Pain intensity was moderate or severe in 75% of chronic pain patients. Among patients with chronic pain, 15.4% were not prescribed, and did not self-medicate with, any analgesic drugs, 52.1% were prescribed analgesics , and 32.5% exclusively self-medicated with analgesics. Moreover, 20.1% of patients with chronic pain also used illicit drugs for pain relief. On multivariate analysis, variables that remained significantly associated with chronic pain were age , and depression . Chronic pain is a highly prevalent condition in patients receiving OAT, and its appropriate management remains uncertain, since insufficient relief and frequent additional self-medications with analgesics or illicit drugs were reported by these patients. Increased awareness among caregivers is urgently needed regarding a systematic and careful assessment, along with an adequate management of chronic pain in patients receiving OAT.Chronic pain and substance use disorders frequently co-occur. Indeed, chronic pain is highly prevalent, affecting 23–68% of patients receiving opioid agonist treatments (OAT) worldwide. The majority of available estimates come from American studies, but data are still lacking in Europe. We aim to provide European estimates of the prevalence of chronic pain in patients receiving OAT using French data, since France is the first European country in terms of number of patients with OAT. The secondary objectives were to characterize the features and management of chronic pain, as well identify associated risk factors. We conducted a multicenter, cross-sectional study, recruiting patients treated either with buprenorphine or methadone in 19 French addiction centers, from May to July 2016. All participants had to complete a semi-directed questionnaire that collected sociodemographic and medical data, pain characteristics, and licit or illicit drug consumption. In total, 509 patients were included. The prevalence of chronic pain was estimated at 33.2% (95% CI: 29.1–37.3). Compared to non-chronic pain patients, chronic pain patients were older (38.4 vs. 36.1 years,  Chronic pain and opioid use disorders are frequently intertwined and represent a worldwide health problem. Indeed, the prevalence of chronic pain is higher in patients receiving opioid agonist treatment (OAT), ranging from 23 to 68% –10, whilTreating both pain and addiction proves to be a significant challenge, and caregivers commonly report that all their diagnostic and therapeutic decisions are subject to ambiguity . Some stThe vast majority of available data are from American studies. As far as we know, no European data are currently available. In 2018, while 680,040 opioid users received an opioid agonist treatment in Europe, more than 178,000 were French patients treated either by buprenorphine±naloxone (65%), or methadone (35%) , 25. We Thus, the aim of this study was to estimate the prevalence of chronic pain in patients receiving OAT, to characterize chronic pain, to describe analgesics treatments, and to identify associated risk factors.This was a cross-sectional study conducted on patients receiving OAT treated either with methadone or buprenorphine. Patients were recruited from 19 addiction centers in France, from May to July 2016. In France, all registered medical doctors are allowed to prescribe buprenorphine without any special education or licensing; regulations allow buprenorphine prescriptions of up to 28 days of take-home doses. In contrast, treatment with methadone is less accessible and requires mandatory initiation within a specialized addiction center or health care facility, and management of the patient can only be transferred to a non-specialist physician once the patient has been stabilized; up to 14 days (syrup) or 28 days (capsule) supply at a time may be prescribed.During the recruitment period, all patients seen in consultation were systematically proposed to participate in the study.To fit the inclusion criteria, all patients were over 18 years, and being treated with methadone or buprenorphine for opioid use disorders. Exclusion criteria were an inability to understand the patients' information and informed consent form, and an undergoing measure of legal protection. All participants received oral and written information which described the study. All participants gave oral consent and their participation was totally voluntary and anonymous.The questionnaire was semi-directed and given during a routine medical consultation. The questionnaire consisted of five parts collecting the following information:Demographic data on gender, age, familial situation, and professional situation.Medical data, on human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection status, consumption of tobacco or alcohol, type (methadone or buprenorphine) and duration of OAT, form of methadone treatment (syrup or capsule), daily dose of OAT, OAT dose splitting, age of the first illicit opioid use, and concomitant psychotropic drug use  were collected according to the medical record and the patient's statement.Chronic pain was defined as any pain experienced for at least 3 months using the following question: “how long have you been experiencing this pain? , excluding patients with answer <3 months.” Then, the Brief Pain Inventory (BPI) was administered to assess the characteristics of chronic pain (intensity and location) and interferences in daily life . The BPIInformation on licit  and illicit drugs used to treat pain during the previous 3 months  and street) was also collected.Psychiatric disorders were measured with a 6-item validated version of the Symptom Checklist-90 (SCL-90) . This brt-test was used to compare quantitative variables. To examine the factors associated with chronic pain in patients receiving OAT, a univariate logistic regression analysis was first performed, followed by a multivariate logistic regression analysis, after checking that basic statistical assumptions were met . Factors was considered significant in univariate analysis (entered into the model if p < 0.25) and accordingly to clinically relevant variables such as age and gender. Associated p-values were computed with corresponding odds ratios (OR), or adjusted OR, and 95% confidence intervals (95% CI). All statistical analyses were performed using SAS for Windows version 9.3 .Data were expressed as frequencies and associated percentages for categorical data and as mean ± standard deviation for quantitative variables. The analysis was conducted using descriptive statistics to compare the characteristics of patients receiving OAT with and without chronic pain. The Chi-square test was used to compare categorical variables, while the Student's This research obtained the approval of the French Research Ethics Committee (CPP Sud-Est 6) on 26th February 2016.During the 3-month recruitment period, the questionnaire was given to 621 patients receiving OAT and a total of 509 agreed to participate in the study (response rate 82%). Of the participants, 166 were buprenorphine-maintained patients (BMPs) and 343 were methadone-maintained patients (MMPs). In patients receiving OAT, the mean age was 36.9 ± 9.2 years, the majority were male (77.8%), single (62.4%), and unemployed (56.5%) . The meaThe prevalence of chronic pain in patients receiving OAT was 33.2% (29.1–37.3), with no difference seen between MMP and BMP groups . The prep = 0.001), street methadone , heroin , street morphine ]. Compared to patients receiving OAT with no chronic pain, the prevalence of withdrawal-related pain in patients receiving OAT with chronic pain was higher, 21.9% (15.7–28.1) vs. 15.1% (11.3–18.90), p = 0.05.The prevalence of withdrawal-related pain in patients receiving OAT was 17.3% (14.0–20.6). Patients with a withdrawal-related pain consumed significantly more street drugs than patients without withdrawal-related pain , and split their OAT more frequently, specifically for pain management .Compared to patients receiving OAT with no chronic pain, patients receiving OAT with chronic pain were significantly slightly older, had a higher rate of unemployment, a higher incidence of psychiatric disorders, and were treated more frequently with psychotropic drugs . The preAmong patients receiving OAT with chronic pain, 15.4% were not prescribed and did not self-medicate with any analgesic drugs, 52.1% were prescribed analgesics but almost half of them (48.9%) also self-medicated for pain management, and 32.5% exclusively self-medicated for pain management. Overall, 37.9% of patients receiving OAT with chronic pain achieved at least half of the maximum possible pain relief.Among patients receiving OAT with chronic pain, non-opioid analgesics were prescribed more frequently than opioid analgesics, 47.3 vs. 21.9%. The most frequently used non-opioid analgesics were acetaminophen (68.8%), non-steroidal anti-inflammatory drugs (45.0%), and nefopam (4.7%). The most frequently used opioid analgesics were tramadol ± acetaminophen, 20.2%; codeine ± acetaminophen, 16.0%; and opium, 4.7%, and morphine, 11.2%; fentanyl, 1.2%; and oxycodone, 0.6%. Furthermore, 20.1% of patients receiving OAT with chronic pain also used illicit drugs for pain relief, including cannabis (15.0%), cocaine (3.0%), and street morphine (3.0%).p = 0.006], being unemployed , concomitant use of psychotropic drugs , SCL6-anxiety , SCL6-depression , and SCL6-psychoticism . Other covariates significant at the p < 0.25 level were buprenorphine maintenance treatment , withdrawal-related pain during the last 7 days , alcohol consumption ≥ 3 glasses per day , and first consumption of illicit opioids in a painful context . Other variables that have been tested but were not significantly associated with chronic pain in patients receiving OAT were gender, marital status, duration of OAT, HIV/HCV/HBV infection, tobacco use, OAT splitting, and concomitant use of illicit drugs.In univariate analysis, general characteristics associated with chronic pain in patients receiving OAT were age , SCL6-anxiety , and SCL6-depression .On multivariate analysis , parametTo the best of our knowledge, this French study is the first survey that provides insights into the prevalence of chronic pain in patients receiving OAT outside the US. The prevalence of chronic pain in patients receiving OAT was estimated at 33.2% (IC 95%: 29.1–37.3), with no difference between MMPs [31.5% (26.6–36.4)] and BMPs [36.8% (29.5–44.1)].In the literature, few studies have focused on the prevalence of chronic pain in patients receiving OAT, with many differences in methodology or chronic pain presence and severity definitions. So any indirect comparison of estimates between studies remains challenging because of methodological issues and absence of an appropriate age- and sex-matched control population.For chronic pain lasting at least 3 months, prevalence estimates in the literature vary from 41.9 to 68.0% in patients receiving OAT , 6. AccoInterestingly, the prevalence estimate in the present field study is very similar to that obtained in a recent data-based epidemiological study conducted by our team using the capture-recapture method on the comprehensive national French reimbursement database. In that work, the prevalence of chronic pain in patients receiving OAT ranged from 23.6% 14.9–46.2) to 32.1% 28.6–36.3). Moreover, compared to a sex- and age-matched control group of patients without OAT, the prevalence of chronic pain was 4-fold higher in patients receiving OAT . This fi4.9–46.2 .6–36.3. Several hypotheses may account for these differences between patients receiving OAT and the general population. Compared to the general population, patients receiving OAT may display particular characteristics regarding pain, such as an opioid-induced hyperalgesia, where a state of increased sensitivity to painful stimuli is observed in patients receiving OAT –33, and - Firstly, the prevalence of analgesics opioid prescription (excluding methadone/buprenorphine) was 2.2-fold lower than non-opioid prescription. Specifically, only 21.9% of patients receiving OAT with chronic pain were prescribed opioid analgesics, even though 75% of patients receiving OAT with chronic pain had moderate or severe chronic pain. Altogether, these findings may indicate either undertreatment or underdiagnosis.- Secondly, only four out of 10 patients reported being effectively relieved of their chronic pain.- Thirdly, among patients receiving OAT with prescribed analgesics, half of them self-medicated with additional analgesics, suggesting an undertreatment and insufficient relief. Several studies showed that 38.0–75.0% of patients receiving OAT with chronic pain also resorted to self-medication, including using over-the-counter drugs , 6, 13.- Fourthly, almost one third of patients receiving OAT with chronic pain were not prescribed any analgesics and self-medicated. It can be speculated that the use of self-medication was intended to supplement the lack of analgesic prescribing. This may suggest the possible absence of a previous appropriate diagnosis of chronic pain by a physician or an underestimation of the intensity of chronic pain.- Fifthly, one out of five patients used illicit drugs, such as cannabis, to relieve their chronic pain. In the literature, several studies have shown that the lack of pain treatment may encourage patients receiving OAT to use licit or illicit opioids, and other drugs such as benzodiazepines or cannabis, to self-treat their pain , 35, 36.These pain-relief seeking behaviors may reflect an inadequate pain diagnosis and management. Some studies reported that practitioners were reluctant to prescribe opioid analgesics (opiophobia) because of concerns surrounding the risk of relapse, risk of misuse, and diversion, as well as the risk of overdose associated with opioid tolerance , 38. Of As mentioned above, a number of comorbidities are associated with an increased prevalence of chronic pain in patients receiving OAT. In the present study, age, anxiety, and depression were clinical factors that were significantly associated with chronic pain in multivariate analysis. This is consistent with previous literature data where age , 28, 40 The coexistence of both a mental health disorder and a substance use disorder is currently acknowledged to be a co-occurring disorder and refers to the concept of “dual diagnosis” , 43. TheThis is the first multicentric study that has provided estimates of the prevalence of chronic pain in patients receiving OAT outside the US, which should bring some perspective to the field, both for France and across Europe. These findings should be useful to help clinicians gain awareness of the need to routinely identify and adequately manage chronic pain in patients receiving OAT. Moreover, the use of validated tools for measuring pain, psychological conditions, and general health make our results robust and reliable.However, this study had several limitations. First, despite the limited sample size, our participants were representative of the larger population managed in specialized centers in France. In particular, the ratio of methadone to buprenorphine prescriptions was realistic, there was a high proportion of males, and the mean age was consistent –47. Yet,The prevalence of chronic pain in patients receiving OAT in this study was far from trivial. Chronic pain was often moderate to severe and interfered significantly with daily life activities. Of interest, the appropriate management of chronic pain in the present study remained uncertain, since insufficient relief and frequent additional self-medications with analgesics or illicit drugs were reported by patients receiving OAT. Given the number of identified barriers for a proper pain management, there is an urgent need to pay systematic attention to pain diagnosis and management in patients receiving OAT. In this context, the elaboration of specific training and guidelines that care-providers could refer to, as well as the development of structured and multidisciplinary pain management programs dedicated to patients receiving OAT, should be strongly encouraged. Finally, patient-focused management needs to be implemented, in the setting of an integrated care of both pain and addiction, to improve individual clinical outcomes along both domains.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Ethique committees CPP Sud-Est VI Clermont-Ferrand. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.1, Jérome Bachelier2, Heiner Brinnel3, Philippe Dubost4, Hugues Leloup5, Van Phuc Nguyen6, Frédéric Plotka-Brun7, Mathilde Poirson8, Pierre Polomeni9, Christine Rouanet10, Sophie Velastegui11 and Pierre Villeger12Mohamed Allouach1 Équipe de Liaison et de Soins en Addictologie (ELSA), Centre Hospitalier de Givors, Givors, France2 Centre de Soins et d'Accompagnement et de Prévention en Addictologie (CSAPA), centre Port-Bretagne, Tours, France3 Centre de Soins et d'Accompagnement et de Prévention en Addictologie (CSAPA), Centre Hospitalier de l'Arbresle, BP116, L'Arbresle Cedex, France4 Centre de Soins et d'Accompagnement et de Prévention en Addictologie (CSAPA), CH Moulins, Moulins, France5 Centre de Soins et d'Accompagnement et de Prévention en Addictologie (CSAPA), Association Nationale de Prévention en Alcoologie et Addictologie (ANPAA), Issoire, France6 Équipe de Liaison et de Soins en Addictologie (ELSA), Centre Hospitalier de Rouanne, Roanne, France7 Centre de Soins et d'Accompagnement et de Prévention en Addictologie (CSAPA) “Fil à Fil”, Association Nationale de Prévention en Alcoologie et Addictologie (ANPAA), Montluçon, France8 Centre de Soins et d'Accompagnement et de Prévention en Addictologie (CSAPA) “Danielle Casanova”, Marseille, France9 Centre de Soins et d'Accompagnement et de Prévention en Addictologie (CSAPA), Hôpital René Muret, Sevran, France10 Centre de Soins et d'Accompagnement et de Prévention en Addictologie (CSAPA), Association Nationale de Prévention en Alcoologie et Addictologie (ANPAA), Clermont-Ferrand, France11 Centre d'Accueil et de Soins des conduites Addictives, CHU, Clermont de l'Oise, France12 Centre de Soins et d'Accompagnement et de Prévention en Addictologie (CSAPA), CHU Limoges, Pôle Addictologie, Limoges, FranceNA and CC developed the concept, devised the study, and reviewed the manuscript. JD takes responsibility for the integrity of the data, the accuracy of the data analysis, and wrote the first draft of the manuscript. J-LK and CC managed the literature searches and made substantial contributions to the data analysis. GB, MD, LP, J-PD, J-MD, PL, and AG provided revision of the intellectual content and final approval of the manuscript. All authors have participated sufficiently in the work to take responsibility for authorship and publication.GB received sponsorship to attend scientific meetings, speaker honoraria, from Lundbeck, Merck-Lipha, Indivior, Bristol-Myers Squibb, Otsuka, Eutherapie, Sanofi Aventis, and AstraZeneca. MD received honoraria for speaking at conferences from Indivior, Recordati, and Camurus Laboratories, and honoraria for consultancy from Indivior, Camurus, and Accord Healthcare. LP received speaker honoraria from Recordati and Indivior laboratories. