P = 0.001), Dysport brand (P = 0.030), and younger age (P = 0.032) [but not sex (P = 0.406)] reduced pain. The only significant findings for 2-week complications were for the associations observed between aging with increased asymmetry  and a need for a retouch . Botulinum toxin dilution with lidocaine alone  can reduce pain without affecting postinjection complications. Toxin brands may cause different extents of pain. Aging, but not sex, may increase pain. Two-week complications were not affected by any factors, except aging in the case of asymmetry and the need for a botulinum toxin retouch.No study has assessed the effects of the incorporation of isolated lidocaine into botulinum toxin for reducing its pain or complications. Studies on the dilution of botulinum toxin with other materials are as well extremely few, small, and limited methodologically. Therefore, we aimed to evaluate, for the first time, the effects of the incorporation of lidocaine alone into botulinum toxin type A on post-injection pain and complications. In this 2-week prospective, multicenter, double-blind randomized placebo-controlled clinical trial, 729 participants  were enrolled. They were randomized into placebo and lidocaine dilutions (about 2:1), and then into two brands of toxins (Dysport versus Xeomin). Hence, there were 4 subgroups. In the 2 experimental subgroups, botulinum toxin was diluted with 2% lidocaine without adrenaline; in the 2 control subgroups, botulinum toxin was diluted with normal saline as a placebo. After injection, the pain level was recorded . After 2 weeks, post-injection complications were assessed based on the participants’ reports and the surgeon’s observations. Data were analyzed using 3-way ANCOVA, multiple binary logistic regression, and bivariable analyses . The mean ± SD pain levels in the lidocaine group (n = 263) and the placebo group (n = 466) were 3.51 ± 2.04 and 4.15 ± 2.35, respectively. The mean ± SD pain levels in the subgroups ‘Xeomin-Lidocaine (n = 61), Dysport-Lidocaine (n = 202), Xeomin-Placebo (n = 133), and Dysport-Placebo (n = 333)’ were respectively 3.39 ± 1.86, 3.55 ± 2.09, 4.61 ± 2.49, and 3.97 ± 2.24. Lidocaine incorporation ( Botulinum toxin type A (BTX-A) has become quite prevalent in the field of cosmetics because it has a low risk of complications and it is minimally invasive13. BTX-A is among the most common cosmetic routines for the treatment of forehead and lateral periorbital rhytides as well as glabellar frown lines14.After the discovery of the blocking effect of botulinum toxin on acetylcholine release and neuromuscular transmission15. The pain of injection is the most common complication reported by patients, which may deter some patients15. Additionally, sometimes the toxin can spread around and unintentionally paralyze unwanted muscles, resulting in complications such as ptosis16. Another challenge is the high vascularization of the areas commonly injected ; this increases the risk of toxin washout at the targeted muscles and inadvertent spread of the toxin into neighboring muscles20. To address these problems, some authors have suggested the incorporation of commonly available lidocaine hydrochloride with epinephrine into the botulinum toxin18. This way, lidocaine may reduce the pain of the toxin, while the vasoconstrictor adrenalin may reduce the spread of the toxin into unwanted areas while at the same time reducing the washout of the toxin and lidocaine.However, the use of botulinum toxin is not without problem3. Some clinicians suggest that excluding the vasoconstrictor adrenalin may increase this desirable effect of lidocaine even more. However, if the vasoconstrictor epinephrine increases the predictability, perhaps the vasodilator lidocaine without epinephrine21 might reduce the predictability and make the botulinum toxin spread around the injection area more than it should. It raises concerns regarding iatrogenic complications without epinephrin. Also, it is possible that without adrenaline, lidocaine is rapidly washed out of the area and becomes attenuated below the effective concentration, losing its anesthetic effects. This is clinically important and warrants assessment.Lidocaine, being a vasodilator, might have extra clinical advantages beyond pain reduction as well. Some surgeons and dermatologists suggest that the incorporation of lidocaine might enhance the efficacy or longevity of the botulinum toxin effectDespite the abovementioned points, no studies have assessed the effect of the incorporation of isolated lidocaine into botulinum toxin on the intensity of botulinum pain or complications. Due to the importance of this subject, and in light of the abovementioned shortcomings in the literature, and since there was no study on the incorporation of lidocaine without any additives such as epinephrine or sodium bicarbonate, we tested whether the addition of isolated lidocaine can reduce the pain of BTX-A. Also, we investigated whether or not the addition of lidocaine without adrenaline may cause more complications. For this purpose, a very large-scale randomized clinical trial was conducted. The null hypotheses were the lack of any effect of lidocaine and the brands of botulinum A toxin (as well as participants’ sex and age) on the injection pain or 2-week post-injection complications.This study was a prospective, parallel-arm, 4-arm, multicenter, triple-blind randomized, placebo-controlled clinical trial performed from 2020 to 2022 on 729 participants in a private clinic and a hospital in Tehran, Iran with a treatment/placebo allocation ratio of about 1:2. All participants were briefed completely before the study and signed written informed consent. The ethics of this study was approved by two independent bodies: the research committee of the Islamic Azad University  as well as an international organization responsible for examining, approving, and registering randomized clinical trials (IRCT.ir) following the Helsinki declaration . After the registration of the study, the sample size was augmented to 729 from an original size of 96 individuals, per more conservative criteria to ensure high power, reliability, and generalizability . The experiments began on 25/04/2021 and continued until May 2022.Included were all patients who had indications for BTX-A injection in the forehead area and had been referred to BouAli Hospital, Tehran, and a private clinic at the time of the examination and who did not have a previous history of an unpleasant postinjection issue. Each person needed to have symmetric mimetic forehead muscle function. Patients with any history of allergy to botulinum toxin type A or lidocaine as well as any history of a neuromuscular disorder would be excluded. Initially, after filling out the file for patients and taking a medical history, all patients with a previous unpleasant history  and all patients with asymmetry in injection sites, eyelid ptosis, and diplopia were excluded.Diagnosis of diplopia was made according to the patient’s statements; asymmetry and ptosis were diagnosed via observation by a specialist physician. Only patients with full data were included; in other words, if a patient would not attend the follow-up session 2 weeks after the injection, the recorded pain score would be discarded as well. The patients lost to follow-up would be replaced by new patients in order to reach the desired sample size.Based on the dilution materials and the Botulinum toxin brands, there were 4 subgroups:A: Each participant received 100 units of BTX-A  at 20 injection points, combined with 1 ml of normal saline without preservatives.B: Each person received 100 units of BTX-A (Dysport) combined with 1 ml of lidocaine 2% without epinephrine at 20 injection points.C: Each individual received 50 units of BTX-A  combined with 1 ml of normal saline without preservatives at 20 injection points.D: Each patient received 50 units of BTX-A (Xeomin) attenuated with 1 ml of lidocaine 2% without epinephrine.The allocation ratio of experimental-to-placebo groups was about 1:2. The allocation ratio of the botulinum toxin brands was determined according to their market availability, i.e. subgroups utilizing the Dysport brand were larger than Xeomin subgroups because Dysport was more available than Xeomin. The amount of botulinum toxin to be used for each patient was instructed by the manufacturer.22. A 29-gauge needle was used in all subgroups . In the placebo group, in which botulinum toxin was diluted with normal saline, the normal saline was a 9% injectable sodium chloride solution without any preservatives . In the experimental group, in which botulinum toxin was diluted with lidocaine, the lidocaine in use was 2% with a preservative . The injection was performed carefully by an experienced surgeon for each person at 20 points , and for the dilution with lidocaine, previous numerous studies on lidocaine in combination with different materials or alone have found it safeSince there was no comparative study on the pain intensity after the injection of BTX-A at the time of designing this research, no effect size was available from the literature. Therefore, the authors assumed a conservative effect size (0.25) as well as a high power (90%), resulting in a sample size of 676 participants. The sample size was augmented to 730 patients to offset additional variables besides pain (i.e. 2-week complications). Since there was no limit on the time frame of the study and also since there was a large number of individuals agreeing to participate, we did not anticipate any particular issues in curating the needed data.The study was triple-blind, meaning that the surgeon, the participant, and the observer were unaware of the materials and grouping: The surgeon administering the botulinum toxin was blinded to the experimental/placebo assignments and the botulinum brands. Although the numbers of units used from the brands differed, their volumes after dilution would be similar and undetectable from each other. The observers were blinded to the treatment/control assignments and to the botulinum brands as well. The patients were blinded to the grouping as well.All documents and questionnaires were coded. The coded documents were kept in sealed envelopes. The person who did the randomization also performed the concealment. She was not involved in any of the examinations.The participants were randomized using a computer program at two levels . First, they were randomized into one of the two groups  with a ratio of about 1:2. Since the study was large and multicentered, and since many people could be excluded or lost to follow-up, an exact ratio of 1:2 was not necessitated. After the first randomization, the individuals were randomized into either of the two brands of BTX-A with a ratio similar to the market share and availability of these brands. The syringes were coded and given to the surgeon who injected the botulinum toxin. The surgeon, who was the same person in all groups, performed the injection and completed the form without knowing the botulinum toxin brand and the dilution material.The post-injection pain was assessed using an 11-level numerical rating scale questionnaire (0 representing no pain and 10 representing maximum and intolerable pain needing emergency attention).24. Ptosis refers to drooping of the upper eyelid and can affect one or both eyelids. In the mild form, drooping eyelids are above the pupil of the eye, but in more severe cases drooping eyelids cover a part of the pupil so that