocks were insufficient, five were because there was limited tumor cellularity and one had no details provided by Foundation Medicine®. These sample types are as follows: one was a bone curettage, two were endobronchial lung biopsies, two were fine needle aspiration biopsies, three were liver core biopsies, one was a liver segmental biopsy and one was a soft tissue core biopsy.In total, 76 patients had Foundation Medicine® testing, all patients were either stage III (15%) or stage IV (85%). The median number of lines of systemic therapy administered prior to Foundation Medicine® testing was 1 . The median time from diagnosis to Foundation Medicine® testing was 550 days . A summary of demographic data can be found in Of the 66 patients that were included for statistical analysis, the median age at time of cancer diagnosis was 56 years (range 19–84). Twenty-seven (41%) patients were male and 39 (59%) female. At time of Foundation MedicineThe most common histological types of cancer identified were: Lung Adenocarcinoma , Colon Adenocarcinoma  and Breast Ductal Carcinoma . A summary of histological types identified are listed in The most common anatomical primary sites of cancer identified were: Lung , Colon  and Breast . A summary of anatomical primary sites identified are listed in ® tests, 107 different mutations were found. The most common Foundation Medicine® mutations identified were: TP53 , CDKN2A , KRAS  and APC . The median number of mutations found per patient was 3. By tumor location site, the median number of mutations found was 8.5 for gastroesophageal junction cancer, five for brain, breast and skin cancer, four for lung cancer, 3.5 for cancer of unknown primary and three for colon and pancreatic cancer. A summary of mutations identified are listed in In 66 Foundation MedicineKRAS n = , 5.6% an® results (six (75%) patients had one Foundation Medicine® result directed therapy, two (25%) patients had three Foundation Medicine® result directed therapies. See Eight of 66 (=12%) patients had actionable mutations identified that led to a direct change in therapy, and those eight patients received 12 therapies directly related to the Foundation Medicine® directed therapies, the clinical benefit rate was 5 which is 42% . In our cohort of patients, the best response to a Foundation Medicine® directed therapy was partial response which was found three times (25%). Six of the eight patients (=75%) who had their treatment modified due to FM® testing had lung cancer.Among the 12 Foundation MedicineThe median survival from the date of diagnosis to death/last follow up in all patients is 34.7 months (IQR = 20.2–49.4 months).® test was performed to the date of death/last known follow up in all patients is 16.8 months (IQR = 4.9–25.4 months).The median survival from the date that Foundation Medicine® testing led to a direct change in therapy, the median survival from the date that Foundation Medicine® test was performed to the date of death/last known follow up is 22.9 months (IQR = 11.5–30.3 months).Among the patients where Foundation Medicine® testing did not lead to a direct change in therapy, the median survival from the date that Foundation Medicine® was test performed to the date of death/last known follow up is 16.5 months (IQR = 3.5–25.0 months).Among the patients where Foundation Medicine® testing. The majority of cases in which Foundation Medicine® testing lead to direct treatment options were lung cancer. Since the time that these reports were sent, some of these mutations would now be identified on routine screening-such as ROS-1 and BRAF. With these cases removed, only five patients would have actionable mutations, based on Foundation Medicine® testing alone. The most common mutation identified was TP53, which is in line with prior research which reports TP53 as the most common mutation in cancer  had treatment altered based on their FM test result. Further, using the OncoKB classification, there were 10 level 1 mutations and eight level 2 mutations identified. The median survival of these patients with stages 3 and 4 disease was 22.9 months in patients with actionable mutations and 16.5 months in those with no actionable mutations. This impressive median survival was in spite of not many actionable mutations being found. There is likely a selection pressure, as patients with the most aggressive cancers would have less likely been able to access Foundation Medicinen cancer .First, to compare the most common mutations found. A study on rare and refractory cancers, found that the most common mutations identified were TP53 (46%), followed by RAS/RAF/APK(45%) . A study®. In our study, 10 patients were excluded due to problems with the sample to be tested. It is known that providing insufficient tissue is the primary reason for failure with next generation sequencing , five of which had G12C mutations. Current research on target therapies such as AMG 510 and MRTX849 have recently reported clinical efficacy in treating G12C mutation positive solid-type tumors , so whilIn conclusion, FM testing has not been routine in this center. Further, while multiple mutations are discovered only a small proportion were actionable mutations, of which some are now part of routine practice anyway. NGS testing is likely to become more widespread, but this research suggests its true clinical impact will be restricted to a minority of patients.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.MM: Creation of project, data extraction and analysis, and manuscript writing. DK: Creation of project, data extraction and analysis, and manuscript writing. PW-P: Creation of project, and manuscript writing and editing. AA: Manuscript writing and editing. BL: Procurement of genetic testing data. Manuscript writing and editing. LM: Data extraction. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.