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Breast reconstruction is most commonly performed using implant-based reconstruction. Patients with subpectoral implant placement with or without latissimus dorsi (LD) muscle coverage can experience muscle pain and animation deformity. Due to minimal literature describing the use of botulinum toxin (BTX-A) treatment for these side effects from implant-based reconstruction, we report our outcomes.A retrospective chart review of breast reconstructive patients for a single surgeon was performed. Patients who underwent BTX-A injection for muscular pain, spasm, or animation deformity were identified and outcomes reviewed. They were also stratified based on radiation treatment and type of muscle flap used.Eleven patients were identified who had a submuscular pectoralis pocket and/or a pedicled latissimus dorsi flap. Nineteen breasts were treated. The average amount of time from the patient’s last surgery to BTX-A injection was 11.2 months. 25–100 units were used per injection with an average of 60 units. Non-irradiated patients had signifycantly lower post-injection capsular contracture Baker grades and significantly lower amounts of BTX-A were injected. Patients who had both pectoralis major muscle and LD implant-reconstruction were significantly less likely to have improvement in pain/tightness. Most patients reported improvement or resolution of their pain and/or animation deformities.Implant-based reconstruction using the pectoralis major and/or LD muscles can be plagued with muscular pain, spasm, and animation deformities. The use of BTX-A is a diagnostic and therapeutic modality for these post-breast reconstruction patients with most patients having resolution of symptoms without the need for additional surgery. It inhibits acetylcholine and substance P release causing muscle paralysis with a less clear mechanism of action causing decreased pain , 2. One Animation deformity can range in severity, from slight discomfort and embarrassment to profound pain and restriction of physical function. It is estimated that at least 75% of subpectoral patients experience some degree of AD, and it is a common cause for revision surgery, with approximately 28% of patients pursuing reoperation . Pectora2.A retrospective chart review of patients undergoing breast reconstruction with a single surgeon was performed. Patients who underwent implant-based reconstruction with supplemental use of the pectoralis major muscle and latissimus dorsi muscle were identified. Those who had persistent post-operative muscular pain, contraction, or animation deformity and underwent BTX-A injection for these symptoms and signs were identified. Their demographic information was reviewed along with the details surrounding the BTX-A injection , as well as the patients’ outcomes. Improvement of muscular pain and animation deformity were the primary endpoints used to determine the need for repeat injection or surgery. This was determined based on the patient’s report, as well as on physical exam. The study was approved by the institutional review board.2.1Botulinum toxin type-A injection was performed in an outpatient clinic without any sedation or local anesthetic. The freeze-dried 100 unit BTX-A vial was reconstituted with 5 mL of sterile sodium chloride (0.9%). The location of the patient’s pain and/or muscle tightness was identified at rest and with activation by having the patient place their fists on their hips while adducting and internally rotating their arms. Occasionally focal areas of muscle spasms can be seen visually, as well as by palpation. In addition, the patient’s reported sites of pain and/or tightness were marked to provide targeted injection including the pectoralis major muscle’s origin . The amoThe areas previously marked during the exam identifies the areas of injection, which are prepped with alcohol. The pectoralis major muscle is palpated under the skin and confirmed with muscle activation. The skin and muscle at the site of the injection is pinched between fingers and the implant is displaced away from the injection site. The injection is performed using the entire length of the 30G ¼ inch needle into the tissue isolated between the fingers. Awareness of the injection location and length of the injecting needle, as well as displacement of the implant was performed to avoid injury to the underlying implant. Of note, the use of BTX-A for these purposes is off-label and not yet approved by the FDA.2.2All statistical analyses were completed using Stata v.15 . The Shapiro-Wilk test was used to determine whether continuous variables were normally distributed. Clinical data were compared between cohorts using Kruskal-Wallis and Fisher’s Exact analyses. The two-tailed threshold for statistical significance was set at an alpha value of 0.05.3.From 2012 to 2019, eleven women meeting inclusion criteria were identified. The average age was 51.5 years (range 34–73 years old) with the majority of patients  having a diagnosis of breast cancer . All patPatient response to the BTX-A injections were assessed during their post-operative visits. The average length of follow-up was 8.5 months (range 8 days to 24.5 months) from the time of the patient’s last BTX-A injection. Two patients were lost to follow up. The majority of remaining patients  reported improvement or resolution of their pain and/or animation deformities, as well as having softening of their capsule contracture to grade 1–2 on exam. Three patients required 2 or more BTX-A injections and 1 patient had denervation of bilateral pectoral nerves due to the severity of the animation deformity that had improved, but recurred, with BTX-A. No adverse complications were associated with BTX-A use including injection site infection, generalized muscle weakness, breathing difficulties or hypersensitivity reactions. When stratifying patients by their history of radiation therapy, 4 patients were identified as having undergone radiation . All of In addition, when analyzing the effects by breast, non-irradiated breasts received significantly lower amounts of BTX-A than irradiated breasts . Patient4.Breast reconstruction is becoming increasingly widespread after mastectomy. The most common approach is implant-based reconstruction with the majority of patients undergoing subpectoral placement versus prepectoral placement , 21, 22.In general, the literature on the use of BTX-A in breast reconstruction is conflicting. A nonrandomized prospective study of 48 patients (22 patients receiving and 26 patients not receiving BTX-A infiltration at the time of mastectomy) reported a significant decrease in post-operative pain and decreased narcotic requirement in the study group . A randoOur results showed that non-irradiated patients had significantly lower Baker grades of capsular contracture post-injection compared to irradiated patients. The non-irradiated breasts also were significantly more likely to demonstrate improvement in symptoms of pain/tightness. This suggests that BTX-A is more efficacious in treating capsular contracture among non-irradiated patients. In addition, non-irradiated patients received a significantly lower amount of BTX-A. These results indicate that the skin and soft tissue changes after radiation may have a negative impact on the effectiveness of BTX-A. When comparing the type of muscle coverage using pectoralis major muscle and/or latissimus dorsi muscle, the combined use of these muscles were significantly less likely to have an improvement in pain/tightness symptoms after injection and a higher post-injection pain score. With muscle being used from two sites, it is not surprising that patients would be more symptomatic as it is likely there is an additive effect when combining both muscles. The limitations associated with this study are its small sample size, retrospective nature, and variable length of follow-up. In addition, while the use of BTX-A has been reported in implant-based reconstruction, a specific methodology still needs to be established. Approaches have ranged from the number of units used to the number and specific locations of the injections, and the optimal dose of BTX-A has yet to be determined.5.The use of BTX-A can be a diagnostic and therapeutic modality for implant-based breast reconstruction patients who experience muscular pain, spasm, and animation deformities due to the manipulation of their pectoralis major and/or latissimus dorsi muscles. This study supplements the available literature that generally supports the use of BTX-A for these symptoms and may negate the need for additional surgery in these patients. Therefore, botulinum toxin A is a promising first-line therapy for post-implant breast reconstruction patients experiencing muscular pain and dysfunction.