it reduces the upper visual amplitude24. Diplopia is another ocular complication associated with botulinum toxin injection. Diplopia is secondary to extraocular muscle dysfunction. The patient complains of diplopia resulting from the injection, usually in the follow-up 1 week after the injection, which occurs following the paralysis of the lateral rectus muscle24. Eyebrow asymmetry is sometimes seen in the upper face third at the tail of the eyebrows, following the injection into the frontalis muscle to treat hyperkinetic forehead lines24.Two weeks after injection, ptosis (assessed by observation), asymmetry (through observation), diplopia (assessed by asking the participant), and any need for a botulinum toxin retouch (expressed by the patient) were recorded. Ptosis of the eyelid is one of the most common ocular complications associated with botulinum toxin injection that appears in the first 2 weeks after botulinum injectionDescriptive statistics and 95% confidence intervals (CIs) were calculated for the pain levels in different groups and subgroups. An independent-samples t-test was used to compare the main groups with each other in terms of their pain and age. Furthermore, a 3-way analysis of covariance (ANCOVA) was used to assess the simultaneous effects of the independent variables  on postinjection pain. Age was a continuous variable recorded as an integer number; it was without any grouping and with a unit of change of 1 year. A Pearson correlation coefficient and a partial correlation coefficient were used to examine the correlation between patients’ age (continuous) and their pain levels. Since the correlations were significant, descriptive statistics and 95% CIs were calculated for patients’ pain in different decades of life (as discrete age groups). As well, a histogram was drawn to show the distribution of patients’ ages. For the assessment of the effects of the same 4 independent variables on each of the 2-week post-injection complications, a point-biserial correlation coefficient, a Fisher, and a multiple binary logistic regression were used. Again, the variable “age” was an integer continuous variable without grouping. However, since its role became significant in some complications, the incidences of complications in different life decades (as discrete groups) were summarized as well. The level of significance was set at 0.05.The participants were briefed completely before the study and signed written informed consents. The ethics of this study was approved by two independent bodies: the research committee of the Islamic Azad University  as well as an international organization responsible for examining, approving, and registering randomized clinical trials (IRCT.ir) in accordance with the Helsinki declaration .P = 0.492). The mean ages of participants in different groups are presented in Table P = 0.703). No harm was identified in this study outside the rare complications of botulinum toxin injection. The trial ended after reaching the desired sample size.After examining and following up 1054 participants, 729 were approved and enrolled in the study  compared to the placebo (both brands combined) and pain reductions in the Dysport group compared with Xeomin. However, no significant difference was observed between the sexes . The partial correlation coefficient  as well detected a weak but significant correlation between age and pain .The Pearson coefficient showed a weak but statistically significant correlation between the individuals’ age and pain , sex (P = 0.704), BTX-A brand (P = 0.177), dilution material , the interaction of sex by brand (P = 0.499), the interaction of sex by dilution material (P = 0.785), the interaction of brand by dilution material (P = 0.578), and the interaction of sex by brand by dilution material (P = 0.574). Since the interactions were all non-significant (P ≥ 0.499), they were removed from the model. The optimized ANCOVA model showed significant effects for the dilution material , and age (P = 0.032). Sex did not have a significant role . Asymmetry was detected in 30 (6.4%) subjects within the placebo group and 9 (3.4%) cases within the lidocaine group . A botulinum toxin retouch was needed in 55 (11.8%) placebo cases and 29 (11.0%) lidocaine patients  placebo participants and 1 (0.4%) lidocaine patient  Xeomin and 3 (0.6%) Dysport cases. Asymmetry was seen in 9 (4.6%) Xeomin and 30 (5.6%) Dysport participants. A BTX-A retouch was needed in 16 (8.2%) Xeomin and 68 (12.7%) Dysport patients. Brands had no significant effect on any of the complications  and no males had ptosis. Asymmetry was observed in 38 females 5.7%) and 1 male (1.6%). A retouch was needed in 78 females (11.7%) and 6 males (9.7%). There was no difference between males and females in terms of any of the complications (asymmetry: .7% and 1P = 0.261). However, it was weakly correlated with asymmetry  and the need for a retouch .The point-biserial correlation coefficient showed that in the 729 patients, age (as a continuous variable without any grouping) was not correlated with ptosis  on the incidence of ptosis Table . However26: a clinical trial of 10 patients only on complications but not pain, a clinical trial of 15 patients only on pain incidence, and two clinical series without any control groups. The clinical trials were as small as 10 and 15 participants25, and only one had examined pain25. One of them suggested that the incorporation of lidocaine and epinephrine does not make the injection outcomes more predictable, nor would it reduce the incidence of pain25; they did not assess the intensity of pain25. The other reported that the addition of lidocaine and epinephrine would make the toxin’s effect appear immediately and therefore increase predictability; they did not assess pain18. Since some of such effects do not appear immediately but after a delay (hours27 to even 2 weeks3), it may be difficult to accurately evaluate the results (such as any symmetries) at the time of injection, and therefore to provide symmetric results16. Hence, methods that can speed up the effects are of value. The longitudinal studies found lidocaine-epinephrine incorporation satisfactory26; however, no control existed to compare their methods. Ravso and Bove26 reported a series of cases with the injection of lidocaine with epinephrine plus botulinum toxin (without any control groups) and asserted that the incorporation of lidocaine might avoid imperfect results following the injection of botulinum toxin26. Kim et al.3 conducted another case series study and concluded that diluting botulinum toxin with lidocaine and epinephrine might improve patient satisfaction with injections for facial rejuvenation, due to faster results, longer effects, less bruising and pain, and improved cosmesis3. de Quadros et al.25 randomized the facial sides of 15 patients to receive botulinum toxin diluted with normal saline or reconstituted with lidocaine and epinephrine; in their study, 3 (20.0%) patients reported pain regarding the side treated with lidocaine, whereas 8 (53.3%) reported pain in the side incorporated with normal saline. Although this difference did not reach the significance level (P = 0.180), there might be a chance to see a statistically significant result if a larger number of patients had been enrolled. They also did not show any statistically significant differences in the frequency of muscle paralysis  and facial symmetry in the application of botulinum toxin diluted merely with saline solution compared to that diluted with lidocaine and epinephrine diluted25. Gassner and Sherris18 assessed the effects of the incorporation of lidocaine plus epinephrine into botulinum toxin on the predictability of botulinum injection in 10 patients18. They reported that the addition of lidocaine with epinephrine could provide the physician with immediate feedback on the extent of paralysis, and thus improve the predictability and safety of botulinum toxin18. As the closest study to our design in terms of the diluents of botulinum, Jung and Kim28 examined the intensity of pain after the injection of botulinum toxin diluted with lidocaine plus sodium bicarbonate in 20 patients and found pain-decreasing effects for the lidocaine-bicarbonate complex28.The findings of this study indicated that the addition of lidocaine (without epinephrine) to botulinum toxin might reduce pain while at the same time, might not increase any complications of injection. There is no similar study that assesses the findings of the current study. There are however, two clinical series and two controversial clinical trial studies on the effect of dilution of botulinum toxin with lidocaine plus epinephrine29. The pain caused by the release of the toxin into the tissues can be reduced via anesthetics such as lidocaine. However, lidocaine incorporated into the toxin does not reduce the needle pain. Therefore, in clinical settings, it is recommended to reduce pain in the early and late phases. It seems that pain occurs mainly on the skin and therefore can be related to the needle gauge and the technique of injection. This could be a reason that when the same person with the same technique injects botulinum toxin, the pain might be similar. However, this hypothesis needs future investigations. Another point is that it is suggested that lidocaine might cause burning sensations and therefore increase pain30. This can in turn be responsible for the observed results, as a confounder. On the other hand, it is said that lidocaine might increase the speed of botulinum action because it can increase blood flow and also numb the muscle and allow it to absorb more botulinum. This as well warrants future research.Upon injection of botulinum toxin, pain can be felt in two stages, once when the needle punctures the skin and tissues and later after the toxin is injected into the tissue. The needle pain can be alleviated by locally anesthetizing the skin using methods such as the EMLA  cream or ice packsThis study was limited by some factors. The number of men was much smaller than the number of women; this was similar to all other studies on botulinum toxin, in which much more women seek such treatments. However, given the very large sample size, even the current number of men may be adequate to obtain proper results. Moreover, the number of one of the brands in use was smaller than the other brand, due to market availability. Furthermore, it would be better to also have positive control groups, in which the toxin was mixed with lidocaine and adrenaline. Nevertheless, that would require about 200 to 300 additional participants, which was not practical. The generalizability of the results may be increased by using various brands of botulinum toxin and enrolling more men. Nevertheless, it may be limited by the ethnic background of the participants, as in any other study.It may be concluded, for the first time, that the addition of lidocaine without epinephrine or any other chemicals to the BTX-A may reduce the pain perceived by the individual during botulinum toxin administration. However, it does not affect the postinjection complications observed after 2 weeks. The injection of the Xeomin brand would be more painful than Dysport, but it might not affect the 2-week complications. People’s age might slightly increase the injection pain as well as two of the complications, i.e. asymmetry and the need for a botulinum toxin retouch. Their sex might not affect pain levels or 2-week post-injection complications.


Early postoperative nausea was significantly less severe after OAGB, while pain was comparable especially at the 12th hour.The aim of our study was to assess and compare postoperative nausea and pain after one anastomosis gastric bypass (OAGB) and sleeve gastrectomy (LSG). Patients undergoing OAGB and LSG at our institution between November 2018 and November 2021 have been prospectively asked to report postoperative nausea and pain on a numeric analogic scale. Medical records were retrospectively reviewed to collect scores of these symptoms at the 6th and 12th postoperative hour. One-way analysis of variance (ANOVA) was used to evaluate effect of type of surgery on postoperative nausea and pain scores. To adjust for baseline differences between cohorts, a propensity score algorithm was used to match LSG patients to MGB/OAGB patients in a 1:1 ratio with a 0.1 tolerance. A total number of 228 (119 SGs and 109 OAGBs) subjects were included in our study. Nausea after OAGB was significantly less severe than after LSG both at the 6th and 12th hour assessment; pain was less strong after OAGB at the 6th hour but not after 12 h. Fifty-three individuals had a rescue administration of metoclopramide after LSG and 34 after OAGB (44.5% vs 31.2%,  The laparoscopic sleeve gastrectomy (LSG) is currently the most common bariatric procedure worldwide , while tAlthough there is a rich body of literature on postoperative nausea and vomit (PONV) after LSG , very liAssessment of these symptoms is particularly important since PONV occurs more frequently after bariatric surgery than after other abdominal surgical procedures –6.Moreover, PONV is responsible for prolonged hospital stay and 30-day readmission , 8Among all weight loss interventions, LSG is undoubtedly the most emetogenic  one, proAnother main issue in the first postoperative hours is pain. Forty percent of patients with morbid obesity complains with severe postoperative pain which can lead to pulmonary complications and increased risk of thromboembolism due to immobility , 11.To reduce the rate of PONV and the severity of postoperative pain, a specific Early Recovery After Bariatric Surgery (ERABS) protocol has been designed , 13.In our institution, ERABS guidelines are not strictly followed, indeed a nasogastric tube is routinely used and total intravenous anaesthesia (TIVA), instead of volatile anaesthetics, is not given to all patients. However, subjects with morbid obesity undergoing bariatric surgery in our hospital receive the same perioperative management.The aim of this study is to retrospectively compare postoperative nausea and pain after OAGB and LSG.All subjects that have undergone primary OAGB and LSG between 1st November 2018 and 1st November 2021 at our university hospital were included in this study. Those individuals who had an early complication or a concomitant procedure , with previous history of abdominal surgery or transferred to the Intensive Care Unit (ICU) immediately after surgery were excluded.not at all to 10 = worst imaginable nausea/pain).Patients undergoing bariatric surgery at our institution are routinely asked to report their pain and nausea on a numeric scale , pain and nausea at the 6th and 12th postoperative hour and preoperative symptoms of gastro-esophageal reflux disease (GERD).gastro-esophageal reflux disease (GERD) was diagnosed according to the Lyon Consensus Conference  criteriaThe choice of the procedure (OAGB or LSG) in our centre is based on patients’ BMI and obesity related diseases. Those individuals with higher BMI or metabolic complications such as Diabetes are more likely to undergo OAGB.Surgical techniques for both procedures have been described in detail elsewhere , 17,but For LSG, a five-trocar approach  was used. The gastrectomy started 4–6 cm from the pylorus over a 38–40 French bougie. Staple line reinforcements or oversewing is not routinely used at our institution.OAGB was routinely performed with a six-port laparoscopic technique. The gastric pouch was constructed by applying one horizontal 45-mm linear stapler at the lesser curvature, just below the left branch of the crow’s foot. Biliopancreatic limb length ranged from 180 to 220 cm depending on the preoperative BMI of patients. All the anastomoses were performed at least 13 cm distally to the GEJ.2 on 8 L/min for 3 min via face mask in ramped position was started. Induction was performed with propofol 2 mg/Kg of lean body weight, fentanyl 2–5 mcg/kg of lean body weight, rocuronium 0.6 mg/kg of ideal body weight followed by intubation. Muscle relaxation was monitored through train-of-four (TOF). Ventilation was performed with tidal volumes of 6–8 mL/Kg to avoid barotraumas and respiratory rates 12–14 breaths/min to maintain normocapnia and Positive End Expiratory Pressure (PEEP) of 5–10 cmH2O. Anaesthesia was maintained with desflurane with a MAC between 0.6 and 1, remifentanil infusion of 0.05–0.25 mcg/kg/min of lean body weight. No abdominal wall block or intraoperative injection of local anaesthetics was performed. Postoperative analgesia was provided with a continuous intravenous administration of ketorolac 90 mg, ondansetron 8 mg and oxycodone 10 mg through an elastomeric infusion pump. All patients assumed Paracetamol 1 g iv every 6 h for 24 as a rescue drug. Intravenous metoclopramide 10 mg was administered in case of severe nausea.After admission to the operating room two intravenous cannulas (16/18-gauge) were inserted; patients were monitored using a five-lead ECG, invasive arterial pressure monitoring, pulse oximeter, capnograph, end-tidal anaesthetic gas (ETAG) concentration monitoring, urine output and temperature. After proper assessment of the airway and anticipation of difficult airway, preoxygenation with 100% OA nasogastric tube was placed and left for the first 24 h after both interventions; liquid diet was started on postoperative day (POD) 3. Subjects were mobilized on POD1.Data are expressed as mean ± SD for continuous variables and as proportion or percentage in case of categorical ones. Continuous and categorical variables were compared using the chi-square and t-test, respectively. One-way analysis of variance (ANOVA) was used to evaluate effect of type of surgery on postoperative nausea and pain scores. To adjust for baseline differences between cohorts, a propensity score algorithm was used to match LSG patients to MGB/OAGB patients in a 1:1 ratio with a 0.1 tolerance. Propensity score matching (PSM) is a well-validated statistical technique that creates comparable groups and allows for accurate assessment of treatment effects. Patients were matched for preoperative age, BMI and GERD.Significant p value was set below 0.05. Data analyses were performed using Statistical Package for Social Science for Windows, version 28 .A total number of 136 primary OAGBs and 178 primary SGs have been performed at our institution in the study period. On the base of exclusion/inclusion criteria, 51 cases (early complication or concomitant procedure) were not eligible for this study, while data on postoperative nausea and pain were not available for 35 patients. Subsequently, 228 (119 SGs and 109 OAGBs) subjects were included in our retrospective comparison. After PSM, two matched groups of 73 subjects each were generated.Patients undergoing the two procedures had comparable age, rate of GERD and female/male ratio at baseline, but BMI was significantly higher in the OAGB group; all preoperative variables resulted comparable at baseline between the matched groups Table .Table 1BOverall values of nausea at the 6th and 12th hour were 5.8 ± 1.2 and 3.7 ± 1.3 respectively, while total scores for pain were 5.9 ± 1.1 and 3 ± 1.th hour but not after 12 h before PSM, while no significant difference for pain was found between the matched groups  block  or multiIn our institution a standardized continuous intravenous injection of painkillers is preferred, and opioids are forbidden as rescue medicines. Before PSM, intensity of this symptom was lower after OAGB at the 6th, but no significant difference was found after matching. Even if the resection and removal of 80% of the stomach induced worse early distress, this was adequately controlled in the first 12 h by our protocol. Indeed, this greater postoperative discomfort after LSG was also demonstrated by the higher rate of additional painkillers administered postoperatively.ERABS guidelines are not strictly followed in our department, therefore a nasogastric tube is routinely placed and oxycodone (elastomeric pump) was administered postoperatively to all patients. Nausea and pain assessments relied totally on a self-reported numeric scale and no validated questionnaire was used. Being this study retrospective, possible confounders and heterogeneity related to preoperative selection bias, which we tried to reduce using PSM. However, this is the first report of these symptoms after OAGB in a large cohort of patients undergoing the same perioperative management.Early postoperative nausea was significantly more severe after LSG rather than after OAGB with a greater percentage of patients requiring rescue medicines.Pain was more intense after LSG at the 6th hour with higher rate of additional painkillers administered in this group. Postoperative discomfort was comparable after PSM.