Surgery is associated with significantly better overall pain relief and lesser endocrine insufficiency in patients with painful obstructive CP. However, considering the invasiveness of surgery, no significant differences in complete or partial pain relief, and heterogeneity of a few parameters between two groups, endoscopic drainage may be firstly performed and surgical drainage may be considered when endoscopic drainage fails.There is limited evidence on the standard care for painful obstructive chronic pancreatitis (CP), while comparisons of endoscopic and surgical modes for pain relief have yielded conflicting results from small sample sizes. We aimed to obtain a clear picture of the matter by a meta-analysis of these results. We searched the Pubmed, Embase, and Cochrane Library databases to identify studies comparing endoscopic and surgical treatments for painful obstructive CP. Pooled effects were calculated by the random effect model. Primary outcomes were overall pain relief , and secondary outcomes were complete and partial pain relief, complication rate, hospitalization duration, and endocrine insufficiency. Seven studies with 570 patients were included in the final analysis. Surgical drainage was associated with superior overall pain relief [OR 0.33, 95% CI 0.23–0.47,  Chronic pancreatitis is a prevailing health topic in the western countries, with a reported prevalence of around 50/100,000 persons . ContribStepwise escalation of treatment aggressiveness has been advocated ,10, starThe current meta-analysis has been registered in the National Institute of Health Research (PROSPERO registration number: CRD42020207014).The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)  and MetaFor the purpose of this meta-analysis, primary outcomes were all levels of pain relief and secondary outcomes were proportions of complete and partial responses, complication rate, hospitalization duration, and endocrine and exocrine insufficiency. For the primary outcomes, pooled rate of overall pain relief is defined as the total proportion of complete and partial pain relief. The pooled rate of complete pain relief corresponds to the composite of Izbicki pain score ≤10, or the absence of painful attacks. At the same time, pooled rate of partial pain relief corresponds to the composite of Izbicki pain score >10 with a more than 50% decrease compared with the baseline score, or a reduction in pain of at least three points on the Melzack score. For the secondary outcomes, the pooled complication rate is defined as endoscopic complications, including pancreatitis, bleeding, stent migration, and surgical complications, including anastomotic leakage and pancreatic fistula. The pooled endocrine and exocrine insufficiency rate is defined as the use of diabetes medication, and as composite of fecal elastase <200 μg/g, pancreatic functioning diagnosant <70%, or new-onset steatorrhea, respectively.2 test result with number less than 25% was regarded as absence of significant heterogeneity. Independent samples test was applied to compare the means of two groups. Funnel plot with Eggar’s test was used to check for publication bias. p values of less than 0.05 were considered statistically significant. Sensitivity analysis was conducted for primary outcome to delineate the accuracy of the pooled results using the receiver-operating characteristics curves.Meta-analysis was performed using R Software, version 4.0.1. Since heterogeneity across the included studies was expected, the random effect model was used instead of the fix model analysis. IThe quality of the three RCTs was assessed with Jadad scoring, which rates a study according to three main criteria: 1, randomization; 2, blinding; and 3, withdrawals and dropouts . The JadThe literature search protocol identified 2616 potential studies . After ep < 0.001, I2 = 4%] , results from four studies ,20,22,23 = 0.40] . Sensiti = 0.40] .The current meta-analysis demonstrated that surgical drainage is associated with better overall pain relief for patients with chronic pancreatitis in comparison to endoscopic stenting. In addition, subgroup analysis showed that surgical treatment was associated with a lower incidence of endocrine insufficiency.Several procedures had been described as a surgical treatment for chronic pancreatitis associated pain. It can be broadly categorized into the drainage type and the resection type. Partington operation—an example of the drainage type—is an ideal one for patients with stricture predominant disease. Regarding the resection type, pancreaticoduodenectomy—pylorus-preserving or not—is a procedure of choice for mass forming chronic pancreatitis in which malignancy cannot be excluded. While Frey’s or Beger’s duodenum-preserving pancreatic head resection can be used to treat pancreatic head mass, multiple strictures and dilated pancreatic duct simultaneously. Choice of procedure depends on the endocrine and exocrine statuses of the patient, the radiological morphology of the pancreas, and the expertise of the surgeon. However, significant difference in the effectiveness in pain relief between different surgical procedures has not been seen, as demonstrated by a recent meta-analysis of RCTs .p < 0.001, I2 = 4%]. As supplemented by the Funnel plot and sensitivity analysis, the chance of confounding effect from publication bias . Head-to-head comparison for surgical and endoscopic complications risked oversimplification due to heterogeneity in the definitions and magnitude of seriousness of various complications. It should be noted that complications after pancreatic surgery and after endoscopic procedures are not equal regarding to fatality and risk of severe morbidity.Several RCTs had consistently reported that surgical drainage might be a more effective means in treating pain associated with obstructive chronic pancreatitis, authorities remained conservative regarding its recommendation ,33. The ion bias  and studion bias  is low. p = 0.03] and less endocrine pancreatic insufficiency  were observed in these patients. However, Boerma et al. . It is understandable that younger patients were more likely to be offered surgery given their better physiological reserve for surgical trauma. However, the potential confounding effect of age difference should not be overlooked. Higher rate of endocrine insufficiency  in the endoscopy group in this meta-analysis could be a result of the natural aging process or a “burnt-out” pancreas damaged by prolonged inflammation.Another point to note is that the age of the patients in this meta-analysis tended to be younger in the surgery group. In the study by Issa et al. , the medRegarding the surgical approach, all studies had a certain proportion of patients who received surgery with a resection component (pancreaticoduodenectomy or Frey’s procedure). For instance, 41.5% (17/41) and 60% (61/76) of the surgical operations in the studies by Issa et al.  and Ditep = 0.13, I2 = 87%], the high I2 value suggested the existence of uncertainty in the pooled result due to heterogeneity. Concerning secondary outcomes, it would be challenging to draw any direct conclusions due to the heterogeneous population definitions and outcome measurements. This is particularly true for length of hospitalization. Although the two approaches resulted in statistically similar duration of hospitalization [OR −0.54, 95% CI −1.23–0.15, There were a few limitations in this meta-analysis. First of all, due to heterogeneity of the definition of pain relief and pain onset in patients with painful obstructive chronic pancreatitis in this meta-analysis, further study with standardized protocol may be required to validate our results. Secondly, only three RCTs were included and they were conducted in different clinical situations; although we tried to contact with authors in each literatures, there was also paucity in data on gender, age, co-morbidities, smoking, alcohol use, and the type of endoscopic therapy in the studies  in the dataset that cannot be examined in a meta-regression model, which limits the quality of results this might weaken the power of this meta-analysis. Last but not least, recent development in laparoscopic/robotic pancreas surgery and advances in endoscopic ultrasound pancreatic intervention were not considered in the current analysis, future studies focusing on these aspects are awaited. In summary, surgery is a promising option to achieve overall pain relief in chronic pancreatitis due to ductal obstruction, with possibly better glycemic profiles in the long run when compared to endoscopic drainage. However, considering the invasiveness of surgery, no significant differences in complete or partial pain relief, and heterogeneity of a few parameters between two groups in our SRMA, endoscopic drainage may be still preferred over surgical drainage as an initial attempt or in patients who are unsuitable for surgery and surgical drainage may be considered when endoscopic drainage fails. A sensible treatment algorithm for patients with painful pancreatitis could be a “step-up” approach with endoscopic treatment first, followed by surgery in the non-responders.