With rising interest in complementary approaches to symptom management, awareness of real-world practice patterns in the incorporation of integrative oncology (IO) into cancer care is limited. Therefore, we examined the reasons for referral, symptom burdens, and clinical outcomes for cancer patients who underwent initial IO consultations.The records of adult patients with cancer who underwent initial outpatient IO consultations at our cancer center for a representative 10-day period at the start of each month for 12 months starting January 1, 2017, were reviewed retrospectively. Patient demographic and medical characteristics and outpatient IO consultation details, including patient-reported outcome measures of symptom burden, were extracted. Descriptive summary statistics and logistic regression were used to analyze the data.P = .002) or peripheral neuropathy , oncology massage for pain , psychology referral for patient’s self-reported anxiety , and mind-body therapies for stress .Among the 473 study patients, 71% were women, breast cancer (42%) was the most common cancer type, and 31% had metastatic cancer. Referring clinicians listed an integrative approach (57%) as the most common reason for referral, followed by diet (26%), pain (19%), discussion of herbs and supplements (18%), and stress (18%). In comparison, patients listed their primary concerns as diet (16%), pain (15%), and an integrative approach to overall health (11%). After the IO consultations, the highest likelihood of subsequent recommendations were acupuncture for hot flashes (odds ratio [OR], Cancer patients’ top concerns regarding IO consultation may not always match providers’ reasons for referral. Longitudinal data analysis is needed to determine the effect of integrative interventions on symptom burden. Witt et al defined IO as “a patient-centered, evidence-informed approach to health care that utilizes mind-body therapies, natural products, and lifestyle modifications from different traditions alongside conventional cancer treatments.” They added that IO “aims to optimize health, quality of life, and clinical outcomes across the cancer care continuum and to empower people to prevent cancer and become active participants before, during, and beyond cancer treatment.” Recommendations for IO and integrative therapies are now included in American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network guidelines.6 This illustrates the increasing interest in studies of real-world practice patterns and IO recommendations.Integrative oncology (IO) is a field that has grown rapidly over the past decade, and most leading U.S. cancer centers are providing complementary and integrative therapies to their patients. Unfortunately, in a survey of 392 oncologists , two-thirds reported not having enough knowledge to discuss the area of herbs and supplements with their patients. This lack of knowledge can lead patients to make independent decisions regarding natural products and alternative therapies while rejecting conventional cancer treatments. Acknowledgment that such choices, which are based on unsubstantiated claims, may not align with the best interests of the patients is crucial. For example, a patient may want to discuss recommendations regarding herbs and supplements to help manage symptoms such as arthralgia caused by treatment with aromatase inhibitors, but the evidence is often stronger for other therapeutic modalities, such as acupuncture. An IO consultation is an opportunity to identify and evaluate symptoms that can be treated with appropriate integrative approaches. Furthermore, in our clinical practice, we educate patients on the appropriate integrative therapies and realign their expectations to help them make informed decisions about their care.11According to the results of the American Society of Clinical Oncology’s second National Cancer Opinion Survey in 2018, 4 in 10 Americans believe that “alternative treatments” may cure cancer and that such treatments often include herbs and supplements.Currently, a clear understanding of the real-world interplay of the differences in patient expectations, physician referral reasons, and clinical recommendations arising from IO consultations is lacking. Therefore, we explored the reasons for referral to IO by clinicians, patient concerns for seeking IO consultations, recommendations in initial IO consultations, and factors associated with recommendation of common integrative therapies.A retrospective study of cancer patients seen for initial consultation in the ambulatory IO clinic at our large comprehensive cancer center was conducted. Encounters analyzed were limited to those taking place during the first 10 days of each month from January 1, 2017, through January 1, 2018. Including the first 10 days of each month ensured that our sample was representative of all patients seen at the IO clinic allowing us to obtain a statistically robust data set for accurate outcome measurements.All patients 18 years or older with a cancer diagnosis were included in the study. The final sample consisted of 473 patients. Waivers of informed consent were obtained, and the study was approved by The University of Texas MD Anderson Cancer Center Institutional Review Board (PA 18-0892). Data were collected via review of each patient’s electronic medical record. Patients reported their top 2 concerns regarding their IO encounters from a list of available topic areas, including an integrative/holistic approach, herb/supplements, diet/nutrition, pain, overall health, and stress/anxiety as well as an “other” category.Our primary outcome was identification of the clinicians’ referral reasons for IO consultation and the patients’ self-reported concerns at the time of the IO encounters as described in the medical record. On the electronic heath record consultation order referral form, referring providers were given the following options as reasons for referral to an IO consultation: diet, exercise, weight management, stress, relaxation, anxiety, depression, nausea, appetite, fatigue, hot flashes, pain, an integrative approach, overall health, sleep, dry mouth, herbs and supplements, and neuropathy. More than one reason could be selected by the referring clinician. When patients arrived for their IO consultations and at follow-up, they listed their self-reported concerns using a modified Measure Yourself Concerns and Wellbeing (MYCaW) assessment.Our secondary outcome was evaluation of the factors associated with recommendation of IO clinical services after consultations. Before each IO consultation and at follow-up, patients completed a series of measures to assess symptom burden  and quality of life (Patient-Reported Outcomes Measurement Information System-10 [PROMIS-10]), with responses immediately available for review by the health care provider (IO physician and/or nurse practitioner). consists of 16 items: 10 core symptoms  plus an additional 6 items including spiritual distress, financial distress, numbness/tingling, hot flashes, dry mouth, and memory problems. Respondents rate the symptoms they have experienced over the past 24 hours on a scale of 0 to 10, with 10 being the worst. A difference of 1 for an individual item is considered a clinically significant difference in that symptom. Subscale scoring is performed as follows: the global distress score  is the sum of the pain, fatigue, nausea, drowsiness, appetite, shortness of breath, anxiety, depression, and well-being scores; the physical distress score  is the sum of the pain, fatigue, nausea, drowsiness, appetite, and shortness of breath scores; and the psychological distress score  is the sum of the anxiety and depression scores.The mESAS is an assessment of global health with 10 self-reported items that are divided into mental health and physical health subscales. Responses are converted into T-score values, with T-score distributions standardized to the mean for the U.S. population. Higher scores represent better global, mental, or physical health.PROMIS-10During IO consultations at our institution, patients are evaluated comprehensively for physical, mind-body, and social needs in the context of their cancer and medical conditions and referred to IO services. Our IO clinical service providers include board-certified physicians, advanced practice providers such as physician assistants and nurse practitioners, licensed acupuncture therapists, licensed massage therapists, psychologists with doctorate qualifications, a registered dietician, a physical therapist, a certified yoga therapist, and a music therapist. At our IO clinic, personalized care for each patient is prioritized, ensuring that their unique needs are met. To achieve this, individualized integrative care plans that consider various factors are developed. These plans may incorporate acupuncture or massage therapy to address symptom control, health psychology, yoga, meditation, or music therapy to address psychological distress; counseling for healthy lifestyle behaviors like diet and exercise; and referrals to nutritionists, physical therapists, or health psychologists. Additionally, providers engage in discussions regarding the risks of and evidence regarding use of herbs and supplements and alternative treatments pursued or considered by patients. The importance of promoting evidence-based information and fostering open communication between patients and health care professionals is emphasized. Empowering patients with accurate knowledge can help them make informed decisions, ensuring that their chosen paths align with their overall well-being. Our recommendations are consistently tailored to the specific requirements of each patient, considering established guidelines and the latest available evidence.P levels of <.05 were considered significant.Descriptive statistics were used to summarize the patients’ demographic and clinical characteristics. The reasons for referral and patient concerns recorded via the MYCaW instrument were summarized using frequencies and percentages. The mESAS and PROMIS-10 scores were summarized with means, SDs, and ranges. All statistical analyses were performed using Stata/MP software . Logistic regression was used to calculate odds ratios (ORs) for the secondary outcomes. An ESAS score of 4 was used as a cutoff for calculating the OR for symptoms predicting recommendation of integrative interventions based on patients’ self-reported symptom burdens. The required minimum sample size was estimated to be 300 patients to estimate the proportion of reasons for referral with a 95% CI having a half-width of less than or equal to 0.06. Unless otherwise stated, all tests were 2-sided, and Our study population consisted of 473 patients. P = .002) for recommending acupuncture, followed by referral for neuropathy . Self-reported ESAS scores of 4 or higher for fatigue, nausea, neuropathy, hot flashes, pain, sleep, and dry mouth significantly predicted recommendation of acupuncture. Initial IO referrals for stress, relaxation, and pain or ESAS scores of at least 4 for pain and anxiety were significantly associated with recommendation of oncology massage. Referral for stress and ESAS scores of at least 4 for anxiety, depression, fatigue, and nausea were markedly associated with psychology referral. Referral for stress and pain and higher ESAS scores for depression, anxiety, and pain significantly predicted recommendation of mind-body therapies.18Our study highlights the real-world implementation of IO practices as a standard of care in a large comprehensive cancer center. An integrative approach, diet/nutrition, and pain were the top 3 reasons for IO referral by providers. In comparison, diet, pain, and an integrative approach were the top 3 concerns that patients wanted to discuss with IO providers as reported using the MYCaW. Referral for hot flashes and neuropathy or a symptom burden with an ESAS score of at least 4 for fatigue, nausea, neuropathy, hot flashes, pain, and dry mouth predicted acupuncture recommendation after IO consultation. Referral for pain and stress or an ESAS score of at least 4 for anxiety and pain predicted oncology massage recommendation. An interesting finding was the recommendation of mind-body therapies for patients referred for pain and an ESAS score of at least 4 for pain. Surprisingly, a significant portion of CAM users, ranging from 20% to 77%, did not disclose their CAM use to their healthcare providers . In a survey of 392 oncologists across US, it was found that, on average, oncologists discussed the use of herbal supplements (HS) with 41% of their patients, with only 26% of these discussions initiated by the oncologist. Notably, 2 out of 3 oncologists felt they lacked sufficient knowledge to answer patient questions about HS, and 59% had not received any education on the topic. The complex nature of patient-provider dynamics, individual perceptions of healthcare needs, varying perspectives on treatment options, and differing priorities could all contribute to this disconnect. Understanding the underlying reasons behind this incongruity is essential for optimizing patient-centered care and improving the alignment between patients’ concerns and providers referral decisions.Although the top 3 priorities of the providers and patients matched, we found an intriguing discrepancy between patient concerns and the reasons cited by providers for making referrals. This misalignment can be attributed to several factors that warrant further investigation. In a review of 21 studies, it was found that the prevalence of complementary and alternative medicine (CAM) use among cancer patients varied widely, ranging from 11% to 95%. The present analysis suggested a shift in patient interests, with new top areas of interest including diet/nutrition, pain, and an integrative approach. Patients understand the significance of a healthy diet in relation to cancer and express a genuine interest in discovering optimal ways to modify their dietary habits to mitigate the risk of cancer recurrence or progression. They also recognize the potential impact of dietary choices on their overall well-being and actively seek guidance in adopting healthy dietary practices to support the journey toward improved health outcomes. This underscores the proactive role that patients play in their own health care as they strive to empower themselves with knowledge and take proactive steps toward reducing their cancer-related risks. National initiatives emphasizing the value of nonpharmacological approaches to pain management and updated pain management guidelines may have influenced both providers’ reasons for referral to and patients’ interest in IO interventions as adjuncts to pain management. Also of note is an overall higher symptom burden reported by referred patients at baseline compared to our prior study, in which we analyzed self-reported symptoms in our center from 2009 to 2013, including a pain score of 2.6 versus 3.5 in the present analysis of patients in 2017. A higher level of baseline pain at IO consultation in the present study than in our previous one may have contributed to our observation of why more patients had an interest in discussing pain as one of their primary concerns than in the previous study. Our findings demonstrate that implementing IO recommendations and guidelines in caring for patients with cancer is feasible.In our earlier analysis of IO consultations, patients’ top MYCaW concerns were an integrative approach (34%), herbs and supplements (34%), and diet/nutrition (21%). In addition, health disparity research in IO settings is sparse, and our retrospective study did not address this issue. However, 23% of our study population was from underserved ethnic/racial groups.Our study had some limitations. For example, it was a retrospective study at a large comprehensive cancer center. Therefore, our results may not be generalizable to IO practices across the globe, especially in community oncology settings. The patients were referred for IO consultation by oncology clinicians, and their settings may differ from those in which patients self-refer for IO clinical services/treatments. Also, we did not report on how availability or lack of insurance coverage may have influenced patient choice in pursuing treatments such as oncology massage or acupuncture or how a lack of health insurance coverage may limit access to IO services. Additional factors that can limit access to IO interventions include increased distance from our institution. We found that patients seen for IO consultation at our center lived a median distance of 98 miles away. Increased distance from our center may have led patients to pursue IO treatments such as massage or acupuncture locally rather than seeking a referral for treatment at our center. We did not account for patients who may have accessed these treatments in their local communities. In the future, we plan to explore treatment completion, in other words, how many patients referred to IO services completed their recommended courses of treatment (adherence) as part of their integrative care plans. New telehealth options for IO developed over the past several years may offer new opportunities to increase access to these interventions.Our study highlights the real-world practice of IO and use of integrative therapies based on patients’ symptoms and reason for referral for IO consultations. An integrative approach, diet/nutrition, and pain were the top referral reasons and patients’ top concerns leading them to seek IO consultations. We found that acupuncture recommendation was predicted by a referral for hot flashes and neuropathy or patient self-reported significant fatigue, nausea, neuropathy, hot flashes, pain, or dry mouth. Oncology massage was predicted by a referral for pain and stress or patient-reported symptoms of anxiety and pain. Mind-body therapies were recommended for patients with pain. Future longitudinal research should focus on examining cancer patient’s symptom response to integrative therapies.