Patients with back pain are common and present a challenge in everyday medical practice due to the multitude of possible causes and the individual effects of treatments. Predicting causes and therapy efficien cy with the help of artificial intelligence could improve and simplify the treatment. In an exemplary collective of 1000 conservatively treated back pain patients, it was investigated whether the prediction of therapy efficiency and the underlying diagnosis is possible by combining different artificial intelligence approaches. For this purpose, supervised and unsupervised artificial intelligence methods were analyzed and a methodology for combining the predictions was developed. Supervised AI is suitable for predicting therapy efficiency at the borderline of minimal clinical difference. Non-supervised AI can show patterns in the dataset. We can show that the identification of the underlying diagnostic groups only becomes possible through a combination of different AI approaches and the baseline data. The presented methodology for the combined application of artificial intelligence algorithms shows a transferable path to establish correlations in heterogeneous data sets when individual AI approaches only provide weak results. Artificial Intelligence (AI) is gaining more and more influence in medical care. However clinical disease presentations are complex and prediction of the progress of a disease for the individual patient is often difficult. Patients with back pain are a typical example as the causes of pain are diverse and complex ranging from simple muscular spasms to malignant tumors or serious injuries. Thus the perception and processing of the complaints as well as the extent of therapeutic success through medical measures show a high interindividual variability .Finding the right cause of back pain and better estimation of success rates of a conservative therapy would help to propose a suitable treatment. This could facilitate the initiation of individually appropriate therapy and the determination of a suitable diagnosis without the excessive use of costly and time-consuming, often invasive diagnostics. An insufficient or too excessive care of patients could be avoided.In recent years, there have been increasingly promising efforts to improve medical care in the field of back pain and spinal therapy through the application of artificial intelligence ,3,4,5,6.To further improve AI prediction, we have developed a combined AI approach. For this purpose, a dataset of 1000 patients with spinal complaints who underwent standardized conservative therapy was utilized. The individual efficiency of this treatment was first examined in a supervised AI approach. Secondly a non-supervised clustering was performed. Then a combination of both approaches by supervised prediction of clusters was established. The joint application of all three approaches then enabled the prediction of diagnostic groups through the analysis of cluster subgroups. This entire process exemplifies how a combination of AI approaches can enable diagnostic prediction.Prospectively collected data of 1000 consecutive patients presented at the Spine Center of the Hessing Foundation in Augsburg, Germany, between August 2018 and January 2020 were used. All patients suffered from back pain and received standardized inpatient conservative therapy. All patients were treated according to the same therapy sequence over 5 days, whereby the therapy modules provided were individually adaptable.Complaints were assessed at baseline and at the end of therapy using the Oswestry Disability Index (ODI) and a visual analogue scale (VAS), separately for leg and back pain. The ODI is based on a questionnaire and ranges from 0 to 100. Higher scores in the ODI indicate a higher disability . VAS is All patients received a combination of different therapeutic measures over 5 days including daily specific spinal infiltrations . Additionally, daily physiotherapeutically guided exercises, balneo-physical applications and learning of pain-coping strategies were carried out in individual and group therapies.Basic demographic data, as well as the ODI value along with separate VAS score for leg and back pain for every patient were assessed on the day of admission. The ODI was re-assessed on the day of discharge following inpatient treatment. The data collected from the 1000 patients were divided into three quality categories. As a result, 100% complete data sets were available for 427 patients. In 211 cases there was an insufficient response regarding the ODI questionnaires (more than one question has not been answered). The remaining 362 records had multiple incomplete data.2 and were thus classified as obese. A total of 31.2% of patients stated that they were regular smokers. In total, 28.9% of the patients had previously undergone spinal surgery.The mean age of the patients was 62.8 years and ranged from 18 to 95 years. 55.2% of patients were female, 44.8% male, 0% diverse. In total, 37.1% of patients had a BMI above 30 kg/mThe data collected from the 1000 patients were stored in a csv file format that was read by the pandas python package . The final parameters used during the machine learning are shown in After identification of categorical variables, these were implemented in a neural net. The rest were continuous variables that have been collected in a separate array as a separate input to the model. The model used had multiple categorical inputs processed via an embedding layer and one input for the continuous variables. All inputs were concatenated and processed through two additional hidden layers with rectified linear activation functions and a subsequent linear output at the last layer. The Keras framework (v. 2.2.4)  with tenFirstly, in a non-supervised approach, the whole dataset was investigated. Therefore we used a Python implementation of an algorithm for dimensionality reduction   to visuaSecondly, we trained a simple shallow neural net to predict the cluster labels assigned. Eventually we identified the most important features within our dataset contributing to the class label hence the cluster they were assigned to by using the python implementation of SHapley Additive exPlanations (SHAP)  which isMachine learning is used in the supervised AI approach, on the one hand, to predict the ODI score at the end of conservative therapy and on the other hand to predict the cluster group of the non-supervised AI approach as described above.In the framework of the cluster group analysis, the ODI at admission was shown to be the most important influencing factor on the cluster grouping  and at tgiven ODI at admission;predicted change in ODI after therapy;predicted cluster group a patient belongs to.Accordingly, the following data are available for an individual patient at the start of treatment:If one analyzes the general ODI values in the predicted cluster group and compares them with the two individual ODI values of the patient (given at admission and predicted at discharge), it becomes possible to identify diagnostic groups based on the ODI characteristics of the patient.The supervised AI model was performed in 5-fold cross-validation and achieved a mean absolute error of 9.06 in the prediction of the ODI value at discharge. A standard deviation of 0.17 was found .In the non-supervised AI model, a clear clustering with three separate areas could be found . TraininAn analysis of the diagnosis subgroups in each cluster in Our supervised AI model for the prediction of ODI scores after conservative treatment can be considered useful to predict the success of conservative treatment of back pain. Unfortunately the absolute error rate of about 9 percentage points on the ODI scale does not lie within the minimum clinical difference (MCID) for the ODI which is also 9%  . For theThe reason for the insufficient prediction rate is not the number but the quality of the data . We showIn a separate analysis, we looked for a way to identify the causes of a patient’s back pain solely on the basis of the data set used here, without performing further diagnostics such as MRI or X-ray.For this purpose, we first conducted a cluster analysis and then established a prediction of these clusters. Further analysis of the clusters led to subgroups that can be identified with the available predictions and baseline data of an individual patient.To our knowledge, the interlinking of a cluster data analysis with a supervised AI for the prediction of cluster subgroups, represents a new approach for AI algorithms to address clinical questions. The diagnosis subgroup into which a patient can be assigned is identified in a kind of decision tree. This is built up from a combined supervised and non-supervised AI and provides distinguishing features based on the ODI on admission, the change in ODI after therapy, and the predicted cluster group. These features can be applied to the subgroups of clusters that are diagnosis-based, allowing the underlying diagnosis of a patient to be determined.The correct cluster for a new patient is predicted with an accuracy of 89.54% in our model. The standard deviation here is 5.25%. These values show that the prediction is possible, but for clinical application, these values should be considered insufficient. From our point of view, an improvement of the data quality is a necessity for an improvement of the prediction, as stated above. In detail, when the dimensionally reduced cluster representation is combined with the detailed analyses of the individual predictions, it becomes apparent that the cluster group “0” probably consists of several individual clusters, but the available data sets cannot produce sufficient discriminatory power to differentiate them further. As a result, the predictions mainly show difficulty in correctly predicting the cluster group “0” (an example of the weakest prediction is shown in Consequently, the diagnosis subgroup prediction based on the cluster prediction is also rudimentary in the present version. Clear differentiation is currently only possible for several diagnosis subgroups. Often only tendencies are recognizable in the current form, which make a definite classification into a diagnosis group difficult. It is well recognized that clinically related diagnostic groups also achieve comparable ODI values . This coSince the data sets used here are the results of a single center and the therapies were carried out in all patients with the same components, we see the main problem to be the insufficient data quality. Secondly, the amount of data in this study could also be considered insufficient as the available data combine a large number of pathologies . We haveAlthough it has been shown that imaging often does not necessarily correlate with the clinical impact of spinal changes , integraThe data set of our methodological study used here has no relevant follow-up data. The predicted ODI value at the time of discharge after inpatient treatment is recorded approx. 5 days after the baseline values were recorded. To make a relevant statement about the success of the therapy, follow-up data would have to be collected several weeks to months after the treatment ,22,23. AThe application of artificial intelligence algorithms in spine therapy is slowly gaining momentum. A few years ago, there were hardly any approaches to using the latest algorithms to optimize therapy for patients with back pain and spine related problems ,24. In tOur presented concept shows that a combination of different AI techniques represents an added value and can be adapted towards clinical challenges. We believe our work can provide another component to further establish artificial intelligence in the treatment of back pain.In this methodological study, we show how different artificial intelligence approaches can be applied in a patient collective, both individually and in combination, to gain insights into the cause of back pain in individual cases.