The bone–patellar tendon–bone (BTB) autograft is associated with difficulty with kneeling after anterior cruciate ligament (ACL) reconstruction; however, it is unclear whether it results in a more painful or symptomatic knee compared with the hamstring tendon autograft.To identify the rate and risk factors for knee pain and difficulty with kneeling after ACL reconstruction.Cohort study; Level of evidence, 3.Primary ACL reconstruction procedures prospectively recorded in the New Zealand ACL Registry from April 2014 to May 2021 were analyzed. The Knee injury and Osteoarthritis Outcome Score (KOOS) was used to identify patients reporting consequential knee pain (CKP), defined as a KOOS Pain subscore of ≤72 points, and severe kneeling difficulty (SKD), defined as a self-report of “severe” or “extreme” difficulty with kneeling. Absolute values of the KOOS Pain and Symptoms subscales were also compared.P < .001). The most important predictor of SKD at 2-year follow-up was the use of a BTB autograft rather than a hamstring tendon autograft . There was no difference between the BTB and hamstring tendon grafts in terms of CKP  or in absolute values of the KOOS Pain  and KOOS Symptoms  subscales.A total of 10,999 patients were analyzed. At 2-year follow-up, 9.3% (420/4492) reported CKP, and 12.0% (537/4471) reported SKD. The most important predictor of CKP at 2-year follow-up was having significant pain before surgery (adjusted odds ratio, 4.10; At 2-year follow-up after primary ACL reconstruction, 9.3% of patients reported CKP, and 12.0% reported SKD. The BTB autograft was associated with difficulty with kneeling, but it did not result in a more painful or symptomatic knee compared with the hamstring tendon autograft. Reconstruction of the anterior cruciate ligament (ACL) is an effective surgical procedure that restores stability to the ACL-deficient knee and allows patients to return to full activities, including pivoting sports. However, it is a major procedure that involves harvesting a graft and drilling tunnels. Avoiding complications such as graft ruptures and residual laxity is critical to the success of surgery in elite athletes. However, general complications such as persistent knee pain and an inability to kneel may be common and affect all patients undergoing ACL reconstruction.31 The BTB autograft is associated with a lower failure rate and a higher rate of return to activity but may be associated with anterior knee pain and difficulty with kneeling after surgery compared with the hamstring tendon autograft. As a result, the choice of a graft is often individualized to the needs of the patient, and the benefits of a safer return to sports must be balanced against the potential consequence of knee pain.The bone–patellar tendon–bone (BTB) and hamstring tendon autografts are the most commonly used grafts in ACL reconstruction. As part of the questionnaire, patients are asked whether they have any difficulty with kneeling on the reconstructed knee. Although it is suggested that the BTB autograft is associated with anterior knee pain,35 there are few studies with a large patient population that have directly compared the rate of knee pain between the BTB and hamstring tendon autografts. Furthermore, studies have failed to differentiate consequential knee pain (CKP) from difficulty with kneeling. Therefore, this study aimed to use prospective data recorded in the New Zealand ACL Registry to identify the proportion of patients who have CKP versus severe kneeling difficulty (SKD) after ACL reconstruction and whether the type of graft influences the rate of these outcomes.The Knee injury and Osteoarthritis Outcome Score (KOOS) is a patient-reported outcome measure that evaluates how symptomatic or painful the knee is after ACL reconstruction. As of 2018, based on comparisons with government health care data, it was estimated that approximately 85% of all primary ACL reconstruction procedures performed in New Zealand were captured by the registry. Patient demographic data are collected through a preoperative self-reported questionnaire. An operative data form detailing each reconstruction procedure is completed by the surgeon. KOOS scores are collected by the registry preoperatively and postoperatively at 6 months, 1 year, and 2 years.The New Zealand ACL Registry is a nationwide registry that began in 2014 and prospectively captures data on patient, surgical, and follow-up variables. Since 2017, it is mandatory for all orthopaedic surgeons who perform ACL reconstruction to actively participate in the registry to achieve recertification.This study received exemption from Health and Disability Ethics Committee review as an audit activity. The operation of the registry has been declared a protected quality assurance activity by the New Zealand Ministry of Health, and all patients recorded in the registry have signed consent forms to participate.Any procedure recorded in the New Zealand ACL Registry from April 2014 to May 2021 was eligible for analysis, allowing for a minimum follow-up of 6 months. Patients who underwent multiligament reconstruction, osteotomy, unicompartmental knee replacement, or revision or contralateral ACL reconstruction before follow-up were excluded.There were 2 primary outcomes analyzed:CKP: defined as a score of ≤72 points on the KOOS Pain subscaleSKD: defined as a self-report of “severe” or “extreme” difficulty when kneeling As part of the Sport and Recreation subscale of the KOOS, patients were asked to rate the difficulty that they had with kneeling as either “none,”“mild,”“moderate,”“severe,” or “extreme.” SKD was therefore defined according to how it was reported. Both primary outcomes were analyzed at 6-month, 1-year, and 2-year follow-up. In addition, absolute values of the KOOS Pain and Symptoms subscales were analyzed at 2-year follow-up.CKP was defined using a cutoff score of ≤72 points on the KOOS Pain subscale, as this was a definition proposed by the Multicenter Orthopaedic Outcomes Network (MOON) group to describe significant knee pain after ACL reconstruction.The predictor variables of interest were analyzed as recorded by the New Zealand ACL Registry through the preoperative patient questionnaire and the operative data form completed by the surgeon. This included patient age, sex, time from injury to surgery, history of knee surgery, graft type (BTB vs hamstring tendon autograft), concomitant anterolateral ligament reconstruction or lateral extra-articular tenodesis, any injury or treatment to the medial or lateral meniscus , a grade 3 or 4 cartilage injury documented at the time of primary ACL reconstruction according to the International Cartilage Regeneration & Joint Preservation Society, and significant knee pain or kneeling difficulty before surgery. The Marx score of patients was also analyzed to compare the activity levels between patients reporting CKP or SKD versus those without such complications.U test. Results were considered statistically significant at P < .05. All analyses were performed using SPSS Statistics .Descriptive statistics were provided as mean values with standard deviations or median values with interquartile ranges. Continuous variables were assessed for normality through the visualization of Q-Q plots and histograms. Univariate analysis was performed using the chi-square test. Multivariate analysis was performed via binary logistic regression to compute odds ratios (ORs) with 95% CIs. All variables including age, sex, time to surgery, previous surgery, concurrent anterolateral ligament reconstruction or lateral extra-articular tenodesis, meniscal treatment, chondral injury, and preoperative CKP or SKD were entered into a forward stepwise regression model to identify independent predictors of postoperative CKP and SKD. Absolute values of the KOOS Pain and Symptoms subscales were compared via the Mann-Whitney A total of 10,999 patients had a minimum follow-up of 6 months and were eligible for analysis . The meaThe overall incidence of CKP was highest at 6-month follow-up, with 15.9% of patients reporting a KOOS Pain subscore of ≤72 points . The incP < .001) (P < .001). However, there was no difference between the BTB and hamstring tendon autografts in the rate of CKP  or in absolute values of the KOOS Pain  and KOOS Symptoms  subscales at 2-year follow-up. The distribution of responses to the extent of difficulty with kneeling reported by patients at 1- and 2-year follow-up is displayed in At 2-year follow-up, 21.3% of patients with a BTB autograft reported SKD compared with 9.4% of patients with a hamstring tendon autograft ( < .001) . On multP < .001) (P < .001) and 1-year  follow-up. Female sex and a grade 3 to 4 chondral lesion were predictive of knee pain at 6 months postoperatively but were not associated with knee pain at 1- or 2-year follow-up.The most important risk factor for CKP after ACL reconstruction at all 3 follow-up time points was the presence of CKP before surgery  . Age wasP < .001) (P < .001) and 1-year  follow-up. At 6-month follow-up, higher odds of SKD were observed in patients aged 21 to 30 years  and in patients with a concomitant grade 3 to 4 chondral lesion , but lower odds of SKD were observed in patients who had undergone medial meniscal resection .Patients who reported SKD before surgery had higher odds of SKD after surgery at all 3 follow-up time points  . In addiOn both univariate and multivariate analyses, patients who reported CKP or SKD also reported lower activity levels at all 3 follow-up time points  and 4. PThe most important finding of this study was that the BTB autograft was associated with difficulty with kneeling after ACL reconstruction, but it did not result in a more painful or symptomatic knee compared with the hamstring tendon autograft. The present study used the same cutoff to define CKP and found an incidence of 15.9% at 6-month follow-up and 9.3% at 2-year follow-up. There are a number of potential causes for knee pain after ACL reconstruction, including a repeat injury, donor-site morbidity, pain at the skin incision site, pain related to hardware fixation, osteoarthritis, and quadriceps muscle weakness.34 Although this study was unable to identify the causes for postoperative knee pain, patients who reported knee pain before undergoing surgery had 4 times the odds of reporting knee pain after surgery. Interestingly, Ware et al performed a prospective study of 72 patients undergoing ACL reconstruction and found that lower preoperative KOOS scores were strongly associated with a more painful and symptomatic knee at 7-year follow-up.This study analyzed 2 different outcomes to differentiate significant knee pain from significant difficulty with kneeling. A study from the MOON group proposed a definition of significant knee pain as a KOOS Pain subscore of ≤72 points, which it found in 9% of patients at 2- and 6-year