Common surgical treatments for trigeminal neuralgia (TN) include microvascular decompression (MVD) and percutaneous procedures . Although the efficacy of each procedure has been documented, direct comparisons of their relative efficacies for TN are lacking. We aimed to directly compare long-term outcomes after first-time MVD with percutaneous surgery in primary  TN and identify predictors of outcome.We conducted a retrospective analysis of prospectively collected data on 185 patients undergoing MVD and 129 undergoing percutaneous surgery. Procedures were performed by one of two neurosurgeons in a single centre; an independent observer collected long-term follow-up data by interviews, using the same outcome measures for all procedures.P <.001). MVD provided superior initial pain relief (P <.001): 87.0% had Barrow Neurological Institute class I or II pain scores after MVD compared with 67.2% after percutaneous surgery. The complication rate for percutaneous procedures was 35.7% and for MVDs was 24.9% (P =.04), including minor and transient complications. Kaplan-Meier analysis demonstrated that MVD provided longer pain relief than percutaneous procedures (P <.001); 25% of patients had recurrence at 96 months following MVD compared with 12 months after percutaneous surgery. Subgroup analysis showed that balloon compression provided more durable relief amongst percutaneous procedures. Multivariate analysis revealed that post-operative numbness and age were prognostic factors for percutaneous procedures .MVD patients were younger than those undergoing percutaneous surgery (MVD provides better initial pain relief and longer durability of relief than percutaneous surgery, although carrying a small risk of major complications. Amongst percutaneous procedures, balloon compression gave the most durable relief from pain. Older age and post-operative numbness were predictors of good outcome from percutaneous surgery. These results can help clinicians to counsel patients with primary TN on neurosurgical treatment selection for pain relief.The online version contains supplementary material available at 10.1007/s00701-021-04793-4. Trigeminal neuralgia (TN) is a syndrome of paroxysmal, severe facial pain in the trigeminal nerve sensory distribution. The more definitive treatment for TN is microvascular decompression (MVD) to relieve the causative physical compression of the trigeminal nerve by a neighbouring blood vessel , 11. OthThe long-term relief rates for MVD have been reported to range between 70 and 80% at 5–10 years in several large series , 42, 52.Here, we performed a retrospective analysis of prospectively collected data from a large patient cohort, comparing long-term outcomes of MVD with percutaneous procedures  in a relatively homogenous population of primary , typical TN patients undergoing first-time surgery. All procedures were performed by only two experienced neurosurgeons in a single centre, and an independent observer collected long-term follow-up data with the same outcome measures to minimise biases.P = 0.055, 2-sided Fisher’s exact test). Cases with MS or repeat surgery have been reported separately [This study had patient consent and institutional ethical board approval. Clinical data for all consecutive patients who underwent surgery for TN in University Hospital Southampton were prospectively collected. Between 1996 and 2012, 622 surgical procedures were performed for TN; 185 patients who had MVD and 129 who had percutaneous surgery  were included in this study . Patient data were collected from operation notes and clinic letters. Routine clinic follow-up of these patients was conducted at 3 months and 18 months after their operation. Additional telephonic follow-up was conducted and/or questionnaires were completed to obtain long-term data. An independent, unbiased research doctor (I.N.) or specialist TN nurse (A.L.) performed these long-term interviews, minimising potential reporting biases from patients being reluctant to disappoint their treating clinician by directly reporting poorer outcomes to them. Follow-up time extended up to 20 years .Initial pain relief (3 months post-procedure) was defined according to the Barrow Neurological Institute (BNI) pain intensity score : ‘class The reporting period began before the availability of cisternography using fine-cut MRI with gradient echo sequences , which became available in our centre from the year 2000; prior to this, lower resolution MRI images with MR angiography alone were used from a 0.5-T scanner. Pre-operatively all MR films were assessed for neurovascular compression (NVC) by the consultant neurosurgeon and a consultant neuroradiologist.All operations were performed by 1 of 2 consultant neurosurgeons (G.V. and O.S.) directly or under their personal supervision. Both surgeons were fully trained and well-experienced in all procedures prior to operating on cases for this study. The decision-making strategy we used for selecting operations for individual patients is in line with published algorithms . MVD wasThe vast majority of patients offered MVD accepted it. A few were unsuitable due to comorbidity, and most without NVC  offered an exploration similarly agreed, expecting a partial sensory rhizotomy if exploration was negative. Patients over 85 years old were excluded for MVD as none was medically suitable. All cases up to 75 years were offered open surgery when fit, as were those up to 80 in reasonable health, and only the exceptionally fit cases aged over 80 years were offered open surgery. Many of the elderly patients however preferred a shorter ‘day-case’ percutaneous procedure, declining open surgery. Records of exact numbers of patients who were offered surgery but declined were not available; however, the senior author is confident of small numbers for those with probable NVC and medically fit who declined MVD, and for those without NVC and offered exploration, who declined this option. Similarly, we do not have records for the exact number of patients with probable NVC who were not offered MVD due to age/medical comorbidities.Although SRS was not available at our centre, patients were referred for SRS to another centre where mass lesions of Meckel’s cave/cavernous sinus could be simultaneously treated by this modality (two patients), or critical anticoagulation ruled out a percutaneous procedure requiring even only temporary reversal (one patient). In these cases, there was no need for immediate pain relief. However, due to limited facilities for SRS in the UK during this study period and geographical distance of these from our centre, SRS was not offered as a ‘surgical’ first-line in primary TN.Percutaneous procedures were performed under general anaesthesia or sedation with fluoroscopic guidance, with minimal variation in technique between cases. For GR, a 20-gauge needle was inserted into the medial foramen ovale following Härtel’s technique, and advanced deep toward the clivus on a lateral projection. After reversal of anaesthesia, contrast was injected with the patient in the sitting position and head flexed forwards; contrast was slowly replaced with glycerol . The needle was then withdrawn, with patient position maintained for at least 2 h. For TC, a similar needle insertion technique was used, with the needle tip placed more laterally in the foramen ovale to reach the trigeminal ganglion. Electrode tip position was confirmed by awake testing before re-sedation and heating the electrode to between 65 and 70°C for 60 s. One thermal lesion was made, except where there was combined V2 and V3 neuralgia with evoked paraesthesiae in only one of these divisions, in which case a second lesion was performed for the other division following needle adjustment and re-testing.Following the same needle insertion technique via the middle of the foramen ovale on its posterior rim, with a soft Fogarty balloon and minor test inflation with contrast to confirm correct balloon configuration, Vn compression entailed balloon inflation with 0.35–0.50 ml of contrast to obtain a ‘pear’ shape (known to improve pain outcomes ), with tFor MVD, the operative technique was similar to that of published techniques , 18, 31.P < .05 for all tests. The 2-sided chi-square test or Fisher’s exact test was used to compare proportions between groups of patients. Kaplan-Meier curves were compared by the log-rank test. Data were censored if there was no pain recurrence at the most recent follow-up. To identify predictors of pain relief, univariate analysis was performed by logistic regression; multivariate logistic regression was performed using those variables exhibiting a P < .2 from univariate analysis.Statistical analysis was performed using IBM SPSS 25  software, with a significance level of P < .001, unpaired two-tailed t-test; range 24.3–83.0 years for MVD and 43.5–93.7 years for percutaneous procedures) and had a shorter duration of pre-operative TN pain .Patients undergoing MVD were significantly younger than those undergoing a percutaneous procedure . Comparing the distributions of initial pain relief demonstrated that MVDs provided significantly better initial relief compared with percutaneous procedures  but not compared with BC when comparing the distributions of pain relief . There were no significant differences in distributions of initial pain relief scores between GR, TC, and BC  was achieved after 16.7%, 10.4%, and 3.8% of GR, TC, and BC procedures, respectively. MVD provided significantly better initial relief than GR and TC  cases of CSF leak requiring temporary CSF diversion with a lumbar drain, 8 (4.3%) cases of minor stroke , 2 (1.1%) cases of chemical meningitis that recovered, and 1 (0.5%) case of deep venous thrombosis (DVT). Two (1.1%) patients reported facial paraesthesiae and 7 (3.8%) reported dysaesthesiae. There was one (0.5%) death after an MVD due to a post-operative posterior fossa haematoma in a patient with underlying but peri-operatively treated coagulopathy. The commonest complications were minor: ataxia (9.7%) and diplopia (5.9%) which improved Fig. .Fig. 3PP = .04, Fisher’s exact test).After a percutaneous procedure, there were 15 (11.6%) cases of minor dysaesthesiae and 3 (2.3%) of major dysaesthesiae, 3 (2.3%) of bothersome numbness, 12 (9.3%) of reduced corneal reflex, and 9 (7.0%) of facial paraesthesiae Fig. . There wP = .006, Fisher’s exact test; Fig. At 3-month follow-up following MVD, 4.3% of patients had mild to moderate facial numbness, and 1.6% had dense numbness; there were no cases of bothersome numbness. In contrast, 90.4% of percutaneous cases developed mild to moderate numbness, and there were significantly more cases of dense (6.1%) and bothersome (2.6%) numbness than with MVD .Subgroup analysis of percutaneous procedures showed that BC generated a greater proportion of cases with dense or bothersome post-operative numbness than GR and TC  analysis for time to recurrence of TN demonstrated that MVD provided significantly longer pain relief compared with percutaneous procedures overall , and non-inferior to BC . The median time to pain recurrence was 29 months (95% CI 16.1–41.9 months) for GR, 30 months (95% CI 8.6–51.4 months) for TC, and not yet reached for BC. Twenty-five percent of patients had pain recurrence at 5 months following a GR, 12 months after a TC, and 26 months after a BC. Although there was no difference in durability of relief after a GR compared with TC , BC provided significantly longer pain relief compared with GR and TC  using univariate analysis. With pre-operative MRI findings of neurovascular contact or compression of Vn, there was a favourable outcome in more cases , and similarly for severe intra-operative NVC  on univariate analysis . On multivariate logistic regression analysis, both age and post-operative numbness remained significant predictors of outcome  TN, using the same outcome measures. Such results have rarely been reported together for direct comparisons , 23, 15.The efficacy of MVD in our study, with 87% of patients achieving initial BNI class I or II pain scores and 25% of patients having pain recurrence by 96 months, is similar to published observations , 4, 43. Previous work has suggested a correlation between sensory loss and pain relief following destructive procedures for TN , 7, whicPreviously reported prognostic factors for MVD include male sex, arterial compression, duration of TN pain, and typical TN , 32, 50.MVD and percutaneous procedures have advantages and limitations. While MVD provides superior long-term pain relief overall, it is a larger and longer operation than percutaneous procedures, requires longer hospital stay, and carries a risk  of serious complications. Patients with ischaemic stroke after MVD in this series had relatively mild neurological deficits that improved. The minor strokes were assumed to be due to disruption or kinking of small brainstem perforators during the mobilisation of the caudal loop of the superior cerebellar artery from deep to the trigeminal nerve root. Most minor strokes were revealed by direct enquiry of patients during routine follow-up, by which time they had recovered fully. In some early MVD cases, polyvinyl alcohol  foam was used and resulted in two cases of chemical meningitis, and thus we decided to use Teflon felt subsequently. In the patient who unfortunately died after MVD due to a cerebellar haematoma, no vein was coagulated intra-operatively, and their pre- and intra-operative correction of modest coagulopathy associated with chronic myeloma was undertaken on haematological advice.Percutaneous procedures are less invasive, simpler to perform, need shorter hospital stay , and can also provide immediate relief. However, percutaneous procedures generally provide shorter durability of relief compared with MVD  and havLimitations of this study include the retrospective nature of the analysis  . PatientFor younger and medically fit patients, MVD should be offered.For older, less medically fit patients or those unwilling to undergo an open operation, balloon compression is suggested as first-line.If balloon compression is not possible, glycerol rhizolysis or thermocoagulation can be offered, although thermocoagulation should be avoided in those with pure V1 pain.Surgical decision-making needs tailoring to the individual patient and depends on many factors. Our large single-centre analysis of first-time surgery for idiopathic and classical (primary) TN shows that MVD provides superior initial quality of relief and also durability of pain relief than percutaneous surgery, although carrying a low risk of major complications. Percutaneous procedures, particularly BC with the reported parameters, provide good pain relief with largely minor complications in patients less suitable for or unwilling to have a major operation. Older age and post-operative numbness are prognostic factors for better outcome after percutaneous procedures. We hope our data will aid surgeons in counselling TN patients for selecting between these procedures, and we propose these guidelines for first-time surgery in primary TN :ESM 1(DOCX 14.7 kb)


Background and Purpose: Transverse abdominis plane (TAP) block has been suggested to reduce post-operative pain after laparoscopic cholecystectomy (LC). However, the literature is divided on whether ultrasound (USG)-guided TAP block is effective for pain control after LC. The present meta-analysis therefore evaluated the efficacy of USG-guided TAP block vs. controls and port site infiltration for pain control after LC.Methods: A comprehensive literature search of online academic databases was performed for published randomized controlled trials (RCTs) for studies published to January 31, 2021. The primary outcome analyzed was post-operative pain score at 0, 6, 12, and 24 h post-surgery, both during rest and while coughing. Secondary outcomes included morphine consumption and post-operative nausea and vomiting (PONV) incidence.Results: A total of 23 studies with data on 1,450 LC patients were included in our meta-analysis. A reduction in pain intensity at certain post-operative timepoints was observed for USG-guided TAP block patients compared to control group patients. No reduction in pain intensity was observed for patients receiving USG-guided TAP block patients vs. conventional Port site infiltration.Conclusion: This meta-analysis concludes that TAP block is more effective than a conventional pain control, but not significatively different from another local incisional pain control that is port site infiltration. Additional prospective randomized controlled trials are required to further validate our findings. Laparoscopic cholecystectomy (LC) is currently the gold standard treatment for symptomatic gall bladder disorders, including cholelithiasis and cholecystitis , 2. HoweTransversus abdominis plane (TAP) block is a regional anesthetic technique that has gradually become an alternative for post-operative pain control. It involves the infusion of local anesthetic into the fascial plane of the abdominal wall where the T6 to L1 nerves are found . ConventA previously published meta-analysis detailing seven randomized controlled trials (RCTs) showed TAP block to be effective when compared with standard analgesia in adults undergoing LC . HoweverThis meta-analysis was performed using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines . A comprRCTs involving adult patients undergoing elective LC that compared the efficacy of USG-guided TAP block against either control or port-site infiltration groups were included. Studies that did not report pain outcomes were not included. Studies where full-texts were not available were not included.All eligible studies were screened by two independent reviewers using the selection criteria listed above. Screening first entailed abstract review, followed by full-text review. Any discrepancies were settled through discussion with a third reviewer. Articles published in a language other than English were machine translated using Google Translate and considered for inclusion. The following information was extracted from each included study: number of patients, investigation groups, types of analgesia used, outcome measurements, treatments, interventions, and adverse effects.The primary outcome evaluated in this study was pain control in LC patients, as measured using 1–10 rating scales such as the visual analog scale (VAS) or numerical rating scale (NRS). Measurements at 0, 6, 12, and 24 h post-operation, both at rest and while coughing, were noted.Secondary outcomes in this study included morphine consumption and post-operative nausea and vomiting (PONV) incidence.Studies were assessed for quality using a modified JADAD score  that evaPublication bias was assessed using funnel plot analysis. Funnel plot asymmetry was assessed using Egger's regression test , 15.I2 statistic. For I2 values >50%, a random-effects model was applied. For I2 values below 50%, a fixed-effect model was applied. Statistical analyses were conducted using Review Manager software .Mean difference (MDs) with 95% confidence intervals (CIs) was calculated for the continuous outcome. Risk ratios (RR) with 95% CIs were calculated for categorical outcomes to estimate pooled findings. Study heterogeneity was evaluated using the Primary screening yielded 118 candidate articles. Of these, 47 underwent full-text screening and review. Ultimately, 23 studies containing data on 1,450 patients met inclusion criteria .A full summary of extracted data from included studies is presented in For the primary outcome of pain control at rest and during coughing, out of 23 studies, 22 studies were included in the analysis for which references have been provided in I2 = 98%, p < 0.0001; 6 h: I2 = 94%, p < 0.0001; 12 h: I2 = 85%, p < 0.0001; 24 h: I2 = 87%, p < 0.0001).Analysis of the included studies suggested significantly reduced pain intensity in patients receiving USG-guided TAP block relative to control group patients at 0, 6, 12, and 24 h post-operation . HoweverA significant reduction in pain intensity while coughing was observed at 0, 6, and 24 h post-operation in USG-guided TAP block patients relative to control group patients . No signI2 = 91%, p < 0.0001).Analysis of seven studies –29, 31 iI2 = 9%, p = 0.36).Analysis of 12 studies , 36, 37 (a) Post-Operative Pain Intensity at Rest for all timepoints ; (b) Post-Operative Pain Intensity during coughing for all timepoints , (c) Morphine consumption during 24 h after operation (p = 0.36), (d) Post-operative nausea and vomiting (PONV) incidence (p = 0.71). All funnel plots showed symmetric shape for all the comparison.No significant publication bias was detected using Funnel plots or Egger's tests for This study evaluated the efficacy of USG guided TAP block for reducing pain intensity at rest and while coughing in LC patients for up to 24 h post-operation. We noted a significant reduction in pain intensity in patients who received USG-guided TAP block relative to control group patients, as well as reduced morphine consumption and incidence of PONV. However, no such reduction was noted when USG-guided TAP block patients were compared to Port site infiltration group patients at rest and during coughing at all post-operative timepoints upto 24 h.Severe pain for LC patients generally occurs during the first 24 h post-surgery, and is thought to arise mainly from visceral tissue damage and the surgical incision (with the latter taking precedent) . As suchOur study has several limitations: (1) included studies had relatively small sample sizes; (2) extended follow-up data on chronic pain, long-term analgesic use, and adverse events was lacking; (3) multiple pain score scales were used; (4) a diverse range of anesthesia dosages were administered across the studies, and (5) insufficient study numbers for important factors such as laproscopic guided TAP block and fentanyl, tramadol, and opioid consumption, thereby precluding subgroup analysis.This meta-analysis concludes that TAP block is more effective than a conventional pain control, but not significatively different from another local incisional pain control that is port site infiltration. Additional prospective randomized controlled trials are required to further validate our findings.