follow-up.35; however, there is variation in how studies define anterior knee pain and subsequently a lack of clarification on whether this is disabling pain that impairs function or whether it could be an alternative description for difficulty with kneeling. Our study found that patients with a BTB autograft were 3 times more likely to report SKD but were not more likely to suffer from significant knee pain or symptoms compared with patients with a hamstring tendon autograft. Other studies have also attempted to differentiate knee pain from kneeling difficulty. In a randomized study of 72 patients performed by Aune et al, no statistically significant difference in knee pain was found between graft types at 2-year follow-up ; however, when patients were asked on a visual analog scale to rate their discomfort when kneeling, 35.5% of patients with BTB grafts reported kneeling problems compared with 18.9% of patients with hamstring tendon grafts (P < .05). In a prospective cohort study of 958 cases, Rousseau et al found that anterior knee pain was more common in patients with BTB grafts in the first 2 years after surgery , but there was no difference after 2 years of follow-up . Last, the Swedish National ACL Register also analyzed absolute values of the KOOS between BTB and hamstring tendon autografts. Both the Swedish and the New Zealand registries have found equivalent scores between graft types for all 5 KOOS subscales at 2-year follow-up, including the Pain and Symptoms subscales.29 Surgeons in various centers have preferred the hamstring tendon autograft because of the association between the BTB autograft and donor-site morbidity. However, it is possible that donor-site morbidity associated with the BTB autograft may not be as clinically significant as previously thought, given the variation and inconsistencies in how it is defined in the literature. Furthermore, these data suggest that there is no difference in overall pain or symptoms between graft types, and therefore, this should not prevent clinicians from using a BTB autograft.Graft choice is the most widely debated topic in ACL reconstruction, and it is unclear whether it is a risk factor for knee pain. Anterior knee pain has been associated with the BTB autograftP < .001) and were more likely to return to their preinjury activity level  compared with patients with a hamstring tendon autograft. Regardless, the findings of this study support the importance of individualizing graft choice before ACL reconstruction. All patients considering ACL reconstruction should be informed of the potential complications as well as the advantages and disadvantages of each graft type. The higher rate of SKD after surgery when using a BTB autograft is a complication that should be considered in select patient populations such as those who may be required to kneel as part of their occupation or sport. In these certain patient populations, the hamstring tendon autograft may be the more appropriate graft choice because of the lower rate of kneeling difficulty. However, the BTB autograft remains the ideal graft choice for athletes undergoing ACL reconstruction, as it provides the highest chance of returning to sport with the lowest risk of reruptures.22An interesting finding from this study was the lower activity levels reported by patients who had CKP or SKD. Although having a painful and symptomatic knee may discourage patients or make them less able to participate in sports, it is unclear why patients who find it difficult to kneel reported lower activity levels. In this study, patients with a BTB autograft were 3 times more likely to report SKD; however, previous studies analyzing the same patients from the New Zealand ACL Registry found that patients with a BTB autograft had higher Marx scores (mean, 7.7 vs 6.3, respectively; 16 Currently, there is no gold standard patient-reported outcome measure for ACL reconstruction.13 However, in this study, the KOOS was not used to assess the success of ACL reconstruction but rather as a tool to compare outcomes between graft types. Second, the patient response rate to the KOOS in this study was 63%, 55%, and 41% at 6-month, 1-year, and 2-year follow-up, respectively. Although loss to follow-up may introduce selection bias, a previous study from the Danish Knee Ligament Reconstruction Registry found no difference in KOOS scores between responders and nonresponders. Furthermore, a similar study from the Swedish National ACL Register analyzed KOOS scores after ACL reconstruction and comparably had a patient response rate of 30% at both 1- and 2-year follow-up. Last, although a strength of registry studies is the availability of prospective data on a large patient cohort, they are limited in their ability to only report associations. They are not able to thoroughly investigate the reason for each association and cannot infer causality. In this study, the potential effect of hardware and implants in contributing to pain was not able to be investigated. It was also not able to identify the reasons for the higher rate of SKD in patients with a BTB autograft. Future randomized controlled trials are needed to further compare the incidence of knee pain versus difficulty with kneeling when comparing graft types and investigate the contributing factors for both outcomes.The main limitation of this study is the use of only 1 type of patient-reported outcome measure: the KOOS questionnaire. As the KOOS was initially designed for use in patients with knee osteoarthritis, several studies have validated its usefulness in ACL reconstruction.At 2-year follow-up after primary ACL reconstruction, 9.3% of patients reported CKP, and 12.0% reported SKD. The BTB autograft was associated with difficulty with kneeling, but it did not result in a more painful or symptomatic knee compared with the hamstring tendon autograft.


Children with pectus excavatum are treated with surgical repair in a procedure known as minimally invasive repair of pectus excavatum (MIRPE). MIRPE causes considerable postoperative pain, resulting in the administration of a substantial dose of opioids. This study aimed to identify perioperative factors that influence the requirement for opioids in children undergoing MIRPE. Retrospective data from children who underwent MIRPE were analyzed. A multimodal analgesic protocol was implemented with a continuous wound infiltration system and administration of non-opioid analgesics. Intravenous opioid analgesics were administered if the pain score was greater than 4. The cumulative opioid use was assessed by calculating the morphine equivalent dose at 6, 24, and 48 h after surgery. Perioperative factors affecting the postoperative opioid use were identified with multiple linear regression analyses. This study included 527 children aged 3–6 years, with a mean age of 3.9 years. Symmetrically depressed chest walls, a lower Haller index, and a lower revised depression index were found to be associated with decreased postoperative opioids. Boys required higher opioid doses than girls. Longer pectus bars (10 inches versus 9 inches) were associated with increased opioid use. Severity indices, gender, and the length of pectus bars influence postoperative opioid requirement in children undergoing MIRPE surgery with multimodal analgesia. Pectus excavatum is the most common congenital deformity of the chest wall and affects more males than females ,2. SurgiMIRPE involves minimal incisions and does not require the rib cartilages to be cut, as in the traditional surgeries. Nevertheless, it is associated with severe postoperative pain lasting for several days ,4,5. OptIn this study, we investigated the perioperative factors that affect postoperative opioid requirement in preschoolers undergoing MIRPE with multimodal analgesia.We collected data from preschoolers aged 3–6 years who underwent pectus excavatum repair using pectus bars in a single university hospital between August 2012 and March 2019. This study was approved by the institutional review board (KC19RESI0271) and has been conducted in adherence with the STROBE guidelines. The data were retrospectively collected from the electronic medical records of patients. Patients were excluded if they had an American Society of Anesthesiologists score of class III or greater, history of pectus excavatum repair, history of chronic pain or preoperative analgesic medications, or inability to accurately express pain due to psychiatric or other disorders such as mental retardation or cerebral palsy. Patients with insufficient or missing data on clinical variables were also excluded from data analysis.A single surgeon exclusively performed the surgical procedures on all patients who were included in this study. The surgical technique utilized in each case was customized based on the individual patient’s unique anatomical features and the severity of the underlying disease. With the patient positioned supine, general anesthesia was administered to the patients. Once the routine draping was completed, both arms were gently suspended overhead using specialized arm slings to maintain an optimal surgical field. For accurate localization of the insertion point for the pectus bar, the surgeon carefully examined and identified the ideal placement by considering the depressed area and bilateral hinge points on the patient’s chest. The pectus bars were skillfully shaped by the surgeon directly at the operating table, meticulously considering the unique morphology of the patient’s chest wall. The appropriate size of the pectus bar was determined based on precise measurements of the horizontal length of the chest wall. Throughout the study, both nine- and ten-inch pectus bars were utilized depending on the patient’s specific needs. In cases where the chest wall presented long or wide depressed areas, the surgeon strategically employed multiple bars to achieve the desired surgical outcome.A small midaxillary skin incision, measuring approximately 1 cm in length, was made on both sides of the chest to introduce the pectus bar. Utilizing pectoscopic visualization and a 20 Fr chest tube as a guide, the bar was carefully passed below the depressed sternum and guided across the mediastinum. To effectively elevate the previously depressed chest wall, the surgeon adeptly flipped the pectus bar by 180° using a specialized flipper. This technique successfully lifted the sternum into its proper position, restoring the normal anatomical alignment. To ensure stability and to prevent any unwanted mobilization of the pectus bar, the surgeon expertly secured it in place using either claw fixators or bridge plates, as deemed appropriate for each patient’s unique situation.Following the fixation of the pectus bars, an immediate anterior–posterior view of the chest was obtained using portable radiography in the operating room. This crucial step allowed for real-time verification of the accurate positioning of the bars and served as an additional safety check to detect any potential complications, such as pneumothorax. In cases where no major bleeding occurred during the intraoperative period, the placement of drains was deemed unnecessary, further contributing to the patient’s comfort and postoperative recovery.According to the institutional protocol, anesthesia was induced with ketamine (1–2 mg/kg) and maintained with sevoflurane and supplemental fentanyl (1–2 mcg/kg) based on vital signs and bispectral index (BIS). Sevoflurane was maintained within 2.0–2.5%, with an air/oxygen mixture comprising 40 to 50% inspired oxygen concentration. The concentration of sevoflurane was adjusted to keep the BIS values between 40 and 60, ensuring optimal anesthesia depth throughout the surgical procedure.Prior to tracheal intubation, the administration of 0.6 mg/kg of rocuronium facilitated smooth and controlled intubation. Mechanical ventilation of 4–6 mL/kg of tidal volume was continued until the end of the surgery. Upon completion of the surgery, neuromuscular blockade was reversed with 0.2 mg/kg of pyridostigmine and 0.1 mg/kg of glycopyrrolate. After tracheal extubation, patients were transferred to the recovery room, where they continued to receive close monitoring and care.