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.WW conceived and designed the study. WW and LW did literature search and analyzed the data. YG wrote the paper, reviewed, and edited the manuscript. All authors have read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Plantar heel pain (PHP) is a common cause of foot complaints, for which treatment with custom-made insoles is frequently applied. So far few studies have investigated patient characteristics that predict response to these treatments. The aim of this secondary exploratory analysis was twofold; firstly, to identify patient characteristics that predict prognosis in patients with PHP treated with insoles, and secondly to identify characteristics that might interact with treatment with insoles.N = 70) or sham insoles (N = 69) were used. At baseline, information was collected on demographics, foot symptoms, foot and ankle range of motion, navicular drop, presence of neuropathic pain, physical activity and other illnesses in the last 12 months. The primary outcome of this study was the Foot Function Index score (FFI) at 26 weeks. Multivariable linear regression models were generated to identify patients characteristics that predict the outcome for each type of intervention .Data from a randomized trial in which participants received either custom insoles  and a lower FFI score at baseline . Explorative analyses in patients treated with insoles showed no significant interaction effects between the type of insole (custom-made versus sham) and any of the potential predictive factors.When communicating about the effect of insoles for PHP clinicians should take sex and the amount of pain and disability at first presentation into account. Women and people with better foot function scores at baseline (according to FFI) might respond better to treatment with insoles in terms of foot function.NTR5346.Trial registration:  Plantar heel pain (PHP), is most commonly defined as pain located at the anteromedial part of the plantar heel during weight-bearing when plantar fascia pathology has not been confirmed by imaging , 2. The Little is known about factors that might predict recovery or response to treatment with insoles in patients with PHP. Whittaker et al. recently found: “People with plantar heel pain who use foot orthoses experience reduced foot pain if they have greater ankle dorsiflexion and lower BMI, while they experience improved foot function if they have lower fear-avoidance beliefs and lower BMI.”  Whereas,For this secondary analysis, data from a previously published randomized trial investigating the effectiveness of treatment with custom-made insoles in patients with PHP were used . PHP wasn = 70). The purpose of the custom-made insole was to influence the biomechanical process to reduce traction on the plantar aponeurosis and to reduce ground reaction force below the tuber calcaneus. The sham insoles were produced according to a standardized procedure, all by the same podiatrist (n = 69). The sham insoles were designed to provide as little mechanical effect as possible, while having a visual effect similar to that of a custom insole. The patients were blinded to the type of insole they received. All patients received an information booklet containing general information on PHP including stretching and strengthening exercises targeted at PHP [Patients allocated to the custom-made insole group were referred to a podiatrist and randomly allocated to receive either a custom-made insole or a sham insole. The custom-made insole was produced according to the standard practice of their podiatrist , were randomly assigned to either ‘left’ or ‘right’.At baseline all participants filled in a questionnaire containing questions regarding demographics: age, sex, weight and length ); general health status: musculoskeletal pain other than in the foot, self-reported illnesses in the last 12 months; foot complaints: affected side , duration of complaints, pain severity , including first step pain, pain in rest and during activity), neuropathic aspect of the pain according to the Doleur Neuropathique 4 ) , the FooPatients that were referred to a podiatrist underwent a standardized physical examination, including the range of motion in the tarsometarsal joint and the first metatarsophalangeal joint (MTP-I) as measured with a goniometer (number of degrees), the navicular drop test (millimeters)  and the At 12 and at 26 weeks participants received questionnaires containing questions on foot function (FFI), self-reported recovery  and pain severity in rest, during activity and first step pain (11-point NRS).The FFI total score at 26 weeks was used as the primary outcome. Secondary outcomes included: the number of patients that reached a minimal important improvement in their total FFI score (an improvement of at least 6.5), the number of patients that considered themselves recovered, the first step pain according to a 11 point NRS and the number of patients that reached a minimal important improvement in their first step pain (an improvement of at least 1.9.)  PotentiaN = 12; range, 0-∞), upper ankle joint dorsiflexion , foot posture index  and FFI total score at 26 weeks   were imputed. 50 Imputations and 20 iterations using fully conditional specification (Markov Chain Monte Carlo (MCMC)) were used [If missing values were completely random and the underlying values were normally distributed, they were imputed and if applicable, the minimum and maximum values were assigned as constraints by the researchers. MTP1 joint dorsiflexion , in patients treated with insoles. The data was checked for outliers, and in case of impossible values, the value was removed. Thereafter, multivariable linear regression analyses with an ENTER model were performed to test the association between the potential prognostic factors as described above and each of the outcomes  after 26 weeks of follow-up in patients treated with insoles.Secondly variables with a significant association with the FFI score at 26 weeks in patients treated with insoles were tested for interaction effects using linear regression, with the allocated treatment in patients treated with custom-made insoles versus sham. All analyses were performed using SPSS v25.0.N = 69, custom insole group N = 70) are presented in Table Baseline characteristics of the 139 included participants (sham insole group (Table ) showed that having unilateral pain , lower score on the DN4 for neuropathic pain , lower BMI , lower baseline FFI score  and lower baseline first step pain score  were significantly associated with lower total FFI score at 26 weeks, indicating better outcomes. In the multivariable analysis, only female sex  and the baseline FFI score  were associated with lower FFI total scores at 26 weeks (R2 = 0.543).The univariate analyses in patients treated with insoles Table  showed tExploratory analyses in patients treated with insoles showed no significant interaction effects between the allocated treatment (custom-made versus sham) and any of the potential predictive factors Table .Table 4All three treatment groups showed improvement over time when compared to baseline, according to the FFI total score, recovery rate and first step pain. Women reported higher symptom and disability scores than men at baseline. Of 16 potential characteristics analyzed in this study, female sex as well as less severe symptoms at baseline were associated to better outcomes at 26 weeks follow-up in patient with PHP being treated with insoles. Of the six characteristics tested for interaction with type of treatment, none had a significant interaction. Although sex had no significant interaction with treatment effect, the confidence interval was wide and included more values on the negative side . Given the small sample size and the exploratory nature of the present analysis, it is possible this study lacked power to demonstrate interaction effects.The FFI total score at 26 weeks was chosen as primary outcome because of its clinical relevance and the fact that a high percentage of patients improved by at least 6.5 points  at 26 weeks when compared to baseline. The choice for this outcome may have influenced the prognostic variables. In this study the FFI total score improved significantly in both treatment groups. At 26 weeks, 79.1% of all participants reached FFI total score MID, while 55.2% self-reported to be recovered. In literature, recovery rates of 80 to 90% within 10 to 12 months are reported . Follow-A high BMI is a known risk factor for the development of PHP and has been found as a prognostic factor for long lasting complaints in patients treated with insoles in a previous study , 18, 33.PHP is more common among females, however the relationship between sex and prognosis was still unknown . In the To our knowledge, so far only one study has focused on patient characteristics that predict response to treatment with insoles in patients with PHP. A strength of this analysis is the fact that is based on a high-quality randomized trial where we found no differences between custom-made insoles and sham insoles . This meThe main limitation of this analysis is the relatively small sample size of 139 patients. The data in the STAP study was not collected with the primary aim to perform these analyses. This limited the power and the number of potential patient characteristics that could be included. Some confidence intervals were wide and further analysis with higher power may potentially identify significant effects. Moreover, the explained variance of the multivariable model was rather low, with an explained variance of 54%.There are no studies on prognostic variables for PHP in populations with another treatment than insoles, it therefore remains unknown, whether the prognostic variables found in this study are representative in a different context.Furthermore, PHP is a condition that can remain symptomatic for over a year in a small percentage of patients . Our folFinally, PHP is a broad term which can cover a range of different pathologies of heel pain. Given the inclusion criteria of the STAP-study, it is possible that the patients included in this study have a range of different causes of heel pain as we did not include the specific criteria of pain at palpation of the medial tubercle of the calcaneus. Therefore, the exact origin of the participants’ s complaints remains unknown. However, exploring a wide differential diagnosis of PHP is often not indicated, since it does not influence clinical decision making . We therFemale sex and less severe initial complaints, in terms of foot function, are associated with lower total FFI score at 26 weeks in patients with PHP who receive treatment with insoles. Future studies should take a difference in response to treatment with insoles for males versus females into account in their design.