® Pain relief system, Halyard, Alpharetta, GA, USA), providing a sustained release of local anesthetics to the affected area. The intercostal blocks involved the percutaneous administration of 0.5–0.75% ropivacaine mixed with 0.9% saline at the 4 to 9th intercostal levels. Each level received 2 mL of local anesthetics, carefully targeted to provide optimal pain relief and minimize postoperative discomfort. The CWIS employed a main pump that contained the local anesthetics. The pump was connected to infusion catheters, equipped with multiple holes to ensure an even distribution of the local anesthetics. The catheter was inserted through the bilateral posterior axillary lines to infuse the local anesthetic around the corresponding intercostal nerve territory. The local anesthetic was aseptically prepared by diluting 270 mL ropivacaine (0.15–0.25%) in normal saline. The concentration of ropivacaine varied based on the patient’s body weight, with 0.15% for those weighing less than 15 kg, 0.2% for those between 16 and 20 kg, and 0.25% for those between 21 and 25 kg. The diluted ropivacaine was continuously administered at a controlled rate of 4 mL/h, and the pump remained in place for up to 72 h postoperatively, ensuring a sustained and controlled release of the local anesthetic to manage pain effectively.As per the multimodal analgesic protocol, a comprehensive approach was adopted, encompassing both intraoperative and postoperative analgesic measures. Following the insertion of the pectus bar, the thoracic surgeon administered intercostal blocks and implanted a continuous wound infiltration system  to 10 (crying face with the worst pain a child can have), provided a reliable and standardized means of quantifying pain. In cases where the pain score exceeded 4, experienced healthcare providers promptly administered intravenous boluses of opioid analgesics to alleviate pain and ensure the patient’s comfort. The selection of opioids, including fentanyl, pethidine, or nalbuphine, was based on the anesthesiologist’s preference.Multimodal analgesic protocol was conducted even after the patients were sent to the ward. The fundamental oral form of analgesic medication was ibuprofen. A dosage of 100–150 mg oral ibuprofen was administered three or four times a day. Experienced healthcare providers assessed the severity of pain every 4 h using the Wong–Baker FACES pain scale. If the pain score was greater than 4, intravenous analgesics were administered. These analgesics was administered in the order of fentanyl (1 mcg/kg)–pethidine (1 mg/kg)–ketorolac (0.4–1 mg/kg). The intravenous analgesics were used in addition to the oral form to ensure rapid and immediate pain relief, particularly during the postoperative fasting period when oral administration might not be feasible.We analyzed the Haller and depression indices from the patients’ CT scans to measure the severity of pectus excavatum. The Haller index (HI) was calculated by dividing the transverse chest diameter by the anterior–posterior diameter from the posterior surface of the sternum to the anterior surface of the vertebral body . The depThe cumulative opioid requirement was calculated as morphine equivalent dose (MED)/kg at 6, 24, and 48 h postoperatively. Doses of opioids other than morphine were converted to morphine equivalents using standard equianalgesic dose conversion ratios . Wong–Baker FACES pain scales were also recorded at the same time points.p-values < 0.05 were considered to indicate statistical significance.Data are presented as mean ± standard deviation or absolute values (percentage), as appropriate. The main outcome was postoperative cumulative opioid consumption. Multiple linear regression analyses were performed to explore the factors influencing the main outcome and to adjust for potential confounding factors. Independent variables selected for inclusion in the model were derived from previously published data and clinical or biological plausibility. These factors included age, sex, height, weight, chest wall symmetry, HI, DI, rDI, length and number of pectus bars used, number of claw fixators used, administered dose of intraoperative fentanyl, concentration of ropivacaine within the CWIS, and cumulative dose of non-opioid analgesics at each time point. SPSS Statistics 18.0 for Windows  was used for statistical analyses. Data from 560 patients were retrospectively collected, and 33 patients were excluded due to missing data. Therefore, data from 527 patients were analyzed in this study. n = 353, 67%), followed by nalbuphine (n = 21) and pethidine (n = 10). A considerable proportion of patients  did not require any opioids in the recovery room, indicating that the intraoperative multimodal analgesic protocol sufficed for pain management without the need for rescue analgesics. Over the postoperative period, pain scores exhibited a significant decline by 24 h following the surgery. Moreover, the necessity for opioid analgesics steadily diminished from 6 to 24 and 48 h postoperatively. The incremental changes in cumulative morphine equivalent dose gradually decreased during this time course. Conversely, the demand for non-opioid analgesics (ketorolac) remained relatively constant at each time point, as mentioned above.In Intriguingly, other preoperative factors, such as age, height, weight, and DI, did not significantly influence postoperative opioid use. Moreover, the number of bars or claw fixators employed did not appear to affect opioid consumption after surgery.We identified perioperative factors that affect postoperative opioid requirements in preschoolers undergoing MIRPE. To the best of our knowledge, this is the first study to investigate postoperative pain following MIRPE in children aged 3–6 years. We analyzed the records of more than 500 patients during an 8-year period, creating one of largest pediatric datasets to date. Our results demonstrate that symmetric chest wall, lower HI and rDI, female sex, and shorter bar length were associated with less postoperative opioid requirement.The results of this study were similar to those of an earlier study that reported that the severity and asymmetry of pectus excavatum affect postoperative opioid analgesic use in patients with a median age of 17 years . The stuAdditionally, the length of the bar was associated with the opioid use during the acute postoperative period. The presence of the bar in the chest can generate postoperative pain due to constant pressure on the ribs and tension applied to the bar’s extremities . We postIn the present study, girls required fewer opioids compared to boys, which contrasts with previous studies in preschool children and adolescents ,15. In aUnderstanding the sex difference in pain intensity and opioid requirement is challenging because pain is a multifactorial phenomenon. Proposed hypotheses include variances in endogenous opioids, neurotransmitters, post-pubertal hormonal effects, and culture-specific gender roles ,19. UnliAdequate postoperative pain control is crucial for enhancing recovery and improving prognosis ,20. WhilAt our institution, we have implemented multimodal analgesia consisting of CWIS and regular administration of non-opioid analgesics for over 10 years in approximately 900 pediatric patients. CWIS was chosen due to its comparable analgesic effect, ease of application, shorter surgery time, and reduced hospital stay compared to thoracic epidural block . Our proAssessing pain in pediatric patients after surgery poses unique challenges due to their limited ability to communicate their feelings and discomfort verbally. This is particularly true for very young children, such as those aged 3 to 4 years, who may not possess the verbal and cognitive skills to express their pain accurately. As a result, healthcare professionals employ various methods and pain assessment tools to evaluate and understand pain intensity in this population, aiming to ensure appropriate pain management and improve the overall well-being of these young patients.The Wong–Baker FACES pain scale is a widely used pediatric pain assessment tool in both clinical and research settings. ,25 This Some of the key advantages of the Wong–Baker FACES pain scale are its ease of use, simplicity, and quick administration. In addition, the Wong–Baker FACES pain scale demonstrated relatively high reliability and validity in postoperative assessments. It exhibits high correlations with other validated pain assessment methods, such as visual analog scales, thereby establishing its reliability and consistency in measuring pain intensity.This study had several limitations. First, it was a retrospective study with some missing variables. Second, the Wong–Baker FACES pain rating scale includes subjective measurements. Although it is a common pain measurement tool in children, it can be inaccurate if the evaluator is inexperienced. However, we consider our data to be reliable because the scale was administered by professional healthcare providers. They are well trained and experienced since they work in a ward where the majority of the patients are children who have received MIRPE. Therefore, our findings may be of value in planning pain management in young children undergoing surgery of a similar extent.In conclusion, asymmetric chest wall, higher Haller index and revised depression index, males, and the insertion of longer chest bars increase postoperative opioid use in pediatric patients undergoing MIPRE. The anesthetic and surgical management of these patients based on our findings may be helpful for adequate postoperative analgesia.


To assess the prevalence and predictors of chronic pelvic pain in a general urology population presenting for evaluation of unrelated non‐painful complaints.Generalized pelvic pain is estimated to afflict between 6% and 26% of women and is often multifactorial in aetiology. A paucity of prospective research exists to characterize chronic pelvic pain patterns and to understand related predictors.This is a prospective, cross‐sectional survey‐based study of female patients presenting to a general urology clinic over a 10‐month period (7/2018–5/2019). Patients completed a 32‐item survey with questions pertaining to demographics, comorbidities and chronic pelvic pain characteristics. Comparison tests  and stepwise multivariable logistic modelling were performed to assess for predictors of chronic pelvic pain.p = 0.001). Univariable logistic regression analysis identified BMI, depression, fibromyalgia, overactive bladder and any bowel symptoms as possible positive predictors of chronic pelvic pain. Final best‐fit multivariable model found overactive bladder, fibromyalgia and presence of bowel symptoms as independent positive predictors of chronic pelvic pain.A total of 181 women completed the survey, with a mean age of 56 years. Overall, 75 (41%) women reported chronic pelvic pain. Those with chronic pelvic pain were younger compared to those without (52 vs 59 years, Our study is one of the few studies that has prospectively analysed chronic pelvic pain and its predictors. The present study identified significant associations with overactive bladder, fibromyalgia and bowel symptoms. Further research is needed to better understand the aetiologies of chronic pelvic pain and the possible relationship with identified clinical predictors. CPP is defined as pain lasting typically 6 or more months that is perceived to be originating from within the pelvis and is often associated with gynaecologic, bowel, lower urinary tract, sexual symptoms or negative cognitive and emotional effects.2terrible pain on average over the past month. Pain location was assessed using a multiple‐choice format that allowed patients to select all of the areas they experience pain  well as a diagram that allowed them to mark on an illustration of a body where they experience pain. Pain quality was assessed by participants self‐reporting pain to be sharp/stabbing, achy/dull, tingling/numbness or pain to touch. Chart review was completed to gather other demographic and comorbidity information not covered in the survey.A prospective, survey‐based, single‐institution study of female patients presenting to a general urology clinic was conducted over a 10‐month period from 7/2018 to 5/2019. Participants were recruited during clinic registration by a study coordinator. Written informed consent was obtained prior to participation in the study. Patients who were less than 18 years old, prisoners or pregnant were excluded. Additionally, patients presenting to clinic with acute pain‐related complaints, such as flank pain, acute pelvic pain or interstitial cystitis, were excluded in order to specifically address CPP. This study was approved by the University of Virginia Institutional Review Board (protocol # 20503). All enrolled participants completed a 23‐item survey with questions relating to demographics, past medical history and pelvic pain symptoms. The questionnaire assessed pain location using detailed anatomic figures as well as through written multiple‐choice questions. Additional multiple‐choice and Likert scale questions addressed pain quality, severity, location and the impact on the patient's life. Pain severity was assessed on a scale of 1–10 with ‘10’ being defined as 2.1Data analysis was performed using the R programming language (Version 4.4.1). Demographic data and presenting concerns were collected. Logistic regression models were constructed with the outcome variable indicating the occurrence of CPP and predictor variables being posited predictors of CPP. These included demographics and comorbid conditions. Univariable logistic regression modelling followed by a final multivariable logistic regression model were conducted. All tests were performed with α = 0.05.3p = 0.001; OR = 1.05, p = 0.01). Multivariable logistic regression model found that fibromyalgia, OAB and bowel symptoms were independent positive predictors of CPP, as seen in Table p = 0.02; OR = 2.65, p = 0.005; OR = 3.46, p < 0.001). Older age was found to be protective against CPP .A total of 187 women completed the survey, with a mean age of 56 years. Six patients were excluded from analysis due to chief complaint of interstitial cystitis or acute pelvic pain that was not elicited during registration. Of the 181 included patients, 75 (41%) reported experiencing CPP. The chief complaints of patients presenting to clinic are represented in Table 4The present study found that fibromyalgia, OAB, bowel symptoms and younger age were independent predictors of CPP, while higher BMI and the presence of depression were found to be possible predictors of CPP. The association between these predicators and CPP is significant as the symptoms of fibromyalgia, OAB and bowel symptoms may distract from the true cause of CPP, making diagnosis and treatment more difficult; additionally, these conditions may play a causal role in CPP and more increase the severity of the condition. Understanding that CPP, fibromyalgia, OAB and bowel symptoms often co‐occur and may be involved the in pathogenesis of CPP is critical to avoiding a delay in diagnosis and appropriately treating these patients.4.1As one of the few studies to prospectively evaluate CPP and its predictors, the present study's finding that fibromyalgia is an independent predictor of female CPP is in line with prior research demonstrating that patients with CPP have a higher incidence of fibromyalgia (4%–31%) compared to the general population.4.2OAB was found to be an independent predictor of CPP in this study population. Prior work has estimated that 24% of patients with CPP also experience urinary symptoms, such as urgency urinary incontinence (UUI), stress urinary incontinence (SUI) and other lower urinary tract symptoms (LUTS).4.3In this study, bowel symptoms, which were defined as self‐reported constipation, bloating, diarrhoea or bowel pain within the last month on the survey, were found to be an independent predictor of CPP. It has been estimated that over 38% of women with CPP have concurrent IBS symptoms and upwards of 37% of CPP is thought to be attributable to a gastrointestinal aetiology with IBS being the most common diagnosis.4.4The finding in the present study that depression serves as a possible positive predicator of CPP builds upon prior studies that have found that patients with CPP have a significantly higher incidence of depression compared to those without pain.4.5The use of a non‐validated questionnaire and self‐report surveys introduced inherent biases and limitations to the present study. In addition, the focus of this study on urology patients at a single institution may limit its ability to be generalize the results to the broader population. Furthermore, excluding patients with chief concerns of acute pain in order to focus on CPP limited our sample size and may have excluded additional patient with CPP. Finally, this study did not include any physical exam findings in the assessment of patients' symptoms, which limits the conclusions that can be drawn regarding the nature and origin of patient's pain.CPP afflicts a large proportion of the female population. This study demonstrated through prospective research a predictive relationship of fibromyalgia, depression, OAB and bowel symptoms to CPP. Further research is needed to elucidate the causality out these relationships. A better understanding of the interplay between these conditions will allow physicians to provide more comprehensive and effective care to their patients.Conceptualization: David Rapp, Haerin Beller and Jacqueline Zillioux. Methodology: Rapp, Haerin Beller, Jacqueline Zillioux and Clinton Yeaman. Formal analysis: Clinton Yeaman, Haerin Beller and Jacqueline Zillioux. Investigation: Clinton Yeaman and Grace Prillaman. Data curation: Clinton Yeaman and Haerin Beller, Jacqueline Zillioux. Writing—original draft preparation: Grace Prillaman. Writing—review and editing: Grace Prillaman, Haerin Beller and Jacqueline Zilliioux. All authors have read and agreed to the published version of the manuscript.The authors declare no conflict of interest.Data S1. Supporting Information.Click here for additional data file.


This journal recently published a paper by Horsted et al.  entitledAlthough the medicinal use of cannabinoids continues to expand, ongoing attempts fail to provide clear evidence of their effectiveness and safety for pain. A considerable number of randomized controlled trials (RCTs) and subsequent systematic reviews and meta‐analysis (SRMA) have not been translated into solid clinical evidence or practice guidance on cannabinoids for chronic pain  allows to consider real‐world observational studies if pointing to consistent and large effects. Indeed, several long‐term observational studies on cannabinoids in chronic pain have been published and six of them were even included in a recent SRMA  and CBD (35 or less mg/day) are sufficient for producing the observed analgesic effect. These doses are lower than those used in previous studies. Second, the study design allowed a comparison between THC, CBD and their combination and indeed showed that patients prescribed THC/CBD were significantly more like to obtain a ≥ 30% pain reduction than THC and CBD as monotherapies. These two findings can clearly be helpful for planning treatment regimens in future RCTs.We have learned that recruiting patients to analgesic RCTs based on their underlying pain conditions  is often insufficient to show efficacy, thus leading to frequent failure of phase II and III analgesic RCTs. However, stratifying patients into sub‐groups according to pain mechanism, patient‐reported outcomes, etc., helped to identify responding versus non‐responding patients and increased assay efficacy. The same principles can also be applicable in real‐world life studies. In other words, rather than looking at the outcomes of the entire group such as magnitude of pain reduction or effect size , one should probably consider categorizing patients into ‘responders’ and ‘non‐responders’ based on a simple validated outcome, and then, based on a broad baseline assessment, identify predictors for becoming a ‘responder’. This will require a careful, multi‐modal and comprehensive baseline assessment of patients, but by focusing on specific outcomes only—will reduce follow‐up burden upon patients and enhance patient compliance.In summary, the growing use of medicinal cannabinoids and the failure of RCTs to provide clear evidence for their efficacy and safety in patients with chronic pain justify the use of additional study designs such as Horsted et al.  real‐worNone.Elon Eisenberg received consulting fees, speaking fees, and/or honoraria from Rafa Laboratories, Syqe medical, Medison, Teva, Pfizer.